November 2022
Psychological effects of the COVID-19 pandemic on healthcare professionals
Elif Dilara Durmaz 1, Muhammed Arca 1, Süleyman Dönmezdil 2
1 Department of Physiotherapy and Rehabilitation, 2 Department of Psychology, Health Sciences University Gazi Yaşargil Training and Research Hospital, Diyarbakır, Turkey
DOI: 10.4328/ACAM.21184 Received: 2022-04-13 Accepted: 2022-06-08 Published Online: 2022-10-11 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1180-1185
Corresponding Author: Muhammed Arca, Department of Physiotherapy and Rehabilitation, Health Sciences University Gazi Yaşargil Training and Research Hospital, Diyarbakır, Turkey. E-mail: muhammedarca.edu@gmail.com P: +90 534 267 30 23 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8104-4985
Aim: In this study, we aimed to investigate anxiety, depression, and sleep problems in healthcare professionals during the pandemic.
Material and Methods: This descriptive and cross-sectional study was conducted with the staff of Diyarbakır Gazi Yaşargil Training and Research Hospital. A total of 170 people were reached for the research. The data collected by the on-line survey method consisted of demographic questions, questions about behavior change due to COVID-19, Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire (PHQ-9), and Insomnia Severity Index (ISI).
Results: It was found that 72.9% of the healthcare professionals had anxiety, 83.5% had depression, and 87.1% had sleep problems. The total score of the GAD-7 scale was found to be significantly higher in those who used personal protective equipment (p=0.021) and those who received infection training (p<0.001). The PHQ-9 scale total score was higher in those 35 years of age and older (p=0.019) and college graduates (p=0.023). The total score of the insomnia severity scale (ISI) was significantly higher in individuals aged 35 years and older (p=0.040), in college graduates (p=0.049), and single/divorced (p=0.009). A significant difference was found between gender, occupation, smoking, fear of infection, burnout status, and total scores on all three scales (p<0.05).
Discussion: Healthcare professionals were found to have high levels of anxiety, depression, and sleep problems. Anxiety, depression, and insomnia problems were higher in women, health technicians, smokers, those with fear of infection, and those with burnout.
Keywords: Anxiety, Coronavirus, Burnout, Depression, Insomnia
Introduction
The COVID-19 (coronavirus disease 2019) pandemic is a global crisis that causes unprecedented changes in our lives. This infectious disease is a newly recognized coronavirus, SARS-CoV-2-induced respiratory infection [1]. Common symptoms of infection are fever, cough, muscle aches, and dyspnea. In more severe cases, pneumonia, severe acute respiratory tract infection, and even deaths may occur [2].
The COVID-19 pandemic is accompanied by psychiatric symptoms and emotional problems that emerge as fear, anxiety, panic, insecurity, and intense stress, which we can define as ‘psychological pandemics’. Healthcare professionals fight the disease on the front lines by risking their lives in all pandemics. Physicians, nurses, and all other assistant health workers working in all health institutions are exposed to the stress of epidemics at the highest level and try to cope with their psychological consequences for a long time [3].
Healthcare professionals face great pressure in the COVID-19 pandemic due to contact with cases, high risk of infection, inadequate protection, lack of experience in disease management. These factors increase the incidence of long-term psychological problems among healthcare professionals, such as fear, anxiety, depression, and insomnia, affecting job efficiency and well-being [4]. It was reported that the rates of insomnia (34% -36%), anxiety (45%), and depressive symptoms (50%) experienced by healthcare professionals during the pandemic were high [5].
In this period, it is vital to understand more comprehensively the psychological burden among healthcare professionals, improve mental health support services, and strengthen mental health services worldwide [6]. This cross-sectional study aimed to investigate the prevalence of psychological problems in different healthcare professionals during the COVID-19 outbreak and determine the effects of demographic characteristics associated with various psychological problems.
Material and Methods
The population of this descriptive and cross-sectional study consisted of staff members of the Health Sciences University Diyarbakır Gazi Yaşargil Training and Research Hospital. The research field study was carried out by online survey method after obtaining permission from the ethics committee (Health Sciences University Diyarbakır Gazi Yaşargil Education and Research Hospital Non-invasive Clinical Research Ethics Committee) and institutional permission. The voluntary basis was taken into consideration in participating in the study, and the participants who did not volunteer to participate in the study were asked not to fill out the questionnaire forms and not take into account the incoming message.
The number of active employees recruited from the hospital staff is 2270 (doctors, nurses, midwives, health officers, physiotherapists, psychologists, dieticians, laborants, health technicians). When the sample size was calculated over 2270 people, it was aimed to reach 187 people while the study’s power was 95%, d: 3% error and the expected average in terms of the variable examined was 5%. A message was sent to the whole sample, and a total of 170 people answered the questionnaire (Response rate: 90.9%).
Volunteers aged 18-65 years without any illness (psychosis, dementia, delirium) that would impair mental balance were included in the study. Those who did not want to participate voluntarily and did not comply with these conditions also constituted the exclusion criteria.
Data collection tools
The questionnaire consists of 5 sections: demographic questions, behavioral change questions due to COVID-19, Generalized Anxiety Disorder, The Patient Health Questionnaire, and Insomnia Severity Index. Demographic questions are available in the first part of the questionnaire form. In the second part of the questionnaire, healthcare professionals were asked questions about the perceived behavior change in their hygiene and social habits after COVID-19. The answers to these questions were scored as ‘I don’t know =0 points’, ‘unchanged=1 point’, ‘slightly changed=2 points’, ‘moderately changed=3 points’, and ‘too much changed=4 points’. The scores ranged from 0 to 28. The relevant scales were also used in the rest of the questionnaire.
Generalized Anxiety Disorder-7 (GAD-7) Test
The Generalized Anxiety Disorder Assessment (GAD-7) is a seven-item instrument. The scale was developed by Spitzer et al. according to DSM IV-TR criteria to evaluate generalized anxiety disorder [7]. Konkan et al. conducted Turkish validity and reliability studies of the scale [8]. Likert-type scale (0=none, 1=many days, 2= more than half of the days, 3=almost every day) was ranked on the 4-level ordinal scale. The scores that can be obtained from the scale are between 0 and 21. The total scores obtained from the scale are the cut-off points for mild, moderate, and severe anxiety as 5, 10, and 15, respectively.
Patient Health Questionnaire-9
The PHQ-9 is a questionnaire prepared for screening depression in administered individuals. This questionnaire consists of a total of nine items questioning the diagnosis of depressive disorder. The scale was developed by Spitzer et al. [9]. Validity and reliability studies in Turkish were conducted by Sarı et al. [10]. Answers are scored as “None”, “A few days”, “More than a week,” and “Almost every day”, with a minimum score of 0 and a maximum score of 3. Scores 1-4 mean no depression, 5-9 mean mild depression, 10-14 mean moderate depression, 15-19 mean partially severe depression, and 20-27 mean severe depression.
Insomnia Severity Index
This scale, which has been found to be valid and reliable tool in Turkish by Boysan M et al. [11], was developed by Morin et al. [12]. This scale is a measurement tool with proven validity and reliability and has practical use in assessing insomnia. It consists of seven questions, and a score of 0-4 is given for each item. The maximum score that can be obtained on the scale is 28. The results are evaluated as clinically insignificant insomnia between 0-7 points, insomnia between 8-14 points, clinical insomnia between 15-21 points, moderate severity between 22-28 points, severe clinical insomnia.
Statistical Analysis
SPSS 22.0 statistical package program was used in the analysis of the data. Descriptive values were indicated by number, percentage, and mean ± standard deviation. Normality analysis of the measuring data was performed using the Kolmogorov-Smirnov test. Student t-test was used to compare the binary groups in the data that fit the normal distribution, and the one-way ANOVA test was used to compare more than two groups. Post-hoc analysis was performed to find out where the difference originated in the triple groups. Multiple regression analysis was performed to compare quantitative data, and p<0.05 was accepted as statistical significance in all analyzes.
Results
Females accounted for 54.7% of the healthcare professionals, 84.7% were university graduates, and 51.8% were married; 48.2% of the participants were nurses/midwives/health officers, 25.3% were physiotherapists/dieticians/psychologists/laborants, 17.1% were doctors, and 9.4% were health technicians. While 68.8% of the employees were non-smokers,, 95.9% have not received any psychiatric treatment so far. While 74.1% of healthcare professionals experienced fear of becoming infected due to the disease, 80% experienced burnout in this process (Table 1). The mean age of the employees was 31.51±6.60 (min=22, max=64) years.
Anxiety (GAD-7≥5) was detected in 72.9% of the employees, depression (PHQ-9≥5) in 83.5%, and sleep problems (ISI≥8) in 87.1% of the employees (Figure 1).
The total score of the GAD-7 scale was found to be significantly higher in those who used personal protective equipment (p=0.021) and those who received infection training (p<0.001). The PHQ-9 scale total score was higher in those aged 35 years and older (p=0.019) and college graduates (p=0.023). The total score of the ISI scale was significantly higher in those aged 35 years and older (p=0.040), in college graduates (p=0.049), and single/divorced (p=0.009). A significant difference was found between gender, occupation, smoking, fear of infection, and burnout status and the total scores on all three scales (p<0.05) (Table 2).
A low level of significant correlation was found in the multiple regression model between anxiety and gender, occupation, smoking, fear of infection, receiving infection training, and burnout (R2=0.22, p<0.001). These variables explain 22% of the total variance for anxiety, and the order of importance of the variables was determined as burnout, receiving infection training, occupation, and fear of being infected.
A low level of significant correlation was found between depression and age, gender, education, occupation, smoking, fear of infection, receiving infection training, and burnout (R2=0.21, p<0.001). These variables explain 21% of the total variance for depression, and the order of importance of the variables was determined as burnout, smoking, fear of infection, gender, and receiving infection training.
A low level of significant relationship was found between insomnia and age, gender, education, occupation, smoking, fear of infection, receiving infection training, and burnout (R2=0.20, p<0.001). These variables explain 20% of the total variance for depression, and the order of importance of the variables was determined as fear of infection, gender, burnout, and smoking (Table 3).
The responses of healthcare professionals to behavioral questions related to COVID-19 are shown in Figure 2. The behavior of healthcare professionals regarding avoiding handshakes (75.3%) and avoiding people with symptoms (66.5%) has changed significantly.
Discussion
While the COVID-19 outbreak has become one of the biggest public health problems seen globally in recent years, it has also severely impacted the health communities. Being under the risk of infectious disease, fear, stress, and intense workload of healthcare professionals may negatively affect their work by reducing their concentration. For this reason, it is essential to evaluate the depression, anxiety, and insomnia problems that employees may experience.
In the first study evaluating psychological factors among healthcare professionals in Turkey, the prevalence of anxiety, depression, and insomnia was 77.6%, 60.2%, and 50.4%, respectively [13]. In a similar study conducted on healthcare professionals in Italy, Rossi et al. reported 8.3% (GAD-7≥15), 24.7% (PHQ-9≥15), and 21.9% (ISI≥22) [14]. In a study evaluating mental health among healthcare professionals in China, it was reported that they found 44.6% (GAD-7≥5) for anxiety, 50.4% (PHQ-9≥5) for depression, and 34.0% (ISI≥8) for insomnia [3]. In our study, the prevalence of anxiety, depression, and insomnia of healthcare professionals was 74%, 83.5%, and 87.1%, respectively. Although the evaluation purposes and the use of the same scale are different, similar results have been obtained in many studies. The values we have found reveal that the situation is getting worse.
Our study found that the relationship between the age variable and depression and insomnia values in healthcare professionals increased significantly. However, age has lost its effect on both depression and insomnia in the multiple regression models. In a study published in China, young (<35 years) healthcare professionals were more likely to develop depressive symptoms and insomnia problems during the COVID-19 outbreak than older participants (≥ 35 years) [15].
In our study, anxiety, depression, and insomnia symptoms were statistically higher in female health workers than in males. Lai et al. demonstrated the effect of gender and stated that women experienced more severe symptoms of depression, anxiety, and insomnia [3]. Zhang et al. found that female gender was one of the most common risk factors for insomnia, anxiety, obsessive-compulsive symptoms, and depression [16]. Biological gender differences, culture, diet, and hormonal changes in women may contribute to higher anxiety, depression, and insomnia rates.
In our study, health technicians’ anxiety, depression, and insomnia symptoms were found to be statistically higher than all other employees. In their study, Que et al. reported that technicians had high psychological problems (anxiety, depression, insomnia, and general psychological problems) [17]. In our study, health technicians had high rates in terms of symptoms because technicians are employed in different places. When nurses and doctors who had to work on the front line in our study were evaluated in terms of these symptoms, the nurses had higher rates than doctors. Zhang et al. found that the risk of insomnia increased in nurses and that being a physician was a protective factor against insomnia [18]. This may be related to the fact that nurses with higher disease sensitivity had a higher workload and a higher risk of direct exposure to COVID-19 patients than doctors.
In our study, the anxiety, depression, and insomnia values of smokers were significantly higher than in those who did not smoke. In multiple regression models, smoking was found to affect depression and insomnia symptoms significantly. Que et al. reported that the occurrence of insomnia symptoms in smokers was 1.7 times higher than in non-smokers [17]. Obviously, smoking, as a tool for relaxation, has no effect on solving psychological problems.
In our study, anxiety, depression, and insomnia symptoms of healthcare professionals who feared being infected were statistically higher than those who did not experience this fear. A study conducted in China found that the rate of anxiety development increased 2.3 times in healthcare professionals due to fear of infection [18]. Zhao et al. reported that the risk of exposure to COVID-19 was significantly associated with anxiety, depression, and insomnia in healthcare professionals [19]. In our study, high anxiety and depression in those who stated that their personal protective use was low may also be related to the development of fear of being infected by their patients.
Influential factors in reducing psychological distress during the pandemic process include knowing infectious diseases and implementing infection control rules. In our study, inadequate training on infectious diseases and pandemics, and inadequate knowledge, significantly increased anxiety and depression values. Zhang et al. reported that extreme uncertainty about inadequate education and disease control of infectious diseases resulted in higher depressive and anxiety symptoms scores in their study [18].
Prolonged pandemics are associated with mental health disorders such as anxiety, depression, and burnout. In our study, anxiety, depression, and insomnia were significantly higher in healthcare professionals who stated that they experienced burnout than in those who did not. Burnout was found to have a significant effect on all three scales in the multiple regression models. Tan et al. reported a significant relationship between anxiety and depression scores and higher burnout scores [20]. In their study, Hu et al. reported that approximately half of the nurses with high anxiety levels experienced moderate and high job burnout levels, as shown in emotional exhaustion, depersonalization, and personal success [21]. Increased interaction with patients, accompanying emotional exhaustion intensity, and psychological difficulty may lead to burnout symptoms in employees.
Adherence to the guidelines recommended by the Centers for Disease Control and Prevention (CDC) increases the safety of healthcare professionals. As in the general population, it is critical to comply with the published protection measures and develop appropriate behaviors (available at: https://www.cdc.gov/coronavirus/2019-ncov/infection-control/control-recommendations.html). A study conducted in Uganda reported that 74% of healthcare professionals had good practice behaviors against COVID-19 [22]. Our study determined that the behaviors changed in general, and the related measures increased. Healthcare professionals generally exhibit good practices in attitudes and behaviors in case of disease prevention and infection.
Limitations
This study has some limitations. This was a cross-sectional online survey that did not represent the sample well. Causal relationships should be interpreted carefully. The number of doctors, nurses, and health technicians participating in this survey was limited, limiting the generalizability of the findings. The results were based on self-reported surveys investigating psychological problems.
Conclusion
During the COVID-19 outbreak in Turkey, healthcare professionals experience high anxiety, depression, and insomnia. Female gender, working as a nurse and health technician, smoking, fear of infection, and burnout were identified as significant risk factors for various mental health problems.
Considering past outbreaks, training and psychiatric support of high-risk healthcare professionals during and after the pandemic should be increased to be prepared for current and future events.
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.
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Elif Dilara Durmaz, Muhammed Arca, Süleyman Dönmezdil. Psychological effects of the COVID-19 pandemic on healthcare professionals. Ann Clin Anal Med 2022;13(11):1180-1185
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How do marital adjustment and quality of life affect infertile couples? A hospital-based study
Sevilay Salur 1, Ruhusen Kutlu 1, Hüseyin Görkemli 2
1 Department of Family Medicine, 2 Department of Obstetrics and Gynecology, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey
DOI: 10.4328/ACAM.21234 Received: 2022-05-18 Accepted: 2022-08-04 Published Online: 2022-08-05 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1186-1190
Corresponding Author: Ruhusen Kutlu, Department of Family Medicine, Meram Medical Faculty, Necmettin Erbakan University, 42080, Konya, Turkey. E-mail: ruhuse@yahoo.com P: +90 332 223 66 01 F :+ 90 332 223 61 81 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8502-0232
Aim: In this study, it was aimed to evaluate marital adjustment and quality of life in infertile couples and to determine on which issues they need support.
Material and Methods: This cross-sectional analytical study was conducted on 222 individuals receiving or planning to receive infertility treatment. Quality of life (QoL) was evaluated with the “ Fertility Quality of Life questionnaire (FertiQol)” and marital adjustment was evaluated with the “Marital Adjustment Scale”.
Results: It was determined that 21.6% (n=48) of the participants were incompatible in marriage, and 78.4% (n=174) were compatible in marriage. Marital adjustment was statistically better in those who were younger (p=0.017), those with a short time of marriage (p=0.004), and those with a short treatment period (p=0.003). A moderately positive and statistically significant correlation was found between the marital adjustment score and the total FertiQol score (r=0.456) (p<0.001).
Discussion: It was observed that marital adjustment and quality of life decreased as the years of marriage increased and the duration of treatment extended. QoL was found to be significantly higher in couples with good marital adjustment. Psychological counseling and support should be given to infertile couples receiving treatment, especially women, and the importance of couples’ support to each other should be emphasized.
Keywords: Marital Adjustment, Infertility, Infertile Couples, Quality of Life
Introduction
Infertility is a male or female reproductive system disease characterized by the absence of clinical pregnancy for 12 months without the use of any family planning method and regular sexual intercourse. It is estimated that 8% to 12% of couples worldwide suffer from it [1-3]. Common factors that cause infertility in both genders are environmental and lifestyle factors such as smoking, excessive alcohol intake and obesity. At the same time, exposure to environmental pollutants and toxins can be directly toxic for oosit and sperm, and this may result in infertility since it reduces the numbers and causes poor quality [4,5].
In a study conducted by Gulec et al. (2011) in our country, it was reported that infertile couples have problems in marital adjustment, and that no significant relationship was found between marital adjustment and sociodemographic characteristics in women and men [6]. In some studies, it was reported that couples receiving treatment perceive the diagnosis and treatment of infertility as a threat, and this perception brings the couples closer to each other, and their marital adjustment increases [7,8]. The ways of coping with infertility of men and women have different results on marital adjustment. Improvement in communication and marriage of the spouses increases as the interest and participation of men in infertility treatment increases [9]. When evaluating the quality of life in infertile couples, studies generally show results that support each other. Infertility is not a life-threatening health problem, but it has negative effects on the quality of life and mental health of individuals. Infertility affects both genders emotionally, but it is reported that the incidence of anxiety and depression is higher in females than males [10].
If the stress levels and psycho-social problems of the couples are addressed and appropriate treatments are developed, the quality of life of the couples and the success of the treatment can be increased. It was observed that the treatment is more successful in couples with high marital adjustment and quality of life. For this reason, in this study, it was aimed to evaluate marital adjustment and quality of life in infertile individuals and to determine on which issues they need support.
Material and Methods
Type of study, place and population
This study was planned as a descriptive and cross-sectional analytical study. The population of the study consisted of patients who applied to Necmettin Erbakan University Meram Medical Faculty, Department of Obstetrics and Gynecology, In Vitro Fertilization (IVF) Center and Infertility Polyclinic for infertility treatment between 01.04.2021 and 15.06.2021. In previous studies, the incidence of infertility in our country was found to be 15%. Since the number of individuals in the population was not known in our study, the number of subjects to be included in the study was calculated as at least 196 infertile patients using the formula n=t².p.q/d². However, the study was completed with 222 participants by adding 10% share due to the possibility of incomplete filling in the survey questions and refusal to participate in the study.
Exclusion criteria
1) Secondary infertile couples
2) Presence of severe psychiatric disease
3) Those whose native language is not Turkish
Ethics committee approval and consent
Necmettin Erbakan University Meram Medical Faculty ethics committee approval was obtained before starting the study (2018/1623 Date: 21.12.2018). Verbal and written consents were obtained from the individuals in accordance with the principles of the Declaration of Helsinki.
Collection of Data
Questionnaires were filled by the researcher using face-to-face interview technique. In the first part of the questionnaire, there were questions to determine the demographic characteristics of the participants. In the second part, quality of life was evaluated with the “The Fertility Quality of Life questionnaire (FertiQol)” and marital adjustment was evaluated with the “Marital Adjustment Scale”.
Marital Adjustment Scale
“Marriage Adjustment Scale”, which was used to measure marital adjustment in the study, was developed by Locke et al. (1959) [10], and its validity and reliability study in our country was performed by Tutarel-Kıslak (1999) [11]. There are a total of 15 items in the scale and the possible scores range from one to 60. High scores indicate marital adjustment, and low scores indicate marital maladjustment. In the present study, the Cronbach’s alpha value of the Marital Adjustment Scale total score was found to be 0.832.
Fertility Quality of Life Scale for people with fertility problems (FertiQol)
FertiQol is ‘Fertility Quality of Life Scale for People with Fertility Problems’ scale developed by Boivin et al. (2011) with 36 questions [12]. Turkish internal reliability study was developed by Cetinbas et al. (2014) [13], and this scale evaluates the quality of life with 36 questions, including core 24 items, 10 items related to treatment, 2 items related to whole life and physical health. There are four subscales in the core part of the FertiQol scale, which consists of 24 questions. These are emotional, mind-body, relational, and social subscales. Each subscale consists of six questions. There are two subscales in the treatment section, and these are treatment environment and treatment tolerance subscale. A higher score means a higher quality of life. To calculate scale scores for the subscale and total scales, the raw score is multiplied by 25/k; k is the number of items in the subscale here. The scale score ranges between 0 and 100 [12]. In the present study, Cronbach’s alpha value of FertiQol total score was found to be 0.874.
Statistical analysis of data
The data were evaluated with the Statistical Package for the Social Sciences (SPSS) 22.0 statistical package program. Frequency and percentage, mean value, standard deviation, highest and lowest values were used for descriptive statistics in statistical analysis. Chi-square test was used for statistical analysis of categorical data, independent t-test was used in paired groups for the data conforming to normal distribution for statistical analysis of quantitative data, One Way ANOVA test (post hoc Tukey test) was used in groups of three or more.
Results
Of the 222 participants in the study, 78.4% (n=174) were female and 21.6% (n=48) were male. The mean age of female participants was 31.22±6.02 (min: 20, max: 46) years, and the mean age of male participants was 34.91±7.03 (min:24, max:53) years. It was determined that 45.0% (n=100) of the participants covered the treatment costs themselves and 69.4% (n=154) received emotional support from their families. When the cause of infertility is examined, 25.7% (n=57) of males, 36.0% (n=80) of females, 22.5% (n=50) of both genders, 15.8% of unknown causes were due.
The mean marital adjustment score was found to be 48.59±8.10 (min:21 max:60). When those who scored below 43 in the marital adjustment questionnaire were considered incompatible in marriage, and those who scored 43 and above were considered as compatible, it was determined that 21.6% (n=48) were incompatible in marriage and 78.4% (n=174) were compatible. The marital adjustment of the participants was statistically better in those with younger age (p=0.017), in those with a short marriage year (p=0.004), and those with a short treatment period (p=0.003). There was no statistically significant relationship between cause of infertility and marital adjustment (p=0.459). The mean total quality of life score of the participants in the study was found to be 67.66±15.38 (min:20.59 max:93.38). A statistically significant relationship was found between gender and quality of life emotional sub-dimension score (p=0.029), mind-body sub-dimension score (p=0.038), and treatment tolerance sub-dimension score (p=0.032). Table 1 shows the comparison of quality of life sub-dimensions according to sociodemographic characteristics.
No statistically significant correlation was found between the total score of quality of life and sub-dimension scores and the location of residence, disease, and family type. There was a statistically significant relationship between economic status and mental sub-dimension score (p=0.018 ab), social sub-dimension score (p=0.033), treatment environment sub-dimension score (p=0.047 ab), total FertiQol score (p=0.035 ab). A statistically significant relationship was found between the duration of marriage and the relational sub-dimension score (p=0.000), treatment tolerance sub-dimension score (p=0.025), and total FertiQol score (p=0.029). Relational sub-dimension score, treatment tolerance sub-dimension score, and total FertiQol score were found to be higher in couples with less than 5 years of marriage. A significant relationship was found between treatment duration and relational sub-dimension score (p=0.010), treatment tolerance sub-dimension score (p=0.021), and total FertiQol score (p=0.016). Relational sub-dimension score, treatment tolerance sub-dimension score and total FertiQol score were found to be higher in patients whose treatment duration was less than 3 years. A significant relationship was found between previous treatment method use and treatment tolerance sub-dimension score (p=0.026). The treatment tolerance sub-dimension score was found to be higher in patients who did not use any treatment method before. Table 2 shows the comparison of quality of life/marriage age, duration, adjustment, and treatment-related characteristics.
A significant relationship was found between the cause of infertility and emotional sub-dimension score (p=0.004 bd p=0.010 cd), social sub-dimension score (p=0.028 bd, p=0.031 cd), total FertiQol score (p=0.026 bd, p=0.024 cd). Emotional sub-dimension, social sub-dimension, and total FertiQol score were found to be significantly higher in unexplained infertility, especially compared to female-induced infertility and infertility of both genders (Table 3).
Discussion
It was observed that marital adjustment and quality of life directly or indirectly affect the results of the treatment in couples undergoing infertility treatment. Infertility affects both couples and its impact on the marital relationship may vary depending on personal coping methods and communication between spouses participating in the treatment. The ways in which men and women cope with infertility affect marital adjustment and the consequences of infertility on marriage. When the literature was examined, it was seen that there were few studies, which examine “marriage adjustment and quality of life” together. In the present study, we think that this study will contribute to the literature because of the detailed examination of the subscores of quality of life and the marital adjustment scale.
When the literature was examined, it was seen that there were conflicting situations reporting positive or negative results of infertility on marital adjustment. It has been reported that infertility brings couples closer together and has positive effects on their marital relations. In these studies, it was stated that the stress and disappointment experienced by infertile couples increase the harmony between couples and contribute to the development of the marital relationship [4,7]. In some studies, infertility itself, and also assisted reproductive techniques can cause sexual dysfunction, depression, anxiety and deterioration in relationships by consuming their physical and emotional energies, and can challenge the coping skills and social support resources of the couple [3,4]. It has been observed that the more men can help their wives to communicate and cope with their stress, the higher their marital adjustment will be [9]. In the present study, it was determined that marital adjustment decreased as age, year of marriage and duration of treatment increased. There was no significant relationship between marital adjustment and gender, education level, occupation, employment status, location of residence, economic status, marriage type, spouse’s education level, spouse’s employment status. In the study conducted by Bodur et al., no relationship was found between the duration of marriage, the duration of infertility, the duration of treatment and anxiety and depression levels [14]. In the study by Halici and Saatci, it was determined there was no significant relationship between marital adjustment and age, marriage age, duration of marriage, education level, spouse’s education, occupation, family structure; and a significant relationship was found between the participants’ previous treatment for infertility, being in employment and being well adjusted in marriage [15]. The detection of significantly higher anxiety and depression in infertile women compared to fertile women may explain the deterioration in marital relations in infertile women. As the income level of both genders increases, marital adjustment increases as well [14,16].
There are also studies reporting that marital adjustment and marital satisfaction do not change depending on fertility [17]. It was reported in some studies that the increasing support of couples undergoing infertility treatment improves their marital adjustment [7]. It was observed that approximately half of the people in the present study have a postgraduate education level. While some of the results in the literature are similar to this study, some of them differ. In the study conducted by Aarts et al., it was stated that 42% had a higher education level [18].
It was observed that a quarter of the participants had male infertility, more than one third of them had female infertility, less than a quarter had infertility resulting from both genders, and approximately one fifth had infertility of unknown cause. In the study by Pedro and Çelik, consistent with this study, it was observed that infertility was mostly caused by women and it was the least unexplained infertility [19]. In the study conducted by Van Empel et al., it was stated that 37% had an unexplained cause of infertility [20]. This situation can be explained by the progress of the examinations and the increase in diagnoses.
There are many studies examining the effect of infertility on the quality of life of couples, and these studies in the literature generally support each other [21]. It is thought that the diagnosis and treatment of infertility may lead to deterioration in the quality of life among couples [17]. In this study, while there was no difference in general quality of life between the genders, it was shown that women had a lower quality of life in terms of emotional sub-dimension, mind-body sub-dimension, and treatment tolerance sub-dimensions. Likewise, in the study conducted by Bolsoy, it was stated that the quality of life of women was lower than that of men [21].
In the study by Karabulut et al., general quality of life, mind-body sub-dimension, social sub-dimension, and treatment tolerance sub-dimension were found to be high in infertile couples treated for less than 5 years [22]. In the study by Çetinbaş, it was found that quality of life scores decreased as the duration of infertility increased [13]. In the study by Çağlar, the quality of life was found to be low in couples with unexplained infertility [23]. In this study, it was observed that the total quality of life score, relational sub-dimension score, and treatment tolerance sub-dimension score decreased as the duration of marriage and treatment increased.
A limitation of the present study is that although the sampled hospital was one of the largest in Konya, the participants in this study were relatively limited to the small number of couples presenting to the clinic for treatment. The most important limitation was that it was performed in a single center and there was no control group consisting of fertile couples. Therefore, the participants of this study were not representative of all infertile couples.
Conclusion
The relational sub-dimension score, treatment tolerance sub-dimension score, and total FertiQol score were found to be higher in couples with a marriage duration of less than 5 years and a treatment period of less than 3 years. FertiQol quality of life score and sub-dimension scores were found to be significantly higher as marital adjustment increased. Psychological counseling and support should be given to people who receive infertility treatment, especially women, and the importance of couples’ support to each other should be explained.
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.
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3. Ashraf DM, Ali D, Azadeh DM. Effect of infertility on the quality of life, a cross- sectional study. J Clin Diagn Res. 2014;8(10):13-5.
4. Cousineau TM, Domar AD. Psychological impact of infertility. Best Pract Res Clin Obstet Gynaecol. 2007;21(2):293-308.
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6. Gulec G, Hassa H, Yalcin E. G, Yenılmez C. Evaluation of the effect of infertility on sexual functions and dyadic adjustment in infertile couples who seek treatment. Turkish Journal of Psychiatry. 2011;22 (3):166-76.
7. Schmidt L, Holstein B, Christensen U, Boivin J. Does infertility cause marital benefit? An epidemiological study of 2250 women and men in fertility treatment. Patient Educ Couns. 2005;59(3):244-51.
8. Kim M, Moon SH, Kim JE. Effects of psychological intervention for Korean infertile women under In Vitro Fertilization on infertility stress, depression, intimacy, sexual satisfaction and fatigue. Arch Psychiatr Nurs. 2020;34(4):211-17.
9. Chaves C, Canavarro MC, Moura-Ramos M. The role of dyadic coping on the marital and emotional adjustment of couples with infertility. Family Process. 2019;58 (2):509-23.
10. Locke HJ, Wallace KM. Short marital-adjustment and prediction tests: Their reliability and validity. Marriage & Family Living. 1959;21(3):251-5.
11. Tutarel-Kıslak S. Reliability and validity study of the marital adjustment scale (TAT). Journal of Psychiatry and Psychology.1999;7(1):50-7.
12. Boivin J, Takefman J, Braverman A. The fertility quality of life (FertiQol) tool: development and general psychometric properties. Fertil Steril. 2011;96(2):409-15.
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14. Bodur NE, Çoşar B, Erdem M. The relationship between dyadic adjustment with demographic and clinical variables in infertile couples. Cukurova Medical Journal. 2013;38(1):51-62.
15. Halıcı EC, Saatci E. Men’s marital adjustment and violence against female partners in couples applying for infertility treatment. Turkish Journal of Family Medicine. 2021;25(1):21-7.
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17. Gorayeb R, Borsari AC, Rosa-e-Silva ACJ. ve Ferriani R. Brief cognitive behavioral intervention in groups in a Brazilian assisted reproduction program. Behav Med. 2012;38(2):29-35.
18. Aarts J, Van Empel I, Boivin J, Nelen W, Kremer J, Verhaak C. J. Relationship between quality of life and distress in infertility: a validation study of the Dutch FertiQol. Hum Reprod. 2011;26(5):1112-8.
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Sevilay Salur, Ruhusen Kutlu, Hüseyin Görkemli. How do marital adjustment and quality of life affect infertile couples? A hospital-based study. Ann Clin Anal Med 2022;13(11):1186-1190
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Factors affecting mortality, morbidity and survival in pylorus-preserving pancreaticoduodenectomy
Esin Sair 1, Yigit Duzkoylu 1, Soykan Arikan 2, Serkan Sari 3
1 Department of Gastroenterologial Surgery Clinic, 2 Department of Surgical Oncology, 3 Department ofGeneral Surgery, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21238 Received: 2022-05-19 Accepted: 2022-06-21 Published Online: 2022-06-24 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1191-1195
Corresponding Author: Yigit Duzkoylu, Department of Surgical Oncology, Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey. E-mail: dryigit@gmail.com P: +90 533 261 25 33 Corresponding Author ORCID ID: https://orcid.org/0000-0001-6894-6896
Aim: Pancreatic tumors are considered highly mortal cancers worldwide, and surgical resection is considered the only curative method. Because of the efficacy of surgery as the gold standard treatment, finding the most accurate technique has been always important in the literature and clinical practice. Herein, we aimed to report our results in patients with periampullary tumors in whom we performed pylorus-preserving pancreaticoduodenectomy.
Material and Methods: We analyzed our results in patients who had been operated with pylorus-preserving pancreaticoduodenectomy for periampullary malignancy in a single tertiary center for 5 years, in terms of operative features, postoperative complications and survival.
Results: A total of 48 patients were involved in the study, and 37 of them had been operated with pylorus-preserving pancreaticoduodenectomy for periampullary malignancy. In 48 patients, 33 were males with a mean age of 60.73 years and 15 were females with a mean age of 56.9 years. The most common localization was pancreatic head (25 patients, 52%). We did not find any converse effects of pylorus-preserving technique on postoperative complications or survival. Although not significant, survival was longer in the group with extended lymph node resection.
Discussion: Although there is still a lack of standardized and randomized prospective studies with large study groups, pylorus preserving technique is accepted as an advantageous option in means of complications and hospital stay. We think that our results are consistent with the literature and may contribute to larger review studies.
Keywords: Pancreatic Cancer, Periampullary Tumors, Pylorus-Preserving Pancreaticoduodenectomy, Whipple Procedure
Introduction
Incidence, history and surgical technique
Pancreatic cancer is considered as one of the most mortal gastrointestinal tract cancers with a 5-year overall survival rate of 5% to 13% [1]. By 2018, it is the fourth leading cause of cancer deaths in the Western World [1]. The tumor is usually found at the head of the organ (60-70%), while 25% are in the body or tail [2]. Pancreatic ductal adenocarcinoma represents most of all pancreatic neoplasms (85-90%) [3].
The gold standard curative treatment of tumors of the periampullary region, including pancreatic head is surgical resection. There are mainly two options of performing the surgery including standard or pylorus resection pancreaticoduodenectomy (prPD) and pylorus- preserving pancreaticoduodenectomy (ppPD). In prPD, resection involves the head of the pancreas with distal stomach, duodenum, distal common bile duct. The standard technique was first introduced by Whipple and Trimble in 1941 [4]. Shortly after following the first surgeons, Watson showed a modified technique preserving the distal stomach and pylorus mainly to decrease operative time and complications due to resected stomach [5]. In prPD, distal stomach and pylorus are resected and a gastrojejunostomy is performed to complete the gastrointestinal tract, while these parts are preserved and a duodenojejunostomy is created in ppPD [4]. Following the introduction of ppPD, the two techniques were compared for many times in various publications, indicating that they were similar in means of operative time, number of transfusions, and blood loss, but ppPD could cause a higher incidence of delayed gastric emptying (DGE) [6]. Although studies concerning the results of the two techniques usually focus on DGE, R0 tumor resection, recurrence rates and disease-free survival have been other important matters about the safety of ppPD [7].
Concerns about ppPD
The main concerns regarding the oncologic safety of ppPD are usually influenced by the fact that this technique was initially introduced for the treatment of benign disorders such as chronic pancreatitis, and later republished for the treatment of periampullary malignancies [5]. Besides these controversies, most of the studies showed that ppPD decreases the operational time, blood loss, need for transfusions with no overall increase in tumor recurrence or survival [7]. Following the doubts of the surgeons about ppPD in terms of insufficient oncologic resection, negative-margins, and nodal dissection [8], none of the randomized controlled trials or meta-analyses have shown statistically significant differences [7].
Delayed gastric emptying, definition, incidence
Not only oncologic results, but also the risk of ppPD-related DGE is still studied and discussed today in various studies [9]. DGE is mainly thought to be caused by the functional defect of the propulsive action, the most important parts of which are the stomach and pylorus [10], and the incidence is reported as very wide in different studies varying between 4.5% and 45% [11]. Unfortunately, the underlying mechanism of DGE is thought to be multifactorial and has not been defined clearly, yet. Publications before 2007 defined DGE as the need for a nasogastric tube still on a postoperative day 7 to 10, while the International Study Group of Pancreatic Surgery (ISGPS) classified and graded DGE in 2007 [12]. Today, researchers focus on interrupted neural connections, local ischemia and partial or complete impairment of hormonal production in the mechanism of DGE [13]. Although DGE is a serious complication, it is not life-threatening itself. But more importantly, it has been shown to be related with other postoperative complications such as fistula and intraabdominal abscesses [14]. DGE impairs and prevents early oral intake, resulting in extended length of hospital stay and delay in postoperative adjuvant chemotherapy, which has a negative impact on survival [10].
In the German prospective single-center PROPP trial, prPD was not shown to be related with decreased incidence or severity of DGE, but conversely tended to have a higher incidence of DGE [15]. On the other hand, there are other published meta-analyses showing ppPD with increased rates of DGE [9]. The controversies are also similar in randomized trials. One of these studies including 33 patients showed 43% DGE in ppPD and zero percent in prPD [16], while another randomized trial did not show any differences between the two techniques [17].
Up to date, there are no high-quality multicentred randomized controlled trials proving the superiority of one of the techniques in means of survival or DGE and other major complications.
Aim of this study
Published studies up to date defined the concerns about ppPD in means of oncologic results and causing DGE, which also decreases the quality of life and survival because of its chronic nature. The results are controversial, and there are no proven facts showing the disadvantages of ppPD. We aimed to show our postoperative results in ppPD patients to investigate and hypothesize that the technique is not disadvantageous in means of oncological results, survival, and DGE as a postoperative complication.
Material and Methods
Following approval of the local ethics committee, the records were analyzed retrospectively. A total of 48 patients were involved in the study, and 37 of them had been operated with pylorus-preserving pancreaticoduodenectomy for a periampullary malignancy in a single tertiary center over a 5-year period. Demographics of the patients, symptoms, comorbid diseases, biochemical tests, tumor features, operational technique, postoperative complications, survival rates were retrospectively analyzed. For statistical analysis, the Mann-Whitney U, Wilcoxon W, Chi-square and Mantel-Cox tests were used. The survival analysis in groups was performed with the Kaplan-Meier method, and the survival comparison between groups and subgroups were performed with the Logrank (Mantel-Cox) test. Statistical significance was accepted as p <0,05.
Results
Thirty-seven of 48 patients were operated with ppPD for a periampullary tumor over a period of 5 years. Of the 48 patients, 33 were males (68,7%) with a mean age of 60.73 years and 15 were females (31,2%) with a mean age of 56,9 years. The most common localization was the pancreatic head (25 patients, 52%). Demographics were not found to be statistically significant with the chi-square test.
Jaundice was the most common preoperative symptom, seen in 40 patients (83,3%), abdominal pain (24 patients, 50%) and pruritus (16 patients, 33,3%) were other common symptoms. Hypertension was the most common comorbid disease which was seen in 13 patients (27,8%), followed by type II diabetes mellitus (n:13) and ischemic heart disease (n:3). Neither symptoms nor comorbidity were found to be statistically significant using the Wilcoxon W and Mann-Whitney U tests.
The mean operation time was 330 minutes (300-360). The mean number of peroperative blood transfusions was 1.2 units (0-3). While ppPD was performed in 37 patients (77,1%), 11 of the patients were accepted as inoperable during the operation. Hepaticojejunostomy could be performed in 9 of these patients, and only a tru-cut biopsy could be performed in the remaining 2 patients. In our operabl ppPD group duct-to-mucosa anastomosis was performed in 27 patients (72,9%) in whom the Wirsung duct was ≥3 mm, while Dunking-type anastomosis was performed in the remaining 10 patients with the Wirsung duct of <3mm. Extended lymph node dissection (LND) was performed in 12 patients (32,4%) increasing the operational time with a mean time period of 20 minutes. Operational features were not found to be significantly significant due to the chi-square test.
Local wound infection was the most common postoperative complication, encountered in 6 patients (12,5%). Other complications were pancreatic fistula, hemorrhage and delayed gastric emptying (DGE). There was no any significant relation between comorbid disease and postoperative complications. There was no any significant relation between biochemical results and postoperative complications. Similarly, the type of anastomosis was not found to be significantly effective in terms of postoperative complications rates. Postoperative hospital stay was 11.1 days in operable patients (8-44), while it was found to be 8.2 days (7-13) in inoperable ones. The significance was determined due to Mann-Whitney U and chi-square tests.
The average survival was found to be 36.3 months (med:26 months) in resected ppPD patients, while it was 13.6 months ( med:12 months) in inoperable patients. The difference was statistically significant (p:0.012) as shown in Table 1. Tumor localization or postoperative complications were not found to significantly affect survival.
Survival rates were analyzed with the Kaplan-Meier method.
Although it was not statistically significant when compared to other operable patients, the average survival was 43.4 months (med:24 months) in the group with extended lymph node dissection ( Table 2 and Figure 1). Significance between these subgroups was performed with Logrank (Mantel-Cox) test.
Discussion
Although pancreaticoduodenectomy has been curative gold standard treatment for periampullary tumors for many years, the efficacy and long-term results of ppPD compared to prPD still remain questionable. Besides numerous published studies, the choice of surgical technique often depends on the practice of the surgeon and the institution. In our study, we aimed to analyse and define our results after performing ppPD and report short- and long-term results. We used statistical methods to determine data in means of short-term complications such as DGE, oncological results such as LND and survival, and overall costs such as length of hospital stay.
Pylorus preserving technique has some advantages with regard to shorter operational time, lesser blood loss and fewer blood transfusions, similar to our results [18]. Patients undergoing ppPD had a lower mortality and shorter hospital stay when compared to prPD [19]. Although in a smaller group of patients, a Cochrane review showed opposite results [11]. In most of the studies, ppPD offers a significantly shorter hospital stay when compared to the standard technique [20]. Previous studies have reported higher rates of postoperative complications, including DGE, which led to longer hospital stay [6]. There are also studies showing that even DGE occurrence did not increase the length of stay following ppPD technique [21]. Although we did not compare with the standard technique, both the rate of DGE was lower and the length of stay was shorter when compared to standard pancreaticoduodenectomy results in the literature.
It is well known that DGE is not mortal itself, but it is a serious complication deteriorating quality of life, even decreasing survival by delaying the start of adjuvant chemotherapy. Underlying mechanisms are thought to be gastric atony following vagatomy, resection of duodenal neural tissues and ischemic injury of distal stomach, intraabdominal complications and decreased motilin levels [22]. There is a remarkable inconsistency in systematic reviews regarding the DGE incidence in terms of surgical technique [23]. The rate of DGE is reported to be between a large scale of percentage, occurring in 19-57% of the patients [12].
Our goal was not only to determine postoperative complications, but also to analyze the oncological outcomes of ppPD technique. The data are retrospective and we did not compare with a prPD group, which is open to bias naturally. Researchers state that long-term survival mostly depends on the extension of LND. Early studies analyzed ppPD technique for oncological concerns in relation tolymph node and margin status [8]. Yeo et al. reported that the standard prPD technique provides a higher number of dissected lymph nodes [24]. More recent studies showed similar results and no significant difference in means of oncological status [6,19]. Although not statistically significant, we provided adequate LND and acceptable survival even without causing a significant increase in the length of hospital stay. Both our survival rates were acceptable in the standard ppPD and the extended LD group, 36.3 and 43.4 months, respectively, which may be a sign of objection to concerns for the oncological results of the ppPD technique.
Conclusion
Pylorus-preserving technique is performed less frequently than the standard resection in the world. Although there are published studies suggesting opposite results, none of the two techniques is significantly superior to another in means of oncological results or overall survival. But today, it is accepted that ppPD has advantages in terms of shorter hospital stay and short-term postoperative complications, which may indicate that the technique is a good choice when the tumor is not on the first part of the duodenum.
There is still a lack of standardized and randomized prospective studies with large study groups comparing the two techniques. In addition to all the published studies, the choice of the surgeon and traditions of a tertiary institute played roles in preferring the resections technique as well as literature findings. The limitations of our study are its retrospective design, the absence of comparison with the standard technique and single-center results, which may lead to statistical bias. Even so, we think that our result may show the advantages of ppPD technique in the literature, which can contribute to larger review studies.
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.
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15. Hackert T, Probst P, Knebel P, Doerr-Harim C, Bruckner H, Klaiber U, et al. Pylorus resection does not reduce delayed gastric emptying after partial pancreatoduodenectomy: a blinded randomized controlled trial (PROPP study, DRKS00004191). Ann Surg. 2018;267(6):1021–7.
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19. Calderon E, Day RW, Sticky CC, Gray RJ, Pockaj BA, Chang YH, et al. Comparative Effectiveness of Pylorus-Preserving Versus Standard Pancreaticoduodenectomy in Clinical Practice. Pancreas. 2020;49(4): 568–73.
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Esin Sair, Yigit Duzkoylu, Soykan Arikan, Serkan Sari. Factors affecting mortality, morbidity and survival in pylorus-preserving pancreaticoduodenectomy. Ann Clin Anal Med 2022;13(11):1191-1195
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Overweight and Obesity: Perception and associated risk factors among women in southern Morocco
Mohamed Boukrim 1, 2, Majdouline Obtel 1, 3, Abderrahlmane Achbani 2,4, Rachid Razine 1, 3
1 Department of Public Health, Faculty of Medicine and Pharmacy, Mohamed V University, Rabat, 2 Department of Nursing, Higher Institute of Nursing Professions and Health Techniques, Marrakech, 3 Department of Public Health, Faculty of Medicine and Pharmacy, Mohamed V University, Rabat, 4 Faculty of Sciences, Ibn Zohr University, Agadir, Morocco
DOI: 10.4328/ACAM.21241 Received: 2022-05-22 Accepted: 2022-07-13 Published Online: 2022-07-26 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1196-1200
Corresponding Author: Mohamed Boukrim, Higher Institute of Nursing Professions and Health Techniques, near Ibn Tofail Hospital, 40000, Marrakech, Morocco. E-mail: boukamo@yahoo.fr / boukrim1967@gmail.com P: +21 266 121 04 58 Corresponding Author ORCID ID: https://orcid.org/0000-0002-9334-1626
Aim: In this study, we aimed to identify the main risk factors associated with overweight and obesity among women in southern Morocco.
Material and Methods: The study was conducted in health centres in the southern region of Morocco. Data were collected using a questionnaire. In addition to socio-demographic information, physical activity was assessed using the International Physical Activity Questionnaire (IPAQ). Information on dietary habits was also collected using the Guideline Score of the French National Nutrition and Health Program (PNNS-GS). Anthropometric data (weight and height) were measured and perception was assessed using the Stunkard body shape assessment scale.
Results: A total of 576 were included in this study. Anthropometric data showed that 37.3% of women were normal weight, 33.9% (IC95% [30.03-37.77]) were overweight and 25.2% were obese (IC95% [21.65-28.75]). The study revealed that overweight was related to socio-demographic status, Sahrawi Arab ethnicity (OR= 1.82; IC95% [1.13-3.93], p=0.013) and mixed race (OR= 2.61, IC95% [1.47- 4.61], p=0.001). However, this relationship was not significant for eating habits and physical activity level. As for parity and maternal breastfeeding, there was a significant relationship with weight gain, as well as positive perception of overweight and desire to gain weight (p>0.001). However, the desire to lose weight protects against overweight (OR=0.46; IC95% [0.30-0.70])
Discussion: Reducing the magnitude of this public health problem requires strategies that address all the factors that can lead to weight gain in the population with a particular emphasis on young women.
Keywords: Overweight, Obesity, Perception, Risk Factors, Women21275
Introduction
Overweight is a disease characterized by excess body fat. It is associated with the development of numerous comorbidities. Its worldwide prevalence has shown a significant increase in recent years. Overweight and obesity have become major public health problems worldwide. They have consequences on physical, psychological and social well-being. The impact of excess weight on health is well known. Indeed, it is a risk factor for type 2 diabetes, cardiovascular disease, hypertension, osteoarthritis and some forms of cancer [1].
The increase in the prevalence of overweight and obesity is thus a growing threat to health, affecting all age groups, ethnic groups and all social classes in all industrialized and developing countries.
In Morocco, women are the most affected by the phenomenon. Indeed, between 2011 and 2018, we note an increase in overweight from 51.4% to 63.4%. As for obesity, it has increased from 26.8% to 29.0% (available at: website: www.sante. gov.ma/Documents /2019/05/ Rapport). A literature review revealed that the risk factors are multiple and their control is complex. They are genetic, ethnic, cultural, and socio-demographic, linked to sedentary and dietary behaviours. Indeed, the incidence of obesity decreases with physical activity [2]. As for diet, studies have shown that the frequency of meals, their daily distribution and the composition of foods are involved in the development of overweight [3,4]. In addition, several studies have indicated that there is a strong association between perceived weight and weight control [5].
The aim of this study was to identify the main risk factors associated with overweight and obesity among women in southern Morocco.
Material and Methods
A multicentre cross-sectional study was conducted on 576 non-pregnant women and over 18 years of age. All consenting women were admitted to the study. Data collection was performed through a standardized questionnaire. It covers sociodemographic and student data, physical activity, diet and their perception of their weight load. Eating habits were assessed using an adequacy score derived from the Guideline Score of the French National Nutrition and Health Program (PNNS-GS) [6]. It is composed of basic questions on the frequency of consumption of major food groups (fruits and vegetables, starchy foods, meat and poultry, dairy products, etc.). Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ), Short Version (available at website: www.ipaq.ki.se). The questionnaire also included anthropometric measurements. Body mass index (BMI) was calculated according to the thresholds adopted by the World Health Organization (available at website: www.who.int/fr/news-room/fact-sheets/detail/obesity-and-overweight). Participants’ perception of body image is measured by the Body Image Rating Scale (Stunkard Figures) [7]. Data processing is done by the statistical data processing software SPSS version 13.0. Categorical variables were described in numbers and percentages and then compared using the chi-square and Fisher’s exact tests according to the conditions for applying each of them. Quantitative variables were described as mean ± standard deviation. Factors associated with obesity/overweight were determined using binary logistic regression by calculating odds ratios (OR) and 95% confidence intervals (CI). In all analyses, a p-value ≤ 0.05 was considered statistically significant.
The study was approved by the Ethics Committee of Mohammed V University in Rabat under the number 50/20 dated 28/06/2020.
Results
The mean age of the study participants was 28.7±10.2 years. Table 1 shows that more than three-quarters of the women were younger than 37 years. The distribution of participants showed that more than half of them (n=309) were married. The proportion of single women was 37% (n=213). As for ethnicity, the results showed that 49% of the participants were of Arab ethnicity and 30% (n=170) were of Sahrawi Arab ethnicity. The distribution of women according to geographical origin showed that the majority (95.1%) lived in urban areas. As for occupation, housewives represented 40.1% (n=231), students 34.4% (n=198) and those with a salaried activity reached 25.5% (n=147). Among female civil servants or employees, 62% (n=93) were engaged in office work and 37.3% (n=56) in manual activity while standing.
Monthly family income showed that about two-thirds (n=362) reported an income of at least 4999 MAD, while 25% (n=144) had an income between 556,03 and 1111,95 USD and only 12% (n=70) of the participants mentioned an income of more than 1112,06 USD. Data on educational levels showed that 36.1% (n=208) of the women had a higher level of education, and 26.6% (n=153) had no more than primary education. The study of the racial groups of the participants showed that 82% (n=471) of the women studied were white and 13% (n=74) were mixed race. The prevalence of obesity and overweight in our study was 25.2% and 33.8% respectively.
As for eating habits, 12.7% of the women could be considered small consumers of fruits and vegetables (less than 3.5 portions per day). On the other hand, 70.5% of the women ate at least five fruits and vegetables daily and 75.1% of the respondents ate starchy foods at least three times a day. Only 3.3% of participants reached the PNNS benchmark for dairy products, while the vast majority (88.7%) ate less. Nearly 80% of the women consumed foods from the “meat, fish, eggs” group once or twice a day. On the other hand, 13.1% of the participants consumed fish products at least twice a week.
As for the intensity of physical activity, more than half of the participants were not very active, while 3.1% were very active (Table 2).
Binary logistic regression analysis (Table 3) showed that an increase in women’s age by one year increased the risk of overweight by 11% to 18% (OR=1.15; 95% CI [1.11 – 1.18]).
Married women were not at risk of developing excess weight (OR= 0.84; CI95% [0.43- 1.62]). On the other hand, being single seemed to be protective against the development of overweight (OR=0.22; CI95% [0.11-0.43]). As for occupation, being a housewife (OR=15.87; CI95% [9.89-25.51]), a public servant (OR=14.29; [7.89-25.91]) or an employee (OR=14; CI95% [6.59-29.76]) was significantly associated with the development of excess weight. Being a student was more associated with a reduced risk of developing overweight (OR=0.07; CI95% [0.43-0.107]). Illiterate women had a 27.5-fold increased risk of developing excess weight (CI95% [12.34-61.29]), whereas women with higher education were protected (OR=0.08, CI95% [0.05-0.12]). Excess weight was correlated with Sahrawi Arab ethnicity (OR= 1.82; CI95% [1.13-3.93]), whereas Amazigh ethnicity was protective (OR= 0.65; CI95% [0.44-0.98]). Moreover, Arab ethnicity and physical activity intensity were not related to overweight. As for dietary habits, no relationship was found between excess weight and compliance with PNNS standards (OR=1.0069; CI95% [0.71-1.42]. However, the analyses showed that among the women studied, the habit of skipping a meal during the day was correlated with weight gain (OR=7.88; CI95% [5.03-12.33].
In addition, women who were satisfied with their body image (OR=0.235; CI95% [0.15-0.35]) and desire to lose weight had protective effects against excess weight (OR=0.46; CI95% [0.30-0.70]). However, women with a desire to gain weight and those with a positive representation towards excessive weight had respectively had a risk of weight gain (OR=25.60; CI95% [13.47-48.64] and OR=1.60; CI95% [1.60-1.03]), (Table 3).
Discussion
Anthropometric data showed that the average body mass index (BMI) was 26.70 ± 5.36 Kg/m2. Thus, one out of three women was overweight and one out of four women was obese. These results confirm this trend in women worldwide [8]. Indeed, a study in Saudi Arabia showed an increase from 21% to 78% in women between 1992 and 2022 [9]. The study showed that the increase in age is related to overweight. This result is supported by other studies (available at: https://drees.solidarites-sante.gouv.fr/publications/les-dossiers-de-la-drees/premiers-resultats-de-lenquete-sante-europeenne-ehis-2019).
Similar to other research [10], the study found that married women had an elevated risk of being overweight (OR=3.03; 95% CI = [2.14- 4.27]). However, being single was protective against this risk (OR=0.25; 95% CI= [0.18- 0.36]). This result could be explained by the beginning of a change in perception towards corpulence and the adoption of lower risk behaviors for obesity as a consequence of their exposure to a Westernized culture [11]. In other results, the risk of overweight was related to the level of education and to the Saharawi ethnic group [12]. This finding is due to the lifestyle in general of Sahrawi women and to their behavior with respect to weight gain, which in their ancestral culture, is highly desired by this population.
In this study, a new result was recorded. Indeed, breastfeeding women had a high risk of becoming overweight (OR=5.28; CI95%= [3.47-8.05]), especially for a period of breastfeeding of one year (OR=3.83; CI95%= [1.41-10.38]). This is due to the excessive eating behaviors and sedentary habits of breastfeeding women in order to increase lactation. The literature has reported that exercise is protective against weight gain [13]. However, the results of the study reported no significant association between physical activity and overweight. This could be explained, on the one hand, by the difficulty of women to classify their physical activities and, on the other hand, the survey used the memory of the last seven days to assess the intensity of physical activity. Authors have reported that balanced diets may have a protective effect on the risk of developing chronic diseases [14] and that obesity is due to an imbalance between calories ingested and calories expended [15]. However, our results showed no relationship between a standard diet and weight gain. The discrepancy between the results could be explained by the fact that in Morocco, and especially in the southern provinces, the nutritional transition is in its early phase. Also, we could mention that meals in Morocco are served in collective dishes and prepared according to the traditional model (tagines, couscous and other Moroccan main meals). This made it difficult to quantify the food taken.
It was also noted that women who skipped meals were more likely to be overweight. These results are in line with those of the 2009 study showing that skipping meals disrupts hormonal and digestive secretions, leading to an increase in energy “storage” and therefore weight gain [10,16].
As for perception, our results showed that the majority of the women studied had correctly estimated their weight, contrary to the results of other studies conducted in Morocco and Tanzania [17,18].
For the perception of the most attractive image for men, the majority had chosen images 3 and 4 that represented normal weight. These results were similar to other studies [18].
Strengths of the study:
It was conducted at the level of Primary Healthcare Centers in all provinces of the region and is the first study to attempt to identify the dietary habits and assess the physical activity of women in the region. The main limitation is its cross-sectional nature.
Conclusion
Our results estimated the first prevalence of overweight in women of southern Morocco. The study focused on sociodemographic factors, factors related to physical inactivity, diet, family history, and the participants’ perception of the phenomenon studied. Reducing the magnitude of this public health problem requires good strategies that consider these major factors that can lead to weight gain, with particular emphasis on young women and students.
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.
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Mohamed Boukrim, Majdouline Obtel, Abderrahlmane Achbani, Rachid Razine. Overweight and Obesity: Perception and associated risk factors among women in southern Morocco. Ann Clin Anal Med 2022;13(11):1196-1200
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The effect of ACE inhibitors on inflammation and clinical end-points in COVID-19 patients
Arzu Gunturk 1, Abidin Yusuf Kavurmaci 2, Yasar Kucukardali 2, Fatma Ferda Kartufan 3, Adnan Ezici 2, Aynur Eren Topkaya 4
1 Department of Internal Medicine, Istanbul Florence Nightingale Hospital, 2 Department of Internal Medicine, Faculty of Medicine, Yeditepe University, 3 Department of Anesthesia and Reanimation, Medistanbul Hospital, Istanbul, 4 Department of Microbiology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey
DOI: 10.4328/ACAM.21243 Received: 2022-05-24 Accepted: 2022-06-29 Published Online: 2022-07-05 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1201-1204
Corresponding Author: Arzu Gunturk, İzzetpaşa Mah, Abide-i Hürriyet Cd, No: 166, 34381, Şişli, İstanbul, Turkey. E-mail: mdarzugunturk@gmail.com P: +90 532 366 97 66 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1941-8699
Aim: COVID-19 infection has affected the whole world. It has been speculated that the virus might hold on to angiotensin-converting enzyme 2 (ACE 2) surfaces of type 2 alveolar cells. ACE inhibitors and angiotensin receptor antagonists (ARBs) are essential antihypertensive and cardiac failure drugs in the guidelines. In this study, we aimed to find the effect of these drugs on clinical, laboratory courses, and outcomes of COVID-19 patients.
Material and Methods: We included 109 patients in this study. There were 43 patients in the ACE/ARB group and 66 patients in the non-ACE/ARB group. The mean age was 60 years in the ACE/ARB group and 52 years old in the non-ACE/ARB group. Basal symptoms, hemogram, CRP, D-dimer, LDH, Ferritin, AST, duration of hospitalization, percentage of intensive care unit (ICU) need, length of stay in ICU were compared between the groups.
Results: The mean age in the ACE/ARB group was higher than in the other group and was statistically significant (p=.027). The initial symptoms were not different. There were no differences between the laboratory results of the groups. The ICU need was higher in the patients who do not use the drug than in the users (p<.020).
Discussion: ACE/ARB usage in COVID-19 patients did not worsen the course of the disease. However, ACE/ARB users before COVID-19 pandemic were taken to ICU at a low rate.
Keywords: COVID-19, Antihypertensives, Angiotensin-Converting Enzyme 2, Angiotensin Receptor Antagonists, Intensive care
Introduction
Coronavirus-19 infection is a pandemic since February 11, 2019. The mechanisms of the infection have not been elucidated [1]. COVID-19 has spikes and binds to the cell surfaces with these spikes. The respiratory surface is especially sensitive to the virus binding. The COVID-19 virus has a 10–20 times higher affinity to ACE-2 receptors than SARS-CoV in the 2003 outbreak [2]. ACE-2 is expressed in coronary and renal vessels and epithelium of the renal tubules [3]. ACE catalyzes the conversion of angiotensin I, to angiotensin II. ACE behaves as a kininase and inhibits bradykinin [4]. Angiotensin II increases vascular resistance and produces vasoconstriction. It also maintains sodium reabsorption and induces the secretion of aldosterone. Angiotensin II is mediated by binding to two specific angiotensin II receptors: type 1 (AT1R) receptor and type 2 (AT2R) receptor [5]. Its effects are seen by AT2R. ARBs inhibit the binding of angiotensin II to AT1R [3]. ACE 2 is a homolog to ACE. ACE 2 cleaves an amino acid from angiotensin II, forming angiotensin [1-7], which regulates a pathway that has opposing physiology to ACE and angiotensin II [6]. This enzyme opposes the pro-inflammatory, pro-oxidative, vasoconstrictive, and fibrotic properties of angiotensin II [7].
Evidence shows that older adults with SARS-CoV-2 infections and cardiovascular diseases, including hypertension, are at risk of developing severe cases [8]. Some studies showed that COVID-19 patients with hypertension account for 20-30% of all patients and increase to 58.3% in the intensive care unit ([ICU]). The Renin-angiotensin system plays a vital role in hypertension and COVID-19 [9].
In this study, it was aimed to investigate whether there is a difference in laboratory values, length of hospital stay, duration of ICU stay between COVID-19 patients using ACE/ARB or not.
Material and Methods
This current study was conducted on COVID patients who were inpatient on March 15, 2020 to May 30, 2020 in Yeditepe University Hospital. Ethical approval for this retrospective, single center clinical trial (number: 1388) was provided by the Yeditepe Clinical Trials Ethical Committee, Istanbul, Turkey (Chairperson Prof T. Çelik) on 17/02/2021. The study was conducted in accordance with the Declaration of Helsinki.
This study included 109 COVID-19 patients admitted to the hospital. . There was no distinction in terms of the gender. Male and female patients were taken without any distinction. The age range was 18-85 years. The inclusion criteria were the presence of COVID-19 diagnosis, Biochemical, Serological and Radiological tests, and hospitalization for more than 72 hours. Exclusion criteria were exceptions to the mentioned age range and lack of patient approval of the study protocol.
The study groups were ACE/ARB drug users for six months before hospitalized and those who did not use these medications for at least six months. The distribution of symptom frequency, age and gender range, hospitalization and length of stay in the ICU, first and last laboratory values, follow-up of these values, and treatment options were compared. The laboratory values that we checked in our patients included Hemoglobin (Hb), Leucocytes (WBC), Neutrophile, Lymphocytes, Thrombocytes (PLT), CRP, Neutrophile/Lymphocyte Ratio (NLR), Ferritin, D-dimer, AST, LDH, BUN, Creatinin, glucose, oxygen saturation.
PCR method for COVID-19: Nasopharyngeal swabs were collected from each patient. Viral transfer tubes (vNAT, Bioeksen, Turkey) were employed to transfer the samples.
SARS CoV-2 Double Gene RT-PCR kit (Bioeksen, Turkey) was used for RNA amplification on the LightCycler 480plate-based RT-PCR instrument (Roche, Switzerland). The SARS-CoV-2 double gene RT-PCR kit targets the SARS-CoV-2 specific N (Nucleocapsid) and Orf1abgene regions. The human RNaseP gene is targeted for sample, nucleic acid extraction, and inhibition control. The shape of the growth curves was examined, and the non-sigmoidal curves were recorded as “negative”. Sigmoidal curves with cycle threshold (Ct) <38 were evaluated as ‘’positive’’. The Ct values of all positive results were recorded.
Statistical Analysis
We retrospectively examined 110 COVID-19 patients. In our study, for statistical calculations, the SPSS program was used. Initial symptoms and laboratory tests of patients, laboratory values during the clinical course and discharge period, length of hospital stay, and duration of intensive care were compared in diabetic and non-diabetic COVID patients. Demographic data, average values and percentages were used in the evaluation.
A categorical Chi-square test was used in data analysis. For parametric data, Student’s T-test was used, Mann-Whitney U test was used for non-parametric data. For comparison, we were examining the course of laboratory data over time. General Linear Model Repeated Measures test was used. Non- Spearman’s Rho test when looking at the correlation of parametric values used.
Results
One hundred and nine patients were included in the study. There were 43 patients in the ACE/ARB group, and 66 patients in the other group, which did not use ACE/ARB drugs. The average age in the ACE/ARB group was 60 years, and 52 years in the non-ACE/ARB group (p=.027) (Table 1).
The initial symptoms of the disease were frequent in the non-ACE/ARB group. But none of them was statistically significant (Table 2).
Duration of hospitalization, duration of ICU, oxygen saturation, CRP, leukocyte, lymphocyte, neutrophils, NLR, platelets, hemoglobin, LDH, AST, D-dimer did not have a statistically significant difference. The percentage of ICU stays was higher in patients not using ACE/ARB (24% vs. 7%) (p=.020). Use of anti-COVID-19 drugs in ACE/ARB users is presented in Table 3.
Discussion
After ACE-2 was found to be important for SARS-COV-2 infection, ACE/ARB therapies were interrogated and caused confusion and fear [10]. Some doctors discontinued these medications and prescribed other antihypertensives. It was also emphasized that “ACE-2 levels could be increased by the use of ACEIs” [11, 12]. Their contention was the upregulation of ACE-2 levels. But there was also no clear evidence for this notion. Some studies defended that ACE/ARBs had a protective effect against ARDS, lung fibrosis, asthma, and chronic obstructive lung disease in animal models [13]. In fact, the upregulation of the ACE-2 is protective for the myocardium [14]. In view of such information, we studied these issues in our hospitalized patients. We compared initial symptoms, laboratory findings, number of patients to be taken to ICU, ICU duration, oxygen saturations with or without ACE/ARB. Initial symptoms besides headache were frequent in ACE/ARB (-) group. Headache was similar in both groups. But these results were not statistically significant. There is the first case-control study that followed the inflammatory status and clinical outcome [15]. In this study, it was detected that ACE/ARB group antihypertensives were superior to other group antihypertensives in reducing highly sensitive CRP and procalcitonin levels. In our study, we compared only CRP levels. But we could not find a statistically significant difference between the groups (p=.287). In the non-ACE/ARB group, the level was slightly higher, but not statistically significant. In our study, the number of patients who needed to be taken to ICU was less in the ACE/ARB group and was statistically significant (p= .020). Clinical outcomes and laboratory findings in our study are similar to the study by Yang et al. [15]. Clinical outcomes were not statistically significant in their study, too. Hypertension has been observed as the leading comorbidity of COVID-19 infection [16]. ACE/ARBs block the renin-angiotensin system and upregulate the ACE-2. SARS-COV-2 binds with10-20-fold higher affinity to the ACE-2 receptor. However, this notion may change according to different races, ages, and sexes. We have some limitations in this study. This study was done with the first outbreak patients. Plaquenil was the first choice in this outbreak. Favipiravir was preferred for extremely sick patients. In our study, this medication was used more frequently in non-ACE/ARB patients. But it was not statistically significant. The sample size may be increased. Bias may exist. Mortality could not be evaluated because of the sample size.
Conclusion
In this study, the number of patients admitted to the ICU was high among non-ACE/ARB patients and was found to be statistically significant. There were no significant differences in other issues.
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
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2. Khashkhusha TR, Chan JSK, Harky A. ACE inhibitors and COVID-19: We don’t know yet. J Card Surg. 2020;35(6):1172-73.
3. Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000;87(5):E1-E9.
4. Isaac-Lam MF. Molecular modeling of the interaction of ligands with ACE2-SARS-CoV-2 spike protein complex. In Silico Pharmacol. 2021;9(1):55.
5. Griendling KK, Lassègue B, Alexander RW. Angiotensin receptors and their therapeutic implications. Annu Rev Pharmacol Toxicol. 1996;36:281-306.
6. Vickers C, Hales P, Kaushik V, Dick L, Gavin J, Tang J, et al. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem. 2002;277(17):14838-43.
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8. Habibzadeh P, Stoneman EK. The Novel Coronavirus: A Bird’s Eye View. Int J Occup Environ Med. 2020;11(2):65-71.
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10. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271-80.e8.
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14. Ocaranza MP, Godoy I, Jalil JE, Varas M, Collantes P, Pinto M, et al. Enalapril attenuates downregulation of Angiotensin-converting enzyme 2 in the late phase of ventricular dysfunction in myocardial infarcted rat. Hypertension. 2006;48(4):572-8.
15. Yang G, Tan Z, Zhou L, Yang M, Peng L, Liu J, et al. Effects of Angiotensin II Receptor Blockers and ACE (Angiotensin-Converting Enzyme) Inhibitors on Virus Infection, Inflammatory Status, and Clinical Outcomes in Patients With COVID-19 and Hypertension: A Single-Center Retrospective Study. Hypertension. 2020;76(1):51-8.
16. Guan WJ, Zhong NS. Clinical Characteristics of Covid-19 in China. Reply. N Engl J Med. 2020;382(19):1861-62.
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Arzu Gunturk, Abidin Yusuf Kavurmaci, Yasar Kucukardali, Fatma Ferda Kartufan, Adnan Ezici, Aynur Eren Topkaya. The effect of ACE inhibitors on inflammation and clinical end-points in COVID-19 patients. Ann Clin Anal Med 2022;13(11):1201-1204
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Temporary splint application in extension to prevent ulnar nerve instability after in situ release
Ömer Ayık 1, Ümit Aygün 2, Murat Altan 3, Soner Özcan 1
1 Department of Orthopaedics and Traumatology – Hand Surgery, Erzurum Regional Training and Research Hospital, Erzurum, 2 Department of Orthopaedics and Traumatology, Faculty of Medicine, Istinye University, VM Medical Park Samsun Hospital, Samsun, 3 Department of Orthopaedics and Traumatology, Sarıkamış State Hospital, Kars, Turkey
DOI: 10.4328/ACAM.21250 Received: 2022-05-29 Accepted: 2022-06-29 Published Online: 2022-07-08 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1205-1209
Corresponding Author: Ümit Aygün, Department of Orthopaedics and Traumatology, Faculty of Medicine, Istinye University, VM Medical Park Samsun Hospital, Samsun, Turkey. E-mail: aygun.umit@yahoo.com, aygun.umit55@gmail.com P: +90 505 558 13 21 Corresponding Author ORCID ID: https://orcid.org/0000-0001-7234-1654
Aim: There is still no definitive consensus on cubital tunnel syndrome (CuTS) surgery, for which various surgical methods have been described. Simple in situ release (ISR) is preferred in primary CuTS due to the disadvantages of the anterior transposition (AT) technique, such as being more invasive, more extended surgery duration, particularly devascularization, worsening nerve function, or wound problems. Nevertheless, instability is occasionally observed when the ulnar nerve comes out of its groove during elbow movements after ISR. In this case, a blocking flap or AT is recommended to protect the nerve in situ. The present study aims to present the clinical results of temporary extension splint application applied to maintain the ulnar nerve in its groove in patients with instability noticed after ISR surgery.
Material and Methods: Twenty-two patients with a mean age of 46 years diagnosed with primary CuTS were included in the study. All patients were provided with an extension splint for two weeks and a commercial cubital tunnel extension splint for two weeks. The mean follow-up time was 20 months.
Results: Clinical outcomes such as Visual Analog Score (VAS), Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, pinch strength, grip strength, 2-point discrimination, recovery of motor functions, and functional and aesthetic satisfaction were positive. Only one patient (4.5 %) required secondary surgery.
Discussion: The simple, temporary extension splinting method is an effective way to address instability that may develop after ISR that is neither time-consuming nor more invasive.
Keywords: Cubital Tunnel Syndrome, In Situ Release, Extension Splint, Instability
Introduction
Cubital tunnel syndrome (CuTS) is the second most common entrapment neuropathy and can be classified as either primary (idiopathic) or secondary (deformation, previous surgery, mass) according to its etiology [1]. Mechanisms such as compression, traction, and friction are responsible for its pathophysiology [1,2]. Conservative treatment is initially recommended for patients with symptoms consistent with CuTS, and surgical methods are used only in patients with no positive response. Diverse surgical procedures such as in situ release (ISR), anterior transposition (AT), and medial epicondylectomy (ME) have been developed; however, there is no traditional gold standard technique. Largely similar outcomes have been obtained with these techniques, as described in many comparative studies [3]. When the advantages and disadvantages are evaluated, the current tendency is toward ISR, a simple, effective, low-morbidity procedure [4]. Elbow hyperflexion, ulnar nerve instability, and anterior subluxation have been observed in patients who underwent ISR due to traction and tension, which are responsible for the etiology of CuTS. The sequelae of an unstable ulnar nerve are associated with surgical failure and persistent neuropathy and often require revision surgery [5]. Nonetheless, it remains unclear how best to manage the unstable ulnar nerve after in situ decompression. Potential remedies include creating a new blocking flap and anterior transposition to protect the nerve in situ [6,7].
In this study, a more straightforward, practical method for ulnar nerve instability, as detected during preoperative elbow hyperflexion examination, following ISR temporary splinting, is applied as an extension where the nerve remains in the correct anatomical position to preserve the clinical consequences of this method.
Material and Methods
Approval was acquired from the local institutional ethical committee, and written informed consent was obtained from all patients. Patients who presented to a single tertiary referral hospital with CuTS between January 2017 and January 2020 were included. Since only primary CuTS patients were included in the study, patients with a history of fracture in the elbow region, varus-valgus deformity of the elbow, compression due to a mass, bilateral subluxation before surgery, and an additional diagnosis of another entrapment neuropathy or surgical release were excluded from the study.
Technique
Following the application of an Esmarch bandage from the proximal humerus under regional block or general anesthesia, the preoperative preparation of the patients was conducted under shoulder hyperabduction and 90° flexion of the elbow. After making an incision of approximately 10-12 cm passing through the center of the olecranon with the medial epicondyle, the medial antebrachial cutaneous nerve branch was exposed and preserved. The ulnar nerve was exposed proximally, as this is more comfortable, and the medial intermuscular septum and Arcade of Struthers, both potential entrapment areas, were released. Then, distally, Osborne’s ligament and the flexor-pronator aponeurosis were released. The nerve was retained in its bed and not circumferentially dissected by the surrounding connective tissue. After all releasing procedures were completed, the elbow was flexed, and the presence of nerve instability was assessed (Figures 1-2).
In anterior dislocations, the procedure was completed by applying a splint at an extension angle of approximately 120-130° that allows wrist movement after the wound closes (Figure 3).
Postoperative Management
The patients were discharged on the same day with oral analgesics. A dressing change was recommended every 3-4 days. Active-passive elbow full extension and elbow flexion up to 90° and unrestricted supination-pronation movements were performed at each dressing change. After approximately two weeks, the sutures and splint were removed, and a cubital tunnel splint was initiated. During the day, the splint was released twice, and passive-active elbow movements were performed in which the patients did not exceed 90° of flexion. After two weeks, the cubital tunnel splint application was terminated, and elbow movements were allowed without restriction. No special rehabilitation program was applied to any patient except for the recommended passive and active elbow movements after surgery.
Clinical Assessment
An independent hand surgeon who did not attend to any of the operations conducted the final follow-up assessment. Medical records were evaluated retrospectively. Upon inspection, intrinsic muscle weakness in hands was classified using the modified McGowan [8] classification system. According to this classification, the claw of small finger, inability to cross-index and middle fingers, positive Froment test, and Wartenberg sign were classified as central intrinsic atrophy. The inability to cross the index and long fingers was classified as a positive Froment test, and the Wartenberg sign was classified as moderate atrophy. The hand without signs of intrinsic atrophy was considered normal. The Tinel test, provocation of pain with the elbow flexion test, and pain levels were evaluated with a visual analog score (VAS). Functional status was assessed with the Quick-Disabilities of the Arm, Shoulder, and Hand (Q-DASH) questionnaire. In all patients, the preoperative and postoperative findings were compared.
The postoperative elbow range of motion (ROM), two-point discrimination (2PD), pinch, and grip strength of the patients were compared with the contralateral side and represented as a percent (%). Elbow flexion-extension ROMs were measured with a goniometer. The ulnar nerve flexion compression test is considered positive if there is numbness, tingling and pain in the ulnar nerve distribution when the elbow is in maximum flexion and supination for 60 seconds. Two-point discrimination (2PD) was measured in the flap area where the best response is taken and in the fifth finger using Baseline® plastic 2PD instrument (Baseline, White Plains, NY, USA). The key-pinch and grip strengths were measured with a Jamar Hydraulic Hand Dynamometer™ and Pinch Meter (Sammons Preston, Bolingbrook, IL, USA), and the mean of three trials was utilized for data analysis.
Patients with pre- and postoperative functional satisfaction and signs of motor atrophy were graded as very disappointed, disappointed, somewhat satisfied, satisfied, or very satisfied in terms of the change in hand aesthetics. The return of the patients to their job was recorded. During elbow hyperflexion, subluxation of the ulnar nerve was noted with palpation.
Statistical Analysis
IBM SPSS Statistics software version 28.0 (IBM Corp., Armonk, NY, USA) was used for the statistical analyses. Mean, median, standard deviation, maximum and minimum were used as descriptive statistical methods. The normality of the distribution was tested using the Shapiro-Wilk’s test. The Wilcoxon signed-rank test was applied to groups with non-normal distribution, whereas the paired t-test was used to compare dependent groups. The chi-square test was used to compare the groups with respect to categorical variables. A p-value of less than 0.05 was accepted as statistically significant.
Results
The mean age of 22 patients (12 males, 10 females) was 46.1 years (range: 26 – 72); 12 right, 10 left, and dominant arm involved 13 patients. The mean time to onset of symptoms was 11.8 months (range: 6 – 26), and the mean follow-up time after surgery was 20 months (range: 12 – 32). According to the modified McGowan classification, 4 patients were Type I, 3 were Type IIA, 9 were Type IIB, and 6 were Type III. According to the electromyographical (EMG) examination, 3 patients were mild, 10 were moderate, 8 were severe, and 1 had no pathological EMG findings. In the inspection, 6 patients had major atrophy, 9 had moderate atrophy findings, and 7 had no internal atrophy findings. Tinel’s sign was positive in 18 patients, and the elbow flexion test was positive in all patients. Routinely, all patients received a similar conservative treatment consisting of oral anti-inflammatory drug therapy, movement modification, and a night splint for three months. Patients who did not respond adequately to conservative treatment were recommended for surgery.
The mean VAS score significantly improved from 6.4 (range: 5 – 8) to 0.63 (range: 0 – 2) (p < 0.001). The mean quick-DASH significantly improved from 40.8 (range: 31.8 – 52, 5) preoperatively to 4.2 (range: 0 – 13.6) at the final follow-up (p < 0.001). Postoperative Tinel’s sign was positive in 2 patients. The elbow flexion test was negative in all patients postoperatively. Compared with the other elbow, the distinction in total elbow ROM was negligible (2% difference). Compared with the contralateral side, patients had an average of 92% (range: 80 – 110) pinch strength and 92.3% (range: 85 – 110) grip strength. Compared with the five fingertips of the opposite hand, 2PD was observed to increase by 130% (range: 100 – 160). These results are similar to published studies evaluating the results of ulnar nerve functions [9]. While 3 of the 6 patients with major atrophy showed improvement, 7 of the 9 patients with moderate atrophy showed improvement. One patient with major atrophy improved to moderate atrophy.
Functionally, before the surgery, 14 patients were very disappointed, and 8 were disappointed; after the surgery, 17 were very satisfied, 4 were satisfied, and 1 was disappointed. Of the 15 patients (9 moderate, 6 major) whose aesthetic satisfaction was questioned preoperatively due to signs of motor atrophy in their hands, 10 were very disappointed, and 5 were disappointed. Postoperatively, 3 patients were very disappointed, 2 were disappointed, 1 somewhat satisfied, 4 satisfied, and 5 very satisfied. All patients returned to their jobs (Table 1) (Figures 1-3).
Complications
After 4 weeks of splint application, instability with elbow hyperflexion was observed in only one (4.5%) male patient. This was expressed as a painful snapping sensation felt with palpation. Improvement was observed following anterior transposition with secondary surgery. Local wound problem was observed in one patient, and complete healing was achieved with oral antibiotic therapy and dressing.
Discussion
Despite being quite common, the treatment of CuTS remains under debate. Although ISR is preferred for primary CuTS surgery, AT is applied widely. In ISR, only the sheath and fascia above the nerve are released, while the nerve remains in its bed. In contrast, the AT procedure involves circular release of the nerve from the medial condyle to approximately 5-6 cm proximal and 5-6 cm distal and moving it to a new bed [10]. This comprehensive release technique comes with some complications. As is known, nerves are fed externally and internally [11]. Since the ISR is left in the nerve bed, its external nutrition is broadly preserved. In AT, on the other hand, approximately 10-12 cm of circular release process leads to a loss of external circulation in this segment, the risk of nerve devascularization, and segmental necrosis [2,12].
Contrary to this view, in the immediate postoperative period after AT, there may be a relative increase in blood flow, which significantly reduces within 3-7 days [13]. In addition to this complication of the AT procedure, which is even discussed and unclear, there is also the risk of increasing scar formation in the new bed [14]. With ISR, the external circulation of the nerve preserved in its bed is less affected, and the surrounding scar formation is minimized.
Some primary CuTS have instability during ISR surgery. Matzon et al. reported an instability rate of 12% in their study [14]. In this case, there are also statements suggesting the AT technique along with techniques that include creating a blocking flap that protects the nerve in its bed [2,4]. Since both procedures require further surgery, we aimed to protect the ulnar nerve in its bed with a non-invasive, low-morbidity splint technique. This technique includes preventing nerve instability by the formation of some pseudo-sheath. As such, instability only persisted in one patient (8%), and AT was applied secondarily. Based on our clinical results, it can be concluded that this method is effective, with a 92% success rate.
The main population of this study consisted of patients with subluxation after ISR. How much nerve subluxation will lead to problems has not been determined in the literature. The first objective classification on this subject was developed by Tang. They recommend the blocking flap technique for early-stage instability, while AT was recommended for gross instability [6]. In this study, instability grading was not performed, and the presence of instability was assumed as anterior dislocation of the nerve out of the ulnar groove and over the medial epicondyle with elbow flexion over 90° during the examination, and AT was not applied in any of the patients.
Surgical time was not evaluated in this study, but our technique has the advantage of creating a new blocking flap in less time than AT, except for an additional splint of 3-5 minutes. The most pertinent limitation of our approach is that the application of a splint for approximately 1 month can be irritating for the patients and may limit movement. No restriction of motion was observed in any of our patients. We attribute this to the fact that splint application was not continued for long enough to develop movement restriction, and passive elbow movements were performed intermittently during dressing changes. A large series study investigating the risk factors for ulnar nerve instability found that the male sex and younger age might cause stronger tricep contraction and, therefore, may be the strongest predictor of instability [14]. In this study, 12 out of 22 patients were male, and the mean age was 46 years. Our results do not support that the male sex and younger age have a higher risk.
This study has some limitations such as its retrospective nature, the limited number of patients for this common surgical pathology, and short- to medium-term follow-up results. Providing long-term results with a larger number of patients will contribute more to the field.
Conclusions
In CuTS, which is particularly common and contains debates that have not yet been clarified, the most preferred surgical method is in situ release, while AT with higher complications is preferred less frequently. In the frequent surgical treatment of CuTS, AT is less preferred because it is more prone to complications. For ulnar nerve instability seen following ISR, it is a method that we could recommend in the light of the positive clinical results we have obtained with temporary extension splinting in temporary extension that does not require additional surgical intervention, despite some techniques that protect the nerve in place or AT recommendations in the literature. Temporary splint in extension as an alternative to AT in ulnar nerve instability following ISR is a practical method that generates positive results.
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
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2. Boone S, Gelberman RH, Calfee RP. The management of cubital tunnel syndrome. J Hand Surg Am. 2015;40(9):1897–904.
3. Zhang D, Earp BE, Blazar P. Rates of Complications and Secondary Surgeries After In Situ Cubital Tunnel Release Compared With Ulnar Nerve Transposition: A Retrospective Review. J Hand Surg Am. 2017;42(4):294.e1-5.
4. Soltani AM, Best MJ, Francis CS, Allan BJ, Panthaki ZJ. Trends in the surgical treatment of cubital tunnel syndrome: an analysis of the national survey of ambulatory surgery database. J Hand Surg Am. 2013;38(8):1551-6.
5. Krogue JD, Aleem AW, Osei DA, Goldfarb CA, Calfee RP. Predictors of surgical revision after in situ decompression of the ulnar nerve. J Shoulder Elbow Surg. 2015; 24(6):634-9.
6. Tang P. The Blocking Flap for Ulnar Nerve Instability After In Situ Release: Technique and a Grading System of Ulnar Nerve Instability to Guide Treatment. Tech Hand Up Extrem Surg. 2017;21(4):137-42.
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14. Matzon JL, Lutsky KF, Hoffler CE, Kim N, Maltenfort M, Beredjiklian PK. Risk Factors for Ulnar Nerve Instability Resulting in Transposition in Patients With Cubital Tunnel Syndrome. J Hand Surg Am. 2016;41(2):180-3.
Download attachments: 10.4328.ACAM.21250
Ömer Ayık, Ümit Aygün, Murat Altan, Soner Özcan. Temporary splint application in extension to prevent ulnar nerve instability after in situ release. Ann Clin Anal Med 2022;13(11):1205-1209
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Analysis of navicular drop test values of patients with plantar fasciitis
Rumeysa Dikici 1, İsmihan İlknur Uysal 2, Ali Yavuz Karahan 3, Zeliha Fazlıoğulları 4
1 Department of Anatomy, Faculty of Medicine, Alanya Alaaddin Keykubat University, Antalya, 2 Department of Anatomy, Faculty of Medicine, Necmettin Erbakan University, Konya, 3 Department of Physical Therapy and Rehabilitation, Faculty of Medicine, Uşak University, Uşak, 4 Department of Anatomy, Faculty of Medicine, Selçuk University, Konya, Turkey
DOI: 10.4328/ACAM.21253 Received: 2022-05-31 Accepted: 2022-07-15 Published Online: 2022-07-20 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1210-1213
Corresponding Author: Rumeysa Dikici, Department of Anatomy, Faculty of Medicine, Alanya Alaaddin Keykubat University, Antalya, Turkey. E-mail: rumeysa.dikici@alanya.edu.tr P: +90 545 553 32 06 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3144-8740
Aim: The aim of this study is to investigate the usability of navicular drop test (NDT) in the diagnosis of plantar fasciitis (PFs).
Material and Methods: Fifty patients aged 35-60 years who were diagnosed with PF in the physical therapy clinic and 50 healthy participants in the same age range were included in this study. Age, height, weight, dominant lower extremity of all participants were determined and body mass index was calculated. The navicular drop test measurements of all participants were performed. Data were compared between the two groups.
Results: The body mass index (BMI) in the PFs group was statistically significantly higher than in the control group (p<0.05). The right foot was dominant (93%) in both groups and PFs was more common on the right side in the patient group (p<0,05). The NDT data were statistically significantly higher in the PFs group on the right and left sides.
Discussion: Besides the fact that BMI is an important risk factor for the formation of PF, an increase in the amount of displacement in the navicular tubercle due to overloading of the extremity may further increase this risk. We believe that the diagnosis of PFs can be supported by NDT in physical examination.
Keywords: Navicular Drop Test, Plantar Fasciitis, Medial Longitudinal Arch, Foot Posture
Introduction
The calcaneus and navicular bones are keystones in foot biomechanics. The tendon of the posterior tibial muscle, a dynamic stabilizer of the medial longitudinal arch, inserts into the navicular tuberosity [1,2]. The plantar fascia, which is a passive stabilizer that supports the arches of the feet, attaches to the medial tubercle of the calcaneus [3]. Repetitive stress/traction exerted by the plantar fascia on the calcaneus is hypothesized to be one of the possible causes of the calcaneal spur [4]. PFs is the most common cause of heel pain in adults [5]. This chronic degenerative process results from micro-tears in the calcaneal junction as a result of biomechanical overuse resulting from prolonged standing or running [6].
The relationship between the tension of the plantar fascia and the height of the arch of the foot is known. Therefore, it is recommended to investigate the relationship between PFs and the position of the navicular bone, which affects the medial longitudinal arch of the foot and thus the tension of the plantar fascia [5]. First described in 1982, NDT is the most widely used clinical test to examine the medial longitudinal arch [7]. This test is used to measure how much the navicular tuberosity height changes position with foot load. The difference between the navicular tubercle height, measured in the sitting position, and the navicular tubercle height measured when the foot is fully loaded on one leg is calculated [8].
This study aims to obtain the NDT data of patients with PFs and individuals who have no complaints in the foot region and to investigate the usability of this test in the diagnosis of PFs.
Material and Methods
This study is a master thesis project. The study protocol was made on the principles of the Declaration of Helsinki and was approved by the Selçuk University Clinical Research Ethics Committee (approval number, 2014/311). At the beginning of the study, all participants were informed and a consent form was filled out.
Two groups were determined according to the physical examination and foot radiographs of the patients who applied to the physical therapy and rehabilitation outpatient clinic. Fifty patients aged 35-60 years who were diagnosed with PFs and 50 volunteers aged 35-60 years who applied with complaints related to upper extremities such as shoulders and elbows and had no complaints in the foot region were included in the study.
The questionnaires and measurements applied to the participants were carried out by the same person in the same circumstances. Patients with ankylosing spondylitis and another known spondyloarthropathy, joint hypermobility syndrome (Beighton score 4 and above [9]), and pregnant women were excluded from the study. In addition, those who had lower extremity surgery, lower extremity length inequalities, and foot deformities such as tarsal coalition and hallux valgus were excluded from the study.
Gender, age, and foot dominance of the participants included in the study were recorded, height (meter, m), weight (kilogram, kg) measurements were made and body mass index (BMI= kg/m²) was calculated [10].
Participants in the plantar fasciitis and control groups were divided into four groups according to body mass indexes (low<20; normal 20-25; overweight 25-30; obese 30-40). All measurements were repeated in both extremities for the patient and control groups. In the patient group, the extremities diagnosed as plantar fasciitis by the physical therapy and rehabilitation physician were also recorded as right, left, and bilateral.
For the NDT, participants were seated in a height-adjustable chair with their hips and knees at 90°. The ankle joint was fixed in the subtalar neutral position [10]. The foot was slowly turned outward until the talus was in a central position and the depressions felt under both toes were even. The navicular tuberosity was palpated approximately 2.5 cm anteroinferior to the medial malleolus tip and then marked with an erasable marker [7].
The navicular tuberosity was marked on a rigid measurement chart with the subtalar joint in neutral position. The map base was in full contact with the ground and the level where the point marked on the skin coincided with it was marked on the map. The distance from the ground to the navicular was measured by millimeters with a ruler [7].
The exact measurement was made while standing (Figure-1a), with an equal amount of body weight on each leg [10]. The navicular height difference in mm between the two points marked on the map between the sitting and standing positions represented the NDT [7,10] (Figure-1b).
This process was repeated 3 times for each participant. This method for measuring NDT has shown good reliability [7,10].
These calculated NDT values were divided into two groups as normal (10 mm ≤) and hyperpronation (>10 mm) [10].
Statistical Analysis:
Statistical analysis of the study was performed using the SPSS program, and a p-value of <0.05 was considered significant. Data were summarized as mean ± standard deviation and percentage, and the chi-square test was used to compare categorical data. Comparisons between the two groups were made using the Student’s t-test (t-test for the independent group) when parametric conditions could be met, and the Mann-Whitney U test when they could not.
Results
The descriptive characteristics of the participants are given in Table-1 (Table-1). While there was no underweight person according to BMI in the PFs group, there were 9 normal weight individuals (18%), 21 overweight individuals (42%), and 20 obese (40%) individuals. The control group consisted of 4 underweight individuals (8%), 19 normal weight individuals (38%), 18 overweight individuals (36%), and 9 obese individuals (18%).
According to the results we obtained, when the Students t-test was performed, the weight and BMI of the individuals in the PFs group were significantly higher than in the control group (p<0.05).
According to foot dominance, 48 people (96%) in the PFs group and 45 people (90%) in the control group were statistically right dominant (p<0.05). In total, 93% were right dominant and 7% left dominant. PFs was diagnosed at a statistically significant rate (52%) on the right side (Table-1).
NDT values were statistically significantly higher in the PFs group than in the control group (p<0.05) (Table-2). As a result of NDT, hyperpronation on the right side was 50% (25 feet) and 30% (15 feet) on the left side (ND>10 mm) in the PFs group. In the control group, all participants (100%) had normal (NDT≤10 mm) values on the right and left sides. In the control group, all participants (100%) had normal (NDT≤10 mm) values for the right and left sides.
Discussion
NDT values in the PFs group were found to be significantly higher than in the control group (p<0.05). This difference suggests that the displacement of the navicular tuberosity, which increases as a result of foot overload as a natural consequence of BMI, is associated with the formation of PFs. In the literature, studies are showing that a high BMI is effective in reducing foot arch and increasing foot pronation, thus increasing the risk of PFs [6,11,12].
Prichasuk and Subhadrabadandhu [12] argued that excessive weight gain, aging, and gender might be important factors that affected the fall of the foot arch and the increase in PFs formation, and also that these factors might lead to the development of plantar heel pain.
In contrast, Menz et al. [13]. reported that there was no relation between the navicular tuberosity height and the formation of PFs. Similarly, Gill [14] observed PFs development in increased arch height. Few studies were conducted to determine the relations between foot biomechanics and PFs. Tauntan et al. [15] argued reported that 19% of patients with PFsis had abnormal arch structure, conversely, Irving et al. [15] argued that chronic plantar heel pain was not associated with the height of the arch.
The rate of increased pronation in patients with PFs is not known completely. Werner et al. [16] found the rate of increased subtalar pronation (hyperpronation) as 53% with PFs. Çınar’s study [17] with 73 PFs patients found that the hyperpronation rate measured by the NDT was 34%. In this study, the rate of hyperpronation (NDT>10 mm) in the right extremity in the PFs group was 50% in the right extremity and 30% in the left extremity. The hyperpronation rate in the control group was 0%.
Rathleff et al. [18] measured dynamic NDT in healthy people as 5±2 mm during running, and static ND as 3±0.5 mm before running. Bennet et al. [19] found mean static NDT measurements of 77 healthy athletes as 8.5±4 mm on the right and 8.7±4 mm on the left. Unver and Bek [20] found static NDT measurements of 12±2 on the right and 13±2 on the left in patients with increased pronation.
In this study, NDT was determined as 10±3 mm on the right and 8.5±3 mm on the left in the plantar fasciitis group. In our study, we determined static NDT as 5±1 mm on the right side and 4±1 mm on the left side in the control group.
In the study, subtalar joint pronation was examined by performing NDT. A significant correlation was found between increased subtalar joint pronation and the incidence of PFs. These data are similar to the results of studies on PFs and healthy groups in the literature. We think that increasing BMI will increase subtalar joint pronation. We believe that this study will contribute to the clinic in the field of foot anatomy and biomechanics.
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.
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Rumeysa Dikici, İsmihan İlknur Uysal, Ali Yavuz Karahan, Zeliha Fazlıoğulları. Analysis of navicular drop test values of patients with plantar fasciitis. Ann Clin Anal Med 2022;13(11):1210-1213
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The effect of COVID-19 infection in pregnancy on childbirth fear and prenatal attachment level in pregnant women: A survey study
Eda Bingül 1, Bakiye Akbaş 2, Berna Aşır 1, Selvihan Tapanoğlu Karaca 1, Sibel Ejder Tekgündüz 1, Ayşe Nur Aksoy 1
1 Department of Obstetrics and Gynecology, Health Sciences University, Erzurum Regional Education and Research Hospital, Erzurum, 2 Department of Obstetrics and Gynecology, Faculty of Medicine, Istinye University, Istanbul, Turkey
DOI: 10.4328/ACAM.21255 Received: 2022-06-11 Accepted: 2022-07-15 Published Online: 2022-07-18 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1214-1218
Corresponding Author: Bakiye Akbaş, Department of Obstetrics and Gynecology, Faculty of Medicine, Istinye University, Istanbul, Turkey. E-mail: bakiyeokumus@gmail.com P: +90 532 240 81 07 Corresponding Author ORCID ID: https://orcid.org/0000-0003-2480-1374
Aim: Fear of childbirth is an emotional stress that affects the mental health and well-being of mothers during pregnancy. The aim of the present study was to compare the prenatal attachment, childbirth fear and hopelessness levels of pregnant women who had and did not have COVID-19 infection during pregnancy.
Material and Methods: This prospective questionnaire study was conducted with participants between the ages of 18 and 40 who had 20 or more gestational weeks. Two groups were formed as follows: Group 1: Participants who had COVID-19 infection, and Group 2: Participants who did not have COVID-19 infection during pregnancy. Patients in both groups were given questionnaires using Wijma Delivery Expectancy/Experience Questionnaire, Prenatal Attachment Inventory and Beck Hopelessness Scale, and the results were recorded.
Results: Childbirth fear and Beck Hopelessness Scale scores were higher in Group 1 than in Group 2 (p < 0.001 and p = 0.023, respectively). The Prenatal Attachment Inventory scale score of Group 2 was higher than that of Group 1 (p = 0.001). A negative correlation was observed between childbirth fear and prenatal attachment scores (p = 0.012, r= -0.250). There was a negative correlation between the Beck Hopelessness Scale score and Prenatal Attachment Inventory scores (p < 0.001, r= -0.416).
Discussion: Covid-19 infection during pregnancy increased the childbirth fear and hopelessness levels in pregnant women while reducing the prenatal attachment level. Pregnant women should be informed about prevention methods against COVID-19 infection and necessary measures should be taken.
Keywords: COVID-19, Fear of Childbirth, Hopelessness, Pregnancy, Prenatal Attachment
Introduction
While dreaming of having a baby, pregnant women may have the fear of childbirth pain, obstetric intervention anxiety and concerns about the baby’s health. Severe childbirth fear can increase the mother’s blood pressure, leading to premature birth and an increase in cesarean section rates due to fetal distress. In addition, it can reduce oxytocin levels, causing prolongation or even arrest of labor [1, 2]. It was reported that due to childbirth fear, women could postpone pregnancy, avoid conception, and pregnant women could decide to terminate the pregnancy or undergo an optional cesarean section [3, 4].
A safe bonding of mother and baby is crucial in the social and emotional development of the baby. During pregnancy, the mother’s love for her baby and the establishment of a bond was defined by Muller [5] as a prenatal attachment. It is known that the basis of mother-baby attachment is laid in the prenatal period. Prenatal attachment begins with the woman’ positive reaction to pregnancy. An attached pregnant believes that she has a connection with her baby, imagines her baby, and considers her as a separate individual. These thoughts cause the mother to show love, compassion and care, to protect, and to interact sensitively with the baby. Prenatal attachment may be affected by the psychological and social state of the mother during the prenatal period. Studies showed that anxiety and depression of the mother affect the level of prenatal attachment [6].
COVID-19 infection spread rapidly around the world and was declared a pandemic by the World Health Organization (WHO). COVID-19 infection is considered a risk factor for pregnant women. As a result of social measures taken due to the COVID-19 pandemic and protocols implemented by health institutions, pregnant women who faced childbirth, which is an irreversible moment of life, did not receive adequate support from their spouses and families, which led to an increase in anxiety and fear levels [7]. Studies reported optional abortions due to concerns about the fate of COVID-19 infection in early gestational weeks [8]. The effect of COVID-19 infection on pregnancy-related fear and anxiety has not been systematically revealed, and information about the clinical characteristics of pregnant women who have the infection is limited.
The aim of the present study was to compare the prenatal attachment, childbirth fear and hopelessness levels of pregnant women who had and did not have COVID-19 infection during pregnancy.
Material and Methods
This prospective survey was conducted on pregnant women with 20 or more gestational weeks and followed up at SBU Erzurum Regional Education and Research Hospital Obstetrics and Gynecology Clinic. The participants were informed before the study and their written approval was obtained. The exclusion criteria for the volunteers in the study were ages younger than 18 and over 40, the presence of fetal anomaly and additional diseases such as hypertension or diabetes, chronic or psychiatric disease, mental illness, unwillingness to participate and previous birth-related negative experiences.
Two groups of patients were formed with the participants in the study: Group 1: Participants who had COVID-19 infection during pregnancy, and Group 2: Participants who did not have COVID-19 infection during pregnancy. Demographic data of the patients along with clinical data such as pregnancy week during the COVID-19 infection, whether hospitalization was required due to COVID-19 infection, need for intensive care and drug use due to COVID-19 infection were recorded. All participants were given Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ) to measure birth fear, Prenatal Attachment Inventory (PAI) to measure prenatal attachment level, and Beck Hopelessness Scale (BHS) to measure levels of hopelessness and were asked to read and answer the questions. Scores of the measurement tools were recorded.
Wijma Birth Expectation/ Experience Scale – Version A (W-DEQ/ A Version)
The scale consisting of 33 items to measure the fear of childbirth experienced by women was developed by Wijma et al. [9]. Responses on the scale are numbered from 0 to 5 where 0 is expressed as “extremely” and 5 as “not at all”. The minimum score on the scale is 0, while the maximum is 165. Higher scores mean higher childbirth fear experienced by women. The scale was adopted to Turkish, and validity and reliability studies were performed by Körükçü et al. [10]. The Cronbach alpha value of the scale was 0.89 and the split-half reliability was 0.91.
Prenatal Attachment Inventory (PAI)
This inventory was developed by Muller [5] in 1993 to measure the level of prenatal attachment in pregnant women and is one of the most commonly used tools in the literature to measure the level of prenatal attachment. The scale, developed to determine the levels of emotion, thought and attachment of women to their babies during pregnancy, consists of 21 items. Each item is a 4-point Likert type: 1: never, 2: sometimes, 3: often, 4: always. The minimum score is 21 and the maximum score is 84 points. Higher scores indicate higher levels of prenatal attachment. Turkish validity and reliability study of the inventory was performed by Yilmaz et al. [11] and Cronbach alpha was 0.84.
Beck Hopelessness Scale (BHS)
This scale was developed by Beck et al. [12] in 1971 to determine an individual’s negative expectations for the future. Turkish validity and reliability study was carried out by Dilbaz et al. [13]. The scale consists of 20 items, scored by 0 or 1 where a compatible response is given a “1” score and an incompatible response is given a “0” score. The resulting arithmetic sum constitutes the total “score of hopelessness”. The scale has no threshold point, and the score ranges between 0 and 20. Higher scores mean higher hopelessness levels of the individual. In this study, the Cronbach Alpha value of the scale was found to be 0.84.
Statistical Analyses
The data were expressed as mean ± standard deviation or n, percentage. The data were analyzed using SPSS software (ver. 13.0). The study groups were compared using the Independent Samples t-test and Chi-square test. Pearson correlation analysis was performed to investigate the relationship between W-DEQ, PAI and BHS scores. p < 0.05 was considered statistically significant.
Results
A total of 100 pregnant women, i.e., 50 people in each group, were included in the study. The groups were demographically similar (Table 1).
It was found that the level of birth fear in patients who had COVID-19 infection during pregnancy was significantly higher than in those who did not (p < 0.001). In addition, prenatal attachment levels were significantly lower in patients with COVID-19 infection during pregnancy compared to those without the infection (p < 0.001). The patients with COVID-19 infection during pregnancy had a higher Beck Hopelessness Scale score than the patients who did not have the infection (p = 0.023) (Table 2). A patient who participated in the study and had COVID-19 infection had shortness of breath that required her to be admitted to the Intensive Care Unit, and most patients (n = 29, 58%) had mild flu infection. No patients required antiviral or steroid use. Based on Pearson’s correlation analysis, a negative relationship was observed between childbirth fear and prenatal attachment scores (r= -0.250, p = 0.012) (Figure 1).
There was no correlation between Beck’s Hopelessness Scale and childbirth fear scores (r = 0.168, p = 0.095). However, there was a negative correlation between Beck’s Hopelessness Scale and Prenatal Attachment scores (r= -0.416, p < 0.001) (Figure 2).
Discussion
While giving birth and transitioning to parenting is a happy life event, it can also be described as a stressful experience. During COVID-19 pandemic, pregnancy and birth management have gained importance. The COVID-19 pandemic is a stressor creating a fear of infection in the pregnant woman. This situation leads pregnant women to an intense isolation, causing them feel unsafe. Besides, difficulties encountered in reaching professionals such as midwives and obstetricians have resulted in a decrease in the level of access to health services by pregnant women. This produced increased fear and anxiety of childbirth in pregnant women [14]. It was stated that pregnant women with social support who could reach health professionals had lower fear of childbirth, lower levels of anxiety experienced during pregnancy and higher prenatal attachment rates, and they adapted more easily to the role of motherhood in the postpartum period [15]. In the present study, we observed that the levels of childbirth fear and the helplessness feeling were higher in pregnant women with COVID-19 disease than in pregnant women who did not have the disease. On the other hand, prenatal attachment level was higher in patients who did not have the infection. It was found that prenatal attachment level had negative correlations with levels of childbirth fear and hopelessness feeling.
Fear of childbirth is a common condition experienced by pregnant women. The person who encounters a frightening situation is distracted, focuses on the factor that causes the threat, and his/her anxiety increases. Such a condition leads a pregnant woman into a negative mood and makes her think that she cannot complete the birth successfully. This vicious cycle leads to negative expectations [4]. A study examining the effect of childbirth fear on the birth process showed that those who had fear of childbirth had a longer birth process, and they more likely needed epidural anesthesia, induction, instrumental delivery and emergency cesarean delivery needs [16]. In a literature review on pregnancy fear, Aksoy [4] stated that infection during pregnancy increased anxiety and childbirth fear of the mother. The fact that the COVID-19-related problems that infected pregnant women may face were not fully known has been shown to cause increased anxiety and childbirth fear due to the effects on health of both their own and their babies [14]. A study evaluating women with and without COVID-19 infection during the pandemic indicated that women who had the infection had higher levels of childbirth fear and anxiety [17]. In line with the results of that study, we observed that the levels of hopelessness and childbirth fear in pregnant women who had COVID-19 infection were higher than in those who did not have the infection.
The COVID-19 pandemic is an international public health emergency affecting the whole world. It was shown that COVID-19 infection led to increased anxiety levels among pregnant women [18]. During the COVID-19 pandemic, social distancing was encouraged all over the world to reduce interactions between people and thus reduce the likelihood of new infections. This has reduced or altered people’s daily activities and led to different levels of psychological pressure that can trigger feelings of loneliness and helplessness or various emotional states such as stress, irritability, physical and mental fatigue, and despair [19]. While depression scores were found similar in both sexes, rates of depression, anxiety and hopelessness were significantly higher in pregnant women [18]. A Canadian study on pregnant women reported that 37 % and 57% of pregnant women experienced clinically severe symptoms of depression and anxiety, respectively [20]. In addition, a study conducted in the United States dealing with women in the perinatal period reported that 36% had high levels of depression and 23% felt hopeless [21]. These findings showed that pregnant women experienced high levels of depression and anxiety after the first days of pandemic compared to the pre-pandemic period. Depression, anxiety and stress experience during pregnancy can cause maternal and fetal health problems in the long term. Mental problems, especially anxiety, despair and depression, was reported to increase pregnancy complications, negatively affect fetal health, and cause low birth weight, premature birth and intrauterine developmental retardation [22]. Therefore, there is an urgent need to understand how the COVID-19 pandemic affects pregnant women and to prevent the occurrence of secondary health problems for them and for their unborn children. In the present study, it was observed that the level of hopelessness was significantly higher among pregnant women with COVID-19 infection compared to pregnant women who did not have the infection.
In the prenatal period, the connection between the mother and fetus forms the main basis of attachment. This plays a decisive role in the relationship between mother and child in the postpartum period. Research showed that the mother’s attachment to her child begins long before birth [23]. Although the mental health of pregnant women is considered as the most important factor affecting prenatal attachment during this developmentally critical period, the physiological condition of the expectant mother in this process and the methods of coping with the stress associated with the diseases that occur during pregnancy are also important factors that are effective in establishing this bond. Kurt et al. stated in their study that in pregnant women who had COVID-19, the anxiety and depression levels were high, and the prenatal attachment rate was low [24]. Tanaçan et al. reported that infection of mother with COVID-19 during pregnancy increased the level of hopelessness, anxiety and depression and decreased the level of prenatal attachment [25]. In line with these results, we observed that the level of childbirth fear and hopelessness were higher in pregnant women who had COVID-19 infection. Besides, we found that prenatal attachment had negative correlations with childbirth fear and hopelessness feeling.
In our literature survey, we did not find any other studies investigating the level of childbirth fear in pregnant women with COVID-19 infection. Our study is important for the literature in terms of presenting new findings. The relatively small number of patients included in the study was the main limitation.
Conclusion
COVID-19 infection during pregnancy increases the level of childbirth fear and despair and reduces the level of prenatal attachment in pregnant women. As the level of childbirth fear and/or despair increases in pregnant women, prenatal attachment levels decrease. Prospective studies involving higher number of pregnant women are needed in this regard. Social and psychologic support should be provided to reduce the level of childbirth fear and helplessness feeling in pregnant women infected with COVID-19. In addition, pregnant women should be informed about prevention methods against COVID-19 infection.
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.
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Eda Bingül, Bakiye Akbaş, Berna Aşır, Selvihan Tapanoğlu Karaca, Sibel Ejder Tekgündüz, Ayşe Nur Aksoy. The effect of COVID-19 infection in pregnancy on childbirth fear and prenatal attachment level in pregnant women: A survey study. Ann Clin Anal Med 2022;13(11):1214-1218
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Accuracy of point of care ultrasound in evaluation of patients with dyspnea and chest pain in the emergency department
Mohammed Ali 1, Salah El Tahan 2, Abdel Aziz El Nekidy 3, Alaa El Din Abdallah 4, Khaled Salah 1
1 Department of Emergency Medicine, 2 Department of cardiology and angiology, 3 Department of Radio diagnosis and intervention, 4 Department of Chest Diseases, Faculty of Medicine, Alexandria University, Alexandria, Egypt
DOI: 10.4328/ACAM.21258 Received: 2022-06-05 Accepted: 2022-08-22 Published Online: 2022-08-25 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1219-1223
Corresponding Author: Mohammed H Ali, Department of Emergency Medicine, Faculty of Medicine, Alexandria University, El- Ramel, Alexandria, Egypt. E-mail: mohammedhassan00155@gmail.com P: +20 100 358 31 19 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8200-2952
Aim: Dyspnea and chest pain are common principal complaints among individuals who present to the Emergency Department (ED). Point of care ultrasound (POCUS) is more accurate than chest X-Ray (CXR) for the diagnosis of diseases most typically found in patients with chest discomfort and dyspnea. In this study, we aimed to assess the diagnostic accuracy of POCUS in cases presented to the emergency rooms with dyspnea and/or chest discomfort.
Material and Methods: Patients with dyspnea and/or chest pain were submitted to POCUS protocol, which includes lung ultrasound, echocardiography, inferior vena cava (IVC) and deep vein thrombosis (DVT) scans between December 2020 and December 2021. Pre- POCUS diagnoses and POCUS diagnoses were compared to final diagnosis to detect the degree of agreement.
Results: One hundred patients were enrolled in this study. POCUS was 100 % accurate in diagnosing cases of pneumothorax; 99 % accurate in diagnosing pleural effusion; 98 % accurate in diagnosing pulmonary edema; and 95 % accurate in diagnosing pneumonia. It has excellent agreement with cases of acute coronary syndrome (ACS), pulmonary embolism (PE), and pneumothorax (kappa index = 1), as well as a nearly perfect agreement with pulmonary edema (kappa index = 0.842).
Discussion: POCUS is a practical and reliable diagnostic tool that can help in narrowing down the differential diagnoses and shortening the diagnostic time in the assessment of patients with dyspnea and/ or chest pain in the ED.
Keywords: Accuracy, POCUS, Dyspnea, Chest Pain
Introduction
Dyspnea and chest pain are common principal complaints among individuals who present to the ED [1]. As there are various possible etiologies of dyspnea, it is difficult to come up with a straightforward dyspnea diagnostic algorithm [2]. Chest pain is caused by numerous causes ranging from self-limited to lethal causes, such as ACS, PE, pneumothorax, and aortic dissection [3]. Although CXR and clinical examination are the most widely utilized techniques in the diagnosis of breathing difficulties, they are still inadequate for definitive diagnosis. Computed tomography (CT) scans are considered the gold standard for identifying most lung diseases, but they are time-intensive and require patient transfer to specialized units [4]. Previously, ultrasound was an unacceptable method for lung evaluation due to the fact that air hinders the ultrasound beams. However, recently, pulmonary ultrasound has become an essential diagnostic tool in emergency and pulmonary medicine as it is radiation-free, non-invasive, and a bedside imaging modality that is used in addition to physical and clinical evaluation [5].
Thoracic ultrasonography has been used to diagnose pulmonary edema, pneumonia, pneumothorax, and pleural effusion [6]. Several protocols have been developed to evaluate the role of pulmonary ultrasound in cardiorespiratory conditions; the most widely used is the BLUE protocol (bedside lung ultrasound in emergency) which was developed by Daniel Lichtenstein. The BLUE protocol was accurate in the diagnosis of 90.5% of causes of respiratory failure [7]. FALLS- protocol (fluid administration limited by lung ultrasound) is another protocol used in circulatory failure depending on cardiac and pulmonary ultrasound [8].
According to studies, POCUS is more accurate than CXR for the diseases most typically found in cases with chest pain and dyspnea [1]. POCUS differs from comprehensive ultrasound examination that is used to answer a precise medical problem [9]. POCUS helps in the evaluation of several conditions such as cardiac arrest, trauma, chest pain, and shortness of breath [10]. Gargano et al. have indicated that combining lung ultrasonography with echocardiography could narrow the differential diagnosis of cardiorespiratory problems [11].
The goal of this study is to assess the diagnostic accuracy of POCUS in the evaluation of patients with dyspnea and/or chest pain in the emergency rooms.
Material and Methods
This cross-sectional study was carried out at the ED of Alexandria Main University Hospital, Egypt, from December 2020 to December 2021. Ethical approval was obtained from Alexandria University Ethical Committee (Reference number 0201345). Informed consent was taken from all patients or their legally acceptable representatives.
Population
Patients were included into the study if they matched the following criteria: age >18 years with a primary complaint of dyspnea and/or chest pain. Patients were excluded if they had an unstable tachyarrhythmia or bradyarrhythmia that leads to a shock state and patients with a known diagnosis were referred from another hospital. The attending clinician made a preliminary diagnosis and treatment plan.
Clinical assessment
Vital signs, general examination and patient’s clinical history were all documented by the emergency clinician. All patients received routine testing electrocardiography (ECG), CXR, and laboratory investigations, such as arterial blood gases, blood assessment, and cardiac enzymes, as part of the hospital’s procedure.
Point-of-care ultrasound
All patients were submitted to an ultrasonography approach after the first examination, which included pulmonary ultrasonography, echocardiography, inferior vena cava evaluation (IVC), and a deep vein thrombosis (DVT) test.
Lung scan was carried out using one of two ultrasound devices: Mind ray DC-30, and DP-20 (Mind ray, Shenzhen, China) with a curvilinear probe (2-5 MHz) and a high-frequency linear probe (5-10 MHz). Ultrasound examinations were performed immediately after the initial assessment in the ED with the patient in the supine or semi-setting position. Lung ultrasound was done for the detection of lung consolidation, pneumothorax, pulmonary edema, and pleural effusion.
POCUS diagnosis of different lung pathologies:
1. Pneumonia was diagnosed by the detection of consolidation or shred sign, with or without effusion.
2. Pulmonary edema was diagnosed by the presence of multiple bilateral B-lines equal or more than three with or without pleural effusion.
3. Pneumothorax was considered in case of absence of lung sliding and the presence of lung point that is pathognomonic for pneumothorax.
4. Pleural effusion was defined as a hypoechoic area between visceral and parietal pleura that may be bilateral.
More than one diagnosis could be present in the same patient.
Echocardiography was carried out using a Vivid machine (General Electric, Boston, USA) with a 2.8-4 MHz phased array probe. The heart contractility, presence or absence of effusion around the heart, equalization of the heart chambers, aortic root diameter, condition of the valves, signs of pericardial tamponade, and regional wall motion abnormalities were examined.
Ultrasound was also used to assess the IVC diameter. Measurement of the maximum diameter at the end of expiration and the minimum diameter at the end of inspiration were obtained.
Finally, ultrasound two-point compression test was used to diagnose DVT in this study [12]. Area of the femoral vein as well as area of the popliteal vein were examined for compressibility; if the vein was not collapsible, a positive test was reported.
The ultrasound protocol was carried out by the emergency physician with four years of experience in the field of emergency ultrasound. All scans were performed without interruption of the patient’s medical care and the duration of ultrasound examination was recorded.
The patient’s age, gender, and comorbidities were all gathered as part of the demographic data. Vital signs at the time of presentation, admission diagnoses, ECG and laboratory investigations such as cardiac biomarkers, and complete blood count, were obtained in the emergency rooms. There are no gold standard tests for all etiologies, thus we used a gold standard test for each etiology: echocardiography performed bycardiologists for cardiac heart failure; CT pulmonary angiography for PE; CT chest for pneumonia, pneumothorax, and pleural effusion and echocardiography and cardiac enzymes investigations for the ACS.
Statistical analysis
Statistical Package for the Social Sciences (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp) was used to analyze the data. Categorical data were represented as numbers and percentages. Quantitative data were expressed as mean and standard deviation. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for lung ultrasound and chest radiography, using CT chest as the gold standard test. The agreement between pre- POCUS diagnosis and POCUS diagnosis was calculated using Cohen’s kappa coefficient. The Kappa values were classified as follows: equal or less than 0.20 as poor agreement; 0.21 to 0.40 as fair agreement; 0.41 to 0.60 as moderate agreement; 0.61 to 0.80 as good agreement; above 0.80 as very good agreement.
Results
This study was conducted on 100 patients with dyspnea and/or chest pain in the ED. Fifty-nine of the studied cases were males (59.0%) and 41 were females (41.0%). The median age was 55 years. Dyspnea was the most reported complaint (60%), followed by chest pain (26%). Eighty percent of the subjects had comorbidities, which included ACS (16%), hypertension (HTN) (38%), COPD/Asthma (20%), heart failure (13%), renal impairment (6%) and liver disease (9%) (Table 1).
The ejection fraction of the left ventricular (LVEF) was decreased in 30% of cases and hyper dynamic in 9% of cases. The most common sonographic findings in the studied patients were bilateral B lines, pleural effusion, and lung consolidation. The size of the IVC was scanned to test volume responsiveness; 35% of patients were volume responsive (flat IVC), whereas 65 % were not (fat IVC). Scans for DVT were positive in 7 cases (Table 1).
The accuracy of CXR and POCUS revealed that the sensitivity and specificity of CXR and POCUS were respectively: 72% and 100% versus 96% and 100% for pleural effusion; 75% and 100% versus 100% and 100% for pneumothorax; 57.9% and 100% versus 73.7% and 100 % for pneumonia; 45.8% and 100% versus 95.8% and 98.7% for pulmonary edema (Table 2).
In this study, the most common final diagnoses were ACS (25 patients, 25%), pleural effusion (25 patients, 25%) and pulmonary edema (24 patients, 24%). The emergency physician was able to correctly diagnose pleural effusion in 18 patients (18%) pre-POCUS compared to 25 patients (100%) post- POCUS (Kappa index = 1). Pulmonary edema was diagnosed in 19 patients (19.0%) pre- POCUS diagnosis and in 24 patients (24%) post- POCUS diagnosis (kappa index = 0.945) (Table 3).
There was a very good agreement between pre-POCUS diagnosis and post- POCUS diagnosis regarding ACS, pericarditis, and musculoskeletal pain (kappa index = 1). There was perfect agreement between POCUS diagnosis and final diagnosis for PE (kappa index = 1). The duration of our echo-ultrasound protocol ranged from 12 minutes to 17 minutes with a median duration of 15 minutes.
Discussion
Focused echocardiography was first used to assess dyspnea in the emergency room in 2001 [13]. It is critical to start rapid focused therapy for pulmonary edema, COPD, pneumonia, and other causes of respiratory distress, however, determining the etiology of dyspnea in unstable patients can be difficult and challenging [14].
There was perfect agreement between POCUS diagnosis and final diagnosis (kappa =1.00) in PE, ACS, and pericarditis, and kappa = 0.945 for pulmonary edema. This is consistent with the findings of Mantuani et al. [14] who discovered that multi-organ POCUS has 100% sensitivity for decompensated heart failure, and Nazerian et al. [15], who emphasized the utility of multi-organ ultrasound in patients with suspected PE.
Our study compared the sensitivities and specificities for CXR and POCUS and discovered that the sensitivity and specificity of CXR and pulmonary ultrasound were: 72% and 100% versus 96% and 100% for pleural effusion; 75% and 100% versus 100% and 100% for pneumothorax; 57.9% and 100% versus 73.7% and 100 % for pneumonia; 45.8% and 100% versus 95.8% and 98.7% for pulmonary edema, respectively. These findings were slightly higher than those of Bekagos et al. who found that chest ultrasound was more accurate than routine CXR in the diagnosis of causes of shortness of breath with sensitivities and specificities of 87.6% and 96.2 % for pulmonary edema; 85.7 %, and 99.0% for pneumonia; 98.2%, and 67.3% for asthma/COPD, 46.2% and 100% for PE, and 71.4% and 100% for pneumothorax, respectively [2]. This could be because our study only looked at a small number of cases.
On the other hand, the sensitivity of pre-POCUS diagnosis was superior to POCUS diagnosis of COPD/asthma with kappa index = 0.828 for pre- POCUS diagnosis and kappa index =0.736 for POCUS diagnosis. Zanobetti et al. had reported the same findings [16]. PE showed kappa index =1, which was superior to the study by Ahn et al., which showed kappa index =0.95. The higher agreement in our study could be due to the integration of lower limb DVT ultrasound in our protocol [17].
An interesting finding was that our protocol identified all cases of ACS, PE, pericardial effusion, and pneumothorax accuracy 100% and Kappa index = 1. This may be due to the integration of focused echocardiography, IVC scan, and DVT scan to lung ultrasound elucidating that merely lung ultrasound is not enough in diagnosing different etiologies of dyspnea.
The duration of our echo-ultrasound protocol ranged from 12 minutes to 17 minutes with a median duration of 15 minutes, this is longer than the scan duration (SD) in research by Russel et al. with an average total time of 12 minutes (SD 4 minutes) to complete [18]. This may be due to the additional parameters being included in our study.
Conclusion
According to the results of this study, POCUS revealed high sensitivity and specificity, therefore it is considered a bedside, dependable, quick, and non-invasive technique. The results imply that it could have a major role in the diagnostic workup of dyspnea and chest pain in the ED, alongside comprehensive echocardiography and CT in difficult scenarios. The use of POCUS by emergency physicians in the detection of different causes of dyspnea and chest pain is feasible, time saving, and avoids unnecessary radiological investigations.
Study limitations
The current study had several limitations. It was a single-center study with small sample size that may hamper some of our findings. Only one physician provided all sonographic tests, hence, the findings may not be applicable to other emergency departments or physicians that perform POCUS as it is user dependent. Patients could not be included consecutively, while the POCUS investigator was not present in the ED, which could have resulted in selection bias. Examiner was not fully blind to the patient’s clinical characteristics, which may also have led to performance bias. One of the study’s limitations is that we did not discriminate between systolic and diastolic heart failure. These limitations should be balanced against the benefits of point-of-care ultrasonography in narrowing the differential diagnosis of dyspnea and chest pain in the ED.
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.
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Download attachments: 10.4328.ACAM.21258
Mohammed Ali, Salah El Tahan, Abdel Aziz El Nekidy, Alaa El Din Abdallah, Khaled Salah. Accuracy of point of care ultrasound in evaluation of patients with dyspnea and chest pain in the emergency department. Ann Clin Anal Med 2022;13(11):1219-1223
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The roles of bun/d-dimer and bun/lactate ratios in indicating mortality in intensive care patients with COVID-19
Soycan Mizrak 1, Ayse Ozdemir 1, Ebru Aladag 2, Nezih Tayyar 3
1 Department of Medical Biochemistry, 2 Department of Anesthesia and Reanimation, 3 Department of Business Administration, Faculty of Medicine, Usak University, Usak, Turkey
DOI: 10.4328/ACAM.21260 Received: 2022-06-11 Accepted: 2022-10-05 Published Online: 2022-10-29 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1224-1228
Corresponding Author: Soycan Mizrak, Department of Medical Biochemistry, Faculty of Medicine, Usak University, 64200, Usak, Turkey. E-mail: soycan.mizrak@usak.edu.tr P: +90 505 686 28 09 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0287-9402
Aim: Coronavirus disease 2019 (COVID-19) is an epidemic disease with variable symptoms and high mortality rates. Therefore, patient follow-up is very significant. We aimed to investigate whether blood urea nitrogen (BUN), D-dimer and lactate parameters, which are laboratory tests used in follow-up, predict mortality.
Material and Methods: The study included 173 COVID-19 patients hospitalized in the pandemic intensive care unit from March 2020 to June 2020. We retrospectively recorded patient age, gender, comorbidity, radiological involvement, oxygen demand, APACHE scores, in-hospital mortality status, BUN, lactate, and D-dimer levels, BUN/D-dimer ratio (BDR), BUN/lactate ratio (BLR). Then we made the statistical comparison between the groups by grouping the patients as discharged and deceased.
Results: Among the patients included in the study, 107 (61.8%) were male and 66 (38.2%) were female. The mean ages between those discharged and those who died in the hospital were 73 and 67.5 years, respectively, and there was a statistically significant difference. The median BUN, d-dimer, lactate and BDR, BLR values of the patients in the non-survivor group were significantly higher than those in the survivor group. BLR had the highest diagnostic ratio (25.03) for estimating in-hospital COVID-19 mortality.
Discussion: We found that BUN, BDR, and BLR levels were reliable predictors of in-hospital mortality in COVID-19 patients. However, BLR was a potent risk assessment tool, especially in defining the risk of in-hospital death.
Keywords: COVID-19, Lactate, Blood Urea Nitrogen, D-Dimer, Mortality
Introduction
In Wuhan, China, there has been an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since December 2019 [1]. Although COVID-19 is primarily a respiratory disease, it can affect multiple organ systems, including the gastrointestinal, hepatic, cardiac, neurological, and renal systems. Therefore, patient follow-up is significantly substantial.
SARS-CoV-2 infection induces a profound inflammatory response that triggers the coagulation cascade. Activation of the coagulation cascade in COVID-19 patients is associated with adverse clinical outcomes, including hypercoagulation status and death. Thrombotic complications and coagulopathies, including disseminated intravascular coagulopathy, are common in COVID-19 and reflect activation of the coagulation cascade, possibly due to viremia or cytokine storm, or possibly superinfection and organ dysfunction. D-dimer is considered the best available laboratory diagnostic marker for hemostatic abnormalities associated with COVID19 [2]. D-dimer is a fibrin degradation product widely used as a biomarker for thrombotic disorders. A D-dimer value of less than 0.5 μg/mL is generally considered normal, and values increase with age and pregnancy. The D-dimer level rises as the severity of community-acquired pneumonia increases. Following the outbreak of the COVID-19 pandemic, D-dimer has been identified as a potential indicator for the prognosis in COVID-19 patients. Elevated D-dimer levels at presentation and significantly increased D-dimer levels (3 to 4 fold) over time are associated with higher mortality, possibly reflecting activation of coagulation from infection/sepsis, cytokine storm, and impending organ failure [3]. There were many studies about the relationship between D-dimer levels and mortality in COVID-19 patients. Although guidelines proposed serial D-dimer measurement for COVID-19 patients, the optimal limit for D-dimer has not yet been determined.
Blood urea nitrogen (BUN) is a nitrogenous end product of protein metabolism and is associated with death in various diseases. BUN represents a surrogate marker to predict persistent organ failure 48 hours after hospital admission in addition to its role in the prediction of kidney function [4]. A multicenter study reported that BUN independently predicted mortality in critically ill patients admitted to the intensive care unit (ICU) [5]. Activation of neurohumoral factors, including the sympathetic nervous system (SNS), renin-angiotensin-aldosterone system (RAS), and arginine vasopressin (AVP), increases flow-dependent urea absorption in the proximal and distal tubules. Elevated blood urea nitrogen (BUN) level can be considered a surrogate marker for neurohumoral activation in heart failure patients [6]. In addition, hyperlactatemia developing with increased hypoxia has traditionally been associated with poor outcomes in critically ill patients, and lactate value is considered one of the most important biomarkers of disease severity in patients with sepsis [7].
Although death rates from COVID-19 are around 2% worldwide, according to the WHO data, some publications report that mortality rates are much higher in patients admitted to the emergency department. This situation may be due to uncertainties and delays in diagnosis and appropriate treatment of the disease. There is a need for an accessible biomarker or calculations that can predict the mortality of COVID-19 patients. In this study, we aimed to investigate the roles of Bun/D-Dımer and Bun/Lactate Ratios, which are laboratory tests used in the follow-up of COVID-19 patients, in predicting mortality.
Material and Methods
The Ethical Committee and the Institutional Review Board of XXX University Faculty of Medicine, where the study was conducted, approved the study design. We reviewed the medical records of 173 patients hospitalized in the pandemic intensive care unit between March-June 2020. We retrospectively analyzed the patient files, and we recorded the APACHE scores, BUN level, lactate, BUN/lactate ratio, D-dimer, BUN/d-dimer ratio, radiological involvement level and age, gender, comorbidity (additional diseases), oxygen requirement, and in-hospital mortality situations of patients. All data were received over the hospital communication system. We made a statistical comparison between the groups by grouping the patients as discharged and deceased using SPSS 20 SPSS 20.0 package program (SPSS Inc., Chicago, IL). We conducted the normality analyses of the data using histograms and the Kolmogorov–Smirnov test. While the normally distributed quantitative data were expressed as mean ± standard deviation values, the non-normally distributed quantitative data were expressed as median values (25–75% quartiles). Categorical variables were expressed as frequency (percentage) values. We investigated the differences between the groups using the Mann–Whitney U test for the non-normally distributed quantitative variables. Intragroup comparisons of the categorical variables were made using the chi-square test. Receiver operating characteristic (ROC) analysis was performed for determining the non-survivor mortality predictive power of the biochemical parameters. The optimum cut-off levels of the biochemical parameters were determined using Youden’s index (sensitivity +1 − specificity). We calculated the sensitivity, specificity, and positive and negative predictive values of the parameters for the optimum cut-off levels. A value of p<0,05 was accepted as statistically significant.
Results
We obtained the patients’ Acute Physiologic and Chronic Health Evaluation (APACHE II) scores by using the patients’ consciousness status, chronic disease status, vital status, and laboratory parameters in the first 24 hours. Results were significantly higher in the non-survivor group than in the survivor group.
Table 2 shows the comorbidity presence in the survivor and non-survivor groups. We compared the frequencies with the chi-squared test. Although the presence of comorbidity was generally significantly higher in the non-survivor group, there was no significant difference in terms of the type of comorbidities (Table 1).
Table 2 shows the rates calculated with the biochemistry parameters measured within the groups using the Mann-Whitney U test. Accordingly, the median BUN, d-dimer, lactate and BDR, and BLR values of the patients in the survivor group were significantly higher than those in the survivor group.
Here, the cut-off value is calculated to indicate mortality, and the specificity and sensitivities were determined according to these cut-offs showed in Table 3. Accordingly, we found the BUN/lactate ratio with the lowest sensitivity and the highest specificity and positive predictive value and the BUN/d-dimer rate with the maximum sensitivity.
If we look at the likelihood ratios, the analyzed parameters are strong indicators that the risk of mortality exists (rule in, LR>1). However, they are not very strong indicators that it does not exist (rule out, LR<1). Diagnostic accuracy rates are between 60-70%, and we observe the highest BUN. The odds ratio is the ratio of occurrence to the absence of events. We found +LR to be the highest in the lactate test and the most helpful parameter in demonstrating mortality risk. Positive Youden indices in all parameters indicate the usability of all of them diagnostically, but the BUN test is the best indicator (Table 3).
If the sensitivity (true positive rate) was plotted against the false positive rate (1-Specificity), the resulting curves are called ROC curves (Receiver Operating Curve).
There is FPR (False Positive Rate) on the X-axis and TPR (True Positive Rate) on the Y-axis in the ROC curve. The higher the level under the curve, the higher the discrimination performance between classes. In estimating in-hospital COVID-19 mortality, the area under the curve (AUC) for BUN was the highest (0.74), and the diagnostic odds ratio was the highest for BLR (25.03) (Figure1).
Discussion
In the study, we showed the power of BUN, lactate, D-dimer, BDR, and BLR ratios in predicting mortality in COVID-19 patients hospitalized in the intensive care unit.
While making parameter selections, we considered the importance of hypoxia in clinical worsening by prioritizing the lung and vascular endothelium, which are the tissues most affected by COVID-19.
There are many studies conducted separately for the BUN test in the CURB-65 scoring system used in the estimation of hospitalization and mortality in the presence of pneumonia [8]; the D-dimer test, is used to exclude thromboembolism and is a prognostic indicator in community-acquired pneumonia [9], and the lactate test, is a prognostic indicator as a product of anaerobic glycolysis [10]. In addition to these studies that show their significance by evaluating individual parameters, our study aims to show the correlation between BLR and BDR levels and in-hospital mortality. However, this study is unique for the simultaneous comparison of these three parameters for mortality estimation. It will contribute to the literature to find an assessment tool with a high diagnostic value that can predict the mortality rate of COVID-19 patients.
In this study, the levels of all parameters looked at were significantly higher in the non-survivor group than in the survivor group. We calculated cut-off values to determine mortality. When lactate exceeded the level of 2.26, it had a high specificity as an indicator of mortality. We showed that mortality increased four times for lactate values above 2.26 mmol/L in the study. Lactate is an established prognostic indicator in critical care. However, extensive additional studies are needed. COVID-19 can be considered a form of sepsis. With this approach, the first Update to the “Surviving Sepsis Campaign Guidelines on the Management of Adults with Coronavirus Disease 2019 (COVID-19) in the ICU” recommends the use of serum lactate measurement to assess fluid therapy response in adults with COVID-19 and shock [11]. In a study of 235 patients, Kayina et al. showed that survivors had higher baseline serum lactate levels [12]. These results are similar to our findings. Also, a retrospective study of 553 patients by Jo et al. showed that baseline serum lactate levels were equivalent to established pneumonia scoring, such as CURB65, which is used to predict the prognosis of patients with community-acquired pneumonia [13]. This research also shows a correlation between BUN levels and lactate levels. Gwak et al. conducted a study with the data from 397 hospitalized patients, 18% of whom admitted to the intensive care unit, and they found an independent association between patients’ initial serum lactate concentration and in-hospital mortality [14]. But these studies did not evaluate the BLR in-hospital mortality. Our study is the first study that shows the correlation between BLR and in-mortality. In addition, the BUN/lactate ratio increased 25 times, which is very significant in our study. We know that BUN is a prominent indicator in end-stage heart, kidney disease, and some life-threatening diseases. In a search conducted with 383 elderly veterans, elevated BUN level was an indicator of the severity of acute and chronic diseases. In addition, BUN ≥ 30 mg / dL detected in the Cox PH model (a model where the danger of one individual is assumed to be proportional to the risk of another individual) was associated with an approximately 2-fold increased risk of mortality [15]. According to many studies, a high BUN level is an indicator of the severity of pneumonia [16]. According to ROC analysis performed to predict in-hospital mortality, BUN levels reached 0.74 AUC in our study. A BUN level above 30.5 mg/dl had an odds ratio of 4.13 in predicting in-hospital mortality of COVID-19 patients. In other words, the mortality rate increased four times at BUN values above 30.5 mg/dL.
D-dimer test, the last parameter we examined, was also significantly higher in the non-survivor group. However, the specificity and sensitivity of the cut-off value we calculated to determine the mortality risk were not significant. These results were similar to a retrospective study of 1065 hospitalized patients in the United States. Navmagon L et al. found that every 1 μg/ml increase in admission D-dimer was associated with a hazard ratio of 1.06 (95% CI 1.04–1.08, p<0.001) for all-cause mortality. However, they found D-dimer to be a poor prognostic test for predicting mortality, with an area under the curve of ROC curves for the D-dimer trend being just 0.67 [17]. Another meta-analysis study done by Gungor et al. showed that patients with elevated D-dimer on admission had a higher risk of mortality (relative risk, RR 1.82) and disease severity (RR 1.58) compared to the patients with normal levels of D-dimer [18]. In Poudel et al.’s study, a higher D-dimer value on hospital admission was significantly associated with in-hospital mortality in patients with COVID-19. D-dimer is a fibrin degradation product, and its primary utility is in the diagnosis and management of thrombotic disorders [3]. Cheng A et al found that the predictive effect of BUN combined with D-dimer had significantly better AUC values than that of the BUN or D-dimer alone, but when we examined the BUN to d-dimer ratio [19], there was no significant differences between the two groups for diagnostic risk determination.
Also, this study had some limitations. The initial values of the patients in the intensive care unit were included in the study, but no comparison could be made with the first admission. In addition, the fact that the treatment protocols we received during COVID-19 were not evaluated in this study was another limitation of the study. Lastly, the fact that this study was a single-center study was likewise a limitation.
In conclusion, accurate and widely available biomarkers may be prognostic and utilized to manage COVID-19 disease. Accordingly, we found that BUN, D-dimer, lactate, BLR, and BUN BDR levels are reliable predictors of in-hospital mortality in patients with COVID-19. Still, the BUN test is the most powerful in showing the risk of in-hospital mortality, while BLR is a powerful assessment tool as a clinical criterion in mortality estimation.
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.
Funding: None
Conflict of interest
The authors declare no conflicts of interest.
References
1. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. 2020; 395(10229): P1054-62
2. Soni M, Gopalakrishnan R, Vaishya R, Prabu P. D-dimer level is a useful predictor for mortality in patients with COVID-19: Analysis of 483 cases. Diabetes Metab Syndr. 2020;14(6):2245-49
3. Poudel A, Poudel Y, Adhikari Y, Aryal BB, Dangol D, Bajracharya T, et al. D-dimer as a biomarker for assessment of COVID-19 prognosis: D-dimer levels on admission and its role in predicting disease outcome in hospitalized patients with COVID-19. PLoS One. 2021;16(8). DOI: 10.1371/journal.pone.0256744
4. Kazory A. Emergence of Blood Urea Nitrogen as a Biomarker of Neurohormonal Activation in Heart Failure. The American Journal of Cardiology. 2010; 106(5):694-700.
5. Wernly B, Lichtenauer M, Vellinga NAR, Boerma EC, Ince C, Kelm M, et al. Blood urea nitrogen (BUN) independently predicts mortality in critically ill patients admitted to ICU: a multicenter study. Clin Hemorheol Microcirc. 2018;69:123–31
6. Miura M, Sakata Y, Nochioka K, Takahashi J, Takada T, Miyata S, et al. Prognostic impact of blood urea nitrogen changes during hospitalization in patients with acute heart failure syndrome. Circ J. 2013;77(5):1221-8
7. Gattinoni, L, Vasques, F, Camporota, L, Meessen, J, Romitti, F, Pasticci, I, et al. Understanding lactatemia in human sepsis. Potential impact for early management. Am J Respir Crit Care Med. 2019;200:582–9
8. Aujesky D, Auble TE, Yealy DM, Stone RA, Obrosky DS, Meehan TP, et al. Prospective comparison of three validated prediction rules for prognosis in community-acquired pneumonia. Am J Med. 2005;118:384-92.
9. Pulivarthi S, Gurram M.K. Effectiveness of D-Dimer as a Screening Test for Venous Thromboembolism: An Update. N Am J Med Sci. 2014; 6(10):491–9
10. GlancyB, Kane DA, Kavazis AN, Goodwin ML, Willis WT, Gladden LB. Mitochondrial lactate metabolism: history and implications for exercise and disease. J Physiol. 2021; 599(3): 863–88.
11. Alhazzani W, Evans L, Alshamsi F, Hylander Møller M, Ostermann M, Prescott H, et al. Surviving sepsis campaign guidelines on the management of adults with coronavirus disease 2019 (COVID-19) in the ICU: 55. Crit Care Med. 2021;49(3):219-34
12. Kayina CA, Haritha D, Soni L, Behera S, Ramachandran Nair P, Gouri M et al. Epidemiological & clinical characteristics & early outcome of COVID-19 patients in a tertiary care teaching hospital in India: a preliminary analysis. Indian J Med Res. 2020;152(2):100–4
13. Jo S, Jeong T, Lee JB, Jin Y, Yoon J, Park B. Validation of modifed early warning score using serum lactate level in community-acquired pneumonia patients. The national early warning score-lactate score. Am J Emerg Med. 2016;34(3):536–41
14. Gwak MH, Jo S, Jeong T, Baek Lee J, Ho Jin Y, Yoon J, et al. Initial serum lactate level is associated with inpatient mortality in patients with community-acquired pneumonia. Am J Emerg Med. 2015;33(5):685–90
15. Sullivan DH, Sullivan SC, Bopp MM, Roberson PK, Lensing SY. BUN as an Independent Predictor of Post-Hospital-Discharge Mortality among Older Veterans. The journal of nutrition, health & aging. 2018; 22(7): 759-65.
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18. Gungor B, Atici A, Baycan OF, Alici G, Ozturk F, Tugrul S, et al. Elevated D-dimer levels on admission are associated with severity and increased risk of mortality in COVID-19: A systematic review and meta-analysis. Am J Emerg Med. 2021;39: 173–9. DOI: 10.1016/j.ajem.2020.09.018
19. Cheng A, Hu L, Wang Y, Huang L, Zhao L, Zhang C. Diagnostic performance of initial blood urea nitrogen combined with D-dimer levels for predicting in-hospital mortality in COVID-19 patients. Int J Antimicrob Agents. 2020; 56(3): 106110.
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Soycan Mizrak, Ayse Ozdemir, Ebru Aladag, Nezih Tayyar. The roles of bun/d-dimer and bun/lactate ratios in indicating mortality in intensive care patients with COVID-19. Ann Clin Anal Med 2022;13(11):1224-1228
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Maternal outcomes during the COVID-19 Pandemic: A Retrospective analysis of the last 5 years
Selvihan Tapanoğlu Karaca 1, Berrin Göktuğ Kadıoğlu 1, Eda Bingül 1, Berna Asır 1, Sibel Tekgündüz 1, Ayse Nur Aksoy 1,2
1 Department of Obstetrics and Gynecology, University of Health Sciences, Erzurum Regional Training and Research Hospital, 2 Department of Anesthesiology, Clinical Research Office, Ataturk University, Erzurum, Türkiye
DOI: 10.4328/ACAM.21262 Received: 2022-06-07 Accepted: 2022-07-13 Published Online: 2022-07-19 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1229-1232
Corresponding Author: Berrin Göktuğ Kadıoğlu, Department of Obstetrics and Gynecology, University of Health Sciences, Erzurum Regional Training and Research Hospital, 25240, Erzurum, Türkiye. E-mail: bgoktug@hotmail.com P: +90 532 267 6 037 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8712-318X
Aim: Coronavirus disease-2019 has caused a significant health crisis all over the world. This study aimed to compare obstetric and gynecological data during the COVID-19 pandemic period with the previous three years.
Material and Methods: For this purpose, over a 5-year period, from January 2017 to December 2021, patient records from the hospital’s electronic data registry were scanned. The extracted data included the number of patients admitted to the outpatient clinic, the number of emergency outpatient visits, the number of patients inserted and removed with an intrauterine device (IUD), abortions, premature rupture of membranes (PROM), intrauterine fetal death (IUFD) and vaginal delivery and cesarean section.
Results: The number of patients who underwent IUD removal decreased in the last two years. Also, the number of patients who underwent IUD insertion in 2020 was very low compared to other years (p<0.01, for all). It was observed that the number of patients diagnosed with PROM decreased in the last three years (p<0.01, for all). There was a statistically significant decrease in the total number of deliveries in the last two years (p<0.01).
Discussion: In conclusion, it is seen that the number of outpatients, the number of emergency outpatients, the number of IUDs removed and the total number of deliveries have decreased in the last two years compared to the previous three years. This may be related to the coronavirus infection, which has caused the pandemic for the last two years.
Keywords: COVID-19, Pregnancy, Vaginal Delivery, Cesarean Section, Abortion, Outpatient Clinic, Emergency Clinic
Introduction
Coronavirus disease-2019, which caused a significant health crisis all over the world, was declared a pandemic by the World Health Organization (WHO) on March 11, 2020 (available at: https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19—11-march-2020). The COVID-19 pandemic has adversely affected the physical capacities of healthcare providers and the workload of healthcare personnel. Various organizational changes were made in inpatient treatment institutions due to the high risk of transmission, some clinics were closed, new units were formed, and patient admissions and surgeries were restricted (available at: https://data.unicef.org/topic/maternalhealth/covid-19/. While evaluating the direct effects of the pandemic on women’s health, its indirect effects should also be taken into account. Although the rates of death from COVID-19 in women of reproductive age are estimated to be low (available at: https://www.who.int/publications/i/item/Pulse survey on continuity of essential health services during the COVID-19 pandemic: interim report, 27 August 2020), it is necessary to assess what changes occur in morbidity due to the interruption of routine health services during the pandemic management and the decrease in the rate of admission to the hospital due to the anxiety of catching the disease [1]. Continuity of reproductive health services is very important for the protection of maternal, newborn, and adolescent health. Particularly, conscious family planning, antenatal care and controls, keeping high-risk pregnancies under control, and intervention for complications are closely related to timely access to health services (available at: https://www.who.int/publications/i/item/Pulse survey on continuity of essential health services during the COVID-19 pandemic: interim report, 27 August 2020). During the pandemic, the WHO reported that hospital admissions for non-communicable diseases were interrupted by 24-64%. Naturally, this situation is reflected in elective surgeries and non-emergency outpatient clinic applications in obstetrics clinics (available at: https://www.who.int/publications/m/item/Rapid assessment of service delivery for NCDs during the COVID-19 pandemic)
This study aimed to compare obstetric and gynecological data during the COVID-19 pandemic period with the previous three years. Also, this study aimed to analyze the patients, who admitted to the obstetrics, gynecology, and emergency outpatient clinic of our hospital in the last five years, including the pandemic period. For this purpose, obstetric and gynecological data for the last five years recorded in the hospital computer system were evaluated retrospectively.
Material and Methods
This study was conducted after obtaining permission from the Ethics Committee of Erzurum Training and Research Hospital, Erzurum, Türkiye. This was a retrospective descriptive study carried out in the Erzurum Training and Research Hospital, University of Health Sciences in Turkey, involving all patients, who were admitted to the Obstetrics and Gynecology Clinics from 1st January 2017 to 31st December 2021. The hospital is located in the Central Region and is the highest referral center for the East Regions of Turkey. It is an 1100-bed facility, of which 120 are dedicated to the Obstetrics and Gynecology department, with bed occupancy of 90%. Over six thousand deliveries are conducted annually with an average cesarean section rate of 20%.
Over a 5-year period, from January 2017 to December 2021, patient records from the hospital’s electronic data registry were scanned and all eligible candidates were enrolled. Inclusion criteria were Obstetrics and Gynecological Clinic admission and complete management data. The exclusion criteria were incomplete management data. The extracted data included the number of patients admitted to the outpatient clinic, the number of emergency outpatient visits, the number of patients inserted and removed with an intrauterine device (IUD), abortion, premature rupture of membranes (PROM), intrauterine fetal death (IUFD) and vaginal delivery and cesarean section.
The data were analyzed using the SPSS version 13 software. The results were presented as mean (standard deviation), number, and percentages (%). To test the normality of the data, the Kolmogorov-Smirnov test was used. The Chi-square test was used for data analysis and P <0.05 was considered statistically significant.
Results
The annual distribution of patients examined in the outpatient clinic and emergency outpatient clinic is presented in Figure 1.
It was observed that the number of patients examined in the two units decreased in 2020 and 2021, and more dramatically in the last 1 year (p<0.01). The number of patients who underwent IUD removal decreased in the last two years. Also, the number of patients who underwent IUD insertion in 2020 was very low compared to other years (p<0.01, for all) (Figure 1). It was observed that the number of patients diagnosed with abortion decreased in 2020, the number of patients with abortion increased in 2021, and the number of patients diagnosed with PROM decreased in the last three years (p<0.01, for all). On the other hand, the number of patients diagnosed with IUFD did not change throughout the years, (Figure 2).
While there was a statistically significant decrease in the total number of deliveries in the last two years (p<0.01), there was no change in the rates of cesarean, vaginal, and primary cesarean deliveries in the last 5 years (Table 1).
Discussion
In this study, obstetric and gynecologic data for two years before the pandemic and three years after the onset of the pandemic were evaluated. During the pandemic process, gynecology and obstetrics polyclinics worked much more dynamically than other disciplines. Despite this, the number of patients admitted to our outpatient clinic gradually decreased towards the end of the pandemic. There were significant curfews, quarantines, and social environment restrictions in the year the pandemic started. The number of hospital admissions decreased gradually in the following years, probably because people saw those in their close circles affected by the disease [2,3]. The reason for this may be the explanation of protection measures in hospitals, the media, and all institutions of the society, the decrease in people’s traffic, the restriction of public transportation, and the fact that patients do not come to the hospital for simple complaints and that they see hospitals as potential areas for the transmission of the COVID-19 virus [4,5]. Interestingly, when the data are examined, a very significant decrease is observed in the number of applications to our emergency outpatient clinic. The results of Nouzarri et al.’s study are also in this direction [6]. We thought that the number of patients who applied to the emergency department decreased because of the anxiety of contracting the disease when the reason for the application was a matter that they could cope with themselves. This may be a warning that we should be more selective in accepting real emergencies in normal times and that we should reconsider our patient admission protocols. However, this may also cause delays due to deferred maintenance in the future. For example, in a systematic review and meta-analysis on the COVID-19 pandemic, it was found that the rate of ectopic pregnancy requiring surgical treatment due to delayed admission increased by 26% [7].
In this present study, it was observed that the total number of births decreased gradually in the last five years. However, no change was detected in the cesarean and vaginal delivery rates. The study by Goyal et al. also supports this finding [3]. On the other hand, while the number of abortions decreased in 2019 and 2020, they increased significantly in 2021. This leads us to ask whether pregnant women were exposed to more infections because they relaxed the measures. In a study conducted in Mexico, it was found that there was a 25% decrease in the number of unwanted children and related abortions, possibly due to decreased sexual activity [8].
In the second year of the pandemic, the rates of IUD insertion and removal decreased significantly and increased again through normalization in the last year. This behavior may be related to the fact that women postpone this non-urgent intervention [1] and especially the decrease in the IUD removal process due to families’ unwillingness to have children during the distressing pandemic period. In a study on postpartum contraception planning during the pandemic period, a significant decrease was observed in hospital admissions with the request for contraception when compared to the pre-covid cohort [9].
The reflection of all these is also observed in the number of births. The number of both cesarean and vaginal births has gradually decreased, and this may be related to the decrease in the patient referral from the periphery due to the pandemic. The decrease observed in PROM rates can be attributed to the fact that pregnant women show less physical activity, stay at home more, and working pregnant women are given administrative leave by making positive discrimination. In the study conducted by Philip et al. [10] in Ireland, it was shown that the decrease in the rate of preterm births was due to the fact that pregnant women were exposed to less work stress and involved in less physical activity. In a study by Rasmussen et al. [11], the effect of influenza on preterm birth was shown. Premature births have also decreased as pregnant women take stricter isolation and protection measures during the pandemic, reducing the possibility of catching influenza. A study conducted in Spain shows that staying at home changes the lifestyle of pregnant women and reduces physical activity [4]. A decrease in stillbirth rates was observed, although not very significant. While IUFD rates were 0.9% in 2017, it was 0.6% in 2021. This decrease can be due to the same reasons. However, in the studies performed by Khalil et al. [12,13], a significant increase in stillbirth rates was detected during the pandemic. Although they did not detect COVID-19 in any of the stillbirths, they attribute this to the fact that 90% of the pregnant women were asymptomatic. We believe that this change in stillbirth rates is caused by social behavior differences during the pandemic.
Conclusion
It is seen that the number of outpatients, the number of emergency outpatients, the number of IUDs removed and the total number of deliveries have decreased in the last two years compared to the previous three years. This may be related to the coronavirus infection, which has caused the pandemic for the last two years.
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. Kingsley JP, Vijay PK, Kumaresan J, Sathiakumar N. The Changing Aspects of Motherhood in Face of the COVID-19 Pandemic in Low- and Middle-Income Countries. Matern Child Health J. 2021;25(1):15-21.
2. Burki T. The indirect impact of COVID-19 on women. Lancet Infect Dis. 2020;20(8):904-5.
3. Goyal M, Singh P, Singh K, Shekhar S, Agrawal N, Misra S. The effect of the COVID-19 pandemic on maternal health due to delay in seeking health care: Experience from a tertiary center. Int J Gynaecol Obstet. 2021;152(2):231-5.
4. Biviá-Roig G, La Rosa VL, Gómez-Tébar M, Serrano-Raya L, Amer-Cuenca JJ, Caruso S, et al. Analysis of the Impact of the Confinement Resulting from COVID-19 on the Lifestyle and Psychological Wellbeing of Spanish Pregnant Women: An Internet-Based Cross-Sectional Survey. Int J Environ Res Public Health 2020;17(16):5933.
5. Holland DE, Vanderboom CE, Dose AM, Moore D, Robinson KV, Wild E, et al. Death and Grieving for Family Caregivers of Loved Ones With Life-Limiting Illnesses in the Era of COVID-19: Considerations for Case Managers. Prof Case Manag. 2021;26(2):53-61.
6. Nourazari S, Davis SR, Granovsky R, Austin R, Straff DJ, Joseph JW, et al. Decreased hospital admissions through emergency departments during the COVID-19 pandemic. Am J Emerg Med. 2021;42:203-10.
7. 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(6):759-72.
8. Marquez-Padilla F, Saavedra B. The unintended effects of the COVID-19 pandemic and stay-at-home orders on abortions. J Popul Econ. 2021;15:1-37.
9. Miller HE, Henkel A, Leonard SA, Miller SE, Tran L, Bianco K, et al. The impact of the COVID-19 pandemic on postpartum contraception planning. Am J Obstet Gynecol MFM. 2021;3(5):100412.
10. Philip RK, Purtill H, Reidy E, Daly M, Imcha M, McGrath D, et al. Unprecedented reduction in births of very low birthweight (VLBW) and extremely low birthweight (ELBW) infants during the COVID-19 lockdown in Ireland: a ‘natural experiment’ allowing analysis of data from the prior two decades. BMJ Glob Health. 2020;5(9):e003075.
11. Rasmussen SA, Jamieson DJ, Uyeki TM. Effects of influenza on pregnant women and infants. Am J Obstet Gynecol. 2012;207(Suppl. 3):S3-8.
12. Khalil A, von Dadelszen P, Kalafat E, Sebghati M, Ladhani S, Ugwumadu A, et al. Change in obstetric attendance and activities during the COVID-19 pandemic. Lancet Infect Dis. 2021;21(5):e115.
13. 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.
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Selvihan Tapanoğlu Karaca, Berrin Göktuğ Kadıoğlu, Eda Bingül, Berna Asır, Sibel Tekgündüz, Ayse Nur Aksoy. Maternal outcomes during the COVID-19 Pandemic: A Retrospective analysis of the last 5 years. Ann Clin Anal Med 2022;13(11):1229-1232
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Relationship between free calcium and adjusted calcium for albumin in patients with hypoalbuminemia
Esma Özdemir Anayurt, Yasemin Erdoğan Döventaş, İbrahim Yılmaz, Macit Koldaş
Department of Medical Biochemistry, Faculty of Medicine, Ministry of Health University, Haseki Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21266 Received: 2022-06-20 Accepted: 2022-09-28 Published Online: 2022-10-11 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1233-1236
Corresponding Author: Yasemin Erdoğan Döventaş, Department of Medical Biochemistry, Ministry of Health University, Haseki Training and Research Hospital, 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: Measurement of total blood calcium is an important test that reflects bone and mineral metabolism. Total calcium is adjusted for albumin in many laboratories. Besides, it should be taken into consideration that adjusting the total calcium for albumin may cause an inaccurate evaluation of free calcium. This study aims to investigate the necessity of adjusted calcium used in biochemistry laboratories and whether ionized calcium measurement provides more benefit in determining the amount of active calcium in the body.
Material and Methods: We retrospectively selected 2092 samples with simultaneous measurements of free calcium, total calcium, albumin, total protein, and pH from the laboratory information system between January 2020 and June 2021. Samples with pH values outside the reference range of (7.35-7.45) and albumin values above the 4 g/dL were not included. In this study, the correlation between corrected total calcium calculated by Payne formula (usually expressed as albumin-adjusted calcium (mg/dL) =total calcium (mg/dL) + [4-albumin (g/dL)]. 0.8) and total calcium levels, total calcium and free calcium level were evaluated in hypoalbuminemia (<4 g/dL).
Results: Moderate relationship was found between free calcium and total calcium (r:0,48). The adjusted calcium values calculated with the Payne formula do not reflect free calcium (r= 0,47). A significant correlation was found between adjusted calcium and total calcium (r:0.72).
Discussion: Adjusted calcium application does not show a free calcium level. With the widespread use of free calcium measurement by most laboratories, the adjusted calcium application should be abandoned.
Keywords: Hypoalbuminemia, Total Calcium, Corrected Calcium, Lonized Calcium
Introduction
Calcium is the fifth most abundant element in the human body. It plays a key role in skeletal mineralization, as well as a wide range of biological functions. Calcium is an essential element that comes into the body only through dietary sources. Calcium requirement is dependent on the state of calcium metabolism, which is regulated by three main mechanisms: intestinal absorption, renal reabsorption, and bone turnover. These in turn are regulated by a set of interacting hormones, including parathyroid hormone (PTH), 1,25-dihydroxy vitamin D [1,25(OH)2D], free calcium itself, and their corresponding receptors in the gut, kidney, and bone [1].
In serum, calcium exists in 3 forms: protein-bound, ionized (free), and complexed (chelated). Protein-bound calcium, which accounts for 40% of serum calcium, cannot be used by tissues. Albumin and globulin are the primary calcium-binding proteins in the serum whereas calmodulin is the primary calcium-binding protein in the cell. Chelated calcium, which accounts for 9% of the serum calcium, allows calcium to be absorbed by various tissues or carried between parts of the body. Serum calcium is often chelated into the ionic complexes of calcium phosphate, calcium carbonate, and calcium oxalate. Finally, free calcium, which makes up 51% of serum calcium, is utilized by the body to maintain physiologic functions [2].
Free calcium measurements in arterial blood collection are affected by many preanalytical factors such as sample collection, storage, transportation, pH changes, hemolysis, calcium-binding by the anticoagulant and sample dilution by the anticoagulant solution [3].
In addition, total calcium measurement is affected by albumin-bound calcium, pH, protein, and especially albumin levels. Due to such preanalytical and biological variables, total calcium levels are corrected for albumin. The most widely used correction formula was proposed by Payne in 1973 [4].
No commercial vendors currently offer a largely automated instrument for the measurement of ionized free calcium [5], and blood gas analyzers are widely used for the measurement of ionized free calcium using the direct-selective electrode (ISE) method. Many authors claim that the measurement of free ionized calcium should be preferred to the albumin- adjusted total calcium based on formulas from the literature [6-,9]. However, if an albumin adjustment is to be made, each laboratory should establish its formula [5-9].
Material and Methods
Patient Population
Data were retrospectively collected from Haseki Training and Research Hospital laboratory information system from January 2020 to June 2021 (n=2092). Simultaneous venous blood collection was performed for serum total protein, albumin, and total calcium measurements, and arterial blood collection was performed for ionized free calcium and pH measurements. Patients with albumin above 4 g/dL and pH other than 7.35-7.45 were excluded. This study was approved by the Health Sciences University Istanbul Haseki Training and Research Hospital Ethics Committee with decision number 252.
Laboratory Measurement Data
The serum albumin, total protein, and total calcium were determined on BeckmanCoulterAU5800 (Beckman Coulter Inc., Brea CA, USA) from January 2020 to November 2020. Rochec701/Cobas 8000 (Roche Diagnostic, Mannheim, (Germany) was used for serum albumin, total protein, and total calcium from November 2020 to June 2021. The Bromocresol green method was used for albumin, the Bıuret Method was used for total protein, and serum total calcium was tested with the NM-BAPTA method on Rochec701/Cobas 8000® analyzer and tested with the Arsenazo method on Beckman Coulter AU5800. The concentration of free calcium was measured using an ion-selective electrode in an automated blood gas analyzer (Rapidlab 1265, Siemens, Germany). To apply Payne’s formula, albumin values were converted to g/dL (g/Lx1/10=g/dL) and ionized calcium values to mg/dL (mmol/Lx4=mg/dL). Standard internal and external quality control procedures were followed for all analytical methods.
Statistical Analysis
Statistical analyzes were performed with the SPSS 22.0 program. The mean and standard deviation values of the data were calculated. Spearman’s Correlation analysis was performed for the data that did not fit the normal distribution with the Shapiro-Wilk test. The statistical significance limit was accepted as p<0.005.
Results
Data of 2092 (female 42.3% and male 57.7%) patients whose total albumin level was below 4 g/dL were analyzed. The mean age was 49.9±12.5 years. The mean and standard deviation values of total calcium, ionized calcium, total protein, albumin, and adjusted calcium are given in Table 1. Of the 2092 patients with albumin values below 4 g/dL, the number of patients with ionized calcium values below 1 mmol/L was 686 (14.3%), and the number of patients with total calcium values below 8 mg/dL was 551 (11.5%). In 76.9% of patients with ionized calcium values <1 mmol/L, albumin values were below 3.5 g/dL. The number of patients with hypocalcemia according to both ionized calcium and total calcium values was observed as 260 (12.4%).
As shown in figures 1 and 2, the correlation between total calcium and adjusted calcium is significant. The linear regression equation between the two methods was ‘Adjusted calcium = 0.657 X Total calcium + 3.57’. The adjusted total calcium value is significantly higher than the measured total calcium value. A moderate relationship was found between free calcium and total calcium (r:0,48). The adjusted calcium values calculated with the Payne formula do not reflect free calcium (r:0,47).
Discussion
Measurement of total calcium is the most commonly used technique worldwide owing to its ready availability, low cost, and resistance to variable transport and storage conditions. It is thus very important to understand the need of estimating free ionized calcium for the management of critically ill patients with disorders of calcium metabolism, especially in settings of cardiac or renal ailments [10].
Changes in albumin levels do not affect free calcium levels. Since calcium has less available albumin for binding, hypoalbuminemia should theoretically decrease the amount of bound calcium and lead to a decreased reported total calcium. Therefore, a patient’s total calcium level may appear low even though free calcium is normal, which can lead to an incorrect diagnosis of hypocalcemia or an overestimation of the extent of existing hypocalcemia.This reason gave rise to formulae for adjusting total calcium for albumin concentration, and there are several formulas in the literature to adjust total calcium levels for albumin [4,11- 15].
In this study, we evaluated the Payne formula [4] for the correction of total calcium and the utility of ionized free calcium measurements in clinical laboratory practice. In our study, in low albumin concentration (albumin <4 g/dL) the correlation between ionized free calcium and total calcium, and adjusted total calcium were moderate agreement. On the contrary total calcium and adjusted calcium showed better agreement. Therefore we propose that this adjustment formula should not be applied.
While the calculation of corrected calcium should theoretically provide a more accurate estimate of physiologically active free calcium in patients with hypoalbuminemia the commonly used correction equations become less accurate as hypoalbuminemia worsens. For example, Payne’s assumption results in an overestimation of the total serum calcium after correction as compared to the free calcium.
Some authors suggest that their local formulas have better performance than formulas from the literature to predict total calcium concentration and also suggest that albumin modification of total calcium determinations should be abandoned in laboratories still using this practice [8, 9,16].
With the widespread use of ionized free calcium measurement in blood gas analyzers with the direction-selective electrode method in clinical laboratories, free ionized calcium should be measured instead of corrected calcium measurement, especially in chronic hemodialysis patients, patients with hyperparathyroidism, critical patients in intensive care units and patients with paraproteinemia such as multiple myeloma who require close monitoring of calcium metabolism [6,17-20].
Limitations
One limitation of our study is that, first, there was a change in the biochemistry autoanalyzer used in the laboratory at the time of the study. Therefore, there were changes in reference values in serum albumin as well as calcium measurements and method differences for calcium. For calcium, the Arsenazo method was used in the Beckman Coulter autoanalyzer and the NM-BAPTA method was used in the Roche autoanalyzer. However, a recent study showed a good correlation between these methods [21].
Second, we could not collect creatinine, eGFR, parathyroid hormone, and electrolyte measurements because we evaluated the data retrospectively.
Since it is a retrospective study, the sources of preanalytical errors that may occur during the sampling of the samples have been ignored.
Conclusion
The commonly used correction formula Payne resulted in low levels of agreement with free ionized calcium and adjusted total calcium. Free ionized calcium measurements are frequently used in clinical biochemistry laboratories, despite the cost of direct ion-selective electrode measurement. We agreed that free ionized calcium measurements will be more accurate, especially in patients who require close monitoring of calcium, and correction formulas should be abandoned.
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.
Funding: None
Conflict of interest
The authors declare no conflicts of interest.
References
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2. Yu E, Sharma S. Physiology, Calcium. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2021.
3. Baird G. Preanalytical considerations in blood gas analysis. Biochem Med (Zagreb). 2013;23(1):19-27.
4. Payne RB, Little AJ, Williams RB, Milner JR. Interpretation of serum calcium in patients with abnormal serum proteins. Br Med J. 1973;4(5893):643-6. DOI:10.1136/bmj.4.5893.643.
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6. Jain A, Bhayana S, Vlasschaert M, House A. A formula to predict corrected calcium in haemodialysis patients. Nephrol Dial Transplant. 2008;23(9):2884-88.
7. Lian IA, Åsberg A. Should total calcium be adjusted for albumin? A retrospective observational study of laboratory data from central Norway. BMJ Open. 2018;8(4):e017703.
8. Pekar JD, Grzych G, Durand G, Haas J, Lionet A, Brousseau T, et al. Calcium state estimation by total calcium: the evidence to end the never-ending story. Clin Chem Lab Med. 2020;58(2):222-31.
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11. Berry EM, Gupta MM, Turner SJ, Burns RR. Variation in plasma calcium with induced changes in plasma specific gravity, total protein, and albumin. Br Med J. 1973;4(5893):640-3.
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14. Marshall RW, Hodgkinson A. Calculation of plasma ionised calcium from total calcium, proteins and pH: comparison with measured values. Clin Chim Acta. 1983;127(2):305-10.
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Download attachments: 10.4328.ACAM.21266
Esma Özdemir Anayurt, Yasemin Erdoğan Döventaş, İbrahim Yılmaz, Macit Koldaş. Relationship between free calcium and adjusted calcium for albumin in patients with hypoalbuminemia. Ann Clin Anal Med 2022;13(11):1233-1236
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The effect of erdosteine on ischemia-reperfusion injury in skeletal muscle of rats
Abdullah Özer 1, Ayşegül Küçük 2, Yiğit Kılıç 3, Serap Gültekin 4, Hayriye Tatlı Doğan 5, Aydan Kılıçarslan 5, Hüseyin Demirtaş 1, Barış Mardin 1, Dilek Erer 1, Tolga Tatar 1, Mustafa Arslan 6
1 Department of Cardiovascular Surgery, Faculty of Medicine, Gazi University, Ankara, 2 Department of Physiology, Faculty of Medicine, Kütahya Health Science University, Kütahya, 3 Department of Pediatric Cardiovascular Surgery, Dr Siyami Ersek Cardiovascular and Thoracic Surgery Training and Research Hospital, Istanbul, 4 Department of Radiology, Faculty of Medicine, Gazi University, Ankara, 5 Department of Pathology, Faculty of Medicine, Yıldırım Beyazıt University, Ankara, 6 Department of Anesthesia and Reanimation, Faculty of Medicine, Gazi University, Ankara, Turkey
DOI: 10.4328/ACAM.21268 Received: 2022-06-13 Accepted: 2022-07-13 Published Online: 2022-07-16 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1237-1240
Corresponding Author: Mustafa Arslan, Department of Anesthesia and Reanimation, Faculty of Medicine, Gazi University, 06510, Ankara, Turkey. E-mail: mustarslan@gmail.com P: +90 312 202 67 39 / + 90 533 422 85 77 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4882-5063
Aim: As a mucolytic agent, Erdosteine has two sulfhydryl groups. These groups function as free radical scavengers, which has protective effects against ischemia- reperfusion (IR) injury. In this study, we aimed to observe the effects of erdosteine on skeletal muscle tissue in a rat lower extremity IR injury model.
Material and Methods: A total of 18 Wistar albino rats were separated into 3 groups (n: 6); Control group (C), IR group (IR) and IR group with erdosteine (IR-E). Erdosteine administered intraperitoneally (150 mg.kg-1). Rat tissues were taken for histopathological and immunohistochemical evaluations after 2 hours of ischemia and 2 hours of reperfusion period.
Results: Blood flow measurements were significantly higher in the IR-E group than in the IR group. In the IR group, endothelial caspase 3 and 8 enzyme expression was significantly higher than C and IR-E groups. Muscle caspase 3 enzyme expression was higher in the IR group than C and IR-E groups. IR and IR-E groups showed increased inflammation, vascular congestion and myositis injury levels than the C group. Also, inflammation, vascular congestion and myositis injury showed a significant decrease in the IR-E group than IR group.
Discussion: As a result, erdosteine has a protective effect against skeletal tissue damage resulting from IR injury in rats. The results show the possibility of clinical administration of erdosteine for I/R injury of skeletal muscle tissue.
Keywords: Skeletal Muscle, Ischemia-Reperfusion, Erdosteine, Caspase 3, Blood Flow, Rat
Introduction
Ischemia-reperfusion (IR) injury is an inevitable, frequent and serious situation. If the muscle’s blood supply is inadequate to meet its needs, ischemia occurs, and if the blood flow is re-established after reperfusion, the substances involved in oxidation play a critical role in the clinical outcome. Reperfusion may unexpectedly cause an increased ratio of mortality and morbidity as extended inflammation and necrotic and apoptotic events caused by reactive oxygen species (ROS) end up in organ injury and systemic complications [1-6].
Erdosteine (N-carboxymethyl)thio)acetyl-homocysteine thiolactone), which is a mucolytic agent, has two sulfhydryl groups. These groups function as free radical scavengers [7]. As a mucociliary transport increaser, erdosteine is used to treat chronic obstructive pulmonary disease. It also inhibits the effects of free radicals produced by cigarette smoke [8]. Animal researche showed that erdosteine has a protective effect against toxic by-products of oxidative stress produced during tissue injuries [9]. Inhibition of LPS-induced NF-kB activation mediates the anti-inflammatory effect of erdosteine [10].
Caspases, initially identified as a family of proteases regulating cell death, have been found to have non-apoptotic functions as well. Effectors of apoptosis are the caspases with short prodomains, caspases-3, 6, and 7. Caspases-2, 8, 9, and 10 are initiators of apoptosis. Caspase-3 and 8 enzyme activity is a good marker for ischemia-induced death pathways [11].
Our aim in this study was to investigate the effect of erdosteine on IR injury in skeletal muscle of rats.
Material and Methods
Animals and Experimental Protocol
This study was carried out in the Gazi University Physiology Laboratory with the approval of the Gazi University Ethical Committee of Experimental Animals. All employed methods were in agreement with approved basics of the Guide for the Care and Use of Laboratory Animals. The present study was undertaken with 18 albino Wistar rats weighing between 250 and 300 g and aged 10 to 12 weeks, raised under identical environmental conditions. The rats were kept at 20–21 °C with a 12:12-h light:dark photoperiod and could access food freely until 2 h before the induction of anesthesia. The 18 Wistar albino rats were randomly divided into four groups, each containing 6 rats. Median laparotomy was done under general anesthesia.
Control group: Median laparotomy was done alone without any additional surgical intervention. After 4 hours of follow-up, skelatal tissue was collected and the animals were sacrificed
IR group: Median laparotomy was performed as well. We clamped the infrarenal part of the aorta with an atraumatic clamp for 2 hours. Then we removed the clamp and allowed reperfusion for 2 more hours. Finally, rats were sacrificed after the skelatal tissue was collected.
IR group with erdosteine: Similar steps were performed, but additionally, before the ischemia period, erdosteine was given (150 mg.kg–1) intraperitoneally for 30 min. Rats were sacrificed at the end of the reperfusion period, which lasted 2 hours, after collecting skelatal tissue samples.
All the rats were given intramuscular ketamine (Ketalar; Parke-Davis; Pfizer, Inc., New York, NY, USA) at a dose of 100 mg kg–1 and xylazine hydrochloride (Alfazyne, 2%; Ege Vet, Ltd., Izmir, Turkey) and intracardiac blood samples (up to 10 ml) were obtained. At the end of reperfusion period, a histochemical and immunohistochemical evaluation of skeletal muscle tissue specimen were performed.
IAA Blood Flow Measurement
Intra-abdominal aorta (IAA) blood flow was recorded. Blood flow measurements were conducted by placing probe on the tissue with a fixed position by a laser Doppler microvascular perfusion monitor (OxyLab LDF; Oxford Optronix Limited, Oxford, UK).
Histochemical and Immunohistochemical evaluation
At the end of each experiment, one of the muscle tissue in each rat was fixed in 10% buffered formalin for 48 h, dehydrated in a graded ethanol series, cleaned in xylene, and embedded in paraffin wax and sections of 5 µm thickness were cut using a sliding microtome (Leica Microsystems, Germany). Tissue sections were stained with hematoxylin-eosin (H&E).
All the sections were performed by the same pathologist who was blinded to the study. The scoring system was used for the histopathological evaluation of the muscle tissues.
Immunohistochemical evaluation
For immunohistochemical studies, complete surface sections of 3-4 μL of poly-L-lysine- coated slides were prepared from formalin fixed paraffin embedded blocks of biopsy specimens in all of the events. The sections were left overnight at 45 degrees.
Deparaffinization, blocking, primer antibody (Caspase 3 and Caspase 8: Citrate 30 min), post-primer, polymer, DAP were used as standard antigen retrieval methods, respectively; in the Bond-maximal immunohistochemistry (Leica) device for Caspase 3 (p11, C-6, 1/400, mouse monoclonal antibody) and caspase 8 (Clone, D-8, 1/205, mouse monoclonal antibody) antibodies immunohistochemically. In the background dye Hematoxylin II for 6 min and the Blue reagent for 4 min were applied.
After Immunohistochemical staining preparations were clarified with xylene and covered with balsam they were washed in water and alcohol.
We evaluated both prevalence and intensity of stromal cells’ and endothelium’s cytoplasmic staining of caspase 3 and caspase 8 in immunohistochemical staining. Intensity of staining was scored as no staining – 0, mild- 1 (prevelance of staining was smaller than 50%) and severe -2 (prevelance of staining was greater than 50%).
Thymus tissue was used for caspase 8 and liver tissue was used for caspase 3 as controls. Cytoplasmic membranous staining of caspases 3 and 8 was considered positive.
Statistical Analysis
All data were processed by variance analysis using SPSS 17.0 for Windows (SPSS Inc., USA). P < 0.05 was considered statistically significant. The data were expressed as mean ± standard error (SE). Variance analysis and the Kruskal– Wallis test were used to evaluate the data. Mann–Whitney U tests with Bonferroni corrections were used to evaluate the variables with significance.
Results
Blood flow measured before IR was similar between groups. Blood flow at the 10th minute after the clamp was similar in the IR and IR-E groups. Blood flow measurements were significantly higher in the IR-E group than in the IR group 10 minutes after the clamp was opened, 10 minutes before the clamp was opened and just before the sacrification (Table 1).
When the groups were compared in terms of skeletal muscle tissue inflammation, there was a significant difference between the groups (p<0.0001). Inflammation was significantly higher in the IR and IR-E groups than in group C (p<0.0001, p=0.002, respectively). In addition, inflammation was significantly lower in the IR-E group than in the IR group (p=0.010) (Table 2, Figure 1).
There was a significant difference between groups in terms of vasodilation in skeletal muscle (p=0.001). Vasodilation was significantly increased in the IR and IR-E groups than in group C (p<0.0001, p=0.002, respectively), (Table 2, Figure 1).
There was a significant difference between the groups in terms of vascular congestion in skeletal muscle (p=0.002). Vascular congestion was significantly increased in the IR and IR-E groups than in group C (p<0.0001, p=0.025, respectively). Furthermore, vascular congestion was significantly reduced in the IR-E group than in the IR group (p = 0.045) (Table 2, Figure 1).
There was a significant difference between the groups in terms of damage to skeletal muscle myocytes (p<0.0001). Myocyte damage was significantly higher in the IR and IR-E groups than in group C (p<0.0001, p=0.003, respectively). In addition, myocyte injury was significantly lower in the IR-E group than in the IR group (p=0.023) (Table 2, Figure 1).
Fibrosis and steatosis were similar between groups.
There was a significant difference between groups (skeletal muscle tissue) in terms of endothelial caspase 8 enzyme activity (p=0.036). Endothelial caspase 8 enzyme activity was significantly higher in the IR group compared to C and IR-E groups (p=0.015, p=0.045, respectively (Table 3, Figure 2).
Caspase 8 enzyme activity was similar between the groups (Table 3).
There was a significant difference between the groups (skeletal muscle tissue) in terms of caspase 3 enzyme activity (p=0.022). Caspase 3 enzyme activity was significantly higher in IR group compared to C and IR-E groups (p=0.015 p=0.015, respectively (Table 3, Figure 3).
There was a significant difference between the groups (skeletal muscle tissue) in terms of endothelial caspase 3 enzyme activity (p=0.036). Endothelial caspase 3 enzyme activity was significantly higher in the IR group compared to C and IR-E groups (p=0.045, p=0.015, respectively (Table 3, Figure 3).
Discussion
We evaluated the effects of erdosteine, a disulphide antioxidant, [9] on skeletal muscle IR injury. Our study shows that treatment with erdosteine notably attenuates the skeletal muscle damage of rats subjected to IR injury. Erdostein has an improving effect on both the oxidative status and the histopathological changes.
Erdosteine increased blood flow in the IR-E group than in the IR group 10 minutes after the clamp was opened, 10 minutes before the clamp was opened and just before the sacrification.
Erdosteine has two blocked sulfhydryl groups. The free sulfhydryl group breaks the disulfide bridges of the mucus glycoproteins causing sputum viscosity to reduce [8,12]. In addition to mucolytic effects, erdosteine has free radical scavenging and antioxidant activities (cardiac toxicity, hepatic toxicity, nephrotoxicity, neurotoxicity, and bleomycin-induced lung fibrosis) [9].
However, erdosteine also has anti-inflammatory and antioxidant effects. As Jang et al. [13] offer that anti-inflammatory effect of erdosteine contributes to the inhibitory effect of erdosteine on inflammatory cytokine synthesis and ROS production. Park et al. [10] suggest that erdosteine exerts anti-inflammatory effects by inhibiting NF-kB activation in LPS-stimulated mouse macrophages. In our study, inflammation was significantly lower in the IR-E group than in the IR group.
We also found that vasodilation was significantly increased in the IR and IR-E groups than in group C, as vascular congestion was significantly reduced in the IR-E group than in the IR group. Therefore, erdosteine may be a useful therapeutic agent for preventing accompanying severe inflammation resulting in vasodilatation. Although fibrosis and steatosis were similar between groups, myocyte injury was significantly lower in the IR-E group than in the IR group.
Caspases play an essential role in the execution of apoptosis as a member of proteolytic enzymes [14]. Some individiuals caspases are activated transiently and lead to apoptosis by affecting different stages of the signal transduction cascade. During apoptosis, after activation of initiator caspases such as caspase 8, a proteolytic cascade begins and effector caspases such as caspase-3 are activated and this leads to the cleavage of several substrates and results in morphological changes observed in apoptosis [15]. Caspases have an important role in the cell death program. Caspase activation’s pharmacological blockade prevents apoptosis. Thus, organ function and survival in animal models of sepsis improve [16].
In this study, endothelial caspase 8 enzyme activity was significantly higher in the IR group compared to C and IR-E groups. Endothelial caspase 3 enzyme activity was significantly higher in the IR group compared to C and IR-E groups.
Conclusion
The present study demonstrated a possible protective effect of erdosteine in skeletal muscle IR injury on the basis of anti-apoptotic and anti-inflammatory systems, confirmed by histopathologic evaluation. The possibility of clinical application of erdosteine in IR injury of the skeletal muscle tissue is suggested by these results. A couple of dose protocols of erdosteine and different time protocols for IR should be investigated in future studies.
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.
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Download attachments: 10.4328.ACAM.21268
Abdullah Özer, Ayşegül Küçük, Yiğit Kılıç, Serap Gültekin, Hayriye Tatlı Doğan, Aydan Kılıçarslan, Hüseyin Demirtaş, Barış Mardin, Dilek Erer, Tolga Tatar, Mustafa Arslan. The effect of erdosteine on ischemia-reperfusion injury in skeletal muscle of rats. Ann Clin Anal Med 2022;13(11):1237-1240
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Predictors of anxiety, depression and health anxiety in COVID-19 infected patients with lung involvement in inpatient units
Faruk Karandere 1, Tacettin Kuru 2, Tayfun Kara 3
1 Department of Internal Medicine, University of Health Sciences, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, 2 Department of Psychiatry, Alaaddin Keykubat University, Alanya Training and Research Hospital, Antalya, 3 Department of Child and Adolescent Psychiatry, Faculty of Medicine, Alanya Alaaddin Keykubat University, Antalya, Turkey
DOI: 10.4328/ACAM.21272 Received: 2022-06-14 Accepted: 2022-07-15 Published Online: 2022-07-18 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1241-1246
Corresponding Author: Tacettin Kuru, Oba District Fidanlık Street, Alanya, 07400, Antalya, Turkey. E-mail: tkuru76@yahoo.com P: +90 505 386 95 49 Corresponding Author ORCID ID: https://orcid.org/0000-0002-0313-558X
Aim: Although numerous community-based studies and case reports have been published on COVID-19 and its psychological effects, studies involving hospitalized patients are limited. The purpose of the present study was to evaluate indicators associated with anxiety, depression, and health anxiety in patients with COVID-19 pneumonia.
Material and Methods: One hundred ninety-eight patients hospitalized with diagnoses of COVID-19 pneumonia were included in the study. Participants’ sociodemographic characteristics and initial presentation variables were obtained from hospital records and information forms. Severity of lung involvement (SLI) was obtained from thoracic computed tomography (CT) records. The Hospital Anxiety and Depression Scale (HADS), and Whiteley Index-7 (WI-7) were applied to all participants.
Results: HADS-A levels were higher among female patients than among men (p=0.003). Higher WI-7 scores were determined in patients with mild SLI compared to those with moderate-severe SLI (p=0.012). HADS-A scores were higher in patients with primary symptoms of dyspnea, and HADS-D scores were higher in participants with primary symptoms of cough (p=0.026 and p=0.008, respectively).
Discussion: Female gender, severity of lung involvement, and symptoms of dyspnea and cough were identified as clinical indicators in terms of mental health evaluation. We think that our results will be a guide for determining the psychiatric support requirements of COVID-19 patients.
Keywords: COVID-19, Anxiety, Depression, Mental Health, Pandemic
Introduction
Coronavirus disease 2019 (COVID-19), caused by the new Coronavirus strain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), currently represents a pandemic. The COVID-19 outbreak was declared a public health emergency by the World Health Organization (2020) (WHO G. Statement on the second meeting of the International Health Regulations (2005) Emergency Committee regarding the outbreak of novel coronavirus (2019-nCoV). Published online 2020). Review studies have shown that COVID-19 not only threatens physical health, but also has an impact on mental health and well-being [1]. However, global interest has largely focused on psychological effects on the general population (for reasons such as quarantine, social restrictions, and impacts on economic well-being, education, and daily life) [2,3]. The diagnosis of COVID-19 has been linked to an increased incidence of new psychiatric diagnoses 14-90 days after treatment among individuals with no previous psychiatric histories [4]. Increasing post-traumatic stress symptoms (PTSS) and increased depression levels have been reported in patients following COVID-19 infection [5,6]. Case reports have observed elevated anxiety levels, suicide, and psychotic disorder during treatment in patients diagnosed with COVID-19 [7,8]. Female sex, a higher level of interleukin (IL)-1β, and greater self-perceived illness severity have been reported to be used for estimating the severity of psychiatric symptoms in patients hospitalized due to COVID-19 [9]. Follow-up studies have reported incidences of 28% for post-traumatic stress disorder (PTSD) in patients completing COVID-19 treatment, 31% for depression, 42% for anxiety, 20% for obsessive-compulsive (OC) symptoms, and 40% for insomnia findings. Overall, 56% of patients scored in the pathological range in at least one clinical dimension [10]. Psychiatric diseases in COVID-19 patients not only lead to mental outcomes, but also impact physical diseases. Anxiety in COVID-19 patients has been shown to be a risk factor for chronic diseases, such as hypertension [11]. Mental disorders associated with the COVID-19 pandemic have been reported to adversely affect treatment outcomes [12]. Identifying clinical risk factors that may give rise to the development of psychiatric disorder may therefore be useful in reducing short- and long-term effects on both the patient and the health care system. Although there have been numerous community-based studies and case reports on the psychological effects of COVID-19 disease, the number of studies involving inpatients is limited. The purpose of the present study was to evaluate the relationship between clinical indicators in patients hospitalized with a diagnosis of COVID-19 and with lung involvement, and anxiety, depression, and disease anxiety.
Material and Methods
Study population
Adult patients hospitalized at the by the Bakirkoy Dr. Sadi Konuk Training and Research Hospital with diagnoses of COVID-19 between 1 July and 15 August, 2020, were included in the study. All participants were positive for coronavirus disease with real-time reverse transcription-polymerase chain reaction analysis from nasopharyngeal swab or oropharyngeal swab specimens. All participants had thoracic computed tomography (CT) findings of COVID-19 infection. Patients meeting intensive care unit triage criteria (respiratory rate ≥30 / minute, oxygen saturation <93% despite nasal oxygen support of 5 l /min and above, partial oxygen pressure <60 mmHg despite nasal oxygen support of 5 l/ min and above, PaO2 / FiO2 <300, hypotension etc.) were excluded from the study. In addition, patients with premorbid psychiatric disorder and histories of mortality in the family due to the pandemic were also excluded from the study. Approval for the study was granted by the Bakirkoy Dr. Sadi Konuk Training and Research Hospital Clinical Research Ethical Committee on 22.06.2020 (decision no. 2020-13-12). All participants were interviewed in strict compliance with protective equipment and isolation rules. Written and verbal consent was obtained from all participants. Participants experiencing difficulty in reading and understanding forms or not completing the process were also removed from the study, which was finally completed with 198 individuals.
CT scan and imaging analysis
Thoracic CT scanning images were evaluated by pandemic hospital radiologists experienced in assessing thoracic imaging in the diagnosis of viral pneumonia in particular. If the patient underwent more than one CT scan during hospitalization, the scan with the most severe findings was included in the analysis. Patients were scanned with spiral CT on admission using a low-dosage, 64-slice, helical CT scanner (Somatom 64, Siemens Healthcare, Forchheim, Germany). Each of the five pulmonary lobes was evaluated using a scoring system of 1 (< 5% involvement), 2 (5–25% involvement), 3 (26–49% involvement), 4 (0–75% involvement), and 5 (>75% involvement). A total general lung score was calculated out of 25. Scores of 0-9 were regarded as mild lung involvement, 10-17 as moderate involvement, and 18-25 as severe involvement. Radiological findings of SARS-CoV-2 pneumonia were classified into three types, mild, moderate or severe involvement [13].
Psychometric instruments
Information concerning participants’ sociodemographic characteristics (sex, education level, employment status, monthly income, history of smoking, chronic illness, etc.) was elicited using the prepared information form.
Hospital Anxiety Depression Scale (HADS); This 14-item scale was developed to identify anxiety and depression in the hospital environment. It contains two subscales – HADS-A for evaluating anxiety and HADS-D for depression. Both subscales consist of seven items scored between 0 and 3. Items 1, 3, 5, 6, 8, 10, 11 and 13 are scored 3, 2, 1 or 0, while items 2, 4, 7, 9, 12 and 14 are scored 0, 1, 2 or 3. Items 1, 3, 5, 7, 9, 11 and 13 are related to anxiety, while items 2, 4, 6, 8, 10, 12 and 14 are concerned with depression. Total scores range from 0 to 21 on both scales. The validity and reliability of the Turkish-language version were studied by Aydemir et al. [14]. In this study, the α coefficient was calculated as 0.80 for anxiety items and 0.75 for depression items.
Whiteley Index (WI-7); WI-7 is widely used to screen for somatization disorder, hypochondriasis, and health anxiety. The questions are answered either Yes or No. Each positive reply is scored 1, and each negative reply is scored 0. A total score between 0 and 7 is obtained. Higher scores indicate greater disease anxiety. The reliability and validity of the Turkish-language version of the scale were studied by Güleç et al. [15]. Coefficient α for the WI-7 items in this study was calculated as 0.75.
Statistical analysis
Frequency and percentage values were calculated for categorical variables, while mean, standard deviation and median values were given for constant variables. The Kolmogorov-Smirnov test was used to assess normality of the distribution of constant variables. The Mann- Whitney U test was used in two-group comparisons of non-normally distributed variables. The Kruskal-Wallis test was used to compare more than two groups. Two-way evaluations of groups with statistical significance were performed using Dunn’s multiple comparisons test with Bonferroni correction. The presence of correlation between scores representing continuous variables was assessed using Spearman’s Rho correlation coefficient. P- values<.05 were regarded as statistically significant. Analyses were performed on ANCSS 11 (Number Cruncher Statistical System, 2017 Statistical Software) software and MedCalc Statistical Software version 18 (MedCalc Software bvba, Ostend, Belgium; http://www.medcalc.org; 2018).
Results
One hundred ninety-eight patients hospitalized with diagnoses of COVID-19 were included in the study. The mean age of the participants was 54.05±16.42. Ninety-two (46.5%) were men and 106 (53.5%) were women. Twenty patients (10.1%) were smokers. In terms of primary symptom distribution, the three most common were cough in 51 patients (25.8%), fever in 49 (24.7%), and fatigue in 36 (18.2%). Rare symptoms (such as sore throat, runny nose, diarrhea, loss of smell, and taste disturbance) were present in 13 (6.6%) patients. Severity of lung involvement (SLI) was mild in 101 cases (51.0%), moderate in 74 (37.4%), and severe in 23 (11.6%). Some cases exhibiting severe involvement could not be included in the study since they met the intensive care criteria. SLI was therefore divided into two groups: mild and moderate-severe. Patients reported the presence of symptoms for a mean 3.12±2.6 days prior to presentation. The mean length of hospitalization when patients were enrolled in the analysis was 9.03 ±6.77 days. When patients were compared in terms of HADS and WI-7 scale scores by gender, HADS-A levels were significantly higher among women than men (p=0.003). No significant gender difference was determined in terms of HADS-D (p=0.189) and WI-7 (p=0.058) scores. Comparison of scale scores based on education revealed a significant difference in terms of HADS-A (p=0.029). However, in two-way comparisons, the literacy only group exhibited significantly higher disease anxiety scores compared to the primary education group (p=0.006). When participants’ occupations were compared in terms of scale scores, significant differences were observed between their HADS-A (p=0.008), HADS-D (p=0.027), and WI-7 (p=0.47) scores. However, in two-way comparisons, HADS-A (p=0.002) and WI-7 (p=0.007) values were significantly higher in the non-working group compared to the public employee group. Two-way comparison revealed no statistically significant difference in terms of HADS-D. No significant relationship was determined between participants’ monthly income levels and HADS-A (p=0.417), HADS-D (p=0.240) and WI-7 (p=0.264) scores. No statistically significant difference was determined in terms of HADS-A, HADS-D, and WI-7 scores between participants with and without additional medical diseases (p=0.774, p=0.687, and p=0.075, respectively). No significant difference was also determined in HADS-A, HADS-D, and WI-7 scores between smokers and non-smokers (p=0.264, p=0.277, and p=0.152, respectively) (Table 1).
Significantly higher WI-7 scores were determined in patients with mild lung involvement than in those with moderate-severe involvement (p=0.012). No significant difference was determined in HADS-A and HADS-D scale scores in terms of SLI distribution (p=0.054, and p=0.270). Analysis of primary symptom distribution and scale scores revealed significantly higher HADS-A scores in patients with dyspnea (p=0.026), while HADS-D scores were significantly higher among patients with primary symptoms of cough (p=0.008). No significant relationship was found between symptoms and scale scores in patients with primary symptoms of fever, joint and muscle pain (Table 2).
Correlation analysis revealed significant positive correlation between the age variable and SLI score and length of hospitalization (rho=0.178, p=0.012 and rho=0.327, p<0.001, respectively). Additionally, WI-7 scores were significantly negatively correlated with SLI scores (rho=-167, p=0.019). As expected, significant positive correlations were observed between HADS-A and HADS-D (rho=0.567, p<0.001), HADS-A and WI-7 scores (rho=0.429, p<0.001), and HADS-D and WI-7 scores (rho=0.286, p<0.001). Significant positive correlation was also determined between SLI score and length of hospitalization (rho=0.271, p<0.001) (Table 3).
Discussion
The results of this study identified various clinical indicators acting as risk factors in mental health in patients diagnosed with COVID-19. These factors are important because new problems are being encountered in mental health services for patients hospitalized during the COVID-19 pandemic, such as risk of transmission, patient isolation, and limited visiting. Female gender, severity of lung involvement, and dyspnea and cough were identified as important clinical indicators in the evaluation of patients’ mental health. Findings from community-based studies show that women experience more severe anxiety symptoms during the COVID-19 pandemic than men [16]. Studies have reported a greater likelihood of anxiety in female patients than in males [9,10]. Anxiety levels were also higher in female patients with lung involvement in the present study. Although higher rates of depression have been reported in female patients in studies involving COVID-19 patients, no statistically significant difference was observed in the present study [10]. We attributed this increased anxiety to the possibility that women are more affected by traumatic events [17]. Both cough and dyspnea can result in severe emotional difficulty and prevent daily functioning. Depression and anxiety disorders are known to be more prevalent, and adversely affect the prognosis in patients with chronic obstructive pulmonary disease with symptoms of cough and dyspnea compared to the general population [18]. Indeed, depression in these patient groups has been reported to be more associated with cough than chronic lung disease [19]. Air hunger has been reported to be capable of triggering anxiety [20]. Dyspnea is a distressing sensation capable of causing psychological trauma. Air hunger has been linked to PTSD, anxiety and depression [21]. Cross-sectional and longitudinal studies have shown that severe dyspnea is associated with greater depressive symptoms [22]. Greater anxiety was observed in the group with dyspnea as the leading symptom in this study, and greater depressive symptoms in the group with cough as the main symptom. As shown in the literature, air hunger triggers anxiety, and we thought that physical discomfort and concerns over stigmatization may also trigger depression in patients. Patients with mild lung involvement registered higher WI-7 scores in the present study. We also observed negative correlation between SLI and WI-7 scores. The WI-7 scale is employed in the evaluation of characteristic such as “bodily preoccupation,” and “disease fear or worrying” in the examination of such psychiatric diagnoses as somatization and hypochondriasis [23]. The COVID-19 pandemic has been shown to cause public panic and hypochondria, and an increase in appropriate health search behavior and demands for health services [24]. We also thought that hypochondriacal suspicion may result in an increased desire to access health services. This may perhaps have resulted in patients being diagnosed without progression of lung involvement. The burden placed on health services by individuals with hypochondriacal suspicion must also, of course, not be ignored.
This study has a number of limitations that are difficult to eliminate during a pandemic. They follow from the compulsory isolation conditions. Due to limited contact with COVID-19 patients, the study was performed only with patients in the hospital’s isolation ward, and the study sample involved a single hospital. Due to the size of the study sample, it was not possible to evaluate rare COVID-19 symptoms. Additionally, due to the cross-sectional nature of the present study, we were unable to observe patients’ mental health symptoms in a dynamic manner, and data were only obtained during visits.
Conclusion
The present study identified various clinical indicators acting as risk factors in terms of effects on the mental health of patients diagnosed with COVID-19. Female gender, severity of lung involvement, and dyspnea and cough symptoms were identified as important clinical determinants in the evaluation of patients’ mental health. We think that our findings will be a useful guide to determining psychiatric support requirements in COVID-19 patients.
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.
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Download attachments: 10.4328.ACAM.21272
Faruk Karandere, Tacettin Kuru, Tayfun Kara. Predictors of anxiety, depression and health anxiety in COVID-19 infected patients with lung involvement in inpatient units. Ann Clin Anal Med 2022; DOI: 10.4328/ACAM.21272
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Evaluation of the pain in COVID-19 patients with musculoskeletal pain: A cross-sectional study
Fatıma Yaman, Muhammed Fatih Özdemir, Merve Akdeniz Leblebicier, Aysun Özlü, Hasan Hüseyin Gökpınar
Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Kutahya Health Sciences University, Kutahya, Turkey
DOI: 10.4328/ACAM.21275 Received: 2022-06-15 Accepted: 2022-08-04 Published Online: 2022-08-09 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1247-1251
Corresponding Author: Fatıma Yaman, Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Kutahya Health Sciences University, 43040, Kutahya, Turkey. E-mail: fatimacakir84@hotmail.com P: +90 506 680 29 26 F: +90 274 223 60 59 Corresponding Author ORCID ID: https://orcid.org/0000-0002-6137-0166
Aim: There is no study that have assessed face-to-face using the multidimensional pain scale in COVID-19 patients with musculoskeletal pain. This study aimed to reveal the pain region, character and severity in COVID-19 patients with musculoskeletal pain.
Material and Methods: This cross-sectional study was carried out in 214 patients who had a positive result of the polymerase chain reaction test within the last five days and at least one musculoskeletal pain symptom, such as fatigue, myalgia, and arthralgia/polyarthralgia. The cases were divided into groups as clinically severe and non-severe. Evaluations were made on the first day of admission. Myalgia symptoms were classified as diffuse and local. The McGill Pain Questionnaire was used for pain regions and caharacters while the Visual Analog Scale (VAS) was for pain intensity.
Results: The frequency of involvement was myalgia (96.3%), fatigue (77.6%) and polyarthralgia (62.6%), respectively. The diffuse myalgia was (53.3%) in all patients. The mean myalgia VAS score in the non-severe group was 5.88±1.83 and 6.25±1.24 in the severe group (p=0.192). The most common pain areas were the back, feet, and knees respectively, and throbbing (40.7%), aching (30.8%), and pricking (26.1%) were the most common characteristics. The suffocating character of the pain was significantly higher in the severe group (p<0.05).
Discussion: Defining disease-specific pain regions, character and severity in COVID-19 patients with musculoskeletal pain is important in managing possible chronic pain.
Keywords: COVID-19, Myalgia, Arthralgia, Neuropathic pain, Pain severity
Introduction
In patients with COVID-19, multisystem symptoms, such as fever, cough, shortness of breath, dizziness, and confusion are detected. These are often accompanied by musculoskeletal symptoms, including fatigue, myalgia, back pain and arthralgia [1,2]. The most common musculoskeletal system symptoms are non-specific musculoskeletal pain; e.g., fatigue, myalgia, back pain, and arthralgia in order of frequency [2].
Although arthralgia is reported as a common symptom, it is often addressed together with myalgia. However, these two need to be considered and defined separately [3]. Additionally, corticosteroids used in the treatment of COVID-19 may increase the severity of myalgia and pain by resulting in damage to the musculoskeletal system.
Zhang et al. [4] suggested that myalgia might be an important predictor of the disease severity in patients with COVID-19 presenting with the tomographic or radiographic involvement of the lung. In this context, it is important to determine the location, sensation character, and severity of musculoskeletal pain, which is present before COVID-19 treatment and in the early symptomatic period of the disease in order to both predict the disease severity and to outline pain management in the long COVID-19 period. In the literature, there are limited studies examining the effects of COVID-19 on the musculoskeletal system [5]. However, to our knowledge, no multi-dimensional prospective study has been conducted with a focus on COVID-19-associated pain and defining the characteristics of this pain. This study aimed to reveal the localization, severity and character of musculoskeletal pain in COVID-19.
Material and Methods
This cross-sectional study was conducted at a University Hospital between July 2021 and December 2021. Approval (2021/09-20) was obtained from the Non-Interventional Research Ethics Committee of the university on 26.05.2021. The study was carried out in accordance with the principles of the Declaration of Helsinki and with permission obtained from the Turkish Ministry of Health.
The study included voluntary patients aged 18-60 years admitted to the pandemic ward of the hospital, who had a positive result of polymerase chain reaction test within the last five days and described musculoskeletal pain due to COVID-19 with a pain severity of 2 to 8 on the 10-cm Visual Analog Scale (VAS). Patients who had multi-organ involvement due to COVID-19 disease and who required intensive care (critical cases), those that were given corticosteroid therapy due to COVID-19, those with any chronic musculoskeletal disease, inflammatory rheumatic disease (rheumatoid arthritis, ankylosing spondylitis, etc.), or neurological (multiple sclerosis, etc.) or psychiatric disease diagnosed in the pre-COVID-19 period, those who had undergone musculoskeletal surgery in the pre-COVID-19 period, patients with diabetes or any other disease that could cause polyneuropathy, and those with a negative PCR test were excluded from the study. Initially, 218 patients with COVID-19 who had musculoskeletal symptoms (weakness, myalgia, and arthralgia/polyarthralgia) were included in the study. However, two patients were excluded because they did not know their body weight and two patients did not want to complete the evaluation. Therefore, the study was completed with 214 patients who had a positive PCR result. According to the clinical classification of COVID-19, the cases were divided into two groups as severe (n = 116) and non-severe (n = 98). As per the literature, the non-severe group consisted of patients with mild symptoms or fever and respiratory tract infection symptoms, who might have pneumonia findings on imaging (respiratory rate <30/min or oxygen saturation >93%). Patients with at least one of the following conditions formed the severe group: respiratory rate ≥30/minute, oxygen saturation ≤93%, or with lung imaging taken due to COVID-19 before and with the presence of more than half lesion progression in lung imaging during the admission [6].
Written informed consent was obtained from the patients after providing them with information about the study.
Evaluations
A socio-demographic form was used to evaluate the sociodemographic characteristics of the patients. The McGill Pain Questionnaire (MPQ) was used to identify painful regions and evaluate the pain character. The evaluations of the patients were performed on the day of admission to the pandemic ward. MPQ was administered by one investigator only (M.F.O.) in a face-to-face interview with each patient.
Evaluation of myalgia
Myalgia was classified as diffuse and local. The patients were asked where on their bodies they felt myalgia. Pain in the common muscle group was defined as ‘diffuse myalgia’, while pain localized in one muscle was defined as ‘local myalgia’. Two anterior and posterior body images (MPQ-first part) were used to define the painful muscle area. They marked the painful muscle area or areas with a pencil and localized the relevant area with their hands.
Evaluation of painful region and polyarthralgia
The patients were asked to mark with a pencil and localize with their hands the relevant area on two body pictures drawn from the anterior and posterior view (MPQ-first part) for the detection of painful joints and other body parts. Each patient was given a special pen for marking to reduce contact during the evaluations. If the painful region included only a single joint or the spine, it was recorded with the name of the anatomical area involved. Polyarthralgia was defined in the presence of more than one different joint involvement in accordance with the literature [7].
Evaluation of MPQ and pain character
MPQ, a multidimensional pain assessment questionnaire, consists of four parts. In the first part, there are two body pictures drawn from the anterior and posterior views of the body to mark the body region or regions affected by pain. In the second part, there are 20-word groups, each including two to six descriptive words to describe pain in terms of sensation, perception, and evaluation. In the third part of MPQ, the relationship of pain with time and factors that increase or decrease pain is questioned. In the last part, an evaluation is made on a rating scale consisting of words describing the severity of pain. In this study, the last part of MPQ was not used since VAS was preferred to assess the severity of pain and polyarthralgia.
Evaluation of pain severity
VAS is a scale that converts pain felt by an individual into a numerical form from 0 to 10 points, with 0 representing no pain and 10 representing the most severe pain ever experienced. In this study, the severity of myalgia was assessed using VAS.
Statistical analysis
The study population consisted of patients from a University Hospital in Turkey. The sample size was calculated using G Power (3.1.9, University of Kiel, Germany), taking into account the results obtained by Tuzun et al. [3] The prevalence value was used to calculate the sample size. As a result, the required minimum number of patients was determined as 214 at the 95% confidence interval with a sampling error of 5% and a prevalence of 16.70%.
The arithmetic mean and percentage values were used to present the data related to the demographic characteristics, symptoms and pain characters of the participants. The chi-square test was used to compare two qualitative values, and the Mann-Whitney U test to evaluate parameters that did not show a normal distribution. The significance value was accepted as p < 0.05. Statistical analyses were performed with IBM SPSS Statistics (IBM Corp. Released 2016. IBM SPSS Statistics for Windows, Version 24.0. Armonk, NY: IBM Corp.).
Results
A total of 214 patients diagnosed with COVID-19 (98 non-severe, 116 severe) were included in the study. Table 1 presents the demographic characteristics of the participants according to disease severity. As per the data in Table 1, there was a statistically significant difference between the patients’ age, education level and the presence of comorbid disease according to the severity of the disease.
In the evaluation of myalgia with VAS, the mean score in the non-severe group was 5.88±1.83, while it was 6.25±1.24 in the severe group (p=0.192). Musculoskeletal Pain Distribution in terms of Disease Severity is shown in Table 2.
When the patients’ musculoskeletal symptoms were examined according to the severity of the disease, common myalgia was observed at a rate of 53.3% in the severe group and 55.1% in the non-severe group (Table 3).
Evaluation of Pain Characters is shown in Table 3. The three most common pain characteristics were throbbing (40.7%), aching (30.8%), and pricking (26.1%). The presence of suffocating, another pain character, was significantly higher in the non-severe group than in the severe cases (p = 0.037). When pain character was examined in terms of pattern over time in all COVID-19 patients, it was described as ‘constant’ (n=129; 60.3%), ‘rhythmic’ (n= 72; 33.6%) and ‘intermittent’ (n=13; 6.1%).
Discussion
Patients infected with SARS-CoV-2 may show a wide range of symptoms involving different systems. In the literature, it has been reported that musculoskeletal symptoms may occur before the development of respiratory system symptoms and findings in COVID-19 [8, 9], and myalgia may be an important predictor of the severity of the disease [4], which increases the importance of evaluating musculoskeletal symptoms in patients with COVID-19. Among the most common musculoskeletal symptoms are fatigue, myalgia, arthralgia, and muscle weakness [10]. In this context, it is essential to not only identify the presence of musculoskeletal pain in COVID-19 but also define the localization and character of pain and determine its relationship with time. However, we found no study in the literature evaluating early musculoskeletal pain associated with COVID-19 using a multidimensional pain scale. The aim of our study was to describe the localization, character and severity of musculoskeletal pain experienced by COVID-19 patients.
Chronic diseases that are more commonly seen in advanced ages also increase the severity of COVID-19 in this patient group [11]. In a study by Wang et al. [12], examining the findings of 138 COVID-19 cases, it was shown that 46.4% of the patients had comorbidities, and those admitted to the intensive care unit had a higher age than those who did not require intensive care. We found the frequency of comorbidities and mean age to be higher in the severe disease group than in the non-severe group, which is consistent with the literature.
The term ‘myalgia’ is often used to describe musculoskeletal symptoms associated with COVID-19. However, some studies have reported that this term is not sufficient and may be confused with joint pain [3.13]. Therefore, the classification of myalgia as diffuse and local and the detailed localization of painful regions can be considered as the strong characteristics of our study. The etiopathogenesis of myalgia and arthralgia due to COVID 19 involves direct damage by the virus to muscle tissue, synovium and cortical bone [14]. Consistent with the literature, the presence of diffuse myalgia was higher than local myalgia in all COVID-19 patients in our study [3]. Furthermore, we detected myalgia as a musculoskeletal symptom in all patients with severe clinical COVID-19. Similarly, in a meta-analysis including 55 studies investigating the effect of clinical symptoms on disease severity in COVID-19 cases, it was emphasized that the frequency of myalgia was higher in the presence of severe disease [15]. Similar to the findings in the literature, a more aggressive inflammatory response in the severe disease group may have triggered myalgia symptoms [16].
In our study, we determined that the severity of myalgia in COVID-19 patients was above moderate level, and there was no significant difference between the groups in terms of pain intensity. In a previous study, in which biopsychosocial factors predicting pain in individuals with COVID-19 were retrospectively evaluated, pain intensity was evaluated using VAS, and the mean VAS score of the patients was found to be 4.04 (SD = 2.23) [17]. The higher pain intensity of our patients may be due to our study being conducted in the acute and painful period of COVID-19. Furthermore, we consider that patients’ increased fear related to the COVID-19 disease in the acute phase and possible sleep problems they experienced may have affected the intensity and perception of pain [18].
It has been stated that the etiopathogenesis of joint and muscle involvement may be common in COVID-19 patients [13]. Therefore, there is a possible relationship between arthralgia and myalgia. In this context, it is also important to define the localization of single joint, spine and multiple joint pain due to COVID-19 in the early period. In our study, the regions of single joint and spine pain caused by COVID-19 were found to be the back, feet, and knees, in order of frequency. In a study investigating pain symptoms in COVID-19, the back and lower limbs were shown to be the most frequently involved musculoskeletal regions [19]. Similar to our study, Tuzun et al. [3], who evaluated musculoskeletal pain associated with COVID-19, noted back and foot pain as one of the most common symptoms.
In our study, the patients described the characteristic of their pain felt as throbbing, aching, and pricking in that order. Furthermore, although suffocating pain was detected in a few patients, it was determined at a significantly higher rate in those with severe clinical symptoms. In the study in which pain syndromes were evaluated in the acute phase of mild to moderate COVID-19, the pain character was defined as numbing, burning, and pressing in order of frequency [7]. Identification of different pain characters compared to our study may be due to the authors’ inclusion of patients who used medication for COVID-19, the elderly, and those with comorbidities that could cause neuropathic pain, as well as the absence of an evaluation performed with a multidimensional pain scale in the previous study. Identifying the pain character in COVID-19 patients with musculoskeletal pain may provide an understanding of different pain mechanisms, which will, in turn, affect the choice of medical treatment. Furthermore, reviewing the current literature, we did not find a study that questioned the character of neuropathic pain in detail and evaluated its localization in COVID-19-patients with musculoskeletal pain.
Majority of our patients described the pattern of their current pain in terms of its relationship with time as ‘constant’. IgM antibodies can be detected from the seventh to the 21st day of the infection in SARS-CoV-2 [20]. Therefore, the continuation of possible viral replication at the time of the evaluation of the patients in our study might have been a factor in the constant nature of pain. We consider that this finding would guide scientific studies investigating the relationship between COVID-19-associated musculoskeletal pain and time.
Differences in some socio-demographic data between groups may have led to a limitation in interpreting the results of the multi-dimensional assessment of pain. This can be stated as a limitation of our study.
Conclusion
It is known that COVID-19 may result in the development of neuropathic pain within weeks or months. Therefore, pain should be detected early, defined, and localized. This study will make an important contribution to the literature by providing early detection of regions of pain, its severity and especially its character in COVID 19 patients with musculoskeletal pain.
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
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2. Cipollaro L, Giordano L, Padulo J, Oliva F, Maffulli N. Musculoskeletal symptoms in SARS-CoV-2 (COVID-19) patients. J Orthop Surg Res. 2020;15(1):178.
3. Tuzun S, Keles A, Yildiran T, Palamar D. Assessment of musculoskeletal pain, fatigue and grip strength in hospitalized patients with COVID-19. Eur J Phys Rehabil Med. 2021;57(4):653-62.
4. Zhang X, Cai H, Hu J, Lian J, Gu J, Zhang S, et al. Epidemiological, clinical characteristics of cases of SARS-CoV-2 infection with abnormal imaging findings. Int J Infect Dis. 2020;94:81-7.
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6. Cai H, Chen Y, Chen Z, Fang Q, Han W, HU S, et al. Handbook of COVID-19 prevention and treatment. Liang T, editors. 1st ed. China: The First Affiliated Hospital, Zhejiang University School of Medicine; 2020. p.1-84.
7. Oguz-Akarsu E, Gullu G, Kilic E, Dinç Y, Ursavas A, Yilmaz E, et al. Insight into pain syndromes in acute phase of mild-to-moderate COVID-19: Frequency, clinical characteristics, and associated factors. Eur J Pain. 2022;26(2):492-504.
8. Pung R, Chiew CJ, Young BE, Chin S, Chen M I-C, Clapham HE, et al. Investigation of three clusters of COVID19 in Singapore: Implications for surveillance and response measures. Lancet. 2020;395(10229):1039-46.
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11. Chen Y, Klein SL, Garibaldi BT, Li H, Wu C, Osevala NM, et al. Aging in COVID-19: Vulnerability, immunity and intervention. Ageing Res Rev. 2021;65:101205.
12. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-69.
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14. Kucuk A, Cumhur Cure M, Cure E. Can COVID-19 cause myalgia with a completely different mechanism? A hypothesis. Clin Rheumatol. 2020;39(7):2103-104.
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Fatıma Yaman, Muhammed Fatih Özdemir, Merve Akdeniz Leblebicier, Aysun Özlü, Hasan Hüseyin Gökpınar. Evaluation of the pain in COVID-19 patients with musculoskeletal pain: A cross-sectional study. Ann Clin Anal Med 2022;13(11):1247-1251
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Allergic rhinitis in the etiology of obstructive sleep apnea
Mustafa Çolak, Nurhan Sarıoğlu, Mehmet Köse, Hikmet Çoban, Fuat Erel
Department of Chest Diseases, Balikesir University, Health Practice and Research Hospital, Balikesir, Turkey
DOI: 10.4328/ACAM.21280 Received: 2022-06-20 Accepted: 2022-07-20 Published Online: 2022-07-26 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1252-1256
Corresponding Author: Mustafa Çolak, Balikesir University, Health Practice and Research Hospital Paşaköy, Bigadiç Road, 10145, Altıeylül, Balıkesir, Turkey. E-mail: drmclk@yahoo.com P: +90 532 680 39 61 F: +90 266 612 12 94 Corresponding Author ORCID ID: https://orcid.org/0000-0002-8458-3535
Aim: In this study, it was aimed to determine the prevalence of allergic rhinitis in patients with obstructive sleep apnea syndrome and to investigate the effect of allergic rhinitis on the severity of obstructive sleep apnea (OSA).
Material and Methods: In our study, patients who applied to our outpatient clinic with complaints of snoring and excessive daytime sleepiness and underwent polysomnography (PSG) and skin prick test (SPT) between 2014-2017 were retrospectively evaluated. The relationship between OSA and allergic rhinitis was evaluated.
Results: The study included 519 cases, 162 females (31,2%) and 357 males (68,8%), with a mean age of 49,26 ± 12,21 (19–85), who were diagnosed with simple snoring and OSA. The prevalence of allergic rhinitis among the OSA groups was 20.8%. Statistically, significant correlation was found when the OSA groups were compared according to age, body mass index and Epworth values (p<0,001, p<0,001, p=0,004, respectively). When the distribution of allergens was examined according to the prick test results performed on the patients, while most common sensitivity was detected to house dust mites (42%), and the second most common sensitivity was detected to grass pollen (39%) in atopic patients, sensitivity to fungal spores and animal hair/epithelium was detected less commonly (9,5%).
Discussion: As a result of our study, we think that allergic rhinitis may contribute to the development of snoring and OSA, and therefore, allergy treatment may improve the clinical picture of snoring and OSA.
Keywords: Sleep Apnea, Allergic Rhinitis, Skin Prick Test
Introduction
Obstructive sleep apnea (OSA) is a clinical disease characterized by recurrent episodes of upper airway collapse during sleep. When the study algorithm was established based on patient complaints and clinical+polysomnography (PSG) data, the prevalence of OSA was observed to be 4% in men and 2% in women [1,2]. There are many predictive causes identified for OSA. Obesity, male gender, age, race, genetics, smoking and alcohol addiction are the most common known causes [3]. Disorders or anatomical variations formed in the upper respiratory tract are also among important factors that can cause OSA. Changes in the upper respiratory tract, especially in the connective tissues, play an important role in the pathophysiology in patients with OSA [4].
Primary symptoms of allergic rhinitis (AR) result from inflammation in the upper respiratory tract after allergen exposure. Nasal congestion is the most disturbing symptom in AR patients and usually occurs with perennial allergens. This complaint, which continues especially at night, causes deterioration in respiratory airflow in the upper respiratory tract and snoring may occur in patients [5].
In a review published in 2014, the prevalence of AR was 10% to 30% in adults and 40% in children [6].
Treatments of inflammation/congestion that develops in the nasal region and causes flow restriction reduce the existing barrier [7].
It is known that Obstructive Sleep Apnea and Allergic Rhinitis are frequently encountered and significantly affect the quality of life of people who are exposed to them. These are diseases to be considered because they are treatable. In our study, we also aimed to investigate the relationship between the current situation and AR, and the structure of the correlation between AR and OSA severity, while including patients who were admitted to our outpatient clinic with complaints of sleep apnea, snoring, and daytime sleepiness in the PSG program to evaluate them in terms of OSA.
Material and Methods
In our study, we retrospectively examined patients over the age of 18 who applied to the Chest Diseases outpatient clinic of our hospital between February 2014 and November 2017 with complaints of snoring and excessive daytime sleepiness, and who underwent PSG. Patients with central apnea and patients with a history of malignancy were excluded from the study.
In order to make a differential diagnosis with OSA for each patient, some tests were performed to exclude other diseases that cause similar symptoms. For this reason, pulmonary function test, skin prick test, hemogram and biochemistry analyses, posterior-anterior chest X-ray were requested from the patients.
The patients were divided into groups according to the severity of OSA and whether they were allergic or not. The prevalence of allergic rhinitis in OSA patients and the relationship between diseases were evaluated.
This study was carried out with the permission of Balıkesir University Faculty of Medicine, Health Practice and Research Hospital Ethics Committee, dated 16.11.2016 and decision number 2016/115.
Skin prick test
The skin prick test is a frequently used method in clinical practice, as it is both inexpensive and easy to apply [8]. The skin prick test was applied to the inner forearm by using standard allergens (Allergopharma, Reinbek, Germany). The test was evaluated 15 minutes after its application. Sensitivity to any allergen was defined as an atopic body.
Polysomnography
The standard PSG process was performed with the 62-channel Embla N7000 vehicle (Medcare Flage, Iceland). Polysomnographic records were scored using the American Academy of Sleep Medicine manual scoring criteria [9]. The patients were categorized in terms of OSA severity as follows: AHI <5 was considered normal (control groups), 5 and <15 were considered mild OSA, 15 and <30 moderate OSA, and 30 and above were considered severe OSA. Patients diagnosed with OSA were divided into 4 groups; simple snoring (114 persons) Group I, mild OSA (125 persons) Group II, moderate OSA (132 persons) Group III, severe OSA (148 persons) Group IV.
Statistical Method
SPSS 23.0 program was used in the analysis of the variables. The conformity of the data to the normal distribution was evaluated using the Shapiro-Wilk test, and the homogeneity of variance was evaluated using the Levene test. While the Independent-Samples T-test was used together with the Bootstrap results in the comparison of two independent groups with each other according to the quantitative data, the Mann-Whitney U test was used with the Monte Carlo simulation technique. In the comparison of independent multiple groups with each other according to quantitative data, the Kruskal-Wallis H Test, one of the nonparametric tests, was used with the results of the Monte Carlo simulation technique, and Dunn’s Test was used for Post Hoc analyses. In a comparison of categorical variables with each other, Pearson’s Chi-Square and Fisher-Freeman-Holton tests were tested with the Monte Carlo Simulation technique and column ratios were compared with each other and expressed according to Benjamini-Hochberg corrected p-value results. Quantitative variables were shown in the tables as mean ± std (standard deviation) and median range (maximum-minimum), while categorical variables were shown as n (%). The variables were analyzed at a 95% confidence level, and a p-value of <0.05 was considered significant.
Results
The study was performed on 519 cases diagnosed with simple snoring and OSA. The mean age of the patients was 49,26 ± 12,21 years, with 162 (31,2%) females and 357 (68,8%) males;
One hundred and six (20,4%) of all patients were evaluated as allergic (Table 1). In OSA groups, the prevalence of allergic rhinitis was 20,8%.
A statistically significant difference was found between OSA severity and gender (p=0,011). The rate of male patients was higher in all groups (p=0,011) (Table 1).
When assessing the severity of OSA and the presence of comorbidity, a significant difference was found between the groups (p<0,01) (Table 1).
When atopy, smoking history and nasal obstruction were compared in all groups according to the severity of OSA, no statistically significant correlation was found (p=0,783, p=0,078 and p=0,751, respectively) (Table 1).
No significant correlation was found between the groups in terms of atopy, smoking history and nasal obstruction when comparing the severity of OSA (p=0,783, p=0,078, p=0,751, respectively) (Table 1).
It was observed that the mean age increased as the severity of OSA increased among the groups (median age was 46 years in Group I, 49 in Group ll, 51 in Group lll, 52 in Group IV) (p<0,001). When Epworth and BMI values were compared between groups; while median Epworth was 7 in group I, it was found as 10 in group IV; while the median BMI was found 28,10 in group I, the median was found as 32,4 in group IV (p=0,004, p<0,001, respectively).
When the allergen types were compared according to the severity of OSA, no significant correlation was found (Table 2).
27,4% of allergic patients and 36,6% of non-allergic patients had comorbidities, and the difference between them was not significant (p=0,076) (Table 3). A history of cardiac and pulmonary disease was found in 19 patients in the non-allergic group and in 1 patient in the allergic group (4,6% vs. 0,9%, respectively).
When the patients were evaluated according to their allergy status; no statistically significant correlation was found between allergic and non-allergic subjects in terms of age, BMI, AHI, lowest nighttime oxygen saturation, Epworth, values (Table 3).
When the total IgE levels of the patients were compared, the total IgE values (115,61) of the allergic patients were found to be higher than in non-allergic patients (n=38), and this highness was found to be statistically significant (p<0,001) (Table 3).
When the distribution of allergens was examined according to the prick test results performed on the patients, the most common sensitivity was detected to house dust mites (42%), and the second most common sensitivity was detected to grass pollen (39%) in atopic patients. Sensitivity to fungal spores and animal hair/epithelium was detected lesser (9,5%). The distribution of allergens is shown in Figure 1.
Discussion
The main event in OSA is the closure of the airway. Agreed predisposing factors for OSA are obesity, male gender, smoking, craniofacial abnormalities, family history, increased pharyngeal soft tissue, and nasal obstruction. Especially male gender and obesity come to the fore [10]. Also in our study, the severity of OSA was found to be higher, especially in males and in patients with high BMI. This situation is explained by the neck structure of the male gender and the increase in pharyngeal adipose tissue in overweight patients.
The prevalence of allergic rhinitis is observed with a frequency varying between 15% and 40%, depending on the population and the methods used [11]. Also in our study, it was similarly found that the prevalence of allergic rhinitis was 20,4% in the entire patient population.
It was reported that hypoxemia caused by OSA and subsequent sympathetic stimulation are risk factors especially for cardiovascular and cerebrovascular diseases [2]. Our study also showed that the severity of OSA increased even more in patients with comorbidities.
One of the predisposing factors for OSA is smoking. Many studies showing a higher prevalence of smoking in OSA patients have attempted to demonstrate the relationship between OSA and smoking [12,13]. In our study, the prevalence of smoking was found to be 34,7% and no significant effect of smoking on the severity of OSA was found. This may be attributed to the multifactorial components of the OSA pathophysiology rather than the inflammatory effect of smoking.
Nasal obstruction was stated as a risk factor especially for OSA. Nasal congestion significantly blocks airflow during sleep and disrupts the normal physiological functions of the nasal cavity, a possible primary factor leading to pharyngeal collapse [14]. In the study by Bozkurt et al., the presence or absence of allergic rhinitis symptoms in patients with Sleep breathing disorder symptoms did not cause significant change in PSG parameters. In the same study, the mean AHI value was found to be higher in the non-allergic group, but this highness was not statistically significant [15]. Also in our study, no relationship was found between the degree of nasal obstruction and the severity of AHI in the absence or presence of nasal obstruction in allergic patients.
The Epworth sleepiness scale is commonly used for screening and distinguishing between individuals with versus without OSA [16]. In the NASAL study, patients with allergic rhinitis reported that they had more difficulty falling asleep (24% vs 8%), woke up more frequently during the night (31% vs 13%), and did not sleep well (26% vs 11%) compared to the general population [17]. However, in another study performed, allergic and non-allergic patients were evaluated, Epworth results were found to be similar between the groups [15]. In our study, there was no difference between allergic and non-allergic patient groups in terms of Epworth values.
AR has been defined as a clinical form accompanied by an IgE-related immune response [18]. Also in our study, the total IgE ratio was higher in the allergy group. No significant difference was found between OSA and non-OSA, and the grade of AHI, in terms of total IgE level. In our study, the total IgE ratio was found to be higher in the allergic group, which is consistent with the literature.
The skin prick test has become routinely used today, due to its ease of application, fast results and cost effectiveness [19]. In a recently published article, the sensitivity and specificity of the skin prick test to aeroallergens were found to be approximately 70-97% [20]. In a study performed, prick test was carried out on patients with a high risk for OSA, and the test was found to be positive in 72,5%. Afterwards, PSG was performed on the patients and OSA was detected in 69,2% of the patients [21]. In a meta-analysis by Yuan Cao et al., the prevalence of AR in adults was found to be 23% and 35% in Sleep disordered breathing/OSA patients [22]. In our study, the prevalence of allergic rhinitis in OSA patients was 20,8%, and in atopic patients in allergen distribution, house dust mite (42%) was the most common, while sensitivity to herbs (39%) was the second most common. However, the effect of house dust mite or grass pollen on the severity of OSA could not be demonstrated.
Conclusion
In our study, the prevalence of allergic rhinitis in OSA patients was 20,8%, and the highest sensitivity was found in relation to house dust mites. Therefore, we concluded that especially perennial allergic rhinitis may be associated with snoring and OSA. As a result of our study, we think that with the treatment of allergic rhinitis, snoring and clinical picture of OSA may be improved. Along with this relationship, we suggest that allergic rhinitis symptoms be questioned within the questions directed to patients with snoring complaints and patients with OSA.
Our study had some limitations. No comparison was made with the healthy population without simple snoring/OSA. Nasal inspiratory flow measurements and rhinomanometry measurements were not performed for the evaluation of nasal obstruction. Non-allergic rhinitis group was not determined among the patients and this group was not evaluated separately. Further and larger studies are needed to determine the relationship between OSA and allergic rhinitis.
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.
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Download attachments: 10.4328.ACAM.21280
Mustafa Çolak, Nurhan Sarıoğlu, Mehmet Köse, Hikmet Çoban, Fuat Erel. Allergic rhinitis in the etiology of obstructive sleep apnea. Ann Clin Anal Med 2022;13(11):1252-1256
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Comparison of the c-reactive protein-mean arterial pressure ratio with critical care prognostic scoring systems
Abuzer Özkan
Department of Emergency Medicine, University of Health Sciences, Umraniye Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21281 Received: 2022-06-18 Accepted: 2022-09-17 Published Online: 2022-09-21 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1257-1261
Corresponding Author: Department of Emergency Medicine, University of Health Sciences, Umraniye Training and Research Hospital, Istanbul, Turkey. E-mail: ebuzerozkan@gmail.com P: +90 505 615 55 50 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4284-0086
Aim: We hypothesized that the C-reactive protein (CRP)-mean arterial pressure (MAP) ratio could predict short-term mortality in critically ill patients. In this study, our aim was to compare the CRP-MAP ratio with the acute physiology and chronic health evaluation (APACHE II) score in predicting the short-term mortality of critically ill patients.
Material and Methods: This research was designed as a prospective observational study and included critically ill patients aged over 18 years, who were admitted to the intensive care unit from the emergency department between December 10, 2021, and March 10, 2022. The patients’ demographic and clinical data and 28-day mortality status were recorded.
Results: We included 169 patients in this study. The median age was 72 (25th-75th percentiles: 61-81) years, and 74 (43%) of the patients were female. The CRP-MAP ratio was significantly higher in the non-survivor group than in the survivor group [1.03 (0.194-2.24) and 0.207 (0.0346-1.1), respectively, p<0.001]. The APACHE II score was also significantly higher in the non-survivor group than in the survivor group [26 (20.8-30) and 21 (15-25.8), respectively, p < 0.001]. The odds ratio of the CRP-MAP value was similar to those of the APACHE II score and blood urea nitrogen-albumin ratio (3.819, 2.545, and 3.67, respectively).
Discussion: There was a significant difference in mortality between the patients with CRP-MAP ratios below and above the cut-off value of 4.2. According to the results of our study, the CRP-MAP ratio was as significant as APACHE II in the prediction of mortality
Keywords: C-reactive Protein, Mean Arterial Pressure, APACHE
Introduction
Critical care patients constitute a group that requires early diagnosis and prompt treatment at the emergency department. Various scoring systems have been developed to predict the clinical deterioration of patients and admit critical cases to the intensive care unit in the early period. These scores can be calculated not only with vital parameters but also with the combination of vital and laboratory parameters [1]. Many scoring systems, such as acute physiology and chronic health evaluation (APACHE II), have been developed to predict prognosis [2], and they are frequently used in intensive care. The APACHE II score is calculated based on the worst values recorded in the first 24 hours of patient admission.
C-reactive protein (CRP), an acute phase protein, is a marker of inflammatory response. It is a predictive biomarker in the prognosis of critically ill patients, with high CRP concentrations having been shown to be associated with poor outcome in patients with sepsis [3,4]. The mean arterial pressure (MAP) is a good predictor of organ perfusion [5]. It has been reported that organ perfusion is impaired in the presence of low MAP. Studies have found that fluctuation in MAP is associated with in-hospital mortality [6]. CRP and MAP alone can predict mortality and poor outcome in diseases such as sepsis. We hypothesized that a parameter to be created with the combination of CRP and MAP could predict mortality in sepsis, as well as other diseases. In this study, our aim was to compare the CRP-MAP ratio with the APACHE II score in predicting the mortality of critically ill patients.
Material and Methods
This research was designed as a prospective observational study and conducted in the emergency department of Umraniye Training and Research Hospital with 657 beds and an average of 1,250 adult emergency admissions per day. Among the cases presented to the emergency department between December 10, 2021, and March 10, 2022, critically ill patients aged over 18 years, who were admitted to the intensive care unit from the emergency department, were included in the study. Trauma cases, patients whose consent could not be obtained, and those referred to other hospitals were excluded from the sample.
Patients’ demographic data, Glasgow Coma Scale scores, vital parameters, comorbidities, laboratory parameters, inotropic agent requirement, and 28-day all-cause mortality were recorded at the time of admission. Heart rate, diastolic blood pressure, systolic blood pressure, and MAP were obtained as vital parameters. Blood parameters, such as hemoglobin, CRP, lactate, whole blood cell count, alanine transaminase, neutrophil count, lymphocyte count, hematocrit, albumin, aspartate aminotransferase, blood urea nitrogen (BUN), and creatinine values were recorded. Comorbidities were noted as congestive heart failure, coronary artery disease, diabetes mellitus, hepatic cirrhosis, chronic obstructive pulmonary disease, chronic kidney disease, hyperlipidemia, cerebrovascular disease, epilepsy, rheumatoid arthritis, malignancy, and hypertension. The mortality status of the patients was obtained from the national death registry system. The APACHE II score, CRP-albumin ratio, and CRP-MAP ratio were calculated. All evaluations were made at the time of the presentation. The primary outcome of the study was 28-day mortality.
Data were analyzed using Jamovi (Version 1.6.21.0; The Jamovi Project, 2020; R Core Team, 2019). Normally distributed data were presented as mean and standard deviation values, and non-normally distributed data as median and interquartile ranges. For the continuous data, Student’s t-test was applied in the presence of normal data distribution, and the Mann-Whitney U test otherwise. Categorical variables were calculated with the chi-square test. A p value <0.05 was considered statistically significant.
Ethical approval was received from the local ethics committee of the hospital. Consent was obtained from the patients or their next of kin if their consciousness level was not sufficient. The study was carried out in full compliance with the rules of the Declaration of Helsinki.
Results
This prospective observational study included 169 patients. The flow chart of the study is given in Figure 1. The median age was 72 (25th-75th percentiles: 61-81) years, and 74 (43%) of the patients were female.
The most common comorbidity was hypertension (n = 98, 58%), followed by diabetes mellitus (n = 56, 33.1%), coronary artery disease (n = 33, 19.5%), and chronic obstructive pulmonary disease (n = 27, 16.0 %). In Table 1, the vital parameters and comorbidities of the patient are given in detail. The short-term mortality rate of our patients was 47.9% (n = 81), and the in-hospital mortality rate was 47.3% (n = 80).
The non-survivor group had significantly higher CRP [84.1
CRP: C-reactive protein; MAP: mean arterial pressure; APACHE: acute physiology and chronic health evaluation
(19.3-177) vs 21 (3.8-114), p < 0.001] and BUN [68.8 (38.9-118) vs 43.1 (30.2-60.5), p < 0.001] values compared to the survivor group. The APACHE II score and CRP-MAP ratio were also significantly higher in the non-survivor group than in the survivor group [26 (20.8-30) vs 21 (15-25.8) and 1.03 (0.194-2.24) vs 0.207 (0.0346-1.1), respectively, p < 0.001 for both]. The detailed laboratory data and scores of the patients are shown in Table 2.
The area under the curve (AUC) values of the CRP-MAP ratio
and the APACHE II score in predicting short term mortality were calculated as 0.670 [95% confidence interval (CI): 0.589-0.752, p <0.001) and 0.665 (95% CI: 0.581-0.744, p < 0.001), respectively. There was no significant difference between the AUC values of the CRP-MAP ratio and the APACHE II score (p = 0.916, DeLong test). The calculated AUC values of the parameters are given in Table 3 and Figure 2. The odds ratio of the CRP-MAP ratio was determined as 3.819 (95% CI: 2.004-7.275, p <0.001).
Discussion
In this prospective study, we compared the predictive ability of the CRP-MAP ratio and APACHE II score for short-term mortality in 169 critically ill patients presenting to the emergency department. There was a significant difference in mortality between the patients with CRP-MAP ratios below and above the cut-off value of 4.2. According to the results of our study, the CRP-MAP ratio was as significant as APACHE II in the prediction of mortality. When we compared the CRP-MAP ratio with the APACHE II score, we did not detect any significant difference in their AUC values.
It is important to make an early prediction of the clinical severity and mortality expectations of patients admitted to the emergency department. This assessment is essential for the care and earlier intervention of patients with high mortality or poor clinical outcome. Scoring systems and laboratory tests developed to predict the poor course of patients should be rapid, inexpensive, and widely available. Therefore, in general, vital parameters and blood values easily accessible at every emergency department are used in survival scoring.
CRP, an acute phase protein, has been used in mortality studies because it is a marker of inflammatory response [7-9]. High CRP concentrations are associated with poor outcomes in patients with sepsis. A study conducted with a multiethnic Brazilian population showed a consistent and independent relationship between CRP and all-cause mortality [7]. In another study, Lin et al. found that high CRP at the time of admission to the emergency department was an important independent risk factor for in-hospital outcome events in patients with acute myocardial infarction. The same study also reported a significant positive correlation between CRP and the Global Registry of Acute Coronary Events risk score (r = .191, p < 0.001) (9). These studies suggest that CRP can be used to predict mortality in critically ill patients.
MAP is used to assess the adequacy of perfusion of vital organs. If MAP stays below 60 mmHg for a long time, end-organ damage may occur [10]. Zanella et al. showed that low MAP was associated with mortality in intensive care patients (hazard ratio: 0.988, CI: 0.982–0.995) [11]. Khanna et al., evaluating 2,766 intensive care patients, reported a significant correlation between low MAP and mortality. The authors also found that a decrease of 10 mmHg in MAP increased the risk of acute kidney injury [12]. According to these studies, MAP may be a predictor of organ damage and mortality.
The combined use of CRP and MAP in a single parameter can increase their ability to predict mortality. This modification is easy to calculate because it does not require additional blood tests or vital parameter measurements. Blood tests used in survival scoring both increase the cost and are difficult to use since they involve the calculation of many parameters. APACHE II is widely used for mortality prediction [13,14]. There are 14 different parameters in the APACHE II scoring system, and therefore this score is difficult to obtain without an automatic calculator [15]. Thus, predictive parameters involving only a few calculations, such as the CRP-MAP ratio are easier than scoring systems with many parameters. This will make the clinician’s job easier.
In our study, the CRP-MAP ratio was as significant as the APACHE II score and the CRP-albumin ratio values in predicting mortality. The multivariate test showed that the CRP-MAP ratio was an independent predictive factor. The odds ratio of the CRP-MAP ratio was similar to the APACHE II score and the BUN-albumin ratio (3.819, 2.545, and 3.67, respectively). To the best of our knowledge, this is the first study to evaluate the CRP-MAP ratio as a predictor of mortality in critically ill patients presenting to the emergency department. We consider that the CRP-MAP ratio is a parameter that can be used to predict short- term mortality among these patients.
Limitation
There are several important limitations to our study. First, the limited sample size of our study reduces the generalizability of our results. Second, the MAP value alone is not associated with mortality in critically ill patients. However, this did not affect the significance of the CRP-MAP ratio in mortality prediction. Previous studies have shown the relationship between MAP and mortality, and we consider that this significant relationship will strengthen the ability of the CRP-MAP ratio to predict mortality in future studies with larger samples. We consider that the reason for the non-significance of the relationship between MAP and mortality in our study was due to the limited number of patients.
Finally, another factor limiting the generalizability of our findings is the single-centered design of the study.
Conclusion
According to the results of our study, the CRP-MAP ratio is as good a predictor as APACHE II in predicting short term mortality in critically ill patients. However, due to the limited sample size and single-center design of our study, our findings should be validated by multicenter studies with larger samples.
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
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2. Basile-Filho A, Lago AF, Menegheti MG, Nicolini EA, Rodrigues LA de B, Nunes RS, et al. The use of APACHE II, SOFA, SAPS 3, C-reactive protein/albumin ratio, and lactate to predict mortality of surgical critically ill patients. Medicine (Baltimore). 2019 28;98(26):e16204.
3. Gunal O, Ulutan F. Diagnostic and Prognostic Value of Procalcitonin in Patients with Sepsis. Int J Infect Dis. 2008;(12):e463.
4. Lobo SMA, Lobo FRM, Bota DP, Lopes-Ferreira F, Soliman HM, Meélot C, et al. C-Reactive Protein Levels Correlate With Mortality and Organ Failure in Critically Ill Patientsa. Chest. 2003;123(6):2043–9.
5. Leone M, Asfar P, Radermacher P, Vincent JL, Martin C. Optimizing mean arterial pressure in septic shock: a critical reappraisal of the literature. Crit Care. 2015;19(1):101.
6. Gao Y, Wang Q, Li J, Zhang J, Li R, Sun L, et al. Impact of Mean Arterial Pressure Fluctuation on Mortality in Critically Ill Patients: Crit Care Med. 2018;46(12):e1167–74.
7. Maluf CB, Barreto SM, Giatti L, Ribeiro AL, Vidigal PG, Azevedo DRM, et al. Association between C reactive protein and all-cause mortality in the ELSA-Brasil cohort. J Epidemiol Community Health. 2020;74(5):421–7.
8. Lin XL, Sun HX, Li FQ, Zhao JY, Zhao DH, Liu JH, et al. Admission high-sensitivity C-reactive protein levels improve the Grace risk score prediction on in-hospital outcomes in acute myocardial infarction patients. Clin Cardiol. 2022;45(3):282–90.
9. Özdemir S, Algin A. Evaluation of the ability of the C-reactive protein-to-albumin ratio to predict short-term mortality in patients with COVID-19. J Clin Med Kazakhstan. 2021 27;18(6):35–9.
10. Campbell N, McGuire S, Carle C. Should all patients with septic shock have a mean arterial pressure threshold of 65 mmHg? Br J Hosp Med. 2020 2;81(9):1–2.
11. Zanella A, Florio G, Antonelli M, Bellani G, Berselli A, Bove T, et al. Time course of risk factors associated with mortality of 1260 critically ill patients with COVID-19 admitted to 24 Italian intensive care units. Intensive Care Med. 2021;47(9):995–1008.
12. Khanna AK, Maheshwari K, Mao G, Liu L, Perez-Protto SE, Chodavarapu P, et al. Association Between Mean Arterial Pressure and Acute Kidney Injury and a Composite of Myocardial Injury and Mortality in Postoperative Critically Ill Patients: A Retrospective Cohort Analysis. Crit Care Med. 2019;47(7):910–7.
13. Patel P, Gupta S, Patel H, Bashar MA. Assessment of APACHE II Score to Predict ICU Outcomes of Patients with AKI: A Single-center Experience from Haryana, North India. Indian Soc Crit Care Med. 2022;26(3):276–81.
14. Mierke J, Nowack T, Loehn T, Kluge F, Poege F, Speiser U, et al. Predictive value of the APACHE II score in cardiogenic shock patients treated with a percutaneous left ventricular assist device. Int J Cardiol Heart Vasc. 2022;40:101013.
15. Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13(10):818–29.
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Abuzer Özkan. Comparison of the c-reactive protein-mean arterial pressure ratio with critical care prognostic scoring systems. Ann Clin Anal Med 2022;13(11):1257-1261
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Is there cardiac risk in Generalized Anxiety Disorder? Does this relationship shed light on future treatment protocols?
Kemal Göçer 1, Onur Hurşitoğlu 2, Elisa Calisgan 3
1 Department of Cardiology, Faculty of Medicine, Kahramanmaras Sutcu Imam University, 2 Department of Psychiatry, Kahramanmaraş Necip Fazıl City Hospital, 3 Department of Physiotherapy and Rehabilitation, Faculty of Health Science, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey
DOI: 10.4328/ACAM.21283 Received: 2022-06-20 Accepted: 2022-07-20 Published Online: 2022-07-25 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1262-1266
Corresponding Author: Elisa Calisgan, Faculty of Health Science, Kahramanmaras Sutcu Imam University, Dulkadiroglu, Kahramanmaras, Turkey. E-mail: elisa.calisgan@inonu.edu.tr P: +90 344 300 40 02 F: + 90 344 300 34 09 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4710-9540
Aim: Generalized anxiety disorder (GAD) is a subtype of anxiety disorder that differs in symptoms and clinical findings. There is excessive and pervasive worry about everyday life conditions, physical performance in GAD. Changes in ventricular repolarization may play a role and interact with this process. Therefore, this study aimed to investigate whether ventricular repolarization parameters interact with the level of GAD and highlight for followed-up treatment.
Material and Methods: One hundred eighteen patients (non-smoker, non-alcoholic) without a previous psychiatric disease who were newly diagnosed with GAD were included in this study between March 2021 and February 2022. One hundred twenty healthy individuals who did not have any psychiatric or organic disorder and whose Hamilton Anxiety Rating Scale (HAM-A) score was below five were taken as the control group. A 12-lead ECG was taken at enrolment. The ventricular repolarization parameters were calculated.
Results: The individuals participating in the study were divided into two groups: GAD and control groups. There was no statistically significant difference between the two groups regarding demographic characteristics. The TG level (p=0.049) was higher than in the GAD group. Six parameters, including age, gender, TG, Tpeak-Tend interval (Tp-e), QT dispersion, and heart rate were entered into logistic regression analysis. QT dispersion (OR: 1.122; 95%Cl:1.081-1.165;p<0.001) and heart rate (OR: 1.039; 95%Cl:1.002-1.076 ;p<0.037) were found to be independent predictors of GAD.
Discussion: QT dispersion associated with ventricular arrhythmia is a simple test that should be closely monitored in patients with GAD and is an important criterion for establishing treatment protocol including drug and physical exercise.
Keywords: QT, Interval, Anxiety Disorder, Electrocardiogram
Introduction
Generalized anxiety disorder (GAD), seen in 5% of the population, is a psychiatric condition characterized by chronic disquiet and worry that is difficult to control [1]. Environmental, biological, and neuropsychological factors play a role in GAD etiopathogenesis [2]. The effects of the autonomic nervous system (ANS) regulating heart rhythm are generally observed in GAD. Sympatho-vagal imbalance triggers stress, which has a negative effect on physical performance and causes GAD. The characteristic symptoms of GAD, such as palpitations, sweating, and tremors, are seen in ANS dysfunction [3]. In addition, ANS dysfunction may cause ventricular repolarization changes and predispose to cardiac arrhythmias [4].
Electrocardiogram (ECG) is one of the most common tests used to diagnose cardiovascular diseases. Measurements of the QT interval and QT dispersion (QTd) in ECG are related to the ventricular repolarization process and are predictors of ventricular arrhythmias. Therefore, prolonged QT interval and QTd can cause sudden cardiac death [5]. T-wave measurements have been recently used to evaluate ventricular repolarization. In studies, T-wave parameters and the ratio of these parameters to QT interval were reported as new indicators for ventricular repolarization. The Tpeak-Tend interval (Tp-e) and QTd, reflecting the transmural dispersion of repolarization are calculated through ECG [6]. Evaluation of these ECG parameters in GAD is considerable for the future prevention and follow-up of primary disease
Material and Methods
Study Design
In this case-control study, 138 consecutive patients (no psychiatric history, no drug use, no smoking or alcohol use) who applied to the psychiatry outpatient clinic and were diagnosed with GAD for the first time according to the GAD criteria of DSM-5 were included between March 2021 and February 2022. Twenty patients with a history of hypertension, left bundle branch block pattern on ECG, anemia, moderate to severe heart valve disease, evidence of active infection, and coronary artery disease were excluded from the study. The remaining 118 patients were included in the study as the GAD group. One hundred-twenty patients were taken as the control group. Hamilton Anxiety Rating Scale (HAM-A) was administered to all participants. The control group consisted of healthy individuals with a HAM-A score below five and without a psychiatric history. In order to conduct this study, the required permission and consent were obtained from the Clinical Research Ethics Committee of the Faculty of Medicine, Kahramanmaras Sutcu Imam University (30.04.2019- decision No: 06).
Definition of Generalized Anxiety Disorder
Generalized anxiety disorder (GAD) was diagnosed according to DSM-5 anxiety GAD criteria. HAM-A test scale was applied to each participant between 13:00 and 14:00 of the day. An environment where the participants felt comfortable was provided. The total score was obtained according to the appropriate answer to 14 questions on the scale.
Electrocardiographic and Echocardiographic Parameters
All participants underwent a 12-lead ECG using Nihon Kohden’s (Tokyo, Japan) ECG device at 50 mm/s speed and 10 mm/mV amplitude at rest. ECGs were evaluated by two specialist physicians using a magnifying glass to obtain an accurate measurement. The QT interval was measured to the time from the start of the QRS complex to the end of the T wave. The QT interval was calculated by averaging leads V4 and V5 if lead V5 was insufficient for the measurement. The QT intervals in the 12 leads were recorded separately to calculate the QTd. The QTd was calculated by subtracting the longest and shortest QT times. The Tp-e interval was measured to the time from the peak of the T wave to the end of the T wave. The end of the T wave was defined as the intersection of the line tangent to the downslope of the T wave with the isoelectric line. Heart rate-corrected QT (cQT) and Tp-e (cTp-e) intervals, Tp-e/QT and Tp-e/cQT ratios were calculated using Bazett’s formula.
Images of all participants were obtained from the parasternal and apical window in the lateral decubitus position using the Philips EPIQ 7C (Philips Healthcare, MA, USA) echocardiography device. Left ventricular ejection fraction was calculated using Simpson’s method.
Statistical Analysis
Statistical Package for Social Sciences (SPSS) for Windows 21 program was used for statistical analysis. Categorical variables were expressed as percentages and continuous variables as mean ± standard deviation. The participants were divided into two groups as GAD and the control group. The Kolmogorov-Smirnov test, skewness, and kurtosis were used for the assessment of normal distribution. The independent t-test was used for continuous variables with normal distribution. The Chi-square test was performed on categorical variables. Binary logistic regression analysis was applied to evaluate the effects of age, gender, triglyceride (TG), Tp-e interval, QTd, and heart rate parameters on GAD. Interobserver agreement of the data was calculated using the Bland-Altman analysis, and intraclass correlation coefficients were used to assess intraobserver agreement. A 2-sided p-value of <0.05 was considered statistically significant.
Results
All participants were separated into two groups: GAD and the healthy control group. Forty-six of the GAD group were male, with the mean age of 36,88 years. The control group consisted of 50 men, with the mean age of 41,7 years. There was no statistically significant difference between the two groups regarding biochemical parameters and demographic characteristics, except for TG (p=0.049) (Table 1). The comparison of the two groups in terms of electrocardiographic findings is shown in Table 2. In addition, box-plot graphs of ECG parameters showing a statistically significant difference between the two groups are shown in Figure 1. A correlation analysis evaluated the relationship between HAM-A score and ECG parameters applied to all participants. Among the parameters shown in Table 3, the Tp-e/QTc ratio parameter was not significantly correlated between the two groups.
Age, gender, TG, Tp-e, QTd, and heart rate were entered into the logistic regression analysis, QTd (OR: 1.122; 95%Cl:1.081-1.165;p<0.001) and heart rate (OR: 1.039; 95%Cl:1.002-1.076 ;p<0.037) were found to be independent predictors of GAD (Table 3).
Discussion
GAD, a branch of anxiety, is a common disease in society. In addition, GAD is associated with many cardiovascular disorders [7]. Ventricular arrhythmia is one of these cardiovascular disorders. Prolonged Qt and Tp-e intervals in ECG cause ventricular arrhythmias by affecting ventricular repolarization [8]. This is the first study we know to compare the QTd, Tp-e and Tp-e/QT parameters, which are new ECG parameters associated with ventricular repolarization, in GAD patients (without any history of psychotropic drugs, smoking, or alcohol).
Anxiety is the cause and consequence of many diseases. Anxiety can affect cardiac functions and lead to conditions that can progress to sudden cardiac death [9]. The mechanism of how it causes sudden cardiac death is not fully explained. However, it has been suggested that this situation can be expressed by ANS dysfunction. Studies show that decreased parasympathetic activity and increased sympathetic activity may predispose to malignant arrhythmias and cause sudden cardiac death [10]. In hypertensive patients with anxiety, cardiac heart rate variability indices, which are indicators of cardiac autonomic imbalance, were found to be correlated with the severity of anxiety [11]. The effect of psychiatric drugs used in the treatment can change the QT interval in the ECG and should be followed closely to prevent arrhythmia complications. QTd, obtained from the difference between maximum QT and minimum QT in the 12-lead ECG, reflects ventricular repolarization instability. This electrical imbalance in ECG leads has been shown to increase susceptibility to malignant ventricular arrhythmias and is associated with sudden cardiac death [12]. We showed that QT and cQT interval durations were found to be higher in the GAD group, and QTd was an independent predictor of GAD. This may be because the max interval times were higher in the GAD group. There are also studies showing that it is not directly involved in ventricular repolarization. Increased QTd in GAD in our study may be a marker of instability of autonomic functions of the heart.
Tp-e interval is one of the parameters that evaluate ventricular repolarization in the ECG. The Tp-e interval has been shown to be superior to QTd in demonstrating ventricular heterogeneity. Tp-e/QT and Tp-e/cQT ratios are not affected by heart rate, Tp-e and QT intervals change with heart rate [13]. Tp-e and Tp-e/QT parameters were found to be predictors of ventricular arrhythmia in studies conducted with schizophrenia and parkinsonian patients with ANS dysfunction [14]. Tp-e interval has also been associated with mortality in Brugada syndrome, ST-elevation myocardial infarction, and congenital QT syndromes. Increased Tp-e may cause malignant ventricular arrhythmias; therefore, it may affect mortality [15]. In our study, while the Tp-e/QT ratio was not different between the two groups and showed a weak correlation with HAM-A score, Tp-e alone was significantly higher in patients with GAD. We can say that both the QT interval and Tp-e interval are higher in the GAD group compared to the healthy control group. The ratio of the two parameters to each other did not make a significant difference in both groups.
Studies prove that GAD is associated with many cardiac and non-cardiac diseases [16]. A relationship was found between high cholesterol and TG levels in GAD patients without coronary heart disease [17]. The TG elevation was found to be higher in the GAD group, similar to this study. In addition, it has been shown that GAD is also correlated with obesity [18]. The BMI values were found to be similar between both groups in our study. Age is an essential factor in GAD. There was an increase in the frequency of GAD and HAM-A score over 65 years of age. This situation has been attributed to organic pathologies that increase with age. In our study, since organic diseases were excluded, the mean age was low and included relatively young adults.
Sadip et al reported the effect of cardiopulmonary exercise on modulating stress, ventricular depolarization and repolarization. They said that stress negatively affects physical performance and cardiac rhythm such as ventricular repolarization. They evaluated stress levels with DASS (depression anxiety stress scale), ECG used for evaluating QTc interval and T peak to T end interval. They found that blowing balloon exercise (part of breathing exercise) improves ECG parameters and decreases the level of stress. They correlated with the level of stress and cardiac arrhythmia. Therefore, they aimed to activate the parasympatho-vagal with physical exercises, which provide active cardiac vagal fiber’s activity connected with the vagal nerve. Also, they determined that when the lung volume increases, SARs (adapting pulmonary stretch receptors) can activate and stimulate the cardiac vagal nerve [19]. This study showed that the Tp-e/QT ratio was not different between the two groups and showed a weak correlation with HAM-A score, Tp-e alone was significantly higher in patients with GAD. We can say that both the QT interval and Tp-e interval are higher in the GAD group compared to the healthy control group. We investigated the connection between anxiety and cardiac arrhythmia parameters for establishing prediction factors for GAD. However, we did not use the treatment protocol for decreasing stress factors and encouraging cardiac parameters, but we will establish the current comprehensive treatment protocol with the next research.
Our study has some limitations. It was conducted with a relatively small number of patients, the type of arrhythmia and the frequency of arrhythmia were not evaluated with 24-hour-Holter ECG recordings. In addition, the patients with GAD were not followed up for many years as a prospective cohort study.
Conclusion
The QTd was an independent predictor of GAD in the comparison of ECG parameters evaluating ventricular repolarization in GAD patients. Patients with GAD should be followed closely regarding ventricular arrhythmia, paying attention to the increase in the QT interval both in drug use and in the follow-up of physical exercises.
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.
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7. Foldes-Busque G, Dionne CE, Turcotte S, Tully PJ, Tremblay MA, Poirier P, et al. Epidemiology and prognostic implications of panic disorder and generalized anxiety disorder in patients with coronary artery disease: rationale and design for a longitudinal cohort study. BMC Cardiovasc Disord. 2021; 21(1): 1-9.
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Kemal Göçer, Onur Hurşitoğlu, Elisa Calisgan. Is there cardiac risk in Generalized Anxiety Disorder? Does this relationship shed light on future treatment protocols? Ann Clin Anal Med 2022;13(11):1262-1266
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Comparison of manual and automatic end-tidal control practices in low-flow anesthesia
Tuğba Arıcı Sofuoğlu, Aysun Postacı
Department of Anesthesiology and Reanimation, University of Health Sciences, Ankara City Hospital, Ankara, Turkey
DOI: 10.4328/ACAM.21289 Received: 2022-06-27 Accepted: 2022-07-28 Published Online: 2022-08-05 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1267-1271
Corresponding Author: Aysun Postaci, Birlik Mah., 435 Cd., 42/4, 06610, Cankaya, Ankara, Turkey. E-mail: aysunposta@yahoo.com P: +90 532 352 03 83 Corresponding Author ORCID ID: https://orcid.org/0000-0003-4455-5342
Aim: In this study, it was aimed to compare the impact of manual and automated end-tidal control implementation in low-flow anesthesia on anesthesia workload, inhalation agent consumption, and hemodynamic parameters of patients.
Material and Methods: In our study, 96 patients were divided into 2 groups as manual controlled low-flow anesthesia and end-tidal controlled low-flow anesthesia. Sevoflurane and O2 consumption and efficiency in the groups, end-tidal O2, inspired and expired sevoflurane values, time to reach target end-tidal O2 and sevoflurane values, time to deviation from target value, hemodynamic values, operation, anesthesia and awakening time, BIS, MAC and temperature values were followed and compared with the Aisys CS² GE anesthesia device.
Results: There was no statistically significant difference between the groups in terms of demographic data, operation, anesthesia, and recovery time and hemodynamic data. O2 consumption was higher, time to reach target end-tidal oxygen and target EtO2 deviation time was longer, O2 efficiency was lower, and the number of interventions was higher in the manually controlled low-flow anesthesia group. There was no difference between the two groups in terms of total sevoflurane consumption and efficiency.
Discussion: It has been concluded that the end-tidal controlled application of low-flow anesthesia does not increase the use of inhalation agents, the O2 sensitivity is higher, it is hemodynamically safe, and the workload of the anesthetist is reduced due to the low number of interventions during the application.
Keywords: Low-Flow Anesthesia, Minimal Flow Anesthesia, Automated End-Tidal Anesthesia, Controlled Anesthesia, Sevoflurane
Introduction
Climate change is regarded as the gravest global health threat in the twenty-first century. It has been suggested that the environmental and economic effects that occur during the delivery of healthcare services can only be reduced by the implementation of sustainable healthcare services. To ensure sustainability in anesthesia, especially anesthetists who control the flow of inhalation agents should consider low-flow anesthesia (LFA) as the up-to-date anesthesia management method of our age and transfer their principles, knowledge, and methods to practices when meeting our daily needs [1,2]. Thanks to the LFA technique significant cost savings and reduced atmospheric pollution can be achieved by minimizing the consumption of anesthetic agents. In addition to these advantages, the low-flow anesthesia technique also contributes to intraoperative protective lung mechanical ventilation techniques by improving the anesthetic gas climate and maintaining heat and humidity [3]. Low-flow inhalation anesthesia is administered using manually controlled or end-tidal controlled techniques. Manually controlled low-flow anesthesia is described as the technique in which the titration of oxygen and anesthetic gas is constantly controlled by the anesthesiologist and manual adjustments are made to achieve adequate depth of anesthesia. End-tidal controlled anesthesia devices, meanwhile, continuously adjust the O2 flow set in inhalation anesthesia administration and the end-tidal concentrations of inhalation anesthetics by giving feedback. Less intervention is of clinical importance in terms of eliminating user distraction, keeping the record, and patient safety [4,5]. This study aimed to compare the effects of manually and automated end-tidal controlled anesthesia practices in low-flow anesthesia technique on anesthesia workload, anesthetic agent consumption, and hemodynamic parameters of the patient.
Material and Methods
Study Group and Randomization:
After obtaining the Ankara City Hospital ethics committee approval (E1-20-10939), and the patient consent, 96 patients with an ASA status of 1-2, aged 18-65 years who underwent elective surgery and were intubated as orotracheal have been included in this prospective randomized, single-blind study between January 2021 and May 2021. The patients admitted to the study were assigned into two groups by sealed envelope randomization; Group 1: Manually Controlled LFA (MC-LFA) and Group 2: End-tidal Controlled LFA (EtC-LFA).
Exclusion Criteria:
Those aged 65 and over, patients with ASA 3 and above, pregnant women, those at risk of malignant hyperthermia, heart failure, end-stage renal and hepatic failure, those with a BMI of > 30 kg/m2, chronic opioid use, and those who had a surgical operation duration of < 1 hour and did not agree to participate in this study were excluded from this study. During the study, patients who could not reach the target end-tidal sevoflurane value before the skin incision, had a bispectral index (BIS) value above 60, developed unexpected intraoperative hypoxia, surgical complications, and lacked data were excluded from the study.
Anesthesia Management
ECG, pulse-oximetry (SpO2), non-invasive arterial blood pressure, body temperature, and BIS were monitored, and the lower and upper limits for the alarm of the monitoring were adjusted for each patient. The patients were pre-oxygenated with an FiO2 = 1 and a flow of 10 L/min for at least 3 min. Anesthesia induction was performed by administering 2 µ/kg fentanyl, 2-2.5 mg/kg propofol, and 0.6 mg/kg rocuronium, and the patients were intubated orotracheally. Sevoflurane administration was started after intubation. The patients were ventilated with the Aisys CS² GE anesthesia device in volume-controlled mode (TV 6-8 mL/kg ideal body weight, + 5 cmH2O PEEP ) and set to maintain end-tidal CO2 (EtCO2) 35 mmHg. In both groups, all patients were followed up by the same two anesthetists. Following the skin incision, remifentanil infusion was started at 1 µ/ kg bolus followed by 0.1-0.5 µ/kg/min, and the infusion dose was modified by dynamic evaluations throughout the operation. During study, KNGSORB (calcium hydroxide, sodium hydroxide, and ethyl violet) was used as CO2 absorbent, and FiCO2 was monitored. The target end-tidal sevoflurane concentration (FetSevo) of the two groups was 1.7-2 % and end-tidal O2 (EtO2) was 35%.
The patient was administered 100% O2 with a flow rate of 4 L/ min for five minutes in the initial high flow period in both groups. In the MC-LFA group, the sevoflurane vaporizer was adjusted to 3% during the high flow period. In the EtC-LFA group, after the patient was connected to the anesthesia device, the end-tidal button was pressed, and Fet-Sevo was set to 1.7-2%. After a five-minute of high flow, the flow rate was reduced by 1L/min in both groups. In the MC-LFA group, anesthesia was maintained with 50% O2 + 50% air and the sevoflurane vaporizer 3-3.5%. Throughout the operation, O2 % and sevoflurane vaporizer interventions were performed to maintain the target value range. Measurements were started when the patient was connected to the ventilator in both groups. The duration of the groups to reach the target sevoflurane and O2 values were noted down. The number of interventions made by the anesthetist to the device in the MC-LFA group was recorded.
From the onset of the operation, the patient’s hemodynamic parameters (HR, MAP), inspired sevoflurane (FiSevo) and inspired O2 (FiO2), FetSevo and EtO2, minimum alveolar concentration (MAC), BIS and body temperature values were recorded. A MAP of < 55 mmHg lasting > 5 minutes was considered to be hypotension. Other parameters checked for the study during the operation were as follows:
• Duration to reach target end-tidal sevoflurane and O2 values,
• O2 and sevoflurane were administered to the patient by the anesthesia device (the oxygen and sevoflurane consumption of the device, L and mL, respectively),
• Sevoflurane and O2 consumption of the patient (V’O2 and V’Sevoflurane were calculated in L, mL/min, respectively, by dividing the amount of O2 and sevoflurane administered to the patient by the anesthesia device by the duration of anesthesia),
• Number of adjustments to reach target FetSevo and EtO2 in the MC-LFA group,
• Deviation duration from target FetSevo and EtO2 values (sec),
• Sevoflurane and O2 sensitivity (obtained by percentage calculation of the ratio of target FetSevo and EtO2 deviation duration to total anesthesia duration) [6],
• Oxygen uptake of the patient throughout the operation was calculated using Brody’s formula (L) [3,7,8],
• Sevoflurane uptake of the patient during the operation was calculated using Lowe’s formula (mL) [3,7,8],
• Sevoflurane efficiency (%, total sevoflurane delivered by the device during anesthesia/patient sevoflurane uptake) [8],
• O2 efficiency (%, total O2 delivered / O2 taken by the device during anesthesia) [8],
• Operation, anesthesia, and awakening time were recorded.
The sevoflurane vaporizer was turned off five minutes before the end of the surgery, but the flow of fresh gas was not changed. At the end of anesthesia, 100% O2 with a flow rate of 6 L/min was set in both groups. The duration between the end of the low fresh gas flow and switching to the high fresh gas flow of the patients and the extubation was recorded as the “awakening time.”.
Determination of Sample Size
The sample size was calculated based on a previous study reported by Wetz AJ et al. [6]. In calculation, G Power 3.1.9. 2 Package program was used. Assuming that the 1.2 ml/s difference between the values of anesthetic gas consumption in MC-LFA and EtC-LFA uses will be considered significant, it was calculated that at least 90 patients should be taken, including 45 patients in each group with a d=0.6 effect size, 80% power, and 0.05 error level.
Statistical Analysis
Mean standard deviation, median, minimum and maximum values were presented in descriptive statistics for continuous data, and percentage values were presented in discrete data. The Shapiro-Wilk test was used to analyze whether the continuous data fit the normal distribution. In the comparison of continuous data in two groups, the t-test was used for data showing normal distribution, and the Mann-Whitney U test was used for data that did not fit the normal distribution. The chi-square test and Fisher’s Exact test were used for group comparisons of nominal variables (in cross-tables). IBM SPSS 20 software was used in the analysis, and the results were considered significant at p <0.05.
Results
In our study, 96 patients were included, and the data of 46 patients who underwent MC-LFA and 45 patients (n=91) who underwent EtC-LFA were analyzed.
Gender, age, height, weight, BMI, ASA, anesthesia, surgery, and recovery times of the patients compared between groups (p > 0.05) are shown in Table 1. In the comparison between the groups, a significant difference was found in total O2 consumption (L), minute O2 (V’O2) consumption (L/min), and O2 efficiency (%) (Figure 1, p< 0.05). It was determined that total O2 consumption (ml) and V’O2 (L/min) were higher, and O2 efficiency was lower in the MC-LFA group. Besides, when the time to reach the target EtO2, the number of interventions to sevoflurane concentration and FiO2 were compared, a significant difference was found (Table 2, p< 0.001). It was observed that the time to reach the target EtO2 was longer, and the number of interventions to the anesthetic gas concentration was higher in the MC-LFA group. A significant difference was found between the groups regarding total target EtO2 deviation time and total O2 sensitivity (Table 2, Figures 2 and 3). In the MC-LFA group, the target EtO2 deviation time was longer and the O2 sensitivity was lower. When total sevoflurane consumption (Table 2) and hemodynamic data (Table 1) were compared in both groups, no significant difference was found.
Discussion
In our study, no difference was found between the two groups regarding sevoflurane consumption, hemodynamic variables, and target anesthetic agent sensitivity. Sevoflurane concentration and number of interventions to FiO2 were higher in the manually-controlled group. When compared in terms of target EtO2 concentration, the findings showed that the deviation from the target was higher, whereas the sensitivity was lower in the manually controlled group. It was concluded that this situation would allow close monitoring in manually-controlled LFA, leading to an increase in the frequency of intervention by the anesthetist, and increase the workload of the anesthetist.
The world population growth and the increase in the number of people able to access healthcare services are causing an increase in the number of surgeries performed every year. The widespread use of sustainable anesthesia practices due to the cost and environmental pollution caused by the increasing anesthesia practices and the increase in technologically superior anesthetic devices make low-flow anesthesia practices more prominent [1,9,10]. In recent years, anesthesia devices that provide constant O2 and inhalation anesthetic concentrations during anesthesia with an automatic feedback control system have been introduced. These devices allow safer delivery of inhalation anesthetics and O2 during low or minimal flow anesthesia [11,12]. Maintenance of hemodynamic stability during anesthesia is of great importance. Skalec et al., in their study, compared the hemodynamic effects of manually and end-tidal controlled low-flow anesthesia and found no significant difference between the two groups [12]. Likewise, in our study, no significant difference was found between manually and end-tidal controlled LFA, in terms of hemodynamic data. Singaravelu and Barclay, in their study without determining the target EtO2 and target FetSevo values with the GE Aisys anesthesia device, reported that the anesthetic agent consumption in the end-tidal controlled group was 40-55% less than in the manually controlled group. However, when the fresh gas flows during the study are examined, it is noticed that the fresh gas flow rate is higher in the manually controlled group at all intervals. The fresh gas flow is higher in the manually controlled group limits the study in terms of comparison of anesthetic agent consumption [5]. In another study by Lucangelo et al., no significant difference was found in terms of anesthetic agent consumption and anesthetic agent efficiency in LFA with manuel control, and EtC with a fresh gas flow of 1 L/min [8]. Besides, Wetz et al. revealed that sevoflurane consumption was lower in the manually controlled group (6 mL/h in the MCA group vs 6.9 mL/h in the EtCA group) in their study, which they restricted to a flow of 0.5 L/min and follow-up of 60 minutes [6]. Mostad et al., on the other hand, reported that in the LFA technique they applied using two different anesthesia devices (Aisys anesthesia device and Flow-I, Maquet), they detected a decrease in desflurane consumption with automatic gas-controlled devices at the end of the first hour of anesthesia [11]. In our study, meanwhile, the total and minute consumption of sevoflurane was 20.24±4.75 mL /min and 0.18±0.01 mL/ min in the EtC-LFA group, and 20.26±5.33 mL /min and 0.17±0.01 mL /min in the MC-LFA group, respectively. The findings obtained in our study are consistent with the results of the study by Lucangelo et al. There is no significant difference between the two groups concerning consumption and efficiency. In another study using Zeus anesthesia device with a fresh gas flow of 1 L/min and desflurane anesthetic agent, oxygen and desflurane consumption were lower in the EtC-LFA group than the MC-LFA group [13]. Different results have been revealed in the studies conducted so far, and this difference may be due to the study design differences and further research on consumption is needed. In the study of Wetz et al., the time to reach the target anesthetic and target EtO2 value, and the deviation time from the target anesthetic and target EtO2 value were shorter in the end-tidal controlled group. Moreover, in this study, an average of eight changes in 60 minutes was made in the manually controlled group to maintain the sevoflurane concentration within the determined range, and an average of five changes to maintain the EtO2 concentration within the targeted range [6]. Lucangelo et al. found the time to reach the target anesthetic concentration in the end-tidal controlled group longer than the manually controlled group in the Aisys (Aisys, GE Healthcare) anesthesia device and with a fresh gas flow of 1 L/min [8]. In our study, it was seen that the target anesthetic concentration was reached in a shorter time in the MC-LFA group, whereas the target EtO2 concentration was reached in a longer time. Throughout total anesthesia, the target EtO2 deviation time was 815 seconds in the EtC-LFA group, and 1800 seconds in the MC-LFA group.
The fact that the number of patients in both groups decreased as the duration of anesthesia progressed can be considered a limitation of our study. We are of the opinion that there may be changes in the anesthetic agent and O2 consumption in longer operations. Considering this situation, we believe that prospective randomized studies with a larger number of patients and longer operation durations can be conducted.
Conclusion
Low flow anesthesia, that is one of the most important components of sustainable anesthesia is an anesthesia technique of our era. Given that end-tidal controlled low-flow anesthesia administrations are hemodynamically safe and O2 sensitivity is higher, anesthetic agent sensitivity and agent consumption are equivalent without the necessity to intervene in the anesthesia device, it was concluded that it would not increase the cost and reduce the workload of the anesthetist.
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.
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Tuğba Arıcı Sofuoğlu, Aysun Postacı. Comparison of manual and automatic end-tidal control practices in low-flow anesthesia. Ann Clin Anal Med 2022;13(11):1267-1271
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Adrenaline auto-injector prescription profiles and clinical features of adult patients: A study from Malatya Province
Ebru Özdemir
Department of Allergy and Immunology, Malatya Training and Research Hospital, Malatya, Turkey
DOI: 10.4328/ACAM.21291 Received: 2022-06-27 Accepted: 2022-07-28 Published Online: 2022-08-03 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1272-1275
Corresponding Author: Ebru Özdemir, Malatya Training and Research Hospital, Allergy and Immunology Department, 44090, Yesilyurt, Malatya, Turkey. E-mail: drpalaebru@yahoo.com P: +90 505 557 38 67 Corresponding Author ORCID ID: https://orcid.org/0000-0003-3738-547X
Aim: Adrenaline auto-injectors (AAIs) are frequently prescribed to patients who have had previous anaphylaxis or conditions with a risk of anaphylaxis. We aimed to evaluate the clinical characteristics of patients who were prescribed AAI, the prescription indications for AAI, and the carriage and usage rates of AAI.
Material and Methods: Patients who were prescribed AAIs between August 2017 and April 2022 in our outpatient clinic were enrolled in the study. Demographic and clinical features of patients, AAI prescription indications, the carriage rate of the AAI, and the reasons for not carrying the device, experience of anaphylaxis after AAI prescription, and patients’ anaphylaxis management methods were recorded.
Results: A total of 191 patients were enrolled (51.8% female) and the mean age of the patients was 40.8±12.6 years. Venom allergy (72.3%) was identified as the most common trigger. The most common symptoms were mucocutaneous manifestations among patients who had experienced anaphylaxis. The carriage rate of AAI was found to be 57.5%, and the most common reason expressed for not carrying AAI was the belief that it was not necessary (51.6%). Nineteen (13%) patients experienced anaphylaxis after the AAI prescription, and 47.4% of these patients used AAI at the time of anaphylaxis.
Discussion: Our findings provide information among the adult population in the eastern region of Turkey regarding the etiological and clinical features of anaphylaxis and patients’ AAI carriage and usage attitudes. Patient education should be repeated at each clinical visit to improve the carriage and usage rates of AAI.
Keywords: Adrenaline Auto-Injector, Anaphylaxis, Etiology, Carriage, Usage
Introduction
Anaphylaxis is an acute-onset, life-threatening reaction that affects different organ systems and requires immediate treatment [1]. The prevalence of anaphylaxis is estimated to be 0.3–5.1%, although it varies depending on geographic regions, populations, and study methodology [2-4]. The increasing incidence of anaphylaxis in recent years causes high economic costs [4]. Mortality, hospitalization, and biphasic reactions can be prevented by immediate intramuscular adrenaline administration [5-7]. National and international guidelines recommend prescribing adrenaline auto-injectors (AAIs) to patients at an increased risk of anaphylaxis [8-9]. However, studies have reported that the rate of AAI prescriptions is low and some patients experiencing anaphylaxis are not prescribed at all [10-12].
Anaphylaxis triggers are generally considered similar according to age groups. In children and young adults, foods, followed by venom and drugs, were reported as the most common triggers. However, in adults and the elderly, venom and drugs are more common. Idiopathic anaphylaxis is also more common in adults and the elderly than in children [13-15].
In this study, we aimed to evaluate the clinical characteristics of patients who were prescribed AAI, the prescription indications for AAI, and the carriage and usage rates of AAI in Malatya Province.
Material and Methods
This study was conducted at the adult allergy and immunology outpatient clinic. We retrospectively reviewed the medical files of patients, and included adult patients in the study who were prescribed AAI for any reason between August 2017 and April 2022. At the prescription visit, patients were trained about how to and when to use AAI by the same allergy specialist and were given an informative brochure. Data on demographic features, clinical history of patients, accompanying diseases (asthma, allergic rhinitis, eczema), AAI prescription indications and prescription date were recorded from the medical files of patients. Data on the carriage rate of the AAI, if they did not carry it on, the reasons for not carrying the AAI, whether the patients experienced anaphylaxis after the AAI prescription, and patients’ anaphylaxis management methods were collected from patients by a short telephone interview. A total of 191 eligible patients were included in the study. The diagnosis of anaphylaxis was established based on the European Academy of Allergy and Clinical Immunology Anaphylaxis guideline [9]. An individual was counted only once during the entire study period, even if they were prescribed AAI more than once. The Turkish Ministry of Health provides all prescribed AAIs, and Penepin (Vem Ilac Sanayi ve Tic. LTD STI, Istanbul, Turkey) has been used as an AAI in our country since November 2016.
Informed consent was obtained from all patients. The study was approved by the ethics committee (2022/90).
Statistical Analysis
All statistical analyses were performed using SPSS for Windows, version 21.0 (IBM Corp., Armonk, N.Y., USA). Quantitative variables were expressed as mean±SD and as medians with IQRs. For categorical variables, frequencies and proportions were used to describe patient characteristics.
Results
Overall, 191 patients who had been previously prescribed AAI were included in our study. Of these, 99 (51.8%) were females. The mean age in the study population was 40.8±12.6 years (min-max: 19-70). An AAI had been prescribed to 140 (73.3%) patients with a compatible history of anaphylaxis and 51 (26.7%) patients who had a condition with a risk of anaphylaxis (such as food allergy or generalized cutaneous reactions due to venom allergy) but had never experienced it. When all patients were evaluated, venom allergy (n=138, 72.3%) was identified as the most common indication for AAI prescription. Other indications were food allergy (n=24, 12.6%), idiopathic (n=11, 5.8%), drug allergy (n=9, 4.7%), and latex allergy (n=2, 1%). The median time elapsed was 2 (min-max: 0.25-4.5) years after the prescription of AAI. General characteristics of the study population are shown in Table 1.
Among 140 patients who had experienced anaphylaxis before the AAI prescription, the most commonly identified causes were venom (73.6%) and foods (11.4%), while 5.7% of the cases were idiopathic. The median number of anaphylaxis that patients experienced was 2 (min-max: 1-8). The most common symptoms were mucocutaneous manifestations in 116 patients (82.9%), followed by cardiovascular manifestations in 98 patients (70%), respiratory manifestations in 73 patients (52.1%), and gastrointestinal manifestations in 35 patients (25%). General characteristics of the patients with a history of anaphylaxis are shown in Table 2.
We were able to interview 146 patients (76.4%) by phone, but were unable to do so with 45 (23.6%). One hundred and twenty-six (126/146, 86.3%) patients obtained AAI after prescription. Eighty-four patients (84/146, 57.5%) responded that they had the AAI with them (60/84, 71.4% at all times; 24/84, 28.6% only where they considered it risky), while 62 patients (62/146, 42.5%) did not. The most common reason expressed for not carrying AAI was the belief that it was not necessary (32/62, 51.6%). Nineteen (13%) patients experienced anaphylaxis after the AAI prescription (hymenoptera sting (n=12, 63.1%), food (n=5, 26.3%), drug (n=1, 5.3%), and idiopathic (n=1, 5.3%)). Nine (47.4%) of these patients used AAI alone or with oral steroids and antihistamines at the time of anaphylaxis. There was no need for a second dose of adrenaline in any of these patients, and no fatal reactions were reported. Characteristics of patients who were interviewed by phone are shown in Table 3.
Discussion
This study reported the etiology, clinical features, and the AAI carriage and usage rates of patients with anaphylaxis or conditions at risk of anaphylaxis in Malatya Province, which is located in the eastern region of Turkey. According to the results of this study, venom allergy was found to be the most common AAI prescription indication, and mucocutaneous manifestations were found to be the most common symptoms. The carriage and usage rates were found to be 57.5% and 47.4%, respectively. The most common reason expressed for not carrying an AAI was the belief that it was not necessary (51.6%).
Anaphylaxis in children and adults has various allergic triggers. These triggers may vary according to different geographic areas. In a study from Japan, food was the most common trigger of anaphylaxis, followed by drugs, in patients older than 15 years old [16]. Medications were found to be the leading cause of anaphylaxis in China [17]. In our study, the most common cause of anaphylaxis was venom. This high rate of venom allergy may be related to the common presence of beekeeping in this geographical region.
It has been reported that in patients experiencing anaphylaxis, cutaneous symptoms occur most frequently (> 90% of cases), followed by respiratory and cardiovascular system symptoms (> 50%) [9]. In our patient population, we found that cutaneous manifestations were the most common symptoms, followed by cardiovascular system and respiratory system signs, in accordance with previous studies.
In the treatment of anaphylaxis, intramuscular adrenaline administration is the first-line intervention [9]. Patients should carry AAI with them at all times because rapid intervention can be life-saving at the onset of anaphylaxis. The main problem with AAI administration is that patients do not always carry the device with them. In our study, 86.3% of patients obtained their AAI after prescription, and this rate was consistent with a previous study [18]. However, eleven (8.7%) of these patients reported that they never carried an AAI with them. In our study, AAI carriage rate was found to be 57.5%. In previous studies, this rate was reported to range from 23% to 79.7% [19,20]. There are studies investigating the factors that affect the carriage of AAI. Unclear physician advice, insufficient patient training, and poor physical features of the device were reported as the most common barriers to carry AAI [21,22]. In our study “the thought that adrenaline is unnecessary” was found to be the most common reason for not carrying the device all the time.
There is limited information regarding medical follow-up after an AAI prescription, and there are few studies that investigate the recurrence rate of anaphylaxis in adults. A study of adult and pediatric patients found that 3% of the whole cohort had a repeat anaphylaxis-related emergency department visit within 1 year after the index reaction, and this rate was 2.8% among adults [23]. In pediatric cases, O’Keefe et al. found a 17.6% annual recurrence rate of anaphylaxis [24]. In the present study, 19 of 146 (13%) patients had experienced anaphylaxis after the AAI prescription. AAI use at the time of anaphylaxis was reported as 47.4%, and this rate was similar to a previous study [25]. However, this usage rate (9/146, 6.2%) is still low when evaluated according to 146 patients. The European Anaphylaxis Registry reported that 12% of patients administered AAI before presenting to the emergency department [14].
Conclusion
Our findings provide information among the adult population in the eastern region of Turkey regarding the etiological and clinical features of anaphylaxis and patients’ AAI carriage and usage attitudes. Patient education about the importance of AAI with clear physician advice should be repeated at every opportunity and at each clinical visit to improve the carriage and usage rates of AAI.
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
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2. Panesar SS, Javad S, de Silva D, Nwaru BI, Hickstein L, Muraro A, et al. EAACI Food Allergy and Anaphylaxis Group. The epidemiology of anaphylaxis in Europe: a systematic review. Allergy. 2013;68(11):1353-61.
3. Nagakura KI, Sato S, Asaumi T, Yanagida N, Ebisawa M. Novel insights regarding anaphylaxis in children – With a focus on prevalence, diagnosis, and treatment. Pediatr Allergy Immunol. 2020;31(8):879-88.
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6. Fleming JT, Clark S, Camargo CA Jr, Rudders SA. Early treatment of food-induced anaphylaxis with epinephrine is associated with a lower risk of hospitalization. J Allergy Clin Immunol Pract. 2015;3(1):57-62.
7. Liu X, Lee S, Lohse CM, Hardy CT, Campbell RL. Biphasic Reactions in Emergency Department Anaphylaxis Patients: A Prospective Cohort Study. J Allergy Clin Immunol Pract. 2020;8(4):1230-38.
8. Orhan F, Civelek E, Sahiner UM, Arga M, Can D, Calıskaner AZ, et al. Anafilaksi: Türk Ulusal Rehberi 2018 (Anaphylaxis: Turkish National Guide 2018). Asthma Allergy Immunol. 2018;16 (Suppl 1):S1-62..
9. Muraro A, Worm M, Alviani C, Cardona V, DunnGalvin A, Garvey LH, et al. European Academy of Allergy and Clinical Immunology, Food Allergy, Anaphylaxis Guidelines Group. EAACI guidelines: Anaphylaxis (2021 update). Allergy. 2022;77(2):357-77.
10. Waserman S, Avilla E, Ben-Shoshan M, Rosenfield L, Adcock AB, Greenhawt M. Epinephrine Autoinjectors: New Data, New Problems. J Allergy Clin Immunol Pract. 2017;5(5):1180-91.
11. Simons FE. World Allergy Organization. Epinephrine auto-injectors: first-aid treatment still out of reach for many at risk of anaphylaxis in the community. Ann Allergy Asthma Immunol. 2009;102(5):403-9.
12. Nakajima M, Ono S, Michihata N, Kaszynski RH, Matsui H, Yamaguchi Y, et al. Epinephrine autoinjector prescription patterns for severe anaphylactic patients in Japan: A retrospective analysis of health insurance claims data. Allergol Int. 2020;69(3):424-8.
13. Orhan F, Canitez Y, Bakirtas A, Yilmaz O, Boz AB, Can D, et al. Anaphylaxis in Turkish children: a multi-centre, retrospective, case study. Clin Exp Allergy. 2011;41(12):1767-76.
14. Grabenhenrich LB, Dölle S, Moneret-Vautrin A, Köhli A, Lange L, Spindler T, et al. Anaphylaxis in children and adolescents: The European Anaphylaxis Registry. J Allergy Clin Immunol. 2016;137(4):1128-37.e1.
15. Oropeza AR, Bindslev-Jensen C, Broesby-Olsen S, Kristensen T, Møller MB, Vestergaard H, et al. Patterns of anaphylaxis after diagnostic workup: A follow-up study of 226 patients with suspected anaphylaxis. Allergy. 2017;72(12):1944-52.
16. Tachizawa N, Tamai D, Takeuchi S, Nishi RI, Terakura M, Sagawa T, et al. Adult anaphylaxis at the department of emergency medicine of Teikyo University Hospital in an urban area of Tokyo. Arerugi. 2020;69(9):900-8.
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19. Robinson M, Koplin JJ, Field MJ, Sasaki M, Peters RL, McWilliam V, et al. SchoolNuts Investigators. Patterns of Carriage of Prescribed Adrenaline Autoinjectors in 10- to 14-Year-Old Food-Allergic Students: A Population-Based Study. J Allergy Clin Immunol Pract. 2019;7(2):437-43.
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Ebru Özdemir. Adrenaline auto-injector prescription profiles and clinical features of adult patients: A study from Malatya Province. Ann Clin Anal Med 2022;13(11):1272-1275
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Management of intraoperative transesophageal echocardiography in aortic valve neocuspidization (Ozaki procedure)
Mustafa Şimşek 1, Sena Sert 2, Türkan Kudsioğlu 1
1 Department of Anesthesiology and Reanimation, 2 Department of Cardiology, Istanbul Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, Turkey
DOI: 10.4328/ACAM.21292 Received: 2022-06-27 Accepted: 2022-08-04 Published Online: 2022-08-08 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1276-1279
Corresponding Author: Mustafa Şimşek, Department of Anesthesiology and Reanimation, Istanbul Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Education and Research Hospital, Istanbul, Turkey. E-mail: mustafasimsek73@gmail.com P: +90 505 778 99 80 F: +90 216 337 97 19 Corresponding Author ORCID ID: https://orcid.org/0000-0001-9903-5307
Aim: This study aims to evaluate the importance and results of intraoperative transesophageal echocardiography (TEE) and postoperative transthoracic echocardiography (TTE) for aortic valve functions in patients undergoing aortic valve neocuspidization (Ozaki) procedure.
Material and Methods: In this study, 50 patients with aortic insufficiency, aortic stenosis, or combined aortic pathology, who underwent aortic neocuspidization in our center between 1 January – 1 October 2021 were prospectively evaluated with intraoperative TEE as well as preoperative and postoperative TTE.
Results: None of the patients had aortic stenosis after surgery. Ten patients (%20,8) had mild, and 2 patients (%4,16) had moderate aortic insufficiency. Mean transvalvular aortic gradient was 7.96(3-16) mmHg, peak transvalvular aortic gradient was 17.04(8-30) mmHg. Peak aortic velocity was 1.66(08-2.6) m/s.
Discussion: Intraoperative TEE and postoperative TTE can help evaluate early outcomes of aortic valve neocuspidization. TTE and TEE are necessary for intraoperative and postoperative management of hemodynamics of patients.
Keywords: Aortic Valve Neocuspidization, Ozaki Procedure, Transesophageal Echocardiography
Introduction
Aortic valve replacement is the gold standard treatment in patients with severe aortic stenosis (AS) and aortic insufficiency (AI). Mechanical and bioprosthetic valves are frequently used for valve replacement. Mechanical valves are associated with mechanical problems in the long term and patients with mechanical valves require lifelong anti-coagulants. Additionally, mechanical valves cannot provide the physiological hemodynamics of native valves [1]. Nowadays, in suitable patients with mitral and tricuspid valve diseases, surgical repair techniques are predominantly considered. However. surgical repair of the aortic valve is rare and usually limited to aortic valve insufficiency [2,3]. In severe calcific aortic valves, surgical repair is not preferred and valve replacement appears to be the only viable option [1]. Autologous pericardium fixated with glutaraldehyde usage was first defined by Duran et al. who reported replacement of the aortic valve using autologous pericardium [4]. Similarly, Ozaki et al replaced aortic valve leaflets separately by using autologous pericardium [1]. However, the sizes of the aortic leaflets usually differ from each other. Replacing aortic leaflets separately results in more efficient aortic valve motion, more physiologic coaptation, and more stable hemodynamics [5,6]. This procedure is advantageous in AS, AI, and also in the case of a small aortic annulus or infective endocarditis [5,7]. The aortic valve and annulus can be assessed by TTE and TEE. Intraoperative TEE evaluation may provide useful information about AS/AI mechanism and grade. TEE allows evaluation of the aortic valve morphology with mid-esophageal long axis, short axis, transgastric, and deep transgastric views. In our study, we present the results of our evaluation of reconstructed aortic valves, whose functions were assessed intraoperatively with TEE and postoperatively with TTE.
Material and Methods
In our center, after obtaining ethics committee approval, 50 patients underwent aortic valve neocuspidization between January 1 and October 1, 2021 due to AS, AI, or a combined aortic valve pathology, whose intraoperative TEE and preoperative- postoperative TTE were recorded prospectively. The mean (IQR) age of the patients was 64.61 years (24-82); 22 (%44) patients were male, and 28 (%56) were female. Ten (%20) patients had combined aortic valve pathology (AS+AI), while 20 (%40) patients had aortic stenosis, and 15 (%30) had aortic insufficiency. Five (%10) patients had concomitant mitral or coronary artery disease. Preoperative TTE, intraoperative TEE, early postoperative TTE, and postoperative 30th day-TTE of the included patients were recorded.
Surgeries were performed under routine monitorization (5-lead ECG, radial artery catheterization, central vein catheterization, SpO2) and were performed under general anesthesia. Patients were administered total intravenous anesthesia (TIVA), including midazolam, fentanyl, rocuronium, and inhalation anesthetics such as sevoflurane if needed. Cardiac functions of all patients were evaluated and recorded by TEE (Vivid 7 GE Vingmed Ultrasound AS Horten, Norway) after induction. After median sternotomy, the autologous pericardium was fixated for 10 minutes in %6 glutaraldehyde; 3 mg/kg of heparin was administered targeting an efficient ACT level (≥450). Cardiopulmonary bypass (CPB) was initiated with aortic and right atrial cannulation. After cross-clamping and aortotomy, the aortic leaflets were resected. Intercommissural distance was measured using the technique defined by Ozaki et al. Leaflets were prepared using glutaraldehyde-fixated autologous pericardium. The aortic valve was then reconstructed one leaflet at a time [1]. The aortotomy sutured closed and the patients were weaned off CPB.
TEE examination was performed on the newly constructed aortic valve. The patients were transferred to the ICU after the completion of surgery. All patients were examined by TTE (Vivid 7 GE Vingmed Ultrasound AS Horten, Norway) before discharge and 30 days after discharge.
Results
Preoperative demographic data
This study included 50 patients with aortic valve pathologies, with a mean (IQR) age of 64.61 years (24-82). Twenty-two (%44) patients were male, and 28 (%56) were female. Ten (%20) patients had combined aortic valve pathology (AS+AI), while 20 (%40) patients had aortic stenosis, and 15 (%30) had aortic insufficiency. Five (%10) patients had concomitant mitral or coronary artery disease. The mean BMI of the patients was 28.7(20.9-34.9) kg/m2 (Table 1).
Preoperative echocardiographic data
The Mean LVEF of the patients was %53.75 (60-65). Forty-six (%92) of the resected aortic valves were tricuspid and 4 (%8) were bicuspid. The mean aortic annulus was 22.07 (11-32) mm, and the mean trans-valvular aortic gradient was 50.14 (12-80) mmHg. The mean peak trans-valvular aortic gradient was 79.89 (20-132) mmHg and the mean peak aortic velocity was 4.43 (2.50-5.70) m/s. The mean aortic valve area was 0.81(0.47-2.20) cm2 (Figure 1, Table 1).
Intraoperative data
The mean operation time was 287.5 (167-520) min. The mean CPB time was 190.2 (117-483) min. The mean aortic clamp time was 136.86 (92-232) min (Table 2).
Postoperative data
Fifty patients underwent aortic valve neocuspidization. Two (%4) patients died in the ICU after surgery. One patient was lost due to vasoplegia syndrome, and the other due to multiorgan failure on the postoperative 14th day. The mean ICU length of stay (LOS) was (n=48) 1.75(1-14) days. The mean hospital LOS was 8.57 (1-20) days. None of the patients required a permanent pacemaker, while 4 (%8) patients developed postoperative atrial fibrillation (AF). No postoperative myocardial infarction was observed. One (%2) patient had postoperative hemiparesis and 2 (%4) patients required postoperative hemodialysis (Table 2).
Postoperative echocardiographic data
No additional operative mortality was observed in the early postoperative period. Forty-eight patients were followed up with TTE. The mean postoperative LVEF was 51.73 (30-60). None of the patients had aortic stenosis. Ten (%20.8) patients had mild AI, and 2 (%4.16) had moderate AI. The mean trans-valvular aortic gradient was 7.96 (3-16) mmHg. The mean peak trans-valvular aortic gradient was 17.04 (8-30) mmHg. The mean peak trans-valvular aortic velocity was 1.66 (0.8-2.6) m/s (Figures 2A-2B, Table 3).
Statistics; Continuous variables were presented as median with interquartile range (IQR), and categorical variables as numbers with percentage. Student’s t-test was used to compare continuous variables, p-value of 0.05 was considered statistically significant.
Discussion
In this study, we aimed to analyze our results with intraoperative TEE, preoperative and postoperative TTE of the patients who underwent aortic valve neocuspidization in our center. We reached six conclusions in this study. First, aortic valve neocuspidization using autologous pericardium is a reliable and safe procedure with low morbidity and mortality. Second, none of the patients needed reoperation due to AI. Third, no permanent pacemaker placement was needed in our patients.
Fourth, no postoperative valve thrombosis or infective endocarditis were detected. Fifth, postoperative aortic gradients were significantly low. Finally, none of the patients had postoperative aortic stenosis. Ten (%20.8) patients had mild AI, and 2 (%4.16) had moderate AI. The mean trans-valvular aortic gradient was 7.96 (3-16) mmHg.
The mean peak trans-valvular aortic gradient was 17.04 (8-30) mmHg. The mean peak trans-valvular aortic velocity was 1.66 (08-2.6) m/s.
The Ozaki procedure is becoming more prominent for aortic valve pathologies. With the growing experience, studies on valve geometry and techniques with autologous pericardial reconstruction are increasing, as well as reports on mid-long-term results. These studies show that the Ozaki procedure can be performed safely and perioperative mortality and morbidity are especially low in isolated aortic valve disease patients. No need for anticoagulants, no valve thrombosis complications, no permanent pacemaker requirement, and low rates of infective endocarditis are also advantages of this technique.
Aortic valve neocuspidization was developed as a standardized technique but has been improved by Ozaki since its original conception. Mild or moderate aortic insufficiency is reported as %7 in larger series after isolated Ozaki procedures. Ozaki et al. [8] reported in their study, which included 850 patients with a mean follow-up of 118 months, that there was a significant drop in aortic gradient postoperatively, and %7.3 of the patients developed moderate AI, and 15 patients required reoperation due to AI. Another study by Mourad et al. [9] showed results similar to Ozaki et al, where %7 of the patients developed moderate AI. In the study conducted by Koechline et al. [10], moderate aortic regurgitation was observed in 7%of cases, similar to the studies of Ozaki et al. In our study, 10 (%20.8) patients had mild, and 2 (4.16%) patients had moderate AI postoperatively. Ozaki et al reported a mean peak gradient of 15.2±6.3 mmHg 8 years after surgery. Mourad et al. [9] reported a mean peak gradient of 6.8±2.9 mmHg after 11 months of surgery. In our study, preoperative peak gradient dropped significantly from 50.14 (12-80) mmHg to 7.96 (3-16) mmHg postoperatively.
Most of our patients (46 patients) had tricuspid and 4 patients had bicuspid valves. The preoperative mean aortic valve area was 0.81 (0.47-2.20) and the postoperative mean aortic valve area was 1.75 (0.52-1.9).
We observed mild AI in 10 of the patients and moderate AI in 2 of the patients after surgery, but no patient required reoperation. In the study by Ozaki et al with a mean follow-up duration of 53 months and 850 patients, 15 patients needed reoperation, with a rate of 0.4 cases per 100 cases per year. The study by Mourad et al, which included 52 patients with a mean follow-up of 11 months, reported 5 patients who required a reoperation, with a rate of 10.3 reoperations/100 patients per year. In our follow-up, no patient required a reoperation, while our follow-up time was comparably shorter. On the other hand, in our series, other than isolated Ozaki procedures, 2 patients underwent concomitant CABG, 2 patients underwent concomitant mitral valve repair, and 1 patient underwent concomitant MVR with a biologic prosthesis.
Detailed preoperative echocardiography is highly important for a detailed evaluation. Intraoperative TEE grants useful information about the mechanism of insufficiency, the adequacy of surgical reconstruction, and residual valve pathology [11]. After anesthetic induction, there is sufficient time to confirm findings of preoperative echocardiography, and evaluation of LVEF, aortic and other valve functions. The cardiac anesthesiologist can perform intraoperative TEE to observe the hemodynamics, ensure myocardial protection, and manage fluid replacement more precisely. After CPB, surgical success can be evaluated with a TEE evaluation via mid-esophageal long-axis view at 120°, checking the functions of the reconstructed aortic valve and the aortic annulus width, and via the short-axis view at 40° for planimetric aortic area measurement. The long axis view can provide information on valve pathology, as well as pathologies at the left ventricular septum and the subaortic level.
Measurements of the aortic valve should be performed in the 110-140° long-axis view from leading edge to leading edge.
Transgastric 5 chamber view is essential for the evaluation of aortic insufficiency and the aortic gradient. During weaning from CPB, the fluid balance, contractility, functions of the other valves, and inotrope requirement can be assessed by TEE examination.
In conclusion, autologous pericardial aortic neocuspidization is a safe surgical procedure that eliminates the need for oral anticoagulants and provides stable hemodynamics with a reduced permanent pacemaker requirement. Perioperative TEE examination is essential for this operation to ensure surgical success and a thorough hemodynamic monitorization.
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. Ozaki S, Kawase I, Yamashita H, Uchida S, Nozawa Y, Matsuyama T et al. Institutional report –Valves Aortic valve reconstruction using self-developed aortic valve plasty system in aortic valve disease. Interact Cardiovasc Thorac Surg. 2011; 12(4): 550-3.
2. Lansac E, Di Centa I, Raoux F, Al Attar N, Acar C, Joudinaud T, et al. A lesional classification to standardize surgical management of aortic insufficiency towards valve repair. Eur J Cardiothorac Surg. 2008; 33(5): 872– 80.
3. Doss M, Sirat S, Risteski P, Martens S, Moritz A. Pericardial patch augmentation for repair of incompetent bicuspid aortic valves at midterm. Eur J Cardiothorac Surg 2008; 33(5): 881–4.
4. Duran CMG, Gometza B, Kumar N, Gallo R, Martin-Duran R. Aortic valve replacement with freehand autologous pericardium. J Thorac Cardiovasc Surg. 1995;110(2): 511-6.
5. Ozaki S, Kawase I, Yamashita H, Uchida S, Nozawa Y, Takatoh M, et al. A total of 404 cases of aortic valve reconstruction with glutaraldehyde-treated autologous pericardium. J Thorac Cardiovasc Surg. 2014; 147(1): 301-6.
6. Doenst T, Kirov H, Moschovas A, Gonzalez-Lopez D, Safarov R, Diab M, et al. Cardiac surgery 2017 reviewed. Clin Res Cardiol. 2018; 107(12): 1087-102.
7. Sá MPBO, Perazzo ÁM, Zhigalov K, Komarov R, Kadyraliev B, Enginoev S, et al. Aortic Valve Neocuspidization with Glutaraldehyde-Treated Autologous Pericardium (Ozaki Procedure) – A Promising Surgical Technique. Braz J Cardiovasc Surg. 2019; 34(5): 610-4.
8. Ozaki S, Kawase I, Yamashita H, Uchida S, Takatoh M, Kiyohara N. Midterm outcomes after aortic valve neocuspidization with glutaraldehyde-treated autologous pericardium. J Thorac Cardiovasc Surg. 2018; 155(6): 2379-87.
9. Mourad F, Shehada SE, Lubarski J, Serrano M, Demircioglu E, Wendt D, et al. Aortic valve construction using pericardial tissue: short-term single-centre outcomes. Interact Cardiovasc Thorac Surg. 2019; 28(2): 183-90.
10. Koechlin L, Schurr U, Miazza J, Imhof S, Maurer M, Erb J, et al. Echocardiographic and Clinical Follow-up After Aortic Valve Neocuspidization Using Autologous Pericardium. World Journal of Surgery. 2020; 44(9): 3171-81
11. Vanoverschelde JL, van Dyck M, Gerber B, Vancraeynest D, Melchior J, de Meester C, et al. The role of echocardiography in aortic valve repair. Ann Cardiothorac Surg. 2013; 2(1): 65-72.
Download attachments: 10.4328.ACAM.21292
Mustafa Şimşek, Sena Sert, Türkan Kudsioğlu. Management of intraoperative transesophageal echocardiography in aortic valve neocuspidization (Ozaki procedure). Ann Clin Anal Med 2022;13(11):1276-1279
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Women in surgery: Analysis of female surgeons in Turkey
Harun Demirci 1, Nurcan Tüfekçi 2, Pelin Kuzucu 3, Atilla Kazancı 1, Seyhan Baburoğlu 4, İlknur Günaydın 4, Pınar Özışık 1
1 Department of Neurosurgery, Faculty of Medicine, Ankara Yıldirim Beyazit University, 2 Department of Family and Consumer Sciences, Faculty of EAS, Hacettepe University, 3 Department of Neurosurgery, Bilkent City Hospıtal, 4 Department of Cardiovascular Surgery, Bilkent Cıty Hospıtal, Ankara, Turkey
DOI: 10.4328/ACAM.21294 Received: 2022-06-30 Accepted: 2022-08-04 Published Online: 2022-08-08 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1280-1283
Corresponding Author: Pelin Kuzucu, Department of Neurosurgery, Bilkent City Hospıtal, Ankara, Turkey. E-mail: drpelinkuzucu@gmail.com P: +90 505 704 13 38 Corresponding Author ORCID ID: https://orcid.org/0000-0003-0484-3753
Aim: When it comes to choosing a medical specialization, the current worldwide lack of interest among women in the surgical branches of medicine is noticeable. Furthermore, the ratio of women to men is quite low and can be attributed to many negative issues.
Material and Methods: We administered a 98-question survey to 196 female surgeons from different branches of medicine. The data were recorded in Microsoft Excel and analyzed using SPSS version 22.0 software.
Results: Our study investigated the factors affecting the progress of women in surgical careers and included 196 participants. The majority of the surgeons who completed the research questions were employees of neurosurgical departments (36.2%). Of the 196 study participants, 49.0% were >40 years of age, and 51.0% were ≤ 39 years of age. Among the surgeons included in our study, 42.6% stated that they had experienced negative interactions with their male colleagues. The participants responded that the good side of being a surgeon was the ability to perform surgery (87.7%), creating differences in patient outcomes (70.4%), and the diversity of tasks (32.1%).
Discussion: Currently, over 50% of medical school students are women, and the surgical profession is typically male-dominated. Worldwide, women surgeons are confronted with gender bias and face numerous challenges and obstacles in terms of competence, work ethic, unequal job opportunities, and undertaking academic or professional leadership roles. Creating a supportive environment where women surgeons can succeed will have a positive impact on society as a whole.
Keywords: Surgeons, Female, Career Mobility, Physicians, Women
Introduction
The surgical profession has traditionally been male-dominated, with women surgeons playing background roles. In some studies, this male-dominated hierarchy is even referred to as “gang culture” or a “men’s club” [1,2]. Today, over 50% of medical school students are women [3]. However, women are less involved in surgical fields, and this has been attributed to factors such as having children, significant lifestyle effects, long and irregular working hours, family responsibilities, inadequate mentoring, and the “pipeline effect,” which theorizes that there is not enough time to see an improvement in numbers.
Changes in the roles of men and women in society and in work–life balance have been instrumental in initiating changes in the patriarchal structure of the surgical profession. Consequently, the number of women in surgery has steadily increased over the past decade. Our study aimed to better understand the factors affecting the progress of women in surgical careers and to collect and analyze data about the experiences of women surgeons in Turkey.
Material and Methods
All experiments were conducted in accordance with the relevant guidelines and regulations under Ethical approval and participation approval. Our study was approved by the ethics committee at Ankara Yıldırım Beyazıt University (meeting date and approval number: 07.09.2020-24). Informed consent was obtained from all participants and/or their legal family.
The subjects in our qualitative study were female surgeons. They were selected using purposive sampling, a non-probability sampling technique. Since age is considered a critical variable in determining the problems experienced by women, we selected women across all age groups so that comparisons could be made.
Our online questionnaire was titled “Women in Surgery: Analysis of Female Surgeons in Turkey.” It was prepared as a Google Form so that the study participants could access it online. Then online questionnaire was sent to surgical science associations and delivered to the study participants through these associations from February 4 to September 7, 2021.
The first page of the research form provided participants with informed consent about the purpose of the research, the time required to complete the questionnaire, the confidentiality of the answers given, the fact that participation was voluntary, and how to contact the researcher.
The questionnaire comprised 98 questions about participants’ demographic characteristics and covered the topics of work intensity, academic research efficiency, career satisfaction, work–life balance, gender opportunities, mentorship, and exposure to harassment.
The data were recorded in Microsoft Excel (Microsoft Corporation, Redmond, WA, USA) and analyzed using SPSS version 22.0 software (IBM Corporation, Armonk, NY, USA). The Chi-Square test of independence was used to statistically evaluate the obtained data. P values < 0.05 were considered statistically significant.
Results
Our study investigated the factors affecting the progress of women in surgical careers and included 196 participants. (Figure 1).
Demographic Information of Female Surgeons
The proportion of participants aged >40 years was 49.0%, and 51.0% were aged ≤39 years. Over half of the participants lived in metropolitan city (Ankara, 34.4%; Istanbul, 33.3%). The proportion of participants who continued their education was 21.0%, while 44.1% worked as specialists. Of the female surgeons who continued their assistant training, 51.0% studied at education and research hospitals and 48.0% at state university hospitals. Over 52.0% of the female surgeons who participated in our survey were employed in academic positions in state-affiliated health institutions and 53.7% in educational research hospitals. Furthermore, 41.3% had worked for 11–20 years and 30.7% for 1–10 years since graduating from medical school. Over half of the respondents (62.8%) were married or living with a partner, 32.1% were single, and 70.6% did not have children.
Workload
Among the participants who completed their education, 48.5% averaged ≥80 working hours per week. In the first 10 years of their career, 72.8% of participants did not devote any time to academic study.
Academic Research Efficiency
We found that 36.7% of participants published articles in peer-reviewed journals. The major influencing factors affecting publication output were time constraints (70.4%), lack of a supervisor (52.0%), and lack of support from the department or institute (50.0%).
Career Satisfaction
The proportion of participants who agreed that if they could turn back the clock, they would make the same career choice again was 48.5%. 63.6% of participants stated that there were no female surgeons at the associate professor/professor level in the department during the assistant process. The proportion of participants who agreed that having other female surgeons in the department during surgical training made their training easier was 50.8%.
Pregnancy
Over half of the study participants (yes, 48.1%; partly, 7.6%) postponed pregnancy due to their work. Furthermore, 9.7% stated that maternity leave following childbirth was not granted at the institutions where they worked (Figure 2).
Gender Opportunities
Among the surgeons included in our study, 42.6% stated that they had experienced negative interactions with their male colleagues. Only 56.2% of participants stated that the program or department where they worked provided equal opportunities for hiring male and female specialist surgeons, and only 54.4% felt that their employer supported equal opportunities for men and women.
Mentoring
We found that 26.0% of women surgeons were members of the women’s group of national associations related to their specialty, and 52.0% were not members of any associations. Furthermore, only 7.4% were trained as mentors. The proportion of participants who stated that it would be beneficial and supportive to create a separate organization for female surgeons was 43.6% (Figure 3).
Leadership
The proportion of participants who stated that they were members of national and international organizations was 16.9%. The rate of personal participation in national and international organizations was 57.6% and 86.7%, respectively, and the rate of personal participation as a mentor was 42.4%.
Becoming a Surgeon
The participants responded that the good sides of being a surgeon were being able to perform surgery (87.7%), creating differences in patient outcomes (70.4%), and the diversity of tasks (32.1%).
The participants responded that the bad sides of being a surgeon were the intensive workload (70.9%), less personal time (61.7%), and the fact that male colleagues consider surgery a job for men, not women (46.4%). Furthermore, they considered that the worst part of being a surgeon was the lack of financial return, statistical analysis, interpersonal conflict in the workplace, and male colleagues who considered that being a surgeon was a man’s job. Additionally, we observed a statistically significant relationship between the age of women and the perception that surgery was a man’s job (P < 0.05).
Discussion
We believe that Surgical careers combine intellectual expertise and manual skills in the treatment of patients and demand greater decisiveness than other medical specialties.
Turkey is a developing country geographically located primarily in Asia. Most Turkish societies have a patriarchal structure that is associated with their culture. [4] In our experience, women can only attain a senior position in their chosen field by making extra effort.
The psychological extension of gender discrimination is a phenomenon that has long been discussed, mainly in relation to the concept of gender schema theory, developed by Sandra Bem in 1981 [5]. This cognitive theory explains how people become genderized and how this leads to social prejudice. The concept of gender schema refers to an organized structure with related expectations based on the biological gender of a person.
Despite the fact that half of all medical students today are women, only a small number chose a surgical specialty. Although the proportion of female general surgeons increased to 32% in 2008, equality is not expected until 2028. Significant gender disparities persist in some surgical specialties, such as cardiothoracic surgery, neurosurgery, and orthopedic surgery (5%–6.5% of women). Nevertheless, the percentage of women in surgery across all specialties increased between 1969 and 2018. However, although the representation of women has increased overall, the annual percentage change rate in neurosurgery, orthopedic surgery, urology, and cardiothoracic surgery has increased more slowly [6]. As of 2017, only 13% of the approximately 70,000 surgeons across multiple specialties in the USA were women [7]. Reasons for this include work–life balance, lack of role models and mentoring, lack of support for pregnancy and parenting, and a culture that is not conducive to women. Delaying pregnancy in favor of career advancement increases the likelihood of fertility and pregnancy complications. Furthermore, 87.96% of female surgeons have fewer children compared with their male counterparts.
Female surgeons spend more time on household responsibilities than their male counterparts. Thus, the balance of responsibilities, both at work and at home, remains an unspoken challenge for many women in academic surgery. It was reported that 57% of female surgeons perceived sexist difficulties in their surgical careers. Furthermore, it was reported in 1994 that 96% of female medical students vs. 0% of male students viewed surgery as “negative” in relation to their gender, and gender attitudes are considered a barrier to the career growth of females in medicine.
Women with a mentor–mentee relationship were reported to have a significantly higher level of satisfaction with their career development. In a Canadian survey, 79% of female respondents stated that they had at least one mentor, and 89% of these mentors were men. Again, the same study showed that the participants wanted to work with women as mentors because they believed that a female mentor would be more helpful in advising on how to balance a career with family life.
A study in 2010 revealed that male attending surgeons were less likely to agree that surgery is a good career for women vs. female surgeons. Additionally, a survey of 663 cardiothoracic surgeons and trainees reported low scores for behavior supportive of women and high scores for behavior unsupportive of women [8].
Positions on editorial boards are important and considered a valuable attribute when opportunities for academic promotion arise [7]. From 1997 to 2017, the number of women serving on editorial boards of high-impact surgical journals increased from 5% to 19%. However, this ratio was much lower than the ratio of men in total [9]. Similarly, it was reported that 43% of surgical conferences did not have women as general speakers [10].
According to the Association of American Medical Colleges, there were only 25 females with the job title of Leader in Surgical Departments in the USA in 2015-2016. As of 2017, only 5% of surgical department heads in the USA were women [11]. Currently, surgical assistants make up 38% of the total number of women in surgery in the USA. Despite this, the number of women in academic surgical positions is surprisingly low.
In society, it is preferable for women to work in jobs that are generally associated with their role as mothers. It is noteworthy that women’s work in the field of surgery is considered distant from their role as mothers. It is possible that the insistence on the view of surgery as a male job is associated with the fact that the male-dominated society does not want to give up such jobs to a woman because men want to maintain their power.
We found that the proportion of participants who responded that the positive side of being a surgeon was job opportunities decreases with age across all specialties. As age decreased, the proportion of the participants who indicated that surgery is considered a male job among both male colleagues (60.0%) and patients (58.0%) is almost double the proportion of those who are older. This may be due to the fact that the number of assistants and specialists participating in our study was high, which is evident from the demographic data, and they are more exposed to negativity and gender discrimination at the beginning of their working life in comparison with associate professors and professors.
In 2015, a social media movement was launched under the title #İLookLikeASurgeon to provide visibility to women in surgery. This movement led to 128 million impressions in 3 months and serves as an indication that the problems faced by female surgeons are global. Thanks to these efforts, the face of surgery has begun to change, but more work needs to be done.
Limitation:
The limitation of our study is that among the surgeons who completed the research questions, employees in neurosurgical departments were the most numerous, which could have led to biased results.
Conclusion
Although gender equality in surgery is progressing, significant discrimination against women continues. Male surgeons should be allies of their colleagues, actively supporting and encouraging the female surgeons with whom they work. Creating an environment where women can contribute, develop, and succeed by working in the best way possible will have a positive impact on society, setting an example for younger generations in the surgical field, as it will in every field.
Acknowledgment
Preparation for publication of this article is partly supported by Turkish Neurosurgical Society.
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
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3. Wood DE. How can men be good allies for women in surgery? #HeForShe. J Thorac Dis. 2021;13(1):492–501.
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5. Starr CR, Zurbriggen EL. Sandra Nem’s gender schema theory after 34 years: A review of its reach and impact. Sex Roles: A Journal of Research. 2017;76(9–10):566–78.
6. Linscheid LJ, Holliday EB, Ahmed A, Somerson JS, Hanson S, Jagsi R, et al. Women in academic surgery over the last four decades. PLoS One. 2020;15(12):e0243308.
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9. Harris CA, Banerjee T, Cramer M, Manz S, Ward ST, Dimick J, et al. Editorial (Spring) Board? Gender Composition in High-impact General Surgery Journals Over 20 Years: Annals of Surgery. 2019;269(3):582–8.
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Download attachments: 10.4328.ACAM.21294
Harun Demirci, Nurcan Tüfekçi, Pelin Kuzucu, Atilla Kazancı, Seyhan Baburoğlu, İlknur Günaydın, Pınar Özışık. Women in surgery: Analysis of female surgeons in Turkey. Ann Clin Anal Med 2022;13(11):1280-1283
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Investigation of endocan level in Rheumatoid Arthritis patients’ serum, and its relationship with disease activity
Halil Yılmaz 1, Firdevs Ulutaş 2, Yaşar Enli 3, Veli Çobankara 2
1 Department of Internal Medicine, 2 Department of Internal Medicine, Division of Rheumatology, 3 Department of Medical Biochemistry, Faculty of Medicine, Pamukkale University, Denizli, Turkey
DOI: 10.4328/ACAM.21298 Received: 2022-07-01 Accepted: 2022-10-20 Published Online: 2022-10-24 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1284-1288
Corresponding Author: Firdevs Ulutaş, Department of Internal Medicine, Division of Rheumatology, Faculty of Medicine, Pamukkale University, Denizli, Turkey. E-mail: firdevsulutas1014@gmail.com P: +90 530 094 46 32 Corresponding Author ORCID ID: https://orcid.org/0000-0001-8441-5219
Aim: Rheumatoid arthritis (RA) is a common chronic rheumatic disease. Endocan is a human endothelial cell-specific molecule. The aim of this study was to investigate the endocan level in RA patients’ serum, and its relationship with disease activity.
Material and Methods: We enrolled 56 patients with RA, 55 patients with fibromyalgia (FMS), and 56 healthy volunteers in this cross-sectional study. Endocan was analyzed with an enzyme-linked immunosorbent assay (ELISA). The Kruskal-Wallis variance analysis was used to compare independent group differences. Chi-square analysis was used for comparison of categorical variables and Spearman correlation analysis was used to examine the relationship between continuous variables. P values <0.05 were considered statistically significant.
Results: The mean age was 44.03±10.79 years among RA patients. The mean disease duration was 64.44±53.82 months in RA patients. Serum endocan levels were similar between the groups including RA, FMS patients, and healthy subjects without any statistical significance (28.27 pg/ml in RA, 29.38 pg/ml in FMS, and 30.12 pg/ml in healthy subjects, p > 0.05). Endocan levels in the serum were also at similar titers in active and inactive RA patients (27.9 pg/ml, 28.64 pg/ml, respectively).
Discussion: We did not find increased levels of serum endocan in rheumatoid arthritis patients compared with fibromyalgia and healthy subjects. New studies with a higher number of patients are necessary for a more clear outcome.
Keywords: Rheumatoid Arthritis, Endocan, Fibromyalgia, DAS-28
Introduction
Rheumatoid arthritis (RA) is a common chronic rheumatic disease that is characterized by synovial inflammation. RA commonly affects middle-aged women with a female/male ratio of 2-5/1. Multiple environmental and genetic factors play a role in underlying etiopathogenetic mechanisms [1]. Although there are various biomarkers that are used for evaluating treatment responses (ESR, CRP), for predicting risky subjects with progressive disease and/or severe disease activity, and for making therapeutic choices (RF, anti-CCP), new biomarkers (such as miR-146a and miR155) are also under investigation in this area [2]. It is also thought that histological patterns of synovial tissue biopsies will guide the choice of treatment modalities in the near future [3]. Thus different searches continue for new biomarkers. Currently, we know that altered blood vessel density is present in inflammatory synovial tissue and angiogenesis occurs via a release of vascular endothelial growth factor (VEGF) as a result of hypoxia. Basic fibroblast growth factor (FGF), angiopoietins and hypoxia-inducible factor-1 (HIF-1) are also associated pro-angiogenic molecules in RA, in addition to proliferative retinopathies and malignancies [4]. Angiogenesis facilitates the accumulation of various inflammatory cells and production of many pro-inflammatory cytokines. Synovial fibroblasts (SFs) and macrophage-like cells play a main role in the destruction of joints in RA patients and recent studies revealed active transmigration of SFs to other joints [5]. Interleukin-1β (IL-1β), (nuclear factor-kB-ligand) RANKL and tumor necrosis factor-alpha (TNF-α) have a destructive effect on affected joints [6]. Ephedrine was noted as one of the possible prospective therapeutic candidate agents due to an inhibitory effect on expressions of prostaglandin E2 (PGE2) and interleukin-6 in RA patients [7]. Ultimately, pannus formation occurs. Active cellular pannus is also a culprit factor in joint destruction. According to present studies, pannus tissue is a granulation tissue that has a proliferative capacity similar to a tumor-like mass [8]. Inhibitors of angiogenesis may have therapeutic effects in treating this proliferative synovitis. Endocan, also known as endothelial cell specific molecule-1 (ESM-1), is a chondroitin/dermatan sulphate proteoglycan that is expressed on the surface of vascular endothelium. Its expression, synthesis or secretion is affected by pro-inflammatory molecules such as TNF-α and VEGF [9]. Besides, endocan expression was induced by adiponectin more powerfully than IL-1β in synovial cells [10]. Endocan regulates cell adhesion in malignant and inflammatory diseases. ESM-1 adheres to lymphocytes through leukocyte function-associated antigen-1 (LFA-1). It could influence the accumulation of lymphocytes to the inflammation site. This proteoglycan also demonstrates Hepatocyte Growth Factor/Scatter Factor (HGF/SF) mediated mitogenic activity in tumor formation and tissue repair [11]. Kim KS et al investigated endocan expression in tissues of patients with RA and osteoarthritis (OA). Endocan was highly expressed in RA synovial tissues and in some OA tissues with concomitant severe inflammation [10]. In this study, we aimed to investigate endocan levels in RA patients’ serum and its possible association with the disease activity.
Material and Methods
This is a cross-sectional comparative study from a single tertiary health center. All individuals included in this study were evaluated by the same rheumatology team at one time. Between September 2015 and December 2016, a total of 76 RA patients admitted to the outpatient rheumatology clinic. We enrolled 56 patients with rheumatoid arthritis who meet the study inclusion and/or exclusion criteria, 55 patients with fibromyalgia (FMS) and 56 healthy volunteers who matched in terms of age and gender at the same time period. All of the RA patients fulfilled the 2010 American College of Rheumatology (ACR) classification criteria [12]. Patients with rheumatoid arthritis were subgrouped as active or inactive based on disease activity score-28 (DAS-28). DAS28 is one of the measurements of RA disease activity calculated on the basis of total information from general health, tender and swollen joints, and acute phase response. Baseline DAS-28 was evaluated in each patient in accordance with EULAR/ACR collaborative recommendations [13]. DAS-28 was calculated with the following formula: (0.56 × √number of tender joints) + (0.28 × √number of swollen joints) + (0.7 × erythrocyte sedimentation rate (ESR) + (0.014 × visual pain scale). The disease with upper values of DAS 28 above 3.2 (≥ 3.2) was accepted as active disease, whereas others with inactive disease. According to current knowledge, FMS is a non-inflammatory biopsychological disease that may be compared with inflammatory rheumatic diseases in clinical trials. Herein, 2010 ACR diagnostic criteria were used to diagnose patients with FMS [14]. All were diagnosed in our tertiary health center at Pamukkale University Faculty of Medicine.
Inclusion criteria were defined as follows: patients older than 18 years, and patients who fulfill each classification criteria for RA and FMS, patients having initial diagnosis by the same rheumatology team in our tertiary health center, and being volunteer for healthy individuals. Exclusion criteria were defined as follows: presence of alcohol use or smoking, having any co-morbidities including hypertension, diabetes mellitus, left ventricle dysfunction, heart valve pathologies, acute coronary syndrome, hypo-hyperthyroidism, liver and/or kidney dysfunction, malignancy or other systemic inflammatory diseases, or having local and/or systemic infectious disease in the recent three months, and RA patients treated with biological agents.
Coagulated blood samples were collected at 8-10 am after 12 hours of fasting. After appropriate centrifugation, all samples were stored at –80 °C until testing. Samples for endocan were examined with an enzyme-linked immunosorbent assay (ELISA) using a special kit (BOOSTER, Pleasanton, CA 94566) after incubating for 1.5 hours at 37C. Biotinylated anti-human ESM-1/Endocan antibody solution was added to each sample. The procedure is based on sandwich ELISA principle. Firstly, a mixture of samples has been made with a target antigen capture antibody, and than unbound parts were removed by washing. After washing, staining with tetramethylbenzidine (TMB) was applied. The final absorbance values of the samples were read using a Kayto RT – 2100c microplate reader at 450 nanometers (nm). Endocan concentrations were reported as pg/mL. C-reactive protein (CRP), ESR, rheumatoid factor (RF) and total leukocyte count were also analyzed with standardized biochemical assessments to determine inflammatory state of the subjects.
This study was approved by the local ethics committee of the tertiary health center (2015/35-1) in accordance with the Helsinki Declaration. All participants approved a patient consent form.
Statistical Analysis
The statistical program SPSS version 23.0 (SPSS Inc., Chicago, IL, USA) was used for data analysis using descriptive statistics. Continuous variables are given as mean ± standard deviation and categorical variables as numbers and percentages. The Kruskal- Wallis is a kind of nonparametric variance analysis that has been used to compare several independent group differences. Chi-square analysis was used for comparison of categorical variables and Spearman’s correlation analysis was used to examine relationships between continuous variables. P-values <0.05 were considered statistically significant.
Results
Three patient groups were similar in terms of age, gender and body mass index (Table 1). The mean age of RA patients was 44.03±10.79 years. The mean disease duration in RA patients was 64.44±53.82 months. Forty-one (n=41, 73.2%) patients with RA were female. RA patients were subgrouped into active or inactive disease. Thirty-one RA patients had active disease, while the rest patients had inactive disease (n=25). Active RA patients had higher ESR and CRP values than inactive patients. Whereas, RF positivity and total leukocyte count were similar between the two RA patient subgroups. 78.6% (n=44) of RA patients were on treatment with methotrexate, followed by 76.8% (n=43) with glucocorticoids, 58.9% (n=33) with sulfasalazine, 17.8% (n=10) with antimalarials and 14.3% (n=8) with leflunomide. Serum endocan levels were similar between the groups including RA, FMS patients and healthy subjects without any statistical significance (28.27 pg/ml in RA, 29.38 pg/ml in FMS, and 30.12 pg/ml in healthy subjects, p >0.05) (Table 1). Values of ESR and CRP were significantly higher in active RA patients compared with inactive patients (Table 2). Serum endocan levels were at similar titers in active and inactive RA patients (27.9 pg/ml, 28.64 pg/ml, respectively) (Table 3). Serum endocan levels had a negative association with ESR, CRP and DAS-28 without statistical significance (r= -0.217, p=0.107 vs r= -0.170, p=0.209 and r= -0.076, p=0.575, respectively) (Table 3).
Discussion
In the present study, we hypothesized that serum endocan may be a biomarker of endothelial cell activation and angiogenesis associated with inflammation. Our findings showed that serum endocan was at similar titers in RA and FMS patients, and healthy controls. Absence of significant differrence between FMS and healthy controls also ensured that endocan was not associated with inflammation. FMS was selected due to beinig non-inflammatory rheumatic disease. Today, endocan is started to be mentioned as a useful biomarker at vascular dysfunction of hypertension, renal disease and advanced cardiovascular disease [15]. Although effects of gender/sex on cardiovascular diseases are not clearly determined and social determinants of biological sex were reviewed comprehensively, cardiovascular diseases are thought to be mostly men diseases [16]. In this context, the similar endocan titers in RA patients and healthy controls may be explained by that the vast majority of the patient group were females.
Paul Balanescu et al showed higher endocan levels in systemic sclerosis (SSc) patients compared with sex- and age-matched healthy controls. They noted that endocan may have a discriminative and predictive role in differentiating diffuse and limited forms and in developing microvascular complications [17]. Ilknur Balta et al also detected increased circulating serum endocan levels in Behçet disease (mean serum levels of endocan were 1.29 ± 0.60 ng/mL) compared with healthy subjects. According to their investigation, serum endocan was higher in patients with ocular symptoms and arthritis. Endocan was correlated with acute phase reactants including ESR, CRP and disease activity [18]. Serum circulating endocan levels were detected at high titers in psoriasis (PSo) patients and correlated with Psoriasis Area and Severity Index (PASI), and high sensitive CRP as an indicator of endothelial dysfunction. The authors suggest its use as a surrogate marker in endothelium-associated pathological diseases [19].
In addition, Göksel Tuzcu et al investigated this molecule in RA patients. They showed that serum endocan was significantly higher in RA patients than healthy controls. In their study, endocan was positively correlated with age, DAS-28 in RA patients and carotid intima-media thickness in the evaluation of pre-atherosclerotic lesions [20]. These are inconsistent with our study results. This may be explained by difference in the mean age of RA patients between the two studies. The patients in their study were older than our RA patients. Besides, they had a much smaller patient group compared with ours, and treatment modalities of the RA patients were not reported in their study. In our study, a vast majority of RA patients were on various treatment modalities. Whereas, various effective treatment modalities and/or medical conditions are related to variations in endocan levels in different diseases. For instance, strict glycemic control decreases serum endocan levels in type 2 diabetes mellitus [21]. The other example is ultraviolet-B (UVB) treatment in patients with psoriasis [22]. Turgay Celik et al also showed that amlodipine and valsartan decreased serum endocan levels in newly diagnosed hypertensive patients. This result was attributed to the anti-inflammatory effects of these two drugs [23]. All of the therapeutic effects mentioned above were explained by the reversal of endothelial dysfunction in each disease. Thus, the absence of a significant correlation between endocan levels and inflammatory markers and/or disease activity score may be attributed to the possible effect of using glucocorticoids, anti-inflammatory drugs and/or immune-modulatory drugs.
Fibromyalgia is the most common widespread pain syndrome in the general population with a prevalence of 2% to 8% and it frequently accompanies various inflammatory diseases [14]. Negative effects of pain and stress on endothelial function were shown in FMS patients [24]. Serum endocan levels were also higher in fibromyalgia patients than healthy controls in the recent literature [25]. In our study, serum endocan levels were similar between fibromyalgia patients and healthy controls. The FMS patients had neither other systemic diseases nor older age compared with literature. Similar endocan levels may be attributed to this condition.
There are several limitations of our study. Firstly, the vast majority of RA patients had ongoing variable treatment modalities including anti-inflammatory and immune-modulatory drugs that could affect endocan levels of serum. Having a heterogeneous patient group with various drugs is also problematic for comparison of subgroups. Patients treated with the same drug or without any drug may be included. But this time, achieving this sample size would be difficult in the same time period. Secondly, concurrent pro-inflammatory and/or pro-angiogenic cytokine analysis was not obtained simultaneously. Although patients who had no comorbidities and any smoking addiction were included in the study in order to decrease the confounding effects of these factors, a relatively small-sized patient groups was another limitation of the study. Absence of a power analysis for determination of the sample size is another limitation.
Conclusion
Serum endocan levels were similar between RA patients, FMS patients, and healthy subjects. Further studies with more homogeneous and large-sized patient groups are needed to validate these results. Also, early-RA patients who are not treated with any conventional/biological agents can provide more accurate knowledge.
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.
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11. Bechard D, Gentina T, Delehedde M, Scherpereel A, Lyon M, Aumercier M, et al. Endocan is a novel chondroitin sulfate/dermatan sulfate proteoglycan that promotes hepatocyte growth factor/scatter factor mitogenic activity. J Biol Chem. 2001;276(51):48341-9.
12. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, et al. 2010 Rheumatoid Arthritis Classification Criteria, An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative. Arhritis Rheum. 2010;62(9):2569-81.
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18. Balta I, Balta S, Koryurek OM, Demirkol S, Mikhailidis DP, Celik T, et al. Serum endocan levels as a marker of disease activity in patients with Behçet disease. J Am Acad Dermatol. 2014;70(2): 291-6.
19. Balta I, Balta S, Demirkol S, Celik T, Akhan M, Kurt O, et al. Elevated serum levels of endocan in patients with psoriasis vulgaris: correlations with cardiovascular risk and activity of disease. Br J Dermatol. 2013;169(5):1066-70.
20. Tuzcu G, Uslu AU, Tuzcu A, Baykara RA, Omma A, Kucuk A. A novel marker relationship between carotid intima media thickness and disease activity score-28 in patients with rheumatoid arthritis: Human endothelial cell-specific molecule-1. Turkish Journal of Medical Sciences. 2019;49(6):1599-605.
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Halil Yılmaz, Firdevs Ulutaş, Yaşar Enli, Veli Çobankara. Investigation of endocan level in Rheumatoid Arthritis patients’ serum, and its relationship with disease activity. Ann Clin Anal Med 2022;13(11):1284-1288
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Evaluation of early thyroidectomy complications
Turgay Karataş 1, Engin Burak Selcuk 2, Mehmet Karatas 3, Atilla Yildirim 4, Davut Ozbag 5, Mahmut Cay 6, Deniz Senol 7, Mehmet Fatıh Korkmaz 8
1 Department of Anatomy, Medical Faculty, Inonu University, Malatya, 2 Department of Family Medicine, Medical Faculty, Inonu University, Malatya, 3 Department of Medical History and Ethics, Medical Faculty, Inonu University, Malatya, 4 Department of General Surgery, Malatya Training and Research Hospital, Malatya, 5 Department of Anatomy, Medical Faculty, Medeniyet University, Istanbul, 6 Department of Anatomy, Medical Faculty, Usak University, Usak, 7 Department of Anatomy, Medical Faculty, Duzce University, Duzce, 8 Department of Orthopedics, Medical Faculty, Medeniyet University, Istanbul, Turkey
DOI: 10.4328/ACAM.21299 Received: 2022-07-01 Accepted: 2022-08-25 Published Online: 2022-08-29 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1289-1292
Corresponding Author: Turgay Karataş, Department of Anatomy, Medical Faculty, Inonu University, Battalgazi, 44050, Malatya, Turkey. E-mail: drkaratas44@hotmail.com P: +90 422 341 07 45 F: +90 422 341 00 36 Corresponding Author ORCID ID: https://orcid.org/0000-0002-1480-606X
Aim: Our aim in this study is to reveal the relationships between patient findings, surgical methods and early thyroidectomy complications.
Material and Methods: The files and operative notes of 308 patients who underwent thyroidectomy within 10 years were reviewed retrospectively. Gender, age, preoperative diagnosis, primary or reoperated cases, the type of thyroidectomy [ bilateral subtotal (BST), bilateral total (BTT), unilateral subtotal (UST) and unilateral total (UTT) ] and early postoperative complications (hypocalcemia, bleeding, nervus laryngeus recurrens (NLR) injury, infection and seroma) were recorded. The peculiarity of this study is that NLR neuromonitoring was not used in thyroidectomy operations.
Results: Of the 308 patients who underwent thyroidectomy, 287 were females and 21 were males. Two hundred eighty three cases of multinodular goiter, 18 cases of nodular goiter and 7 thyroid cancers were operated; 180 BTT, 100 BST, 17 UTT + UST, 7 UST and 4 UTT were applied. Complications were seen in a total of 20 (6.49%) patients who underwent 19 BTT and 1 BST. The only complication in BST was bleeding. There were 10 (3.24%) hypocalcemia, 4 (1.29%) bleeding, 2 (0.649%) NLR injury, 2 (0.649%) infections and 2 (0.649%) seromas. In terms of the frequency of early thyroidectomy complications, hypocalcemia was the first (P=0.0047). In addition, the rates of hypocalcemia and NLR injury were higher in reoperated patients than in primary patients (P<0.05).
Discussion: The most common complication was hypocalcemia. NLR injury and hypocalcemia rates were higher in reoperated cases who underwent BTT.
Keywords: Goiter, Thyroid Surgery, Thyroidectomy, Complication
Introduction
Thyroid diseases are one of the most common endocrine diseases [1]. Thyroid gland surgery is performed for malignant diseases of the thyroid, multinodular or nodular goiter, thyroiditis, graves disease, compression findings and cosmetic reasons [2,3].
Thyroid surgery in the hands of experienced surgeons is one of the safest procedures currently performed. Although complications after surgical removal of the thyroid gland are rare, the consequences can be life-threatening [4].
Nowadays, total thyroidectomy is frequently performed in the surgical treatment of the thyroid. Although the rate of complications after thyroidectomy is low, hypoparathyroidism, nervus laryngeus recurrens (NLR) injury, respiratory tract obstruction, hyperthyroidism crisis, wound infection and hematoma have been reported as the most important postoperative complications [3,4].
In this study, we aimed to determine the relationship between early complications of thyroidectomy and gender, age, preoperative diagnosis, primary – reoperated cases and thyroidectomy procedures.
Material and Methods
Files and surgical notes of 308 patients who underwent thyroidectomy for 10 years without neuromonitorization in the general surgery clinic were reviewed retrospectively. Gender, age, preoperative diagnosis [multinodular goiter (mng), nodular goiter (ng) and thyroid cancer (thyroid ca)], primary – reoperated patients, thyroidectomy procedure [bilateral total thyroidectomy (BTT), bilateral subtotal thyroidectomy (BST), unilateral total thyroidectomy (UTT) and unilateral subtotal thyroidectomy (UST)] and early postoperative complications [hypocalcemia, hematoma, nervus laryngeus recurrens (NLR) injury, infection and seroma] were recorded.
The relationship between early complications after thyroidectomy and gender, age, diagnosis, primary – reoperated patients and thyroidectomy procedure was investigated.
Statistical analysis: Data were summarized by number (percentage), mean ± standard deviation and median (min-max) by variable type. The suitability of numerical variables to normal distribution was examined using the Shapiro-Wilk test. Pearson’s chi-square and Yates exact tests were used to determine whether there was a statistically significant relationship between qualitative variables. The Mann-Whitney U test was used to determine whether there was a statistically significant difference between the subcategories in terms of quantitative variables. P<0.05 was considered statistically significant. IBM SPSS Statistics 22.0 software was used for analysis.
Results
Of the 308 patients who underwent thyroidectomy, 287 (93.18%) were females and 21 (6.81%) were males. The age range was 16-75 years. The mean age was 41±12 years. The age range of the males was 25-56 years and the mean age was 41±10 years. The female age range was 16-75 years and the mean age was 41±12 years.
Two hundred eighty three (91.88 %) patients had multinodular goiter (mng), 18 (5.84%) had a single nodule (ng) and 7 (2.27%) had thyroid cancer. Mng was detected in 20 (95.2%) males, 263 (91.6%) females, Ng 1 (4.8%) male, 17 (5.9%) females, and thyroid cancer in 7 (2.4%) females, respectively. There was no significant difference between males and females in terms of diagnoses (P>0.05).
Three hundred and one patients (97.72%) were primary and 7 (2.28%) were reoperated cases. As a thyroidectomy procedure, 180 patients (58.44%) were treated with BTT, 100 patients (32.46%) with BST, 17 patients (5.5) with UTT + UST, 7 patients (2.27%) with UST and 4 patients (1.29%) with UTT.
Early postoperative complications were observed in 20 patients (6.49%). Hypocalcemia in 10 patients (3.24%), hematoma in 4 patients (1.29%), nervus laryngeus recurrens (NLR) injury in 2 patients (0.649%), wound infection in 2 patients (0.649%) and seroma in 2 patients (0649%) were observed. Among the complications, hypocalcemia was significantly higher than other complications (P=0.0047).
The relationship between complications and gender, age, diagnosis, primary – reoperated patients and thyroidectomy procedures were investigated.
Only hematoma was seen in one male patient (4.76%), and no other complications were observed. Complications such as 10 (3.5%) hypocalcemia, 3 (1.04%) hematomas, 2 (0.7%) NLR injuries, 2 (0.7%) wound infections and 2 (0.7%) seromas occurred in female patients. There was no significant difference between male and female patients in terms of complications (P>0.05). In addition, there was no significant correlation between age and complications in statistical analysis (P>0.05).
No complications were observed in the patients with Ng. Hypocalcemia was observed in 1 patient (14.3%) with thyroid cancer patients, other complications were not observed. Hypocalcemia in 9 (3.2%), hematoma in 4 (1.41%), NLR injury in 2 (0.7%), wound infection in 2 (0.7%) and seroma in 2 (0.7%) patients with Mng were observed. There was no significant difference between diagnoses in terms of complications (P>0.05).
Complications of early thyroidectomy in primary and reoperated patients are given in Table 1. Hypocalcemia and NLR injury rates in reoperated patients were significantly higher than in primary patients (P=0.018, P=0.045), (Table 1). In one reoperated patient, bilateral NLR injury occurred and the patient underwent urgent tracheostomy. In a primary patient, unilateral NLR injury occurred.
Complications in thyroidectomy procedures are given in Table 2. There was no significant difference among all thyroidectomy procedures in terms of the complications (P>0.05), (Table 2).
In addition, only BTT and BST procedures were compared in terms of complications. There was no significant difference between BTT and BST in terms of hematoma, NLR injury, wound infection and seroma rates. However, a significant difference was found between BTT and BST in terms of hypocalcemia (P=0.016), (Table 3).
Discussion
The incidence of thyroid disease in the general population is very high. The thyroid is a small endocrine gland that produces hormones that regulate the body’s various metabolic activities. Thyroid diseases can be grouped into benign and malignant types [5].
Thyroid diseases are are common in women. In a study, among 2266 patients who underwent thyroidectomy, 16.2% were males, 83.8% were females and the mean age was 44.6 (17-78) (M: 47.9 F: 44) [3]. In our study, 93.18% of the patients were female and 6.81% were male. The mean age was 41 ± 12 years. The mean age of males was 41±10 years, and the mean age of females was 41±12 years.
Thyroidectomy is a common operation in general surgery clinics. Surgical procedures are performed in malignant thyroid diseases, multinodular and nodular goiter, chronic thyroiditis, compression findings and cosmetic reasons [2]. The majority of our patients who underwent thyroidectomy (91.88%) consisted of patients with multinodular goiter. In both female and male patients who underwent surgery, the diagnosis was often multinodular goiter. There was no significant difference between males and females in terms of diagnoses (P>0.05).
Mortality after thyroidectomy is negligible, and its complications are less than 3%. Complications associated with thyroidectomy are related to the type of disease, the extent of the disease, surgical procedures, training and experience of the surgeon [6,1]. Postoperative complications such as hypoparathyroidism, vocal cord paralysis, infection, hemorrhage and hematoma may occur. Vocal cord paralysis is one of the frequent and serious complications of one or two NLR injuries. Hypocalcemia and postoperative bleeding are also important complications [2]. In our study, postoperative complications were observed in 20 (6.49%) patients, and these values were higher than the values in the literature, and we had no mortality.
The most common early complication of thyroid surgery is hypocalcemia (20-30%) [7]. We observed hypocalcemia in 10 patients (3.24%), and hypocalcemia was significantly higher than other complications (P<0.05). Our hypocalcemia value was lower than the literature.
There is a significant relationship between gender and surgical procedure and the development of early hypocalcemia. Hypocalcemia is found in 42% of the female and 21.4% in the male. In addition, the incidence of hypocalcemia is 38.8% in patients who underwent total thyroidectomy and 13.8% in patients underwent lobectomy [8]. In the present study, there was no significant difference between male and female gender, and among all surgical procedures in terms of incidence of hypocalcemia (P>0.05). However, hypocalcemia rates in the reoperated patients were significantly higher than in primary patients (P<0.05). When BTT and BST procedures were compared in terms of incidence of hypocalcemia, hypocalcemia was found to be significantly more common in the BTT procedure (P<0.05).
One of the most common early complications of thyroid surgery is the injury of NLR (5-11%). Injury of bilateral NLR is a rare life-threatening complication (conditions requiring immediate treatment occur in less than 0.1% of cases) [7]. NLR injury was observed in two patients (0.649%), and this rate was lower than the literature values. One of these patients was primary and the other was reoperated patient. Bilateral NLR injury occurred in the reoperated patient, and unilateral NLR injury occurred in the primary patient.
In the literature, it is reported that NLR injury is mostly in total thyroidectomies [4]. In addition, it is reported that the probability of complications is 10.6 times higher in patients who underwent complementary thyroidectomy [9]. In our study, there was no significant difference among all surgical procedures in terms of NLR injury (P>0.05). However, a significant difference was found between reoperated and primary patients in terms of NLR injury (P<0.05). NLR injury was significantly higher in the reoperated patients. We found that reoperation is the most important factor that increases the risk of NLR injury.
In the study of Doran et al, it was reported that wound exploration was performed at a rate of 1.2% due to bleeding in the postoperative period [10]. Our postoperative bleeding rate was found to be 1.29% and this rate was close to the literature values.
The overall incidence of seroma in patients undergoing thyroidectomy has been reported as 2.2%, and wound infection as 0.36% [11,12]. The incidence of seroma (0.649%) in our study was found to be below the values in the literature, but wound infection incidence (0.649%) was high.
Conclusion
Early postoperative thyroidectomy complications (hypocalcemia and NLR injury) were found to be significantly higher in patients who underwent reoperation. For this reason, we think that the patients who will be reoperated should be paid maximum attention in their operations.
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
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3. Yıldırım K , Özlem N. Tiroidektomi Uygulanan Hastaların Retrospektif Analizi (Retrospective Analysis of Patients Undergoing Thyroidectomy). Ahi Evran Med J. 2018;2(2): 35-8.
4. Rao J S. Clinical Study of Post Operative Complications of Thyroidectomy. IOSR-JDMS. 2016;15(9): 20-6.
5. Padur AA, Kumar N, Guru A, Badagabettu SN, Shanthakumar SR, Virupakshamurthy MB, et al. Safety and effectiveness of total thyroidectomy and its comparison with subtotal thyroidectomy and other thyroid surgeries: a systematic review. J Thyroid Res. 2016; 2016:7594615. DOI: 10.1155/2016/7594615.
6. Durgun C, Böyük A, Girgin S, Kapan M, Önder A, Gümüş M, et al. Comparison of the early complications of total and subtotal thyroidectomy in the multinodular goitre. Turkish Journal of Surgery. 2011;27(1): 15-19.
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10. Doran HE, Wiseman SM, Palazzo FF, Chadwick D, Aspinall S. Post-thyroidectomy bleeding: analysis of risk factors from a national registry. Br J Surg. 2021;108(7):851-7.
11. Ramouz A, Rasihashemi SZ, Daghigh F, Faraji E, Rouhani S. Predisposing factors for seroma formation in patients undergoing thyroidectomy: Cross-sectional study. Ann Med Surg. 2017;23:8-12.
12. Elfenbein DM, Schneider DF, Chen H, Sippel RS. Surgical site infection after thyroidectomy: a rare but significant complication. J Surg Res. 2014;190(1):170-6.
Download attachments: 10.4328.ACAM.21299
Turgay Karataş, Engin Burak Selcuk, Mehmet Karatas, Atilla Yildirim, Davut Ozbag, Mahmut Cay, Deniz Senol, Mehmet Fatıh Korkmaz. Evaluation of early thyroidectomy complications. Ann Clin Anal Med 2022;13(11):1289-1292
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Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis; Evidence from 1100 ERCP cases
Esat Taylan Ugurlu
Department of General Surgery, Health Science University, Sanliurfa Mehmet Akif Inan Education and Research Hospital, Şanlıurfa, Turkey
DOI: 10.4328/ACAM.21392 Received: 2022-09-15 Accepted: 2022-10-26 Published Online: 2022-11-01 Printed: 2022-11-01 Ann Clin Anal Med 2022;13(11):1293-1295
Corresponding Author: Esat Taylan Ugurlu, Department of General Surgery, Health Science University, Sanliurfa Mehmet Akif Inan Education and Research Hospital, Şanlıurfa, Turkey. E-mail: doktoramca_1971@hotmail.com P: +90 531 905 25 77 Corresponding Author ORCID ID: https://orcid.org/0000-0001-5273-1583
Aim: Since post-ERCP pancreatitis (PEP) is considered the most common complication of ERCP, it has been the focus of research to explore its prevention. Identifying patients with high-risk factors for PEP is one of the most important aspects for PEP prevention. Patients with high-risk factors should be carefully evaluated and alternative treatment and diagnostic techniques may be preferred instead of ERCP.
Our aim in this study is to determine the risk factors in patients who develop pancreatitis after endoscopic retrograde cholangiopancreatography procedure and to determine an early and appropriate diagnosis and treatment approach in these patients.
Material and Method: 1100 ERCPs performed by a single operator were included in this study. Post-ERCP pancreatitis (PEP) developed in 222 patients after the procedure. ERCP indications, age, gender, clinical findings, comorbidities and imaging frequencies of the patients who developed PEP were recorded before and after the procedure.
Result: 20.1% of the patient who underwent ERCP developed PEP. It was found that comorbidity and stent placement increased the development of PEP in patients who underwent ERCP. It was found that performing ERCP with the pre-incision method reduces the rate of PEP development. It was found that ERCP indications had no effect on the development of PEP. It was found that the rate of hospitalization in the intensive care unit increased in patients who developed PEP. It was found that the rate of PEP development decreased as operator experience increased.
Discussion: The risk of PEP is multifactorial, and the effects of some risk factors can be minimized or completely eliminated. Different patient-related risk factors can help predict PEP.
Keywords: ERCP, PEP, Risk Factors
Introduction
The most common complication of endoscopic retrograde cholangiopancreatography (ERCP) is pancreatitis [1-3]. New onset and progressive abdominal pain or typical symptoms of pancreatitis, at least 3-fold elevated amylase value starting after the procedure and lasting longer than 24 hours, hospital stay longer than one day were considered as post-ERCP pancreatitis (PEP) [3].
The frequency of PEP has been reported as 1-40% in various studies [3]. Predicting possible complications and their course is important to reduce risk and mortality [3]. Various risk factors have been identified for the development of complications, especially PEP [3]. The relationship between PEP and female gender, young age, previous PEP history, presence of recurrent pancreatitis attacks, sphincter of Oddi dysfunction, percutaneous biliary intervention and difficult cannulation has been proven in various studies [2, 4].
Discussions on risk factors for PEP are still ongoing. Further studies are needed to clarify the early and definitive diagnosis, risk and severity classification, as well as the treatment of pancreatitis after ERCP [3].
The aim of this study is to determine the risk factors in patients who develop PEP in ERCPs performed in our clinic and to share our experiences.
Material and Methods
In this study, 1110 ERCP data performed in Şanlıurfa Mehmet Akif Inan Training and Research Hospital General Surgery ERCP Unit between May 2019 and December 2021 were analyzed retrospectively. Ethics committee approval for the study was obtained from Harran University Clinical Research Ethics Committee (13.12.2021-22/13.00). All selected ERCP experiences were interventions by a single general surgeon. PEP developed in 222 patients after ERCP. ERCP indications, age, gender, clinical findings and comorbidities of patients who developed PEP were examined. Patients under 18 years of age were excluded from the study.
Patients who were followed up and treated with the diagnosis of pancreatitis were evaluated with clinical, laboratory and imaging methods (CECT). The revised Atlanta Classification was used for staging of severity in acute pancreatitis [5].
Statistical Analysis
Data were evaluated using the IBM SPSS Statistics 20.0 package software (IBM, New York, USA). Data were given as number of units (n), percentage (%) and mean±standard deviation. Statistical analyzes were performed using unpaired t-test and chi-square test depending on the appropriate variable. A p -value <0.05 was considered significant.
Results
Of the 1100 patients who underwent ERCP, 222 (20.1%) developed clinically and laboratory proven PEP. Comorbidity was found to increase PEP development of PEP in patients who underwent ERCP (x2=3.93; p=0.047). Stent insertion in patients who underwent ERCP was found to increase the rate of PEP development (x2=9.1; p=0.002). It was found that stent insertion in ERCP did not affect the development of PEP according to comorbidity status (x2=1.03; p=0.25). It was found that performing ERCP with the pre-incision method decreased the probability of developing PEP (x2=18.28; p<0.0001). ERCP indications were found to have no effect on the development of PEP (x2=1.07; p=0.90). Patients who developed PEP had a high rate of hospitalization in the intensive care unit (x2=17.02; p<0.0001) (Table 1). In this series, the incidence of PEP was 172 in the first 800 patients and 50 in the last 300 patients.
Of the 1110 patients in whom we performed ERCP, 422 had additional disease [(Hypertension (n=147), diabetes mellitus (n=121), coronary artery disease (n=40), Congestive heart failure (n=24), Hyperlipidemia (n=11), Cerebro Vascular Disease (n=13), Hypothyroidism (n=8), Chronic renal failure (n=9), Hydatid Cyst (n=4), GIS Malignancy (n=2), Inflammatory Bowel Disease (n=2) and Others (n=41)]. PEP developed in 98 patients with additional disease.
Discussion
In this study, it was found that gender, comorbidity, stenting and pre-incision increased PEP in patients who underwent ERCP (Table 1). In addition, it was found that patients who developed PEP had a higher need for intensive care compared to those who did not. The important aspect of this study is that all 1100 ERCP procedures were performed by a single general surgeon. In this way, personal differences were eliminated. It was observed that the PEP development rate decreased as the operator’s experience increased.
PEP is the most common complication in the ERCP procedure and may be risky in patients with high risk factors [6]. The pathophysiology of PEP is still controversial. It has a multifactorial pathophysiology. However, evaluation of patient-related risk factors, pharmacological measures, and technical procedures applied to the patient may contribute to the prevention of PEP [7]. Identifying patients with high risk factors for PEP is one of the most important aspects for the prevention of PEP [7]. Patients with high risk factors should be carefully evaluated and alternative treatment and diagnostic techniques may be preferred instead of ERCP [7].
Most of the studies in the literature have shown that young age, female gender, absence of chronic pancreatitis, suspected Sphincter of Oddi dysfunction (SOD), recurrent pancreatitis and previous PEP history play a very important role in creating a high risk for PEP [3, 7, 8]. The most common limit accepted in studies investigating the relationship between age and PEP occurrence is 60 years, and 70 years is ranked2nd in the literature [3, 9, 10]. In this study, the mean age of the patients who developed PEP was found to be 60.2±19.0 years. In a retrospective cohort study by Katsinelos et al. involving a total of 2,715 patients, it was revealed that the history of acute pancreatitis was the only important risk factor, and the role of age and gender in the development of the disease was denied [11]. Based on 7 prospective, multicenter studies, SOD, female gender, younger age, and previous history of pancreatitis are risk factors for PEP [3].
The incidence of PEP has been reported to be 2.1-24.4% due to heterogeneous patient populations, different levels of endoscopic expertise, and procedure differences. In this study, the frequency of PEP was found to be 20.1%. This rate is in line with previously reported studies. Operator experience is also important in PEP. The lack of appropriate training or experience of endoscopists has also been associated with the development of PEP. A multicenter study (1191 patients) by Lee et al. showed that less experienced endoscopists (<200 ERCPs) are an independent risk factor for PEP [12]. In this study, it was observed that the rate of PEP development in patient series decreased as experience increased. It is thought that this finding should be taken into account in ERCP applications.
Prophylactic pancreatic stent placement has been reported to be effective in preventing PEP [13]. Our findings support these studies. In this study, it was found that the rate of PEP decreased significantly in patients with stent placement.
In this study, it was found that PEP development was less in patients who underwent the Pre-incision method. Pancreatic stent placement and endoscopic nasobiliary drainage from procedural techniques have been reported to be beneficial in the prevention of PEP [7]. These results underline the importance of appropriate interventional method.
It has been reported that the method to be preferred in patients with high risk factors according to the ERCP indication is effective in preventing PEP [14, 15]. Therefore, identifying patient-related risk factors is one of the most important aspects of prevention from PEP. However, in our study, it was found that there was no significant difference between the ERCP indication and the development of PEP.
The limitation of this study is that comorbidity rates were not determined in patients who did not develop PEP.
Conclusion
Early diagnosis and severity stratification of pancreatitis after ERCP greatly influence the outcome of the patient. Discussions on risk factors for PEP are still ongoing. Further studies are needed to clarify the early and definitive diagnosis, risk and severity classification, as well as the management of pancreatitis after ERCP.
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
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Esat Taylan Ugurlu. Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis; Evidence from 1100 ercp cases. Ann Clin Anal Med 2022;13(11):1293-1295
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