Lipoprotein subfractions in patients with depression: The lipoprint system
Tarkan Yazıcı 1, İlkay Bahçeci 2, Süheyl Uçucu 3, Bülent Bahçeci 4
1 Department of Medical Biochemistry, Turkish Ministery of Health Sıtkı Koçman University Research and Training Hospital, 2 Department of Medical Microbiology, School of Medicine, Recep Tayyip Erdoğan University, Rize, 3 Department of Medical Biochemistry, Turkish Ministry of Health Mugla Public Health Care Laboratory, Mugla, 4 Department of Psychiatry, School of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey
DOI: 10.4328/ACAM.20815 Received: 2021-08-13 Accepted: 2021-10-19 Published Online: 2022-03-28 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):470-474
Corresponding Author: Tarkan Yazıcı, Department of Medical Biochemistry, Turkish Ministery of Health Sıtkı Koçman University Research and Training Hospital, Mugla, Turkey. E-mail: email@example.com P: +90 532 542 69 88 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7028-7401
Aim: The aim of the study is to investigate the relationship between depression and changes in 25-OH Vitamin D and Lipoprotein serum levels, which have been suggested to be associated with Central Nervous System neurotransmission and certain psychiatric disorders.
Material and Methods: The study included a patient group consists of 40 depressive individuals who have applied to the Psychiatry outpatient clinic of our hospital and have been first diagnosed with depression according to SCID-1 (Structured Clinical Interview for DSM IV Axis I Disorders) criteria and had no psychiatric or systemic disease that could affect the result, as well as a control group of 40 healthy individuals with similar demographic characteristics. In the collected serum samples, 25-OH vitamin D, LDL, HDL, VLDL, total cholesterol, and TG levels were measured enzymatically and spectrophotometrically; Apolipoprotein Al and Bl00 levels were measured nephelometrically, LDL and HDL subfractions were measured using the Lipoprint System, and then the results were evaluated statistically.
Results: Atherogenic LDL 3 and LDL 4 were significantly higher in the patient group (p=0.001 and p=0.0155, respectively). The mean LDL particle diameter (LDL Mean) was significantly lower in the patient group (p=0.0017). There was no significant difference between the patient and control groups in terms of Buoyant LDL, but Small Dense LDL levels were significantly higher in the patient group (p=0.008 and p<0.001, respectively). LDL 1 Subfraction level of the patient group was statistically significantly higher than the control group (p = 0.0046). There was no significant difference in LDL 2 (p=0.356O).
Discussion: According to the results, LDL 3, LDL 4, and Small Dense LDL serum levels of the patients with depression were found to be higher. The fact that Small Dense LDL has a long circulation time in the blood, atherogenic and proinflammatory properties, better penetrability into the arterial intima layer and is considered as a risk factor in the CVD group, suggests that the risk of atherosclerosis, inflammation and CVD may be higher in patients with depression.
Keywords: Lipoprotein, 25-OH Vitamin D, Depression, Atherosclerosis, Small Dense LDL, LDL Subfractions, Buoyant LDL
The density of lipoprotein is related to the number of lipids and proteins in a particle . The particle size decreases as the amount of cholesterol in the lipid core of particles decreases . In ultracentrifugation, large and light lipoproteins accumulate on the top, and small and heavy ones at the bottom. As a result, chylomicrons (CMs) are classified into five groups: very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL) .
Recent studies have shown that HDL subgroup analysis is more determinant in the identification of coronary artery disease risk compared to total HDL measurement [4-6]. Another study identified three HDL subgroups such as large HDL (HDL-L), intermediate HDL (HDL-I) and small HDL (HDL-S) based on the analysis of normolipidemic and dyslipidemic plasma samples . A significant difference was found between HDL-L and HDL-S subgroups in dyslipidemic and normolipidemic plasma samples. The development of atherosclerosis is inversely proportional to HDL-L and directly proportional to HDL-S .
LDL is divided into subgroups according to chemical composition, density and particle size. Small LDL particles are more atherogenic since they show reduced affinity for LDL receptors, greater binding to the endothelial proteoglycans, and better penetration to the arterial intima layer . Today, several methods such as nuclear magnetic resonance, gel electrophoresis, lipoprint system, ultracentrifugation and high-performance gel filtration chromatography are used to determine LDL subgroups. However, the reference method in this regard is not certain .
Apoproteins are involved in the water solubility of lipoproteins as well as their recognition by cell receptors, thus facilitating their receptor-mediated endocytosis .
Vitamin D is synthesized in the skin from 7-dehydrocholesterol by UV irradiation at a wavelength of 290-310 nm in the form of cholecalciferol, which is the main source of endogenous Vitamin D .
Depression is not just a mental breakdown but a set of symptoms and signs named as a depression. It is a syndrome including symptoms such as slowness in thinking, speaking, and movements, stillness, unworthiness, guilt, tiredness, loss of attention and concentration, reluctance, loss of motivation, pessimist thoughts and feelings, and slowing of physical activities, in general, a deeply sad emotional state .
It was demonstrated that free fatty acids and cholesterol levels in the blood increase in emotional arousal in psychiatric disorders . While it has been suggested that Vitamin D and depression are inversely proportional to each other, i.e. decreased Vitamin D levels increase the risk of depression; studies have shown that levels below 20 ng/ml cause depression .
In light of all this information, our study aims to investigate the relationship between depression and changes in 25-OH vitamin D and lipoprotein serum levels, which have been suggested to be associated with Central Nervous System neurotransmission and certain psychiatric disorders.
Material and Methods
Within the scope of this prospective study, a control group consisting of 40 patients (9 males (22.5%), 31 females (77.5%)) and 40 healthy volunteers (16 males (40%), 24 females (60%)) who applied to University Training and Research Hospital Psychiatric Clinic were included in the study. Ethical approval was obtained from Training and Research Hospital Local Ethics Committee and the study was carried out in accordance with the Helsinki Declaration.
The sample group included 40 patients who have applied to the Psychiatry outpatient clinic of our hospital with psychiatric complaints, and who have been first diagnosed with depression according to the SCID-I (Structured Clinical Interview for DSM IV Axis I Disorders) criteria (an interview tool that was structured by the interviewer and is applied to investigate the diagnosis of Axis I mental disorders and whose validity-reliability have been confirmed by Çorapoğlu et al. (1999)) , and who have not received any treatment yet and had no pathological disease other than depression, as well as 40 healthy controls. Venous blood samples were collected from the sample group of 80 individuals, between 8:00 am and 10:30 am, following a 12-hour fasting and a 15-minute rest, in vacuum tubes with gel and without anticoagulant. The tubes were left for at least 15 minutes to ensure that they were clotted and then centrifuged at 3000 rpm for 15 minutes. The serum samples were aliquoted and stored in a freezer at -20oC for the tests, which would not be run on the same day. Then, the samples were left at 2-8 degrees to thaw one day before the study day, and taken out from the refrigerator at an early hour and left to reach the study temperature.
25-OH Vitamin D levels were measured on the Architect i 2000 device using the ‘Microparticle Enzyme Immunoassay Method’ (Abbott Diagnostics, USA). Total cholesterol, LDL, VLDL, HDL, triglyceride levels were measured using the ‘Enzymatic-Photometric Method’ on the Architect cl6000 device (Abbott Diagnostics, USA). Apoprotein A, Apoprotein B, Lipoprotein (a) levels were measured on the Image 800 device using the “Nephelometric Method’’ (Beckman Coulter, USA). Lipoprotein subfractions were run using the “Non-denaturing Polyacrylamide Gradient Gel Electrophoresis (PAGE)” lipoprint method. First, the samples were treated with “Sudan Black B”, which binds the cholesterol in serum lipoproteins. At pH = 8.2-8.6, three mA current was applied on the tube heads during the electrophoresis that lasted nearly one hour. Lipoproteins were sorted by particle size in the form of bands stained with lipophilic stain.
’McdCalc’ (version 188.8.131.52) statistical software was used to evaluate data from the sample group. The Kolmogorov-Simimov test was used to determine whether the data of the patient and control groups fit the normal distribution. The independent t-test was used to evaluate the data of the patient and control groups that were normally distributed. The Mann Whitney U test was applied to compare the patient and control groups not fitting the normal distribution. The significant difference between the groups was evaluated within the 95% confidence interval (p <0.05). Box-Whisker plots were used for the graphical representation of the patient and control group data.
As a result of the statistical analysis of the analytes examined in our study, the p -values of the average, standard deviation, minimum, maximum and statistical significance level of the measurements and demographic information made in the healthy control group and patient group are shown in Table 1 and Table 2.
When both groups were statistically evaluated in terms of socio-demographic characteristics, no significant difference was found (P>0.05).
The calculation is made as follows, if the mean LDL diameter is below 163°A:
LDL 1 Buoyant LDL
LDL 2 + LDL 3 + LDL 4 + LDL 5 + LDL 6 + LDL 7 = Small Dense LDL
And, as shown below, if the mean LDL diameter is above 163°A:
LDL 1 + LDL 2= Buoyant LDL
LDL3 + LDL 4 + LDL 5 + LDL 6 + LDL 7=Small Dense LDL.
In the results obtained from the patient group and the control group, even 25-OH Vitamin D levels were low (below 20ng/ml) in both groups, the results of the patient group were not considered statistically significant (p=0.001). No statistically significant difference was found between total cholesterol, TG, HDL, LDL, Apolipoprotein B-100, and HDL subfraction results (p>0.05). Examining LDL subfractions results, they were not significantly higher in the control group (p=0.0046). There was no significant difference in LDL 2 (p=0.35). Atherogenic LDL 3 and LDL 4 were significantly higher in the patient group (p=0.001, p=0.0155, respectively). The mean LDL particle diameter (LDL Mean) was significantly lower in the patient group (p=0.0017). There was no significant difference between the patient and control groups in terms of Buoyant LDL (p=0.008), but Small Dense LDL values were significantly higher in the patient group (p<0.001).
In this study, we aimed to investigate the relationship between depression and the changes in 25-OH Vitamin D and Lipoprotein serum levels, which have been to be suggested to be associated with Central Nervous System neurotransmission and certain psychiatric disorders.
While it is accepted that there is an inverse relationship between Vitamin D, whose receptors in the Central Nervous System have been shown and efficiency have been discussed, and depression risk, i.e. decreased serum Vitamin D levels increase depression risk, the study conducted by Milaneschi et al.  showed that levels below 20 ng/ml cause depression . As a result of our enzymatic and spectrophotometric measurements, serum Vitamin D levels were below 20 ng/ml in both groups, but were statistically significantly higher in the patient group than in the control group, which was contrary to the literature (p=0.0013). While this is considered significant for the patient group, this lower value in the control group may be associated with the low number of samples in the patient and control group included in the study, independent of the symptoms of depression.
In the studies conducted by Melin et al. , and Chang et al. , it was demonstrated that free fatty acids and cholesterol levels in the blood increase with emotional arousal in psychiatric disorder. Maes et al.  found that in depressive patients and their first-degree relatives, blood cholesterol levels as well as esterified cholesterol rates were lower than in the normal group, and suggested that less esterification of cholesterol may lead to an increase in the cell membrane fluidity, thus leading to depression.
The relationships between total cholesterol in serum and depressive disorders have been investigated, but their relationship with other lipids and depressive disorders has been rarely discussed. The ratio of serum HDL level to total cholesterol was reported to be statistically significantly lower in patients with major depression compared to controls . There are studies showing that serum LDL levels are significantly higher in women in the group consisting of patients with major depressive disorder compared to the control group, while it is significantly lower in men in the same group . In the meta-analysis of 36 studies and conducted by Jane et al. , serum LDL was generally significantly lower. While in some studies TG levels were found to be higher in patients with major depressive disorder ; no significant difference was found in the study by Özcankaya et al .
In our study on this controversial issue, we investigated total cholesterol, TG, VLDL, HDL and LDL levels in the serum samples collected from the patient and control groups. We did not find a significant difference between the two groups as a result of the statistical comparison of the depressive patient and healthy control groups (p>0.05). The oxidation of Apo B-100 increases atherosclerosis with the formation of several pro-inflammatory products . Due to these characteristics, Apolipoprotein A-I and Apolipoprotein B-100 were chosen among many types of apolipoproteins, and their serum levels were measured nephelometrically. However, no statistically significant difference was found in serum Apolipoprotein A-I and Apolipoprotein B-100 levels between the patient and control groups (p>0.05).
Among the methods used for the determination of lipoprotein subfractions, the Lipoprint System is the first and only system approved by the FDA for the quantitative and qualitative measurement of LDL and HDL subgroups. Now, it is possible to measure small dense LDL, IDL, and HDL subgroups with high atherogenicity, which cannot be measured with other methods. In lipoprint, which is a linear polyacrylamide gel electrophoresis, lipoprotein particles are resolved with the effect of electric current without using the gradient gel of the gel matrix. Lipoprotein distribution is consistent with the distribution performance of the ‘Continuous Gradient Ultracentrifugation’ method .
Large HDL is inversely proportional to atherosclerosis, while small HDL has a positive relationship with atherosclerosis, since it infiltrates within the vessel wall . In our study, HDL subfractions were classified in 10 subgroups. These 10 subgroups were divided into three sub-classes; the first three were Large HDL, the next four were intermediate HDL, and the last three were small HDL. As a result of the measurements with the lipoprint method, no significant difference was found in terms of HDL subfractions between the depressive patient group and the healthy control group in all of the three subgroups (p>0.05). The fact that there was no significant difference in Apolipoprotein A-I level supported our finding in the current study (p>0.05).
In the study by Vega et al. , LDL subfractions were divided into two classes, such as small dense LDL and Buoyant LDL; in the calculation, the controversial LDL 2 was associated with LDL diameter; the LDL 2s of the LDLs with a mean diameter above 263°A were named as Buoyant LDL. LDLs 2s with a mean diameter above 263°A were included in the small dense LDL class. This is caused by the fact that Small Dense LDL is extremely prone to lipid peroxidation, although it is less involved in the oxidative stress pathway of Buoyant LDL . In our study, LDL subfractions were divided into seven subgroups. Among these subgroups, LDL 1 was found to be significantly higher in the control group; there was no significant difference in terms of LDL 2 in both groups, but LDL 3 and LDL 4, whose atherogenicity was shown to be high, were found to be significantly higher in the patient group. Given the diameters of LDL subfractions, the mean diameter in the patient group was found to be significantly smaller than the control group. Atherogenic small dense LDL subfractions were found to be significantly higher in the patient group compared to the control group, which may increase the risk of susceptibility to lipid peroxidation and exposure to atherogenicity in these lipoprotein fractions in the depression group.
The finding of such a difference in LDL subfractions, although there was no significant difference between the control and patient groups for all other lipoprotein and apolipoprotein levels, is explained by the fact that Small Dense LDL particles show increased affinity for LDL receptors, greater binding to the endothelial proteoglycans, susceptibility to lipid peroxidation, and better penetration to the arterial intima layer. Small Dense LDL has a long circulation time in the blood, atherogenic and proinflammatory properties, better penetrability into the arterial intima layer, and is considered a risk factor in CVD group, which suggests that the risk of atherosclerosis, inflammation and CVD may be higher in patients with depression. Thus, higher Small Dense LDL levels in the patient group suggest that the risk of atherosclerosis may be higher in depressed individuals.
Limitations of the study
Although the study has been carefully prepared, we are still aware of its limitations and shortcomings. Firstly, as discussed above, our study population carries limited possibilities for exploring causal relationships and does not provide clinical follow-up, therefore it may not adequately reflect the general population and the relationship between depression and lipoprotein. Secondly, the number of patients and control groups can be increased, and gender differences can be examined, resulting in a wide range of data for Turkish society for males and females.
In memory of our esteemed teacher Prof. Dr. Hasan EFE, who contributed to this article and passed away during the publication phase.
Scientiﬁc Responsibility Statement
The authors declare that they are responsible for the article’s scientiﬁc content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientiﬁc review of the contents and approval of the ﬁnal version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
1. Ivanova EA, Myasoedova VA, Melnichenko AA, Grechko AV, Orekhov AN. Small dense low-density lipoprotein as biomarker for atherosclerotic diseases. Oxid Med Cell Longev. 2017; 2017:1273042
2. Ito F, Ito T. High-Density Lipoprotein (HDL) Triglyceride and Oxidized HDL: New Lipid Biomarkers of Lipoprotein-Related Atherosclerotic Cardiovascular Disease. Antioxidants (Basel). 2020; 9(5): 362.
3. Sinning D, Leistner DM, Landmesser U. Impact of lipid metabolism parameters on the development and progression of coronary artery disease. Herz. 2016;41(4):273-80
4. Kingsbury KJ, Bondy G. Understanding the essentials of blood lipid metabolism. ProgCardiovasc Nurs. 2003;18(1):13-8.
5. Mannarino E, Pirro M. Molecular biology of atherosclerosis. Clin Cases Miner Bone Metab. 2008;5(1):57.
6. Morgan J, Carey C, Lincoff A, Capuzzi D. High-density lipoprotein subfractions and risk of coronary artery disease. Current Atherosclerozis Reports. 2004;6(5):359-65.
7. Masulli M, Patti L, Riccardi G, Vaccaro O, Annuzzi G, Ebbesson SO, et al. Relation among lipoprotein subfractions and carotid atherosclerosis in Alaskan Eskimos (from the GOCADAN Study). Am Journal Cardiology. 2009; 104(11):1516-21.
8. Landray MJ, Edmunds E, Li-Saw-Hee FL, Hughes BA, Beevers DG, Kendall MJ, et al. Abnormal low-density lipoprotein subfraction profile in patients with untreated hypertension.QJM. 2002; 95(3):165-71.
9. Chung M, Lichtenstein AH, Ip S, Lau J, Balk EM. Comparability of methods for LDL subfraction determination: A systematic review. Atherosclerosis. 2009; 205(2):342-8.
10. Holick MF. Vitamin D: the underappreciated D-lightful hormone that is important for skeletal and cellular health. Current Opinion in Endocrinology. Diabetes and Obesity. 2002; 9(1):87-98.
11. Žmitek K, Hribar M, Hristov H, Pravst I. Efficiency of Vitamin D Supplementation in Healthy Adults is Associated with Body Mass Index and Baseline Serum 25-Hydroxyvitamin D Level. Nutrients. 2020; 12(5):1268.
12. Kremer M, Becker LJ, Barrot M, Yalcin I. How to study anxiety and depression in rodent models of chronic pain? Eur JNeurosci. 2021; 53(1):236-70.
13. LeMoult J, Gotlib IH. Depression: A cognitive perspective. Clin Psychol Rev. 2019; 69:51-66.
14. Wagner CJ, Musenbichler C, Böhm L, Färber K, Fischer AI, von Nippold F, et al. LDL cholesterol relates to depression, its severity, and the prospective course. Prog Neuropsychopharmacol Biol Psychiatry. 2019; 92:405-11.
15. Melin EO, Thulesius HO, Hillman M, Svensson R, Landin-Olsson M, Thunander M. Lower HDL-cholesterol, a known marker of cardiovascular risk, was associated with depression in type 1 diabetes: a cross sectional study. Lipids Health Dis. 2019; 287:e228.
16. Konuk N, Kiran S, Tamam L, Karaahmet E, Aydin H, Atik L. Duygudurum Bozukluklari Olçeği’nin Türkçe Uyarlamasiniin Bipolar Bozukluk Taramasinda Geçerliği [Validation of the Turkish version of the mood disorder questionnaire for screening bipolar disorders]. Turk Psikiyatri Derg. 2007; 18(2):147.
17. Milaneschi Y, Shardell M, Corsi AM, Vazzana R, Bandinelli S, Guralnik JM, et al. Serum 25-hydroxyvitamin D and depressive symptoms in older women and men. J Clin Endocrinol Metab. 2010; 95(7):3225-33.
18. Vega GL, Ma PT, Cater NB, Filipchuk N, Meguro S, Garcia-Garcia AB, et al. Effects of adding fenofibrate (200 mg/day) to simvastatin (10 mg/day) in patients with combined hyperlipidemia and metabolic syndrome. Am J Cardiol. 2003; 91(8):956-60.
19. Chang NT, Su TC. Investigating the association between familial hypercholesterolemia and perceived depression. Atherosclerosis. 2019; 36:31-6.
20. Maes M, Delanghe J, Meltzer HY, Scharpé S, D’Hondt P, Cosyns P. Lower degree of esterification of serum cholesterol in depression: relevance for depression and suicide research. Acta Psychiatr Scand. 1994; 90(4):252-8.
21. Ancelin ML, Carrière I, Boulenger JP, Malafosse A, Stewart R, Cristol JP, et al. Gender and genotype modulation of the association between lipid levels and depressive symptomatology in community-dwelling elderly (the ESPRIT study). Biological Psychiatry. 2010; 68(2):125-32.
22. Persons JE, Fiedorowicz JG. Depression and serum low-density lipoprotein: A systematic review and meta-analysis. J Affect Disord. 2016; 206:55-67.
23. Özcankaya R, Delibaş N. Psikiyatrik Belirtiler ve Serum Lipid Düzeyleri Arasındaki İlişki (The Relationship Between Psychiatric Symptoms and Serum Lipid Levels). Klinik Psikiyatri Dergisi /Journal of Clinical Psychiatry. 2001; 4(4):241-8.
24. Camont L, Chapman MJ, Kontush A. Biological activities of HDL subpopulations and their relevance to cardiovascular disease. Trends Mol Med. 2011;17(10):594-603.
25. Khajehnasiri F, Mortazavi SB, Allameh A, Akhondzadeh S, Hashemi H. Total antioxidant capacity and malondialdehyde in depressive rotational shift workers. J Environmental and Public Health. 2013; 150-696.
Download attachments: 10.4328:ACAM.20815
Tarkan Yazıcı, Süheyl Uçucu. Lipoprotein subfractions in patients with depression: The lipoprint system. Ann Clin Anal Med 2022;13(5):470-474
Post-recovery pulmonary function test and thorax CT correlations in COVID-19 survivors
Adem Melekoglu 1, Mufide A. Ozkarafakili 2, Derya Ozturk 1
1 Department of Emergency Medicine, 2 Department of Pulmonary and Chest Diseases, Sisli Hamidiye Etfal Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20913 Received: 2021-10-22 Accepted: 2022-04-06 Published Online: 2022-04-08 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):475-479
Corresponding Author: Derya Ozturk, Department of Emergency Medicine, University of Health Sciences, Sisli Hamidiye Etfal Education and Research Hospital, Halaskargazi Cd., 34371, Sisli, Istanbul, Turkey. E-mail: firstname.lastname@example.org P: +90 505 279 55 05 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7318-0725
Aim: Long-COVID has been described as persistent symptoms involving multiorgan systems in COVID-19 survivors. This single-centred study investigated the correlation between pulmonary function test (PFT) and thorax computed tomography (CT) results in COVID-19 survivors after six months of follow-up period.
Material and Methods: Patients recovered from COVID-19 aged between 18 and 50 years were included in this study and divided into two groups according to PFT results as patients with normal PFT results (PFT normal; n = 74) and with PFT results with restrictive pattern (PFT restrictive; n = 12). The primary aim of this study was to try to predict the prognosis of long-term chronic pulmonary system diseases using pulmonary function test, thorax CT and laboratory findings in the sixth month after recovery.
Results: There were no significant differences between the patients in PFT normal and PFT restrictive groups in terms of symptoms and CT findings at admission. On the other hand, the rate of dyspnoea and exertional dyspnoea was significantly more pronounced in patients in PFT restrictive group, while there were no significant differences between CT findings. Both univariate and multivariate regression analyses showed that percent forced expiratory volume in one second (%FEV1) and percent forced vital capacity (%FVC) results are associated factors in discriminating normal and PFT results with restrictive pattern in COVID-19 survivors.
Discussion: PFTs should be included in follow-up evaluations of COVID-19 patients in order to elucidate the post-COVID-19 pulmonary abnormalities.
Keywords: Computed Tomography, COVID-19, Long-COVID, Pulmonary Function Test
Coronavirus Disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), emerged from China in December 2019 and has continued to affect the humanity worldwide as an exceptional challenge . The route of infection of the virus is mainly via air droplets and aerosol . Its presentations include symptoms of respiratory illness together with other symptoms including fever, cough, myalgia, shortness of breath, loss of taste / smell in symptomatic individuals [3, 4], while substantial number of individuals were reported as asymptomatic COVID-19 cases .
Since its emergence, a remarkable effort has been made for the diagnosis, management, treatment, and prevention of the disease. However, chronic impacts of the disease on the patients still remain elusive. Long-lasting symptoms may be present in patients after recovery from severe or moderate COVID-19 , however, individuals showing “mild” symptoms who were stated to require care at home and isolation with the expectation of the recovery from infection also had post-COVID-19 syndrome (Long COVID) [7, 8]. The term of long COVID is used to describe persistent symptoms with the involvement of multiorgan systems after recovery from the acute infection [9, 10].
Many individuals that were recovered from COVID-19 shared their experiences through social media, blogs, and traditional media. Aside from these anecdotal indications, several studies about long COVID were published. However, more studies regarding the long-lasting effects of COVID-19 are needed. The primary aim of this study was to try to predict the prognosis of long-term chronic pulmonary system diseases in patients that were diagnosed with COVID-19 before May 2020 in the emergency room (ER) of a tertiary Education and Research Hospital emergency service serving as Pandemic Hospital and recovered after treatment by analysing the pulmonary function test, tomography, and laboratory findings on the sixth month after recovery. The secondary aim of this study was to identify the symptoms that affect the quality of life of patients to take early measures for chronic diseases that may arise in the future.
Material and Methods
Study group and design
The single-centred study was conducted between 01/01/2021 and 01/02/2021 after approval of the local Clinical Research Ethics Committee (date: 22.12.2020, number: 3072). All procedures were performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments. Authors have complied with the international guidelines, the “Regulations on Pharmaceutical Research,” enforced by The Ministry of Health of Turkey published in the 27089 numbered Official Journal dated 23 December 2008 and also with other regulations published at a later date. Our study included a total of 86 patients who admitted to ER in our hospital, which served as a pandemic hospital. The inclusion criteria were being aged between 18 and 50 years, having a positive COVID-19 polymerase chain reaction (PCR) test result before May 2020, having no known pulmonary and / or neurological and / or neuropsychiatric disorders, being non-smoker and having a complete medical record. Patients who were younger than 18 years or older than 50 years, with negative PCR test result, without complete medical record, with known pulmonary and / or neurological and / or neuropsychiatric disorders and smokers were excluded from the study. All patients included in this study were either transferred from ER to the service or discharged and none of the patients were hospitalized in the intensive care unit (ICU).
Patients’ information was accessed from the hospital electronic information system. Medical records of the volunteers after the first admission, before May 2020, including complete blood counts, comorbidity, laboratory parameters, computed tomography (CT) results and demographical characteristics were also accessed and investigated. The patient group who met the inclusion criteria were contacted by phone and informed about the study, and the tests and analyses to be performed were explained in detail. Patients who volunteered to participate in the study were invited to the hospital during the weekdays with a maximum of five patients for each day with an appointment. Written informed consents of the patients were obtained on arrival to the hospital for their anonymized information to be published in this article.
Patients’ demographical characteristics (age, gender and whether they were healthcare workers or not), complaints present at the first admission, treatment that they received were recorded. Moreover, complete blood count, blood biochemistry (glucose, urea, creatinine, lactate dehydrogenase (LDH), C-reactive protein (CRP)), d-dimer, ferritin, troponin, arterial blood gas measurements (pH, CO2 and SO2) were performed at the first admission and six-months follow-up. Thorax CT results obtained at the first admission and six-months follow-up were compared. Symptoms that patients experienced within six months after recovery were also recorded.
Pulmonary function test (PFT) was performed on the patients at the first admission and six-months follow-up by an experienced technician using the device Spirolab III with Colour LCD (MIR; Rome, Italy). Patients were evaluated based on the percent predicted forced expiratory volume in one second (FEV1%), percent predicted forced vital capacity (FVC%), FEV1/FVC and forced expiratory flow at 25-75% of the pulmonary volume (FEF25-75) according to the guidelines published by American Thoracic Society , and were required to have FEV1/FVC > 70% to eliminate any obstructive lung disease. PFTs were conducted triplicates and the most accurate tests were used for the analysis.
Statistical analyses were conducted using SPSS version 27.0 (IBM, USA). In descriptive statistics, mean, standard deviation (SD), median, minimum and maximum values, frequency and ratio were used. The Kolmogorov-Smirnov test was used to evaluate the distribution of the data. Quantitative independent data were analysed using an unpaired t-test in case the normal distribution criteria were met, or the Mann-Whitney U test in case they were not normally distributed. Qualitative independent data were analysed using the Chi-square test, and when the conditions for the Chi-square test were not met, Fischer’s exact test was used. Univariate or multivariate logistic regression analyses were performed to investigate the level of effect.
The mean age of the patients was 36.9 ± 9.1 years and most of the patients admitted to the ER were females (57%; Table 1). Cough was the most pronounced symptom at the admission (62%) and this was followed by fever (57%) and dyspnoea (43%; Table 1). The other symptoms are weakness-myalgia (36%), throat pain-headache (16%), sputum (7%), diarrhea (6%) and loss of odour-taste (6%). The general condition of the most of the patients at the admission were good (Table 1), while CT findings of the patients were found as severe (43%) and moderate (42%; Table 1; Figure 1 and 2). Most of the patients admitted to ER were outside of the healthcare sector (76%; Table 1). Treatment of the 48 patients continued in the clinics after discharge from ER (Table 1). The mean duration of the hospital stay was 3.6 ± 3.6 days (Table 1).
In the group of PFT restrictive, FEV1% and FVC% values were significantly lower than the group with PFT normal (p<0.05), while FEV1/FVC and FEF25-75 values did not differ (p>0.05) (Table 2). The ratio of male patients in the group of PFT restrictive was significantly higher than the group of PFT normal (p<0.05). There were no differences in age between the two groups (p>0.05). On the other hand, other parameters such as symptom at the admission, general condition at ER admission, CT findings at the admission (Figure 1a, c and Figure 2a), duration of the hospital stay, and medical treatment of the patients did not differ between the groups. On the other hand, there were no differences between two groups with regards to complete blood count, blood biochemistry, d-dimer, ferritin, troponin, and arterial blood gas measurements at the first admission and six-months follow-up (p>0.05).
Persistent symptoms were observed in 28 patients (32.5%). In the PFT restrictive group, the rate of persisting symptoms was significantly higher than in the group with PFT normal group six months after the first admission (p<0.05; Table 2). Among persistent symptoms, rates of dyspnoea on exertion and dyspnoea were significantly higher in PFT restrictive group than in the normal PFT group found at month six of the follow-up (p<0.05), however, rates of other persisting symptoms including diarrhea, loss of odour-taste and cough investigated on the follow-up examination did not differ between the groups (p>0.05; Table 2). On the other hand, the presence of abnormal CT findings (fibrosis, small nodule, atelectasis, pleural thickening, attenuation, emphysema, traction bronchiectasis, interlobular thickening) as well as the type of the abnormality when examined six months after the first admission did not differ between the groups (p>0.05; Figure 1b, d and Figure 2b).
The level of effects of gender, FEV1%, FVC%, persistent symptom six months after the first admission and dyspnoea on exertion six months after the first admission were investigated using both univariate and multivariate logistic regression models. In the univariate model, significant effects of gender, FEV1%, FVC%, persistent symptoms six months after the first admission and dyspnoea on exertion six months after first admission (p<0.05) were observed in the differentiation of group of patients in PFT normal and PFT restrictive (Table 3). On the other hand, in the multivariate model, FEV1% and FVC% were found to be significant and independently effective in the differentiation of patients in PFT normal and PFT restrictive groups (p <0.05; Table 3).
Long COVID has been reported in patients recovered from COVID-19. In the present study, we investigated the pulmonary function and long-lasting symptoms in COVID-19 patients six months after recovery. Although the condition of the patients was generally improved, patients with PFT results with restrictive patterns at the evaluation still had dyspnoea and dyspnoea on exertion at a significantly higher rate than the patients with normal PFT results six months after recovery. Moreover, FEV1% and FVC% were found to be effective in the differentiation of post-COVID patients in PFT normal and PFT restrictive groups in both univariate and multivariate logistic regression models.
In this study, around one-third of the patients showed long-lasting symptoms that was consistent with previous studies [12, 13]. Although fatigue was the most common persistent symptom after recovery from COVID-19 in previous studies [12-15], in our study, participants did not report fatigue as long-lasting symptoms in both PFT normal and PFT restrictive groups. On the other hand, most common long-lasting symptom was dyspnoea on exertion in both groups in our study group and dyspnoea and dyspnoea on exertion was found to be significantly higher in the PFT restrictive group. Dyspnoea has been implicated to affect the quality of life of the patients after recovery from COVID-19 . Moreover, in several other studies, patients reported declined quality of life [12, 17].
One of the limitations of our study was the relatively small sample size of the single-centre cohort. Moreover, performing baseline PFTs, such as PFT on the day before discharge, might have been relevant to observe the recovery of the patients within the follow-up period. Longer- term studies are required to assess the pulmonary sequelae in COVID-19 survivors.
In our study, we observed that CT results in both PFT normal and PFT restrictive groups did not differ. On the other hand, we observed that FEV1% and FVC% were associated with the long-term complications of COVID-19 after recovery. Studies highlighting the PFT data have been very limited in post-COVID-19 patients [17-19]. As previously suggested , our study suggests that PFT can be performed in patients recovered from COVID-19 and should be included in the follow-up procedures of the patients in order to elucidate the post-COVID-19 pulmonary abnormalities.
Scientiﬁc Responsibility Statement
The authors declare that they are responsible for the article’s scientiﬁc content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientiﬁc review of the contents and approval of the ﬁnal version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
1. Lai CC, Shih TP, Ko WC, Tang HJ, Hsueh PR. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges. Int J Antimicrob Agents. 2020;55(3):105924.
2. van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. N Engl J Med. 2020;382(16):1564-7.
3. Lovato A, de Filippis C, Marioni G. Upper airway symptoms in coronavirus disease 2019 (COVID-19). Am J Otolaryngol. 2020;41(3):102474.
4. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506.
5. Wölfel R, Corman VM, Guggemos W, Seilmaier M, Zange S, Müller MA, et al. Virological assessment of hospitalized patients with COVID-2019. Nature. 2020;581(7809):465-9.
6. Townsend L, Dowds J, O’Brien K, Sheill G, Dyer AH, O’Kelly B, et al. Persistent Poor Health Post-COVID-19 Is Not Associated with Respiratory Complications or Initial Disease Severity. Ann Am Thorac Soc. 2021; 18(6):997-1003.
7. Gandhi RT, Lynch JB, Del Rio C. Mild or Moderate Covid-19. N Engl J Med. 2020;383(18):1757-66.
8. Goërtz YMJ, Van Herck M, Delbressine JM, Vaes AW, Meys R, Machado FVC, et al. Persistent symptoms 3 months after a SARS-CoV-2 infection: the post-COVID-19 syndrome? ERJ Open Res. 2020;6(4). DOI: 10.1183/23120541.00542-2020.
9. Greenhalgh T, Knight M, A’Court C, Buxton M, Husain L. Management of post-acute covid-19 in primary care. BMJ. 2020;370:m3026.
10. Lopez-Leon S, Wegman-Ostrosky T, Perelman C, Sepulveda R, Rebolledo PA, Cuapio A, et al. More than 50 Long-term effects of COVID-19: a systematic review and meta-analysis. medRxiv. 2021;. DOI: 10.1101/2021.01.27.21250617.
11. Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG, Hall GL, et al. Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med. 2019;200(8):e70-e88.
12. Logue JK, Franko NM, McCulloch DJ, McDonald D, Magedson A, Wolf CR, et al. Sequelae in Adults at 6 Months After COVID-19 Infection. JAMA Netw Open. 2021;4(2):e210830.
13. Tenforde MW, Billig Rose E, Lindsell CJ, Shapiro NI, Files DC, Gibbs KW, et al. Characteristics of Adult Outpatients and Inpatients with COVID-19 – 11 Academic Medical Centers, United States, March-May 2020. MMWR Morb Mortal Wkly Rep. 2020;69(26):841-6.
14. Carfì A, Bernabei R, Landi F. Persistent Symptoms in Patients After Acute COVID-19. Jama. 2020;324(6):603-5.
15. Garrigues E, Janvier P, Kherabi Y, Le Bot A, Hamon A, Gouze H, et al. Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. J Infect. 2020;81(6):e4-e6.
16. Santus P, Tursi F, Croce G, Di Simone C, Frassanito F, Gaboardi P, et al. Changes in quality of life and dyspnoea after hospitalization in COVID-19 patients discharged at home. Multidiscip Respir Med. 2020;15(1):713.
17. van der Sar-van der Brugge S, Talman S, Boonman-de Winter L, de Mol M, Hoefman E, van Etten RW, et al. Pulmonary function and health-related quality of life after COVID-19 pneumonia. Respir Med. 2021;176:106272.
18. George PM, Barratt SL, Condliffe R, Desai SR, Devaraj A, Forrest I, et al. Respiratory follow-up of patients with COVID-19 pneumonia. Thorax. 2020;75(11):1009-16.
19. Hull JH, Lloyd JK, Cooper BG. Lung function testing in the COVID-19 endemic. Lancet Respir Med. 2020;8(7):666-7.
Download attachments: 10.4328:ACAM.20913
Adem Melekoglu, Mufide A. Ozkarafakili, Derya Ozturk. Post-recovery pulmonary function test and thorax CT correlations in COVID-19 survivors. Ann Clin Anal Med 2022;13(5):475-479
Galanin-like peptide and leptin levels in polycystic ovary syndrome patients: A case-control study
Fehmi Unal 1, Osman Oğuz 2
1 Department of Obstetrics and Gynecology, 2 Department of Biochemistry, Istanbul Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20988 Received: 2021-12-10 Accepted: 2022-01-19 Published Online: 2022-01-25 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):480-485
Corresponding Author: Fehmi Unal, Department of Obstetrics and Gynecology, Istanbul Training and Research Hospital, Istanbul, Turkey. E-mail: email@example.com P: +90 533 770 43 96 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8182-2051
Aim: In this study, we aimed to evaluate serum galanin-like peptide (GALP) and leptin levels in women diagnosed with polycystic ovary syndrome (PCOS) and to evaluate its relationship with obesity and insulin resistance.
Material and Methods: This study was conducted with 46 PCOS patients and 33 healthy women matched with a body mass index (BMI). Demographic characteristics of the patients [age, body mass index (BMI), number of births, menstrual characteristics, ovarian and endometrium characteristics], cholesterol, HOMA-IR, GALP, Leptin, AMH, FSH, LH, PRL, DHEA-SO4 and Testosterone levels were measured.
Results: A total of 79 individuals, 46 of whom (58.2%), with a mean age of 25.61 ± 7.15 years (14-43), were diagnosed with PCOS, and 33 of whom (41.8%) were in the healthy control group with similar features in terms of BMI, were included in our study. There was no difference between the groups in terms of GALP levels (3.4 vs. 5.5 ng/ml) (p=0.563). Leptin (10.2 vs. 4.5 ng / ml), AMH (7.3 vs. 2.6 ng / ml) and total testosterone (67.1 ± 25.12 vs. 40.1 ± 19.05 ng / dL) levels in the PCOS group were found to be higher than those in the control group (p<0.001).
Discussion: Our study showed that patients with PCOS had higher leptin and AMH levels than women in the healthy control group with similar BMI values, but there was no significant difference found between the two groups in terms of GALP levels.
Keywords: Galanin-Like Peptide, Leptin, Polycystic Ovary Syndrome
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in women of reproductive age with a prevalence of 6-25% . The syndrome is associated with obesity, insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus (T2DM) and dyslipidemia [1,2].
Leptin is an adipokine, which affects oocyte maturation and activates ovarian enzymes involved in steroidogenesis, such as luteinizing hormone (LH) and follicle stimulation (FSH) .
The physiological relationship between leptin and GALP has been evaluated in several studies [4,5]. The presence of the leptin receptor in GALP-containing cells in the arcuate nucleus of rats and macaques has been demonstrated in morphological studies [5,6]. These observations showed that GALP can be regulated by a central and peripheral leptin-derived mechanism to control feeding behaviour. GALP levels are involved in nutritional regulation, and are thought to be associated with inflammation, sexual behaviour, and stress.
Although it has been shown that leptin levels are increased in non-obese patients with PCOS, there are not enough data on GALP levels . The aim of this study was to evaluate serum leptin and GALP levels of patients with PCOS and to evaluate their relationship with metabolic parameters.
Material and Methods
A group of 46 PCOS and 33 healthy women with a matched body mass index (BMI) was included in our study. Patients were selected from the outpatient gynaecology clinics of our hospital. The control group patients had nonspecific complaints and had no pathological findings. Demographic information of the patients was recorded. Pelvic ultrasonography was performed and recorded in all cases.
The diagnosis of PCOS was made according to the Rotterdam criteria . Each patient’s, Ferriman – Gallwey scores (FGS), height (cm), and weight (kg) were measured. BMI was calculated according to the following formula: BMI = body weight (kg) / height square (m2). Patients were defined as normal or underweight for those who were <25 kg/m2 and overweight for those ≥25 kg/m² based on WHO criteria. The FGS scores of 6 or higher were defined as hirsutism .
All patients diagnosed with secondary etiologies of hyperandrogenism, diagnosed with chronic diseases, using any medications, smokers and those regularly consuming alcohol were excluded from the study.
The control group consisted of healthy individuals with a FGS score <6, a regular menstrual cycles, normal androgen levels, a negative history for chronic diseases and normal ovaries in ultrasound examination. Smokers or alcohol users and patients taking any medications were excluded from the study.
Biochemical and hormonal tests
Venous blood samples were obtained at 9 am, between days 3-5 of the spontaneous or progesterone-induced menstrual cycle. Fasting plasma glucose (FPG), HDL, LDL and triglyceride levels were measured using spectrophotometric analyses (Beckman Coulter AU5800 (Beckman Coulter, CA) analyzer (Abbott Diagnostics, USA)). Fasting serum insulin (FSI), FSH, luteinizing hormone (LH), prolactin (PRL), dehydroepiandrosterone sulfate (DHEAS), total testosterone (TT), and thyroid-stimulating hormone (TSH) were measured immunoenzymatically (UniCelDxI800 analyzer (Beckman Coulter, CA)). The homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was calculated using the following formula: HOMA-IR = Fasting blood glucose (mmol / L) x Fasting blood plasma insulin (mU / mL) / 22.5. Serum anti-Mullerian hormone (AMH) concentration was determined using an automated electrochemiluminescence immunoassay (ECLIA) and Roche-Cobas E411 (Roche Diagnostics, Germany).
Measurements of Leptin and GALP levels
After routine analysis, the separated serum was stored at -80°C for determination of GALP and leptin levels. Serum leptin levels were determined using the DRG-Leptin ELISA Kit® (DRG instruments-GmbH, Germany), a solid phase enzyme-linked immunosorbent assay based on the sandwich ELISA. The range in plasma leptin concentration levels was obtained according to the manufacturer’s instructions. Serum GALP levels were measured by an enzyme-linked immunosorbent assay (Sandwich ELISA) using a commercially available matched Human Galanin-like Peptide Elisa Kit® (Bioassay Technology Lab, Shanghai, China). According to the manufacturer’s specification, the assay range for GALP was 0.156-10 ng / ml and the mean sensitivity was 0.039 ng / ml, intra-assay precision was CV% <8% and inter-assay precision was CV% <10%, respectively. All measurements were done in pairs, and the average of the two measurements was taken into account. The ELISA method procedure was carried out according to the instructions provided by the manufacturer.
The SPSS 26.0 (IBM, New York, USA) program was used in the analysis of variables. The Kendall’s tau-b test was used to examine the correlations of quantitative variables with each other. For the relationship between the classification of the cut-off value calculated according to the variables of the groups and the actual classification, sensitivity, specificity and accuracy rates were analyzed and expressed using ROC (Receiver Operating Curve) curve analysis. Logistic regression and neural network (Multilayer Perceptron-Radial Basis), two of the consulting machine learning methods, were used to find and predict the variable of greatest importance in the patient and healthy groups. The results of a Neural Network (Multilayer Perceptron) analysis, which is the most successful model among these methods, were used. Gradient descent was used for the optimization algorithm, hyperbolic tangent as the hidden layer activation function and exponential and softmax were used as the output layer activation function. Due to some missing data set, the training data set was set as 100%, while the Testing data set as 0%. Quantitative variables were expressed as mean ± SD (standard deviation) and median (Minimum / Maximum) in the tables, while categorical variables were shown as n (%). Variables were analyzed at a 95% confidence level, and a p-value of less than 0.05 was significant.
Our study was approved by the Ethics Committee of the hospital (Approval No:2194/21.02.2020). Informed consent was obtained from each patient and signed before the examination.
A total of 79 individuals, 46 of whom (58.2%), with a mean age of 25.61 ± 7.15 years (14-43), were diagnosed with PCOS, and 33 of whom (41.8%) were in the control group with similar BMI, were included in our study. The average age of the control group was found to be higher than in the PCOS group (27 years vs. 21.5 years) (p<0.001) (Table 1). There was no difference between the groups in terms of GALP levels (3.4 ng/ml vs. 5.5 ng/ml) (p=0.563). Leptin (10.2 ng / ml vs. 4.5 ng / ml), AMH (7.3 ng / ml vs. 2.6 ng / ml), and total testosterone (67.1 ± 25.12 ng / dL vs. 40.1 ± 19.05 ng / dL) levels in the PCOS group were higher than those of the control group (p<0.001). While the HOMA-IR and fasting insulin levels of the patients in the PCOS group were found to be higher than those in the control group, the results of fasting blood glucose and cholesterol measurements were similar. FSH, LH and E2 levels were found to be higher in the control group than in the PCOS group (p=0.006, p=0.041 v p<0.001; respectively) (Table 1). TSH, DHEA-SO4 and PRL levels were similar in both groups. As expected, hirsutism and menstrual irregularity were found to most common complaints in the PCOS group (p<0.001).
A low level of negative correlation was found between GALP and age, BMI, fasting blood glucose and non-HDL cholesterol levels in the total patient and control groups. A low positive correlation was observed between leptin level and BMI, HOMA-IR, fasting insulin, total cholesterol level, non-HDL cholesterol level, LDL, triglyceride, TSH and T. testosterone. However, a low negative correlation was found between triglyceride and E2 levels and leptin (Table 2).
No significant difference was found between menstrual irregularity and BMI (<25, 25-30, >30 kg/m2) group distributions in terms of GALP and leptin levels in the control group. There was no significant difference in GALP and leptin levels in the PCOS group with menstrual irregularity, hirsutism, and morphological findings compatible with PCOS (p>0.05). However, patients with a BMI of <25 kg/m2 had a higher GALP value than patients with a BMI of 25-30 kg/m2 (p<0.001). The leptin level of the patients with a BMI of 25-30 25 kg/m2 was found to be higher than that of the patients with <25 v >30 kg/m2 (p<0.001).
When all participants were evaluated, it was found that women with menstrual irregularity, hirsutism and PCOS-compatible morphological findings had higher leptin levels and as BMI increased, leptin levels also increased. This status could not be shown for GALP (p>0.05).
The effect values for the change in GALP levels were determined to be age (57%), BMI (35%), non-HDL cholesterol (6%) and fasting blood glucose (4%), respectively. The effect values for the change in leptin levels were determined to be BMI (63%), non-HDL cholesterol (10%), HOMA-IR (8%) and triglyceride (5%) levels, respectively. In an analysis of those findings, which showed that they were significant for the diagnosis of PCOS in our study, testing with the Ensemble-learning Method found that GALP levels were 22.4% and leptin levels were 17.3% (Table 3).
We evaluated GALP and leptin levels in PCOS patients and their relationship with obesity and insulin resistance. In our study, patients with PCOS had higher AMH and leptin levels than those in the control group, but there was no significant difference between the GALP levels.
A history of weight gain is usually detected before the development of PCOS, and a healthy lifestyle change has been shown to reduce body weight and to lower testosterone in women with PCOS . The prevalence of PCOS in obese women seeking help for weight loss is 28.3% . However, in another study, PCOS prevalence was shown to be independent of obesity . Parallel to this, most of the patients in our study were non-obese. In this respect, our study is notable in that it identified a higher rate of non-obese PCOS patients.
The pathophysiology underlying PCOS is not fully understood . Previous studies have reported a higher prevalence of obesity in PCOS patients compared to healthy women . A recent study showed that an imbalance in adipokine secretion was not only associated with a higher likelihood of PCOS, but also with hyperandrogenism and increased ovarian follicle number. This result also suggests the role of adipokines in the different pathophysiological pathways of PCOS .
Many studies have suggested that HOMA-IR be used as a standard measure for diagnosing insulin resistance . In our study, both groups had similar BMI values, and HOMA-IR levels were found to be higher in PCOS patients compared to control group.
Several studies found that leptin levels were higher than control groups of similar age. Opposite results were also published. The reason for this difference can be explained by the differences in the PCOS diagnostic criteria used to enroll the patients and the fact that PCOS patients with high leptin levels are also obese people. It was thought that obesity was the main reason for the increase in leptin levels, and that the leptin level has limited diagnostic discrimination in non-obese PCOS patients [12,15].
The putative role of GALP in regulating reproductive functions was thought to be a potential molecular link in the leptin/insulin and GnRH relationship to GALP [7,16,17]. In this sense, it has been postulated that reproductive dysfunction associated with diabetes is a defect in the function of GALP-expressing neurons . It has been shown that more than 85% of GALP-containing neurons express leptin receptors and that leptin increases GALP mRNA expression in the hypothalamus [6,17]. Leptin inhibits the insulin-mediated stimulation of gonadotropin-induced ovarian steroidogenesis.
GALP elicits LH release following intracerebral injections in rats . Moreover, GALP-induced LH secretion is blocked by the administration of the GnRH receptor antagonist in both rats and macaques; this suggests that GALP probably stimulates GnRH secretion through an intermediate cell [18,19]. This short-term effect of GALP in rats  appears to be similar in size to that of galanin and is thought to be due to GALP binding to galanin receptors [20,21]. Since GALP is found to be an important factor in the initiation of GnRH secretion and the regulation of LH secretion caused by GnRH, higher GALP levels are expected in patients with PCOS . Increased LH release occurred following intracerebral injections of GALP in mice . In addition, GALP has been shown to have a stimulating effect depending on estrogen . As far as we know, only one study on GALP in patients with PCOS have been conducted yet . Although Nyagolova et al. found higher GALP levels in PCOS patients, in our study, we could not find a significant difference between healthy women and PCOS patients regarding GALP levels.
When all the participants in our study were evaluated, women with menstrual irregularity, hirsutism, and PCOS-compatible morphological findings had higher leptin levels and as BMI increased, leptin levels also increased. We assume that GALP secretion disturbances may occur in PCOS subjects, however, we could not find similar results in reports that show a positive correlation of GALP levels with BMI, even though studies are still limited .
Some limitations of our study draw attention. PCOS group consisted of younger patients compared to similar studies, so it was thought that metabolic disorders may not have progressed sufficiently. In conclusion, we found that patients with PCOS had higher AMH and leptin levels than the control group with similar BMI values, but there was no significant difference between the two groups in terms of GALP levels.
Scientiﬁc Responsibility Statement
The authors declare that they are responsible for the article’s scientiﬁc content including study design, data collection, analysis and interpretation, writing, some of the main line, or all of the preparation and scientiﬁc review of the contents and approval of the ﬁnal version of the article.
Animal and human rights statement
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. No animal or human studies were carried out by the authors for this article.
Conflict of interest
None of the authors received any type of financial support that could be considered potential conflict of interest regarding the manuscript or its submission.
1. Garvey WT, Mechanick JI, Brett EM, Garber AJ, Hurley DL, Jastreboff AM, et al. American association of clinical endocrinologists and American college of endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity: Executive summary. Endocr Pract. 2016;22(7):842–84.
2. No authors listed. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81(1):19-25.
3. Childs GV, Odle AK, MacNicol MC, MacNicol AM. The Importance of Leptin to Reproduction. Endocrinology. 2021;162(2):204.
4. Takenoya F, Hirako S, Wada N, Nonaka N, Hirabayashi T, Kageyama H, et al. Regulation of Feeding Behavior and Energy Metabolism by Galanin-like Peptide (GALP): A Novel Strategy to Fight Against Obesity. Curr Pharm Des. 2018;24(33):3926-33.
5. Cunningham MJ, Scarlett JM, Steiner RA. Cloning and distribution of galanin-like peptide mRNA in the hypothalamus and pituitary of the macaque. Endocrinology. 2002;143(3):755-63.
6. Takenoya F, Hirayama M, Kageyama H, Funahashi H, Kita T, Matsumoto H, et al. Neuronal interactions between galanin-like-peptide- and orexin- or melanin-concentrating hormone-containing neurons. Regul Pept. 2005;126(1-2):79-83.
7. Nyagolova PV, Mitkov MD, Orbetzova MM, Terzieva DD. Kisspeptin and galanin-like peptide (galp) levels in women with polycystic ovary syndrome. Int J Pharmaceut Med Res. 2016;4(5):7-12.
8. Matheson E, Bain J. Hirsutism in Women. Am Fam Physician. 2019;100(3):168-75.
9. Alvarez-Blasco F, Botella-Carretero JI, San Millán JL, Escobar-Morreale HF. Prevalence and characteristics of the polycystic ovary syndrome in overweight and obese women. Arch Intern Med. 2006;166(19):2081-6.
10. Yildiz BO, Knochenhauer ES, Azziz R. Impact of obesity on the risk for polycystic ovary syndrome. J Clin Endocrinol Metab. 2008;93(1):162-8.
11. Badawy A, Elnashar A. Treatment options for polycystic ovary syndrome. Int J Womens Health. 2011;3:25-35.
12. Pasquali R, Gambineri A, Pagotto U. The impact of obesity on reproduction in women with polycystic ovary syndrome. BJOG. 2006;113(10):1148-59.
13. Bicer M, Alarslan P, Guler A, Demir I, Aslanipour B, Calan M. Elevated circulating levels of secreted frizzled-related protein 4 in relation to insulin resistance and androgens in women with polycystic ovary syndrome. J Endocrinol Invest. 2020;43(3):305-313.
14. Bu Z, Kuok K, Meng J, Wang R, Xu B, Zhang H. The relationship between polycystic ovary syndrome, glucose tolerance status and serum preptin level. Reprod Biol Endocrinol. 2012;10:10.
15. Pehlivanov B, Mitcov M. Serum leptin levels correlate with clinical and biochemical indices of insulin resistance in women with polycystic ovary syndrome. Eur J Contraception Reprod Health Care. 2009;14:153–9.
16. Krasnow SM, Fraley GS, Schuh SM, Baumgartner JW, Clifton DK, Steiner RA. A Role for Galanin-Like Peptide in the Integration of Feeding, Body Weight Regulation, and Reproduction in the Mouse. Endocrinology. 2003;144(3):813–22.
17. Lawrence C, Fraley GS. Galanin-like peptide (GALP) is a hypothalamic regulator of energy homeostasis and reproduction. Front Neuroendocrinol. 2011;32(1):1-9.
18. Matsumoto H, Noguchi J, Takatsu Y, Horikoshi Y, Kumano S, Ohtaki T, et al. Stimulation Effect of Galanin-Like Peptide (GALP) on Luteinizing Hormone-Releasing Hormone-Mediated Luteinizing Hormone (LH) Secretion in Male Rats. Endocrinology. 2001;142(8):3693–6.
19. Cunningham MJ, Shahab M, Grove KL, Scarlett JM, Plant TM, Cameron JL, et al. Galanin-Like Peptide as a Possible Link between Metabolism and Reproduction in the Macaque. J Clin Endocrinol Metab. 2004;89(4):1760–6.
20. Gundlach AL. Galanin/GALP and galanin receptors: role in central control of feeding, body weight/obesity and reproduction? Eur J Pharmacol. 2002;440(2-3):255-68.
21. Matsumoto Y, Watanabe T, Adachi Y, Itoh T, Ohtaki T, Onda H, et al. Galanin-like peptide stimulates food intake in the rat. Neurosci Lett. 2002;322(1):67-9.
22. Uenoyama Y, Tsukamura H, Kinoshita M, Yamada S, Iwata K, Pheng V, et al. Oestrogen-dependent stimulation of luteinising hormone release by galanin-like peptide in female rats. J Neuroendocrinol. 2008;20(5):626–31.
23. Fang P, Yu M, Gu X, Shi M, Zhu Y, Zhang Z, et al. Circulating galanin and galanin like peptide concentrations are correlated with increased triglyceride concentration in obese patients. Clin Chim Acta. 2016;461:126-9.
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Fehmi Unal, Osman Oğuz. Galanin-like peptide and leptin levels in polycystic ovary syndrome patients: A case-control study. Ann Clin Anal Med 2022;13(5):480-485
Pain beliefs of hemodialysis patients and non-pharmacological methods they use to relieve pain
Safiye Yanmış 1, Mukadder Molllaoğlu 2
1 Department of Internal Medicine Nursing, Faculty of Health Science, Erzincan Binali Yıldırım University, Erzincan, 2 Department of Nursing, Faculty of Health Science, Sivas Cumhuriyet University, Sivas, Turkey
DOI: 10.4328/ACAM.20992 Received: 2021-12-13 Accepted: 2022-03-03 Published Online: 2022-03-13 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):486-491
Corresponding Author: Safiye Yanmış, Department of Internal Medicine Nursing, Faculty of Health Science, Erzincan Binali Yıldırım University, Erzincan, Turkey. E-mail: firstname.lastname@example.org P: +90 446 226 58 61 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9095-4048
Aim: This study was carried out to determine hemodialysis patients’ pain beliefs and nonpharmacological methods used by patients for pain.
Material and Methods: The research was carried out between July-September 2020. The study was conducted with 103 patients who volunteered to participate in the study, who did not have communication and psychological problems, and who had been on hemodialysis treatment for at least 6 months. The data were collected using patient information form, non-pharmacological methods form used by patients for pain, and a Pain Beliefs Scale. The descriptive statistical methods, Student’s t-test, the One-way Anova and Tukey’s Post Hoc were used in the statistical analysis of the study data.
Results: It was determined that 49.5% used pharmacological methods to relieve pain, 39.8% used non-pharmacological methods to relieve pain. Among the non-pharmacological methods used in pain relief, the most used methods are massage (24.2%) and cold application (14.5%), respectively. It was found that patients’ pain beliefs scale the psychological score average was higher than organic score average.
Discussion: In the study, the nonpharmacological methods that patients use most for pain relief were massage and cold application. It was determined that the patients attribute pain to psychological reasons rather than organic ones. To reduce pain in hemodialysis patients, it is important to apply analgesic treatment according to the doctor’s request, to use nonpharmacological methods used in pain relief by providing interdisciplinary communication and to evaluate the results.
Keywords: Hemodialysis, Nursing, Non-Pharmacological Methods, Pain Beliefs, Pain
End-stage renal disease (ESRD) is a health problem with a very high morbidity and mortality rate both in Turkey and in other countries of the world . ESRD is not only a progressive and chronic loss of kidney functions, but also a life-threatening process . In this process, renal replacement therapies such as organ transplantation and dialysis are applied to ensure the continuity of life . The aim of hemodialysis (HD) treatment is to increase the quality of life of individuals, to enable them to maintain their roles and responsibilities, and to increase their self-care abilities .
Patients with ESRD are faced with many HD treatment-induced complications . The vast majority of patients have difficulties in coping with these complications. Of these problems, the leading one is pain, a symptom that impairs the quality of life in the hemodialysis patient group [5,6]. Chronic pain experienced by HD patients, which is difficult to manage with traditional treatment methods, arises as a result of vascular disorders, diabetes, changes in the musculoskeletal system, and accumulation of metabolic wastes in the body . As reported in several studies, 50% of HD patients experience pain, and more than 50% of these patients describe their pain as moderate or severe . In another study, it was emphasized that pain felt by HD patients increases their depression and worsens their sleep quality and quality of life .
Although pain develops due to tissue damage and has an organic basis, psychosocial factors are also involved in its etiology. The patient’s genetic structure, emotional and cultural characteristics, beliefs and personal characteristics affect the frequency and severity of the pain he or she experiences and his or her strength to cope with pain . In studies, it is reported that the beliefs of individuals who experience pain about whether the origin of the pain is organic or psychological may create differences in their coping strategies . Therefore, determining patients’ pain beliefs and evaluating the coping methods chosen according to the pain belief play an important role in managing pain effectively.
Pharmacological pain management is complex in patients with ESRD, due to factors such as toxic effects of medication and difficulty in coping with pain. Accordingly, patients often prefer non-pharmacological methods in addition to pharmacological agents in coping with pain due to the highly toxic effects of pharmacological agents and the patients’ unwillingness to use too many drugs . As reported in the literature, among the complementary methods frequently used by patients with renal failure, there are non-pharmacological methods such as consumption of herbal products, relaxation, hypnosis, acupuncture, acupressure, yoga, massage, music, reflexology and aromatherapy [11,12]. It has also been reported that the rate of using herbal supplements by patients with chronic renal failure (CRF) ranges from 16.8% to 45% (patients with chronic renal failure (CRF) use herbal supplements at rates ranging from 16.8% to 45%) . In another study, methods frequently used by HD patients to cope with pain were determined as massage and hot-cold application . The number of patients undergoing HD due to CRF is increasing, and the pain symptom they suffer affects their daily life and quality of life adversely. In this case, since knowing the pain characteristics and beliefs of hemodialysis patients can affect their knowledge, skills, and pharmacological and non-pharmacological methods they use in pain management, determining these characteristics and encouraging them to cooperate with health professionals are of great importance. Therefore, the present study was conducted to determine the pain beliefs of hemodialysis patients and the non-pharmacological methods they use to overcome their pain.
Material and Methods
The design of the study
This descriptive, correlative, and cross-sectional study population consisted of patients who received hemodialysis treatment in the Dialysis Unit of a hospital between July-September 2020.
Population and sample
Of the patients in the study population, 103 who over the age of 18, who received hemodialysis treatment, which started at least six months ago while the study was conducted, who had no communication or psychiatric problems, and volunteered to participate in the study, comprised the sample of the study.
Data collection tools
The study data were collected using the Patient Information Form, and the Pain Beliefs Questionnaire (PBQ).
The Patient Information Form developed through a literature review consists of items questioning the sociodemographic characteristics, disease and treatment-related characteristics form to assess the Pain Experience and Non-Pharmacological Methods.
PBQ developed by Edwards et al.  consists of 2 sub-dimensions (Psychological Beliefs and Organic Beliefs) and 12 items. The Turkish validity and reliability study of the PBQ was conducted by Berk in 2006 . The Cronbach’s Alpha internal consistency coefficient of the scale in Berk et al.’s study was 0.71 for the Organic Beliefs sub-dimension and 0.73 for the Psychological Beliefs sub-dimension . In the present study, the Cronbach’s Alpha internal consistency coefficient was 0.82 for the Organic Beliefs sub-dimension and 0.77 for the Psychological Beliefs sub-dimension.
Evaluation of data
The SPSS (Statistical Package for the Social Sciences) 24.0 package program was used to analyze the data obtained. The result of the Shapiro–Wilk normality test indicated that the data were normally distributed. (p>0.05). The descriptive statistical methods, Student’s t-test, the One-way ANOVA, and Tukey’s Post Hoc were used in the statistical analysis of the study data. P-values less than 0.05 were considered statistically significant.
Before the study was conducted, ethical approval to conduct the study was obtained from the Clinical Research Ethics Committee of a university (Approval number: 06/29, Date of approval: June 22, 2020). The patients participating in the study were informed about the study and their written consent indicating that they volunteered to participate in the study was obtained. They were told that the personal information they provided would not be disclosed to anyone by the researcher in accordance with the confidentiality principle.
The mean age of the patients participating in the study was 56.93±13.81 years, and the mean duration of hemodialysis treatment they underwent was 6.58±5.76 years. Of the participants, 61.2% were men, 76.7 % married, 63.1% were primary school graduates, 55.3% had a middle economic level, 10.7% were smokers, 44.7% took their medications sometimes, 92.2% underwent hemodialysis treatment 3 times a week, and 76.7% had a comorbid chronic disease, 67% experienced pain sometimes, 73.8% experienced pain after hemodialysis, and 57.3% experienced musculoskeletal pain. While 49.5% of the participating patients preferred the pharmacological method to overcome pain, 39.8% preferred the non-pharmacological method. Of those who preferred the most used non-pharmacological method, massage (24.2%) and cold application (14.5%) (Table 1).
It was found the Psychological Beliefs sub-dimension score average of the BPQ was higher than the organic score average (Table 2).
The mean score of illiterate participants who took medication regularly, experienced pain continually, experienced pain during and after the dialysis, experienced musculoskeletal pain and headache obtained from the Organic Beliefs sub-dimension was higher than in other participants (p<0.05). The participants who used a non-pharmacological method for pain obtained higher mean scores from the Psychological Beliefs sub-dimension than did the participants who did not use a non-pharmacological method (p<0.05) (Table 3).
Pain has been reported as one of the most common symptoms experienced by patients undergoing hemodialysis [5,6]. The pain experienced by hemodialysis patients adversely affects the coping process, their functional capacity, sleep quality and therefore quality of life . Since pain is also affected by psychosocial factors, patients’ beliefs, expectations, attitudes to cope with pain, and social support have an impact on their pain management .
In the present study, 88.4% of the patients experienced pain, and 67% of the patients who experienced pain experienced it sometimes. In a study conducted with hemodialysis patients, the prevalence of pain was 81% . In another study, the prevalence of pain was determined as 8.2% . In Fleishman et al. (2018)’ s study conducted with hemodialysis patients, 82% of the patients experienced pain.
In the present study, 73.8% of the patients experienced pain after hemodialysis. Dikmen and Aslan (2020) reported that 74.2% of patients experienced pain after hemodialysis sessions. In the present study, 57.3% of the participants experienced musculoskeletal pain. In the literature, it has been reported that 60-65% of hemodialysis patients have pain originating from the musculoskeletal system [5,6].
Hemodialysis patients often prefer non-pharmacological methods in addition to pharmacological agents in coping with pain because pharmacological agents have high toxic effects and patients do not want to take too many drugs . While 49.5% of the participants preferred the pharmacological method, 39.8% preferred the non-pharmacological method. Among the nonpharmacological methods used in pain relief, the most used methods are massage (24.2%) and cold application (14.5%), respectively. In a study, CRF patients were reported to use herbal supplements to cope with pain at rates ranging from 16.8% to 45% . In another study, HD patients frequently used such methods as massage and hot-cold application to cope with pain . In a study conducted with patients with CRF in our country, Turkey, 25.2% of the patients used one of the non-pharmacological methods. Of them, 50.6% used mind-body techniques, 32.6% used massage therapy, and 16.8% used herbal products. The most preferred herbal products were garlic and linden tea .
In the present study, 39.8% of the participants preferred the non-pharmacological method. In the literature, it is stated that patients with CRF prefer non-pharmacological methods because they feel physically and emotionally good, they want to prevent health problems, and they think that it is safer than traditional treatments [11,21]. In addition, it is emphasized that if patients use a non-pharmacological method, they often do not share the method they use with the healthcare team . Although pain develops due to tissue damage and has an organic basis, psychosocial factors are also involved in its etiology . Therefore, evaluation of pain from both organic and psychosocial aspects is of great importance [9,22].
In the present study, the Psychological Beliefs sub-dimension score average of the BPQ was higher than the Organic Beliefs sub-dimension score average. Hemodialysis patients believe that psychological factors are the cause of pain. In Ozer et al. (2020)’ s study hemodialysis patients attribute the cause of their pain to psychological factors rather than organic factors. Pain is an unpleasant sensory and emotional experience associated with a person’s experiences . The fact that the treatment of patients with renal failure, which is a chronic disease, lasts life-long, leads to the loss of workforce and dependence of these patients on family members, brings physiological, economic and mental problems related to the disease . In the light of this information, the fact that patients who undergo HD treatment believe that psychological reasons are the cause of their pain, is an expected result.
The mean score of the illiterate participants obtained from the Organic Beliefs sub-dimension was higher than that of the other participants. Cornally and McCarthy (2011) stated that organic beliefs were associated with health-seeking behavior and help demand, which is thought to pave the way for illiterate individuals receiving hemodialysis treatment to display health-seeking behavior more and to demand help more than individuals with a high education level, and therefore to believe in the organic dimension of pain.
The mean score of the participants who never took their medication regularly, obtained from the Organic Beliefs sub-dimension, was higher than that of participants who always or sometimes took their medication regularly. The need to benefit from an invasive treatment such as HD to survive, and experiencing pain negatively affect patients’ compliance with treatment . Therefore, it is thought that patients with increased non-adherence to treatment due to lack of self-management strength believe in the organic beliefs dimension, which indicates that pain is stable and unchanging.
The mean score of the participants who experienced continuous pain, obtained from the Organic Beliefs sub-dimension, was higher than that of the participants who sometimes experienced pain or did not experience pain at all. The mean score of the participants who suffered from musculoskeletal pain obtained from the Organic Beliefs sub-dimension was higher than that obtained by the participants who did not experience pain. The type and the severity of the pain experienced by the patients affected the pain beliefs of the patients, which should be taken into account during the comprehensive assessment of pain. In their study, Baird and Haslam (2013) determined that of the participants, those who experienced pain frequently and especially those who experienced musculoskeletal pain had high levels of organic pain beliefs. This suggests that the continuous experience of pain and the type of pain lead to the belief that the pain is of organic origin, such as a damage or injury to the body.
The mean score of the participants who experienced pain during and after dialysis, obtained from the Organic Beliefs sub-dimension was higher than was that obtained by the participants who did not experience pain. In a study, it was stated that patients experienced pain during and after dialysis, and the patients defined the severity of pain as moderate or severe . It is thought that due to the intensity of pain experienced by the patients during and after dialysis, their belief in the organic dimension of pain is stronger.
Participants who used non-pharmacological methods to cope with pain obtained a higher mean score from the Psychological Beliefs sub-dimension than those who did not use non-pharmacological methods. In the literature, it is stated that psychological factors such as anxiety and depression affect psychological beliefs of pain, and that techniques such as distraction and relaxation should be used in pain management . Accordingly, the fact that individuals who receive HD treatment and use non-pharmacological methods in the treatment of pain believe that pain is of psychological origin is an expected result.
In the present study, the most commonly used non-pharmacological treatment methods to relieve pain were massage and hot-cold application, and the patients attributed the cause of pain to psychological causes rather than organic ones. As is known, nephrology nurses are expected to diagnose and manage symptoms, to plan care, and to comprehensively evaluate the needs of caregivers of individuals with end-stage renal disease. In a nursing intervention performed to reduce pain in hemodialysis patients, evaluation of the location, severity, characteristic and degree of pain, questioning of the factors that reduce/increase pain, determination of pain beliefs, determination of the non-pharmacological treatment method preferred by the patients to cope with pain, application of analgesic treatment upon the doctor’s request, the use of the non-pharmacological method preferred by the patient in pain relief by providing interdisciplinary communication and evaluation of the results are of great importance. Within this context, nurses should inform their patients about the possible risks, benefits and limitations of the methods used, be able to answer their questions, establish clear communication and monitor patients for the effects of these methods.
We like to thank all of the participant patients for their contributions to our study. In addition, We like to thank for assessing language of our study to Mustafa Demir.
Scientiﬁc Responsibility Statement
Animal and human rights statement
Conflict of interest
1. Varol E, Sivrikaya SK. Quality of life in chronic renal failure and nursing. J DU Health Sci Inst. 2018; 8(2): 89-96.
2. Thurlow JS, Joshi M, Yan G, Norris KC, Agodoa LY, Yuan CM, et al. Global epidemiology of end-stage kidney disease and disparities in kidney replacement therapy. Am J Nephrol. 2021; 52(2): 98-107.
3. Çağlar M, Zedelenmez A. How is enough dialysis assessed correctly in hemodialysis patients? Nephrol Nurs J. 2019; 14(2): 70-4.
4. Bakan A, Köstek O, Ecder SA, Özkök A, Odabaş AR. Complications of hemodialysis. Türkiye Klinikleri J Nephrol. 2015; 8(2): 40-7.
5. Yeşil S, Karslı B, Kayacan N, Süleymanlar G, Ersoy F. Pain evaluation in patients with chronical renal failure undergoing hemodialysis. Pain. 2015; 27(4): 197-204.
6. Ghonemy TA, Allam HM, Elokely AM, Kadry YA, Omar HM. Chronic pain in hemodialysis patients: Role of bone mineral metabolism. Alexandria J Med. 2016; 52(4): 337–42.
7. Roy DA, Mateti UV, Shenoy P, Srinidhi BC. Association of sleep quality, pain severity, and depression in patients undergoing maintenance hemodialysis. J Appl Pharm Sci. 2020; 10(10): 50-3.
8. Henschke N, Kamper SJ, Maher CG. The epidemiology and economic consequences of pain. Mayo Clin Proc. 2015; 90(1): 139-47.
9. Baird AJ, Haslam RA. Exploring differences in pain beliefs within and between a large nonclinical (workplace) population and a clinical (chronic low back pain) population using the pain beliefs questionnaire. Phys Ther. 2013; 93(12): 1615-24.
10. Koncicki HM, Brennan F, Vinen K, Davison SN. An Approach to Pain Management in End Stage Renal Disease: Considerations for General Management and Intradialytic Symptoms. Semin Dial. 2015; 28(4): 384-91.
11. Durmaz Akyol A, Yildirim Y, Toker E, Yavuz B. The use of complementary and alternative medicine among chronic renal failure patients. J Clin Nurs. 2011; 20(7-8): 1035-43.
12. Ovayolu N, Ovayolu Ö, Güngörmüş Z, Karadağ G. Complementary Treatments in Kidney Failure. Nephrol Nurs J. 2015; 10(1): 40-6.
13. Tangkiatkumjai M, Boardman H, Praditpornsilpa K, Walker DM. Prevalence of herbal and dietary supplement usage in Thai outpatients with chronic kidney disease: a cross-sectional survey. BMC Complement Altern Med. 2013; 13: 153.
14. Kafkia T, Vehviläinen-Julkunen K, Sapountzi-Krepia D. Assessment and management of pain in hemodialysis patients: A pilot study. Prog Heal Sci. 2014; 4: 53-60.
15. Edwards LC, Pearce SA, Turner-Stokes L, Jones A. The Pain Beliefs Questionnaire: an investigation of beliefs in the causes and consequences of pain. Pain. 1992; 51(3): 267-72.
16. Yuksel A, Tambag H, Karakoyun A. The Relationship between Pain Beliefs and Psychiatric Symptoms of Patients with Fibromyalgia Syndrome. Duzce Med J. 2019;21(3): 238-42.
17. Weisbord SD, Mor MK, Green JA, Sevick MA, Shields AM, Zhao X, et al. Comparison of symptom management strategies for pain, erectile dysfunction, and depression in patients receiving chronic hemodialysis: a cluster randomized effectiveness trial. Clin J Am Soc Nephrol. 2013; 8(1): 90-9.
18. Dos Santos PR, Mendonça CR, Noll M, Borges CC, Alves PM, Dias NT, de Sousa Romeiro AM, Barbosa MA, Porto CC. Pain in Hemodialysis Patients: Prevalence, Intensity, Location, and Functional Interference in Daily Activities. Healthcare (Basel). 2021; 9(10): 1375.
19. Fleishman TT, Dreiher J, Shvartzman P. Pain in Maintenance Hemodialysis Patients: A Multicenter Study. J Pain Symptom Manage. 2018; 56(2): 178-84.
20. Dikmen RD, Aslan H. The Effects of the symptoms experienced by patients undergoing hemodialysis treatment on their comfort levels. J Clin Nephrol Ren Care. 2020; 6: 60.
21. Erdoğan Z, Atik DÖ, Çınar S. Complementary and alternative medicine methods in chronic renal failure. Arch Med Res. 2014; 23: 773-89.
22. Ozer Z, Turan GB, Celikbilek F. Relationship Between Pain Beliefs and Pain Management in Hemodialysis Patients. Nephrol Nurs J. 2020; 15(3): 226-34.
23. Vicdan AK, Karabacak BG. The use of patient education Roy Adaptation Model haemodialysis. J Hum Sci. 2014; 11(2): 209-20.
24. Cornally N, McCarthy G. Chronic pain: the help-seeking behavior, attitudes, and beliefs of older adults living in the community. Pain Manag Nurs. 2011; 12(4): 206-17.
25. Lynch PG, Abate M, Suh H, Wadhwa NK. Magnesium and muscle cramps in end stage renal disease patients on chronic hemodialysis. Adv Nephrol. 2014; 2014: 1-6.
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Safiye Yanmış, Mukadder Molllaoğlu. Pain beliefs of hemodialysis patients and non-pharmacological methods they use to relieve pain. Ann Clin Anal Med 2022;13(5):486-491
Socioeconomic characteristics and risk factors for breast cancer: A case-control study in the Souss-Massa region, Morocco
Zakariae Cherrat 1,2, Rachid Razıne 1,2, Bouchra Amaouı3, Youssef Bouchrıtı 4, Ahmed Id Moussa 5, Majdouline Obtel 1,2
1 Department of Public Health, Clinical Research and Epidemiology (LBRCE), Faculty of Medicine and Pharmacy, Mohamed V University, Rabat, 2 Department of Public Health, Laboratory of Social Medicine, Faculty of Medicine and Pharmacy, Mohamed V University, Rabat, 3 Department of Radiology, Faculty of Medicine and Pharmacy, Ibn Zohr University, Agadir, 4 Geosciences and Environment Team, Faculty of Sciences, Ibn Zohr University, Agadir, 5 ES-SAADA Laboratory for Medical Analysis, Inezgane, Morocco
DOI: 10.4328/ACAM.20993 Received: 2021-12-15 Accepted: 2022-02-04 Published Online: 2022-02-09 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):492-496
Corresponding Author: Zakariae Cherrat, 21, Crown Prince City, Inezgane, Morocco. E-mail: email@example.com P: +66 215 50 65 Corresponding Author ORCID ID: https://orcid.org/0000-0003-1463-0874
Aim: Across the world, breast cancer is the most common type of cancer affecting women. In Morocco, convincing evidence between several risk factors and breast cancer has been established. The objective of this study is to investigate the socio-economic characteristics and risk factors for breast cancer among women at the Souss-Massa Regional Oncology Center (SMROC).
Material and Methods: A case-control study was conducted at the SMROC. Between May 1 to the end of September 2021, 300 women were recruited, including 150 cases and 150 age-matched controls. Information on the socioeconomic profile of cases and controls and risk factors was obtained using a questionnaire administered by two investigators. The database was created in Excel and statistical analysis was performed using Epi-Info software (version 7).
Results : Low socioeconomic level (OR: 6.7292; 95% CI: 4.0488 – 11.1841), BMI (OR 11.4545; 95% CI: 6.1416 – 21.3636), low Daily Physical Activity (OR: 91.8333; 95% CI: 34.9146 – 241.5423), benign breast disease (OR: 10.5455, 95% CI: 4.0290 – 27.6014), age at first menstruation (OR: 7. 8533; 95% CI: 4.6940 – 13.1389), nulliparity (OR: 2.4225; 95% CI: 1.3244 – 4.4310), use of hormonal contraception (OR: 2.1667; 95% CI: 1.1940 – 3.9318), absence of breastfeeding (OR: 2.2190; 95% CI: 1.2575 – 3.9156), were associated with an increased risk of breast cancer.
Discussion: Our study confirms the multi-factoriality of breast cancer. It is essential to further promote early detection and preventive measures, especially among high-risk population. These results must be confirmed by a multicenter study at the national level.
Keywords: Socioeconomic Characteristics, Risk Factors, Breast Cancer, Morocco
Breast cancer in women is a public health problem. The worldwide incidence of breast cancer was 55.2 per 100,000 women, with a mortality rate of 13.0% . Breast cancer is the most common type of malignancy affecting women worldwide. In 2018, the global incidence of this type of cancer in women over 50 years of age was 154.8 per 100,000 women . According the International Agency for Research on Cancer, the future incidence of the disease will reach 3.19 million new cases by 2040 .
In Morocco, despite the early detection program for breast and cervical cancer, implemented since 2011 , breast cancer is constantly increasing. It is the first type of malignant tumors in Moroccan women, in terms of both incidence and mortality, with a particularity of affecting young women . Indeed, 11.7 K new cases of breast cancer are detected and 3.7 K deaths in 20201. The future forecast of this type of cancer is expected to reach 16018 new cases in 2030 .
In the absence of a cancer registry for the southern regions of Morocco, statistics from the SMROC, as a public structure that covers the entire population of the four southern regions in terms of cancer care, have shown an increase in the incidence of breast cancer in women for the years 2018, 2019 and 2020, with 310, 323 and 349 new cases, respectively. The occurrence of cancer is due to multitude of factors. The objective of this study was to determine the socio-economic characteristics and risk factors for cancer among women managed at the SMROC level.
Material and Methods
Type, population and location of the study
This is a case-control study conducted at the SMROC. A total of 300 women (150 cases and 150 age-matched controls) were recruited between 01 May and 30 September 2021. The study included women over 18 years of age, under the care of the SMROC, and with histological confirmation of breast cancer.
Information on the socio-economic characteristics of cases and controls (age, marital status, menopausal status, place of residence, level of education, occupation, household income) and risk factors was obtained using a questionnaire administered by two investigators. A pre-test of the questionnaire was conducted with 5 women to verify the relevance of the questions.
The analysis included a description of the study population according to different characteristics and a comparison between cases and controls according to risk factor exposure. Determination of the study population was performed via Open Epi software. The database was created in Excel and statistical analysis was performed using Epi-Info software (version 7). A p value < 0.05 was used to indicate statistical significance.
Our study was approved by the Biomedical Research Ethics Committee of the Faculty of Medicine and Pharmacy of Rabat, number 30/21. Authorization for data collection was granted by the Souss-Massa Regional Health Directorate and the ROC. Participation in this study was strictly voluntary, and all patients were informed of the purpose of the study, and were given the right to withdraw at any stage during the study without giving any excuses. Written informed consent from the women to participate in the study was obtained before the survey was started.
Table 1 presents the socioeconomic characteristics of the cases and controls in our study. Multivariate analysis of the results showed no statistically significant association between breast cancer and the variables age, marital status and menopausal status of the women. Nevertheless, exposure to this type of cancer is observed more in women over 40 to under 50 years of age, in single and widowed women, and in postmenopausal women. However, there was a statistically significant association between breast cancer and rural origin of women (OR: 2.0932; 95% CI: 1.2773 – 3.4303, p < 0.05). Compared to controls, cases had a lower socioeconomic level (OR: 6.7292; 95% CI: 4.0488 – 11.1841).
Table 2 describes the risk factors for breast cancer. The cases and controls, for the most part, did not consume alcohol or tobacco, so the risk calculation is not applicable. As for body mass index (BMI), the risk was significantly elevated in women who were overweight by more than 25 to less than 30 kg/m² and more than 30 kg/m² respectively (OR: 11.4545; 95% CI: 6.1416 – 21.3636, p < 0.001) and (OR 8.6114; 95% CI: 3.9092 – 18.9694, p < 0.001). Compared with controls, the risk was significantly elevated in cases with low daily physical activity (< 15min/day) (OR: 91.8333; 95% CI 34.9146 – 241.5423). Compared with controls, patients had a history of benign breast disease (OR: 10.5455, 95% CI: 4.0290 – 27.6014). The risk was high in women with a family history of breast cancer (OR: 5.9847, 95% CI: 3.0317 – 11.8139). For diabetes, risk indicated the existence of an association but was not statistically significant. For hormonal risk factors in cases and controls in our study, women who had their first menstrual period before the age of 12 years had a significantly higher risk of breast cancer compared to controls (OR: 7.8533; 95% CI: 4.6940 – 13.1389). Among 150 patients, 70 were menopausal, 63.75% of whom had undergone menopause after the age of 47 years. Regarding risk factors related to reproduction and the use of certain treatments, nulliparous women had a significantly higher risk of breast cancer than controls (OR: 2.4225; 95% CI: 1.3244 – 4.4310). As for breastfeeding, women who never breastfed had an elevated risk of breast cancer compared with those who did (OR: 2.2190; 95% CI: 1.2575 – 3.9156). For hormonal contraception, the risk was significantly elevated in women who had used it for more than 10 years (OR: 2.1667; 95% CI: 1.1940 – 3.9318). For contraceptive use at menopause, the results showed no difference.
The present study analyzed the socio-economic profile and risk factors of breast cancer in women at the SMROC in Agadir. In our study, the average ages in cases and controls were 40 and 49 years, respectively, in agreement with the results of the study by Khalis et al. (2018) . In contrast, Znati et al. (2014), showed that younger women (aged 35 years and younger) were most exposed . This can be explained by the unhealthy lifestyle adopted by women and the use of hormonal contraception. The results of our study showed no difference in age, marital status, menopausal status and place of residence. These data are consistent with the study by Khalis et al. (2018) . This is explained, perhaps, by the change in women’s lifestyles in the two settings. We found a significant association between low socioeconomic status and breast cancer risk (OR: 6.7292; 95% CI: 4.0488 – 11.1841). These results corroborate with the study by Berger et al. (2012) . This association may be due to financial difficulties and inequality in access to early diagnosis and care of breast cancer.
Our study did not reveal an association between smoking status and alcohol consumption. Contrary to the results of a national study, which found an association between breast cancer and smoking . The particularities of the Moroccan community culture, considering alcohol and tobacco use by women as socially repressed behavior, are explanatory reasons for this situation. In fact, smoking is not considered an established risk factor for breast cancer .
For BMI, our study found a statistically significant association between high BMI and breast cancer risk (OR: 11.4545; 95% CI: 6.1416 – 21.3636). Several epidemiological studies have considered overweight and obesity a risk factor for breast cancer in women [3,7,8]. This is mainly due to the interaction between fat cells (a component of breast tissue) and breast cancer cells. Excess fat tissue in obese women is a risk factor .
Our study showed a highly significant association between lack of regular physical activity and breast cancer risk (OR: 91.8333; 95% CI: 34.9146 – 241.5423). In addition, regular physical activity reduces the risk of breast cancer by approximately 35% . It is suggested that regular moderate physical activity confers protection against breast cancer .
Regarding the personal medical history, 40% of the cases had a benign breast disease. At this level, we found a significant difference between cases and controls (OR: 10.5455; 95% CI: 4.0290 – 27.6014). One idea supports this finding: Certain non-cancerous breast conditions may cause a slight increase in the risk of breast cancer in women when associated with increased cell counts (atypical hyperplasia; complex fibroadenoma; sclerosing adenosis; papillomatosis; radial scarring; fibrocystic breast changes). One study confirmed that proliferative lesions without atypia increase the risk of breast cancer by a factor of two, while hyperplastic lesions with atypia increase this risk by at least four times .
For diabetes, our study did not show a statistically significant association between diabetes and breast cancer. Our study found that only 24.67% of the cases had diabetes, contrary to the study by Bernard et al. (2016) . The association between diabetes and breast cancer is explained by other factors such as lack of physical activity, overweight, dietary habits.
As for the family history of breast cancer, we found a difference between cases and controls (OR: 5.9847; 95% CI: 3.0317 – 11.8139). Several studies have associated family history with the risk of breast cancer [3,8]. This may be due to genetic mutations, especially in the BRCA1 and BRCA2 genes, which are involved in about 65% of hereditary forms of breast cancer .
Furthermore, our study revealed a highly significant association between early age at first menstruation and increased risk of breast cancer (OR: 7.8533; 95% CI/ :4.6940 – 13.1389). In a meta-analysis, early age at first menstruation was associated with breast cancer risk (OR: 1.05; 95% CI: 1.04-1.05) . This relationship is explained by early and prolonged exposure of the breast to estrogen during ovarian activity .
According to several studies, late age at menopause is a risk factor for breast cancer [3,15,16]. Our study did not reveal an association between late age at menopause and increased cancer risk. The increased risk of breast cancer in women with late age at menopause is explained, perhaps, by prolonged and high breast exposure to estrogen and progesterone .
Nulliparity is considered, according to several epidemiological studies, an established risk factor for female breast cancer [18,19]. Our study did not show an association between nulliparity and breast cancer risk. The explanations given for the protective effect of pregnancy against breast cancer are: decreased estrogen and progesterone levels, increased sex hormone-binding globulin levels and pregnancy-induced differentiation of breast tissue [20,21].
Breastfeeding reduces the risk of breast cancer, especially if prolonged and even in patients with the BRCA131 mutation . Our results did not show a protective effect of breastfeeding against breast cancer. Another study found a protective effect of breastfeeding against breast cancer . Our results did not show an association between the absence of breastfeeding and breast cancer risk. Several pathophysiological mechanisms explain the protective effect of breastfeeding against breast cancer: decrease in the number of ovulatory cycles, cellular differentiation of the mammary epithelium during lactation, excretion of carcinogens through milk .
Regarding the use of hormonal contraception, high frequencies were recorded in cases (63.76%) and controls (74.00%), with no difference noted between the two categories. These results differ from those revealed by a cohort study, which confirmed that the risk of breast cancer was higher in women who were using or had recently used contemporary hormonal contraceptives than in women who had never used hormonal contraceptives, and this risk increased with duration of use (RR= 1.38; 95% CI: 1.26 -1.51) . This may be due to the high concentration of hormonal contraceptives in the bloodstream. This may be due to the high concentration of combined estrogen-progestin in hormonal contraceptives .
We excluded the use of contraception during menopause from the analysis because of the low frequency revealed in cases (3.80%) and controls (7.04%).
Our study confirms the association between the risk factors studied and the emergence of breast cancer in the exposed population in the Souss-Massa region. It is essential to carry out a multicenter study in order to generalize the results to all women in Morocco.
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Animal and human rights statement
Conflict of interest
1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A et al. Global cancer statistics 2020 : GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021 ; 71(3):209-49.
2. Abbass F, Bennis S, Znati K, Akasbi Y, Amrani JK, El Mesbahi O, et al. Epidemiological and biologic profile of breast cancer in Fez-Boulemane, Morocco. EMHJ-Eastern Mediterranean Health Journal. 2011; 17 (12): 930-6.
3. Khalis M, Chajès V, Moskal A, Biessy C, Huybrechts I, Rinaldi S, et al. Healthy lifestyle and breast cancer risk: a case-control study in Morocco. Cancer Epidemiol. 2019; 58:160-6.
4. Znati K, Bennis S, Abbass F, Akasbi Y, Chbani L, Elfatemi H, et al. Breast cancer in young women in northeastern Morocco. Gynecology obstetrics and fertility. 2014 ; 42(3):149-54.
5. Berger F, Doussau A, Gautier C, Gros F, Asselain B, Reyal F. Impact of socioeconomic status on the severity of initial breast cancer diagnosis. Journal of epidemiology and public health. 2012; 60(1):19-29.
6. Nkondjock A, Ghadirian P. Risk factors for breast cancer. Medicine/Science. 2005; 21(2):175-80.
7. Al Jarroudi O, Abda N, Seddik Y, Brahmi SA, Afqir S. Overweight: is it a prognostic factor in women with triple-negative breast cancer? Asian Pac J Cancer Prev. 2017; 18(6): 1519-23.
8. Khalis M, Charbotel B, Chajès V, Rinaldi S, Moskal A, Biessy C, et al. Menstrual and reproductive factors and risk of breast cancer: A case-control study in the Fez region, Morocco. PloS one. 2018; 13(1): e0191333.
9. McMichael AJ. Food, nutrition, physical activity and cancer prevention. Authoritative report from World Cancer Research Fund provides global update. Public Health Nutr. 2008; 11(7):762-3.
10. Ligibel JA, Campbell N, Partridge A, Chen WY, Salinardi T, Chen H, et al. Impact of a mixed strength and endurance exercise intervention on insulin levels in breast cancer survivors. J Clin Oncol. 2008; 26(6): 907-12.
11. Key TJ, Verkasalo PK, Banks E. Epidemiology of breast cancer. Lancet Oncol. 2001; 2(3): 133-40.
12. Bernard L, Reix N, Benabu JC, Gabriele V, Mathelin C. Cancer du sein et diabète de type 2: des interactions complexes. Gynécologie Obstétrique & Fertilité. 2016; 44(12):701-11.
13. Collaborative Group on Hormonal Factors in Breast Cancer. Menarche, menopause, and breast cancer risk : individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. Lancet Oncol. 2012; 13(11):1141-51.
14. Clavel-Chapelon F. Cumulative number of menstrual cycles and breast cancer risk: results from the E3N cohort study of French women. Cancer Causes Control. 2002; 13(9): 831-8.
15. Kawai M, Minami Y, Kuriyama S, Kakizaki M, Kakugawa Y, Nishino Y, et al. Reproductive factors, exogenous female hormone use and breast cancer risk in Japanese: the Miyagi Cohort Study. Cancer Causes Control. 2010; 21(1):135-45.
16. Oran B, Celik I, Erman M, Baltali E, Zengin N, Demirkazik F, et al. Analysis of menstrual, reproductive, and life-style factors for breast cancer risk in Turkish women. Medical Oncology. 2004; 21(1):31-9.
17. Parsa P, Parsa B. Effects of Reproductive Factors on Risk of Breast Cancer: A. Asian Pacific Journal of Cancer Prevention. 2009; 10: 545-50.
18. Gao YT, Shu XO, Dai Q, Potter JD, Brinton LA, Wen W, et al. Association of menstrual and reproductive factors with breast cancer risk: results from the Shanghai Breast Cancer Study. Int J Cancer. 2000; 87(2): 295-300.
19. Huo D, Adebamowo CA, Ogundiran TO, Akang EE, Campbell O, Adenipekun A, et al. Parity and breastfeeding are protective against breast cancer in Nigerian women. Br J Cancer. 2008; 98(5): 992-6.
20. Lee E, Ma H, McKean-Cowdin R, Van Den Berg D, Bernstein L, Henderson BE, et al. Effect of reproductive factors and oral contraceptives on breast cancer risk in BRCA1/2 mutation carriers and noncarriers: results from a population-based study. Cancer Epidemiology and Prevention Biomarkers. 2008; 17(11): 3170-8.
21. Russo J, Moral R, Balogh GA, Mailo D, Russo IH. The protective role of pregnancy in breast cancer. Breast Cancer Res. 2005; 7(3): 1-12.
22. Freund C, Mirabel L, Annane K, Mathelin C. Allaitement maternel et cancer du sein. Gynécologie obstétrique & fertilité. 2005; 33(10): 739-44.
23. Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and abortion : collaborative reanalysis of data from 53 epidemiological studies, including 83 000 women with breast cancer from 16 countries. The Lancet. 2004; 363(9414): 1007-16.
24. Mørch LS, Skovlund CW, Hannaford PC, Iversen L, Fielding S, Lidegaard Ø. Contemporary hormonal contraception and the risk of breast cancer. New England Journal of Medicine. 2017; 377(23): 2228-39.
25. Zolfaroli I, Tarín JJ, Cano A. Hormonal contraceptives and breast cancer: Clinical data. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2018; 230: 212-16.
Download attachments: 10.4328:ACAM.20993
Zakariae Cherrat, Rachid Razıne, Bouchra Amaouı, Youssef Bouchrıtı, Ahmed Id Moussa, El Majdouline Obtel. Socioeconomic characteristics and risk factors for breast cancer: A case-control study in the Souss-Massa region, Morocco. Ann Clin Anal Med 2022;13(5):492-496
Simultaneous and consecutive operation comparison in bilateral hallux valgus surgery
Kadri Yıldız, Mehmet Eşref Encan, Mehmet Şah Sakçı
Department of Orthopaedics and Traumatology, School of Medicine, Kafkas University, Kars, Turkey
DOI: 10.4328/ACAM.20994 Received: 2021-12-14 Accepted: 2022-01-26 Published Online: 2022-02-28 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):497-501
Corresponding Author: Kadri Yıldız, Kafkas Universitesi Tıp Fakültesi Ortopedi ve Travmatoloji ABD, Ana Kampüs, 36000, Kars, Turkey. E-mail: firstname.lastname@example.org P: +90 538 545 05 59 / +90 474 225 21 06 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8164-7687
Aim: This study aims to determine whether simultaneous bilateral hallux valgus surgery is advantageous over consecutive operations.
Material and Methods: Patients who underwent bilateral hallux valgus surgery were separated into groups Group A and B. Group A included patients who underwent simultaneous bilateral hallux valgus surgery, and Group B who received the consecutive hallux valgus surgery using a Modified Chevron osteotomy techniques with mini-incision. Clinical and radiological databases, complications, mean costs of analgesic drugs, the duration time of surgical operations, the length of hospital stay, the cost of implants, the cost of each group, hospital costs for each patient were determined. The mean in FAOS (Foot and Ankle Outcome Score) scores were calculated for both groups postoperatively.
Results: Patients with bilateral hallux valgus (n=175) were chosen among the hallux valgus patients (n=479). Of these, bilaterally operated patients were accessible about 2/3 (n=101). In Group A (n=30), there were 21 females and 9 males, aged 22–58 years ( mean 41.45±15.12). In Group B (n=35), there were 27 females and 8 males, aged 27–61 years ( mean 45.33±12.64). There was no significant difference in demographic characteristics (p≤0.449) and the follow-up time (p<0.05) between the two groups. The mean hospitalization duration was also shorter in Group A (p≤0.001).
Discussion: Our results demonstrated that simultaneous bilateral hallux valgus surgery is statistically cheaper than consecutive bilateral hallux valgus operation. But, FAOS had slightly better courses in the consecutive bilateral hallux valgus operations compared to simultaneous bilateral hallux valgus operations.
Keywords: Hallux Valgus, Bilateral, Simultaneous, Consecutive, Cost-Effectiveness
In the literature, many studies have evaluated bilaterally versus unilateral surgery in orthopedics; however, the number of studies comparing outcomes of bilateral versus unilateral foot surgery is limited [1, 2]. In 2009, Fridman et al compared unilateral versus bilateral first ray surgery in a prospective study of 186 consecutive cases according to patient satisfaction, costs, and complications . Lim WSR et al. demonstrated that simultaneous minimally invasive percutaneous surgery (MIS) was suitable for patients with bilateral hallux valgus . Seo JH et al. declared that distal Chevron Metatarsal Osteotomies (DCMO) in elder patients (≥60 years), even one-stage bilaterally, were effective and safe .
In this retrospective cross-sectional study, a comparison between outcomes of one-stage bilateral procedures versus consecutive surgeries for bilateral HV was performed. The main objective of this study was to detect costs, complications and outcomes associated with both surgical approaches for bilateral HV. The clinical and radiological outcomes of the patients who underwent one-stage and consecutive HV surgeries were retrospectively analyzed and compared. Our research aims to detect both functional outcomes and cost-effectiveness.
Material and Methods
Databases of all patients who underwent HV surgery were extracted from the hospital archive records between November 2017 and April 2019. Simultaneous bilateral HV surgery was only applied in those patients who volunteered for this procedure with a patient consent form. In the decision for simultaneous surgery following conditions were taken into account: i) consent of the patient, ii) good general health of the patient. The power analysis for the sample size was provided. Patients were separated into groups Group A and B. Group A included those patients who underwent one-stage HV surgery and Group B included those patients who received consecutive HV surgeries. A clinical researcher, who was blinded to the study, collected all information from the databases.
All patients were evaluated for surgical contraindications in ordinary local routines. All patients were exposed to the same pre-operative protocols and imaging studies for bilateral HV surgery. A single senior surgeon performed all procedures using medial, over the web skin incisions for each osteotomy. Modified Chevron osteotomy techniques with mini-incision and tourniquets were applied for all patients .
Standard second-generation cephalosporin antibiotic treatment regimens were given to all patients before and after surgery. The same preoperative and postoperative care conditions were provided for all patients. Clinical and radiological databases were set up to evaluate patients in both groups. Clinical trials were done at the sixth month, and the first year for all patients in both study groups. For clinical follow-up assessments, x-rays images were collected for radiologic evaluation. Outcomes of demographic features consisted of age (year), gender, and frequency. The outcomes of clinical evaluation are preoperative risk evaluation (ASA grading), operation duration (min), hospitalization duration (TL), postoperative pain scoring (VAS), analgesic need (several times), analgesia cost (TL), implant counts (TL), implant cost (TL), total duration in operation theatre (min), invoice (TL), immobilization duration (min), the mean in FAOS (Foot and Ankle Outcome Score) values. FAOS consists of pain, activities of daily living, sport and recreational activities foot and ankle related quality of life (QOL), and other symptoms. The outcomes of radiological evaluation are the HV measurements. It includes HVA, IMA, distal metatarsal articular angle (DMAA), proximal phalangeal articular angle (PPAA). Complications during postoperative periods were recorded. Mean FAOS (Foot and Ankle Outcome Score) scores related to pain, activities of daily living, sport and recreational activities, foot and ankle related QOL (Quality of Life) and other symptoms were calculated for both groups in the postoperative sixth month and during the first year of clinical follow-up [6,7]. A special rehabilitation team was established for the postoperative rehabilitation of these patients. This program was carried out in a very controlled manner for patients, especially in a single session. Some patients in the single session group were mobilized by loading onto the heels with a walker. The remaining patients were mobilized with a wheelchair. The special program for all patients was applied. This program consisted of passive and active exercise chains. Passive and active exercise chains are that the programs were carried out by placing the loading on the heel (with a walker providing contact from multiple points to the ground) under the control of Physical Therapy and Rehabilitation physicians and physiotherapists in our hospital.
SPSS® versions 20 statistical software (SPSS Inc., Windows®, IL, USA) was used. Independent sample tests and Mann-Whitney U tests were used for all parameters. A p-value less than 0.05 was considered statistically significant.
Overall, 175 patients were diagnosed with bilateral HV and 101 of the 175 patients were operated on for bilateral HV over a 3-years period. Overall, 30 patients underwent one-stage HV surgery (Group A) and 35 patients underwent consecutive HV surgeries (Group B). Some of the 36 patients could not be included in the study group because they did not meet the inclusion criteria, some did not want to participate in the study, and some of them had problems in patient follow-up. Bilateral modified Chevron osteotomies with mini-incision (<4 cm) were performed for patients who had bilateral HV in a single surgical session (Group A) versus those who had the procedure in consecutive surgical sessions (Group B) (Figure 1).
The demographic, clinical, and surgical characteristics of both groups are demonstrated in Table 1. There was no significant difference between the groups for gender and age distribution. The mean in age was 41,45±15,12 years [median 50,0 years (22-58)] in Group A, and 45,33±12,64 years [median 47,5 years (27-61)] in Group B. The mean in age (year) was 41.7±11.36 in female patients in Group A, 40.9±13.86 in male patients in Group A; and 40.9±10.96 in female patients in Group B, 41.6±12.57 in male patients in Group B. There was no statistical difference
between two groups and genders. There was no significant difference in all demographic characteristics (p≤0.449). ASA grades were similar between the two groups (I or II). The mean duration of follow-up was also similar between the two groups (p<0.05). In Group A, there were 21 females and 9 males, aged 22–58 (mean 41.45±15.12) years. In Group B, there were 27 females and 8 males, aged 27–61 (mean 45.33±12.64) years. Significant differences were detected between the two groups for mean operative time, length of stay and hospital charges (p≤0.001). The mean total anesthesia duration was shorter in Group A than in Group B (p≤0.001). The mean hospitalization duration was also shorter in Group A (p≤0.001).
The mean total cost differences between the groups are demonstrated in Table 2. All total costs were lower in Group A than in Group B (p≤0.001). The median length of hospital stay in Group A was 2.91±0.70 days, while that in Group B, it was 5.58±1.56 days. The mean analgesia costs were 54.09±16.28 TL (Turkish Liras) in Group A and 115.03±22.88 TL in Group B (p≤0.001). The mean implant costs in Group A were 1044.73±297.99 TL and 1233.92±175.24 TL in Group B (p≤0.091). The mean anesthesia costs were 1438.27±287.19 TL in Group A, 2848.42±463.45 in Group B (p≤0,000). The mean total hospitalization costs were 2536.09±200.49 TL in Group A and 4197.37±220.52 in Group B (p≤0.001). This indicates that total hospitalization costs were approximately two-fold higher in Group B (p≤0.001). The one-stage procedure was relatively lower in costs as it was 60.42% less in total hospital costs.
When considering the mean values of hallux valgus correction rates, the comparison of the postoperative and preoperative radiographic changes was significant in both groups (p<0.05). There was no significant difference between the groups for complications in the sixth month and the first year of follow-up (p>0.05). As surgery-related complications, one superficial infection was detected in the first year in Group A, and one superficial infection in the sixth month and a deep wound infection in the first year were detected in Group B. As time-related complications, there were no complications in both groups in the sixth-month follow-up. On the first-year follow-up, one fixation failure was detected in the first year in Group A, and two complications as one fixation failure and the other one was wound detachment were detected in Group B. In the other complications, dizziness was detected in the first year in Group A, depression was detected in the first year in Group B, but the relationship of both complications with the surgery was not clear.
Both groups used short leg splint for 6 weeks after each surgery subsequently. The mean FAOS (Foot and Ankle Outcome Score) scores were for pain, activities of daily living, sport, and recreational activities, foot and ankle related QOL and other symptoms respectively 31 (SD 18.2), 31 (SD 12.4), 23 (SD 19.3), 29 (SD 17.7), and 13 (SD 11.3) in Group A and 29 (SD 19.8), 37 (SD 13.8), 27 (SD 17.6), 32 (SD 23.4), and 19 (SD 12.2) in Group B in the sixth month follow-up. The mean FAOS (Foot and Ankle Outcome Score) scores for pain, activities of daily living, sport and recreational activities, foot and ankle related QOL and other symptoms respectively 29 (SD 19.4), 52 (SD 13.8), 25 (SD 22.1), 31 (SD 29.6), 29 (19.7) in Group A and 28 (SD 18.6), 54 (SD 13.4), 31 (SD 18.6), 47 (SD 28.7), 30 (SD 19,9) in Group B in the first year of follow-up. When comparing scores as time-related, there was a significant difference for activities of daily living, sport, and recreational activities and foot and ankle related QOL in Group B compared to Group A, respectively (p≤0.05) and (p≤0.004). FAOS scores were shown in Table 3.
Postoperative rehabilitation procedures were the same in the two groups. All patients were evaluated for successful range of motion (ROM) at the final follow-up. There was a significant difference in mean analgesic costs between the two groups (p≤0.001).
In our study, the simultaneous bilateral procedure resulted in a lesser duration of anesthesia and hospitalization. The simultaneous bilateral operation also had significantly lower costs. Besides, consecutive surgical operations were significantly more expensive than one-stage operations. The simultaneous bilateral HV surgery had shorter hospitalization, less total anesthetic time, and greater economic advantages compared to the consecutive HV surgery. Simultaneous bilateral HV surgery had shorter operative and anesthetic times, possibly due to mismanagement of time among auxiliary health personnel involved in the consecutive operations. In Group A, the length of hospital stay was shorter and faster rehabilitation was observed. The biomechanical outcomes of these two groups were not significantly different. FAOS scores were better for activities of daily living, sport and recreational activities and foot and ankle related QOL in Group B compared to Group A in the sixth month and in the first year of follow-up.
Simultaneous bilateral procedure deserves to be investigated for the following reasons: i) simultaneous bilateral procedure reduces surgery and hospital costs, ii) with the operation performed in a single session, the patient can be treated in a shorter time, which has a positive psychological effect on the patient, iii) complications due to operations and immobilization are seen less compared consecutive sessions, iv) simultaneous bilateral procedure can reduce patient burden.
In Turkey, prevalence estimations for HV, bunionettes, and hammertoes were calculated as 54.3%, 13.8% and 8.9%, respectively, and positive family history rates were 53.2%, 61.2%, and 56.1% for the same case series, respectively, with associated deformities, which are more common in females (p<0.001). A study declared that constricting shoes might affect HV incidence in women (p<0.001) and bunionette incidence in both genders (p<0.01) . It appears that the estimated prevalence of HV varies between 21 to 70% in epidemiologic studies . Bilateral HV was reported to occur at a rate of 16.9% (6.0% in the left foot, 7.0% in the right foot; p<0.001) and at a rate of 21.2% in women (7.6% in the left foot; 8.2% in the right foot), and 11.0% in men (3.9% in the left foot; 5.4% in the right foot) [10,11].
Over time, mini-invasive techniques have become more popular for HV surgery because they are associated with reduced patient anxiety related to anesthesia. As the first serious book study about minimally invasive foot surgery in the literature, De Prado’s book described these less invasive techniques; the author also discusses an algorithm that has been defined as surgical operation on only one foot at the same time . With the exception of Carvalho’s study, there are currently no studies on the simultaneous bilateral correction of HV . Reverdin-Isham, a distal metatarsal osteotomy, was associated with revolutionized correction of simple to severe hallux abducto valgus deformities, which was done after the exostectomy . The authors declared that this modification provided a successful, minimal disability in daily life, a cost-effective method as minimal incision surgery for HV surgery. Recently, many studies have outlined the advantages of minimally invasive and percutaneous techniques for orthopedic procedures [15-17]. Carvalho et al investigated differences between minimally invasive percutaneous operations for one foot versus both feet at the same surgical time . Arthroscopy and percutaneous mini-incision (1–3 mm) osteotomies were performed for these minimally invasive HV techniques. They emphasized that the simultaneous bilateral percutaneous HV surgery could provide the same results as a unilateral operation, and therefore, recommended one-stage HV surgery because of socio-economic reasons .
Our study is the first study about single-session bilateral HV surgery according to our literature review. Our study also sheds light on this subject, which is constantly wondered, in terms of cost-effectiveness. However, the limitations of our study were as follows: 1) the number of patients was limited, 2) the study design was retrospective, which had inherent limitations, 3) the follow-up was relatively short, 4) in terms of cost-effectiveness, a much more qualified study could be done with the help of relevant economics disciplines, 5) a comprehensive study could be done in the form of a meta-analysis involving much more medical centers.
Our findings here have emphasized the following: (1) postoperative complications in the groups were similar with both methods, (2) both groups had similar clinical outcomes and ROMs, (3) FAOS scores had slightly better courses in consecutive operations, (4) the simultaneous bilateral procedure decreased hospitalization and total hospital costs, (5) from an economic point of view, the simultaneous bilateral procedure has meaningful financial advantages.
The simultaneous bilateral procedure is safe and resulted in similar post-operative toe functions compared with the consecutive procedures. The simultaneous bilateral procedure had some advantages such as single anesthetic exposure, lower medical costs, and shorter hospitalization. Complications due to operations and immobilization of a simultaneous bilateral procedure are less than consecutive sessions. Consecutive procedures doubled the costs of anesthesia and complication rates. However, consecutive operations had better functional outcomes compared to the simultaneous bilateral procedure in FAOS evaluations. QOL was higher in consecutive HV surgery procedure patients.
The simultaneous bilateral procedure has positive psychological effects on the patient with shorter hospitalization duration time. Also, the simultaneous bilateral procedure has advantages because of reducing the patient burden. Our results indicate that simultaneous bilateral procedure had the cost-saving feature and therefore we conclude that this procedure may be more optimal for healthy patients due to economic reasons and its features of minimally invasive operation.
Scientiﬁc Responsibility Statement
Animal and human rights statement
Conflict of interest
1. Fridman R, Cain JD, Weil L Jr, Weil LS Sr, Ray TB. Unilateral versus bilateral first ray surgery: a prospective study of 186 consecutive cases–patient satisfaction,
the cost to society, and complications. Foot Ankle Spec. 2009; 2(3): 123-9.
2. Lim WSR, Rikhraj IS, Koo KOT. Simultaneous bilateral hallux valgus surgery:
Percutaneous or conventional? Early results of a matched study from a tertiary
institution. Foot Ankle Surg. 2020; 6: S1268-7731(20)30079-5.
3. Seo JH, Lee HS, Choi YR, Park SH, Lee JH, Chun H. Outcomes of Simultaneous Bilateral vs Unilateral Distal Chevron Metatarsal Osteotomy in Hallux Valgus Patients Aged ≥60 Years. Foot Ankle Int. 2021; 29. DOI: 1071100721996707.
4. Murray O, Holt G, McGrory R, Kay M, Crombie A, Kumar CS. Efficacy of outpatient bilateral simultaneous hallux valgus surgery. Orthopedics. 2010; 33(6): 394.
5. Donnelly RE, Saltzman CL, Kile TA, Johnson KA. Modified chevron osteotomy for hallux valgus. Foot Ankle Int. 1994; 15(12): 642-5.
6. Roos EM, Brandsson S, Karlsson J. Validation of the Foot and Ankle Outcome
Score for Ankle Ligament Reconstruction. Foot & Ankle Int. 2001; 22(10): 788-94.
7. Yusuf F, Liu G, Wing K, Crump T, Penner M, Younger A, et al. Validating the Foot and Ankle Outcome score for measuring foot dysfunction among hallux valgus surgery patients using item response theory. Foot Ankle Surg. 2019; 4: pii: S1268-7731(19)30200-0.
8. Şaylı U, Altunok EÇ, Güven M, Akman B, Biros J, Şaylı A. Prevalence estimation and the familial tendency of common forefoot deformities in Turkey: A survey of 2662 adults. Acta Orthop Traumatol Turc. 2018; 52(3):167-–73.
9. Okuda H, Juman S, Ueda A, Miki T, Shima M. Factors Related to Prevalence of Hallux Valgus in Female University Students: A Cross-Sectional Study. J Epidemiol. 2014; 24(3): 200–8.
10. Rolfson O, Digas G, Herberts P, Karrholm J, Borgstrom F, Garellick G. One-stage bilateral total hip replacement is cost-saving. Orthop Muscul Syst. 2014; 3: 4.
11. Chan WC, Musonda P, Cooper AS, Glasgow MM, Donell ST, Walton NP. One-stage versus two-stage bilateral
unicompartmental knee replacement: a comparison of immediate post-operative
complications. J Bone Joint Surg Br. 2009; 91(10): 1305–9.
12. De Prado M, Ripoll PL, Golano P. Hallux valgus. In: Masson, editor. Cirurgia
Percutanea del Pie. Barcelona: Masson (SA); 2003. p. 57–94.
13. Carvalho P, Viana G, Flora M, Emanuel P, Diniz P. Percutaneous hallux valgus treatment: Unilaterally or bilaterally. Foot Ankle Surg. 2016; 22(4): 248–53.
14. Isham SA. The Reverdin-Isham procedure for the correction of hallux abducto
valgus. A distal metatarsal osteotomy procedure. Clin Podiatr Med Surg. 1991;
15. Maffulli N, Longo UG, Marinozzi A, Denaro V. Hallux valgus: effectiveness and
safety of minimally invasive surgery. A systematic review. Br Med Bull. 2011;
16. Bauer T, Biau D, Lortat-Jacob A, Hardy P. Percutaneous Hallux Valgus correction using Reverdin-isham osteotomy. Orthop Traumatol Surg Res. 2010; 96(4): 407–16.
17. Magnan B, Bortolazzi R, Samaila E, Pezzè L, Rossi N, Bartolozzi P. Percutaneous distal metatarsal osteotomy for correction of hallux valgus, Surgical technique. J Bone Joint Surg Am. 2006; 88: 135–48.
18. Wagner E, Ortiz C, Torres K, Contesse I, Vela O, Zanolli D. Cost effectiveness of different techniques in hallux valgus surgery. Foot Ankle Surg. 2016; 22(4): 259–64.
Download attachments: 10.4328:ACAM.20994
Kadri Yıldız, Mehmet Eşref Encan, Mehmet Şah Sakçı, Simultaneous and consecutive operation comparison in bilateral hallux valgus surgery. Ann Clin Anal Med 2022;13(5):497-501
Evaluation of knowledge and attitudes of pregnant women about infant oral health and their oral hygiene
Aycan Dal Dönertaş 1, Çağdaş Çınar 2
1 Department of Pediatric Dentistry, Faculty of Dentistry, Nigde Omer Halisdemir University, Niğde, 2 Department of Pediatric Dentistry, Faculty of Dentistry, Gazi University, Ankara, Turkey
DOI: 10.4328/ACAM.20997 Received: 2021-12-15 Accepted: 2022-01-18 Published Online: 2022-01-27 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):502-506
Corresponding Author: Aycan Dal Dönertaş, Department of Pediatric Dentistry, Faculty of Dentistry, Nigde Omer Halisdemir University, 51240, Merkez, Niğde, Turkey. E-mail: email@example.com P: +90 537 723 40 89 Corresponding Author ORCID ID: https://orcid.org/0000-0002-5876-4586
Aim: The aim of this study was to investigate the necessary oral hygiene practices and knowledge level of pregnant women both for themselves and their children.
Material and Methods: Five hundred fifty-five pregnant mothers and mothers with children under 12 months who applied to Gazi University Faculty of Medicine, Pediatrics, Obstetrics and Gynecology Clinics, were surveyed. The first part of the questionnaire consisted of the socio-demographic data of the mothers, the second part consisted of oral health questions related to the mother during the pregnancy period, and the third part consisted of oral health questions about the baby. The data obtained from the survey results were analyzed using IBM SPSS Statistics 17.0 (IBM Corporation, Armonk, NY, USA).
Results: 68.8% of the participants stated that auxiliary dental hygiene devices should be used to provide oral hygiene; 68.1% of the participants thought that there was a relationship between periodontal diseases and pregnancy outcomes. 62% of women reported they should go to the dentist for a dental consultation during pregnancy; 44.7% of the participants reported the baby’s teeth should be brushed after the first tooth eruption, and the majority (64.7%) thought they should be brushed 2 times a day.
Discussion: Our findings are in line with previous reports. Income level was significantly associated with increased use of auxiliary dental hygiene devices and the knowledge that pregnancy could lead to gum problems (p<0,001). Educational level was significantly associated with knowledge about the need for dental consultation, the importance of baby’s general and oral health during pregnancy, and also the knowledge about vertical transition. The time and frequency of tooth brushing did not show a statistically significant difference when the number of pregnancies was examined (p>0,05). However, postgraduate mothers had a significantly higher difference (p<0,001).
Keywords: Infant, Knowledge, Oral Health, Pregnancy, Attitudes
Perinatal oral health is a crucial component of obstetric practice, with significant impacts on maternal, fetal, and infant health. Perinatal period is the period starting from 20th-28th weeks of pregnancy and including the first 1-4 weeks after the birth. Infantile period is defined as the time until 12 months of age . Current data suggest that patients with poor oral health, in addition to the progressive deterioration in their own dental diseases, have an increased risk of miscarriage, premature birth, and fetal growth restriction .
At first glance, infant and oral health may not appear to be closely related. Ultimately, most babies are born without teeth and usually spend the first half of the infantile without teeth. Even so, oral health is also a concerned in infancy, because infantile period is a critical time to acquire both good and bad habits that have the potential to affect the general health of the individual as well as the future oral health of adolescents and their adulthood .
In this study, we aimed to evaluate the knowledge level of mothers about oral hygiene practices for themselves and their babies.
Material and Methods
Participants in the present study were pregnant women or women with children under 12 months of age who applied to Gazi University Faculty of Medicine, Obstetrics and Gynecology Clinics, in the capital of Turkey. As a result of power analysis, the minimum number of people was determined. A self-designed 29-question survey was conducted to measure oral care knowledge levels for pregnant mothers and mothers with children under 12 months of age. A total of 441 pregnant women and 114 recent mothers were interviewed, and a total of 555 interviews were conducted. The study was approved by Gazi University Faculty of Dentistry Research Ethics committee on 06/02/2018 and was conducted in full accordance with the World Medical Association Declaration of Helsinki. Since the questionnaire was self-designed, content validity was established by a panel of experts at Gazi University Faculty of Dentistry. After verbal consent, the survey was carried out by one person and done face to face.
Items in the questionnaire included demographics, oral hygiene knowledge, practice during pregnancy, and oral hygiene knowledge and practice for infant.
Data were statistically analyzed using IBM SPSS Statistics 17.0 (IBM Corporation, Armonk, NY, USA). The Kolmogorov-Smirnov test was used to determine whether the distribution of continuous and discrete numerical variables was close to normal. The assumption of homogeneity of variances was investigated using Levene’s test. Descriptive statistics; mean ± standard deviation was used for continuous and discrete numerical variables, number of cases, and percentages (%) for categorical variables. In the case of 2×2 cross tables, if the expected frequency is less than five, in at least one of the cells, the categorical data were evaluated using Fisher’s Final Probability Test. Continuous Corrected Chi-Square test was used to test the expected frequency between 5-25. Otherwise, Pearson’s chi-square test was used.
According to socio-demographic data, the results indicated that the majority of 36.9% were between the 30-34 age years old, 34.2% were <30 years old, and 28,8% were ≥35 years old. According to the educational level of the participants, nearly half of the participants with 45.9% had a university degree, while 11.2% had less than a high school education; 21.8% were at the high school level and 21.1% were at the postgraduate level. In terms of economic status, the majority of volunteers (38.2%) earned as a total family income by month >6000 Turkish Liras (TL); and only 11.2% earned <2000 TL monthly. In terms of pregnancy, the majority of the participants (79.4%) were pregnant mothers who had not given birth yet. It was observed that more than half of the participants (53.5%) had their first pregnancy, and 14.6% had more than two pregnancies.
Null hypothesis 1:
Participants with high income would report less use of auxiliary dental hygiene devices than participants with less income. About 82.1% of participants with high income stated that auxiliary dental hygiene devices should be used during pregnancy (p<0,001) than participants with less income (Table 1). The analysis revealed a statistically significant relationship between income and the use of auxiliary dental hygiene devices during pregnancy. Therefore, null hypothesis 1 was rejected.
Null hypothesis 2:
Participants with high income would report less knowledge about the relationship between pregnancy and periodontal diseases than participants with less income.This null hypothesis was rejected, as Pearson’s Chi-square analysis showed a statistically significant relationship between family income and knowledge about the relationship between pregnancy and periodontal diseases (p<0,001). About 79.2% of participants with high income showed knowledge about the existence of a possible relationship between pregnancy and periodontal diseases (Table 1).
Null hypothesis 3:
Participants with high income would report fewer dental visits during pregnancy than participants with less income. About 69.8% of participants with high income reported that visiting a dentist during pregnancy was necessary (p<0,001) than participants with less income (Table 1). The analysis revealed a statistically significant relationship between income and visiting a dentist during pregnancy. Thus, null hypothesis 3 was rejected.
Null hypothesis 4:
Highly educated mothers and pregnant women would report less knowledge about the relationship between pregnancy and a baby’s general and oral health than less educated mothers and pregnant women. This null hypothesis was rejected as Pearson’s Chi-square analysis showed a statistically significant relationship between educational level and knowledge about the relationship between pregnancy and a baby’s general and oral health. About 68.4% of postgraduate mothers and pregnant women pointed out that oral health of the mother is important during pregnancy for baby’s general health (p=0,009). Also, 70.1% of postgraduate mothers and pregnant women stated that mother’s feeding during pregnancy affects the health of the baby’s teeth (p=0,015) (Table 2).
Null hypothesis 5:
As the number of pregnancies is increases, women would report less knowledge about when and how often a baby’s teeth should be brushed than women who have fewer number of pregnancies. The participants were asked the questions ‘’When to start brushing the baby’s teeth ?’’ and ‘’How often should the baby’s teeth be brushed?’’ and Pearson’s Chi-square analysis revealed no statistically significant relationship between the number of pregnancies and the knowledge about brushing time and frequency (p>0,05) (Table 3). Therefore, the above null hypothesis was accepted.
Null hypothesis 6:
Highly educated mothers and pregnant women would report less knowledge about vertical transition of caries than less educated mothers and pregnant women. This null hypothesis was rejected, as Pearson’s Chi-square analysis showed a statistically significant relationship between educational level and knowledge about vertical transition of caries. About 58.1% of postgraduate mothers and pregnant women predicated that dental caries can be caused from the mother to the child by kissing the baby on the mouth (p=0,009), and 65% of them indicated that dental caries can be caused from the mother to the child by controlling the food in the spoon with the mother’s mouth during the feeding of the baby (p=0,014) (Table 2).
Due to the lack of studies on the knowledge of oral hygiene among Turkish women during pregnancy and infant oral health information, a study investigating the knowledge of mothers on these subjects was deemed appropriate. The power analysis required a minimum of 480 participants, and we gave questionairre to 555 women within one year. As the assessment of knowledge during pregnancy in the present study was based on self-reports, the validity of the results might be questioned.
General advice to patients from oral health professionals worldwide is that they usually need to brush their teeth twice a day with excipients such as fluoride toothpaste at the appropriate concentration. Regular toothbrushing twice a day with fluoride toothpaste is widely recommended for all age groups [3,4]. In a study conducted by Chung et al.  on pregnant women, 88% of mothers reported brushing at least twice a day, and 42% reported using dental floss at least once a day. Low income was associated with more poor oral hygiene outcomes. In addition, Malkawi et al.  reported that 62.4% of pregnant mothers regularly brushed their teeth, but 73.2% did not use auxiliary oral hygiene products such as floss or mouthwash. In the study of Ozen et al. , it is reported that 57% of pregnant women brushed their teeth more than once a day, and 93% of them brushed once a day. They also reported that 8% of pregnant women used dental floss, and 3% had mouth rinse water.
Our findings are in line with these previous reports; 67.4% the of participants stated that teeth should be brushed twice a day, while 13.5% of them indicated that they should be brushed once a day. When asked about the use of auxiliary hygiene products such as floss and mouthwash, 68.8% of the participants answered ‘yes’, 19.6% of them answered ‘no’. At income level >6000 TL, the ratio of ’yes’ response compared to other income levels was statistically significant and higher (p<0,001).
In the second and third trimesters of pregnancy, pregnancy-associated gingivitis is observed by an increased prevalence and severity of the disease. Although the number of plaques is relatively low during pregnancy, the main symptoms of gingival inflammation tend to occur . With proper oral hygiene during pregnancy, plaque cleaning and oral care can minimize gingival inflammation . In the study conducted by Gonik et al. , 61% of those who went to the state hospital and 72% of pregnant women who went to a private center agreed that pregnancy could cause worsening gingival health. Ozen et al.  reported that among pregnant Turkish women, 68.7% stated that they experienced oral health problems during pregnancy and that pregnancy could cause gingival problems.
In the present study, very similar findings with these studies were found, and 68.1% of the women who participated in our survey stated that pregnancy caused gingival problems. Women with high-income level knew that pregnancy could lead to gum problems. The results were found to be significantly higher than those with low income (p<0,001).
Women who do not visit a dentist during pregnancy may pretend like they do not have oral health problems, or have excuses including that they have insufficient time, that dental treatment may harm the fetus or that they fear dental services [11-13]. In a cohort study conducted in London, 35% of mothers did not receive oral health advice during pregnancy . In the study conducted among pregnant women in the north of Jordan, 68.2% of the respondents knew that they needed dental consultation during pregnancy, but only 39.5% received dental consultation during pregnancy. A statistically significant relationship was found between the level of education and knowledge about the need for dental consultation during pregnancy .
The present study also confirmed these studies; 62% of participants indicated that it is necessary to go to the dentist during pregnancy. The ratio of mothers reporting the needed to go to the dentist during pregnancy was found to be statistically significant both in terms of education levels and income level (p<0,001).
Ozen et al.  reported that 75% of pregnant women stated a relationship between pregnancy and oral health. However, only 47% of women reported that oral and dental health problems might affect pregnancy outcomes . In a similar study conducted by Gonik et al. , only 7% of pregnant women stated that poor oral hygiene status could lead to miscarriages, and only 12% of pregnant women had knowledge about the correlation between poor oral hygiene and early birth. Studies have shown that reducing maternal oral levels of Streptococcus mutans, the bacteria responsible for caries, reduces vertical transfer to the newborn and lowers the risk of tooth decay. As an important finding, these studies have shown that mothers do not know that bacterial colonization occurs before the child’s first teeth eruption [10,15,16].
Conversely, the present study found a better result than the findings of these studies; 58% of the participants reported that the health of the mother during pregnancy was important for the general health of the baby, and the results showed a statistically significant difference between the educational level of the participants (p=0,009). In addition, more than half of our participants (58.6%) stated that the nutrition of the mother during pregnancy will affect the health of the baby’s teeth and again results showed a statistically significant difference when the educational level was examined (p=0,015).
Correia et al.  reported that 26.1% of mothers stated they did not think about the time to brush their baby’s teeth and 7.8% indicated they were not sure; 49.6% of mothers planned to start brushing their baby’s teeth as soon as the first tooth emerged; 11.3% of them planned to do so when the baby started eating solid foods.
Similar results were found in the present study; 44.7% of the participants stated that tooth brushing should start when the first tooth erupted, and 42.2% indicated it was appropriate to brush after all the primary teeth have erupted. The time and frequency of tooth brushing did not show a statistically significant difference when the number of pregnancies was examined (p>0,05). However, postgraduate mothers have a significantly higher difference (p<0,001).
The similarity of S. mutans genotype between mother and child varies between cultures. In American society, S. mutans similarity between mother and child was found to be 71% , in Japan 70% , in Brazil 81% , whereas in Chinese society, this rate was found to be 45% . In Turkish society, S. mutans between mother and child were reported as 24% . In the study by Gonik et al. , the ratio of mothers who reported that kissing from the baby’s mouth may be related to S.mutans transition and may lead to childhood caries were 12% in the state hospital and 7% in a private center. Regarding sharing the spoon with baby, 16% of mothers in the state hospital and 22% of mothers in the private center thought that this behavior could cause decay transition.
In the present study, compared to the findings of other studies, the percentage of correct answers was found to be much higher; 46.5% of the participants reported that tooth decay can be transmitted from mother to child by kissing the baby; 53.2% stated that during common spoon use, there may be bacterial transmission from mother to child, and this may cause caries formation. Mothers with postgraduate degrees were more likely to answer correctly to the question about the kissing of the baby (p=0,009) and the question about the use of the same spoon as the baby (p=0,014).
Mothers’ knowledge and practices help to create more effective strategies to benefit babies. More studies are needed to identify pregnant mothers at a high risk for caries and to improve effective oral health for both themselves and their babies. It is important to better educate women who are pregnant or have a newborn about oral and dental health.
Scientiﬁc Responsibility Statement
Animal and human rights statement
Conflict of interest
1. American College of Obstetricians and Gynecologists Women’s Health Care Physicians; Committee on Health Care for Under-served Women. Committee Opinion No. 569: Oral health care during pregnancy and through the lifespan. Obstet Gynecol. 2013;122(2 Pt 1):417-22.
2. Brecher EA, Lewis CW. Infant Oral Health. Pediatr Clin North Am. 2018;65(5):909-21.
3. Dye BA, Tan S, Smith V, Lewis BG, Barker LK, Thornton-Evans G, et al. Trends in oral health status: United States, 1988-1994 and 1999-2004. Vital Health Stat. 2007;248:1-92.
4. dos Santos AP, Nadanovsky P, de Oliveira BH. A systematic review and meta-analysis of the effects of fluoride toothpastes on the prevention of dental caries in the primary dentition of preschool children. Comm Dent Oral Epidemiol. 2013;41(1):1-12.
5. Chung, LH, Gregorich SE, Armitage GC, Gonzalez-Vargas J, Adams SH. Sociodemographic disparities and behavioral factors in clinical oral health status during pregnancy. Comm Dent Oral Epidemiol. 2014;42(2):151-9.
6. Malkawi ZA, Tubaishat RS. Knowledge, practice and utilization of dental services among pregnant women in the north of Jordan. J Contemp Dent Pract. 2014;15(3):345-51.
7. Ozen B, Ozer L, Basak F, Altun C, Acikel C. Turkish women’s self-reported knowledge and behavior towards oral health during pregnancy. Med Princ Pract. 2012;21(4):318-22.
8. Mariotti A. Plaque-related gum diseases. In Lindhe J, Lang NP, editors. Clinical Periodontology and Implant Dentistry. Copenhagen: Wiley-Blackwell; 2015;6:366-80.
9. Christensen LB, Jeppe-Jensen D, Petersen PE. Self-reported gingival conditions and self-care in the oral health of Danish women during pregnancy. J Clin Periodontol. 2003;30(11):949-53.
10. Gonik B, Wilson E, Mayberry M, Joarder BY. Pregnant Patient Knowledge and Behavior Regarding Perinatal Oral Health. Am J Perinat. 2017;34(7):663-7.
11. Gaffield ML, Gilbert BJ, Malvitz DM, Romaguera R. Oral health during pregnancy: an analysis of information collected by the pregnancy risk assessment monitoring system. J Am Dent Assoc. 2001;132(7):1009-16.
12. Al Habashneh R, Guthmiller JM, Levy S, Johnson GK, Squier C, Dawson DV, et al. Factors related to utilization of dental services during pregnancy. J Clin Periodontol. 2005;32(7):815-21.
13. Saddki N, Yusoff A, Hwang YL. Factors associated with dental visit and barriers to utilisation of oral health care services in a sample of antenatal mothers in Hospital University Sains Malaysia. BMC Public Health. 2010;10(75):562-8.
14. Correia PN, Alkhatrash A, Williams CE, Briley A, Carter J, Poston L, et al. What do expectant mothers need to know about oral health? A cohort study from a London maternity unit. BDJ Open. 2017;3:17004.
15. da Silva Bastos Vde A, Freitas-Fernandes LB, Fidalgo TK, Martins C, Mattos CT, de Souza IP, et al. Mother-to-child transmission of Streptococcus mutans: a systematic review and meta-analysis. J Dent. 2015;43(2):181-91.
16. Binks C, Duane B. Mother-to-child transmission of Streptococcus mutans. J Evid Based Dent Pract. 2015;16(2):39-40.
17. Li Y, Wang W, Caufield PW. The fidelity of mutans streptococci transmission and caries status correlate with breast-feeding experience among Chinese families. Caries Res. 2000;34(2):123-32.
18. Lapirattanakul J, Nakano K, Nomura R, Hamada S, Nakagawa I, Ooshima T. Demonstration of mother-to-child transmission of Streptococcus mutans using multilocus sequence typing. Caries Res. 2008;42(6):466-74.
19. Klein MI, Florio FM, Pereira AC, Hofling JF, Goncalves RB. Longitudinal study of transmission, diversity, and stability of Streptococcus mutans and Streptococcus sobrinus genotypes in Brazilian nursery children. J Clin Microbiol. 2004;42(10):4620-6.
20. Hames-Kocabas EE, Ucar F, Kocatas Ersin N, Uzel A, Alpoz AR. Colonization and vertical transmission of Streptococcus mutans in Turkish children. Microbiol Res. 2008;163(2):168-72.
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Aycan Dal Dönertaş, Çağdaş Çınar. Evaluation of knowledge and attitudes of pregnant women about infant oral health and their oral hygiene. Ann Clin Anal Med 2022;13(5):502-506
The relationship between fear of COVID-19 and affective symptoms of bipolar patients during the COVID-19 pandemic
Emine Nur Çorum 1, Emrullah Dündar 2
1 Department of Occupational Therapy, 2 Department of Psychiatry, Fatih Community Mental Health Center, Haseki Education and Research Hospital, İstanbul, Turkey
DOI: 10.4328/ACAM.20998 Received: 2021-12-15 Accepted: 2022-03-04 Published Online: 2022-03-13 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):507-511
Corresponding Author: Emine Nur Çorum, Fatih Community Mental Health Center, Haseki Education Research Hospital, 34091, Istanbul, Turkey. E-mail: firstname.lastname@example.org P: +90 212 531 51 04 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9661-4423
Aim: This study aims to examine the relationship between fear of COVID-19 and affective symptoms of patients with bipolar disorder in Turkey. Another aim of the study is to reveal whether participants’ fear of COVID-19 changes according to various socio-demographic characteristics.
Material and Methods: In the study, data were collected from 100 people with bipolar disorder using a face-to-face survey method by a set of scales including the Young Mania Rating Scale, the Hamilton Depression Rating Scale and the Fear of COVID-19 Scale. The data collection process was carried out in October 2020 and January 2021.
Results: The results of the study showed that 53% of the participants had a moderate level of fear of COVID-19, and 45% had a low level of fear. According to the results of the regression analysis, fear of COVID-19 explains 23.1% of the total variance in the mania state. In addition, female bipolar disorder patients were found to have a greater fear of COVID-19 than men.
Discussion: As a result of this study, it was revealed that the manic symptoms of bipolar disorder patients reduced the fear of COVID-19. In this process, detailed scans and interventions for this diagnostic group will be important.
Keywords: Bipolar Disorder, Fear of COVID-19, Pandemic, Mental Disorders
Infectious diseases are a group of diseases that have existed for centuries and have important effects on the development of humanity . The recent novel coronavirus-2019 (COVID-19) worldwide pandemic emerged as a pneumonia pandemic in China in December 2019 . The first case of coronavirus emerged in Turkey on 11 March 2020, and the same date as the World Health Organization declared a pandemic . The Turkish government enforced many measures to mitigate the spread of COVID-19, such as enforcing spatial distancing, the use of medical face masks, closing schools, encouraging self-isolation, and quarantining individuals returning from abroad . While these measures exist to slow the spread of COVID-19, the potential adverse psychiatric effects should not be ignored.
The difficulty of controlling COVID-19 can result in devastating economic, social and psychological effects. These effects can arise from the fear of being infected, infecting others, dying, and/or losing loved ones. Additionally, concerns such as the inability to receive the necessary medical care or the possibility of losing a job. as a result. can also weigh heavily on the mind of the individual . The continual following of news and developments concerning COVID-19 (especially via social media, which may include misinformation) is also a factor that increase fear of COVID-19 .
Fear is a concept that is representative in the physical, interpersonal, cognitive and behavioral domains [1,7]. It is a natural response to danger and important for managing an appropriate response to the threat . On the other hand, fear can have catastrophic results. With chronic, disproportionate and high level of fear, individuals may not think clearly and lose the control mechanism over the situation.
COVID-19 stress and fear of COVID-19 are increasingly researched constructs in the general population [1,2,4]. Although individuals with mental illness are more vulnerable to their psychological health than the general population , it is unfortunately overlooked during the COVID-19 pandemic.
BD is a chronic affective disorder characterized by dramatic changes in mood, thinking, behavior and attitude . BD is thought to be more sensitive to serious life events, such as pandemics, earthquakes that can disrupt biological and social rhythms, by some mechanisms related to circadian rhythm regulation .
Bipolar disorders (BD) are chronic and recurrent disorders that affect >1% of the global population. BD is a chronic affective disorder characterized by dramatic changes in mood, thinking, behavior and attitude . In patients with bipolar disorders, the lock-down associated with COVID-19 pandemic has a high probability to function as a trigger for a more severe and unstable illness course characterized by increased risk of affective lability, impulsivity, and risk-taking behavior, alcohol or substance use disorders, and higher rates of suicide attempts .
The sudden changes that occurred could have significantly impacted psychiatric patients’ mental health, as well as having reduced their opportunity to access psychiatric services. Knowing the COVID-19 fear level in BD patients and its possible relationship with variables such as sociodemographic and affective symptoms will contribute to the planning of interventions for this patient group. This will inform evidence-based strategies for patient care in the clinic and help to mitigate long-term symptom exacerbation and adverse psychological outcomes in these individuals.
This study was conducted to determine what the COVID-19 fear level is in BD patients, whether it changes according to sociodemographic characteristics, and its relationship with manic and depressive symptoms, which are the affective symptoms of the disease.
Material and Methods
Procedure and Participants
This study was conducted in a community mental health center located in Istanbul province of Turkey. Istanbul is one of the critical cities in the COVID-19 pandemic due to its crowded population and its location on the transit route. This center serves patients with serious mental illnesses who are treated and followed up on an outpatient basis. During the pandemic period, for patients presenting to the center, psychiatric examinations and treatments in this center were conducted face-to-face by complying with infection precautions. Patients aged 65 years and older with comorbid problems and were not willing to come to the center due to the concerns of infection were served by phone. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), 113 eligible individuals diagnosed with BD were consecutively interviewed by trained research interviewers. Inclusion criteria for the participants were defined as a) being treated at a community mental health center for at least 1 year b) Age 18 years and above. c) Have been clinically stable for the last 3 months (stabilization was defined as the absence of hospital admissions or a major change in treatment over the past 3 months).
Patients with a manic episode, moderate-severe depression, catatonia, active alcohol or substance abuse, and intellectual disability were excluded from study.
The interview team consisted of a psychiatrist and an occupational therapist. After receiving verbal informed consent, they were invited to answer a series of questions contained in the study scales. If the patient was unable to provide valid informed consent (based on the caregiver’s response), additional informed consent was obtained from primary caregivers. After the psychiatrist determined the psychiatric symptoms of the patients, the occupational therapist applied the Fear of COVID-19 scale.
The study included 113 patients; 7 patients were excluded from the study because they did not want to participate, 4 patients’ relatives did not give their consent, and 2 patients were thought to be in the exacerbation period. Demographic information of the participants was obtained from the electronic registration system. The COVID-19 Fear Questionnaire, Young Mania Rating Form, and Hamilton Depression Rating Scale were administered to all participants.
This study was carried out in a period when there was no curfew between October 2020 and January 2021, after obtaining the approval of the Institute Ethics Committee (AV/IEC/2020/193), in accordance with the principles of the Declaration of Helsinki. Assessments
Fear of COVID-19 Scale:
It will be used to determine the fear of COVID-19. Consisting of 7 questions, the scale was designed in a 5-point Likert type. The maximum score that can be obtained from the scale is 35, and the lowest score is 7. The high score obtained from the scale indicates the high fear of COVID-19. The scale was developed by Ahorsu et al. The Turkish validity and reliability study was performed by Haktanır et al [6,12].
Young Mania Rating Scale:
Research was conducted on mania and depression in order to determine the mood of the patients. “Young Mania Rating Scale” was used in the determination of mania states. It was developed by Young R.C et al. and its Turkish validity and reliability study was performed by Karadag F. et al [13,14].
While filling out the scale, the last 48 hours of the patient are taken into consideration. The opinion of the clinician is more important than what the patient says. This was not applied in this study, but in a validity and reliability study participated, if the clinician could not make a decision for items with 0-4 points (for example, whether it was 2 or 3), he should give the higher score, and for items with 0-8 points, he should get the intermediate value (i.e., if it is not possible to decide whether 2 or 4 3 points) is recommended. It is not used to make a diagnosis, but to determine the severity of the current manic state. It is accepted that each upper step in the scale includes the lower steps before it. It is applied with an interview of 15-30 minutes. The patient’s own statements are allowed. Apart from the evaluation at the time of the interview, information can be obtained from the service personnel or the patient’s family. A total score and a score over 20 are usually considered a cut-off for a manic episode.
Hamilton Depression Rating Scale:
It is a 17-item scale based on the evaluator’s rating, used to measure the severity of depression in patients. It was published by Max Hamilton in 1960 . It is the most widely used method to measure the degree of depression. The items of the scale related to difficulty falling asleep, waking up in the middle of the night, waking up early in the morning, somatic symptoms, genital symptoms, weight loss, and insight were graded between 0 and 2, and other items between 0 and 4. It is used by the specialist to determine whether the symptom in each item is present in the patient and the degree of severity such as mild, moderate, severe, by asking the questions for that item and basing on the answers. The total score of the scale, ranging from 0 to 53, is obtained by summing the ratings, and an increase in the score indicates an increase in the severity of depression. The highest score is 53 points. A score of 0 to 7 indicates no depression, a score of 8 to 15 indicates mild depression, a score of 16 to 28 indicates moderate depression, and a score of 29 and above indicates severe depression. The validity and reliability study of the scale for Turkey was done by Akdemir et al .
Data analysis was done with the SPSS version 22 program. Descriptive statistics (mean, standard deviation (SD) and frequency) were calculated for all demographic and clinical variables. The compatibility of numerical features with the normal distribution was examined using the Shapiro-Wilks test. The effects of demographic characteristics on COVID-19 fear score, Young Mania score and Hamilton Depression score were determined with the Analysis Covariance (ANCOVA) model. Age, gender, marital status, educational status, employment status and presence of a chronic disease were included in this model together and adjusted effects were determined. In addition, the COVID-19 score was categorized as in previous studies and divided into 3 . Relationships between scale scores were analyzed using the Pearson correlation analysis. The limit of significance for all statistics was chosen as p≤0.05.
A total of 100 people, 60 of whom were men (60%), participated in the study. The mean age of the participants was 42,12 years. In addition, out of 100 people, 73 were single, 15 were university graduates, 31 were high school graduates and 54 were primary school graduates, 27 were working and 29 had chronic diseases (Table 1).
After obtaining the total scale scores of the individuals, the results given in Table 1 were obtained by studying the relations between these scores and the demographic characteristics of the patientsCOVID-19 Fear Total Score was found to be significantly higher in women (P=0.048). In addition, Young Mania Total Score was found to be significantly higher in those who were single (P=0.050), high school graduates (P=0.025) and those with chronic diseases (P=0.050). The Hamilton Depression Total Score was found to be significantly higher in the unemployed (P=0.015) (Table 1).
In addition, 43% of the participants have a low level of fear of COVID-19. 55% are mild, 2% of them have a high level of fear of COVID-19 (Figure 1).
According to the results of the linear regression analysis, as the Young mania total score increases by 1 point, the fear of COVID-19 score decreases by 0.231 points (Table 2). No significant relationship was found between depression and fear of COVID-19 (p=0.737).
The aim of our study was to measure the levels of COVID-19 fear and any possible relationship with affective symptoms in patients with BD and to identify possible differences in terms of sociodemographic factors. To our knowledge, this is the first study to examine the relationship between fear of COVID-19 and affective symptoms in BD patients.
Our study showed that the majority of the BD patient group had a low-to-moderate degree of COVID-19 fear, and it has been shown that the state of mania reduces the fear of COVID-19.
We found that the fear of COVID-19 does not differ by age, marital status, educational status, professional status and the presence of chronic diseases, except for gender. Women had a higher fear of COVID-19 than men. Studies in healthy population have also shown that women have a greater fear of COVID-19 than men [21,22]. This may be related to the fact that the female gender is shown as a predictor of the negative psychological impact of the COVID-19 epidemic and that women are exposed to higher levels of stress, anxiety and depression, and its psychological impact is a greater epidemic.
It is stated that the burden of traumas such as earthquakes, economic crises, and pandemics may play an important role in BD patients . It is thought that BD patients may be more stressed in this process, which may complicate treatment and increase interpersonal stigma . In the light of these considerations, it can be expected that BD patients will have a high fear of COVID-19. However, contrary to expectations, the fear of COVID-19 was found to be low to moderate in the vast majority of BD patients (43%-55%). This may indicate that BD patients may already be socially isolated and have low social functioning, so they are less affected by the COVID-19 pandemic and do not have a high level of fear.
On the other hand, having a low or high fear of COVID-19 may be related to the degree of compliance with protective measures. According to the results of a study, fear of COVID-19 is shown as a predictor of positive behavioral change (eg, social distance, improved hand hygiene) related to the epidemic . In other words, the existence of the fear of COVID-19 had a positive effect on the fight against the epidemic. Moderate and low levels of fear of COVID-19 in BD patients raises doubts about compliance with pandemic precautions.
According to the results of our study, we found that the fear of COVID-19 was lower in BD patients with manic symptoms. This means that the increase in manic symptoms in BD patients reduces the fear of COVID-19. This brings to mind the risky behaviors frequently seen in BD patients. It is known that risky behaviors increase in BD patients compared to normative examples. These behaviors are more evident in manic periods. In this period, neurobiological mechanisms related to emotions, persistent impulsivity, cognitive deficits, and reward increase risk-taking .
In our study, no relationship was found between fear of COVID-19 and depression. On the contrary, studies conducted in healthy populations have found significant relationships between fear of COVID-19 and depression [6,24,25]. In a study, despite the fact that there seems to be a lesser association between fear and depression, cases of suicide have been reported in the population due to fear of COVID-19 . This indicates that not only depression but also other factors related to stress should be investigated.
The absence of a control group is a limitation of the study. Repeating future studies with healthy controls will provide a comparative perspective and will be useful. In addition, the moderate and low level of fear of COVID-19 in BD patients raises doubts about compliance with pandemic precautions. It will be useful to investigate this issue in future studies.
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1. Özmen S, Özkan O, Özer Ö, Yanardağ MZ. Investigation of COVID-19 Fear, Well-Being and Life Satisfaction in Turkish Society. Soc Work Public Health. 2021;36(2):164-77.
2. Satici B, Saricali M, Satici SA, Griffiths MD. Intolerance of Uncertainty and Mental Wellbeing: Serial Mediation by Rumination and Fear of COVID-19. Int J Ment Health Addict. 2020;1-12.
3. Rasanathan K, Evans TG. Primary health care, the Declaration of Astana and COVID-19. Bull World Health Organ. 2020;98(11):801-8.
4. Saricali M, Satici SA, Satici B, Gocet-Tekin E, Griffiths MD. Fear of COVID-19, Mindfulness, Humor, and Hopelessness: A Multiple Mediation Analysis. Int J Ment Health Addict. 2020;1-14.
5. Montemurro N. The emotional impact of COVID-19: From medical staff to common people. Brain Behav Immun. 2020; 87:23-4.
6. Ahorsu DK, Lin CY, Imani V, Saffari M, Griffiths MD, Pakpour AH. The Fear of COVID-19 Scale: Development and Initial Validation. Int J Ment Health Addict. 2020;1-9.
7. Schimmenti A, Starcevic V, Giardina A, Khazaal Y, Billieux J. Multidimensional Assessment of COVID-19-Related Fears (MAC-RF): A Theory-Based Instrument for the Assessment of Clinically Relevant Fears During Pandemics. Front Psychiatry. 2020; 11:748.
8. Pappas G, Kiriaze IJ, Giannakis P, Falagas ME. Psychosocial consequences of infectious diseases. Clin Microbiol Infect. 2009;15(8):743-7.
9. Chang S, Zhang Y, Jeyagurunathan A, et al. Providing care to relatives with mental illness: reactions and distress among primary informal caregivers. BMC Psychiatry. 2016;16(1):80.
10. Vieta E, Berk M, Schulze TG, et al. Bipolar disorders. Nat Rev Dis Primer. 2018;4:18008.
11. Murray G, Gottlieb J, Swartz HA. Maintaining Daily Routines to Stabilize Mood: Theory, Data, and Potential Intervention for Circadian Consequences of COVID-19. Can J Psychiatry. 2021;66(1):9-13.
12. Haktanir A, Seki T, Dilmaç B. Adaptation and evaluation of Turkish version of the fear of COVID-19 Scale. Death Stud. 2020:1-9.
13. Karadag F, Oral ET, Yalcın F, Eren E. Young Mania Rating Scale reliability and validity in Turkey. Türk Psikiyatri Derg. 2001;13:107-114.
14. Young RC, Biggs JT, Ziegler VE, Meyer DA. A Rating Scale for Mania: Reliability, Validity and Sensitivity. Br J Psychiatry. 1978;133(5):429-35.
15. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. 1960; 23:56-62.
16. Akdemir A, Turkcapar H, Orsel S, Demirergi N, Dağ İ, Ozbay M. Reliability and validity of the Turkish Version of Hamilton Depression Rating Scale. Compr Psychiatry. 2001; 42:161-5.
17. Malik S, Ullah I, Irfan M, et al. Fear of COVID-19 and workplace phobia among Pakistani doctors: A survey study. BMC Public Health. 2021;21(1):833.
18. Mazza M, Marano G, Janiri L, Sani G. Managing Bipolar Disorder patients during COVID-19 outbreak. Bipolar Disord. 2020;22(8):870-1.
19. Stefana A, Youngstrom EA, Chen J, et al. The COVID-19 pandemic is a crisis and opportunity for bipolar disorder. Bipolar Disord. 2020;22(6):641-3.
20. Harper CA, Satchell LP, Fido D, Latzman RD. Functional Fear Predicts Public Health Compliance in the COVID-19 Pandemic. Int J Ment Health Addict. 2020:1-14.
21. Broche-Pérez Y, Fernández-Fleites Z, Jiménez-Puig E, Fernández-Castillo E, Rodríguez-Martin BC. Gender and Fear of COVID-19 in a Cuban Population Sample. Int J Ment Health Addict. 2020:1-9.
22. Liu Y, Ning Z, Chen Y, et al. Aerodynamic analysis of SARS-CoV-2 in two Wuhan hospitals. Nature. 2020;582(7813):557-60.
23. Mamun M. A, Griffiths M. D. First COVID-19 suicide case in Bangladesh due to fear of COVID-19 and xenophobia: Possible suicide prevention strategies. Asian Journal of Psychiatry. 2020; 51: 102073.
24. Alyami M, Henning M, Krägeloh CU, Alyami H. Psychometric evaluation of the Arabic version of the Fear of COVID-19 Scale. International journal of mental health and addiction. 2021;19(6), 2219-32.
25. Bitan D. T, Grossman-Giron A, Bloch Y, Mayer Y, Shiffman N, Mendlovic S. Fear of COVID-19 scale: Psychometric characteristics, reliability and validity in the Israeli population. Psychiatry Research. 2020; 289: 113100.
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Emine Nur Çorum, Emrullah Dündar. The relationship between fear of Covid-19 and affective symptoms of bipolar patients during the Covid-19 pandemic. Ann Clin Anal Med 2022;13(5):507-511
Investigation of the effect of COVID-19 on upper extremity trauma
Hasan Atacan Tonak 1, Yener Aydin 2, Mustafa Icen 2, Bahadir Alimoglu 2, Haluk Ozcanli 2
1 Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, 2 Department of Orthopedics and Traumatology, Faculty of Medicine, Akdeniz University, Antalya, Turkey
DOI: 10.4328/ACAM.20999 Received: 2021-12-15 Accepted: 2022-01-18 Published Online: 2022-01-25 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):512-515
Corresponding Author: Hasan Atacan Tonak, Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Akdeniz University, 07058, Campus, Antalya, Turkey. E-mail: email@example.com P: +90 505 278 22 54 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3545-936X
Aim: Our study aims to evaluate the upper extremity trauma that admitted to our hospital from April 11, 2020, to June 1, 2020, the days when the restrictions were applied in Turkey, and to investigate the effect of COVID-19 on upper extremity trauma by comparing with the data of a year ago between the same dates.
Material and Methods: Demographic information, trauma details, and region, and the treatment method of patients with any upper extremity trauma who were over the age of 18 and admitted to the hospital between April 11, 2019, and June 1, 2019 (2019-Before Restrictions) and between April 11, 2020, and June 1, 2020 (2020-Lockdown) were examined retrospectively.
Results: In 2019-Before Restrictions, 218 patients and in the 2020-Lockdown, 163 patients were admitted to the hospital due to upper extremity trauma. The number of hospital admissions with upper extremity trauma during the 2020-Lockdown was 25.22% less than that of those in 2019-Before Restrictions, (p<0.05). While the number of patients admitted to the hospital due to fractures in the upper extremity during 2019-Before Restrictions, was 89 (Open Fracture=32, Closed Fracture=57), this number was observed to decrease to 48 (Open Fracture=11, Closed Fracture=37) in the 2020-Lockdown (p<0.05).
Discussion: It was determined that there was a decrease in upper extremity trauma during 2020-Lockdown compared to the same dates of the previous year. It is possible to state that quarantine practices applied to prevent the spread of COVID-19 affect the decrease in upper extremity trauma.
Keywords: COVID-19, Upper Extremity, Hand, Trauma, Fracture
A new coronavirus, which emerged in late 2019 and is transmitted through droplets, has been detected [1, 2]. The World Health Organization (WHO) declared a global state of emergency for the disease caused by this virus on January 30, 2020 and then named this new virus SARS-CoV-2 and the disease COVID-19 on February 11, 2020 [3, available at: www.who.int/emergencies/diseases/novel-coronavirus-2019]. Official authorities announced that the first case of COVID-19 was detected in Turkey on March 11, 2020, the day the WHO declared this global epidemic a pandemic [available at: www.who.int/emergencies/diseases/novel-coronavirus-2019, available at: https://covid19.saglik.gov.tr/TR-66935/genel-koronavirus-tablosu.html]. In the following days, COVID-19 infections continued to increase in Turkey, and it was announced that as of March 16, 2020, all schools and universities would suspend education and then continue with online education [available at: https://tr.wikipedia.org/wiki/T%C3%BCrkiye%27de_COVID-19_pandemisi#cite_note-daily.sabah]. All countries had to close the workplaces, schools, universities, and social areas and implement mandatory quarantine due to the ongoing global COVID-19 pandemic. While restaurants, cafes, museums, classrooms, shopping centers, hotels, barbers, hairdressers and beauty centers, coffee shops, sports halls, concert venues, night clubs, and wedding/engagement halls are temporarily closed; all citizens were forbidden to have picnics and barbecues in forests, parks, and gardens. All sports leagues in the country have been postponed, and all sports competitions have been canceled until further notice [available at: https://tr.wikipedia.org/wiki/T%C3%BCrkiye%27de_COVID-19_pandemisi#cite_note-daily.sabah]. Official authorities first started a curfew for people aged 65 and over in order to reduce the spread of the pandemic and maintain social distance between people. Later, this restriction expanded in a way to include children and youth aged 20 and younger. People were urged not to travel abroad or leave their house unless absolutely necessary [available at: https://tr.wikipedia.org/wiki/T%C3%BCrkiye%27de_COVID-19_pandemisi#cite_note-daily.sabah]. On April 11-12, curfews were declared in 31 cities, which is how mass curfews began. Curfews, which have been continuing at regular intervals since this date, continued until June 1, 2020, together with “controlled social life” [available at: https://tr.wikipedia.org/wiki/T%C3%BCrkiye%27de_COVID-19_pandemisi#cite_note-daily.sabah].
Current COVID-19 measures and restrictions have also inevitably changed practices in hospitals and healthcare . When the literature was reviewed, the studies showing how upper extremity trauma were affected by the current pandemic during both restriction and reopening periods during the pandemic were studies either on the experience of hand surgeons or on the elbow and shoulder only, or on the immature elbow and shoulder joint [3-5]. Conducting a comprehensive retrospective analysis of the upper extremity trauma of COVID-19 in the light of our current knowledge will be valuable in showing how upper extremity trauma has changed. Hence, the hypothesis of our study is restrictions in the pandemic process may lead to a decrease in upper extremity trauma. Therefore, our study aims to evaluate the upper extremity trauma that admitted to our hospital serving in Antalya [available at: http://www.antalya.gov.tr/nufus], which is the 5th most crowded city of Turkey in terms of population, from April 11, 2020, to June 1, 2020, the days when the restrictions were applied in Turkey, and to investigate the effect of COVID-19 on upper extremity trauma by comparing with the data of a year ago between the same dates.
Material and Methods
The hospital records of a total of 551 patients who were admitted due to trauma to Akdeniz University Faculty of Medicine Orthopedics and Traumatology Department between April 11, 2019, and June 1, 2019 (2019-Before Restrictions) and between April 11, 2020, and June 1, 2020 (2020-Lockdown) were retrospectively analyzed. A total of 218 patients with any upper extremity trauma (aged between 18 and 86, with a mean age of 40.21±16.76 years), 67 females and 151 males in 2019-Before Restrictions, and 48 females and 115 males in total, 163 upper extremity trauma patients (aged between 18 and 88, with a mean age of 40.52±15.18 years) in the 2020-Lockdown, those who were older than 18 years of age and had any upper extremity trauma were included in the study. Those under the age of 18 and who had trauma in any region other than upper extremity trauma were not included in the study.
Demographic information, trauma details, and region, treatment method (surgical or conservative) of the patients were obtained using the MIA-MED (Version 184.108.40.20621, MIA Technology Inc.) hospital system. The study was approved by Akdeniz University Faculty of Medicine Clinical Research Ethics Committee (70904504/277, Decision No: KAEK-307).
The Windows-based SPSS (IBM SPSS Statistics, Version 23.0, Armonk, NY, USA) package program was used for statistical analysis of the data obtained in our study. Categorical data were expressed as mean, standard deviation, numbers, frequency, and percentage. To compare 2019-Before Restrictions and 2020-Lockdown, the Chi-square or Fisher exact test was used. Statistical significance was determined as p<0.05.
Between April 11, 2019, and June 1, 2019 (2019-Before Restrictions), 218 patients, and between April 11, 2020, and June 1, 2020 (2020-Lockdown), 163 patients were admitted to the hospital due to upper extremity trauma. The number of hospital admissions with upper extremity trauma during 2020-Lockdown was 25.22% less than that of those in 2019-Before Restrictions (p<0.05). Demographic characteristics of the patients are presented in Table 1.
While the number of patients admitted to the hospital due to fractures in the upper extremity during 2019-Before Restrictions was 89 (Open Fracture=32, Closed Fracture=57), this number was observed to decrease to 48 (Open Fracture=11, Closed Fracture=37) in 2020-Lockdown (p<0.05). Among the patients admitted to the hospital due to fracture, the number of patients with a fractured humerus was 23 during 2019-Before Restrictions and 6 during 2020-Lockdown. There was no statistical difference between the two periods in terms of the presence of dislocation (2019-Before Restrictions=5, 2020-Lockdown=6; p>0.05).
In terms of soft tissue injuries, 152 patients were determined in 2019-Before Restrictions and 105 patients in 2020-Lockdown (p>0.05). In 2019-Before Restrictions, 129 (59.2%) of 218 patients were treated surgically, and 89 (40.8%) received conservative treatment, while 89 (54.6%) of 163 patients in 2020-Lockdown were treated surgically and 74 (45.4%) received conservative treatment. Information about other upper extremity trauma is presented in Table 2 and Table 3.
The quarantine practices and curfews applied due to the COVID-19 pandemic led to a different experience for humanity,
and the kind of changes that occurred in the data on upper extremity trauma throughout this process was an object of interest. In our study, we compared the upper extremity trauma between April 11 and June 1, 2020, when quarantine was applied during the COVID-19 pandemic, which continues as a global epidemic and affected many areas of life, and the data of the previous year between the same dates and examined the effect of COVID-19 on upper extremity trauma. Our study revealed that the number of patients admitted to our hospital due to upper extremity trauma was 25.22% less in 2020, when quarantine was implemented during the COVID-19 pandemic, compared to the previous year. In a study investigating the effect of COVID-19 on shoulder and elbow trauma, the decrease in the number of patients during the COVID-19 period was similar to our study . Likewise, Fyllos et al.  have reported that the number of patients with orthopedic problems in the upper extremity was significantly lower in 2020 compared to a year ago. Another study on the effects of COVID-19 quarantine on hand surgery applications has reported a 32% decrease in patients compared to the previous year . The decrease in patient numbers observed in our current study is consistent with the literature. The quarantine practices applied to prevent the COVID-19 pandemic have prevented situations such as traffic accidents, work accidents, and sports injuries that may cause trauma in the upper extremity, and therefore this suggests that it leads to a decrease in upper extremity trauma. However, as have been stated by Gumina et al.  it should also be taken into account that patients with mild trauma may not have been admitted to the hospital due to the fear of being infected with the coronavirus. Similarly, it is possible that maintaining a more relaxed lifestyle  together with the first shock experienced during the quarantine period results in a decrease in upper extremity trauma.
During the 2020-Lockdown, although there was a significant decrease in the humerus (23 to 6) and hand (38 to 17) fractures, the numbers for other upper extremity regions remained almost the same. A study investigating the effect of curfews on hand and upper extremity injuries revealed a 65% decrease in all upper extremity injuries . In similar studies, where a decrease was detected in upper extremity injuries, it has been observed that there was a decrease, however, the rate was not very high [10, 11]. In our study, there was a 25.22% decrease in all upper extremity traumas, and the results are consistent with the literature. Moreover, our study determined that with the decrease in the number of patients with upper extremity trauma during the 2020-Lockdown, a decrease was detected in both surgical and conservative treatments. Atia et al.  reported performing surgical procedures with a 20% decrease in lockdown in 2020. This situation, which we encountered in our study, reveals that the decrease in both treatment methods due to the decrease in the number of patients is an expected result. We considered that decrease in both surgical and conservative treatments resulted from patients attending less activity and hospital admissions because of minor trauma in quarantine practices during the restriction process.
The decrease in soft tissue injuries in our current study supports the studies in the literature indicating the decrease in upper extremity soft tissue injuries during the COVID-19 period [12, 13]. Although this decrease in our study was not statistically significant, it is remarkable that the decrease in tendon injuries decreased during the 2020-Lockdown. Tendon injuries can occur from open cuts in the hand, trauma such as injury, and crushing with a sharp object [14, 15]. On the other hand, it is known that the most common causes of hand injury are tool and machinery use . It is possible to state that there is a decrease in soft tissue injuries resulting from not being in workplace environments that may cause soft tissue injuries and not using devices and machines in the workplace due to quarantine practices, and preventing sports trauma in closed sports centers.
There are strengths and limitations in our study. The strength of our study is that there are not many studies that specifically evaluate the effects of COVID-19 only on the entire upper extremity. In similar studies, either some parts of the upper extremity or all trauma patients were included [3, 5, 16, 17]. The fact that it is a single-centered study may prevent the generalization of the results of our study can be stated as a limitation. Therefore, multicenter studies are needed.
We found that there was a decrease in upper extremity trauma in 2020-Lockdown compared to the same dates in the previous year. Therefore, the hypothesis of our study was accepted. It is possible to state that quarantine practices applied to prevent the spread of COVID-19 affect the reduction in upper extremity trauma.
Scientiﬁc Responsibility Statement
Animal and human rights statement
Conflict of interest
1. Carraturo F, Del Giudice C, Morelli M, Cerullo V, Libralato G, Galdiero E, et al. Persistence of SARS-CoV-2 in the environment and COVID-19 transmission risk from environmental matrices and surfaces. Environ Pollut. 2020; 265(Pt B): 115010.
2. Thomas P, Baldwin C, Bissett B, Boden I, Gosselink R, Granger CL, et al. Physiotherapy management for COVID-19 in the acute hospital setting: clinical practice recommendations. J Physiother. 2020; 66(2): 73-82.
3. Gumina S, Proietti R, Polizzotti G, Carbone S, Candela V. The impact of COVID-19 on shoulder and elbow trauma: an Italian survey. J Shoulder Elbow Surg. 2020; 29(9): 1737-42.
4. Qazi UA, Sutton J, Farner SC, Bhandari L. Impact of the COVID-19 Pandemic on the Practice of Hand and Upper Extremity Surgeons. Cureus. 2020; 12(12): e12072.
5. Gumina S, Proietti R, Villani C, Carbone S, Candela V. The impact of COVID-19 on shoulder and elbow trauma in a skeletally immature population: an Italian survey. JSES Int. 2021; 5(1): 3-8.
6. Fyllos A, Varitimidis S, Papageorgiou F, Karamanis N, Alexiou K, Veloni A, et al. Upper extremity emergencies during SARS-COV-2 pandemic: Turnout trends. Injury. 2021; 52(3): 387-94.
7. Atia F, Pocnetz S, Selby A, Russell P, Bainbridge C, Johnson N. The effect of the COVID-19 lockdown on hand trauma surgery utilization. Bone Jt Open. 2020; 1(10): 639-43.
8. Bussing A, Rodrigues Recchia D, Dienberg T, Surzykiewicz J, Baumann K. Awe/Gratitude as an Experiential Aspect of Spirituality and Its Association to Perceived Positive Changes During the COVID-19 Pandemic. Front Psychiatry. 2021; 12: 642716.
9. Pichard R, Kopel L, Lejeune Q, Masmoudi R, Masmejean EH. Impact of the COronaVIrus Disease 2019 lockdown on hand and upper limb emergencies: experience of a referred university trauma hand centre in Paris, France. Int Orthop. 2020; 44(8): 1497-501.
10. Facchin F, Messana F, Sonda R, Faccio D, Tiengo C, Bassetto F. COVID-19: Initial experience of hand surgeons in Northern Italy. Hand Surg Rehabil. 2020; 39(4): 332-3.
11. Hwee J, Chiew J, Sechachalam S. The Impact of Coronavirus Disease 2019 (COVID-19) on the Practice of Hand Surgery in Singapore. J Hand Surg Am. 2020; 45(6): 536-41.
12. Murphy T, Akehurst H, Mutimer J. Impact of the 2020 COVID-19 pandemic on the workload of the orthopaedic service in a busy UK district general hospital. Injury. 2020; 51(10): 2142-7.
13. Pidgeon TE, Parthiban S, Malone P, Foster M, Chester DL. Injury patterns of patients with upper limb and hand trauma sustained during the COVID-19 pandemic lockdown in the UK: a retrospective cohort study. Hand Surg Rehabil. 2021; 40(3): 235-40.
14. Peters SE, Jha B, Ross M. Rehabilitation following surgery for flexor tendon injuries of the hand. Cochrane Database Syst Rev. 2021; 1: CD012479.
15. Patillo D, Rayan GM. Open extensor tendon injuries: an epidemiologic study. Hand Surg. 2012; 17(1): 37-42.
16. Turgut A, Arli H, Altundag U, Hancioglu S, Egeli E, Kalenderer O. Effect of COVID-19 pandemic on the fracture demographics: Data from a tertiary care hospital in Turkey. Acta Orthop Traumatol Turc. 2020; 54(4): 355-63.
17. Carkci E, Polat B, Polat A, Peker B, Ozturkmen Y. The Effect of the Coronavirus 2019 (COVID-19) Pandemic on the Number and Characteristics of Orthopedic Trauma Patients in a Tertiary Care Hospital in Istanbul. Cureus. 2021; 13(1): e12569.
Download attachments: 10.4328:ACAM.20999
Hasan Atacan Tonak, Yener Aydin, Mustafa Icen, Bahadir Alimoglu, Haluk Ozcanli. Investigation of the effect of Covid-19 on upper extremity trauma. Ann Clin Anal Med 2022;13(5):512-515
Cross-cultural adaptation and validation of the arabic version of the brace questionnaire used for the treatment of adolescents with idiopathic scoliosis
Sarah M. Ali, Nadia A. Fayaz, Sara M. Samir
Department of Physical Therapy for Musculoskeletal Disorder and İts Surgery, Faculty of Physical Therapy, Cairo University, Egypt
DOI: 10.4328/ACAM.21001 Received: 2021-12-16 Accepted: 2022-01-26 Published Online: 2022-02-07 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):516-520
Corresponding Author: Sarah M. Ali, Department of Physical Therapy for Musculoskeletal Disorder and Its Surgery, Faculty of Physical Therapy, Cairo University, Cairo, Egypt. E-mail: Sarah.firstname.lastname@example.org P: +20 103 344 26 56 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8138-3028
Aim: Brace questionnaire (BrQ) is widely used in order to evaluate the impact of brace treatment in adolescent scoliosis on the quality of life. However, it had been translated to different languages, it has not been translated or validated for the Arabic language.
Material and Methods: The Brace questionnaire was translated into Arabic language and back-translated, cross-culturally adapted by experts and according to the international guidelines, then was given to 51 adolescent idiopathic scoliosis patients (46 females and 5 males) were undergoing brace treatment to evaluate its reliability and validity. Reliability was assessed using Cronbach’s alpha for internal consistency and intraclass correlation coefficient (ICC) values for test-retest reliability with a 1-week interval between the tests. Concurrent validity had been made using Pearson’s Correlation Coefficient by correlating the brace questionnaire and the scoliosis research society-22 questionnaire.
Results: The Cronbach’s alpha of the Arabic BrQ was 0.918, the intraclass correlation coefficient (ICC) was 0.938, and the Pearson correlation coefficient between the Arabic Brace questionnaire and Scoliosis research society 22 was 0.758 (p < 0.001).
Discussion: The translated BrQ demonstrated a very good correlation between the Arabic brace questionnaire and the scoliosis research society 22, internal consistency values and concurrent validity were comparable to those of prior studies, wearing the brace and keeping it on for a long time has been shown to have negative effects on overall life quality. Treatment of scoliosis with a brace should not be restricted to clinical and radiological aspects, but should also involve therapeutic education regarding the quality of life.
Keywords: Brace Questionnaire, Quality of Life, Adolescent Idiopathic Scoliosis
Scoliosis is a three-dimensional deformity characterized by spinal deviation in the frontal plane, decreased kyphosis in the sagittal plane, and fixed vertebral rotation in the transverse plane . Adolescent idiopathic scoliosis is considered the most common type affecting children around puberty .
Early diagnosis and treatment are critical in limiting the progression of the curve . I would like this sentence to be removed. Patients with progressive idiopathic scoliosis above 25° but still undergrowth and before maturity, are advised to use the brace alone or in combination with exercises, which showed better results in correcting the curve progression, improving Cobb angle, respiratory functions and back muscle endurance than those used exercises alone (without bracing) [4, 5].
Bracing involves wearing a brace for about 18 hours, which may increase up to 23 per day till skeletal maturity [4, 6]. The adolescent’s life and quality of life are adversely affected by idiopathic scoliosis in addition to wearing the brace during everyday time; sleeping, eating, schooling for several years, creating physical and psychological stresses. Such stresses not only in adolescent patients, but affect the whole family, therefore the influence of bracing on quality of life need to be addressed .
The Arabic version of the Scoliosis Research Society 22 questionnaire is valid and reliable to assess health-related quality of life in adolescents with spinal deformities. It is made up of 22 items that are scored in five categories (1–5), with higher scores indicating a higher quality of life. However, it does not consider bracing treatment and how it affects the quality of life .
The Brace questionnaire is a valid and effective measuring tool, designed to evaluate the quality of life of patients with adolescent idiopathic scoliosis wearing a brace. It is mainly composed of 34 items organized into eight domains (general health perception, physical functioning, emotional functioning, self-esteem and aesthetics, vitality, school activity, bodily pain, and social functioning) . It has already been validated and culturally adapted for different languages such as English, Greek , Italian , Chinese [11, 12], French , Turkish , Polish , Persian , and Korean , but it hasn’t been validated for the Arabic language yet. Thus the purpose of this study was to perform a cross-cultural adaptation of the brace questionnaire (BrQ) into the Arabic language and then test its validity and reliability on adolescents with idiopathic scoliosis.
Materials and Methods
The reliability and validity of the Arabic version of the brace questionnaire used for the treatment of adolescent idiopathic scoliosis were investigated using a prospective cross-sectional design. The study was approved by the Ethics Committee of Faculty of Physical Therapy, Cairo University (P.T.REC/012/003140). The research was conducted between February 2021 and October 2021.
Fifty-one male and female adolescents with idiopathic scoliosis, aged between 9 to 18 years, wearing a brace for at least 3 months, were recruited from scoliosis medical clinics with no history of previous spinal surgery or deformity rather than idiopathic scoliosis, and no systemic or infectious diseases met the inclusion criteria. All patients and their parents signed consent forms before participating in the study, and they were informed about the research goals, any participant or parent who refuses to finish can withdraw at any moment. Initially, demographic data, curve shape, type, location, Cobb’s angle of the main curve, date and time of brace wearing, prescribed treatment, in addition to contact information were all documented in the datasheet.
Material and Methods
Brace questionnaire was created in order to assess how well scoliosis patients are doing after wearing a brace, 34 questions in total, divided into eight categories . The answers are grouped into either ‘’always’’, ‘’most of the time’’, ‘’occasionally’’, or ‘’never’’. Each question is assigned a value, and the total is multiplied by 20 during the scoring process. To arrive at a final score, multiply the sum of all individual scores by 34. The entire questionnaire should take between 10 and 12 minutes to complete. The scores range from 20 to 100. A high score indicates a higher quality of life.
Scoliosis research society-22 questionnaire consists of five domains, function/activity, pain, self-image/appearance, mental health, and satisfaction with management, each item’s score ranges from 1 to 5, with a total score ranging between 22 and 110 . Arabic translation of the SRS-22 questionnaire was developed and tested for reliability and validity among Arabic-speaking idiopathic scoliosis patients .
The Brace questionnaire was translated into Arabic language and cross-culturally adapted according to Wild et al’s guidelines . Regarding the preparation phase of Wild et al., it was not necessary to ask and take permission from the BrQ authors, because the Brace Questionnaire is not copyright protected. At first, the Brace questionnaire was translated from English to Arabic by two independent translators from the department of linguistics, Ain Shams University.
A single Arabic translation of the questionnaire was created after the differences between the two versions of the questionnaire were set out. After that, the combined text was back translated into its original language. After that, the back translation was examined to see how it compares to the original questionnaire. Then experts in the physical therapy and medical field, whose mother tongue is Arabic, examined the translation. Eight patients with adolescent idiopathic scoliosis took part in a cognitive debriefing to see how well the Arabic version of the questionnaire translates. The results of this cognitive debriefing were reviewed and finalized by interpreting the pilot testing results and checking for any misconceptions. Before writing a final report documenting the translation process, the final Arabic revision was proofread to look for mistakes. Then each patient was asked to complete the questionnaires. The translated Arabic BrQ and the Arabic version of SRS-22 were administered in the same setting and the patients were instructed to set up a second setting 1 week later to re-complete the brace questionnaire , or if this was not possible to some individuals, questionnaires were sent and received via e-mail. the scores were calculated according to Vasiliadis et al. .
Data processing & Statistical analysis
This part of the study is intended to present the collected data of the brace questionnaire through measuring Concurrent validity, which was done using Pearson’s Correlation Coefficient (r). Correlation values of 0.40 or above were considered satisfactory (r ≥ 0.81–1.0 as excellent, 0.61– 0.80 very good, 0.41–0.60 good, 0.21–0.40 fair, and 0–0.20 poor) [21, 22].
Reliability assessment of the Arabic version of the brace questionnaire was determined by calculating Cronbach’s α for internal consistency and intraclass correlation coefficient (ICC) values for test-retest reliability. Cronbach’s alpha ranges from 0 to 1 and values ≥0.7 indicate adequate internal consistency for scale, Test-retest reliability was examined using the Intraclass Correlation Coefficient (ICC). Values of ICC vary from 0 (totally unreliable) to 1 (perfectly reliable) and values above 0.80 were considered as evidence of excellent reliability .
All Statistical analyses were carried out using SPSS version 23.00 software (IBM Corporation, Illinois, USA). Alpha level was set at 0.05.
Descriptive Analysis of subjects’ general characteristics
As shown in Table 1, the study group consisted of 51 patients (5 boys and 46 girls), with mean age, body mass, height, and BMI values of 14.05±2.53 years, 49.29±10.73 kg, 155.97±9.19 cm, and 20.06±3.40 kg/m2 , respectively.
-Intra rater reliability of brace questionnaire
Table 2 and Figure 1, show the Brace questionnaire at the 1st and 2nd occasions by the same tester (intra-rater reliability). The total value brace questionnaire mean ±SD was (70.5±12.83) for the first reading of the main tester and (71.24±12.10) for the second reading for the same tester after one week. The intra-rater reliability using the Intra-class Correlation Coefficient (ICC) showed that there was a high reliability of pain subscale (with ICC=0.938 and P-value=0.0001*).
Internal consistency (correlation of items in the questionnaire)
The internal consistency was measured by Cronbach’s alpha. Results revealed that the internal consistency of observer scale of the brace questionnaire was high with Cronbach’s alpha = 0.918. Which confirms a very high level of internal consistency of the brace questionnaire.
Validity of Arabic Brace questionnaire
The concurrent validity was tested by correlating the Arabic Brace questionnaire with a measure of Scoliosis research society 22 (r < 0.20 = poor; 0.21 < r < 0.40 = fair; 0.41 < r < 0.60 = good, 0.61 < r < 0.8=very good, r >0.80= excellent).
Concurrent validity was assessed by calculating the Pearson correlation coefficient between the Arabic Brace questionnaire with a measure of Scoliosis research society 22 (Table 3).
The Pearson correlation coefficient (r) between the mean value of Arabic Brace questionnaire with the mean value of Scoliosis research society 22 was 0.758. The results indicated that Scoliosis research society 22 was significantly associated with Arabic Brace questionnaire (p-value=0.0001*). The overall correlation between the two administrations was very good.
The BrQ was translated and culturally adapted in several countries, but there was no Arabic version available, and the findings of our study supported the use of the culturally adapted Arabic BrQ in adolescents with idiopathic scoliosis wearing a brace. In conclusion, the translated BrQ revealed a very good correlation between the Arabic brace questionnaire and the scoliosis research society 22 with the Pearson correlation coefficient (r) 0.758, a high level of internal consistency (Cronbach’s alpha = 0.918), and excellent reliability ( ICC=0.938).
The findings of this study were comparable to those of previous studies with internal consistency 0.82 , 0.94 , 0.89 , 0.96 , 0.85 , 0.95 , 0.94 , 0.96 , and 0.913 .
The translated BrQ concurrent validity of our study was also comparable to previous studies with Pearson correlation coefficient (r) 0.826 , 0.743 , 0.64 , and 0.712 .
As known, wearing the brace and its daily duration have a negative impact on overall life quality . The use of a brace to treat scoliosis should not be limited to the clinical and radiological aspects of the deformity, but should also include therapeutic education about quality of life throughout the treatment period , for that reason, improving the quality of life is important to increase treatment compliance among scoliosis brace wearers, positively impacting the treatment quantity .
The cross-sectional design of the current study, as well as the small sample size available in the cross-cultural adaptation process, limited this study, however, the English, French, Italian, Turkish versions had a smaller sample size compared to our sample and the Persian was similar to our study.
The Arabic version of the brace questionnaire was valid, reliable with high internal consistency. The current findings indicate that the Arabic BrQ is a useful instrument for assessing the quality of life of adolescent idiopathic scoliosis patients who are being treated with a brace. We recommend using a larger sample size in future research and using the Arabic version of the BrQ to evaluate its ability to detect changes in brace-related quality of life.
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Animal and human rights statement
Conflict of interest
1. Romano M, Minozzi S, Zaina F, Saltikov JB, Chockalingam N, Kotwicki T, et al. Exercises for adolescent idiopathic scoliosis. Spine. 2013; 38(14): 883–93.
2. Addai D, Zarkos J, Bowey AJ. Current Concepts in the Diagnosis and Management of adolescent idiopathic scoliosis. Child`s Nervous System. 2020; 33(11): 570–80.
3. Ziwei Z, Fang L, Ru L, Xiaorong C. The effects of exercise therapy on adolescent idiopathic scoliosis: An overview of systematic reviews and meta-analyses. Complement Ther Med. 2021; 58:102697.
4. Negrini S, Donzelli S, Aulisa A G, Czaprowski D, Schreiber S, de Mauroy, et al. 2016 SOSORT guidelines: Orthopaedic and rehabilitation treatment of idiopathic scoliosis during growth. Scoliosis Spinal Disord. 2018; 13(1). DOI: 10.1186/s13013-017-0145-8.
5. Gao C, Zheng Y, Fan C, Yang Y, He C, Wong M. Could the Clinical Effectiveness Be Improved under the Integration of Orthotic Intervention and Scoliosis-Specific Exercise in Managing Adolescent Idiopathic Scoliosis? A Randomized Controlled Trial Study. American Journal of Physical Medicine and Rehabilitation. 2019; 98(8): 642–8.
6. Roye BD, Simhon ME, Matsumoto H, Bakarania P, Berdishevsky H, Dolan LA, et al. Establishing consensus on the best practice guidelines for the use of bracing in adolescent idiopathic scoliosis. Spine Deformity. 2020; 8(4):597–604.
7. Pham VM, Houlliez A, Carpentier A, Herbaux B, Schill A, Thevenon A. Determination of the influence of the Chêneau brace on the quality of life of adolescents with idiopathic scoliosis. Annales de Readaptation et de Medecine Physique. 2008; 51(1): 3–15.
8. Caronni A, Donzelli S, Zaina F, Negrini S. The Italian Spine Youth Quality of Life questionnaire measures health-related quality of life of adolescents with spinal deformities better than the reference standard, the Scoliosis Research Society 22 questionnaire. Clinical Rehabilitation. 2019; 33(8):1404–15.
9. Vasiliadis E, Grivas TB, Gkoltsiou, K. Development and preliminary validation of Brace Questionnaire (BrQ): A new instrument for measuring quality of life of brace treated scoliotics. Scoliosis. 2006; 1-7.
10. Aulisa AG, Guzzanti V, Galli M, Erra C, Scudieri G, Padua L. Validation of Italian version of Brace Questionnaire (BrQ). Scoliosis. 2013; 8(1):13.
11. Chan SL, Cheung K, Cheung J, Chan LL, Lo E. Validation of Chinese Version of Brace Questionnaire from its Original Greek Version. J Spine. 2019; S8. DOI: 10.4172/2165-7939.S8-003
12. Liu S, Zhou G, Xu N, Mai S, Wang Q, Zeng L, et al. Translation and validation of the Chinese version of Brace Questionnaire (BrQ). Translational Pediatrics. 2021; 10(3): 598–603.
13. Deceuninck J, Tirat-Herbert A, Rodriguez Martinez N, Bernard J C. French validation of the Brace Questionnaire (BrQ). Scoliosis Spinal Disord. 2017; 12:18.
14. Gür G, Yakut Y, Grivas T. The Turkish version of the Brace Questionnaire in brace-treated adolescents with idiopathic scoliosis. Prosthetics and Orthotics International. 2018; 42(2):129–35.
15. Kinel E, Kotwicki T, Podolska A, Białek M, Stryła, W. Polish validation of Brace Questionnaire. Eur Spine J. 2012; 21(8):1603–8.
16. Rezaee S, Jalali M, Babaee T, Kamali M. Reliability and concurrent validity of a culturally adapted persian version of the brace questionnaire in adolescents with idiopathic scoliosis. Spine Deformity. 2019; 7(4):553–8.
17. Lim JM, Goh TS, Shin JK, Kim DS, Lee CS, Lee JS. Validation of the Korean version of the Brace Questionnaire. British Journal of Neurosurgery. 2018; 32(6): 678–81.
18. Asher M, Lai SM, Burton D, Manna B. The Reliability and Concurrent Validity of the Scoliosis Research Society-22 Patient Questionnaire for Idiopathic Scoliosis. SPINE. 2003; 28(1) .
19. Haidar RK, Kassak K, Masrouha K, Ibrahim K, Mhaidli H. Reliability and validity of an adapted Arabic version of the scoliosis research society-22r questionnaire. Spine. 2015; 40(17): E971–7.
20. Wild D, Grove A, Martin M, Eremenco S, McElroy S, Verjee-Lorenz A, et al. Principles of good practice for the translation and cultural adaptation process for patient- reported outcomes (PRO) measures: report of the ISPOR Task Force for translation and cultural adaptation. Value Health. 2005; 8(2):94–104.
21. Nunnally JC, Bernstein IH. Psychometric theory. (3rd ed. New York: McGraw-Hill; 1994.
22. Norman G, Streiner D. Biostatistics: The bare essentials. Toronto: Mosby; 1994.
23. Deyo RA, Diehr P, Patrick DL. Reproducibility and responsiveness of health status measures. Statistics and strategies for evaluation. Control Clin Trials. 1991; 12(Suppl.4):S142–58.
24. Wang H, Tetteroo D, Arts J J C, Markopoulos P, Ito K. Quality of life of adolescent idiopathic scoliosis patients under brace treatment: a brief communication of literature review. Quality of Life Research. 2021; 30(3):703–11.
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Sarah M. Ali, Nadia A. Fayaz, Sara M. Samir. Cross-cultural adaptation and validation of the arabic version of the brace questionnaire used for the treatment of adolescents with idiopathic scoliosis. Ann Clin Anal Med 2022;13(5):516-520
Association of root canal treatment and tooth extraction: A clinical audit
Hassan Mohammad 1, Haleema Sadiya 2, Wajid Ali Chatha 1, Saad El Shafey 1
1 Department of Anatomy, College of Medicine, 2 Department of Dentistry, Northern Border University, Arar, Kingdom of Saudi Arabia
DOI: 10.4328/ACAM.21004 Received: 2021-12-16 Accepted: 2022-01-19 Published Online: 2022-01-27 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):521-523
Corresponding Author: Hassan Mohammad, Department of Anatomy, College of Medicine, Northern Border University, Arar, Kingdom of Saudi Arabia. E-mail: email@example.com P: +96 653 864 08 14 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5456-0888
Aim: Dental caries is the most prevalent chronic disease in early childhood in most communities worldwide. Several studies have been conducted and documented a high prevalence of early childhood caries (ECC). The present study aimed to determine the association of root canal treatment that may or not lead to tooth extraction.
Material and Methods: A descriptive study was conducted among 156 patients in the Dental clinic of the university health center. Caries experience was measured using the World Health Organization caries criteria. Descriptive statistics and SPSS were used to calculate the qualitative parameters.
Results: The mean age of patients was 27 years. The statistical analysis revealed that dental caries was significantly associated with inadequate oral hygiene. Adequately done root canal treatment may save the tooth from extraction.
Discussion: The high rate of dental caries and tooth extraction recorded in this study strongly emphasized the necessity of community-based preventive programs and professional dental care.
Keywords: Root Canal, Caries, Pulp, RCT, Tooth Extraction
Oral health has not improved over the last 25 years, according to the Global Burden of Disease 2015 study , the age-standardized prevalence rate of untreated caries in primary teeth was 7.8% (573 million children), and 126 million children worldwide had incident cases of caries in primary teeth in 2015. According to the WHO, dental caries is still the most common chronic disease in early childhood in a number of communities around the world, affecting both the child and family’s quality of life and is considered a public health issue [2, 3]. Individuals are susceptible to tooth decay and injury throughout their lives. If RCT is not performed properly after the dental pulp has become irrevocably implicated in infection and necrosis, this can lead to apical bone loss [4-6].
Caries is one of the most common chronic diseases in the globe. Untreated caries affects approximately 2.4 billion individuals, or 35% of the world’s population. Despite massive public resources devoted to caries prevention, the global prevalence of untreated caries has remained stable in recent decades . Untreated caries can be extremely costly in terms of both time and money. Every year, hundreds of billions of dollars are lost as a result . Caries prevention is an important public health aim because of the high prevalence linked with a hefty disease burden. Surgical problems, implant loss, bone loss, peri-implant soft tissue, mechanical, and esthetic/phonetic issues are all possible issues with dental implants. Surgical problems are the most dangerous for patients, as they might result in hemorrhage, neurosensory problems, neighboring tooth destruction, and so on . One of the most difficult aspects of caries therapy is the treatment of deep carious lesions that approach the pulp. Total caries removal may result in tooth discomfort, pulp exposure, or the necessity for pulpotomy, pulpectomy, or indirect pulp capping [10, 11].
Conservative and ultraconservative caries care methods, such as stepwise caries excavation and partial caries removal, have been proposed in the literature in an attempt to reduce these problems [12, 13]. The most common surgical dental operation is tooth extraction, and the majority of antibiotics recommended in dentistry are given following tooth extraction . Removal of an impacted lower third molar is the most intrusive treatment and can result in complications such as swelling, trismus, bleeding, and infection .
Material and Methods
Ethical approval was obtained from the ethics committee of the University for the planned study. The patients’ data for this retrospective study was collected from the University health center’s dental clinic. Data were collected for a period from November 2019 to August 2020 from the health center’s record room after obtaining permission. The parameters collected included the patient’s age, gender, tooth, which was removed, and tooth that received root canal treatment. Caries experience was measured using the World Health Organization caries criteria. The investigators evaluated restorations radiographically as well as clinically. Descriptive data were analyzed using SPSS software. The percentage/frequency were calculated for the parameters.
The study population consisted of 156 patients aged 4 to 58 years with a mean age of 27 years. The statistical analysis revealed that dental caries was significantly associated with inadequate oral hygiene. The results provided strong evidence for the advisability of leaving behind infected dentin, the removal of which would put the pulp at risk of exposure. However, the significant association of root canal treatment and tooth extraction was found to be stronger among females. Individuals with worse perceptions of their oral health were more likely to report negative impacts fairly/very often, regardless of their gender. The association between impact prevalence and clinical oral health status measures was fairly comparable. However, there were some differences, particularly with respect to the impact of dental caries experience.
The removal of bacteria from diseased root canals and the prevention of subsequent infection are both critical to the success of endodontic treatment. Endodontic failure and disease persistence are frequently caused by an inability to identify and reach affected regions. Dental caries, periodontal disease experience and tooth loss are associated with functional and psychosocial impacts among males and females.
A pathological condition, ‘External root resorption’ can result from a variety of mechanical or chemical stressors, including infection, pressure, trauma, or orthodontic tooth movement. Although radiography is the most common way to identify root resorption, clinical signs such as pain, edema, and tooth mobility can also be used to diagnose it. Treatment options can vary by case and try to address the source of resorption, while also assisting in the regeneration of the resorptive lesion. It can jeopardize a tooth’s longevity to the point where it may need to be extracted early. As a result, it is critical to get a diagnosis and treatment as soon as possible.
In RCT, an inflammatory or infected pulp is removed, and the inside of the tooth is cleaned, sanitized, filled, and then sealed with a restorative substance. Although the treatment has a high success rate, persistent symptoms or infection recurrence can happen in 10% to 15% of cases . In a comprehensive review, tooth survival between two and ten years after initial root canal therapy was found to be between 86 and 93% . A second root canal treatment (Root canal Re-treatment) is indicated in many cases of infection or symptom recurrence. Apicoectomy is a technique in which the root tip, or apex is removed together with the contaminated tissue, and then a root end filling (retrofilling) is put to seal the area when root canal re-treatment fails (Availableat: http://www.colgateprofessional.com/patient-education/articles/apicoectomy). In patients under 45 years old, upper anterior or premolar teeth, cases without preoperative pain, lesions without periodontal involvement, lack of perforating lesions, and teeth with only one periapical surgery are all related with a better chance of apicoectomy success . In the event that the apicoectomy fails, the tooth may have to be extracted. Endodontic microorganisms and their metabolites must be removed during root canal treatment because they may compromise the periodontium’s integrity. Sinus tracts that extend to the gingival sulcus or furcation area can heal with adequate endodontic therapy. Endodontic treatment alone is frequently insufficient to heal the combined lesion, and adequate periodontal treatment is required to affect secondary periodontal disease. Wrong tooth extraction is a regular problem among dentists and dental specialists, but it can be avoided.
Caries problems necessitate the extraction of the majority of the teeth. After caries, the prevalence of root broken extracted teeth comes as a major complication. Root canal therapy and retreatment, occlusal stresses, inappropriate prosthetic treatment, and parafunctional habits are all linked to root fractures. Because of the complexity of these lesions, it is critical to get a correct diagnosis in order to get the best therapy and outcomes. As a result, a thorough extraoral and intraoral examination, periapical and Cone beam computed tomography (CBCT) radiographic imaging, periodontal analysis, and the use of additional tests to assess tooth viability should all be carried out.
This review has presented the different modalities to reduce inflammatory complications after tooth extractions. Despite the fact that the number of patients requiring tooth extractions was substantially larger in the dental clinic, the number of tooth extractions was practically the same. In practice, dentists must have sufficient knowledge of the origin, categorization, diagnosis, and treatment techniques of endodontic-periodontal illness in order to increase treatment effectiveness.
Before settling on a final treatment plan, dentist can use the full investigation to help them make a proper diagnosis. The treatment outcomes in this study revealed that primary endodontic lesions can be controlled without surgical intervention by root canal treatment alone, if the dentist has a sufficient understanding of the diagnosis, treatment techniques, and treatment intervals. In brief, prompt and proper treatment of such lesions can help avoid subsequent consequences like tooth loss.
Scientiﬁc Responsibility Statement
Animal and human rights statement
Conflict of interest
1. Kassebaum NJ, Smith AGC, Bernabé E, Fleming TD, Reynolds AE, Vos T, et al. GBD 2015 Oral Health Collaborators. Global, Regional, and National Prevalence, Incidence, and Disability-Adjusted Life Years for Oral Conditions for 195 Countries, 1990-2015: A Systematic Analysis for the Global Burden of Diseases, Injuries, and Risk Factors. J Dent Res. 2017; 96(4):380-7.
2. Corrêa-Faria P, Paixão-Gonçalves S, Paiva SM, Pordeus IA. Incidence of dental caries in primary dentition and risk factors: a longitudinal study. Braz Oral Res. 2016; (5): 20;30.
3. Alkhtib A, Ghanim A, Temple-Smith M, Messer LB, Pirotta M, Morgan M. Prevalence of early childhood caries and enamel defects in four and five-year old Qatari preschool children. BMC Oral Health. 2016; 16(1):73.
4. Selwitz RH, Ismail AI, Pitts NB. Dental caries. Lancet. 2007; 369(9555):51-9.
5. Saoud TMA, Ricucci D, Lin LM, Gaengler P. Regeneration and Repair in Endodontics-A Special Issue of the Regenerative Endodontics-A New Era in Clinical Endodontics. Dent J (Basel). 2016; 4(1):3.
6. Celik EU, Yapar AG, Ateş M, Sen BH. Bacterial microleakage of barrier materials in obturated root canals. J Endod. 2006;32(11):1074-6.
7. Kassebaum NJ, Bernabé E, Dahiya M, Bhandari B, Murray CJ, Marcenes W. Global burden of untreated caries: a systematic review and metaregression. J Dent Res. 2015;94(5):650-8.
8. Listl S, Galloway J, Mossey PA, Marcenes W. Global Economic Impact of Dental Diseases. J Dent Res. 2015;94(10):1355-61.
9. Goodacre CJ, Bernal G, Rungcharassaeng K, Kan JY. Clinical complications with implants and implant prostheses. J Prosthet Dent. 2003;90(2):121-32.
10. Oen KT, Thompson VP, Vena D, Caufield PW, Curro F, Dasanayake A, et al. Attitudes and expectations of treating deep caries: a PEARL Network survey. Gen Dent. 2007; 55(3):197-203.
11. Thompson V, Craig RG, Curro FA, Green WS, Ship JA. Treatment of deep carious lesions by complete excavation or partial removal: a critical review. J Am Dent Assoc. 2008;139(6):705-12.
12. Ricketts DN, Kidd EA, Innes N, Clarkson J. Complete or ultraconservative removal of decayed tissue in unfilled teeth. Cochrane Database Syst Rev. 2006;(3). DOI: 10.1002/14651858.CD003808.pub2.
13. Kidd EA. Clinical threshold for carious tissue removal. Dent Clin North Am. 2010;54(3):541-9.
14. Kim H, Kim MK, Choi H. Factors affecting the rate of antibiotic prescription in dental practices. Journal of Korean Academy of Oral Health 2017;41:28-35.
15. Arteagoitia I, Diez A, Barbier L, Santamaría G, Santamaría J. Efficacy of amoxicillin/clavulanic acid in preventing infectious and inflammatory complications following impacted mandibular third molar extraction. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100(1):11-8.
16. Lieblich SE. Endodontic surgery. Dent Clin North Am. 2012;56(1):121-32.
17. Ng YL, Mann V, Gulabivala K. Tooth survival following non-surgical root canal treatment: a systematic review of the literature. Int Endod J. 2010;43(3):171-89.
18. Serrano-Giménez M, Sánchez-Torres A, Gay-Escoda C. Prognostic factors on periapical surgery: A systematic review. Med Oral Patol Oral Cir Bucal. 2015;20(6):715-22.
Download attachments: 10.4328:ACAM.21004
Hassan Mohammad, Haleema Sadiya, Wajid Ali Chatha, Saad El Shafey.Association of root canal treatment and tooth extraction: A clinical audit. Ann Clin Anal Med 2022;13(5):521-523
Gastric residual volume management in a neurosurgery intensive care unit: A randomized controlled trial
Burcu Totur Dikmen 1, Meryem Yavuz van Giersbergen 2, Taşkın Yurtseven 3
1 Department of Surgical Nursing, Faculty of Nursing, Near East University, Nicosia, Cyprus,2 Department of Surgical Nursing, Faculty of Nursing, Ege University, İzmir, Turkey, 3 Department of Neurosurgery, Faculty of Medicine, Ege University, İzmir, Turkey
DOI: 10.4328/ACAM.21008 Received: 2021-12-20 Accepted: 2022-01-21 Published Online: 2022-03-08 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):524-529
Corresponding Author: Burcu Totur Dikmen, Department of Surgical Nursing, Faculty of Nursing, Near East University, Near East Boulevard, 99138, Nicosia, TRNC Mersin 10, Turkey. E-mail: firstname.lastname@example.org P: +90 392 223 64 64 Corresponding Author ORCID ID: https://orcid.org/0000-0002-4221-6112
Aim: This randomized controlled trial aimed to analyze the impact of discarding or returning the aspirated gastric residual volume (GRV) on biochemical values in adult patients.
Material and Methods: The sample of the study consisted of three groups who have just begun to be fed enterally via a nasogastric tube. The first, second and control groups each included 30 patients. In the first group, GRV aspirated from the patients was given back to the patients, while in the second group, GRV was discarded. The third group was the control group, GRV was not checked.
Results: Between the three groups there was no statistically significant difference in GRV, the blood levels of aspartate amino transferase (AST), alanine amino transferase (ALT), C-reactive protein (CRP), prealbumin, transferrin, cholesterol, hemoglobin, hematocrit, urea, creatinine, electrolyte and glucose (p>.05), but the levels of triglycerides and phosphorus varied significantly among the three groups (p<.05).
Discussion: There is no difference was found between the groups of returning, discarding the aspirated GRV and control group, in terms of patients’ AST, ALT, CRP, hemoglobin, hematocrit, transferrin, prealbumin, total cholesterol, urea, creatinine, sodium, potassium, chlorine, calcium, magnesium and glucose values, but differences were found between the groups in triglyceride and phosphorus values.
Keywords: Gastric Residual Volume, Intensive Care Units, Nursing, Neurosurgery
Enteral nutrition is being increasingly used with the development of technology, enteral feeding formulas and ingredients [1-3]. However, lung aspiration, tube blockage, intolerance, regurgitation, vomiting, diarrhea and esophagitis are frequently seen complications . In order to reduce to a minimum, the possible complications of enteral nutrition and to evaluate gastrointestinal function, nurses perform gastric residual volume (GRV) checking [5,6,7].
In clinical practice, after the GRV is measured, some nurses discard the gastric contents, while others return it partially or completely to the patient [8,9].
Advantages and disadvantages of GRV management
There are studies, which support the return of the GRV aspirated from the patient because it contributes to the maintenance of the gastric content and the liquid electrolyte balance [10,11]. However, other studies recommend that the GRV aspirated from the patients be discarded in order to avoid complications such as tube contamination, the risk of infection and blockage, and to prevent the accumulation of volume related to gastric emptying [12,13]. There is no consensus in the literature as the frequency of GRV monitoring, minimum and maximum GRV [4,9,10,11], what constitutes a high GRV with values ranging from 50 ml to 500ml, whether to return the aspirated GRV to the patient or to discard it, and the effect on biochemical values [14,15].
The present study was conducted to analyze the impact of discarding or returning the aspirated GRV on biochemical values in adult patients.
Material and Methods
Design and Sample
This prospective, randomized controlled trial was conducted on 90 patients who were admitted to the Neurosurgery Intensive Care Unit (ICU) of a University Faculty of Medicine in western Turkey.
The data collection was performed between October 2013-July 2014. The sample of the study consisted of three groups. The first and second groups provided basic data, while the control group formed a necessary step in the randomized controlled study. The groups included 30 patients each, who had just begun enteral feeding via a nasogastric tube, who had a planned stay in the ICU of at least seven days, who had achieved hemodynamic stabilization, and who conformed to the inclusion criteria of the research. The inclusion criteria of the research were patients aged 18 or over, fed enterally via a nasogastric tube, no head trauma, no diarrhea, no mechanical intestinal obstruction, no paralytic ileus, no generalized peritonitis, no acute pancreatitis, no inflammatory bowel disease, no gastrointestinal bleeding, no short intestine syndrome, no morbid obesity, no diabetes mellitus, not having undergone abdominal surgery, not having undergone abdominal radiotherapy within the previous six weeks and voluntary participation in the study.
In order to conduct the study, written approval was obtained from the Clinical Research Ethics Committee of the University Faculty of Medicine (reference date and number: 11.04.2012; 12-3/4), the Scientific Research Projects Commission of the University Faculty of Medicine Dean’s Office (Reference date and number: 16.05.2013; 42490658-417-7902), a Neurosurgery Department of the University Faculty of Medicine (Reference date and number: 26.06.2013; 47700900-700), the Project and Special Services Coordination Centre of the Dean’s Office of the University Medicine Faculty (Reference date and number: 08.10.2013; 589-14758), and from the patients in a Department of Neurosurgery ICU, in the case of conscious patients from the patients themselves and in the case of unconscious patients from their close relatives.
A stratified randomization technique was used in this study. Patients were stratified and matched based on age and gender. Randomization occurred anytime from ICU admission, after assessment by the anesthesiologist, the ICU physician and the clinical nurse specialists that the patient was likely to receive enteral nutrition for seven or more days.
Four hundred fifty-one patients were assessed for eligibility and 283 patients were randomized. The trial ended when the sample size (30 patients for each group) was reached. The CONSORT (Consolidated Standards of Reporting Trials) flow diagram records the reasons for withdrawals. One hundred ninety-three patients were dropped out of the trial, because they were hospitalized less than seven days or they were exitus (Figure 1). Data Collection Instruments
A patient monitoring form developed by the researchers based on the literature was used as a data collection instrument [2,4,6,9,10,15,16,17]. The form recorded the patients’ age, gender, diagnosis, Glasgow Coma Scale (GCS), descriptive characteristics such as weight and height, Nutritional Risk Screening 2002 (NRS 2002) and Simplified Acute Physiology Score II (SAPS II) scores, calories to be taken daily, the use of medications, basic vital signs, the amount of nutrients taken, daily fluid balance, amount of GRV aspirated, amount of GRV returned or discarded, complications of the gastrointestinal system, and the results of biochemical blood analysis, of aspartate aminotransferase (AST), alanine aminotransferase (ALT), C-reactive protein (CRP), prealbumin, total cholesterol, transferrin, triglyceride, hemoglobin, hematocrit, urea, creatinine, potassium, calcium, magnesium, chlorine, phosphorus and glucose.
After the randomization procedure, evaluations were performed, and the total daily calories to be taken by patients were determined using the Schofield Formula.
In terms of nutrients, a nutritionally complete, fiber-enriched and ready-to-use enteral tube feeding mixture was used, which provided full and balanced nutrition. These mixtures were given in a regular manner to the patients using enteral feeding sets with calibrated feeding pumps and 14 Fr polyurethane nasogastric feeding tubes.
Feeding was started for patients in the first, second and control groups at 20mL/h, and nutrients given were steadily increased until the targeted number of calories was reached. When this target was reached, checking of the GRV was started in the patients of first and second groups. For the control group patients, the enteral feeding protocol of the ICU where the study was conducted was taken as a base, and GRV checking was not performed.
The GRV checking was performed at 12:00, 18:00, 00:00 and 06:00 in accordance with the steps of the GRV checking operation. Before and after each GRV check of patients in groups one and two, and in patients in the control group after an interval of five minutes, vital signs were recorded. Since gastric residual volume was not checked in the control group, vital signs were measured five minutes after the measurement to obtain the comparison data.
To make it easier to aspirate the gastric contents of patients in groups one and two, 30 mL of air was put into the stomach. After this, a 60 mL syringe was used to check the GRV. When no more gastric content could be taken, the stomach was regarded as empty. During the check of GRV, no position change was performed [2,10]. After the GRV check in groups one and two, and after an interval of six hours in the control group, 30 mL of tap water was given to prevent the nasogastric tube from blocking .
In checking the GRV of patients in the first group, it was planned to give back at most 500 mL of the aspirated contents . All aspirated contents of patients in the second group were discarded, and the GRV of patients in the control group was not checked. The venous blood samples were taken from patients on the first, fourth and seventh day of the study at 06:00 to evaluate the values of biochemical testing (Table 1).
Data obtained from study participants were analyzed using the Statistical Package for the Social Sciences (SPSS) for Windows 20.0 (IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp.). Patient and cohort characteristics were described using mean and standard deviation (SD) or median and interquartile range (IR), as appropriate. Age, gender, diagnosis, calories received, vital signs, scores of NRS 2002 and SAPS II, prokinetic agent used and biochemical blood analysis were compared between the first, second and control groups.
Numeric and percentage distributions of the data were examined. Conformity with the numeric data to a normal distribution was evaluated with the Shapiro-Wilk Test. The One-Way Anova Test and the Bonferroni Test were applied to numeric data with a normal distribution. The Kruskal-Wallis Test, the Wilcoxon-Rank Test and the Mann-Whitney Test were applied to numeric data that did not show normal distribution. The Chi-Square Test was applied to non-numeric data. Statistical significance was taken as 95%, and the confidence interval as p<.05.
General Characteristics of Patients
Male patients accounted for 50% of all groups. The mean age of the first group patients was 44.47±18.36 (Min: 18, Max: 83) years, in the second group- 43.77±16.99 (Min: 18, Max: 78) years, and in the control group- 40.77±16.44 (Min:21, Max:77) years. The majority of the patients included in this study had brain tumors. It was determined that all patients were using H2 receptor antagonists and that 66.7% of them were using prokinetic agent.
No statistically significant difference was found between patients’ age, gender, diagnosis, GCS, SAPS II, NRS 2002 mean scores, amount of calories received, and use of H2 receptor antagonists or prokinetic agent (Table 2).
Results of Gastric Residual volume, Vital Signs, and Biochemical Blood Values
Median values of GRV of patients on days when biochemical blood tests were performed as follows: 1st day, first group: 19.00-11.50 (Min:5, Max:58) and second group: 20.75-19.31 (Min:3, Max:49) (U=393.50, p=.40), 4th day, first group: 90.50-98.75 (Min:26, Max:259) and second group: 97.50-113.00 (Min:17-Max:291) (U=416.00, p=.615), 7th day, first group: 53.00-62.25 (Min:9, Max:205) and second group: 42.50-63.25 (Min:9, Max:190) (U=396.00, p=.42). No statistically significant difference was found between the groups in amounts of GRV when biochemical tests were performed (Table 3).
Statistically no significant difference was found between the groups in systolic blood pressure and pulse rate before, after the GRV checking and control group (p>.05). A statistically significant difference was found between the groups in diastolic blood pressure, and body temperature evaluation before, after the GRV checking and control group (p<.05).
As seen in Figures 2 and 3, there was no difference between the groups of patients in the study in terms of hemoglobin, hematocrit, transferrin, prealbumin, total cholesterol, urea, creatinine, sodium, potassium, chlorine, calcium, magnesium and glucose values (p>.05), but a difference was found between the groups in triglyceride and phosphorus values (p<.05). On the other hand, no statistically significant difference was found between the groups in gastrointestinal system complications such as vomiting, diarrhea, abdominal distension or constipation (p>.05).
Monitoring GRV is one of the most traditional, widely accepted and common practices in assessing the tolerance of a patient to enteral nutrition and preventing pulmonary aspiration in nursing practices in the ICUs’ [13,18]. A national survey among the American Association of Critical Care Nurses (AACN) indicated that more than 97% of nurses reported measuring GRV . However, in recent guidelines and studies, it is not recommended as a routine care [15,16,19].
Studies have shown different results in GRV measurements with enteral feeding tubes of different diameters; with wide diameter feeding tubes, there was a greater development of reflux, while with narrow diameter tubes, blockage occurred more frequently [6, 20, 21,22].
In a study in which gastric volume measurements were performed 890 times on 137 patients, it was reported that there was no difference between the GRV amounts measured with 14 Fr and 18 Fr nasogastric tubes, but that the GRV measured with a 10 Fr nasogastric tube was approximately half of that of other tubes . In a study performed with 40 enteral feeding patients in an ICU, the mean GRV of patients in whom a 10 Fr nasogastric tube was used was found to be 108±35 mL, while when a 16 Fr tube was used it was 137±20 mL . The GRV amount specified in the study is quite high compared to the present study. All patients included in the study were fed enterally with 14 Fr polyurethane nasogastric tubes, and aspiration of the GRV was performed using 60 mL syringes. Patients’ head height was maintained at 30-45°. Care of the nasogastric tubes was conducted in accordance with the literature [6,20,21]. In this way, standardization was provided for all patients, and the effects of the use of different sizes of nasogastric tubes and aspiration syringes and different head angles were reduced to a minimum.
In the studies of gastric residue and complications in ICU patients who were being fed enterally with standard products with or without fibers, it was found that throughout the days of monitoring, the amounts of GRV in the groups were similar [23,24]. In our study, patients were fed enterally with fiber products, and no difference was found between the amounts of the GRV in the first and second groups.
According to the studies, there was no statistically significant difference in vital signs and oxygen saturation before and after procedure in the 1st and 7th days [10,23]. In the present study, it was found that gastric residual volume measurement had no effect on vital signs. Our findings were similar to other studies.
Randomized controlled trials have indicated that the return of gastric residues provided more benefits for fluid and electrolyte balance, but did not increase gastric intolerance [4,10,23,24]. Although there is no consensus on how much gastric residual volume should be returned [16,25], there are studies indicating that up to 250 ml can be returned [10,23].
In the other studies, no difference was found in the development of complications when GRV was returned or discarded [4,24], except that an increase was seen in sodium and chlorine values and a decline in potassium values .
In Juvé-Udina et al’s  study on the impact of returning or discarding aspirated GRV on patients’ liquid electrolyte levels, patients were monitored for at least 48 hours, and no difference was reported between the groups in terms of sodium, potassium and protein values, but blood sugar values were higher in the group in which GRV was returned .
In some studies, returning and discarding gastric residual volume in patients fed enterally, according to the days, it was reported that there was no difference in the values of prealbumin, glucose, cholesterol, AST, ALT, creatinine, sodium, potassium, chlorine, magnesium or calcium [10,23,24]. The biochemical values in our study were similar with the literature. However, triglyceride values in both groups were lower on the 1st day than on the 7th day, and phosphorus values were higher than on the 1st day.
In conclusion of the present study, no difference was found between the groups in terms of patients’ AST, ALT, CRP, hemoglobin, hematocrit, transferrin, prealbumin, total cholesterol, urea, creatinine, sodium, potassium, chlorine, calcium, magnesium and glucose values, but differences were found between the groups in triglyceride and phosphorus values.
In recent guidelines and studies of enteral feeding, routine measurement of GRV is not recommended. According to our study results, our recommendations regarding this situation are as follows:
• It is possible to remove routine GRV measurement from the standard nursing care in the ICU.
• If there is a requirement for measuring GRV, to reduce the incidence of gastric dysmotility complications such as regurgitation, vomiting, aspiration, and ventilator-associated pneumonia (VAP) in patients, discarding of GRV may be recommended.
• Attention should be paid to the amount of returning GRV.
• Returning GRV could lead to better optimization of enteral feeding to achieve caloric targets and biochemical values balance.
The authors thank the ICU patients and their families for their participation in this study, as well as Hatice Uluer for the statistic analysis advice, Alec Rylands for the proofreading of the manuscript.
Scientiﬁc Responsibility Statement
Animal and human rights statement
Funding: This study was funded by the Scientific Research Project Evaluation Committee of Ege University Medicine Faculty (project number: 2013-TIP-046).
Conflict of interest
1. Meijers JM, Tan F, Schols JM, Halfens RJ. Nutritional care; do process and structure indicators influence malnutrition prevalence over time? Clin Nutr. 2014;33(3):459-65.
2. Moreira TV, McQuiggan M. Methods for the assessment of gastric emptying in critically ill, enterally fed adults. Nutr Clin Pract. 2009;24(2):261-73.
3. Koekkoek KWAC, van Zanten ARH. Nutrition in the critically ill patient. Curr Opin Anaesthesiol. 2017;30(2):178-85.
4. Booker KJ, Niedringhaus L, Eden B, Arnold JS. Comparison of 2 methods of managing gastric residual volumes from feeding tubes. Am J Crit Care. 2000;9(5):318-24.
5. Bruni A, Garofalo E, Grande L, Auletta G, Cubello D, Greco M, et al. Nursing issues in enteral nutrition during prone position in critically ill patients: A systematic review of the literature. Intensive Crit Care Nurs. 2020;60:102899.
6. Metheny NA, Mills AC, Stewart BJ. Monitoring for intolerance to gastric tube feedings: A national survey. Am J Crit Care. 2012;21(2):e33-40.
7. Xu LC, Huang XJ, Lin BX, Zheng JY, Zhu HH. Clinical nurses’ nasogastric feeding practices in adults: A multicenter cross-sectional survey in China. J Int Med Res. 2020;48(4):300060520920051.
8. Ichimaru S. Methods of enteral nutrition administration in critically ill patients: Continuous, cyclic, ıntermittent, and bolus feeding. Nutr Clin Pract. 2018;33(6):790-5.
9. Zaloga G.P. The myth of gastric residual volume. Crit Care Med. 2005;33(2):449-50.
10. Juvé-Udina ME, Valls-Miró C, Carreño-Granero A, Martinez-Estalella G, Monterde-Prat D, Domingo-Felici CM. To return or to discard? Randomised trial on gastric residual volume management. Intensive Crit Care Nurs. 2009;25(5):258-67.
11. Metheny NA, Stewart J, Nuetzel G, Oliver D, Clouse RE. Effect of feeding-tube properties on residual volume measurements in tube-fed patients. JPEN J Parenter Enteral Nutr. 2005;29(3):192-7.
12. Matlow A, Jacobson M, Wray R, Goldman C, Streitenberger L, Freeman R, et al. Enteral tube hub as a reservoir for transmissible enteric bacteria. Am J Infect Control. 2006;34(3):131-3.
13. Wang Z, Ding W, Fang Q, Zhang L, Liu X, Tang Z. Effects of not monitoring gastric residual volume in intensive care patients: A meta-analysis. Int J Nurs Stud. 2019;91:86-93.
14. Momenfar F, Abdi A, Salari N, Soroush A, Hemmatpour B. Studying the effect of abdominal massage on the gastric residual volume in patients hospitalized in intensive care units. J Intensive Care. 2018;6:47.
15. Wiese AN, Rogers MJM, Way M, Ballard E. The impact of removing gastric residual volume monitoring and enteral nutrition rate titration in adults receiving mechanical ventilation. Aust Crit Care. 2020;33(2):155-61.
16. Taylor BE, McClave SA, Martindale RG, Warren MM, Johson DR, Braunschweig C, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of critical care medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr. 2016;44(2):390-438.
17. Boullata JI, Carrera AL, Harvey L, Escuro AA, Hudson L, Mays A, et al. ASPEN Safe Practices for Enteral Nutrition Therapy Task Force, American Society for Parenteral and Enteral Nutrition. ASPEN Safe Practices for Enteral Nutrition Therapy. JPEN J Parenter Enteral Nutr. 2017;41(1):15-103.
18. Elke G, Felbinger, TW, Heyland DK. Gastric residual volume in critically ill patients: A dead marker or still alive? Nutr Clin Pract. 2015;30(1):59-71.
19. Bruen T, Rawal S, Tomesko J, Byham-Gray L. Elimination of routine gastric residual volume monitoring improves patient outcomes in adult critically ill patients in a community hospital setting. Nutr Clin Pract. 2020;35(3):522-32.
20. Williams TA, Leslie G, Mills L, Leen T, Davies H, Hendron D, et al. Frequency of aspirating gastric tubes for patients receiving enteral nutrition in the ICU: A randomized controlled trial. JPEN J Parenter Enteral Nutr. 2014;38(7):809-16.
21. Bartlett Ellis RJ, Fuehne J. Examination of accuracy in the assessment of gastric residual volume: A simulated, controlled study. JPEN J Parenter Enteral Nutr. 2015;39(4):434-40.
22. Blumenstein I, Shastri YM, Stein J. Gastroenteric tube feeding: Techniques, problems and solutions. World J Gastroenterol. 2014;20(26):8505-24.
23. Behairy AS, El-Sedawy DSE. Effect of returning versus discarding gastric aspirate on the occurrence of gastric complications and comfort outcomes on enteral feeding patients. J Nat Sci Res. 2014;4(15):21-9.
24. Yasuda H, Kondo N, Yamamoto R, Asami S, Abe T, Tsujimoto H, et al. Monitoring of gastric residual volume during enteral nutrition. Cochrane Database Syst Rev. 2021;9(9):CD013335.
25. Wen Z, Xie A, Peng M, Bian L, Wei L, Li M. Is discard better than return gastric residual aspirates: A systematic review and meta-analysis. BMC Gastroenterol. 2019;19(1):113.
Download attachments: 10.4328:ACAM.21008
Burcu Totur Dikmen, Meryem Yavuz van Giersbergen, Taşkın Yurtseven.Gastric residual volume management in a neurosurgery intensive care unit: A randomized controlled trial. Ann Clin Anal Med 2022;13(5):524-529
Is it possible to evaluate the hypernatremia with ultrasonographic vena cava parameters?
Dilek Atik 1, Basar Cander 3, Emre Gokcen 2, Ramazan Unal 3, Cesareddin Dikmetas 3,Nuray Kılıc 2
1 Department of Emergency Medicine, Karamanoglu Mehmetbey University, Karaman, 2 Department of Emergency Medicine, Yozgat Bozok University, Yozgat, 3 Department of Emergency Medicine, Health Sciences University, Kanuni Sultan Suleyman Research and Training Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21012 Received: 2021-12-20 Accepted: 2022-01-21 Published Online: 2022-01-25 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):530-534
Corresponding Author: Dilek Atik, Acil Tıp Ana Bilim Dali, Karamanoglu Mehmetbey Universitesi, İbrahim Öktem Cd., 70100, Karaman, Turkey. E-mail: email@example.com P: +90 354 212 44 42 F: +90 354 217 10 72 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3270-8711
Aim: In this study, we aimed to evaluate the relationship of inferior vena cava (IVC) respiratory variation with hypernatremia due to fluid response, and to evaluate its applicability in determining SNa levels in these patients.
Material and Methods: Geriatric patients with dehydration and hypernatremia were included in the study. In the inferior vena cava (IVC) measurement, the diameter of the IVC was measured for each patient by different emergency physicians using experienced and trained sonography. This prospective, cross-sectional and observational study was conducted as a double centre study from January to July 2020.
Results: The evaluation was performed on 103 patients. Of the 103 dehydrated patients included in the study, 78 (75.7%) had mild hypernatremia (Serum Sodium (SNa)145-154 mEq/L), and 25 (24.3%) patients had severe hypernatremia (SNa>155 mEq/L). When patients with hypernatremia were divided into two groups as mild and severe, the diagnostic efficiency of the VCI diameter, IVCCI parameters and the ROC curve and AUC, cut-off, sensitivity and specificity were discriminately analyzed to guide the patient’s condition in the patient follow-up. For the VCI diameter parameter, the AUC, cut-off, sensitivity and specificity were 0.893 %, 14.7%, 65.2% and 95.2%, respectively. IVCCI AUC, cut-off, sensitivity, and specificity were 0.756, 56.19, 73.9% and 70%, respectively.
Discussion: IVC and IVCCI can be used to identify patients with dehydration-induced hypernatremia and determine disease severity, and moreover, they can be used as a useful tool in the assessment of adequate fluid volume replacement in the follow-up of these patients.
Keywords: Inferior Vena Cava (IVC), IVCCI; Dehydration, Geriatric Patients, Ultrasonography, Hypernatremia
Dehydration is a clinically important health problem in elderly . People over 65, whom we called the geriatric age group in this study, tend to develop hypernatremia due to age-related physiological changes, such as decreased thirst, impaired ability to concentrate urine, and decreased total body water. In the literature, the prevalence of hypernatremia is reported to be 3.7%, especially in the elderly population . Hypernatremia can be grouped in two ways. The serum sodium value, which is called mild hypernatremia and seen in approximately 1-3% of hospitalized patients, is above 145 mmol/L [1,3]. Although severe hypernatremia is seen less frequently, it is defined as Serum Sodium (SNa) being above 155 mmol/L. Mortality rates have increased up to 37%-55%, especially in patients with hypernatremia . It is known that invasive and non-invasive measurements are used in the volume assessment of patients [5,6]. In some studies in the literature, it has been reported that the VCI USG measurement is useful in evaluating the volume status, especially in hypotensive and hypovolemic patients . The importance of USG use in the paediatric age group, especially regarding dehydration, is emphasized [8,9]. However, there is no study evaluating the relationship between vena cava parameters, especially in patients with geriatric hypernatremia, which is the subject of our study.
In this study, we aimed to evaluate the relationship of inferior vena cava (IVC) respiratory variation with hypernatremia due to fluid response, and to evaluate its applicability in determining SNa levels in these patients.
Material and Methods
This diagnostic test evaluation was carried out in two centres between 01.01.2020-01.07.2020. This study is a prospective, cross-sectional and observational study, including geriatric patients with signs of dehydration and hypernatremia. The patients were included in the study consecutively between the dates of the study. A healthy control group was also included in the study, provided that it consisted of volunteers. The study was conducted as a double centre study at Yozgat Bozok Üniversitesi Emergency Medicine Clinic and Kanuni Sultan Suleyman Research and Training Hospital Emergency Medicine Clinic. This study was approved by the Ethics Committee of Yozgat Bozok University with the number 2019-10-239.(30.10.2019).
Working Environment and Population
Our target group was geriatric patients with dehydration and hypernatremia. The inclusion criteria are outlined below:
– Patient age above 65
– Physical hydration assessment of patients based on 7 signs of physical dehydration (tachycardia (>100 bpm), low systolic blood pressure (<100 mm Hg), dry mucosa, dry armpits, weak skin turgor, sunken eyes, and long capillary filling time (>2 seconds) was evaluated (13). Patients with these physical characteristics were included in the study.
– An SNa level above 145 mEq/L
Physical examination findings and laboratory evaluations of the patients included in the study were recorded by a separate emergency medicine specialist. In the inferior vena cava (IVC) measurement, the diameter of the IVC was measured for each patient by different emergency physicians using experienced and trained sonography.
The HM70A with Plus ultrasound system (Samsung Medison Co., Ltd, Seoul, Korea) were available at both hospitals and were used to make the necessary measurements during this study. A 1-7 MHz curve probe was used. The IVC diameter was measured between the junction of the hepatic vein-IVC and IVC-right atrium during inspiration. Using a convex probe or sector probe, it was held in the subxiphoid area to show the right armpit, and the entrance of the right atrium and vena cava inferior was found. The IVC diameter was monitored for 30 seconds in M-Mode and the screen was frozen, on which, the diameter of the IVC was measured from the narrowest (IVC min) and widest (IVC max) location. The VCI expands on expiration and narrows on inspiration.
The GPower 3.1 software (Universität Kiel, Kiel, Germany) was used to clarify the adequacy of the sample size in all calculations for this study prior to data collection. Type 1 was determined as 23 persons for every three groups (healthy, control and 2 patient groups) with 0.05 error and an 85% power analysis. We recorded demographic data and basic clinical characteristics of the patients and the healthy group who agreed to participate in the study together with the respiratory variations in the IVC diameter. For statistical analysis, the IBM SPSS Statistics 22 (IBM Inc., Armonk, NY, USA) program was used. When evaluating the data in the study, if it was qualitative, the Chi-Square test was used; and numerical values were expressed as mean ± standard deviation. The Kruskal-Wallis H test was used in statistical evaluations according to the status of the variables that were statistically nonparametric and the correlated variables were categorical (nominal or ordinal) and a numerical independent group. Spearman’s rank correlation method was used in nonparametric data for correlations between data. According to the clinical results, the VCI and CI activities in hypernatremia were evaluated with the Receiver-Operating Characteristics Curve (ROC curve). The results were evaluated for a significance level of p < 0.05.
Between January 1, 2020 and July 1, 2020, a total of 37,210 patients over the age of 65 applied to the emergency services of the two hospitals. Hypernatremia was found in 107 patients with clinical dehydration. Four patients were excluded from the study because they had previously been diagnosed with diabetes insipidus. Of the 103 dehydrated patients included in the study, 78 (75.7%) had mild hypernatremia (Serum Sodium(SNa): 145-154 mEq/L), and 25 (24.3%) patients had severe hypernatremia (SNa > 155 mEq/L). The lowest measured serum sodium was 146 mmol /L and the highest measured serum sodium was 176 mmol /L. The mean age of the patients was 74.6 years (standard deviation, 9.6), 34 (33.3%) of the patients were female and 69 (66.7%) were male.
Table 1 shows the clinical evaluation of the patients’ physical dehydration symptoms. The clinical evaluation consisted of 7 physical signs of dehydration. Compared to the hypernatremia groups, low systolic blood pressure was found to be lower in severe hypernatremia than in the mild hypernatremia group (< .05). Axillary board and capillary filling findings of more than 2 seconds were found to be higher in the severe hypernatremia group compared to the mild hypernatremia group (< .05).
Within the scope of the research, when vital signs, mean arterial pressure (MAP) and the shock index of the groups were evaluated, the pulse and shock index were significantly higher in the severe hypernatremia group as shown in Table 2 (< .05). Systolic blood pressure and MAP were found to be significantly lower in the severe hypernatremia group compared to the mild hypernatremia and control groups (< .05). When the relationship between physiological parameters and hypernatremia levels was evaluated, there was a high level of correlation with systolic blood pressure in a negative direction and a positive direction with the shock index (<.05).
Laboratory parameters due to dehydration were higher in severe hypernatremia than in the control group and mild hypernatremia, and there was a significant difference between the groups (< .05). However, there was no significant difference between the groups in glucose laboratory parameters (> .05). (Table 2).
When the measured IVC and Inferior vena cava collapsibility index (IVCCI) of the groups were evaluated, the mean IVC in the severe hypernatremia group was 14.5 mm, and this difference was found to be significant as shown in Table 2 (< .05), and it was > 50% in severe and mild hypernatremia. IVCCI between groups was significantly higher in severe hypernatremia (< .05). Evaluating the correlation between sodium levels of the groups, IVCCI and IVC showed a negative high-level relationship between the sodium level and the diameter of the IVC (r: -669; p = 0.000). A moderate positive correlation was found between the vena cava collaboration index (IVCCI) and sodium level (r: 0.407; p: 0.028). When the correlation between MAP, IVCCI and VCI diameter was evaluated, a moderate correlation between VCI and mean arterial pressure was found (r: .626; p = 0.000). However, no positive or negative correlation of mean arterial pressure with IVCCI was found (r: 0.092;p: 0.356).
ROC analysis for IVC and IVCCI parameters
The ROC curve and AUC, cut-off, sensitivity and specificity were analyzed to evaluate the diagnostic efficiency of the VCI diameter and IVCCI parameters in hypernatremia patients compared to those with normal sodium levels. Accordingly, the AUC, cut-off, sensitivity and specificity of IVCCI were 0.908, 50.05%, 78,6% and 96.6%, respectively. For the VCI diameter parameter, the AUC,cut-off, sensitivity and specificity were 0.863%, 19.2%, 77.7% and 86.4%, respectively.
When the patients with hypernatremia were divided into two groups as mild and severe, the diagnostic efficiency of the VCI diameter, IVCCI parameters and the ROC curve and AUC, cut-off, sensitivity and specificity were discriminately analyzed to guide the patient’s condition in the patient follow-up. Parameters with AUC <0.6 and P> 0.05, which were not found to be statistically significant, were excluded. For the VCI diameter parameter, the AUC, cut-off, sensitivity and specificity were 0.893 %, 14.7%, 65.2% and 95.2%, respectively. IVCCI AUC, cut-off, sensitivity, and specificity were 0.756, 56.19, 73.9% and 70%, respectively (Table 3) (Figure 1,2).
We investigated the correlation between IVC respiratory variations and hypernatremia values in patients with dehydrated hypernatremia. In addition, we examined whether the IVC diameter and IVCCI parameters of clinicians from the first treatment stage were sufficient to determine the severity of the disease in our patient group. Therefore, we aimed to determine the IVC diameter and IVCCI cut-off values. In this study, cases with IVC over 14.5 mm and a IVCCI above 56.19% were associated with severe hypernatremia.
Hypernatremia due to dehydration in geriatric individuals is a disease associated with significant morbidity and mortality. In addition to investigating the underlying causes of hypernatremia, urgent diagnoses and treatments in particular, reduce the mortality rates of patients . In the studies conducted, an inferior vena cava measurement via an ultrasound, which is used as a predictor of volume status, stands out .
When the physical properties of dehydrated patients are evaluated in our study, among the 7 physical dehydration findings, differences were found in systolic blood pressure, axillary dryness and capillary filling, especially in the severe hypernatremia patient group when compared to the other group. Fortes et al. reported that only systolic blood pressure was an auxiliary parameter among the seven findings in their study . However, in our study, there was a prolongation of capillary filling in addition to systolic blood pressure. We think that in the severe hypernatremia group, the fluid deficit is due to the addition of circulatory disorders as it increases.
In the literature, it is emphasized that the shock index (SI), which combines systolic blood pressure and pulse, is a strong predictor, especially in hypovolemia . In previous studies, the shock index has been reported to be significant, especially in diseases with fluid deficit, hypovolemic shock, and trauma patients with bleeding . It was found in our study that as the intravascular fluid deficit increases, the severity of hypernatremia increases and the SI cut-off value above 1.09 can be considered an important parameter for diagnosis in patients with possible severe hypernatremia. The results of our study showed that shock index data correlated moderately with the diameter of the vena cava. Shock index and ultrasonographic methods are repeatable, and when considered non-invasive, they can provide clinical benefit by providing a dynamic information flow in patient management in addition to the physical examination and laboratory findings.
The inferior vena cava (IVC) is a primary vessel that varies with respiration, blood volume, and right heart function. However, it also reflects the fluid status of the patient [15,16]. Studies in the literature report the use of respiratory variation measurements in the inferior vena cava in conditions such as dehydration, sepsis and hypotension [12,17]. In our study, especially in patients with hypernatremia due to dehydration, as the severity of the disease and fluid deficit increased, the diameter of the vena cava decreased. In our study, a high level of correlation was found between VCI diameter and blood sodium level. In severe hypernatremia, the VCI diameter was 14.5 mm and in mild hypernatremia, it was 18.3 mm. In some studies in the literature, it is reported that VCI, especially with a diameter of less than 2.1 cm, supports the presence of hypovolemia [18,19]. Although the patient group and methodology of these studies are different from our study, our study obtained similar results because hypovolemia occurred in both studies. Hypovolemia is an important clinical entity that often requires rapid diagnosis and treatment in the emergency room. Ultrasonography has an important place in the estimation of intravascular volume in the emergency department. Prediction of sodium balance in patients with ultrasonographic hypovolemia can provide clinicians with a clinical prediction during a patient follow-up.
Due to the widespread use of USG in critically ill patients, the use of IVC and IVCCI instead of CVP, which is a widely used invasive method in the assessment of volume status, is increasing . In the IVCCI measurement evaluated in our study, it was significantly higher in severe hypernatremia and mild hypernatremia compared to the healthy group. In addition, when the correlation with IVCCI hypernatremia was examined, a moderate relationship was found. In a study conducted with septic shock patients in the literature, the correlation between CVP and IVC respiratory variations has been reported, and mortality has high IVCCI and low IVC diameters . Pasquero et al. unlike our study, emphasize that measured VCI and IVCCI are particularly effective in evaluating volume status in patients with hypovolemic hypernatremia . In our study, besides the VCI parameter, the cut-off value of IVCCI is 49.9% in patients with clinical dehydration compared to the normal population, and when the disease severity is evaluated, we think that the presence of IVCCI with more than 56.19% collapsibility will support severe hypernatremia.
This study had some limitations. One of these limitations is that it offers a new application in the current disease. There is a lack of VCI measurement in clinical practice in the patient group we worked with. For these reasons, multi-centre studies with larger populations are needed.
Since the insufficient or excessive correction of blood sodium level affects the prognosis of patients with hypernatremia, correct diagnosis and appropriate treatment are very important. IVC and IVCCI can be used to identify patients with dehydration-induced hypernatremia and determine disease severity, and moreover, they can be used as a useful tool in the assessment of adequate fluid volume replacement in the follow-up of these patients. We think that the results of this study will also guide future studies that aim to guide clinical treatment.
Scientiﬁc Responsibility Statement
Animal and human rights statement
Conflict of interest
1. AlZahrani A , Sinnert R, Gernsheimer J. Acute kidney injury, sodium disorders, and hypercalcemia in the aging kidney: diagnostic and therapeutic management strategies in emergency medicine. Clin Geriatr Med. 2013;29(1):275-319.
2. Turgutalp K, Özhan O, Gök Oğuz E, Yılmaz A, Horoz M, Helvacı I, et al.Community-acquired hypernatremia in elderly and very elderly patients admitted to the hospital: clinical characteristics and outcomes. Med Sci Monit. 2012; 18(12):729-34.
3. Adrogué HJ, Madias NE. Hypernatremia. N Engl J Med. 2000;342(20):1493–9.
4. Alshayeb HM, Showkat A, Babar F, Mangold T, Wall BM. Severe hypernatremia correction rate and mortality in hospitalized patients. Am J Med Sci. 2011;341(5):356-60.
5. Ciozda W, Kedan I, Kehl DW, Zimmer R, Khandwalla R, Kimchi A. The efficacy of sonographic measurement of inferior vena cava diameter as an estimate of central venous pressure. Cardiovasc Ultrasound. 2016;14(1):33. DOI: 10.1186/s12947-016-0076-1.
6. Kılıç Y, Bas SS, Kayhan GE, Güleç MS. Internal Jugular Vein Ultrasonography in Prediction of Postspinal Hypotension. J Coll Physicians Surg Pak. 2020; 30(12):1256-61.
7. Phad N, de Waal K, Jones M. Agreement and reliability of the velocity time integral method and the method of disks to determine stroke volume in preterm infants. Early Hum Dev. 2018;125:31–4.
8. Zhao J, Wang G. Inferior vena cava collapsibility index is a valuable and non-invasive index for elevated general heart end-diastolic volume index estimation in septic shock patients. Med Sci Monit. 2016;22:3843–48.
9. Yildizdas D, Aslan N. Ultrasonographic inferior vena cava collapsibility and distensibility indices for detecting the volume status of critically ill pediatric patients. J Ultrason. 2020;20(82):e205-9.
10. Shah MK, Workeneh B, Taffet GE. Hypernatremia in the geriatric population. Clin Interv Aging. 2014;9:1987-92.
11. Schefold JC, Storm C, Bercker S, Pschowski R, Oppert M, Krüger A, et al. Inferior vena cava diameter correlates with invasive hemodynamic measures in mechanically ventilated intensive care unit patients with sepsis. J Emerg Med. 2010;38(5):632-7.
12. Fortes MB, Owen JA, Raymond-Barker P, Bishop C, Elghenzai S, Oliver SJ, et al. Is this elderly patient dehydrated? Diagnostic accuracy of hydration assessment using physical signs, urine, and saliva markers. J Am Med Dir Assoc. 2015;16(3):221-8.
13. El Ayadi AM, Nathan HL, Seed PT, Butrick EA, Hezelgrave NL, Shennan AH, et al.Vital Sign Prediction of Adverse Maternal Outcomes in Women with Hypovolemic Shock: The Role of Shock Index. PLoS One. 2016;11(2):e0148729.
14. Campos-Serra A, Montmany-Vioque S, Rebasa-Cladera P, Llaquet-Bayo H, Gràcia-Roman R, Colom-Gordillo A, et al. The use of the Shock Index as a predictor of active bleeding in trauma patients. Cir Esp. 2018;96(8):494-500.
15. Phad N, de Waal K, Jones M. Agreement and reliability of the velocity time integral method and the method of disks to determine stroke volume in preterm infants. Early Hum Dev. 2018;125:31–4.
16. Zhao J, Wang G. Inferior vena cava collapsibility index is a valuable and non-invasive index for elevated general heart end-diastolic volume index estimation in septic shock patients. Med Sci Monit. 2016;22:3843–8.
17. Kaçar CK, Uzundere O, Yektaş A. A Two Parameters for the Evaluation of Hypovolemia in Patients with Septic Shock: Inferior Vena Cava Collapsibility Index (IVCCI), Delta Cardiac Output. Med Sci Monit. 2019;25:8105-11.
18. van der Meer IM, Bots ML, Hofman A, del Sol AI, van der Kuip DA, Witteman JC. Predictive value of noninvasive measures of atherosclerosis for incident myocardial infarction: the Rotterdam Study. Circulation. 2004;109(9):1089-94.
19. Akkaya A, Yesilaras M, Aksay E, Sever M, Atilla OD. The interrater reliability of ultrasound imaging of the inferior vena cava performed by emergency residents. Am J Emerg Med. 2013;31(10):1509-11.
20. Pasquero P, Taulaigo AV, Albani S, Sitia E, Berchialla P, Borio L, et al. Inferior vena cava point of care ultrasound: new perspectives in management of hyponatraemia. Crit Ultrasound J. 2014;6(Suppl. 2):A9.
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Dilek Atik, Basar Cander, Emre Gokcen, Ramazan Unal, Cesareddin Dikmetas,Nuray Kılıc. Is it possible to evaluate the hypernatremia with ultrasonographic vena cava parameters? Ann Clin Anal Med 2022;13(5):530-534
Increase in cesarean delivery rates is the biggest obstacle to the reduction of feto-maternal morbidity
Department of Obstetrics and Gynecology, Istanbul IVF-Center, Istanbul, Turkey
DOI: 10.4328/ACAM.21015 Received: 2021-12-22 Accepted: 2022-02-04 Published Online: 2022-02-05 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):535-538
Corresponding Author: Ramazan Ozyurt, Istanbul IVF-Center, Istanbul, Turkey. E-mail: firstname.lastname@example.org P: +90 532 748 34 90 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6822-2222
Aim: Cesarean delivery, whose incidence is already high, has started to increase due to the increase in both labor induction and multiple pregnancy rates due to ART. The cesarean section rate to reduce maternal and fetal morbidity should be 10% or less. This study was planned to compare cesarean and vaginal delivery rates, indications, fetal and maternal morbidity and mortality rates performed in Istanbul Training and Research Hospital over a ten-year period.
Material and Methods: During the ten-year period between January 2000 and January 2009, 17150 patients who gave birth were included in the study. Demographic data of the patients were obtained retrospectively from their files. Maternal age, gravida, parity, length of hospital stay and cesarean section indications were recorded. Those who had one or more previous cesarean sections and those who had previous cesarean section due to myomectomy constituted the secondary cesarean section group. Those who had a cesarean section for the first time constituted the primary cesarean section group. Frequency of normal and cesarean delivery rates, indications for cesarean section, early and late maternal and fetal morbidity and mortality rates were compared.
Results: The total number of patients participating in the study, including normal vaginal delivery and cesarean section, was determined as 17150. While 9310 of them gave birth by cesarean section, 7840 cases delivered vaginally. While the number of patients with previous and repeated cesarean section was 3180, the number of patients with first cesarean section was 6130. Previous and repeated cesarean sections were recorded as the most common cesarean indication (48%). The second most common cesarean indication is fetal distress (18.4%). The third most common indication for cesarean section is cephalo-pelvic incompatibility (11.2%), which was found in 67 cases. The fourth most common cesarean indication is presentation-position anomaly, which was detected in 53 cases (8.8%). When compared with the primary cesarean section group, the rates of hemorrhage, urinary infection, fever, wound dehiscence and re-operation were found to be significantly higher in the secondary cesarean section group. When compared with the secondary cesarean section group, fetal birth weight was found to be significantly higher in the primary cesarean section group. Fetal length, head circumference, 1st and 5th minute APGAR scores were found to be similar in both groups.
Discussion: Despite efforts by healthcare providers and governments to promote normal vaginal delivery, both cesarean section and feto-maternal morbidity continue to increase.
Keywords: Cesarean Section, Vaginal Delivery, Fetal Morbidity, Maternal Morbidity
Cesarean section, which is the most frequently performed surgical intervention in the world, was a procedure that surgeons avoided until the end of the 19th century due to its high mortality. Thanks to the low transverse uterine incision recommended by Kerr, accepted by everyone, and the development of new surgical techniques, cesarean section has now become a routine surgical practice. If we include all pregnant women, one out of every seven cases gives birth by cesarean section, while one out of five primigravid patients gives birth by cesarean section. Most of the indications for cesarean section are due to obstetric reasons. However, indications related to maternal request constitute a large percentage and pave the way for many fetal and maternal complications .Three of the 4 cases who had a cesarean section can have a vaginal delivery in their next pregnancy. This due to the fact that most indications for cesarean section are due to the conditions specific to that moment . However, the increase in cesarean rates up to 35% in the last decade has led to an increase in maternal and fetal complication rates and has started to cause financial problems in the budgets of states. For this reason, health providers have applied a number of measures to reduce cesarean section rates. Although it has been suggested that mothers who have had a cesarean delivery can have their next birth vaginally, this has not been very successful. Although there is a low risk of 0.2-1.5%, the risk of uterine rupture after cesarean section has kept patients away from vaginal delivery. Vaginal delivery cannot be recommended in patients with a history of uterine rupture, those who have undergone surgery with a vertical incision, and those who have had more than two cesarean sections. However, the confidence of the couples in the cesarean section and the mothers’ ability to have this procedure by asking their physicians have been the biggest obstacles to reducing the cesarean rates. Even an increase in maternal morbidity and mortality was not enough to reduce cesarean rates [2,3].
This study was planned for a comprehensive analysis of all normal deliveries and cesarean sections in Istanbul Training and Research Hospital between 2000 and 2009. Frequency of normal and cesarean delivery rates, indications for cesarean section, early and late maternal and fetal morbidity and mortality rates were compared.
Material and Methods
During the ten-year period between January 2000 and January 2009, 17150 patients who gave birth in Istanbul Training and Research Hospital Gynecology and Obstetrics Clinics were included in the study. Demographic data of the patients were obtained retrospectively from their files. Maternal age, gravida, parity, length of hospital stay and cesarean section indications were recorded. Those who had one or more previous cesarean section and those who had previous cesarean section due to myomectomy constituted the secondary cesarean section group. Those who had cesarean section for the first time constituted the primary cesarean section group. Frequency of normal and cesarean delivery rates, indications for cesarean section, early and late maternal and fetal morbidity and mortality rates were compared. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee, and approval for the study was obtained from the Institutional Review Board.
Analyses of all data were performed on SPSS 21 (SPSS Inc., Chicago, IL, USA). In addition to descriptive statistical methods (mean, standard deviation) in the evaluation of the data, an independent t-test was used in the comparison of paired groups, the chi-square test was used in the comparison of qualitative data, and a paired t-test was used in the repeated measurements of the groups. The results are given as mean±SD in both text and tables. P<0.05 cases were considered statistically significant.
The total number of patients participating in the study, including normal vaginal delivery and cesarean section, was determined as 17150. While 9310 of them gave birth by cesarean section, 7840 cases delivered vaginally. While the number of patients with previous and repeated cesarean section was 3180, the number of patients with first cesarean section was 6130. Demographic characteristics of primary and secondary cesarean section groups are given in Table 1. Previous and repeated cesarean sections were recorded as the most common cesarean indication (48%). The second most common cesarean indication is fetal distress (18.4%). The third most common indication for cesarean section is cephalo-pelvic incompatibility (11.2%), which was found in 67 cases. The fourth most common cesarean indication is presentation-position anomaly, which was detected in 53 cases (8.8%).
When compared with the primary cesarean section group, the rates of hemorrhage, urinary infection, fever, wound dehiscence and re-operation were found to be significantly higher in the secondary cesarean section group (Table 2). When compared with the secondary cesarean section group, fetal birth weight was found to be significantly higher in the primary cesarean section group. Fetal length, head circumference, 1st and 5th minute APGAR scores were found to be similar in both groups (Table 3). Thrombophlebitis, wound infection, pneumonia, atelactasis and endometritis were found as etiological causes in cases with fever. Four out of the five patients in the secondary cesarean section were reoperated for postpartum bleeding control. In one case, surgery was performed to intervene in bladder injury. In the primary cesarean section group, re-operation was performed to intervene in a case that developed atony.
Because of the increased risk of urinary tract infection, fever, wound dehiscence, neonatal mortality, and postoperative surgery in patients undergoing emergency cesarean section, most of the cesarean section procedures are planned. However, even if it is performed under elective conditions, the risk of maternal and fetal mortality and morbidity due to cesarean continues . Some authors have proposed to characterize lower segment caesarean section as normal birth with an interesting suggestion. However, the increase in mortality and morbidity rates provided important proof that this recommendation is unrealistic. WHO gave the real indication rate of cesarean section to be 15% to protect mother and baby life and emphasized that normal delivery refers to vaginal delivery . The significant increase in hemorrhage, wound dehiscence, urinary tract infection, thromboembolism, the need for transfusion, and placentation anomalies in subsequent pregnancies compared to vaginal delivery in the post-cesarean period is evidence that vaginal delivery is a physiological mode of delivery .
The most common cesarean indication in the patients participating in our study consisted of patients with a previous cesarean section history. Fetal distress and cephalopelvic incompatibility are the second and third frequencies, respectively. These indications are similar to the results of previous studies. Maternal and fetal complication rates were significantly higher in the patient group with a previous cesarean section compared to those with a first cesarean section. However, except for fetal weight, other demographic parameters were similar in old and new cesarean section groups. The risk of reoperation was lower in the primary cesarean section group compared to the secondary cesarean section group [5-7].
Repeated cesarean deliveries continue to increase maternal morbidity and mortality by causing pathological placentation, obstetric bleeding and peripartum hysterectomy. Cesarean deliveries after maternal request have a very wide range and vary from 1 to 50%. Especially in private hospitals, cesarean rates after maternal request exceed 60%. Two other important reasons leading to an increase in cesarean section rates are increased labor induction and decreased instrumental delivery. In the light of all these data, cesarean sections planned with maternal request and fear of delivery have taken their place as the most common indications. In our study, the rates of cesarean section performed as a result of maternal request were not recorded. Cesarean section due to increased labor induction or decreased instrumental delivery rates was also an important group in our study [7,8].
In patients with a history of severe cardiovascular disease and previous sphincter injury, the mode of delivery should be decided by considering the advantages and disadvantages of normal delivery. In these cases, the preference is mostly for cesarean delivery. In our study, cesarean delivery was performed upon maternal request in four patients with a history of sphincter rupture. In pregnant patients with cardiovascular problems, endocarditis prophylaxis was performed and cesarean delivery was preferred. In IVF pregnancies, both physician preference and patient preference were in the direction of cesarean section. The preferred mode of delivery, especially in multiple pregnancies, was recorded as cesarean section. In most clinics, the diagnosis of fetal hypoxia is made with cardiotocography or scalp-lactate samples. In pregnant women whose cervix is not open enough, the diagnosis is made only by cardiotocography. In our cases, fetal hypoxia was diagnosed with a cardiotocograph. In patients diagnosed with severe preeclampsia, diabetes mellitus or rhesus immunization, cesarean section was preferred as the delivery method with a multidisciplinary approach [9-11].
As a result, a significant increase was observed in cesarean section rates in the last decade due to fetal hypoxia secondary to labor induction or prolonged labor. The news about maternal request, fear of giving birth, and uterine rupture from the press and social media has also become an important cesarean indication. Uterine scar due to previous surgeries, breech presentation and multiple pregnancies due to IVF are other important cesarean indications. Fetal hypoxia due to prolonged labor is another common cesarean indication. The WHO recommended cesarean rates are 10% or less to reduce maternal and fetal mortality . Cesarean section rates above these rates will lead to a continuation of feto-maternal morbidity and mortality.
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1. Sharma S, Dhakal I. Cesarean vs Vaginal Delivery: An Institutional Experience. J Nepal Med Assoc. 2018;56(209):535-9.
2. Vääräsmäki M, Raudaskoski T. Pregnancy and delivery after a cesarean section. Duodecim. 2017;133(4):345-52.
3. Yang XJ, Sun SS. Comparison of maternal and fetal complications in elective and emergency cesarean section: a systematic review and meta-analysis. Arch Gynecol Obstet. 2017;296(3):503-12.
4. Li HT, Zhou YB, Liu JM. The impact of cesarean section on offspring overweight and obesity: a systematic review and meta-analysis. Int J Obes (Lond). 2013; 320.
5. Waldenström U, Hildingsson I, Ryding EL. Antenatal fear of childbirth and its association with subsequent caesarean section and experience of childbirth. Br J Obstet Gynaecol. 2006;113(6):638–46.
6. Keag OE, Norman JE, Stock SJ. Long-term risks and benefits associated with cesarean delivery for mother, baby, and subsequent pregnancies: Systematic review and meta-analysis. PLoS Med. 2018;15(1):e1002494.
7. Betrán AP, Ye J, Moller A-B, Zhang J, Gülmezoglu AM, Torloni MR, et al. The increasing trend in caesarean section rates: global, regional and national estimates: 1990–2014. PLoS One. 2016;11(2):e0148343.
8. Asselmann E, Garthus-Niegel S, Martini J. Personality impacts fear of childbirth and subjective birth experiences: A prospective-longitudinal study. PLoS One. 2021;16(11):e0258696.
9. Juan J, Gil MM, Rong Z, Zhang Y, Yang H, Poon LC. Effect of coronavirus disease 2019 (COVID-19) on maternal, perinatal and neonatal outcome: systematic review. Ultrasound Obstet Gynecol. 2020;56(1):15-27.
10. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 2002; 77(1):67–75.
11. Silver RM. Abnormal placentation: Placenta previa, vasa previa, and placenta accreta. Obstet Gynecol. 2015;126(3):654–8.
12. Lannon SM, Guthrie KA, Vanderhoeven JP, Gammill HS. Uterine rupture risk after periviable cesarean delivery. Obstet Gynecol. 2015;125(5):1095–100.
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Ramazan Ozyurt. Increase in cesarean delivery rates is the biggest obstacle to the reduction of feto-maternal morbidity. Ann Clin Anal Med 2022;13(5):535-538
Evaluation of sexual functions between suffers of chronic spontaneous urticaria and psoriasis
Mehmet Yunus Meydan 1, Ayşe Nilhan Atsü 2, Nazlı Caf 1, Zafer Türkoğlu 1
1 Department of Dermatology, Başakşehir Çam and Sakura City Hospital, 2 Faculty of Health Sciences, İstanbul Kent University, Istanbul, Turkey
DOI: 10.4328/ACAM.21016 Received: 2021-12-22 Accepted: 2022-01-24 Published Online: 2022-02-09 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):539-543
Corresponding Author: Nazlı Caf, Department of Dermatology. Olimpiyat Bulvarı Yolu, Başakşehir Çam and Sakura City Hospital, Başakşehir, Istanbul, Turkey. E-mail: email@example.com P: +90 212 909 60 00 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9364-9236
Aim: Chronic dermatological diseases may have psychosocial effects such as sexual dysfunction. In this study, we aimed to evaluate the effects of chronic spontaneous urticaria (CSU) and psoriasis on sexual functions in comparison with healthy individuals.
Material and Method: Patients having psoriasis and CSU were enrolled. Healthy controls were obtained from volunteered patients applied for dermo-cosmetic product consultation. Thirty male and 30 female participants were included in every group. Beck Depression and Anxiety scales were administered to all participants. Female Sexual Function Index (FSFI) scale was applied to female participants and International Index of Erectile Function (IIEF) scale to males. Dermatology Life Quality Index (DLQI), Urticaria Activity Score of 7 (UAS7), and Urticaria Control Test (UCT) were applied to the patients belonging to CSU group. Data were analyzed with the IBM SPSS (Statistical Package for the Social Sciences) 22.0 program.
Results: Beck Anxiety scores did not differ between the groups (p>0.005). FSFI did not differ significantly between psoriasis and CSU groups (p>0.005), but it was significantly higher in healthy controls. IIEF did not differ between psoriasis and CSU groups. DLQI and UAS7 were negatively correlated with IIEF and FSFI sub-parameters (p<0.01).
Discussion: Our study is unique in evaluating sexual functions in CSU, psoriasis patients, and healthy individuals; therefore, adds to the literature. The psychosocial effects of chronic dermatoses such as CSU and psoriasis are not limited to depression, anxiety, and sleep disorders. Sexual functions should also be assessed and included in the treatment plan.
Keywords: Psoriasis, Chronic Urticaria, Sexual Dysfunction
Urticaria (wheals) is defined as a vascular reaction in the skin presenting with erythematous plaques. Its classic symptom is severe itching but burning and stinging may occur. Urticarial plaques may be accompanied by angioedema [1,2]. If urticaria episode lasts longer than 6 weeks, it is called chronic urticaria. Chronic urticaria is divided into chronic inducible and spontaneous forms (=idiopathic) .
Body image may be influenced by skin lesions, and this may cause sexual dysfunctions . Studies have reported that CSU patients, both males and females, have sexual dysfunction [4,5]. Psoriasis may lead to sexual dysfunction and 40-56% of patients experience sexual impairment .
Since skin is exposed to the environment, dermatological diseases affect self-confidence, and quality of life. Especially itching and chronic dermatoses may cause various psychiatric pathologies such as anxiety, depression and sleep disorders. It is important to be aware of these negative effects for holistic treatment [7,8].
Dermatology-specific scales include some questions about sexual life, they cannot fully evaluate sexual functions. Sexual functions have been investigated in many dermatological diseases, but there are no studies comparing CSU with psoriasis and healthy controls. The aim of this study is to compare sexual functions in patients who have CSU with psoriasis patients and healthy controls.
Material and Methods
The observational case-controlled study was conducted at Başakşehir Çam and Sakura City Hospital between March 15 and 15 May 2021. Ethics committee approval was obtained (Istanbul Kanuni Sultan Suleyman Training and Research Hospital Clinical Research Ethics Committee. Date:11/03/2021, Issue:2021.03.91).
Thirty female and 30 male patients were included in all three groups. Psoriasis and CSU patients were taken from follow-up outpatient clinics. Healthy controls were obtained from volunteered patients applied for dermo-cosmetic product consultation. Written informed consent was obtained from all participants.
Beck Depression and Beck Anxiety scales were applied to all participants. Urticaria Activity Score of 7 (UAS7), Urticaria Control Test (UCT) and Dermatology Life Quality Index (DLQI) were applied to CSU group. Psoriasis Area Severity Index (PASI) and DLQI scores of patients were calculated in psoriasis group.
The Female Sexual Function Index (FSFI) was administered to females and the International Index of Erectile Function (IIEF) was applied to males in every group.
The inclusion and exclusion criteria were as follows:
Being sexually active between the ages of 18-45, having regular menstrual cycles for female patients, patients who are able to take note of their symptoms on a daily basis.
Cute urticaria, urticarial vasculitis, isolated angioedema, women in pregnancy and lactation period, applying alternative treatments and diets up to 6 weeks before the study, alcohol dependence, illiteracy, being in menopause, systemic and/or psychiatric diseases that may affect sexual functions, history of hysterectomy, active sexually transmitted disease.
Scales for the evaluation of sexual functions:
Turkish validity studies of both indexes are present in the literature.
i)Female Sexual Function Index (FSFI)
The scale is a 19-item questionnaire developed as a multidimensional self-report tool to evaluate the sexual functioning in women within the last month. This questionnaire consists of questions in six domains, including desire, arousal, lubrication, orgasm, satisfaction, and pain, scored by patients’ self-reports. The total score is also calculated .
ii)International Index of Erectile Function (IIEF)
The questionnaire consisted of 15 self-evaluation questions assessing the last four weeks. Six questions of this questionnaire are about erectile function, 2 questions about sexual desire, 2 questions about orgasmic function, 3 questions about sexual satisfaction and 2 questions about general satisfaction. Each subgroup is scored within itself in addition to the total score .
Demographic, clinical and examination characteristics between groups
There was no significant difference between the groups in terms of age, gender, educational status, number of children, smoking, weight, and height (p>0.005) (Table 1).
No significant difference was found between the disease groups in terms of DLQI scores (p>0.005). Disease duration, family history, drug use rate were higher in psoriasis group compared to CSU group (p=0.000, p=0.024, p=0.040, respectively). The presence of triggering stress was higher in CSU group compared to psoriasis group (p=0.000).
Intragroup data of the CSU patients
The duration of attacks was 5.4 + 2.2 (Median= 7.0, Min=0 Max=7) times/week, and 36.7% (n=22) of the CSU patients were accompanied by angioedema. The response of these patients to antihistamine was as follows: 48.3% (n=29) had no response, 45% (n=27) had partial response, and 6.7% (n=4) had a complete response. UAS7 scores were 26.2 + 14.0 (Median= 28.0, Min=0 Max=44); UCT scores were 10.0 + 7.0 (Median= 11.0, Min=0 Max=40).
Intragroup data of the psoriasis patients
PASI scores were 9.0 + 4.3 (Median= 8.0, Min=3.2 Max=19.0). There was no genital involvement in 93.3% (n= 56). Four male patients had genital involvement.
Anxiety, depression, and sexual function data between groups
Beck Anxiety scores were not significantly different between the groups (p>0.005). A significant difference was found between the groups in terms of Beck Depression scores and was higher in CSU group (p=0.034).
All IIEF sub-parameters (erectile dysfunction (p=0.002), orgasmic function (p=0.000), sexual desire (p=0.000), sexual satisfaction (p=0.000), overall satisfaction (p=0.000) and the total score (p= 0.000)) were higher in the control group.
All FSFI sub-parameters (desire-related (p=0.000), arousal-related (p=0.000), lubrication-related (p=0.000), orgasm-related (p=0.000), general satisfaction (p=0.000), pain (p=0.000) and the total score were higher in the control group.
Post hoc analysis was performed to demonstrate the relationships between Beck Depression, IIEF and FSFI scores. No significant difference was found between the groups in terms of Beck Anxiety score (p>0.005). Beck Depression score was significantly higher in CSU group compared to controls (p=0.009).
Sub-parameters of IIEF and general total score did not differ significantly between CSU and psoriasis groups (p>0.005), all the scores were higher in the control group (p=0.015, p=0.015; p=0.000, p=0.000; p=0.000, p=0.000; p=0.000, p=0.000; p=0.000, p=0.000; p=0.000, p=0.000 respectively).
The FSFI sub-parameters and total score scores did not differ significantly between psoriasis and CSU groups (p>0.005), but they were higher in healthy controls (p=0.000, p=0.000; p=0.000, p=0.000; p=0.000, p=0.000; p=0.000, p=0.000; p=0.000, p=0.000; p=0.000, p=0.000 respectively).
No correlation was observed between disease duration and IIEF sub-parameters in psoriasis group (p>0.005). DLQI, PASI and genital involvement were negatively correlated with IIEF sub-parameters (p<0.01).
There was no correlation between disease duration and FSFI sub-parameters in psoriasis group (p>0.005). DLQI and PASI were negatively correlated with FSFI sub-parameters (p<0.01).
No correlation was observed between disease duration, accompanying angioedema and IIEF sub-parameters in CSU group (p>0.005). DLQI and UAS7 were negatively correlated with IIEF sub-parameters (p<0.01). UCT was positively correlated with IIEF sub-parameters (p<0.01) (Table 2).
No correlation was observed between disease duration, accompanying angioedema, and FSFI sub-parameters in CSU group (p>0.005). DLQI and UAS7 were negatively correlated with FSFI sub-parameters (p<0.01). UCT was positively correlated with FSFI sub-parameters (p<0.01) (Table 3).
Health is the totality of physical and mental health, and sexual health is also included in this definition.
In a study investigating sexual dysfunction and symptoms in CSU, mood disorders and sexual dysfunction were found to be higher in both male and female CSU patients compared to healthy controls, and IIEF and FSFI scores were negatively correlated with UAS7 . In our study, DLQI and UAS7 were negatively correlated with IIEF sub-parameters in males. In females, a negative correlation was found between DLQI and UAS7 with FSFI sub-parameters. Thus, our results were in concordance with the current literature. In other words, parameters that assess sexual function are all affected in both male and female patients with CSU.
It was reported that the scores of UCT were associated with sexual dysfunction, which is more prominent in female urticaria patients compared to healthy controls. Moreover, the same study revealed that as the disease activity increases, sexual disfunction also increases . In our study, UCT was positively correlated with FSFI and IIEF sub-parameters, whereas UAS7 score was negatively correlated. As urticaria was controlled, a decrease in sexual dysfunction was observed. Thus, our results were evaluated in accordance with the currrent literature. However, there was no difference in sexual dysfunction between individuals having CSU and psoriasis. The fact that sexual dysfunction was statistically lower in the control group compared to the disease groups suggested that the disease groups evaluated in this study may cause similar effects on sexual function due to their chronic nature.
In a study evaluating sexual functions in women with psoriasis, it was reported that sexual desire, arousal and satisfaction decrease with severity of psoriasis . In our study, PASI was negatively correlated with IIEF and FSFI sub-parameters. Since psoriasis is a disease that affects the appearance and may be located in visible areas, it is usual to cause social stigmatization, decrease in self-confidence, and affect sexual functions. Stigmatization was not evaluated in our study and further studies are recommended.
In a study conducted by Ermertcan et al., total IIEF score indicating sexual dysfunction was significantly lower in men with psoriasis compared to healthy controls. In addition, orgasmic function was significantly reduced in psoriasis patients. However, no correlation was found between total IIEF score, PASI, and DLQI . In our study, DLQI and PASI were negatively correlated with IIEF sub-parameters. In other words, we found that orgasmic function was also significantly affected like all other parameters.
Studies have reported that erectile dysfunction is higher in men with psoriasis, and this rate is 43.8%. [13, 14]. It has also been reported that this condition is independent of DLQI, duration of psoriasis, and genital involvement . In a study by Goulding et al., no difference was found between healthy control and psoriasis groups considering erectile dysfunction . Thus, in the current literature, the results of studies evaluating the sexual fissions in men with psoriasis vary. In our study, genital involvement in male patients was found to be negatively correlated with all sub-parameters of IIEF. The small number of patients (n:4) with genital involvement in our study may have created this difference. Large-scale human studies are needed that only reveal the relationship.
In a study conducted by Alariny et al., in which depression, anxiety and sexual functions were evaluated in psoriasis patients and their partners, it was found that self-confidence was lower, and anxiety and depression were higher compared to healthy controls . Although self-confidence was not evaluated in our study, depression was found to be higher CSU group compared to the other groups. However, no significant difference was found between the three groups in anxiety scores. The reason for the higher depressive scores in patients with CSU may be the sudden onset of the disease and the unpredictability of its course.
In a study by Ertaş et al., sexual dysfunction was higher in female patients with CSU accompanied by angioedema compared to the patients without angioedema . In our study, however, no significant difference was observed between FSFI sub-parameters in patients with angioedema. Additional studies in which genital angioedema is specifically questioned and the severity of angioedema is evaluated will help to shed light on this issue.
In a study, in which sexual functions of both genders were evaluated in vitiligo and CSU patients, sexual desire and lubrication were lower in women with both vitiligo and urticaria compared to healthy controls. In addition, orgasm and satisfaction were found to be reduced in both diseases compared to controls. In male patients having vitiligo and CSU, although no significant difference was found in other sub-parameters, orgasm and satisfaction were lower compared to healthy controls. However, the intergroup levels of involvement of patients with vitiligo and CSU were not evaluated in this study. In addition, the Arizona Sexual Experience Scale (ASEX) scale was used instead of the IIEF and FSFI. However, in ASEX, similar to the scales we use, sexual desire, vaginal lubrication-penile erection, ability to reach orgasm and satisfaction from orgasm are evaluated . In another study, the sexual disorders of patients with psoriasis and neurodermatitis were compared with healthy controls, and increased sexual dysfunction, including orgasmic function, was found in both diseases compared to healthy controls . In our study, sexual dysfunction was higher in both psoriasis and CSU patients compared to the control group, but there was no statistical difference between the two diseases.
There are some limitations in our study. The association with treatment types was not determined. Evaluations of other quality of life assessments in urticaria (CU-Q2oL and UAS31) were not questioned due to the possibility of prolonged contact time during COVID-19 pandemic. Besides, patients with inducible urticaria were not assessed.
Sexual dysfunction was detected in both sexes in psoriasis and CSU compared to healthy controls. There are many studies that strongly demonstrate sexual dysfunction in psoriasis but the number of studies is very few in CSU. This study revealed that CSU causes sexual dysfunction at least as much as psoriasis. It is very important to evaluate and treat sexual functions, which are a component of quality of life in chronic dermatological diseases.
We thank Dr. Utkan Kızıltaç for his help in forming the hypothesis, and Dr. Şenay Ağırgöl, Dr. Ozan Yıldırım and Dr. Bilgen Erdoğan for their assistance during the writing process.
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1. James W, Elston D, Treat J, Rosenbach M, Neuhaus IM. Andrews’ Diseases of the Skin 13th edition. Elsevier;
2. Weller K, Giménez-Arnau A, Grattan C, Asero R, Mathelier-Fusade P, Bizjak M, et al. The Chronic Urticaria Registry: rationale, methods and initial implementation. J Eur Acad Dermatology Venereol. 2021;35(3):721-9.
3. Simsek N, Evli M, Uzdil N, Albayrak E, Kartal D. Body Image and Sexual Self-confidence in Patients with Chronic Urticaria. Sex Disabil. 2020;38(1):147-59.
4. Skrzypulec-Frankel A, Bieniek K, Kasperska-Zajac A. The association between sexual dysfunctions and severity of symptoms in patients with chronic spontaneous urticaria. Allergy, Asthma Clin Immunol. 2018;14(1):20-1.
5. Ertaş R, Erol K, Hawro T, Yılmaz H, Maurer M. Sexual Functioning Is Frequently and Markedly Impaired in Female Patients with Chronic Spontaneous Urticaria. J Allergy Clin Immunol Pract. 2020;8(3):1074-82.
6. Kwan Z, Baharum N, Yong SS, Mohd Affandi A, Johar A. Sexual difficulties and associated factors among patients with psoriasis in Malaysia: data from the Malaysian Psoriasis registry. Psychol Heal Med. 2020; DOI:10.1080/13548506.2020.1831557
7. Jaworski M. Is sexology necessary in dermatology? Review of most common sexual dysfunction in skin disorders. Our Dermatology Online. 2017;8(3):341-7.
8. Duarte G, Calmon H, Radel G, Oliveira M de FP de. Psoriasis and sexual dysfunction: links, risks, and management challenges. Psoriasis Targets Ther. 2018; 8:93-9.
9. Zincir H, Demir G, Günaydın Y, Ozen B. Sexual Dysfunction in Married Women With Urinary Incontinence. Sex Dysfunct Androl. 2018;15(4):193-8.
10. Neijenhuijs KI, Holtmaat K, Aaronson NK, Holzner B, Terwee CB, Cuijpers P, et al. The International Index of Erectile Function (IIEF)—A Systematic Review of Measurement Properties. J Sex Med. 2019;16(7):1078-91.
11. Khaled H, El-Sabagh E, Bazid H. Female sexual dysfunction in patients with psoriasis and vitiligo: An Egyptian pilot study. J Egypt Women’s Dermatologic Soc. 2021;18(1):22-34.
12. Türel Ermertcan A, Temeltaş G, Deveci A, Dinç G, Güler HB, Öztürkcan S. Sexual dysfunction in patients with psoriasis. J Dermatol. 2006;33(11):772-8.
13. Wojciechowska-Zdrojowy M, Reid A, Szepietowski JC, Wojciechowski A. Analysis of Sexual Problems in Men With Psoriasis. J Sex Marital Ther. 2018;44(8):737-45.
14. Cabete J, Torres T, Vilarinho T, Ferreira A, Selores M. Erectile dysfunction in psoriasis patients. Eur J Dermatology. 2014;24(4):482-6.
15. Goulding JMR, Price CL, Defty CL, Hulangamuwa CS, Bader E, Ahmed I. Erectile dysfunction in patients with psoriasis: Increased prevalence, an unmet need, and a chance to intervene. Br J Dermatol. 2011;164(1):103-9.
16. Alariny AF, Farid CI, Elweshahi HM, Abbood SS. Psychological and Sexual Consequences of Psoriasis Vulgaris on Patients and Their Partners. J Sex Med. 2019;16(12):1900-11.
17. Sukan M, Maner F. The problems in sexual functions of vitiligo and chronic urticaria patients. J Sex Marital Ther. 2007;33(1):55-64.
18. Mercan S, Altunay IK, Demir B, Akpinar A, Kayaoglu S. Sexual dysfunctions in patients with neurodermatitis and psoriasis. J Sex Marital Ther. 2008;34(2):160-8.
Download attachments: 10.4328:ACAM.21016
Mehmet Yunus Meydan, Ayşe Nilhan Atsü, Nazlı Caf, Zafer Türkoğlu.Evaluation of sexual functions between suffers of chronic spontaneous urticaria and psoriasis. Ann Clin Anal Med 2022;13(5):539-543
Evaluation of corneal endothelial morphology in type 2 diabetes mellitus with specular microscopy
Murat Serkan Songur 1, Murat Akansel 1, Seray Aslan Bayhan 1, Tekin Yıldırım 2, Hasan Ali Bayhan 1
1 Deparment of Ophthalmology, 2 Deparment of Internal Medicine, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey
DOI: 10.4328/ACAM.21019 Received: 2021-12-23 Accepted: 2022-01-24 Published Online: 2022-01-25 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):544-547
Corresponding Author: Murat Serkan Songur, Deparment of Ophthalmology, Faculty of Medicine, Yozgat Bozok University, Çapanoğlu Mahellesi, Cemil Çiçek Caddesi, Yozgat, 66100, Turkey.
E-mail: firstname.lastname@example.org P: +90 505 798 85 28 F: +90 354 217 10 72 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6234-3680
Aim: In this study, we aimed to evaluate the corneal endothelium using a specular microscopy in patients with type 2 diabetes mellitus (DM).
Material and Methods: The right eyes of 30 DM patients without any ocular findings, 30 DM patients with non-proliferative diabetic retinopathy (NPDR), and 30 DM patients with proliferative diabetic retinopathy (PDR) were evaluated in the study. Cell density (cells/mm2), corneal thickness (µ), hexagonal cell ratio (%), and coefficient of variation (cell area standard deviation/mean cell area, µm2) of the corneal endothelium of these patients were assessed with a specular microscope.
Results: There was no significant difference between the groups in terms of corneal thickness. While there was no significant difference between the control group and the group with NPDR in terms of endothelial cell density, hexagonality and coefficient of variation, a significant difference was found between the PDR group and both the control and NPDR groups.
Discussion: Since we found that disease progression leads to deterioration in corneal endothelial morphology in type 2 DM patients, we believe that it is important to try to prevent disease progression by controlling the blood glucose levels and using specular microscopy during follow-up and treatment in these patients.
Keywords: Type 2 Diabetes Mellitus, Specular Microscopy, Corneal Endothelium, Hexagonality, Coefficient of Variation
The corneal endothelium consists of a single non-renewable layer of predominantly hexagonal cells. Corneal endothelial cells keep the stroma dry by actively removing water, which is a vital function in maintaining normal corneal transparency . The corneal tissue is avascular. Maintaining normal corneal metabolism depends on a critical oxygen level, below this level, a series of acute metabolic events, including an increase in stromal lactate, a decrease in intercellular pH, and an increase in corneal hydration may occur . Oxygen required for basic metabolism of the cornea is primarily obtained from the atmosphere through tears and diffusion on the anterior surface of the cornea. The aqueous humor in the anterior chamber also supplies oxygen to the cornea .
Diabetes mellitus (DM) is a metabolic disorder resulting from a defect in insulin secretion, insulin action, or both. Insulin deficiency also causes chronic hyperglycemia by causing disorders in carbohydrate, fat and protein metabolism. As DM progresses, increasing tissue and vascular damage leads to serious diabetic complications such as retinopathy, nephropathy, and neuropathy [4,5].
DM is divided into two main groups as type 1 and type 2. Individuals with type 1 diabetes have little or no endogenous insulin secretory capacity and therefore require insulin therapy to survive . Type 2 diabetes is the most common form of diabetes and is characterized by disorders in insulin secretion and insulin resistance . Diabetes is seen in 5-7% of the world’s population .
Specular microscopy (SM) is a non-invasive approach for the qualitative, quantitative and morphometric evaluation of corneal endothelial functions . SM enables determination of corneal thickness, cell density (CD), which indicates the number of cells per mm2 of the corneal endothelium, pleomorphism, which indicates variation in cell shape in the endothelium, and polymegathism, which indicates variation in individual cell area. Pleomorphism shows the hexagonal cell ratio, and polymegathism shows the coefficient of variation, determined by the ratio of the cell area standard deviation to the mean cell area.
Diabetic retinopathy is angiopathy with involvement of retinal capillaries. Patients are divided into two groups as non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). Microaneurysms, soft and hard exudates, intraretinal microvascular abnormalities are seen in NPDR. If neovascularization, vitreous hemorrhage, tractional retinal detachment and macular edema are detected, the disease is classified as PDR .
Corneal cells have a very limited mitotic capacity. Therefore, when cell loss occurs, adjacent cells expand and shift to maintain endothelial continuity. This causes an increase in polymegathism and pleomorphism . Cell loss and endothelin status can be more precisely determined based on the assessment of polymegathism and pleomorphism.
Diabetic patients are susceptible to corneal epithelial disorders such as superficial punctate keratopathy and epithelial erosion . In addition, permanent epithelial defects and recurrent erosions may occur in the corneal epithelium during vitreoretinal surgery and photocoagulation . This shows that the cornea is more sensitive to pathologies in diabetic patients. Our aim in this study was to evaluate corneal endothelial morphology using specular microscopy in patients with type 2 diabetes.
Material and Methods
This cross-sectional prospective study was conducted in our hospital’s ophthalmology outpatient clinic between January 2020 and January 2021. Before the initiation of the study, informed consent was obtained from the patients and ethical committee approval was obtained from the Ethics Committee of our hospital. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
All patients underwent a complete and detailed ophthalmologic evaluation, including best-corrected visual acuity, slit lamp biomicroscopy, Goldmann applanation tonometry, intraocular pressure measurement (IOP), pachymetry, triple-mirror contact lens gonioscopy, and fundoscopy. Afterwards, right eyes of all patients were photographed with specular microscopy (Specular Microscope CEM-530, NIDEK). Cell density (CD), hexagonal cell ratio (HEX), corneal thickness (CT) and coefficient of variation (CV) in the corneal endothelium were assessed from the SM images.
Patients with glaucoma, uveitis, retinal disease, hypertensive retinopathy, epiretinal membrane and retinal detachment, corneal disease, pseudoexfoliation syndrome, high myopia and hyperopia (>6D), corneal opacity, patients who could not cooperate during SM, those with a history of ocular trauma and surgery, and those who used eye drops and contact lenses were excluded from the study. In addition, patients with dementia, Parkinson’s disease, epilepsy, vascular disease, and psychiatric disease were excluded from the study.
Statistical analysis was performed using the SPSS® 22.0 (Statistical Package for Social Sciences, IBM Inc., Chicago, IL, USA) package program. The variables were investigated using analytical methods (Kolmogorov-Smirnov/Shapiro-Wilk’s test) to determine if they were normally distributed. Descriptive analyses were presented using means and standard deviations for normally distributed variables and median and interquartile range for the non-normally distributed and ordinal variables. One way ANOVA was used to compare normally distributed variables and Levene’s test was used to assess the homogeneity of the variances. Kruskal-Wallis tests were conducted to compare non-normally distributed variables. An overall p-value of less than 0.05 was considered statistically significant.
The right eyes of 30 DM patients without any ocular findings, 30 DM patients with NPDR, and 30 DM patients with PDR were evaluated. Socio-demographic characteristics of the patients are shown in Table 1.
We evaluated corneal thickness (µ), endothelial cell density (cells/mm2), hexagonal cell ratio in endothelium (%) and coefficient of variation (µm2) in all patients using SM. We determined that there was a significant difference between the PDR group and both the NPDR and control groups in terms of CD, HEX and CV. However, no significant difference was found between the NPDR group and the healthy control group. No significant difference was found between the three groups in terms of CT. The data are summarized in Table 2.
In our study, when we compared the control group, which consisted of type 2 DM patients without any ocular findings, with DM patients with NPDR, no significant difference was found in terms of corneal endothelial parameters. A significant difference was found in endothelial cell density (CD), hexagonal cell ratio (HEX) and coefficient of variation (CV) between PDR and both the control and NPDR groups. However, no significant difference was found between the three groups in terms of CT.
In DM, pathologies such as corneal edema, delayed corneal wound healing, decreased corneal sensitivity, neurotrophic ulcer, Descemet’s membrane wrinkles, corneal endothelial morphology and dysfunction can be observed . Similar to our findings with PDR patients, Sabanci et al. compared non-diabetic and diabetic patients and found that corneal thickness was higher in diabetic patients . Studies conducted by Ermiş, Özdamar, and Lee also reported increased corneal thickness in diabetic patients [15, 16]. It is thought that diabetes causes damage to the corneal endothelium, and this damage causes fluid collection in the cornea by disrupting the corneal hydration balance . Another study suggested that there might be changes in corneal thickness due to inadequate barrier and pump function in the corneal endothelium in DM . Lee et al.’s study compared the corneal morphology of diabetic patients with that of the healthy control group, and a decrease in HEX and CD and an increase in CV were found in the diabetes group .
Although it is reported in the literature that the increase in corneal thickness in diabetic patients is due to corneal hydration, the effect of hyperglycemia on the biomechanical properties of collagen has also been implicated. Hyperglycemia accelerates the non-enzymatic glycosylation of biological macromolecules. Glycosylation of corneal collagens causes formation of irreversible cross-links between corneal collagens, and it is thought that this may contribute to the increase in corneal thickness and corneal stiffness .
It has been reported that corneal endothelial cell density and hexagonal cell percentage are decreased, while the coefficient of variation is increased in patients with type 2 DM compared to the healthy control group . We obtained similar results in diabetic patients with PDR. On the other hand, Arıcı et al. reported an increase only in CT values in diabetic patients compared to the control group, with no significant difference in other parameters .
In conclusion, we found that corneal endothelial parameters deteriorate when diabetes reaches the PDR stage. This situation can lead to both an increase in the susceptibility to corneal diseases and healing problems after cataract surgery in patients with PDR. For this reason, we think that it would be very beneficial to prevent disease progression by strict glucose regulation in type 2 DM patients.
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1. Wilson SL, El Haj AJ, Yang Y. Control of scar tissue formation in the cornea: strategies in clinical and corneal tissue engineering. J Funct Biomater. 2012;3(3):642-87.
2. Brennan NA. A model of oxygen flux through contact lenses. Cornea. 2021;20(1):104-8.
3. Carbonaro F, Hysi PG, Fahy SJ, Nag A, Hammond CJ. Optic disc planimetry, corneal hysteresis, central corneal thickness, and intraocular pressure as risk factors for glaucoma. Am J Ophthalmol. 2014;157(2):441-6.
4. Bearse MA, Han Y, Schneck ME, Barez S, Jacobsen C, Adams AJ. Local multifocal oscillatory potential abnormalities in diabetes and early diabetic retinopathy. Invest Ophthalmol Vis Sci. 2004;45(9):3259-65.
5. Seki M, Tanaka T, Nawa H, Usui T, Fukuchi T, Ikeda K, et al. Involvement of brain-derived neurotrophic factor in early retinal neuropathy of streptozotocin-induced diabetes in rats: therapeutic potential of brain-derived neurotrophic factor for dopaminergic amacrine cells. Diabetes. 2004;53(9):2412-9.
6. DeFronzo RA, Ferrannini E, Keen H, Zimmet P, editors. International Textbook of Diabetes Mellitus; 3 ed Chichester: Wiley; 2004.p.3-14.
7. DeFronzo RA, Zimmet P, Alberti G, editors. International Textbook of Diabetes Mellitus. 2nd ed. Chichester: Wiley; 1997.p.635-712.
8. Cheng HT, Xu X, Lim PS, Hung KY. Worldwide epidemiology of diabetes-related end-stage renal disease, 2000–2015. Diabetes Care. 2021;44(1):89-97.
9. Krachmer JH, Mannis MJ, Holland EJ, editors. Cornea: Fundamentals, Diagnosis and Management, 3rd ed Philadelphia, PA: Elsevier Mosby; 2010:177–203.
10. Klein R, Klein BE, Moss SE, Cruickshanks KJ. The Wisconsin Epidemiologic Study of diabetic retinopathy. XIV. Ten-year incidence and progression of diabetic retinopathy. Arch Ophthalmol. 1994;112(9):1217-28.
11. Gekka M, Miyata K, Nagai Y, Nemoto S, Sameshima T, Tanabe T, et al. Corneal epithelial barrier function in diabetic patients. Cornea. 2004;23(1):35-7.
12. Bikbova G, Oshitari T, Tawada A, Yamamoto S. Corneal changes in diabetes mellitus. Current Diabetes Reviews. 2012;8(4):294-302.
13. Lee JS, Oum BS, Choi HY, Lee JE, Cho BM. Differences in corneal thickness and corneal endothelium related to duration in diabetes. Eye. 2006;20(3):315-18.
14. Sabanci S, Pekel G, Dellal F. Comparison of Central Corneal Thickness Measurements in Diabetic and Non-Diabetic Subjects. MN Oftalmoloji. 2013;20(3):149-52.
15. Lee JS, Oum BS, Choi HY, Lee JE, Cho BM. Differences in corneal thickness and corneal endothelium related to duration in diabetes. Eye. 2006;20(3):315-8.
16. Ozdamar Y, Cankaya B, Ozalp S, Acaroglu G, Karakaya J, Ozkan SS. Is there a correlation between diabetes mellitus and central corneal thickness? J Glaucoma. 2010;19(9):613-6.
17. Verkman AS, Ruiz-Ederra J, Levin MH. Functions of aquaporins in the eye. Prog Retin Eye Res. 2008;27(4):420-33.
18. Bikbova G, Oshitari T, Tawada A,Yamamoto S. Corneal changes in diabetes mellitus. Current Diabetes Reviews. 2012;8(4):294-302.
19. Robert L, Menasche M, Robert AM, Renard G. Effect of high glucose concentration on corneal collagen biosynthesis. Ophthalmologica. 2006;220(5):317-22.
20. Roszkowska AM, Tringali CG, Colosi P, Squeri CA, Ferreri G. Corneal endothelium evaluation in type I and type II diabetes mellitus. Ophthalmologica. 1999;213(4):258-61.
21. Arici C, Hatipoglu E, Arslan O, Dikkaya F, Sultan P, Gundogdu S. The Corneal Endothelial Morphology, Density and Central Thickness in Type 2 Diabetes Mellitus. Turkiye Klinikleri J Med Sci 2014;34(2):210-4.
Download attachments: 10.4328:ACAM.21019
Murat Serkan Songur, Murat Akansel, Seray Aslan Bayhan, Tekin Yıldırım, Hasan Ali Bayhan. Evaluation of corneal endothelial morphology in type 2 diabetes mellitus with specular microscopy. Ann Clin Anal Med 2022;13(5):544-547
Scientometric analysis of methanol intoxication literature: Global publication output between 1980 and 2019
Umut Payza 1, Engin Şenel 2, Fatih Esad Topal 1, Zeynep Karakaya 1, Mehmet Göktuğ Efgan 1
1 Department of Emergency Medicine, Katip Celebi University, Ataturk Research and Training Hospital, İzmir, 2 Department of Dermatology and Venereology, Hitit University, Corum, Turkey
DOI: 10.4328/ACAM.21020 Received: 2021-12-23 Accepted: 2022-02-07 Published Online: 2022-02-08 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):548-553
Corresponding Author: Mehmet Göktuğ Efgan, Department of Emergency Medicine, Katip Celebi University, Ataturk Research and Training Hospital, İzmir, Turkey. E-mail: email@example.com P: +90 546 674 19 70 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0794-1239
Aim: Scientometrics refers to the analysis of scientific literature related to a certain field. Even though the number of publications on methyl alcohol poisoning has recently increased, there has been no bibliometric or scientometric analysis conducted to date. In 2020 in particular, cases of methyl alcohol poisoning have increased due to the COVID-19 pandemic, which is expected to draw greater attention to this field.
Material and Methods: All data used in this study were collected from four databases accessed via the Web of Science. All studies published between 1980 and 2019 identified by searching for the keywords “methanol” and “poisoning” were included in the study. The relationship between the number of publications and productivity and characteristics of countries was analyzed with Spearman’s correlation test, while GunnMap and VOSviewer were used to create infographics and infomaps. This study was conducted in accordance with the Declaration of Helsinki
Results: A total of 744 articles, most of which were original (79.70%), were identified from the four databases accessed via the Web of Science. An analysis of the number of publications by country ranked the United States in the first place, with 174 articles (23.387 %), while the Czech Republic was found to have the most productive researchers. The most popular area was toxicology (20.565%), and Charles University was the most productive institution. It was found that the number of publications and citations did not increase over the years
Discussion: The developed countries dominated the literature on methyl alcohol poisoning. It was further observed that articles on methyl alcohol abuse started to appear in 2020 in developing countries, which can be attributed to the COVID-19 pandemic, and the mistaken belief that it has anti-viral properties. Since the diagnosis and treatment of methyl alcohol poisoning are gaining significance, we recommend that researchers be encouraged to make further studies in this area.
Keywords: Bibliometrics, Citation Analysis, Methanol, Intoxication, Scientometrics
Methanol, also known as methyl alcohol, is a toxic alcohol widely used in various range of products such as fuels, solvents and clothing  . Cluster poisoning and outbreaks of intoxication were reported in the literature due to consumption of the products containing a high concentration of methanol [2-5]. At the end of 2019, a cluster of patients with pneumonia was reported from the city of Wuhan in Hubei Province of China . First, the cause of this disease was unknown. Later, the cause of the pneumonia was identified as a novel coronavirus, and the outbreak evolved to a pandemic affecting all the world in months (World Health Organization; 2020. Available at: http://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/news/news/2020/3/who-announces-covid-19-outbreak-a-pandemic.2020). As of today, according to the official figures announced, the total number of SARS-CoV-19 cases worldwide has reached 60 million with over 1 million deaths (Available at: https://www.worldometers.info/coronavirus/. Published March 2020. Accessed November 24, 2020). In the SARS-CoV-19 pandemic, outbreaks of methanol intoxication due to the false belief that consumption of alcohol prevents virus infection were reported in different regions of the world [7,8,9,10,11].
Scientometrics, also known as the “science of science”, is a novel academic field investigating publication trends, patterns and providing information on the productivity of authors, institutions, journals and countries . To the best of our knowledge, academic literature lacks a scientometric study evaluating methanol intoxication literature. In this study, as the first trial in academic literature, we aimed to perform a holistic scientometric analysis of methanol intoxication literature.
Material and Methods
The Web of Science (WoS, Clarivate Analytics, USA) Core Collection was the major database for our scientometric analysis. WoS has been reported to be the most reliable database in the academic world, and therefore we chose WoS as the search source for our scientometric evaluation . All documents produced between 1980 and 2019 were included in the study by using a search string containing the keywords (“methanol” AND “intoxication”). WoS GunnMap 2 was our tool to generate infomap revealing the global distribution of the academic productivity of methanol intoxication literature (GunnMap, 2020. Available at : http://lert.co.nz/map/. Accessed January 10, 2020). VOSviewer version 1.6.15 (Centre for Science and Technology Studies, Leiden University, The Netherlands) was a freeware for creating scientometric networks in our study (Vosviewer, 2020. Available at : https://www.vosviewer.com/. Accessed January 10, 2020). This study was conducted in accordance with the Declaration of Helsinki.
General Features of the Literature
Between 1980 and 2019, a total of 744 articles were published in the literature on methanol intoxication, and only 183 documents were open access. The peak year of the production was 2013 with 43 documents, and the most indexed document type was original article, followed by letter and review (79.704, 5.78 and 5.376%, respectively; Table 1). The most studied areas were Toxicology, Internal Medicine and Pharmacology (20.565, 14.919 and 12.5%, respectively; Table 1).
Productivity of the Countries, Source Titles, Authors and Institutions
The USA was ranked as the top productivity country with 174 articles (23.387%), followed by Turkey, Czechia, Canada and Germany (n=62, 46, 43 and 36 items, respectively; Figure 1). Global production of the publications was distributed irregularly, and nearly no documents were published from African countries, except for Egypt, Tunisia, Nigeria and Kenya (Figure 2). The journals contributing the most to the literature were Clinical Toxicology, Journal of Toxicology and Forensic Science International (2.957, 2.554 and 2.285%, respectively; Table 1). Interestingly, seven of topmost productive researchers were from Czechia, and the most prolific author in the literature was Zakharov S from Charles University in Czechia with 31 papers (4.167% of all production in the literature; Table 1). Charles University was also the most contributor institution of the literature with 36 documents, and the first four places were occupied by Czechian institutions (Table 1). The USA had only one organization in the list of top ten institutions, Medical College of Wisconsin, although it ranked first in the list of the most productive countries list (Table 1).
Citation analysis and Scientometric Network Analyses
H-index of the methanol intoxication literature was calculated as 48, and the average citation per item was 14.84. The total number of citations was 11,041 (8,239 without self-citations). The peak year for citations was 2019 with 910 records (Figure 3). The most cited document in methanol intoxication literature was the original article titled “Therapeutic photobiomodulation for methanol-induced retinal toxicity” published in Proceedings of the National Academy of Sciences of the United States of America in 2003. The most used keywords were noted as “methanol”, “poisoning”, “ethanol”, “hemodialysis” and “intoxication” (Table 2).
Articles related to the treatment of retinal damage and the most cited publications were analyzed (Table 3).
Evaluation of the Period of Pandemic (2020)
Since it is a specific and uncompleted period, we decided to assess publications produced in the COVID-19 pandemic. Our search on WoS retrieved 18 articles indexed in 2020, and there were 14 original articles in the literature with two reviews and two letters. Czechia ranked first with 4 articles as in our general analysis, including the period 1980-2019, followed by Iran, Turkey and the USA (n=2, 2, 2 documents, respectively). The most productive institutions in this period were Charles University, General University Hospital in Prague and Czech Academy of Sciences (n=3, 3, 2 items, respectively). This ranking of the institutions was the same as in the general analysis, and all three institutions were from Czechia. The most prolific authors were Diblik P, Kotikova K, Vaneckova M, Zakharov S. All authors had the same number of publications (3 documents) and all were from Czechia.
The terms “scientometrics” and “bibliometrics”, referring to the statistical analysis of academic literature investigating the scientific characteristics of a field, including such factors as authors, countries, keywords and publication trends, are almost identical and interchangeable. Bibliometric analyses are used to assess global scientific productivity in biomedical fields. A literature review of methanol poisoning produces limited results, and so can be considered insufficient for the assessment of global scientific productivity. To the best of our knowledge, the present study is the first to analyze global research efficiency in the field of methanol poisoning, covering the years between 1980 and 2019. On the condition that an adequate number of standardized indicators are used, such studies may support an analysis of diagnosis and treatment success in methanol poisoning, and provide information on historical changes of poisoning. It should be noted, however, that bibliometric studies have certain limitations, since they do not take into account the quality of publications 
In the 1980–2019 period, scientists published 744 articles on methanol poisoning, peaking in 2013 when 43 articles were published. An analysis of each country’s contribution to literature places the United States in first place in terms of output over the last 39 years, with 174 articles, while Turkey, the Czech Republic, Canada and Germany have steadily increased their share. While the United States ranked first as the most productive country in terms of the number of articles, the country’s contribution to literature was lower than that of the Czech Republic, where Charles University made the greatest institutional contribution to literature with 36 articles on four institutions from the same country made it into the top ten. In comparison, only one institution from the United States – the Medical College of Wisconsin – was listed in the top ten. Zakharov S., a researcher at Charles University in the Czech Republic was found to be the most prolific author, with 31 articles, mainly on toxicology, internal diseases and pharmacology.
The categorization mapping presented in Table 1 is the results of an analysis of the relationship between these topics and the years of publication.
An analysis of the top 10 journals containing articles on methanol poisoning found that six (60 percent) were listed as “toxicology journals”, while the remaining four were in the “forensic science” (20 percent), “kidney disease” (10 percent) and “emergency medicine” (10 percent) categories. ‘’Clinical Toxicology’’, the ‘’Journal of Toxicology’’, and ‘’Forensic Science International’’ made the greatest contributions to the literature. In the literature review, toxicology was the most searched field, with the most popular keywords being methanol, poisoning, ethanol and hemodialysis, with most searches made to identify antidotes and effective treatment methods for poisoning.
The h-index of methanol poisoning literature was calculated as 48. The total number of citations was 11,041, and 2019 was the busiest year, with 910 citations. The article cited most in methanol poisoning literature was “Therapeutic Photobiomodulation for Methanol-induced Retinal Toxicity”, published in the Proceedings of the National Academy of Sciences of the United States of America in 2003. The article investigates the treatment of retinal damage secondary to poisoning, and presents treatment options for poisoning, like the other most-cited publications (Table 3).The COVID-19 pandemic introduced a novel methyl alcohol poisoning risk to the field. Shortly after the initial outbreak, rumors began to circulate in social media that the consumption of alcohol or mouthwash could prevent or treat COVID-19, which led to an increase in poisoning rates involving the consumption of industrial ethanol, as well as in the number of deaths from alcohol poisoning. At the time of writing in 2020, a total of 18 articles have been published, 14 of which are original research articles, investigating cases of methanol poisoning related to COVID-19 [7,9,10], and it is thought that the number of methanol poisoning cases may increase if the pandemic continues.
On the condition that standardized indicators are used, such studies may be very useful for the analysis of innovative approaches to the diagnosis and treatment of methanol poisoning, and may provide information on developments in the field of poisoning management.
It should be noted, however, that bibliometric studies have certain limitations, since they do not take into account the quality of the reviewed publications .
The present study details the general diagnosis and treatment trends related to methanol poisoning researches. Despite the limitations of bibliometric studies, the present study can be argued to present a comprehensive picture of scientific studies of methanol poisoning.
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Animal and human rights statement
Conflict of interest
1. Rulisek J, Waldauf P, Belohlavek J, Balik M, Kotikova K, Hlusicka J, et al. Health-related quality of life determinants in survivors of a mass methanol poisoning outbreak: six-year prospective cohort study. Clinical Toxicology. 2020; 58(9):870-80.
2. Paasma R, Hovda KE, Tikkerberi A, Jacobsen D. Methanol mass poisoning in Estonia: Outbreak in 154 patients. Clinical Toxicology. 2007;45(2):152-7.
3. Zakharov S, Pelclova D, Urban P, Navratil T, Diblik P, Kuthan P, et al. Czech mass methanol outbreak 2012: Epidemiology, challenges and clinical features. Clinical Toxicology. 2014;52(10):1013-24.
4. Rostrup M, Edwards JK, Abukalish M, Ezzabi M, Some D, Ritter H, et al. The Methanol Poisoning Outbreaks in Libya 2013 and Kenya 2014. PLoS One. 2016;11(3):e0152676
5. Onyekwere N, Nwadiuto I, Maleghemi S, Maduka O, Numbere TW, Akpuh N, et al. Methanol poisoning in South-South Nigeria: Reflections on the outbreak response. The Journal of Public Health in Africa. 2018;9(1):49-53.
6. Senel E, Topal FE. Holistic Analysis of Coronavirus Literature: A Scientometric Study of the Global Publications Relevant to SARS-CoV-2 (COVID-19), MERS-CoV (MERS) and SARS-CoV (SARS). Disaster Medicine and Public Health Preparedness. 2020; 13:1-8.
7. Simani L, Ramezani M, Roozbeh M, Shadnia S, Pakdaman H. The outbreak of methanol intoxication during COVID-19 pandemic: prevalence of brain lesions and its predisposing factors. Drug Chem Toxicol. 2020; 1-4.
8. Gulen M, Satar S, Avci A, Acehan S, Orhan U, Nazik H. Methanol poisoning in Turkey: Two outbreaks, a single center experience. Alcohol. 2020; 88:83-90.
9. Delirrad M, Mohammadi AB. New Methanol Poisoning Outbreaks in Iran Following COVID-19 Pandemic. Alcohol Alcohol. 2020;55(4):347-8.
10. Aghababaeian H, Hamdanieh L, Ostadtaghizadeh A. Alcohol intake in an attempt to fight COVID-19: A medical myth in Iran. Alcohol. 2020;88:29-32.
11. Nikoo MH, Arjangzadeh A, PakfetratM, Boogar SS, Mohammadkarimi V, Ostovan VZ, et al. Electrocardiographic findings of methanol toxicity: A cross-sectional study of 356 cases in Iran. BMC Cardiovascular Disorders. 2020;20(1): 415
12. Şenel E. Evolution of homeopathy: A scientometric analysis of global homeopathy literature between 1975 and 2017. Complement Ther Clin Pract. 2019;34:165-73.
13. Shultz M. Comparing test searches in PubMed and Google Scholar. J Med Libr Assoc. 2007;95(4):442-5.
14. Johnson M, Cohen J, Grudzinskas G. The uses and abuses of bibliometrics. Reproductive Biomedicine Online. 2012, 24(5):485-6
Download attachments: 10.4328:ACAM.21020
Umut Payza, Engin Şenel, Fatih Esad Topal, Zeynep Karakaya, Mehmet Göktuğ Efgan. Scientometric analysis of methanol intoxication literature: Global publication output between 1980 and 2019. Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):548-553
Surgical treatment of displaced radial neck fractures in children with metaizeau technique: Late-term results
Hakan Koray Tosyalı 1, Sertan Hancıoğlu 1, Hüseyin Kaya 2, Güvenir Okçu 1, Kemal Aktuğlu 2
1 Department of Orthopedic and Traumatology, Faculty of Medicine, Celal Bayar University, Manisa, 2 Department of Emergency Medicine, Faculty of Medicine, Ege University, Izmir, Turkey
DOI: 10.4328/ACAM.21021 Received: 2021-12-23 Accepted: 2022-01-24 Published Online: 2022-02-02 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):554-557
Corresponding Author: Hakan Koray Tosyalı, Department of Orthopedic and Traumatology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey. E-mail: firstname.lastname@example.org / email@example.com P: +90 532 450 78 55 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1624-1912
Aim: In this study, we aimed to analyze the functional and radiological outcomes of displaced radial neck fractures in children treated with the Metaizeau technique .
Material and Methods: This was a retrospective study, and data were collected prospectively. Thirty-eight patients with grade III and grade IV radial neck fractures according to the classification of Judet et al were managed surgically by Metaizeau technique. All patients were surgically treated with percutaneous k-wire leverage reduction and retrograde transphyseal k-wire fixation. The functional results were evaluated using the Metaizeau functional scoring system. Clinical evaluation and results were performed using the Mayo elbow performance score (MEPS), ROM of the elbow (flexion, extension) and forearm (supination, pronation) was measured with a goniometer. Complications were also evaluated.
Results: The average follow-up time was 64.9 months (28 -120 months), there were no patients with nonunion, avascular necrosis, infection, posterior interosseous nerve (PIN) injury, heterotopic ossification or radioulnar synostosis. There were 31 (88.5 %) excellent or good results and 4 (11.5 %) fair results according to the Metaizeau classification. The final X-rays showed fracture healing in all patients. No patient developed complications.
Discussion: Intramedullary pinning, as described by Métaizeau, is a reliable and reproducible surgical method to treat radial neck fractures in children, which provides excellent or good results and has a low risk of complications. Level of evidence IV (case series and systematic review of level IV studies).
Keywords: Radial Neck Fracture, Pediatric Elbow Injury, Pediatric Trauma, Metaizeau Technique
Radial neck fractures, usually a result of a fall on an outstretched hand with an extended elbow, are rare and demanding problem in the pediatric population. The capitulum of the humerus strikes against the proximal radius, which may result in the occurrence of a fracture.
They account for about 1% of all pediatric fractures and about 5-10% of all pediatric elbow injuries .
Nondisplaced radial neck fractures and fractures with an angulation of less than 300, Judet I and II fractures can be treated with nonoperative management with cast immobilisation and will heal with good results . Radial neck fractures with angulations of more than 300, Judet III-IV fractures have a high risk of unacceptable outcomes when treated conservatively . In spite of an anatomical reduction during the operation, the results after open reduction were analyzed as moderate or worse. Open reduction has been associated with a high incidence of periarticular ossification, disruption of epiphyseal blood supply and avascular necrosis, early physeal closure, bleeding, nerve palsy, and the risk of radioulnar synostosis .
In order to avoid these undesired complications, Metaizeau described a technique which contained closed extracapsular reduction by intramedullary pinning . Intramedullary nailing with correct technique combines the advantage of closed reduction and stable internal fixation. The aim of this study was to analyze the functional and radiological outcomes of displaced radial neck fractures treated with the Metaizeau technique and to evaluate our late- term results .
Material and Methods
This was a retrospective study and data were collected prospectively. The study protocol was approved by University of Health Sciences, Izmir Bozyaka Education and Research Hospital Local Ethics Committee (No: 4 Date: 13.01.2015). Thirty-eight patients with grade III and grade IV radial neck fractures according to the classification of Judet et al were managed surgically using Metaizeau technique. According to the Judet classification, there are four types of fractures  (Table 1) (Figure 1).
All Judet grade I and II fractures and radial neck fractures associated with other injuries, previous elbow injury, and follow-up time shorter than 24 months were excluded from the study. The study was carried out during the period between June 2004 to January 2015 at two university-based centers. Three patients were lost to follow-up, the remaining 35 patients (15 male and 20 female) for analysis. All fractures were closed and had no vascular or neuronal injury. Between 2nd and 10th years after injury, patients returned for clinical and radiological assessments and also evaluation of elbow function.
The radiological result was graded as 4 category
1. excellent: the fracture healed anatomically
2. good: the fracture healed with less than 20 degree angulation
3. fair: the fracture healed with 20-40 degree angulation
4. poor: the final angulation was more than 40 degree
Patients with avascular necrosis were graded as a poor result
Functional results were evaluated using the Metaizeau functional scoring system (Table 2) . The loss of movement in any direction is the main subject of the Metaizeau functional scoring system. The result was graded as excellent, good, fair and poor.
Clinical evaluation and results were performed using the Mayo elbow performance score (MEPS), ROM of the elbow (flexion, extension) and forearm (supination, pronation) was measured with a goniometer. Mayo elbow performance score analyzes pain, joint stability, range of motion and patient’s function to undertake daily living activities (Table 3) .
Our operative technique used in this study was proposed by Métaizeau in 1980 (Figure 2) (7). A K-wire is contoured and the last 3mm are bent more sharply. All patients received general anesthesia and injured elbow was screened using a high-resolution image intensifier. Elbow was prepared and draped free using the image intensifier as the operating surface. An intravenous antibiotic (Cefazolin 1 g, Bilim ilaç) was given to all patients preoperatively. A 2 cm skin incision was made along the lateral border of the distal radius. After careful blunt dissection, protecting the superficial branch of the radial nerve and superficial veins, a bone awl or a 2.5-mm drill bit was used to penetrate the cortex, the entry point was marked 2 cm proximal to the physis.
A 1.5-2.0-mm K-wire, according to the patient’s size, in a T-handled chuck, was introduced into the medullary canal and then hammered gently upward until its tip reached the displaced epiphysis.
This was followed by turning the k-wire 180 degrees around its long axis in order to relocate the radial head. After the sharp point faces inwards, it produces a medial shift of the proximal fragment, decreases the translation and reduces it. After the reduction was gained, the end of the nail was cut and the skin was closed.
The elbow was immobilized with a long-arm cast for 2 -3 weeks. The elbow was mobilized after the removal of the cast. Flexion-extension ROM exercises were started firstly, and after 1 week, pronation-supination ROM exercises were started. Follow-up anteroposterior and lateral plain radiographs were taken 3 weeks and 6 weeks after nail removal, and thereafter at an interval of 3 months. The nail was removed at a mean time of 5 months postoperatively.
We treated a total of 38 patients with the Metaizeau technique during the period between 2004-2015 at two university-based centers. Three patients were lost to follow-up after surgery and were excluded from the study, remaining a total of 35 patients for analysis.
There were 15 girls and 20 boys with an average age of 9.1 ± 2.1 years ( 4 – 12 years ). The average follow-up time was 64.9 months (28 -120 months).
There were 15 grade 3 (50%), 10 grade 4A (16,6%) and 5 grade 4B (33,3%) fractures according to the Judet classification modified by Métaizeau , and no associated lesions.
At the latest follow-up, there were 31 (88.5 %) excellent or good results and 4 (11.5 %) fair results according to the Metaizeau classification. According to the Mayo Elbow Performance score, all elbows had excellent outcomes and ranged between 85-100 points (Mean 98). At final follow up there was an enlargement of the radial head and neck in nine patients and premature physeal closure in four patients. In spite of those findings, only three patients had fair results in this group. There were no patients with nonunion, avascular necrosis, infection, posterior interosseous nerve (PIN) injury, heterotopic ossification or radioulnar synostosis.
Treatment of pediatric radial neck fractures is not certain. Fractures with the angulation of less than 30 degrees can be treated conservatively, but the angulation of up to 30 degrees, especially Judet 3 and 4 fractures, require additional treatment with various methods .
In the literature, the age period for radial neck fracture is between 4 and 14 years [10,11]. This is clarified by the fragility of the cartilage of the epiphysis. Male to female ratio is 1:1 . The literature was similar to ours concerning the average age of patients and their gender. In our study, there were 15 girls and 20 boys, and the youngest child was 4 years, the oldest was 12 years old.
Some literature reported that radial neck fractures with an angulation up to 50° in children under the age of 10 had good results with conservative treatment , whereas other literature reported excellent results for surgically reducted and fixed radial neck fractures with an angulation over 30° . In our series, we operated every type 3 and 4 fractures in all cases.
Surgical options involve open or closed reduction and internal fixation with pins or screws. No matter how the reduction is good, there have been more complications in open management surgery. The technique of closed reduction and intramedullary pinning of radial neck fractures in the pediatric population was firstly described by Metaizeau . In the literature, Basmajian et al. reported that better outcomes are directly related with less invasive treatment methods .
Compared to closed reduction, open reduction has higher rates of premature epiphyseal fusion, elbow stiffness, overgrowth of the radius head, and heterotopic ossifications . Also, the blood supply of the radial epiphysis can lead to avascular necrosis of the radial head in open reduction [17,18] .
Some reports suggest that open surgery should only be exceptional, due to the high risk of devascularization [19-21].
Because of this, we do not prefer open reduction in our cases. In addition to our series, late complications were noted in 9 patients. Four patients had premature physeal closure and nine patients had an enlargement of the radial head. But none of the nine had a stiffness of the elbow. It shows that surgical option used is one of the provoked factors of the final functional range of motion. Like our study, some literature reported that the stiffness of the elbow is seen especially after open surgery reduction  and late treated fractures.
Apart from this, we had no radial head necrosis, nonunion, infection, posterior interosseous nerve (PIN) injury, heterotopic ossification or radioulnar synostosis during follow-up in our patients.
A variety of factors such as age, fracture severity and the treatment method are related to the outcome of treatment for pediatric radial neck fractures. However only one of them, the treatment method, can be directly chosen by the surgeon.
Intramedullary pinning, as described by Métaizeau, is a reliable and reproducible surgical method to treat radial neck fractures in children, which provides excellent or good results and has a low risk of complications. But we know that more serious fractures are usually treated with more aggressive methods and it may be related with complications.
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Animal and human rights statement
Conflict of interest
1. Prathapkumar KR, Garg NK, Bruce CE. Elastic stable intramedullary nail fixation for severely displaced fractures of the neck of the radius in children. J Bone Jt Surg Br. 2006;88:358e361
2. Tarallo L, Mugnai R, Fiacchi F, Capra F, Catani F. Management of displaced radial neck fractures in children: percutaneous pinning vs. elastic stable intramedullary nailing. J Orthop Traumatol. 2013;14(4):291-7.
3. Waters PM, Stewart SL. Radial neck fracture nonunion in children. J Pediatr Orthop. 2001; 21:570–6.
4. Qiao F, Jiang F. Closed reduction of severely displaced radial neck fractures in children. BMC Musculoskelet Disord. 2019;20(1):567.
5. Metaizeau JP. Reduction and osteosynthesis of radial neck fractures in children by centromedullary pinning. Injury. 2005;36(S):75–7.
6. Judet H, Judet J. Fractures and orthopedique de l’ enfant. Paris: Maloine; 1974: 31e39
7. Metaizeau JP, Prevot J, Schmitt M. Reduction and ﬁxation of fractures of the neck of the radius by centromedullary pinning. Original technique. Rev Chir Orthop Reparatrice Appar Mot. 1980; 66(1): 47–9.
8. Duckworth AD, Watson BS, Will EM, Petrisor BA, Walmsley PJ, Court-Brown CM, et al. Radial head and neck fractures: functional 294 results and predictors of outcome. J Trauma. 2011;71(3):643-8.
9. Falciglia F, Giordano M, Aulisa AG, Di Lazzaro A, Guzzanti V. Radial neck fractures in children: results when open reduction is indicated. J Pediatr Orthop. 2014;34(8):756-62.
10. Çevik N, Cansabuncu G, Akalin Y, Otuzbir A, Öztürk A, Özkan Y. Functional and radiological results of percutaneous K-wire aided Métaizeau technique in the treatment of displaced radial neck fractures in children. Acta Orthop Traumatol Turc. 2018;52(6): 428-34.
11. Canale ST. Fractures and dislocations in children. Philadelphia, PA: Campbell´s Oper Orthop Mosby/Elsevier; 2003. p. 1391-1420.
12. AlAubaidi Z, Pedersen NW, Nielsen KD. Radial neck fractures in children treated with the centromedullary Métaizeau technique. Injury. 2012;43 (3):301-5.
13. Trabelsi A, Khalifa MA, Brahem R, Jedidi M, Bouattour K, Osman W, et al. Radial neck fracture in children: anatomic and functional results of Metaizeau technique. Pan Afr Med J. 2020;36:144.
14. Tarallo L, Mugnai R, Fiacchi F, Capra F, Catani F. Management of displaced radial neck fractures in children: percutaneous pinning vs. elastic stable intramedullary nailing J Orthop Traumatol. 2013;14 (4): 291-7.
15. Basmajian HG, Choi PD, Huh K, Sankar WN, Wells L, Arkader A. Radial neck fractures in children: experience from two level-1 trauma centers. J Pediatr Orthop B. 2014;23(4):369-74.
16. Schmittenbecher PP, Haevernick B, Herold A, Knorr P, Schmid E. Treatment decision, method of osteosynthesis and outcome in radial neck fractures in children: a multicenter study. J Pediatr Orthop. 2005;25(1):45-50.
17. Hardman J, Al-Hadithy N, Hester T, Anakwe R. Systematic review of outcomes following fixed angle intramedullary fixation of distal radius fractures. Int Orthop. 2015;39(12):2381-7.
18. Guyonnet C, Martins A, Marengo L, Mansour M, Rousset M, Samba A, et al. Functional outcome of displaced radial head fractures in children treated by elastic stable intramedullary nailing J Pediatr Orthop B. 2018; 27:296-303.
19. Zimmerman RM, Kalish LA, Hresko MT, Waters PM, Bae DS. Surgical management of pediatric radial neck fractures J Bone Joint Surg Am. 2013; 95:1825-32.
20. Hemmer J, Happiette A, Muller F, Barbier D, Journeau P. Prognostic factors for intramedullary nailing in radial neck fracture in children. Orthopaedics & Traumatology: Surgery & Research. 2020; 106(7): 1287-91.
21. Stiefel D, Meuli M, Altermatt S. Fractures of the neck of the radius in children: early experience with intramedullary pinning. J Bone Jt Surg. 2001 1;83(4): 536-41
22. Cossio A, Cazzaniga C, Gridavilla G, Gallone D, Zatti G. Pediatric radial neck fractures: one-step percutaneous reduction and fixation. Injury. 2014; 45 (Suppl. 6): 80-4.
Download attachments: 10.4328:ACAM.21021
Hakan Koray Tosyalı, Sertan Hancıoğlu, Hüseyin Kaya, Güvenir Okçu, Kemal Aktuğlu. Surgical treatment of displaced radial neck fractures in children with metaizeau technique: Late-term results. Ann Clin Anal Med 2022;13(5):554-557
Optical coherence tomography findings in patients with beta thalassemia major
Cenk Zeki Fikret 1, Filiz Yildirim 2, Nil Irem Ucgun 3, Ozlem Evren Kemer 3
1 Department of Ophthalmology, Ankara City Hospital, 2 Clinic of Internal Medicine, Polatlı Duatepe Goverment Hospital, 3 Department of Ophthalmology, University of Health Sciences, Ankara City Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.21028 Received: 2021-12-27 Accepted: 2022-02-10 Published Online: 2022-02-28 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):558-562
Corresponding Author: Filiz Yildirim, Clinic of Internal Medicine, Polatlı Duatepe Goverment Hospital, Polatlı, 06900, Ankara, Turkey. E-mail: firstname.lastname@example.org P: +90 544 411 22 89 F: +90 312 243 10 12 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6151-2697
Aim: In this study, we aimed to evaluate macular ganglion cell layer + (GCL+), retinal nerve fiber layer (RNFL), choroidal thickness and Hood report pathologies with swept-source optical coherence tomography (SS-OCT) in beta-thalassemia major patients.
Material and Methods: Twenty-four eyes of 24 multi and regular blood transfused beta-thalassemia major patients on chelation therapy (thalassemic group) and age- and sex- matched 25 eyes of 25 healthy individuals (control group) were included in the study. Macular GCL+, peripapillary total RNFL, and subfoveal choroidal thickness measurements were obtained in patients with beta-thalassemia major. SS-OCT images were collected from Topcon DRI OCT Triton SS-OCT (Topcon, Tokyo, Japan). Glaucoma and Hood reports were derived from Rescan 3D(H)+Line(H) mode. Choroidal thickness was measured from macular radial mode.
Results: In the thalassemic group, the mean values were 74.00±7.18 µm for macular GCL+ thickness; 122.75±11.37 µm for total RNFL; 423.08±32.64 µm for choroidal thickness; 255.50±18.48 µm for macular thickness. In the control group, the mean values were 61.84±8.04 µm for macular GCL+ thickness; 108.88±4.98 µm for total RNFL; 323.00±26.94 µm for choroidal thickness; 249.12±17.07 µm for macular thickness. GCL+, total RNFL and choroidal thickness in the thalassemic group were significantly thicker than in the control group (p<0.001). There was no difference between the two groups in terms of macular thickness (p>0.05). There was a positive correlation between choroidal thickness and ferritin levels in the thalassemic group (r=0.630, p<0.01).
Discussion: RNFL and GCL+ values are important, but we must also review the Glaucoma and Hood reports on patients with beta thalassemia major to detect ocular involvement. Choroidal thickness measurements should also be performed in these patients. The positive correlation between ferritin levels and choroidal thickness in thalassemic patients suggests that ferritin levels may be effective in ocular findings.
Keywords: Thalassemia Major, GCL, RNFL, Choroidal Thickness, OCT
Beta-thalassemia is a hereditary blood disease with a beta chain synthesis anomaly of hemoglobin. Beta-thalassemia can either be asymptomatic or cause severe anemia. It is classified as Beta-thalassemia major, intermedia and minor. Beta-thalassemia major is also named “Cooley’s Anemia” and “Mediterranean Anemia”. Individuals with beta-thalassemia major are usually visible in the first two years of life. It progresses with severe anemia that requires regular red blood cell transfusion. Beta-thalassemia intermedia is a disease accompanied with milder anemia, rarely requiring red blood cell transfusion. Beta-thalassemia minor is observable in asymptomatic individuals who have the disease with mild anemia .
Beta-thalassemia can cause some ocular abnormalities as a result of anemia, blood transfusion, iron overload, and chelation therapy. Jafari et al.  detected ocular pathologies, including dry eye, cataract, color vision deficiency, visual field defects, and retinal pigment epithelium degeneration in thalassemic patients. Barteselli et al.  detected pseudoxanthoma elasticum-like (PXE-like) changes, which are peau d’orange, angioid streaks, pattern dystrophy-like changes, and optic disc drusen. It has been reported that increased retinal vascular tortuosity is a common finding in patients with beta-thalassemia major. Pigmentary degeneration occurs in the macula and peripheral retina secondary to desferrioxamine treatment used in patients with beta-thalassemia major. It has been reported that macular monitoring with fundus autofluorescence is useful in detecting desferrioxamine toxicity. Night blindness, visual field defects, deterioration in color vision, abnormal dark adaptation, and decreased visual acuity due to optic neuropathy have been reported after high doses of desferrioxamine treatment [4, 5].
Measurement of retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness by optical coherence tomography is important for the detection of optic nerve pathologies. Some authors have reported in the literature that RNFL thicknesses are thinning or not changing in Beta-thalassemia patients [6, 7].
It is frequently reported that visual loss of function and RNFL thinning are parallel. It is widely used to follow optic nerve pathologies with RNFL, but in diseases such as optic disc edema, RNFL can be measured thick despite thinning [8, 9]. Therefore, it is necessary to evaluate GCL and RNFL together and even Hood report to detect suspected optic nerve involvement in patients. In this study, we aimed to examine the changes at Hood report parameters in macular GCL+ and RNFL in patients with beta-thalassemia major.
Material and Methods
Ankara City Hospital Ethics Committee approval (E1-1321-2020) was obtained for this study, the tenets of the Declaration of Helsinki were observed.
All data were evaluated retrospectively. All individuals included in our study were examined between May 2019 and November 2021 in Ophthalmology Department.
Twenty-four eyes of 24 multi and regular blood transfused beta-thalassemia major patients Thalassemic group on chelation therapy (thalassemic group) and age and sex-matched 25 eyes of 25 healthy individuals (control group) were included in the study. Detailed ophthalmic examination and SS-OCT analyses were performed in all beta-thalassemia major patients and healthy individuals. SS-OCT images were collected from Topcon DRI OCT Triton, SS-OCT (Topcon, Tokyo, Japan). Glaucoma, Hood report were obtained from Rescan 3D(H)+Line(H) mode. Choroidal thickness was measured in macular radial mode. Macular GCL+ (GCL+ inner plexiform layer), peripapillary total RNFL and subfoveal choroidal thickness were analyzed in both group. GCL thickness and probability maps were acquired from macular cube scans. RNFL thickness and probability maps were obtained from disk cube scans.
The exclusion criteria were retinal abnormalities, optic disc disorders, cup/disc ratio abnormalities, intraocular pressure higher than 21 mmHg, neurological disease, myopia or hyperopia >3.0 diopters, corneal abnormalities, history of ocular surgery or ocular trauma.
Statistical analyses were performed using the program SPSS. An independent t-test and Mann-Whitney U test were used for statistical analysis of the data. A p -value less than 0.05 was considered statistically significant. The quantitative data were presented as mean± standard deviation (SD). Pearson’s correlation test was utilized to evaluate the relationship between the data.
The mean age was 24.42±4.60 (18-38) years in beta-thalassemia major patients, and 25.44±5.08 (19-37) years in healthy individuals (p=0.464). There were 15 females and 9 males in the thalassemic group, and 14 females and 11 males in the control group (p=0.664). There was no difference between the two groups in terms of gender and age.
Intraocular pressure in the thalassemic group was 15.08±2.16 (11-18) and 15.04±2.09 (11-19) mmHg (p=0.943) in the control group.
GCL+, total RNFL and choroidal thickness in the thalassemic group were significantly thicker than in the control group (p<0.05). Table 1 shows macular GCL+, RNFL, macular and choroidal thickness measurements, IOP, ferritin and hemoglobin levels (mean±SD) in both groups.
RNFL thickness and GCL+ Macula 6 Sector Grid thickness increased in 62.5% of our patients as observed in Patient A. There is also extreme thickening in GCL+ thickness (retinal view) in the Hood report (Figure 1). We named this view ‘super normal GCL’. No retinal or optic nerve pathologies such as macular edema or vitreomacular traction syndrome were found in these patients to explain this view.
In 37.5% of our beta-thalassemia major patients, as in Patient B, RNFL and GCL+ Macula 6 Sector Grid thickness measurements were consistent with their age. Hood reports of these patients showed thinning at GCL+ thickness (Retinal view) (Figure 2). We named this view ‘unsurprisingly GCL’, because this appearance was as described in the literature for beta-thalassemia major patients.
Serum ferritin levels were 1570.12±253.57 ng/mL and hemoglobin levels were 9.86±1.06 (gr/dL) in the patients with beta-thalassemia major.
All patients with beta-thalassemia major were receiving deferoxamine therapy as chelating agents.
Serum ferritin levels were 102.52±39.87 ng/mL and hemoglobin levels were 13.64±0.78 (gr/dL) in the control group. Ferritin levels were higher in the thalassemic group (p<0.001) and hemoglobin levels were higher in the control group (p<0.001).
A positive correlation was found between choroidal thickness and ferritin levels in the thalassemic group (r=0.630, p<0.01), (Figure 3). A negative correlation was found between choroidal thickness and age in both groups (p<0.05).
There was no correlation between serum ferritin levels and RNFL, GCL+, macular thickness in beta-thalassemia major patients.
In this study, we found that total RNFL, GCL+ and choroidal thickness were significantly thicker in patients with beta-thalassemia major compared to the control group. There was a positive correlation between choroidal thickness and ferritin levels in the thalassemic group.
Ulusoy et al.  did not find any difference between beta-thalassemia major patients and the control group when they measured RNFL and GCL+ thicknesses with spectral domain OCT. They found that choroidal thickness is significantly thinner in patients with beta-thalassemia major. Some authors found thinner RNFL measurements in children with beta-thalassemia major. They also reported a correlation between RNFL thickness and serum ferritin and hemoglobin levels in thalassemic patients [6, 11].
There are studies reporting choroidal thinning in pediatric thalassemic patients [12, 13]. Reinera et al.  investigated that blood pressure and blood volume signals can trigger parasympathetic vasodilation of the choroidal vasculature. This may be the reason why we measure the choroid thicker in patients with beta-thalassemia major.
Ocular involvement occurs in up to 85% of thalassemic patients. Retina is the most commonly affected ocular tissue. These patients receive blood transfusions as a result of severe anemia. Repeated transfusions are the cause of siderosis. Iron accumulates in the retinal pigment epithelium (RPE) and causes an increase in oxidative stress. Retinal findings are observed as degeneration of the RPE, retinal venous blood engorgement, an increase in vascular tortuosity and angioid lines. It is difficult to differentiate the etiology because similar retinal findings occur due to chelation therapy [15-18].
Disc hyperemia (12.5%) and an increase in cup-disc ratio (37.5%) are seen in thalassemic patients. Optic atrophy has been reported as a probability of 17.5%. A correlation between the cup-disc ratio and serum ferritin and hemoglobin levels has been reported in thalassemic patients [15-18]. While decreased a-wave amplitude was detected in electroretinograms of these patients, no pathology was found in the visual evoked potential (VEP) response .
Negi et al.  found that VEP values in children with thalassemia were not different from the control group. However, upon detailed examination of the patients, abnormalities were found in VEP examinations in patients with high serum ferritin levels. It has been reported that these patients may have subclinical optic sensory neuropathy. They reported that optic neuropathy seen in thalassemia patients should not always be considered as neurotoxicity to deferoxamine.
Ocular manifestations of desferrioxamine toxicity include RPE pigment changes, night blindness, centrochecal scotoma, peripheral visual field narrowing, optic disc edema, optic neuropathy and optic atrophy. Most of the ocular changes depend on the severity of thalassemia. To prevent ocular complications, it may be beneficial to lower serum iron and ferritin levels with iron-chelating agents [4, 21, 22].
The limitation of this study is that it cannot be determined whether ocular involvement is associated with the disease or iron chelating agents. The exact cause of the increases in total
RNFL and GCL+ thickness in the thalassemic group cannot be distinguished. It is necessary to measure the RNFL and GCL+ values of each patient, however, we can learn more about the patient’s condition by examining glaucoma and Hood reports. It is also important to examine the GCL+ thickness (Retinal view) in the Hood reports of these patients and the GCL+ Macula 6 Sector Grid thickness in the glaucoma report. In addition, RNFL and GCL+ probability views also facilitate diagnosis. Therefore, it is recommended that RNFL and GCL+ measurements should be performed periodically in patients with beta-thalassemia major for early diagnosis and treatment.
The main finding in our study is the positive correlation between choroidal thickness and ferritin levels. Increases in choroidal thickness in the thalassemic group may be secondary to
inflammation caused by increased ferritin levels. Keeping ferritin levels under control in patients with thalassemia is also important in terms of preventing ocular involvement.
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Animal and human rights statement
Conflict of interest
1. Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis. 2010; 5: 11.
2. Jafari R, Heydarian S, Karami H, Shektaei MM, Dailami KN, Amiri AA, et al. Ocular abnormalities in multi-transfused beta-thalassemia patients. Indian J Ophthalmol. 2015; 63(9): 710-5.
3. Barteselli G, Dell’arti L, Finger RP, Charbel Issa P, Marcon A, Vezzola D, et al. The spectrum of ocular alterations in patients with beta-thalassemia syndromes suggests a pathology similar to pseudoxanthoma elasticum. Ophthalmology. 2014; 121(3): 709-18.
4. Liaska A, Petrou P, Georgakopoulos CD, Diamanti R, Papaconstantinou D, Kanakis MG, et al. β-Thalassemia and ocular implications: a systematic review. BMC Ophthalmol. 2016; 16: 102.
5. Heydarian S, Jafari R, Dailami KN, Hashemi H, Jafarzadehpour E, Heirani M, et al. Ocular abnormalities in beta thalassemia patients: prevalence, impact, and management strategies. Int Ophthalmol. 2020; 40: 511-27.
6. Uzun F, Karaca EE, Yerlikaya GY, Fındık H, Akın M. Retinal nerve fiber layer thickness in children with beta-thalassemia major. Saudi J Ophthalmol. 2017; 31: 224-8.
7. Acer S, Balcı YI, Pekel G, Ongun TT, Polat A, Çetin EN, et al. Retinal nerve fiber layer thickness and retinal vessel calibers in children with thalassemia minor retinal nerve fiber layer thickness and retinal vessel calibers in children with thalassemia minor. SAGE Open Med. 2016; 4: 1-5.
8. Hood DC, De Cuir N, Blumberg DM, Liebmann JM, Jarukasetphon R, Ritch R, et al. A single wide-field OCT protocol can provide compelling information for the diagnosis of early glaucoma. Trans Vis Sci Tech. 2016; 5: 1-15.
9. Kardon R. The role of the macula OCT scan in neuro-ophthalmology. J Neuroophthalmol. 2011; 31(4): 353-61.
10. Ulusoy MO, Turk H, Kıvanç SA. Spectral domain optical coherence tomography findings in Turkish sickle-cell disease and beta thalassemia major patients. J Curr Ophthalmol. 2019; 31(3): 275-80.
11. Aksoy A, Aslan L, Aslankurt M, Eser O, Garipardic M, Okumus S, et al. Retinal fiber layer thickness in children with thalassemia major and iron deficiency anemia. Semin Ophthalmol. 2014; 29(1): 22-6.
12. El-Shazly AAEF, Elkitkat RS, Ebeid WM, Deghedy MR. Correlation between subfoveal choroidal thickness and foveal thickness in thalassemic patients. Retina. 2016; 36: 1767-72.
13. Atifoglu HB, Kucuk B, Duru N, Altunel O, Gulhan A, Ozen M, et al. Assessing posterior ocular structures in β-thalassemia minor. Int Ophthalmol. 2018; 38: 119-25.
14. Reinera A, Fitzgeralda MEC, Del Mar N, Chunyan L. Neural control of choroidal blood flow. Prog Retin Eye Res. 2018; 64: 96-130.
15. Abdel-Malak DSM, Dabbous OAE, Saif MYS, Saif ATS. Ocular manifestations in children with β thalassemia major and visual toxicity of iron chelating agents. J Am Sci. 2012; 8: 633-7.
16. Kumble D, Sekhon PK, Devi CG. Ocular involvement in beta thalassemia major: a prospective study in an Indian cohort. Int J Contemp Pediatr. 2017; 4: 780-2.
17. Saifa AT, Saif PS, Dabous O. Fundus changes in thalassemia in Egyptian patients. Delta J Ophthalmol. 2017; 18: 20-5.
18. Bhoiwala DL, Dunaief JL. Retinal abnormalities in β-thalassemia major. Surv Ophthalmol. 2016; 61(1): 33-50.
19. Dettoraki M, Kattamis A, Ladas I, Maragkos K. Electrophysiological assessment for early detection of retinal dysfunction in β-thalassemia major patients. Graefes Arch Clin Exp Ophthalmol. 2017; 255(7):1349-58.
20. Negi B, Bhardwaj P, Sharma S, Sharma M, Thakur P. Visual evoked potential in children with thalassemia. Int J Res Rev. 2020; 7: 439-42.
21. Lakhanpal V, Schocket SS, Jiji R. Deferoxamine (Desferal)-induced toxic retinal pigmentary degeneration and presumed optic neuropathy. Ophthalmology. 1984; 91(5): 443-51.
22. Di Nicola M, Barteselli G, Dell’Arti L, Ratiglia R, Viola F. Functional and structural abnormalities in deferoxamine retinopathy: A review of the literature. Biomed Res Int. 2015; 2015: 24961.
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Cenk Zeki Fikret, Filiz Yildirim, Nil Irem Ucgun, Ozlem Evren Kemer. Optical coherence tomography findings in patients with beta thalassemia major. Ann Clin Anal Med 2022;13(5):558-562
Efficacy of a home exercise program on balance, kinesiophobia, pain and quality of life in post-COVID-19 patients
Aysun Özlü, Fatıma Yaman, Merve Akdeniz Leblebicier, Dilan Bulut Özkaya
Department of Physical Medicine and Rehabilitation, Kutahya Health Science University, Kutahya, Turkey
DOI: 10.4328/ACAM.21033 Received: 2021-12-30 Accepted: 2022-02-02 Published Online: Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):563-567
Corresponding Author: Aysun Özlü, Kütahya Sağlık Bilimleri Üniversitesi, Kütahya, Türkiye. E-mail: email@example.com P: +90 505 398 94 44 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1912-6039
Aim: In this study, we aimed to determine the effects of a home exercise program on patients who treated for COVID-19 in the pandemic ward.
Material and Methods: In this randomized, clinical, single-blinded, controlled study, 82 patients who were discharged after completing their COVID-19 treatment were included in the study, and demographic data were recorded by dividing them into two groups as experimental (n=42) and control (n=40). Joint range of motion (ROM) and balance exercises were recommended for the experimental group as a home exercise program, while the control group did not receive any intervention. The home exercise program was implemented 5 days a week for 4 weeks. All the patients were evaluated in terms of quality of life (Nottingham Health Profile (NHP)), kinesiophobia (Tampa Scale of Kinesiophobia), balance (Berg Balance Scale), pain (Visual Analog Scale) before and after the intervention.
Results: In both groups, a statistically significant difference was observed in the quality of life, balance and pain levels after the intervention (p<0.05). After the intervention, there was a statistically significant improvement in kinesiophobia in the experimental group (p<0.05), no statistically significant difference was found in kinesiophobia in the control group (p<0.05). In the comparison between the groups after intervention, a statistically significant difference was observed in terms of quality of life (NHP part 2), kinesiophobia, balance, with the results being in favor of the experimental group.
Discussion: ROM and balance exercises for post-COVID-19 patients at the time of discharge are effective in improving quality of life, balance and kinesiophobia, but their effects on pain remain unclear.
Keywords: Home Exercise Program, Balance, Kinesiophobia, COVID-19
Coronaviruses (CoVs) are a large group of viruses, which cause a variety of diseases ranging from the common cold to more serious clinical conditions, such as severe respiratory syndromes . Since it was declared a global pandemic, the most important issue with a kind of Coronavirus named COVID-19 has been its high rate of transmission, infecting millions of people worldwide and causing mortality in some cases. In addition to mild symptoms, such as fever, dry cough, and fatigue, approximately 80% of patients develop respiratory distress or respiratory failure symptoms and require hospitalization or intensive care .
Patients who stay in the inpatient ward for a long time have limited mobility in terms of exercise and endurance, which creates many problems. Studies have shown that appropriately structured, guided and supervised physical exercise programs have positive effects on the course of the disease by affecting the patient’s inflammatory state through the recovery of antioxidant defenses . In studies conducted in the literature, exercise prescriptions, including rehabilitation (e.g., joint range of motion exercises) and pulmonary exercises after COVID-19, have been conducted to have positive effects on the endurance of respiratory and cardiovascular systems and quality of life of patients . In hospitalized patients, regardless of the reasons for hospitalization, immobility causes disruption in the balance components (weakness in the lower extremities, grip problems, and falls) . In this respect, individuals infected with COVID-19 are also at risk of having balance problems. Kinesiophobia is defined as the fear of movement and is especially seen in diseases that require long-term hospitalization, present with balance problems or affect the musculoskeletal system . It has been predicted that patients may have problems in moving and returning to work after a history of hospitalization due to COVID-19.
So that, this study is the first study in the literature to examine the effects of such a home exercise program on balance, kinesiophobia, pain and quality of life of post-COVID-19 patients.
Material and Methods
Ethics Committee Approval was received on December 30, 2020 with the decision number 2020-08/06.
This randomized, clinical, single-blinded, controlled study was initially planned to include 90 patients who had been admitted to the pandemic ward of Physical Medicine and Rehabilitation Hospital with a diagnosis of COVID-19, completed their treatment, and were ready to be discharged. However, 4 patients did not meet the inclusion criteria, 4 did not attend their follow-up evaluation; therefore, the study was completed with 82 patients. All the patients included in the study received inpatient intervention for 14-21 days. None of the patients received intervention in the intensive care unit. The inclusion criteria were age 18-65 years, hospitalization in the pandemic ward due to moderate and severe COVID-19 pneumonia, and having completed COVID-19 treatment, oxygen saturation of over 95% at the time of discharge.
1. Diagnosis of advanced cardiac or lung disease for which exercise would be contraindicated
2. Presence of a cognitive disorder, receiving psychotherapy or any psychiatric treatment, ф disease affecting the central nervous system
3. Being illiterate
4. Having hearing, vision problems and vertigo or a disease that can cause vertigo
5. Inadequate function of any extremity that would prevent exercise
6. The presence of a balance disorder or a disease that can disrupt the balance (Parkinson’s disease, a disease with cerebellum involvement, etc.)
The patients were randomized into two groups using the computer-assisted randomization method. The first group was prescribed a home exercise program, the second group was only followed up. All the patients were evaluated with the Nottingham Health Profile (NHP), Tampa Scale of Kinesiophobia (TSK), Berg Balance Scale (BBS), and Visual Analog Scale (VAS)-pain before the intervention and at the fourth week of intervention.
Range of motion (ROM) exercises for the neck, shoulder, elbow, wrist, and fingers in the upper extremity, and the waist, hip, knee, ankle and toes in the lower extremity and balance exercises were planned as single leg stance, tandem standing stance, tandem walking, and sit-up exercises (available at: https://www.tftr.org.tr/uploads/Sokaga-cikma-yasagi-spor-yapmaya-engel-degil.pdf). These exercises were performed 5 days a week for a total of 4 weeks (totally 10 times each exercises). If patients had any complaint, such as pain, nausea, dizziness, chest pain, and palpitations during the exercise, they were asked to terminate the exercise and inform the responsible researcher. The continuity of the exercises was checked by the responsible physician by phone call every week. Written brochures were also given to the experimental group, and they were asked to mark the days when they did the prescribed exercises.
All the patients provided written consent and filled in a demographic form, including questions on gender, age, smoking, chronic disease, physical activity, experienced fatigue, and had musculoskeletal pain after the diagnosis of COVID-19.
On a 10-point VAS scale, with 0 representing no pain and 10 representing very severe pain, all responses were recorded.
NHP consists of two parts. In the first part, a total of 38 items were scored based on yes-no questions presented under six subscales, namely pain, sensory reactions, sleep, social isolation, physical activity and energy (totally min=0, max= 600). In the second part, 7 questions assess whether the disease affects the individual’s paid work, housework, social life, relationship with other people, sexual life, hobbies, holidays (min=0, max=7). The validity and reliability studies of the Turkish version have been previously undertaken .
TSK consists of 17 items, each scored from 1 (strongly disagree) to 4 (strongly agree). (min=17, max= 68) The validity and reliability of the Turkish version of this scale have been previously confirmed .
BBS consists of a total of 14 items and instructions to follow for each item. Each item is scored from 0 to 4 (min=0, max=56). The Turkish validity and reliability of BBS have been previously established .
tatistical analyses were performed using the IBM SPSS Statistics v. 24.0. Frequency tables and descriptive statistics were used. The conformity of the variables to the normal distribution was examined using visual (histogram and probability graphs) and analytical (Shapiro-Wilk test) methods. In accordance with normal distribution parametric methods, the independent-samples t-test (Z-table value) was used to compare the measurement values of the two independent groups. The significance of p-value was accepted as p < 0.05 in all statistics. In the power analysis via G*Power software v. 220.127.116.11. sampling calculation, the required sample size was obtained as 28 patients by taking the alpha value (p) as 0.05 and power as 95% .
Demographic data and pre-intervention analysis are given in Table 1. There was no statistically significant difference between the groups (p > 0.05).
The post-intervention versus pre-intervention assessment revealed a statistically significant difference in the NPH part 1 and 2, TSK, BBS and VAS scores in the experimental group (p<0.01). In the control group, there was a statistically significant difference in all these parameters except for the TSK score in the post- intervention evaluation (p> 0.05) (Table 2).
In the comparison between the groups after intervention, there was a statistically significant difference in terms of the NHP part 2, TSK and BBS scores, and this significance was in favor of the experimental group. However, no significant difference was observed between the two groups in terms of their post- intervention NHP part 1 and VAS scores (Table 3) (p > 0.05).
In this study, a significant improvement was found in both groups in terms of quality of life, balance and pain levels in the pre- intervention and post- intervention evaluations, while the improvement in kinesiophobia was significant only in the experimental group. In post-intervention comparisons between the groups, a statistically significant difference was observed in the NHP part 2, TSK and BBS scores in favor of the experimental group.
In the literature, many patients discharged from the hospital after COVID-19 intervention are reported to have deteriorated respiratory function, decreased exercise capacity, reduced muscle strength, activity restrictions, and impaired quality of life, and this process can last up to six months [11-15]. In addition, in a previous study evaluating 280 patients who were discharged, 61.4% of these patients complained of decreased activity, and their needs were reported as exercise, diet regulation, and traditional Chinese medicine practices in order of frequency .
When patients discharged from the hospital after COVID-19 pneumonia treatment were examined, even after six weeks, there was still a significant impairment in the quality of life parameters (except pain), evaluated with the Short Form-36 questionnaire . Consistently, in the current study, after implementing the home exercise program, the experimental group was found to have significantly improved NHP part 2 scores, which focus on areas of life commonly affected by health.
In a review on exercise program approaches, breathing, aerobic, strengthening and balance exercises were recommended as part of rehabilitation . In light of this suggestion, we included exercises program and observed more positive results in the quality of life, balance and kinesiophobia parameters in the exercises group.
To our knowledge, this is the first study to evaluate COVID-19-related kinesiophobia. In a previous study examining kinesiophobia with chronic obstructive pulmonary disease, the rate of kinesiophobia was found to be significantly higher in patients with chronic obstructive pulmonary disease compared to healthy volunteers. The authors predicted that kinesiophobia might be associated with dyspnea, fatigue, and chronic diseases . Similarly, in the current study, there was a significant improvement in the kinesiophobia values in the experimental group after the intervention, both compared to the control group and pre- intervention values.
In this study, balance exercises undertaken at home provided improvement in the BBS score; i.e., balance parameters, which is in agreement with the literature. In a study including 25 patients who had received COVID-19 intervention, 25 patients with acute exacerbation of chronic obstructive pulmonary disease and 25 healthy volunteers, it was determined that the static and dynamic balance parameters of the patients with a COVID-19 diagnosis were worse compared to the healthy volunteers .
Although we detected an improvement in both groups in terms of pain parameters compared to the initial parameters, neither group had a significant advantage over the other. In the literature, the incidence of headache is reported to increase in patients who have had COVID-19, which has resulted in the coining of the term ‘new daily persistent headache’ . In 143 patients who were evaluated 60.3 days after the first symptom of COVID-19, joints and chest were determined to be the most common areas of pain . However, there is a need for further studies involving more patient groups to reveal the causes of pain areas in patients after the COVID-19 infection.
As there is an improvement in the natural course of every disease, in the current study, an improvement was observed in the quality of life, balance and pain parameters compared to the initial parameters also in the control group. However, in the literature, it has been suggested that elderly patients with hypertension, chronic obstructive pulmonary disease, diabetes and other chronic diseases are at higher risk, and the course of comorbidities is more severe in these patients with COVID-19 . Further studies are needed to clearly reveal the factors affecting recovery.
The limitations of this study are that the localization of pain was not questioned and the type of chronic disease was not specified.
Significant improvement was found in both groups in terms of quality of life, balance, and pain levels in the post- intervention evaluation compared to the pre- intervention evaluation. However, the improvement in kinesiophobia was only significant in the experimental group. In post-intervention comparisons between the groups, a significant difference was observed in the NHP part 2, TSK and BBS scores in favor of the experimental group. The improvements in the quality of life, kinesiophobia and balance parameters of the experimental group compared to the control group are very important in terms of clearly revealing the factors affecting recovery after COVID-19 disease.
Scientiﬁc Responsibility Statement
Animal and human rights statement
Conflict of interest
1. Xu J, Zhao S, Teng T, Abdalla AE, Zhu W, Xie L, et al. Systematic comparison of two animalto-human transmitted human coronaviruses: SARS-CoV-2 and SARS-CoV. Viruses. 2020;12(2):244.
2. Kamal M, Abo Omirah M, Hussein A, Saeed H. Assessment and characterisation of post-COVID-19 manifestations. Int J Clin Pract. 2021;75(3):13746.
3. Bektas A, Schurman S.H, Franceschi C, Ferrucci L. A public health perspective of aging: Do hyper-inflammatory syndromes such as COVID-19, SARS, ARDS, cytokine storm syndrome, and post-ICU syndrome accelerate short- and long-term inflammaging? Immun. Ageing. 2020;17(23):1-10.
4. Gu R, Xu S, Li Z, Gu Y, Sun Z. The safety and effectiveness of rehabilitation exercises on COVID-19 patients: A protocol for systematic review and meta-analysis. Medicine (Baltimore). 2020;31;99(31):1-5.
5. Uz TS, Razak ÖA, Erdençler DS. The Effect Of Risk Factors For Falls on Activities of Daily Living and Quality of Life in Geriatric Patients. Turk J of Geriatrics. 2011;14(3):245-52.
6. Begümhan T, Usgu G, Usgu S, Çınar MA, Dinler E, Kocamaz D. Investigation of Kinesiophobia, State and Trait Anxiety Levels in Patients with Lower Extremity Ligament Injury or Fracture History. Turk J Sports Med. 2019;54(3):175-82.
7. Kücükdeveci AA, McKenna SP, Kutlay S, Gürsel Y, Whalley D, Arasil T. The development and psychometric assessment of the Turkish version of the Nottingham Health Profile. Inter J of Rehab Res. 2000;23(1):31-8.
8. Yilmaz ÖT, Yakut Y, Uygur F, Ulug N. Tampa Kinezyofobi Ölçeği’nin Türkçe versiyonu ve test-tekrar test güvenirliği. Turk J Phys Med Rehab. 2011;22(1):44-9.
9. Şahin F, Büyükavcı R, Sağ S, Doğu B, Kuran B. Berg Denge Ölçeği’nin Türkçe Versiyonunun İnmeli Hastalarda Geçerlilik ve Güvenilirliği (Validity and Reliability of the Turkish Version of the Berg Balance Scale in Stroke Patients). Turk J Phys Med Rehab 2013;59:170-5.
10. Olezene CS, Hansen E, Steere HK, Giacino JT, Polich GR, Borg-Stein J, et al. Functional outcomes in the inpatient rehabilitation setting following severe COVID-19 infection. PLoS One. 2021;16(3):1-8.
11. Huang C, Huang L, Wang Y, Li X, Ren L, Gu X, et al. 6-Month consequences of COVID-19 in patients discharged from Hospital: a cohort study. Lancet. 2021;397(10270):220–32.
12. Lopez-Leon S, Wegman-Ostrosky T, Perelman C, Sepulveda R, Rebolledo P, Cuapio A, et al. More than 50 long-term effects of COVID-19: a systematic review and meta-analysis. medRxiv. 2021;1:1-14.
13. Belli S, Balbi B, Prince I, Cattaneo D, Masocco F, Zaccaria S, et al. Low physical functioning and impaired performance of activities of daily life in COVID-19 patients who survived hospitalisation. Eur Respir J. 2020;56(4):1-4.
14. Paneroni M, Simonelli C, Saleri M, Bertacchini L, Venturelli M, Troosters T, et al. Muscle strength and physical performance in patients without previous disabilities recovering from COVID-19 pneumonia. Am J Phys Med Rehabil. 2021;100:105–9.
15. Zhu S, Gao Q, Yang L, Yang Y, Xia W, Cai X, et al. Prevalence and risk factors of disability and anxiety in a retrospective cohort of 432 survivors of coronavirus Disease-2019 (Covid-19) from China. PLoS One. 2020;15(12):1-17.
16. Li Z, Zheng C, Duan C, Zhang Y, Li Q, Dou Z, et al. Rehabilitation needs of the first cohort of post-acute COVID-19 patients in Hubei, China. Eur J Phys Rehabil Med. 2020;56(3):339–44.
17. Van der Sar-van der Brugge S, Talman S, Boonman-de Winter L, De Mol M, Hoefman E, van Etten RW, et al. Pulmonary function and health-related quality of life after COVID-19 pneumonia. Respir Med. 2021;176:1-4.
18. Demeco A, Marotta N, Barletta M, Pino I, Marinaro C, Petraroli A, et al. Rehabilitation of patients post-COVID-19 infection: a literature review. J Int Med Res. 2020;48(8):1-10.
19. Vardar-Yagli N, Calik-Kutukcu E, Saglam M, Inal-Ince D, Arikan H, Coplu L. The relationship between fear of movement, pain and fatigue severity, dyspnea level and comorbidities in patients with chronic obstructive pulmonary disease. Disabil Rehabil. 2019;41(18):2159-163.
20. Giardini M, Arcolin I, Guglielmetti S, Godi M, Capelli A, Corna S. Balance performance in patients with post-acute COVID-19 compared to patients with an acute exacerbation of chronic obstructive pulmonary disease and healthy subjects. Int J Rehabil Res. 2021:1-6.
21. Liu JWTW, de Luca RD, Mello Neto HO, Barcellos I. Post-COVID-19 Syndrome? New daily persistent headache in the aftermath of COVID-19. Arq Neuropsiquiatr. 2020;78(11):753-4.
22. Carfì A, Bernabei R, Landi F. Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020;11;324(6):603-5.
23. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020;17;323(11):1061-9.
Download attachments: 10.4328:ACAM.21033
Aysun Özlü, Fatıma Yaman, Merve Akdeniz Leblebicier, Dilan Bulut Özkaya. Efficacy of a home exercise program on balance, kinesiophobia, pain and quality of life in post-Covid-19 patients. Ann Clin Anal Med 2022;13(5):563-567
COVID-19 in pediatric patients: Data from a training and research hospital
Emine Yurdakul Erturk 1, Ozden Aksu Sayman 1, Onur Yalcin 2
1 Department of Pediatrics, 2 Department of Pediatric Surgery, Ordu University, Training and Research Hospital, Ordu, Turkey
DOI: 10.4328/ACAM.21038 Received: 2022-01-01 Accepted: 2022-02-03 Published Online: 2022-02-10 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):568-572
Corresponding Author: Emine Yurdakul Erturk, Department of Pediatrics, Faculty of Medicine, Ordu University, 52200, Altınordu, Ordu, Turkey. E-mail: firstname.lastname@example.org P: +90 505 389 27 71 F: +90 452 226 52 28 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5366-647X
Aim: Coronavirus Disease-19 (COVID-19), caused by severe acute syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide emergency. It is known that the course of the disease in pediatric COVID-19 is milder, with a better prognosis and lower rate of deaths. However, epidemiological and clinical data on children with COVID-19 are still scarce. The aim of this study is to describe the demographic, clinical and laboratory findings of children with COVID-19.
Material and Methods: Medical records of patients aged under 18 years who had polymerase chain reaction (PCR) test for SARS-CoV-2 between March 15, 2020 and September 14, 2020 were examined retrospectively.
Results: Of the 108 children infected with SARS-CoV-2, 52 (48.1%) were female, 56 (51.9%) were male, and the median age was 9 years (0-17 years). The most common presentation symptoms included fever (54.6%), fatigue or myalgia (32.4%), and cough (30.5%). Of all patients, 63.9% (n=53) had lymphopenia. Seventy (67.3%) cases with COVID-19 had a contact history. The median time from symptom onset to diagnosis was 1 (0-8) day. Posteroanterior chest X-ray was ordered in 80.5% (n=87) of the SARS-CoV-2 PCR positive patients, and only 5.7% (n=5) had findings in favor of infiltration. Chest computed tomography was ordered in four (3.7%) children, and one (25%) of them had findings consistent with COVID-19. Eight patients were hospitalized, one of whom was followed-up in the intensive care unit, and no patients died.
Discussion: A better understanding of the clinical and laboratory characteristics of COVID-19 infection in children is very important in developing influential strategies to manage the disease.
Keywords: Children, COVID-19, SARS-CoV-2
COVID-19, which has become the first epidemic of the 21st century, can be seen in all age groups, mostly adults. The initial data from China at the beginning of the epidemic showed that children younger than the age of 18 accounted for only 2.4% of all reported cases . In the early days of COVID-19 epidemic, it has been suggested that children were not susceptible to COVID-19 infection; however, later it became clear that children could also become infected with COVID-19, although less frequently . The largest cohort study on the characteristics of laboratory confirmed COVID-19 in European children showed that the disease was most prevalent in children <1 year of age . However, data reanalyzed in China, indicated that children represent 12% of the cases . As of June 2021, 12.4% of all cases in the United States of America were children, and the incidence of the disease in children has increased approximately 7.5 times when compared with the previous year (available at : https://www.cdc.gov/mmwr/volumes/69/wr/mm6914e4.htm).
The number of people infected by the virus is increasing globally day by day, and according to the WHO as of June 10, 2021, the number of cases worldwide was 174.061.995, while 3.758.560 people died (available at: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports).
Although children are susceptible to SARS-CoV-2 infection, rather than the potential effects of the infection on this group, it was focused on their potential roles to prevent community transmission . The view that COVID-19 has a mild course on children is also common; although the reasons for this are not fully established, several theories have been proposed, including thymic function in children, immune system differences such as cross-reactive immunity against common cold coronaviruses and the differences in the expression of angiotensin-converting enzyme-2 (ACE2), which is the entry receptor of the virus . However, this view has also been questioned recently due to the reports of children who presented with a very severe hyperinflammatory syndrome called multisystem inflammatory syndrome in children (MIS-C) . Although the number of children affected by COVID 19 has increased, data relating the situation in children are still limited .
The aim of this study was to report the findings obtained from pediatric patients evaluated with a suspicion of COVID-19 in a training and research hospital in the North of Turkey.
Material and Methods
In this descriptive study, medical records of pediatric patients aged under 18 years who were evaluated with a pre-diagnosis of COVID-19 in the pediatrics clinic of our hospital between March 15, 2020 and September 14, 2020 were examined retrospectively. Ethics approval was received from the Clinical Researches Ethics Committee of our hospital (Date: 28/04/2020, Number: 139).
In line with the guideline prepared by the Coronavirus Scientific Advisory Board in Turkey on SARS-CoV-2, suspicious cases were diagnosed and evaluated. Combined naso-oropharyngeal swabs were taken for the reverse transcriptase-polymerase chain reaction (RT-PCR) test from the patients who met the criteria specified in the guideline. Suspected cases found positive for reverse transcriptase-polymerase chain reaction were accepted as confirmed COVID-19 cases (available at: https://covid19bilgi.saglik.gov.tr/depo/rehberler/COVID- 19_Rehberi.pdf). The patient information flowchart is shown in Figure 1.
Patients’ demographic characteristics such as age and gender, and clinical characteristics including, referral presentation time, symptoms and findings, history of exposure comorbidities (e.g. congenital heart disease, chronic lung disease, immunodeficiency, hematological disease), time from the onset of complaints to the confirmation of diagnosis, laboratory findings such as complete blood count, C-reactive protein (CRP) and blood biochemistry, chest X-ray and computed tomography (CT) images were examined retrospectively from the medical records of the hospital.
Statistical analysis was conducted with SPSS version 21.0 (Statistical Package for Social Sciences, IBM Inc., Armonk, NY, USA) package program. For descriptive statistics, categorical data are expressed as frequency (n) and percentage (%), while continuous data are expressed as mean, standard deviation and median, minimum-maximum.
A total of 18.680 children presented to the pediatric emergency service of our hospital during the study period. Samples were taken from 697 (3.7%) children with suspected COVID-19. Of these children, 320 (45.9%) were females, and 377 (54.1%) were males. The mean age of the children was 8.1 ± 5.5 years. Of the patients who underwent COVID-19 PCR test, 529 (75.9%) tested negative, and 108 (15.5%) were positive for COVID-19. Sixteen (2.3%) samples could not be evaluated since they were not suitable, and 44 (6,.3%) due to system problems and the problems experienced while carrying the samples. Fifty-two (48.1%) positive cases were female, and 56 (51.9%) were male. The mean age of children with COVID-19 was 8.8 ± 5.2 years. A posteroanterior chest X-ray was ordered in 87 (80.5%) of the 108 children with positive PCR for SARS-CoV-2 positive. On the X-ray images, only 5 (5.7%) children were found to have infiltration findings. Thoracic computed tomography (CT) was performed in four (3.7%) children who had posteroanterior chest X-ray and one (25%) was found to have CT findings consistent with COVID-19. The most common presenting symptom of patients with a positive SARS-CoV-2 PCR result was fever. Seventy (64.8%) patients with COVID-19 had a contact history. Characteristics and symptoms of COVID-19 positive patients are shown in detail in Table 1. Apart from these symptoms, three children presented with nasal congestion, three children with chest pain, and three children with complaints of loss of smell and taste. Of these patients, only the SARS-CoV-2 PCR samples of the children who had loss of taste and smell were found as positive.
It was found that PCR samples were taken from the children after a mean of 1 (0-8) day. While August was the month when the highest number of samples was taken, the highest positivity rate (30%) was found in July. The number of samples taken by month and positivity is shown in Figure 2.
Blood tests were ordered in 83 (76.8%) of the 108 cases whose COVID-19 PCR samples were found positive. Blood test results were evaluated considering the normal limits of age groups and shown in detail in Table 2.
One hundred (92.5%) of the positive cases were followed up as outpatients, while eight (7.5%) were hospitalized. Of the hospitalized patients, only one (12.5%) patient was hospitalized in the pediatric intensive care unit, while the remaining seven (87.5%) patients were followed up in the pediatric wards. Detailed information about hospitalized positive cases is shown in Table 3.
Although there has been an increase in published data on pediatric patients from the beginning of COVID-19 pandemic up to today, it can be seen that most of the studies still include data of adult patients.
At the beginning of the pandemic, it was known that the number and death risk of pediatric COVID-19 patients were lower compared to adults . On February 25, 2020, the first data from China, where the virus originated, showed that the incidence of cases was 0.9% and death rate was 0% in children younger than 10 years of age, while these rates were 1.2% and 0.2% (1 death), respectively in children between 10 and 19 years of age . The April 10, 2020 dated weekly report of CDC about COVID-19 in the USA stated that 1.7% of the cases were children younger than 18 years old and there were 3 deaths among the pediatric cases included in this analysis (available at https://www.cdc.gov/mmwr/volumes/69/wr/mm6914e4.htm). In a study conducted in China at the beginning of the epidemic, SARS CoV-2 positivity was reported in 171 (12.3%) of 1391 children, and it was reported that one of these children died . In a study by Korkmaz et al. from Turkey, SARS CoV-2 positivity was found in 21.5% of the children evaluated with a suspicion of COVID-19 and all of the evaluated patients were reported to be recovered . In another study with 581 children, the positivity rate was reported as 14.6% with one death . In the present study, the rate of children infected with SARS CoV-2 was 15.5% and no patients died. Differences in SARS CoV-2 positivity rates of our study and those of the study by Korkmaz et al. might be caused by differences in the technique of taking naso-oropharyngeal swabs, keeping and carrying the samples, amounts of viral load and virus kinetics.
It has been reported that children infected with SARS CoV-2 are mostly males [3, 9, 12]. However, there are also epidemiological studies, which report that girls are more commonly affected by the epidemic . In the present study, the rate of SARS CoV-2 positive boys was higher (51.9%). The gene (Angiotensin-converting enzyme-2ACE2), which SARS-CoV-2 uses as an entry to the host cell, is located on the X chromosome. ACE2 levels in circulation are higher in men when compared with women . This may be partially responsible for the higher frequency and severity of the disease in men when compared with women.
A total of 582 pediatric COVID-19 cases reported from 21 European countries including Turkey have been evaluated in a multi-centred cohort study. According to this study, COVID-19 is most common in children younger than two years old and older than 10 years old . In the studies conducted at the beginning of the pandemic in China in which distribution was evaluated according to age groups, it was shown that COVID-19 pediatric cases were more common in children between the ages of six and 15 [9, 12]. In the present study, more than two thirds of SARS-CoV-2 positive children were between the ages of five and 18. According to the CDC data, the mean age of children infected with COVID-19 is 11 years (available at: https://www.cdc.gov/mmwr/volumes/69/wr/mm6914e4.htm). In a study conducted on a similar number of patients, Dong et al. found the mean age of children as seven years . In studies conducted in Turkey, Yayla et al. found mean age as eight in a study examining 77 COVID-19 patients  and Korkmaz et al. as 9.5 years in a study examining 81 patients . Similarly, in the present study, the median age of the children with COVID-19 was nine years.
Fever and cough are the most common clinical symptoms in children with COVID-19 [3, 9, 14]. In some patients, symptoms such as fatigue, muscle pain, nasal obstruction, runny nose, sore throat, headache, dizziness, vomiting, diarrhea, abdominal pain, loss of taste and smell can also be seen . In addition, there may be patients with only cough or diarrhea without fever as well as asymptomatic carriers . It was reported that the complaints of the first pediatric case with serious lung involvement reported in Wuhan city of China were diarrhea and vomiting . In a systematic review evaluating 38 studies including a total of 1124 COVID-19 cases, the most common symptoms were reported as fever (47.5%) and cough (41.5%), respectively. In a study examining 220 SARS CoV-2 positive pediatric patients in Turkey, the most common three symptoms were reported as fever (40.5%), cough (35.9%) and muscle pain/fatigue (16.4%), respectively. The other complaints reported in the same study included headache, sore throat, diarrhea, shortness of breath, vomiting, loss of taste and smell, redness in the eyes . Similar to the literature, in our study the most common complaints were fever, fatigue, myalgia and cough.
In the present study, the mean time from the onset of symptoms to the diagnosis was one day, and this rate was smaller than the results of other pediatric studies [12, 17]. This result may be due to our national health policy and our hospital’s facilities and working conditions. In studies, the rate of contact history is higher than 90% and it is stated that in general the infected person contacted is a family member [1, 3, 9, 17]. In our study, 64.8% of the cases had a contact history. The reason for our lower rate than the literature may be the fact that contact with individuals who were not confirmed was not included in the rate. The highest positivity rate was found in July (30%) within the time period of our study. As of June 1, 2020, travel restrictions and curfews were ended in Turkey. This situation caused the violation of mask, distance and hygiene rules with the arrival of many people from outside Ordu due to reasons such as visiting, holiday and hazelnut harvest and this might have been effective in the significant increase in positivity rate in July.
Leukopenia, lymphopenia and increased inflammatory markers (erythrocyte sedimentation rate, C-reactive protein or procalcitonin) are the most frequently reported laboratory findings in children and adolescents with COVID-19 . In addition, although the data are limited when compared with adults, lymphopenia, high C-reactive protein, procalcitonin, D dimer and creatine kinase myocardial isoenzyme (CK-MB) levels are laboratory findings associated with more serious disease . When the laboratory results in our study were examined, a remarkable finding was lymphopenia seen in more than half of the patients (63.9%).
Chest X-ray, lung ultrasonography, and high resolution lung tomography (HR-CT) are used in COVID-19 patients as imaging techniques . However, chest X-ray is not recommended as the first imaging option since it does not give normal imaging results in the early stages of the disease . In the present study, chest X-ray was ordered in 80.5% of the patients, but infiltration was found only in 5.7%. Findings consistent with COVID-19 were seen only in one of the four patients who underwent thoracic CT. The fact that we had little experience about pediatric COVID-19 patients during the study period and the risk of radiation exposure during CT scanning in children continued to be a big concern, which might have affected our choice of imaging methods. We believe that more specific radiological studies are needed to diagnose children with COVID-19.
Weekly COVID-19 hospitalization survey data show an increase in hospitalization rates in children, although these rates are still low when compared with adults (available at https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports). In a small study from Madrid, it was reported that four (10%) of the 41 children with SARS-CoV-2 infection were taken to the intensive care unit . In another study, intensive care was required in only three of the 220 patients . In the current study, only eight (7.5%) patients were followed-up in the hospital, with one admitted to the intensive care unit. All patients hospitalized in the intensive care unit, including a 5-year-old patient who was hospitalized due to respiratory distress, were discharged with recovery after follow-up and completion of treatment.
A better understanding of clinical, laboratory and radiological findings of pediatric COVID-19 cases will contribute to a better understanding of the epidemiological features of SARS-CoV-2 infection, and therefore, taking effective measures to prevent the disease and develop management strategies.
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Conflict of interest
1. She J, Liu L, Liu W. COVID-19 epidemic: Disease characteristics in children. J Med Virol. 2020;92(7):747-54.
2. Kabeerdoss J, Pilania RK, Karkhele R, Kumar TS, Danda D, Singh S. Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: immunological mechanisms, clinical manifestations and management. Rheumatol Int. 2021;41(1):19-32.
3. Garazzino S, Montagnani C, Donà D, Meini A, Felici E, Vergine G, et al. Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020 [published correction appears in Euro Surveill. 2020 Jul;25(29):]. Euro Surveill. 2020;25(18):2000600.
4. Sun D, Li H, Lu XX, Xiao H, Ren J, Zhang FR, et al. Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center’s observational study. World J Pediatr. 2020;16(3):251-9.
5. DeBiasi RL, Song X, Delaney M, Bell M, Smith K, Pershad J, et al. Severe Coronavirus Disease-2019 in Children and Young Adults in the Washington, DC, Metropolitan Region. J Pediatr. 2020;223:199-203.e1.
6. Brodin P. Why is COVID-19 so mild in children? Acta Paediatr. 2020;109(6):1082-3.
7. De Luca CD, Esposito E, Cristiani L, Mancino E, Nenna R, Cortis E, et al. Covid-19 in children: A brief overview after three months experience. Paediatr Respir Rev. 2020;35:9-14.
8. The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19) — China, 2020[J]. China CDC Weekly, 2020, 2(8): 113-22.
9. Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 Infection in Children. N Engl J Med. 2020;382(17):1663-5.
10. Korkmaz MF, Türe E, Dorum BA, Kılıç ZB. The Epidemiological and Clinical Characteristics of 81 Children with COVID-19 in a Pandemic Hospital in Turkey: an Observational Cohort Study. J Korean Med Sci. 2020;35(25):e236.
11. Yayla BCC, Aykac K, Ozsurekci Y, Ceyhan M. Characteristics and Management of Children With COVID-19 in a Tertiary Care Hospital in Turkey. Clin Pediatr (Phila). 2021;60(3):170-7.
12. Dong Y, Mo X, Hu Y, Qi X, Jiang F, Jiang Z, et al. Epidemiology of COVID-19 Among Children in China. Pediatrics. 2020;145(6):e20200702.
13. Patel SK, Velkoska E, Burrell LM. Emerging markers in cardiovascular disease: where does angiotensin-converting enzyme 2 fit in? Clin Exp Pharmacol Physiol. 2013;40(8):551-9.
14. Götzinger F, Santiago-García B, Noguera-Julián A, Lanaspa M, Lancella L, Carducci FIC, et al. COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study. Lancet Child Adolesc Health. 2020;4(9):653-61.
15. Jahangir M, Nawaz M, Nanjiani D, Siddiqui MS. Clinical manifestations and outcomes of COVID-19 in the paediatric population: a systematic review. Hong Kong Med J. 2021;27(1):35-45.
16. Chen F, Liu ZS, Zhang FR, Xiong RH, Chen Y, Cheng XF, Wang WY, Ren J. First case of severe childhood novel coronavirus pneumonia in China]. Zhonghua Er Ke Za Zhi. 2020;58(0):E005.
17. Cura Yayla BC, Özsürekçi Y, Aykaç K, Oygar PD, Gürlevik SL, İlbay S, et al. Characteristics and Management of Children with COVID-19 in Turkey. Balkan Med J. 2020;37(6):341-7.
18. Safadi MAP, Silva CAAD. The Challenging and Unpredictable Spectrum of COVID-19 in Children and Adolescents. Rev Paul Pediatr. 2020;39:e2020192.
19. Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE, Shah P, et al. Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. JAMA. 2020;324(3):259-69.
20. Shen KL, Yang YH, Jiang RM, Wang TY, Zhao DC, Jiang Y, et al. Updated diagnosis, treatment and prevention of COVID-19 in children: experts’ consensus statement (condensed version of the second edition). World J Pediatr. 2020;16(3):232-9.
21. Tagarro A, Epalza C, Santos M, Sanz-Santaeufemia FJ, Otheo E, Moraleda C, et al. Screening and Severity of Coronavirus Disease 2019 (COVID-19) in Children in Madrid, Spain [published online ahead of print, 2020 Apr 8] [published correction appears in JAMA Pediatr. 2020 Oct 1;174(10):1009]. JAMA Pediatr. 2020;e201346.
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Emine Yurdakul Erturk, Ozden Aksu Sayman, Onur Yalcin. Covid-19 in pediatric patients: Data from a training and research hospital. Ann Clin Anal Med 2022;13(5):568-572
Relationship between inflammation related index and coronary artery disease in low-to-moderate risk patients with stable chest pain
Department of Cardiology, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21039 Received: 2022-01-02 Accepted: 2022-02-08 Published Online: 2022-02-09 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):573-578
Corresponding Author: Ferıt Boyuk, Department of Cardiology, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Istanbul, Turkey. E-mail: email@example.com P: +90 539 287 78 60 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2313-1495
Aim: Coronary artery disease is the leading cause of mortality and morbidity worldwide. Recently, inflammatory markers found and measured in the complete blood count have been used as precursors in many clinical situations. In this study, we aimed to investigate the relationship between inflammatory-related hemogram parameters and coronary artery disease in low-to-moderate risk patients with stable chest pain.
Material and Methods: A total of 101 patients who underwent CT coronary angiography between 2018 and 2020 were included in the study. Patients were classified as those with normal coronaries, coronary plaques, and severe coronary stenosis. Severe coronary stenosis was represented as at least one of >50% stenotic coronary vessels and the relationship between hemogram parameters and coronary artery disease was retrospectively investigated.
Results: There was no significant difference between healthy, coronary plaque, and severe stenosis groups in terms of RDW, Platelet to Lymphocyte Ratio (PLR), and Monocyte to High Dens Lipoprotein Ratio (MHR). The only significant difference among the groups was for neutrophil/lymphocyte ratio (NLR)(p=0.015). NLR was significantly higher in the severe coronary stenosis (44.46±8.65) compared to the healthy (1.76±0.58) and coronary plaque (1.77±0.64) (p=0.005 and 0.012; respectively) groups. No difference was found between the healthy and coronary plaques in terms of NLR (p=0.989).
Discussion: Although we did not identify a parameter that could be defined as a diagnostic value among these indexes, NLR appears to be stronger than others in the low-to-moderate risk group.
Keywords: Chest Pain, Angiography, Platelet, Lymphocyte, Neutrophil, Monocyte
Coronary artery disease (CAD) is among the leading causes of mortality and morbidity worldwide. Morphological and functional evaluation is important for its correct treatment . As is well-known, oxidative damage and inflammatory stress play an important role in the pathogenesis of CAD . Conclusive determination of inflammatory markers would be helpful in the determination of cardiovascular risk and evaluation of the efficacy of the treatment. Correct determination of these inflammatory biomarkers will bring about novel treatment approaches in the future.
Coronary syndromes are associated with simple lipid accumulation. Studies have shown inflammatory cell accumulation and platelet aggregation at the site of endothelial damage and plaque rupture . In this term, the Neutrophil/lymphocyte ratio (NLR) is an important marker in the diagnosis and prognosis of cardiovascular diseases. In studies related to increased NLR, it has been shown to be associated with poor prognosis and increased mortality in CAD and heart failure . NLR has proven to be a strong predictor of mortality following cardiac events . Considering the immune-inflammatory nature of the atherosclerotic process, it is obvious that stressors and internal and adaptive mechanisms are well-reflected by NLR . Although there are numerous studies in the literature about the relationship between NLR and coronary artery disease, our knowledge of the distribution and cut-off values of NLR remains limited . Again, information about whether NLR can be prognostic for CAD in patients in the low-to-moderate group is limited.
Monocytes are the main source of proinflammatory mediators in atherogenesis. High-density lipoprotein (HDL) inhibits pro-inflammatory and pro-oxidative features of monocytes. HDL also inhibits macrophage migration and efflux of low-density lipoproteins. In light of these findings, monocyte accumulation and a decrease in HDL will be expected. Considering that CAD is a chronic inflammatory process, the monocyte/HDL ratio (MHR) may have a predictor potential for CAD . An increased number of platelets indicates an increase megakaryocytic proliferation and increased thrombocytosis . The decreased number of lymphocytes shows immune depression and causes an increase in cardiac adverse events .
In this study, we aimed to investigate whether NLR, platelet/lymphocyte ratio (PLR), and MHR altered in CAD. We also investigated their prognostic significance in patients who were presented with stable chest pain and underwent computed tomographic coronary angiography (CTCA).
Material and Methods
Since the study was intended to be retrospective, ethical approval was waived. However, the necessary permission was obtained from the hospital management for using patients’ data. A total of 150 patients with clinical, laboratory, and CTCA data between 2018 and 2020 were included in the study. Based on patient data, patients with stable chest pain were categorized as low-to-moderate risk. Patients with a history of coronary intervention, severe valvular disease, heart failure, or malignancy that could change inflammatory biomarkers, autoimmune disease, renal and hepatic failure, and a history of chronic infectious disease were excluded from the study. Patients using drugs such as corticosteroids that could change NLR levels were also excluded. Finally, a total of 101 patients were involved in the present study. They were divided into three groups: those with normal coronaries, those with plaque detected, and those with severe stenosis. Severe stenosis was represented as at least one of >50% stenotic coronary vessels.
Blood samples were collected from the antecubital vein with an atraumatic puncture and immediately sent to the laboratory. Ethylene-diamine-tetraacetic acid (EDTA) containing tubes were used for the hemogram. A complete blood count, including the differentials, was performed using an automated blood cell counter (Mindray BC 6800). The biochemical panel was calculated with a Cobos 6000 (Roche diagnostics) autoanalyzer. NLR was obtained by dividing the neutrophils count by the lymphocytes count, PLR by dividing the platelets count by the lymphocytes count, and MHR by dividing the monocytes number by HDL.
Computed Tomographic Coronary Angiography
All patients underwent the 128-slice CT coronary angiography procedure (Ingenuity Elite 128 Slice-PHILIPS). 100cc IV contrast agent was given at a rate of 5 mL/sec and volumetric axial sections were acquired. The volume rendering technique (VRT) was reconstructed with processing methods after maximum intensity projection (MIP) and multi-planar reformation (MPR). The axial sections and reformatted images were evaluated together. Patients with a heart rate ≥70/min were given iv beta-blockers.
The variables were analyzed using SPSS v25 (IBM Corporation, Armonk, New York, United States) statistical software. The normality of univariate data was evaluated with the Shapiro-Wilk Francia and variance homogeneity with the Levene test. Among the parametric methods, one-way ANOVA was used to compare multiple independent groups with each other in terms of quantitative data, while Fisher’s Least Significant Difference (LSD) test was used for post hoc analysis. Receiver Operating Curve (ROC) analysis was used for the diagnostic differentiation of the normal and severe coronary stenosis groups according to inflammatory biomarkers. In the tables, quantitative variables are expressed as mean±SD (Standard Deviation), while categorical variables are shown as n (%). The variables were examined at a 95% confidence interval and p<0.05 values were considered statistically significant.
There was no statistically significant difference between healthy, coronary plaque, and severe coronary stenosis groups in terms of RDW, PLR, and MHR variables (p=0.763, p=0.082, p=0.092, and p=0.594; respectively). There was a significant difference in terms of NLR (p=0.015). The mean NLR was higher in the severe coronary stenosis group (44.46±8.65) when compared to healthy (1.76±0.58) and coronary plaque (1.77±0.64) (p=0.005 and p=0.012; respectively) (Figure 1). No significant difference was found between the healthy and coronary plaque groups in terms of NLR (p=0.989) (Table 1).
The results of ROC analysis performed to distinguish the healthy and coronary plaque groups according to RDW, PLR, and MHR variables were not significant (p>0.05) (Figure 2). The results of the ROC analysis (diagnostic value) performed to distinguish the healthy and severe coronary stenosis groups according to the inflammatory biomarkers (diagnostic value) were not significant (p>0.05) (Table 2). The diagnostic value of inflammatory biomarkers in distinguishing the healthy and coronary plaques was not significant (p>0.05) (Table 2).
In the present study, we investigated the inflammation-related index including NLR, PLR, MHR, and RDW that have a possible diagnostic potential in CAD, with their prognostic significance in patients who were presented with stable chest pain and underwent CTCA. In all these indexes, NLR positively differentiated in patients with coronary stenosis on angiography.
Besides conventional coronary angiography, new modalities showing CAD have been developed with high sensitivity and specificity. CTCA stands out as an investigation method with high sensitivity and high negative predictive value . In the last two decades, the radiation dose has dropped to 2 mSv owing to the technological advancements in CTCA. On the other hand, the exercise stress test shows CAD by 64%, the negative predictive value of CTCA is 100% . Studies have shown that CTCA is more cost-effective and has begun to replace myocardial perfusion scintigraphy in low-to-moderate risk patients presented with chest pain. It has also been included in international guides [13, 14]. Hence, we analyzed patients who underwent CTCA because of the increasing importance of this technique.
Two decades ago, we knew that CAD can be easily improved with the treatment of hypertension and hyperlipidemia. However, deaths from CAD are continuing to increase, and cardiovascular disease will remain the leading cause of mortality in the next few decades . All these reasons show the necessity of new risk categorizations and treatment approaches for CAD. Numerous biomarkers have been studied to reduce CAD-related mortality and morbidity. As inflammation plays a major role in atherosclerosis, studies have focused on this area. Atherosclerosis begins with intimal proliferation and inflammation . Among numerous inflammatory biomarkers, a significant association has been found between white blood cells, their subtypes, and CAD . NLR stands out among these inflammatory biomarkers. Furthermore, NLR has been associated with many cardiovascular diseases. The association of NLR with cardiac arrhythmia, CAD, chronic renal failure, and acute coronary syndrome has been well-defined .
Some studies have shown the presence of polymorphonuclear (PMN) cells in the coronary thrombus area in patients undergoing coronary intervention. PMNs secrete neutrophil extracellular traps (NTEs) in the lesion site. NETs have a high level of proinflammatory and prothrombotic properties. They are positively correlated with the infarction area. Again, a high level of NTEs causes ST-segment resolution to be more difficult . Unlike neutrophils, lymphocytes adjust the adaptive mechanisms of the immune system, with helper T cells specifically reducing and limiting inflammation. Low lymphocyte count is associated with poor outcomes in patients with acute coronary syndrome. Studies have identified an association between low lymphocyte count and increased atherosclerosis . In our study, a significantly higher NLR ratio in groups with coronary stenosis indicates the importance of this ratio in the development and progression of atherosclerosis. Wikananda et al. compared the GRACE risk score and NLR in patients with acute myocardial infarction. NLR was significantly higher in patients with a high GRACE score . Acet et al. found that NLR was significant in STEMI patients with a high TIMI risk score . All of these studies have been conducted in patients who had severe coronary stenosis and myocardial infarction. Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a heterogeneous entity in which the inflammatory process plays a role in etiopathogenesis. MINOCA was included in the 2017 guidelines by the European Society of Cardiology. Interestingly, this group of patients with myocardial infarction has no significant coronary stenosis . It is thought that inflammation plays a critical role in this group of CAD. In a study by Gürdal et al., NLR was found to be significantly higher in patients who presented with ST-elevation MI (STEMI) and were grouped as MINOCA . All these findings suggest that NLR can provide important information in patients with acute coronary syndrome.
In a recent study, Monocyte count and MHR were reported as potential bio indexes in adverse clinical events occurring in acute coronary syndrome . In contrast, we found no correlation between MHR and CAD. This may be attributed to much more intense inflammation and decreased HDL in acute coronary syndrome. In our study, a lower MHR compared to acute coronary syndrome could be expected because the patients in our study group were with stable CAD.
Detecting coronary artery disease much earlier will be cost-effective and will reduce patient mortality and morbidity. Therefore, we included patients with stable chest pain who were taken into the low-to-moderate risk group and who underwent CTCA. Thus, reducing risk factors with inexpensive biomarkers with a prognostic value in the very early stage of coronary artery disease will positively contribute to cardiovascular mortality and morbidity. Another objective of our study was that inflammatory biomarkers are not included in cardiovascular risk scoring systems such as GRACE and SYNTAX. An increase in the number of such studies in the literature will facilitate the inclusion of these inexpensive and readily calculated biomarkers in risk scorings and the definition of their cut-off values.
The study had some limitations. The retrospective nature of the study design and the relatively small number of patients may be considered as the main limitation. The lack of possible long-term follow-up and limited pairwise comparison can also be considered as another important limitation.
In the present study, we investigated the inflammation-related index including NLR, PLR, MHR, and RDW that have a possible diagnostic potential in CAD, with their prognostic significance in patients who were presented with stable chest pain and underwent CTCA. Although we did not identify a parameter to be defined as a diagnostic value among these indexes, NLR appears to be stronger than others in the low-to-moderate risk group.
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1. Writing Group Members, Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, et al. Executive Summary: Heart Disease and Stroke Statistics–2016 Update: A Report From the American Heart Association. Circulation. 2016;133(4):447-54.
2. Stoner L, Lucero AA, Palmer BR, Jones LM, Young JM, Faulkner J. Inflammatory biomarkers for predicting cardiovascular disease. Clin Biochem. 2013;46(15):1353-71.
3. Libby P, Ridker PM, Hansson GK. Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol. 2009;54(23):2129-38.
4. Sahin DY, Elbasan Z, Gür M, Yildiz A, Akpinar O, Icen YK, et al. Neutrophil to lymphocyte ratio is associated with the severity of coronary artery disease in patients with ST-segment elevation myocardial infarction. Angiology. 2013;64(6):423-9.
5. Azab B, Chainani V, Shah N, McGinn JT. Neutrophil–lymphocyte ratio as a predictor of major adverse cardiac events among diabetic population: a 4-year follow-up study. Angiology. 2013;64(6):456-65.
6. Wang X, Zhang G, Jiang X, Zhu H, Lu Z, Xu L. Neutrophil to lymphocyte ratio in relation to risk of all-cause mortality and cardiovascular events among patients undergoing angiography or cardiac revascularization: a meta-analysis of observational studies. Atherosclerosis. 2014;234(1):206-13.
7. Forget P, Khalifa C, Defour JP, Latinne D, Van Pel MC, De Kock M. What is the normal value of the neutrophil-to-lymphocyte ratio? BMC Res Notes. 2017;10(1):12.
8. Ganjali S, Gotto Jr AM, Ruscica M, Atkin SL, Butler AE, Banach M, et al. Monocyte-to-HDL-cholesterol ratio as a prognostic marker in cardiovascular diseases. J Cell Physiol. 2018;233(12):9237-46.
9. Wu Y, Wu H, Mueller C, Gibson CM, Murphy S, Shi Y, et al. Baseline platelet count and clinical outcome in acute coronary syndrome. Circ J. 2012;76(3):704-11.
10. Núñez J, Sanchis J, Bodí V, Núñez E, Heatta AM, Miñana G, et al. Therapeutic implications of low lymphocyte count in non-ST segment elevation acute coronary syndromes. Eur J Intern Med. 2009;20(8):768-74.
11. Budoff MJ, Dowe D, Jollis JG, Gitter M, Sutherland J, Halamert E, et al. Diagnostic performance of 64-multidetector row coronary computed tomographic angiography for evaluation of coronary artery stenosis in individuals without known coronary artery disease: results from the prospective multicenter ACCURACY (Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography) trial. J Am Coll Cardiol. 2008;52(21):1724-32.
12. Maffei E, Seitun S, Martini C, Palumbo A, Tarantini G, Berti E, et al. CT coronary angiography and exercise ECG in a population with chest pain and low-to-intermediate pre-test likelihood of coronary artery disease. Heart. 2010;96(24):1973-9.
13. Task Force Members, Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology [published correction appears in Eur Heart J. 2014;35(33):2260-1. Eur Heart J. 2013;34(38):2949-3003.
14. Min JK, Gilmore A, Budoff MJ, Berman DS, O’Day K. Cost-effectiveness of coronary CT angiography versus myocardial perfusion SPECT for evaluation of patients with chest pain and no known coronary artery disease. Radiology. 2010;254(3):801-8.
15. Wong ND. Epidemiological studies of CHD and the evolution of preventive cardiology. Nat Rev Cardiol. 2014;11(5):276-89.
16. Park JB. Neutrophil-to-Lymphocyte Ratio for Risk Assessment in Coronary Artery Disease and Carotid Artery Atherosclerosis. J Cardiovasc Ultrasound. 2016;24(2):104-5.
17. Kaya H, Ertaş F, Islamoğlu Y, Kaya Z, Atilgan ZA, Cil H, et al. Association between neutrophil to lymphocyte ratio and severity of coronary artery disease. Clin Appl Thromb Hemost. 2014;20(1):50-4.
18. Acet H, Ertaş F, Akıl MA, Oylumlu M, Polat N, Yıldız A, et al. New inflammatory predictors for non-valvular atrial fibrillation: echocardiographic epicardial fat thickness and neutrophil to lymphocyte ratio. Int J Cardiovasc Imaging. 2014;30(1):81-9.
19. Mangold A, Alias S, Scherz T, Hofbauer T, Jakowitsch J, Panzenböck A, et al. Coronary neutrophil extracellular trap burden and deoxyribonuclease activity in ST-elevation acute coronary syndrome are predictors of ST-segment resolution and infarct size [published correction appears in Circ Res. 2021;128(2):e26. Circ Res. 2015;116(7):1182-92.
20. Seaoud E, Mohamed AAHA, Elkot MA. The Role of the Platelet/Lymphocyte Ratio and Neutrophil/Lymphocyte Ratio in Predicting High-Risk Heart Score in Patients Admitted with Non-ST Elevation Acute Coronary Syndrome. Pulse (Basel). 2020;8(1-2):66-74.
21. Wikananda G, Ariawan E, Husin M. The relationship between neutrophil to lymphocyte ratio (NLR) at admission and GRACE mortality risk score in acute myocardial infarction patient at Tabanan Regency Hospital in 2017. Intisari Sains Medis. 2019, 10(1):205-8.
22. Acet H, Ertaş F, Bilik MZ, Akıl MA, Özyurtlu F, Aydın M, et al. The relationship between neutrophil to lymphocyte ratio, platelet to lymphocyte ratio and thrombolysis in myocardial infarction risk score in patients with ST elevation acute myocardial infarction before primary coronary intervention. Postepy Kardiol Interwencyjnej. 2015;11(2):126-35.
23. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2018;39(2):119-77.
24. Gürdal A, Keskin K, Siğirci S, Yildiz SS, Kiliçkesmez KO. Prognostic Value of the Neutrophil-to-Lymphocyte Ratio in Patients With Myocardial Infarction With Non-obstructive Coronary Arteries. Angiology. 2020;71(9):812-6.
25. Sun M, Zhao D, Zhang Y, Zhai Y, Ye M, Wang X, et al. Prognostic Utility of Monocyte to High-Density Lipoprotein Ratio in Patients With Acute Coronary Syndrome: A Meta-Analysis. Am J Med Sci. 2020;359(5):281-6.
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Ferıt Boyuk. Relationship between Inflammation related Index and Coronary Artery Disease in Low-To-Moderate Risk Patients With Stable Chest Pain. Ann Clin Anal Med 2022;13(5):573-578
Assessment of post-COVID-19 clinical manifestations after recovery in healthcare professionals
Anam Arshad 1, Iram Arshad 1, Muhammad Humayun 1, Asmara Syed 2, Ekramy Elmorsy 2, Syed Sajid Hussain Shah 2
1 Department of Biochemistry, Central Park Medical College, Lahore, Pakistan, 2 Department of Pathology, Faculty of Medicine, Northern Border University, Arar, Kingdom of Saudi Arabia
DOI: 10.4328/ACAM.21042 Received: 2022-01-05 Accepted: 2022-02-09 Published Online: 2022-02-16 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):579-582
Corresponding Author: Anam Arshad, Department of Biochemistry, Central Park Medical College, Lahore, Pakistan.
E-mail: firstname.lastname@example.org P: +92 320 000 87 67 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3879-4291
Aim: In this study, we aimed to assess the COVID -19 clinical manifestations after recovery from illness among healthcare professionals.
Material and Methods: After ethical approval, a structured questionnaire has been distributed among healthcare professionals who were willing to participate in the study. The questionnaire contained forty questions, which were divided into four sections.
Results: A total of 126 participants completely filled the questionnaire, including 65 (51.6%) females and 61(48.4%) males. Fatigability is the most common (38.1%) post-COVID clinical manifestation in healthcare professionals. Other common post- COVID clinical manifestations are numbness in the face/ arms/legs (34.2%), cough (23%), muscle pain (20.6%) and anxiety/depression (20.6%) in order of frequency.
Discussion: The presence of fatigue, anxiety, cough and hair fall was observed in women healthcare workers up to 2 months even after recovery from mild to moderate disease.
Keywords: COVID-19, Clinical Manifestations, Health Professionals
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the worldwide pathogen, caused coronavirus disease 2019 (C OVID-19), has impulse morbidity and mortality at prodigious scale . Patients suffered divergent symptoms like fever, dry cough, and fatigue. About 80% of cases showed mild manifestation, but sever cases may progress, causing respiratory distress or respiratory failure that increased the need for intensive care unit (ICU) . Respiratory manifestations may also coexist with hematological, olfactory, renal, gastrointestinal, hepatic, cardiac, neurological, cutaneous and gustatory symptoms . Diagnosis of COVID-19 is done through polymer chain reaction (PCR), computed tomography (CT) scan, and blood test . While acute symptoms were predominant during coronavirus disease 2019 (COVID-19) and most of the patients completely recovered, although fraction of patients experiencing long-term health consequences is now increasing . COVID-19 associated ailments sustain beyond three weeks after the onset of symptoms and chronic COVID-19 manifestations extending more than 12 weeks after the emergence of symptoms are defined as post-COVID syndrome(PCS). Post-COVID syndrome was first time defined by Greenhalgh et al . Communal post-COVID traits include fatigue, dyspnea, olfactory and gustatory dysfunction, chest pain, myalgia, and sleep and mental disorders [7, 8]. Individuals may experience symptoms for several months that disrupt the work activity and quality of life . PCS complete clinical picture is complex and far from being understood. However, viral tropism is defined by the entry into cells through a widely expressed ACE2 receptor, making it a potential threat of damage to many organs either in acute or chronic form . Leading pathophysiologic methods of COVID-19 include the following: direct viral toxicity; endothelial damage and microvascular damage; immune system dysregulation and hyperinflammatory regeneration; hypercoagulability leading to situ thrombosis and macro thrombosis . The objective of this study is to investigate the post-COVID-19 manifestation after recovery from illness and to mitigate the long-term medical effects of COVID -19 and the duration of symptoms in healthcare professionals.
Material and Methods
Following ethical approval from the institutional research committee, a structured questionnaire has been designed for the collection of data from the recovered cases of COVID-19 regarding the post-COVID-19 clinical manifestations. The questionnaire consists of 40 questions, which are subdivided into four sections. The first section covers the socio-demographic data of the participants, such as age, gender and educational level. The second section contains of 8 questions regarding co-morbidities. The third section is comprised of 8 questions about the symptoms experienced during the COVID-19 disease, while the section four contains of 20 questions that are related to post-COVID-19 clinical manifestations.
After the approval of this research project by the institutional ethical & review board, the questionnaire has been distributed among those health care professionals who have recovered from COVID-19 and are willing to participate in this research project. This study has been conducted in November 2021. No personal identification such as name, phone number or email address has been collected. The analysis of the completely filled questionnaire was carried out using a computer software.
During the study period, a total of 126 participants completely filled the questionnaire, which included 65 (51.6%) females and 61(48.4%) males. Participants were divided into six groups according to their age. In group one, the age ranged from 18 to 25 years, and the majority of the participant belonged to this group, which comprised 71 (56.3%) of the total study participants of 126 (100%). The second age group (26 – 35 years) included 20 (15.9%) participants, while other groups 46-55 years = 16 (12.7%), 36-45 years = 10(7.9%), 56-65 years = 8 (6.3%) and more than 65 years =1 (0.8%) in order of frequency, respectively. The majority of the participants (68 (54.1%)) were undergraduate students, while 40 (31.7%) medical professionals had post-graduate degrees . The remaining categories included 10 (7.9%) graduates and 8 (6.3%) post-graduate students. Among the participants of this research project, the majority had no comorbidity 91(72.2%), while 18 (14.3%) of the participants had hypertension, 8 (6.3%) had diabetes mellitus, and 8 (6.3%) had asthma. Six (4.8 %) participants had chronic joint disorder, while 5 (4%) had cardiovascular disease, and one person (0.8%) had chronic kidney disease.
During the COVID-19 disease, the study participants experienced the following symptoms, in the order of frequency: fever 102 (81%), fatigue 97 (77%), headache 69 (54.8%), loss of taste 59 (46.8%), loss of smell 51 (40.5%), shortness of breath 43 (34.1%) and insomnia 31 (24.6%), while 8 persons (6.3%) did not develop any symptoms. Details of post-COVID-19 clinical manifestations are shown in Table 1.
Pakistan has been hit by COVID-19 although the number of patients recovering from COVID-19 is increasing daily. Post-recovery manifestations and long-lasting symptoms are not well written in the literature . This study primarily focused on the prognosis of COVID-19 and the impact of the current epidemic on healthcare professionals. Moreover, we aimed to establish a relationship between post-COVID syndrome and the age of individuals requiring long-term support. We observed that 72.3% (91/126) with mild to moderate disease were found to have long-term health consequences after two months, defined by the presence of at least one symptom (fatigue, insomnia, breathlessness) after mild disease. These symptoms can be called post-COVID-19 Syndrome as they are related to SARS-CoV2 infection .
Our study demonstrates that there is a range of symptoms that persisted beyond the phase of illness due to COVID-19, out of which nonspecific symptoms were predominantly referred to as post COVID syndrome. In this study, 48 people out of 72.3 experienced fatigue and peripheral neuropathy 43 out of 126 participants, majority of them were females of the younger age group (18-25) without any comorbidity. Fatigue has previously been reported as one of the most common symptoms of PCS . The possible physical link to fatigue may be endothelial dysfunction in the capillaries of the brain recently described in Nauen et al . According to data published by Townsend et al., we noted that even patients with mild illness may initially develop fatigue as a leading symptom of PCS . In accordance with the previously published data, our results show that women are more likely to be affected by PCS .
In addition, peripheral neuropathy was observed in female participants of younger age group about 41%. Factors contributing to the neuropathology of COVID-19 can be categorized as direct infection, severe systemic inflammation, neuroinflammation, microvascular thrombosis and neurodegeneration . A series of autopsies have shown that SARS-CoV-2 can cause changes in the parenchyma of the brain and blood vessels, possibly due to the effects on blood-brain and barriers to cerebrospinal fluid, which cause inflammation in neurons, supporting cells and vasculature of the brain . Cerebral injury biomarkers, such as raised peripheral blood levels of neurofilament light chain, have been seen in patients with COVID-19 .
After recovery, our participants also reported other symptoms like anxiety, muscle pain, and some dermatological manifestations i.e. hair loss. Significantly more females developed post-COVID-19 hair loss, anxiety, depression, and fatigue when compared to male participants (p < 0.05). The pathophysiology of post-COVID syndrome is poorly understood, hyper inflammatory condition, oxidative stress, cytokine storm, and DNA damage have been thoughtful but ongoing research is needed to guide potential therapies . Cough was the persistent respiratory symptom expected in post-COVID syndrome seen in male participants. Previous outbreaks of SARS-CoV have demonstrated consistent respiratory symptoms, limiting pattern of pulmonary function metrics associated with muscle weakness in six to eight weeks following discharge from hospital . Hair loss may be caused by telogen effluvium as a result of viral infection or a stress response . Biotin supplementation and 5% Minoxidil are recommended for hair loss beyond six to nine months . Our study suggested that post-COVID 19 manifestations can be seen in mild or moderate disease even in the younger age group.
Taken together we suggest that SARS-CoV-19 symptoms are more frequent in females and PCS can occur in younger healthcare workers despite mild to moderate disease. Efficient methods of physical rehabilitation and surveillance programs are required for healthcare professionals to improve the well-being of frontline workers. Moreover, recovered people should be highly observant about future complications.
Female healthcare workers of the younger age group showed a high prevalence of post-COVID syndrome after a mild to moderate course of the ailment. Younger participants are long-haulers, whereas elderly subjects have a higher risk of getting serve disease. Moreover, healthcare workers should validate the need for a systemic evaluation, physical and mental rehabilitation.
We wish to thank all the participants who contributed to our study. Special thanks to Saad Sohail Salahuddin, Saim Saad and Ms. Naila Kousar.
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1. Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, et al. Post-acute COVID-19 syndrome.Nature Medicine 2021;27(4):601-15.
2. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. Jama. 2020;323(13):1239-42.
3. Lai C-C, Ko W-C, Lee P-I, Jean S-S, Hsueh P-R. Extra-respiratory manifestations of COVID-19. Int J Antimicrob Agents. 2020;56(2):106024.
4. Udugama B, Kadhiresan P, Kozlowski HN, Malekjahani A, Osborne M, Li VY, et al. Diagnosing COVID-19: the disease and tools for detection. ACS nano. 2020;14(4):3822-35.
5. Augustin M, Schommers P, Stecher M, Dewald F, Gieselmann L, Gruell H, et al. Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study. The Lancet Regional Health-Europe. 2021;6:100122.
6. Maltezou HC, Pavli A, Tsakris A. Post-COVID Syndrome: An Insight on Its Pathogenesis. Vaccines. 2021;9(5):497.
7. Dicpinigaitis PV, Canning BJ. Is there (will there be) a post-COVID-19 chronic cough? Springer; 2020.
8. Havervall S, Rosell A, Phillipson M, Mangsbo SM, Nilsson P, Hober S, et al. Symptoms and functional impairment assessed 8 months after mild COVID-19 among health care workers. Jama. 2021;325(19):2015-6.
9. Gupta A, Madhavan MV, Sehgal K, Nair N, Mahajan S, Sehrawat TS, et al. Extrapulmonary manifestations of COVID-19. Nat Med. 2020;26(7):1017-32.
10. Iqbal A, Iqbal K, Ali SA, Azim D, Farid E, Baig MD, et al. The COVID-19 sequelae: a cross-sectional evaluation of post-recovery symptoms and the need for rehabilitation of COVID-19 survivors. Cureus. 2021;13(2).
11. Marshall M. The lasting misery of coronavirus long-haulers. Nature. 2020;585(7825):339-42.
12. Townsend L, Dyer AH, Jones K, Dunne J, Mooney A, Gaffney F, et al. Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection. Plos one. 2020;15(11):e0240784.
13. Nauen DW, Hooper JE, Stewart CM, Solomon IH. Assessing brain capillaries in coronavirus disease 2019. JAMA neurology. 2021;78(6):760-2.
14. Barsky AJ, Peekna HM, Borus JF. Somatic symptom reporting in women and men. Journal of general internal medicine. 2001;16(4):266-75.
15. Heneka MT, Golenbock D, Latz E, Morgan D, Brown R. Immediate and long-term consequences of COVID-19 infections for the development of neurological disease. Alzheimers Res Ther. 2020;12(1):1-3.
16. Desforges M, Le Coupanec A, Stodola JK, Meessen-Pinard M, Talbot PJ. Human coronaviruses: viral and cellular factors involved in neuroinvasiveness and neuropathogenesis. Virus Res. 2014;194:145-58.
17. Ameres M, Brandstetter S, Toncheva AA, Kabesch M, Leppert D, Kuhle J, et al. Association of neuronal injury blood marker neurofilament light chain with mild-to-moderate COVID-19. J Neurol. 2020;267(12):3476-8.
18. Bektas A, Schurman SH, Franceschi C, Ferrucci L. A public health perspective of aging: do hyper-inflammatory syndromes such as COVID-19, SARS, ARDS, cytokine storm syndrome, and post-ICU syndrome accelerate short-and long-term inflammaging? Immunity & Ageing. 2020;17(1):1-10.
19. Chan K, Zheng J, Mok Y, Li Y, LIU YN, Chu C, et al. SARS: prognosis, outcome and sequelae. Respirology. 2003;8(Suppl.1):S36-40.
20. Huang C, Huang L, Wang Y, Li X, Ren L, Gu X, et al. 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. The Lancet. 2021;397(10270):220-32.
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Anam Arshad, Iram Arshad, Muhammad Humayun, Asmara Syed, Ekramy Elmorsy, Syed Sajid Hussain Shah. Assessment of post-Covid-19 clinical manifestations after recovery in healthcare professionals. Ann Clin Anal Med 2022;13(5):579-582
Evaluation of the oxidant/antioxidant status in patients with brucellosis treated with a combination of two types of antibiotics
Department of Biochemistry, Health Science Faculty, Cankiri Karatekin University, Cankırı, Turkey
DOI: 10.4328/ACAM.21045 Received: 2022-01-14 Accepted: 2022-04-12 Published Online: 2022-04-13 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):583-587
Corresponding Author: Emrah Caylak, Saglık Bilimleri Fakultesi, Karatekin University, 18200, Cankiri, Turkey. E-mail: email@example.com P: +90 544 613 49 99 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0408-9690
Aim: This study aimed to evaluate the oxidant/antioxidant status of patients treated for brucellosis and to determine the effects of a combination of antimicrobial agents (doxycycline, streptomycin and rifampicin) that could be used in the treatment of brucellosis.
Material and Methods: Sixty (60) acute patients with brucellosis and thirty (30) healthy volunteers were enrolled in the study. Doxycycline-streptomycin (DOX-STR) and doxycycline-rifampicin (DOX-RIF) were used in the treatment of brucellosis. MDA levels, total oxidant status (TOS), and superoxide dismutase, catalase levels and total antioxidant capacity (TAC) were determined in patients treated with brucellosis. Also, TOS/TAC index (OSI) was calculated.
Results: Before therapy, MDA, TOS, SOD, catalase levels and OSI value were significantly higher, and TAC was significantly lower in brucella patients compared with healthy subjects (p < 0.001). After therapy, MDA, TOS, SOD, catalase levels, and OSI value significantly decreased, and plasma TAC levels significantly increased compared to the pre-treatment group, especially in the DOX-STR regimen (p < 0.001).
Discussion: Over-production of oxidants and depletion of TAC in patients with brucellosis are associated with inflammatory nature of brucellosis. Measurement of oxidant/antioxidant status may be useful for monitoring patients who are recovering, and the treatment of patients with antibiotic combination, especially (DOX-STR) will ameliorate their antioxidant system.
Keywords: Brucellosis, Total Oxidant Status (TOS), Total Antioxidant Capacity (TAC), Oxidative Stress Index (OSI), Treatment; Antibiotic Combination
Human brucellosis, also known as “Mediterranean” or “Malta fever”, is a zoonosis and transmitted to humans through direct contact with infected animals or by eating their products. It causes loss of appetite and body weight, undulant fever, arthritis, spondylitis, endocarditis, osteomyelitis. It is an important public health and affects people in Turkey or developing countries such as the Middle East, Asia, Africa, Mediterranean countries of Europe and South America (WHO. Brucellosis fact sheet N173. WHO, Geneva, Switzerland; 1997.p.23-37).
Brucella organisms are gram-negative coccobacillus, facultative intracellular bacteria that reside and replicate in a vacuolar compartment within macrophages of the infected human. Numerous studies reported that lipopolysaccharides found in the outer membranes of brucella bacteria increase nitric oxide (NO) production in macrophages through IFN-γ; and thus superoxide and hydrogen peroxide have an important effect in protecting against brucella [1,2]. Experimental studies has identified the production of reactive oxygen species (ROS) by induced macrophage activation with IFN-γ [1-4].
Previous studies have found an increment in the expression of antioxidant enzymes such as NO reductase, superoxide dismutase (SOD), catalase (CAT) in brucella patients [5,6]. This outcome was attributed to increased free radical production and antioxidant depletion. Thus, the resulting oxidative stress plays an important role in the pathogenesis of brucellosis . Generally, this situation was monitored with determining the total oxidant/antioxidant status. The therapeutic power of antibiotic combinations used in patients within the scope of this study will also be determined by oxidative stress and antioxidant agents that will be measured before and after treatment in patients, and will further contribute to the determination of effective treatment protocols.
Material and Methods
Brucella-infected individuals attending the outpatient Clinic of Infectious Diseases at the Cankiri State Hospital were enrolled in the study. The study was approved by the Research Ethics Committee of the University of Zonguldak Karaelmas/Turkey (2011/06). Sixty brucella-infected patients aged 18 – 50 years (32 men and 28 women), and 30 healthy controls aged 19 – 45 years (15 men and 15 women) were included in the study. Table 1 shows demographic features of individuals. No statistically significant difference was found between the groups (age, gender, body mass index (BMI), BMI score, and waist circumference).
Patients were assigned to the Brucella-infected group if they had an epidemiological history (contact with animals and animal products), clinical symptoms (hyperhidrosis, undulant fever and joint pain, etc.), and confirmed laboratory findings (determination with blood culture, serum agglutination test [SAT] with titres ≥ 1/160). Exclusion criteria for the patient and control groups were pregnancy, drug use, alcohol or tobacco use , obesity (BMI ≥ 30), gastro/metabolic/inflammatory diseases, abdominal surgery.
Brucellosis is usually treated with antibiotic combinations such as doxycycline-streptomycin (DOX-STR) and doxycycline-rifampicin (DOX-RIF) (Joint FAO/WHO Expert Committee on Brucellosis. Joint FAO/WHO Expert Committee on Brucellosis: sixth report. WHO Technical Report Series No. 740. Geneva; 1986.p.56-7). Treatment regimens of the patients with brucellosis in this study were 200 mg/day orally doxycycline plus 1 g/day intramuscularly streptomycin for 45 days or 200 mg/day orally doxycycline plus 600 mg/day orally rifampicin for 45 days.
Sample Collection and Processing
Blood specimens (5mL) before and after treatment were collected by venipuncture from participants and inoculated in bottles including anticoagulant (EDTA). The samples of 2 mL were stored at –70 °C until further analysis of MDA, total oxidant status (TOS), SOD, CAT, and total antioxidant capacity (TAC).
Analytical Procedures and Instruments
Firstly, oxidative stress parameters MDA and TOS were analyzed in plasma samples. MDA levels were analyzed using a modified method of Trichloroacetic Acid– Thiobarbituric Acid (TCA – TBA), at 532 nm spectrophotometrically. MDA values were expressed as mmol/L . An automated measurement method developed by Erel was used in the determination of TOS . In this method, oxidants present in the sample oxidize the ferrous ion complex to ferric ion. The color intensity is then measured at 660 nm spectrophotometrically, and this indicates the total amount of oxidants present in the sample. The results were expressed in µmol H2O2 equiv./L.
Secondly, the antioxidant enzyme (SOD, CAT) levels and TAC were analyzed. Plasma SOD activity was measured using Nitro Blue Tetrazolium (NBT) technique . The volume of 3 ml of SOD assay mixture consisted of 0.1 ml ethanol phase (ethanol–chloroform 5/3 volume and plasma 1 volume), 0,05 mL xanthine oxidase 2.85 mL of solution containing 0.12 mM xanthine, 0.12 mM NaEDTA, 30.6 µM nitro blue tetrazolium, and 0.06 g/L bovine serum albumin (BSA). The reaction was stopped with 1 mL of 0.02 mM CuCl2, and the absorbance was recorded at 560 nm. SOD activity was expressed in terms of IU/g Hb. Plasma CAT activity was measured by the Aebi method . In the assay, 0.05 mL of plasma, 0,5 mL hydrogen peroxide, 1,5 mL 100 mM phosphate buffer (pH 7), 0,95 mL were mixed and kinetic measurement was recorded using destruction of hydrogen peroxide with CAT at 240 nm. The activity was expressed as k/mg protein. An automated measurement method developed by Erel was used in the determination of TAC levels . In this assay, the hydroxyl radical is produced by the Fenton reaction and when the sample is added to the mixture, the antioxidants in the sample suppressed the oxidative reactions, preventing color change. Thus, we can measure the total antioxidant capacity of the sample. Briefly, 0.03 mL of plasma sample, and 0,5 mL of reagent 1 were mixed, and then 0.067 mL of reagent 2 was added. Differences in the absorbance of the solution at 660 nm were measured after 30 s and 5 min. TAC levels were expressed in mmol Trolox equiv./L.
Finally, the percentage of TOS to the TAC was calculated to obtain the oxidative stress index (OSI), an indicator of the degree of oxidative stress.
While evaluating the findings obtained in the study, the SPSS program (Statistical Package for Social Sciences 13.0, USA) was used for statistical analysis. The Mann-Whitney-U test and Spearman’s correlation analysis were used to compare differences between groups. The level of significance, p-value was 0.001 and all data in the tables were expressed as mean ± SD.
Hematological and biochemical data at the initiation and after 45 days of combined antibiotic therapy are shown in Table 2. As can be seen in Table 2, increased white blood cell, glucose, aspartate amino-transferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), C-reactive protein (CRP), very low-density lipoprotein (LDL), total cholesterol levels were found in patients with brucellosis compared to healthy controls. Decreased total bilirubin, creatinine, lactate dehydrogenase (LDH), high-density lipoprotein (HDL) levels were found in the same group compared to controls.
Table 3 described the oxidative and anti-oxidative parameters for all participants. Significantly increased MDA, TOS, SOD and CAT levels were found in patients with acute brucellosis compared to healthy controls (p < 0.001). On the other hand, significantly decreased TAC levels were found in patients with acute brucellosis compared to the controls (p < 0.001). Also, the TOS/TAS ratio (OSI index) was significantly higher, in patients with acute brucellosis than in the healthy controls (p < 0.001). When comparing two treatments with the patient group, the oxidant/antioxidant status of the patients normalized after the treatment period.
Table 3 also shows outcome data for patients treated with the antibiotic combination DOX-STR or DOX-RIF. When comparing the two treatment regimens, there was no significant difference (p> 0.05). Comparison of different antibiotic combinations showed the benefit of using DOX-STR. Thus, a non-statically significant normalization of the oxidant/antioxidant status of patients was due to DOX-STR treatment in patients with acute brucellosis.
With regard to disease progression, some biochemical parameters, such as AST, ALT, GGT and CRP levels were significantly higher in patients with acute brucellosis compared to healthy controls. When comparing those parameters of the brucella group before and after treatment, a significant decrease was observed, indicating the effectiveness of the treatment. These results were consistent with other studies [12,13].
When an infectious bacterium enters the body, macrophages and dendritic cells are activated for antigen processing in the normal immune response, leading to an overproduction of reactive oxygen species in inflammatory diseases such as brucellosis [1,2]. Antioxidant enzymes such as superoxide dismutase, catalase, myeloperoxidase, and NO reductase play a very important role in the elimination of ROS species and are associated with the bacterial defense system in Brucella . In the present study, these changes were analyzed by monitoring the oxidants such as MDA, TOS and antioxidants such as SOD, CAT, TAC and OSI. In this study, patients with brucellosis had significantly increased MDA, TOS, SOD, CAT levels and OSI value compared with healthy controls. Additionally, significantly decreased TAC levels were found in patients with acute brucellosis than in controls. In a numerous studies, these biomarkers of oxidative/antioxidative have been investigated in acute brucellosis. In a rat model, found an increase in MDA levels in plasma and tissues such as the brain, liver, and spleen, and CAT activity in the liver. Esen et al.  observed significantly decreased serum paraoxonase–arylesterase (PON) activities, TAC and thiols levels, while increased lipid hydroperoxide, TOS and OSI values in acute brucellosis patients than in controls. Otherwise, Karahocagil et al.  found significantly decreased CAT activity in the brucella patients than in controls. Karaagac et al.  measured the TAC and TOS levels in patients before and after therapy, and calculated OSI. They determined significantly higher TOS and OSI levels and lower TAC values in brucella patients when compared to those before and after therapy. After treatment, they reported decreased TOS and OSI levels, whereas TAC levels increased. It is thought that the elevation of free oxygen radicals and a decrease in antioxidant capacity may have an importance in the pathogenesis of brucellosis.
Antibiotic combinations such as doxycycline – streptomycin (DOX-STR) and doxycycline – rifampicin (DOX-RIF) are commonly used in the treatment of brucellosis. In two different meta-analyses evaluating antibiotic combinations in brucellosis, the usage of DOX-STR is reported to be superior to that of DOX-RIF [18,19]. According to our data, DOX-STR regimen was superior in the normalization of aminotransferases, and another probable reason may be related to the hepatotoxicity of rifampicin . In the present study, these effects of antibiotic regimens were analyzed by monitoring the oxidant and antioxidant status of the post-treatment groups compared to controls. DOX-STR treatment of patients with brucellosis further reduced MDA, TOS, SOD, CAT levels, and OSI value compared with healthy controls. Additionally, it is also observed that the same regimen further increased plasma TAC levels after therapy. These results indicate that the use of DOX-STR regimen particularly improves the antioxidant status of the brucella patients, and this should be taken into consideration in designing treatment.
It is thought that the rise of free oxygen radicals and the decrease of antioxidant capacity may play a role in the pathogenesis of brucellosis. The antioxidant status of the blood can be determined by measuring the total oxidant/antioxidant status. In this study, the therapeutic power of antibiotic combinations used in patients was determined by the oxidant and antioxidant agents measured before and after treatment in patients, and the addition of antioxidants to effective treatment protocols for brucella will make an extra contribution.
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1. Celli J. Surviving inside a macrophage: the many ways of Brucella. Res Microbiol. 2006;157:93-8.
2. Akbulut H, Celik I, Akbulut A. Cytokine levels in patients with brucellosis and their relations with the treatment. Indian J Med Microbiol. 2007;25:387-90.
3. Jiang X, Leonard B, Benson R, Baldwin CL. Macrophage control of Brucella abortus: role of reactive oxygen intermediates and nitric oxide. Cell Immunol. 1993;151:309-19.
4. Lapaque N, Moriyon I, Moreno E, Gorvel JP. Brucella lipopolysaccharide acts as a virulence factor. Curr Opin Microbiol. 2005;8:60-6.
5. Abdel-Fattah A, Mohamed GA. Interleukin-1β, tumor necrosis factor-α, and oxidative stress biomarkers in cows with acute Brucella abortus infection. Comp Clin Pathol. 2021; 30:311–15.
6. Serefhanoglu K, Taskin A, Turan H, Timurkaynak FE, Arslan H, Erel O. Evaluation of oxidative status in patients with brucellosis. Braz J Infect Dis. 2009;13(4):249-51.
7. Esterbauer H, Cheeseman KH. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol. 1990;186:407-21.
8. Erel O. A novel automated method to measure total antioxidant responseagainst potent free radical reactions. Clin Biochem. 2004;37:112-9.
9. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34(3):497-500.
10. Aebi H. Catalase. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Academic Pres Inc., New York and London, 1974.p.673-7.
11. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem. 2004;37:277-85.
12. Shi Y, Gao H, Pappas G, Chen Q, Li M, Xu J, et al. Clinical features of 2041 human brucellosis cases in China. PLoS One. 2018;13(11):e0205500.
13. Özdem S, Tanır G, Öz FN, Yalçınkaya R, Cinni RG, Savaş Şen Z, et al. Bacteremic and Nonbacteremic Brucellosis in Children in Turkey. J Trop Pediat. 2022;68(1), fmab114.
14. Melek IM, Erdogan S, Celik S, Aslantas O, Duman T. Evaluation of oxidative stress and inflammation in long term Brucella melitensis infection. Mol Cell Biochem. 2006;293:203-9.
15. Esen R, Aslan M, Kucukoglu ME, Cıkman A, Yakan U, Sunnetcioglu M, Selek S, et al. Serum paraoxonase activity, total thiols levels, and oxidative status in patients with acute brucellosis. Wien Klin Wochenschr. 2015;127:427–43.
16. Karahocagil MK, Aslan M, Ceylan MR, Cıkman A, Sunnetcioglu M, Kucukoglu ME, et al. Serum myeloperoxidase activity and oxidative stress in patients with acute brucellosis. Clin Biochem. 2012;45:733-6.
17. Karaagac L, Koruk ST, Koruk I, Aksoy N. Decreasing oxidative stress in response to treatment in patients with brucellosis: could it be used to monitor treatment? Int J Infect Dis. 2011;15:346-9.
18. Farzada K, Arshidb YA, Amirhosseinc S, Behnama MG, Mohsena A, Hadi P. Drug resistance of clinical and environmental isolates of Brucella species in Iran: a meta-analysis. Rev Med Microbiol. 2018;29(4):166-72.
19. Zheng R, Xie S, Lu X, Sun L, Zhou Y, Zhang Y, Wang K, et al. A systematic review and meta-analysis of epidemiology and clinical manifestations of human brucellosis in China. BioMed Res Int. 2018;1-10.
20. Erdem H, Ulu-Kilic A, Kilic S, Karahocagil M, Shehata G, Eren-Tulek N, et al. Efficacy and tolerability of antibiotic combinations in neurobrucellosis: results of the Istanbul study. Antimicrob Agents Chemother, 2012;56(3):1523-8.
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Emrah Caylak. Evaluation of the oxidant/antioxidant status in patients with brucellosis treated with a combination of two types of antibiotics. Ann Clin Anal Med 2022;13(5):583-587
Comparison of maternal and perinatal outcomes of pregnancies with frozen and fresh embryo transfers at term pregnancy
Jule Eriç Horasanlı, Hasan Energin, Enes Ferlibaş
Department of Gynecology and Obstetrics, Meram Faculty of Medicine, Necmettin Erbakan Üniversity, Konya, Turkey
DOI: 10.4328/ACAM.21046 Received: 2022-01-08 Accepted: 2022-02-11 Published Online: 2022-02-22 Printed: 2022-05-01 Ann Clin Anal Med 2022;13(5):588-591
Corresponding Author: Jule Eriç Horasanlı, Department of Gynecology and Obstetrics, Meram Faculty of Medicine, Necmettin Erbakan Üniversity, Konya, Turkey. E-mail: firstname.lastname@example.org P: +90 555 479 33 94 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8738-7126
Aim : In our study, we aimed to compare maternal and perinatal outcomes of frozen and fresh embryo transfers, induced by single or double embryo transfer with in vitro fertilization (IVF) at term pregnancy.
Material and Methods: After obtaining ethics, our study was performed retrospectively assessing pregnancies in women between the ages of 18 and 40 induced with single or double embryo transfer with IVF between the years 2010 and 2020. Maternal outcomes such as oligohydramnios, polyhydramnios, preeclampsia, placenta previa, placenta accreta syndrome (PAS), and hysterectomy were examined in all groups. Perinatal outcomes including birth weight, time of delivery, small for gestational age (SGA), large for gestational age (LGA), appropriate for gestational age (AGA), preterm labor, Apgar score of infant at five minutes, and intensive care requirement were also investigated.
Results: No difference was observed in terms of oocyte number collected, neonatal intensive care requirement, Apgar scores, postpartum hysterectomy, and blood transfusions. There was no difference between the groups in birth weight, preterm labor, and delivery time. There was no significant difference between the groups in SGA, LGA, and AGA. Polyhydramnios and oligohydramnios were significantly higher in the fresh transfer group (p = 0.006 and p = 0.006, respectively). Among perinatal parameters, the frequency of placenta previa was significantly higher in the frozen transfer group (p = 0.001). The frequency of placenta accreta and preeclampsia was not significantly different.
Discussion: Placenta previa was higher in the frozen transfer group, suggesting frozen embryo transfer increases the risk of placenta previa. Oligohydramnios and polyhydramnios were higher in the fresh transfer group.
Keywords: IVF, Frozen Transfers, Fresh Transfers, Outcomes, Term Pregnancy
Despite regular sexual intercourse, one out of every six couples experiences infertility and wishes to have a healthy child with assisted reproductive technology (ART) . Cryopreservation has become an essential part of ART and was used in approximately 40% of all in vitro fertilization (IVF) cycles in 2015 . Embryo cryopreservation is an almost routine practice in IVF applications because it prevents multiple pregnancies by allowing for the transfer of fewer embryos. Protection from the risk of ovarian hyperstimulation syndrome (OHHS) is also an advantage . Frozen embryo transfer (FET) may lead to better obstetric results by providing better placental development compared to fresh transfers since it creates a good endometrial microenvironment. However, some studies suggest that FET may have a negative effect on obstetric results. There can be a greater risk of congenital malformations in frozen embryo transfers compared with fresh embryo transfers Animal studies have shown increased large for gestational age results due to epigenetics [4,5].
Recent studies show that the risk of developing pregnancy-induced hypertension (PIH) and placenta accreta is higher in the FET group than in the fresh embryo transfer group [6,7]. IVF patients have more postpartum hemorrhage in their deliveries than the general population. During postpartum bleeding, hysterectomy, blood transfusions, and intensive care may be required. Thus, frequent applications of embryo cryopreservation and total freeze strategies may cause neonatal, perinatal, and maternal consequences [8,9].
Our aim in this study was to investigate retrospectively the maternal and perinatal outcomes of frozen and fresh embryo transfers, induced by single or double embryo transfer with in vitro fertilization (IVF) at term pregnancy.
Material and Methods
After obtaining ethics, our study was performed retrospectively assessing pregnancies in women between the ages of 18 and 40 induced with single or double embryo transfer with IVF between the years 2010 and 2020. (the Ethics Committee approved the study protocol (protocol no:2686- 09.07.2020) Perinatal and maternal results were obtained from screening patient information files for patients who had frozen or fresh embryo transfer and gave birth after 37 gestational weeks. Informed consent was obtained from all patients. In the patient groups, age, body mass index (BMI), education, smoking, number of eggs collected (oocyte count), embryo transfer day, and transfer type (frozen or fresh embryo transfer) were recorded. Maternal outcomes such as placenta previa, placenta ccrete spectrum (PAS), postpartum hemorrhage, and the associated need for blood transfusion and hysterectomy were investigated in all groups. As fetal parameters, delivery time, birth weight, small for gestational age (SGA: birth weight less than the 10-percentile adjusted for gestational week), large for gestational age (LGA: birth weight above the 90 percentile adjusted for gestational age), appropriate for gestational age (AGA), 5-minute Apgar score, and intensive care (NICU) requirement were investigated. Births before the 37th gestational week were accepted as term births. The presence of polyhydramnios and oligohydramnios were also examined. Single amnion vertical pocket fluid length over 8 cm was classified as polyhydramnios and values below 2 cm as oligohydramnios.
Patients who received single or double embryo transfer with IVF (fresh or frozen embryo transfer), gave birth after 37th weeks of gestation.
Patients with vanishing twins were excluded from the study, although their pregnancies continued individually. Miscarriages were not included. Multiple pregnancies were not included in the study. Chronic hypertensive patients and patients with previously diagnosed type 1 and type 2 diabetes were excluded from the study.
Maternal and perinatal outcomes were described using mean, standard deviation, frequency, and percentages. Groups were compared using the chi-square and ANOVA tests. All analyses were performed using SAS University Edition 9.4 program. A p-value <0.05 was considered significant.
A total of 297 patients were evaluated in the study. The fresh transfer group had 165 patients (55.6%), the frozen transfer (FET) group had 132 patients (44.4%). There was no difference in socio-demographic characteristics such as age, smoking, and education (p = 0.60 and p = 0.7, respectively). The BMI values were higher in the fresh transfer group (p = 0.01) (Table 1). Hysterectomy was not performed for any of the patients in the groups. There was no difference in terms of blood transfusions (p = 0.17). There was no significant difference in the number of oocytes obtained in the groups (p = 0.06). No significant difference was observed between the groups in the perinatal parameters SGA, LGA, and AGA (p = 0.41). There was no difference between the groups in terms of birth weight (p = 0.88), and time of delivery (p = 0.09). Although there was no statistically significant difference between the groups in neonatal intensive care requirement (p = 0.22), it was required for 20.45% of the FET group, 14.55% of the fresh transfer group. Newborn Apgar scores were similar in all groups (p = 0.08) (Table 2). There was no significant difference in gestational diabetes mellitus incedence between fresh ET and FET groups. Oligohydramnios and polyhydramnios were significantly higher in the fresh transfer group (p = 0.006 and p = 0.006). The frequency of placenta previa was significantly higher in the frozen group (p = 0.001).
Cryopreservation has recently become an important part of ART and has changed the transfer policies towards single embryo transfer. FET embryos have played an important role in modern ART therapy in protecting from over hyperstimulation syndrome and multiple pregnancy. After the first successful cryopreservation, embryo freezing procedures were performed for 20 years by various methods . While slow freeze embryo cryopreservation was preferred in the first years, the vitrification method has recently depended not only on embryo quality, but also on endometrial receptivity and the uterine environment. Supra-physiological hormonal levels such as high estradiol levels observed during controlled ovarian stimulation (COS) can adversely affect embryo implantation, replacing it . Obstetric outcomes in IVF are important for maternal and infant health, and success altering the microenvironment and implantation, leading to adverse obstetric and perinatal outcomes. Ovarian stimulation causes an increase in the risk of LBW in fresh embryo transfer cycles . Since no ovarian stimulation was used in patients in whom a donor oocyte was used, no statistical difference was observed in LBW in either FET or fresh cycles and no increase in preterm delivery was observed. Preterm birth, LBW, and low Apgar scores are reported to be significantly lower in FET cycles . However, Spijkers et al. found that the rate of preterm birth before 37 weeks of gestation was not different between fresh and FET transfers (2). Despite this, it is thought that endometrial receptivity improves in FET cycles (14,15). Improving endometrial conditions results in the proper placental development .
An increase in the risk of high birth weight and LGA is observed in FET cycles compared to fresh cycles [16,18]. Pinborg et al. attributed the development of LGA to the overgrowth of tissues to compensate for cell loss during freezing and thawing and to weight differences in culture media due to the influence of epigenetic factors . Although the higher incidence of LGA fetuses in FET embryos does not appear to be clinically important, the risk of increased Cesarean section rates, metabolic disorders, stillbirth, traumatic deliveries, and birth asphyxia increases . Other reasons may be the quality of the embryo itself or maternal factors . In this study, we found no difference in the FET and fresh transfer groups in LBW, birth weight, and SGA, LGA, and AGA perinatal results.
Obstetric and reproductive results in IVF practice are important in terms of maternal and infant health . The biggest concern in fresh transfers is the disruptive effect of COS on the endometrium and uterus. Some investigators report good IVF results because of a better endometrial environment in FET cycles compared to fresh embryo transfers . Contrary to these findings, other studies report some side effects and negative obstetric outcomes in FET cycles . Sazonova et al. mentioned an increased risk of PIH, preeclampsia, and placenta accreta in single FET cycles compared to fresh cycles . We found no significant difference in the risk of developing preeclampsia between the Fresh ET group and the FET group.
Obstetric bleeding is reported with a higher rate in ART cycles, but the mechanism is not fully known. It has been suggested that fresh embryo transfers in IVF patients, endometriosis, hormone treatments, and events during the implantation period may be responsible for the bleeding and suboptimal endometrial function is a critical mechanism. A study reported that antepartum bleeding after fresh embryo transfers is due to increased estradiol concentrations in proportion to the number of oocytes collected that indirectly affects the endometrium [7,21]. Some researchers report that estrogen and progesterone are given in FET cycles, imitating normal physiology, and there is a question of a better endometrial environment . Some authors found a high risk of developing placenta previa in ART and concluded that implantation occurs in the lower uterine segment due to uterine contractions during transfer . Several studies report higher rates of placenta previa in ART singleton pregnancies compared to spontaneous pregnancies . In a study comparing fresh cycles with FET cycles, a lower risk of placenta previa was found . However, in some studies, the risk of developing placenta previa was not different between FET and fresh cycles [8-22]. In our study, we observed that the risk of placenta previa was significantly higher in FET pregnancies.
PAS is a rare complication after ART. This improper development of the placenta can cover a wide spectrum from hysterectomy to maternal emergencies. The study of Ishihara in 2014 demonstrated this increase in FET cycles. They also stated that the increased risk of placenta accreta in FET cycles is not related to patient characteristics, and the reason for this increase is due to low estradiol levels, thin endometrium, and uncontrolled extravillous trophoblast invasion or only cryopreservation . In this study, there was no difference between the groups in the risk of developing PAS.
Studies have shown that problems such as polyhydramnios and oligohydramnios are more common in patients with ART than in normal gestational patients . In another study, a 114% increased risk of polyhydramnios and oligohydramnios was reported in ART . In our study, a statistically significant increase was observed in both the FET and fresh groups compared to natural conception and was higher in the fresh embryo group.
Consequently, the safety of ART procedures is more important than pregnancy and implantation rates. There is an increased risk of placenta previa in the FET embryo group. This situation contains risks for the life of the mother and fetus. In the fresh embryo group, there was an increased risk of polyhydramnios and oligohydramnios. We think that more detailed studies should be done to understand the obstetric and perinatal consequences of cryopreservation. The limitation of this study was that it was retrospective and ignored various protocols of cryopreservation that could affect implantation. Before the studies evaluating obstetric and perinatal outcomes between FET cycles and fresh cycles become clear, “freeze all” strategies should be approached more cautiously.
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Animal and human rights statement
Conflict of interest
1. Kuwayama M, Vajta G, Kato O, Leibo SP. Highly efficient vitrification method for cryopreservation of human oocytes. Reprod Biomed Online. 2005; 11(3): 300-8.
2. Rienzi L, Gracia C, Maggiulli R, LaBarbera AR, Kaser DJ, Ubaldi FM, et al. Oocyte, embryo and blastocyst cryopreservation in ART: systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for the development of global guidance. Hum Reprod Update. 2017;23(2):139-55.
3. Ginström Ernstad E, Spangmose AL, Opdahl S, Henningsen AK A, Romundstad LB, Tiitinen A et al Perinatal and maternal outcome after vitrification of blastocysts: a Nordic study in singletons from the CoNARTaS group. Human Reproduction. 2019; 34(11): 2282-2289.
4. Liu SY, Teng B, Fu J, Li X, Zheng Y, Sun XX. Obstetric and neonatal outcomes after transfer of vitrified early cleavage embryos. Hum Reprod. 2013; 28(8): 2093-100.
5. Spijkers S, Lens JW, Schats R, Lambalk CB. Fresh and frozen-thawed embryo transfer compared to natural conception: differences in perinatal outcome. Gynecol Obstet Investigat. 2017; 82(6): 538-46.
6. Estudillo E, Jiménez A, Bustamante-Nieves PE, Palacios-Reyes C, Velasco I, López-Ornelas A. Cryopreservation of Gametes and Embryos and Their Molecular Changes. Int J Mol Sci. 2021;22(19):10864.
7. Ishihara O, Araki R, Kuwahara A, Itakura A, Saito H, Adamson G. D. Impact of frozen-thawed single-blastocyst transfer on maternal and neonatal outcome: an analysis of 277,042 single-embryo transfer cycles from 2008 to 2010 in Japan. Fertil Steril. 2014; 101(1):128-33.
8. Roque M, Valle M, Guimarães F, Sampaio M, Geber S. Freeze-all policy: fresh vs. frozen-thawed embryo transfer. Fertility and sterility. 2015; 103(5):1190-3.
10. Joshi N, Kissin D, Anderson JE, Session D, Macaluso M, Jamieson DJ. Trends and correlates of good perinatal outcomes in assisted reproductive technology. Obstet Gynecol. 2012; 120(4): 843.
11. Thurin A, Hausken J, Hillensjö T, Jablonowska B, Pinborg A, Strandell A, et al. Elective single-embryo transfer versus double-embryo transfer in in vitro fertilization. The New England Journal of Medicine. 2004; 351(23): 2392–402.
12. Cui M, Dong X, Lyu S, Zheng Y, Ai J. The Impact of Embryo Storage Time on Pregnancy and Perinatal Outcomes and the Time Limit of Vitrification: A Retrospective Cohort Study. Front Endocrinol (Lausanne). 2021;12:724853.
13. Lee S H, Lee JH, Park YS, Yang KM, Lim CK. Comparison of clinical outcomes between in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in IVF-ICSI split insemination cycles. Clin Exp Reprod Med. 2017; 44(2): 96.
14. Kalra SK, Ratcliffe SJ, Coutifaris C, Molinaro T, Barnhart KT. Ovarian stimulation and low birth weight in infants conceived through in vitro fertilization. Obstet Gynecol. 2011; 118(4):863-71.
15. Källén B, Finnström O, Nygren KG, Olausson PO. In vitro fertilization (IVF) in Sweden: infant outcome after different IVF fertilization methods. Fertil Steril. 2005; 84(3):611-17.
16. Barnhart KT. Introduction: are we ready to eliminate the transfer of fresh embryos in in vitro fertilization? Fertil Steril. 2014; 102(1): 1-2.
17. Maheshwari A, Pandey S, Shetty A, Hamilton M, Bhattacharya S. Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of frozen thawed versus fresh embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril. 2012; 98(2): 368–77.e779.
18. Pinborg A, Loft A, Henningsen A KA, Rasmussen S, Andersen A N. Infant outcome of 957 singletons born after frozen embryo replacement: the Danish National Cohort Study 1995–2006. Fertil Steril. 2010; 94(4): 1320-7.
19. Roque M. Freeze-all policy: is it time for that? J Assist Reprod Genet. 2015; 32(2):171-6.
20. Sazonova A, Källen K, Thurin-Kjellberg A, Wennerholm U. B, Bergh C. Factors affecting obstetric outcome of singletons born after IVF. Hum Reprod. 2011; 26(10): 2878-86.
21. Jackson R A, Gibson KA, Wu YW, Croughan MS. Perinatal outcomes in singletons following in vitro fertilization: a meta-analysis. Obstet Gynecol. 2004; 103(3): 551-63.
22. Shapiro BS, Daneshmand S T, Garner FC, Aguirre M, Hudson C, Thomas S. Evidence of impaired endometrial receptivity after ovarian stimulation for in vitro fertilization: a prospective randomized trial comparing fresh and frozen–thawed embryo transfer in normal responders. Fertil Steril. 2011; 96(2):344-8.
23. Zhu L, Zhang Y, Liu Y, Zhang R, Wu Y, Huang Y, et al. Maternal and live-birth outcomes of pregnancies following assisted reproductive technology: a retrospective cohort study. Scie Rep. 2016; 6(1):1-11.
24. Qin J, Liu X, Sheng X, Wang H, Gao S. Assisted reproductive technology and the risk of pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies: a meta-analysis of cohort studies. Fertil sterility. 2016; 105(1):73-85.
Download attachments: 10.4328:ACAM.21046
Jule Eriç Horasanlı, Hasan Energin, Enes Ferlibaş. Comparison of maternal and perinatal outcomes of pregnancies with frozen and fresh embryo transfers at term pregnancy. Ann Clin Anal Med 2022;13(5):588-591