Depression, anxiety, stress, and health quality of life in vulvovaginal candidiasis

Depression, anxiety, stress, and health quality of life in vulvovaginal candidiasis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Depression, anxiety, stress, and health quality of life in vulvovaginal candidiasis Fahimeh Baghbani, Laleh Tajadiny, Setareh Aghakouchak-Afshari, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3988836/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Candidal vulvovaginitis is a common fungal infection among women, affecting nearly 80% of adult women. Chronic and recurrent cases significantly impact the quality of life, often due to prolonged and indiscriminate use of antifungal drugs, leading to resistance. This resistance can result in prolonged, costly treatment and notable emotional and psychological effects. The study aims to compare the psychological effects of depression, anxiety, and stress, as well as quality of life, in women with recurrent candidal vulvovaginitis to those with non-recurrent forms of infection. Methods The study first gathered demographic information from individuals with recurring and non-recurring candidal vulvovaginitis in health centers across Kerman City using a relevant questionnaire. Additionally, the impact of Candida vulvaginitis infection on stress, anxiety, and depression levels was assessed using a researcher-made questionnaire adapted from the DASS questionnaire. Furthermore, the participants' physical and mental well-being was evaluated using the SF-36 health-related quality of life questionnaire, consisting of 8 questions and 6 components. Results A total of 84 women participated in the study: 42 with recurrent vulvovaginal candidiasis (RVVC) and 42 without RVVC. After analyzing the data from the completion of two questionnaires by patients in the two groups, a significant difference in Quality of Life (QoL) was observed between them (P=0.03). However, no significant differences were found between the two groups in terms of depression (P=0.674), anxiety (P=0.938), and stress (P=0.615). Conclusion Vulvovaginal candidosis significantly affects women's QoL and mental health worldwide. While its impact varies among infection forms, no significant differences were found in stress, anxiety, and depression. Clinical intervention should focus on addressing these effects, and further research with control groups is warranted for deeper understanding. Candidiasis Recurrent Vulvovaginal Candidiasis Quality of Life Depression Anxiety Stress Introduction Genital tract infections pose common challenges for women ( 1 ). Vulvovaginitis stands as a prevalent impetus for women seeking consultation with healthcare professionals, demonstrating associations with detrimental reproductive and psychosocial outcomes. Vaginitis is responsible for more than 10 million office visits annually ( 2 ). Vaginitis, characterized by inflammation and infection of the vagina, presents symptoms such as itching, irritation, unusual malodorous discharge, leukorrhea, and dyspareunia. The World Health Organization identifies Candida, Trichomonas, and bacterial infections as primary contributors to vaginitis, collectively constituting about 90% of vaginal infections ( 1 ). Vulvovaginal candidiasis (VVC) represents inflammation and infection of the vagina with the Candida species. It is the second most common cause of vaginitis, after bacterial vaginosis (BV) ( 2 ). Research indicates that the incidence of this issue is infrequent before menarche and diminishes notably in postmenopausal ages ( 1 ). Conditions affecting the vulval skin frequently result in a substantial disease burden, characterized by debilitating symptoms and anatomical changes. These conditions, being chronic in nature, exert a profound impact on the physical, psychological, and sexual health of many women, influencing both the manifestation of symptoms and the effects of treatment ( 3 ). Recurrent Vulvovaginal Candidiasis (RVVC) is defined as experiencing three or more bacteriologically proven episodes of VVC per year, with an estimated prevalence of 5% among menstruating women. The definition of RVVC is consensus-based rather than evidence-based ( 4 , 5 ). Cronich Vulvovaginal Candidiasis (CVVC), in contrast to RVVC, is characterized by continuous and unremitting symptoms rather than episodic occurrences ( 4 ). Various studies conducted in diverse countries have revealed differing rates of candidiasis infection ( 1 ). The prevalence of candidiasis varies across different regions. In Nigeria, the reported rate was 6.5%, while in Turkey, using both culture method and clinical diagnosis, it was reported as 17.4% and 14.1%, respectively. Another study from Nigeria reported a prevalence of 18.9% for this infection ( 6 ). In Iran, in the cities of Tabriz, Sanandaj, Hamedan, Yazd, and Shiraz, the prevalence was reported to be between 25–45% ( 7 ). Recurrent vulvovaginal candidiasis (RVVC) is defined as experiencing four or more episodes of candidiasis per year. According to a study conducted across five European countries and the United States, the prevalence of RVVC ranged from 29–49% ( 8 ). In another study in Sweden in 2009, the incidence of RVVC, using fungal culture for diagnosis, was estimated as 29.8% ( 9 ). In Iran, in Sari, the incidence was reported as 24.2% ( 1 ). The incidence of vaginal candidiasis is influenced by various factors, including the use of antibiotics, pregnancy, diabetes mellitus, oral contraceptive pills, human immunodeficiency virus (HIV) infection, wearing tight and nylon underwear without proper ventilation, vaginal douching, immunosuppressive drug use, intrauterine device placement, numerous sexual activities, local vaginal immune deficiency, the use of tampons over sanitary napkins, and engagement in oral sex. It's noteworthy that each of these factors may contribute to the incidence of recurrent chronic candida.There is also some largely indirect evidence that psychological problems contribute to the incidence of RVVC ( 10 ). Depression, helplessness, hopelessness, and stressful life events may lead to the disease by inhibiting the immune systems of individuals ( 1 ). According to a study, 77% of women were clinically disease-free after 1 year of long-term maintenance therapy, whereas 60% were re-colonised. The poor therapeutic outcome in RVVC leads to a massive impairment of quality of life (QoL) as well as sexual health in affected women ( 11 ). Besides vulvovaginal discomfort, including pain, burning, and itching, dysuria and dyspareunia, recurrent vulvovaginal candidiasis (RVVC) might be indicated by the presence of redness, swelling, abrasions, and cracks in the vulvovaginal region. In more serious instances, vulvodynia, characterized by persistent pain, could also manifest ( 12 ). Patients often experience enduring pain and functional limitations, such as avoiding sexual intercourse, ongoing dysuria, and depression, leading to a notable decline in quality of life. Although the precise connection between vulvodynia and prior Candida infections remains incompletely explored, evidence suggests that over 70% of women with vulvodynia have a background of recurrent vulvovaginal candidiasis (RVVC) ( 13 – 16 ). In some studies, women with RVVC showed significantly lower QoL, especially regarding satisfaction with general health, well-being, self-perception of their own physical and mental health, and satisfaction with social interactions, when compared to a healthy control group. The authors found significantly impaired QoL scores in affected women, even when they previously received treatment ( 10 , 12 ). This dysfunction is recognized to cause notably reduced productivity in both professional and daily activities. Research has indicated elevated levels of burnout and stress among women with RVVC, highlighting its impact on overall functioning. Despite access to extended treatment options, the recurrence of vulvovaginal candidiasis persists as a prevalent challenge ( 12 ). The aforementioned research background highlights the chronic nature of a disease that is among the most common chronic disorders of the female reproductive system, accompanied by bothersome physical symptoms such as itching, inflammation, and two sexual dysfunction disorders. On the other hand, it imposes considerable financial costs on patients, emphasizing the doubled importance of paying attention to the mental health of these women. This study delves into the comparative investigation of the specific impact of vulvovaginal candidiasis on the levels of stress, anxiety, and depression caused by the symptoms in affected women, as well as their quality of life among both recurrent and acute affected groups. Materials and methods Initially, the confidentiality of the results and the preservation of confidentiality were explained, and written informed consent was obtained from the individual for sample collection. All patients presenting symptoms of vulvovaginitis (burning, itching, pain in the vulva and vagina, and altered cheesy discharge) were included in the study. Patients who had used topical or oral antifungal medications in the two weeks before sampling were excluded from the study. After selecting individuals with vulvovaginal candidiasis, their demographic information including age, nationality, marital status, number of children, education level, employment status, duration of illness, and duration of treatment was gathered through interviews and recorded on the respective questionnaire forms. What matters at this stage is that based on the census sampling method, women experiencing the recurrence of the disease three times or more in the past year were placed in the recurrent group, while those experiencing the disease twice or less in the past year were placed in the acute group. The primary questionnaire, which assesses depression, anxiety, and stress associated with vulvovaginal infections, as well as the quality of life questionnaire related to health, was completed by women in both groups. Cases diagnosed with acute or chronic vulvovaginitis in their medical history and clinical examination completed the questionnaires after receiving an explanation and providing informed consent. After collecting data from the samples in both groups, the data were categorized and classified, and central tendency and dispersion indices were calculated using appropriate software. They were presented in the form of frequency tables and suitable diagrams. Tools: SF-36 Questionnaire: The SF-36 questionnaire consists of 36 items, which are used to calculate eight subscales: physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH). Scores for the SF-36 scales range between 0 and 100, with higher scores indicating a better HRQOL ( 17 ). Researcher-developed Questionnaire: The researcher-developed questionnaire is the assessment Tool for depression, anxiety, and stress associated with vulvovaginal infections which was derived from the DASS questionnaire. This tool has achieved an acceptable level of content and face validity. The Depression, Anxiety and Stress Scale − 21 Items (DASS-21) is a set of three self-report scales designed to measure the emotional states of depression, anxiety and stress. Each of the three DASS-21 scales contains 7 items, divided into subscales with similar content ( 18 ). Study design: The present study is a descriptive cross-sectional investigation conducted in 2021 to examine and compare anxiety, stress, depression, and health-related quality of life in women with recurrent and acute forms of vulvovaginal candidiasis in the cities of Kerman and Sirjan. Participants: The study population included all women suffering from vulvovaginal candidiasis who had been referred to healthcare centers in Kerman and Sirjan between May 2020 and December 2021 with symptoms of vulvovaginitis and expressed consent to participate in the study. Inclusion criteria: The eligibility criteria for patients were as follows: (a) Acute or chronic vulvovaginitis based on clinical diagnosis (b) willingness to participate in the study (c) absence of diagnosed psychiatric illness by a physician. Exclusion criteria: We excluded the patients with these conditions from the study, just if the participants had inadequate responses to questionnaires. Sample size calculation: The sample size, calculated based on a similar previous study ( 19 ) with a confidence level of 95% and a power of 80% using the formula for comparing proportions in two independent communities, was determined. In the previous study, the anxiety ratio was reported as 73% in the intervention group and 43% in the control group. Eventually, a sample size of 42 individuals was obtained in each group. Statistical analysis: For data analysis, appropriate parametric and non-parametric tests were employed based on the distribution type of quantitative data to determine significant relationships among relevant variables, using a significance level of 0.05 and a statistical power of 80%. To compare qualitative variables such as history of the disease, medication history, nationality, marital status, employment status, and education level between the recurrent and acute vulvovaginal candidiasis groups, the chi-square test was utilized. Furthermore, for comparing quantitative variables like age, number of children, disease occurrences in a year, and duration of treatment between the two groups, the independent t-test was employed. If the data did not conform to a normal distribution, the independent t-test was still utilized for comparing scores of anxiety, stress, depression, and quality of life between the two groups. Ethical Consideration: In this study, patient information has been kept confidential, and sampling was carried out with patient consent without any additional interference in the patient's treatment process. Patients entered the study upon their consent and completion of the informed consent form. Result Tables 1 and 2 delineate clinical and demographic characteristics across the two groups. Disparities were observed in age(p < 0.001), number of children (p = 0.01), level of education (p = 0.028), duration of infection (p < 0.001), history of infection with similar symptoms (p < 0.001), hypertension (p = 0.038) and diabetes (p = 0.012). Therefore, linear regression analysis was employed to assess the impact of these variables on comparing the groups regarding their quality of life. In Table 3 , linear regression models were utilized to compare group differences in subdomains of the SF-36 questionnaire, revealing notable variations in mean scores across subdomains such as physical functioning (p = 0.021), role physical health (P = 0.029), role emotional (p = 0.037), and health change (p = 0.002), indicating higher scores in patients with acute candidiasis compared to those with recurrent candidiasis. Additionally, the total score of quality of life was significantly higher in the acute group than in the recurrent group (p = 0.03). Table 4 showcases the comparison between the groups in terms of anxiety, depression, and stress ( based on the questionnaire taken from the DASS questionnaire) using linear regression models. Noteworthy, there were no significant differences observed between the groups in mean anxiety (p = 0.938), depression (p = 0.674), and stress (p = 0.615) scores. Table 1 Demographic characteristics of patients in the two groups Variable Group Title of exam Test statistics P-Value Acute number (Percentage) Recurrent number (Percentage) Age ≤ 35 45(50) 4( 19 ) Chi-Square 11.011a 0.001 > 35 30(40) 17(81) Nationality Iranian 70(93.3) 20(95.2) Fisher 0.102a 1000 Afghan 5(6.7) 1(4.8) Marital status Single 13(17.3) 1(4.8) Fisher 2.082a 0.291 Married 62(82.7) 20(95.2) The number of children 0 9(13.8) 5(23.8) Chi-Square Pearson 0.019 1 19(29.2) 2(9.5) 2 19(29.2) 2(9.5) ≥ 3 18(27.7) 12(57.1) Occupation Student and Unemployed 11(14.7) 1(4.8) Fisher’s exact test 2.813 0.260 Housewife 45(60) 17(81) Freelancer and employee 19(25.3) 3(14.3) Education illiterate 6(8.2) 6(30) Fisher’s exact test 8.8285 0.012 Diploma and less 32(43.8) 10(50) Bachelor’s degree and higher 35(47.9) 4( 20 ) Table 2 Clinical characteristics of patients in the two groups Variable Group Title of exam Test statistics P-Value Acute number (Percentage) Recurrent number (Percentage) Duration of infection 1≥ 34(50.0) 2(9.5) Chi-Square Pearson 19.609a 0.000 2 13(19.1) 1(4.8) ≥ 3 21(30.9) 18(85.7) Duration of treatment 0 9(23.5) 6(30) Fisher’s exact test 6.679 0.074 1≥ 20(50.0) 4( 20 ) 2 6(15.0) 3( 15 ) 3≤ 5(12.5) 7(35.5) History of infection with similar symptoms Yes 32(42.7) 21(100) Chi-Square Pearson 21.808a 0.000 No 43(57.3) 0(0.00) Symptoms of infection Altered secretion 45(70.3) 14(66.7) Fisher’s exact test 2.305 0.295 Pain, itching or burning 14(21.9) 3(14.3) All 5(7.8) 4(19.0) Method of contraception Condom 18(28.1) 3(15.0) Fisher’s exact test 8.374 0.121 Natural panning 11(17.2) 3(15.0) Nothing 9(14.1) 3(15.0) Menopause 5(7.8) 7(35.0) Tablet 9(14.1) 2( 10 ) Other cases 12(18.8) 2( 10 ) Taking psychiatric drugs Yes 6(8.0) 3(14.3) Fisher’s exact test 0.763a 0.405 No 69(92.0) 18(85.7) Blood pressure Yes 5(6.7) 5(23.8) Fisher’s exact test 5.167a 0.038 No 70(93.3) 16(76.2) Diabetes Yes 7(9.3) 7(33.3) Fisher’s exact test 7.586a 0.012 No 68(90.7) 14(66.7) Immune system Yes 1(1.3) 2(9.5) Fisher’s exact test 3/636a 0.120 No 74(98.7) 19(90.5) Cortone use Yes 0(0.00) 1(4.8) Fisher’s exact test 3.609a 0.219 No 75(100) 20(95.2) rheumatologic Yes 2(2.7) 0(0.00) Fisher’s exact test 0.572a 1.000 No 73(97.3) 21(100) Table 3 Comparison of the patients’ QoF in the two groups Variable Group P-Value Acute standard deviation ± Average Recurrent standard deviation ± Average Physical Functioning 84.66 ± 25.90 54.28 ± 32.29 0.021 Role Physical Health 82.33 ± 35.53 36.90 ± 38.42 0.029 Role Emotional 77.77 ± 38.49 45.00 ± 42.26 0.037 Energy Fatigue 60.81 ± 18.45 41.90 ± 17.56 0.597 Emotional Well Being 66.54 ± 17.37 52.00 ± 15.64 0.433 Social Functioning 74.83 ± 19.87 58.33 ± 12.07 0.072 Pain 73.73 ± 24.84 54.28 ± 22.37 0.993 General Health 61.46 ± 19.84 49.04 ± 18.41 0.882 Health Change 51.33 ± 18.33 33.75 ± 23.33 0.002 Quality Total 71.17 ± 19.60 47.27 ± 18.31 0.037 Table 4 Comparison of the patients’ psychological characteristics in the two groups Variable Group P-Value Acute standard deviation ± Average Recurrent standard deviation ± Average Depression 9.70 ± 4.24 13.19 ± 5.8 0.674 Anxiety 8.81 ± 3.5 10.95 ± 4.6 0.938 Stress 9.70 ± 4.2 13.19 ± 5.8 0.615 Discussion The study revealed that women with recurrent vulvovaginal candidiasis (RVVC) exhibited a significantly greater adverse impact on their quality of life, as evidenced by mean values (± SD) of 47.27 ± 18.31 compared to the acute group 71.17 ± 19.60. Furthermore, the study's findings indicated that such a significant negative effect was evident in certain subdomains of quality of life in the RVVC group, including physical functioning (54.28 ± 32.29), physical role functioning (36.90 ± 38.42), emotional role functioning (45.00 ± 42.26), and health change (33.75 ± 23.33) compared with the acute VVC group. However, no significant differences were observed between the two groups in other subdomains of the health-related quality of life questionnaire (SF-36). Besides different impacts on Quality of life among these two groups, it was observed that depression, anxiety, and stress were not significantly different between them. Exploring the background of the studies, we found no research exactly comparing acute vulvovaginal candidiasis (VVC) with recurrent vulvovaginal candidiasis (RVVC) in terms of Quality of Life (QoL) and other psychological factors. It appears that this study, for the first time, compared the QoL and also stress, anxiety, and depression of RVVC with VVC. In a previous study, the Short-Form Health Survey (SF-36) was utilized to measure health-related QoL in 101 healthy women and 102 women with RVVC. The results demonstrated that women with RVVC had lower physical and mental composite scores compared to controls ( 10 ). This finding is consistent with the current study's results, indicating that the RVVC group experienced more negative effects than the VVC group in the physical functioning subdomain. On the other hand, a study focusing on patients suffering from chronic vulvovaginal candidiasis (CVVC) reported a very significant impact on their Quality of Life (QoL) before and after treatment. CVVC, unlike RVVC, is characterized by continuous and unremitting symptoms rather than episodic occurrences ( 4 ). A similar finding was observed in a retrospective, single-center cohort study, which highlighted the immense impact of vulval disease on QoL, particularly in patients with CVVC. These findings underscore the significant influence of treatment on the lives of CVVC patients and emphasize the importance for clinicians to consider the effect of such infections on patients' QoL ( 3 ). A sub-analysis of a randomized, controlled, double-blinded study revealed that women with recurrent vulvovaginal candidiasis (RVVC) experienced high QoL impairment and sexual health issues. However, a 6-month maintenance treatment resulted in a significant improvement in both QoL and sexual health. Unlike our study, this investigation utilized the EQ-5D-5L questionnaire, which assesses various aspects including mobility, body hygiene, everyday routine, pain, and fear/depression ( 12 ). Despite similarities in finding an adverse effect on physical function in the RVVC group, our study did not find a significant difference in pain and depression between recurrent and acute infected women. Furthermore, Aballéa et al. conducted a study on QoL in RVVC patients across five European countries (Spain, Germany, France, the United Kingdom, and Italy) and the United States, using both the EQ-5D-5L and 36-item short form survey (SF-36). They reported that the QoL of women during and between acute episodes was significantly lower than that of the average population, even with therapy ( 20 ). It's noteworthy that in our study, selected patients were not undergoing treatment, whereas many of the conducted studies investigated the difference in QoL before and after treatment. It has been demonstrated that there is a strong relationship between vaginal infections and health-related quality of life (QoL) in women diagnosed with such infections, significantly impacting their daily activities. Infected women with vaginal infections are more likely to experience effects on emotional well-being and role limitations due to physical problems. SF-36 QoL dimensions were found to be affected among women with recurrent vulvovaginal candidiasis (RVVC) in general ( 21 ). These infections pose a threat to women's health and have negative impacts on their QoL. Due to the personal nature of vaginal infections, they are often avoided or overlooked. Despite the severe influence of symptoms on the QoL of affected women, vaginal infections have historically been relatively underexplored subjects and may have been viewed as taboo or stigmatized issues ( 22 ). Another study demonstrated that women with chronic vaginal symptoms such as recurrent vulvovaginal candidiasis (RVVC), vestibulitis syndrome, and inflammatory vulvovaginitis had high rates of mental disorders. The results revealed a significant relationship between depression, anxiety, and stress and a history of RVVC. These findings suggest that levels of depression, anxiety, and stress in patients with RVVC are higher than in healthy individuals. This finding aligns with another study which indicated that both chronic stress and reduced antioxidant capacity may serve as predisposing factors for RVVC. This implies that dysregulation of immune function, which can be associated with poorer mental health parameters, may increase the risk of RVVC ( 1 ). Some studies have also indicated that patients with RVVC are more likely to suffer from clinical depression, poorer self-esteem, high stress levels, feelings of frustration, sexual dysfunction, and dissatisfaction with life ( 4 ).However, although our study did not find meaningful differences in the levels of anxiety, stress, and depression between the recurrent and acute groups, it appears that for more precise results, a control group (consisting of healthy women) may be necessary. This study should be considered as a preliminary investigation laying the groundwork for larger, prospective interventional studies in patients with vulvovaginal candidiasis (VVC). A better understanding of the psychological effects in women with candidal vulvovaginitis and providing suitable solutions to reduce psychological problems in these patients are essential goals. Ultimately, improving the health of society as a whole is a practical objective of this research. Conclusion In conclusion, vulvovaginal candidosis affects numerous women worldwide, negatively impacting their Quality of Life (QoL) and psychological well-being, including depression, stress, and anxiety. The present study's findings indicate that the severity of its impact on QoL varies between different forms of the infection (recurrent and acute), while no significant differences were observed in terms of stress, anxiety, and depression. Clinical practice should prioritize attention and intervention to address the effects of vulvovaginal candidosis on patients' QoL. Furthermore, further studies are needed to delve deeper into the correlation between this infection and QoL, as well as its influence on patients' mental health, ideally incorporating a control group for more comprehensive understanding. Declarations Ethics approval and consent to participate This study achieved the ethical code IR.KMU.REC.1399.086, from ethic committee of Kerman University of Medical Sciences. Informed consent was obtained from all subjects. Consent for publication Not applicable Availability of data and materials Data will be available per request via contact corresponding author Atefeh Ahmadi ( [email protected] /00989133979580). Competing interests All authors declare no competing interest Funding Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran (grant number: 98001093) Authors' contributions F.B. wrote the last draft, L.T. and M.SH. and A.KB. and M.D. collected the data, M.G. and F.M. wrote the methodology and data analysis, S.AA. idea of the research and wrote the proposal, A.A. did the research management and wrote the first draft Acknowledgements Thanks a lot from Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences to support this research. References Moshfeghy Z, Tahari S, Janghorban R, Najib FS, Mani A, Sayadi M. 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Aballéa S, Guelfucci F, Wagner J, Khemiri A, Dietz J-P, Sobel J, et al. Subjective health status and health-related quality of life among women with recurrent vulvovaginal candidosis (RVVC) in Europe and the USA. Health and quality of life outcomes. 2013;11(1):1-13. Rashad MR, Mohamed HSE, Emara HA, Elsabiey FI, Salim HM. Quality Of Life among Women Diagnosed With Vaginal Infection. Zagazig Nursing Journal. 2022;18(1):52-69. Reichman O, Margesson LJ, Rasmussen CA, Lev-Sagie A, Sobel JD. Algorithms for Managing Vulvovaginal Symptoms—a Practical Primer. Current infectious disease reports. 2019;21:1-9. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3988836","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":276342994,"identity":"a4d3c187-7165-4bd1-9a35-1161222b740f","order_by":0,"name":"Fahimeh Baghbani","email":"","orcid":"","institution":"Kerman University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fahimeh","middleName":"","lastName":"Baghbani","suffix":""},{"id":276342995,"identity":"d25906f1-67ba-482d-a9de-798c49092da1","order_by":1,"name":"Laleh Tajadiny","email":"","orcid":"","institution":"Kerman University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Laleh","middleName":"","lastName":"Tajadiny","suffix":""},{"id":276342996,"identity":"3b7b116b-5a15-445f-a6ba-364514e6ea9f","order_by":2,"name":"Setareh Aghakouchak-Afshari","email":"","orcid":"","institution":"Jiroft University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Setareh","middleName":"","lastName":"Aghakouchak-Afshari","suffix":""},{"id":276342997,"identity":"cdec7aeb-6103-4c2b-aa7c-9ca5a504ba0d","order_by":3,"name":"Maryam Soleimani-Houni","email":"","orcid":"","institution":"Jiroft University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Maryam","middleName":"","lastName":"Soleimani-Houni","suffix":""},{"id":276342998,"identity":"4b95ecfd-9be1-4cec-b99b-4a94b00c70af","order_by":4,"name":"Ali Khaksar Baniasadi","email":"","orcid":"","institution":"Kerman University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ali","middleName":"Khaksar","lastName":"Baniasadi","suffix":""},{"id":276342999,"identity":"927c9c64-74f5-4d6f-9990-191418acb847","order_by":5,"name":"Masumeh Ghazanfarpour","email":"","orcid":"","institution":"Kerman University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Masumeh","middleName":"","lastName":"Ghazanfarpour","suffix":""},{"id":276343000,"identity":"d099eb51-e997-4116-ac70-c6d4d4246280","order_by":6,"name":"Firoozeh Mirzaee","email":"","orcid":"","institution":"Kerman University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Firoozeh","middleName":"","lastName":"Mirzaee","suffix":""},{"id":276343001,"identity":"3ce4118f-9673-43f0-a506-f73a9c7aeebb","order_by":7,"name":"Maryam Dehghanipour","email":"","orcid":"","institution":"Sirjan University of Medical Sciences","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Maryam","middleName":"","lastName":"Dehghanipour","suffix":""},{"id":276343002,"identity":"746a48b8-ae84-4a47-94eb-7ca1e1f12e5b","order_by":8,"name":"Atefeh Ahmadi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAklEQVRIie3PPUvEMBjA8YRCpitdvW9hJ0c/iItF0OnZO9QjRyFd1DmD9r7C3dK55YHcUnA9UPDKgZsQF+kg4lMRB6GtboL5Q14I+RHCmMv1BxM0LGMlLVFmbUyr58lBEgjG9SdRXNcd4cNkqr7IsfB81Z2NkP2HtJI2uT8KshO18/Nz2hBp46KfGBHNtXkEXTdZeFOsQSOX/KK+GyCTg91EIMhNJPeeCgOSiMdVPzk0wXP6+oaw6Ih/bWAxRugVnnKFsNxEaurLBJbj5DScX14hrOomDbUpYUWkGvwLYiPbF4R8fdZsbTKD/BarbRv3k+/hx1z++D41+81ll8vl+ie9A/X0boifmwfXAAAAAElFTkSuQmCC","orcid":"","institution":"Kerman University of Medical Sciences","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Atefeh","middleName":"","lastName":"Ahmadi","suffix":""}],"badges":[],"createdAt":"2024-02-25 19:30:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3988836/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3988836/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":58187666,"identity":"1f104d6b-47e4-4f1e-9e4d-441e7305484c","added_by":"auto","created_at":"2024-06-12 07:44:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":543145,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3988836/v1/bde932ec-d051-4e8c-a7c8-58b60217a3ab.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Depression, anxiety, stress, and health quality of life in vulvovaginal candidiasis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGenital tract infections pose common challenges for women (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Vulvovaginitis stands as a prevalent impetus for women seeking consultation with healthcare professionals, demonstrating associations with detrimental reproductive and psychosocial outcomes. Vaginitis is responsible for more than 10\u0026nbsp;million office visits annually (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Vaginitis, characterized by inflammation and infection of the vagina, presents symptoms such as itching, irritation, unusual malodorous discharge, leukorrhea, and dyspareunia. The World Health Organization identifies Candida, Trichomonas, and bacterial infections as primary contributors to vaginitis, collectively constituting about 90% of vaginal infections (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eVulvovaginal candidiasis (VVC) represents inflammation and infection of the vagina with the Candida species. It is the second most common cause of vaginitis, after bacterial vaginosis (BV) (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Research indicates that the incidence of this issue is infrequent before menarche and diminishes notably in postmenopausal ages (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Conditions affecting the vulval skin frequently result in a substantial disease burden, characterized by debilitating symptoms and anatomical changes. These conditions, being chronic in nature, exert a profound impact on the physical, psychological, and sexual health of many women, influencing both the manifestation of symptoms and the effects of treatment (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eRecurrent Vulvovaginal Candidiasis (RVVC) is defined as experiencing three or more bacteriologically proven episodes of VVC per year, with an estimated prevalence of 5% among menstruating women. The definition of RVVC is consensus-based rather than evidence-based (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Cronich Vulvovaginal Candidiasis (CVVC), in contrast to RVVC, is characterized by continuous and unremitting symptoms rather than episodic occurrences (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eVarious studies conducted in diverse countries have revealed differing rates of candidiasis infection (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). The prevalence of candidiasis varies across different regions. In Nigeria, the reported rate was 6.5%, while in Turkey, using both culture method and clinical diagnosis, it was reported as 17.4% and 14.1%, respectively. Another study from Nigeria reported a prevalence of 18.9% for this infection (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In Iran, in the cities of Tabriz, Sanandaj, Hamedan, Yazd, and Shiraz, the prevalence was reported to be between 25\u0026ndash;45% (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Recurrent vulvovaginal candidiasis (RVVC) is defined as experiencing four or more episodes of candidiasis per year. According to a study conducted across five European countries and the United States, the prevalence of RVVC ranged from 29\u0026ndash;49% (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). In another study in Sweden in 2009, the incidence of RVVC, using fungal culture for diagnosis, was estimated as 29.8% (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). In Iran, in Sari, the incidence was reported as 24.2% (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe incidence of vaginal candidiasis is influenced by various factors, including the use of antibiotics, pregnancy, diabetes mellitus, oral contraceptive pills, human immunodeficiency virus (HIV) infection, wearing tight and nylon underwear without proper ventilation, vaginal douching, immunosuppressive drug use, intrauterine device placement, numerous sexual activities, local vaginal immune deficiency, the use of tampons over sanitary napkins, and engagement in oral sex. It's noteworthy that each of these factors may contribute to the incidence of recurrent chronic candida.There is also some largely indirect evidence that psychological problems contribute to the incidence of RVVC (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Depression, helplessness, hopelessness, and stressful life events may lead to the disease by inhibiting the immune systems of individuals (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAccording to a study, 77% of women were clinically disease-free after 1 year of long-term maintenance therapy, whereas 60% were re-colonised. The poor therapeutic outcome in RVVC leads to a massive impairment of quality of life (QoL) as well as sexual health in affected women (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Besides vulvovaginal discomfort, including pain, burning, and itching, dysuria and dyspareunia, recurrent vulvovaginal candidiasis (RVVC) might be indicated by the presence of redness, swelling, abrasions, and cracks in the vulvovaginal region. In more serious instances, vulvodynia, characterized by persistent pain, could also manifest (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Patients often experience enduring pain and functional limitations, such as avoiding sexual intercourse, ongoing dysuria, and depression, leading to a notable decline in quality of life. Although the precise connection between vulvodynia and prior Candida infections remains incompletely explored, evidence suggests that over 70% of women with vulvodynia have a background of recurrent vulvovaginal candidiasis (RVVC) (\u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). In some studies, women with RVVC showed significantly lower QoL, especially regarding satisfaction with general health, well-being, self-perception of their own physical and mental health, and satisfaction with social interactions, when compared to a healthy control group. The authors found significantly impaired QoL scores in affected women, even when they previously received treatment (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). This dysfunction is recognized to cause notably reduced productivity in both professional and daily activities. Research has indicated elevated levels of burnout and stress among women with RVVC, highlighting its impact on overall functioning. Despite access to extended treatment options, the recurrence of vulvovaginal candidiasis persists as a prevalent challenge (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe aforementioned research background highlights the chronic nature of a disease that is among the most common chronic disorders of the female reproductive system, accompanied by bothersome physical symptoms such as itching, inflammation, and two sexual dysfunction disorders. On the other hand, it imposes considerable financial costs on patients, emphasizing the doubled importance of paying attention to the mental health of these women. This study delves into the comparative investigation of the specific impact of vulvovaginal candidiasis on the levels of stress, anxiety, and depression caused by the symptoms in affected women, as well as their quality of life among both recurrent and acute affected groups.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003eInitially, the confidentiality of the results and the preservation of confidentiality were explained, and written informed consent was obtained from the individual for sample collection. All patients presenting symptoms of vulvovaginitis (burning, itching, pain in the vulva and vagina, and altered cheesy discharge) were included in the study. Patients who had used topical or oral antifungal medications in the two weeks before sampling were excluded from the study. After selecting individuals with vulvovaginal candidiasis, their demographic information including age, nationality, marital status, number of children, education level, employment status, duration of illness, and duration of treatment was gathered through interviews and recorded on the respective questionnaire forms. What matters at this stage is that based on the census sampling method, women experiencing the recurrence of the disease three times or more in the past year were placed in the recurrent group, while those experiencing the disease twice or less in the past year were placed in the acute group. The primary questionnaire, which assesses depression, anxiety, and stress associated with vulvovaginal infections, as well as the quality of life questionnaire related to health, was completed by women in both groups. Cases diagnosed with acute or chronic vulvovaginitis in their medical history and clinical examination completed the questionnaires after receiving an explanation and providing informed consent. After collecting data from the samples in both groups, the data were categorized and classified, and central tendency and dispersion indices were calculated using appropriate software. They were presented in the form of frequency tables and suitable diagrams.\u003c/p\u003e \u003cp\u003eTools:\u003c/p\u003e \u003cp\u003eSF-36 Questionnaire: The SF-36 questionnaire consists of 36 items, which are used to calculate eight subscales: physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH). Scores for the SF-36 scales range between 0 and 100, with higher scores indicating a better HRQOL (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eResearcher-developed Questionnaire: The researcher-developed questionnaire is the assessment Tool for depression, anxiety, and stress associated with vulvovaginal infections which was derived from the DASS questionnaire. This tool has achieved an acceptable level of content and face validity. The Depression, Anxiety and Stress Scale \u0026minus;\u0026thinsp;21 Items (DASS-21) is a set of three self-report scales designed to measure the emotional states of depression, anxiety and stress. Each of the three DASS-21 scales contains 7 items, divided into subscales with similar content (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eStudy design:\u003c/p\u003e \u003cp\u003eThe present study is a descriptive cross-sectional investigation conducted in 2021 to examine and compare anxiety, stress, depression, and health-related quality of life in women with recurrent and acute forms of vulvovaginal candidiasis in the cities of Kerman and Sirjan.\u003c/p\u003e \u003cp\u003eParticipants:\u003c/p\u003e \u003cp\u003eThe study population included all women suffering from vulvovaginal candidiasis who had been referred to healthcare centers in Kerman and Sirjan between May 2020 and December 2021 with symptoms of vulvovaginitis and expressed consent to participate in the study.\u003c/p\u003e \u003cp\u003eInclusion criteria:\u003c/p\u003e \u003cp\u003eThe eligibility criteria for patients were as follows: (a) Acute or chronic vulvovaginitis based on clinical diagnosis (b) willingness to participate in the study (c) absence of diagnosed psychiatric illness by a physician.\u003c/p\u003e \u003cp\u003eExclusion criteria:\u003c/p\u003e \u003cp\u003eWe excluded the patients with these conditions from the study, just if the participants had inadequate responses to questionnaires.\u003c/p\u003e \u003cp\u003eSample size calculation:\u003c/p\u003e \u003cp\u003eThe sample size, calculated based on a similar previous study (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) with a confidence level of 95% and a power of 80% using the formula for comparing proportions in two independent communities, was determined. In the previous study, the anxiety ratio was reported as 73% in the intervention group and 43% in the control group. Eventually, a sample size of 42 individuals was obtained in each group.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis:\u003c/h2\u003e \u003cp\u003eFor data analysis, appropriate parametric and non-parametric tests were employed based on the distribution type of quantitative data to determine significant relationships among relevant variables, using a significance level of 0.05 and a statistical power of 80%. To compare qualitative variables such as history of the disease, medication history, nationality, marital status, employment status, and education level between the recurrent and acute vulvovaginal candidiasis groups, the chi-square test was utilized. Furthermore, for comparing quantitative variables like age, number of children, disease occurrences in a year, and duration of treatment between the two groups, the independent t-test was employed. If the data did not conform to a normal distribution, the independent t-test was still utilized for comparing scores of anxiety, stress, depression, and quality of life between the two groups.\u003c/p\u003e \u003cp\u003eEthical Consideration:\u003c/p\u003e \u003cp\u003eIn this study, patient information has been kept confidential, and sampling was carried out with patient consent without any additional interference in the patient's treatment process. Patients entered the study upon their consent and completion of the informed consent form.\u003c/p\u003e \u003c/div\u003e"},{"header":"Result","content":"\u003cp\u003eTables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e delineate clinical and demographic characteristics across the two groups. Disparities were observed in age(p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), number of children (p\u0026thinsp;=\u0026thinsp;0.01), level of education (p\u0026thinsp;=\u0026thinsp;0.028), duration of infection (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), history of infection with similar symptoms (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), hypertension (p\u0026thinsp;=\u0026thinsp;0.038) and diabetes (p\u0026thinsp;=\u0026thinsp;0.012). Therefore, linear regression analysis was employed to assess the impact of these variables on comparing the groups regarding their quality of life.\u003c/p\u003e \u003cp\u003eIn Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, linear regression models were utilized to compare group differences in subdomains of the SF-36 questionnaire, revealing notable variations in mean scores across subdomains such as physical functioning (p\u0026thinsp;=\u0026thinsp;0.021), role physical health (P\u0026thinsp;=\u0026thinsp;0.029), role emotional (p\u0026thinsp;=\u0026thinsp;0.037), and health change (p\u0026thinsp;=\u0026thinsp;0.002), indicating higher scores in patients with acute candidiasis compared to those with recurrent candidiasis. Additionally, the total score of quality of life was significantly higher in the acute group than in the recurrent group (p\u0026thinsp;=\u0026thinsp;0.03).\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e showcases the comparison between the groups in terms of anxiety, depression, and stress ( based on the questionnaire taken from the DASS questionnaire) using linear regression models. Noteworthy, there were no significant differences observed between the groups in mean anxiety (p\u0026thinsp;=\u0026thinsp;0.938), depression (p\u0026thinsp;=\u0026thinsp;0.674), and stress (p\u0026thinsp;=\u0026thinsp;0.615) scores.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic characteristics of patients in the two groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTitle of exam\u003c/p\u003e \u003cp\u003eTest statistics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP-Value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAcute\u003c/p\u003e \u003cp\u003enumber\u003c/p\u003e \u003cp\u003e(Percentage)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRecurrent\u003c/p\u003e \u003cp\u003enumber\u003c/p\u003e \u003cp\u003e(Percentage)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026le;\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45(50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eChi-Square\u003c/p\u003e \u003cp\u003e11.011a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30(40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17(81)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNationality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIranian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70(93.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20(95.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFisher\u003c/p\u003e \u003cp\u003e0.102a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAfghan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(4.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMarital status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSingle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(17.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFisher\u003c/p\u003e \u003cp\u003e2.082a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.291\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMarried\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62(82.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20(95.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eThe number of children\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(13.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(23.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eChi-Square\u003c/p\u003e \u003cp\u003ePearson\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19(29.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(9.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19(29.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(9.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18(27.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12(57.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eOccupation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStudent and Unemployed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(14.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eFisher\u0026rsquo;s exact test\u003c/p\u003e \u003cp\u003e2.813\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.260\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHousewife\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45(60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17(81)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFreelancer and employee\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19(25.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(14.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eEducation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eilliterate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6(30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eFisher\u0026rsquo;s exact test\u003c/p\u003e \u003cp\u003e8.8285\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiploma and less\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32(43.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10(50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBachelor\u0026rsquo;s degree and higher\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35(47.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics of patients in the two groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTitle of exam\u003c/p\u003e \u003cp\u003eTest statistics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP-Value\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAcute\u003c/p\u003e \u003cp\u003enumber\u003c/p\u003e \u003cp\u003e(Percentage)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRecurrent\u003c/p\u003e \u003cp\u003enumber\u003c/p\u003e \u003cp\u003e(Percentage)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eDuration of infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u0026ge;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34(50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eChi-Square\u003c/p\u003e \u003cp\u003ePearson\u003c/p\u003e \u003cp\u003e19.609a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(19.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(4.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21(30.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18(85.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eDuration of treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6(30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eFisher\u0026rsquo;s exact test\u003c/p\u003e \u003cp\u003e6.679\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.074\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u0026ge;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20(50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u0026le;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(35.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHistory of infection with similar symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32(42.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21(100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eChi-Square\u003c/p\u003e \u003cp\u003ePearson\u003c/p\u003e \u003cp\u003e21.808a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e43(57.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eSymptoms of infection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAltered secretion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45(70.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14(66.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eFisher\u0026rsquo;s exact test\u003c/p\u003e \u003cp\u003e2.305\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003e0.295\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePain, itching or burning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14(21.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(14.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAll\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4(19.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003eMethod of contraception\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCondom\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18(28.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003eFisher\u0026rsquo;s exact test\u003c/p\u003e \u003cp\u003e8.374\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e0.121\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNatural panning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(17.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(15.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNothing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(14.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(15.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMenopause\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(7.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(35.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTablet\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(14.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOther cases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(18.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTaking psychiatric drugs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3(14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFisher\u0026rsquo;s exact test\u003c/p\u003e \u003cp\u003e0.763a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.405\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69(92.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18(85.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eBlood pressure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(6.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5(23.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFisher\u0026rsquo;s exact test\u003c/p\u003e \u003cp\u003e5.167a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70(93.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16(76.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7(9.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7(33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFisher\u0026rsquo;s exact test\u003c/p\u003e \u003cp\u003e7.586a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68(90.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14(66.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eImmune system\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(1.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2(9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFisher\u0026rsquo;s exact test\u003c/p\u003e \u003cp\u003e3/636a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.120\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74(98.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19(90.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCortone use\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1(4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFisher\u0026rsquo;s exact test\u003c/p\u003e \u003cp\u003e3.609a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.219\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75(100)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20(95.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003erheumatologic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2(2.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0(0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFisher\u0026rsquo;s exact test\u003c/p\u003e \u003cp\u003e0.572a\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73(97.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21(100)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of the patients\u0026rsquo; QoF in the two groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP-Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAcute\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003estandard deviation\u0026thinsp;\u0026plusmn;\u0026thinsp;Average\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eRecurrent\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003estandard deviation\u0026thinsp;\u0026plusmn;\u0026thinsp;Average\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysical Functioning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e84.66\u0026thinsp;\u0026plusmn;\u0026thinsp;25.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e54.28\u0026thinsp;\u0026plusmn;\u0026thinsp;32.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRole Physical Health\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e82.33\u0026thinsp;\u0026plusmn;\u0026thinsp;35.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e36.90\u0026thinsp;\u0026plusmn;\u0026thinsp;38.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRole Emotional\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e77.77\u0026thinsp;\u0026plusmn;\u0026thinsp;38.49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e45.00\u0026thinsp;\u0026plusmn;\u0026thinsp;42.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEnergy Fatigue\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e60.81\u0026thinsp;\u0026plusmn;\u0026thinsp;18.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e41.90\u0026thinsp;\u0026plusmn;\u0026thinsp;17.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.597\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmotional Well Being\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e66.54\u0026thinsp;\u0026plusmn;\u0026thinsp;17.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e52.00\u0026thinsp;\u0026plusmn;\u0026thinsp;15.64\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.433\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSocial Functioning\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e74.83\u0026thinsp;\u0026plusmn;\u0026thinsp;19.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e58.33\u0026thinsp;\u0026plusmn;\u0026thinsp;12.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.072\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e73.73\u0026thinsp;\u0026plusmn;\u0026thinsp;24.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e54.28\u0026thinsp;\u0026plusmn;\u0026thinsp;22.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.993\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGeneral Health\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e61.46\u0026thinsp;\u0026plusmn;\u0026thinsp;19.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e49.04\u0026thinsp;\u0026plusmn;\u0026thinsp;18.41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.882\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHealth Change\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e51.33\u0026thinsp;\u0026plusmn;\u0026thinsp;18.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e33.75\u0026thinsp;\u0026plusmn;\u0026thinsp;23.33\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQuality Total\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e71.17\u0026thinsp;\u0026plusmn;\u0026thinsp;19.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e47.27\u0026thinsp;\u0026plusmn;\u0026thinsp;18.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.037\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of the patients\u0026rsquo; psychological characteristics in the two groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP-Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eAcute\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003estandard deviation\u0026thinsp;\u0026plusmn;\u0026thinsp;Average\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003eRecurrent\u003c/b\u003e\u003c/p\u003e \u003cp\u003e\u003cb\u003estandard deviation\u0026thinsp;\u0026plusmn;\u0026thinsp;Average\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDepression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e9.70\u0026thinsp;\u0026plusmn;\u0026thinsp;4.24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e13.19\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.674\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnxiety\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e8.81\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e10.95\u0026thinsp;\u0026plusmn;\u0026thinsp;4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.938\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStress\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e9.70\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e13.19\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.615\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe study revealed that women with recurrent vulvovaginal candidiasis (RVVC) exhibited a significantly greater adverse impact on their quality of life, as evidenced by mean values (\u0026plusmn;\u0026thinsp;SD) of 47.27\u0026thinsp;\u0026plusmn;\u0026thinsp;18.31 compared to the acute group 71.17\u0026thinsp;\u0026plusmn;\u0026thinsp;19.60. Furthermore, the study's findings indicated that such a significant negative effect was evident in certain subdomains of quality of life in the RVVC group, including physical functioning (54.28\u0026thinsp;\u0026plusmn;\u0026thinsp;32.29), physical role functioning (36.90\u0026thinsp;\u0026plusmn;\u0026thinsp;38.42), emotional role functioning (45.00\u0026thinsp;\u0026plusmn;\u0026thinsp;42.26), and health change (33.75\u0026thinsp;\u0026plusmn;\u0026thinsp;23.33) compared with the acute VVC group. However, no significant differences were observed between the two groups in other subdomains of the health-related quality of life questionnaire (SF-36). Besides different impacts on Quality of life among these two groups, it was observed that depression, anxiety, and stress were not significantly different between them.\u003c/p\u003e \u003cp\u003eExploring the background of the studies, we found no research exactly comparing acute vulvovaginal candidiasis (VVC) with recurrent vulvovaginal candidiasis (RVVC) in terms of Quality of Life (QoL) and other psychological factors. It appears that this study, for the first time, compared the QoL and also stress, anxiety, and depression of RVVC with VVC. In a previous study, the Short-Form Health Survey (SF-36) was utilized to measure health-related QoL in 101 healthy women and 102 women with RVVC. The results demonstrated that women with RVVC had lower physical and mental composite scores compared to controls (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). This finding is consistent with the current study's results, indicating that the RVVC group experienced more negative effects than the VVC group in the physical functioning subdomain.\u003c/p\u003e \u003cp\u003eOn the other hand, a study focusing on patients suffering from chronic vulvovaginal candidiasis (CVVC) reported a very significant impact on their Quality of Life (QoL) before and after treatment. CVVC, unlike RVVC, is characterized by continuous and unremitting symptoms rather than episodic occurrences (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). A similar finding was observed in a retrospective, single-center cohort study, which highlighted the immense impact of vulval disease on QoL, particularly in patients with CVVC. These findings underscore the significant influence of treatment on the lives of CVVC patients and emphasize the importance for clinicians to consider the effect of such infections on patients' QoL (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA sub-analysis of a randomized, controlled, double-blinded study revealed that women with recurrent vulvovaginal candidiasis (RVVC) experienced high QoL impairment and sexual health issues. However, a 6-month maintenance treatment resulted in a significant improvement in both QoL and sexual health. Unlike our study, this investigation utilized the EQ-5D-5L questionnaire, which assesses various aspects including mobility, body hygiene, everyday routine, pain, and fear/depression (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Despite similarities in finding an adverse effect on physical function in the RVVC group, our study did not find a significant difference in pain and depression between recurrent and acute infected women.\u003c/p\u003e \u003cp\u003eFurthermore, Aball\u0026eacute;a et al. conducted a study on QoL in RVVC patients across five European countries (Spain, Germany, France, the United Kingdom, and Italy) and the United States, using both the EQ-5D-5L and 36-item short form survey (SF-36). They reported that the QoL of women during and between acute episodes was significantly lower than that of the average population, even with therapy (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). It's noteworthy that in our study, selected patients were not undergoing treatment, whereas many of the conducted studies investigated the difference in QoL before and after treatment.\u003c/p\u003e \u003cp\u003eIt has been demonstrated that there is a strong relationship between vaginal infections and health-related quality of life (QoL) in women diagnosed with such infections, significantly impacting their daily activities. Infected women with vaginal infections are more likely to experience effects on emotional well-being and role limitations due to physical problems. SF-36 QoL dimensions were found to be affected among women with recurrent vulvovaginal candidiasis (RVVC) in general (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). These infections pose a threat to women's health and have negative impacts on their QoL. Due to the personal nature of vaginal infections, they are often avoided or overlooked. Despite the severe influence of symptoms on the QoL of affected women, vaginal infections have historically been relatively underexplored subjects and may have been viewed as taboo or stigmatized issues (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAnother study demonstrated that women with chronic vaginal symptoms such as recurrent vulvovaginal candidiasis (RVVC), vestibulitis syndrome, and inflammatory vulvovaginitis had high rates of mental disorders. The results revealed a significant relationship between depression, anxiety, and stress and a history of RVVC. These findings suggest that levels of depression, anxiety, and stress in patients with RVVC are higher than in healthy individuals. This finding aligns with another study which indicated that both chronic stress and reduced antioxidant capacity may serve as predisposing factors for RVVC. This implies that dysregulation of immune function, which can be associated with poorer mental health parameters, may increase the risk of RVVC (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Some studies have also indicated that patients with RVVC are more likely to suffer from clinical depression, poorer self-esteem, high stress levels, feelings of frustration, sexual dysfunction, and dissatisfaction with life (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).However, although our study did not find meaningful differences in the levels of anxiety, stress, and depression between the recurrent and acute groups, it appears that for more precise results, a control group (consisting of healthy women) may be necessary.\u003c/p\u003e \u003cp\u003eThis study should be considered as a preliminary investigation laying the groundwork for larger, prospective interventional studies in patients with vulvovaginal candidiasis (VVC). A better understanding of the psychological effects in women with candidal vulvovaginitis and providing suitable solutions to reduce psychological problems in these patients are essential goals. Ultimately, improving the health of society as a whole is a practical objective of this research.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, vulvovaginal candidosis affects numerous women worldwide, negatively impacting their Quality of Life (QoL) and psychological well-being, including depression, stress, and anxiety. The present study's findings indicate that the severity of its impact on QoL varies between different forms of the infection (recurrent and acute), while no significant differences were observed in terms of stress, anxiety, and depression. Clinical practice should prioritize attention and intervention to address the effects of vulvovaginal candidosis on patients' QoL. Furthermore, further studies are needed to delve deeper into the correlation between this infection and QoL, as well as its influence on patients' mental health, ideally incorporating a control group for more comprehensive understanding.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study achieved the ethical code IR.KMU.REC.1399.086, from ethic committee of Kerman University of Medical Sciences. Informed consent was obtained from all subjects.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/em\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Data will be available per request via contact corresponding author Atefeh Ahmadi ([email protected]/00989133979580).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare no competing interest\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eNeuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran (grant number: 98001093)\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eF.B. wrote the last draft, L.T. and \u0026nbsp;M.SH. and A.KB. and M.D. collected the data, M.G. and F.M. wrote the methodology and data analysis, S.AA. idea of the research and wrote the proposal, A.A. did the research management and wrote the first draft\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThanks a lot from Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences to support this research.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMoshfeghy Z, Tahari S, Janghorban R, Najib FS, Mani A, Sayadi M. Association of sexual function and psychological symptoms including depression, anxiety and stress in women with recurrent vulvovaginal candidiasis. Journal of the Turkish German Gynecological Association. 2020;21(2):90.\u003c/li\u003e\n\u003cli\u003eBrown H, Drexler M. Improving the diagnosis of vulvovaginitis: perspectives to align practice, guidelines, and awareness. Population health management. 2020;23(S1):S-3-S-12.\u003c/li\u003e\n\u003cli\u003eWu M, Kherlopian A, Wijaya M, Fischer G. Quality of life impact and treatment response in vulval disease: Comparison of 3 common conditions using the Vulval Quality of Life Index. Australasian Journal of Dermatology. 2022;63(4):e320-e8.\u003c/li\u003e\n\u003cli\u003eNguyen Y, Lee A, Fischer G. Quality of life in patients with chronic vulvovaginal candidiasis: a before and after study on the impact of oral fluconazole therapy. Australasian Journal of Dermatology. 2017;58(4):e176-e81.\u003c/li\u003e\n\u003cli\u003eSobel JD. Recurrent vulvovaginal candidiasis. American journal of obstetrics and gynecology. 2016;214(1):15-21.\u003c/li\u003e\n\u003cli\u003eEmeribe AU, Nasir IA, Onyia J, Ifunanya AL. Prevalence of vulvovaginal candidiasis among nonpregnant women attending a tertiary health care facility in Abuja, Nigeria. Research and Reports in Tropical Medicine. 2015;6:37-42.\u003c/li\u003e\n\u003cli\u003eRoozbahani F, Kariman N, Mojab F, Nasiri M. Effect of Myrtus communis capsule on vaginal candidiasis treatment. Pajoohandeh Journal. 2013;18(5):242-9.\u003c/li\u003e\n\u003cli\u003eFoxman B, Muraglia R, Dietz J-P, Sobel JD, Wagner J. Prevalence of recurrent vulvovaginal candidiasis in 5 European countries and the United States: results from an internet panel survey. Journal of lower genital tract disease. 2013;17(3):340-5.\u003c/li\u003e\n\u003cli\u003eWeissenbacher T, Witkin S, Ledger W, Tolbert V, Gingelmaier A, Scholz C, et al. Relationship between clinical diagnosis of recurrent vulvovaginal candidiasis and detection of Candida species by culture and polymerase chain reaction. Archives of gynecology and obstetrics. 2009;279:125-9.\u003c/li\u003e\n\u003cli\u003eZhu Y-X, Li T, Fan S-R, Liu X-P, Liang Y-H, Liu P. Health-related quality of life as measured with the Short-Form 36 (SF-36) questionnaire in patients with recurrent vulvovaginal candidiasis. Health and Quality of Life Outcomes. 2016;14:1-6.\u003c/li\u003e\n\u003cli\u003eLuz RAD, de Deus JM, Valadares AL, Conde DM. Evaluation of sexual function in Brazilian women with and without chronic pelvic pain. Journal of Pain Research. 2018:2761-7.\u003c/li\u003e\n\u003cli\u003eLietz A, Eckel F, Kiss H, Noe‐Letschnig M, Farr A. Quality of life in women with chronic recurrent vulvovaginal candidosis: A sub‐analysis of the prospective multicentre phase IIb/III Prof‐001 study. Mycoses. 2023.\u003c/li\u003e\n\u003cli\u003eFoster DC, Falsetta ML, Woeller CF, Pollock SJ, Song K, Bonham A, et al. Site-specific mesenchymal control of inflammatory pain to yeast challenge in vulvodynia afflicted and pain-free women. Pain. 2015;156(3):386.\u003c/li\u003e\n\u003cli\u003eFalsetta ML, Foster DC, Woeller CF, Pollock SJ, Bonham AD, Haidaris CG, et al. Identification of novel mechanisms involved in generating localized vulvodynia pain. American journal of obstetrics and gynecology. 2015;213(1):38. e1-. e12.\u003c/li\u003e\n\u003cli\u003eYano J, Sobel JD, Nyirjesy P, Sobel R, Williams VL, Yu Q, et al. Current patient perspectives of vulvovaginal candidiasis: incidence, symptoms, management and post-treatment outcomes. BMC women\u0026apos;s health. 2019;19:1-9.\u003c/li\u003e\n\u003cli\u003eDovnik A, Golle A, Novak D, Arko D, Takač I. Treatment of vulvovaginal candidiasis: a review of the literature. Acta Dermatovenerol Alp Pannonica Adriat. 2015;24(1):5-7.\u003c/li\u003e\n\u003cli\u003ehttps://www.rand.org/health-care/surveys_tools/mos/36-item-short-form/scoring.html [Internet]. Available from: https://www.rand.org/health-care/surveys_tools/mos/36-item-short-form/scoring.html.\u003c/li\u003e\n\u003cli\u003eLovibond SH. Manual for the depression anxiety stress scales. Sydney psychology foundation. 1995.\u003c/li\u003e\n\u003cli\u003eIrving G, Miller D, Robinson A, Reynolds S, Copas AJ. Psychological factors associated with recurrent vaginal candidiasis: a preliminary study. Sexually transmitted infections. 1998;74(5):334.\u003c/li\u003e\n\u003cli\u003eAball\u0026eacute;a S, Guelfucci F, Wagner J, Khemiri A, Dietz J-P, Sobel J, et al. Subjective health status and health-related quality of life among women with recurrent vulvovaginal candidosis (RVVC) in Europe and the USA. Health and quality of life outcomes. 2013;11(1):1-13.\u003c/li\u003e\n\u003cli\u003eRashad MR, Mohamed HSE, Emara HA, Elsabiey FI, Salim HM. Quality Of Life among Women Diagnosed With Vaginal Infection. Zagazig Nursing Journal. 2022;18(1):52-69.\u003c/li\u003e\n\u003cli\u003eReichman O, Margesson LJ, Rasmussen CA, Lev-Sagie A, Sobel JD. Algorithms for Managing Vulvovaginal Symptoms\u0026mdash;a Practical Primer. Current infectious disease reports. 2019;21:1-9.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Candidiasis, Recurrent Vulvovaginal Candidiasis, Quality of Life, Depression, Anxiety, Stress","lastPublishedDoi":"10.21203/rs.3.rs-3988836/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3988836/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCandidal vulvovaginitis is a common fungal infection among women, affecting nearly 80% of adult women. Chronic and recurrent cases significantly impact the quality of life, often due to prolonged and indiscriminate use of antifungal drugs, leading to resistance. This resistance can result in prolonged, costly treatment and notable emotional and psychological effects. The study aims to compare the psychological effects of depression, anxiety, and stress, as well as quality of life, in women with recurrent candidal vulvovaginitis to those with non-recurrent forms of infection.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study first gathered demographic information from individuals with recurring and non-recurring candidal vulvovaginitis in health centers across Kerman City using a relevant questionnaire. Additionally, the impact of Candida vulvaginitis infection on stress, anxiety, and depression levels was assessed using a researcher-made questionnaire adapted from the DASS questionnaire. Furthermore, the participants' physical and mental well-being was evaluated using the SF-36 health-related quality of life questionnaire, consisting of 8 questions and 6 components.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 84 women participated in the study: 42 with recurrent vulvovaginal candidiasis (RVVC) and 42 without RVVC. After analyzing the data from the completion of two questionnaires by patients in the two groups, a significant difference in Quality of Life (QoL) was observed between them (P=0.03). However, no significant differences were found between the two groups in terms of depression (P=0.674), anxiety (P=0.938), and stress (P=0.615).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eVulvovaginal candidosis significantly affects women's QoL and mental health worldwide. While its impact varies among infection forms, no significant differences were found in stress, anxiety, and depression. Clinical intervention should focus on addressing these effects, and further research with control groups is warranted for deeper understanding.\u003c/p\u003e","manuscriptTitle":"Depression, anxiety, stress, and health quality of life in vulvovaginal candidiasis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-05 13:27:32","doi":"10.21203/rs.3.rs-3988836/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0190af76-f698-4231-9929-5c41e8fc21ac","owner":[],"postedDate":"March 5th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-12T07:36:50+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-05 13:27:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3988836","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3988836","identity":"rs-3988836","version":["v1"]},"buildId":"omnImTCwR2MFx8CMYfrG7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}