Quality of life (QoL) is the intellectual and emotional wellbeing of an individual, which is determined by many factors. The most measurable are the sense of happiness, occupational satisfaction, quality of interpersonal relationships and sex life. Obsessive-compulsive disorder (OCD) is a chronic mental disorder diagnosed by the presence of obsessions and compulsions that disrupt normal psychosocial functioning. Despite early onset, treatment is delayed (OCD-DTI) and unsatisfactory.The primary objective of this study is to assess selected correlates of the sense of happiness among patients with OCD. The secondary objective is to compare the sense of happiness with healthy people.Seventyfive OCD patients and equal number of healthy subjects were compared using a Polish adaptation of the Oxford Happiness Questionnaire (OHQ-23).r = −0.479), the number of obsessive-compulsive personality traits (r = −0.323), the number of other comorbid mental disorders (r = −0.272), the level of aggression (r = −0.448), impulsivity (r = −0.301), depressiveness (r = −0.357), and the sexual dysfunctions (r = −0.279). The latter were much more common in individuals with OCD compared to healthy subjects (66.67 vs. 12%). The level of loneliness was over two times higher in the study group compared to controls (27 vs. 12%). The mean delay in treatment onset was 13 years. Conclusions. Assessment of aspects of QoL should be an integral part of the diagnostic and therapeutic process in OCD.We found a significant negative correlation between sense of happiness and the severity of OCD ( Quality of life (QoL) is defined by the World Health Organization (WHO) as “individuals’ perceptions of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards, and concerns” . In mediper se (Obsessive-compulsive disorder (OCD) is one of conditions that reduce QoL . OCD is per se . The effper se , 28. Theper se . For OCDper se , 29, 30.per se , 32. OCDper se  and up tper se  is anothper se , 34. Obsper se , 35, 36.per se .Obsessive-compulsive disorder is known to deteriorate QoL, depending on the presence of various factors , 12. In The aim of this study is to reassess some aspects of QoL in patients with OCD. The primary objective is to assess selected correlates of the sense of happiness  among patients with OCD. The secondary objective is the comparison of the sense of happiness and its ingredients between patients and healthy people. We also verified whether wellbeing in OCD depends on age, gender, severity of symptoms, duration and treatment delay, the quality of sexual life, the number of comorbid mental disorders and OCPD, the severity of depression, mania, aggression and impulsivity.N = 66). A smaller number (N = 9) were treated in our psychiatric unit (for follow-up). The control group consisted of 75 individuals without mental disorders. Volunteers were selected from among medical personnel and then from among their colleagues . We did not use media advertising in the study. The exclusion criterion for the healthy group was the presence of a mental disorder (including OCD). In the control group, the significant variables were to find volunteers similar in age and gender to group 1. None of the healthy volunteers were associated with the OCD group. Both groups formed naturally (by random chance) in terms of income, habitat and culture. Group 1 was assessed for correlations between various aspects of wellbeing: sense of happiness, life satisfaction, sense of strength, sense of perceived and control over one’s own life, quality of sexual life and age, gender, the severity of OCD symptoms, the total number of comorbid mental disorders, presence of OCPD as well as the level of depression, mania, aggression and impulsivity. We also assessed treatment duration and delay in group 1. Then we compared the study group with the control group for a sense of happiness , and quality of sexual life.The study group included 75 patients diagnosed with and treated for OCD. The primary inclusion criterion was a diagnosis of OCD. To avoid bias, we decided to select the majority of patients without sudden OCD exacerbation and without severe mood disorders. For this reason, the vast majority of patients were randomly selected from our outpatient department  employed in center that diagnose and treat mental disorders, with extensive experience in the diagnosis and therapy of OCD. Each of the investigators was trained for all the diagnostic tools used. The obtained results were each time assessed simultaneously by at least two researchers to ensure the reliability of the research. None of the patients had any problems with defining their gender identity. The following diagnostic tools were used:1.-Brown Obsessive Compulsive Scale (Y-BOCS). The tool is used to measure OCD severity and to monitor treatment outcomes. It measures five OCD parameters . Total score indicates OCD severity as subclinical (0–7), mild (8–15), moderate (16–23), severe (24–31) and extremely severe (32–40)  .2.The Oxford Happiness Questionnaire; Polish version (OHQ-23). The tool is used to assess global mental wellbeing in the following dimensions: a sense of happiness . The minimum and maximum total score is 23 and 138, respectively. OHQ-I (life satisfaction and sense of strength) consists of 14 statements; the minimum and maximum score is 14 and 84, respectively. OHQ-II (sense of meaning and control) consists of nine statements; the minimum and maximum score is 9 and 54, respectively .3.Arizona Sexual Experiences Scale (ASEX). This screening tool consists of five items quantifying sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm . A high total score (≥19) indicates the presence of sexual disorders .4.Hamilton Depression-Rating Scale (HDRS-17). This multi-element questionnaire is used for the diagnosis of depressive disorders and the assessment of recovery. The answers are rated from 0 to 4. The total score indicates the severity of depression  .5.Young Mania Rating Scale (YMRS) is an 11-item tool to assess manic symptoms. The answers are rated on a 5-point scale (0–4), except for 4 items, which are scored 0–8. The total score of ≥ 29 is considered the cut-off point for severe mania .6.Hypomania Check List (HCL-32). The tool investigates the presence of hypomanic and manic symptoms. HCL-32 is a self-assessment questionnaire consisting of 7 parts. It assesses mood, activity, and drive. A score of ≥ 14 is the cut-off point that may indicate hypomania or mania .7.Buss-Perry Aggression Questionnaire (BPAQ). This 29-item tool is used to assess the general level of aggression and its components: physical aggression (PA)–9 items; verbal aggression (VA)–5 items; anger (A)–7 items; hostility (H)–8 items .8.Barratt Impulsiveness Scale (BIS-11) is a 30-item tool to measure the three theoretical subtraits of impulsiveness; i.e.,–cognitive, motor, and non-planning impulsiveness .9.The total number of comorbid mental disorders (OCD-Com). The prevalence (the order is random) was assessed for the most common comorbidities of OCD: MDD, BD, AD and AUD. It was assumed that only the total number of comorbid mental disorders would be relevant to the study (0 to 4). All these disorders were diagnosed retrospectively based on medical history and treatment records provided, verified in accordance with the DSM 5 criteria by psychiatrists .10.The occurrence of OCPD was assessed separately (according to DSM 5 criteria verified by psychiatrists), as it was assumed to be conducive to ego-syntonic obsessions . The survey was based on questions correlating with obsessive-compulsive personality traits. Four or more traits  were considered significant for diagnosis. .11.Questions regarding duration and delay of OCD treatment were diagnosed retrospectively based on medical history and treatment records provided.U test was used to test the significance of differences between the group of patients and healthy controls. The level of statistical significance was set at α ≤ 0.05.Excel 2016 and Statistica version 13.3 were used for data processing. The normality of the distribution of variables was verified with the Shapiro–Wilk test. The correlation matrix was prepared using the Spearman rank correlation coefficient. The Mann–Whitney The description of the study and control group in terms of age, gender, education, occupational activity, and interpersonal relations is presented in r = −0.272). A negative relationship was also found between the OHQ of patients with selected psychopathological phenomena such as the severity of OCD symptoms , number of OCPD traits (r = −0.323), the severity of aggression  and impulsivity  and the severity of depression  and sexual dysfunctions . As for life satisfaction and sense of strength (OHQ I), significant negative correlations were observed with the severity of compulsions (r = −0.449), aggression (r = −0.482) and impulsivity (r = −0.311), as well as with the severity of depressive symptoms (r = −0.366) and sexual dysfunctions (r = −0.249). Meanwhile, the sense of meaning and control (OHQ II) showed significant and negative correlations with the number of comorbid mental disorders (r = −0.360), the severity of OCD symptoms (r = −0.391), the number of OCPD traits (r = −0.372), aggression (r = −0.282), severity of depressive symptoms (r = −0.294), and the severity of sexual dysfunctions (r = −0.239). All correlations were statistically significant at p ≤ 0.05  significantly and negatively correlated with the number of comorbid mental disorders , as well as its subscales: life satisfaction, sense of strength  and sense of meaning and control . Happiness was found to be significantly lower in the OCD group. The observed differences are presented in The assessment of the significance of differences in happiness between OCD patients and healthy controls showed statistically significant differences in the sense of happiness  were found in 66.67% of the OCD respondents  and 12% of healthy controls . They were more common among women  than men . Women most often reported lack of pleasure from orgasm (54.84%), complete inability to achieve orgasm (51.61%), and vaginal dryness during intercourse (41.94%). Complete failure to achieve orgasm (52.63%) and inability to achieve erection (36.84%) were the most common dysfunctions reported by men.r = 0.003; OHQ-I: r = 0.042; OHQ-II r = −0.061). Gender also did not significantly differentiate any of the OHQ parameters .No significant correlation was found between age and any of the happiness variables: (OHQ: The mean OCD treatment delay was 13 years (from <1 year to 44 years). The analysis of correlations between the variables in the OCD group revealed no statistically significant relationships for the OCD-DTI parameter.It is difficult to explore all dimensions of the quality of life in OCD patients. Theoretically, their number may be infinite, and therefore immeasurable. In this study, two factors determined the final selection of the predictors investigated. First, the severity of symptoms that are commonly considered to cause discomfort  was assessed. Secondly, factors commonly considered important for existential wellbeing  were analyzed. Happiness measured with The Oxford Happiness Questionnaire (the OHQ-23 version) was the leading predictor of QoL.Our study confirmed significant wellbeing deficits in OCD patients compared to healthy individuals. This was found for all studied dimensions: subjective happiness, perceived control over one’s own life, problems in interpersonal relationships, as well as sexual and occupational life. It is worth noting that the percentage of people who did not have relationships in the study group was over two times higher than in the control group (27 vs. 12%). It should be assumed that loneliness was not a conscious choice of the affected person, but a consequence of OCD.Almost 67% of respondents reported problems in their sexual life, which confirms the results of previous studies in this area 54–73%) and the cited thesis that problems in relationships are one of the most common causes of poor quality sex –73% and . It is tObsessive-compulsive disorder resulted in occupational disability in over 25% of respondents. This result is definitely unfavorable, especially since until recently, OCD was considered a neurotic disorder (obsessive compulsive neurosis) . ConsideThe strongest and most detrimental effect on ability to happiness was noted for the severity of OCD. This confirms the disastrous psychosocial consequences of the intensification of OCD symptoms and requires no further interpretation.We have also shown that OCD is often accompanied by other mental disorders. The mean number of comorbidities in the study group is 1.35 Com; most often, two (44% responders) and one . The co-existence of three additional psychiatric disorders was found in 9.33% of the subjects, and none of the patients had four comorbidities. Our study did not verify whether it was co-morbidity, co-incidence, or co-occurrence. It was important to demonstrate this phenomenon, which should be assumed to have contributed to reduced happiness, especially through the investigated negative impact on the sense of meaning and control over one’s own life (OHQ-II). Further research is needed to assess this topic in more detail.per se, and increases disease severity, ultimately increasing treatment resistance  have a particularly negative impact on QoL . It is wsistance .Following up on previously cited studies, it was found that a significant problem in patients with OCD is a increase in symptoms of depression, aggression and impulsivity. It remains a rhetorical question and further research is needed to investigate on whether they are a consequence or a psychological component of OCD. Regardless of the etiological uncertainties, all these factors negatively correlated with happiness, life satisfaction, sense of strength, meaning and control (OHQ). The presence of depression, aggression and impulsivity certainly makes it difficult (or impossible) to maintain interpersonal or professional relationships, as confirmed by the results of our study. Thus, it can reduce the holistic aspects of a patient’s quality of life.The study found that the mean treatment delay was up to 13 years. Although no significant association was found between OCD-DTI and all aspects of wellbeing studied, this result encourages further clinical reflection. It is worse compared to the results obtained many years ago by Hollander et al.  and simiThe study did not confirm that the QoL in OCD patients depends on age or gender. When analyzing the lack of such relationships, it should be taken into account that the vast majority of elderly respondents (regardless of gender) sought long-term psychiatric treatment, which could have contributed to improved QoL.Certain limitations of this study should be noted. First of all, the study investigated only selected (most transparent) aspects of QoL in patients with OCD, which means that there are still some areas of wellbeing that require further exploration. The relatively small study sample made it difficult to generalize the obtained results and relate them to the general population of OCD patients. Some limitations result from difficulties in objectivizing the data from the interview, especially in terms of embarrassing information, e.g., data on sexual dysfunctions, which may be the reason for their non-disclosure by some patients, both in the study and the control group. At this point it should be noted that ASEX tests were mostly conducted by women, which could induce male patients to underestimate their sexual problems. Adverse effects of commonly used OCD medications (SSRI), which may reduce sexual satisfaction, should also be considered. The high percentage of comorbidities in the study group makes it difficult to draw conclusions about the sense of happiness of patients with isolated OCD. It should be noted that a limited number of comorbidities were investigated, and their course was not taken into account. The problem of comorbidity, due to its extensiveness, will be analyzed in detail in another study. OCD delay–the result may be confounded due to a small group of patients with OCD. The two groups investigated were matched only in terms of age and gender, while the other variables  were different. This may have made it difficult to compare them and affected the strength of the correlations reported in the results.1.Obsessive-compulsive disorder reduces ability to happiness and other aspects of QoL.2.Loneliness, existential and sexual frustration are psychosocial consequences of OCD.3.In addition to symptoms severity, depression, aggression, and impulsivity are factors that destabilize wellbeing in OCD. These are not included in common definitions of OCD. Therefore, they are worth considering and treating them.4.Other mental disorders should be co-diagnosed and co-treated to improve all aspects of QoL in OCD.5.The diagnosis of OCD is severely delayed.6.Assessment of specific aspects of QoL–especially a sense of happiness–should be an integral part of the diagnostic and therapeutic process in OCD.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Bioethics Committee at the Silesian Medical Chamber. The patients/participants provided their written informed consent to participate in this study.MŻ: development of research aims, scope, methodology, collection and analysis of research data, literature review, and creation of the main text (main author). MB: development of research aims and methodology, collection and analysis of research data, literature review, and co-authorship of the main text. RŻ: collection and analysis of research data, preparation of text fragments, and literature review. AW-B: collection and analysis of research data, preparation of text fragments, development of research aims and methodology, and literature review. PD: statistical analysis of research data, preparation of text fragments, and verification of methodological assumptions. NF-M: collection and analysis of research data and literature review. MP and HJ-Z: collection and analysis of research data and verification of methodological assumptions. PG: collection and analysis of research data, verification of methodological assumptions, and aims of the study. All authors contributed to the article and approved the submitted version.


Ambulatory care sensitive conditions (ACSCs) are defined as clinical conditions for which the risk of emergency hospital admission can be reduced by timely and effective ambulatory care. However, the actual status of patients with ACSCs who are transported by ambulance and their outcomes have not been fully elucidated. The purpose of this study was to reveal characteristics and outcomes of patients with ACSCs who were transported by ambulance using population-based registry data in Osaka, Japan.This descriptive epidemiological study was conducted in the 5-year period from January 2016 to December 2020, and included patients who were transported by ambulance due to sudden illness. In this study, ACSC was further classified into acute ACSCs, chronic ACSCs, and preventable ACSCs based on the ICD-10. The number of patients transported by ambulance for ACSCs per 100,000 population in each age group was calculated for each year. In addition, Poisson regression models were used to assess the trend in the number of ACSCs patients transported by ambulance.n = 69,621; chronic ACSCs, n = 12,250; preventable ACSCs, n = 96,036; and non-ACSCs, n = 1,394,245). The overall median age was 71 years . Patients with acute ACSCs (median age: 76 years [IQR: 60-84]) and chronic ACSCs (median age: 80 years [IQR: 72-87]) were older, while patients with preventable ACSCs were younger (median age: 66 years [95%CI: 3-81]) and included a high proportion of children . Regarding the outcome after treatment at the emergency department, 42.6%  of patients were hospitalized, while 82.3%  of patients with chronic ACSCs were hospitalized. No change was observed in adults (P = 0.001) or elderly (age ≥65 years) individuals (P = 0.376) with preventable ACSCs, however, among children, the number increased until 2019 (732.5) and then decreased in 2020 (371.8) (P = 0.392).A total of 1,572,152 patients were included in this study (acute ACSCs, In this study, patients with chronic ACSCs were predominantly elderly, while patients with preventable ACSCs were polarized between children and the elderly. Among patients with preventable ACSCs, there was no change over time in adults and children, but there was a marked decrease among the elderly after 2020. Internationally, national health systems are facing the problem of an increasing number of elderly individuals who require nursing care . On the In the 1990s, ambulatory care sensitive conditions (ACSCs) were defined as clinical conditions for which the risk of emergency hospital admission can be reduced by timely and effective ambulatory care . AmbulatIn Osaka prefecture, a population-based patient registry (ORION) for all patients transported by ambulance is in operation, and data on all patients transported by ambulance in Osaka Prefecture from ambulance dispatch to hospital discharge have been continuously collected since 2015 , 7. The 2  for continuous variables, and the actual number and percentage for categorical variables. Age groups were classified as follows: child (0–19 years), adult (20–64 years), and elderly (≥65 years). The number of patients transported by ambulance for ACSCs per 100,000 population in each age group was calculated for each year. Because we assumed that ACSC patients transported by ambulance were rare, Poisson regression models were applied to assess the trend in the number of ACSCs patients transported by ambulance. The time of day when the ambulance was requested was classified as daytime (9:00–17:59) or nighttime . All statistical analyses were performed using the SPSS software program .n = 69,621; chronic ACSCs, n = 12,250; preventable ACSCs, n = 96,036; and non-ACSCs, n = 1,394,245). n = 48,416)], followed by acute tubule-interstitial nephritis  ], followed by essential hypertension  ], followed by pneumoniae due to Streptococcus pneumoniae  ] . The mos18,309)] . The mos 1,647)] .P = 0.092) or elderly individuals (P = 0.305), while the number of these patients decreased among adults (P = 0.028).P = 0.756) or elderly individuals (P = 0.236), but the number of these patients decreased among children (P = 0.001).P = 0.001) or elderly individuals (P = 0.376), but among children, the number increased until 2019 (732.5) and then decreased to 371.8 in 2020 (P = 0.392).In this study, we revealed the characteristics and outcomes of patients with ACSCs using a population-based registry for emergency patients transported by ambulance in Osaka, Japan. Patients with chronic ACSCs were predominantly elderly, while patients with preventable ACSCs were polarized between children and the elderly. Patients with acute ACSCs were more frequently transported in the summer, while those with chronic ACSCs and preventable ACSCs were more frequently transported in the winter. Although there was no change over time in adults and children, there was a marked decrease among the elderly with preventable ACSCs after 2020. An increase in the number of patients transported by ambulance due to ACSCs, which do not cause serious illness if the patients properly manage their daily medications and physical condition, would have a serious impact on the emergency medical system. Therefore, it is necessary to reveal the actual status of patients with ACSCs among those transported by ambulance. Japan is one of the countries with high proportion of elderly people in the world, and there has been no studies using population-based data in Japan, which makes this study highly novel. This study, which revealed the characteristics and outcomes of patients with ACSCs using population-based data, is useful not only for further understanding the reality of patients with ACSCs, but also for considering health policies in relation to ACSCs.In this study, volume depletion and urinary tract infection  were common among patients with acute ACSCs. Regarding age group, the proportion of elderly patients in this population was higher than that of emergency patients due to sudden illness other than ACSCs. ACSCs have been reported in many countries, mostly in European countries and Brazil –20. HoweSecond, patients with chronic ACSCs included a higher proportion of patients with heart failure and essential hypertension, a higher proportion of elderly individuals, and a higher proportion of males. An observational study in Switzerland reported that heart failure and chronic obstructive pulmonary disease (COPD) were the main causes of hospitalization for elderly patients with ACSCs . In an oIn this study, the number of patients with preventable ACSCs was high in both children and elderly individuals, and the most common diseases were bacterial pneumonia, pneumococcal pneumonia, and influenza. In Japan, the elderly individuals can be vaccinated against these diseases free of charge under the public health system; however, children are not covered by the health system and their parents must pay the full cost of vaccination . It is vThe present study was associated with some limitations. First, it was no possible to assess the patients with ACSCs who visited hospitals and clinics on their own, because this study included patients transported by ambulance. Second, because the patient transport by ambulance due to ACSCs is a rare occurrence, a Poisson distribution was assumed and Poisson regression analysis was performed in this study. On the other hand, the Poisson assumption may cause overdispersion problem because the variance is not able to determine in the Poisson distribution. Third, the generalizability of this study is high because we analyzed a dataset collected over several years in metropolitan area of Japan including urban and rural areas. However, this study was an analysis of data from Japan and may lack validity outside of Japan. Next, because this was a retrospective observational study, we were not able to reveal other variables that were not collected in the ORION system.In this study, patients with chronic ACSCs were predominantly elderly, while patients with preventable ACSCs were polarized between children and the elderly. Among patients with preventable ACSCs, there was no change over time in adults and children, but there was a marked decrease among the elderly after 2020. We will continue to evaluate the impact of factors such as the increase of the elderly and the COVID-19 pandemic on patient transport by ambulance due to ACSCs.iryotaisaku-g02@sbox.pref.osaka.lg.jp.The data analyzed in this study is subject to the following licenses/restrictions: The data that support the findings of this study are available from the Osaka Prefectural Government, but the availability of these data are restricted. Data cannot be shared publicly because of the Protection Ordinance for Personal Information in Osaka Prefecture. Requests to access these datasets should be directed to Osaka Prefectural Government, YK, AK, and YY carried out the study protocol. YK, AK, and TK undertook the statistical analysis and graphical representation of the data. YK, TK, and JO revised the draft. All authors participated in the completion of the study and contributed to and approved the final manuscript.This study was supported by the Japan Society for the Promotion of Science KAKENHI (Grant No. JP21K09071).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This study aimed to explore the effects of Baduanjin-based cardiac rehabilitation on cardiac function and quality of life in patients with coronary heart disease who have undergone percutaneous coronary intervention.PubMed, the Excerpta Medica Database, the Cochrane Library, Web of Science, the Wanfang, SINOMED, the China Science and Technology Journal Database and China National Knowledge Infrastructure were searched for appropriate articles from their respective inception until March 30, 2021. Meta-analysis was conducted with the RevMan 5.3 software.P < .00001], increased the Seattle angina questionnaire and SF-36 health survey scale scores  and decreased the scores of Zung self-rating anxiety scale and self-rating depression scale .A total of 11 studies including 1025 patients were considered. Compared with conventional Western medicine, Baduanjin improved the left ventricular ejection fraction of patients [mean difference (MD) = 2.83, 95% confidence interval (CI) , Our findings showed that Baduanjin exercise improved cardiac function and quality of life and alleviated patients’ anxiety and depression. Percutaneous coronary intervention (PCI) is a common therapeutic strategy that improves angina symptoms.,3 However, during follow-up, there are still recurrences of cardiovascular events after PCI, and patients usually suffer from low-quality life. Cardiac rehabilitation (CR) has been advocated by numerous clinical guidelines for patients with CHD after PCI. Combined with routine therapy, exercise-based CR is a convenient and safe option, according to the guidelines of the American Heart Association. Moreover, mild to moderate intensity physical exercise has been reported to have protective effects on survival for patients post-PCI surgery.Coronary heart disease (CHD), also called coronary artery disease, is the most common cause of death worldwide.,9 Studies have showed that Baduanjin exercise as a complementary and alternative therapy for patients with cardiovascular disease improved the clinical outcome of cardiovascular patients and reduced the occurrence of adverse cardiovascular events. This exercise activates a sequence of natural self-regulatory/self-healing mechanisms to stimulate the balanced release of endogenous neurohormones, is easy to master in a short period of time and is suitable for all age groups. A growing number of randomized controlled trials (RCTs) have been carried out to explore the effects of Baduanjin exercise on the cardiac rehabilitation of patients with CHD after PCI. Regrettably, the sample sizes of these studies have been small.As a traditional Chinese exercise, Baduanjin  combines meditation with gentle movements and has been widely practiced in China to treat diseases.Therefore, we performed a systematic review of RCTs to evaluate the effects of Baduanjin exercise on cardiac rehabilitation in patients with CHD after PCI to provide more powerful evidence for treating post-PCI CHD patients in the clinic.We followed the methods of Li, Xing-Xing et al 2021.The protocol was registered in PROSPERO (No. CRD42020216513). In addition, it was also prepared based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement guidelines.Patients at least 18 years old with CHD who underwent a Baduanjin exercise intervention after PCI were included without limitations on race, gender, education or economic level.Baduanjin exercise was used for CHD patients post-PCI surgery. Included variations in intensity, frequency and duration were acceptable.Patients in the control group received conventional Western medicine (CWM) or conventional exercise (CE).The primary outcomes included left ventricular ejection fraction (LVEF). The secondary outcomes included the scores of the seattle angina questionnaire (SAQ), SF-36 health survey scale (SF-36), zung self-rating anxiety scale (SAS) and self-rating depression scale (SDS).We collected all available RCTs of Baduanjin exercise-related therapies for CHD after PCI.The specific exclusion criteria were as follows: non-RCTs, case reports, animal experiments, research advances, reviews, expert opinions and conference articles; patients who received other exercise measures in addition to Baduanjin exercise; duplicate articles, studies with incorrect data, inconsistency or incomplete and unavailable literature.We searched 4 English electronic databases and 3 Chinese literature databases for studies published before November 29, 2020: PubMed, the Excerpta Medica Database, Cochrane Library, Web of Science, the Wanfang database, SINOMED, China Science and Technology Journal Database and China National Knowledge Infrastructure. In addition, there was no restriction on language. Using PubMed as an example, details of the search strategy were shown in Table All authors received specific training on items for systematic reviews and meta-analyses protocols before the implementation of the study. The review process was independently conducted by 2 authors using blinding to reduce bias. Disagreements were settled first by discussion and then by consulting a 3rd author for arbitration. RCTs that were duplicated and did not meet the eligibility criteria were removed.The information required was as follows: basic information: title, the 1st author’s name, and year of publication; study characteristics: interventions, course of treatment, and duration; subject characteristics: sample size, gender, age, and underlying disease; and outcomes and specific adverse reactions. When there was uncertain information in the included studies, the final decision was made through discussion among team members.Two colleagues separately assessed the quality of the included RCTs via the Cochrane Collaboration tool, and in the case of disagreement, a 3rd author was asked for advice. Review items comprised random sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting and other bias. Depending on the characteristics of the included literature, the reviewers classified studies as having low, high, or unclear risk of bias.χ2 and I2 test were used to assess heterogeneity among the included RCTs. A fixed-effect model was used when heterogeneity was low . However, when heterogeneity was high , we further analyzed its potential sources based on the following 3 aspects: clinical heterogeneity, methodological heterogeneity, and statistical heterogeneity.All data were statistically analyzed using RevMan5.3 software from the Cochrane Collaboration. Discontinuous variables were expressed as the risk ratio with a 95% confidence interval (CI). For continuous data, if the unit or the measurement instrument was consistent, the mean difference (MD) with 95% CI is used, otherwise, the standard mean difference with a 95% CI was used. The  Egger and Begg test were constructed to evaluate publication bias.We evaluated clinical heterogeneity 1st, and if there was obvious clinical heterogeneity, a subgroup analysis was performed. If clinical heterogeneity was manifested and subgroup analysis could not be conducted, only descriptive analysis was used. After excluding clinical and methodological heterogeneity, statistical heterogeneity was considered, and a random-effect model was used.Subgroup analysis was performed to reduce the clinical heterogeneity between groups.We carried out the sensitivity analyses to evaluate the reliability of results. The methods included changing the type of analysis (random-effect model or fixed-effect model), eliminating each of the included studies 1 by 1 and then combining the effect quantity.Original authors were contacted where possible to obtain missing information. Studies that cannot be supplemented or corrected with the required information were eliminated.Egger and Begg test were conducted to evaluate the publication bias.The ethical approval was not necessary for this meta-analysis.The search of 8 databases identified 319 articles for further evaluation , of which 191 were removed after reviewing due to duplicate records. After reading the titles and abstracts, 94 were excluded for various reasons. Finally, only 11 studies met our inclusion criteria after screening full texts. Figure –26 involving 1025 participants and performed in China from 2017 to 2020 were included in this study. The average age of the patients ranged from 47.7 to 69.64 years old. Most of the trials had more males than females. All included patients were diagnosed with CHD and successfully underwent PCI according to guidelines. All studies claimed that the baseline characteristics were comparable between groups. In 4 studies,–26 the control group used CWM plus CE. The remaining studies–22 were designed to compare a Baduanjin plus CWM group with a group treated with the same CWM alone. Of the 11 studies, 6 reported LVEF, 4 reported the SAQ score, 3 reported the SF-36 score, 3 reported the SAS score, 2 reported the SDS score, and only 1 reported adverse effects. The duration of the intervention ranged from 1 to 24 weeks. CWM mainly consisted of aspirin, clopidogrel, angiotensin-converting inhibitor or angiotensin II receptor blocker, β-blocker and statins. The dosage and type of CWM allowed the guidelines for CHD. Characteristics of the included studies are listed in table Eleven RCTs–18 used a computer to generate random sequences, 7 RCTs–21,24–26 adopted a random number table, and 1 RCT used random sampling. The remaining RCT only mentioned “randomly” in their full text but did not describe the specific methods used for random sequence generation and was therefore assessed to have an unclear risk of bias in this item. Most of the RCTs were assessed as having an unclear risk of bias on allocation concealment,,22 which had a low risk of bias because of the use of envelope concealment. All studies were reviewed as having an unclear risk of bias on performance bias and selective reporting. Only 1 study applied blinding to the outcome assessment and was therefore assessed as having a low risk of bias. The other 10 RCTs–26 were evaluated as having an unclear risk bias because of the lack of information available to determine the risk. Four RCTs,21,22,26 reported dropout patients and explained the reason, however, they did not use intention-to-treat analysis to process missing data, and therefore, the risk of bias of reporting incomplete outcome data was judged as high. The remaining 7 RCTs–20,23–25 claimed that there was no dropout and were evaluated as having a low risk of bias. All RCTs were evaluated as having a low risk of other bias because they reported that the baseline characteristics were comparable between the groups.Figures P < .00001) than the CWM group, with low heterogeneity  , with low heterogeneity   than the CWM group. Consistently, based on the SAQ, physical limitations, anginal stability, anginal frequency, and disease perception were significantly different between the 2 groups, with differences of 3.70  in physical limitations, 14.6  in anginal stability, 8.22  in anginal frequency and 8.35  in disease perception. However, there was no obvious difference in treatment satisfaction . High or low heterogeneity was found between the Baduanjin and the CWM groups in addition to anginal frequency.The SAQ scores were reported in 4 studies as follows: 153 in the Baduanjin group and 154 in the CWM group. The SAQ was divided into 5 subscales: physical limitations, anginal stability, anginal frequency, treatment satisfaction and disease perception. A higher score indicates improved quality of life. In this study, the SAQ scores were presented as different values (posttreatment–pretreatment). As shown in Figure P < .00001) , P < .00001], 1.36 , 0.75 , 0.62 , 0.70, 0.90 , 01] Fig. .Only 1 study reported adverse events during study period. One patient in the CWM group died of cardiac arrest during hospitalization, and 1 patient in the Baduanjin group withdrew from the study because of a recent diagnosis of non-Hodgkin’s lymphoma during follow-up. These adverse events were not related to the interventions.Sensitivity analysis was conducted to evaluate the robustness of our findings. There are 2 ways of sensitivity analysis, which include changing the model or eliminating individual studies 1 by 1. The results demonstrated that the effect values were consistently stable, indicating that the results of our study were relatively stable.P = .334 for Egger test and P = .462 for Begg test; SF-36: P = .181 for Egger test and P = .368 for Begg test; SAS: P = .201 for Egger test and P = .296 for Begg test; SDS: P = 1.000 for Begg test).Except for SAQ, other outcomes did not show significant publication bias  was superior to CE. No increased risk of adverse events was associated with Baduanjin exercise. Thus, these findings supported the applicability of Baduanjin in CHD patients after PCI. However, some heterogeneity existed in this systematic review, which was related to the training intensity and duration of Baduanjin and to a low quality of studies.. LVEF is a common parameter for the assessment of cardiac function. The results of this study suggested that LVEF in the Baduanjin group was higher than that in the CWM group, and there was a statistical difference, which was consistent with the results of Gai TT et al Baduanjin is an aerobic exercise with a low intensity. It has been demonstrated that regular aerobic exercise changed the myocardial microstructure, reduced myocardial fibers, improved the elasticity of the valve, enhanced sympathetic excitability, and increased catecholamines in the blood, thereby enhancing myocardial contractility and improving the heart’s pumping capacity.,30 Therefore, Baduanjin should be developed as a potential method for the treatment of CHD.Baduanjin exercise improved cardiac function. Most patients with CHD usually had cardiac dysfunction Baduanjin exercise is of great benefit to people’s health and heart-related diseases and is suitable for any population, as well as for different ages. It is also low risk and be used to improve the quality of life of CHD patients. Baduanjin improved the quality of life by increasing the SAQ and SF-36 scores. These results suggested the value of Bduanjin in CHD treatment. Patients from the postintervention group were most likely to have a better health-related knowledge, mastered self-care skills, and increased daily activities to improve their cardiac function, quality of life and prognosis.Baduanjin exercise improved the quality of life. Patients with CHD usually experience impaired quality of life. Psychological factors such as anxiety and depression are prognostic adverse factors in patients with CHD.,35This study showed that Baduanjin exercise was associated with the improvement in the symptoms of anxiety and depression in patients with CHD after PCI. Baduanjin emphasizes the mind-body integration and is considered an effective exercise for health promotion. With symmetrical body postures and movements, breathing control, a meditative state of mind and mental focus, bad emotions, such as anxiety and depression, are alleviated and released, which plays a positive role in the mental health of patients. Moreover, numerous studies in both healthy and disease-based populations have shown that meditation improves anxiety, depression, or overall well-being.Baduanjin exercise alleviated patients’ negative emotions. There are data suggesting that approximately 40% of CHD patients suffer from anxiety and depression.There were several limitations to this meta-analysis. First, unexplained high heterogeneity might have affected the results of the subgroup meta-analysis, although strict inclusion criteria were applied to ensure the inclusion of high-quality RCTs. Second, we did not assess cardiopulmonary function owing to the lack of data in multiple studies. In the future, cardiopulmonary function in CHD patients who accept Baduanjin exercise should be analyzed. Third, because of the lack of hard end points, such as the rate of rehospitalization or mortality, more RCTs involving hard outcomes should be conducted in the future. Therefore, this study requires further improvement in the future because we did not analyze the effects of Baduanjin exercise with different intensities, times, and frequencies on cardiac function, quality of life and psychological status of CHD patients after PCI. In addition, the literature on Baduanjin exercise therapy is limited, and the total sample size is relatively small. Hence, high-quality RCTs with a larger sample size are needed to confirm and generalize the results.Baduanjin exercise was safe and effective in improving cardiac function and quality of life in patients with CHD after PCI, and should be used as a complementary and alternative therapy for CR to treat CHD and other related chronic diseases.Conceptualization: Xingxing Li, Zongjing Fan.Funding acquisition: Yang Wu, Zongjing Fan.Methodology: Quan Lin, Rongpeng Liu, Yang Wu.Project administration: Quan Lin, Zongjing Fan.Writing – original draft: Xingxing Li.Writing – review & editing: Xingxing Li, Zongjing Fan.


The fruit juice industry generates pomace as a valuable by-product especially rich in polyphenols, dietary fibers, vitamins, minerals, and unsaturated fatty acids. In the cookies used in this study, 30% of the gluten-free flour was replaced with dried and ground blueberry and raspberry pomace, rich source of polyphenols, dietary fibers, linoleic and alpha-linolenic acid. In order to examine whether the addition of blueberry and raspberry pomace in cookie formulation can have beneficial effects on certain blood parameters and anthropometric measurements, the designed cookies were tested in 20 healthy, normally fed female subjects, aged 30–50 years (41.35 ± 8.58 years) over four-week dietetic intervention study. Significant changes in the composition of fatty acids serum phospholipids, decrease in LDL-cholesterol level (20.16%), increase in adiponectin level (25.52%) and decrease in ALT and AST values were observed, thus indicating that inclusion of cookies containing blueberry and raspberry dried and ground pomace to usual diet might have positive effects on certain cardiovascular risk factors and liver function indicators. During the juice processing, a large quantity of valuable bioactive compounds remains in the pomace. According to the study of Khanal et al.  more thaConcerning the health-promoting effects of bioactive compounds from blueberry and raspberry, this dietetic intervention (pilot) study was organized to investigate the potential health effects of blueberry and raspberry pomace in concentrated (dried and ground) form, incorporated in food system. Cookies were included in daily diet, to evaluate the effect of blueberry and raspberry on certain factors strongly correlated with cardiometabolic risk , as well as on biomarkers of hepatic and renal function and anthropometric measurements. To the best of the author's knowledge, this is the first dietetic intervention study that investigates the potential health benefits of bioactive compounds from blueberry and raspberry pomace incorporated into the food system. These ingredients were chosen to be incorporated into gluten-free cookies to design the functional food product primarily intended for the population with coeliac disease, but also suitable for the healthy population.The dietetic intervention study was conducted according to the Declaration of Helsinki and was approved by the Ethics Committee of the Clinical Center of Vojvodina, Novi Sad, Serbia . Women of reproductive age were selected for the study, considering the possible effect of sex hormones on the level of lipids and lipoprotein status. Also, following the results of studies that examined the therapeutic efficacy of statins in reduction of CV risk in primary and secondary prevention and showing the dependence on gender, we included only female subjects in the study. The study included 20 healthy women, aged 30–50 years (41.35 ± 8.58 years), with no pre-existing any active or chronic disease, with no plan to alter eating and exercise habits for the duration of the study. Smokers, subjects in acute stress situations or with infections, as well as those with recent  weight changes and any supplementation with micronutrients and hormonal contraception, as well as pregnant or menopausal women, patients with hepatic, psychiatric or malignant disorders were excluded from the study. During the 4 weeks study, all participants consumed four cookies (32 g) per day without a change in dietary habits. Control group was not formed because the aim was to measure significance of changes before and after treatment, and not to measure therapeutic efficiency. The study was organized as a pilot study, as a small scale preliminary study. The cookies were produced according to the procedure given in Šarić et al. , packed 2 (kg/m2). Body weight was measured using a balanced beam scale, to the nearest 0.1 kg. Body height was measured using a Harpenden anthropometer , to the nearest 0.1 cm.Body weight  and body height  were measured and body mass index was calculated as BW/BHBlood samples were collected prior the intervention study (baseline) and at the end of the study, after 12 h fasting period, into sample tubes for serum and tubes with ethylenediaminetetraacetic acid (EDTA) as an anticoagulant for plasma. Biochemical parameters were determined from serum on the day of samples collection. Samples from EDTA tubes were centrifuged , for the separation of plasma, and aliquots were stored at −80°C for further analyses.Serum levels of triglycerides, total cholesterol, HDL, LDL, creatinine, urea, and uric acid were measured using the standard biochemical methods. All biochemical parameters were determined using Hitachi 912 automatic bioanalyser  with reagents from Analyticon Biotechnologies AG . Total cholesterol was determined by the enzymatic colorimetric CHOD-PAP method, triglycerides by the GPO-PAP method, HDL cholesterol by an enzymatic colorimetric direct HDL assay, and low density lipoprotein (LDL) by a homogeneous enzymatic direct LDL assay. Fasting plasma glucose was determined using GOD-PAP (glucose oxidase – phenol and aminophenazone) method. Creatinine was determined according to Jaffe reaction kinetic method using alkaline picrate reagent, while a blood urea nitrogen by a kinetic method using the coupled urease/glutamate dehydrogenase (GLDH) enzyme system. The level of uric acid in the blood was determined using modified PAP method.Total lipids in plasma were extracted with a mixture of chloroform/methanol  by a slightly modified method of Folch.  The lipip values lower than 0.05 was considered statistically significant.Statistical analysis of the data obtained by the dietetic intervention study was performed using the SPSS (version 11.0) software. The results are given as mean values with standard deviations. The normality test was Shapiro-Wilk before statistical analysis. Since all variables showed normal distribution, statistical comparisons of means were performed using the paired Student's t-test. p < 0.01) reduction of LDL-cholesterol level was observed at the end of study (20.16%). The level of total cholesterol, HDL-cholesterol and triglycerides was not changed significantly, and can be categorized as desirable lipid status, both before and after the study. Fasting and postprandial glucose levels were not significantly changed and they were within the reference range. Parameters relevant to liver function (AST and ALT) were found to be significantly (p < 0.05) lower at the end of study, while serum creatinine, urea and uric acid value were not significantly changed. As a parameter related to anti-inflammatory effects which can contribute to prevention of atherosclerosis, adiponectin was determined at the beginning and the end of the study and significant (p < 0.05) increase of its concentration was observed (25.52%). However, the highest impact of the cookie consumption on certain blood parameters was noticed during the study for fatty acid profile of serum lipids (p < 0.05) in saturated fatty acids (SFA) was observed with the highest decrease in palmitic (16:0) acid concentration (5.88%). On the other hand, the percentage of docosapentaenoic acid  and docosahexaenoic acid  was significantly (p < 0.05) increased after the intervention period. Accordingly, the percentage of total n-3 fatty acid significantly (p < 0.01) increased, while the ratio of n-6/n-3 significantly (p < 0.05) decreased at the end of the study.This study was performed on normal weight female subjects who included in their diet 32 g of the tested cookies per day, without a change in dietary habits. Anthropometric characteristics and biochemical parameters are shown in m lipids . SignifiBy using blueberry and raspberry pomace in the form of dried powder, a significant concentration of their bioactive compounds was achieved in the cookie formulation. The previous results  indicateConcerning the profile of cookies' bioactive compounds, the study was designed to monitor changes in composition of fatty acids serum phospholipids and certain blood parameters of normal weight female subjects who included cookies in their diet without change in dietary habits . The evaSignificant increase in DPA and DHA after the intervention can be attributed to high daily intake of α-linolenic acid. These fatty acids with documented positive effects on brain function can be obtained directly from the diet or synthesized in the body from α-linolenic acid (ALA) . HoweverThe level of adiponectin, which is supposed to have an important role in the development of atherosclerosis and insulin resistance, was also determined within the study. Recent studies indicate the inversely proportional relationship of adiponectin concentration in the blood and metabolic syndrome as well as its anti-inflammatory and anti-atherogenic potential in the treatment of metabolic syndrome and type 2 diabetes , 28. TheAlthough the results of this pilot dietetic intervention study primarily emphasized the potential health benefits of consumption the cookies with concentrated blueberry and raspberry bioactive compounds, further investigation of the achieved positive effect should to be conducted in a randomized double blind placebo control study which will include coeliac patients of both sexes. Nevertheless, one can find a cookie formulation as an inspiring model for a functional confectionery formulation. Furthermore, the food industry by-products rich in bioactives were used, which is in line with circular bioeconomy demands.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The dietetic intervention study was conducted according to the Declaration of Helsinki and was approved by the Ethics Committee of the Clinical Center of Vojvodina, Novi Sad, Serbia . The patients/participants provided their written informed consent to participate in this study.TP contributed to experimental work, statistical analysis, writing-original draft. BŠ contributed to conception, experimental work, writing-original draft and editing. PJ, JM, and AA contributed to experimental work. ES contributed to experimental work and supervision. AMi and AMa contributed to conception, supervision and writing-review. All authors contributed to the article and approved the submitted version.This work is financed by the Ministry of Education, Science and Technological Development of the Republic of Serbia (TR 31029 and 451-03-68/2022-14/2022) and 451-03-68/2022-14/200015.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


In the clinical course of diseases such as arboviruses, skin rashes may appear, as is often seen in other infectious diseases. The aim of this study was to estimate the prevalence of arboviruses and other infectious causes of skin rash in a tertiary health unit in Manaus, Amazonas state, Western Brazilian AmazonFundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD) from February 2018 to May 2019. Individuals of either gender, aged over 18 years, were invited to participate voluntarily. Infection by Zika virus (ZIKV), dengue virus (DENV), chikungunya virus (CHIKV), Mayaro virus (MAYV), Oropouche virus (OROV) and measles was evaluated using RT-qPCR . Immunodiagnostic tests for EBV, CMV, HIV, syphilis, rubella and measles were also performed. A total of 340 participants were included, most were female  with an average age of 36.5 years (SD ± 12.2 years). The highest prevalence was of ZIKV monoinfections , followed by DENV  and CHIKV infection . No cases of MAYV, OROV or rubella were found. Other causes of skin rash were detected: measles , parvovirus B19 (0.9% 3/340), HIV  and syphilis 0.6% (2/340). The co-infections identified were ZIKV+HIV , ZIKV+measles , ZIKV+parvovirus B19 , ZIKV+EBV , EBV+parvovirus B19 , CMV+parvovirus B19 , CMV+syphilis , ZIKV+EBV+parvovirus B19  and CMV+EBV+parvovirus B19 . Approximately one quarter of patients had no defined cause for their skin rash .This was a cross-sectional study of patients presenting with rash who sought care at Despite the benign clinical evolution of most of the diseases diagnosed in this series of cases, syndromic surveillance of diseases such as syphilis and HIV are of utmost importance. Periodic serosurveillance might also aid in evaluating the trends of endemic diseases and eventual outbreaks. Arboviruses are transmitted to humans by infected arthropods mostly mosquitoes, many of which lay their eggs in containers with standing water in our homes. Dengue and Zika are some of the examples of these viruses that are responsible for affecting many people in big cities every year. The illnesses can cause fever, malaise, and red patches on the skin that may or may not itch. This study aimed to investigate whether people with red patches on their skin had these diseases transmitted by mosquitoes, in Manaus, Brazil. In addition, we investigated whether they were ill from other causes, as several other illnesses can also cause red patches on the skin. The exams were carried out on 340 people, men and women over 18 years of age. It was identified that 231 people were sick from arboviruses, 227 of which were sick from Zika, 3 from dengue and 1 from chikungunya. Other causes of red spots were also identified, as was the case of sexually transmitted infections syphilis and HIV, with two and three positive cases for each disease, respectively. In addition, some cases of diseases such and measles, which are transmitted by sneezing or coughing, have been identified. Alphavirus (Togaviridae family) and Flavivirus (Flaviviridae family); other members that can affect human health are from the Bunyaviridae, Reoviridae, and Rhabdoviridae families [Arboviruses are a group of viruses that are transmitted by arthropods. Most arboviruses belong to the genera families . These cfamilies .Arboviruses are responsible for over 40,000 deaths per year worldwide and a high burden and cost to health systems ,4. CasesIn addition to the economic impacts, some arboviruses interfere directly with the patient’s occupational life; for example, although most CHIKV-infected patients show full recovery after the acute phase of the disease, severe arthralgia can last weeks or months, whereas ZIKV is capable of developing a syndrome called Guillain-Barré, which causes weakness and generalized muscle paralysis . ZIKV inArboviruses can cause a variety of clinical presentations that range from mild to life threatening symptoms. However, the clinical condition of arbovirus infections is usually constituted by fever, headache, myalgia, arthralgia, and joint edema . More thIn arboviruses, the type of rash may vary according to the virus causing the disease, and it may appear between the first and twelfth day after the onset of the first symptoms ,13. In cOther viral infections, such as HIV, parvovirus B19, Epstein-Barr mononucleosis and cytomegalovirus, rubella and measles, may also cause skin rashes, as well as bacterial infections, such as syphilis, whose classic palm-plantar rash appears in the secondary stage of the disease .During 2018, there was a resurgence of measles cases in northern Brazil, which was mainly associated with the increase in Venezuelan immigrants combined with the low vaccination coverage, and contributed to the outbreak of cases in all age groups .The current study aims to estimate the prevalence of arbovirus infection and other infectious causes in patients with acute skin rashes who were treated at a tertiary health unit in Manaus, Brazil.The study protocol was approved by the Ethics Review Board (ERB) of the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD) under CAAE number 80961517.6.0000.0005 and protocol number 2.611.564, and followed the Guidelines and Norms Regulating Research on Human Subjects established in National Health Council Resolution 466/12/MS. Written informed consent was obtained from all the participants.2. In 2018, its population was estimated at 2,145,444 inhabitants, the population density of the municipality was 158.06 inhab/km2 and the Municipal Human Development Index (HDI) was 0.737. It is the most populous city in the northern region and the seventh most populous in Brazil. The majority of the population (99.5%) lives in the urban areas of the municipality [Manaus , located in the Brazilian Amazon (at the confluence of the Negro and Solimões Rivers), is the capital of the Amazonas state, in northern Brazil and has a territorial area of 11,401,092 kmFMT-HVD, is a tertiary health unit for the diagnosis, treatment, and monitoring of tropical and infectious diseases in the Western Brazilian Amazon. Patients can seek medical assistance directly or be referred to the hospital from primary-level healthcare units.This is a cross-sectional study based on convenience sampling conducted with patients with acute rashes, with or without fever, who sought care at the FMT-HVD from February 2018 to May 2019. Individuals of either sex aged 18 years and over, who had skin rashes and the ability to provide formal consent were invited to voluntarily participate in the study. Pregnant women were excluded from the study.After voluntary consent, patients were seen by the physician and biological samples (blood and urine) were collected. Blood was obtained by venipuncture for HIV 1 and 2 immunochromatographic testing  and TR DPP-HIV 1e 2-SSP , and syphilis  testing. Positive results for HIV through immunochromatographic testing were confirmed by detection of anti-HIV antibodies using ELISA  and syphQUICKSTRIP rapid pregnancy test  was used to test women’s urine.Blood plasma was used in serological and molecular biology techniques in order to evaluate infections caused by Zika, dengue, chikungunya, Mayaro, parvovirus B19, Epstein-Barr, cytomegalovirus, measles and rubella. Urine samples were used to evaluate Zika, chikungunya and measles infections. The hCG ZIKV, DENV, CHIKV, MAYV, OROV and measles infections were evaluated using RT-qPCR  analysis of plasma and urine. A ZDC Kit , which is approved by the National Health Surveillance Agency/ANVISA (registration no. 80142170032), was used to evaluate ZIKV, DENV and CHIKV infection, while MAYV, OROV and measles infections were evaluated according to the methodologies described by Waggoner et al.  and HummParvovirus B19, Epstein-Barr, cytomegalovirus, measles and rubella infections were assessed through qualitative detection of IgM class antibodies using ELISA and the Euroimmun kit  according to the manufacturer’s instructions. Reagent and undetermined samples were revaluated using the electrochemiluminescence method. The commercial kit for the LIAISON analyzer  was used to establish confirmation via immunodiagnosis.Confirmed infection with dengue, chikungunya, Zika, Mayaro, or Oropouche was defined as a positive result by RT-qPCR for each one of these diseases.Confirmed infection with parvovirus B19, rubella, mononucleosis caused by Epstein-Barr, and cytomegalovirus were defined as positive result after using the electrochemiluminescence method.Confirmed infection of measles was defined as a positive IgM result in an immunodiagnostic test or a positive RT-qPCR result from a urine sample according to the criterion of the Brazilian Ministry of Health.Confirmed infection with HIV and syphilis were defined as a positive result from immunochromatographic testing confirmed by detection of anti-HIV antibodies by ELISA and syphilis was confirmed by quantifying antibody titers against syphilis using VDRL, according to the protocol of the Brazilian Ministry of Health.t test to compare means in cases where the distributions were parametric; for non-parametric distribution, we used the Mann-Whitney test. The significance level defined was p < 0.05, and the confidence level was 95%.All clinical and laboratory data obtained from patients were collected through standardized questionnaires and recorded using Epi Info software . Analysis was performed using Stata software version 13 . Descriptive analysis was presented by percentage distribution according to each category and mean and standard deviation were calculated for the continuous variables. The Pearson Chi-square test and Fisher exact test were used to determine the association between categorical variables. We used the Between February 2018 and May 2019, a total of 435 patients with acute rash sought care at FMT-HVD, of which 340 were included in this study .See The average age of the patients was 36.5 years , 67.1% were females (228/340) and 86.2% were brown-skinned (293/340). The most frequent signs and symptoms observed in all patients were a skin rash with a maculopapular characteristic , with a mean evolution of 2.3 days (SD ± 1.7 days) from the onset of symptoms until medical attention was sought at FMT-HVD. Pruritus , arthralgia , edema , conjunctival hyperemia  and fever  were the other sign and symptoms observed in the included patients. The mean time from the onset of general signs and symptoms to the moment of collection of biological material for diagnosis was 3.9 days (SD ± 2.4 days) in the population. By stratifying in a period of days, we observed that most patients  experienced 3 to 5 days of signs and symptoms, followed by the group of patients from 0 to 2 days of symptoms .A similar pattern for baseline and clinical characteristics was observed with regard to the confirmed ZIKV cases .p = 0.0401. We did not find significant statistical difference in the signs and symptoms between ZIKV-positive versus patients that tested positive for other infections.The average age of the ZIKV-positive patients was 38.4 years , the majority were female  and brown-skinned . The mean quantity of days since the onset of symptoms the moment of collection of biological material for diagnosis in ZIKV-positive patients versus patients that tested positive for other infections was 3.8 ± 2.3 (minimum: 1 day maximum: 16 days) versus 4.6 ± 2.3 ; See See See See A total of 25.3% (86/340) of patients were negative for all infectious agents tested in this study. The baseline and clinical characteristics of them are described in supporting information .Our findings reveal that a total of 340 patients, 74.7% (256/340) tested positive for at least one of the diseases evaluated in this study. The highest frequencies corresponded to arbovirus monoinfections such as ZIKV , followed by other etiologies such as measles , DENV , parvovirus B19  and CHIKV . HIV and syphilis monoinfections accounted for 0.3% (1/340) and 0.6% (2/340). Monoinfections by EBV and CMV were not observed.Accordingly, in the context of screening for agents that cause rash, the frequency of ZIKV was higher. Arboviruses have a variety of signs and symptoms that are often confused with other infectious diseases. Therefore, many cases can be clinically misdiagnosed. All participants included in this study had a clinical history that was suggestive of arbovirus infection. However, we also investigated and found other causes of skin rash due to the possibility that other infectious agents were responsible for these febrile and non-febrile illnesses.The participants of this study were mostly women with an average age of 36 years, which demonstrates that this would potentially be the gender and age group most affected by arboviruses. Other studies have also found similar results and have suggested that women are possibly more affected by arboviruses because they are in the home environment for longer periods and, since transmission is mainly at home and in peridomestic areas, the difference may be justified by the higher exposure, or because they tend to be more inclined to seek the health services ,25. The Regarding the prevalence of arboviruses, ZIKV monoinfection presented a high prevalence . High ZIKV prevalence has already been observed in several states of Brazil, as this disease was in a state of outbreak, especially in the southeast and northeast . Few stuAedes aegypti co-infections with DENV and ZIKV strains to demonstrate that this mosquito population has a higher efficiency and a preference for transmitting ZIKV in DENV co-infections in the vector, which may justify the low prevalence of DENV and CHIKV during the period of the ZIKV outbreak in Manaus.DENV and CHIKV presented low prevalence in this study. Chaves et al.  used expDENV outbreaks have already been described in the last twenty years in the city of Manaus, and the last one occurred in 2011. That year, a prevalence of 38.4% (260/677) of cases was detected in the same tertiary health unit where we conducted our study. Furthermore, thirteen patients were co-infected with more than one DENV serotype and six (46.1%) of them had a more severe clinical presentation of the disease. Numerous serious cases were recorded, as well as the proof of circulation of the four serotypes of the disease in the region ,32.In our study, no cases of MAYV and OROV infection were found. The last outbreaks of MAYV and OROV in Manaus were recorded in 2007 and 2008, which included three records of severe manifestations of central nervous system infections by OROV –35. In 2Our study revealed some cases of co-infections. It has already been mentioned that we used only IgM antibody quantification to diagnose some of the rash-causing diseases . Most of the co-infections in this study involved these viruses. The simultaneous appearance of IgM that was reactive for more than one virus is not a new phenomenon in diagnostic virology. In these cases, for example, studies indicate that a primary infection can be confirmed by antibody avidity as another immunodiagnosis option. Avidity tests will confirm a primary infection by detecting low avidity specific IgG or rule out a primary infection by detecting high avidity specific IgG . HoweverIn the study population, a single ZIKV and HIV co-infection was evidenced. Information on the influence of ZIKV infection on the clinical course of HIV is scarce and requires studies that are able to clarify whether HIV infection can worsen the clinical course of ZIKV infection or vice versa .We also observed a single ZIKV and measles co-infection, and this finding is important because, during arbovirus outbreaks, paying attention only to morbilliform rash can mask the possible diagnosis of other infectious agents such as measles. The availability of serological tests, a complete medical history, and physical examinations are an important part in the diagnosis and the screening of patients for common infections such as measles and should be considered during an arbovirus outbreak as this infection still remains endemic in several parts of the world, as well as in places where diseases were reintroduced, as in the case of Brazil. Other co-infections including ZIKV were ZIKV+parvovirus B19  and ZIKV+EBV . The interactions between these diseases should be studied in greater depth.We also noticed measles cases , which is an infectious disease that has supposedly been eliminated from Brazil . In 2018Classically, measles is characterized by an acute febrile illness associated with a erythematous, maculopapular rash. The illness begins with fever and typically at least one of the three “Cs”: cough, coryza, and conjunctivitis. Koplik’s spots appear on the buccal mucosa as small white papules and provide an opportunity to clinically diagnose measles a day or two before the rash. The rash appears 3–4 days after the onset of fever, first on the face and behind the ears, and then spreads to the trunk and extremities, coinciding with development of the adaptive immune response. The fever and catarrhal symptoms typically peak with the rash, which persists for 3–4 days .In our study, patients diagnosed with measles had mild symptoms, many of which resembled symptoms of arboviruses, and, at the time of care, they did not have the classic flu-like symptoms (cough and coryza). The average of the days since the onset of symptoms to the time of medical care and collection of specimens for laboratory diagnosis was 4.3 days (SD ± 2. 5 days). Most measles-positive patients had between 3 to 5 days . Many of the cases were treated in the first months of 2018, which was the beginning of the measles outbreak in Manaus, and a time when there was no efficient screening system for suspected cases in the city. As such, some mild cases, such as those in this study, may have received other diagnoses of exanthematic diseases that were not measles. However, during the outbreak period, this study showed a significant prevalence of the disease, which can be explained by the establishment of a screening and care system for suspected measles cases in the unit where we carried out our study. This was right after the disease outbreak since it is the reference institution for infectious diseases in Manaus.Sexually transmitted infections, such as HIV and syphilis, are also responsible for rashes ,13, and The rash of secondary syphilis can be widespread or localized; pustular, macular, papular, or scaly in appearance; and might mimic other dermatological processes including pityriasis rosea, psoriasis, drug eruptions. Symptoms like malaise, myalgia, sore throat, headache or low-grade fever can commonly occur, but are not so frequent. Due to its multiple forms of clinical manifestations, many clinicians may not initially suspect the disease. Without treatment, lesions of secondary syphilis can disappear spontaneously without scars. Resolution of untreated manifestations of secondary syphilis can take weeks to several months . In our p < 0.05) [Among the other causes of rash in the evaluated patients, parvovirus B19 monoinfection  was observed. Most cases of parvovirus B19, for example, are described in the child population, but some studies demonstrate the occurrence of cases in adult individuals. In a study carried in Campinas, Brazil, that investigated etiologies of illnesses that cause rashes and fever showed a frequency of 2.5% (30/519) of parvovirus B19 infection. In another study conducted in Cuba, the frequency of rashes caused by parvovirus B19 was 10.7% (32/298), and 11 positive cases (34.4%) were in people from 20 years and older ( < 0.05) . The ide < 0.05) .As previously mentioned, all patients had skin rash and clinical history of arbovirus infection. However, 25.3% (86/340) of patients were negative for all infectious agents tested in this study. We believed that most of these participants who tested negative for all infections would be infected with an arbovirus, as they presented clinical signs that were suggestive of these diseases at the time of inclusion, but the method employed was not able to detect a possible low viral load in plasma and urine. Some studies reveal that, in diseases such as ZIKV, high viral load titers can be detected in other body fluids for a period greater than or equal to those found in urine. Shedding of ZIKV RNA in saliva and urine from a female patient until 29 days after the onset of symptoms was reported in Italy in 2016 . AnotherShedding in saliva and urine has also been demonstrated for other vector-borne flaviviruses, such as dengue ,51 and WWe cannot rule out the possibility that these 25.3% undiagnosed patients presented an initial picture of other diseases that were not infectious. There is a possibility that skin rash associated with fever or without fever is indicative of a possible rheumatological disease, for example. Furthermore, the possibility of other circulating viral diseases that cause acute rash (though not included in this series) cannot be excluded.This study has some limitations in such as it may not be feasible to recommend routine testing for all fever-rash cases as broadly as was done in this study because of the high costs and difficulties associated with this method. There is also the possibility of cross-reactions in the serological tests used, though the use of avidity tests can confirm a primary infection as a diagnostic option, or molecular biology techniques followed by genetic sequencing would bring greater reliability to the results. Furthermore, the infectious diseases detected in this work are due to the FMT-HVD being a health care facility that serves the population of Manaus through spontaneous demand, as well as through referencing done by other health facilities in the city Manaus and the interior of the state of Amazonas. Some people with cases of rashes undoubtedly remained at home or received clinical diagnosis in other health units in Manaus. It is important to highlight the role of FMT-HVD as a sentinel health unit in the monitoring and laboratory diagnosis of numerous health problems in the western Amazon region of Brazil.The detection of different rash-causing pathogens provides valuable feedback to clinicians and patients. The positive cases of diseases such as measles show that vaccination policies should be strengthened for immune preventable diseases such as measles, as well as the implementation of better vector control strategies for decreasing the number of cases of arboviruses. Furthermore, it is worth mentioning that sexually transmitted infections, such as HIV and syphilis, are important causes of rashes and should be remembered at the time of clinical care.The results reveal that 74.7% (254/340) of the patients enrolled in the study were positive for one or more of the infections evaluated by us. The highest prevalence was for ZIKV monoinfection in rash patients who participated. Although low prevalence of DENV and CHIKV has been observed, these cases cannot be underestimated. No cases of MAYV, OROV or rubella were found. Our findings may reflect regional variations and important causes of rash, like measles, HIV and syphilis. However, they may also be influenced by limitations in testing, as well as a low viral load at the time of sample collection. For an endemic region for arborviruses, among other viruses that cause acute rash, a good alternative for surveillance actions would be the use of serological tests for screening in periods of greater rainfall; a period in which there are higher frequencies of cases such as DENV and ZIKV, for example, in addition to ongoing monitoring changes in diseases dynamics over the time. The results herein may aid surveillance and control strategies for diseases such as arboviruses and other diseases that cause manifestations of skin rash.S1 TableaMean ± Standard deviation. bUnadjusted p-value. cMann-Whitney test. dFisher exact test. eMinimum value: 1 day of symptom in the general population group, Zika positive group and negative group for all rash-causing infectious diseases tested in this study. Maximum value: 17 days of symptoms in the general population group, 16 days in the Zika positive group and 17 days in the negative group for all diseases tested.(DOCX)Click here for additional data file.S2 TableaMean ± standard deviation.(DOCX)Click here for additional data file.S3 TableaMean ± standard deviation.EBV: Epstein-Barr; CHIKV: Chikungunya virus; CMV: Cytomegalovirus; HIV: Human Immunodeficiency Virus; ZIKV: Zika virus. (DOCX)Click here for additional data file.S1 File(PDF)Click here for additional data file.S2 File(XLSX)Click here for additional data file.


BackgroundHypothyroidism is a common endocrine disorder worldwide. Studies on the prevalence of hypothyroidism in different geographical territories of India are sparse. Data on the prevalence of hypothyroidism in India's coal mine areas are lacking. Therefore, we conducted a cross-sectional study to determine the prevalence of hypothyroidism in the adult population living in the coal mine areas of West Bokaro, Jharkhand, India.MethodsIn total, 1484 individuals of both sexes attending the outpatient department (OPD) of Tata Central Hospital, West Bokaro, Jharkhand, with varied symptoms were screened for thyroid-stimulating hormone (TSH) levels from January 2021 to February 2022. The age of the study participants ranged from 15 to 80 years.ResultsIn total, 366 participants had hypothyroidism . The prevalence of hypothyroidism was greater in women than in men. Among the 366 patients with hypothyroidism, 311 were women and 55 were men, and the ratio was 5.5:1. The percentage of the population having hypothyroidism was 24% in this study, which is higher than that reported in other parts of India; however, our results are similar to those of a study conducted in Assam in 2017. Among patients with high TSH levels, 47%, 25%, and 19% had TSH in the range of 5.6-7.5, 7.6-10.6, and 10.6-20 μU/mL, respectively.ConclusionsSubclinical and overt hypothyroidism are common in eastern India. Patients with undiagnosed fatigue and weight gain must be screened for TSH levels. Hypothyroidism is no longer a rarity, and coal mine areas are no exception to this phenomenon. A population‑based epidemiological study of thyroid disorders in coal mine areas is an urgent need. Hypothyroidism is a common endocrinological problem worldwide. The global burden of hypothyroidism is significant. In the developed world, hypothyroidism prevalence is approximately 4-5% -3 and thHypothyroidism results from low levels of thyroid hormone with varied etiology and manifestations. Untreated hypothyroidism increases morbidity and mortality. The patient's presentation can vary from asymptomatic disease to myxoedema coma. Presently, hypothyroidism can be easily diagnosed with simple blood tests and can be treated with an exogenous thyroid hormone.This observational study was conducted to determine the hypothyroidism prevalence in patients visiting the outpatient department (OPD) of Tata Central Hospital, West Bokaro, Jharkhand.A single-centre, observational study was conducted in the West Bokaro coal mine area, Jharkhand, India, to study hypothyroidism prevalence among the adult population. Thyroid abnormalities were diagnosed based on laboratory results of TSH. Patients with a history of hypothyroidism and receiving levothyroxine therapy or those with serum TSH > 5.50 μU/mL were considered to have hypothyroidism. The TSH of all the participants was measured at the same laboratory on a chemiluminescent immunoassay platform by using dimension equipment from Siemens. A reference range of 0.3-5.5 μU/mL was considered normal.The information for the study was collected from patients visiting the OPD at Tata Central Hospital, West Bokaro coal mine area, Jharkhand, from January 2021 to February 2022.Previous studies have shown that the prevalence of hypothyroidism is 10.9%. This established the proportion under the null hypothesis as 0.11. To calculate the sample size for binomial data, using a non-inferiority alternate hypothesis to infer a relative difference with a type one error of 5% and power of 80%, to detect a minimum detectable difference of 3% and a dropout of 20%, a minimum sample size of 800 will be adequate. The sample size was calculated manually by using one sample proportion formula.A total of 1484 individuals of both sexes in the age group of 15-90 years were included in the study. These patients presented to the OPD with vague symptoms of weight gain, cold intolerance, menstrual irregularities, lethargy, and fatigue. After a thorough clinical examination, TSH screening was performed on all of them, and the results obtained were analyzed.All patients in the age group of 15-90 years who consented to participate in the study were included in the study. Patients aged <15 or >90 years were excluded. Furthermore, pregnant women and patients with acute or chronic systemic illnesses were excluded. Moreover, patients taking steroids, lithium, amiodarone, or other drugs that can interfere with thyroid function tests were excluded. Additionally, patients who have undergone thyroid surgery or radiotherapy to the head/neck area were excluded.A detailed history of any chronic illness and drug intake history  was obtained. A detailed clinical examination was performed to exclude any chronic or acute systemic illness. Laboratory investigations including tests for biochemical parameters  were performed where deemed necessary.A total of 366 of 1484  participants received a diagnosis of hypothyroidism, which is similar to the findings of a study by Mahanta et al. from Assam Medical College  in 2017 Data were collected using MS Excel . Continuous variables were expressed as mean (SD), median, and ranges; categorical variables were expressed as numbers and percentages. The age-wise distribution of the participants is presented in Table Hypothyroidism is a common endocrine disorder in India and other parts of the world. The clinical manifestations of hypothyroidism are varied, including weight gain, cold intolerance, menstrual irregularities, lethargy, and fatigue. The clinical spectrum of hypothyroidism varies from asymptomatic subclinical hypothyroidism through overt hypothyroidism to life-threatening myxoedema coma. Women are more prone to hypothyroidism than men. The prevalence of hypothyroidism was found to be common in the 35-45-year age group (Table The male-to-female ratio in this study was 1:5.5 (Figure The high prevalence of hypothyroidism in the present study is probably due to referral bias because candidates were sent for sampling based on clinical symptoms. Hence, this figure may be higher than the actual prevalence in the general population. However, the high prevalence of 24% (Figure In an epidemiological study conducted in eight cities in India, Unnikrishnan et al.  reportedLimitationsThis study being a cross‑sectional observational study, the study participants were not followed‑up. Moreover, sampling was performed based on clinical signs and symptoms. Furthermore, the study results are subject to referral bias, which may account for the high prevalence of overt hypothyroidism found in our study. Free T3 and free T4 analyses were not conducted in our study, and hence, patients with central hypothyroidism were not excluded. Additionally, the evaluation for autoimmune thyroid diseases with the levels of antithyroid antibodies such as thyroid peroxidase antibodies was not performed.Hypothyroidism is a significant health problem in India and worldwide. Our study provides an idea of the prevalence of this entity in the coal mine areas of West Bokaro. Subclinical and overt hypothyroidism is common in eastern India. Hypothyroidism is common in women, usually presenting as vague manifestations. The common presenting complaints are fatigue, body aches, weight gain, constipation, menstrual irregularities, and infertility. Therefore, any individual presenting with undiagnosed fatigue, weight gain, and menstrual irregularities should be subjected to TSH screening. Given the findings of the present study and considering its limitations, a long‑term population‑based, follow‑up study of thyroid disorders in the coal mine areas of India is needed.