March 2022
Sigma metrics and quality goal index: A new road map in clinical chemistry
Yasemin Erdoğan Döventaş 1, Hatice Erdoğan 2
1 Medical Biochemistry, 2 Medical Microbiology, Ministry of Health University, Haseki Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20677 Received: 2021-04-29 Accepted: 2021-07-11 Published Online: 2022-02-16 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):241-244
Corresponding Author: Yasemin Erdoğan Döventaş, Ministry of Health University, Haseki Training and Research Hospital, Medical Biochemistry, Istanbul, Turkey. E-mail: yasemined@gmail.com P: +90 532 548 59 51 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3166-841X
Aim: Sigma measurements are a standard tool for quality assessment of test performance in a laboratory. In this study, we aimed to calculate sigma metrics and quality goal index (QGI) for 28 biochemical parameters. Sigma values of each assay were calculated, based on the bias and coefficient of variation from internal quality control (IQC) and external quality assurance scheme (EQAS).
Material and Methods: External quality assessment (EQA) and internal quality control data for 28 parameters in a biochemical laboratory were collected from July 2019 to February 2020. The sigma values of each assay were calculated, based on the bias, total error allowable, and coefficient of variation, according to the quality goal index, the main causes of poor performance were determined to guide quality improvement. This study was conducted in the Haseki Training and Research Hospital Biochemistry Laboratory. Sigma metrics calculation was performed as (TEA − Bias)/CV for 28 biochemistry parameters analyzed with AU5800 [Beckman Coulter (BC), USA]. Total allowable errors were followed as per Clinical Laboratory Improvement Amendments (CLIA) guidelines.
Results: At IQC 1, eight of the 28 parameters (AST, ALT, LDH, CK, ALP, HDL, T. Bil
and D. Bil) showed world-class performance. At IQC 2, three of the 28 parameters (ALP, T.bil, and Crea) achieved 6 sigma (world-class performance), and three parameters (Amilase, K, Cl, and Lipase) showed world-class performance for EQC. The quality goal index (QGI) was calculated for items with analysis performance < 3 sigma, and the main causes of poor performance were determined to guide quality improvement.
Discussion: Sigma metric analysis provides a benchmark for the laboratory to design a protocol for IQC, address poor assay performance, and assess the efficiency of the existing laboratory process. Six Sigma methodology is an effective tool for evaluating the performance of biochemical analytes and conducive to quality assurance and improvement. The quality goal index is a calculation that complements this method.
Keywords: Internal quality control (IQC), External quality control (IQC), Quality goal index (QGI), Six sigma
Introduction
Medical Laboratories must produce accurate, precise, and comparable results for correct diagnosis and treatment practices. For this purpose, each of the preanalytical, analytical, and post-analytical processes must be continuously checked and improved. The purpose of clinical laboratory tests is to support the diagnosis, monitor treatment, and assess the risk of disease progression. To have value for creating clinical conclusion, an individual laboratory test result must have a total error small enough to reflect the biological condition being assessed [1]. Also, clinical laboratory testing results are important for ensuring patient safety. Approximately two-thirds of important clinical decisions on patient management are based on laboratory test results [2]
In clinical laboratories, medical technologists are trained to focus on achieving Quality Control (QC) results within the defined acceptable limits [3]. The “Six Sigma Methodology” is a quality management tool based on statistical calculations, focused on process variables, and providing information about the procedure. The sigma value of a test is a well-defined and quantitative measurement of the quality of this test. Six Sigma is a quality management method to improve assay quality. The sigma methodology has mainly been applied to pre-analytical and analytical processes in clinical laboratories, focusing on the evaluation of biochemical and immunoassay tests. The higher the sigma values, the lower the chance of false test results by the laboratory. It can easily quantify the exact number of errors by combining bias, precision, and total allowable error (TEa). A sigma level < 3 is an indication of a poor performance procedure, whilst good performance is indicated by a sigma level > 3. A Sigma level of 6 or greater indicates world-class performance [4]. In this study, we aimed to evaluate our laboratory analytical performance with the Clinical Laboratory Improvement Amendments (CLIA) criteria performance (available at: https://www.cms.gov/Regulations-and-Guidance/Legislation/CLIA).
The quality goal index (QGI) is a newer parameter to represent the relative extent to which both bias and precision meet their respective quality goals [6]. In this study, the performance of 28 analytes was evaluated by calculating sigma values from coefficient of variation (CV), bias, and TEa. In addition, QGI analyses were further performed to identify problems related to the measurement procedures for analytes with a sigma value <3 [7]
Material and Methods
This is a retrospective study, and the data required for the study were extracted between July 2019 to February 2020 in the Haseki Training and Research Hospital Biochemistry Laboratory. Sigma metrics calculation was performed as (TEA − Bias)/CV for 28 biochemistry parameters analyzed with AU5800 [Beckman Coulter (BC), USA]. The CV was calculated based on IQC data (BC control serum two-level/one run per day).
This study included the following 28 clinical biochemistry parameters: Albumin(Alb), Alanine Aminotransferase (ALT), Alkaline phosphatase (ALP), Aspartate Aminotransferase (AST), Amylase (Amy), Anti-streptolysin-O (ASO), Iron (Fe), Unsaturated Iron Binding Capacity (UIBC), Direct Bilirubin (D.Bil), Phosphorus (P), Calcium (Ca), Chloride (Cl), Total Cholesterol (T.Chol), Creatinine(Crea), Creatine Kinase (CK), Glucose (Glu), Gamma-Glutamyl Transferase (GGT), High-Density Lipoprotein Cholesterol (HDL), Lactate Dehydrogenase (LDH), Lipase (Lps) , Magnesium (Mg), Potassium (K), Total protein (T.prot), Total bilirubin (T.bil), Sodium (Na), Triglycerides (Trig), Blood urea nitrogen (BUN), Uric acid (UA). The sigma metrics were calculated by the following formula: [Sigma = (TEa − Bias)/CV] [8]. Whereas TEa is a total allowable error, and bias and CV are the indicators of systematic and random errors, respectively.
QGI represents the relative extent to which both bias and precision meet their respective quality goals. It was calculated using the following formula: [QGI = Bias/1.5 CV]. QGI represents the reason behind the lower sigma value i.e., imprecision, inaccuracy, or both. For analytes that fall short of Six Sigma quality, a QGI score of < 0.8 indicates imprecision, QGI > 1.2 indicates inaccuracy, and QGI score of 0.8-1.2 indicates both imprecision and inaccuracy [8].
CV is the standard deviation (SD) expressed as a percentage and is a measure of the variability of an assay [CV = (SD/Mean) × (100)].
Bias is the systematic difference between the expected results obtained by the laboratory test method and the results that would be obtained from an accepted reference method.
TEa was followed as per the CLIA guidelines (Clinical Laboratory Improvement Amendments (CLIA) | CMS). The total error (TE) of parameters was also calculated by the following formula: [TE = Bias + 1.65 CV] [7].
Results
The bias %, CV%, TEa, sigma, and QGI values of clinical chemistry tests are shown in Table 1. Sigma values calculated with TEa, bias, and CV are shown in Table 2. The QGI according to sigma values are provided in Table 3.
While IQC eight analytes (AST, ALT, LDH, CK, ALP, HDL, T.Bil and D.Bil ) showed an ideal performance of ≥6 sigma for level 1; five analytes (T.prot, UIBC, Alb, Chol, and Lipase) showed an average performance of <3 sigma for IQC 1. Also, IQC three analytes (ALP, T.bil, and Crea) showed a performance of ≥6 sigma for level 2; five analytes (T.chol, Alb, P, Fe, UIBC, and Lipase) showed an average performance of < 3 sigma for level 2. Sigma values of BUN, Glu, AST, Alb, Fe, and HDL were below 3 for EQA. Sigma values Amilase, K, Cl, and Lipase were ≥ 6 for EQA. Sigma values of Glu, BUN, UA, Crea, Trig, AST, Amilase, Ca, P, Mg, Na, K, Cl and ASO were in the range of 3 to 6 For IQC 1. Sigma values of Glu, BUN, UA, Crea, Trig, AST, Fe, Na, D.bil, Amilase, Ca, Na, K, Cl, HDL, ASO and Lps were in the range of 3 to 6 for IQC 2. Also, EQC fourteen analytes (Crea, Trig, ALT, GGT, CK, LDH, CK, ASO, T.Bil ,D.Bil, Aml, Ca, P, Mg, UIBC) showed a performance in the range of 3 to 6 sigma .Sigma value > 6 was found, ALP T-Bil and LDH for both levels of IQC. Sigma values of UIBC and T.chol for both levels of IQC were lower than 3. But EQAs of these tests were in the range of 3 to 6.
Table 3 summarizes the QGI ratio of analytes with lower sigma values (< 3). The quality goal index (QGI) was calculated for items with analysis performance <3 sigma and the main causes of poor performance were determined to guide quality improvement. QGI ratio indicated that out of three and four parameters of IQC1 and IQC2 failed to meet Six Sigma quality
performances. The main problem was an inaccuracy in the case
of UIBC, lipase, and total cholesterol (QGI > 1.2), imprecision in
the case of Alb, P, iron level 2 (QGI < 0.8), and both imprecision and inaccuracy for UIBC (IQC2).
Discussion
Good laboratory practice (GLP) requires every individual laboratory to design a customized Individualized Quality Control Plan (IQCP), a protocol based on Sigma values obtained from Sigma metric analysis (ISO – ISO 15189:2012 – Medical laboratories -Requirements for quality and competence. Available at: https://www.iso.org/standard/56115.html). The incorporation of sigma metrics results in the reduction of laboratory errors by maintaining six standard deviations between the parameter average and its upper and lower limits [9].
Nanda et all. determined that six sigma values were greater than 6 for some routine biochemistry tests (AST, ALT, ALP, total bilirubin, and uric acid) on Cobas Integra analyzer. Sigma values less than 3 were calculated for total protein, albumin, total cholesterol, and chloride tests in their study [10]. When these data are compared with our study, it is seen that a sigma value less than 3 is calculated for Alb and UIBC. T.prot and Cl are greater than 3 in our study. Sigma value was found to be less than 3 for albumin in both studies. But EQAS results were good for both of them.
Parameters with low sigma values should be improved with a strict QC strategy. The six-sigma concept is important in controlling the quality of laboratory tests [10]. Total analytical errors may differ according to accepted error classifications such as Richos, Rilibak, CLIA [11]. However, sigma metric evaluation can be more objective because it is obtained from systemic and randomized error values, bias, and standard deviation [12]. In our study, unlike other sigma’s metric clinical chemistry analyzes, we also calculated the quality target index. Our aim here was to identify the problem. Unlike previous studies, we calculated the QGI in tests with sigma values. We have considered their total analytical error value. UIBC, lipase, Fe, P, and total cholesterol were short of sigma metrics with a value < 3. QGI ratio for parameters with sigma < 3 depicted inaccuracies in the case of total cholesterol, UIBC, and lipase (QGI > 1.2), imprecision in the case of tests Albumin, Iron and Phosphor (QGI < 0.8), and imprecision and inaccuracy in the case of UIBC level 2. There are certain limitations in the sigma metrics system because we have observed no problems in the CV % and bias % of glucose (level 2), urea (level 2), and total cholesterol (level 2 and level 3), but sigma shows a lesser value. In the case of AST and ALT, the calculated TEa is higher compared to the allowable error as per CLIA, which is reflected in the QGI and sigma metrics. The tests we analyzed in the biochemistry laboratory were below total analytical error values according to CLIA. This showed us that each laboratory should also perform sigma analysis besides TEA values. We also tried to identify problems by making a QGI evaluation. We have reviewed our daily quality control frequency.
A simple guideline for choosing Westgard rules and levels of IQC processed are as follows: for biochemical parameters with Sigma Scale 6 or above (excellent performance), evaluate with one level of QC per day (alternating levels between days) and follow 1-3 s Westgard rule alone. With Sigma Scale 4–6 (good/acceptable performance), evaluate with two levels of control once daily and follow 1-3 s, 2-2 s, R4 s Westgard multi rules. With Sigma Scale 3–4 (poor performance), use two levels of controls twice daily and follow 1-3 s, 2-2 s, R4s, and 4-1 s Westgard’s multi rules. With the Sigma Scale of <3 (problem analyte), root cause analysis should be performed; method performance must be improved before the method can be routinely used.[9]
Finally, sigma metric analysis provides a benchmark for the laboratory to design a protocol for IQC, address poor assay performance, and assess the efficiency of the existing laboratory process.
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.
Funding: None
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.
References
1. McPherson RA. Henry’s Clinical Diagnosis and Management by laboratory methods. St. Louis, MO: Elsevier; 2017.
2. Aslan D, Sert S, Aybek H, Yılmaztürk G. Assessment of Total Clinical Laboratory Process Perfomance: Normalized OPSpecs Charts, Six Sigma and Patient Test Results. Turk J Biochem. 2005; 30(4):296- 305.
3. Singh B, Goswami B, Gupta VK, Chawla R, Mallik V. Application of Sigma Metrics for the Assessment of Quality Assurance in Clinical Biochemistry Laboratory in India: A Pilot Study. Ind J Clin Biochem. 2011; 26(2):131–35
4. Aslan D, Demir S. Six-sigma quality management in laboratory medicine. Turk J Biochem. 2005; 30 (4):272-8.
5. Verma M, Dahiya K, Ghalaut VS, Dhupper V. Assessment of quality control system by sigma metrics and quality goal index ratio: a roadmap towards preparation for NABL. World J Methodol. 2018; 8(3):44-50.
6. Kumar BV, Mohan T. Sigma metrics as a tool for evaluating the performance of internal quality control in a clinical chemistry laboratory. J Lab Physicians. 2018; 10(2):194-9.
7. Nevalainen D, Berte L, Kraft C, Leigh E, Picaso L, Morgan T. Evaluating laboratory performance on quality indicators with the Six Sigma scale. Arch Pathol Lab Med. 2000; 124(4):516-19.
8. Westgard JO, Westgard SA. The quality of laboratory testing today: an assessment of sigma metrics for analytic quality using performance data from proficiency testing surveys and the CLIA criteria for acceptable performance. Am J Clin Pathol. 2006; 125(3):343-54.
9. Westgard JO. Six sigma quality design and control, 2nd edition. Madison WI: Westgard QC Inc.; 2006. p. 338.
10. Nanda SK, Ray L. Quantitative Application of Sigma Metrics in Medical Biochemistry. J Clin Diagn Res. 2013; 7(12):2689-91.
11. Nar R, Emekli DI. The evaluation of analytical performance of immunoassay tests by using Six-Sigma method. J Med Biochem. 2017; 36(4):301-8.
12. Hens K, Berth M, Armbruster D, Westgard S. Sigma metrics used to assess analytical quality of clinical chemistry assays: importance of the allowable total error (TEa) target. Clin Chem Lab Med. 2014; 52(7):973-80.
Download attachments: 10.4328:ACAM.20677
Yasemin Erdoğan Döventaş, Hatice Erdoğan. Sigma metrics and quality goal index: new road map in clinical chemistry. Ann Clin Anal Med 2022;13(3):241-244
Citations in Google Scholar: Google Scholar
This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of the license, visit https://creativecommons.org/licenses/by-nc/4.0/
Measuring depression and anxiety level and determining concerns regarded to pandemic in doctors and nurses working in operating room
Kadriye Acar 1, Hüseyin Acar 2, Erdinç Kamer 3, Gülay Oyur Çelik 4
1 Department of Surgery Room, Izmir Katip Çelebi University, Atatürk Training and Research Hospital, 2 Department of Emergency Medicine, Izmir Katip Çelebi University, Atatürk Training and Research Hospital, 3 Department of General Surgery, Izmir Katip Çelebi University, Atatürk Training and Research Hospital, 4 Department of Surgery Nursing, Faculty of Health Sciences, Izmir Katip Çelebi University, Izmir, Turkey
DOI: 10.4328/ACAM.20686 Received: 2021-05-03 Accepted: 2021-07-26 Published Online: 2022-02-21 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):245-249
Corresponding Author: Hüseyin Acar, Department of Emergency Medicine, Izmir Katip Çelebi University, Atatürk Training and Research Hospital, İzmir, Turkey. E-mail: dracar@hotmail.com P: +90 (532) 500 90 29 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1905-7133
Aim: One of the most important conditions for healthcare professionals to work efficiently during the pandemic is to ensure complete physical and mental well-being. This study was planned to measure the depression and anxiety levels of nurses and doctors working in the operating room during the COVID-19 pandemic, and to determine the causes of anxiety related to the pandemic.
Material and Methods: This study is a cross-sectional, descriptive and region-stratified survey study. This study was conducted with operating room nurses and doctors who volunteered to participate. Participants were administered a survey consisting of 13 questions that questioned the reasons for concern about COVID-19 in addition to the Beck Anxiety Scale and Beck Depression Scale.
Results: There was no difference between doctors and nurses regarding anxiety and depression symptoms. Anxiety level was higher in men. Depression and anxiety levels were high in those who worked for sixteen years and over, while depression and anxiety levels were significantly lower in the 18-35 age group. The most worrisome situation for healthcare professionals was the possibility of working in a unit where they had never worked before. The working area that the participants considered the most risky one in relation to COVID-19 was the emergency operating room.
Discussion: We observed that participants showed mild depression symptoms and moderate anxiety. Also, psychological conditions of the younger participants were better.
Keywords: Depression, Anxiety, COVID-19, Pandemic, Healthcare workers
Introduction
COVID-19 disease has spread rapidly, affecting the world and becoming a global public health problem [1]. COVID-19 may progress without any symptoms or with mild symptoms such as fever, cough, sore throat, shortness of breath, fatigue and weakness. On the other hand, severe symptoms such as pneumonia, acute respiratory distress syndrome, and multiple organ dysfunction, and even death may be seen [2,3]. The high mortality, morbidity and transmission rate of the disease have led to various precautions in many countries [1,4].
During the pandemic, to prevent COVID-19 transmission, while the entire population is urged to stay at home and even some sanctions are applied, on the contrary, healthcare professionals have to work in an extremely risky environment in hospitals. Additionally, they may become physically and mentally tired due to reasons such as increased workload, the need to work in different areas unfamiliar to them, difficulties of working with protective equipment, the need for triage of patients, and anxiety about not being able to access protective equipment [5-7]. The loss of physical and mental health of healthcare workers reduces work efficiency and makes the fight against COVID-19 even more difficult [7]. This situation reveals that the mental health of healthcare workers should be protected as well as their physical health [5,6]. In order to develop approaches to protect the mental and physical health of healthcare professionals, first of all, the problems experienced during the pandemic should be determined and solution strategies should be developed based on these problems. In particular, healthcare workers who are in direct contact with patients, such as operating room nurses and doctors, may be at risk for both COVID-19 and psychological problems.This study aims to determine the depression and anxiety levels of nurses and doctors working in the operating room during the pandemic and the causes of anxiety associated with COVID-19 .
Material and Methods
This study is a descriptive, cross-sectional, region-stratified and multi-center survey study. This study was carried out between 10.5.2020 and 30.6.2020 with nurses and doctors working in the operating room who were volunteered to participate in the study. Permission was obtained from the Izmir Public Health Directorate and the Local Ethics Committee. In this study, we included the operating room doctors and nurses from 5 hospitals serving in the province of Izmir and accepting COVID-19 patients. The participants consisted of surgeons from all branches, anesthesiology and reanimation specialists and all nurses working in the operating room. In order to collect study data, we sent the survey link we prepared to the participants via e-mail and asked the participants to fill in the survey online. The principal investigator examined the survey results and excluded participants who filled the survey incompletely or incorrectly. The survey included the Beck Anxiety Index (BAI), Beck Depression Scale (BDS), socio-demographic characteristics of the participants and a survey consisting of 13 questions prepared to determine the reasons for concern about COVID-19. In order to identify these questions, first we questioned 50 healthcare professionals working in our hospital about their concerns regarding COVID-19 by asking open-ended questions. Later, we prepared our 13-question questionnaire based on the most common answers to these questions. Operating room nurses and doctors who volunteered to participate were enrolled in the study. The 21-questionTurkish validity and reliability study of BAI was conducted by Ulusoy, Şahin and Erkmen (1998) and the Turkish version was found to be valid and reliable. The scale measures the degree of anxiety symptoms experienced by an individual. Each item on the scale is scored between 0 and 3 according to the intensity of the experienced symptom. A score between 0 and 63 can be obtained on the scale. A high score indicates the severity of the anxiety. On the scale, 8-15 points indicate mild, 16-25 points indicate moderate, and 26-63 points indicate severe anxiety.8 BDI, the other scale used, was developed by Beck et al. in 1979 and is a 21-question scale that questions how a person feels over the previous week. The validity and reliability study of the BDI was performed by Hisli (1989) and was found to be valid and reliable.9 On the scale, each question can be scored between 0 and 3 points, with 0-16 points indicating mild depressive symptoms, 17-29 points- moderate, and 30-63 points- severe depressive symptoms.10
Data, recruited from online survey results were analyzed using IBM SPSS 25 program for Windows. For descriptive statistics, the median ± IQR was given for numerical variables, and number and percentage values were given for categorical variables. As a result of the Kolmogorov- Smirnov test, it was understood that the data did not show a normal distribution, and the Mann-Whitney U test was used for comparison of two independent groups, and the Kruskal-Wallis test was used for comparison of three or more independent groups. Bonferroni Correction was used to obtain appropriate p-value for pairwise comparison of groups, performed to find out which variable caused the difference in multi-group comparison. Statistical significance was accepted as p <0.05.
Results
Among 528 participants, 256 (48.5%) were men and 272 (51.5%) were women. The mean age of the participants was 41.17 ± 7.178 years, 284 (53.8%) were nurses and 244 (46.2%) were doctors. The BDS mean score of the participants was 16.47 ± 13.741 and the BAI mean score was 21.73 ± 12.161. The demographic characteristics of the participants are presented in Table 1.
The reasons for participants’ concerns about COVID-19 are presented in Table 2.
When we compare the BAI and BDS scores in terms of descriptive data of the participants, we found that there was a significant difference between these inventories in terms of age, department where the participant worked, and work experience of the volunteer (Table 3). According to post-hoc analysis, the difference in BAI score between the departments where the participants worked was associated with significantly higher anxiety scores of the participants working in the obstetrics and gynecology department, and the difference in BDS was associated with significantly lower depression scores of those working in the anesthesia and reanimation department (Table 3). We observed that the difference between age groups in BAI was caused by the 18-34 age group, and the anxiety scores of the participants in the 18-34 age group were significantly lower. In Beck depression, a significant difference was found among all age groups. While the lowest depression score was in the 18-34 age group and the highest was in the 50-64 age group, we observed that the depression score increased as the age increased. We observed a significant difference in BAI among the groups determined according to the participants’ work experience. The difference was associated with the group of 16 years and above, which is significantly higher than all other groups. For BDS, this difference arises from the 1-5 years group, whose depression score is lower than the other groups, and the 16 years and above group with higher depression scores than the other groups.
The vast majority of the participants (21%) stated that the emergency operating room was the most risky working area in terms of COVID-19, while Orthopedics and Traumatology were the least risky.
Discussion
Despite all the difficulties, healthcare professionals are fighting COVID-19 with extraordinary effort and determination. However, this struggle not only exhausts healthcare workers, but also puts their physical and mental health in serious danger [11-13]. Given that COVID-19 will remain a serious health crisis, healthcare professionals will need to maintain a high alert state for a long time. The negative effects of the pandemic on the psychology of healthcare workers will make it more difficult for healthcare workers to fight the disease. We planned this study to determine the depression and anxiety levels of nurses and doctors working in the operating room during the pandemic, and the causes of anxiety related to the pandemic. A total of 528 doctors and nurses participated in this cross-sectional and regional stratified study. According to the literature, healthcare workers struggling with infectious diseases experience certain psychological problems. Studies conducted during the previous acute respiratory syndrome (SARS) epidemic have shown that the epidemic negatively affected healthcare workers [14,15]. In a training hospital in Southern Taiwan, 17.3% of 135 healthcare workers who came into contact with patients with suspected SARS during the SARS epidemic developed significant mental symptoms [14]. In a study conducted in Toronto, new psychological problems were observed in 5% of healthcare workers after the SARS epidemic in Toronto [15]. Studies conducted during the COVID-19 pandemic show that psychological problems such as anxiety, depression and insomnia are common among healthcare workers [16,17]. While it was stated that mental health symptoms were high among healthcare workers treating COVID-19 patients in China, 50.4% of the participants reported symptoms of depression and 44.6% of them reported symptoms of anxiety [17]. A study conducted in China showed that during the COVID-19 epidemic, nearly half of healthcare workers experienced anxiety and depression, and more than half had general psychological problems [16]. In this study, we found that the doctors and nurses who took care of patients in the operating room diagnosed with COVID-19 showed mild symptoms of depression and experienced moderate anxiety. Nurses and doctors were similar in terms of anxiety level and depression symptoms. The anxiety and depression scores of the participants in the 18-34 age group were significantly lower than in other age groups, and the 50-64 age group had the highest depression score. The reason for this was thought to be the increase in morbidity and mortality with increasing age for COVID-19.
There is evidence in the literature suggesting that the female gender is a risk factor for depression and anxiety [18,19]. According to the results of this study, while the level of anxiety was higher in men compared to women, there was no statistical difference in terms of the symptoms of depression. Considering the results of our study, higher anxiety levels in men may be associated with the pandemic, but this should be supported by further studies.
Having contacts with COVID-19 patients while working, witnessing the physical pain and death of patients, increased workload, anxiety caused by working in a new department, they are not used to, fear of not being able to provide effective care, anxiety about inadequate medical equipment, the possibility of transmitting the diseases to other people, the fear of being stigmatized by others if they are caught with COVID-19, the need to wear uncomfortable protective equipment can expose healthcare workers to intense stress and affect negatively their psychology [13, 20-22]. Most of the nurses and doctors who participated in this study stated that even if the patient did not have COVID-19, they were still worried, they thought that they would be caught with COVID-19, no matter how careful they were, they were afraid of transmitting the disease to their relatives if they become infected with COVID-19 and they were afraid of not seeing their relatives. While the rate of those who were afraid of not having access to protective equipment and up-to-date information was low, a high percentage (81.8%) of the participants were worried about being assigned to a new field unfamiliar to them. Nearly half of the participants were worried about not being able to get tested for COVID-19, and more than half of them worried that their needs would not be met if they got the disease.
Previous studies show that healthcare professionals who are directly involved in the diagnosis, treatment and care of COVID-19 patients show higher symptoms of depression and experience higher anxiety [17,23]. On the contrary, in this study, although the anxiety level of healthcare workers working in the area of Anesthesia and Reanimation was the same as in other units, depression scores were lower than those working in other departments. The reason for the lower depression level of the participants working in anesthesia and reanimation was attributed to the fact that those working in this department received more frequent training, became aware of current information earlier, and were more experienced in protecting methods, as they worked in intensive care units and provided care and treatment to more COVID-19 positive patients than others. We think that the significantly higher anxiety level of the health care workers in the Obstetrics and Gynecology department may be due to the fact that there are more emergency cases such as cesarean section in this department, and this issue should be investigated.
The majority of the participants in the study stated that the emergency operating room was the most risky working area in terms of COVID-19. This was followed by anesthesia and reanimation, neurosurgery, respectively. Orthopedics and traumatology, general surgery, gynecology and obstetrics were reported as the ones with the lowest risk, respectively. Looking at this result, we think that the suspense caused by the impossibility of testing for COVID-19 before emergency surgeries and the concern that the surgeries involving the head and neck region are close to the patient’s respiratory tract cause healthcare professionals to think that these surgeries are more risky.
Various practices such as meeting the basic needs of healthcare professionals, providing social support, open communication, clarity in job description, flexible working hours, and the ability to benefit from psychological help without fear of being stigmatized by others will have a positive psychological effect on healthcare professionals [11,20]. Considering the results of this study, we see that the need to work in a department where they have not worked before is the leading cause of concern of healthcare workers regarding pandemic. Additionally, fear of getting COVID-19, fear of not being able to see their relatives and fear of not reaching personal protective equipment are among other common concerns about pandemic among healthcare professionals.
This study has some limitations. Firstly, a new scale could be developed measuring the anxiety and depression level of healthcare workers regarding the pandemic. But in this study, we just aimed to determine concerns about COVID-19. Maybe further studies can be performed to develop a scale. In addition, although there are non-pandemic reasons that play a role in anxiety and depression, these reasons were not included in the study.
Conclusion
Our findings reveal that doctors and nurses working in the operating room have mild depression symptoms and moderate anxiety. We see that the compulsory changes made in the distribution of healthcare workers in health institutions and in the new tasks defined for healthcare workers due to the pandemic, the difficulties experienced while working, and the anxiety they feel for their families are among the causes of concerns about the pandemic. These concerns may be the cause of anxiety and depression in healthcare workers. Thus, it can be said that taking measures such as training healthcare professionals on crisis management, providing the necessary psychological support for healthcare workers and improving the working conditions of healthcare workers will prevent the deterioration of the psychological status of healthcare workers in cases such as a pandemic and increase work efficiency.
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.
Funding: None
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.
References
1. Paudel S, Dangal G, Chalise A, Bhandari TR, Dangal O. The Coronavirus Pandemic: What Does the Evidence Show? J Nepal Health Res Counc. 2020; 18(1):1-9.
2. Singhal T. A Review of Coronavirus Disease-2019 (COVID-19). Indian J Pediatr. 2020; 87(4):281-6.
3. Lai CC, Liu YH, Wang CY, Wang YH, Hsueh SC, Yen MY, et al. Asymptomatic carrier state, acute respiratory disease, and pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): Facts and myths. J Microbiol Immunol Infect. 2020; 53(3):404-12.
4. Kamer E, Çolak T. What to do when a patient infected with COVID-19 needs an operation: a pre-surgery, peri-surgery and post-surgery guide. Turk J Colorectal Dis. 2020; 30:1-8.
5. Houghton C, Meskell P, Delaney H, Smalle M, Glenton C, Smalle M, et al. Barriers and facilitators to healthcare workers’ adherence with infection prevention and control (IPC) guidelines for respiratory infectious diseases:, a rapid qualitative evidence synthesis. Cochrane Database Syst Rev. 2020; 4(4):CD013582.
6. The Lancet. COVID-19: protecting health-care workers. Lancet. 2020; 395(10228): 922.. DOI: 10.1016/S0140-6736(20)30644-9.
7. Kang L, Li Y, Hu S, Chen M, Yang C, Yang BX, et al. The mental health of medical workers in Wuhan,, China dealing with the 2019 novel coronavirus. Lancet Psychiatry. 2020; 7(3):e14. DOI: 10.1016/S2215-0366(20)30047-X.
8. Ulusoy M, Şahin N, Erkmen H. Turkish Version of the Beck Anxiety Inventory: Psychometric Properties. Journal of Cognitive Psychotherapy. 1998;12:163-72.
9. Hisli N. Beck Depresyon Envanterinin üniversite öğrencileri için geçerliği, güvenirliği (Validity and reliability of the Beck Depression Inventory for university students). Psikoloji Derg/ Journal of Psychology. 1989; 7:3-13.
10. Beck At, Ward Ch, Mendelson M, Mock J, Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry. 1961; 4:561-71.
11. Petzold MB, Plag J, Ströhle A. Dealing with psychological distress by healthcare professionals during the COVID-19 pandemia. Nervenarzt. 2020; 91(5):417-21.
12. Tsamakis K, Rizos E, Manolis AJ, Chaidou S, Kympouropoulos S, Spartalis E, et al. COVID-19 Pandemic and Its Impact on Mental Health of Healthcare Professionals. Exp Ther Med. 2020;19(6):3451-3.
13. El-Hage W, Hingray C, Lemogne C, Yrondi A, Brunault P, Bienvenu T, et al. Les professionnels de santé face à la, pandémie de la maladie à coronavirus (COVID-19): quels risques pour leur santé mentale ? [Health professionals facing the coronavirus disease 2019 (COVID-19) pandemic: What are the mental health risks? Encephale. 2020; 46(3S):S73-S80. French.
14. Lu YC, Shu BC, Chang YY, Lung FW. The mental health of hospital workers dealing with severe acute respiratory syndrome. Psychother Psychosom. 2006; 75(6):370-5.
15. Lancee WJ, Maunder RG, Goldbloom DS. Prevalence of psychiatric disorders among Toronto hospital workers one to two years after the SARS outbreak. Psychiatr Serv. 2008; 59(1):91-5.
16. Que J, Shi L, Deng J, Liu J, Zhang L, Wu S, et al. Psychological impact of the COVID-19 pandemic on healthcare workers: a cross-sectional study in China. Gen Psychiatr. 2020; 33(3):e100259.
17. Lai J, Ma S, Wang Y, Cai Z, Hu J, Wei N, et al. Factors Associated With Mental Health Outcomes Among Health Care Workers Exposed to Coronavirus Disease 2019., JAMA Netw Open. 2020; 3(3):e203976. DOI:10.1001/jamanetworkopen.2020.3976.
18. Tee ML, Tee CA, Anlacan JP, Aligam KJG, Reyes PWC, Kuruchittham V, et al. Psychological impact of COVID-19 pandemic in the Philippines. J Affect Disord. 2020; 277:379-91. DOI:10.1016/j.jad.2020.08.043
19. Dubey S, Biswas P, Ghosh R, Chatterjee S, Dubey MJ, Chatterjee S, et al. Psychosocial impact of COVID-19. Diabetes Metab Syndr. 2020; 14(5):779-88. DOI: 10.1016/j.dsx.2020.05.035.
20. Heath C, Sommerfield A, von Ungern-Sternberg BS. Resilience strategies to manage psychological distress among healthcare workers during the COVID-19 pandemic: a narrative review. Anaesthesia. 2020; 75(10):1364-71.
21. Maunder RG, Leszcz M, Savage D, Adam MA, Peladeau N, Romano D, et al. Applying the lessons of SARS to pandemic influenza: an evidence-based approach to mitigating the stress experienced by healthcare workers. Can J Public Health. 2008; 99(6):486-8.
22. Albott CS, Wozniak JR, McGlinch BP, Wall MH, Gold BS, Vinogradov S. Battle Buddies: Rapid Deployment of a Psychological Resilience Intervention for Health Care Workers During the COVID-19 Pandemic. Anesth Analg. 2020; 131(1):43-54.
23. Zhang WR, Wang K, Yin L, Zhao WF, Xue Q, Peng M, et al. Mental Health and Psychosocial Problems of Medical Health Workers during the COVID-19, Epidemic in China. Psychother Psychosom. 2020; 89(4):242-50. DOI: 10.1159/000507639.
24. Smith E, Macdonald R. Managing health information during disasters. Health Inf Manag. 2006; 35(2):8-13.
Download attachments: 10.4328:ACAM.20686
Kadriye Acar, Hüseyin Acar, Erdinç Kamer, Gülay Oyur Çelik. Measuring depression and anxiety level and determining concerns regarded to pandemic in doctors and nurses working in operating room. Ann Clin Anal Med 2022;13(3):245-249
Citations in Google Scholar: Google Scholar
The impact of COVID 19 pandemic on pattern of cancer mortality in Najran, Saudi Arabia: A single-cancer center experience
Ahmed M. Badheeb 1, Mohamed A. Badheeb 2, Hamdi Alhakimi 3
1 Departmant of Medical Oncology, Oncology Centre, King Khalid Hospital, Najran, Saudi Arabia, 2 Departmant of Medicine, King Khalid Hospital, Najran, Saudi Arabia, 3 Department of Public Health Sciences, Uttech university, Uttech, Netherlands, Holland
DOI: 10.4328/ACAM.20778 Received: 2021-07-09 Accepted: 2021-08-20 Published Online: 2022-02-05 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):250-252
Corresponding Author: Ahmed Mohamed Badheeb, Oncology Centre, King Khalid Hospital, 1120, Najran, Saudi Arabia. E-mail: Badheebdr@gmail.com P: +96 653 831 84 39 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9753-5583
Aim: To explore the association between mortality and Covid infection, age, sex, site of cancer, stage, and the interval between the last dose of chemotherapy given within the last 30 days before death.
Material and Methods: Adult cancer patients who died of cancer in King Khalid Hospital in Najran -Saudi Arabia , were included in this retrospective observational study. We compared mortality patterns in a period of 6 months in 2020 (March to August) with the corresponding period of 2019.
Results: 50 dead adult cancer patients were included, 24 in 2019 and 26 in 2020. Among them, 21% vs 42% were younger than 65 years of age; 61% vs 62% were males, for the years 2019 & 2020 respectively. The top three killers in 2019 were colorectal, gastro-esophageal cancers, and hepatocellular carcinoma, while in 2020 were colorectal, hepatocellular carcinoma, and lymphomas. About 16.7% of patients died within 30 days of receiving anti-cancer treatment in 2019 in comparison with 7.7% in 2020. The difference in the 30-days mortality after receiving anti-cancer treatment was not statistically significant between 2019 and 2020 (p=0.329).
Discussion: The Year 2020, the time of the COVID-19pandemic, was not associated with a significant increase in the short-term mortality among patients with malignancy in Najran, Saudi Arabia. Our results generally reflect the crucial role of strict preventive national measures in saving lives and warrants further exploration.
Keywords: COVID 19, SARS-CoV-2, Mortality, Malignancy, Cancer
Introduction
Cancer is the main barrier for improving life expectancy. Factors like aging and changes in lifestyle are the main risk factors associated with increasing incidence and mortality of cancer1. Due to serious outcomes associated with COVID-19, it is expected to find higher levels of mortality in cancer patients than those in the normal population. Patients with cancer are usually susceptible to infectious diseases, and it is known that infections are a leading cause of death among this patient population2. Cancer may result in a weakened immune system due to the negative effect on immune cells, affecting their quantity or quality, as is the case in leukemia or lymphoma. Cancer therapy itself, whether it is surgery, radiotherapy, or chemotherapy, disturbs the immune system in various ways and results in an increased risk of infection3. Globally, cancer is the second leading cause of death with over 10 million death in 2018 4,5.
Patients with cancer are likely to have other comorbidities, whether due to age or exposure to cancer risk factors, such as smoking, obesity, and other lifestyle choices. Chronic diseases and comorbidities were identified previously as risk factors for COVID-19 mortality. All these factors lead to the predisposition of patients with cancer to a high risk of acquiring infectious diseases with a worse outcome than patients without cancer6.
The first COVID-19 case was confirmed in Saudi Arabia on the the 2nd of March 2020. The total number of reported cases of COVID-19 has reached 357,872 cases, recovered 347,513, with 5,919 deaths (last updated the 2nd of December 2020). Whilst there are still no data available on COVID-19 cases by their age group and other demographic factors in Saudi Arabia, the lower mortality rate might be a reflection of the young population in the kingdom and the strict preventive national measures78.
The aim of this paper is to describe the pattern of cancer mortality in Najran region during the COVID-19 pandemic and
to explore the association of cancer mortality during Covid pandemic with age, sex, site and stage of cancer, and the interval between the last dose of chemotherapy given within the last 30 days before death.
Material and Methods
Adult cancer patients who died of cancer in King Khalid Hospital in Najran Saudi Arabia, irrespective of the cancer stage and treatment type, were included in this retrospective observational study. The target population included adults aged ≥ 18 years who were histologically diagnosed with cancer, irrespective of the cancer stage, and class of anti-cancer treatment received, aiming to explore the association with age, sex, site of cancer, stage, and the interval between the last dose of chemotherapy given within the last 30 days before death. Cases with non-histologically confirmed diagnosis with cancer, or have incomplete record were excluded. The hospital was following the preventive measures as recommended by the ministry of health including the contact precautions, emergency department triage for probable cases, isolation in the wards and Intensive care unit and staff biweekly home-isolation to limit the exposure.
We selected the start date of March 2020 in concordance with the announcement of the first confirmed COVID-19 case in Saudi Arabia, while the end date was August 31 2020 in concordance with the drop of the cases and resumption of the near-normal life. We compared these 6 months in 2020 (March to August) with the corresponding period of 2019. Data were extracted from the electronic medical records based on the monthly mortality report for the medical department. Patient data confidentiality was maintained, and the declaration of Helsinki was followed.
Results
50 dead adult cancer patients were included, 24 in 2019 and 26 in 2020. Among them, 21% vs 42% were younger than 65 years of age; 61% vs 62% were males, for the years 2019 & 2020
respectively. Regarding the metastatic stage, 91% vs. 85% for the years 2019 & 2020 respectively. The leading causes of death in 2019 were colorectal, gastro-esophageal cancers, and hepatocellular carcinoma, while in 2020 were colorectal, hepatocellular carcinoma, and lymphomas (figure 1). About 16.7% of patients died within 30 days of receiving anti-cancer
treatment in 2019 in comparison with 7.7% in 2020. The difference in the 30-days mortality after receiving anti-cancer treatment was not statistically significant between 2019 and 2020 (p=0.329). The main direct cause of death in the two years was cancer progression (figure 2) , while COVID-19 was the direct cause in only 3% of the cases (figure 3).
Discussion
To the best of our knowledge, this study is the first trial evaluating the effect of the COVID-19 pandemic on cancer patients in Najran- Saudi Arabia9. Our study revealed a comparable mortality for cancer patients before and during COVID-19 pandemic. There is a doubling of the death risk in the year 2020 among patients younger than 65 (42% vs 21%), this can be explained by the death of two young lymphoma cases, including a case with tumor lysis syndrome complicated with hyperkalemia and another case that developed respiratory distress with rapid deterioration, but no positive COVID-19 testing was proved on them.
A Korean study revealed a death rate of 64% in patients with chronic comorbidities during the pandemic, including those with cancer. The low mortality among our patients can be explained by the implementation of extra precautionary measures to ensure that these vulnerable patients are not exposed to the virus10.
The limitation of our study is the small number of patients and the retrospective nature of the study design. Covid 19 testing was done only for the suspected cases as per the regulation of the ministry of health.
It is prudent to ensure that all possible precautionary measures be implemented to protect oncology patients from being exposed to Covid 19; developing additional protective measures, such as a vaccine, is important to prevent infection in this vulnerable population. Developing effective antiviral treatment will help in saving the lives of affected patients11.
Conclusions
The Year 2020, the time of the COVID-19 pandemic, was not associated with a significant increase in the short-term mortality among patients with malignancy in Najran, Saudi Arabia. Our results generally reflect the crucial role of strict preventive national measures in saving lives and warrants further exploration.
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.
Funding: None
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.
References
1. Jazieh A-R, Alenazi TH, Alhejazi A, Al Safi F, Al Olayan A. Outcome of oncology patients infected with coronavirus. JCO Glob Oncol. 2020;6:471-475.
2. Badawi A, Ryoo SG. Prevalence of comorbidities in the Middle East respiratory syndrome coronavirus (MERS-CoV): a systematic review and meta-analysis. Int J Infect Dis. 2016;49:129-133.
3. Al-Otaibi ST. The battle against Coronavirus disease 2019 (COVID-19) in the Kingdom of Saudi Arabia: Public health perspective. Saudi Med J. 2020;41(12):1285-1292.
4. Alsofayan YM, Althunayyan SM, Khan AA, Hakawi AM, Assiri AM. Clinical characteristics of COVID-19 in Saudi Arabia: A national retrospective study. J Infect Public Health. 2020;13(7):920-925.
5. Ljungman P, Gleaves CA, Meyers JD. Respiratory virus infection in immunocompromised patients. Bone Marrow Transplant. 1989;4(1):35-40.
6. Bernard-Stoecklin, S., Nikolay, B., Assiri, A. et al. Comparative Analysis of Eleven Healthcare-Associated Outbreaks of Middle East Respiratory Syndrome Coronavirus (Mers-Cov) from 2015 to 2017. Sci Rep 9, 7385 (2019). https://doi.org/10.1038/s41598-019-43586-9
7. Alyami MH, Naser AY, Orabi MAA, Alwafi H, Alyami HS. Epidemiology of COVID-19 in the Kingdom of Saudi Arabia: An Ecological Study. Front public Heal. 2020;8.
8. Tashkandi E, Al‑Abdulwahab A, Basulaiman B, et al. Mortality and morbidity of curative and palliative anticancer treatments during the COVID‑19 pandemic: A multicenter population‑based retrospective study. Mol Clin Oncol. 2021;14(4):1-11.
9. Badheeb AM, Nagi NM, Badheeb MA. Cancer Pattern among Adults in Najran, Saudi Arabia – 2014-2019. Int J Innov Res Med Sci. 2020;5(10):485-487. doi:10.23958/ijirms/vol05-i10/979
10. Sanchez-Pina JM, Rodríguez Rodriguez M, Castro Quismondo N, et al. Clinical course and risk factors for mortality from COVID-19 in patients with haematological malignancies. Eur J Haematol. 2020;105(5):597-607.
11. Algaissi AA, Alharbi NK, Hassanain M, Hashem AM. Preparedness and response to COVID-19 in Saudi Arabia: Building on MERS experience. J Infect Public Health. Published online 2020.
Download attachments: 10.4328:ACAM.20778
Ahmed M. Badheeb, Mohamed A. Badheeb, Hamdi Alhakimi. The impact of COVID 19 pandemic on pattern of cancer mortality in Najran, Saudi Arabia: A single-cancer center experience. Ann Clin Anal Med 2022;13(3):250-252
Citations in Google Scholar: Google Scholar
Comparison of dual-task performance in healthy geriatric individuals from different age groups
Yasemin Martin 1, Duygu Şahin 2, Filiz Altuğ 3, Hanifegül Taşkıran 4
1 Private Empathy Consulting Special Education and Rehabilitation Center, Denizli, 2 Department of Physiotherapy and Rehabilitation, Institute of Health Science, Hacettepe University, Ankara, 3 School of Physical Therapy and Rehabilitation, Pamukkale University, Denizli, 4 Department of Physiotherapy and Rehabilitation, Istanbul Aydin University, İstanbul, Turkey
DOI: 10.4328/ACAM.20868 Received: 2021-09-21 Accepted: 2021-10-21 Published Online: 2021-10-28 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):253-257
Corresponding Author: Duygu Şahin, Division of Physical Therapy and Rehabilitation, Institute of Health Science, Hacettepe University, Ankara, Turkey. E-mail: fztduygusahin@gmail.com P: +90 553 524 40 74 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2914-7976
Aim: The aim of this study was to compare the dual-task performance of healthy geriatric individuals in different age groups.
Material and Methods: One hundred and two healthy geriatric individuals were included in our study (Group 1: aged 65-75 years, Group 2: aged 75-84 years). In single-task, Montreal Cognitive Assessment Scale was used to evaluated cognitive performance; Timed Up and Go Test, 30 Seconds Sit-to-Stand Test and 10 Meter Walking Test were applied to evaluate motor performance. Dual-task performance was evaluated as motor-motor and motor-cognitive. The Dual-Task Questionnaire was applied to determine how difficult it was for the individuals during the dual-task.
Results: In single-task comparisons, a significant difference was found in favor of Group 1 in all assesments. While there was a significant difference in favor of Group 1 in motor-motor dual-task performance duration and motor-cognitive dual task performance duration (p= .000), there was no statistically significant difference in motor-motor dual-task performance (p=0.791) and motor-cognitive dual task performance (p=0.475) between groups. For Dual-Task Questionnaire, a significant difference was found between the two groups in favor of Group 1 (p= .000).
Discussion: Correspondingly with the decrease in physical and cognitive functions that occur with aging, a decrease in dual-task performance and performance durations were observed. Analyzing the studies conducted in the literature and more comprehensive studies on this subject will guide authors and clinicians.
Keywords: Aging, Cognition, Geriatrics, Rehabilitation
Introduction
Aging begins with childhood and progresses with adulthood, and as time passes, the physical and mental independence of a person decreases, these all are structural and functional changes that negatively affect the musculoskeletal, cognitive and motor functions of living beings. [1]. According to the new age range list of the World Health Organization (WHO), which updates age groups to reflect changing and developing technology, 66 and 79 age range is defined as middle-age and age over 80 is defined as elderly [2]. On the other hand, gerontologists classified old age as ‘young-old’ between 65-74 years, ‘middle-old’ between 75-84 years, and ‘advanced-old’ over 85 years [3].
A dual-task is the measurement of two (sometimes more) information sources that are often processed simultaneously, as a result of sharing attention with dual-task performance [4]. On the dual-task scale, while the capacity of attention is used extensively in dual tasks performed simultaneously, attention can be divided according to the priority and degree of difficulty of the given tasks. Accordingly, changes in attention capacity and difficulty level may create problems in performing either or both of the tasks. Individuals are often asked to maintain a certain level of performance in the primary task under dual- task conditions. When the demands of concurrent tasks exceed the available processing capacity, one or two jobs are expected to deteriorate in performance [5].
Brustio et al. reported in their study on women in the young, middle’, and old age groups that older women showed worse physical performance under dual-task performance compared to young and middle-aged groups [6]. In parallel with this, in another study investigating dual task performance among young adults, middle-aged and older adults, it was reported that dual task performance was affected by age, therefore mobility and cognitive tasks were negatively affected by age [7]. In addition to all these, there is no study in the literature comparing dual-task performance in geriatric individuals of different age ranges.
The aim of this study was to examine the motor-motor and motor-cognitive performances that affect dual-task performance in healthy geriatric individuals in different age groups. We hypothesized that, in parallel with the decrease in physical and cognitive functions that occur with aging, ‘advanced-old’ geriatric individuals had a greater decrease in dual-task performance.
Material and Methods
Participants and Study Setting
This is a cross-sectional study, which included participants during their evaluation at an orthopedic clinic in Turkey during the study recruitment period (March 2019- January 2020). All participants were informed about the study prior to the study and written informed consent was obtained.
The study was approved by the Pamukkale University Institutional Review Board (25.12.2018/24). Informed consent was obtained from volunteers who wanted to participate in the study.
The sample size calculation was based on effect size strength (d:0.5), assuming a 95% confidence interval and power of 80%, when at least 102 people (Group 1: 51 individuals between 65-74 years of age, Group 2: 51 individuals between 75-84 years of age) were included in the study. Taking into account the estimated dropout rate, 110 participants needed to be recruited [8,9].
A total of 110 healthy geriatric individuals aged between 65-85 years were included in the study. The demographic characteristics of all participants are presented in Table 1. The Hodkinson Mental Test (HMT) was applied to the patients under the guidance of a physiotherapist [10]. Healthy elderly people with an HMT score of 8 and above, divided into two groups (ratio 1:1) according to gerontologists, were classified as [3]; Group 1: 65-74 years old (n= 51) and Group 2: 75-84 years old (n= 51) (Figure 1).
The inclusion criteria were as follows:
– Agreement to participate in the study;
– age 65-85 years;
– Being healthy;
– Getting a score of 8 and above on the Hodkinson Mental Test (HMT)
– Absence of any motor dysfunction that would prevent performing tests on the lower and upper extremities.
Healthy geriatrics who used more than 3 drugs that could affect motor or cognitive levels and had a diagnosed orthopedic or neurological problem were excluded from the study.
Outcome Measurement
HMT is a test that is used for the assessment of memory and orientation in the elderly. Each correct answer is scored with 1 point in the 10-question form. Scores from 6 and above indicate normal functions, 4-6: moderate impairment, 0-3: severe impairment [10]. Subjects who received 8 or higher scores were included in the study.
The Montreal Cognitive Assessment Scale (MoCA) was applied to evaluate the cognitive functions of the participants. This test measures 8 different cognitive functions: attention and concentration, executive functions, memory or delayed memory, language, visual spatial function, isolation, calculation and orientation. The highest score that can be obtained on the test is 30 in total. A score of 21 points or more is considered normal [11,12].
Timed Up and Go Test (TUG) is a test that evaluates fall risk and mobility in individuals. The test is carried out using a 40 cm high chair and a stopwatch are used to conduct the test. An area of 3 meters is determined in front of the chair. The patient is asked to stand up from the chair, walk at a normal speed, sit down and lean on the chair, and this time displays the duration of the test in seconds. For adult individuals, if they complete this test in more than 12 seconds, it is defined as a falling risk [13].
The 30- second Sit-to-Stand Test (30s-CST) is a test that evaluates the sit-to-stand activity, lower extremity strength, and dynamic balance of the subject. A chair with a seat height of around 44 cm and a recline (no arms if possible) and a stopwatch are needed. Once the person has settled comfortably in the chair in full contact, he crosses his arms and holds his shoulders freely. It is necessary to ensure that the individual gets up completely upright and sits back on the chair. The stopwatch starts from the moment of first start, and the number of times a person sits and stands up within 30 seconds is recorded. If the number of times a patient is able to stand from a sitting position in 30 seconds is less than 10, this result indicates lower extremity weakness [14].
The 10- Meter Walking Test (10MWT) is used to evaluate normal gait. In this test, the individual is asked to walk at a daily walking speed in an area of 10 meters whose limits are determined. Timing starts when the foot reaches the start line and ends when it crosses the finish line. Two attempts are made and the best value is recorded as the result in meters/second [15].
In order to evaluate the motor-motor dual-task performance (MMDTP) of the participants in this study, the task of carrying 2 glasses on the tray was given during the 10-meter walking test. At the starting point of the predetermined 10-meter distance, individuals were asked to hold a standard-sized tray that they could hold, and two standard glasses were left on it. The stopwatch was started by giving the start command to the individuals, and they were asked to complete the 10 m distance without dropping the glasses [16].
In order to evaluate the motor-cognitive dual-task performance (MCDTP), participants were assigned the task of counting down the days of the week from Sunday during the 10-meter walking test. The participant who came to the starting point was asked to start on Sunday and walk at the same time to count down. Although he stopped to think about the days, time passed and he was expected to complete the 10-meter distance [17].
Dual-Task Performances are calculated separately for motor-motor and motor-cognitive tasks [18];
• MMDTP = 100 x [(dual task score – walking single task) / single task walking]
• MCDTP= 100 x [(dual task score – walking single task) / single task walking]
The Dual Task Questionnaire (DTQ) was used to obtain information about the difficulties experienced by individuals in their daily life in situations requiring dual tasks while performing these tasks. The dual-task questionnaire consists of 10 questions. Each question is scored as very frequent (4), frequent (3), occasionally (2), rarely (1), and never (0). The total score is calculated by adding the answers given to all questions and divided into 10 [19].
Statistical Analysis
The study data were evaluated using the Statistical Package for Social Sciences 20.0 program for Windows and through the analysis of the descriptive statistics. Before the statistical analysis, the Kolmogorov–Smirnov test was used to assess the normality of the data. Differences between the groups were compared using the parametric test (T-test) for data conforming to the normal distribution, and the non-parametric (Mann-Whitney U) statistical tests for the data that did not comply with the normal distribution. The Chi-square analysis was used to analyze differences between categorical data. In all statistics, p <0.05 was considered significant [20].
Results
The flow of participants is shown in the flowchart in Figure 1. Among the 110 individuals who consented to participate, four were not included, and four of them were excluded from the study because they scored less than 8 on the HMT. The 102 participants were allocated to Group 1: Individuals between 65-74 years of age (n=51) and Group 2: Individuals between 75-84 years of age (n=51). There was a statistically significant difference between the groups in terms of education levels (p=0.001) and hobby habits (p=0.013). The baseline characteristics of the participants are shown in Table 1.There was a statistically significant difference between Group 1 and Group 2 in favor of Group 1, in both motor-motor dual task time (MMDTT) (z=4.89, p=0.000) and motor-cognitive dual task time (MCDTT) (z=5.54, p=0.000). There was no statistical difference in DTMMP (z=0.26, p= 0.791) and DTMCP (z=2.04, p=0.475) in between the two groups (Table 3). Additionally, there was a statistically significant difference for DTQ (z=3.65, p=0.000) between two groups in favor of Group 1 (Table 3).
Discussion
This cross-sectional study aimed to compare the dual task performance in healthy geriatric individuals in different age groups. The results demonstrated that Group 1 showed better scores than Group 2 in terms of MoCA, TUG, 30s-CST and 10MWT in single task performance. Additionally, the results demonstrated that Group 1 showed better scores than Group 2 in terms of MMDTP, MCDTP, MMDTT, MCDTT an DTQ scores.
In our study, MoCA was used for cognitive performance evaluation in a single performance evaluation. Gluhm et al. applied MoCA on 254 healthy individuals aged 20-89 years and reported that the MoCA score decreased with increasing age [21]. Similarly, Malek-Ahmadi et al. on the other hand, divided geriatric individuals between the ages of 70 and 99 into 3 groups, each with a 10-year age range, and examined the MoCA score; they reported higher MoCA performance in the younger group [22]. In parallel with these studies, our study found that healthy geriatrics in Group 1 showed statistically higher MoCA performance than in Group 2.
In our study, TUG, 30sCST, and 10 MWT were used for motor performance evaluation in a single performance evaluation. Yüksek and Cicioğlu divided healthy geriatric individuals aged 65-75 years into 3 groups and examined their 30sCST performance and reported that the younger group performed better [23]. In parallel with this study, in our study, healthy geriatric individuals in Group 1 showed statistically better TUG, 30sCST and 10 MWT performances than individuals in Group 2.
Considering the studies examining the effect of age on dual task performance, Olivier et al. examined whether postural control is affected by cognitive tasks in children and adults aged 7-11 years. It has been reported that 8-11-year- old children perform better than 7- year-old children in dual task performance, but they cannot reach the level of adults. The reason for this is thought to be related to the increase in attention capacity in children around the age of 8 years [24]. Brustio et al. examined dual task performance on elderly (72.74 ± 5.95), middle-aged (47.82 ± 5.06) and young (25.12 ± 3.00) adult women. Cognitive dual-task performance with timed get- up- and- go test while counting down from three; manual dual-task performance was evaluated with the timed get- up- and- go test while carrying a glass of water. At the end of the study, older women showed worse mobility performance under the dual-task condition compared to younger and middle-aged groups [6]. In another study by Brustio et al., age-related differences in dual-task performance in both mobility and cognitive tasks were investigated in a sample of the elderly (72.63±5.57), middle-aged (46.69±4.68) and young (25.34±3.00) male and female adults. According to the results of the study, physical and cognitive performance, and hence dual task performance were affected in older adults [7]. According to these results obtained from the studies, while the dual-task performance continues to increase from the age of 8 to adulthood and begins to decrease with aging [6,7,24]. In parallel, in our study, a decrease was observed in single-task performances, dual-task performance times and dual-task performances. In our study, we also questioned how much difficulty individuals have while performing dual-task performance with the Dual-Task questionnaire, and we found that individuals have more difficulty in tasks that require dual-task performance as they get older.
The fact that our study was conducted only on geriatric individuals who applied to an orthopedic clinic may be considered as a limitation of our study. Different results may be obtained in studies to be conducted in more than one clinic or in different provinces with more cases with different sociodemographic histories. Another limitation is that the basic tasks of the individuals participating in our study and the additional tasks given to the basic tasks are applied to all individuals in the same order. In addition, in our study, we did not identify any limitations in terms of education level. We think that the fact that there was no restriction according to education level may have affected the results of MoCA and thus the results of dual-task performance.
Future studies are required to investigate dual-task performance with more participants by making changes in the order of tasks in geriatric individuals where sociodemographic characteristics and cognitive functions are more clearly determined.
In summary, in parallel with the decrease in physical and cognitive functions that occur with the advancement of age, a decrease in dual task performances and performance times have been observed in geriatric individuals.
Conclusion
In summary, in parallel with the decrease in physical and cognitive functions that occur with aging, a decrease in dual task performances and performance times was observed in geriatric individuals.
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.
Funding: None
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.
References
1. Koldaş ZL. What is aging and cardiovascular aging? Turk Kardiyol Dern Ars 2017; 45 (Suppl 5): 1-4.
2. Çataloğlu S. Old Age, Value and Technology. International Journal of Human Studies 2018; 1(1): 25-33.
3. Soyuer F, Soyuer A. Yaşlılık ve Fiziksel Aktivite (Aging and Physical Activity). İnönü Üniversitesi Tıp Fakültesi Dergisi/ Journal of Inonu University Faculty of Medicine. 2008; 15(3): 219-24.
4. Verhaeghen P, Steitz D, Sliwinski M, Cerella J. Aging and dual-task performance: a meta-analysis. Psychol Aging. 2003; 18(3): 443-60.
5. Abernethy B. Dual-task methodology and motor skills research: Some applications and methodological constraints. J Hum Mov Stud. 1988; 3: 14: 101-32.
6. Brustio P, Magistro D, Rabaglietti E, Liubicich M. Age-related differences in dual task performance: A cross-sectional study on women. Geriatr Gerontol Int. 2017; 17(2): 315-21.
7. Brustio P, Magistro D, Zecca M, Rabaglietti E, Liubicich M. Age-related decrements in dual-task performance: Comparison of different mobility and cognitive tasks A cross sectional study. PLoS One. 2017; 12(7): e0181698.
8. Hollman JH, Youdas JW, Lanzino DJ. Gender differences in dual task gait performance in older adults. Am J Mens Health. 2011; 5(1): 11-7.
9. Faul F, Erdfelder E, Lang A-G, Buchner A. G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2017; 39(2): 175-91.
10. Laudisio A, Marzetti E, Pagano F, Cocchi A, Franceschi C, Bernabei R, et al. Association of metabolic syndrome with cognitive function: the role of sex and age. Clin Nutr. 2008; 27(5): 747-54.
11. Lima LCA, Ansai JH, Andrade LP, Takahashi ACM. The relationship between dual-task and cognitive performance among elderly participants who exercise regularly. Braz J Phys Ther. 2015; 19(2): 159-66.
12. Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I et al. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005; 53(4): 695-9.
13. Padsiadlo D, Richardson S. The timed Up & Go: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991; 39(2): 142-8.
14. Jones CJ, Rikli RE, Beam WC. A 30-s chair-stand test as a measure of lower body strength in community-residing older adults. Res Q Exerc Sport. 1999; 70(2): 113-19.
15. Wolf SL, Catlin PA, Gage K, Gurucharri K, Robertson R, Stephen K. Establishing the reliability and validity of measurements of walking time using the Emory Functional Ambulation Profile. Phys Ther. 1999; 79(12): 1122-33.
16. Nordin E, Moe-Nillsen R, Ramnemark A, Lundin-Olsson L. Changes in step-width during dual-task walking predicts falls. Gait Posture. 2010; 32(1): 92–7.
17. Rocha E, Carpes F. Impact of two different dual tasks on obstacle crossing in elderly. Fisioter Pesq. 2015; 22(4): 386-91.
18. Weightman MM, McCulloch K. Chapter 8: Dual-task assessment and intervention. In: Weightman MM, Radomski MV, Mashima PA, Roth CR, editors. Mild TBI Rehabilitation Toolkit, 1st ed. Fort Sam Houston: Office of The Surgeon General Borden Institute; 2014.p. 321-33.
19. Evans J, Greenfield E, Wilson B, Bateman A. Walking and talking therapy: improving cognitive-motor dual-tasking in neurological illness. J Int Neuropsychol Soc. 2009; 15(1): 112-20.
20. Cohen J. Statistical power analysis for the behavioral sciences, 1st ed. New York: Lawrence Erlbaum Associates; 1988.
21. Gluhm S, Goldstein J, Loc K, Colt A, Van Liew C, Corey-Bloom J. Cognitive performance on the mini-mental state examination and the montreal cognitive assessment across the healthy adult lifespan. Cogn Behav Neurol. 2013; 26(1): 1-5.
22. Malek-Ahmadi M, Powell JJ, Belden CM, O’Connor K, Evans L, Coon DW, et al. Age- and education-adjusted normative data for the Montreal Cognitive Assessment (MoCA) in older adults age 70–99. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2015(6); 22 :755-61.
23. Yüksek S, Cicioğlu İ. Assessment of Physical Fitness Level of Healthy Individuals Aged 65-75 Years. Turkish Journal of Geriatrics. 2005; 8(1): 25-33.
24. Olivier I, Cuisinier R, Vaugoyeau M, Nougier V, Assainte C. Age-related differences in cognitive and postural dual-task performance. Gait Posture. 2010; 32(4): 494-9.
Download attachments: 10.4328:ACAM.20868
Yasemin Martin, Duygu Şahin, Hanifegül Taşkıran, Filiz Altuğ. Comparison of dual-task performance in healthy geriatric individuals from different age groups. Ann Clin Anal Med 2022;13(3):253-257
Citations in Google Scholar: Google Scholar
Comparison of glucose concentration stability in serum and plasma tubes
Nilgun Isiksacan 1,2, Pinar Kasapoglu 1, Alev Kural 1, Zeynep Levent Cirakli 1, Munevver Mert 1, Yuksel Gulen Cicek 1, Sehide Baz 1, Duygu Teksoz 1, Sebnem Tekin Neijmann 1
1 Department of Biochemistry, University of Health Sciences, Bakirköy Dr. Sadi Konuk Training and Research Hospital, 2 Department of Immunology, University of Health Sciences, Istanbul, Turkey
DOI: 10.4328/ACAM.20887 Received: 2021-10-07 Accepted: 2022-01-17 Published Online: 2022-01-25 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):258-262
Corresponding Author: Nilgun Isiksacan, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Zuhuratbaba Mah., Tevfik Saglam Cad., No:11, 34180, Bakirkoy, Istanbul. E-mail: nisiksacan@gmail.com P: +90 532 494 49 95 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0230-6500
Aim: The objective of this study is to research the stability of glucose in samples collected into serum and plasma tubes, according to centrifuging following different waiting periods, and to identify which glucose tube would be most suitable for accurate glucose measurement in laboratories.
Material and Methods: A total of 12 venous blood samples were collected from volunteers subjected to OGTT (n=20) after fasting and after administering 75g of glucose. Serum (VACUETTE®CAT Serum Separator Clot Activator) and plasma (VACUETTE®FC Mix Tube) tubes were used. Centrifugation was performed as follows: in the 1st group, immediately at hour 0, group 2, and 3 after having been kept at room temperature for respectively 2 hours, and 4 hours.
Results: No significant changes were identified among the fasting and postprandial blood glucose measurements in the plasma tubes at 0, 2, and 4 hours (p>0.05). Significant changes were identified among the fasting and postprandial blood glucose measurements in the serum group at 0, 2, and 4 hours (p=0.001; p<0.01).
Discussion: Our study demonstrated that the plasma tube was most effective in preventing a clinically significant change in glucose concentration at room temperature.
Keywords: Glucose, Pre-Analytical Phase, Stability
Introduction
Diabetes mellitus (DM) is a chronic and serious disease that occurs when the pancreas is unable to produce sufficient insulin or the body is unable to effectively use the insulin it produces, and it is characterized by high blood glucose levels [Available
online at: https://www.who.int/publications/i/item/9789241565257]. Even though they may be below the diagnostic threshold for DM, blood glucose levels higher than optimal are an important source of mortality and morbidity [Available online at: https://www.who.int/publications/i/item/9789241565257]. A laboratory plasma glucose test is essential for diagnosing DM, impaired fasting glucose and/or impaired glucose tolerance, and especially for screening, and for diagnosing gestational DM in cases where HbA1c cannot be used [1,2]. On the other hand, there are studies using different sample types and different techniques for HbA1c measurements in various clinical and point care conditions [1,2]. Therefore, it is clear that plasma glucose measurement must be accurate and definitive for accurate patient classification according to international guidelines [1].
The analytic methods primarily used for glucose assessment are enzymatic analyses based on hexokinase (recommended) or glucose oxidase reaction [1]. These methods have been standardized with an inter-laboratory ambiguity (CV) <2.6% [2].
The diagnostic criterion for DM is ≥126 mg/dL fasting plasma glucose, which is a diagnostic point selected according to microvascular complications such as diabetic retinopathy [1].
The fact that phlebotomy units are nowadays located at a distance from central laboratories causes a delay of several hours in processing samples [3]. Since cellular metabolism is a process that continues even after phlebotomy, time and temperature conditions during the transfer of the samples become the most critical variables [3].
It is a known fact that glucose concentration decreases in samples kept in whole blood [4]. A 5-7% in vitro reduction per hour due to glycolysis has been reported in plasma glucose samples not centrifugated immediately [1]. In order to minimize in vitro glycolysis, the American Diabetes Association (ADA) and the National Academy of Clinical Biochemistry (NACB) recommend immediately placing an ice slurry in the sample tube, and separating the plasma from the cells in 30 minutes, and, if this is not possible, a sample tube containing a fast glycolysis inhibitor should be used [1].
Sodium fluoride/potassium oxalate (NaF/KOx) is the most widely found additive among glucose inhibitors. This tube ensures better glucose stabilization compared to conventional serum and lithium heparin tubes, but its effectiveness is inadequate [4]. The inhibiting effect of sodium fluoride (NaF) on glycolysis emerges only 2-3 hours after phlebotomy and causes a decrease in glucose concentration during this period [1].
Glucose concentration decreases >6% in NaF/KOx plasma samples kept at RT without having been centrifugated. After this period, the plasma glucose consumption rate drops, and at the end of a 4-hour period, the decrease in the glucose concentration reaches a maximum of 8%. Clinically significant hemolysis is seen in a maximum of 94% of the samples processed using the NaF/KOx additive [4].
The use of an FC Mix-citrate buffer tube instead of a tube containing NaF generates more stable and reliable results in the plasma glucose of samples kept at room temperature (RT) without centrifuging [4].
In recent years, the use of phlebotomy tubes containing NaF and citrate buffer have been recommended: acidification of blood to pH of <5.9 inhibits hexokinase and phosphofructokinase, which are enzymes that are involved in the upper stages of glycolysis, therefore causing a faster inhibition [1].
Glucose-specific plasma tubes containing NaF, citrate and EDTA were used in order to minimize glycolysis in our study. Our objective was to research the stability of the glucose in the samples collected into the serum and plasma tubes according to different centrifugation delays and to identify which tube would be most suitable for accurate estimation of glucose in a routine laboratory setting.
Material and Methods
The study was conducted with 20 volunteers subjected to an oral glucose tolerance test (OGTT) at the Xxxx Xxxx University, Xxxx Xxx Xxxx Xxxx Xxxx Hospital. Pregnant patients were excluded. A total of 12 venous blood samples per subject were collected. Six tube consisted of three serum and three plasma for 0. hour, 2nd hour, and 4th hour centrifugation in fasting and the same design were used for postprandial measurements. Namely, two batches of samples were taken after fasting, and after consuming a 75g glucose solution. 454243-VACUETTE® Tube 2.5 ml Z Serum Gel Clot Activator, 13×75 (Greiner Bio-One-Austria) tubes were used for serum, and 454513-VACUETTE® FC Mix 3 ml 13×75 (Greiner Bio-One-Austria) tubes were used for plasma. The serum tubes were turned upside-down 5-10 times, and the plasma tubes 10 times following phlebotomy. The collected samples were processed in 3 groups; the 1st group consisted of samples centrifugated immediately at hour 0. The 2nd group consisted of samples centrifugated after a delay of 2 hours. The 3rd group consisted of samples centrifugated after a delay of 4 hours (Table 1). Centrifugation was performed at 1800g for 10 minutes. The samples were analyzed using a Beckman Coulter AU 5821 instrument and glucose kit.
In OGTT patients, vascular access is established at hour 0. To ensure compliance with the optimum phlebotomy procedure at hour 0 and hour 2, phlebotomy was performed using a vascular access adapter (450210- VACUETTE® SAFELINK Holder with male luer-lock-Greiner Bio-One-Austria).
Ethics approval was obtained from the local committee (2020 / 532). Informed consent was obtained from all individuals included in this study.
Statistical Examinations
The NCSS (Number Cruncher Statistical System) 2007 (Kaysville, Utah, USA) software was used. When evaluating the study data, descriptive statistical methods were used. The compatibility of quantitative data with normal distribution was tested using the Shapiro-Wilk test. Repetitive measurements variance analysis was used in the intragroup comparison (IGC) of quantitative variables demonstrating a normal distribution, and the Bonferroni adjusted dual ratings were used in evaluating dual comparisons. The Friedman Test was used in the intragroup comparisons of quantitative variables that did not exhibit a normal distribution, and the Bonferroni adjusted Wilcoxon signed-ranks test was used in evaluating dual comparisons. The Related groups t-test was used in the intragroup comparisons of quantitative variables demonstrating normal distribution. The Wilcoxon signed-ranks test was used in the intragroup comparisons of quantitative variables that did not demonstrate a normal distribution. Statistical significance was accepted as p<0.05.
Results
The results were evaluated by comparing blood glucose measurements performed in the plasma and serum tubes after fasting, and after the administration of glucose.
The mean 6.3±2.12, 13.36±3.67, 20.00±3.08 mg/dL differences found between the fasting plasma and serum measurements at hour 0, hour 2 and hour 4 were significant (p=0.001; p<0.01), respectively. No significant changes were identified among the fasting glucose measurements in the FC Mix group at 0, 2 and 4 hours (p>0.05). Significant changes were identified among the fasting glucose measurements in the serum group at 0, 2 and 4 hours (p=0.001; p<0.01) (Table 2). According to the results of dual comparison, the decrease in the mean of 7.45±3.76 mg/dL in fasting measurements at 2 hours compared to hour 0 was significant (p=0.001; p<0.01). The decrease in mean of 12.79±3.29 mg/dL in fasting measurements at 4 hours compared to hour 0 was also significant (p=0.001; p<0.01). The decrease in mean of 5.34±2.09 mg/dL in fasting measurements at 4 hours compared to hour 2 was significant as well (p=0.001; p<0.01) (Figure 1).
The difference in mean 6.63±3.67, 13.5±3.64, 20.65±3.58 mg/dL found between the postprandial plasma and serum measurements at hour 0, hour 2 and hour 4 was significant (p=0.001; p<0.01), respectively. No statistically significant changes were identified among the postprandial blood glucose measurements in the plasma group at 0, 2, and 4 hours (p>0.05). Significant findings were identified among the postprandial glucose measurements in the serum group at 0, 2 and 4 hours (p=0.001; p<0.01) (Table 2). According to the results of the dual comparison performed in order to identify the difference, the decrease in mean of 7.14±4.21 mg/dL in postprandial glucose measurements at 2 hours compared to hour 0 was significant (p=0.005; p<0.01). The decrease in mean of 14.51±5.72 mg/dL in postprandial measurements at 4 hours compared to hour 0 was also significant (p=0.001; p<0.01). Additionally, the decrease in mean of 7.38±3.13 mg/dL in postprandial measurements at 4 hours compared 2 hours was significant (p=0.005; p<0.01) (Figure 1).
Discussion
The citrate buffer/citric acid solution contained in the FC Mix plasma tube ensures pH-dependent enzyme inactivity, the EDTA acts as an anticoagulant, and NaF results in enzyme inhibition. Our study demonstrated that the plasma tube was most effective in preventing a clinically significant change in glucose concentration at RT.
This study provides useful data on the most suitable glycolysis inhibitor tube. The results have demonstrated that significant variation in glucose results is generated when the plasma tube is compared with serum in normal participants.
The serum data have demonstrated that the recommended 30-minute coagulation period is sufficient to allow important changes and that long-term contact with cells causes glucose consumption. In simple terms, this demonstrates that standard serum tubes are not suitable for accurate glucose estimation under normal laboratory processing conditions.
In the real world, samples in most laboratories are not processed and analyzed within 1 hour after being taken, but the serum is almost always used for the routine monitoring of glucose concentration and subsequent patient management.
The latest manuals on preanalytical and analytical conditions published by the ADA, the American Association of Clinical Chemistry (AACC, 2011), and the World Health Organisation (WHO, 2006) recommend the following: glycolysis must be minimized by immediate separation of the plasma from cells by centrifugation, or by placing the tubes on ice immediately after phlebotomy, and performing centrifugation within 30 minutes [5].
Since applying either method is logistically difficult in everyday practice, it is a widespread practice to add NaF to the blood collection tube as a glycolysis inhibitor [5]. However, the inhibitory effect of NaF on glycolysis emerges only 2-3 hours after phlebotomy resulting in a decrease in glucose concentration during this period [1]. Therefore, the use of NaF alone as a glycolysis inhibitor is considered inadequate by the AACC and WHO [6].
The combination of different anticoagulants in plasma tubes offers an important advantage in the preservation of glucose compared to tubes containing only serum, heparin, EDTA, NaF/KOx or citrate.
It is clear that the prevention of glycolysis would give rise to a more accurate diagnosis and timely management of patients, which, in turn, may be useful, reducing risks for patients and the healthcare system; in the same manner, it will render results more reliable during lengthy storage periods before the analysis is completed.
ADA and NACB manuals recommend that plasma glucose analyses must be performed in tubes that are treated according to the gold standard for handling blood samples, or in collection tubes that contain a fast-acting glycolysis inhibitor such as a citrate buffer [6].
Serum, lithium-heparin or NaF/EDTA tubes, used on their own, miss the analytical target for the allowed deviation. This way, plasma tubes allow accurate identification of glucose, which is among the fundamental criteria for diagnosing DM.
Citrate buffer generates samples with a lower rate of hemolysis compared to NaF. It has been demonstrated that the glucose concentration measured in samples containing citrate buffer yields more stable and accurate results compared to the glucose value measured in samples containing other additives. The hexokinase enzyme in the plasma of hemolyzed samples erroneously decreases the glucose concentration measured using the reference hexokinase measurement method [4].
The evaluation of the plasma glucose in the samples measured in the tubes containing citrate buffer reflects the real (in vivo) glucose concentration more reliably. These innovations in additives give rise to important questions relating to the existing glucose reference ranges for diagnosis, which have been identified and verified using other additives [4].
The literature emphasizes that the transition from tubes containing NaF to tubes containing a citrate buffer causes a marked increase in the existing value ranges of glucose measurements for the diagnosis of DM. This increase necessitates further research to identify whether it is necessary to re-evaluate the reference ranges and the threshold values for diagnosis [4].
The tube we have used is a special blood collection tube containing a combination of EDTA anticoagulant, NaF, and citrate. The VACUETTE® FC Mix Tube, contains additives in dry/powder form.
The use of the glycolysis inhibitor in granular form offers a pre-analytic advantage by eliminating any dilution effect that may occur as a result of insufficient tube filling when using a liquid additive [7].
In short, when a gel barrier separates the serum from the cells, glucose is very stable; however, the separation of the serum from the cells in 30 minutes is not a practical solution to the glycolysis problem in practice, since the period of time expiring between collection and centrifugation is variable and uncontrolled.
Conclusion
The objective of this study was to identify the most suitable tube for accurate glucose estimation in a routine laboratory under identical conditions. In summary, the use of an plasma tube is useful for obtaining more accurate results and a reliable glucose concentration, higher stability in glucose levels that otherwise change in time, samples with less hemolysis compared to NaF tubes, and to prevent the risk of misdiagnosis in DM based on false low glucose results stemming from uncentrifuged samples [4].
Since the combination of additives in the plasma tube offers an important advantage in the protection of glucose levels compared to the serum tube, plasma tube is the most suitable tube to minimize glycolysis. It prevents false-negative findings in diagnosing DM due to its characteristics of preventing glucose loss and maintaining stability through long waiting periods prior to analysis. Our results demonstrated that the plasma tube was most effective in preventing a clinically significant change in glucose concentration at room temperature.
Acknowledgment
We are grateful to all the volunteers, who kindly donated their blood for the experimental work. We thank Greiner Bio-One Turkey for providing the tubes and sampling devices free of charge. We acknowledge also the following colleagues for their participation in the multi-center study: Seda Çağlar.
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.
Funding: None
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.
References
1. Graziella B, Mariarosa C, Martina M, Claudia LC, Anna RB, Andrea M et al., Effectiveness of citrate buffer-fluoride mixture in Terumo tubes as an inhibitor
of in vitro glycolysis. Biochem Med. 2016;26(1):68-76.
2. Sahingoz Erdal G, Isiksacan N, Koser M, Kocamaz N. Hemoglobin A1c Measurement Using Point of Care Testing. Istanb Med J. 2020;21;37-1.
3. Gordana J, Ana B, Andrea S, Lara MK, Sanja D, Sandra D, et al. Glucose is stable during prolonged storage in un-centrifuged Greiner tubes with liquid citrate buffer, but not in serum and NaF/KOx tubes, but not in serum and NaF/KOx tubes. Clin Chem Lab Med. 2015;54:411-8.
4. Giuseppe L, Mads N, Janne C, Joao TG, Edmee van DL, Ana-Maria S. Gregory S. Makowski, editors. Blood Glucose Determination: Effect of Tube Additives. Adv Clin Chem. 2018;84:101-123.
5. Eline A E van der H, Marion JF, Amanda MDK, Marc HMT, Sjoerd AA van den B, Robbert JS. Technical and clinical validation of the Greiner FC-Mix glycaemia tube. Clin Chem Lab Med. 2017;55(10):1530-6.
6. David BS, Mark A, George LB, David EB, Andrea RH, Sue K, et al. Executive summary: guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem. 2011;57(6):793-8.
7. Graziella B, Mariarosa C. The new Greiner FC-Mix tubes equal the old Terumo ones and are useful as glucose stabilizer after prolonged storage of samples. Biochem Med (Zagreb). 2017;27:030901.
Download attachments: 10.4328:ACAM.20887
Nilgun Isiksacan, Pinar Kasapoglu, Alev Kural, Zeynep Levent Cirakli, Munevver Mert, Yuksel Gulen Cicek, Sehide Baz, Duygu Teksoz, Sebnem Tekin Neijmann. Comparison of glucose concentration stability in serum and plasma tubes. Ann Clin Anal Med 2022;13(3):258-262
Citations in Google Scholar: Google Scholar
Characteristics of patients with acute coronary syndrome in the COVID-19 pandemic
Emine Altuntas, Kanber Ocal Karabay, Songül Usalp, Bayram Bagırtan, Ali Bayraktar, Filiz Celebi, Behzat Ozdemir, Sükrü Cetin
Department of Cardiology, Sancaktepe Sehit Professor Ilhan Varank Education and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20894 Received: 2021-10-10 Accepted: 2021-11-02 Published Online: 2021-12-14 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):263-267
Corresponding Author: Emine Altuntas, Sancaktepe Sehit Professor Ilhan Varank Education and Research Hospital, Namık Kemal Street, No:7, Sarıgazi Emek, Istanbul, Turkey. E-mail: emine_altuntas@hotmail.com P: +90 216 606 33 00 F: +90 216 606 33 97 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5887-5422
Aim: Coronavirus disease 2019 (COVID-19) has caused thrombotic disease. In this study, we aimed to determine the demographic and clinical characteristics of acute coronary syndrome (ACS) patients infected with COVID-19 and to investigate whether they differ from patients with ACS without COVID-19 in terms of these characteristics.
Material and Methods: The study was designed as a single-center retrospective study. Thirty- three COVID-19 infected ACS patients (Group 1) and 100 ACS patients without COVID-19 infection (Group 2) were included in the study.
Results: The groups were compared in terms of coronary angiographic data. Twenty-eight (84.8%) patients in Group 1 and 74 (74%) patients in Group 2 were presented as non-ST elevation myocardial infarctus. Patients were compared in terms of baseline Thrombolysis in Myocardial Infarctus (TIMI) flow, thrombus stage, myocardial blush (end), using of thrombus aspiration catheter, stent thrombosis, and TIMI flow after percutaneous coronary intervention, and it was observed that there was no statistical difference between the groups (p> 0.05).
Discussion: COVID-19 infection can cause plaque rupture, myocardial damage, coronary spasm and cytokine storm by triggering the coagulation and inflammation process. The fact is that we did not encounter an increased thrombus load in this study.
Keywords: Thrombosis, Inflammation, Acute Coronary Syndrome, COVID-19
Introduction
The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been affecting the entire world since December 2019, causing the 2019 coronavirus (COVID-19) epidemic. The virus primarily affects the respiratory system. Although some coronavirus carriers are asymptomatic, others experience severe pneumonia and acute respiratory distress syndrome (ARDS). During the clinical course or even after recovery, the virus can affect other organs, especially the cardiovascular system [1].
COVID-19 infection can cause acute myocardial damage, heart failure, arrhythmia, acute coronary syndrome, and thromboembolism during and after the disease process. SARS-COVID-2 binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) protein. This protein is found in high amounts in pericytes. Once the virus attaches to this protein, it can enter the cell and disrupt the microvascular circulation. Thus, cardiovascular complications can occur. In addition, the current inflammatory process is believed to cause platelet activation, endothelial dysfunction, and stasis [1,2].
Mortality and morbidity rates are high in COVID-19 patients with cardiovascular disease. In this study, we aimed to determine the demographic and clinical characteristics of patients infected with COVID-19 and acute coronary syndrome and to investigate whether they differ from patients with acute coronary syndrome (ACS) who were not infected with COVID-19 in terms of these characteristics.
Material and Methods
Patient selection
This single-center retrospective study included 33 patients with acute ACS and COVID-19 infection (Group 1) and 100 patients with ACS without COVID-19 infection (Group 2). The diagnosis of acute coronary syndrome was made according to the diagnostic criteria of the European Society of Cardiology (ESC) non-ST elevation myocardial infarction (NSTEMI) guideline published in 2020 [3] and the ST-elevation myocardial infarction (STEMI) guideline published in 2017 [4]. The diagnosis of COVID-19 was first made on the basis of clinical findings and computed thoracic tomography, and then confirmed by COVID-19 swab test using real-time reverse transcriptase–polymerase chain reaction (RT-PCR). Patients with clinical and tomographic findings compatible with COVID-19 were found to be positive for COVID and treated accordingly. Patients who were not pregnant and aged> 18 years were included in the study. The medical history of patients was obtained from hospital records. Patients with out-of-hospital cardiac arrest who did not achieve return of spontaneous circulation were excluded from the study. This study was conducted by the COVID-19 Scientific Research Evaluation Commission of the Ministry of Health of the Republic of Turkey, with approval of the study on 31/05/2020 and the approval of the Ethics Committee of Sancaktepe Sehit Prof. Dr. Ilhan Varank Education and Research Hospital, Clinical Research Ethics Committee No. 1 (date: 18/11/2020, No. 2020-43).
Evaluation of blood sample tests
Total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, fasting blood glucose and thyroid-stimulating hormone were studied from the blood samples that were taken after at least 8 hours of fasting. Creatinine, albumin, C- reactive protein (CRP), procalcitonin, fibrinogen, D-dimer, high-sensitivity troponin I (hs troponin I), and complete blood count were studied from the blood tests taken immediately after admission to the hospital.
Echocardiographic evaluation
Heart chamber diameters, valvular pathology, systolic pulmonary artery pressure, and ejection fraction (EF) (measured using the modified Simpson method) data were obtained from the apical and parasternal axes with a 2.5 MHz transducer and echocardiography machine (Vivid 5; GE Healthcare, Inc. Chicago, IL, USA).
Coronary angiography
STEMI patients had immediate coronary angiography, while those with NSTEMI who did not have high-risk criteria underwent coronary angiography within the first 24-48 hours. All patients received a loading dose of acetylsalicylic acid 300 mg and clopidogrel 600 mg, or ticagrelor 180 mg before the procedure. During the procedure, all patients were loaded with iv heparin at a rate of 70-100 IU / kg.
A panel of 2 interventional cardiologists, blinded to patient COVID-19 status, retrospectively reviewed cine-angiographic images of all patients and scored pre- and post-percutaneous coronary intervention (PCI) TIMI flow in the infarct-related artery, thrombus burden pre- and post-PCI, and myocardial blush grade.
Follow-up
Patients in-hospital mortality, their admission to the hospital with acute coronary syndrome, cerebrovascular event, heart failure at the end of the first month, and combined total death rates were obtained from the medical records.
Statistical analysis
IBM SPSS Statistics for Windows, Version 18.0 (IBM Corp., Armonk, NY, USA) was used to perform the statistical analysis. Shapiro- Wilk test was used to assess the normality of distribution of the variables. Quantitative variables with normal distribution were specified as mean ± standard deviation, and non-normally distributed variables were specified as median (interquartile range). Categorical variables were shown as numbers and percentages. The non-normally distributed variables were assessed with the Mann-Whitney U test, while normally distributed variables were assessed with an independent sample Student’s t-test.
Results
The average age in Group 1 was 65.9 years, and 59.75 years in Group 2, and there was no significant difference. In Group 1, 21 (63%) individuals were males. In Group 2, 74 (74%) of the patients were male, and the two groups were considered similar in this respect. In the COVID-19 patient group, 19 (57.57%) patients had positive nasal swabs, on the other hand, lung involvement on non-contrast thoracic tomography was typical for COVID 19 pneumonia in 14 (42.43%) patients. The groups were compared in terms of chronic disease history. Patients with a history of coronary intervention were more common in the COVID 19 patient group. Hypertension (HT) was more common in the control group. There was a significant difference between the groups in terms of these two diseases (p = 0.001 and 0.024, respectively). Other demographic and clinical characteristics are summarized in Table 1.
The patients were compared in terms of laboratory test results. Hemoglobin, lymphocyte count, albumin, total cholesterol and triglyceride levels were higher in Group 2 (p= 0.041; 0.001; 0.000; 0.018; 0.05, respectively). In Group 1, the levels of CRP, and D-dimer were high (p = 0.000; 0.006, respectively), which led to a significant statistical result. Other laboratory results are summarized in Table 1. Patients were also compared in terms of coronary angiographic characteristics. Twenty-eight (84.8%) patients in the COVID 19 group and 74 (74%) in the control group presented with NSTEMI. On the other hand, 5 patients (15.2%) in Group 1 (15.2%) and 26 patients (26%) in Group 2 presented with STEMI. There was no statistical difference between the groups in terms of these characteristics (p> 0.05). Other angiographic features are summarized in Tables 2, 3.
Discussion
This study summarizes data from patients with and without COVID-19 who were admitted to a primary percutaneous intervention center and underwent coronary imaging. The patients included in the study were not divided into NSTEMI and STEMI groups. Therefore, this study differs from other coronary imaging studies.
The main finding of our study is that in patients with COVID-19 and ACS the thrombus burden was not higher than in ACS patients without COVID-19 infection.
One of the important features of COVID-19 infection is the microcirculatory endothelial damage in pulmonary circulation and other vascular beds [5]. Since COVID-19 directly infects vascular endothelial cells, causing cellular damage and apoptosis, the antithrombotic activity of the luminal surface is remarkably decreased. Subsequently, damage of the endothelium leads to procoagulant changes in the vascular lumen, the formation of immunothrombosis, and organ malcirculation [6]. Choudry et al. studied 39 STEMI patients with COVID-19 and 76 STEMI control patients. In this study, there were no significant differences between the groups in terms of basal TIMI, basal thrombus stage, or target vessel post-PCI TIMI, but differences were observed in terms of myocardial blush (end) stage, modified thrombus stage using an aspiration catheter, stent thrombosis, and multiple vessel intervention. It was observed that stent thrombosis and thrombus aspiration catheter use were more common, and the modified thrombus and myocardial blush stages were higher in the COVID-19 group [7]. Unlike the study by Choudry et al., in two separate studies involving 28 and 18 STEMI patients, it was reported that lesions with high thrombus load were not more common in COVID patients [8,9]. In our study, there were no significant differences between the groups in terms of these parameters. Even after separating patients into STEMI and NSTEMI groups, there were no significant differences in our study. This may be due to the small study population. Similar to the study by Choundry et al., the duration of stay in the hospital and intensive care unit was longer in the COVID-19 group [7].
It has been determined that HT is more common in COVID-19 patients, and the disease is more severe in those with HT [10]. It has been suggested that HT causes the immune system to work irregularly. In our study, HT was more common in the control group, whereas past history of PCI was more common in the COVID-19 group.
COVID-19 infection is an inflammatory process that causes coagulation activation and endothelial dysfunction. It was observed that cardiac and coagulation biomarker levels were elevated during COVID-19 infection. Increased D-dimer and troponin levels have been associated with increased mortality and morbidity [11]. Although the groups in this study were found to be similar in terms of hs-troponin I, D-dimer levels were found to be higher in the COVID-19 patient group.
The bone marrow response to COVID-19 infection changes the course of the disease. Excessive immune reaction causes a cytokine storm, leading to increased risk of death [12]. CRP, procalcitonin, neutrophil, lymphocyte, albumin, and fibrinogen levels and the neutrophil/lymphocyte ratio can be used to predict this response and the course of the disease. In some studies, it has been found that lymphocyte levels are low and neutrophil levels are high in patients with severe COVID-19 [13,14]. In addition, in severe cases, high levels of CRP, procalcitonin, and fibrinogen have been observed. On the other hand, albumin levels are low. In the study mentioned above, it was determined that hemoglobin, lymphocyte, and albumin levels were low in COVID-19 patients, whereas fibrinogen was higher and close to the statistically significant limits.
It has been previously shown that some viral infections affect cholesterol levels [15]. It has been shown in a study conducted on pig testicular cells and hamster renal cells that the depletion of cholesterol from the cell membrane of the SARS-CoV-2 virus causes a decrease in the severity of viral infection [16]. Wei et al. compared cholesterol levels of patients infected with COVID-19 with those of the normal population and showed that total cholesterol, HDL, and LDL were lower in the patient group [17]. This result has been supported by other studies (Hu X, Chen D, Wu L, He G, Ye W. Low Serum Cholesterol Level Among Patients with COVID-19 Infection in Wenzhou, China. Available at: https://ssrn.com/abstract=3544826) [18]. In our study, it has been proven that total cholesterol levels and triglyceride levels are lower in patients infected with COVID-19.
Study limitations
The small number of patients in the study is the greatest limitation. The inclusion of patients with high hs-troponin I and patients with ST-elevation or depression is an additional limitation.
Conclusion
In conclusion, although COVID-19 infection activates the coagulation and inflammation cascade and triggers thromboembolic events, we did not encounter increased thrombus burden among the groups in this study. This may be because the fact that the SARS-CoV-2 virus causes myocardial damage via plaque rupture, hypoxia, cytokine storm, coronary spasm.
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.
Funding: None
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.
References
1. Hendren NS, Drazner MH, Bozkurt B, Cooper LT. Description and Proposed Management of the Acute COVID-19 Cardiovascular Syndrome. Circulation. 2020;141(23):1903-14.
2. Babapoor-Farrokhran S, Gill D, Walker J, Rasekhi RT, Bozorgnia B, Amanullah A. Myocardial injury and COVID-19: Possible mechanisms. Life Sci. 2020;253:117723.
3. Barbato E, Mehilli J, Sibbing D, Siontis GCM, Collet JP, Holger T, et al. Questions and answers on antithrombotic therapy and revascularization strategies in non-ST-elevation acute coronary syndrome (NSTE-ACS): a companion document of the 2020 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J. 2021;42(14):1368-78.
4. Ibanez B, James S, Agewall S, Antunes MJ, Ducci CB, 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.
5. Wichmann D, Sperhake JP, Lütgehetmann M, Steurer S, Edler C, Heinemann A, et al. Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study. Ann Intern Med. 2020;173(4):268-77.
6. Dolhnikoff M, Duarte-Neto AN, de Almeida Monteiro RA, da Silva L, de Oliveire EP, Saldiva P et al. Pathological evidence of pulmonary thrombotic phenomena in severe COVID-19. J Thromb Haemost. 2020;18(6):1517-9.
7. Choudry FA, Hamshere SM, Rathod KS. High thrombus burden in patients with COVID-19 presenting with ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2020;76(10):1168-76.
8. Stefanini GG, Montorfano M, Trabattoni D. ST-elevation myocardial infarction in patients with COVID-19: clinical and angiographic outcomes. Circulation. 2020;141(25):2113-6.
9. Bangalore S, Sharma A, Slotwiner A, Yatskar L, Harari R, Shah B, et al. ST-Segment Elevation in Patients with Covid-19 – A Case Series. N Engl J Med. 2020;382(25):2478-80.
10. Guzik TJ, Mohiddin SA, Dimarco A, Patel V, Savvatis K, Marelli-Berg FM, et al. COVID-19 and the cardiovascular system: implications for risk assessment, diagnosis, and treatment options. Cardiovasc Res. 2020;116(10):1666-87.
11. Zhou F, Yu T, Du R, Fan G, Liu Y, Xiang J, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-62.
12. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med. 2020;8(5):475-81.
13. Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020;71(15):762-8.
14. Henry BM, de Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clin Chem Lab Med. 2020;58(7):1021-8.
15. Tien PC. Hepatitis C Virus-Associated Alterations in Lipid and Lipoprotein Levels: Helpful or Harmful to the Heart? Clin Infect Dis. 2017;65(4):566-7.
16. Ren X, Glende J, Yin J, Schwegmann-Wessels C, Herrler G. Importance of cholesterol for infection of cells by transmissible gastroenteritis virus. Virus Res. 2008;137(2):220-4.
17. Peng Y, Wan L, Fan C, Zhang P, Wang X, Sun J, et al. Cholesterol Metabolism—Impacts on SARS-CoV-2 Infection Prognosis. medRxiv. 2020. DOI: 10.1101/2020.04.16.20068528.
18. Nie S, Zhang Z, Zhang Z. Metabolic disturbances and inflammatory dysfunction predict severity of coronavirus disease 2019 (COVID-19): a retrospective study. medRxiv. DOI: 10.1101/2020.03.24.20042283.
Download attachments: 10.4328:ACAM.20894
Emine Altuntas, Kanber Ocal Karabay, Songül Usalp, Bayram Bagırtan, Ali Bayraktar, Filiz Celebi, Behzat Ozdemir, Sükrü Cetin. Characteristics of patients with acute coronary syndrome in the COVID-19 pandemic. Ann Clin Anal Med 2022;13(3):263-267
Citations in Google Scholar: Google Scholar
Impact of mechanical endometrial injury on clinical pregnancy rates in women with clomiphene-resistant polycystic ovary syndrome
Suat Suphan Ersahin 1, Aynur Ersahin 2
1 Department of Obstetrics and Gynecology, Altınbas University, 2 Department of Obstetrics and Gynecology, IVF-Center, Medical School, Bahcesehir University, Istanbul, Turkey
DOI: 10.4328/ACAM.20910 Received: 2021-10-18 Accepted: 2021-11-09 Published Online: 2021-11-15 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):268-271
Corresponding Author: Suat Suphan Ersahin, Department of Obstetrics and Gynecology, Altınbas University, Istanbul, Turkey. E-mail: suphanersahin@hotmail.com P: +90 533 341 75 66 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7180-7413
Aim: In this study, it was aimed to evaluate the effect of mechanical endometrial injury before letrozole treatment on clinical pregnancy rates in patients with clomiphene-resistant polycystic ovary syndrome (PCOS).
Material and Methods: Thirty women with PCOS who could not achieve ovulation despite 150 mg of clomiphene citrate (CC) daily were included in the study. Patients in the PCOS group were equally divided into two groups before letrozole treatment (n=15). Group 1: Endometrial injury was performed with a pipelle cannula in the midluteal phase, and letrozole treatment was started in the next cycle. Group 2: In this group of patients endometrial injury was not performed. Letrozole treatment was started in these patients in the next cycle. Twenty patients with unexplained infertility were taken as a control.
Results: Beta hCG was found positive in 4 of 15 patients with endometrial injury in the PCOS group (26.6%). Beta hCG was found positive in 3 of 15 CR-PCOS cases who did not undergo injury (20%). Although beta hCG positivity was higher in the injury group, the difference was not significant (p=0.34). Clinical pregnancy was detected in 3 cases (20%) in patients with injury in the PCOS group. Similarly, clinical pregnancy was detected in 3 of the patients without injury (20%). In the control group, beta hCG positivity and clinical pregnancy rate were detected in 2 out of 10 patients with mechanical endometrial injury (20%).
Discussion: Mechanical endometrial injury before letrozole treatment does not increase clinical pregnancy rates both in women with clomiphene-resistant PCOS and unexplained infertility.
Keywords: Clomiphene-Resistant, PCOS, Unexplained Infertility, Mechanical Endometrial Injury, Clinical Pregnancy
Introduction
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder with subfertility metabolic and hormonal disorders, affecting approximately 10% of women of reproductive age [1,2]. Systemic inflammation can lead to additional morbidities such as insulin resistance and endothelial dysfunction. Due to the high androgen synthesis and anovulation, a large proportion of PCOS cases suffer from subfertility. An increase in insulin levels causes hyperandrogenemia by stimulating LH-mediated IGF and androgen synthesis in follicles [3,4]. Endometrial decidualization is impaired due to hyperinsulinemia and increased androgen levels due to insulin resistance. In addition, hypoandrogenemia leads to subfertility by decreasing the expression of endometrial receptivity genes. Receptivity is further impaired, as increased insulin impairs hepatic degradation of androgens and decreases IGFBP synthesis in the endometrial stroma [5-7].
First-line treatment in subfertile PCOS patients is ovulation stimulation with clomiphene citrate (CC). Patients who do not ovulate despite six months of CC therapy are diagnosed with CC-resistant PCOS. In patients who do not respond to CC treatment, second-line treatment is the use of aromatase inhibitor (AI). In cases where pregnancy cannot be achieved with AI, the third step approach is ovarian drilling or ART. Ovulatory dysfunction and hyperandrogenemia are the two mechanisms most frequently accused of decreased fertility in subfertile PCOS patients [1-3]. However, in the last decade, disruption in endometrial receptivity genes due to androgen elevation has also been suggested as a cause of subfertility [4]. The fact that high testosterone levels reduce homeobox gene expression indicates the role of the endometrium in decreasing fertility [4-6].
Mechanical endometrial injury is a widely used method of increasing pregnancy rates in patients with a history of recurrent implantation failure. It has been reported that mechanical injury performed with a pipelle cannula or accompanied by hysteroscopy in patients with two or more failed IVF/ICSI attempts increases endometrial receptivity and leads to an increase in pregnancy rates [8,9]. There are no studies investigating the effect of endometrial injury before starting AI treatment in clomiphene citrate-resistant PCOS cases. This study was planned to investigate the effect of mechanical endometrial injury in the cycle before starting AI treatment on clinical pregnancy rates in patients with CC resistant PCOS.
Material and Methods
A total of 50 infertile patients, 30 of whom were diagnosed with PCOS and 20 with unexplained infertility, were included in the study. Thirty patients in the PCOS group consisted of clomiphene-resistant cases who did not ovulate despite the use of 150 mm/day CC. The control group consisted of 20 patients who did not have the laboratory and skin manifestations of PCOS and who were diagnosed with unexplained infertility. After the evaluation of ovulatory function, tubal patency and semen analysis, if no etiology was found, the diagnosis of unexplained infertility was made. The study was started after obtaining patient consent and approval from the local ethics committee. PCOS was defined according to the revised Rotterdam criteria, which require two of the following three manifestations: (i) oligo-anovulation or anovulation (oligomenorrhoea or amenorrhoea); (ii) high concentrations of androgen in the bloodstream (biological hyperandrogenism) and/or clinical signs of androgen surplus (hyperandrogenism); and (iii) polycystic ovaries shown by ultrasonography (more than 12 follicles measuring 2-9 mm on at least one ovary). When CC treatment fails, defined as no ovulation after six months of treatment at an appropriate dose, the patient is regarded as resistant to CC. Induction with letrozole was planned as second- line treatment in PCOS patients in whom the diagnosis of CC resistance was certain. The patients in the PCOS group were equally divided into two groups before letrozole treatment (n=15). Group 1: Endometrial injury was performed with a pipelle cannula in the midluteal phase (LH+7-9) and letrozole treatment was started in the next cycle. Mechanical injury was performed in accordance with previous studies. The Pipelle cannula was introduced through the cervix into the fundus. The piston of the cannula was withdrawn to create negative pressure and suction. Then the catheter was pushed back and forth in the cavity and withdrawn. The procedure was repeated until most of the cavity was injured. Group 2: In this group of patients, the pipelle cannula was passed through the cervix and advanced to the fundus, but no injury was made. Letrozole treatment was started in these patients in the next cycle. Twenty patients with unexplained infertility were taken as a control group and equally divided into two groups. While the injury was applied to 10 of the patients in Group A, the remaining ten patients were not injured (Group B). The patients in Group A were injured with a pipelle cannula 7-9 days after the LH peak. The Pipelle cannula was placed along the cervix of the patients in Group B, but no injury was performed. Women with endometrioma or hydrosalpinx thought to affect implantation were not included in the study.
In the post-injury cycle, patients in the PCOS group were given a letrozole tablet twice a day for 5 days, starting from the 3rd day of the cycle. The patients in the control group were given CC (150 mg/day) three times a day for five days in the post-injury cycle. CC was started between days 2-6 of the cycle. The cycle was monitored with ultrasound examination and mid-luteal serum progesterone levels. Patients in both groups were offered timed intercourse between days 12-18 of the cycle. Primary outcome measures were positive beta hCG rate and clinical pregnancy rates. Clinical pregnancy rate is defined as evidence of a gestational sac, confirmed by ultrasound examination at the 4th week of transfer. Beta hCG values and clinical pregnancy rates of the patients in both groups were recorded and compared both within and between the groups
Statistical analysis
The analysis of collected data was performed using the Statistical Package for Social Sciences software 21.0 for Windows package software (SPSS, Inc., Chicago, IL, USA). The parameters studied in the PCOS and control groups showed normal distributions, which were confirmed by the one sample Kolmogorov-Smirnov test. The Mann- Whitney U test for continuous variables and Pearson’s chi square test for categorical variables were used. Data are presented as mean ± SD. Clinical pregnancy and positive beta-hCG rates were given as percentages. P<0.05 was used for determining statistical significance.
Results
Mechanical endometrial injury was successfully performed in patients in both groups. Except for mild inguinal pain, cramping and spotting, no serious complications developed. Beta hCG was found positive in 4 of 15 patients with endometrial injury in the PCOS group (26.6%). Beta hCG was found positive in 3 of 15 women with PCOS who did not undergo mechanical endometrial injury (20%). Although beta hCG positivity was higher in the injury group, the difference was not significant (p=0.34). Clinical pregnancy was detected in 3 out of 15 women with endometrial injury in the PCOS group (20%). Similarly, clinical pregnancy was detected in 3 out of 15 patients with PCOS without injury (20%). There was no significant difference between the PCOS groups in terms of CPR (p=0.07).
In the control group, beta hCG positivity was detected in 2 out of 10 patients with mechanical endometrial injury (20%). Likewise, positive pregnancy test rate was detected in 2 out of 10 patients in the non-injured group (20%). The difference between the two groups was recorded as insignificant (p=0.50). In the control group, clinical pregnancy was detected in 2 out of 10 patients with endometrial injury (20%). Similarly, clinical pregnancy was detected in 2 out of 10 patients without endometrial injury (20%). In the control group, CPR was found to be similar in patients with and without endometrial injury.
Discussion
If there is no ovulatory response to clomiphene citrate treatment in infertile PCOS patients, low-dose gonadotropin can be added to CC or aromatase inhibitor therapy can be started. Insulin-sensitizing drugs can be added to increase ovulatory performance and reduce insulin resistance [2]. All these applications provide an effective treatment as long as they are accompanied by lifestyle changes and weight loss. Aromatase inhibitors can also be used as a second line treatment. The aromatase inhibitor letrozole at a dose of 2.5 mg/day can be used as an alternative treatment to induce ovulation in women who have failed to respond to CC. Letrozole can provide a highly effective ovulatory process in CC-resistant pCOS cases [10,11]. However, despite the multiplicity of medical approaches, many PCOS patients have to go to ART. We designed this study to test whether mechanical endometrial injury before letrozole affects pregnancy rates in a CC resistant PCOS population.
First, we divided our patients diagnosed with CC-resistant PCOS into two groups. In the first group, we performed mechanical endometrial injury with a pipelle cannula in the midluteal phase of the cycle before starting letrozole and 7-9 days after the LH peak. We recommended timed sexual intercourse for patients after ovulation stimulation with letrozole in the next cycle. We gave letrozole treatment to our CC resistant patients in the second group without causing mechanical injury. We divided the control group patients, consisting of patients diagnosed with unexplained infertility, into two groups and performed endometrial injury in one group and did not perform in the other group. We compared the positive pregnancy test rates and clinical pregnancy rates in the PCOS and control groups, both within and between groups. In CC-resistant PCOS cases, mechanical endometrial injury before letrozole treatment did not lead to a significant increase in either positive pregnancy test rates or clinical pregnancy test rates. Similarly, mechanical endometrial injury did not significantly change positive pregnancy test rates and clinical pregnancy rates in patients with unexplained infertility. When PCOS and unexplained infertile groups were compared among themselves, clinical pregnancy rates were found to be similar.
In the last decade, the possibility of endometrial receptivity defect has become increasingly important both in PCOS patients and unexplained infertile patients [10,11]. This study, in which we planned to determine whether mechanical endometrial injury affects pregnancy rates by stimulating the expression of both inflammation and receptivity genes in these two patient groups, was investigated for the first time in the literature [8,9]. As a result of our study, we showed that mechanical injury does not have a positive contribution to pregnancy rates.
Conclusion
Despite the limited number of cases, our results are clinically important. As a result of this study, we have once again confirmed the idea that mechanical injury is not a very effective approach except for patients with recurrent implantation failure. It is important to continue treatment by following conventional approaches in both CC-resistant PCOS patients and unexplained infertile patients. It will be possible to make clearer recommendations on this issue thanks to randomized controlled studies to be carried out by increasing the number of cases. As a result, mechanical injury before aromatase inhibitor treatment in CC-resistant PCOS does not positively increase fertility outcomes.
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.
Funding: None
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.
References
1. Celik O, Aydin S, Celik N, Ugur K, Yavuzkir S, Hatirnaz S, et al. Molecular role of peptides/proteins in subfertility of polycystic ovarian syndrome. Cell Mol Biol (Noisy-le-grand). 2019;65(3):32-40.
2. Morgante G, Massaro MG, Di Sabatino A, Cappelli V, De Leo V. Therapeutic approach for metabolic disorders and infertility in women with PCOS. Gynecol Endocrinol. 2018;34(1):4-9.
3. Dou L, Zheng Y, Li L, Gui X, Chen Y, Yu M, et al. The effect of cinnamon on polycystic ovary syndrome in a mouse model. Reprod Biol Endocrinol. 2018;16(1):99.
4. Senturk S, Celik O, Dalkilic S, Hatirnaz S, Celik N, Unlu C, et al. Laparoscopic Ovarian Drilling Improves Endometrial Homeobox Gene Expression in PCOS. Reprod Sci. 2020;27(2):675-80.
5. Cermik D, Selam B, Taylor HS. Regulation of HOXA-10 expression by testosterone in vitro and in the endometrium of patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88(1):238-43.
6. Giudice LC, Dsupin BA, Irwin JC. Steroid and peptide regulation of insulin-like growth factor-binding proteins secreted by human endometrial stromal cells is dependent on stromal differentiation. J Clin Endocrinol Metab. 1992;75(5):1235-41.
7. Dumesic DA, Richards JS. Ontogeny of the ovary in polycystic ovary syndrome. Fertil Steril. 2013;100(1):23-38.
8. Barash A, Dekel N, Fieldust S, Segal I, Schechtman E, Granot I. Local injury to the endometrium doubles the incidence of successful pregnancies in patients undergoing in vitro fertilization. Fertil Steril. 2003;79(6):1317-22.
9. Lensen S, Sadler L, Farquhar C. Endometrial scratching for subfertility: everyone’s doing it. Hum Reprod. 2016;31(6):1241-4.
10. Wang R, Kim BV, van Wely M, Johnson NP, Costello MF, Zhang H, et al. Treatment strategies for women with WHO group II anovulation: systematic review and network meta-analysis. BMJ. 2017;356:j138.
11. Franik S, Eltrop SM, Kremer JA, Kiesel L, Farquhar C. Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2018;5(5):CD010287.
Download attachments: 10.4328:ACAM.20910
Suat Suphan Ersahin, Aynur Ersahin. Impact of mechanical endometrial injury on clinical pregnancy rates in women with clomiphene-resistant polycystic ovary syndrome. Ann Clin Anal Med 2022;13(3):268-271
Citations in Google Scholar: Google Scholar
Chromatographic and hematological comparison of sickle cell carriers and hemoglobin D los angeles carriers
Süheyl Uçucu 1, Talha Karabıyık 2
1 Department of Medical Biochemistry, Muğla Public Health Care Laboratory, Muğla, 2 Department of Medical Biochemistry, Bursa City Hospital, Bursa, Turkey
DOI: 10.4328/ACAM.20914 Received: 2021-10-28 Accepted: 2021-12-06 Published Online: 2021-12-08 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):272-275
Corresponding Author: Süheyl Uçucu, Department of Medical Biochemistry, Muğla Public Health Care Laboratory, Muğla, Turkey. E-mail: suheyllucucu@gmail.com P: +90 555 306 28 74 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6320-2457
Aim: Sickle cell trait and Hb D-Los Angeles (β121Glu→Gln) variant have complete blood count (CBC) and chromatographic similarities. Therefore, the differential diagnosis of these hemoglobinopathies is problematic. The aim of this study was to differentiate hemogram results between patients diagnosed with Hb S carrier and Hb D Los Angeles carrier, to compare with HPLC thalassemia screening tests hematologically and chromatographically, and to discuss their distinctive features.
Material and Methods: The study included 128 Hemoglobin D Los Angeles and 110 Hemoglobin S carriers. Age, sex, RBC, Hb, HTC, MCV, MCH, RDW, serum iron, TIBC, ferritin, HbA2, HbF, HbA0, abnormal peak retention time (RT) and area under the peak were examined.
Results: A statistically significant difference was detected in serum RBC levels, abnormal hemoglobin, retention time, and Hb A2 levels (p=0.036, p<0.001, p<0.001, p<0.001, respectively) between Hb D Los Angeles and Hb S carriers, while levels of abnormal hemoglobin in Hb S and Hb D Los Angeles carriers were between 24.6% and 44.6% in Hb S carriers, it was between 32.2-43% in Hb D carriers. The average RT levels were 1.02 in HbS, and 0.96 in Hb D. Hb A2 levels were significantly higher in Hb S carriers.
Discussion: Although the Hb D-Los Angeles variant and the Hb S carrier profile have similar CBC and electrophoretogram, they can be distinguished from each other using RT, HbA2, and abnormal hemoglobin levels. RT and HbA2 levels seem to be the main discrimination factors, but it should not be forgotten that they do not always have sufficient discrimination power. Molecular diagnostic methods such as PCR or DNA sequencing should be used for definitive diagnosis.
Keywords: Hemoglobinopathies, Hb D-Los Angeles, Sickle Cell, Hb S, HPLC
Introduction
Hemoglobinopathies affect millions of people around the world. It causes the birth of hundreds of thousands of babies with hemoglobin disorders and the deaths of hundreds of thousands of babies worldwide each year [1, 2].
Even though it is endemic in regions such as Sub-Saharan Africa, Asia, Mediterranean Countries, and the US in general, its prevalence is increasing even in Northern European countries where it is not commonly seen [2]. Migrations that have occurred alter the gene pool [3, 4]. Mutations are transmitted to different populations by genetic drift. Therefore, new variants continue to be added to the gene pool each year [5, 6].
Turkey is a region where many civilizations were founded, and the genetic variability is abundant. For this reason, the diversity and frequency of hemoglobinopathy have increased concordantly. Rare variants in different geographies have been detected [6]. Variant types and prevalence vary widely in Turkey by region. However, the most common hemoglobin variants in the world and in Turkey are sickle cell carriage (Hb S (β6Glu→Val)) and Hb D-Los Angeles (β121Glu→Gln).
In sickle cell trait, valine amino acid replaces glutamic acid due to a point mutation at codon 6 of beta globin gene on chromosome 11 [2, 7]. As a result of this point mutation, Hb S which polymerizes under conditions such as pH change, deoxygenation and dehydration and causes sickling of erythrocytes, is formed. According to the data of WHO, while Africa is the most common place in the world, it is the Mersin-Hatay region in our country. Its prevalence varies between 0.3% and 44% [3, 8]. Even though sickle cell carriage is generally known to be harmless, it is now known that it can lead to complications and may be associated with conditions such as kidney diseases, thrombosis, stroke, arthritis, pain crises, spleen sequestration, and shock [9-11]. In addition, a genetic modifying factor that may coexist with Hb S may also lead to a very severe course of the phenotype [9].
While Hb D Los Angeles being Hb A/D heterozygous or Hb D/D homozygous does not lead to a clinical phenotype, simultaneous inheritance with different variants can lead to a variable spectrum of clinical conditions from mild to severe [12, 13].
These two variants, which affect millions of people around the world, are similar in terms of hematological (CBC), alkaline electrophoretic mobility, concentration and HPLC profiles. Differential diagnosis of these hemoglobinopathies is therefore problematic [2, 7].
In this study, hemogram results of patients diagnosed with Hb S carrier and Hb D Los Angeles carrier will be compared with HPLC thalassemia screening tests hematologically and chromatographically and their distinctive features will be discussed.
Material and Methods
This study was carried out retrospectively between 01.01.2015 – 01.06.2021. Ninety (38%) women and 148 (62%) men aged 11-67 years who applied to the Thalassemia Diagnosis, Treatment and Research Center were included in the study. Patients included in the study did not have hypothyroidism problems, iron deficiency anemia, nutritional disorder or alpha thalassemia suspicion, kidney diseases, thrombosis, stroke, arthritis and shock.
Ethical approval was obtained from the MSKÜEAH (Muğla Sıtkı Koçman University Training and Research Hospital) Research and Ethics Committee (registration no. 111). The study was conducted in accordance with the Helsinki Declaration principles.
The study included 128 Hemoglobin D Los Angeles and 110 Hemoglobin S carriers. Age, sex, RBC, Hb, HTC, MCV, MCH, RDW, serum iron, TIBC, ferritin, HbA2, HbF, HbA0, abnormal peak retention time (RT) and the area under the peak were examined.
Complete blood cell parameters and indices were determined using Sysmex XN 1100 (Sysmex Diagnostic, Japan). Hemoglobin variant analysis was performed using the Primus Ultra II device (Trinity Biotech Diagnostic, Ireland) which is based on high-pressure liquid chromatography (HPLC). Serum iron, TIBC levels were measured by Photometric Method in the Cobas 501 (Roche Diagnostics, Germany) analyzer. Ferritin levels were measured by ECLIA Method and in Cobas 501 (Roche Diagnostics, Germany) device.
Statistical analysis
Jamovi 1.6.15 program was used for statistical analysis. The Shapiro-Wilk test was used to determine the data’s conformity to the normal distribution. Independent T-test was used to evaluate the normally distributed variables. The Mann-Whitney U test was used for the evaluation of the variables that did not fit the normal distribution. The P-value < 0.05 was accepted as statically significant.
Results
The sociodemographic data of the patients and the minimum and maximum values of the tests are presented in Table 1. There was a statistically significant difference in serum RBC levels, abnormal hemoglobin, retention time, and Hb A2 levels (p=0.036, p<0.001, p<0.001, p<0.001, respectively) between Hb D-Los Angeles carriers and Hb S carriers.
Discussion
In this study, hemogram results of patients diagnosed with Hb S carrier and Hb D Los Angeles carrier between 2015 and 2021 were compared with HPLC thalassemia screening tests haematologically and chromatographically, and their distinctive features were discussed.
The results of hematological studies of Hb S carriers and Hb D Los Angeles carriers showed that one of the most important distinguishing variables was HbA2 levels. The mean HbA2 level was 4.16% ± 0.45% in Hb S carriers, and 2.26% ± 0.61% in Hb D Los Angeles carriers, and this difference was statistically significant (p<0.001). In agreement with this study, Fonseca et al. compared sickle cell anemia and alpha thalassemia genotypes, it was reported that Hb A2 concentrations were affected in the presence of HbS or HbC, and their levels increased slightly [14]. In a study conducted by Suh et al. it was reported that HbA2 levels increase in the presence of HbS or HbC hemoglobin [15, 16]. Moreover in the study by Şokrani et al., in which they evaluated HbA2 levels in sickle cell anemia patients in the HPLC system, it was reported that HbA2 levels were high [16]. However, in the case of simultaneous eluting of HbS with HbA2 in HPLC systems, sometimes part of Hb S may overlap HbA2 and cause false height [15, 16] This may cause the sickle cell carrier to be mistakenly interpreted as Hb S/Beta. In this case, parental screening should be performed. Besides, it should be kept in mind that Hb A2, which is one of the hematological data, may cause false lows or false highs in conditions such as iron deficiency, megaloblastic anemia, alpha thalassemia, delta gene mutations, hypothyroidism, and paraproteinemia, and it does not have sufficient discrimination between Hb S and Hb D on its own [7,17].
One of the most important distinguishing variables among the variants in HPLC systems is the RT difference, which is formed depending on the elution pattern [18]. Although the Hb S retention time has a course around 1.01 and the Hb D retention time is around 0.96, it can rarely be detected at lower or higher RT than Hb S and HbD normally are [18].
A statistically significant difference was detected in serum RBC levels between Hb S carriers and Hb D Los Angeles carriers (p<0.001). A possible explanation for this situation is that the population we used includes different genders and age ranges, and there may be a significant difference in these parameters in Hb S and Hb D carriers due to the difference in the reference values of RBC parameters in the pediatric and geriatric groups [19].
In addition, abnormal hemoglobin levels showed statistically significant difference between Hb S carriers and Hb D Los Angeles carriers (p<0.001). While the minimum and maximum values of abnormal hemoglobin in Hb S and Hb D Los Angeles carriers rangebetween 24.6% and 44.6% in Hb S carriers, it is between 32.2% and 43% in Hb D carriers. According to our study, both variants can be in the percentage range of each other. For this reason, although there is a statistically significant difference on the basis of population in terms of abnormal hemoglobin, it may not have sufficient distinguishing features individually.
In a study by Anagnostopoulos et al., they examined the effect of the presence of Hb S and HbA2 in different devices and an increase in HbA2 levels was found [20].
There are a limited number of detailed studies on the hematological and molecular basis of Hb D. In the study by Higgins et al., it has been reported that HbDs cause falsely low HbA2 levels and HbS falsely cause high HbA2 levels [21]. This situation is generally compatible with other studies in the literature and our study results. The fact that HbD and HbS migrating together in alkali cellulose acetate electrophoresis leads to the mixing of the two variants and they cannot be separated from each other. Therefore, HbD and Hb S were tried to be distinguished in acidic citrate electrophoresis. In acidic citrate electrophoresis, false levels can be detected as a result of HbD migrating with HbA [7].
Although, today, with the ease of access to technology, Hb S and Hb D are now more easily separated in methods such as HPLC and capillary electrophoresis, which are widely used, it should be kept in mind that it can be confused due to gradient program errors, analytical errors, software differences, and common biochemical features [18]. Existing guidelines state that the Hb S variant should be confirmed with another technique with caution [13].
Conclusion
In conclusion, the Hb D-Los Angeles variant and the Hb S carrier profile have similar hemogram and electrophoresis, they can be distinguished from RT levels, HbA2 levels, and abnormal hemoglobin levels. Although RT and HbA2 levels seem to be the main distinguishing points, it should not be forgotten that they do not always have sufficient distinctiveness. In the presence of different pathophysiological variants, it may lead to misdiagnosis and affect subsequent generations [7, 17].
The most powerful side of this study is that, to the best of our knowledge, this is the first study investigating the differences between Hb S and Hb D Los Angeles carriers using HPLC. Molecular diagnostic methods such as PCR and DNA chain analysis should be used for definitive diagnosis.
Limitations of the study
The main limitation of our study is the inability to compare phenotype, genotype, and hematological data due to the inaccessibility of patients’ clinical status and genotype data. More comprehensive comparisons can be made by taking samples from different regions of Turkey.
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.
Funding: None
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.
References
1. Piel FB, Hay SI, Gupta S, Weatherall DJ, Williams TN. Global burden of sickle cell anaemia in children under five, 2010–2050: modelling based on demographics, excess mortality, and interventions. PLoS medicine. 2013; 10(7): e1001484.
2. Hazzazi A A, Ageeli MH, Alfaqih AM, Jaafari A A., Malhan H M, Bakkar M M Epidemiology and characteristics of sickle cell patients admitted to hospitals in Jazan region, Saudi Arabia. J Appl Hematol. 2020. 11(1): 10.
3. Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Global epidemiology of haemoglobin disorders and derived service indicators. Bulletin of the World Health Organization. 2008. 86(6): 480-7.
4. Lee J S, Cho S, Park SS, Seong MW. Molecular basis and diagnosis of thalassemia. Blood Research. 2021. 56(S1): S39-43.
5. Weatherall DJ. The inherited diseases of hemoglobin are an emerging global health burden. Blood. 2010; 115(22): 4331-6.
6. De Sanctis V, Kattamis C, Canatan D, Soliman AT, Elsedfy H, Karimi M, et al., β-thalassemia distribution in the old world: an ancient disease seen from a historical standpoint. Mediterr J Hematol Infect Dis. 2017; 9(1): e2017018.
7. Bain BJ. Haemoglobinopathy diagnosis. USA: John Wailey & Sons; 2020. p.30-44
8. Canatan D. Thalassemias and hemoglobinopathies in Turkey. Hemoglobin. 2014; 38(5):305-7.
9. Xu JZ, Thein SL. The carrier state for sickle cell disease is not completely harmless. Haematologica. 2019; 104(6):1106.
10. Naik RP, Smith-Whitley K, Hassell KL, Umeh NI., De Montalembert M, Sahota P, Kato G J. Clinical outcomes associated with sickle cell trait: a systematic review. Ann Intern Med. 2018. 169(9):619-27.
11. Goodman J, Hassell K, Irwin D, Witkowski E H, Nuss R. The splenic syndrome in individuals with sickle cell trait. High Alt Med Bioly. 2014; 15(4): 468-71.
12. Randolph TR. Hemoglobinopathies (structural defects in hemoglobin), in Rodak’s Hematology: Clinical Principles and Application. . St Louis, MO: Elsevier; 2019. p. 394-423.
13. Khera R., Singh, T., Khuana N., Gupta N., Dubey A. P. HPLC in characterization of hemoglobin profile in thalassemia syndromes and hemoglobinopathies: a clinicohematological correlation. Indian J Hematol Blood Transfus. 2015; 31(1): 110-15.
14. Fonseca SFD, Amorim T, Purificação A, Gonçalves M, Boa-Sorte N. Hemoglobin A2 values in sickle cell disease patients quantified by high performance liquid chromatography and the influence of alpha thalassemia. Rev Bras Hematol Hemoter. 2015; 37:296-301.
15. Suh D D, Krauss J S, Bures K. Influence of hemoglobin S adducts on hemoglobin A2 quantification by HPLC. Clin Chem. 1996; 42(7): 1113-14.
16. Shokrani M, Terrell F, Turner EA, Aguinaga MD. Chromatographic measurements of hemoglobin A2 in blood samples that contain sickle hemoglobin. Ann Clin Lab Sci. 2000; 30(2): 191-4.
17. Phylipsen M, Gallivan MVE, Arkesteijn SGJ, Harteveld C L, Giordano P C. Occurrence of common and rare δ-globin gene defects in two multiethnic populations: thirteen new mutations and the significance of δ-globin gene defects in β-thalassemia diagnostics. Int J Lab Hematol. 2011; 33(1): 85-91.
18. Ou CN, Rognerud CL. Diagnosis of hemoglobinopathies: electrophoresis vs. HPLC. Clin Chim Acta. 2001; 313(1-2): 187-94.
19. Adeli K, Raizman JE, Chen Y, Higgins V, Nieuwesteeg M, Abdelhaleem M, et al. Complex biological profile of hematologic markers across pediatric, adult, and geriatric ages: establishment of robust pediatric and adult reference intervals on the basis of the Canadian Health Measures Survey. Clinical Chemistry. 2015; 61(8): 1075-86.
20. Anagnostopoulos K, Tentes I, Kalleas C, Margaritis D, Toli A, Pendilas D, et al. . H. Effect of HbS in the determination of HbA2 with the Menarini HA-8160 analyzer and comparison with other instruments. Int J Lab Hematol. 2009; 31(6):665-72.
21. Higgins TN, Khajuria A, Mack M. Quantification of HbA2 in patients with and without β-thalassemia and in the presence of HbS, HbC, HbE, and HbD Punjab hemoglobin variants: comparison of two systems. Am J Cclin Pathol. 2009; 131(3):357-62.
Download attachments: 10.4328:ACAM.20914
Süheyl Uçucu, Talha Karabıyık. Chromatographic and hematological comparison of sickle cell carriers and hemoglobin D los angeles carriers. Ann Clin Anal Med 2022;13(3):272-275
Citations in Google Scholar: Google Scholar
Students’ perception of factors affecting learning
Muhammad Humayun 1, Ambreen Khalid 2, Asmara Syed 3, Ekramy Elmorsy 3, Iram Arshad 1, Syed Sajid Hussain Shah 3
1 Department Of Biochemistry, Central Park Medical College, Lahore, Pakistan, 2 Department Of Physiology, Shalamar Medical And Dental College, Lahore, Pakistan, 3 Department of Pathology, Faculty of Medicine, Northern Border University, Arar, Kingdom of Saudi Arabia
DOI: 10.4328/ACAM.20916 Received: 2021-10-23 Accepted: 2021-11-12 Published Online: 2021-11-19 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):276-278
Corresponding Author: Muhammad Humayun, Department Of Biochemistry, Central Park Medical College, Lahore, Pakistan. E-mail: mrhumayundr@gmail.com P: +92 332 841 01 80 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8128-6191
Aim: In this study, we aimed to evaluate the perception of medical students of external factors, which influence their learning process.
Material and Methods: The study was conducted in the Central Park Medical College Lahore in August – September 2021. The questionnaire was distributed to the medical students who wished to participate in this study. Two hundred and one completely filled proformas have been received, which were analyzed using computer software.
Results: The analysis of the two hundred and one completely filled proformas revealed that factors, which strongly influence the learning process include teaching by teachers with excellent teaching strategies/skills, having a separate room for study, 24/7 library availability, and revision of important component/topics in special revision sessions at the end of the course.
Discussion: The evaluation of the factors that influenced the learning process of the students from the students’ point of view is vital for teachers and administrators of the institution because improvements made in this regard will enhance the performance and academic achievements of the students. The most important factors that have an impact on the learning process of the students are teaching strategies and a comfortable environment.
Keywords: External Factors, Learning, Medical Students
Introduction
Teaching and learning are the key steps in the progress and development of the human race. The development of effective plans and application of appropriate strategies for the process of learning are of vital importance. There are many factors, which may yield an impact on the learning process. The important influencing factors include internal motivation of the learners such as willingness to learn, mental and physical capabilities. However, external factors also contribute a lot to the learning process, which may include teaching strategies, infrastructure and an encouraging atmosphere.
The academic achievement of the students is influenced by the educational infrastructure facilities [1]. The type of institution (public/private) and income of the parents also affect the academic performance of the students [2]. The culture also has an impact on learning [3]. Teaching strategies revealed influence on the students’ academic achievements [4]. Another important factor, which affects the learning process is the use of information technology [5]. Parental education is also an external factor influencing the children’s learning [6].
The aim of the present study is to assess the opinion of the medical students regarding the external factors, which influence their learning process.
Material and Methods
A questionnaire has been designed that included questions regarding the factors, which influence the learning process of students. This questionnaire contained twenty questions. After receiving ethical approval from the institutional ethics review board, the questionnaire was distributed among the medical students who consented to participate in this research. Medical students from the Central Park Medical College in Lahore participated in this study. This study was carried out in August and September 2021. This questionnaire lacks any personal identification like participants’ name, cell phone number and email address. Completely filled proformas were analyzed using a computer software.
Statistical analysis:
Completely filled questionnaires were considered for data analysis. Microsoft excel was used to get the average of responses of students to each parameter and total score.
Results
In the present study, 201 completely filled proformas were received from the willing participants. The analysis of the data revealed that according to the students’ point of view regarding the factors, which strongly influence their learning process include teaching by teachers with excellent teaching strategies/skills (average score: 4.7), having a separate room for study (average score: 4.7), 24/7 library availability (average score: 4.6), a well as revision of important component/topics in the special revision sessions at the end of the course (average score: 4.6). The results are shown in Table 1.
Other factors, which may affect the learning process of students in the opinion of students, include conduction of lectures containing difficult conceptual contents in the beginning of the day (average score: 3.9), conduction of practical sessions after the delivery of lectures of the respective topic (average score: 4.3), presentation of students in the small groups of 10-20 students (average score: 3.5), highlighting important things (in bold with different colors) in the slides of lectures (average score: 4.3), lecture theaters/laboratories with appropriate temperature such as air conditioning and heating (average score: 4.5), teaching by high qualified teachers (average score: 4.4), types of seats of the lectures theater wooden benches/plastics /soft sofa (average score: 4.1), conduction of tests on the first working day of every week (average score: 3.5), conduction of tests in alternative weeks (average score: 3.9), posttest/exam discussion in class (average score: 4.5), having a shared room for study (average score: 2).
Discussion
The data analysis in the present study revealed that according to the perception of the students, the strongest factor, which influences students’ learning process is the excellent teaching strategies used by teachers. A study published by Urrutia–Aguilar ME et al showed that the teaching strategies have an impact on the learners’ academic achievements [7]. Good teaching exerts a strong influence on learners [8].
In our study, the second most important factor that affects the learning of medical students is the availability of separate rooms for the study as per students’ point of view. A peaceful and comfortable environment without distracting factors plays an important role in the learning process. Even the classroom environment such as temperature and ventilation influenced the students’ examination scores [9].
The current study revealed that the third most influencing factor in the learning process is the availability of library facility round- the- clock (24/7) and revision of important components/topics in the special revision sessions at the end of the course. The library use is closely related to academic achievement [10]. More use of the library in the college of medicine is quite important for the growth and development of the learners.
In our study, the majority of the students favors 24/7 library availability. The students also expressed their strong opinion regarding the revision of the important topics at the end of the course, which may reinforce the learning. According to the students’ perception, other factors, which may affect the learning process include round- the- clock uninterrupted power supply (electricity), posttest/exam discussion in class and lecture theaters/laboratories with an appropriate temperature (air conditioning and heating). The learning process and the students’ academic performance are also influenced by environmental factors such as noise, wall colors, room lights and open space [11].
The study and assessment of the factors, which may influence the learning of the students from the students’ point of view, are also important for the teachers and administrators of the institution, as they may affect student performance and academic achievements and may influence the ranking of the institution nationally as well as internationally.
Conclusion:
The external factors such as excellent teaching strategies, peaceful and comfortable environment, as well as the facility of library are of importance in the learning process according to the students’ viewpoint.
Acknowledgment
The authors are very grateful to Jannat Zaib Mir and Mohtashim Dar for their help in the collection of the data.
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.
Funding: None
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.
References
1. Sulemana M, Ngah I, Majid M. The Perspective of Students on Factors Affecting Their Academic Performance at the Tertiary Level. Journal of Education, Society and Behavioural Science. 2014; 4(8):1021-8.
2. Ali S, Haider Z, Munir F, Khan H, Ahmed A. Factors Contributing to the Students Academic Performance: A Case Study of Islamia University Sub-Campus. Am J Educ Res. 2013; 1(8):283-9.
3. Kang H, Chang B. Examining Culture’s Impact on the Learning Behaviors of International Students from Confucius Culture Studying in Western Online Learning Context. Journal of International Students. 2016; 6(3):779-97.
4. Cordero JM, Gil-Izquierdo M. The effect of teaching strategies on student achievement: An analysis using TALIS-PISA-link. J Policy Model. 2018; 40 (6):1313-31.
5. Negi PS, Negi V, Pandey AC. Impact of Information Technology on Learning, Teaching and Human Resource Management in Educational Sector. International Journal of Computer Science and Telecommunications. 2011; 2(4):66-72
6. Qaiser A , Zakaria M , Shaheen N , Iqbal F , Aziz A , Hashmi IQJ. Medical Students Perception of Supportive Factors Regulating their Self-Regulated Learning. Pakistan Journal of Medical & Health Sciences. 2020;14(1): 86-8.
7. Urrutia-Aguilar ME, Fuentes-García RS, Vélez HG, Beck E, Arciniega MA, Guevara-Guzmán R. Impact of Teaching Strategies on Medical Student Academic Performance. Glob J Health Sci. 2018; 10(2):19-27.
8. Mustapha R, Bunian S, Rahman S, Husain MY, Bahtiar RA. Environmental Factors and Students’ Learning Approaches: A Survey on Malaysian Polytechnics Students. Journal of Education and Learning. 2014; 8 (4):387-98.
9. Haverinen-Shaughnessy U, Shaughnessy RJ. Effects of Classroom Ventilation Rate and Temperature on Students’ Test Scores. PLoS ONE. 2015; 10(8): e0136165.
10. Banleman K, Adjoa YF. An Analysis of the Correlation Between Academic Library Use and Student’s Academic Performance: A Case Study of UDS -Wa Campus. Information and Knowledge Management. 2017;7(3):13-20
11. Gilavand A. Investigating the Impact of Environmental Factors on Learning and Academic Achievement of Elementary Students: Review. International Journal of Medical Research & Health Sciences. 2016;5(7S):360-9
Download attachments: 10.4328:ACAM.20916
Muhammad Humayun, Ambreen Khalid, Asmara Syed, Ekramy Elmorsy, Iram Arshad, Syed Sajid Hussain Shah. Students’ perception of factors affecting learning. Ann Clin Anal Med 2022;13(3):276-278
Citations in Google Scholar: Google Scholar
The epidemiology of poisoning in emergency department in Turkey
Cüneyt Arıkan, Ejder Saylav Bora, Güner Yurtsever, Osman Sezer Çınaroğlu, Hüseyin Acar, Tutku Duman Şahan, Fatih Esad Topal
Department of Emergency Medicine, İzmir Katip Çelebi University, Atatürk Research And Training Hospital, İzmir, Turkey
DOI: 10.4328/ACAM.20917 Received: 2021-10-23 Accepted: 2021-11-11 Published Online: 2022-01-25 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):279-282
Corresponding Author: Ejder Saylav Bora, Emergency Medicine, İzmir Katip Çelebi University, Atatürk Research And Training Hospital, İzmir, Turkey. E-mail: saylavbora@hotmail.com / ejdersaylav@gmail.com P: +90 532 450 78 55 Corresponding Author ORCID ID: https://orcid.org/0000-0002-2448-2337
Aim: Poisoning has a high potential mortality and morbidity. In order to prevent poisonings and reduce the risk of mortality and morbidity, it is necessary to determine the poisoning profile. Along with changes in medicine, technology and sociocultural life, the poisoning profile also changes over time. It is essential to keep up-to-date information on the subject in order to control poisoning.
Material and Methods: Poisoning cases admitted to the emergency department between 2016 and 2020 were retrospectively reviewed. Patients aged 18 years and older were included in the study. Patients younger than 18 years of age and those with missing data were excluded from the study. Demographic, etiological and clinical features of poisonings were analyzed.
Results: A total of 774 subjects with a mean age of 39.1±15.4 were included in the study. Of these subjects, 472 (61%) were male. The most common mechanism of poisoning was intentional exposures (n=418, 54%). It was known which substance 737 (95.2%) patients were exposed to, and a total of 1030 substances that caused poisoning were identified. Medications (n=579, 56.2%) were the first among the exposed substances, and antidepressants (n=152, %26.3) were the first among the medications. Poisoning with alcohol and its derivatives (n=282, 27.4%) was in the second place. The rate of hospitalization in the inpatient service was 50.8% (n=393), intensive care unit was 13.8% (n=107) and the mortality rate was 4.4% (n=34). The statistical significance between unintentional poisonings, the subjects who used antidote and the subjects who underwent hemodialysis and mortality was high (p values, respectively: p<0.001, p<0.001, p<0.001).
Discussion: This study is one of the that contain up-to-date information in large case series in the field of toxicology. Poisonings were most often caused by intentional exposure. Among the substances that cause poisoning, medications, alcohol and its derivatives are in the first two places. Hospitalization, ICU admission and mortality rates are high in poisonings, which creates a serious economic and social burden for the health system.
Keywords: Poisoning, Intoxication, Emergency Department, Antidote
Introduction
Poisoning constitutes an important disease group in the emergency department (ED) with high potential mortality and morbidity [1]. The rate of admission to the ED with poisoning varies between 0.27% and 1.4% in Turkey [2,3]. This rate has been reported as 0.64% in United States [4], between 0.39% and 5% in European countries [5,6], and 0.82% in Taiwan [7]. Between 5% and 14% of intensive care unit (ICU) admissions are due to poisoning [8].
The cause of poisoning can be clearly identified in some cases, but sometimes it is very difficult to diagnose [1]. The causes and forms of poisoning can vary between countries, as well as between different geographical regions of the same country [9]. Determining the poisoning profile in a country or a particular region is crucial for identifying risks, taking necessary precautions, and managing cases [3]. In addition, the profile of poisoning may change over time with the effect of new treatment methods in modern medicine, advances technology, sociocultural changes. It is essential to record the cases and keep the relevant information up-to-date for the prevention and better management of poisonings [2].
In this study, it was aimed to determine the demographic, etiological and clinical characteristics of acute poisoning cases admitted to the ED.
Material and Methods
2.1. Study design and settings
This study was carried out in the adult ED of a tertiary health institution affiliated with the university in the city center of Izmir, with a population of 4.4 million, located in the west of Turkey. Poisoning cases admitted to the adult ED, which has an admissions of approximately 60,000 yellow and red coded patients (excluding trauma) annually, during the 5-year period between ‘January 1, 2016-December 31, 2020’ were analyzed retrospectively. Approval for the study was obtained from the Izmir Katip Çelebi University Non-Interventional Clinical Research Ethics Committee (Date 18.02.2021 and Decision No 0044).
2.2. Study population
Among the patients who presented to the ED, patients aged 18 years and older who had at least one of all the diagnostic codes containing the word “poisoning” (F10-19, T36-61, T96, X40-49, Y10-19, Y91) according to the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) were included in the study. A total of 774 subjects were included in the study. Patients younger than 18 years of age and patients with missing data will be excluded from the study.
2.3. Data collection and processing
From the medical records of the subjects, age, gender, place of residence (province, district, countryside), time of admission to the hospital (hour, month and year), mechanism of poisoning (intentional, unintentional, adverse reaction and other) and type or name of the exposed substance, the number of exposed substances (single, two, more than two, unknown), the status of receiving counseling from a The National Poison Information Center (NPIC), the use and name of antidote, the need for hemodialysis, the hospitalization status, mortality and cost information were obtained. Subjects were divided into six groups according to age groups as 18-24, 25-34, 35-44, 45-54, 55-64 and ≥65. The time of admission to the hospital was grouped according to the year, month and time of the day of admission. The hours of the admission day are divided into daytime (08:00-15:59), evening (16:00-23:59) and night (00:00-07:59). The factors that cause poisoning are divided into 8 main groups as medications, recreational drugs, alcohol and its derivatives, gases, pesticides, bite/sting by animals, others (foods, corrosives, etc.) and unknown. Medications are divided into subgroups. These subgroups are psychotropic drugs, antidepressants, psychostimulant drugs, anticonvulsant drugs, analgesic and myorelaxant drugs, cardiovascular system drugs, gastrointestinal system drugs, antibiotics, antivirals and antifungals, vitamins, antihistamines, and others. (antidiabetics, hormones, herbal products, etc.) The cost of the subjects was calculated based on the Social Security Institution invoice.
2.4. Outcome measures
In this study, it was aimed to determine the most common causes of poisoning and the antidotes used in the ED. In addition, factors related to mortality and total costs of subjects were also calculated.
2.5. Data analysis
IBM SPSS Statistics 23 (SPSS Inc., Chicago, USA) program was used for data analysis. Descriptive statistics were expressed with frequency, percentage, mean and standard deviation values. The suitability of the data to the normal distribution was evaluated using the Shapiro-Wilk test, skewness-kurtosis values, and Q-Q plots. In the comparison of two independent groups, Independent Samples t-Test was used for data conforming to normal distribution. The chi-square test was used to compare two or more categorical groups. Values with p value less than 0.05 were considered significant. All statistics were performed at 95% confidence interval.
Results
In the 5-year period, in which approximately 300.000 yellow and red coded patients (excluding trauma) were admitted, the number of patients who presented to the ED due to poisoning was 774. Of these subjects, 472 (61%) were male. The mean age of the subjects who presented was calculated as 39.1±15.4, the mean age of men as 42.7±14.8, and the mean age of women as 33.5±14.7. Based on age groups, the highest number of subjects are between the ages of 25-34 (n=172, 22.2%) (Table 1).
Most of the subjects are living in the city center (n=621, %80.2). Most of the subjects presented during the daytime, between 08:00 and 15:59 (n=319, 41.2%). The highest number of presentations were made in 2018 (n=174, 22.1%), the least in 2020 (n=108, 14.0%). The months with the highest number of presentations are October (n=80, 10.3%), June (n=76, 9.8%) and February (n=74, 9.6%) (Graph 1).
The most common mechanism of poisoning was intentional exposure (n=418, 54%). A total of 1030 exposed substances causing poisoning were detected in 737 (95.2%) of 774 subjects. The cause of poisoning in 37 (4.8%) subjects was unknown. Of the subjects, 167 (21.6%) were poisoned with more than one substance and 71 (9.2%) were poisoned with more than two substances (Table 2). Poisonings occurred mostly with medications (n=579, 56.2%), and among medications, antidepressants (26.3%) and analgesic – myorelaxant drugs (n=134, 23.1%) were the most common ones. Poisoning with alcohol and its derivatives (n=282, 27.4%) was the most common following medications (Table 2).
Among all poisonings, the most common cause was sucidal attempts (n=407, 52.6%). When the number of suicide attempts by months was analyzed, no significant difference was found (p=0.285).
NPIC was called for 469 (60.6%) of the subjects and counseling service was obtained. In total, specific antidotes were used 161 times for 127 (16.4%) subjects, and hemodialysis was applied to 87 (11.2%) subjects. The most commonly used specific antidotes were ethyl alcohol (n=46, 28.6%), oxygen (n=22, 13.7%) and fomepizole (n=21, 13.0%) .
The number of subjects treated in the ICU was 107 (13.8%), the number of subjects treated in the service was 393 (50.8%). The mean length of stay in the hospital (including the observation period in the ED) was 5.9±9.9 days, and the average cost per subject was calculated as approximately 1762.6±4787.6 TL.
Mortality due to poisoning occured in 34 (4.4%) of the subjects (Table 3). A statistically significant relationship was found between unintentional poisoning and mortality, one of the poisoning mechanisms (p<0.001). The statistical significance between the subjects who used antidote and the subjects who underwent hemodialysis and mortality was high (p values, respectively: p<0.001, p<0.001). In the mortality group, the mean age (44.4 ± 17.3) was found to be statistically significantly higher than the others (33.8±15.3) (p=0.004) (Table 3), but no statistical significance was found when looking at the age groups (p=0.210). No statistically significant was found between gender, poisoning time, exposure to more than one substance, duration of hospitalization and mortality (p values, respectively: p=0.240, p=0.603, p=0.886, p=0.487).
Discussion
Poisoning is a universal public health problem that especially threatens the young population. It constitutes an important patient group among critically ill patients admitted to the ED. This study is one of the rare studies that contain up-to-date information in large case series in the field of toxicology in Turkey [2,3].
The prevalence of poisoning cases admitted to the ED varies according to countries, regions, cities and hospitals [2-7]. In the present study, this rate was found to be 0.25% and it is similar to studies conducted in recent years [3,5].
In many studies conducted in Turkey and in the world, it has been reported that poisoning cases are more common in women [2-5]. The number of studies reporting that male subjects are in the majority is less [10]. In this study, the majority of subjects (61%) were male. Similar to other studies in the literature, the majority of subjects (63.7%) are adults between the ages of 18-45 [2-5].
It has been reported in previous studies that hospital admissions are most common in the hours before midnight [3,5]. In this study, the highest number of admissions was during the daytime hours between 08:00 and 15:59 (n=319, 41.2%). Looking at the number of cases by year, it is seen that the least number of cases is in 2020. This may be related to the significant decrease in the number of patients admitted to the hospital in the first period of the Covid-19 pandemic.
Among all poisoning cases, the most reported case as the cause of poisoning was suicidal attempt [3,5] and in this study, the rate of suicidal attempt was found to be 52.6%. When the number of suicide attempts by months was analyzed, no significant difference was found (p=0.285). Subjects poisoned more than one exposed substance were 21.6% of all subjects. Poisonings occurred mostly with medications (56.2%). Among the medications, poisoning with antidepressants and analgesic-myorelaxant drugs take place in the first two ranks. Similar results were reported in two studies conducted with large patient groups in Turkey [2,3]. Although poisoning with alcohol and its derivatives (27.4%) and recreational drugs (5.6%) was found to be quite high compared to these two studies [2,3], it is similar to many studies conducted abroad [1,5,11,12]. Intoxication with alcohol and its derivatives and drugs is 3-7 times more common in male than in female [13]. In our study, male gender was detected more frequently. We think that this is due to the differences in the causes of poisoning. In addition to supportive treatment for poisonings, specific antidote treatments were administered to eligible subjects. Ethyl alcohol and fomepizole were at the top of the list of the most commonly used antidotes, similar to the high incidence of poisoning with alcohol and its derivatives.
Poison counseling centers are institutions that provide regional or country-wide services for poisoning. Doctors called NPIC in the study for 60.6% of the subjects and received consultancy service. This issue is one of the important points emphasized by the authors. We recommend calling poison control centers in all cases in order to contribute to obtaining more accurate and reliable data on a national scale and to get information about current treatment approaches.
A significant amount of the subjects admitted to the ICU consists of cases of poisoning. Mortality rates of 0.09-2.8% have been reported in previous studies [2,12,14]. In this study, the rate of hospitalization was 50.8%, the rate of admission to the ICU was 13.8%, and the mortality rate was 4.4%. When another study with similar hospitalization and ICU admission rates is examined, it is seen that the mortality rate was higher in this study [5]. This may be explained by the higher number of subjects (11.2%) who underwent hemodialysis compared to other studies [9]. Extracorporeal treatments such as hemodialysis are usually the treatment options used in high-dose or fatal toxicity situations where other treatment methods do not benefit [15]. When the factors that may be associated with mortality are evaluated, the significance of the mortality rate in unintentional poisonings is higher than in other groups. (p<0.001). This may be due to the inability to control the amount of the agent exposed in unintentional poisonings. The mortality rate was also statistically significant in subjects given specific antidote therapy and subjects underwent hemodialysis (p values, respectively: p<0.001, p<0.001). We think that this situation is related to high dose exposure.
The length and cost of hospital stay were also calculated. The mean hospital stay of the subjects was 5.9±9.9 days and the average cost to the healthcare system was calculated as 1762.6 ± 4787.6 TL. The psychosocial burden and losses caused by these cases on subjects, their relatives and healthcare workers are out of the scope of this study.
Conclusion
Poisoning especially threaten the young population. Hospitalization, ICU admission and mortality rates are high in poisonings, which creates a serious economic and social burden for the health system. The data obtained during present study can provide important and up to date information about the characteristics of poisoning cases seen in this region, and can guide the preventative actions for cases of poisoning. There is a need for more extensive and detailed studies across the country in order to better understand poisonings and raise awareness on this issue.
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.
Funding: None
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.
References
1. Lam SM, Lau AC, Yan WW. Over 8 years experience on severe acute poisoning requiring intensive care in Hong Kong, China. Hum Exp Toxicol. 2010; 29(9):757-65.
2. Avsarogullari L, Senol V, Akdur O, Akin A, Durukan P, Ozkan S. Characteristics of acute adult poisonings in a university hospital emergency department in central Turkey: a three-year analysis. J Pak Med Assoc. 2012; 62(2):129-33.
3. Zöhre E, Ayrik C, Bozkurt S, Kose A, Narci H, Cevik I, et al. Retrospective analysis of poisoning cases admitted to the emergency medicine. Arch Iran Med. 2015; 18:117–122.
4. Gummin DD, Mowry JB, Beuhler MC, Spyker DA, Brooks DE, Dibert KW, et al. 2019 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 37th Annual Report. Clin Toxicol (Phila). 2020; 58(12):1360-1541.
5. Kristinsson J, Palsson R, Gudjonsdottir GA, Blondal M, Gudmundsson S, Snook CP. Acute poisonings in Iceland: a prospective nationwide study. Clin Toxicol (Phila). 2008; 46(2):126–32.
6. Schaper A, Ebbecke M. Intox, detox, antidotes – Evidence based diagnosis and treatment of acute intoxications. Eur J Intern Med. 2017; 45:66-70.
7. Chen CK, Chan YL, Su TH. Incidence of intoxication events and patient outcomes in Taiwan: A nationwide population-based observational study. PLoS One. 2020 23;15(12):e0244438.
8. Irwin RS, Rippe JM, editors. Irwin ve Rippe’nin Yoğun Bakım Tıbbı (6rd ed) 2014, (Çeviri Ed: Tulunay M, Cuhruk H). Ankara: Güneş Tıp Kitapevleri; 2014. p.1433.
9. Koylu R, Dundar ZD, Koylu O, Akinci E, Akilli NB, Gonen MO, et al. The experiences in a toxicology unit: a review of 623 cases. J Clin Med Res. 2014; 6(1):59-65.
10. Bjornaas MA, Hovda KE, Mikalsen H, Andrew E, Rudberg N, Ekeberg O, et al. Clinical vs. laboratory identification of drugs of abuse in patients admitted for acute poisoning. Clin Toxicol (Phila). 2006; 44(2):127-34.
11. Singh O, Javeri Y, Juneja D, Gupta M, Singh G, Dang R. Profile and outcome of patients with acute toxicity admitted in intensive care unit: Experiences from a major corporate hospital in urban India. Indian J Anaesth. 2011; 55(4):370-4.
12. Lund C, Teige B, Drottning P, Stiksrud B, Rui TO, Lyngra M, et al. A one-year observational study of all hospitalized and fatal acute poisonings in Oslo: epidemiology, intention and follow-up. BMC Public Health. 2012; 12:858.
13. Fiscella K, Noonan M, Leonard SH, et al. Drug- and Alcohol-Associated Deaths in U.S. Jails. J Correct Health Care. 2020;26(2):183-193
14. Goksu S, Yildirim C, Kocoglu H, Tutak A, Oner U. Characteristics of acute adult poisoning in Gaziantep, Turkey. J Toxicol Clin Toxicol 2002; 40: 833-7.
15. Ouellet G, Bouchard J, Ghannoum M, Decker BS. Available extracorporeal treatments for poisoning: overview and limitations. Semin Dial. 2014; 27(4):342-9.
Download attachments: 10.4328/ACAM.20917
Cüneyt Arıkan, Ejder Saylav Bora, Güner Yurtsever, Osman Sezer Çınaroğlu, Hüseyin Acar, Tutku Duman Şahan, Fatih Esad Topal. The epidemiology of poisoning in emergency department in Turkey. Ann Clin Anal Med 2022;13(3):279-282
Citations in Google Scholar: Google Scholar
Acute rheumatic fever: Presentation with early arthritis in adults
İsmail Dogan 1, Osman Nuri Koyun 2 , Hakan Apaydın 3
1 Department of Rheumatology and Internal Medicine, Medicine Faculty, Ankara Yıldırım Beyazıt University, Ankara, 2 Department of Internal Medicine, Medicine Faculty, Hitit University, Corum, 3 Rheumatology Clinic, Ankara City Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.20919 Received: 2021-10-23 Accepted: 2021-11-09 Published Online: 2021-11-14 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):283-285
Corresponding Author: İsmail Doğan, Rheumatology Clinic, Ankara City Hospital, Bilkent, Çankaya, Ankara, Turkey. E-mail: dridogan@hotmail.com P: +90 505 477 01 36 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7603-9484
Aim: Acute rheumatic fever (ARF) is a common disease in Turkey, most common between the ages of 6 and 20 years. It is rare in adults, and its clinical course differs from that in children. The aim of the study was to determine the clinical course of ARF in adults.
Material and Methods: Five patients who were admitted to our rheumatology outpatient clinic in a tertiary medical center located in Çorum province, with early-onset arthritis between 2017 and 2020 were diagnosed with ARF-associated arthritis. Acute rheumatic fever-associated arthritis was diagnosed according to Jones’s criteria.
Results: The age of the cases was between 35 and 56 (mean age 45.6 years), two of them were men and three were women. One patient had atrial fibrillation and one had coronary artery disease as comorbidities. Arthritis developed in all patients after a history of tonsillitis in the last 15-21 days, and morphological changes suggesting valve involvement were detected in the echocardiogram. Two of the patients had a previous history of ARF.
Discussion: Acute rheumatic fever should be considered in the differential diagnosis of arthritis that develops after an upper respiratory tract infection in adults with post-streptococcal reactive arthritis.
Keywords: Acute Rheumatic Fever, Arthritis, Carditis
Introduction
Acute rheumatic fever (ARF) is an inflammatory reaction that presents with joint, cardiac, neurological and dermatological symptoms 2-3 weeks after group A beta-hemolytic streptococcal infection. It is most commonly seen between the ages of 5-14 years. Its incidence is reported to be 0.5-3: 100.000 in developed countries and 20-100: 100.000 in developing countries [1].
Turkey is among the countries with a medium-high risk for developing ARF [2]. Since the advent of antibiotics, the incidence of rheumatic heart disease (RHD) has been low in developed countries [3,4]. However, clinically inapparent streptococcal infections or symptomatic patients not seeking care are common reasons of delayed diagnosis of ARF in developed countries [3]. This delay in diagnosis and proper management is notorious for leading to the development of RHD, which is caused by autoimmune damage of cardiac tissue and can result in severe valvular damage requiring valvular surgery [5].
Early diagnosis and management of ARF is crucial since the risk of valvular damage can be reduced with proper treatment [3]. ARF is a rare condition in adults therefore, while juvenile ARF may be overdiagnosed, the diagnosis may be overlooked in adults with rheumatic symptoms whose cardiac state inexplicably deteriorates [6]. In one of the most recent studies, it was reported that the clinical manifestations of ARF in adults were similar to that seen with ARF in children, with migratory polyarthritis being the most common manifestation [7]. In 2015, the Jones criteria were revised with the addition of monoarthritis and polyarthralgia to migratory polyarthritis and subclinical carditis findings in echocardiography as major criteria in medium-high risk populations [8]. In this study, we present case series of adult ARF, presenting with arthritis.
Material and Methods
The study was approved by the Ethics Committee (No. E1-20-324). Five adult patients who were admitted to our rheumatology outpatient clinic with early-onset arthritis between 2017-2020 and who were diagnosed with ARF-related arthritis according to Jones criteria [8] were included in this report.
Hospital records of the cases were retrospectively reviewed. Arthritis, carditis, Sydenham chorea, erythema marginatum,
subcutaneous nodule, fever, arthralgia, echocardiography, electrocardiogram findings, anti-streptolysin O antibody titer follow-up, erythrocyte sedimentation rate, comorbid diseases, applied medications and treatment responses were recorded.
Statistical analysis was performed using the Statistical Package for Social Science (SPSS) software, version 15.0 statistical package program (IBM Inc.; Chicago, IL, USA). Demographic and clinical variables were summarized as proportions.
Results
The ages of the patients ranged from 35 to 56 years (mean age 45.6 years), two males and three females. One patient had coronary artery disease, and one patient had atrial fibrillation as comorbidity. All of them had a history of tonsillitis 15-21 days ago. Two patients had a previous anamnesis of ARF. Clinical and laboratory findings of the cases are given in Table-1.
The patients were diagnosed with acute rheumatic fever-related arthritis with a gradual increase of ASO titer within 2 weeks, migratory polyarthritis, carditis findings with echocardiography, fever and high sedimentation rate according to revised Jones criteria. For differential diagnosis of early arthritis, antinuclear antibody, anti-CCP, rheumatoid factor, uric acid and Brucella agglutination serum levels of patients were found to be negative.
As a treatment, non-steroidal anti-inflammatory drugs, oral methyl prednisolone (16 mg/day) and benzathine penicillin G (1.2 million units/4 weeks-intramuscular) were prescribed. The methylprednisolone dose was gradually decreased and discontinued according to the clinical follow-up in medium 4-6 weeks.
In one patient who was using warfarin for atrial fibrillation, intramuscular depo-penicillin was not given due to the risk of hemorrhage. In another patient with coronary artery disease with a planned coronary by-pass operation, methyl prednisolone was given at a dose of 4mg/day. Arthritis symptoms in all patients improved with treatment. Regular cardiology follow-ups for carditis were recommended.
Discussion
In our cases, arthritis and carditis were the major signs of ARF. Other major findings such as chorea, subcutaneous nodule and erythema marginatum were absent. Echocardiographic findings of carditis were detected in all cases. Our findings were similar to the ARF case series published in 1980, in which arthritis and carditis were among the only defined major criteria for adults [6]. In a study of 35 cases, all but one patient had migratory polyarthritis, none had chorea, erythema marginatum, or subcutaneous nodules. Carditis occurred in eight, manifested by pericarditis in four and new significant murmurs developed in four [9]. In an adult ARF series of 31 cases, arthritis was the most common major criterion. However, unlike other series, cardiac involvement was a prominent feature [10]. In a case series of 14 adult patients with ARF, all had arthritis, 4 patients had carditis. One patient had erythema marginatum, while chorea and subcutaneous nodules were not seen. Of these, only 3 had a childhood history of rheumatic fever [11]. On the other hand, two patients had a childhood history of rheumatic fever in our study.
ARF in adults was studied on the basis of an analysis of 23 patients, together with a review of a further 466 published cases [6]. In contrast to juvenile ARF, in this study, only arthritis (83%) and carditis (35%) were major criteria for the diagnosis in an analysis of 23 patients [6]. In a series of 25 ARF patients, the incidence of prolonged PR-interval was found to be higher with adult-onset disease [12]. Likewise, all patients had prolonged PR-interval in our study. ARF is more common in adults than previously recognized. Therefore, clinicians should be aware of this condition and include it in their differential diagnosis of febrile patients with arthritis [12].
Post-streptococcal reactive arthritis (PSRA) should be considered in the differential diagnosis of ARF. Sahin et al. reported a series of 43 cases in adults (6 ARF, 37 PSRA). In the PSRA group, unlike the ARF group, mono-oligo arthritis was more frequent than migrating arthritis. No signs of fever and carditis were detected in any of the cases [13]. In our study, there was migrating arthritis and fever in ARF cases, and all of them had signs of carditis in echocardiography.
ARF is no longer a public health problem in developed countries with high socioeconomic status. But its prevalence in school-age children >2/100.000, all age>1/1000th of the developing countries, including Turkey; take part in middle-high risk countries [2].
The incidence of ARF is high in children aged 5-14 years. ARF is not usually seen in children under 5 years of age. It is rare to be seen as the first episode in adults over 30 years of age, and the risk of recurrence decreases in adults over 40 years of age. Although there is no significant gender discrepancy, heart involvement is reported to be more common in females [5]. In our report, ARF was detected as the first episode in patients over 30 years of age for 3 cases. Recurrence was observed in 2 cases over 40 years old with an anamnesis of ARF.
The diagnosis of ARF is often more difficult for several reasons because of similarities to other polyarthritis common in adults, such as early rheumatoid arthritis, systemic lupus erythematosus, gout and the like, and major symptoms such as Sydenham chorea, erythema marginatum and carditis are less common in adults. In addition, in a patient with previous rheumatic heart disease, the presence of heart murmurs, as well as of various non-specific findings such as fever, increased acute phase reactants and electrocardiographic abnormalities may demonstrate complications of rheumatic heart disease other than recrudescence of activity.
Our rheumatology clinic is the only rheumatology clinic in Çorum province with a population of 500,000, and the fact that only 5 cases were detected in adult patients presenting with arthritis in 2 years may suggest that ARF is not frequently presented with arthritis in adults in that region. However, further studies of the incidence of ARF cases presenting with carditis to cardiology and chorea to neurology clinics in adulthood may be indicative of the incidence of ARF in adulthood.
Acute rheumatic fever-related arthritis is not a common condition in adult patients and should be kept in mind for patients with arthritis after upper respiratory tract infections since early recognition may prevent heart complications.
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.
Funding: None
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.
References
1. Stollerman GH. Rheumatogenic group A streptococci and the return of rheumatic fever. Adv Intern Med. 1990;35:1-25
2. Eroğlu AG. Update on diagnosis of acute rheumatic fever: 2015 Jones criteria. Turk Pediatri Ars. 2016;51(1):1-7.
3. Seckeler MD, Hoke TR. The worldwide epidemiology of acute rheumatic fever and rheumatic heart disease. Clin Epidemiol. 2011;3:67-84.
4. Gerber MA, Baltimore RS, Eaton CB, Gewitz M, Rowley AH, Shulman ST, et al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation 2009;119(11):1541-51.
5. Karthikeyan G, Guilherme L. Acute rheumatic fever. Lancet. 2018;392(10142):161-74.
6. Ben-Dov I, Berry E. Acute rheumatic fever in adults over the age of 45 years: an analysis of 23 patients together with a review of the literature. Semin Arthritis Rheum. 1980;10(2):100-10.
7. Sellers AL, Levine EB. Acute rheumatic fever in adults. Permanente J. 2000;4(4):30–5.
8. Gewitz MH, Baltimore RS, Tani LY, Sable CA, Shulman ST, Carapetis J et al. American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young. Revision of the Jones Criteria for the diagnosis of acute rheumatic fever in the era of Doppler echocardiography: a scientific statement from the American Heart Association. Circulation. 2015;131(20):1806-18.
9. Adatto IJ, Poske RM, Pouget JM, Pilz CG, Montgomery MM. Rheumatic fever in the adult. JAMA. 1965;194(10):1043-8.
10. Whitelaw DA. Acute rheumatic fever in adults. S Afr Med J. 1990;78(6):305-8.
11. Feuer J, Spiera H. Acute rheumatic fever in adults: a resurgence in the Hasidic Jewish community. J Rheumatol. 1997;24(2):337-40.
12. Kasitanon N, Sukitawut W, Louthrenoo W. Acute rheumatic fever in adults: case report together with an analysis of 25 patients with acute rheumatic fever. Rheumatol Int. 2009;29(9):1041-5.
13. Sahin K, Karaaslan Y. P21-Retrospective analysis of laboratory data and treatments of 43 adult patients followed up with the diagnoses of acute rheumatic fever (ARF) and post-streptococcal reactive arthritis (PSRA). Pediatr Rheumatol Online J. 2017; 15(Suppl 1.):37.
Download attachments: 10.4328:ACAM.20919
İsmail Dogan, Osman Nuri Koyun, Hakan Apaydın. Acute rheumatic fever: Presentation with early arthritis in adults. Ann Clin Anal Med 2022;13(3):283-285
Citations in Google Scholar: Google Scholar
Comparison of the short term outcomes between transobturator tape (TOT) and tension free vaginal tape (TVT) procedures in the treatment of urinary incontinence
Cengiz Andan
Department of Obstetrics and Gynecology, TC Ministry of Health Health Sciences University, Gazi Yasargil Diyarbakır Training and Research Hospital, Diyarbakir, Turkey
DOI: 10.4328/ACAM.20936 Received: 2021-11-03 Accepted: 2021-12-12 Published Online: 2021-12-15 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):286-290
Corresponding Author: Cengiz Andan, Elazig Road, 10. Km, Üçkuyular Locality, 21070, Kayapınar, Diyarbakır, Turkey. E-mail: mdcengizandan@gmail.com P: +90 532 610 08 52 / +90 412 258 00 60 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6609-3284
Aim: In this study we aimed to compare effectiveness transobturator tape (TOT) and tension free vaginal tape (TVT) procedures that we performed in our gynecology clinics in female patients with SUI and MUI.
Meterial and Methods: In this study, a total of 194 patients who presented to the gynecology clinic of our hospital with the complaint of urinary leakage, who were diagnosed with SUI/MUI, and operated using TOT and TVT were retrospectively evaluated. Patients’ demographic data, examination findings, urodynamic test, stress test, Q-tip test, pad test, ultrasonography and operational outcomes were compared between the two groups.
Results: Of all patients, 128 were in the TOT and 66 in the TVT group. No statistically significant difference was found between both groups in terms of age, BMI, parity and duration of incontinence. The mean operation time was 20.3±5.9 minutes in the TOT group and 30.4±6.7 minutes in the TVT group, and the mean operation time was statistically significantly shorter in the TOT group. Postoperative residue values were significantly higher in the TVT group compared to the TOT group. The most common complication in both groups was pain in the postoperative 1st week, and it was found in 21 (16%) patients in the TOT group and 6 (9%) patients in the TVT group.
Discussion: There is no significant difference between the two procedure types in terms of continence and quality of life, although TOT procedure gave better results in terms of operation time, length of stay in the hospital and complication rates.
Keywords: Urinary incontinence, TOT, TVT, complications, QoL
Introduction
Urinary incontinence (UI) is defined by the International Continence Society (ICU) as “the involuntary leakage of urine that can be shown objectively and becomes a social or hygienic problem” [1]. The symptoms of UI are highly prevalent among women and have a substantial impact on quality of life (QoL). The prevalence of UI has been reported between 5-72% in adult women [2]. Since it is observed frequently, UI leads to important social, hygienic, emotional and sexual problems and creates a significant economic burden, especially in societies where geriatric population is high. UI related comorbidities include decreased QoL and productivity, increased anxiety and depression, urinary tract and skin infections, risk of fall in elderly women and increased caregiver burden [3].
UI may be transient or chronic. Chronic UI is classified as stress UI (SUI), urge UI (UUI) and mixed UI (MUI), overflow and functional [4]. UI and subtypes are determined through medical history, physical exam, laboratory tests and imaging. UI is definitely a treatable disorder using appropriate methods. Because pathophysiologies of UI subtypes are different, highly different methods are used in the treatment. Two important problems that cause incontinence in 95% of UI patients are urethral sphincter insufficiency and involuntary detrusor contractions [5, 6]. UI is treated with conservative methods such as medical therapy, pelvic and periurethral muscle physiotherapy, mechanical devices and behavioral therapy as well as surgical methods especially in patients with sphincteric insufficiency. There is still no consensus on how to effectively treat UI, and superiority of one method over the other is debatable [7]. In addition, comparison of the methods used in different studies is difficult, because patient populations are not similar, different types and severity of incontinence is investigated, and there are differences among studies in terms of diagnostic method and criteria and surgical method performed. Finally, outcome and success of UI treatment depend on the experience of the practitioner [8]. It is important to decide the method to be used after the pathophysiology underlying incontinence and UI type are determined as a result of detailed urognyecological investigations. Each technique has unique application difficulties, risks, benefits and complications. In this study we aimed to compare the effectiveness of TOT and TVT procedures that we performed in our gynecology clinics in female patients with SUI and MUI.
Material and Methods
In this study, patients who presented to the gynecology clinic of our hospital with the complaint of urinary leakage, who were diagnosed with SUI/MUI, and operated using TOT and TVT were retrospectively evaluated. Patients were divided into two groups as TOT and TVT according to the procedure performed, based on the discretion of the surgeon and the patient’s preference, and success of the treatment, short term complications, postoperative early period symptoms and QoL were compared between the groups.
Patients’ demographic data, examination findings, urodynamic test, stress test, Q-tip test, pad test, ultrasonography and operational outcomes were obtained from the information system of our hospital and recorded. QoL and severity of the symptoms were evaluated in the preoperative and postoperative period with the Urinary Distress Inventory (UDI-6).
Medical histories were received and the patients were questioned about age, parity, menopause status, regularly used drugs, systemic diseases (diabetes mellitus, neurologic diseases, COPD etc.), duration of incontinence, numbers of voiding at night and during day, and previous gynecological operations. All patients’ height and weight were measured and BMI values were calculated (m2/Kg). In the gynecologic exam of the patients, cystorectocele, descensus uteri and presence of additional pathologies were investigated. Complete blood counts and urine culture were performed in all patients and those with infections detected were evaluated again after being treated.
The diagnosis of SUI was first made subjectively by stress test, by evaluating the sensation of the urine in the bladder in lithotomy position. Mobility of the bladder neck was evaluated with the Q-tip test; the amount of change between straining and resting angles of a cotton swab with the tip inserted in the urethral meatus with 200 mL of urine in the bladder was recorded. Mobility of the bladder neck was accepted as positive where this angle was ≥ 30degrees. The severity of UI was determined with the standard one-hour pad test. Preoperative and postoperative residual urine volumes were measured in all patients.
The UDI-6 survey that was developed in 1994 as 19 items and then shortened to 6 items was used in order to determine the effect of urinary leakage on QoL [9]. In addition, in the postoperative subjective evaluation, the patients were asked how they were compared to the past, and they answered as worse, the same, better and I have no complaints.
Ethics Considerations
Before the beginning, the study protocol was approved by the Local Ethics Committee of our hospital with the 2021/904 numbered decision. This study was performed in line with the ethical principles of the Declaration of Helsinki.
Statistical Analysis
Data obtained in the study were statistically analyzed using SPSS (Statistical Package for Social Sciences) for Windows v 15.0 software. When study data were evaluated, in addition to descriptive statistics (Mean, Standard deviation), Student t test was used for the comparison of normally distributed quantitative parameters and Chi-square test for the comparison of qualitative parameters. p<0.05 values were considered statistically significant.
Results
A total of 194 patients who underwent TOT or TVT for treatment of UI were included in the study. Of all patients, 128 were in the TOT and 66 in the TVT group. Seventy-three (57%) patients in the TOT group underwent TOT operation alone, while 55 (43%) patients underwent additional operations in addition to TOT. Nine (13.6%) patients in the TVT group underwent TVT operation alone, while 57 (86.4%) patients underwent additional operations in addition to TVT. When subtypes of UI were examined, SUI was found in 108 (84.3%) patients in the TOT group and 35 (53%) patients in the TVT group, while MUI was detected in 20 (15.7%) patients in the TOT and 31 (47%) patients in the TVT group.
The mean age of all patients was 47.9±5.78 years. The mean age was found as 46.1±7.9 years in the TOT group and 51.4±1.6 years in the TVT group, and the difference was not statistically significant (p>0.05). No statistically significant difference was found between both groups in terms of BMI, parity and duration of incontinence (for all p>0.05). Distribution of the demographic and clinical features according to the groups is given in Table 1.
The mean operation time was 20.3±5.9 minutes in the TOT group and 30.4±6.7 minutes in the TVT group, and the mean operation time was statistically significantly shorter in the TOT group (p<0.05). Again length of stay in hospital was significantly shorter in the TOT group (1.3±0.3 days) compared to the TVT group (2.1±0.6 days) (p<0.05). Comparison of the operational data between the groups is given in Table 2.
Two (1.5%) patients in the TOT group and 2 (3%) patients in the TVT group had been operated previously for UI, while 20 (15.6%) patients in the TOT group and 31 (46.9%) patients in the TVT group had received medical therapy due to incontinence. In the pelvic examination, pelvic organ prolapse was found in 62 (48.4%) patients in the TOT group and 37 (56.1%) patients in the TVT group based on the POP-Q system. The difference between preoperative and postoperative hematocrit values was found as 5.1±0.8 in the TOT group and 7.6±1.1 in the TVT group (p<0.05). Although Q tip test (degree) and ped test (gram) values decreased in both groups postoperatively compared to before operation (p<0.05), no statistically significant difference was found between the two groups (p>0.05) (Figure 1). Postoperative residue values were significantly higher in the TVT group compared to the TOT group. On the other hand, significant decreases were found in postoperative UDI-6 scores in both groups (p<0.05). However, the difference between the groups was not statistically significant (p>0.05).
When perioperative and postoperative complications were examined, the most common complication in both groups was pain in the postoperative 1st week, and it was found in 21 (16%) patients in the TOT group and 6 (9%) patients in the TVT group. Distribution of the perioperative and postoperative complications according to the groups is presented in Table 3.
Finally, satisfaction of the patients for the operation was postoperatively evaluated and the results are shown in Figure 2.
Discussion
UI is a common but less diagnosed and treatable disease in women. More than 200 million people are estimated to have UI problem worldwide [10]. In the USA, approximately 32 billion USD is spent for the treatment of UI each year, and this figure is greater than the amount spent for dialysis and by-pass surgery [10]. The disease has numerous etiological causes and the most common subtype of UI is SUI, which is in the form of pure in 50% and mixed in 36% of the patients. In our study population, pure SUI was found in 73.7% and mixed SUI in 26.3% of the patients. Among many methods used for the treatment of UI, synthetic grafts have been proven to be superior over biomaterials in terms of durability and long-term success. With the introduction of TVT, which was developed by Petros and Ulmsten in 1995, and TOT, which was developed by Delorme in 2001, UI treatment has evolved with healing rates up to 80% [11]. In our study, we analyzed the outcomes and complications of TOT and TVT.
UI is almost always resulted from an underlying treatable condition, it is underreported to medical staff [12]. In our study, 52.9% of the patients presented to the hospital due to other reasons, but the diagnosis of UI was established as a result of investigation and examination. However, only 2% of the patients had been operated for UI previously, and 26.3% had received medical therapy, but surgery was planned due to failure of the previous treatments.
Age alone is not a risk factor for UI. However, age-related changes in the urinary system are associated with a higher risk of developing UI. UI is associated with changes in physiology, comorbidities, medications and functional impairment, especially in elderly. As the age increases, changes characterized by the increased frequency of contractions that can not be inhibited, abnormal relaxation patterns of the detrusor and decreased bladder capacity are seen. Yalcin et al. reported increased incidence of UI complaints after 40 years of age [13]. In our study, the mean age of the patients was found as 47.9 years.
Obesity is one of the risk factors associated with incontinence. Possibly, increased intraabdominal pressure with obesity worsens SUI. In a study by Ross et al., TOT and TVT methods were compared and the mean BMI value of all patients was found as 28 kg/m2 [14]. The mean BMI value of our patients was 29.4 kg/m2. In our study, no significant difference was found between the TOT and TVT groups in terms of age, BMI, parity, type and duration of incontinence.
In their randomized controlled study, de Tayrac et al. compared TOT and TVT, and the mean operation time was found as significantly shorter with TOT (27 vs 15 minutes) [15]. In the present study, consistent with the literature, the mean operation time was found as 30.2 minutes in the TVT group and 20.8 minutes in the TOT group, and the difference was statistically significant in favour of the TOT method (p<0.05). We think that the most important factor affecting operation time is education and experience of the surgeon.
In our study, postoperative residue value was found to be significantly higher with TVT compared to the TOT method. Similar results were reported in the literature [11].
In a study, duration of hospitalization was found as 1.6 days in the TVT group and 1.2 days in TOT group [11]. In our study, the mean length of stay in the hospital was found as 2.1 days in the TVT group and 1.3 days in the TOT group. In the studies by Zhang et al. [16] and Oliveira et al. [17], TOT significantly decreased the length of stay in the hospital.
Complications encountered during surgical treatment of UI can be intraoperative and postoperative. Intraoperative complications include the need for blood transfusion, bladder injury, vaginal wall perforation, urethral injury, bowel injury, cardiac arrhythmias etc. The most common postoperative complications are infections requiring antibiotics, urinary tract infection, myocardial infarction, pelvic abscess, re-admissions and emergency service presentations. In recent years, TOT has replaced TVT as a preferred method with shorter operation time and length of stay and less complications [18]. In addition, since TVT is a blindly performed method, it is open to vascular, gastrointestinal and urethral injuries [19]. Theoretically TOT sling is located in a more acute angle compared to TVT and it is not possible to prevent urine flow during voiding with TOT. However, this procedure does not completely eliminate the risk of bladder perforation and nerve injury [20]. Therefore, studies in the literature have focused on comparison of these two techniques. In a study by Potic et al. comparing the complications with TVT and TOT, overall rate of complications was reported to be lower with TOT method [11]. In the same study, the most common complications in the TVT group were reported as intraoperative hemorrhage, bladder perforation, pain, infection and de novo urgency [11]. In a meta-analysis by Huang et al. including 11 studies with 2515 patients, pooled results indicated that TOT decreased complication rates compared to TVT method [21]. Similarly, in our study overall complication rate was higher in the TVT group. The most common complications included bladder and urethra injury, de novo urgency, pain, permanent urinary retention and opening of the mesh.
Questionnaires for the evaluation of patient outcomes for the treatment of UI should be fully understandable to patients so that the results can be interpreted correctly. Studies have reported significant decreases in UDI-6 scores after surgery compared to preoperative values in both TOT and TVT groups, while the decrease in UDI-6 scores was significant in favour of the TOT group as the follow-up duration increased [11, 22]. Similarly, in our study although dramatic decreases were observed in UDI-6 scores, no significant difference was found between the groups.
In a study with 82 patients in the TOT group and 58 patients in the TVT group, subjective and objective SUI healing rate was found as 86.6% in the TOT group and 84.5% in the TVT group [23]. We evaluated the success of TOT and TVT operations that we have performed for the treatment of UI with subjective evaluations of our patients. In our study, consistent with the literature, the subjective success rate was found as 90% in the TOT group and 85% in the TVT group.
Study Limitations
The main limitation of this study is its retrospective design. In addition, long-term outcomes could not be studied. We hope that our findings will provide contribution to the debate in the literature regarding superiority of these methods over each other.
Conclusion
The results of this study indicate that there is no significant difference between the two procedure types in terms of continence and quality of life, although TOT procedure gave better results in terms of operation time, length of stay in the hospital and complication rates. However, further studies with wide series and longer follow-up are needed to draw more definitive conclusions.
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.
Funding: None
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.
References
1. Aoki Y, Brown HW, Brubaker L, Cornu JN, Daly JO, Cartwright R. Urinary incontinence in women [published correction appears in Nat Rev Dis Primers. 2017 Nov 16;3:17097]. Nat Rev Dis Primers. 2017;3:17042.
2. Cerruto MA, D’Elia C, Aloisi A, Fabrello M, Artibani W. Prevalence, incidence and obstetric factors’ impact on female urinary incontinence in Europe: a systematic review. Urol Int. 2013;90:1–9.
3. Kwak Y, Kwon H, Kim Y. Health-related quality of life and mental health in older women with urinary incontinence. Aging Ment Health. 2016; 20(7):719-726.
4. Hu JS, Pierre EF. Urinary Incontinence in Women: Evaluation and Management. Am Fam Physician. 2019;100(6):339-348.
5. Myers JB, Mayer EN, Lenherr S; Neurogenic Bladder Research Group (NBRG.org). Management options for sphincteric deficiency in adults with neurogenic bladder. Transl Androl Urol. 2016;5(1):145-157.
6. Rodrigues P, Hering F, Campagnari JC. Involuntary detrusor contraction is a frequent finding in patients with recurrent urinary tract infections. Urol Int. 2014;93(1):67-73.
7. Lin L, Huang MC, Su TH, Lau HH. Comparison between tension-free vaginal tape and transobturator tape in treating stress urinary incontinence after vaginal mesh surgery. Taiwan J Obstet Gynecol. 2018;57(4):528-531.
8. Sivalingam N, Teng YH, Chong XY, Low CH, Manocha SK, Intan Sabreena MS. Incidence of vaginal erosion with different synthetic materials for suburethral sling in the treatment of Stress Urinary Incontinence: A systematic review. Med J Malaysia. 2018;73(3):147-153.
9. Utomo E, Korfage IJ, Wildhagen MF, Steensma AB, Bangma CH, Blok BF. Validation of the Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) in a Dutch population. Neurourol Urodyn. 2015;34(1):24-31.
10. Dinç A. (2018). Prevalence of Urinary Incontinence During Pregnancy and Associated Risk Factors. Lower urinary tract symptoms, 10(3), 303–307.
11. Potić M, Ignjatović I, Bašić D. Tension free vaginal tape (TVT) vs Transobturator tape (TOT) complications and outcomes. Acta Chir Iugosl. 2014;61(1):81-84.
12. Neki NS. Urinary Incontinence in Elderly. Journal of Krishna Institute of Medical Sciences University, 2016; 5:5-13.
13. Yalcin O, Timur S, Ozbas A, Özerdoğan N, Aslan E & Beji NK. Urinary Incontinence Prevalence and Risk Factors in Women Aged 20 and Over in Malatya. International Journal of Urological Nursing, 2011; 5(2), 65–72.
14. Ross S, Tang S, Eliasziw M, et al. Transobturator tape versus retropubic tension-free vaginal tape for stress urinary incontinence: 5-year safety and effectiveness outcomes following a randomised trial. Int Urogynecol J. 2015;27(6):879–886.
15. De Tayrac R, Deffieux X, Droupy S, Chauveaud-Lambling A, Calvanèse-Benamour L, Fernandez H. A prospective randomized trial comparing tension-free vaginal tape and transobturator suburethral tape for surgical treatment of stress urinary incontinence. Am J Obstet Gynecol. 2004 Mar;190(3):602-8. doi: 10.1016/j.ajog.2003.09.070. Retraction in: Am J Obstet Gynecol. 2005 Feb;192(2):339. PMID: 15041987.
16. Zhang Y, Jiang M, Tong XW, Fan BZ, Li HF, Chen XL. The comparison of an inexpensive-modified transobturator vaginal tape versus TVT-O procedure for the surgical treatment of female stress urinary incontinence. Taiwan J Obstet Gynecol. 2011;50(3):318–321.
17. Oliveira R, Botelho F, Silva P, et al. Exploratory study assessing efficacy and complications of TVT-O, TVT-Secur, and Mini-Arc: results at 12-month follow-up. Eur Urol. 2011;59(6):940–944.
18. Vahudin Z, Apostolos PL, Mohammad-Reza RJ, Hammerer P, Dembowsk J, Witt J, Wucherpfennig W. TOT vs TOT:com par i son in terms of con ti nence re sults, com pli ca tions and qual ity of life af ter a me dian fol – low-up of 48 months. Int Urol Nephrol 2010;42:915-920.
19. Jones R, Abrams P, Hilton P, Ward K, Drake M. Risk of tape-related complications after TVT is at least 4%. Neurourol Urodyn. 2010;29(1):40-41.
20. Long CY, Hsu SC, Wu TP, Fu JC, Su JH. Effect of laparoscopic hysterectomy on bladder neck and urinary symptoms. Aus NZ J Obstet Gynaecol 2003; 43:65-9.
21. Huang ZM, Xiao H, Ji ZG, Yan WG, Zhang YS. TVT versus TOT in the treatment of female stress urinary incontinence: a systematic review and meta-analysis. Ther Clin Risk Manag. 2018;14:2293-2303.
22. Abdel-fattah M, Mostafa A, Familusi A, Ramsay I, Ndow J. Pro spec tive ran dom ized con trolled trial of transobturator tapes man age ment of urodynamic stress in con ti nence in women:3 year outcomes from the eval u a – tion of transobturator tapes study. Eur Urol 2012;62: 843-851.
23. Barry C, Lim YN, Muller R et al. A multi-centre, randomised clinical control trial comparing the retropubic (RP) approach versus the transobturator approach (TO) for tension-free, suburethral sling treatment of urodynamic stress incontinence: the TORP study. Int Urogynecol J Pelvic Floor Dysfunct. 2008 Feb;19(2):171-8.
Download attachments: 10.4328:ACAM.20936
Cengiz Andan. Comparison of the short term outcomes between transobturator tape (TOT) and tension free vaginal tape (TVT) procedures in the treatment of urinary incontinence. Ann Clin Anal Med 2022;13(3):286-290
Citations in Google Scholar: Google Scholar
Effects of the pathological characteristics on the presence of multicentric thyroid tumors in the contralateral lobe
Muhammet Pamukcu 1, Emine Demir 1, Mehmet Akif Aydin 2
1 Department of Otorhinolaryngology, 2 Department of General Surgery, Altinbas University, Medical Park Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.20952 Received: 2021-11-15 Accepted: 2021-12-17 Published Online: 2021-12-20 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):291-294
Corresponding Author: Mehmet Akif Aydin, Department of General Surgery, Altinbas University, Bahcelievler Medical Park Hospital, 34160, Bahçelievler, Istanbul, Turkey. E-mail: mdmehmetakifaydin@gmail.com P: +90 212 484 14 84 Corresponding Author ORCID ID: https://orcid.org/0000-0002-3324-1412
Aim: In this study, we aimed to investigate the effects of pathological tumor characteristics on the presence of a multicentric tumor in the contralateral lobe in papillary thyroid carcinoma (PTC).
Material and Methods: A total of 46 patients aged over 18 years who underwent total thyroidectomy due to PTC in our clinic were retrospectively evaluated. Patients’ demographic data such as age and gender, preoperative USG findings, postoperative pathological findings, lobe localization, and the presence of nodules in the contralateral lobe were recorded. In addition, tumor size, presence of nuclear atypia, mitotic activity, vascular invasion and extrathyroidal spread of the tumor and the presence of lymph node metastasis were obtained from pathological reports. Patients were divided into two groups as multicentric and non-multicentric, and the data were compared between these groups.
Results: The mean age of the patients was 44.9±12.3 years. Twenty-three patients had papillary thyroid microcarcinoma and 23 patients had papillary thyroid carcinoma. Postoperative pathological examination revealed multicentric PTCs in 15 patients . No statistically significant difference was found between patients with and without multicentric contralateral lobe tumors in terms of primary tumor diameter, nuclear atypia, mitotic activity, tumor necrosis, vascular invasion, extrathyroidal spread and lymph node metastasis (for all p>0.05).
Discussion: The pathology of the tumor in the contralateral lobe of the primary nodule can be seen with preoperative USG in the majority of patients with PTC. The presence of a multicentric tumor in the contralateral lobe is not correlated with tumor size and pathological characteristics of the tumor.
Keywords: Papillary Thyroid Carcinoma, Microcarcinoma, Multifocal, Multicentric, Tumor Size, Metastasis
Introduction
Papillary thyroid cancer (PTC) is the most common (85%) histological subtype of thyroid carcinomas with an increasing incidence [1]. PTC rarely shows aggressive behavior and usually has a good prognosis; however, it should be evaluated carefully due to the potential for distant metastasis [2]. Total thyroidectomy followed, in appropriately selected cases, by radioiodine ablation is a well-established surgical treatment option for the management of PTC [3]. This approach has several advantages: complete removal of the thyroid gland allows detection and ablation of metastatic disease and eliminates the possibility of residual carcinoma undergoing anaplastic transformation [4].
Although PTC often has an insidious course, tumors with some clinicopathological features may exhibit a more aggressive course. Among these, multifocality is often considered a high-risk factor for progression of PTC, prompting more aggressive treatments [5]. Multifocality is defined as the presence of PTCs in two or more foci. Multifocal PTC may present as microcarcinoma or larger lesions in two or more locations within the thyroid gland. Studies have shown that multifocality mostly involves the dominant nodule and surrounding microcarcinomas by approximately 90% [6, 7]. Multifocality occurs in 20-30% of PTC cases, but this rate is highly variable depending on the methodology used and the extent of the histopathological sampling, and the incidence of multifocal PTC is reported to increase [8]. On the other hand, multifocality may lead to undertreatment or overtreatment, depending on how a clinician uses it as a prognostic factor [5].
Arising of thyroid nodules independently in the contralateral lobe is defined as multicentricity. Multicentric occurrence of PTCs may be common, possibly higher than 30%. The exact mechanisms underlying multicentric PTCs are yet to be fully understood. Bilateral thyroid nodules are commonly detected by ultrasonography (US) in patients with pathologically confirmed PTC in one lobe [9]. The incidence of contralateral lobe nodules has been reported as high as 48% in patients diagnosed with unilateral PTC [10]. According to the 2015 American Thyroid Association (ATA) guidelines, the presence of contralateral lobe thyroid nodules may be considered criteria for recommending total or completion thyroidectomy [11].
The prognostic value of multifocality/multicentricity remains controversial, leading to a major challenge in the clinical management of PTC [5]. Some retrospective studies have reported a correlation between multifocality/multicentricity and the prognosis of PTC, while others reported no difference between multifocal and unifocal disease [12, 13]. There are insufficient literature studies investigating multicentric contralateral thyroid lobe carcinomas. Therefore, in this study, we aimed to investigate the effects of pathological tumor characteristics on the presence of multicentric tumor in the contralateral lobe in papillary thyroid carcinoma.
Material and Methods
Before the study began, the study protocol was approved by the local ethics committee with the 11.11.2021 dated and 2/2021.K-81 numbered decision. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). Patient consent was waived as the study was conducted retrospectively.
Patients aged over 18 years, who underwent total thyroidectomy duo to PTC in our clinic between 2016 and 2020 were retrospectively evaluated. Patients under 18 years old, those with recurrent carcinomas, non-papillary histology, distant metastasis at presentation, patients who underwent subtotal thyroidectomy and those with missing preoperative and postoperative data were excluded from the study.
Patients’ demographic data such as age and gender, preoperative USG findings, postoperative pathological findings, lobe localization and the presence of nodules in the contralateral lobe were recorded. In addition, tumor size, presence of nuclear atypia, mitotic activity, vascular invasion and extrathyroidal spread of the tumor, and the presence of lymph node metastasis were obtained from the pathological reports.
The lobe with the nodule of larger diameter was considered a tumor lobe. Patients with cancerous nodules in the contralateral lobe were considered to have multicentric carcinoma. Multicentric characteristic of the tumors was confirmed with postoperative pathological examination. Patients were divided into two groups as multicentric and non-multicentric, and the data obtained were compared between the two groups.
Statistical Analysis
Statistical analysis of the data obtained in this study was performed using SPSS version 20.0 (SPSS, Statistical Package for Social Sciences, IBM Inc., Chicago, IL, USA) statistical software. Continuous variables were expressed as mean±standard deviation, and categorical variables as frequency (n) and percentage (%). The independent t-test was used to compare variables between the groups.The p values <0.05 were considered statistically significant.
Results
The study included 46 patients, aged between 20-76 years, who underwent total thyroidectomy due to PTC in our clinic during the study period. Of all patients, 29 (63.0%) were female and 17 (37.0%) were male. The mean age of the patients was 44.9±12.3 years. Twenty-three (50.0%) patients had papillary thyroid microcarcinoma and 23 (50.0%) patients had papillary thyroid carcinoma. Tumor localization was found as the right lobe in 23 (50.0%) and the left lobe in 23 (50.0%) patients. The mean tumor diameter was measured as 14.0±10.7 (range: 3-45) mm.
The patients were divided into two groups, based on the presence of contralateral lobe tumors, as multicentric and non-multicentric. In the preoperative USG examination, 33 (71.7%) patients had contralateral lobe nodules, while 13 (28.3%) patients had no contralateral lobe nodules. Ten (76.9%) of the 13 non-multicentric patients had no carcinoma in both preoperative USG examination and postoperative pathological evaluation. In the remaining three (23.1%) patients, while no nodule was detected on postoperative USG examination, postoperative pathological outcome was reported as contralateral lobe tumor. All of these patients had microcarcinomas.
In the multicentric group (n=33), postoperative pathological outcomes were reported as contralateral lobe tumors (multicentric) in 12 (36.4%) patients. Therefore, a total of 15 patients (3+12) were considered to have multicentric PTCs. The distribution of the PTCs according to the preoperative USG and postoperative pathological findings is shown in Figure 1.Carcinoma and microcarcinoma distributions of the PTCs are given in Table 1.
In the multicentric group (n=33), postoperative pathological outcomes were reported as contralateral lobe tumors (multicentric) in 12 (36.4%) patients. Therefore, a total of 15 patients (3+12) were considered to have multicentric PTCs. Carcinoma and microcarcinoma distributions of the PTCs are given in Table 1.
Pathological reports of the multicentric and non-multicentric groups were compared. Accordingly, no correlation was found between carcinoma/microcarcinoma distinction and the presence of contralateral lobe tumors (p=0.099). No statistically significant difference was found between the patients with multicentric and non-multicentric tumors in terms of the primary tumor diameter (p=0.077). In addition, no statistically significant difference was found between the patients with and without contralateral lobe tumors in terms of nuclear atypia (p=0.12), mitotic activity (p=0.076), tumor necrosis (p=0.15), vascular invasion (p=0.67), extrathyroidal spread (p=0.99) and lymph node metastasis (p=0.35).
Discussion
In this study, we investigated the effects of several tumor characteristics on the presence of contralateral lobe tumors, namely multicentricity. Multicentricity in PTC is not defined as a factor affecting prognosis in guidelines. However, studies have associated multicentric PTC’s with increased recurrence rates, lymph node involvement, distant metastasis and mortality [14]. The rate of multicentric PTCs has been reported between 18%-87% in the literature [15]. In the present study, the rate of multicentric PCTs was found as 28.3% with preoperative USG and 32.6% according to the postoperative pathological examination. In a study by Zhang et al. including 221 patients with PTC, the rate of multicentric tumors was 21.7% [8]. In a study by Iscan et al., the rate of multicentricity was found as 23% in PTCs < 5 mm [16]. The rate of multicentric tumors found in our study was consistent with the rates reported in previous studies.
Although not fully understood, the pathogenesis of multilocal PTCs can be explained by both multicentric occurrence and intrathyroidal metastasis. However, there is still controversy in the explanation of multifocality. It is important to clarify this issue in order to guide treatment decisions and to determine prognosis in patients with PTCs [17]. Multifocal PTC is usually defined as small foci surrounding the primary tumor. There is no consensus in the literature on the effect of multifocal PTC on prognosis in terms of recurrence [12]. To our knowledge, there is no study evaluating the multicentric cancer focus seen only in the contralateral lobe of the thyroid lobe where the primary nodule is located, which may explain the lack of consensus on prognosis in the literature on multifocal PTC. Since the disease in the same lobe can be eliminated with partial surgery such as lobectomy, any millimetric focus that cannot be seen with preoperative USG in the contralateral lobe can cause a recurrence. We did not evaluate recurrence in our patients; however, we performed total thyroidectomy in all patients. The effect of any nodule in the lobe on revision surgery over time can be evaluated with further studies by following the contralateral lobe in patients who underwent partial thyroidectomy.
PCT prognosis has been shown to be associated with several factors including tumor size, vascular invasion, extrathyroidal spread, and the presence of lymph node metastasis. However, on the contrary, there are studies that could not find such associations [18, 19]. We found that the presence of multicentric PTC in the contralateral lobe was not correlated with pathological characteristics such as nuclear atypia and mitotic activity of the primary tumor, necrosis and vascular invasion. In addition, the presence of multicentric PTC in the contralateral lobe was not associated with extrathyroidal spread and lymph node metastasis. Perhaps if we had evaluated multifocality for more than one tumor in the same lobe, we would have obtained different data. However, we evaluated the individual tumor in the contralateral lobe, and the data we obtained showed that both tumors did not have interrelated effects.
In the present study, we demonstrated that the majority (13/15, 87%) of the contralateral lobe PCTs can be detected through preoperative USG examination, and the remaining tumors that could not be detected with preoperative USG were microcarcinomas. Papillary microcarcinomas < 10 mm can also be detected by USG. However, it is very difficult to detect patients with a tumor size ≤ 3 mm using USG [20]. In our study, 3 of 13 patients without nodules detected by preoperative USG had papillary microcarcinoma in the pathological reports.
We think that this should be taken into account in preoperative patient evaluations. Tumor size ≥ 20 mm in PTC affects pathological features such as lymph node metastasis and extrathyroidal spread, making the tumor more aggressive [21]. In a study by Lin et al., the mean size of the dominant focus was shown to be significantly smaller in a multicentric tumor compared to the unifocal tumor [22]. On the contrary, in a study by Hwang et al., no correlation was found between the tumor size and multicentricity [23]. Similarly, in the present study, no significant correlation was found between the presence of a multicentric tumor in the collateral lobe and the size of the primary tumor. This may be related to the fact that the mean tumor size of the patients in our study was < 20 mm.
Study Limitations
The major limitations of this study are its retrospective nature and a relatively small number of patients. In addition, tumor sizes could be classified and multifocal/multicentric tumor distinction could be made considering the invasion in relation with the primary tumor.
Conclusion:
The pathology of the tumor in the contralateral lobe of the primary nodule can be seen with preoperative USG in the majority of patients with PTC. It should be remembered that there may be microcarcinoma foci in patients without pathology detected by USG. In addition, the presence of a multicentric tumor in the contralateral lobe is not correlated with tumor size and pathological characteristics of the tumor.
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.
Funding: None
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.
References
1. Brito JP, Yarur AJ, Prokop LJ, McIver B, Murad MH, Montori VM. Prevalence of thyroid cancer in multinodular goiter versus single nodule: a systematic review and meta-analysis. Thyroid. 2013;23(4):449-55.
2. Davies L, Welch HG. Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg. 2014;140(4):317-22.
3. Donatini G, Castagnet M, Desurmont T, Rudolph N, Othman D, Kraimps JL. Partial Thyroidectomy for Papillary Thyroid Microcarcinoma: Is Completion Total Thyroidectomy Indicated?. World J Surg. 2016;40(3):510-15.
4. Baloch MN, Razzak SA, Mehmood Z, Naz S, Altaf S. Malignancy in contralateral thyroid lobe. Open J Thyroid Res. 2019; 2(1): 15-17.
5. Wang F, Yu X, Shen X, Zhu G, Huang Y, Liu R, et al. The Prognostic Value of Tumor Multifocality in Clinical Outcomes of Papillary Thyroid Cancer. J Clin Endocrinol Metab. 2017;102(9):3241-50.
6. de Matos PS, Ferreira AP, Ward LS. Prevalence of papillary microcarcinoma of the thyroid in Brazilian autopsy and surgical series. Endocr Pathol. 2006;17(2):165-73.
7. Kim JM. The clinical importance of multifocality on tumor recurrence in papillary thyroid carcinoma. Gland Surg. 2021;10(1):273-8.
8. Zhang L, Wei WJ, Ji QH, Zhu YX, Wang ZY, Wang Y, et al. Risk factors for neck nodal metastasis in papillary thyroid microcarcinoma: a study of 1066 patients. J Clin Endocrinol Metab. 2012;97(4):1250-7.
9. Ritter A, Bachar G, Hirsch D, Benbassat C, Katz O, Kochen N, et al. Natural History of Contralateral Nodules After Lobectomy in Patients With Papillary Thyroid Carcinoma. J Clin Endocrinol Metab. 2018; 103(2):407–14.
10. Ibrahim B, Forest VI, Hier M, Mlynarek AM, Caglar D, Payne RJ. Completion thyroidectomy: predicting bilateral disease. J Otolaryngol Head Neck Surg. 2015;44(1):23.
11. Wu ZG, Yan XQ, Su RS, Ma ZS, Xie BJ, Cao FL. How Many Contralateral Carcinomas in Patients With Unilateral Papillary Thyroid Microcarcinoma Are Preoperatively Misdiagnosed as Benign? World J Surg. 2017;41(1):129–35.
12. Al Afif A, Williams BA, Rigby MH, Bullock MJ, Taylor SM, Trites J, et al. Multifocal Papillary Thyroid Cancer Increases the Risk of Central Lymph Node Metastasis. Thyroid. 2015;25(9):1008-12.
13. Leboulleux S, Rubino C, Baudin E, Caillou B, Hartl DM, Bidart JM, et al. Prognostic factors for persistent or recurrent disease of papillary thyroid carcinoma with neck lymph node metastases and/or tumor extension beyond the thyroid capsule at initial diagnosis. J Clin Endocrinol Metab. 2005;90(10):5723-9.
14. Kuo SF, Chao TC, Chang HY, Hsueh C, Yang CH, Lin JD. Prognostic evaluation of patients with multicentric papillary thyroid microcarcinoma. J Formos Med Assoc. 2011;110(8):511-17.
15. Mazeh H, Samet Y, Hochstein D, Mizrahi I, Ariel I, Eid A, et al. Multifocality in well differentiated thyroid carcinomas calls for total thyroidectomy. Multifocality in well-differentiated thyroid carcinomas calls for total thyroidectomy. Am J Surg. 2011;201(6):770-5.
16. Iscan Y, Sormaz IC, Tunca F, Giles Senyurek Y. Multicentricity Is More Common in Thyroid Papillary Microcancer with a Preoperative Diagnosis Compared to Incidental Microcancer. Eur Thyroid J. 2019;8(5):256-61.
17. Nakazawa T, Kondo T, Tahara I, Kasai K, Inoue T, Oishi N, et al. Multicentric occurrence of multiple papillary thyroid carcinomas–HUMARA and BRAF mutation analysis. Cancer Med. 2015;4(8):1272-80.
18. Ricci JA, Alfonso AE. Multifocal micropapillary thyroid cancer: a new indication for total thyroidectomy? Am Surg. 2012;78(11):1211-14.
19. Neuhold N, Schultheis A, Hermann M, Krotla G, Koperek O, Birner P. Incidental papillary microcarcinoma of the thyroid–further evidence of a very low malignant potential: a retrospective clinicopathological study with up to 30 years of follow-up [published correction appears in Ann Surg Oncol. 2011 Nov;18(12):3528]. Ann Surg Oncol. 2011;18(12):3430-6.
20. Ito Y, Miyauchi A, Kihara M, Higashiyama T, Kobayashi K, Miya A. Cite Share. Patient age is significantly related to the progression of papillary microcarcinoma of the thyroid under observation. Thyroid. 2014;24(1):27-34.
21. Ito Y, Fukushima M, Kihara M, Takamura Y, Kobayashi K, Miya A, et al. Investigation of the prognosis of patients with papillary thyroid carcinoma by tumor size. Endocr J. 2012;59(6):457-64.
22. Lin JD, Chao TC, Hsueh C, Kuo SF. High recurrent rate of multicentric papillary thyroid carcinoma. Ann Surg Oncol. 2009;16(9):2609-16.
23. Hwang E, Pakdaman MN, Tamilia M, Hier MP, Black MJ, et al. Bilateral Papillary Thyroid Cancer and Associated Histopathologic Findings. J Otolaryngol Head Neck Surg. 2010;39(3):284-7.
Download attachments: 10.4328:ACAM.20952
Muhammet Pamukcu, Emine Demir, Mehmet Akif Aydin. Effects of the pathological characteristics on the presence of multicentric thyroid tumors in the contralateral lobe. Ann Clin Anal Med 2022;13(3):291-294
Citations in Google Scholar: Google Scholar
Effectiveness of D-dimer, CRP, procalcitonin and white blood cell count in non-traumatic acute abdomen
Omer Yalkin 1, Fatih Altintoprak 1, Mustafa Yener Uzunoglu 1, Taner Kıvılcım 1, Ihsan Hakki Ciftci 2 , Fehmi Celebi 1
1 Department of General Surgery, 2 Department of Microbiology, Faculty of Medicine, Sakarya University, Sakarya, Turkey
DOI: 10.4328/ACAM.20966 Received: 2021-11-22 Accepted: 2021-12-22 Published Online: 2021-12-23 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):295-299
Corresponding Author: Omer Yalkin, Department of General Surgery, Faculty of Medicine, Sakarya University, Sakarya, 54100, Turkey. E-mail: mdomeryalkin@gmail.com P: +90 506 976 65 55 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0311-5885
Aim: This prospective study investigates the effects of changes in leukocyte, CRP, D-dimer and procalcitonin levels during the treatment process of patients admitted to hospital with pre-diagnosis of non-traumatic acute abdominal pain on the decision about the treatment method.
Material and Methods: Patients included in the study were divided into 3 groups: those who underwent surgical treatment within the first 24 hours (Group-1), those who underwent surgical treatment within 24-48 hours (Group-2), and those who were discharged without surgical treatment after at least 48 hours of follow-up (Group-3). At the end of the treatment process, the change in the levels of leukocytes, CRP, D-Dimer and PCT values were examined in each group.
Results: A total of 141 patients (Group-1: 41 patients, Group – 2: 33 patients and Group – 3: 67 patients) were included in the study. The level of WBC tended to decrease in Group – 3 patients (p=0.001). The level of CRP tended to increase in Group – 2 patients (p=0.001) and decrease in Group – 3 patients (p=0.067) compared to the levels at the time of admission. The level of PCT was lower in Group-3 patients from the time of admission (p=0.005). D-dimer level in Group-3 patients tended to decrease compared to the level at the time of admission (p=0.096).
Discussion: Changes in these laboratory values add valuable information for clinicians and may prevent unnecessary surgical intervention in some patients.
Keywords: Abdominal Pain, Acute Abdomen, Emergency Surgery
Introduction
All pathologies resulting from non-traumatic causes with a sudden onset and that last less than a week, and progress with abdominal findings, are examined under “acute abdomen (AA)” [1,2]. In this syndrome, which is widely encountered in emergency services and constitutes an important part of emergency surgeries, reaching the right diagnosis as soon as possible is significant because the pathological condition can progress rapidly and reach life-threatening levels [1]. The most important step in diagnosis is to decide whether the etiological cause requires surgical treatment or medical treatment.
Early determination of the etiologic factor in non-traumatic acute abdominal pain and rapid intervention in a patient with surgical pathology are among the most important factors in decreasing mortality and morbidity rates [1]. When abdominal pain is evaluated in all patients admitted to emergency departments, etiological factors were non-specific in 75-80% of the patients, and these patients could be treated without requiring hospitalization, and the remaining 20-25% of patients required hospitalization for further examinations [3]. Despite all the examinations carried out at the time of admission to the hospital, a clear decision could not be made about whether surgical intervention is necessary for 40-45% of this hospitalized patient group, and medical treatment decision was made according to the results of clinical follow-up [4].
In the diagnosis of non-traumatic AA, the laboratory parameters that were evaluated when making surgical decisions were blood leukocyte levels and C-Reactive Protein (CRP) level [5]. In recent years, clinical studies have shown that D-dimer and procalcitonin (PCT) levels are valuable in making a decision about surgery for patients in need of emergency surgery [6]. However, studies in the literature were conducted using the values of these laboratory parameters, measured only at the time of admission to the hospital, that is, based on the results of a single evaluation of these parameters [7,8].
In this study, it was investigated whether changes in WBC, CRP, D-dimer and PCT levels in patients admitted to the hospital with AA pre-diagnosis could be effective in determining the treatment method.
Material and Methods
The study was carried out in Sakarya University Faculty of Medicine Hospital between August 2013 and January 2015. For this prospective study, approval was obtained from Sakarya University Faculty of Medicine Clinical Research Ethics Committee (Ethics committee no: 16214662.050.01.04/24). The study was recorded in Clinical Trials with the reference number 2013-08-06-002. Informed consent was obtained from the patients.
This study was carried out with the patients, aged 18-65 years, who were admitted to the General Surgery Clinic with a prediagnosis of non-traumatic acute abdominal pain and were volunteer to participate in the study. Patients who were <18 years of age, >65 years of age, those with a history of external trauma (blunt or penetrating) in the last 6 months, pregnant women, those who gave birth in the last 6 months, or in lactation at the time of admission, and those with a history of abdominal or extra-abdominal major surgery in the last 1 year were excluded from the study.
Design of study groups:
Patients were grouped as follows:
Patients whose surgery decision was made on the day of admission to the hospital (within the first 24 hours) (Group – 1), and patients whose surgery decision was made within 24-48 hours after the first 24 hours of medical follow-up (Group – 2), and patients who were discharged after at least 48 hours of medical follow-up without making surgery decision (Group – 3).
Collecting blood samples:
D-dimer and PCT values were studied in addition to the routine Hemogram and CRP tests carried out in the groups once a day, for the periods specified. According to this protocol, the above-mentioned laboratory tests were performed one time before surgery in Group – 1; two times in Group – 2, on Day 0 and Day 1; and three times in Group – 3, on Day 0, Day 1 and Day 2.
Statistical Analysis
NCSS (Number Cruncher Statistical System) 2007 (Kaysville, Utah, USA) software was used for statistical analysis. When evaluating the study data, along with descriptive statistical methods (mean, standard deviation, median, frequency, ratio, minimum, maximum), the Kruskal-Wallis test was used to compare three or more groups that did not show a normal distribution in quantitative data and Mann-Whitney U test was used to determine the group that caused the difference. The Friedman test and Wilcoxon Signed Ranks test were used for intra-group comparisons of non-normally distributed variables and evaluation of binary comparisons, respectively. Diagnostic and screening tests (sensitivity, specificity, PKD, NKD) and ROC Curve analysis were used for cut-off parameters. The level of significance was p<0.01 and p<0.05.
Results
The study was performed with the total of 141 patients, including 41 patients (29.1%) whose surgery decision was made on Day zero, 33 patients (23.4%) who were operated on Day 1, and 67 patients (47.5%) who were followed up without surgery. Sixty (42.5%) of the patients were female and 81 (57.5%) were male, and the mean age was 44 (18-65) years.
Group – 1 included 13 female (31.7%) and 28 (68.3%) male patients, 41 patients in total. The mean age of the patients was 35 (25-52) years. The final diagnosis of patients was as follows: acute appendicitis in 24 patients (58.6%), intestinal obstruction in six patients (14.6%), intestinal phytobezoar in four patients and colorectal malignancy in two patients, incarcerated inguinal hernia in four patients (9.8%), acute cholecystitis in two patients (4.9%), necrosis of the appendix epiploica in two patients (4.9%), intestinal perforation due to colon malignancy in one patient (2.4%) and mesenteric ischemia in one patient (2.4%), negative laparotomy (with the preliminary diagnosis of mesenteric ischemia) in one patient (2.4%). The average length of hospitalization was three (2-5) days. Two patients (4.9%) developed a superficial surgical site infection without mortality.
Group – 2 consisted of 33 patients, 14 (42.4%) were females and 19 (57.6%) were males. The mean age of the patients was 35 (26-40) years. Final diagnoses of patients were as follows: Acute appendicitis in 25 patients (75.7%), acute cholecystitis in three patients (9.1%), intestinal obstruction in two patients (6.1%), segmental intestinal ischemia in one patient (3%), peptic ulcer perforation in one patient (3%) and incarcerated inguinal hernia in one patient (3%) (clinical follow-up due to spontaneous reduction one day ago). The average length of hospitalization was three (3-5) days. Three patients (9.7%) developed a superficial surgical site infection with no mortality.
Group – 3 involved 67 patients, 33 (49.3%) were females and 34 (50.7%) were males. The mean age of the patients was 54 (41-62) years. Final diagnoses of patients were as follows: Cholecystitis in 25 patients (37.3%), ileus in 18 patients (26.9%), non-specific abdominal pain in 17 patients (25.4%), reduced inguinal hernia in two patients (3%), colon diverticulitis in two patients (3%), acute pancreatitis in two patients (3%), and ureteral stone one patient (1.5%) The average length of hospitalization was 4.3 (4-5) days. There was no morbidity or mortality. The diagnosis of diverticulitis and pancreatitis patients was known at the first admission and they were followed up to see if surgery would be needed. The patient with a diagnosis of ureteral stone could not be diagnosed at the first admission and was followed up with a diagnosis of abdominal pain. Ureteral stone was detected in the urinary system ultrasonography, performed 48 hours later.
Table 1, Table 2 and Table 3 showed WBC, CRP, D-Dimer and PCT results of the groups.
According to the groups, there was a statistically significant difference between the patients’ WBC measurements at day 0 (p=0.002; p<0.01). According to the results of the Mann-Whitney U test, the WBC value of the patients who were followed without surgery was significantly lower on Day 0 and Day 1, compared to the patients who were operated (p=0.002; p=0.011; p<0.05). No statistically significant difference existed among the CRP measurements of the patients on day 0, according to the groups (p>0.05). There was no statistically significant difference among the D-dimer measurements of the patients on day 0, according to the groups (p>0.05). No statistically significant difference was found among the procalcitonin measurements of the patients on day 0, according to the groups (p>0.05).
The mean decrease of 254.55±2548.79 in the WBC measurement on the 1st day was not statistically significant compared to day 0 (p> 0.05). The mean decrease of 20.61±61.25 in the CRP measurement on the 1st day was statistically significant compared to day 0 (p=0.003; p<0.01).
The mean decrease of 150.55±459.97 in the D-Dimer measurement on the 1st day was statistically significant compared to day 0 (p=0.027; p<0.05). The mean decrease of 0.48±1.39 in the procalcitonin measurement on the 1st day was statistically significant compared to day 0 (p=0.001; p<0.01).
There was a statistically significant difference among the WBC measurements of the patients on days 0, 1 and 2 (p=0.001; p<0.01). According to the results of the Wilcoxon Signed Ranks test, conducted to determine the difference, the mean 1370.15±1980.51 decrease in WBC measurement on day 1 was statistically significant compared to day 0 (p=0.001; p<0.01). The mean 2076.12±2772.76 decrease in WBC measurement on day 2 was statistically significant compared to day 0 (p=0.001; p<0.01). The mean 705.97±1801.67 decrease in WBC measurement on day 2 was statistically significant compared to day 1 (p=0.002; p<0.01). WBC values of the patients who were followed up without surgery were significantly lower than in those who were operated on day 0 (p=0.002; p <0.01). According to ROC analysis, a WBC cut-off value ≥108 predicted the diagnosis with a sensitivity of 70.73%, specificity of 56.72%, a positive predictive value of 50.0% and a negative predictive value of 76.0% ( Figure 1).
There was a statistically significant difference among the CRP measurements of the patients on days 0, 1 and 2 (p=0.001; p<0.01). According to the results of the Wilcoxon Signed Ranks test, conducted to determine the difference. The mean 3.06 ± 26,02 decrease in CRP measurement on day 2 was statistically significant compared to day 1 (p=0.009; p<0.01).
There was a statistically significant difference among the D-Dimer measurements of the patients on days 0, 1 and 2 (p=0.001; p<0.01). According to the results of the Wilcoxon Signed Ranks test conducted to determine the difference. The mean 118.16±966.23 decrease in D-Dimer measurement on day 2 was statistically significant compared to day 1 (p=0.020; p<0.01).
There was a statistically significant difference among the Procalcitonin measurements of the patients on days 0, 1 and 2 (p=0.005; p<0.01). According to the results of the Wilcoxon Signed Ranks test conducted to determine the difference. The mean 0.18±2.31 decrease in Procalcitonin measurement on day 2 was not statistically significant compared to day 0 (p=0.086; p<0.01). The mean 0.15±1.50 decrease in Procalcitonin measurement on day 2 was statistically significant compared to day 1 (p=0.043; p<0.01).
Discussion
In patients in whom it was impossible to decide whether treatment should be surgical or medical for patients who were admitted to the hospital due to non-traumatic AA at the time of admission, the parameters indicated in the literature as a guideline can be listed as PCT [9], D-Dimer [10], Interleukin-1, Interleukin-1 receptor, Interleukin-1 receptor antagonist [11], Interleukin-6 [12], Plasma lactate concentration [13] and Neopterin [14] in addition to leukocyte and CRP [5]. In our study, the values of 4 parameters, which were used more frequently within the above-mentioned parameters, were examined not only at the time of admission to hospital but also during treatment process.
In our study, the leukocyte level was higher in the groups with surgical treatment than in the group treated without surgery, and this was an expected result, consistent with the literature. However, using leukocyte level alone could be misleading among laboratory parameters because some patients with normal leukocyte levels (Group – 1: 4.600/mm3, Group – 2: 4.900/mm3) underwent surgical treatment and also there were patients with a significantly higher leukocyte level (23.600/mm3) at the time of admission to the hospital in the group that did not undergo surgical treatment.
Considering the facts that there was no statistically significant difference among the CRP measurements in all groups in day 0 in our study and there was a decrease in CRP levels in follow-up in Group – 2, whereas there was a decrease in the follow-up in Group – 3, we believe that the value of CRP at the time of patient’s admission alone should not be effective in determining the treatment method, and that the change in CRP in the treatment process is more valuable. On the other hand, the fact that CRP levels were higher in the group who underwent surgery than in the group without surgery supports the idea that CRP may be a useful parameter in deciding about surgery; however, we think that only evaluating the CRP level at the time of admission may be misleading.
Considering the facts that no statistically significant difference was found between D-Dimer measurements at the time of admission of the patients according to the groups in our study, and the D-dimer level, which was high in all groups at the time of admission, continued to increase in the group who underwent surgery during follow-up, but decreased in the medical treatment group, it is thought that the change in D-Dimer level, rather than the value at the time of admission of the patient, may be more valuable in determining the treatment modality. In addition, we think that the statistically significant decrease in D-dimer levels on the 2nd day of measurements in Group – 3 patients, who showed no statistically significant increase on Day 1, according to the value of day 0, and the increase in the D-dimer value in the early period will not support the right decision for surgery, on the contrary, a decrease in D-dimer value in the following days is more valuable in supporting the decision to move away from the surgery decision.
In our study, we attribute a normal PCT level to the fact that pathological event has just started in patients (Group -1) with the decision to undergo surgery and the result of the PCT reflecting the time of admission to the hospital. A statistically significant increase in PCT measurement on day 1 compared to day 0 in patients operated on day 1 (Group -2) and an increase in the level of PCT during the follow-up period can be interpreted as helpful in deciding on surgery. Furthermore, the fact that the PCT values in patients in Group – 3 were low from the day of the admission and continued to decrease in the follow-up period supports this interpretation. Dias et al. analyzed a total of 58 patients who presented with acute abdomen [15]. Plasma PCT (value >5 ng/mL) could be used to predict the requirement for surgery in patients presenting with acute abdomen. In our study, the PCT value was not found to be statistically significant.
Conclusion
In conclusion, in patients with non-traumatic acute abdominal pain, changes in CRP, D-Dimer and PCT values are more valuable in the clinical process than their level at the referral stage in determining the main treatment methodology (surgical treatment or medical treatment), and that the evaluation in the clinical process may prevent unnecessary surgical interventions.
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.
Funding: None
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.
References
1. Pemmerl S, Hüfner A. Das akute Abdomen: Ätiologie und Klinik [The Acute Abdomen: Etiology and Clinical Presentation]. Dtsch Med Wochenschr. 2020;145(21):1535-43.
2. Bokemeyer A, Ochs K, Fuhrmann V. Akutes Abdomen: Diagnostik [Acute Abdomen: Diagnostic Management]. Dtsch Med Wochenschr. 2020;145(21):1544-51.
3. Stefanidis D, Richardson WS, Chang L, Earle DB, Fanelli RD. The role of diagnostic laparoscopy for acute abdominal conditions: an evidence-based review. Surg Endosc. 2009;23(1):16-23.
4. Laméris W, van Randen A, Dijkgraaf MG, Bossuyt PM, Stoker J, Boermeester MA. Optimization of diagnostic imaging use in patients with acute abdominal pain (OPTIMA): Design and rationale. BMC Emerg Med. 2007;7:9.
5. Chi CH, Shiesh SC, Chen KW, Wu MH, Lin XZ. C-reactive protein for the evaluation of acute abdominal pain. Am J Emerg Med. 1996;14(3):254-6.
6. Icoz G, Makay O, Sozbilen M, Gurcu B, Çalışkan C, Firat O, et al. Is D-dimer a predictor of strangulated intestinal hernia? World J Surg. 2006;30(12):2165-9.
7. Cui W, Liu H, Ni H, Qin X, Zhu L. Diagnostic accuracy of procalcitonin for overall and complicated acute appendicitis in children: a meta-analysis. Ital J Pediatr. 2019;45(1):78.
8. Gavela T, Cabeza B, Serrano A, Casado-Flores J. C-reactive protein and procalcitonin are predictors of the severity of acute appendicitis in children. Pediatr Emerg Care. 2012;28(5):416-19.
9. Wu JY, Chen HC, Lee SH, Chan RC, Lee CC, Chang SS. Diagnostic role of procalcitonin in patients with suspected appendicitis. World J Surg. 2012;36(8):1744-9.
10. Akyildiz H, Akcan A, Oztürk A, Sozuer E, Kucuk C, Yucel A. D-dimer as a predictor of the need for laparotomy in patients with unclear non-traumatic acute abdomen. A preliminary study. Scand J Clin Lab Invest. 2008;68(7):612-17.
11. Lennard AC. lnterleukin-1 Receptor Antagonist. Crit Rev Immunol. 2017;37(2-6):531-59.
12. Tanaka T, Kishimoto T. The biology and medical implications of interleukin-6. Cancer Immunol Res. 2014;2(4):288-94.
13. Lange H, Jackel R. Usefulness of plasma lactate concentration in the diagnosis of acute abdominal disease. Eur J Surg.1994; 160: 381–4.
14. Mengucuk ME, Ayten R, Bulbuller N, Godekmerdan A, Basbug M, Mungan I. Role of C-reactive Protein, Procalsitonin and Neopterin in the Diagnosis of Acute Appendicitis. Fırat Medical Journal. 2010; 15(1): 40-43.
15. Dias BH, Rozario AP, Olakkengil SA. Role of inflammatory markers as predictors of laparotomy in patients presenting with acute abdomen. ANZ J Surg. 2015;85(10):755-9.
Download attachments: 10.4328:ACAM.20966
Omer Yalkin, Fatih Altintoprak, Mustafa Yener Uzunoglu, Taner Kıvılcım, Ihsan Hakki Ciftci , Fehmi Celebi. Effectiveness of D-dimer, CRP, procalcitonin and white blood cell count in non-traumatic acute abdomen. Ann Clin Anal Med 2022;13(3):295-299
Citations in Google Scholar: Google Scholar
Impact of a supervised pulmonary rehabilitation program on postoperative dyspnea in patients undergoing cardiac surgery
Osman Esen 1, Hatice Dilek Özcanoğlu 2
1 Department of Anesthesiology and Reanimation, Vocational School of Health, İstinye University, 2 Department of Anesthesiology and Reanimation, University of Health Sciences, Mehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, İstanbul, Turkey
DOI: 10.4328/ACAM.20969 Received: 2021-11-22 Accepted: 2021-12-22 Published Online: 2022-01-01 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):300-303
Corresponding Author: Osman Esen, Zümrütevler Mah., Handegül Sokak, No:98/16, Maltepe, İstanbul, Turkey. E-mail: drosmanesen@gmail.com P: +90 505 677 13 85 F: +90 216 457 38 00 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6280-5064
Aim: This prospective study aimed to analyze the impact of postoperative in-hospital pulmonary rehabilitation on pulmonary outcomes in patients who underwent cardiovascular surgery.
Material and Methods: This study was carried out on subjects who underwent cardiovascular surgery and were scheduled for a supervised pulmonary rehabilitation program following the cardiac surgery in our institute. The BORG scale of perceived exertion, a 100 points VAS scale for the severity of perceived dyspnea, and Respiratory Distress Assessment Instrument (RDAI) score were applied before and after completion of pulmonary rehabilitation program. Dyspnea, orthopnea, tachypnea, anxiety, cough and presence of sputum were also recorded prior to and subsequent to pulmonary rehabilitation. Blood gas analysis was also carried out before and after pulmonary rehabilitation.
Results: BORG scale score (1.89±0.07 vs. 1.21±0.05, p=0.001), VAS scale scores for dyspnea (5.7±0.4 vs. 8.5±0.8, p<0.001), and RDAI scores (4.2±0.5 vs. 7.8±1.2, p<0.001) improved significantly following pulmonary rehabilitation. The prevalence of dyspnea and tachypnea also reduced following pulmonary rehabilitation. No significant change was observed in blood gas analysis results.
Discussion: Application of a supervised pulmonary rehabilitation program including removal of bronchial secretions, postural drainage, percussion, vibration and aspiration and patients positioning improves self-reported dyspnea in patients who underwent cardiac surgery.
Keywords: Pulmonary Rehabilitation, Dyspnea, Cardiac Surgery
Introduction
Surgical stress and anesthesia deteriorate the ventilation/perfusion balance through the reduction of functional residual capacity as a consequence of the inhibition of the hypoxic pulmonary vasoconstrictive response, elevation of the diaphragm, and reduction in mucociliary clearance [1]. Moreover, the absence of a cough reflex and the presence of artificial airway and related mucosal damage may result in pulmonary infections, particularly ventilator-associated pneumonia. Cardiovascular surgery is a major surgery that may further deteriorate pulmonary function due to the devastating nature of the surgical procedure and postoperative pain associated with mid-line thoracotomy [2,3].
Pulmonary rehabilitation is a multidisciplinary intervention developed to improve exercise capacity, functional status, and health-related quality of life, and to reduce dyspnea and fatigue among patients with chronic respiratory conditions. The role of pulmonary rehabilitation in postoperative outcomes in patients with chronic obstructive pulmonary disease is well established [4]. Pulmonary rehabilitation also led to promising improvements in exercise capacity, dyspnea, and health-related quality of life in patients undergoing lung transplantation and lung volume reduction surgery [5,6]. Studies on patients with lung cancer have also revealed that pulmonary rehabilitation lowers the risk of postoperative complications and reduces the length of hospital stay. Despite satisfactory evidence regarding the role of pulmonary rehabilitation on postoperative outcomes and health-related quality of life in patients undergoing lung surgery, there is no evidence of its role in pulmonary outcomes in subjects undergoing cardiovascular surgery.
This prospective study aimed to analyze the impact of postoperative in-hospital pulmonary rehabilitation on pulmonary outcomes in patients who underwent cardiovascular surgery.
Material and Methods
This study was carried out on subjects who underwent cardiovascular surgery at Mehmet Akif Ersoy Training and Research Hospital, Department of Thoracic and Cardiovascular Surgery, between May 2016 and November 2016. Written informed consent was obtained from all subjects. The study was approved by the local ethics committee and conducted in accordance with the Declaration of Helsinki. All subjects received supervised pulmonary rehabilitation coordinated by a physical medicine and rehabilitation specialist for a minimum duration of 20 minutes, twice daily until discharge. Pulmonary rehabilitation programs, including improvement of bronchial hygiene and removal of bronchial secretions, postural drainage, percussion, vibration, and aspiration, were applied to all subjects following cardiac surgery. Subjects with postoperative pulmonary atelectasis were positioned according to the localization of the atelectatic lung area to improve the ventilation/perfusion ratio.
The demographic and clinical features of the study participants were recorded prior to enrollment. The BORG scale of perceived exertion (6 points indicating no feeling of exertion and 20 points indicating very, very hard), VAS scale of 100 points for the severity of perceived dyspnea (0 points indicating no dyspnea and 100 points indicating severe dyspnea perceived ever), and respiratory distress assessment instrument (RDAI) score (0 points indicating no respiratory distress and 17 points indicating severe respiratory distress) were applied before and after completion of the pulmonary rehabilitation program.
The Borg CR10 scale is a tool for measuring an individual’s effort and exertion, breathlessness, and fatigue during physical work [7]. The individuals were asked to circle or tick the number that best describes breathlessness from 0 to 10; 0 indicates no exertion at all and 10 indicates maximal) on average over the last 24 h.
The RDAI score was originally developed to assess the response to treatment of bronchiolitis [8]. However, recent data indicate that the RDAI score can also be used to predict short-term outcomes of acute lower respiratory tract infections [9]. The RDAI score is the sum of the row scores, including wheezing in expiration, inspiration, and lung fields, and supraclavicular, intercostal, and subcostal retractions, with a total range of 0 to 17; higher scores indicate more severe disease.
Dyspnea, orthopnea, tachypnea, anxiety, cough, and sputum were also recorded before and after pulmonary rehabilitation. The mean systolic and diastolic blood pressure, heart rate, and respiration rate were recorded. Blood gas analysis was performed before and after pulmonary rehabilitation (ABL800 FLEX blood gas analyzer, Radiometer, Brønshøj, Denmark).
Differences in BORG scale scores, VAS scale scores, and RDAI scores and in the prevalence of dyspnea, orthopnea, and tachypnea between the pre-and post-rehabilitation periods were the primary outcome measures of this study. Changes in blood gas analysis parameters, including pH, SaO2, pO2, pCO2, and HCO3, was the secondary outcome measure.
Statistical analysis
All analyzes were performed using SPSS v21 (SPSS Inc., Chicago, IL, USA). The Shapiro-Wilk test was used to determine whether the variables were normally distributed. Data are presented as mean ± standard deviation or median (minimum–maximum) for continuous variables according to the normality of distribution and frequency (percentage) for categorical variables. The paired samples t-test was used to analyze normally distributed continuous variables. The McNemar test was used to compare pre-and post-rehabilitation prevalence of dyspnea, orthopnea, tachypnea, anxiety, cough, and presence of sputum. Two-tailed p-values of less than 0.05, were considered statistically significant.
Results
A total of 50 patients (mean age 57.5±8.2 years, 70% males) who underwent cardiac surgery in our institute and underwent pulmonary rehabilitation subsequent to the surgery were included in this study. Baseline demographic and clinical features of the study group are shown in Table 1. Thirty-seven subjects underwent cardiac surgery for multivessel coronary artery disease, 12 subjects with valvular disease, and 1 subject with congenital heart disease. Comparison of pre-and post-rehabilitation BORG scale scores, VAS scale scores for dyspnea, and RDAI scores and blood glucose results are presented in Table 2. BORG scale score (1.89±0.07 vs. 1.21±0.05, p=0.001), VAS scale scores for dyspnea (5.7±0.4 vs. 8.5±0.8, p<0.001), and RDAI scores (4.2±0.5 vs. 7.8±1.2, p<0.001) improved significantly following pulmonary rehabilitation. The prevalence of dyspnea and tachypnea was also reduced following pulmonary rehabilitation. Moreover, systolic blood pressure decreased from 137±19 mmHg to 131±19 mmHg after pulmonary rehabilitation; however, no significant changes were observed in diastolic blood pressure, heart rate, and respiratory rate with pulmonary rehabilitation. The pre-and post-rehabilitation pH, SaO2, pO2, pCO2, and HCO3 were similar.
Discussion
These findings reveal that pulmonary rehabilitation leads to significant improvement in pulmonary function, as indicated by improved BORG, VAS, and RDAI scores and reduced frequency of dyspnea and tachypnea following the adoption of pulmonary rehabilitation measures.
Standardized rehabilitation of patients admitted to the intensive care unit usually includes respiration exercises, manual hyperinflation, and percussive techniques, active and passive joint exercises, patient positioning, and ambulation and muscle exercises [10,11]. Special measures used to facilitate weaning are used in mechanically ventilated patients. However, despite standardized rehabilitation programs, postoperative patients are at high risk for pulmonary complications as a consequence of depressed mucociliary clearance, suppressed cough, and resultant reduction in lung volumes and retention of secretions. All these factors contribute to the development of atelectasis and impaired respiratory function, which further precipitate pulmonary infections. The development of pulmonary complications is associated with significant morbidity and mortality and may prolong hospital stay [12-14]. Patients undergoing cardiovascular surgery are at high risk for postoperative pulmonary complications resulting from pulmonary injury related to cardiopulmonary bypass, mechanical ventilation, and surgical manipulation of the thoracic cavity [15]. Several reports indicate that approximately 10% to 25% of patients undergoing cardiac surgery experience pulmonary complications. Development of pulmonary complications following cardiac surgery has been reported to be associated with a four-fold increase in mortality and prolonged intensive care unit stay. Long-term mortality has been shown to increase in patients with pneumonia following cardiac surgery. Intraoperative lung-protective ventilation techniques, including lower tidal volumes, lower driving pressures, and positive end-expiratory pressure, have been shown to reduce pulmonary complications after cardiac surgery [16-18].
Despite the detrimental impact of cardiovascular surgery on pulmonary function, the role of pulmonary rehabilitation in the ICU and the ward following cardiac revascularization surgery and valvular surgery is questionable. This study is the first to demonstrate that supervised pulmonary rehabilitation significantly reduces dyspnea and tachypnea in patients who undergo cardiac surgery. The pulmonary rehabilitation program performed in our institute includes removal of bronchial secretions, postural drainage, percussion, vibration and aspiration, and body positioning performed to overcome atelectasis. We speculate that a supervised pulmonary rehabilitation program leads to an improvement in dyspnea by cleansing the airway, promoting effective ventilation, and reducing the atelectatic lung areas, thus improving vital capacity. However, further randomized, prospective studies with larger sample sizes are required to address the role of pulmonary rehabilitation programs in pulmonary function.
The present study has some limitations that need to be mentioned. First, pulmonary rehabilitation was applied only during the postoperative period. Therefore, we could not provide data concerning the role of a preoperative pulmonary rehabilitation program in patients scheduled for cardiac surgery. Second, we did not perform a mortality analysis and did not investigate the role of pulmonary rehabilitation in cardiovascular outcomes. Thus, further studies investigating the role of pulmonary rehabilitation in cardiovascular outcomes are required.
Conclusion
Application of a supervised pulmonary rehabilitation program including removal of bronchial secretions, postural drainage, percussion, vibration, and aspiration, and patient positioning improves self-reported dyspnea in patients who undergo cardiac surgery. Further prospective, randomized, and controlled trials are required to address the role of pulmonary rehabilitation in other cardiovascular outcomes.
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.
Funding: None
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.
References
1. Haines KL, Agarwal S. Postoperative Pulmonary Complications-A Multifactorial Outcome. JAMA surgery. 2017;152(2):166-7.
2. Ji Q, Mei Y, Wang X, Feng J, Cai J, Ding W. Risk factors for pulmonary complications following cardiac surgery with cardiopulmonary bypass. Int J Med Sci. 2013;10(11):1578-83.
3. Tabuchi Y, Morimoto Y, Yano Y, Tawara Y, Sato S, Tanigawa K, et al. Risk Factors for Post-operative Respiratory Failure and Respiratory Tract Infections Following Cardiovascular Surgery. Kyobu Geka. The Japanese Journal of Thoracic Surgery. 2017;70(13):1051-62.
4. Troosters T, Casaburi R, Gosselink R, Decramer M. Pulmonary rehabilitation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005;172(1):19-38.
5. Nici L, Donner C, Wouters E, Zuwallack R, Ambrosino N, Bourbeau J, et al. American Thoracic Society/European Respiratory Society statement on pulmonary rehabilitation. Am J Respir Crit Care Med. 2006;173(12):1390-413.
6. Celli BR. Chronic respiratory failure after lung resection: the role of pulmonary rehabilitation. Thorac Surg Clin. 2004;14(3):417-28.
7. Williams N. The Borg Rating of Perceived Exertion (RPE) scale. Occupational Medicine. 2017;67(5):404-5.
8. Lowell DI, Lister G, Von Koss H, McCarthy P. Wheezing in infants: the response to epinephrine. Pediatrics. 1987;79(6):939-45.
9. Khan HI, Nasir A, Malih KA. Use of modified Respiratory Distress Assessment Instrument (RDAI) score to determine short-term morbidity in children with acute lower respiratory tract infections (ALRI). Pakistan Journal of Medical and Health Sciences. 2009;3(3):253-7.
10. Spruit MA. Pulmonary rehabilitation. Eur Respir Rev. 2014;23(131):55-63.
11. Spruit MA, Singh SJ, Garvey C, ZuWallack R, Nici L, Rochester C, et al. An official American Thoracic Society/European Respiratory Society statement: key concepts and advances in pulmonary rehabilitation. Am J Respir Crit Care Med. 2013;188(8):e13-e64.
12. Gallart L, Canet J. Post-operative pulmonary complications: Understanding definitions and risk assessment. Best Pract Res Clin Anaesthesiol. 2015;29(3):315-30.
13. Marseu K, Slinger P. Peri-operative pulmonary dysfunction and protection. Anaesthesia. 2016;71(1):46-50.
14. Savas Bozbas S, Ulubay G, Sarinc Ulasli S, Bozbas H, Sezgin A. Risk factors for post-operative pulmonary complications and mortality in cardiac transplantation patients. Annals of Transplantation. 2009;14(4):33-9.
15. Zochios V, Klein AA, Gao F. Protective invasive ventilation in cardiac surgery: A systematic review with a focus on acute lung injury in adult cardiac surgical patients. J Cardiothorac Vasc Anesth. 2018;32(4):1922-36.
16. Mathis MR, Duggal NM, Likosky DS, Haft JW, Douville NJ, Vaughn MT, et al. Intraoperative Mechanical Ventilation and Postoperative Pulmonary Complications after Cardiac Surgery. Anesthesiology. 2019;131(5):1046-62.
17. Brown PP, Kugelmass AD, Cohen DJ, Reynolds MR, Culler SD, Dee AD, et al. The frequency and cost of complications associated with coronary artery bypass grafting surgery: results from the United States Medicare program. Ann Thorac Surg. 2008;85(6):1980-6.
18. Ibañez J, Riera M, Amezaga R, Herrero J, Colomar A, Campillo-Artero C, et al. Long-term mortality after pneumonia in cardiac surgery patients: a propensity-matched analysis. J Intensive Care Med. 2016;31(1):34-40.
Download attachments: 10.4328:ACAM.20969
Osman Esen, Hatice Dilek Özcanoğlu. Impact of a supervised pulmonary rehabilitation program on postoperative dyspnea in patients undergoing cardiac surgery. Ann Clin Anal Med 2022;13(3):300-303
Citations in Google Scholar: Google Scholar
Evaluation of the clinical characteristic of psychiatric patients who are among the risk groups in the COVID-19 pandemic
Pınar Mutlu 1, Demet Gulec Oyekcin 2, Arzu Mirici 1, Uğur Gönlügür 1
1 Department of of Chest Diseases, 2 Department of Psychiatry, Çanakkale 18 Mart University , Çanakkale, Turkey
DOI: 10.4328/ACAM.20970 Received: 2021-11-26 Accepted: 2022-01-13 Published Online: 2022-02-23 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):304-308
Corresponding Author: Pınar Mutlu, Kepez Hamidiye Mah., Rauf Denktaş Cad., Konakkale Sitesi, A1, D:15, Merkez, Çanakkale, Turkey. E-mail: pinarmutlu78@yahoo.com P: +90 505 262 95 29 Corresponding Author ORCID ID: https://orcid.org/0000-0002-7496-0026
Aim: The pandemic caused by COVID-19 has been a major concern for public health worldwide. Traditional medical practices need to be adapted quickly to meet the needs of vulnerable patients due to the COVID-19 outbreak. One of these patient groups is the mentally ill. Although COVID-19 itself affects mental health, this study aimed to investigate the clinical characteristics of COVID-19 patients who were previously diagnosed with mental illness.
Material and Methods: Patients older than 18 years of age with COVID-19 pneumonia, PCR positive or negative, thoracic CT compatible with COVID-19 pneumonia, and who also had been diagnosed with psychiatric disease between 1 April – 1 October 2020 were included in the study. Psychiatric diagnoses of the patients, drugs they used, places they lived, PCR results, CT results, comorbidities, the treatment of COVID-19, and the final status of the patients were evaluated.
Results: Between the specified dates, the number of patients with COVID-19 with psychiatric disease was 37 (28.24%) out of 131. The average age of patients with COVID-19 was 56.63±11.25 years, and the average length of stay in the hospital was 5.57±1.52 days. There were 35 (94.6%) patients living in a nursing home. There were 26 patients (70.3%) with a previous history of psychiatric illness, and 23 of them (62.2%) had psychotic disorders. During the treatment period, 27 (73.0%) of the patients received multiple pharmacotherapies, and atypical antipsychotic drugs (51.4%) were mostly prescribed.
Discussion: As a result, in our study, we determined that living in nursing homes, having a psychiatric disorder, and taking multiple pharmacotherapies due to this psychiatric disorder increase the possibility of getting COVID-19.
Keywords: COVID-19, Psychiatric Disorder, Nursing Home, Antipsychotic
Introduction
COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China at the end of 2019, spread worldwide, causing the pandemic [1]. Multiple risk factors have been identified as serious consequences of COVID-19 [2]. These factors include age over 65 years and the presence of chronic obstructive pulmonary disease asthma, cardiovascular disease, hypertension, diabetes, chronic kidney disease, obesity, malignancy, or anti-inflammatory biological agents [2, 3]. COVID-19 is essentially considered a respiratory disease; most of the guidance and studies have focused on such physical symptoms and their management.
Existing medical comorbidities and old age are associated with severe disease and high mortality rate [3]. Mental illness itself is associated with both high mortality as well as daily habits, lifestyle, socioeconomic status, which can affect clinical outcomes and comorbidity prognosis of COVID-19 [4]. In the COVID-19 pandemic, the negative effects were exacerbated because of the lack of mental health services that were already difficult to carry out. [5]. However, the psychological effects of COVID-19, from short-term boredom and loneliness due to quarantine, to long-term symptoms of anxiety, depression, and post-traumatic stress have been described [5, 6]. In addition, when factors such as loneliness, stigma, and misinformation on social media are added, healthy people are also significantly affected negatively [6-8]. Although enough studies have been done on the psychiatric disorders that occur as a result of the COVID-19 outbreak, the relationship between pre-existing psychiatric disease and the COVID-19 outbreak has not been adequately illuminated. This study aimed to investigate the clinical characteristics of patients diagnosed with psychiatric illness who received COVID-19 treatment between 1 April – 1 October 2020.
Material and Methods
The study was carried out retrospectively in XXXXX XXXX University Hospital between 1 April – 1 October 2020. This study was conducted in accordance with the tenets of the Declaration of Helsinki, and written informed consent was obtained from all subjects. Ethics committee approval for the study was received from the XXXXX XXXXX University Clinical Research Ethics Committee (20.10.2021, Approval No. 2011-KAEK-27/2021-E.2000066204). Patients over 18 years of age who were diagnosed with COVID-19 pneumonia, PCR positive or negative, thorax CT compatible with COVID-19 pneumonia, and who had been diagnosed with a psychiatric disease were included in the study. Throughout the specified period, 37 of 131 patients diagnosed with COVID-19 met the specified criteria and were included in the study. Psychiatric diagnoses of the patients, drugs they used, place of residence, PCR results, CT results, comorbidities, COVID-19 treatment applied, and the latest status of the patients were included as potentially important factors.
Statistical Analyses
The SPPS 25 statistical package program (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp.) was used to evaluate data, which expresses variables using mean ± standard deviation, percentage and frequency values. The variables were evaluated after checking the preconditions for normality and homogeneity of variances (Shapiro-Wilk and Levene’s test). Categorical data were analyzed with Fisher’s Exact Test and Chi-Square test. In cases where the expected frequencies were less than 20%, an evaluation was made with the “Monte Carlo Simulation Method” to include these frequencies in the analysis. The significance level of the tests was taken as p <0.05 and p <0.01.
Results
Between the specified dates, the number of patients with COVID-19 with psychiatric disease was 37 (28.24%). The average age of psychiatric patients with COVID-19 participating in the study was 56.63±11.25 years and the average length of stay in the hospital was 5.57±1.52 days. There were 12 (32.4%) female patients and 25 (67.6%) male patients. In the latest status, 32 (86.5%) of the patients followed were discharged, 10 patients (10.8%) were taken to the intensive care unit, and 1 patient died. General characteristics of psychiatric patients were similar to the general patient population (Table 1).
Demographic characteristics of psychiatric patients with COVID-19 are shown in Table 2. There were 35 (94.6%) patients living in a nursing home. There were 26 (70.3%) patients with a previous history of psychiatric illness, and 23 of them (62.2%) had psychotic disorders. The most common disease throughout the study was schizophrenia (n = 18, 48.6%). During the treatment period, 27 (73.0%) of the patients received multiple pharmacotherapies, and atypical antipsychotic drugs (51.4%) were mostly prescribed.
When the subgroups of psychiatric diseases were compared, there was a statistically significant difference between PCR 2, treatment of COVID-19 pneumonia, admission thorax CT and latest status variables in both patients with a previous diagnosis of psychiatric disease and patients with a current psychiatric diagnosis (p < 0.05) (Table 3). The most positive results in terms of PCR 2 results were in those with psychotic diseases in both groups. COVID-19 pneumonia was mostly present in those with psychotic diseases. A patient who died from COVID-19 had neurocognitive impairment.
Discussion
Approximately 1/3 of the patients followed up for this study in the COVID-19 ward had psychiatric illness. Most psychiatric patients were staying in the nursing home, and these patients received multiple pharmacotherapies for their psychiatric disorders.
Mental illness negatively affects the results of many medical conditions [9]. People with mental disorders often have a worse prognosis and a higher mortality rate when diagnosed with any illness than the general population, as accompanying medical comorbidities cannot be screened [10]. There is little evidence that those with any mental illness have susceptibility levels to infection with SARS-CoV-2 or clinical consequences after infection. During the COVID-19 pandemic, individuals with mental illness are at high risk not only because of their illness, but also due to low socioeconomic status, social isolation, and cognitive impairments. At the same time, patients with mental health disorders may be prone to the COVID-19 outbreak due to their comorbid illnesses, smoking habits, or long-term effects of the psychotropic drugs they use. Moreover, psychiatric treatment is a medical concern in COVID-19 [11].
Studies have been conducted to examine the effects of drugs used in the treatment of mental diseases, especially on the respiratory system. In studies of antidepressants, there was no increased risk of respiratory distress and overall mortality in patients with chronic obstructive pulmonary disease (COPD) (including elderly patients) exposed to tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) [12]. However, another recent study found that elderly patients taking SSRIs and serotonin–norepinephrine reuptake inhibitors (SNRIs) have an increased risk of COPD worsening or hospitalization and death from COPD [13]. The onset of pneumonia, especially aspiration pneumonia, can be triggered by psychotropic drugs. Studies have reported that treatment with antipsychotic drugs increases the risk of pneumonia in patients with schizophrenia, Alzheimer’s, and dementia [14-16]. In the general population, furthermore, psychotropic drugs may also increase the risk of hospitalization for pneumonia [17,18]. Ishii et al. [19] determined in their study that psychiatric illness and psychotropic medication use did not affect outcomes of pneumonia patients. Also, in the same study, it was observed that psychiatric illness and psychotropic medication use did not change mortality from pneumonia, but the length of hospital stay in these patients was slightly longer compared to other patients [19]. In our study, approximately one-third of the COVID-19 patients followed were psychiatric patients. This high rate indicates that the rate of COVID-19 in those with mental illness is higher than in the general population. Most of the patients in our study were receiving multiple pharmacotherapies and mostly used antipsychotic drugs. We think that multiple pharmacotherapies make it easier to get COVID-19 pneumonia in these patients. However, the length of hospital stay and mortality rates of psychiatric patients who received multiple pharmacotherapies and other COVID-19 patients were similar. In other words, multiple pharmacotherapies made it easier to get COVID-19, but it did not affect his prognosis in the hospital.
Although isolation and quarantine are highly effective methods of controlling infectious diseases, they may not be applied all the time or everywhere. It has been difficult to implement it effectively, especially in nursing homes where the elderly and mental patients are staying. In the pre-pandemic studies, it was shown that the outbreaks in nursing homes were caused by the delay in the implementation of protection measures and insufficient isolation [20]. Although COVID-19, a droplet-transmitted infection, is easily transmitted in institutional settings such as nursing homes, advanced age and multiple comorbidities are risk factors for deaths from COVID-19. Comorbidities related to severe disease and death from COVID-19 include chronic lung disease, cardiovascular disease, hypertension, diabetes mellitus, chronic kidney disease, cancer, and dementia. In one study, it was reported that 61% of residents living in nursing homes have dementia, 32% have severe cognitive impairment, and 40% have behavioral anxiety related to their dementia (available at: https://www.cihi.ca/en/profile-of-residents-in-residential-and-hospital-based-continuing-care-2018-2019). These behavioral issues are particularly important at a time when physical distance becomes a mandatory social prescription, such as during the COVID 19 outbreak (available at: https://www.cihi.ca/en/dementia-in-canada/dementia-care- across-the-health-system/dementia-in-long-term-care). Indeed, one study reported that around two-thirds of nursing home residents (with a 33% mortality rate) and 16 visitors and 50 staff were infected over a 3 week period [21]. In addition, it has been documented that a significant proportion of COVID-19-related deaths in Italy and Spain are nursing home residents [22]. According to the results of the study published by the Office of National Statistics in the UK, almost half of the deaths in the nursing home due to COVID-19 from the beginning of the pandemic until June 2020 were people who appeared to have dementia or Alzheimer’s disease (available at: https://www.ons.gov.uk/peoplepopulationandcommunity/birthsdeathsandmarriages/deaths/articles/deathsinvolvingcovid19inthecaresectorenglandandwales/dbetweenweekending20march2020andweekending2april2021) In our study, 95% of the patients with psychiatric disorders were living in a nursing home. It is clear that living in a nursing home is a potential risk for COVID-19. Especially in Europe and the United States, death rates have been high due to the COVID-19 outbreak for those living in nursing homes. Despite the high incidence of COVID-19 in the nursing home in our study, the mortality rates were similar to the general population.
In conclusion, our study determined that living in nursing homes, having a psychiatric disorder, and taking multiple pharmacotherapies due to that psychiatric disorder increase the possibility of getting COVID-19. The results of our study need to be confirmed by larger studies.
Acknowledgment
We would like to acknowledge the www.makaletercume.com for their outstanding scientific proofreading and editing services that was provided for this manuscript.
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.
Funding: None
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.
References
1. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020; 324(8):782-93.
2. Jordan RE, Adab P, Cheng KK. Covid-19: risk factors for severe disease and death. BMJ. 2020; 368:m1198.
3. Yang JM, Koh HY, Moon SY, Yoo IK, Ha EK, You S, et al. Allergic disorders and susceptibility to and severity of COVID-19: A nationwide cohort study. J Allergy Clin Immunol. 2020; 146(4):790-8.
4. Lee SW, Yang JM, Moon SY, Yoo IK, Ha EK, Kim SY, et al. Association between mental illness and COVID-19 susceptibility and clinical outcomes in South Korea: a nationwide cohort study. Lancet Psychiatry. 2020; 7(12):1025-31.
5. Brooks SK, Webster RK, Smith LE, Woodland L, Wessely S, Greenberg N, et al. The psychological impact of quarantine and how to reduce it: rapid review of the evidence. Lancet. 2020; 395(10227):912-20.
6. Xiang YT, Yang Y, Li W, Zhang L, Zhang Q, Cheung T, et al. Timely mental health care for the 2019 novel coronavirus outbreak is urgently needed. Lancet Psychiatry.2020; 7(3):228-9.
7. Adalja AA, Toner E, Inglesby TV. Priorities for the US Health Community Responding to COVID-19. JAMA 2020; 323(14):1343-4.
8. Yao H, Chen JH, Xu YF. Patients with mental health disorders in the COVID-19 epidemic. Lancet Psychiatry. 2020; 7(4):e21.
9. Momen NC, Plana-Ripoll O, Agerbo E, Benros ME, Borglum AD, Christensen MK, et al: Association between Mental Disorders and Subsequent Medical Conditions. N Engl J Med. 2020; 382(18):1721-31.
10. Erlangsen A, Andersen PK, Toender A, Laursen TM, Nordentoft M, Canudas- Romo V. Cause-specific life-years lost in people with mental disorders: a nationwide, register-based cohort study. Lancet Psychiatry. 2017; 4(12):937-45.
11. Orsini A, Corsi M, Santangelo A, Riva A, Peroni D, Foiadelli T, et al. Challenges and management of neurological and psychiatric manifestations in SARS-CoV-2 (COVID-19) patients. Neurol Sci. 2020; 41(9):2353-66.
12. Pollok J, Van Agteren JE, Carson-Chahhoud KV. Pharmacological interventions for the treatment of depression in chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2018; 12(12):CD012346.
13. Vozoris NT, Wang X, Austin PC, Stephenson AL, O’Donnell DE, Gershon AS, et al. Serotonergic antidepressant use and morbidity and mortality among older adults with COPD. Eur Respir J. 2018;52(1).
14. Kuo CJ, Yang SY, Liao YT, Chen WJ, Lee WC, Shau WY, et al. Second-generation antipsychotic medications and risk of pneumonia in schizophrenia. Schizophr Bull. 2013; 39(3):648-57.
15. Lampela P, Tolppanen AM, Tanskanen A, Tiihonen J, Lavikainen P, Hartikainen S, et al. Use of antidementia drugs and risk of pneumonia in older persons with Alzheimer’s disease. Ann Med. 2017; 49(3):230-39.
16. Tolppanen AM, Koponen M, Tanskanen A, Lavikainen P, Sund R, Tiihonen J, et al. Antipsychotic Use and Risk of Hospitalization or Death Due to Pneumonia in Persons With and Those Without Alzheimer Disease. Chest. 2016; 150(6):1233-41.
17. Chen TY, Winkelman JW, Mao WC, Liu CL, Hsu CY, Wu CS. The Use of Benzodiazepine Receptor Agonists and the Risk of Hospitalization for Pneumonia: A Nationwide Population-Based Nested Case-Control Study. Chest. 2018; 153(1):161-71.
18. Gambassi G, Sultana J, Trifiro G. Antipsychotic use in elderly patients and the risk of pneumonia. Expert Opin Drug Saf. 2015;14(1):1-6.
19. Ishii H, Kushima H, Kinoshita Y, Matsumoto T, Watanabe K, Fujita M. The limited impact of psychiatric disease and psychotropic medication on the outcome of hospitalization for pneumonia. J Infect Chemother. 2018; 24(12):1009-12.
20. Lee MH, Lee GA, Lee SH, Park YH. A systematic review on the causes of the transmission and control measures of outbreaks in long-term care facilities: Back to basics of infection control. PLoS One. 2020; 15(3):e0229911.
21. McMichael TM, Currie DW, Clark S, Pogosjans S, Kay M, Schwartz NG, et al. Epidemiology of Covid-19 in a Long-Term Care Facility in King County, Washington. N Engl J Med. 2020; 382(21):2005-11.
22. Fallon A, Dukelow T, Kennelly SP, O’Neill D. COVID-19 in nursing homes. QJM.2020; 113(6):391-92.
Download attachments: 10.4328:ACAM.20970
Pınar Mutlu, Demet Gulec Oyekcin, Arzu Mirici, Uğur Gönlügür. Evaluation of the clinical characteristic of psychiatric patients who are among the risk groups in the COVID-19 pandemic. Ann Clin Anal Med 2022;13(3):304-308
Citations in Google Scholar: Google Scholar
Assessment and management of the SARS-CoV-2 infection: A secondary center experience
Ahmet Cem Yardımcı 1, Erdem Ergen 2, Elif Ergene 3, Yasemin Seckın Guner 3, Muzaffer Karnap 3, Hatice Ballı 1, Duygu Demırbas Keskın 4, Hulya Yuksel 4, Fusun Bocutoglu 5, Veysel Celal Akbel 2, Serkan Yıldız 6, Derya Kalyoncu 7
1 Department of Infectious Diseases and Clinical Microbiology, 2 Depatment of Ophthalmology, 3 Department of Internal Medicine, 4 Department of Otorhinolaryngology, 5 Department of Obstetrics and Gynecology, 6 Department of Urology, 7 Department of Pediatrics, Istinye State Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21009 Received: 2021-12-18 Accepted: 2022-02-04 Published Online: 2022-02-07 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):309-313
Corresponding Author: Ahmet Cem Yardimcı, Istinye State Hospital, Istinye Street, No:98, 34465, Sariyer, Istanbul, Turkey. E-mail: cemyardimci@gmail.com P: +90 212 323 44 44 / +90 506 336 98 71 F: +90 212 323 44 44 Corresponding Author ORCID ID: https://orcid.org/0000-0002-4727-3239
Aim: The aim of the study was to evaluate the management and outcomes of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a secondary hospital.
Material and Methods: This study included 699 hospitalized patients who had positive rRT-PCR for SARS-CoV-2 and/or typical findings of COVID-19 on chest computed tomography (CT). Demographics, comorbidities, initial laboratory tests on admission, treatment modalities, complications and outcomes were evaluated retrospectively.
Results: The mean age was 57.0±15.6 (range:16-94 years), and male to female ratio was 1.24; 58.7% of the patients had at least one underlying comorbidity, the most common was hypertension; 18.1% of the patients had lymphopenia, 35.7% hyperferritinemia, 58.3% had increased lactate dehydrogenase, and 58.5% had increased D-dimer. Chest CT revealed moderate and severe stages in 57.9% of the patients. Hydroxychloroquine was given to 37.2% and favipiravir to 67.1% of the patients. No significant difference was observed between treatment groups in terms of mortality (P=0.487); 5.8% of the patients were transferred to the ICU, 75.6% of whom needed non-invasive and 36.5% invasive mechanical ventilation. The overall case-fatality rate was 0.9.
Discussion: Older age, male gender, low lymphocyte count, CT findings, including bilateral involvement and severe stage were significantly associated with poor prognosis and mortality.
Keywords: Adults, COVID-19, Outcome, SARS-CoV-2, Treatment
Introduction
The World Health Organization (WHO) designated coronavirus disease 2019 (COVID-19) in February 2020, declared it a pandemic on March 11, 2020. The clinical spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is wide-ranging from asymptomatic infection, mild upper respiratory tract illness, and pneumonia to life-threatening severe disease, even death [1-3].
To our knowledge, no previous studies have been conducted among patients with COVID-19 in secondary hospitals of our country. Here, we present clinical assessment, management and outcomes of the patients with SARS-CoV-2 infection in a secondary hospital.
Material and Methods
11,392 real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) tests were taken from the patients who admitted with suspicious symptoms or signs of COVID-19 to the emergency department of a secondary hospital in Istanbul between March 31 and May 30, 2020 and September 1 and December 31, 2020. 2448 of rRT-PCR tests were positive and 8670 were negative. A total of 699 patients who had positive rRT-PCR for SARS-CoV-2 and/or typical findings of COVID-19 at chest computed tomography (CT) were hospitalized and involved in this retrospective observational study. Three wards with 43 beds, and 6 beds in the intensive care unit (ICU) were reserved for COVID-19 patients.
Demographics, comorbidities, medications, triage vitals, symptoms and signs on admission, initial laboratory tests, PCR results, inpatient treatment, complications and outcomes were extracted retrospectively from electronic medical records.
Oropharyngeal and nasopharyngeal swab samples were taken from all of the patients at the emergency department before hospitalization and were transferred to a laboratory authorized by the Ministry of Health Public Health Office. rRT-PCR tests for SARS-CoV-2 were performed using Biospeedy COVID-19 RT-qPCR Detection Kits (Bioksen, Istanbul, Turkey).
All of the patients underwent routine blood examinations as complete blood count, biochemical tests, lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin, D-dimer on admission. Cardiac enzymes, procalcitonin (PCT) and fibrinogen were tested if clinically indicated. Chest CT scan was also performed in every patient on admission.
The diagnosis of COVID 19 disease was based on the WHO guidance and the New Coronavirus Pneumonia Prevention and Control Program (fifth edition) published by the National Health Commission of China. Acccording to clinical features on admission, the patients were classified as mild, moderate, severe and critical cases. CT findings were classified as; 0: Normal, 1: Mild (ground-glass opacity and consolidation, lesions can be single or multiple and may de located in both lung lobes), 2: Moderate (large lesions in more than one lobe in both lungs, various sizes of consolidation and fibrosis), 3: Severe (lesions are diffuse in both lungs and in different density, white lung sign due to involvement of large areas of lung) [4]. Patients with oxygen saturation rate ≤ 93% were given oxygen support by nasal cannula or face masks. The standard treatment protocol recommended by the National Ministry of Health Public Health Office included oral oseltamivir (Tamiflu®) 2×75 mg/day due to the inability to rule out seasonal influenza, oral hydroxychloroquine (Plaquenil®) 2×400 mg loading dose and 2×200 mg/day maintenance dose and oral azithromycin 1×500 loading dose and 1×250 mg/day maintenance dose for 5 days during the first wave of the outbreak. Routine electrocardiography was performed before the initiation of treatment to rule out QT interval prolongation. If no improvement was observed, oral favipiravir or lopinavir 200 mg/ritonavir 50 mg (Kaletra®) 2×2 was initiated. Favipiravir (Favicovir®) was given at a loading dose of 2×1600 mg and 2×600 mg/day maintenance dose, and especially was preferred in the second wave. Additionally, vitamin C (1×3 gr) was used.
Later in the outbreak, low molecular weight heparin (LMWH), as Enoxaparin, was started according to body mass index (BMI< 40/kg/m2 1×40 mg/day, and BMI > 40/kg/m2 2×40 mg/day subcutaneously) to prevent venous thromboembolism. If creatinine clearance (CrCl)< 30 ml/min, standard dose of heparin (5000 U 2×1 or 3×1/day, subcutaneously) was recommended by National Ministry of Health guidelines. Methylprednisolone 40-80 mg/day intravenously was also added to the treatment protocol. If no response was observed with CS and signs of macrophage activation syndrome (MAS), including persistent fever, continuously increasing CRP, ferritin (> 700 μg/L), and D-dimer levels, lymphopenia, thrombocytopenia, neutrophilia and deterioration of liver function tests were detected, tocilizumab (Actemra®) 1×200-400 mg was administered.
Patients who clinically decompensated (tachypnea respiratory rate>30/min, dyspnea, refractory hypoxemia, hypotension ) and had decreased oxygen saturation rate (<90%) despite treatment, oxygen support, and prone positioning were transferred to ICU.
The study protocol was approved by the local ethics committee (No:2/2021.K-08).
Statistical analysis
Statistical analysis was performed using SPSS 15.0 software (SPSS Inc, Chicago,IL,U.S.A.). Results were expressed as numbers and percentages for categorical variables and means ± SD, minimum and maximum for numerical variables. The analysis was conducted using the chi-square test. As the numerical variables did not meet the normal distribution, comparisons between two independent groups were made using the Mann-Whitney U test. P- values of <0.05 were considered statistically significant.
Results
The mean age of 699 patients was 57.0±15.6 (range:16-94 years), and male to female ratio was 1.24. The median duration of hospitalization was 6.4±4.8 days, significantly higher in patients with both diabetes mellitus (DM) and hypertension (HT) than in other patients (P=.003).
Overall, 58.7% of the patients had at least one underlying comorbidity. The most common comorbidity was HT, followed by DM, cardiovascular disease, asthma and chronic obstructive pulmonary disease (COPD). Clinical and demographic characteristics of the patients are shown in Table 1.
18.1% of the patients had lymphopenia, 35.7% hyperferritinemia, 58.3% increased LDH, 1.9% thrombocytopenia, 58.5% increased D-dimer, 45.5% increased PCT and 22.9% hyponatremia. The laboratory findings of the patients are shown in Table 2.
When compared, no statistically significant differences were obtained in terms of complete blood count, biochemical parameters, and CT findings among patients according to age, sex, and underlying comorbidity except increased PCT levels in patients with DM and both DM and HT.
26.6% of the patients whose RT-PCR tests were negative, but had CT findings suggesting COVID-19 disease were accepted to be infected and given treatment. The combination of hydroxychloroquine, azithromycin and oseltamivir treatment was given to 20.2% of the patients in the first wave, and favipiravir monotherapy was given to all of the patients (n=426) in the second wave (Table 3). No significant difference was observed between treatment groups hydroxychloroquine and favipiravir in terms of mortality (2.3% vs 3.3%, P=.487).
1.49% of the patients who received favipiravir developed bradycardia responsive to atropine. Only 3 patients had rash due to drug side effects or the disease itself.
51.9% of the patients were treated with CS. Only two patients received pulse steroids. No significant difference was observed in mortality between patients who received CS, predominantly in the second wave, and those who did not (P=.487).
Tocilizumab was given to 5.7% (n=40) of the patients, all in the second wave; 60% of these patients were discharged and 37.5% (n=15) were transferred to our ICU; 33.3% (n=5) of our patients in ICU underwent invasive mechanical ventilation (IMV), 93.3% non-invasive ventilation (NIV) and 40% of them died; 80% of the patients treated with tocilizumab developed elevated liver enzymes up to five times upper normal limits, gradually returning to normal levels during follow-up. Convalescent plasma was given to 6 patients, 50% of whom died.
5.8% of the patients (n=41) were transferred to the ICU; 68.2% of these patients were male, and the mean age was 63.3±12.3. NIV was required in 75.6% of the patients in the ICU, whereas 36.5% of the patients underwent IMV. The patients in ICU had predominantly HT and DM (only HT in 4 patients, only DM in 2, and both HT and DM in 14). Only 7 patients had asthma and/or COPD; 34.1% of ICU patients had no underlying comorbidity.
The overall mortality rate was 3.7 and 42.8% in our ICU. Respiratory failure was the most common complication, followed by cardiac arrest in the ICU. None of the patients survived among patients who underwent IMV. Older age, male sex, low lymphocyte count, CT findings including bilateral involvement and severe stage, and the need for IMVwere associated with poor prognosis and mortality (P=.047, P=.048, P=.029, P=.047, P<.001, and P<.001, respectively).
92.4% of our patients were discharged, only 1.5% (n=10) of them with an oxygen concentrator. During the study period, 2.4% of the patients, and 16.6% of the patients in ICU were transferred to other ICUs in the city due to lack of beds or more advanced care. Six patients with leukemoid reactions were referred to the hematology outpatient clinic, and one of them was diagnosed with chronic myeloid leukemia. Follow-up after discharge from the electronic health records, which includes all inpatient and outpatient visits of the patients, revealed that only 8 patients (5 in other hospitals and 3 at home) died. The rate of readmission within 30 days was 1.28.
Discussion
Previously reported studies among patients with COVID-19 have stated that older age, male gender and comorbidities were significantly associated with the severity of the disease and mortality [1-3,7-13]. Similarly, 55.5% of our patients were male and the median age was 57. It has been reported that 13-73.4% of the patients had comorbidities [8,9,13]; 58.7% of our patients had at least one accompanying comorbidity. The most common one was HT in our study, compatible with the other studies [2,7,8,11,12,14] followed by DM [3,7,8,19,12], and cardiovascular diseases [3]. The incidence of COPD and asthma was lower in our patients (5.9% and 8.9%, respectively), as in the other studies [1-3,5,9,13].
Elevated CRP, ferritin, D-dimer, and PCT were indicators of poor prognosis [1-3,10,12]. Lymphopenia due to viral particle-induced cytoplasmic damage and apoptosis was also correlated with the severity of disease and mortality [1,2,10,11,14]. In our study, we observed that 18.1% of the patients had lymphopenia on admission, mostly associated with severe disease, and continue to decrease as the disease progressed, improved gradually in survivors, but remained low in non-survivors.
Mo et al. [8] reported that besides increased CRP and LDH levels, thrombocytopenia, low level of albumin, elevated neutrophil and AST were also correlated with poor prognosis, in contrast, we did not observe significant differences in these parameters among patients according to disease severity, treatment modality, and mortality. Increased levels of troponin [2,3,12] and progressive elevation of PCT [13], particularly in patients with critical disease were related with poor prognosis [2,3,12]. Significantly higher levels of PCT were observed in our patients with DM, and both DM and HT due to high inflammatory response rather than secondary bacterial infection, but this was not associated with mortality.
It has been stated that CT is more reliable than RT-PCR testing due to false-negative results [3,15]. Thus, CT was performed in all of our patients on admission. Mo et al. [8] and Feng et al. [12] reported that an increased incidence of bilateral pneumonia and pleural effusion was associated with severity of disease and poor prognosis. Chest CT revealed that 78.7% of our patients had bilateral lung involvement, and 57.9% of them had a moderate and severe stage, significantly in the second wave. Only two patients had pleural effusion, which regressed with treatment.
Currently, no effective proven antiviral treatment for patients with COVID-19 has been identified. Although Food and Drug Administration (FDA) cautions against the use of hydroxychloroquine due to arrhythmias, Satarker et al. [16] stated that hydroxychloroquine plus azithromycin can reduce viral load. Researchers who predominantly preferred hydroxychloroquine treatment [1,5,10] reported the rate of mortality as 21%, 2.8%, 20% and 21.2%, respectively. Although no statistically significant difference was observed in terms of mortality between treatment groups in this study, it was slightly higher in the group treated with favipiravir (3.3% vs 2.3%), which may be explained by the fact that the patients who had more severe disease were hospitalized in the second wave when compared with the first wave.
Many guidelines and reports stated that CS were contraindicated or not recommended due to complications, including prolonged viremia, hyperglycemia, avascular necrosis, bacterial superinfections, and psychosis [17,18]. Increased risk of disease progression, increased use of antibiotics, prolonged fever and length of hospital stay were also reported [19]. Some researchers proposed that the use of CS treatment was not significantly associated with mortality [17,18], while according to others, early CS might reduce inflammatory response, and prevent the progression of COVID-19 disease [19,20].
The Chinese Thoracic Society has developed an expert consensus statement on the use of corticosteroids in 2019-nCoV pneumonia, and stated that CS should be given low-to-moderate doses (≤0·5–1 mg/kg per day methylprednisolone or equivalent) for ≤7 days [21]. Li et al. [23] observed no difference between patients who were given low-dose ( < 2 mg/kg) and high-dose ( >2 mg/kg) CS; 51.9% of our patients, particularly in the second wave of the outbreak were given CS. No side effects were observed with CS treatment other than hyperglycemia in this study.
Tocilizumab was proposed to reduce the progression of the disease and the need for noninvasive or invasive mechanical ventilation or death in hospitalized patients with COVID-19 pneumonia. Gupta et al. [22] reported that the risk of mortality was lower in critically ill patients treated with tocilizumab in the first 2 days of ICU admission compared with those who did not; 5.7 % of the patients received tocilizumab, of whom 37.5% were transferred to ICU, 60% were discharged and 40% died. In our opinion, tocilizumab reduces the progression of the disease, the need for ICU and IMV.
The rate of patients who needed intensive care has been reported to be 5-15.7% in different studies [1,9]. Mortality varies from 2.08% to 78% in patients with COVID-19 disease [5,7,12], and from 1.4% to 72% among ICU patients with COVID-19 [2,8,14]. In the studies conducted in our country, mortality rates between 2.08 and 10.5% [13,14] have been reported; 5.8% of our patients were transferred to the ICU and 36.5% of them underwent IMV. The mortality rate was 42.8% in our ICU. Approximately 50% of the patients in ICU had HT and DM. Strikingly, one-third of these patients had no underlying comorbidity.
Limitations of the study were being a single-center retrospective study, lack of smoking history, failure to record oxygen saturation rate on admission at the emergency department, inability to detect other common viruses (Influenza A and B, RSV, Adenovirus), inability to calculate BMI due to workload and the urgent start of the supportive treatment.
In conclusion, older age, male sex, low lymphocyte count, CT findings including bilateral involvement and severe stage were associated with a poor prognosis in this study. The voluntarism and cooperation of the doctors from various clinics and nursing staff were of great importance in the fact that hospitalization periods were short and the mortality rates were similar to those in higher-level tertiary hospitals.
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.
Funding: None
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.
References
1. Casas-Rojo JM, Antón-Santos JM, Millán-Núñez-Cortés J, Lumbreras-Bermejo C, Ramos-Rincón JM, Roy-Vallejo E, et al; en nombre del Grupo SEMI-COVID-19 Network. Clinical characteristics of patients hospitalized with COVID-19 in Spain: results from the SEMI-COVID-19 Registry. Rev Clin Esp (Barc). 2020; 220(8):480–94. DOI: 10.1016/j.rceng.2020.07.003.
2. Borobia AM, Carcas AJ, Arnalich F, Álvarez-Sala R, Monserrat-Villatoro J, Quintana M, et al. On behalf of the covid hulp working group. A cohort of patients with COVID-19 in a major teaching hospital in Europe. J Clin Med. 2020; 9(6):1733. DOI: 10.3390/jcm9061733.
3. Petrilli CM, Jones SA, Yang J, Rajagopalan H, O’Donnell L, Chernyak Y, et al. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. BMJ. 2020; DOI: 10.1136/bmj.m1966.
4. Saeed GA, Gaba W, Shah A, Al Helali AA, Raidullah E, Al Ali AB,et al Correlation between chest CT severity scores and the clinical parameters of adult patients with COVID-19 pneumonia. Radiol Res Pract. 2021; 2021:6697677. DOI:10.1155/2021/6697677
5. Bhandari S, Singh A, Sharma R, Rankawat G, Banerjee S, Gupta V, et al. Characteristics, Treatment Outcomes and Role of Hydroxychloroquine among 522 COVID-19 hospitalized patients in Jaipur City: An Epidemio-Clinical Study. J Assoc Physicians India. 2020; 68(6):13-19.
6. Iaccarino G, Grassi G, Borghi C, Ferri C, Salvetti M, Volpe M. SARS-RAS Investigators. Age and multimorbidity predict death among COVID-19 patients: Results of the SARS-RAS study of the Italian society of hypertension. Hypertension. 2020; 76(2):366-72.
7. Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L, Castelli A, et al. COVID-19 Lombardy ICU Network. Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020; 323(16):1574-81. DOI: 10.1001/jama.2020.5394.
8. Mo P, Xing Y, Xiao Y, Deng L, Zhao Q, Wang H, et al. Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China. Clin Infect Dis. 2020; DOI: 10.1093/cid/ciaa270.
9. Özger HS, Aysert Yıldız P, Gaygısız Ü, Uğraş Dikmen A, Demirbaş Gülmez Z, Yıldız M, et al. The factors predicting pneumonia in COVID-19 patients: preliminary results from a university hospital in Turkey. Turk J Med Sci. 2020; 50(8):1810-16. DOI: 10.3906/sag-2005-385.
10. Lin L, Lu L, Cao W, Li T. Hypothesis for potential pathogenesis of SARS-CoV-2 infection-a review of immune changes in patients with viral pneumonia. Emerg Microbes Infect. 2020; 9(1):727-32. DOI: 10.1080/22221751.2020.1746199.
11. 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; 395:497–506.
12. Feng Y, Ling Y, Bai T, Xie Y, Huang J, Li J, et al. COVID-19 with different severities: a multicenter study of clinical features. Am J Respir Crit Care Med. 2020; 201(11):1380-8. DOI: 10.1164/rccm.202002-0445OC.
13. Acar HC, Can G, Karaali R, Börekçi Ş, Balkan İİ, Gemicioğlu B, et al. An easy-to-use nomogram for predicting in-hospital mortality risk in COVID-19: a retrospective cohort study in a university hospital. BMC Infect Dis. 2021; 21(1):148. DOI: 10.1186/s12879-021-05845-x.
14. Ersan G, Akkiraz Baç G, Yüksel Ö, Yildiz FS, Papila C, Arsu G, et al. The demographic and clinical features of 479 COVID-19 patients: A single-center experience. Mediterr J Infect Microb Antimicrob. 2020; 9:9.
15. Ai T, Yang Z, Hou H, Zhan C, Chen C, Lv W, et al. Correlation of Chest CT and RT-PCR Testing for Coronavirus Disease 2019 (COVID-19) in China: A Report of 1014 Cases. Radiology. 2020; 296(2):E32-E40. DOI: 10.1148/radiol.2020200642.
16. Satarker S, Ahuja T, Banerjee M, E VB, Dogra S, Agarwal T, et al. Hydroxychloroquine in COVID-19: Potential Mechanism of Action Against SARS-CoV-2. Curr Pharmacol Rep. 2020; 1-9. DOI: 10.1007/s40495-020-00231-8.
17. Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet. 2020; 395(10223):473-5. DOI: 10.1016/S0140-6736(20)30317-2.
18. Li Q, Li W, Jin Y, Xu W, Huang C, Li L, et al. Efficacy Evaluation of Early, Low-Dose, Short-Term Corticosteroids in Adults Hospitalized with Non-Severe COVID-19 Pneumonia: A Retrospective Cohort Study. Infect Dis Ther. 2020; 9:823–36. DOI:10.1007/s40121-020-00332-3.
19. Recovery Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al. Dexamethasone in Hospitalized Patients with Covid-19 – Preliminary Report. N Engl J Med. 2020;. DOI: 10.1056/NEJMoa2021436.
20. Liu F, Ji C, Luo J, Wu W, Zhang J, Zhong Z, et al. Clinical characteristics and corticosteroids application of different clinical types in patients with corona virus disease 2019. Sci Rep. 2020; 10(1):13689. DOI: 10.1038/s41598-020-70387-2.
21. Zhao JP, Hu Y, Du RH, Chen ZS, Jin Y, Zhou M, et al. [Expert consensus on the use of corticosteroid in patients with 2019-nCoV pneumonia]. Zhonghua Jie He He Hu Xi Za Zhi. 2020; 43(3):183-4. DOI: 10.3760/cma.j.issn.1001-0939.2020.03.008.
22. Gupta S, Wang W, Hayek SS, Chan L, Mathews KS, Melamed ML, et al. STOP-COVID Investigators. Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19. JAMA Intern Med. 2021; 181(1):41-51. DOI: 10.1001/jamainternmed.2020.6252.
Download attachments: 10.4328:ACAM.21009
Ahmet Cem Yardımcı, Erdem Ergen, Elif Ergene, Yasemin Seckın Guner, Muzaffer Karnap, Hatice Ballı, Duygu Demırbas Keskın, Hulya Yuksel, Fusun Bocutoglu, Veysel Celal Akbel, Serkan Yıldız, Derya Kalyoncu. Assessment and management of the SARS-CoV-2 infection: A secondary center experience. Ann Clin Anal Med 2022;13(3):309-313
Citations in Google Scholar: Google Scholar
Comparison of pre-pandemic normal period and COVID-19 pandemic period births: Quantitative outlook
Besim Haluk Bacanakgil, Işık Kaban
Department of Obstetrics and Gynecology, Istanbul Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21026 Received: 2021-12-25 Accepted: 2022-02-07 Published Online: 2022-02-09 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):314-316
Corresponding Author: Besim Haluk Bacanakgil, Department of Obstetrics and Gynecology, Istanbul Training and Research Hospital, 34103, Istanbul, Turkey. E-mail: bhalukb@gmail.com P: +90 532 237 07 24 Corresponding Author ORCID ID: https://orcid.org/0000-0002-4723-7297
Aim: In this study, we aimed to determine whether the COVID-19 pandemic has a negative effect on quantitative birth data by comparing it with the pre-pandemic normal period.
Material and Methods: In our tertiary center, 4743 births in the March 2019-February 2020 pre-pandemic normal period were quantitatively compared and analyzed with 4522 births in the March 2020- February 2021 pandemic period.
Results: In the pandemic period, the number of births decreased by 4.66% compared to the normal period. The mean gestational week was prolonged during the pandemic period. In pre-pandemic and pandemic periods, there was no statistically significant difference between the mode of delivery, cesarean section type, preterm birth, stillbirth, newborn birth weight and Apgar score (≤7).
Discussion: When we evaluated the annual quantitative data of the normal and pandemic periods, it was seen that the COVID-19 pandemic did not have a significant negative effect on births, except for a slight decrease in the birth rate. However, this does not mean that COVID-19 protection and hygiene measures will be abandoned until the pandemic process is over.
Keywords: COVID-19, Pandemia, Birth, Newborn
Introduction
Coronavirus disease (COVID-19) was detected in Wuhan, China in December 2019, but was declared a “pandemic” in the world by the World Health Organization (WHO) in March 2020. Simultaneously, the first case was detected in Turkey in March 2020, and the Ministry of Health declared a nationwide “pandemic”. Since then, COVID-19 continues to threaten the health and the socioeconomic status of societies. One of the segments exposed to the epidemic is pregnant women. In this study, we aimed to compare the pandemic period with the normal (pre-pandemic) period and see whether the COVID-19 pandemic has a negative effect on births.
Material and Methods
The births over 500 gr or 22 weeks in the normal pre-pandemic period from March 2019 to February 2020 and during the pandemic period from March 2020 to February 2021 in the Gynecology and Obstetrics Clinic of Istanbul Training and Research Hospital, a tertiary center in Istanbul/Turkey, were included in the study. The data of the cases such as age, week of birth, mode of delivery, newborn characteristics were documented and analyzed retrospectively. Statistical analyzes were performed using SPSS version 17.0 program. The conformity of the variables to the normal distribution was examined using histogram graphics and the Kolmogorov-Smirnov test. Mean, standard deviation and median values were used in descriptive analyses. Categorical variables were compared with the Pearson’s Chi-square test. In cases where the data did not show a normal distribution, paired groups were evaluated with the Mann-Whitney U test. Cases with a P-value below 0.05 were considered statistically significant. The study was approved by the Ethics Committee of Istanbul Training and Research Hospital (Ethics Committee No:2021/2919).
Results
The median maternal age was 28 years in both periods.
Pre-pandemic normal period and pandemic period birth data are shown in Table 1. In our center, there were 4743 births in the normal period and 4522 births in the pandemic period. In the normal period, there were 33 twins, 2 triplets, 1 quadruplet, and in the pandemic period, 26 twins and 1 triplet were born. There was no statistically significant difference between delivery mode, cesarean section type, singular and multiple births, stillbirths and preterm births in both periods.
During the pandemic, the total number of of births decreased by 4.66% compared to the normal period. It was determined that the mean gestational age in the pandemic period was higher than during the normal period (p<0.001). However, when the periods were analyzed according to the lower week groups, no significant difference was found between term and preterm deliveries (Table 2).
Newborns were evaluated in terms of 1st and 5th Apgar scores, while there was no difference between the 1st-minute scores, the 5th-minute average Apgar score was found to be higher in the normal period (p<0.001) (Table 3).
However, there was no difference below 7 for both periods (p>0.05).
Discussion
In our study conducted in one-year periods, it seems that the COVID-19 pandemic did not have a negative effect on normal and cesarean deliveries, primary and repeated cesarean sections, live and stillbirths, term and preterm deliveries, birth weight and Apgar score (below 7). Similar results were also reported by McDonnell et al [1], de Melo et al [2], Herzberger et al [3], Wood et al [4]. Khalil et al [5] and Chmielewska et al [8], except for stillbirth results, reported the same findings. Although Khalil et al [5] and Chmielewska et al [6] reported an increase in stillbirth during the pandemic, it is currently unclear whether this is a direct or indirect result of COVID-19.
While there was no significant periodical difference between our term and preterm deliveries, it was observed in our study that the average gestational week was prolonged during the pandemic period. Wood et al [4], on the other hand, did not detect a difference between the periods in the mean gestational age. However, their study covers a period of 3 months.
When we look at our total number of births, there was a 4.66% decrease in the pandemic period compared to the pre-pandemic period. In other periodical comparative studies in the literature, the number of births is close to each other [3-5]. This decrease in our population is believed to be due to the fact that pregnant women prefer less dense and small health centers instead of our busy center for giving birth due to community-based concern and fear of COVID-19. As a matter of fact, it has been reported that COVID-19 has negative psychosocial effects on pregnant women and leads to a significant decrease in prenatal care visits [6-8]. This may also explain the prolongation of the mean gestational week during the pandemic period.
Conclusions
Except for the decrease in the total number of births in our population, the COVID-19 pandemic does not seem to have a negative effect on the mode of delivery, primary/repeat cesarean section, preterm birth, stillbirth, birth weight and Apgar score. However, meticulous application of protection methods such as mask, distance, hygiene and vaccination should not be abandoned until the pandemic ends.
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.
Funding: None
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.
References
1. McDonnellS, McNamee E, Lindow SW, O’Connell MP. The impact of the Covid-19 pandemic on maternity services: A review of maternal and neonatal outcomes before, during and after the pandemic. Eur J Obstet Gynecol Reprod Biol. 2020;255:172-6.
2. De Melo GC, De Araujo KCGM. COVID-19 infection in pregnant women, preterm delivery, birth weight, and vertical transmission a systematic review and meta-analysis. Cad Saude Publica. 2020;36(7):e00087320. DOI: 10.1590/0102-311×00087320.
3. Herzberger EH, Efros O, Herzberger S, Biron-Shental T, Shechter-Maor G. Differences in obstetric healthcare utilization and delivery complications before and after the COVID-19 pandemic-a retrospective study. J Matern Fetal Neonatal Med. 2021;28:1-6.
4. Wood R, Sinnott C, Goldfarb I, Clapp M, McElrath T, Little S, Preterm Birth During the Coronavirus Disease 2019 (COVID-19) Pandemic in a Large Hospital System in the United Statets. 2021;137(3):403-4.
5. Khalil A, von Dadelszen P, Draycott T, Ugwumadu A, O’Brien P, Magee L. Change in the Incidence of Stillbirth and Preterm Delivery During the COVID-19 Pandemic. JAMA. 2020;324(7):705-6.
6. Chmielewska B, Barratt I, Townsend R, Kalafat E, van der Meulen J, Gurol-Urganci I, et al. . Effects of the COVID-19 pandemic on maternal and perinatal outcomes: a systematic review and meta-analysis. Lancet Glob Health. 2021; 9:e759-72.
7. Kotlar B, Gerson E, Petrillo S, Langer A, Tiemeier H. The impact of the COVID-19 pandemic on maternal and perinatal health: a scoping review. Reprod Health. 2021;18:10. DOI:10.1186/s12978-021-01070-6.
8. Sahin BM, Kabakci EN. The experiences of pregnant women during the COVID-19 pandemic in Turkey: A qualitative study. Women Birth. 2021;34(2):162-9.
Download attachments: 10.4328:ACAM.21026
Besim Haluk Bacanakgil, Işık Kaban. Comparison of pre-pandemic normal period and COVID-19 pandemic period births: Quantitative outlook. Ann Clin Anal Med 2022;13(3):314-316
Citations in Google Scholar: Google Scholar
Clinical outcome of multidisciplinary patients hospitalized with the decision of emergency physicians
Özcan Yavaşi, Mehmet Altuntaş
Department of Emergency Medicine, Faculty of Medicine, Recep Tayyip Erdoğan University, Rize, Turkey
DOI: 10.4328/ACAM.21027 Received: 2021-12-25 Accepted: 2022-02-01 Published Online: 2022-02-02 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):317-320
Corresponding Author: Özcan Yavaşi, Department of Emergency Medicine, Recep Tayyip Erdoğan University Research and Training Hospital, 53020, Rize, Turkey. E-mail: ozcanyavasi@yahoo.com.tr P: +90 464 213 04 91 / +90 505 237 53 68 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8641-7031
Aim: In this study, we aimed to compare clinical outcomes of multidisciplinary patients who were admitted by the decision of emergency physicians (EPs) with that of patients, who were admitted after the consensus decision of consultant physicians in terms of number of consultation, emergency department (ED) and hospital length of stay (LOS), need for intensive care unit (ICU), transfer status after hospitalization and outcome.
Material and Methods: This was a retrospective observational study. The multidisciplinary medical patients who were above 18 years of age and need hospitalization were included. The patients were divided into two groups: Group I consisted of those who were hospitalized by the decision of EPs, and Group II consisted of patients who were hospitalized after a consensus reached between consulting physicians. Mann-Whitney U test and Chi-square tests were used for comparisons.
Results: Of the 1143 hospitalized patients, 204 (17.85%) were in Group I and 939 (82.15%) were in Group II. Group I patients needed more consultations in the ED, had higher ED-LOS, need more ICU, and were more commonly transferred to other departments after hospitalization. As the number of consultations increases, the ED-LOS increases accordingly in both groups. Although Group I patients seem to be more commonly transferred (p = 0.001), overall hospital-LOS between the two groups was similar (p = 0.143). The transferred patients in Group I had a higher hospital-LOS compared to non-transferred patients (p = 0.001).
Discussion: The authorization of EPs to hospitalize multidisciplinary patients to the most related department seems to be feasible because overall hospital-LOS does not change.
Keywords: Emergency Department, Consultation, Multidisciplinary Patient, Hospitalization
Introduction
Emergency departments (EDs) play a major role in all hospitalizations in the United States [1]. ED admission increases by an average of 1.8% per year worldwide, making ED crowding a growing problem and significantly increasing ED length of stay (ED-LOS) [2]. Immediately after patients reach EDs, they are involved in a chain of processes such as triage, registration, diagnosis, treatment, consultation, and hospitalization. During these processes, some problems are experienced including long waiting times, insufficient bed capacity, and the fact that patients who require a multidisciplinary approach are not primarily admitted by other specialists or consultants [3,4]. An important aspect of emergency medicine is the consultation process. Need for admission to a ward or intensive care unit (ICU), getting an expert opinion, providing treatment or a specific procedure, exclusion of specific diagnosis, transfer of care, and outpatient follow-up are the main reasons for ED consultation [5,6]. During the consultation process, consultant physicians should admit, take care and follow the patients during hospitalization for an efficient functioning system [3,7,8].
In Turkey, emergency medical care is free of charge, and the simplest route to a hospital bed is through EDs. During an ED shift, patients requiring a multidisciplinary approach are consulted by multiple specialist physicians. When a consensus is reached between the consultant physicians for the hospitalization of a patient, the consultant physician takes responsibility for the patient care [9]. In many circumstances, because of patient rights regulation and malpractice lawsuits, physicians hesitate to hospitalize this difficult patient group. In 2009, the Turkish Ministry of Health declared the following policy: ED patient follow-up should not exceed 24 hours. Within this period, patients with an unestablished diagnosis, or patients with an indication for admission but whose clinical state is related to more than one specialty, are reevaluated, and admission decisions to a hospital bed of the most appropriate specialty should be made by the attending emergency physician (EP) or hospital administrative specialist (HAS), and the related specialty consultant should be notified. The responsibility for follow-up, care, and treatment of the patient belongs to the related specialty consultants. In practice, this means that if consultants do not take care of the patients that are at risk for adverse clinical outcomes, the EP makes the decision of admission to the related specialty by giving them primary care of the patient. Then patient is transferred to the related specialty unit, out of the ED. If the patient care is served by general practitioners, as in secondary level hospitals, this decision is made by the HAS from other specialties. Consultation processes of the patients continue during the time they are hospitalized in these units, and the follow-up and treatment responsibility of some patients may be transferred to another specialty unit. Although this process often causes controversy among medical disciplines, it relieves the stressful working conditions of EPs. To our knowledge, this study is the second in the literature regarding the applicability of this policy.
The aim of this study is to compare the clinical outcome of multidisciplinary patients who were admitted with the decision of EPs with that of patients, who were admitted with the consensus decision of consultant physicians in terms of number of consultation, ED and hospital-LOS, need for ICU, transfer status after hospitalization and outcome.
Material and Methods
This was a retrospective observational study. The local institutional ethics committee approved the study (2020/75). This study was conducted at the ED of a tertiary care research and training hospital between January 1 and December 31, 2019. This ED serves approximately 150,000 patients annually, and the overall hospitalization rate is around 5-10%. The patients who were above 18 years of age and needed hospitalization, consulted to two or more specialties were included in the study. Exclusion criteria were patients <18 years of age, all discharged patients from ED, patients hospitalized by surgical departments, patients who needed only one consultation, and patients whose data were not reached. Patients who died in the ED during diagnostic work-up before an admission decision were also excluded because these patients were shown as ‘discharged from ED’ in the hospital database system.
Data regarding number of consultations in the ED, ED-LOS (minutes), hospital-LOS (days) were automatically derived from the hospital database management system by the database stuff. Data regarding age, gender, need for ICU, transfer status between departments after hospitalization, and the outcome (discharge or death) were collected by reviewing all patient records and ED patient charts by two EPs. The patients were divided into two groups. The first group (Group I) consisted of those who were hospitalized by the decision of EPs, and the second group (Group II) consisted of patients who were hospitalized after a consensus reached between consulting physicians.
Statistical Analysis
Data were analyzed with Statistical Package for the Social Sciences (SPSS) version 23.0 (IBM Corp. Armonk, NY, USA). Normality distribution was examined with Kolmogorov-Smirnov or Shapiro-Wilk tests. The Mann-Whitney U test was used in the comparison of data that were not normally distributed. Data that were not normally distributed were shown as median and interquartile range (IQR). The Chi-square test was used in the comparison of categorical data. Categorical data were shown as number and frequency (percentage). The significance level was p<0.05.
Results
During the study period, 133100 patients presented to the ED, and 9497 (7.13%) patients were hospitalized. After excluding patients according to the exclusion criteria, 1143 (0.86%) hospitalized patients who were consulted to two or more medical specialties in the ED were included. Of the 1143 patients, 204 (17.85%) were hospitalized by the decision of EPs (Group I) and 939 (82.15%) were hospitalized by the consensus decision of consulting physicians (Group II) (Figure 1).
Comparison of these two groups according to age, gender, number of consultations, ED-LOS, hospital-LOS, need for ICU, outcome, transfer status after hospitalization are shown in Table 1. The patients who were hospitalized by the decision of EPs were older, need more consultations in the ED, have higher ED-LOS, need more ICU care and more commonly transferred to other departments after hospitalization.
As the number of consultations increases the ED-LOS increases accordingly in both groups. Patients who were admitted with the decision of EPs have higher ED-LOS. No patient died during the ED boarding time, that is the time spent from admission decision to location to an inpatient bed in the departments.
During hospitalization, 29 of 204 (14.22%) patients in Group I and 26 of 939 (2.77%) patients in Group II were transferred to another department for care after the stabilization of the acute primary condition. Although Group I patients seems to be more commonly transferred (p = 0.001), overall h-LOS between two groups were similar (p = 0.143).The transferred patients in Group I have higher h-LOS compared to non-transferred patients (p = 0.001). The transferred patients in Group II have similar h-LOS compared to non-transferred patients (p = 0127) (Table 2).
Distribution of 204 patients who were hospitalized with the decision of EPs, according to the departments are as following: 51 (25%) in chest diseases, 45 (22.06) in internal medicine, 31 (15.20%) in infectious diseases, 26 (12.75%) in cardiology, 18 (8.82%) in nephrology, 12 (5.88%) in gastroenterology, 9 (4.41%) in neurology, 8 (3.92%) in medical oncology, and 4 (1.96%) in hematology departments, respectively.
Discussion
Overcrowding and increased ED-LOS in EDs is one of the most critical problems facing hospitals worldwide. As the ED-LOS and boarding time from ED increase, the risk of delirium and mortality also increases [10-12]. Overcrowding occurs when the number of patients exceeds the capacity of the treatment area, leading to reduced quality of care [13]. England, Australia, Canada, and New Zealand have introduced legal regulations to reduce overcrowding in EDs. The “Four hours rule”, issued in England in 2004, requires 98% of ED patients to be discharged from the EDs after four hours of presentation. Although this ruling was controversial, the percentage of patients meeting this requirement without affecting quality has increased [14,15]. Australia passed a similar law in 2008, effectively reducing ED overcrowding and the general death rate [16,17]. In a study conducted in 2005 at a hospital in which EPs were authorized to send stable patients who needed admission directly to appropriate patient beds in the internal medicine ward, it was found that this rapid admission policy caused a decrease in the ED-LOS [18]. In the Republic of Korea, after the removal of the necessity of consultation for hospitalization to internal medicine clinics, except for specific procedures such as endoscopy and coronary angiography, it was found that hospitalization decisions by EPs reduced the ED-LOS without significant adverse effect on death or hospital length of stay [8].
During the last two decades, the condition of patients in large EDs has shifted toward more severe, more complicated, and older patients who require multiple consultations [19]. In addition to its effects on hospital-LOS and eventually overcrowding in ED, multiple consultations also have adverse effects on patient care. Although this is a common and essential aspect of emergency medicine practice, little research has been conducted on this subject. In a study conducted in Canada, a consensus of 89.3% (458/513 patients) was reached between EPs and consultants for patient outcomes [20]. In another study conducted in Japan, 95% (1153/1215 patients) consensus was reached about patient outcome [21]. In our study, conducted on hospitalized patients, this rate was found to be 82.15% (939/1143 patients).
As the number of consultations increases, ED-LOS increases accordingly. This is similar to published literature [4,19].
In a study comparing the periods before and after the application of the Australian National Emergency Access Target in 2012, Perera et al. found that the number of transfers between departments within 48 hours increased from 0.84% to 7.1% in hospitalized patients (RR, 7.93; 95% CI, 5.98-10.51; p <0.001) [22]. In the present study, this rate is found to be 14.22% (29/204). However, we think that in-hospital transfers occurred not due to misdiagnosis but due to changing clinical situations during follow-up in units or after the acute condition recovered.
The mortality is similar between the two groups (p = 0.119). In a small study including 57 patients from Turkey, they found no mortality, transfer after hospitalization and ICU need among patients hospitalized with EP decision [4]. In that study, 23% of the patients were hospitalized with the diagnosis of anemia. We believe that our patients were more complicated that require a multidisciplinary approach.
Limitations
The limitations of the present study are as follows: firstly, this was a retrospective study, and the patient population was reached by examining the consultation notes on the hospital electronic database. Secondly, it is a single-centered study. Thirdly, there are a limited number of studies in the literature to compare our findings. Well-designed multi-institutional observational studies are needed to further address this issue.
Conclusion
Our study is important in terms of being one of the few studies that examines the hospitalization decisions made by EPs. Difficulties in taking care of this multidisciplinary patient group by clinicians have made EPs a kind of referee or decision-maker. Authorization of EPs to hospitalize multidisciplinary patients to the most related specialty department seems to be feasible because overall hospital-LOS does not change.
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.
Funding: None
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.
References
1. Pitts SR, Vaughns FL, Gautreau MA, Cogdell MW, Meisel Z. A cross-sectional study of emergency department boarding practices in the United States. Acad Emerg Med. 2014;21(5):497-503.
2. Wyatt S, Child K, Hood A, Cooke M, Mohammed MA. Changes in admission thresholds in English emergency departments. Emerg Med J. 2017;34(12):773-9.
3. Kessler C, Kutka BM, Badillo C. Consultation in the emergency department: a qualitative analysis and review. J Emerg Med. 2012;42(6):704-11.
4. Aslan N, Durmuş E, Güner NG, Güneysu F, Çatal F, Yürümez Y. Review of patients who are hospitalized by emergency medicine specialist. Anatolian J Emerg Med. 2021;4(3):96-101.
5. Lee PA, Rowe BH, Innes G, Grafstein E, Vilneff R, Wang D, et al. Assessment of consultation impact on emergency department operations through novel metrics of responsiveness and decision-making efficiency. CJEM. 2014;16(3):185-92.
6. Van der Veen D, Heringhaus C, de Groot B. Appropriateness, reasons and independent predictors of consultations in the emergency department (ED) of a Dutch tertiary care center: a prospective cohort study. PLoS One. 2016;11(2):e0149079.
7. Geskey JM, Geeting G, West C, Hollenbeak CS. Improved physician consult response times in an academic Emergency Department after implementation of an institutional guideline. J Emerg Med. 2013;44(5):999-1006.
8. Choi Y, Jeong J, Kim BG. Admission Decisions Made by Emergency Physicians Can Reduce the Emergency Department Length of Stay for Medical Patients. Emerg Med Int. 2020;2020:8392832.
9. Erenler AK, Akbulut S, Guzel M, Cetinkaya H, Karaca A, Turkoz B, et al. Reasons for overcrowding in the emergency department: experiences and suggestions of an education and research hospital. Turk J Emerg Med. 2014;14(2):59-63.
10. Singer AJ, Thode HC Jr, Viccellio P, Pines JM. The association between length of emergency department boarding and mortality. Acad Emerg Med. 2011;18(12):1324-9.
11. Emond M, Grenier D, Morin J, Eagles D, Boucher V, Le Sage N, et al. Emergency department stay associated delirium in older patients. Can Geriatr J. 2017;20(1):10-4.
12. Van Loveren K, Singla A, Sinvani L, Calandrella C, Perera T, Brave M, et al. Increased emergency department hallway length of stay is associated with development of delirium. West J Emerg Med. 2021;22(3):726-35.
13. Haydar SA, Strout TD, Baumann MR. Sustainable mechanism to reduce emergency department (ED) length of stay: the use of ED holding (ED transition) orders to reduce ED length of stay. Acad Emerg Med. 2016;23(7):776-85.
14. Weber EJ, Mason S, Freeman JV, Coster J. Implications of England’s four-hour target for quality of care and resource use in the emergency department. Ann Emerg Med. 2012;60(6):699-706.
15. Mason S, Weber EJ, Coster J, Freeman J, Locker T. Time patients spend in the emergency department: England’s 4-hour rule – a case of hitting the target but missing the point? Ann Emerg Med. 2012;59(5):341-9.
16. Geelhoed GC, de Klerk NH. Emergency department overcrowding, mortality and the 4-hour rule in Western Australia. Med J Aust. 2012;196(2):122-6.
17. Mitra B, Cameron PA. Emergency department overcrowding and mortality after the introduction of the 4-hour rule in Western Australia. Med J Aust. 2012;196(8):499-500.
18. Quinn JV, Mahadevan SV, Eggers G, Ouyang H, Norris R. Effects of implementing a rapid admission policy in the ED. Am J Emerg Med. 2007;25(5):559-63.
19. Brick C, Lowes J, Lovstrom L, Kokotilo A, Villa-Roel C, Lee P, et al. The impact of consultation on length of stay in tertiary care emergency departments. Emerg Med J. 2014;31(2):134-8.
20. Woods RA, Lee R, Ospina MB, Blitz S, Lari H, Bullard MJ, et al. Consultation outcomes in the emergency department: exploring rates and complexity. CJEM. 2008;10(1):25-31.
21. Iwata M, Yamanaka K, Kitagawa Y. The level of agreement regarding patient disposition between emergency physicians and consultants in the emergency department. Int J Emerg Med. 2013;6(1):4-7.
22. Perera ML, Davies AW, Gnaneswaran N, Giles M, Liew D, Ritchie P, et al. Clearing emergency departments and clogging wards: National Emergency Access Target and the law of unintended consequences. Emerg Med Australas. 2014;26(6):549-55.
Download attachments: 10.4328:ACAM.21027
Özcan Yavaşi, Mehmet Altuntaş. Clinical outcome of multidisciplinary patients hospitalized with the decision of emergency physicians. Ann Clin Anal Med 2022;13(3):317-320
Citations in Google Scholar: Google Scholar
Edible lactarius mushrooms poisoning: An emergency department experience
Bora Cekmen
Department of Emergency Medicine, Faculty of Medicine, Karabuk University, Karabuk, Turkey
DOI: 10.4328/ACAM.21029 Received: 2021-12-28 Accepted: 2022-02-01 Published Online: 2022-02-02 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):321-324
Corresponding Author: Bora Cekmen, Alparslan Cd., No:1, Şirinevler, 78200, Karabük Merkez, Karabük, Turkey. E-mail: ebrosrian@gmail.com P: +90 541 681 77 98 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3348-8375
Aim: We aimed to examine the reasons for applying to the emergency department after eating Lactarius species mushrooms, which are consumed quite frequently in our region, and the relationship between the clinical outcomes of the patients and their laboratory values.
Material and Methods: This was a cross-sectional study. Patients older than 18 years of age who presented to the emergency department with various signs and symptoms after eating mushrooms were included in the study. The patient’s age, gender, comorbidities, and laboratory data were recorded from the hospital information system. Complaints of the patients at the time of admission, the treatment, which was given in the emergency department, the presence and duration of hospitalization were recorded.
Results: The number of patients included in the study was 34, 19 (55.9%) of whom were women and 17 (50%) of the patients were hospitalized. The most common comorbidity was diabetes (38.2%), and the most common symptom was nausea (61.8%). The CRP value of the inpatients was 7.60 [4.30-14.80], the potassium value was 4.57 (±0.43), and the aPTT value was 29.30 [27.10-33.70], which was statistically higher than in the patients who were not hospitalized (p-values were 0.022, 0.042, and 0.030 respectively).
Discussion: Lactarius mushrooms are edible mushroom species that are benign but can cause gastrointestinal symptoms. CRP can be a useful laboratory value to predict gastrointestinal symptoms and to determine the decision to hospitalization.
Keywords: Mushroom, Poisoning, Nausea, Emergency, Hospitalization
Introduction
Although there are approximately 5000 known mushroom species, only around 100 have been reported to be poisonous and their toxicity has been recorded [1]. Morbidity and mortality due to toxic mushroom consumption continue to be a health issue in numerous countries. The annual mortality is still unknown [2]. Although it varies depending on the species, toxicity due to mushroom consumption can range from mild gastrointestinal manifestations to several organs’ failure, and death [3]. In the diagnosis, identification of the mushroom, symptoms, and laboratory parameters are used. Previous studies have demonstrated the incidence of poisoning or mild symptoms arising from the consumption of edible mushroom species [4].
Lactarius mushrooms (Lactarius deliciosus, L. deterrimus, L. volumes, and L. salmonicolor) are edible mushroom species that grow in woodlands and are consumed due to their unique taste [5]. These mushroom species are also grown in the pine and oak forests in Turkey and are consumed and sold in the open markets [6]. This type of mushroom is also common in our region [7]. Although there are several studies on toxic mushroom poisoning in the literature, there have only been a few studies conducted on the toxicity resulting from edible mushroom species, especially Lactarius species. To the best of our knowledge, this study is one of the few reports on the Lactarius species, which has the highest number of poisoning cases.
In the present study, we aimed to examine the reasons for the admission of patients to the emergency department after consuming Lactarius mushrooms, which are consumed frequently in our region, and the relationship between the clinical outcomes of the patients and their laboratory findings.
Material and Methods
Study Design:
This cross-sectional study included patients who were admitted to a tertiary emergency department following complaints after consuming mushrooms. Hospitalization of the patients depended on the timeframe within which the clinical symptoms emerged after the consumption of the mushrooms; those who developed clinical symptoms after ≥6 hours were hospitalized. The study was conducted in accordance with the Declaration of Helsinki and was initiated after approval of the Local Ethics Committee (approval no:2021/781).
Patient Selection:
This study included patients over the age of 18 who presented to the emergency department with various clinical symptoms after consuming mushrooms. In the clinic, the patients were shown photos of various mushroom species to determine the mushroom (Figure 1).
In this way, the mushroom species were identified, and the information was recorded in the hospital information system. Patients who had consumed Lactarius mushrooms were also determined in this manner. The exclusion criteria included patients who were under the age of 18, whose laboratory parameters or demographic data could not be accessed, and those for whom the information system did not list the mushroom species consumed or showed that the consumed mushroom species were not Lactarius.
Data Collection:
Data on the age, gender, and comorbidities of the patients, as well as their urea, creatinine, AST, ALT, C-reactive protein (CRP), white blood cell (WBC), sodium, potassium, INR, and aPTT levels were obtained from the hospital information system. The symptoms of the patients at the time of admission (nausea, vomiting, stomachache), information on the treatment provided in the emergency department (intravenous fluids, anti-emetic, anti-spasmolytic, antacid), and duration of hospitalization were also recorded.
Outcome:
The determination of the relationship between the clinical outcomes and the laboratory findings of the patients admitted to the emergency department due to Lactarius mushroom poisoning.
Statistical Analysis:
The IBM SPSS Statistics 22 (IBM SPSS, Turkey) software was used for the statistical analysis of the data. The Shapiro–Wilk test was employed to check the normal distribution of the parameters. The data were presented using descriptive statistical methods (mean, standard deviation, median, interquartile range, and frequency). Quantitative parameters between the groups were compared using the Mann–Whitney U test. The Chi-square test was used to compare qualitative data, and the level of significance was taken as p <0.05.
Results
A total of 59 patients were included in the study. Of these, 14 were excluded due to the consumption of cultivated mushrooms, six of the patients could not identify the type of mushroom consumed, and four patients lacked the required data. The final number of patients included in the study was 34, 19 (55.9%) of whom were women and 17 (50%) of the patients were hospitalized.
In the entire patient group, the most common comorbidity was diabetes (13 [38.2%] patients). The most common symptom was nausea (61.8%). The most administered treatment was intravenous fluid therapy (32 [94.1%] patients). Data on patient demography, comorbidities, and treatments are summarized in Table 1.
The WBC levels of the patients were 11963 (±3122), while the CRP levels were 7.10 (2.40–10.30). The levels of the other parameters were determined to be within the normal range in the entire patient group, which is summarized in Table 2.
On comparing laboratory findings of inpatients and outpatients, the CRP levels of the inpatients were 7.60 (4.30–14.80), potassium levels were 4.57 (±0.43), and the aPTT levels were 29.30 (27.10–33.70), which was significantly higher than in outpatients (p values were 0.022, 0.042, and 0.030, respectively). No significant difference was found between other laboratory parameters (Table 3).
Discussion
Locals who live in the regions where edible Lactarius mushrooms grow have been consuming them for several years [7]. Although edible mushrooms are frequently consumed, they are known to produce toxic effects. These mushrooms do not contain specific toxins; however, problems during their collection, transportation, and storage and a decrease in the trehalase activity in those who consume it can cause nausea, vomiting, increased gastrointestinal gas, abdominal bloating, and diarrhea [4,8]. In our study, vomiting, nausea, diarrhea, and abdominal pain in patients were observed.
Symptoms that develop due to edible mushroom poisoning are usually benign and the treatment is symptomatic and supportive [9]. In addition, antiemetics can be administered, especially in patients with early-onset gastrointestinal symptoms who are admitted to the hospital with nausea or vomiting [10]. In the present study, 94.1% of the patients were administered intravenous fluids, and 67.6% were given antiemetics.
Previous literature has reported on allergic reactions caused by mushrooms. Even nontoxic edible mushrooms, which are thought to be safe to consume, can cause abdominal discomfort [11]. Trehalose, also known as mushroom sugar, is a disaccharide that is broken down in the small intestine by the enzyme trehalase [12]. Trehalose cannot be broken down at low levels of this enzyme, which causes a kind of intolerance. Developing this intolerance generates a slight inflammation of the intestines. CRP is an acute inflammatory protein that rapidly increases during inflammation or infection [13]. In our study, significant differences were found in the CRP levels between the hospitalized and discharged patients. This can be associated with the severity of intolerance generated in the patients.
For the evaluation of the symptoms that developed due to mushroom consumption, it is imperative to first identify the species of mushrooms consumed by the patients admitted to the hospital and rule out the possibility of consuming any poisonous mushrooms [4]. However, a few studies in the literature show that edible mushroom species are the most common cause of mushroom poisoning [14]. Although the mortality rate is low in non-amatoxin mushroom poisoning, mortality from edible mushrooms is extremely rare. In the present study, 50% of the patients were hospitalized for follow-ups due to late-onset (≥6 hours) symptoms, but no mortality was observed in any of the patients.
Conclusion
Lactarius mushrooms are edible mushroom species that are benign but can cause gastrointestinal symptoms. CRP can be a useful laboratory value to predict gastrointestinal symptoms and to determine the decision to hospitalization.
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.
Funding: None
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.
References
1. Keller SA, Klukowska-Rötzler J, Schenk-Jaeger KM, Kupferschmidt H, Exadaktylos AK, Lehmann B, et al. Mushroom Poisoning-A 17 Year Retrospective Study at a Level I University Emergency Department in Switzerland. Int J Environ Res Public Health. 2018;15(12):2855.
2. White J, Weinstein SA, De Haro L, Bédry R, Schaper A, Rumack BH, et al. Mushroom poisoning: A proposed new clinical classification. Toxicon. 2019;157:53-65.
3. Chan CK, Lam HC, Chiu SW, Tse ML, Lau FL. Mushroom poisoning in Hong Kong: a ten-year review. Hong Kong Med J. 2016;22(2):124-30.
4. Gawlikowski T, Romek M, Satora L. Edible mushroom-related poisoning: A study on circumstances of mushroom collection, transport, and storage. Hum Exp Toxicol. 2015;34(7):718-24.
5. Falandysz J. Mercury accumulation of three Lactarius mushroom species. Food Chem. 2017;214:96-101.
6. Afyon A, Konuk M. Zonguldak yöresi makrofungusları üzerine bir araştırma (A research on macrofungi of Zonguldak region). Ot Sistematik Botanik Dergisi/ Journal of Herb Systematic Botany. 2002; 9(1): 121-8.
7. Onbaşılı D, Çelik G, Katırcıoğlu H, Narin İ. Antimicrobial, Antioxidant Activities and Chemical Composition of Lactarius deliciosus (L.) Collected from Kastamonu Province of Turkey. Kastamonu University Journal of Forestry Faculty. 2015; 15(1): 98-103.
8. Montalto M, Gallo A, Ojetti V, Gasbarrini A. Fructose, trehalose and sorbitol malabsorption. Eur Rev Med Pharmacol Sci. 2013;17(2):26-9.
9. Trueb L, Carron PN, Saviuc P. Intoxication par les champignons [Mushroom poisoning]. Rev Med Suisse. 201314;9(394):1465-70.
10. Brayer AF: Mushroom Poisoning. In: Tintinalli JE, editor. Emergency Medicine A Comprehensive Study Guide. 9th ed New York: McGraw-Hill; 2020. pp. 1404-9.
11. Hannuksela M. Jos metsään haluat mennä nyt [About forest allergens]. Duodecim. 2013;129(13):1346-50.
12. Semenza G, Auricchio S. Small-intestinal disaccharidases. In:Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The metabolic basis of inherited disease. 6th ed. New York: McGraw-Hill; 1989. p. 2975-97.
13. Sproston NR, Ashworth JJ. Role of C-Reactive Protein at Sites of Inflammation and Infection. Front Immunol. 2018;9:754.
14. Schenk-Jaeger KM, Rauber-Lu¨thy C, Bodmer M, Kupferschmidt H, Kullak-Ublick GA, Ceschi A, et al. Mushroom poisoning: a study on circumstances of exposure and patterns of toxicity. Eur J Inter Med. 2012; 23(4): 85-91.
Download attachments: 10.4328:ACAM.21029
Bora Çekmen. Edible lactarius mushrooms poisoning: An emergency department experience. Ann Clin Anal Med 2022;13(3):321-324
Citations in Google Scholar: Google Scholar
Pre-Endoscopic viral screening of children during the Covid-19 pandemic
Erkan Dogan 1, Eylem Sevinc 2, Nergiz Sevinc 3, Erhan Basar 4
1 Department of Pediatric, 2 Department of Pediatric Gastroenterology and Hepatology, 3 Department of Public Health, 4 Department of Microbiology, School of Medicine, University of Karabuk, Karabuk, Turkey
DOI: 10.4328/ACAM.21037 Received: 2021-12-31 Accepted: 2022-02-08 Published Online: 2022-02-09 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):325-329
Corresponding Author: Erkan Dogan, Department of Pediatric, School of Medicine, University of Karabuk, Karabuk, Turkey. E-mail: drerkandogan@hotmail.com P: +90 542 357 67 15 Corresponding Author ORCID ID: https://orcid.org/0000-0003-1620-4123
Aim: Transmission of SARS-CoV-2 infection can easily occur through direct or close contact with infected people, just as with other infectious diseases. Therefore, it is important to detect it prior to the intervention for protecting the health of both the healthcare worker and the patient. In the study, it was aimed to determine the seropositivity rates of acute respiratory syndrome coronavirus 2, hepatitis A, hepatitis B, hepatitis C virus and human immune deficiency virus infections among children who underwent gastrointestinal endoscopy.
Material and Methods: The study was conducted at the Department of Pediatric Gastroenterology of the Karabuk University in Turkey from December 2020 to December of 2021. A total of 175 children were included in the study. The study was divided into three age groups as follows: 1-6 years old, 7-12 years old and 13-18 years old. All children were screened for acute respiratory syndrome coronavirus 2, hepatitis A, hepatitis B, hepatitis C virus and human immune deficiency virus infections.
Results: The median age was 12.5 years (1-18). The seroprevalence of acute respiratory syndrome coronavirus 2, Anti-HAV IgM, Anti-HAV IgG, HBsAg, Anti-HBs, Anti-HCV, Anti-HIV and were detected 0.57%, 0.57%, 42.8%, 0%, 58.8%, 1.1% and 0 % respectively. The seroprevalence of Anti-HAV IgG was significantly higher in children aged 1-6 years than in the group aged 13-18 years (95.7 vs 25.2: χ2=48.1, p=0.001).
Discussion: Although seroprevalence rates prior to endoscopy were low in this study, viral screening, except for hepatitis A infection, is essential for the safety of both patients and healthcare.
Keywords: Endoscopy, Hepatitis, HIV; SARS-CoV-2, Screening
Introduction
Viral hepatitis poses a significant burden for both children and adults worldwide. Although hepatitis B (HBV) and hepatitis C (HCV) infections in adults are among the most common chronic viral infections worldwide, they are rare in childhood [1]. In contrast to HBV and HCV, hepatitis A (HAV) infection, which is generally asymptomatic is the most common cause of childhood hepatitis, especially in underdeveloped and developing countries [2]. Just like viral hepatitis, the human immunodeficiency virus (HIV) infections are a global public problem around the World [3].
It has been known for a long time that infections and diseases can easily spread through the blood and some body fluids and are important risk factors for healthcare workers. Considering the direct transmission of microorganisms such as HBV, HCV, HIV, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) /COVID 19 and some bacterial agents from the patient to healthcare workers [4-6], routine serological tests for the presence of infective pathogens before endoscopy and surgical procedures play an important role in the protection of healthcare workers [6].
Although pre-endoscopic screening for HBV, HCV and HIV is routinely performed in almost all endoscopy centers in the world, very few studies have been reported on SARS-CoV-2 screening and these studies were done in adults [7,8].
Therefore, the purpose of the present study was twofold:
(1) To determine the seroprevalence of HAV, HBV, HCV, HIV and SARS-CoV-2 in children who underwent endoscopy; (2) to investigate whether SARS-CoV-2 infection and Hepatitis A tests have a routine place as a screening test in children prior to endoscopy. To our knowledge, this is the first study to investigate the seroprevalence of HAV, HBV, HCV, HIV and SARS-CoV-2 in children undergoing endoscopy.
Material and Methods
The cross-sectional study was conducted at the Department of Pediatric Gastroenterology of the Karabuk University Hospital in Turkey from December 2020 to December 2021. The study population consisted of 175 children who underwent upper and lower gastrointestinal (GI) endoscopy. The participants were divided into three age groups as follows: 1-6, 7-12 and 13-18 years old.
The children undergoing GI endoscopy were screened for HAV, HBV, HCV, HIV and SARS-CoV-2 infections. The screening for Anti-HAV IgM, Anti-HAV IgG, HBsAg, Anti-HBs, Anti-HCV and Anti-HIV was carried out using enzyme-linked immunosorbent assay (ELISA) Architect I2000SR (Abbott Diagnostic, USA). Nasal swabs for SARS-CoV-2 test from children were taken by an experienced nurse 24 hours prior to endoscopy. Nasopharyngeal samples were tested by CFX96 Touch Real-Time PCR Detection System-Bio-Rad, Turkey. If any of the serological indicators was positive, the result was accepted as “seropositivity”, if all serological indicators were negative, the result was accepted as “seronegativity”.
Statistical Analysis
The data were analyzed with SPSS version 21.0 software for Windows. Numerical variables were expressed as median (min-max), and categorical variables were expressed as percentages. The Kolmogorov-Smirnov test was carried out to determine the normality of data distribution. Age, Anti-HAV IgM, Anti-HAV IgG, HBsAg, Anti-HBs, Anti-HCV, Anti-HIV and SARS-CoV-2 had abnormal data distribution. Comparison of categorical data was carried out with the chi-square test. A p- value of less than 0.05 was considered statistically significant.
Ethical approval for the study was obtained from the Turkish Health Ministry Ethical Review Committee (No. 2021/770). All participants’ parents provided written informed consent.
Results
The median age of 175 children was 12.5 years (1-18). Of the 175 children, 118 (66.7%) were female and 57 (33.3%) were male. All children were vaccinated against hepatitis B, 122 of them (69%) were vaccinated against hepatitis A. The study was divided into three age groups as follows: 1-6 years old (13.1%), 7-12 years old (21.1%) and 13-18 (65.8%) years old. The Anti-HAV IgM, Anti-HAV IgG, HBsAg, Anti-HBs, Anti-HCV, Anti-HIV and SARS-CoV-2 seropositivity were detected 1 (0.57%), 75 (42.8%), 0 (%0), 103 (58.8%), 2 (1.1%), 0 (0 %) and 1 (0.57%), respectively (Table 1).
Of the 175 children, 1 (0.57%) was positive for SARS-CoV-2. Anti-HAV IgG seroprevalence according to the age groups 1-6, 7-12 and 13-18 years old were 95.7%, 64.9% and 25.2%, respectively. Anti-HAV IgG seropositivity was significantly higher in children aged 1-6 years than in the group aged 13-18 years (95.7 vs 25.2: χ2=48.1, p=0.001). A decrement in Anti-HAV IgG seropositivity with age was found in older age groups. Seropositivity rates by age group are presented in Table 2. No significant differences in overall Anti-HAV IgM, Anti-HAV IgG, HBsAg, Anti-HBs, Anti-HCV, Anti-HIV and SARS-CoV-2 seropositivity rates were observed between females and males (Table 3).
Discussion
Screening for HAV, HBV, HCV, HIV, in addition to the SARS-CoV-2 virus, which causes pandemic all around the world, before interventional procedures such as endoscopy is particularly important for preventing infectivity and transmission [5,9]. In this study, HBsAg and anti-HIV seropositivity were not detected in any of the patients aged between 1-18 years. Besides the seropositivity rates for Anti-HAV IgM, Anti-HAV IgG, Anti-HBs, Anti-HCV and test positivity rate of SARS-CoV-2 were detected as 0.57%, 42.8%, 58.8%, 1.1% and 0.57%, respectively.
According to the World Health Organization (WHO) data, HAV, which can be sporadic or epidemic, affects 1.4 million people annually [2,10]. According to WHO data, Turkey is among the middle-level endemic countries with a seropositivity rate of 70% of the population under 30 years old. However, HAV seropositivity rates vary between regions in our country [10]. In a study byAriyarathna et al., in Sri Lanka with 1403 children, the rate of anti-HAV IgG seropositivity between the ages of 1-10 and 11-20 were reported as 70.4% and 66.8%, respectively [11]. In a study by Hayajneh et al. (2015) in Jordan, HAV sero-prevalence rates among the age categories of 2-4 years, 5-9 years, 10-14 years and 15-19 years were reported as 32%, 44%, 63% and 78%, respectively, and reported the need for a more comprehensive and effective vaccination [12]. On the other hand, in the study by Atik et al. in 2021, the rate of anti-HAV IgG seropositivity between the ages of 0-10 and 11-17 were reported as 63.1% and 38.8%, respectively [13]. Although studies from both Turkey and the world have not evaluated children before endoscopy, our study found a statistically significant increase for the anti-HAV IgG seropositivity rate in children between the ages of 1-6 when compared with children aged between 13-18, and we also determined that the seroprevalence decreases with increasing age (95.7% between the ages of 1-6, 64.9% between the ages of 7-12, 25.2% between the ages of 13-18) (p=0.001). Both the results of this study and the results reported by both Ariyarathna and Atik, support the point of view that “Anti-HAV IgG seroprevalence decreases with increasing age”.
Screening of cases for HBV and HCV infections before invasive procedures such as endoscopy and surgical procedures, early diagnosis and preventing transmission by horizontal route are important both for health service providers and for public health [1,2,5].
In the study by Jemilohun et al., which included 432 patients who underwent endoscopy in Nigeria in 2019, the prevalence of HBV, HCV and HIV were reported as 4.3%, 2.1% and 1%, respectively [5]. In the study by Gańczak et al., which included 1652 patients in Poland, it was reported that anti-HIV positivity was not detected in any of the patients, and the prevalence of HBsAg and anti-HAV were 0.6% and 0.9%, respectively [14]. In the study by Deveci et al., HBsAg seropositivity was reported as 0.3% before the endoscopy procedure in Elazig, and the seropositivity rates according to the age groups were reported as 15.9% for 1-4 years old, 27.6% for 5-9 years old, 31.7% for 10-14 years old and 19.4% for 15-18 years old. In the same study, the seropositivity rate of anti-HCV was reported as 0.3% [15]. In the seroprevalence study by Cifci et al., with patients who underwent upper GI endoscopy in Konya, the seropositivity rates of HBsAg and anti-HCV were reported as 2.9% and 0.5%, respectively [16]. While we did not detect any HBsAg seropositivity in our study, Jemilohun et al. (4.3%), Gańczak et al. (0.6%), and Ciftci et al. (2.9%) reported higher rates in their studies that were conducted with adults different from our study. It was thought that this difference was due to the difference in distribution between the age groups of patients included in the study, as well as the role of vaccination of the patients included in the study.
The mean value of anti-HBs seropositivity was determined as 58.8% in our study. On the other hand, seropositivity rates among the age groups were determined as 82.6% for the 1-6 age group, 48.6% for the 7-12 age group, 57.4% for the 13-18 age group. We found that the highest rate of anti-HBs seropositivity was in the 1-6 age group. In the same center, between January 2015 and December 2016, we found the seropositivity rates of 0.2% for HBsAg, 61.1% for anti-HBs and 0.1% for anti-HCV in children aged between 0-18 years. According to age subgroups, we reported the seroprevalence rates for anti-HBs as 77.8% between 0-1 years, 71.3% between 2-6 years and 57.9% between 7-18 years of age [17].
In our seroprevalence study, we found that the rate of seropositivity for anti-HBs increased over the years. We found that the seroprevalence positivity rates in our study were higher than the rates reported by Deveci et al. It was thought that the difference in anti-HBs positivity rates might be due to differences in the regions where the studies were carried out, distribution of cases according to age groups and differences in the socio-economic levels of the groups. These results show that routine hepatitis B vaccination is applied effectively.
We found in our study that the seropositivity of anti-HCV was 1.1% in the tests performed before endoscopy in children aged between 1-18 years. While the rate in the study by Jemilohun et al. (2.1%) with adult patients was higher than in our study, Gańczak et al. (0.9%) and Cifci et al. (0.5%) reported similar rates with our study. Besides, Deveci et al., reported a lower rate of anti-HCV in their study with the childhood age group (0.3%) when compared with the results of our study. The difference in rates was thought to be due to differences between age groups in addition to regional differences.
Tests before interventional procedures (endoscopy, surgery, etc.) help in the early diagnosis of undiagnosed HIV infected patients, and are important for preventing infectivity and transmission [3,6]. In a study by Saltzman et al., in the USA, the rate of transmission by mucocutaneous spread for HIV infection was reported as 0.1% [18]. In another study by Caillot et al., in France, it was reported that the lifetime risk of HIV infection of the person performing the interventional procedure was 0.15% [19]. Kırgezen et al. reported that 0.2% of the patients who underwent tonsillectomy included in the study had anti-HIV seropositivity [20]. In studies of Tekin et al., [21] and Deveci et al. [15], anti-HIV seropositivity was not reported in any of the children. In our study, similar to the result of Tekin et al., and Deveci et al., HIV positive case was not detected. Besides, these rates were also lower than the results of studies conducted in high-risk countries for HIV.
SARS-CoV-2 is transmitted by droplet route and by contact with virus-contaminated surfaces. Transmission has also been demonstrated during the incubation period in individuals who are asymptomatic or have symptoms of the disease [6,9]. The identification of asymptomatic cases with a positive SARS-CoV-2 PCR test will provide significant benefits in protecting the health of both the patient and healthcare professionals. In addition, pre-endoscopic SARS-CoV-2 screening is important for the prevention of contagiousness.
In a multi-center study in Spain by Hernández et al., the rate of antibody positivity in tests that were performed before the endoscopic procedure was 1.9% in 211 patients who underwent endoscopy. In addition to that, they reported that SARS-CoV-2 PCR positivity was not detected in any of these patients [22]. In the study by Lin et al., a total of 1295 pediatric patients in 3 different hospitals in the USA were included and the rate of SARS-CoV-2 PCR test positivity was reported as 0.93% [9]. In another study by Bloom et al., in the USA, it was reported that the SARS-CoV-2 test was positive in 3.6% of the adult patients without any symptoms in pre-operative screening tests [23]. In the study by Singer et al. in the USA, which included 4739 patients of all age groups without preoperative symptoms, it was reported that the SARS-CoV-2 PCR test result was positive in 0.13% of the cases [24]. In another study by Azılı et al., in which cases under the age of 18 who had no preoperative history, symptoms or signs for COVID-19 were included, it was reported that 0.9% of the cases had positive SARS-CoV-2 PCR test results [25].
In our study, we found a positive SARS-CoV-2 PCR test result in 0.57% of children aged between 1-18 years who had no symptoms before the endoscopy procedure. In studies conducted by Hernández et al. (1.9%), Lin et al. (0.93%) and Azılı et al. (0.90%), when vaccination programs were not implemented at the beginning of the pandemic, SARS-CoV-2 PCR test results were found to be relatively higher than the rate we found in our study conducted in the 2nd year of the pandemic. On the other hand, the result (0.13%) was relatively low in the study of Singer et al., which covered all age groups compared to the result of our study, and we thought that this difference might be due to the difference in age distribution between these studies.
The most important limitation of this study is the presence of the limited number of studies about COVID-19 in children. Therefore, we compared our results with a limited number of studies. The second limitation is that we could not measure neutralizing antibody level against SARS-CoV-2 infection due to funding problems. Another limitation is that the results of this study cannot be generalized since it is a single-center study.
Conclusion
Despite limitations, the present study revealed that the seropositivity rates of SARS-CoV-2 and Anti-HAV IgM were extremely low in children who underwent endoscopy. Even though the seroprevalence rate of SARS-CoV-2 was low in the study, just as other viral hepatitis and HIV, routine screening of the SARS-CoV-2 prior to the endoscopic procedure can help prevent transmission of the virus between patients and healthcare workers in healthcare facilities. Moreover, the study demonstrated that there is no need for routine Anti-HAV screening prior to endoscopy procedure as the children have a high anti-HAV seroprevalence rate.
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.
Funding: None
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.
References
1. Jefferies M, Rauff B, Rashid H, Lam T, Rafiq S. Update on global epidemiology of viral hepatitis and preventive strategies. World J Clin Cases. 2018;6(13):589-99.
2. Razavi H. Global Epidemiology of Viral Hepatitis. Gastroenterol Clin North Am. 2020;49(2):179-89.
3. Ford N, Ball A, Baggaley R, Vitoria M, Low-Beer D, Penazzato M, et al. The WHO public health approach to HIV treatment and care: looking back and looking ahead. The Lancet Infectious Diseases. 2018;18(3):e76-e86.
4. Karim HMR. Practice and reasons for routine pre-operative investigations among anaesthesiologists and surgeons: An online survey. Indian J Anaesth. 2017;61(11):933-5.
5. Jemilohun AC, Elikwu CJ, Ezuduemoih DE. How useful is routine pre-endoscopy viral screening? International Journal of Infection Control. 2019;15(3):1-7
6. Sultan S, Siddique SM, Altayar O, Caliendo AM, Davitkov P, Feuerstein JD, et al. AGA Institute Rapid Review and Recommendations on the Role of Pre-Procedure SARS-CoV-2 Testing and Endoscopy. Gastroenterology. 2020;159(5):1935-48.
7. Dalal A, Sonika U, Kumar M, George R, Kumar A, Srivastava S, et al. COVID-19 Rapid Antigen Test: Role in Screening Prior to Gastrointestinal Endoscopy. Clin Endosc. 2021;54(4):522-5.
8. Chiu PWY, Ng SC, Inoue H, Reddy DN, Ling Hu E, Cho JY, et al. Practice of endoscopy during COVID-19 pandemic: position statements of the Asian Pacific Society for Digestive Endoscopy (APSDE-COVID statements). Gut. 2020;69(6):991-6.
9. Lin EE, Blumberg TJ, Adler AC, Fazal FZ, Talwar D, Ellingsen K, et al. Incidence of COVID-19 in Pediatric Surgical Patients Among 3 US Children’s Hospitals. JAMA surgery. 2020;155(8):775-7.
10. Dunn R, Wetten A, McPherson S, Donnelly MC. 2021’de viral hepatit: Kalan zorluklar ve bunlarla nasıl başa çıkmalıyız. World J Gastroenterol. 2022;28(1):76- 95
11. Ariyarathna N, Abeysena C. Sero-prevalence of viral hepatitis A in a district of Sri Lanka: a community based cross-sectional study. BMC Infect Dis. 2019;19(1):443.
12. Hayajneh WA, Balbeesi A, Faouri S. Hepatitis A virus age-specific sero-prevalence and risk factors among Jordanian children. J Med Virol. 2015;87(4):569-74.
13. Kula Atik T, Cetin Duran A, Avcu G. Retrospective Evaluation of Hepatitis A Seropositivity in Various Age Groups in Balıkesir Province. Bozok Medical Journal. 2021;11(2):7-14.
14. Gańczak M, Szych Z. Rationale against preoperative screening for HIV in Polish hospitals: a prevalence study of anti-HIV in contrast to anti-hepatitis C virus and hepatitis B surface antigen. Infect Control Hosp Epidemiol. 2009;30(12):1227-9.
15. Deveci U, Acar U. Seroprevalence of hepatitis B virus, hepatitis C virus and human immunodeficiency virus in children undergoing endoscopy in our pediatric gastroenterology clinic. J Pediatr Inf. 2020;14(1):e5-e8
16. Cifci S, Bıyık M, Asıl M, Sayın S, Ataseven H, Demir A. The Prevalence of HBsAg, Anti HCV and Anti HIV Before Upper Gastrointestinal Endoscopy. Viral Hepatitis Journal. 2014;20(2):78-80
17. Doğan E, Sevinç E, Kuru C. Seroprevalence of HAV, HBV, and HCV in Pediatric Patients in Karabuk. Akademik Gastroenteroloji Dergisi. 2017;16(3): 97-100.
18. Saltzman DJ, Williams RA, Gelfand DV, Wilson SE. The surgeon and AIDS: twenty years later. Arch Surg. 2005;140(10):961-7.
19. Caillot JL, Voigloi EJ, Gilly FN, Fabry J. The occupational viral risk run by French surgeons: a disturbing perspective. AIDS. 2000;14(13):2061-2.
20. Kırgezen T, Seden N, Övünc O, Yigit Ö. Seroprevalence of HBV, HCV and HIV positivity in patients undergoing tonsillectomy. The Praxis of Otorhinolaryngology. 2009;7(3):151-6.
21. Tekin A. Seroprevalences of HBV, HCV and HIV among Children who Examined Before Elective Surgery in Mardin province. Konuralp Medical Journal 2011;3(3):7-11.
22. Hernández Camba A, Marcelino Reyes R, Hernández-Guerra M, Blasco Amato ÓA, Bennemann P, De La Riva N, et al. Pre-procedural antibody testing for SARS-CoV-2 in the routine endoscopic practice. Rev Esp Enferm Dig. 2021;113(2):116-8.
23. Bloom JA, Erlichman Z, Tian T, Doron S, Chen L, Mansur K, et al. The prevalence of asymptomatic carriers of COVID-19 as determined by routine preoperative testing. J Infect Prev. 2021;22(1):7-11.
24. Singer JS, Cheng EM, Murad DA, de St Maurice A, Hines OJ, Uslan DZ, et al. Low prevalence (0.13%) of COVID-19 infection in asymptomatic pre-operative/pre-procedure patients at a large, academic medical center informs approaches to perioperative care. Surgery. 2020;168(6):980-6.
25. Azılı M, Öztorun C, Erten EE, Güney D, Ertürk A, Keskin G, et al. The Prevalence of COVID-19 in Asymptomatic Cases and Its Effect on Complication Development in Children Scheduled for Emergency and Urgent Surgery. Journal of Pediatric Disease. 2021;15(5):415-9.
Download attachments: 10.4328:ACAM.21037
Erkan Dogan, Eylem Sevinc, Nergiz Sevinc, Erhan Basar. Pre-Endoscopic viral screening of children during the Covid-19 pandemic. Ann Clin Anal Med 2022;13(3):325-329
Citations in Google Scholar: Google Scholar
Clinical results of closed intramedullary nailing in femoral diaphysis fractures
Bedrettin Akar 1, Mehmet Bülent Balioğlu 2
1 Department of Orthopedics and Traumatology, Sakarya Yenikent State Hospital, Sakarya, 2 Department of Orthopedics and Traumatology, Basaksehir Cam Sakura City Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21053 Received: 2022-01-11 Accepted: 2022-02-14 Published Online: 2022-02-19 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):330-334
Corresponding Author: Bedrettin Akar, Yenidoğan Mahallesi, Arslanağzı Sokak, No: 4, Yenidoğan, İzmit, 41000, Kocaeli, Turkey. E-mail: drbedrettin@gmail.com P: +90 532 208 96 52 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7461-1777
Aim: Although there are many methods in the surgical treatment of femoral diaphyseal fractures (FDF), the preferred methodnowadays is Anterograde closed intramedullary nail (AKIMN) application. While giving the clinical results of our operations and AIMN applications due to FDF, at the same time, in this study, we aimed to present the most accurate options to the orthopedic researchers who are looking for indications by mentioning other treatment methods.
Material and Methods: In our retrospective study, in 25 patients with a mean age of 33.5 years who were urgently admitted to the Istanbul Training Hospital Orthopedics and Traumatology clinic due to FSF between 1997 and 1999, different models (Orthofix, Russel Tailor, Ünku type 1) and different locking types (Static and Dynamic) of AIMN were applied. During the mean follow-up period of 24.5 months, radiological and clinical examinations of the patients were performed. Evaluation of the results was done according to Thoresen criteria [25].
Results: Seventeen patients came to control visits. Nonunion and malunion were not seen in those who came to the control. In clinical and functional examination, it was observed that hip and knee joint movements were comfortable and functional loss did not develop. According to Thoresen criteria, 14 patients were evaluated as very good, one patient was good due to pain in the tuberositas region, one patient was evaluated as moderate due to 5-degree valgus deformity, and one patient was evaluated as bad due to post-op infection.
Discussion: AIMN is the first preferred method in the treatment of femoral diaphysis fractures caused by high-energy traumas. Since the fracture line is not opened, the amount of bleeding and the risk of infection decrease, the mobilization start time is shortened, and union is accelerated.Static locking should be preferred in order to prevent shortening and rotation in segmental fractures. Reamerization of the medulla accelerates the union and shortens the healing process.
Keywords: Femoral Fractures, Intramedullary Nailing, Orthopedic Surgery, Secondary Injury, Osteosynthesis, Fracture
Introduction
FDF occurs with high-energy traumas (traffic accident, falling from a height, gunshot wounds, etc.) and causes significant mortality and morbidity in patients. Although it can be seen at almost any age, it is especially common in young men [1,2,6,9]. FDF, which accounts for 8% of all fractures, was treated with conservative methods until the 20th century [4,5,7,15]. In these years, bed rest, plaster cast and traction were the treatment options.The first successful IMN application started in 1940 by Küntscher. A force of 280 newtonmeters is required to break an adult human femur, values above this value spread to the soft tissue.Winquist-Hansen classified femoral diaphysis fractures according to the degree of fragmentation. (Table 1) This classification is categorized as types 1,2,3 and 4 [3,9,18]. The currently accepted classification is the AO classification, and a coding system is used to define the type of fracture, resulting in 27 different models [24].
(3=femur, 2=diaphysis) Femur fracture has a high union potential and a low rate of pseudoarthrosis [3,8,11,13]. The aim of treatment is to achieve a quality union by providing the desired length and alignment with early mobilization[5,13,19]. In the early stages of fracture healing, although the intramedullary nail fills the canal completely, the periosteal circulation can still circulate the outer half of the cortex.The rapid union and remodeling of fractures after closed intramedullary nailing is due to excessive collateral circulation around the femoral diaphysis.If the medullary canal is wider in one fragment than the other, rotational forces control is weakened. In this case, locking screws are needed. These screws should be at least 2 cm away from the fracture line to ensure adequate stability [4,7,11,18].
Since static intramedullary nailing will delay the union of the fracture, it should be dynamized 8-12 weeks after the operation [3,8,14,22]. If dynamization is performed without adequate cortical stability and bone regeneration, it may result in shortening. It increases the stability of the fracture line by providing a wider contact surface between the bone and the nail. The entrance hole of the femoral nail should be from the anterior part of the piriform fossa just medial to the greater trochanter [5,9,16,24)]. The disadvantages of remerization include fat embolism and a temporary decrease in endosteal blood flow. However, until endosteal blood flow is restored, periosteal blood flow provides adequate support [2,21].
Material and Methods
AKIMN was applied to 25 patients who applied to Istanbul Training Hospital Orthopedics and Traumatology clinic between 1997-1999 due to FDF. The study was approved by the Ethics Committee of the institute of Health Sciences Sakarya University ( E-71522473-050.0104-92635-548 ). Nail locking with different brands (Orthofix-Italy, Russel Tailor -USA, Ünku tip 1-Turkey) was applied to 17 patients who came to control (mean age of 33.5 (12 – 66) years, 16- males (64%), 9- females (36%). Static nail locking was applied to14 patients (56%), dynamic to 11 patients (44%).The mean follow-up period was 29.1 months (11 – 41).In addition to FDF, 7 patients had different types of fractures (fractures of the wrist, humerus, forearm, tibia, clavicle, etc.); 14 patients (56%) were left, 11 patients (44%) were right.Etiological reasons of fractures were traffic accidents in 13 patients (52%), 11 patients fell from a height (44%) and in 1 patient, due to dropping heavy weight.According to the AO classification, 18 patients had 32-A fractures and 7 patients had 32-B type fractures. The average time between admission to the hospital and the operation was 5 days (3-11) .
Skeletal traction was applied to the patients during the period from hospitalization to the day of operation. One patient was type 2 open fracture according to Gustilo-Anderson classification and prophylactic antibiotic treatment was applied. All of our patients were operated in the supine position on the traction table under the guidance of a scope. Orthofix type nails were applied in 19 of the patients (76%), Russell Taylor in 4 patients, Ünku in 1 patient, and rare nail from tuberculum adductorium in 1 patient.The average nail thickness used in the cases was 11.3 mm (10 mm-13 mm), and the average nail length was 39.4 cm (36 cm–42 cm).Quadriceps and hamstring exercises were started in patients in the early postoperative period. In the first 4-6 weeks, partial weight-bearing was performed with crutches until the radiological findings of union were obtained.Unsupported walking was allowed at 12 weeks. 1,3,6,12 of the patients.Radiological and clinical controls of the patients were performed at 1, 3, 6, and 12 months.
Results
Thoresen’s classification table was used in the evaluation. In this table, fracture axis, ipsilateral knee motion arc, pain and presence of edema were divided into 4 categories. The patients were classified as excellent, good, moderate and poor (25). A patient with a good clinical outcome was transferred to a subgroup because of poor radiological evaluation. It was determined by clinical examinations that union and hip-knee functions were good in all those who came to the control. According to Thoresen criteria, 14 of our 17 patients (82.3%) were evaluated as very good, 1 patient was evaluated as good due to pain in the tuberositas region (5.8%), 1 patient was evaluated as moderate due to post-op valgus deformity (5.8%), 1 patient was evaluated as poor due to developing infection (5.8%) (Figure 2).
One patient presented with type 2 open fracture according to the Gustilo Andersen classification. Purulent discharge started to come from the incision in the 1st month after the intramedullary locking nail was applied to the patient. Selective antibiotic therapy was applied to the patient who was interned. In one patient, 20-degree valgus deformity developed on early post-op radiographs because the distal fragment could not be dominated during intramedullary nailing. Thereupon, the patient was revised 3 days later. In the long-term follow-ups of the patient, it was determined that the valgus deformity of 5 degrees remained, but in the clinical examination, the hip and knee movements were normal and the patient had no complaints. Skeletal traction was applied to the patients with a Kirschner wire passed through the tuberositas tibia before surgery. However, although one of our patients did not have any complaints due to the operation, it was observed that he had pain in the tuberositas tibia region that increased with walking (Figure 3). Fourteen patients who underwent static locking were dynamized at the end of 12-16 weeks, after the callus formation was sufficient in the radiological controls. In all patients, the femur was reamerized, and the thickest nail that could provide maximum contact between the nail and the medulla was preferred.
Discussion
While FDF is usually caused by high-energy traumas in young people, it can develop with low-energy traumas (falling at home, etc.) in the elderly population [1,2,8,22]. In AIMN application, the fracture union time is much shorter than open IMN, since the fracture line is not opened, the fracture hematoma is not evacuated and it is worked away from the fracture line.Generally, reference is made to the anterograde entrance to the pyriform fossa.There are also different references in the literature such as trochanteric and retrograde entry.In our study, we used anterograde piriform fossa entry [2,7,13,16].
Ayman El –Menyar et al. in their meta-analysis study, stated that there was no significant difference showing that early or late IM nailing accelerated union and healing in this type of fractures [3]. In our series, the average time between hospitalization and operation was 5 days.
Reamerization techniques of the medullary canal in FDF provide both mechanical and biological support to intramedullary nailing.Local formations accumulated in the fracture area by reamerization support the union by functioning like a bone graft containing osteoprogenitor cells and inductive molecules.While union is 98.5% in reamerized intramedullary nails (RIN), this rate is 84% in unreamerized nails (URIN).In their study, A-Bing Li et al. showed that RIN improves the union rate of fractures, shortens the union time, and reduces the incidence of nonunion or delayed union [6]. Reamerization may damage the blood flow of the inner cortical bone, but as a reaction, the periosteal blood flow may increase 6-fold, which can stimulate fracture healing; It has also been stated that RIN can provide greater stability and reduce the risk of implant replacement [7,11,17,23]. Clatworthy et al. concluded that fracture stability is an important determinant of rapid union [15]. A wider nail can be placed in the medullary canal after reamerization to improve cortical contact and provide greater stability. Farrar et al. reported that a tight-fitting nail increases the periosteal reaction [17]. Kanerva administered RIN to 42 patients and URIN to 39 patients in a series of 81 patients [4].
Bone union rate is much faster in the RIN group.The blood loss may be greater, but it will never be at the level that requires a blood transfusion [4]. Thorosen et al. applied RIN to 48 patients and said that the results were very good [25]. Kalenderer applied URIN to 77 patients and stated that the lack of stability in the URIN caused by insufficient bone-implant surface contact was eliminated by the use of locking nails . In our study, we applied RIN to all patients. In IMN application, it is clearly seen that the RIN technique has distinct advantages over the URIN technique in terms of both stability and joining time. Brumback and Virkus reported that IMN techniques may cause embolization by causing a slight decrease in endosteal blood flow and an increase in intramedullary pressure, but this effect is temporary; this complication is slightly more pronounced in URIN than in RIN [21]. Nader Helmy et al evaluated the functional results of FDF treated with anterograde IMN through piriform fossa entry using 2 different objective measurements (KinCom muscle test and Gait analysis) [16]. Isokinetic muscle testing and gait analysis were performed on the patients’ hip abductor, hip extensors, and knee extensors using a KinCom muscle testing machine.As a result, he stated that AKIMN applications caused mild muscle weakness in the hip abductor and extensors, which returned to normal in the following periods, and did not cause any change in the gait model in the gait analysis [16]. The majority of the authors argue that static locking is appropriate in order to prevent shortening and rotation in FDF. In our study, we applied static locking to 14 patients and dynamic locking to 11 patients. Static locking is load-bearing, dominates shortening and rotation, but osteoporosis develops in the bone when the stress is reduced.
Jiang et al. stated that with static locking, the length and rotation of the fracture line are preserved while micro-movement is limited [13]. Many studies have been conducted in the literature on when dynamization will occur after static locking.In order to accelerate the union of the fracture in patients, dynamization should be started from 12 -16 weeks when sufficient callus formation is seen. Thorosen started dynamization on average after 10-12 weeks, Winquist after 12 weeks, Brumback after 14 -16 weeks, Durakbaş after 9 weeks.Since the load on the implant after dynamization will create stress on the bone, this situation stimulates callus formation and increases the hardness of the existing callus [1,2,5,12]. In our study, we applied dynamization starting from 12 weeks in cases where we used static locking.The results of fixation with IMN in adolescent with FDF are satisfactory.Rigid IMN can be used easily in adolescents aged 12 and over. In our series, we applied rigid IMN to 2 of our 3 patients under the age of 15 and flexible IMN to 1 of our patients.Complications such as shortening, rotation, and avascular necrosis were not observed in the patients [6,9,14,20].
Segmental diaphyseal fractures of the femur are problematic for both the surgeon and the patient.Finelli et al. operated 6 patients with segmental fractures with IMN and reported the mean time to union as 7.2 months [20]. Kosuke Hamahashi et al., in their study of 17 patients with segmental fractures who had undergone IMN, stated that the displacement of the segmental part significantly affected and delayed union, and they took the 10 mm displacement of the segmental part as a reference point [5]. The surgeon is likely to consider open reduction using a bone clamp or cerclage wire, as prevention of displacement of 10 mm or more is not possible with closed maneuvers. [4]In our study, we applied IMN to 1 patient with segmental fracture. Complications such as shortness, rotation, and infection did not develop in the patient, and complete union was observed in the 5th month. It has been stated in the literature that the IMN technique can be used safely in open FDF. Gansslen et al. applied IMN to 56 patients who developed FDF as a result of gunshot injury, achieving complete union in 23 weeks and no infection was observed in the series [23]. In our study, 2 patients had type 2 open fractures, and one had post-op infection, which was treated with room-specific antibiotics.
Conclusion:
1. Anterograde closed IMN technique is the first preferred method in FDF.
2. In FDF with segmental fragments, static locking must be done in order to prevent shortening and rotation.
3. Reamerization of the femoral medulla accelerates the union.
4. Patients should be mobilized on the 1st post op day, and hip and knee joint movements should be started early.
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.
Funding: None
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.
References
1. Angadi DS, Stepherd D.E.T, Vadivelu R. Rigid intramedullary nail fixation of femoral fracturesin adolescents: what evidence in is available? J Orthopaed Traumatol. 2014; 15:147-53.
2. Gabarre S, Alberada J, Gracia L, Puertolas S, Ibarz E, Herrera A. Influenza of gap size,screw configuration,and nail materials in the stability of anterograde reamed intramedullary nail in femoral transverse fractures. Injury.2017;48 (Suppl. 6): S 40-6.
3- El-Menyar, A., Muneer, M., Samson, D., Al-Thani, H., Alobaidi, A., Mussleman, P, et al. Early versus late intramedullary nailing for traumatic femur fracture management: meta-analysis. Journal of Orthopaedic Surgery and Research,2018 Jun 28. 13(1): 160
4. Kanerva, M., Pärnänen, T., Jokinen, J., Haaja, J., Ritvanen, A., & Schlenzka, D. Multi-axis fatigue experimentation system of intramedullary implants for femur and tibia. Journal of Orthopaedic Research. J.Orthop.Res.2020May;38(5):984-995
5. Hamahashi K, Uchiyama Y, Kobayashi Y, Ebihara G, Ukai T, Watanabe M. Clinical outcomes of intramedullary nailing of femoral shaft fractures with third fragments: a retrospective analysis of risk factors for delayed union. Trauma Surg Acute Care Open. 2019;4 (1):e-000203.
6. Li AB, Zhang WJ, Guo WJ, Wang XH, Jin HM, Zhao YM. Reamed versus unreamed intramedullary nailing forthe treatment of femoral fractures: A meta- analysis of prospective randomized controlled trials. Medicine (Baltimore).2016; 95(29):e42-48.
7. Ghouri, S. I., Alhammoud, A., & Alkhayarin, M. M. (2020). Does Open Reduction in Intramedullary Nailing of Femur Shaft Fractures Adversely Affect the Outcome? A Retrospective Study. Advances in Orthopedics, 2020, 1–5.
8. Song, S.-H. (2019). Radiologic Outcomes of Intramedullary Nailing in Infraisthmal Femur-Shaft Fracture with or without Poller Screws. BioMed Research International, 2019, 1–4.
9. Ricci WM, Gallagher B, Haidukewych GJ.Intramedullary nailing of femoral shaft fractures: Current Concept. J Am AcadOrthop Surg. 2009;17(5):296-305
10. Summers, S., & Krkovic, M. Bone transport with magnetic intramedullary nails in long bone defects. European Journal of Orthopaedic Surgery & Traumatology, 2020; 31(6), 1243–1252.
11. Wu, K.-J., Li, S.-H., Yeh, K.-T., Chen, I.-H., Lee, R.-P., Yu, T.-C.,Wu, W.-T. The risk factors of nonunion after intramedullary nailing fixation of femur shaft fracture in middle agepatients. Medicine,2019.98(29),e16559.
12. Rosemberg, D. L., Goiano, E. O., Akkari, M., & Santili, C. Effects of a telescopic intramedullary rod for treating patients with osteogenesis imperfecta of the femur. Journal of Children’s Orthopaedics,2018. 12(1), 97–103.
13. Jiang M, Li C, Yi C, Tang S. Early intramedullary nailing of femoral shaft fracture on outcomes in patients with severe chest injury. A meta analysis. Sci Rep. 2016; 6:30566.
14. BaixauliSr F, Baixauli EJ, Sánchez-Alepuz E, Baixauli F Jr ‘’Interlocked intramedullary nailing for treatment of open femoral shaft fractures. Clin Orthop Relat Res. 1998;(350):67-73.
15. Clatworthy MG, Clark DI, Gray DH, Hardy AE. Reamed versus unreamed femoral nails. A randomised prospective trial. J Bone Joint Surg Br. 1998;80(3):485-9.
16. Helmy N, Jando VT, Lu T, Chan H, O’Brien PJ. Muscle function and functional outcome following standard anterograde reamed intramedullary nailing of isolated femoral shaft fractures. J-Orthop-Trauma.2008;22(1):10-5.
17. Grundnes O, Reikerås O. Closed versus open medullary nailing of femoral fractures. Blood flow and healing studied in rats. Acta Orthop Scand. 1998;69 (2):177-80.
18. Kossmann T, Trentz O. Intramedullary nailing in closed femoral fractures. Ortopade. 1996;25(3):207-15.
19. Herrera A, Rosell J, Ibarz E, Albareda J, Gabarre S, Mateo J, et al. Biomechanical analysis of the stability of antergrade reamed intramedullary nails in femoral spiral fractures. Injury. 2020;51(Suppl1.):S74-9.
20. Finelli, C. A., dos Reis, F. B., Fernandes, H. A., Dell’Aquila, A., Carvalho, R., Miki, N., … Salles, M. J. C. Intramedullary reaming modality for management of postoperative long bone infection: a prospective randomized controlled trial in 44 patients. Patient Safety in Surgery,2019;13(1).215-3
21. Brumback R J,Virkus W W. Intramedullary nailing of the femur: reamed versus nonreamed. J Am Acad Orthop Surg. 2000;8(2):83-90.
22. Deshmukh RG, Lou KK, Neo CB, Yew KS, Rozman I, George J. A technique to obtain correct rotational alignment during closed locked intramedullary nailing of the femur. Injury. 1998;29(3):207-10.
23. Gänsslen A, Gösling T, Hildebrand F, Pape HC, Oestern HJ. Femoral shaft fractures in adults: treatment options and controversies. Acta Chir Orthop Traumatol Cech. 2014;81(2):108-17.
24. Denisiuk M, Afşari A. Femoral Shaft Fractures. Treasure Island (FL): StatPearls Publishing;2020.
25. Thoresen BO, Alho A, Ekeland A, Strømsøe K, Follerås G, Haukebø A. Interlocking intramedullary nailing in femoral shaft fractures.Areport of forty-eight cases. J Bone Joint Surg Am.1985;67(9):1313-20.
Download attachments: 10.4328:ACAM.21053
Bedrettin Akar, Mehmet Bülent Balioğlu. Clinical results of closed intramedullary nailing in femoral diaphysis fractures. Ann Clin Anal Med 2022;13(3):330-334
Citations in Google Scholar: Google Scholar
Protective effects of quercetin against sepsis-induced oxidative damage on rat kidneys
Mehmet Duran 1, Murat Bıçakçıoğlu 2, Nezir Yılmaz 1,Bilge Aydın Türk 3, Mevlüt Doğukan 1, Hamza Nakır1, Zümrüt Doğan 4
1 Department of Anesthesiology and Reanimation, Faculty of Medicine, Adıyaman University, Adıyaman, 2 Department of Anesthesiology and Reanimation, Faculty of Medicine, İnönü University, Malatya, 3 Department of Pathology, Faculty of Medicine, Adiyaman University, Adiyaman, 4 Department of Anatomy, Faculty of Medicine, Adiyaman University, Adiyaman, Turkey
DOI: 10.4328/ACAM.21057 Received: 2022-01-14 Accepted: 2022-02-19 Published Online: 2022-02-22 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):335-339
Corresponding Author: Mehmet Duran, Department of Anesthesiology and Reanimation, Faculty of Medicine, Adıyaman University, Adıyaman, Turkey. E-mail: md021979@hotmail.com P: +90 505 689 54 04 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7568-3537
Aim: Sepsis is a clinical pathology, characterized by a severe and exaggerated inflammatory response. One of the most frequently damaged organs in sepsis is the kidney. Quercetin has anti-inflammatory, anti-proliferative, and antioxidant effects. In this study, it was aimed to examine the protective effects of quercetin on the kidneys.
Material and Methods: In the scope of this study, 31 rats were planned to be used in the experiments. The groups and number of animals were as follows: Group 1: 1.5 ml saline, Group 2: 1.5 ml olive oil, Group 3: intestinal ligation and puncture procedure was used to create experimental sepsis method. Group 4: 20 mg/kg quercetin was administrated by gavage. Group 5: quercetin was administered in intragastrically at doses of 20 mg/kg. In biochemical analyzes of kidney tissue samples, BUN, creatinine, MDA and GSH values were checked. Cell damage, inflammation and fibrosis were evaluated histopathologically.
Results: As a result of this study, tissue GSH levels were significantly different between groups 3 and 4 (p= 0.001). In terms of BUN value, it was found to be significantly higher in group 3 (p= 0.002). In tissue histology, glomerulitis (p= 0.001), tubular cell necrosis (p= 0.001) and mesenchymal matrix increase (p= 0.001) were different between groups 3 and 4. Finally, no fibrosis was observed in any group (p> 0.05).
Discussion: Quercetin has protective effects on kidney tissue against organ damage caused by sepsis.
Keywords: Quercetin, Sepsis, Antioxidant, Cecal Ligation
Introduction
Sepsis is a life-threatening organ dysfunction, resulting from an exaggerated host response to a suspected or defined infection [1]. The main reason for morbidity and mortality for septic patients is remote organ damage or multi-organ failure syndrome. The kidney is one of the most frequently damaged organs in sepsis.
Acute kidney injury (AKI) was detected in 19% of sepsis cases with mild clinical symptoms, 23% of moderately severe cases and 51% of severe sepsis cases. Sepsis constitutes 50% of the etiology of AKI for critically ill patients hospitalized in the intensive care unit. The development of AKI for patients with sepsis has been reported as an independent risk factor that increases mortality [2,3].
Quercetin is a flavonoid with anti-inflammatory and antioxidant effects, found naturally in many vegetables and fruits. Recent studies have reported that quercetin has protective effects on the kidneys [4].
In this study, it was aimed to investigate the protective effects of quercetin on the kidneys with an experimental sepsis model.
Material and Methods
It was planned to use 32 Spraque Dawley rats weighing 280-300 g in this study. Five groups were created by dividing animals randomly (Table 1). The animals were kept at room temperature 22 ± 2°C and in rooms with half-day light and dark cycles with food and water ad-libitum. One of them in the quercetin group died during the study.
Ketamine hydrochloride (70 mg/kg Ketalar; Eczacıbaşı, İstanbul, Turkey) and xylazine hydrochloride (20 mg/kg Rompun; Bayer Türk İlaç Ltd. Şti.) were administered intramuscularly to the rats under the supervision of a veterinarian for anesthesia.
Quercetin Application:
20 mg/kg quercetin was dissolved in olive oil daily for 2 weeks and given by gavage.
Sepsis Model with Cecal Ligation:
Under general anesthesia (combination of ketamine + xylazine), the rat was placed in the supine position and fixed on to the operating table. Initially, the operation area was shaved and disinfected. Later on, the abdomen was opened 2 cm from the front of the genital prominence towards the cranial. In rats, the caecum was exposed and the distal of iliocecal valve was ligated (3/0 suture). An 18G needle was used to puncture the intestinal tissue. The skin and subcutaneous tissues were covered with 3/0 silk first, and subcutaneous fluid was supplemented according to the animal’s weight [5]. BUN and creatinine were planned to be checked by taking blood tissue.
Preparation of Tissue Homogenates:
Sterile saline at +4 °C was used to wash the kidney tissue, cold chain principles were performed to cut small sections and placed in Eppendorf tubes and kept at -860 °C until analysis.
Analysis of MDA Level:
Beuge and Aust defined the thiobarbituric acid reaction (TBARS) method that analyzes tissue MDA concentration as a lipid peroxidation marker [6]. For homogenization of the lung tissue, 10% trichloroacetic acid was used, then centrifuged. The superficial liquid parts were mixed with an equal volume of 0.67% thiobutyric acid, then incubated in boiling water at 90 °C for 15 minutes. After that, they were cooled and centrifuged. MDA concentrations that were measured under 532 nm absorbance were expressed as nmol/g.
GSH Analysis:
It was measured by the glutathione reaction in the tube with 5,5’-dithiobis 2-nitrobenzoic acid to acquire a yellow-greenish color and to determine the amount of reduced glutathione by reading the light intensity of this color in a spectrophotometer with a wavelength of 410 nm.
Histological Evaluation:
The obtained tissues were histopathologically stained with H&E (Hematoxylin-Eosin) staining method, then cell damage was evaluated in terms of inflammation and fibrosis. Glomerular sclerosis, glomerulitis and mesangial matrix increases were evaluated. The presence of inflammatory cells in the glomeruli was defined as glomerulitis. It was graded as 0 if there was no glomerulitis, 1 if it was rare, and 2 if it was widespread. Tubulointerstitial area was evaluated for interstitial fibrosis and interstitial inflammation. Tubulitis, atrophy and tubular necrosis were evaluated. There were two patterns of acute tubular necrosis. The first one was tubular coagulation necrosis and the other was single-cell necrosis and shedding. In single-cell necrosis, the epithelium was flattened, vacuolized, pale and flattened, and its brush-like ends disappeared. Tubules were evaluated for single-cell necrosis, vacuolization, and brush border damage. It was evaluated as 0 if it was absent, 1 if it was present in 25% or less of the tubules, 2 if it was present in 26-50%, and 3 if it was present in more than 50% [7].
Statistical Analysis:
SPSS 15.0 software for Windows (SPSS Inc.) was used for statistical analysis. The Kolmogorov-Smirnov test was used to determine whether the data were normally distributed. One Way ANOVA or Kruskal-Wallis H tests were chosen according to their suitability for the comparison of the groups. The groups, found to be significant as a result, were compared using the Tukey multiple range test or the dual Mann-Whitney U test (for those with a p-value <0.005, applying Bonferroni correction (i.e., and 0.05/10 comparisons), the results were reported as mean±SD or median (min-max). P value <0.05 was considered statistically significant.
Ethical statement
The study was approved by the Adiyaman University Animal Experiments Local Ethics Committee (ADYÜ-HADYEK) (approval No. 2019/048).
Results
Glomerular sclerosis formation was not observed in any group. As a result of histological scoring for glomerulitis (P=0.001), there was a statistically significant difference between group 3 (had sepsis), group 4 (was treated with quercetin), and the other groups. No statistical differences were found between groups 3, 4 and the other groups (groups 1, 2 and 5) (P>0.05).
Tubular necrosis and tubular atrophy were not observed in any group in histological examination of the tubules. Although no acute tubular necrosis in the form of coagulation necrosis was observed, tubular single cell necrosis was present. In the comparison between groups in terms of tubular single cell necrosis, there was a statistically significant difference in groups 3 and 4 compared to the other groups (P=0.001). In addition, there was no difference between groups 1, 2 and 5 in terms of tubular single cell necrosis, vacuolization, and brush border damage (P>0.05). Moreover, there was no statistically significant difference between groups 3 and 4 (P>0.05).
In the histological examination of the tubulointerstitial area, interstitial fibrosis and interstitial inflammation were not observed in any group. While there was a statistical difference between groups 3,4 and the other groups in histological scoring for mesenchymal matrix increase (P=0.001), there was no statistical difference among themselves and between groups 1, 2 and 5 (P>0.05). Graph of the mean values of the groups for tubular necrosis, glomerulitis, and mesenchymal matrix increase were shown in Figure3.
Besides, BUN and creatinine values in the blood were compared statistically, and no difference was observed between the groups in terms of creatinine values (P>0.05), while the mean value of the BUN values in group 3 was different from all the other groups (P=0.002) (Table 2).
Furthermore, when comparing GSH and MDA between groups, there was a statistical difference between GSH values in group 3 compared to all the other groups (P=0.001). Among MDA levels, although the highest MDA level was observed in group 3, this difference was not statistically significant (P>0.05). Mean values of MDA and GSH of the groups and their standard deviations were given in Table 2.
Discussion
The pathophysiology of sepsis-induced AKI development is complex and multifactorial. Changes in renal hemodynamics, endothelial damage, tissue infiltration of inflammatory cells, intraglomerular thrombosis, cell necrosis, and tubular occlusion contribute to the pathophysiology [8]. Understanding the pathophysiology of a disease is always the cornerstone for the development of new diagnostic and therapeutic strategies. Although quercetin is not in a position to treat or prevent the AKI that will develop, it can alleviate the effects of acute kidney injury caused by sepsis.
In the literature, the protective effects of quercetin on AKI that develop for various reasons have been mentioned [9-11]. Wang et al. [12] showed that quercetin has a kidney protective effect by inhibiting the ferroptosis pathway in their study. In the study by Yagmurca et al. [9], quercetin reduced the kidney toxicity caused by doxorubicin. In addition, there are many studies showing that other antioxidant substances except quercetin reduce kidney toxicity that develops for various reasons. Also, literature studies show that various antioxidant substances, except for quercetin, are effective in kidney damage caused by sepsis. Tasanarong et al. [13] showed in their study that the antioxidant effect of Phyllanthus emblica extract is effective in contrast-induced AKI. In studies with ferulic acid, which is a phenolic compound with antioxidant activity, Mir et al. [14] found that ferulic acid was effective against AKI caused by LPS, Bacanlı et al. [15] stated that it was effective against oxidative damage caused by sepsis. Zang et al. [16] reported that coumarins obtained from Hydrangea paniculata were effective against sepsis-induced AKI by antioxidant and anti-inflammatory ways. In this study, it was observed that tissue GSH levels that reflecting the antioxidant activity was the highest in the sepsis group and significantly higher than the sepsis+quercetin group. Antioxidant activity was lower in the group of rats with sepsis given quercetin. Likewise, tissue MDA activity was lower in the sepsis-induced group than in the quercetin treated rats with sepsis-induced AKI. This was thought to be due to the antioxidant effect of quercetin.
Although serum creatinine is used in the diagnosis and staging of acute kidney injury, acute changes in creatinine value lag behind both kidney injury and recovery. In addition, despite kidney damage in sepsis, an increase and then a decrease are observed in creatinine and BUN values [17]. In the study by Doi et al., they found that sepsis caused a decrease in creatinine values. In the study they found that, while the creatinine values were slightly increased in mice with sepsis with CLP method, the highest increase was observed in mice with nephrectomy. However, creatinine level was lower in mice with sepsis with nephrectomy and CLP. As a result, sepsis reduces creatinine production, which masks the rise in serum creatinine after sepsis, potentially complicating early detection of acute kidney injury [18]. In this study, a slight increase in creatinine level was found in the group with sepsis, but this increase was not statistically significant. However, there was a significant increase in the BUN value of the same group. In this study, BUN and creatinine values in a single section at the 24th hour of CLP application were also studied. It has been thought that a significant increase in BUN values and a slight increase in creatinine values are compatible with the literature.
Sepsis causes various pathological changes in the kidney histologically. There are many mechanisms for these changes. Sun et al. [19] showed in their study that, autophagy can be reduced by deacetylation of P53 in kidney damage caused by sepsis. Zheng et al. [20] observed a decrease in the histopathological changes in sepsis in their study with Rhizoma Coptidis extract. In this histological examination, it was observed that tubular damage was present in groups with sepsis. Although the histological changes in the group with sepsis given quercetin were less severe than the group with sepsis alone, they were not different enough to create a significant difference between the scoring results. Although quercetin alleviated the histological changes, it did not cause a sufficient change to correct the pathology caused by sepsis.
The lack of serial measurements was the weak point of this study. This may prevent us from seeing an increase or decrease in some parameters. However, it has been believed that the time chosen for the sampling is sufficient to show the effectiveness of sepsis and quercetin among the groups.
In conclusion, quercetin is a flavonoid whose antioxidant effect is well-known. The authors believe that quercetin, which has antioxidant and anti-inflammatory effects, has protective effects on kidney tissue against organ damage caused by sepsis.
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.
Funding: None
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.
References
1. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock. Intensive Care Med. 2017;43(3):304-77
2. Majumdar A. Sepsis-induced acute kidney injury. Indian J Crit Care Med.
2010;14(1):14-21.
3. Ma S, Evans RG, Iguchi N, Tare M, Parkington HC, Bellomo R, et al. Sepsis-induced acute kidney injury: A disease of the microcirculation. Microcirculation. 2019;26(2):e12483.
4. Bahar E, Lee GH, Bhattarai KR, Lee HY, Kim HK, Handigund M, et al. Protective role of quercetin against manganese-induced injury in the liver, kidney, and lung; and hematological parameters in acute and subchronic rat models. Drug Des Devel Ther. 2017;11:2605-19.
5. Hubbard WJ, Choudhry M, Schwacha MG, Kerby JD, Rue LW 3rd, Bland KI, et al. Cecal ligation and puncture. Shock. 2005;24(1):52-7.
6. Mathew D, Nair CK, Jacob JA, Biswas N, Mukherjee T, Kapoor S, et al. Ascorbic acid monoglucoside as antioxidant and radioprotector. J Radiat Res. 2007;48(5):369-76.
7. Kilciksiz S, Demirel C, Erdal N, Gürgül S, Tamer L, Ayaz L, et al. The effect of N-acetylcysteine on biomarkers for radiation-induced oxidative damage in a rat model. Acta Med Okayama. 2008;62(6):403-9.
8. Zarjou A, Agarwal A. Sepsis and acute kidney injury. J Am Soc Nephrol. 2011;22(6):999-1006.
9. Yagmurca M, Yasar Z, Bas O. Effects of quercetin on kidney injury induced by doxorubicin. Bratisl Lek Listy. 2015;116(8):486-9
10. Liu T, Yang Q, Zhang X, Qin R, Shan W, Zhang H, et al. Quercetin alleviates kidney fibrosis by reducing renal tubular epithelial cell senescence through the SIRT1/PINK1/mitophagy axis. Life Sci. 2020;257(118116):118116.
11. Sánchez-González PD, López-Hernández FJ, Dueñas M, Prieto M, Sánchez-López E, Thomale J, et al. Differential effect of quercetin on cisplatin-induced toxicity in kidney and tumor tissues. Food Chem Toxicol. 2017;107:226-36
12. Wang Y, Quan F, Cao Q, Lin Y, Yue C, Bi R, et al. Quercetin alleviates acute kidney injury by inhibiting ferroptosis. J Adv Res. 2021;28:231-43.
13. Tasanarong A, Kongkham S, Itharat A. Antioxidant effect of Phyllanthus emblica extract prevents contrast-induced acute kidney injury. BMC Complement Altern Med. 2014;14(1):138
14. Mir SM, Ravuri HG, Pradhan RK, Narra S, Kumar JM, Kuncha M, et al. Ferulic acid protects lipopolysaccharideinduced acute kidney injury by suppressing inflammatory events and upregulating antioxidant defenses in Balb/c mice. Biomed Pharmacother. 2018;100:304-15.
15. Bacanlı M, Aydın S, Taner G, Göktaş HG, Şahin T, Başaran AA, et al. The protective role of ferulic acid on sepsisinduced oxidative damage in Wistar albino rats. Environ Toxicol Pharmacol. 2014;38(3):774-82.
16. Zhang S, Ma J, Sheng L, Zhang D, Chen X, Yang J, et al. Total Coumarins from Hydrangea paniculata Show Renal Protective Effects in Lipopolysaccharide-Induced Acute Kidney Injury via Anti-inflammatory and Antioxidant Activities. Front Pharmacol. 2017;8:872.
17. Li JL, Li G, Jing XZ, Li YF, Ye QY, Jia HH, et al. Assessment of clinical sepsis-associated biomarkers in a septic mouse model. J Int Med Res. 2018;46(6):2410-22.
18. Doi K, Yuen PS, Eisner C, Hu X, Leelahavanichkul A, Schnermann J, et al. Reduced production of creatinine limits its use as marker of kidney injury in sepsis. J Am Soc Nephrol. 2009;20(6):1217-21.
19. Sun M, Li J, Mao L, Wu J, Deng Z, He M, et al. p53 Deacetylation Alleviates Sepsis-Induced Acute Kidney Injury by Promoting Autophagy. Front Immunol. 2021;12:685523.
20. Zheng Y, Shi X, Hou J, Gao S, Chao Y, Ding J, et al. Integrating metabolomics and network pharmacology to explore Rhizoma Coptidis extracts against sepsisassociated acute kidney injury. J Chromatogr B Analyt Technol Biomed Life Sci. 2021;1164:122525
Download attachments: 10.4328:ACAM.21057
Mehmet Duran, Murat Bıçakçıoğlu, Nezir Yılmaz, Bilge Aydın Türk, Mevlüt Doğukan, Hamza Nakır, Zümrüt Doğan. Protective effects of quercetin against sepsis-induced oxidative damage on rat kidneys. Ann Clin Anal Med 2022;13(3):335-339
Citations in Google Scholar: Google Scholar
Relationship between the beliefs on social appearance, anxiety, and intolerance of uncertainty in rhinoplasty patients
Fatih Yığman 1, Serhat İnan 2
1 Department of Psychiatry, Faculty of Medicine, Ufuk University, 2 Department of Otorhinolaryngology, Faculty of Medicine, Başkent University, Ankara, Turkey
DOI: 10.4328/ACAM.21071 Received: 2022-01-21 Accepted: 2022-02-21 Published Online: 2022-02-21 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):340-344
Corresponding Author: Fatih Yığman, Department of Psychiatry, Faculty of Medicine, Ufuk University, Ufuk University Street, No:2, 06510 Çankaya, Ankara, Turkey. E-mail: dr.yigman@gmail.com P: +90 535 695 81 26 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6052-7662
Aim: Rhinoplasty is a surgical procedure performed for functional and/or cosmetic purposes. The purpose of the study is to evaluate the psychological factors that determine patient satisfaction in rhinoplasty surgery.
Material and Methods: A total of 121 patients (85 women, 36 men) participated in the study. Sociodemographic data form, social appearance anxiety scale (SAAS), beliefs about appearance scale (BAAS), short form of intolerance of uncertainty (IUS) scale and rhinoplasty outcomes evaluation questionnaire (ROEQ) were applied to the participants before and at the 3rd- month control after rhinoplasty.
Results: Before and after the operation, patients were divided into two groups, according to their SAAS scores. Preoperative BAAS, preoperative SAAS and postoperative REOQ scores were significantly higher in the group of patients whose SAAS scores decreased after the operation. It was determined that the change in ROEQ scores could be predicted by the change in SAAS scores (β=-0.454, p<0.005).
Discussion: Psychological factors such as appearance anxiety can act as a bridge between patient satisfaction and rhinoplasty outcomes. This study indicates a complex cognitive process and suggests that multidisciplinary approaches may be important to improve patient satisfaction after rhinoplasty.
Keywords: Rhinoplasty, Physical Appearance, Patient Reported Outcomes, Cognitive Psychology
Introduction
Rhinoplasty is a complex surgery that not only aims to correct the shape or functional defect of the nose, but also affects the psychology of the patient. Among the surgical procedures applied to the face, this operation is a difficult surgical intervention in terms of patient satisfaction and prediction of functional and aesthetic results [1]. The nose is one of the most distinctive and characteristic structures of the face. The shape of the nose before and after the surgery is frequently interpreted by both the patients’ and the people around them. It is thought that the underlying reason of the increasing rhinoplasty applications in recent years may be related to the appearance of the nose rather than the functional contribution of rhinoplasty.
Appearance is not only a physical condition, it is a complex process that also includes the meaning, interpretation and emotions related to appearance. Beliefs about appearance are the thoughts that consist of both a person’s thoughts about his/her body and appearance, and about possible views of the outside world on his/her body and appearance. These thoughts can affect people’s self-worth and social interactions. According to cognitive theory, emotions arise on the ground of thoughts. Consequently, negative beliefs about appearance can also cause anxiety. Elements of appearance such as height, weight, skin color, facial features can cause social appearance anxiety. In summary, social appearance anxiety is the negative affectivity that people experience because of their thought that they will be negatively evaluated because of their physical characteristics [2].
Another important concept is uncertainty. It is known that uncertainty can increase positive and negative affectivity depending on its context [3]. Intolerance of uncertainty is a cognitive structure that includes emotional, cognitive and behavioral processes [4]. Intolerance of uncertainty represents an important cognitive construct in relation to negative affectivity. The uncertainty that people experience before such an important surgery, will have an impact on their emotional and cognitive processes.
Facial appearance plays an important role in social life, therefore also has a great psychological effect. Studies have shown that quality of life increases after cosmetic surgery [5, 6]. However, the idea of the relationship between the search for cosmetic surgery and the presence of psychopathology, which was emphasized in previous periods, is no longer on the agenda. However, it has been reported that certain psychosocial factors may affect the interest and satisfaction in cosmetic surgery [7]. However, studies on these factors have generally focused on personality disorder and body dysmorphic disorder.
The aim of this study is to investigate the relationship between rhinoplasty patients’ beliefs about their appearance, their anxiety about their social appearance, and their satisfaction with rhinoplasty. This study, in which preoperative and postoperative evaluations are made regarding thoughts, emotions and uncertainties within the scope of cognitive theory, is an exploratory study.
Our basic hypothesis was that after rhinoplasty surgery, patient satisfaction would increase, negative beliefs about appearance would decrease, appearance anxiety and intolerance of uncertainty would decrease.
Material and Methods
This study was approved by the Baskent University Institutional Review Board and Ethics Committee (Project no: KA 20/459). Written informed consent was obtained from all participants.
The study prospectively included 121 consecutive participants who underwent rhinoplasty surgery at Baskent University, Department of Otorhinolaryngology between June 2020 and November 2021. A sociodemographic data form, social appearance anxiety scale, beliefs about appearance scale, short form of intolerance of uncertainty scale and rhinoplasty outcomes evaluation questionnaire were applied to the participants. Scales were applied twice before the operation and at the 3th-month-control after the operation. Exclusion criteria were defined as the diagnoses of body dysmorphic disorder, substance use disorder, psychotic disorder, mental retardation, illiteracy to fill the scales and patients who underwent closed technique rhinoplasty and revision rhinoplasty.
Scales
Sociodemographic data form:
It is a form prepared by the research team to examine the participants’ sociodemographic data such as age, gender, occupation, and additional disease.
Social appearance anxiety scale (SAAS):
It is a 5-point Likert-type scale consisting of 16 items developed to assess the social appearance anxiety of individuals [8]. The validity and reliability study of the scale in Turkish, was conducted in our country [9]. High scores in this scale indicate a high level of social appearance anxiety.
Beliefs about appearance scale (BAAS):
It is a one-dimensional, self-reporting, 20-item scale developed to measure dysfunctional thoughts and beliefs about appearance [10]. High scores indicate dysfunctional thoughts about one’s appearance. Validity and reliability studies of the scale were carried out in Turkish, and it was confirmed that it is a valid and reliable measurement tool also for studies in our country [11].
Intolerance of Uncertainty Scale -12 (Intolerance of uncertainty -IUS-12):
It is a 12-item scale created to evaluate people’s thoughts and attitudes towards uncertainty [12]. The total score that can be obtained from the scale varies between 12 and 60. High scores indicate a high level of intolerance of uncertainty. The Turkish validity and reliability study of the scale was conducted previously [13].
Rhinoplasty Outcomes Evaluation Questionnaire (ROEQ):
The ROEQ was developed to evaluate rhinoplasty outcomes and consists of six questions (two for each of physical, emotional, and social factors) related to patient satisfaction [14]. ROEQ, Turkish reliability and validity study was performed [15]. This scale is applied before and after the operation to evaluate rhinoplasty satisfaction.
In this study, preoperative and postoperative scale scores were defined as preX and postX.
Statistical Analysis
All data (categorical and continuous) were analyzed using the Statistical Package for Social Science windows version 15.0 (SPSS) web software. The Kolmogorov-Smirnov test was used to evaluate whether the data fit the normal distribution or not. Quantitative data were evaluated as mean percentage and standard deviation, and categorical variables were evaluated using Pearson’s Chi-square test. Independent Sample t-test was used to compare the means of independent variables between groups. Paired samples t-test was used to compare the pre-test and post-test of the scales. The Pearson Correlation test was used to evaluate the correlation between the scores in the scale. To investigate the effect of the scale scores on each other, the differences between the post-test and pre-test scores were calculated, followed by evaluation of the differences in scores through linear regression analyses. The level of statistical significance was accepted as 0.05 in all tests.
Results
A total of 85 female (70.2%) and 36 male (20.8%) participants were included in the study. The mean age of the participants was 27.43 ± 8.58 years. According to their pre- and post-operative SAAS scores, the participants were divided into two groups: patients with increased (n= 75) and decreased (n=46) anxiety. There were no participants whose pre-operative and post-operative SAAS scores did not change. There was no significant difference between the two groups in terms of age (p=0.233) and gender (p=0.779). PreBAAS (preoperative BAAS), preSAAS (preoperative SAAS), postROEQ (postoperative ROEQ) scores were found to be significantly higher, and postSAAS and preROEQ scores were significantly lower in the SAAS decreasing group. When preoperative and postoperative test scores of the scales were examined within each group, it was found that SAAS scores decreased and ROEQ scores increased significantly in the SAAS decreasing group. In the group with increasing SAAS, all scale scores increased significantly (Table 1).
In the next step, the correlations between the scores preoperative and postoperative the scales were examined. According to the correlation analysis, a significant negative correlation was found between preROEQ scores and preBAAS (r=-.256), postBAAS (r=-.211), preSAAS (r=-.327), postSAAS (r=-.210) and preIUS (r=-.202) scores (Table 2).
Finally, a two-stage regression analysis was applied to evaluate the effects on the change in ROEQ values. In the first stage, the effect of age and gender was evaluated and no significant impact was found on difference of ROEQ (ROEQdiff) scores (p = 0.414). In the second stage, after keeping the effect of age and gender constant, the impact of changes on difference of IUS (IUSdiff), difference of BAAS (BAASdiff), and difference of SAAS (SAASdiff) scores were examined. According to this model, SAASdiff scores were found to significantly predict ROEQdiff scores (F(5,115) = 3.215, p=0.002) (Table 3).
Discussion
According to our findings, we were largely unable to confirm our hypotheses. In particular, we found that, contrary to our expectations, post-operative anxiety increased in a significant number of patients. We found that negative beliefs about appearance and intolerance of uncertainty increased in patients with increased appearance anxiety. We found no difference in the scores of negative beliefs and intolerance of uncertainty in patients with reduced appearance anxiety. Rhinoplasty satisfaction increased in both groups, but this increase was more prominent in patients with reduced appearance anxiety. Finally, we determined the predictive effect of the change in SAAS scores on the change in ROEQ scores. We have discussed possible interpretations of our findings below.
Although the surgical procedure is executed well technically, the main factor determining the success of surgery is patient satisfaction. If the patient is dissatisfied, even technically good execution of the procedure does not indicate that the procedure has been successful [16]. It is known that surgeons who perform rhinoplasty surgery tend to select appropriate patients in order to increase their chances of obtaining successful results and to reduce the probability of experiencing medicolegal problems [17]. This may be an appropriate approach in patients with significant underlying psychiatric problems, such as body dysmorphic disorder. On the other hand, it may be an ethically important problem to provide a chance to the patients to receive medical treatment based on psychological factors. Instead, providing a multidisciplinary approach to health services regarding psychiatric factors would be a more appropriate option.
Patient satisfaction in rhinoplasty surgery is also affected by factors other than the surgical procedure. Factors such as the patient’s beliefs about the appearance of nose, anxiety about appearance, and uncertainty about post-operative appearance may affect the postoperative satisfaction of the patient. There are methodological problems in many studies evaluating the psychological factors of cosmetic surgery applications. It is obvious that only cross-sectional preoperative or postoperative evaluations can affect the objectivity of the results. For example, a patient may display a cognitive bias after the operation, making more positive evaluations oа the results to justify the behavior of undergoing operation [18]. Therefore, patient satisfaction cannot be evaluated unidimensionally. In addition, the decrease in post-operative anxiety may be a result of the reduction of high pre-operative anxiety. Low expectations from surgery may also result in an exaggeratedly positive outcome [18]. At this point, it is important to evaluate the effects of pre- and postoperative cognitive factors, emotions and uncertainty associated with the surgery. Contrary to our expectations, we found that appearance anxiety increased in most of the patients after the surgery. The increase in cosmetic expectations in rhinoplasty operations may cause an increase in appearance anxiety related to the desire to be liked after surgery. A predominance of negative beliefs about appearance and increased uncertainty about being liked after surgery might be associated with these results.
While defining a patient suitable for plastic surgery, Gorney suggests that a low degree of deformity and high anxiety are associated with dissatisfaction [19]. It is also known that patients that have irrational or high expectations are associated with post-operative dissatisfaction [20]. Similarly, we think that high anxiety and negative beliefs significantly affect satisfaction scores. Our results point out that the severity of negative beliefs may be associated with anxiety and satisfaction.
In a study conducted with 56 patients in Turkey, individuals with high preoperative social appearance anxiety were found to have lower postoperative satisfaction rates [21]. According to our results, similarly, satisfaction rates were significantly higher in the group with reduced post-operative anxiety. A prospective study conducted in the United Kingdom at general surgery, Ear Nose and Throat (ENT) and maxillofacial surgery clinics compared 51 plastic surgery operations that changed appearance, with 105 surgical operations that did not change appearance. Postoperative depression and anxiety scores decreased in both groups. However, reduction in anxiety and body region-specific appearance distress was found to be greater in plastic surgery operations [18]. As a result of this study, the importance of a more detailed investigation of the role of cognitive factors associated with cosmetic surgery was emphasized. In our study, anxiety was found to be increased in a significant number of patients. One of the possible reasons for this may be that we used a questionnaire that focused on appearance anxiety when assessing anxiety. The relationship of anxiety with appearance rather than factors related to surgery might have led to different results.
Postoperative edema may decrease by 2/3 at the end of the 1st month, 95% at the 6th month, and 97.5% at the end of the first year [22] Accordingly, it takes about a year for the nose to take its permanent shape. Factors such as the fact that the nose is visible to everyone, the comments that patient receives from his/her environment, and the expectation of rapid change may have increased the anxiety during the postoperative recovery period. In another study, although there was no change in edema and ecchymosis in patients who underwent postoperative infraorbital taping, anxiety decreased [23]. In this regard, it would be beneficial to investigate methods that can provide physical encouragement, such as applying massage besides accurate information, to reduce the patient’s postoperative appearance anxiety.
In our study, we did not detect a significant effect of age and gender on satisfaction. We have concerns about those other studied factors will cause patients to be stigmatized and will decrease their chance of receiving medical treatment. Furthermore, it is obvious that these results from previous studies are controversial. In another review from 2006, psychological outcomes in plastic surgery were associated with poor methodological quality, pointing to the difficulty of commenting on treatment efficacy [24]. The adjusted R-squared values we determined in the simple linear regression analyzes are very modest. However, considering our analysis based on the change between pre- and post-scale scores instead of the direct scores of the scales, these values can be considered to be statistically significant. From a methodological point of view, we think that our findings are important.
In this study, it can be said that in terms of methodology, psychological factors are discussed in more detail on the ground of cognitive theory. However, it could be a problem that it did not include a control group, and the effects of some other possible cognitive factors were not included in evaluation. The following statement has been added to the discussion section. Post-surgical anxiety, beliefs about appearance, intolerance to uncertainty may change over time. Therefore, re-evaluation of similar scales in the long term may lead to different results. Finally, the results in this study reflect Turkish society, and it should be noted that interpretations of appearance may produce different results in different societies. Despite the limitations of the study, we think that it will make an important contribution to the literature in terms of revealing the functional and aesthetic results of rhinoplasty as well as the psychology of the patient with pre- and post-operative evaluations.
Conclusion
The objective of this study was to determine the psychological factors between rhinoplasty surgery and patient satisfaction. For this purpose, we aimed to evaluate patient satisfaction through considering thoughts, emotions, and uncertainty on the ground of cognitive theory. This relationship points out a complex process and further research is needed. We suggest that postoperative satisfaction can be increased with appropriate preoperative evaluation and in case of need a multidisciplinary approach.
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.
Funding: None
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.
References
1. Swartout B, Toriumi DM. Rhinoplasty. Curr Opin Otolaryngol Head Neck Surg. 2007;15(4):219-27.
2. Leary MR, Kowalski RM. Social anxiety. New York: Guilford Press; 1995.
3. Yığman F, Fidan S. Intolerance of Uncertainty as a Transdiagnostic Factor. Current Approaches in Psychiatry. 2021;13(3):573-87.
4. Dugas MJ, Hedayati M, Karavidas A, Buhr K, Francis K, Phillips NA. Intolerance of uncertainty and information processing: Evidence of biased recall and interpretations. Cognit Ther Res. 2005;29(1):57-70.
5. Herruer JM, Prins JB, van Heerbeek N, Verhage-Damen GW, Ingels KJ. Negative predictors for satisfaction in patients seeking facial cosmetic surgery: a systematic review. Plast Reconstr Surg. 2015;135(6):1596-605.
6. Litner JA, Rotenberg BW, Dennis M, Adamson PA. Impact of cosmetic facial surgery on satisfaction with appearance and quality of life. Arch Facial Plast Surg. 2008;10(2):79-83.
7. Javo IM, Sørlie T. Psychosocial characteristics of young Norwegian women interested in liposuction, breast augmentation, rhinoplasty, and abdominoplasty: a population-based study. Plast Reconstr Surg. 2010;125(5):1536-43.
8. Hart TA, Flora DB, Palyo SA, Fresco DM, Holle C, Heimberg RG. Development and examination of the social appearance anxiety scale. Assessment. 2008;15(1):48-59.
9. Doğan T. Adaptation of the Social Appearance Anxiety Scale (Saas) to
Turkish: A Validity and Reliability Study. Hacettepe University Kournal of Education. 2010;39(39):151-9.
10. Spangler DL, Stice E. Validation of the beliefs about appearance scale. Cognit Ther Res. 2001;25(6):813-27.
11. Tekin EG, Doğan T. The internal consistency reliability and construct validity of the Turkish translation of the beliefs about appearance scale. Journal of Human Sciences. 2014;11(1):1178-87.
12. Carleton RN, Norton MPJ, Asmundson GJ. Fearing the unknown: A short version of the Intolerance of Uncertainty Scale. J Anxiety Disord. 2007;21(1):105-17.
13. Sarıçam H, Erguvan FM, Akın A, Akça MŞ. The Turkish short version of the Intolerance of Uncertainty (IUS-12) Scale: The study of validity and reliability. Route Educational and Social Science Journal. 2014;1(3):148-57.
14. Alsarraf R. Outcomes research in facial plastic surgery: a review and new directions. Aesthetic Plast Surg. 2000;24(3):192-7.
15. Çelik M, Altıntaş A. The turkish version of the rhinoplasty outcomes evaluation questionnaire: validation and clinical application. Balkan Med J. 2019;36(2):129-33.
16. Ching S, Thoma A, McCabe RE, Antony MM. Measuring outcomes in aesthetic surgery: a comprehensive review of the literature. Plast Reconstr Surg. 2003;111(1):469-82.
17. Kucur C, Kuduban O, Ozturk A, Gozeler MS, Ozbay I, Deveci M, et al. Psychological evaluation of patients seeking rhinoplasty. Eurasian J Med. 2016;48(2):102-6.
18. Moss TP, Harris DL. Psychological change after aesthetic plastic surgery: a prospective controlled outcome study. Psychol Health Med. 2009;14(5):567-72.
19. Gorney M, Martello J. Patient selection criteria. Clinics in plastic surgery. 1999;26(1):37-40.
20. Gorney M. Recognition and management of the patient unsuitable for aesthetic surgery. Plast Reconstr Surg. 2010;126(6):2268-71.
21. Tulacı KG, Arslan E. Evaluating The Effect Of Social Appearance Anxiety On Patient Satisfaction In Septorhinoplasty. KBB-Forum. 2020;19(3):318-323
22. Pavri S, Zhu VZ, Steinbacher DM. Postoperative edema resolution following rhinoplasty: a three-dimensional morphometric assessment. Plast Reconstr Surg. 2016;138(6):973e-9.
23. Tulaci KG, Arslan E, Tulaci T, Tastan E, Yazici H. Evaluating the Effect of Infraorbital Region Taping Procedure on Patient Anxiety, Satisfaction, Edema, and Ecchymosis Level on Primary Septorhinoplasty. J Craniofac Surg. 2020;31(5):1322-6.
24. Cook SA, Rosser R, Salmon P. Is cosmetic surgery an effective psychotherapeutic intervention? A systematic review of the evidence. J Plast Reconstr Aesthet Surg. 2006;59(11):1133-51.
Download attachments: 10.4328:ACAM.21071
Fatih Yığman, Serhat İnan. Relationship between the beliefs on social appearance, anxiety, and intolerance of uncertainty in rhinoplasty patients. Ann Clin Anal Med 2022;13(3):340-344
Citations in Google Scholar: Google Scholar
Do complications of pancreatic cancer surgical treatment change in the aging world?
Orhan Aras 1, Rıdvan Yavuz 1, Hüseyin Çiyiltepe 1, İsmail Gömceli 2
1 Department of Gastroenterology Surgery, University of Health Science, Antalya Training and Research Hospital, 2 Department of General Surgery, Antalya Bilim University, Antalya, Turkey
DOI: 10.4328/ACAM.21078 Received: 2022-01-22 Accepted: 2022-02-22 Published Online: 2022-02-23 Printed: 2022-03-01 Ann Clin Anal Med 2022;13(3):345-349
Corresponding Author: Orhan Aras, Department of Gastroenterology Surgery, Antalya Training and Research Hospital, Varlık Mahllesi, Kazım Karabekir Cd., D Blok, Muratpaşa, 07050 Antalya, Turkey. E-mail: drorhanaras@hotmail.com P: +90 505 397 10 77 F: +90 242 249 44 62 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6390-116X
Aim: The elderly population in the community population is increasing day by day. Pancreatic malignancies have poor survival and high mortality and morbidity rates. In our study, we aimed to evaluate the effect of age on pancreaticoduodenectomy surgery.
Material and Methods: Patients who underwent pancreaticoduodenectomy between 2012 and 2020 were divided into 3 groups according to their age (60 years and younger group 1, 60-80 years old group 2, 80 years and older group 3). Early mortality and morbidity outcomes between the groups were compared.
Results: Parallel to the increase in age, a statistically significant increase was found in the ASA score (p:0.000), length of stay in the intensive care unit (p:0.021), mortality (p:0.003) and morbidity (p:0.021) rates between the groups.
Discussion: Considering the increasing elderly population in the world, we found that surgical intervention such as pancreaticoduodenectomy with high comorbidity can be performed with higher mortality and morbidity risks compared to younger patients.
Keywords: Pancreas Cancer, Pancreaticoduodenectomy, Mortality, Morbidity, Age
Introduction
The number of elderly people in the population of the society is increasing day by day [1]. While the proportion of the elderly population in the total population is 9.5% in 2020, this situation is expected to increase to 16.3% in 2040 and 22.6% in 2060 [2].
There is a parallelism between the increase in life expectancy and the incidence of cancer. It is predicted that by 2035, 14 million new cancer cases will be detected, constituting almost 60% of the global cancer incidence [3]. It is estimated that pancreatic cancer, which is in the 4th place in cancer-related deaths today, will rise to the second place in cancer-related deaths by 2030 [4].
Despite advances in the diagnosis and treatment of pancreatic cancer, the 1-year survival rate is 24% [5]. While the 5-year survival rate is reported as 5% in patients with successful surgical resection, the median survival in locally advanced or metastatic disease is 6-11 and 2-6 months, respectively [6]. In addition, pancreaticoduodenectomy operations for pancreatic cancer have a morbidity rate of 40-50% and a mortality rate of 1-3%, even in experienced centers [7]. In elderly patients, pancreatic cancer is associated with higher perioperative mortality and morbidity rates, higher need for intensive care unit stay, and higher hospital readmission rates [8].
The increase in the average life expectancy, the increase in the incidence of pancreatic cancer with age, and the high mortality and morbidity of pancreatic surgery have made pancreatic surgery in elderly patients a contradiction. In our study, we aimed to evaluate the effect of advanced age on morbidity and mortality in pancreaticoduodenectomy operations.
Material and Methods
This retrospective study was conducted with the approval of the Institutional Review Board No. 2021-056. All study procedures were performed in accordance with local ethical standards and with the 1964 Helsinki Declaration and its amendments.
Patient selection and groups
The data of patients who underwent pancreaticoduodenectomy for a mass located in the head of the pancreas between 2012 and 2020 were reviewed retrospectively. Patients who did not receive neoadjuvant therapy, did not undergo portal vein resection and whose pathology results were adenocarcinoma were included in the study. The patients were divided into 3 groups according to their age. They were grouped as 60 years old and below, 60-80 years old and 80 years old and above. Patients aged 60 and below were named group 1, patients aged 60-80 years were named group 2, and patients aged 80 and over were named group 3.
Patients’ ages, genders, ASA (American Society of Anesthesiologists) scores, postoperative complications, early mortality, and length of stay in the service and intensive care unit were recorded. The most important parameter was postoperative complications, which were classified according to Clavien and Dindo. Those who died during hospitalization or within the first 30 days after discharge were considered as early mortality. Secondly, hospitalization times (intensive care and service times separately) and postoperative pathological stages were compared between the groups.
Preoperative preparation, surgical technique and postoperative follow-up Nutritional support was started for patients with low preoperative albumin value and it was aimed to have an albumin value of 3 g/dl and above. Preoperative low molecular weight heparin (1mg/kg Enoxaparin Sodium) was started in all patients, and prophylaxis was administered with preoperative 1st generation cephalosporin (Cefazolin 30mg/kg) to patients who did not receive routine antibiotherapy.
All patients were operated by the same experienced surgeons. Anastomosis type was preferred according to the characteristics of the pancreatic tissue and duct. The main bile duct was anastomosed to the jejunum with intermittent or continuous suture techniques. The pylorus was not preserved in all patients, and Braun anastomosis was added after gastrojejunostomy anastomosis.
Postoperatively, all patients were followed up according to a standard procedure. On the 1st, 3rd and 5th days, drain amylase was studied from both drains and leak staging was performed as defined by the pancreatic leak group in 2016 [9]. Oral feeding was started on the 3rd day in all patients who did not show any leakage. Antibiotics other than those recommended by infectious diseases were not given during discharge, and nutritional support with low molecular weight heparin was given to all patients.
Statistical analysis
The data were analyzed using SPSS software, version 23 (Chicago, IL). Descriptive data were expressed as mean±SD and compared using the one-way ANOVA. Categorical variables were expressed as percentages and compared using the Chi-square test. A p-value <0.05 was considered statistically significant.
Results
The data of all 153 patients who underwent pancreaticoduodenectomy in our clinic between 2012 and 2020 were reviewed retrospectively. The mean age of the patients was 65.7±12.2 years. Of the patients, 85 (55.6%) were male and 68 (44.4%) were female. The mean hospitalization day in the intensive care unit was 3.95±5.46 days, and the total hospitalization time (service and intensive care unit) was 12.89±8.13 days. When the ASA scores were evaluated, 38 (24.8%) of the patients were ASA I, 74 (48.4%) ASA II, 41 (26.8) ASA III. The morbidity assessment of the patients was performed according to the Clavien Dindo classification. Delayed gastric emptying (DGE), post-pancreatectomy hemorrhage, and POPF were classified based on the International Study Group of Pancreatic Surgery definitions [10-12]. Pancreatic fistula with antibiotic revision, wound infection, gastric emptying difficulty that did not require endoscopic intervention, respiratory distress that regressed with medical treatment, ileus that did not require postoperative surgical intervention, bleeding that did not require surgical or radiological interventional procedures, constituted Class II complications. In the treatment of these complications, if endoscopic, interventional or surgical intervention was required, it was noted that these patients had class 3 complications. It was noted that patients with organ failure had 4th class complications, and those who lost their lives during hospitalization or within the first 30 days after discharge due to postoperative complications were 5th class complications. Mortality was detected in 27 (17.6%) of the patients.
The patients were divided into 3 groups according to their age. Group 1 consisted of patients aged 60 years and younger (n:47, 30.7%), group 2 patients aged 60-80 years (n:82, 53.6%), group 3 patients aged 80 years and older (n: 24, 15.7%). The mean age was 51.6±7.27 years in the 1st group, 68.6±5.3 years in the 2nd group and 83.5±3.1 years in the 3rd group, and it was statistically significant (p:0.000). In the gender evaluation between groups, 24 (51.1%) of group 1 were male and 23 (48.9%) were female. In Group 2, there were 33 men (40.2%), 49 (59.8%) women, while in Group 3 there were 12 (50%) men and 12 (50%) women. No gender difference was found between the 3 groups (p: 0.530).
The mean total hospital stay of the patients was 11.09±6.85 days in group 1, 13.76±8.62 days in group 2 and 13.46±8.45 days in group 3, and there was no statistically significant difference (p:0.187). However, when the mean length of stay in the intensive care unit was evaluated, it was 2.96±5.12 days in group 1, 3.72±4.81 days in group 2 and 6.67±7.31 days in group 3; the difference was detected (p:0.021).
When ASA scores were examined, the number of ASA I patients in group 1 was 38 (80.9%) and ASA II patients were 9 (19.1%). There was no patient with an ASA score of III. In Group 2, there were no ASA I patients, and 64 (78%) of the patients were ASA II and 18 (22%) were ASA III. When group 3 was evaluated, only 1 (4.2%) of the patients were ASA II and 23 (95.8%) were ASA III. There was a statistically significant difference in ASA scores between the groups (p:0.000) (Table 1).
In the evaluation of morbidity between groups, morbidity was not observed in 66% (n:31) of group 1, 47.6% (n:39) of group 2 and 33.3% (n:8) of group 3. The highest rate of Clavien Dindo 2 complications was seen in the groups (17% in group 1, 31.7% in group 2 and 25% in group 3). In the evaluation of complications between groups, group 3 had the highest complication rate and it was found to be statistically significant (p: 0.021).
When mortality rates were examined, 5 (10.6%) patients in group 1, 12 (14.6%) in group 2, and 10 (41.7 %) patients in group 3 died during hospitalization or within the first 30 days after discharge. These rates were evaluated as statistically significant (p:0.003). When the causes of mortality were examined, 4 patients in group 1 died due to failure to control the pancreatic fistula, and 1 patient due to intra-abdominal sepsis developing without pancreatic fistula; In group 2, 7 patients with pancreatic fistula died, 2 patients with respiratory failure, 1 patient with bleeding, 1 patient as a result of uncontrollable biliary fistula, and 1 patient died after intra-abdominal infection that developed without pancreatic fistula that could not be controlled; In group 3, 6 patients died due to uncontrollable pancreatic fistula, 2 patients died due to respiratory failure, 1 patient died due to acute myocardial infarction, and 1 patient died after intra-abdominal infection that could not be controlled. Of the 27 patients, 17 (63%) died due to uncontrollable pancreatic fistula, 4 (14.8%) due to respiratory failure, 1 (3.7%) due to myocardial infarction, 1 (3.7%) due to aneurysmatic bleeding that could not be stopped by interventional radiology, 1 (3.7%) died due to uncontrolled biliary fistula, 2 (7.4%) died as a result of intra-abdominal infection and subsequent abdominal sepsis without fistula (Table 2).
Discussion
Pancreaticoduodenectomy surgery for pancreatic head masses has a high morbidity and mortality in the early period. In the long term, the 5-year survival is around 5% [13]. Considering the potential comorbidity risks in the elderly population, the application of this surgical procedure in the elderly population causes disagreements [14,15]. However, considering that the elderly population in the society will increase, the necessity of this surgical procedure should be investigated in the advanced elderly population [16]. In our study, we found higher rates of mortality and morbidity in the pancreaticoduodenectomy procedure in elderly patients compared to other age groups. Considering the increasing elderly population in the world, we found that surgical intervention with high comorbidities such as pancreaticoduodenectomy can be performed with higher mortality and morbidity risks compared to younger patients.
There was no statistically significant difference between the total hospital stay of the patients (p: 0.187). However, the length of stay in the intensive care unit was found to be significantly longer in the elderly patient group (p:0.021). This situation was in parallel with the increase in ASA score, which increased with age after comorbidities. However, although the length of stay in the intensive care unit was longer, no significant difference was found in the total length of stay (p: 0.187). It was determined that the hospitalization times in the service were not similar to the intensive care hospitalizations, but were shorter or the same. We think that the reason for the shorter or the same length of stay in the service and the longer length of stay in the intensive care unit may be the anxiety caused by comorbidity rather than the needs of the patients. We think that another factor affecting this situation is the long duration of intensive care unit stay before mortality in elderly patients with high mortality rate.
When early complications are evaluated according to the Clavien Dindo classification, they increase with age. This rate was 34% in the early age group, 52.4% in the middle age group and 66.7% in the elderly patient group. We think that this statistically significant (p: 0.021) situation is associated with a significant increase in the ASA score (p: 0.000) in parallel with the increase in age. In the study by Cerullo M et al., the increase in the ASA score and the increase in the incidence of gastrointestinal system surgical complications confirms this situation [17]. Like the morbidity rate, the mortality rate increases with age. Shahir MA et al. stated in their study, that this was the result of the increasing rate of comorbidity with age [18]. In our study, we found significantly higher mortality and morbidity rates in elderly patients compared to other age groups (p:0.003, p: 0.021). Andreas L. et al. evaluated the results of 722 patients and reported that pancreatic fistula was the most feared complication with a high mortality (40%) and morbidity rate [19]. In our study, we found that the most common cause of mortality and morbidity in all 3 groups was pancreatic fistula.
In the latest evaluations of the European Society of Medical Oncology (ESMO) and the National Comprehensive Cancer Network (NCCN, available at:https://www.nccn.org/guidelines/), which are among the international guidelines, surgical intervention is not considered as a contraindication in elderly patients. However, it has been emphasized that poor functional status may be a reason to avoid surgery. In the European Registration of Cancer Care (EURECCA) consortium guideline, it was determined that the best results would be obtained with tumor resection and chemotherapy in stage I-II pancreatic cancer patients over 70 years of age [20]. There are studies indicating that minimal inflammatory response and early-term results are positively affected in this group, which has high comorbidity with minimally invasive techniques. However, it has been recommended to be done by experienced teams [21]. In our study, we found that the stage of pancreatic cancer did not increase with age, like other parameters, and age had no effect on the stage of pancreatic cancer (p:0.592). This supports that technical difficulties of surgical procedures do not increase in elderly patients. However, the patient should be evaluated as a whole and the treatment should be individualized. V. Lopez et al. showed that advanced surgical procedures have increased mortality and morbidity in patients over 80 years of age [22], and this result was in line with our study. Considering the increase in advanced age and the number of elderly patients, this problem is growing day by day. However, we think that oncological treatments to be developed will be effective in solving this problem. However, we think that today, in advanced elderly patients with worse condition, preoperative preparation and controlling the diseases that cause comorbidity, and surgeries with high mortality and morbidity such as pancreaticoduodenectomy can be performed by experienced clinics.
This study has some limitations. First of all, the retrospective nature of the study, the small number of patients, the fact that the patients were not grouped according to their comorbidities, and the patients who were given preoperative nutritional support were not included in a separate group or excluded from the study.
Conclusion
The incidence of pancreatic cancer patients with high mortality and morbidity rates with the increase in life expectancy will increase gradually in the elderly population. In our study, we found that age further increases mortality and morbidity in pancreaticoduodenectomy surgery. We found that this situation was caused by the increase in the ASA scores of the patients with age. We think that pancreaticoduodenectomy surgery can be performed in elderly patients by considering the existing mortality and morbidities by experienced clinics after appropriate preoperative preparation.
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.
Funding: None
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.
References
1. Osman C, M Burc Y. Evaluation of long-term oncological outcomes of colon cancer resections in octogenarian and nonagenarian patients Annals of Medical Research. 2020;27(1):755-9
2. Urvaylıoğlu AE, Gedik E. Investigatıon of the social policies in terms of elderly health. Akademik Hassasiyetler. 2021;8(16): 265-82.
3. Pilleron S, Sarfati D, Janssen-Heijnen M, Vignat J, Ferlay J, Bray F, et al. Glo bal cancer incidence in older adults, 2012 and 2035: A population-based study. Int J Cancer. 2019;144(1):49-58.
4. Rahib L, Smith BDS, Aizenberg R, Rosenzweig A B, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014; 74(11):2913-21
5. Rawla P, Sunkara T, Gaduputi V. Epidemiology of Pancreatic Cancer: Global Trends, Etiology and Risk Factors. World J Oncol. 2019;10(1):10-27.
6. Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer Lancet. 2011;378(9791):607-20.
7. Mogal H, Vermilion SA, Dodson R, Hsu FC, Howerton R, Shen P, et al. Modified Frailty Index Predicts Morbidity and Mortality After Pancreaticoduodenectomy. Ann Surg Oncol. 2017; 24(6): 1714–21.
8. Park HM, Park SJ, Han SS, Kim, SH. Surgery for elderly patients with resectable pancreatic cancer, a comparison with nonsurgical treatments: a retrospective study outcomes of resectable pancreatic cancer BMC Cancer. 2019;19(1):1090.
9. Bassi C, Marchegiani G, Dervenis C, Sarr M, Hilal MA, Adham M, et al. Surgery The 2016 update of the International Study Group (ISGPS) definition and grading of postoperative pancreatic fistula: 11 Years After 2017 Surgery. 2017;161(3):584-91.
10. Wente MN, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, Izbicki JR, et al. Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS) Surgery. 2007;142(5):761-8.
11. Wente MN, Veit JA, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, et al. Postpancreatectomy hemorrhage (PPH): an International Study Group of Pancreatic Surgery (ISGPS) definition Surgery. 2007;142(1):20-5.
12. Baker MS, Sherman KL, Stocker SJ, Hayman AV, Bentrem DJ, Prinz RA, et al. Using a modification of the Clavien-Dindo system accounting for readmissions and multiple interventions: defining quality for pancreaticoduodenectomy. J Surg Oncol. 2014;110(4):400-6.
13. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet‐Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87-108.
14. Beltrame V, Gruppo M, Pastorelli D, Pedrazzoli S, Merigliano S, Sperti C, et al. Outcome of pancreaticoduodenectomy in octogenarians: Single institution’s experience and review of the literature. J Visc Surg. 2015;152(5):279-84.
15. Adham M, Bredt LC, Robert M, Perinel J, Lombard-Bohas C, Ponchon T, et al. Pancreatic resection in elderly patients: should it be denied? Langenbecks Arch Surg. 2014;399(4):449-59.
16. Riall TS. What is the effect of age on pancreatic resection? Adv Surg. 2009;43(1):233-49.
17. Cerullo M, Gani F, Chen SY, Canner JK, Yang WW, Frank SM, et al. Physiologic correlates of intraoperative blood transfusion among patients undergoing major gastrointestinal operations. Surgery. 2017;162(2):211-22.
18. Shahi MA, Lemmens VEPP, Van de Poll-Franse LV, Voogd AC, Martijn H, Janssen-Heijnen MLG. Elderly patients with rectal cancer have a higher risk of treatment-related complications and a poorer prognosis than younger patients: a population-based study. Eur J Cancer. 2006;42(17):3015-21.
19. Luu AM, Krasemann L, Fahlbusch T, Belyaev O, Janot-Matuschek M, Uhl W, et al. Facing the surgeon’s nightmare: Incidence and management of postoperative pancreatic fistulas grade C after pancreaticoduodenectomy based on the updated definition of the International Study Group of Pancreatic Surgery (ISGPS). J Hepatobiliary Pancreat Sci. 2020;27(4):171-81.
20. Groen JV, Douwes TA, van Eycken E, van der Geest LG, Johannesen TB, Besselink MG, et al. Treatment and Survival of Elderly Patients with Stage I–II Pancreatic Cancer: A Report of the EURECCA Pancreas Consortium. Ann Surg Oncol. 2020;27(13):5337-46.
21. Hendi M, Mou Y, Lu C, Pan Y, Zhang B, Chen K, et al. Laparoscopic pancreaticodoudenectomy: An excellent approach in elderly patients, a multicenter, comparative study Laparoscopic pancreaticodoudenectomy An excellent approach in elderly patients, a multicenter, comparative study Medicine (Baltimore). 2020;99(38):e22175.
22. Lopez-Lopez V, Gómez-Ruiz AJ, Eshmuminov D, Cascales-Campos PA, Alconchel F, Arevalo-Perez J, et al. Surgical oncology in patients aged 80 years and older is associated with increased postoperative morbidity and mortality: A systematic review and meta-analysis of literature over 25 years. Surg Oncol. 2020;33:81-95.
Download attachments: 10.4328:ACAM.21078
Orhan Aras, Rıdvan Yavuz, Hüseyin Çiyiltepe, İsmail Gömceli. Do complications of pancreatic cancer surgical treatment change in the aging world? Ann Clin Anal Med 2022;13(3):345-349
Citations in Google Scholar: Google Scholar