Background: Thrombocytosis is a common finding in hospitalized patients and is of two main types, essential thrombocytosis (ET) and reactive thrombocytosis (RT). It is important to distinguish the two due to increased risk of developing marrow fibrosis, acute leukemia, and thrombosis in the former. Molecular studies are the main tools to differentiate the two but are not available in all hospitals. We aimed to design a highly sensitive scoring system using routine lab data to classify thrombocytosis as essential or reactive.Methods: A total of 145 patients were enrolled in this study. Potential predictors included patient demographics and clinical laboratory parameters. Receiver operating characteristic curve analysis was used to decide the optimal cutoff level. Multivariate logistic regression with forward model selection method was performed to decide the predictors.Results: The risk scores by multivariate analysis were as follows: 1 point for WBC > 13,500/μL; 2.5 points for Hb > 10.9 g/dL; 3 points for platelet count > 659,000/μL; and 2 points for MPV > 9.3 fL. The cut off value was set as 4.5 points, and sensitivity of 91.1% and specificity of 75.8% were noted.Conclusion: In this study, we investigated lab data and developed a high-sensitivity convenient-to-use scoring system to differentiate ET from RT. The scoring system was assigned to the resulting model to make it more economical, simple, and convenient for clinical practice. Platelets play an important role in bleeding and blood clotting. The normal platelet count in adults ranges from 150,000 to 450,000 per microliter. A condition in which the platelet count exceeds 450,000/μL is defined as thrombocytosis. Thrombocytosis is a common finding in hospitalized patients and is reported in patients admitted for trauma , and treStudies have reported that 80 to 90% of the cases are diagnosed with reactive thrombocytosis . Reactiv12 cells/liter, thrombovascular complications are rare. In contrast, more thrombotic events are reported with essential thrombocytosis  without JAK2V617F mutation and cytoreductive therapy during follow-up were identified as RT. ET was diagnosed based on the presence of any one of the following criteria: (1) JAK2V617F mutation, (2) CALR mutation, (3) bone marrow examination showing results typical for ET such as a hypercellular bone marrow, increased numbers of megakaryocytes, giant megakaryocytes, clusters of megakaryocytes, or other dysplastic megakaryocytic changes, as per the 2016 WHO guidelines . In our Potential predictors including patient demographics and clinical laboratory parameters, including age, sex, white blood cell (WBC) counts, hemoglobin (Hb) level, mean corpuscular volume (MCV), platelet counts (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and differential WBC count were considered for predicting ET. It is standard practice to perform clinical laboratory tests when patients suffer from thrombocytosis. Thus, these values are readily available. Furthermore, medical records of the patients were assessed to determine the etiology of thrombocytosis.U test for quantitative variables and Chi-square test for qualitative variables were performed to evaluate the differences in subject characteristics between the two groups.Summary statistics including mean with standard deviation and the frequency with the percentage were provided for quantitative variables and qualitative variables, respectively. The Mann-Whitney p < 0.05 in the multivariate analysis were referred statistically significant and were incorporated into the risk prediction model. The regression coefficient from each factor was transformed to a risk score by dividing its regression coefficients by the smallest regression coefficient among the factors and rounding the quotients to the nearest integer for developing the risk scoring system. The optimal cutoff value of the risk scoring system and the corresponding sensitivity and specificity, based on the optimal cutoff value, were obtained using the ROC curve analysis.The receiver operating characteristic (ROC) curve analysis was used to decide the optimal cutoff value of each potential predictor, based on the Youden index. The area under curve (AUC), cutoff level, and the corresponding sensitivity and specificity based on the decided cutoff level were calculated for each potential predictor. Multivariate logistic regression with forward model selection method was performed to determine the predictors for predicting ET. In the model, each potential predictor was redefined as a two-level factor based on its cutoff value, obtained from the ROC curve analysis. The Hosmer-Lemeshow goodness-of-fit test was further used to evaluate the calibration ability of the prediction model. Factors with p values were two-sided, with a value < 0.05 considered statistically significant. All data were analyzed using SPSS software .All P < 0.05).A total of 145 patients were enrolled in this study; 66 patients were diagnosed with ET and 79 had RT. The characteristics of the two groups are presented in Among patients with ET, 42 patients (63.7%) had JAK2 V617F mutation, 15 patients (22.7%) had CALR mutation, and 9 patients (13.6%) were negative for both JAK2 V617F and CALR mutations . The etiology in patients diagnosed with RT included 19 (24.1%) cases with iron-deficiency anemia without cancer, 34 (43%) with infection, 17 (21.5%) with malignancy, and 9 (11.4%) with other causes.p = 0.531).Multivariate logistic regression analysis demonstrated four independent risk predictors for distinguishing ET and RT based on forward model selection method: WBC (/μL), Hb (g/dL), platelet count (/μL), and MPV (fL) . Thus, wWe assigned risk scores relative to the regression coefficient of each variable that showed statistical significance in the multivariate analysis : 1 pointSince thrombocytosis is a common finding in hospitalized patients, distinguishing between ET and RT is important for determining the treatment plan and to ensure a good prognosis. Thus, we have developed a reliable, convenient-to-use, and economical scoring system, comprising four evaluable factors, to distinguish between ET and RT. This model utilizes routine laboratory data for differentiating the two types of thrombocytosis. The simplicity of the scoring system and the high sensitivity are important strengths of our model. This makes it capable of verification by other users, including clinicians, thus enabling its widespread use.Essential thrombocytosis may result in the development of myelofibrosis and acute leukemic transformation, while RT is generally regarded as benign and has infrequently been reported to cause severe and even fatal complications , 16. ManWang et al. attempted to use amount of IGF-1 receptor in the differential diagnosis. The levels of IGF-1R were significantly elevated in ET groups compared to in RT groups or controls . RyningeSince the discovery of JAK2V617F, CALR, and MPL mutations as phenotypic driver mutations in essential thrombocytosis –11, the P < 0.01) and had a sensitivity of 65% and specificity of 89%  could help distinguish ET and RT; additionally, CBC can be easily performed at all clinics and hospitals. Sehayek et al. used the platelet parameters and aggregation to compare essential with reactive thrombocytosis. The results showed that MPV was significantly lower in patients with ET vs. those with RT. A platelet volume distribution width ≥10.5 was found in 50 and 21% of ET and RT patients, respectively. But the authors had only enrolled 15 patients with ET . Toprak y of 89% . In our Although only a few patients who might miss the diagnosis of ET, the risk of thrombotic events, marrow fibrosis, and acute leukemia transformation were still needed to consider. Therefore, distinguishing between the two types is essential for clinical practice. For the purpose of this study, we hope to design the scoring system for “screening.” High sensitivity and convenience to use are more important than specificity.This study still has several limitations. First, an inherent selection bias due to the retrospective study design cannot be avoid. And we only enrolled the ET patients who was diagnosed with bone marrow examination and molecular study by hematologists. The RT patients were enrolled with thrombocytosis once and then recovery of platelet count later. If the patients did not refer to the hematologic department, they had been excluded from this study. An overt selection bias was noted. Although above, we hope to design the scoring system for the doctors of family medicine or general practitioners, except hematologists and help them to aware of ET. Second, the sample size was still small although we have collected more cases than previous submission. A further prospective cohort with a larger sample size is needed to validate our screening scoring system.In this study, we used just one routine lab data to build a high-sensitivity scoring system to screen the patients with thrombocytosis to possible ET patients and possible RT ones. The four factors were white blood counts, hemoglobin level, platelet counts, and MPV. The scoring system was assigned to the resulting model to make it more economical, simple, and convenient for clinical practice. We hope to design a scoring system for family medicine or general practitioners to identify possible bone marrow disease and consult hematologists, and then transfer the patients to hematologists for further bone marrow examination and molecular studies. If the patients were found and transferred to hematologists, further treatment, including cytoreduction, prevention from thrombosis, evaluation about myelofibrosis or leukemic transformation, will be greatly helpful for these patients.wuyifeng43@gmail.com.The data analyzed in this study is subject to the following licenses/restrictions: Due to IRB, raw data were generated at Hualien Tzu Chi Hospital. Derived data supporting the findings of this study are available from the corresponding author Yi-Feng Wu on request. Requests to access these datasets should be directed to Yi-Feng Wu, The studies involving human participants were reviewed and approved by Institutional Review Board of Buddhist Tzu Chi General Hospital . Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.C-LS, T-CH, and Y-FW contributed to data analysis and manuscript editing. T-FW, W-HH, and S-CC collected the data of patients. C-LS and T-CH helped in manuscript preparation. Y-FW contributed to the supervision of the whole process. All authors contributed to the article and approved the submitted version. The work reported in the above for publications has been done by all authors.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.


Participation in community affairs and activities is beneficial to the mental health of older adults. The current study attempted to confirm the mediating role of sense of community (SoC) between community participation (CP) and subjective well-being (SWB), and the moderating role of neuroticism between CP and SoC. A total of 465 older adults aged ≥65 years from China participated in both two-wave online surveys. The self-developed Community Participation questionnaire, the SoC scale, and the Neuroticism subscale were used to assess CP, SoC, and neuroticism, respectively. The four indicators of SWB were assessed by the Satisfaction with Life Scale, Positive Affect and Negative Affect Schedule, and the Center for Epidemiological Studies-Depression scale. The results revealed that CP was associated with three indicators of SWB including life satisfaction, positive affect, and depressive symptoms, SoC mediated the above associations, and neuroticism negatively moderated the association between CP and SoC, after controlling for age, sex, education, spouse status, monthly income, and physical health. CP enhances older adults’ SWB through increasing their SoC. When compared to those older adults with a higher score of neuroticism, the enhancing effect of CP on SoC is stronger for those with lower scores of neuroticism. According to the convoy model, individuals continuously change their identities and roles, create new needs and expectations, and replace convoy memberships through their life-span and life-course ,2. Old aAccording to the aging in place theory, older adults want to age in place, live with family and friends, and remain independent and autonomous; they also expect to have more opportunities to participate in social community activities which can help them form strong senses of security and belongingness of community ,9. The aDespite the robust link between CP and subjective well-being (SWB) being well-established by a growing literature, understanding the basic mechanisms requires further efforts of researchers in different fields. Several studies emphasized the role of perceived support in the link between community engagement with well-being ,13,14. SAlthough CP has been shown to be positively associated with SoC, this does not mean that all individuals can equally benefit from this process and contribute to growth of one’s SoC. Inferring from a person–environment interaction perspective , individFor decades, SoC has become one of the most commonly used concepts and the focus of empirical research in field of community psychology. SoC is defined as “a perception of similarity to others, an acknowledged interdependence with others, a willingness to maintain this interdependence by giving to or doing for others what one expects from them, and the feeling that one is part of a larger dependable and stable structure” . Some reBoth CP and SoC are closely relevant to quality of life and mental health of community-dwelling residents, including older residents. A meta-analysis indicated a moderate association between CP and SoC; this correlation was quite stable across all studies included in the meta-analysis . On the Researchers have revealed the positive significance of SoC in influencing one’s mental health and SWB ,30,31,32Neuroticism is one of more foundational traits and reflects some kind of universal and cross-cultural personality tendency. According to Eysenck’s personality theory, introversion–extraversion and emotional stability–instability (or neuroticism) are two basic personality dimensions. Neuroticism reflects one’s emotional instability and is relevant to how people create or maintain available social networks . The stuThe association between community participation and sense of community may be vary with individual features. Inferring from a perspective of person–environment interaction, a few intriguing studies have revealed the interaction effect of individual characteristics and community characteristics on SoC ,41,42,43According to the Diathesis–Stress model, the associations between environmental factors and psychological outcomes can be moderated by personal traits . PersonaMost existing studies have confirmed the close relationship between CP and SWB. However, the reason why CP affects the subjective well-being of old adults remains to be explored, in particular, the psychological mechanisms of the association between CP with Chinese characteristics and SWB of old people. It is worth noting that the old adults with different characteristics may achieve different degrees of SWB by participating in community activities. Thus, it is necessary to examine interaction effect between environmental factors and personality traits for the old people in the context of community.The current study had three aims. First, we hoped to explore whether CP is associated with SWB ; second, whether SoC mediates above associations; third, whether neuroticism moderates the association between CP and SoC among old people. The hypotheses were as follows:Hypothesis 1 (H1).CP is associated with SWB indicated by life satisfaction, positive affect, negative affect, and depressive symptoms.Hypothesis 2 (H2).SoC mediates the association between CP and SWB.Hypothesis 3 (H3).Neuroticism moderates the association between CP and SoC.The sample was drawn from a national project on the organizational participation and quality of life of older adults. The ethics committees of the corresponding authors’ affiliation approved this project. Participants were provided online informed consent before the investigation was formally conducted. Community-dwelling residents aged 65 years and above were selected as participants from urban communities in five cities in China. The investigators adopted the convenience sampling to recruit participants by posting recruitment posters in the community and sending recruitment information in community Wechat groups. The investigators were trained to further ensure that they could understand the purpose of the survey and response participants’ questions. Participants answered questions on Questionstar—an online survey platform in China—due to prevalence of COVID-19 during the investigation process. After the questionnaires were collected, the investigators deleted some invalid questionnaires by screening whether the answers were the same or in order. The current project has completed two wave surveys with an interval of six months (the first wave survey was conducted in June 2020 and the second wave was conducted in December 2020). A total of 1576 valid questionnaires were collected in the first wave survey and 986 valid questionnaires were collected in the second wave survey. Finally, a total of 465 participants effectively completed both wave surveys. In the valid sample, there were 149 men and 316 women see . DemograCommunity participation questionnaire referred to the community participation survey, with five items published in a recent study which included community residents’ organizations or neighborhood committees, volunteer service associations, wedding and funeral councils or similar organizations of residential communities, organizations based on interests, hobbies, and training, or community charitable organizations . In our 2 = 13.52 (p < 0.001), χ2/df(8) = 1.69, CFI = 0.98, TLI = 0.96, RMSEA = 0.06 (90% CI: 0.00–0.10), SRMR = 0.03). As a result, the summated mean scores represented the overall level of CP of older adults in China.Participants were asked to answer the level of participation in community organizations using a five-point scale . The reliability and validity of questionnaires were well verified. First, Cronbach’s alpha coefficient for all six items was 0.72, and coefficients of all pairwise correlations were positive and significant. Second, all participants were randomly divided into two equally sized sub-samples. Sub-sample 1 (n = 233) was used to conduct an exploratory factor analysis (EFA), and sub-sample 2 (n = 232) was used to conduct a confirmatory factor analysis (CFA). EFA showed that only one eigenvalue was above 1.0 (2.74); this single factor accounted for 45.72% of the total variance, and the factor loadings of all items were over 0.40. CFA indicated that the single-factor structure had an acceptable goodness of fit  Personality Scales . The neuSWB is a comprehensive psychological index to measure individuals’ life quality and generally includes three aspects: life satisfaction, positive affect, and negative affect . Since nSWLS was used to assess one’s general satisfaction with life and reflects cognitive aspects of SWB . The ChiThe PANAS was often used to assess one’s general emotional respects of SWB and comprised positive and negative affect during the past month . The ChiCESD scale with 10 items was used to assess one’s depressive symptoms during the last month . The resDemographic and socio–economic factors as covariates included age, sex, education, spouse status, monthly income, and physical health. Overall physical health was assessed by a single-item: “Compared to people your own age, please rate your physical health on the whole” . Participants reported individual monthly income as the indicator of economic status with a 5-grade income list (from “less than 2000 CNY” to “more than 8000 CNY”). The grade scores of physical health and monthly income were treated as continuous variables in the analysis see .2) and freedom degree, CFI, TLI, RMSEA, and SRMR.SPSS 24.0 version  program was used to examine the descriptive statistics and correlation analyses. Mplus 8.0  was emplM = 2.36, SD = 0.64). About 64.9% of older adults reported a relatively high level of participation in at least one type of community organization . Participants had higher sense of community, life satisfaction and positive affect, lower depressive symptoms and negative affect, and moderate neuroticism when compared to the middle values , χ2/df(22) = 3.23, CFI = 0.97, TLI = 0.91, RMSEA = 0.07 (90% CI: 0.06–0.09), SRMR = 0.06. The goodness of fit was not excellent but basically acceptable [We conducted the moderated mediation model analysis after a mere mediation model. The goodness of fit of the moderated mediation model was as follows: χceptable . The resThe findings provide a new perspective for exploring paths and conditions whereby CP affects SWB. Meanwhile, policy-makers and managers can take advantage of these insightful findings to advance active aging in basic-level community.First, Hypothesis 1 was partly confirmed. The older adults having a higher frequency of CP often reported higher life satisfaction and positive affect, and lower depressive symptoms. The benefits of CP were confirmed again, which were consistent with previous main findings. As the Declaration of Madrid on aging emphasizes, participation, accompanying health and security, is one of core standards of active and successful aging . The resSecond, Hypothesis 2 was confirmed. SoC, to a large extent, accounts for the effects of CP on nearly all four indicators of SWB. Some relevant theories and empirical studies give some inspirations from different perspectives. Firstly, psychological empowerment theory believes that CP empowers individuals with sense of competence or self-control, and enables them to independently cope with affairs of their residential community . Extant Third, Hypothesis 3 was confirmed. Neuroticism negatively moderated the effect of CP on SoC. We also found that neuroticism is negatively associated with SoC. Emotional instability as adverse side of neuroticism is related to the sense of belonging, attachment to community, and reciprocal trust among residents ,74. ReleIt should be acknowledged that the current study has unique theoretical and practical contributions. First, despite a mass of evidence having confirmed the positive benefits of community participation on enhancing SWB, the relevant mechanisms based on residential community remain insufficient in the Chinese context. These findings offer further evidence for the aging-in-place theory and provide the direction for construction and implementation of age-friendly communities, which contribute to active aging. Second, this study explored the determinants of SoC from individual characteristics and social context. The findings of the current study further supplement person–environment interaction thought, based on specific personality and community organization and the Diathesis–Stress model ,45. The Several limitations in the design and methods should be pointed out. First, we adopted a two-wave longitudinal design with six months apart to examine the association between CP and SWB and relevant mediating and moderating mechanisms. Some scholars have proposed that conducting a complete mediating analysis needs at least three occasions of measurement, and adopted a cross-lagged analysis ,76. TherThis study is a meaningful exploration to understand the significance of CP and the relevant mechanisms in maintaining and enhancing SWB among older adults. First, the findings supplement further evidence about benefits of CP on mental health and quality of life among older adults. Second, SoC as a psych-socio factor mediates the link between CP and SWB. Third, there were individual differences in the benefits of CP on SoC. Limitations and questions surrounding current study would provide direct guidance for future studies in field of community and aging psychology. These findings and thoughts will also provide some insights for community management and services on successful and healthy aging.


Background: Asthma is one of the most burdensome childhood disorders. Growing evidence disclose intestinal dysbiosis may contribute to asthma via the gut-lung axis. Constipation can lead to alteration of the gut microbiota. The clinical impact of constipation on asthma has not been researched. Therefore, we aim to assess whether pediatric constipation influence the risk of developing asthma by a nationwide population-based cohort study.Methods: We analyzed 10,363 constipated patients and 10,363 individuals without constipation between 1999 and 2013 from Taiwan's National Health Insurance Research Database. Analysis of propensity score was utilized to match age, sex, comorbidities, and medications at a ratio of 1:1. In addition, multiple Cox regression analysis was performed to evaluate the adjusted hazard ratio of asthma. Furthermore, sensitivity tests and a stratified analysis were performed.Results: After adjustment for age, sex, comorbidities, and medications, constipated patients had a 2.36-fold greater risk of asthma compared to those without constipation . Furthermore, the severity of constipation is associated with an increased risk of asthma; the adjusted hazard ratio was 2.25, 2.85, and 3.44 within < 3, 3–12, and ≥12 times of laxatives prescription within 1 year, respectively (p < 0.001).Conclusion: Constipation was correlated with a significantly increased risk of asthma. Pediatricians should be aware of the possibility of asthma in constipated patients. Further research is warranted to investigate the possible pathological mechanisms of this association. Asthma is one of the most burdensome childhood disorders. It has been estimated that more than 9 million children in the United States  and moreIn recent years, constipation has been shown to be a causative factor in bowel dysbiosis and therapeutic administration has been increasingly applied. Such therapies include probiotics, prebiotics, or synbiotics, which are thought to help regulate the intestinal microbiota . MoreoveThis study analyzed data from the National Health Insurance Research Database (NHIRD), which contains the healthcare data of almost 99% of Taiwan's entire population, i.e., ~23 million NHI beneficiaries. The database includes all insurance claims data, including outpatient visits, emergency visits, and hospitalizations. The Longitudinal Health Insurance Database, (LHID) is a subset of the NHIRD comprising one million individuals randomly sampled from the 23 million NHI beneficiaries for the period from 1999 to 2013. The patients' data were de-identified prior to release to the researchers, in accordance with privacy protocols. Written consent from study subjects was not required and waived by the Institutional Review Board of Chung Shan Medical University Hospital (IRB no. CS15134), because the NHIRD comprises de-identified data for research purposes. The study carried out in accordance with IGH-GCP requirements and the essence of Declaration of Helsinki.The population was composed of patients aged ≤ 18 years old with newly diagnosed constipation (ICD-9-CM codes = 564.0) from 2000 to 2012. To ensure accuracy of diagnoses, we excluded any diagnosis of constipation before 2,000 and only patients with at least three outpatient visits or one hospitalization were selected for inclusion in the final analysis. The index date of this cohort was set as the first date of diagnosis of constipation. Furthermore, to ensure that all individuals had new-onset asthma, we ruled out any diagnosis of asthma (ICD-9-CM = 493) happening before the index date.The outcome variable was defined as a diagnosis of asthma with at least three outpatient visits or once hospitalization and a prescription for an anti-asthmatic medication including inhaled corticosteroids (ICSs), short-acting β-agonists, and systemic corticosteroids within 1 year . The pat2), population ratio of people with college or above educational levels, population ratio of elder people over 65 years old, population ratio of people of agriculture workers and the number of physicians per 100,000 people. The comorbidities were defined as occurring within 1 year prior to the index date with at least three outpatient visits or once hospitalization. In addition, corticosteroids, antihistamines, and antibiotics during the study period were included and defined as usage for at least ≥30 days. To evaluate the severity of constipation, we collected additional information on the total numbers of prescriptions for laxatives [anatomical therapeutic chemical (ATC) classification system code A06A], which were given within 1 year after the index date.The baseline characteristics were age, sex, urbanization, allergic rhinitis (ICD-9-CM = 477.9), allergic conjunctivitis , atopic dermatitis (ICD-9-CM = 691), and bronchiolitis (ICD-9-CM = 466.1). The degree of urbanization was clustered into urban, suburban, and rural by population density . Whenever the ASD was <0.1, the characteristics of the two groups were deemed to be similar . Cox proThe flowchart is shown in p < 0.001). Compared with women, men had a significantly higher risk of asthma . In term of comorbidities, we observed that people with atopic dermatitis or bronchiolitis had a relatively higher risk of asthma . By contrast, patients using corticosteroids, antihistamines, or antibiotics during the study for a period of at least 30 days had a lower risk of asthma .P < 0.001). Patients aged 0–6 and 13–18 years in the constipation group had a 2.22-fold and 1.76-fold greater risk of asthma . Among females, compared with those without constipation, there was a 2.62-fold higher risk of asthma in patients with constipation . Among males, there was 1.89-fold higher risk of asthma in patients with constipation . Furthermore, constipated patients had a higher likelihood of asthma, regardless of urbanization, comorbidities and medications.As shown in P <0.001), 2.85-fold , and 3.44-fold  higher risk of developing asthma in constipated patients with < 3, 3–12, and ≥12 times of laxatives prescription within 1 year, respectively. There appeared to be a dose-effect relationship between constipation severity and risk of asthma. The Kaplan–Meier curves are shown in P < 0.001.In this research, children with constipation had a 2.36-fold higher risk for developing asthma than non-constipated individuals, regardless of age, sex, comorbidities, or medications. As far as we know, this is the largest epidemiological study utilizing a nationwide longitudinal population-based dataset to explore the association between constipation and asthma. The findings could be of pathophysiological and clinical importance. Our results highlight the considerably higher risk of asthma in children with constipation. Constipation might be influential in the development of asthma. Pediatricians should be mindful of the possibility of asthma in constipated children. Moreover, constipated patients should be informed of the potential risk of developing asthma and be provided with applicable management for asthma as required. Our findings further highlight the importance of maintaining appropriate bowel habits in order to prevent constipation, which could in turn mitigate risk of asthma.We also observed that the risk of developing asthma was appreciably increased in children with atopic dermatitis and bronchiolitis. Atopic dermatitis is a chronic inflammatory skin disorder and is regarded as the beginning of the “atopy march” , which rClostridiums spp., whereas Bacteroides stercoris and Faecalibacterium prausnitzii were depleted in individuals with asthma  and related regulations of the National Health Insurance Administration and NHRI , and an agreement must be signed by the applicant and his/her supervisor upon application submission. The datasets generated and analyzed during the current study are available from the authors on reasonable request.The LHID is a subset of the NHIRD, a database of all medical claims in Taiwan's NHI system. The usage of NHIRD is limited to research purposes only. Only Taiwanese citizens who fulfill the requirements for conducting research projects are eligible to apply for access to the National Health Insurance Research Database (NHIRD). Applicants must follow the Personal Data Protection Act . Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin. Written informed consent was obtained from the individual(s), and minor(s)' legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.Y-CH and M-CW drafted the manuscript. JW revised the manuscript critically. All authors provided a substantial contribution to the conception, design, interpretation of the work, and approved the final version of the manuscript.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.


Little is known about the importance of non-technical skills for the adherence to guidelines, when teams of midwives, obstetricians, anesthesiologists, and pediatricians resuscitate and support the transition of newborns. Non-technical skills are competences underpinning successful teamwork in healthcare. These are usually referred to as leadership, situational awareness, communication, teamwork, decision making, and coping with stress and fatigue.By review of videos of teams managing newborns with difficult transition, we aimed to investigate whether the level of the teams' non-technical skills was associated with the degree of adherence to guidelines for newborn resuscitation and transitional support at birth.1 = poor, 3 = average and 5 = excellent). The outcome was the clinical performance score of the team assessed according to adherence of the European Resuscitation Counsel (ERC) guideline for neonatal resuscitation and transitional support. The ERC guideline was adapted into the checklist TeamOBS-Newborn to facilitate a structured and simple performance assessment . Interrater agreement was analyzed by intraclass correlation (ICC), Bland-Altman analysis, and Cohen's kappa weighted. The risk of high and low clinical performance was analyzed on the logit scale to meet the assumptions of normality and constant standard deviation.Four expert raters independently assessed 43 real-life videos of teams managing newborns with transitional difficulties, two assessed the non-technical score and two assessed the clinical performance. Exposure was the non-technical score, obtained by the Global Assessment Of Team Performance checklist (GAOTP). GAOTP was rated on a Likert Scale 1–5  2.4–22.5] of high clinical performance score compared to teams with average non-technical score. In addition, we found a dose response like association. The specific non-technical skills associated with the highest degree of adherence to guidelines were leadership and teamwork, coping with stress and fatigue, and communication with parents. Inter-rater agreement was high; raters assessing non-technical skills had an interclass coefficient (ICC) 0.88 (95% CI 0.79–0.94); the neonatologists assessing clinical performance had an ICC of 0.81 (95% CI 0.66–0.89).Teams with an excellent non-technical score had five times the chance of high clinical performance compared to teams with average non-technical skills. High performance teams were characterized by good leadership and teamwork, coping with stress, and fatigue and communication with parents. The first breath of a newborn initiates the transition from placental dependence to independent life . An unsuThe skills to support transition and resuscitate the newborn are essential for every healthcare provider working in the delivery ward. Most newborns adapt well to life after birth. However, some 5–10%) need positive pressure ventilation but only few (0.1–0.3%) receive chest compressions . A prere–10% needAll resuscitation teams try to follow current guidelines to produce the best infant outcomes, but performance may fall short of expectations . As a reThe purpose of this study was to utilize video recording in the delivery rooms to investigate whether the level of non-technical skills in interdisciplinary teams of midwives, obstetricians, anesthesiologists, and pediatricians was associated with the degree of adherence to newborn resuscitation guidelines.Real-life video-recordings of newborns were collected from November 2014 to February 2016 at two Danish hospitals; Aarhus University Hospital and Horsens Regional Hospital. Aarhus University Hospital, with ~5,000 deliveries per year, provides maternal care level III  and neonAll 17 delivery suites at the two hospitals were equipped with two or three high-definition mini-dome surveillance cameras and a microphone in the ceiling to cover an oblique view of the room, and the neonatal resuscitation table. Recordings were automatically activated by blue tooth as described previously . In caseExposure was the non-technical score obtained by the Global Assessment Of Team Performance checklist (GAOTP) developed by Morgan et al. , 15. TheThe checklist included six dimensions:Communication with patient/parents: Excellent team performance was defined as sharing information with the parents and when possible, involving parents in the newborns care.1) Task/case management: excellent team performance was scored if urgency of the clinical situation was recognized, goals were set and communicated with the team and resources were effectively utilized.2) Leadership and teamwork: excellent team performance was scored if roles were quickly established, a leader was identified, leader encouraged participation and identified opportunities for improvement, and team's roles, and responsibilities were clear.3) Situational awareness: excellent team performance was scored if there was early recognition and a rapid response to a critical situation, if extra personnel were summoned in a timely fashion, and team members remained vigilant, and alert to the clinical situation.4) Communication with team members: excellent team performance was scored if communication was focused with clear questions and instructions directed to a specific person, receiver acknowledged receipt of message and confirmation that requested actions was completed.5) Environment of the room: excellent team performance was scored if the environment was orderly and controlled, voices remained calm and focused, no sign of stress or fatigue among team members.6) 1” was a poor non-technical score, “3” was an average non-technical score, and “5” was an excellent non-technical score  Initial assessment and support of transition, 7 items; (3) A-problems, 5 items; (4) B-problems, 4 items; (5) C-problems, 4 items; and (6) Global score. The raters assessed all items according to the ERC guideline in three levels: 0 points (not done or done incorrectly), 1 point  and 2 points (done correctly and in a timely manner). We also included the category Cannot be assessed or not indicated  . The score of each item was then multiplied by the assigned weight of the item and totaled to give a weighted score, i.e., a percentage of the highest possible score . To assess 'high clinical performance' we used the ERC guideline (“checklist”) as one of two parts of the evaluation. The second part of the evaluation was a global score of patient safety introduced in order to allow the experienced raters to provide the team with a numeric score from 0 to 100 on a visual analog scale; with 100 reflecting best expert standard. The TeamOBS-newborn tool resulted in a clinical performance score from 0 to 100, where low clinical performance was 0–59, average clinical performance was 60–84, and high clinical performance was 85–100  guideline for neonatal resuscitation and transitional support. In both hospitals all healthcare providers in the Labor and Delivery units  were trained by the ERC guideline. As the guideline was updated during the study, both the more recent and the previous guideline was accepted as part of our checklist, e.g., in the assessment of heartrate we accepted any assessment as there was no specific recommendation for heart rate measurement in the 2010 guideline and the 2015 guideline recommended this be changed to a 3-led electrocardiogram. The ERC guideline was adapted into the checklist 'sessment , 18. Thes 85–100 . Two expNone of the raters were involved in the delivery or the management of the newborn.All videos were included following informed consent in conformity with the Danish penal code §264. Gaining informed consent during labor was not acceptable according to the Danish Health Act §43–44. Women were informed about the research project TeamOBS during antenatal visits. All women who planned to give birth in one of the two Labor and Delivery wards were informed between gestational week 18–28 by oral and written information provided by a sonographer or a midwife. Whether the woman accepted or denied participation was noted in her medical record. If participation was declined cameras were inactivated. If participation was accepted the cameras were activated automatically by staff's mobile devices if resuscitation of the newborn was initiated. The use of any recording should be approved within 48 h after delivery by all persons present in the room; i.e., the woman giving birth, her husband or any other person she had asked to be present, and all healthcare providers. If written consent was missing from one person the video was automatically deleted. The research project TeamOBS was approved legally and ethically in May 2014 by the Central Denmark Region, the Danish Data Protection Agency (2012-58-006) and the Research foundations of central Denmark (1-16-02-257-14).3” and the highest non-technical score “5” was estimated using spline regression analysis. The risk of high and low clinical performance was analyzed on the logit scale to meet the assumptions of normality and constant standard deviation .Agreement among raters was identified by the intraclass correlation (ICC) and Bland-Altman analysis . The noneviation . 95% conFrom November 2014 to February 2016, we informed all women, expecting to give birth at one of the study hospitals about the research project. Consent was declined by few healthcare providers, mothers, or relatives. We included 43 videos of teams managing newborns. Of these, 58% of the newborns received continuous positive airway pressure (CPAP), 28% received five inflations breaths, 23% were suctioned, and 2% received chest compressions and 42% needed no further intervention.Raters assessing non-technical skills achieved an ICC of 0.88 (95% CI 0.79–0.94); the neonatologists assessing clinical performance achieved an ICC of 0.81 (95% CI 0.66–0.90), Teams with low and average clinical performance  often had a lower score due to the use of CPAP to a newborn who was judged by the experts to have no need or due to delayed assessment of the newborn's heartrate. The clinical performances and the non-technical score were correlated and showed a dose-response like association . Thus, aHigh performing teams demonstrated excellent team behavior in the non-technical dimensions: leadership and teamwork, coping with stress and fatigue, and communication with the newborn's parents. The mean differences are listed in Teams with an excellent non-technical score had five times more likely to have a high clinical performance than teams with an average non-technical score. The clinical performance and the non-technical score were strongly correlated with a dose-response like association. High performing teams demonstrated excellent team behavior in leadership and teamwork, coping with stress and fatigue, and communication with parents.The main strength of this study was that evaluation of the management of difficult transition was based on real-life video recordings of teams of midwives, obstetricians, anesthesiologists, and pediatricians managing newborns. The technical solution was also a strength as our automated activation of cameras ensured enrolment of videos both day and night. Another strength was the systematic video analyses as four trained raters assessed all videos independently by use of structured and validated checklists and a high interrater agreement .The study was somewhat limited by the small number of videos, which reduced the possibility of performing sub-analyses, e.g., related to team construction, or level of newborn life support needed. However, to optimize learning from this study we insured that only newborns thought to be in need of transitional support or resuscitation participated in the study. We believe, that our study population corresponded to a random sample of the entire population of newborns with similar needs.a priori. However, it was developed by stringent use of the detailed version of the current ERC guideline and the inter-rater agreement was high  and the Research foundations of central Denmark (1-16-02-257-14). The patients/participants provided their written informed consent to participate in this study.LB, LH, GE, NF, NU, OK, TH, and TM contributed to conception and design of the study. LB, LH, and OK contributed to data collection. LB, KH-H, TH, and GE assessed the videos. LB, NU, and TH contributed in data analysis. All authors contributed to the writing of this work. All authors contributed to the article and approved the submitted version.We thank the following organizations and departments for financial support: Tryg Foundation (Trygfonden) (Grant ID No. 109507); the Regional Hospital in Horsens, the Aarhus University Hospital, Department of Obstetrics and Gynecology; and the Regional Postgraduate Medical Education Administration Office North.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.


Chronic kidney disease (CKD) is a major public health issue because of the rising number of patients with the risk of progression to end-stage renal disease. The retinal micro-vasculatures provide a unique window to assess systemic microcirculation. Optical Coherence Tomography Angiography (OCTA) parameters may provide a non-invasive method for systemic correlation. This research aims to compare the association of OCTA parameters in different causes of CKD.This is a single-center cross-sectional study on patients with CKD at the Universiti Kebangsaan Malaysia Medical Centre over 2 years. Patients with CKD were divided into three groups: DM group (diabetic CKD), HPT group (hypertensive CKD), and AG group (autoimmune-related glomerulonephritis CKD). The OCTA parameters, namely, the foveal avascular zone (FAZ), vascular density (VD), perfusion density (PD), and macular volume (MV), were measured and recorded using OCTA. Blood and urine analyses were taken as the patient’s CKD profile. The demographic data, the OCTA parameters and the CKD profiles, were analyzed using SPSS version 23.p < 0.001, p = 0.001, respectively). When compared with the control group for VD and PD, there were significant differences between the DM-control group  even when the age variable was considered, but no significant difference when comparing the HPT-control and the AG-control. There was a significant correlation between age, FBS, and HbA1c with VD and PD. There was no significant association between CKD profile and FAZ.The right eyes of 232 patients were included. The median age of the control and CKD subjects were 36 and 61 years old respectively. The proportion of the subjects under the control, diabetes mellitus (DM), HPT, and AG group were 30.6, 53.4, 5.6, and 10.4% respectively. There was no significant difference in FAZ, but there is a significant difference in the VD, PD, and MV between the control and CKD groups. There was a statistically significant difference between the three different causes of CKD in VD and PD (Our study showed the meaningful reduction of VD and PD in patients with diabetes and CKD. However, the use of OCTA to screen or predict CKD in patients living with diabetes mellitus, hypertension, or autoimmune nephritis was not shown to be useful. CKD is ications . The leaications .The rate of progression from CKD to ESRD depends on the underlying causes and many other factors. A lower estimated GFR, higher albuminuria, younger age, male sex, lower serum albumin, calcium and bicarbonate, and a higher serum phosphate predict faster progression to kidney failure . BesidesThe retinal micro-vasculatures provide a unique window to assess systemic microcirculation. The pathological and hemodynamic abnormalities in the various systemic causes of CKD may occur throughout the body and post an effect on the retinal vasculature. Retinal vessel changes can be a useful indicator of cumulative and early microvascular damage in systemic micro-vasculopathies . Based oFurther studies are needed to compare the association of the retinal microvasculature abnormalities in CKD and whether there are differences among the various causes of CKD. Traditional fluorescein angiography (FA) and indocyanine green angiography (ICGA) are used to investigate the status of the retinal and choroidal vascular systems. However, FA and ICGA have limitations as they need intravenous dye administration, are time-consuming and are unable to provide 3-dimensional (3-D) images. A study reported there are potentially serious side effects following intravenous sodium fluorescein . The intThis single-center, cross-sectional study was conducted in the Universiti Kebangsaan Malaysia Medica Centre (UKMMC) between October 2019 and May 2021. Ethical approval was obtained from the UKM Medical Research and Ethics Committee under research code: GGPM-2019-023 before data collection. This research aimed to compare the association of OCTA parameters in different types of CKD. Moreover, this study aimed to investigate the association of OCTA parameters with CKD profile in different types of CKD.Patients with ages ranging from more than 18 years old and less than 75 years old with CKD who are on regular follow-up at UKMMC were enrolled in this study. The exclusion criteria were dialysis or ESRD patients, patients with renal transplant, patients with underlying malignancy, patients who are in active infection, pregnancy, inadequate quality of OCTA image , and patients who are not able to give consent. All subjects have no pre-existing eye diseases and are not on the regular care in the eye clinic. Subjects with underlying DM have no pre-existing diabetic retinopathy or maculopathy based on their latest yearly fundus photo screening done by the primary care physician.The patients with CKD were divided into three groups: DM group (diabetic CKD), HPT group (hypertensive CKD), AG group (autoimmune-related glomerulonephritis CKD).2 that is present more than three months with or without evidence of kidney damage  guideline as eGFR of <60 ml/min/1.73 my damage . The sevy damage . PatientThe CKD subjects were categorized under the DM group (diabetic CKD) when he or she was previously diagnosed DM patients or had his/her venous fasting plasma glucose ≥7.0 mmol/L or 2-h post-prandial glucose ≥11.1 mmol/L if symptomatic, or a positive repeated glucose value in asymptomatic patients .Hypertensive CKD patients are defined as patients with hypertension with no other significant systemic diseases that would become a confounding factor. The CKD subjects were categorized under the HPT group (hypertensive CKD) when the CKD subjects were previously diagnosed for hypertension or having a persistent elevation of systolic blood pressure of 140 mmHg or greater and/or a diastolic pressure of 90 mmHg or greater, taken twice on two separate occasions .The CKD subjects were categorized under the AG group (autoimmune-related glomerulonephritis CKD) when he or she was previously diagnosed as having systemic lupus erythematosus (SLE) with kidney involvement or IgA nephropathy. Patients with SLE and renal involvement were recruited when he or she were previously diagnosed with SLE by a rheumatologist and/or based on European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria . PatientThe control group consisted of healthy subjects with no visual symptoms, absence of retinal disease, no major comorbidities such as DM, hypertension, hypercholesterolemia, and autoimmune diseases.All patients who fulfill inclusion criteria will be informed about the study protocol and written informed consent was obtained from each patient who participated in this study.The sample size was calculated based on G power version 3.1.9.7. It was based on the effect size of 0.25, the power of a statistical test of 0.8, and statistical significance at alpha 0.05 with four groups; the calculated sample size was 180 (45 participants per group).The subjects were interviewed for demographic data , past medical history, treatment history, and current therapy.The investigations included CKD profile and OCTA. The most recent three months’ laboratory data was collected while the patients without a most recent three months’ laboratory data proceeded with peripheral blood collection for laboratory analysis on the day of examination. Peripheral blood (15–20 ml) was collected from patients in a sterile container  and sent for CKD profile. The CKD profile consists of a few tests, namely, full blood count (FBC), fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, triglyceride, serum urea, serum creatinine, serum alanine transferase (ALT), serum alkaline phosphatase (ALP), serum albumin, serum calcium, serum phosphate, sodium, potassium, and urine protein creatinine index (UPCI). The OCTA was conducted on both eyes by using Cirrus HD-OCT 500  after dilating the pupils with 1% tropicamide and 2.5% phenylephrine hydrochloride. The OCTA scans (6 mm × 6 mm) centered on the fovea were obtained. Cirrus OCT Angiography provided images of the retinal and choroidal vasculature. The results were interpreted by two ophthalmologists in UKMMC. OCTA microvascular parameters measured include foveal avascular zone (FAZ), parafoveal vascular density (VD), parafoveal perfusion density (PD), and macular volume (MV) . The rigp-value < 0.05 was considered statistically significant. All the statistical analyses were performed using the IBM SPSS Statistics version 23.Kruskal-Wallis test was performed to determine the relationship between causes of CKD and OCTA microvascular parameters whereby the OCTA parameters were not normally distributed. The OCTA parameters between different causes of CKD and control were compared using the Mann-Whitney test. The association between OCTA parameters and CKD profile was determined by using Spearman’s correlation. Quade’s ANCOVA was used to control the covariate in the analysis of OCTA parameters between groups. The normality of the variables was tested with the Kolmogorov-Smirnov test. A two-tailed There were 232 subjects enrolled in this study. The study subjects consisted of 71 (30.6%) control subjects and 161 (69.4%) CKD subjects. Among the CKD subjects, it consisted of 124 (53.4%) diabetic CKD subjects, 13 (5.6%) hypertensive CKD subjects, and 24 (10.4%) autoimmune-related glomerulonephritis CKD. The median age of control subjects and CKD subjects were 36 and 61 years old respectively. The study population is made up of 109 (47.0%) male subjects and 123 (53%) female subjects. The study subjects consisted of 149 (64.2%) Malay, 54 (23.3%) Chinese, 28 (12.1%) Indian, and 1 (0.4%) other. 2. There was a significant difference in VD, PD, and MV between the control group and the CKD group. The median of VD, PD, and MV for the control group were 18.3, 45.3, 10.3 mm3, respectively. While the median of VD, PD, MV for the CKD group were 17.1, 42.2, 9.8 mm3, respectively . By comparing each of the different causes of CKD to the control group using the Mann-Whitney test, we found that there was no significant difference between the different causes of CKD and FAZ after age adjustment. However, there was a significant difference between different causes of CKD and MV . On the other hand, there were significant differences between the DM group and the control group in terms of VD and PD . Quade’s ANCOVA was performed whereby the age was considered and VD and PD were still significantly associated with the DM group . However, there was no significant difference in terms of VD and PD when comparing HPT group with the control group and the AG group with the control group. On the other hand, there was a significant and strong correlation between age and VD and PD , while there was a weak correlation between age and MV .Based on the Kruskal-Wallis test , there wp < 0.001, r: −0.350, p < 0001, r: −0.313 respectively). Moreover, HbA1c was also significantly associated and fairly correlated with VD and PD . There was no significant association between CKD profile and FAZ. Spearman correlation was used to study the association between OCTA parameters and CKD profile. FBS was significantly associated and fairly correlated with VD and PD , FBS and HbA1c (considerably higher in DM group), and even age (significantly lower in the control group). This finding was supported by previous studies done by Oliverio et al., Fujiwara et al., and Wu et al. that FAZ is not affected by age, gender, present and level of CKD, and present and level of diabetes . TherefoOn the other hand, VD and PD are significantly lower in patients with diabetic CKD when compared with the control. However, this difference is not observed when comparing the control with other causes of CKD (HPT group and AG group). The significant association between VD, PD, and diabetic CKD was still valid after controlling age as a covariate using Quade’s ANCOVA. However, we recognized the higher age distribution in the diabetic CKD compared to the control group, and this may pose some limitations in the ANCOVA analysis. The evidence of a strong correlation between HbA1c and FBS (significantly higher in the DM group) with VD and PD showed the present and higher level of diabetes would reduce the VD and PD in patients with CKD. The earlier studies on OCTA parameters in diabetes showed significant change in patients with DM and correlated with the level of DM control, FBS, and HbA1c . Urea anMacular volume (MV) was significantly different between control and CKD groups but no further difference between various causes of CKD. This is likely due to the difference in the age between control and CKD as macular volume is reported reduced by age by Overall, the significant difference in VD, PD, MV between the control group and the CKD group in this study was due to the combination of age difference and component of DM as one of the CKD subgroups. Further analysis in this study showed only VD and PD in the DM group were significantly lower after controlling age as a covariate. Looking at the previous studies with various results on the effect of different systemic vascular diseases on retinal vasculature, this study added further value by showing aging, DM, and its related parameters (HbA1c and FBS) pose more effect on the retinal vasculatures as measured by non-invasive OCTA.The limitations of this study are not able to include some other systemic factors that may have implications on the retinal vasculature, which are blood pressure and body mass index (BMI). The effect of these two factors on retinal vasculature and OCTA parameters are so far inconclusive by previous studies. The fast and non-invasive nature of OCTA scanning provides a good opportunity to quantitatively measure the retinal microvasculature. Our study showed the meaningful reduction of VD and PD, particularly in patients with diabetes and CKD. However, the use of OCTA to screen or predict CKD in patients living with DM, hypertension, or autoimmune nephritis was not shown to be useful from this study.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 UKM Medical Research and Ethics Committee under research code: GGPM-2019-023. The patients/participants provided their written informed consent to participate in this study.WW, RMu, and RMo contributed to the conception and design of the study. MY contributed to the funding acquisition. MY, MO, KT, SH, and AM contributed to the data curation and formal analysis. MY and MO contributed to the writing-original draft. MY and WW contributed to the writing-review and editing. All authors contributed to the article and approved the submitted version.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.


The influence of preexisting factors on the clinical course of patients with subarachnoid hemorrhage (SAH), such as patient age, arterial hypertension, and aneurysm characteristics, is still a matter of debate. However, the specific impact of the exact aneurysm location has not received adequate attention. Therefore, the aim of this study was to investigate the influence of aneurysm location as a preexisting factor on the clinical course and mortality.The data of consecutive patients with aneurysmal SAH who were treated from October 2010 to July 2020 were retrospectively analyzed. We distinguished four aneurysm locations: the anterior complex, internal carotid artery (ICA), middle cerebral artery (MCA), and posterior circulation. Logistic regression analysis and receiver operating characteristics were used to investigate the influence of aneurysm location on the occurrence of acute hydrocephalus, Delayed Cerebral Ischemia (DCI), neurological outcome, and in-hospital mortality. Neurological outcome was assessed 3 months after discharge using the Glasgow Outcome Scale.p = 0.001). Delayed cerebral ischemia occurred most frequently in patients with an anterior complex aneurysm and least frequently in MCA aneurysms (p = 0.014). In ICA aneurysms, mortality was 2.56-fold higher than in patients with aneurysms of the anterior complex (p = 0.006). An additional ROC analysis showed a good prediction for in-hospital mortality when taking the aneurysm's location into account [AUC.855 (CI.817 −0.893)].A total of 603 patients were included in this study. Patients with MCA aneurysms were 2.52 times less likely to develop acute hydrocephalus compared to patients with anterior complex aneurysms (The aneurysm's location proved to be a significant predictor of acute hydrocephalus, DCI, and in-hospital mortality, demonstrating the impact of this preexisting biological factor on the course of SAH. Aneurysmal subarachnoid hemorrhage (SAH) remains a disease with high morbidity and mortality rates . Recent Many parameters have been described, such as blood clot thickness and scores for the extent of hemorrhage severity  .In addition, there is evidence that several other pre-existing factors, independent of the hemorrhage severity, may also have an impact on outcome including patient age, aneurysm size and location, and a history of hypertension –5.As for location, it has been repeatedly postulated that patients with SAH from a posterior circulation aneurysm are likely to have a worse outcome , 6, 7. HAll patients treated at our institution with an aneurysmal SAH from October 2010 to July 2020 who were 18 years or older were included in this retrospective single-center study.The aneurysmal nature of the hemorrhage was verified by cerebral digital subtraction angiography, cranial CT (cCT) angiography, and/or MRI angiography. Patients in whom no aneurysm could be identified or who died prior to sufficient diagnostics were excluded from further analysis. When multiple aneurysms were identified, the data shown refer to the symptomatic aneurysm.btO2-measurement, if applicable. Vasospasm is suspected by transcranial Doppler sonography (TCD) if the mean flow velocity in the middle cerebral artery is above 140 cm/s and above 120 cm/s in the anterior cerebral artery, respectively. In case of TCD suspicion of vasospasm, we perform a CT scan including CT angiography and CT perfusion imaging according to our local treatment protocol. In addition, the MAP is increased to values of 90–100 mmHg and nimodipine is administered continuously intravenously to ensure the dosage  were assessed at the first encounter with a physician. Furthermore, data on the clinical course, such as development of an acute hydrocephalus, type of aneurysm treatment , development of delayed cerebral ischemia (DCI) according to Vergouwen et al.  and outcThe outcome data were extracted from the electronic patient file which contained the examination results of either visits at our outpatient clinic and/or detailed reports from rehabilitation units. Acute hydrocephalus was diagnosed by experienced senior physicians on the base of image morphology in correlation with the clinical presentation of patients.Regarding the location of aneurysms, four groups were distinguished in analogy to the classification in the Subarachnoid Hemorrhage International Trialists (SAHIT) study: anterior complex , and pericallosal artery), internal carotid artery , middle cerebral artery (MCA), and posterior circulation , superior cerebellar artery (SUCA), anterior inferior cerebellar artery (AICA), and posterior cerebral artery) , 5.® version 25 . The statistical level of significance was set to p < 0.05. The statistical analysis of the data was performed by univariable analysis using the Fisher's exact test, chi-square test, Kruskal-Wallis test, or ANOVA tests depending on the scale and distribution of measurements. In a next step, acute hydrocephalus, DCI, favorable outcome, and in-hospital mortality were pre-defined as outcome parameters of interest. For each outcome parameter, a logistic regression analysis was performed to determine the independent predictive value of aneurysm location and covariates at baseline which have been described in the literature and showed a significant association in univariate analysis. All shown odds ratios (OR) are adjusted ORs for covariates calculated in the respective regression model.Statistical analyses were performed using the IBM SPSSA favorable outcome was defined as a value greater than or equal to 4 on the Glasgow Outcome Scale (GOS) 3 months after discharge.In order to evaluate the predictive performance of known predictors combined with aneurysm location, receiver operating characteristic (ROC) curves and corresponding areas under the curve (AUC) were calculated.This study was conducted according to the Declaration of Helsinki, local and institutional laws, and was reported to the local ethical committee (No. WF-065/21).Between October 2010 and July 2020, 633 patients with aneurysmal SAH were treated in our institution. A total of 603 patients were eligible for further analyses.n = 242) of the aneurysms were located in the anterior complex and in 93 cases, the aneurysm was located in the posterior circulation. The mean diameter of aneurysms was 7.2 mm (± 5.2). Details are presented in The mean age of patients was 55.1 ± 13.5 years. A total of 40.1%  patients died during their hospital stay with the majority of patients (94.9%) dying from SAH-specific causes . In six cases, there were non-SAH specific causes . Of these non-SAH specific deaths, three cases were in patients with aneurysms of the anterior complex, one patient with aneurysm of the ICA, and two patients with the aneurysm of the MCA.p < 0.001). Delayed cerebral ischemia occurred most frequently in patients with an anterior complex aneurysm . Vertebrobasilar aneurysms showed the highest in-hospital mortality at 26.9%, followed by ICA aneurysms (26.4%). Aneurysm of the anterior complex and MCA aneurysms showed the lowest mortality . However, WFNS grade did not differ significantly between locations (p = 0.622). Next, regression analyses were used to determine the independent predictive value of aneurysm location and predefined parameters described in the literature regarding mortality and functional outcome in SAH patients (p < 0.001), Fisher grade (p < 0.001), and aneurysm location (p < 0.001) showed a significant association with acute hydrocephalus and were, therefore, included in the regression analysis  as were aneurysms of the ICA (84.3%) and aneurysms of the anterior complex (79.4%). MCA aneurysms, on the other hand, were treated mainly by microsurgical clipping (80.5%). Depending on aneurysm location, significant differences in the clinical course were found on univariable analyses . Patientpatients  11–19).–19.p < 0ysis see . Age, sep = 0.008), Fisher grade (p = 0.005), acute hydrocephalus (p < 0.001), and aneurysm location (p = 0.041) revealed a significant association in univariate testing while age, sex, arterial hypertension, initial pupil status, treatment modality, occurrence of rebleeding, and aneurysm diameter did not reach significance.For DCI as a dependent variable, WFNS grade . Patients with ICA aneurysms were 2.56-fold more likely to die .Patients with aneurysms of the posterior circulation were 2.92-fold more likely to die than patients with aneurysms of the anterior complex  times less likely to develop acute hydrocephalus.In addition to mortality, further clinical events were investigated. Fisher grade and WFNS grade as well as aneurysm location were independent predictors of acute hydrocephalus in the logistic regression analysis . With rep = 0.014; OR: 0.52; CI: 31–0.86).In the regression analysis, acute hydrocephalus was found to be an independent predictor of DCI. However, SAH patients with an MCA aneurysm were 1.93 times less likely to present with DCI during the course than patients with an aneurysm of the anterior complex  after 3 months. Logistic regression showed age, WFNS and Fisher grade, and absence of DCI as predictors of a favorable outcome at 3 months. The location of the aneurysm had no independent predictive value.Receiver operating curves were calculated for all outcome variables for which location was predictive  using the parameters of their respective regression analysis. For the prediction of in-hospital mortality, AUC was 0.86 (CI.82–0.89) shown in . The AUCScores, such as WFNS grading, represent the gold standard in prognostic assessment in SAH patients , 21. In The relevance of the exact location of the symptomatic aneurysm as a preexisting biological condition in relation to the prognosis has not received adequate attention , 22.Some studies were able to show that SAH patients with an aneurysm of the posterior circulation have a worse functional outcome than patients with an anterior circulation aneurysm , 8, 23. The aim of this study was to evaluate whether the distinct location of an aneurysm in SAH patients has an influence on the clinical course and in-hospital mortality.Konczalla et al.  found anWFNS and Fisher grade have also been associated with the development of acute hydrocephalus which could be reproduced in our cohort , 26.Similarly, previously described parameters predicting the mortality and outcome in SAH patients were examined such as age, WFNS score, pupil status, and rebleed –16. All Lee et al.  were ablReceiver operating curves showed only a small AUC for DCI. Efforts have been described in the literature to predict DCI by means of a clinical score . Very loThis finding suggests that the neurological outcome depends, to a certain extent, on the course after hemorrhage as well as on initial non-modifiable parameters such as bleeding severity. In contrast, mortality, which in many cases occurs during the early phase after hemorrhage (death was ascertained after a median of 8 days), seems to depend largely on preexisting factors including aneurysm location.The retrospective analysis of the database and the single-center design of this study present limitations. Another limitation is the relatively long period of time covered by the data, which means that although a larger cohort was studied, performance bias cannot be ruled out because treatment algorithms have changed over the years. For example, there is no longer any hemodilution or hypervolemia, which in some cases was still the case at the beginning of the study, since efficacy of triple-H could not be verified , 30. FurIn addition, the location has a clear influence on the type of treatment (as shown in Furthermore, it remains to be noted that neurological and clinical complications not studied in this work, such as intracranial hypertension, seizures, ventriculitis, and pulmonary complications, also correlate with mortality and clinical outcome in SAH patients. These factors represent a potential bias.In summary, we were able to show significant differences in the clinical course and in-hospital mortality rates with respect to aneurysm location. Aneurysms of the internal carotid artery and posterior circulation aneurysms were associated with the highest case fatality rates. The risk of occurrence of an acute hydrocephalus was highest for aneurysms of the posterior circulation. Aneurysms of the MCA showed the lowest risk of developing DCI.The rationale to treat asymptomatic aneurysms is mainly based on two considerations: the risk of rupture and the associated risk of serious neurological damage. Therefore, our data may have an impact on the second aspect since aneurysm location is already determined at the time of diagnosis of the unruptured aneurysms. This demonstrates the independent relevance of underlying biological factors to estimate the prognosis and to advise patients more precisely on the consequences of a possible bleeding.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 Local Ethics Committee Ärztekammer Hamburg Weidestr. 122b 22083 Hamburg. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.JG supervised the study, designed the study question, interpreted the data, and drafted the manuscript. AP and TP collected the data. MW contributed to the data interpretation. LD and PC helped to interpret the data and conceive the study questions. TS contributed to the overall design of the study, supervised the study, conceived the study question, designed the analysis plan, and analyzed and interpreted the data. All authors revised the manuscript.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.


Objective: This study aimed to compare the time in physical activity (PA)  and sedentary behavior (SB)  between Medical (MED) and Physical Education (PE) students who underwent remote classes imposed by the COVID-19. In addition, we compared symptoms of depression and anxiety and sleep quality.Methods: A cross-sectional study (272 MED and 95 PE students). The International Physical Activity Questionnaire (IPAQ), Beck Inventory , and Pittsburgh Sleep Quality were used to assess PA and SB, anxiety and depression symptoms, and quality of sleep, respectively. The data are presented as median and interquartile intervals 25–75.Results: We observed statistically significant differences between MED and PE students for MVPA , SB Total , and anxiety symptoms .Conclusion: Together, our findings indicate that MED students spent less time in MVPA and more time in SB than PE students. MED students also presented worse mental health in the pandemic situation imposed by the COVID-19. The COVID-19 pandemic  leisure-Home isolation may impact levels of physical activity   and sedePA and SB are associated with mental health and sleep quality . For exaStudents were drastically affected by the COVID-19 pandemic since education systems adopted remote classes. Under normal conditions, most university students already did not meet the recommendation of PA and spent approximately 7–8 h per day in SB . In the Although it is still possible to speculate that the PA and SB of PE students were negatively influenced during the COVID-19 pandemic, in the same way as MED students, due to the change from regular classes to remote classes. On the other hand, despite the possible negative impact of the pandemic on PA and SB, engagement of PE students in the practical demands related to the physical education classes characteristic of their course and associated internships, may confer some advantage compared to MED students. However, this assumption still needs to be elucidated.th to 12th semesters). Furthermore, lack of resources and staffing, coupled with reduced staff numbers through contamination with the virus, may have further increased the stressful situations related to medical work demand , moderate and vigorous (MVPA)] and SB  between MED and PE students who underwent remote classes, imposed due to the COVID-19 pandemic. In addition, we compared depression and anxiety symptoms and sleep quality of MED and PE students, and the first and second halves of the courses. We hypothesized that MED students would spend less time in PA and more time in SB and demonstrate worse mental health than PE students, with differences between the first and second halves of the MED course.st to 12th semester) and PE (1st to the 8th semester) were invited to participate in the study. Participants were contacted via message application or e-mail. If the participant agreed to participate, they were sent an online form containing the consent form and questionnaires to assess demographic characteristics, PA, SB, depression and anxiety symptoms, and sleep quality. For better comprehension of the collected information, initially, the student representative of the groups (WhatsApp group administrator) sent the research questionnaire link directly to the WhatsApp group. After 4 days, the authors (TB and KC) were added to these WhatsApp groups and again sent the research questionnaire link and were available to clarify any doubts. Of 1,400 students from 30 distinct classes contacted, 367 students  answered the questionnaire. No students directly stated that they did not want to participate in the survey. Despite the groups being unbalanced, we emphasize that, in percentage terms, ~25% of the students in each course were evaluated.This is a cross-sectional study, which was approved by the local Ethics and Research Committee , and followed the precepts of the Declaration of Helsinki. The data were collected between September 2020 and February 2021. All students agreed and signed the consent form. Students aged ≥18 years from MED .The sample size was determined using G-Power software , inputting an α error (0.05) and power (1 – β error = 0.90). Since the literature is scarce concerning comparisons of PA and SB between MED and PE students, we assumed an arbitrary moderate effect size (Cohen' d) of 0.4. Calculations were based on an independent The times of PA  and SB  were assessed by the International Physical Activity Questionnaire (IPAQ), which contains eight questions about PA and SB considering the routine of the previous seven days. This tool is widely used and validated for the Brazilian population . The IPAAnxiety and depression symptoms were assessed by the Beck Anxiety Inventory (BAI) and Beck Depressive Inventory (BDI) , 23, whiThe BDI is also a validated tool for the Brazilian population  and showSleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI), validated for the Brazilian population . The PSQst to 4th and 5th to 8th in PE; 1st to 6th and 7th to 12th in MED). Logistic regression models were used to evaluate the association between course (MED or PE), and dichotomous variables: MVPA (<300 min per week vs ≥300 min per week), SB (< than 8 h vs ≥ than 8 h). Additionally, the association between course (MED or PE) and continues variables: anxiety symptoms (points of BAI), depression symptoms (points of BDI), and sleep quality (points of PSQI) were evaluated. Results from the logistic regression models were presented as odds ratios (ORs). The presence of relationships between numerical variables , was examined with the Spearman Correlation Test. Data were analyzed using IBM SPSS Statistics, version 22 . The significance level was set at P ≤ 0.05.Data are presented as mean (standard deviation), or median and interquartile range (IQR) for continuous variables. Categorical variables are shown as absolute and frequencies (%). Normality and equality of variances were tested using the Kolmogorov-Smirnov test and Levene test, respectively. Non-parametric data are shown as median and interquartile range (IQR: 25 – 75). The Mann-Whitney test was used to assess differences between groups (PE and MED) and between the first and second halves of the courses (1p > 0.05). However, when comparing specific components of PSQI, we observed greater scores in sleep duration and habitual sleep efficiency for MED students compared to PE students (both p < 0.05). On the other hand, PE students showed greater scores for use of sleeping medication and daytime dysfunction than MED students (both p < 0.05).The MED students presented worse scores related to anxiety symptoms [median above the cut-off for high anxiety symptoms – >12 points - SÆMUNDSSON et al. (2011)] , physicast to 4th and 5th to 8th in PE; 1st to 6th and 7th to 12th in MED) regarding anxiety symptoms (BAI), depression symptoms (BDI), and variables related to the level of physical activity (LPA and MVPA) and SB .st to 4th and 5th to 8th in PE; 1st to 6th and 7th to 12th in MED) did not present differences for anxiety and depression symptoms, physical activity (LPA and MVPA), and SB . Furthermore, for sleep quality (PSQI), we did not verify differences between the first and second halves of the course in MED (1st to 6th and 7th to 12th), but differences were verified between the first and second halves of the course in PE (1st to 4th and 5th to 8th), for sleep latency and sleep disturbances.The first and second halves of the courses (1p < 0.001) and a decrease in reporting >8 h per day of SB , SB and Anxiety symptoms (0.17 p < 0.001), Anxiety symptoms and Depression symptoms (0.67 p < 0.001), Depression symptoms and Sleep quality (0.58 p < 0.001), and Sleep Quality and Anxiety symptoms (0.55 p < 0.001).Significant correlations were observed of MVPA and Depression symptoms (−0.23 st to 6th semesters and. 7th to 12th semesters) and in PE (1st to 4th semesters and 5th to 8th semesters) considering the symptoms of anxiety and depression, LPA, MVPA, and SB . In addition, no differences were observed for initial and final semesters in sleep quality (PSQI) for MED students, while for PE students, initial and final semesters presented differences in sleep latency and sleep disturbances components, but not for the Global PSQI score. PE students present ORs  of meeting MVPA recommendations. Significant correlations were verified of MVPA and Depression symptoms and Anxiety symptoms, as well as Anxiety symptoms and Depression symptoms, Depression symptoms and Sleep quality, and Sleep Quality and Anxiety symptoms.The current study aimed to compare MED and PE students during the COVID-19 pandemic, considering the time of PA (LPA and MVPA) and SB , symptoms of anxiety and depression, and sleep quality. Our main finding indicates that MED students perform shorter MVPA, longer SB, and have more anxiety symptoms than PE students. In addition, we observed better scores of sleep duration and habitual sleep efficiency and worse scores of use of sleeping medication and daytime dysfunction in MED students than PE students. However, the Global PSQI score was similar between groups. We also highlight the lack of differences between the first and second halves of the course in MED  and depression (33.7%) summarized in 14 studies   were higher than the prevalence of anxiety (31.9%) summarized in 17 studies  . The absThe relationship between lower MVPA and higher symptoms of depression and anxiety in the general population is well-described in the literature , 36 and Additionally, we highlight the extensive literature indicating that MED students and even medical professionals present impairments in mental health , 40. AltEspecially during the pandemic, a systematic review with 64 studies indicated that restrictions to reduce COVID-19 transmission affected PA and SB in the general population . In thisn = 5,153) showed poor sleep quality in 60.4% of the sample analyzed , we suggest there is a strong need to facilitate medical students to spend more time in PA and to reduce SB. We highlight the importance of providing strategies to increase the PA of university students, especially MED students, who showed poor physical activity levels . In thisThe strengths of this study included university students with different characteristics of PA (MED and PE), with high COVID-19 exposure in São Paulo City. Our study is not free of limitations. First, we included only one university. Second, despite the wide use of self-report tools for PA and SB measures, mental health may underestimate our findings. Finally, we could not investigate possible psychiatric conditions, such as a diagnosis of depression or anxiety disorders, in more detail.In conclusion, our results indicate that MED students spend less time in MVPA and more time in SB than PE students and presented worse mental health in the pandemic situation imposed by COVID-19.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 Ethics and Research Committee of Santo Amaro University . The patients/participants provided their written informed consent to participate in this study.TM and KS: conceptualization, methodology, formal analysis, investigation, writing original draft, writing review and editing, and visualization. TG, AS, LN, and AB: writing original draft and writing review editing. SG: formal analysis and writing review editing. CF: conceptualization, methodology, writing original draft, and writing review editing. FR: writing review editing. LN: conceptualization, methodology, formal analysis, writing original draft, and writing review, supervision. All authors contributed to the article and approved the submitted version.The work was supported by the Grants 2020/08869-0, 2021/13699-9, 2021/14033-4 by São Paulo Research Foundation (FAPESP) in Brazil.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.


The expansion of the pharmacist-led services has resulted in increased demand to have evidence in terms of necessity, efficacy, and cost. Evidence-based practice is crucial to provide the best patient health outcomes and pharmacy practice research can play a key role in this regard. This commentary provides a background of pharmacy practice research, and then, it highlights three key recommendations based on a systematic review of the literature. The systematic review of the literature on pharmacy practice research has been conducted in 12 Middle Eastern Arab Countries. The three key recommendations include (a) identification of research priorities by health authorities in each country; (b) pharmacy practice research culture to be nurtured and promoted with academic researchers and practitioners; and (c) shifting pharmacy practice research towards applied, interventional, and implementation studies Pharmacy practice research can generate evidence to inform policymakers. It also conveys the value for potential new roles and services , 2. TherPharmacy practice is an important component in the health system of high-income countries . HoweverMedline/PubMed and Scopus were used to screen and retrieve the articles. The articles published in the English language related to any aspect of pharmacy practice in 12 countries Bahrain, Iraq, Kingdom of Saudi Arabia, Kuwait, Lebanon, Oman, Palestine, Qatar, Syria, United Arab Emirates, Yemen, and Jordan during 2009–2019 were included.Seven themes came out from these selected articles. Medication use was the predominant 30.78% (302) theme, followed by pharmacy practice and pharmacist services 22.73% (223), pharmacy education 16.61% (163), medication safety and pharmacovigilance 13.56% (133), pharmacoeconomics and pharmaceutical marketing 8.22% (77), clinical research 6.73% (66), medicines information, and public health promotion1.81% (17). The Kingdom of Saudi Arabia (KSA), Jordan, Qatar, and the UAE were the leading countries to publish research. Studies are scarce regarding the implementation of pharmacy services. Following is a key set of recommendations based on these findings [Planning and setting an agenda for pharmacy practice research are needed. This agenda-setting needs to be done by the Ministries of Health in these countries. It will maximize the value of the studies and will also help bridge the gaps in the pharmacy practice research. This can also help in avoiding the repetition of ideas and resources. Girolamo and Reynders (2020) and Dawoud, D. et. Al., also emphasized the need to have a pharmacy practice research priorities related to the COVID-19 pandemic , 9.Universities and academic institutions are proposed to take the lead and creating a national health research hub. A network of researchers can help build large-scale studies. The combination of knowledge, skills, and resources that will be accessible in the research networks collectively will promote the research outcomes with valid and reliable results. This practice had a remarkable influence in several developed countries, and therefore, it is suggested that a similar approach could be used in the Middle East countries too –12. CurrIn the recent review of the literature, it was observed that there was a lack of interventional studies assessing pharmacy services. The literature was also scant on the development of new services . PharmacA health system can only be strengthened by applying evidence-based practice hence robust studies are needed which are large scale, and of applied, interventional nature showing multidisciplinary and cross-disciplinary collaboration.