Acute respiratory distress syndrome (ARDS) is associated with increased morbidity and mortality in the elderly population (≥65 years of age). Additionally, age is widely reported as a risk factor for the development of ARDS. However, the underlying pathophysiological mechanisms behind the increased risk of developing, and increased severity of, ARDS in the elderly population are not fully understood. This is compounded by the significant heterogeneity observed in patients with ARDS. With an aging population worldwide, a better understanding of these mechanisms could facilitate the development of therapies to improve outcomes in this population. In this review, the current clinical evidence of age as a risk factor and prognostic indicator in ARDS and the potential underlying mechanisms that may contribute to these factors are outlined. In addition, research on age-dependent treatment options and biomarkers, as well as future prospects for targeting these underlying mechanisms, are discussed. Acute respiratory distress syndrome (ARDS) is a common yet complex syndrome that develops in critically ill patients. Clinically, ARDS presents as acute hypoxemia and the presence of bilateral pulmonary infiltrates that cannot be fully ascribed to heart failure or fluid overload –3. This The world's population is aging; over 65s are expected to account for 1 in 6 of the population by 2050, an increase from 1 in 11 in 2019 . With a per se as a risk factor for ARDS. Patients with ARDS often carry multiple risk factors and co-morbidities, some of which may be influenced by age themselves, which makes isolating the influence of age particularly challenging. Epidemiological studies frequently report the mean/median age of patients with ARDS at 55–65 years, making it a disease of late middle-age rather than exclusively old age   reported the ARDS-related mortality was highest in those ≥80 and ≤4 years  and APACHE  . These sn = 600) . The autn = 600) . Subsequn = 600) . Within n = 600) . Severaln = 600) , 41. It n = 600) , 43]. Whn = 600) , 43. A l≤4 years . Other i≤4 years . While a≤4 years , 45. Ind≤4 years –48. FurtA number of factors influence disease severity in ARDS including features of the immune system, vasculature and structural components of the airway, as highlighted in in vitro these cells had increased propensity to produce MIP-1α in response to LPS  cell counts, protein concentration, and cytokines such as the neutrophil chemoattractant CXCL1/KC in comparison to younger mice –51. Altee to LPS . Impairme to LPS . In addie to LPS  and the e to LPS  were obse to LPS . Impairee to LPS . The oute to LPS , 59. In e to LPS . This sue to LPS , 61 and e to LPS  effects  in ARDS . Recentl in ARDS , 63. OveIn addition to the immune system, age-related changes in structural components of the airway and vasculature may also contribute to ARDS pathogenesis. Within the vasculature, changes in the expression of angiopoietin-2 (Ang-2) have been linked to disease severity in ARDS . Ang-2 iin vivo models of fibrosis, improving lung function and physical health (The structural components and mechanics of the lung also play an important role in airway pathophysiology. Aging is associated with changes in lung function and respiratory mechanics. Increased compliance and decreased small airway diameter in the elderly increase the severity of lung injury under mechanical ventilation . In addil health . A declil health  and indul health , highligl health . RAGE sil health , 79. Uprl health , 80. Trel health . Increasl health .Biomarkers represent an important tool in diagnostics and patient stratification. However, to date, no single specific ARDS biomarker has been validated . Analysiin vivo (in vivo (Conclusive evidence to support age-dependent differences in treatment responses is lacking. However, there is evidence from both in vivo , 85 and in vivo , 86 to s(in vivo . Clinica(in vivo , 89. Fur(in vivo –92. Pote(in vivo . The acc(in vivo , 94. In Research to date has highlighted the significant analytical challenges that ARDS presents due to its complex etiology. Although aging may alter the immune system, vasculature, and airway epithelium to promote the pathogenesis of ARDS, further work is needed to elucidate these mechanisms and this will be critical to improving our understanding of the effects of aging on the risk of developing ARDS and its severity. While more remains to be learned, accumulation of senescent cells along with increased oxidative damage, defective autophagy, and increased vascular permeability due to age-related changes are likely to play a role. A better understanding of the contributions of these individual factors along with the potential impact of co-morbidities could help direct future therapeutic strategies. A clearer understanding of the treatment options that are most beneficial for elderly patients with ARDS will be vitally important to reduce mortality in this subpopulation. Cell therapies represent a promising therapeutic option in ARDS , and theAll authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.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.


Previous studies have linked apical periodontitis (AP) to inflammatory bowel disease (IBD). The aim of this study was to compare the prevalence of AP and root canal treatment (RCT) in patients with ulcerative colitis (UC) and Crohn´s disease (CD). A cross-sectional study, including 28 patients with Crohn´s disease and 26 with ulcerative colitis, was conducted. AP was diagnosed as radiolucent periapical lesions (RPLs), using the periapical index score (PAI). Student’s t test, 2 test and multivariate logistic regression were used in the statistical analysis.p = 0.97). The multivariate analysis, including all the above covariates, shows that both in UC and CD patients the prevalence of RCT was similar . Periapical status was significantly associated with endodontic status , regardless of IBD type. Multivariate logistic regression run with age, gender, number of teeth, number of RFT, periodontal disease and the type of IBD as covariates, taking as dependent variable and outcome “periapical status” , showed that both UC and CD patients had the prevalence apical periodontitis (OR = 1.03; C.I. 95% = 0.25 – 4.31;  The results of the present study show similar frequency of AP and RFT in both UC and CD patients. The type of IBD does not appear to affect the prevalence of radiographically detectable periapical lesions or the prevalence of root canal treatment. Key words:Apical periodontitis, Crohn’s disease, inflammatory bowel disease, toot canal treatment, ulcerative colitis. Inflammatory Bowel Diseases (IBD) include Crohn's disease (CD) and ulcerative colitis (UC), two recurrent and chronic inflammatory processes of the gastrointestinal tract characterized by diffuse inflammation of the intestinal mucosa. CD affect, in most cases, terminal ileum, but can affect any segment of the gastrointestinal tract, from the mouth to the anus. On the other hand, UC affects the large bowel, being the distal colon the most affected region . Oral maOn the other hand, when caries progression causes irreversible pulpitis and pulp necrosis, root canal poly-microbial antigenic content escapes through the apical foramen, invading the periapical tissues. Then, an inflammatory response develops, named apical periodontitis . Apical In the last years, an association between AP and some systemic diseases, such as diabetes mellitus  and card- Patients’ selectionParticipants were recruited among patients with IBD receiving treatment at the San Juan de Dios University Hospital  between the years 2017 and 2019. Patients diagnosed as CD and UC according to the international investigational protocols and following the Montreal classification of IBD , were co- Radiographic examinationRadiographic periapical status was diagnosed on the basis of examination of digital panoramic radiographs of the jaws. Two trained radiographic technicians, with over ten years of experience, took the panoramic radiographs using a digital ortho-pantomograph machine .- Radiographic evaluationThe periapical status was assessed using the “Periapical Index” (PAI) score , consideFor each patient, the following data were recorded on a structured form: (a) number of teeth present; (b) number and location of teeth having identifiable radiolucent periapical lesions, (c) number and location of root-filled teeth, and (d) number and location of root-filled teeth having identifiable radiolucent periapical lesions.- Observers’ calibrationTwo blinded observers, with extensive clinical experience in endodontics, assessed the periapical status in radiographs. Previously, the observers had participated in a calibration course for PAI system, consisting of 100 radiographic images of teeth, some root-filled and some not, kindly provided by Dr. Ørstavik. The observers assigned one of the PAI scores to each tooth, using visual references for the five categories within the scale .Then, the results were compared to a “gold standard atlas”, also provided by Dr. Ørstavik. Cohen Kappa was calculated (0.78 – 0.85). Intra-observer reproducibility was also evaluated for each examiner scoring the radiographs of 20 patients, randomly selected. After recalibration in the PAI system, these first results were compared with those of a second evaluation of the same 20 patients carried out one month later. The intra-observer agreement test on PAI scores on the 20 patients produced a Cohen’s Kappa ranging 0.83 - 0.94. For inter-observers variability the Cohen’s Kappa ranged 0.75 - 0.84. The consensus radiographic standard was the simultaneous interpretation by the two examiners of the panoramic radiograph of each patient.- Statistical analysisThe prevalence of AP and RCT was evaluated on the total number of individuals and the total number of teeth. The minimal sample size (n = 49) was calculated using the sample size calculator software of the National Center for Advancing Translational Sciences  (http://www.sample-size.net/sample-size-proportions/) for the comparison of proportions in two independent samples, with continuity correction. They were taken into account a two-sided significance level of 5% , and 80% power  to detect a hypothesized difference between the proportion of the two types of IBD of 30 points.p value ≤ 0.05 was considered statistically significant.Raw data were entered into Excel . All analyses were done in an SPSS environment . The Student t test, 2 test, and logistic regression analysis were used to determine the significance of differences between groups. Data are reported as mean ± standard deviation. According to the established significance level, a p > 0.05). Patients with UC showed similar average number of teeth with AP (0.5 ± 0.8) as patients with CD (0.5 ± 0.9) (p > 0.05). There were also no significant differences between the two types of IBD in the number of RFT or in the number of RFT with AP. The prevalences of periodontal disease and smoking habits were also similar in both UC and CD patients (p > 0.05).The distribution of analysed variables in the two groups is shown in p > 0.05). There were no differences between both groups in the number of patients with one or more RFT (p = 0.60) or in the number of patients with one or more RFT with RPL (p = 0.43).Taking the patient as a reference , in the To further investigate the variables influencing periapical status, multivariate logistic regression was run with age, gender, number of teeth, number of RFT, periodontal disease and the type of IBD, taking as dependent variable and outcome “periapical status”  .p = 0.97) was not significant, indicating that both UC and CD patients had the same likelihood of having apical periodontitis. The only variable that was significantly associated with the periapical status was the number of RFT .In the multivariate analysis, including all the above factors as covariates, the type of IBD  was not significant, indicating that the likelihood of having RFT was the same both in UC and CD patients. Periapical status was significantly associated with endodontic status .Finally, to analyze the variables influencing the endodontic status, multivariate logistic regression was run with age, gender, number of teeth, periapical status, periodontal disease and the type of IBD, taking as dependent variable and outcome “endodontic status”  . In the This cross-sectional study aimed to investigate the prevalence of AP and RCT in patients with UC and CD. The null hypothesis tested, i.e. there are no significant differences in the prevalence of endodontic variables between UC and CD patients, has been confirmed. No significant differences in periapical status or endodontic status have been found between patients with UC and patients with CD.Patients were recruited by means of the same system used in previous studies ,8,9. BotThe two compared samples of patients with UC and CD had a similar age, gender, and BMI distribution. They also showed no significant differences in the number of teeth and the number of RFT, two variables significantly associated to radiographically diagnosed periapical lesions . The perPeriapical status has been evaluated using the ‘periapical index’ (PAI) , which aResults of many cross-sectional studies suggest an association between AP and systemic diseases , such asOne of the diseases whose relationship with endodontic pathology has been recently investigated has been IBD, including UC and CD ,9,19. ThBefore its association to apical periodontitis, several studies had investigated the relationship of IBD with periodontal disease . The patApical periodontitis has similar etiology and pathogenesis to that of periodontal disease , but fewet al.  and in CD patients (36%) were comparable and similar to that found in previous studies,9. No diet al. , who fou . Periapical radiolucent lesions associated to RFT are interpreted as persistent chronic AP, but can also correspond to healing lesions after RCT, especially if the time elapsed since treatment was less than 2 years. It has been shown that periapical lesions in patients with IBD taking biologic medications heal faster after RCT (Similarly, no differences were found between the two types of IBD in the number of RFT with periapical lesions. The percentage of patients with at least one RFT associated to RPLs was similar in both types of IBD (fter RCT . Taking Multivariate logistic regression analyzes demonstrated a strong significant association between the periapical status and the endodontic status, not influenced by the type of IBD. This result is consistent with numerous previous studies in which it is concluded that the number of RFT is a factor directly linked to the number of periapical lesions .The biological links between endodontic infection and IBD can be various. In IBD, a dysbiosis of the gut microbiota could contribute not only to the development of intestinal disorder, but also to the extra-intestinal inflammatory oral diseases , such asThe results of this study should be carefully evaluated, as it has some limitations. It is worth mentioning that has not been considered important factors influencing the prevalence of AP and RCT, such as educational level, socioeconomic status, diabetes, caries, quality of coronal restorations, quality of endodontic treatment, history of trauma .The results of the present study show similar frequency of AP and RFT in both UC and CD patients. The type of IBD does not appear to affect the prevalence of radiographically detecTable periapical lesions or the prevalence of root canal treatment.


N = 1,616) in Japan to know the association of PEs over a life time, as well as the two components, hallucinatory experiences (HEs) and delusional experiences (DEs), with lifetime experience of hikikomori . Logistic regression analysis was used to estimate the association between any PE, any HE, and any DE; and hikikomori, adjusting for socio-demographics and other psychopathologies . Any PE was significantly associated with hikikomori  after adjustment for sociodemographic factors, although the association attenuated after adjusting for other psychopathologies. Any DE remained significantly associated with hikikomori, even after adjustment for all the covariates . Any HE was not significantly associated with hikikomori. DEs may be associated with hikikomori. However, because the study sample was small and the temporal association between DEs and hikikomori was unclear, a future study is needed to examine a causal relationship between DEs and hikikomori.Psychotic experiences (PEs) may be associated with hikikomori. In the present study, we analyzed interview data from a community-based representative sample ( Hikikomori  is a public mental health concern worldwide, as well as in Japan . HikikomPrevious studies investigated a variety of factors associated with the occurrence of hikikomori, including socio-cultural influences, e.g., the social structure, the school context, and family relationships –9. In adPsychotic experiences (PEs) refer to a broad spectrum of hallucinatory and delusional symptoms from clinical to subthreshold, that often are milder than symptoms of schizophrenia , 15. PEsPEs have two components: hallucinatory experiences (HEs) and delusional experiences (DEs) . These tThis cross-sectional study aimed to preliminarily explore the association between lifetime experienes of PEs and hikikomori in a national sample of community-living adults in Japan, based on the World Mental Health Japan Second Survey . While We conducted the WMHJ2 Survey by using a two-stage random sampling method from 2013 to 2015 among community residents in Japan . The surHikikomori was measured by a single item, defined as a state of social withdrawal for more than 6 months, communicating only with family members and rarely leaving the house for work or school, measured by a module developed in a previous study. Participants were classified into those with or without any experience in the lifetime . Respondents were asked if they had ever experienced hikikomori .The CIDI Psychosis Module was composed of six PE types. The six PE types consisted of two items related to HEs  and four items related to DEs  , 32. ResMental disorder in the past 12 months was measured by using the WHO-CIDI 3.0 , 33. MenAge, gender, education, and income were examined as sociodemographic factors. Education was divided into four groups: junior high school graduates, high school graduates, some college, and university graduates or higher. Annual household income included the respondent's own earned income, spouse's income, income from others, social security income, and other income. We imputed the missing values of income by their age, sex, education, employment status and household size . Howeverp < 0.05 was considered statistically significant.Logistic regression analysis was used to estimate the association between any PE and hikikomori, any HE and hikikomori, and any DE and hikikomori. Hikikomori was analyzed as a dependent variable. Sociodemographic variables were adjusted for in Model 1 and Mental disorder in the past 12 months and having ASD trait were additionally adjusted for in Model 2. Fisher's exact test was performed to examine the association between the proportions of PEs and the presence of hikikomori. SPSS (Windows version 26) was used for statistical analysis and a n = 6), PEs (n = 27), and ASD trait (n = 126); these respondents were excluded, which left an analytic sample of 1,616 respondents. p = 0.04) and any DE (p = 0.01) among those who had experienced hikikomori were significantly higher than among those who had not experienced it, but the proportion with any HE was insignificant (p = 0.33). These p-values were obtained by Fisher's exact test.Among 2,450 total survey respondents, 1,775 answered the questionnaire on hikikomori. Some of these respondents had missing values on demographic variables , -(2), -(3), and -(4)] approved the aims and procedures of this study before it began. The patients/participants provided their written informed consent to participate in this study.NY was the principal investigator who conceptualized and designed the study, analyzed data, and drafted the article. KW, DN, HI, HT, TT, MU, and NK made a critical revision of the article and gave final approval for the version to be published. 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.


Conclusion: RESPOND’s large, diverse study population and standardized clinical endpoints puts the consortium in a unique position to respond to the diverse modern challenges for PLWH.Background: the International Cohort Consortium of Infectious Disease (RESPOND) is a collaboration dedicated to research on HIV and other infectious diseases. Methods: RESPOND is a flexible organization, with several independent substudies operating under one shared governance. HIV-related variables, including full antiretroviral therapy (ART) history, are collected annually for all participants and merged with substudy specific data into a shared data pool. Incident clinical events are reported using standardized forms. Prospective follow-up started 1/10/17 (enrolment) with retrospective data collected back to 01/01/12. Results: Overall, 17 cohorts from Europe and Australia provided data on 26,258 people living with HIV (PLWH). The majority (43.3%) of the population were white, with men-sex-with-men accounting for 43.3% of the risk for HIV acquisition. The median age was 48 years (IQR 40–56) and 5.2% and 25.5% were known to be co-infected with hepatitis B or C. While 5.3% were ART-naïve, the median duration on ART was 10.1 years (4.8–17.6), with 89.5% having a VL <200 copies/mL and the median CD4 count being 621 cells/µL (438–830). Malignancies ( The International Cohort Consortium of Infectious Disease (RESPOND) was formed in 2017 as a prospective, multi-cohort collaboration for the study of infectious diseases, with a special focus on people living with HIV (PLWH). RESPOND was founded upon the groundwork laid by outstanding European HIV cohort collaborations such as EuroSIDA, the Collaboration of Observational HIV Epidemiological Research Europe (COHERE), and Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) studies, and utilizes a similar, well-established infrastructure ,4.RESPOND offers a research framework with a flexible organization, applying a common data model across different substudies, utilizing one shared data pool. Additionally, all involved in RESPOND can contribute to the ongoing scientific agendas. Together, these dynamic features facilitate responses to a broad range of unmet research needs.The large size of RESPOND allows scientific questions to be addressed that individual cohorts do not have the size to investigate themselves. Furthermore, the heterogeneous study population with participants from across the whole of Europe and Australia and a high degree of data quality—including the central validation of standardized clinical event definitions—ensure that the results are reliable and applicable to a broader population of PLWH. RESPOND will address clinically relevant research questions, such as the risk and outcomes of non-AIDS comorbidities and the possible relationship to long-term ART exposure; to the outcomes and treatment of viral hepatitis B (HBV), hepatitis C (HCV), and tuberculosis (TB) co-infections; and to support public health initiatives.In this cohort profile, we will detail RESPOND’s organization, substudies, data collection and quality assurances, baseline characteristics, scientific findings to date, and focus areas going forward.https://chip.dk/Studies/RESPOND/Study-documents ..6].To minimize the risks of selection and survival bias to the greatest extent possible, individuals who had died or had been lost to follow up in the period 1/1/2012–1/10/2017 were enrolled for the initial merger .The consortium is overseen by an Executive Committee (EC), which is composed of scientific stakeholders, representatives from the three largest participating cohorts, and the chairs from Scientific Steering Committee (SSC) . The rolThe scientific agendas that drive the consortium’s scientific progression are formed under several substudies termed scientific interest groups SIGs; . These shttps://chip.dk/Studies/RESPOND) or by contacting the RESPOND secretariat .The RESPOND SIGs are formed and managed by two scientific moderators that are responsible for organizing all scientific activities within the SIG and for ensuring a contemporary research agenda. Relevant variables for SIG analyses may or may not already be collected as part of the standard RESPOND data collection. If a collection of new variables is needed, funds for the collection of these and following analysis must first be obtained, and this relies on the SIG participants and moderators. Therefore, the time from conceptualizing to a functioning SIG largely depends on the SIG’s scientific focus and the availability of data. More information on the initiation of a SIG in RESPOND can be obtained via the RESPOND webpage (Secretariat functions and data management are handled by the Coordinating Centre (CC). The statistical centers located at University College London, England, and Kirby Institute Sydney, Australia, manage data cleaning, statistical analyses, and support for cohort-led specific analyses.At present, there are three operational SIGs: The Clinical Outcomes of Antiretroviral Treatment (Outcomes) SIG, the Hepatitis SIG, and the Public Health SIG. A TB SIG is under formation .The Outcomes SIG investigates the incidence of, risk factors for, and outcomes related to non-AIDS comorbidities and the use of individual antiretroviral agents (ARVs). The Hepatitis SIG explores specific questions relevant for PLWH co-infected with HBV (with or without hepatitis D virus) and HCV. The purpose of the Public Health SIG is to implement studies of broader public health relevance using cohort clinical data in collaboration with EU surveillance institutions such as the European Center for Disease Control (ECDC), the World Health Organization (WHO), and other European-wide public health projects.All the members of a SIG may propose scientific projects . Two appThe first data merger for RESPOND took place in 2017, collecting data for the period 01/01/12–01/10/2017. Since then, prospectively collected data from cohorts are annually submitted to the RESPOND CC and merged with the RESPOND data pool.The clinical and demographic variables collected by RESPOND are summarized in RESPOND collects and stores data in the HIV Cohorts Data Exchange Protocol (HICDEP) format , detaileBoth REST and REDCap users will be met with multiple automated quality assurance checks when uploading or entering data. These built-in checks enable sites and cohorts to correct errors before data submission. Within a week of submission, raw datasets from individual cohorts are assessed for completeness and correctness by staff at the RESPOND CC. The cohorts are queried and asked to clarify and immediately resubmit corrected data as appropriate. After data cleaning, the statistical center produces comprehensive summaries of the data quality and completeness and provides individual feedback to cohorts, with the intent of improving data prior to the next data submission. In brief, assessments are made for all specific core variable since the last data submission. Correctness is assessed by a wide range of checks, aimed at identifying unintuitive reporting or systematic import errors .Information on clinical events is collected using non-identifiable data on study-specific Case Report Forms (CRFs) for the following events: myocardial infarction (MI), stroke, invasive cardiovascular procedure , end-stage liver and renal disease (ESLD and ESRD), and AIDS- and non-AIDS defining malignancy . Opposite from the routine follow-up data, CRFs are collected in real time from the period the 1st of December to the 1st of July. After CRFs are received at the CC, events are validated by a specially trained medical doctor following a prespecified algorithm , which mSubstantial quality assurance steps are in place to limit the potential underreporting of clinical events, including the assessment of the incidence rates of events reported from all individual cohorts. Likewise, the proportions of queried and dismissed events are continuously monitored to identify areas where individual cohorts may need to focus their attention and increase the amount and quality of collected data. Further, if a CRF does not contain the adequate information to allow for central validation, the cohorts are queried up to three times.By 1/10/17, 17 cohorts had agreed to engage in the consortium; 15 cohorts contributed to the first data merger, with a total of 26,258 individuals . Two addAt the study enrollment, the median age was 48 years ; 24.9% were younger than 40 years and 14.6% were older than 60 years. Women (25.7%) and persons of non-white ethnicity (27.6%) made up a substantial proportion of the study population. The RESPOND participants originated mainly from Western- (51.2%) and Southern Europe (26.6%), with 12.5% from Central Eastern- or Eastern Europe and 9.7% from Northern Europe . Heterosexual contact and injecting drug use, respectively, accounted for 34.3% and 14.9% of the risk factors for HIV acquisition, with men-who-have-sex-with-men (MSM) being the largest group (43.4%). Hepatitis B- or C co-infection were seen in 5.2% and 25.5% of the participants. At the time of enrollment into RESPOND, the majority (89.5%) of participants had a VL <200 copies/mL and 67.0% had a CD4 count >500 cells/µL. The nadir CD4 count was ≤50 cells/µL for 16.4%. The median baseline date was 06/17 [12/15–09/17].While 5.3% were ART-naïve at enrollment, the median duration of ART was 10.1 years (4.8–17.6), a. Doluten = 351 (50.4%), of which 35.9% were NADM and 14.5% were ADM; At time of the first data merger, the CC had received and centrally validated >90% of all expected event forms, with a total of 716 events. The predominant events were malignancies , or VL at ART initiation , without finding strong evidence that the differences in treatment response were different in the key subgroups.In a second analysis by Neesgaard et al. , the virRESPOND have also focused analyses on the contemporary question of ART strategies with two (2DR) or three drug (3DR) combinations. Greenberg et al.  comparedThe Public Health SIG recently presented proof of concept data from a method of using data from a random sample of patients to estimate a clinic’s percentage of individuals virologically suppressed on ART to construct the right-hand side of the continuum of care in settings with fragmented data to support surveillance as well as quality control .RESPOND is a large multicenter cohort consortium with the participation of 17 large, pre-existing cohorts from across Europe and Australia. At present (2020), more than 34,000 PLWH have been enrolled. Building on the sound scientific collaborations ongoing for more than three decades in the EuroSIDA, COHERE, and D:A:D multicohort studies, RESPOND represents a flexible yet well-structured framework for addressing unmet scientific questions for HIV and other infectious diseases.The development of well-tolerated, effective ART is one of the great milestones in modern medical history, having transformed HIV from a deadly progressive infection into a chronic condition for those with access to care . HoweverDue to the large size, substantial heterogeneity, extended follow-up time, and systematic collection of centrally validated endpoints, RESPOND is in a unique position to conduct well-powered pharmacovigilance studies and to assess the impact of demographics, traditional risk factors, HIV-related factors, and ART on a wide range of comorbidities. RESPOND will systematically assess the safety of newer ARVs, with a particular focus on INSTIs and other ARVs that may still be used in only a subset of PLWH and that therefore require a large dataset to reliably assess the longer term outcomes. Furthermore, the large number of persons under follow-up will allow RESPOND to focus on well-defined clinical endpoints, where individual cohorts may have too limited statistical power to conduct reliable analyses. In addition, the large and diverse composition of the consortium population provides the possibility of subgroup analyses stratified by clinical characteristics such as sex, smoking status, and age, in addition to stratifications based on geographical- and economic regions. Thus, the results will be broadly generalizable to the population of PLWH seen in routine clinical care in across Europe and Australia.Going forward, RESPOND will help generate pivotal information necessary for tailoring ART to meet the individual needs of an aging population of PLWH and to gain insights into the development and outcomes of comorbidities.The RESPOND data pool already holds a significant amount of data on ARV exposures, comorbidities, and mortality, with the most common clinical events being CVD and malignancies. Therefore, RESPOND will focus on these clinical events in the shorter term. More specifically, analysis investigating the possible associations between cumulative INSTI exposure and the risk of CVD and malignancies are ongoing. Other analyses will investigate weight gain and dyslipidemia in PLWH using contemporary ART and causes of death in PLWH within RESPOND. Additional follow-up time will allow the analysis of other less frequently occurring comorbidities and the possible relation to the use and discontinuation of modern ART.While HIV is the main focus area of RESPOND for the immediate future, there is a significant amount of research activity revolving around other co-infections within the consortium. Founded in the EuroSIDA cohort study network, the Hepatitis SIG has now been incorporated into the consortium and has recently added HCV treatment data and HBV-DNA to the already collected information on HCV-RNA and hepatitis serology. Among the ongoing research areas are the long-term outcomes of direct acting antivirals, HCV reinfection rates, and HBV/HDV co-infections. In addition, plans are being made to identify biomarkers predicting the development of hepatocellular carcinoma and investigations on the impact of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in PLWH.TB is a leading cause of infection-related deaths worldwide , with hiWhile these substudies do not provide an exhaustive list of co-infections for the population of PLWH, they show the ability of RESPOND to incorporate the standardized data collection of newly proposed data items across the network. As such, there is no limitation on which substudies can be undertaken within the consortium if there is a strong academic driving force and research need behind it.The public health SIG was created to support the use of HIV cohort data to address public health challenges. Collaboration between national surveillance institutions and clinical cohorts can help address gaps in data availability; however, many countries have poor cross-communication or lack those channels for data sharing.To reach the ambition of the 90-90-90 goals launched by the United Nations program on HIV/AIDS in 2014 , reliablThe linked pilot PrEP and Resistance project  [The ability to quickly utilize the network within and around RESPOND is in part possible due to RESPOND’s widely used HICDEP-based data collection. This model also facilitates partnerships with other collaborations, as exemplified by the European Union’s horizon 2020 project Common Action Against HIV/TB/HCV Across the Regions of Europe (CARE) , where bAs RESPOND is a non-randomized observational collaboration, the inherent limitations of possible missing data, selection bias, and unmeasured confounding apply for all analyses. To address the data quality and completeness, RESPOND employs a comprehensive and rigorous quality assurance system consisting of both automated and manual checks to ensure a high degree of data completeness and quality. In addition, the size of the study makes it possible to adjust for a wide range of possible confounding factors and perform adequately powered interaction and/or subgroup analyses. In addition, RESPOND will explore modern statistical methods such as causal inference, bioinformatics, and artificial intelligence.At present RESPOND does not systematically collect data on resistance or HIV-subtype—both of which are subject to considerable heterogeneity in our study population ,33, nor As the participating cohorts are based in Europe or Australia, the conclusion from RESPOND studies may not necessarily extend to PLWH from countries outside these regions and from resource-limited settings. Additionally, RESPOND includes only individuals from HIV cohorts able to comply with the RESPOND data collection principles and requirements.In conclusion, RESPOND is a newly formed, flexible, and open consortium based on a well-established infrastructure and dedicated to research related to HIV and other infectious diseases. RESPOND has a geographically diverse study population; has a large data pool containing key HIV-related and study-specific information; employs a rigorous data quality program; and includes a collection of standardized, centrally validated clinical outcomes. These qualities place the consortium in a unique position to respond to a wide range of modern challenges for PLWH.


Stylogaster Macquart (Diptera: Conopidae) is sister to the remainder of the Conopidae. While all other Conopidae are endoparasitoids of aculeate Hymenoptera, species of Stylogaster appear to be endoparasitoids of ‘orthopteroids’, as the only confirmed rearing records are from crickets and cockroaches. Many calyptrate flies have been observed with Stylogaster eggs attached, but since no Stylogaster have been reared from any dipterans, it is still unknown if these flies are hosts, results of accidental oviposition or carry the eggs to the actual hosts. In this study, we report our findings of Stylogaster eggs on blow flies  attracted to millipede defence secretions in Tanzania. Out of seven different species collected and a total of 301 specimens, only flies of the genus Tricyclea Wulp had Stylogaster eggs attached. Out of 133 Tricyclea collected, 32 (24%) had Stylogaster eggs attached and, with one exception, all eggs were attached to the abdomen. The lifecycle of Stylogaster is summarised and discussed with a particular focus on dipteran egg-carriers.The genus  Stylogaster Macquart (Diptera: Conopidae) presents intriguing challenges with regard to the biology of its included species. The genus is remarkably distinct, with all species characterised by an extremely long, geniculate proboscis, elongate and tapering female terminalia and a harpoon-like anti-micropylar end of the egg  and Afrotropical regions , but species are also found in parts of North America, Asia, the Philippines, New Guinea, eastern Australia, Tasmania and New Caledonia  each of Conopidae, Heleomyzidae, Lauxaniidae and Syrphidae  following army ants and he observed Stylogaster ovipositing on unspecified “other insects”, but he provided no rearing records. Firm evidence of actual parasitisation is still restricted to Stylogaster from immature cockroaches, as well as from one cricket in Kenya; Stylogasterbiannulata (Say) as reared repeatedly from Gryllusrubens Scudder in USA, Florida; and Stylogasterneglecta Williston from the cricket Oecanthusnigricornis  sampled from Canada (southern Ontario) and USA (New York State). The presence of Stylogaster eggs on various calyptrate flies has led to speculation about possible dipteran hosts, but as no larvae of Stylogaster have been found within any fly and no adults have been reared, this is still uncertain . All material for this project has been deposited at the Natural History Museum of Denmark.Specimens of potential egg-carriers were collected (by TP) by placing injured or crushed local juliform millipedes in a white plastic tray or on a sheet of white cloth. The flies attracted to the millipedes where collected using a hand net and stored in 70% ethanol for further examination. All collections where made on 21 August 2018 at the same locality in Tanzania: Mizimu camp, Udzungwa Mountains National Park, Morogoro Region, which is montane rainforest at an altitude of 769 m a.s.l.  for 24 hours at room temperature to macerate all soft tissue, then immersed in acetic acid, washed in distilled water, dehydrated in ethanol and transferred to glycerol for examination. After examination, all structures were stored in glycerol in a microvial pinned with the specimen. Each specimen with A series of photographs was taken using a Visionary Digital Imaging System with a Canon EOS 7D and stacked using Zerene Stacker version 2.0 . Superimposed photographs were edited using Adobe Photoshop® CS6 and GIMP 2.10. Drawings were digitally inked using Adobe Illustrator® CS6.Stylogaster hosts or egg-carriers and of other details of relevance for Stylogaster biology.A thorough search was made in relevant literature for all records of Phumosia Robineau-Desvoidy (one species), Hemigymnochaeta Corti (four species) and Tricyclea Wulp (two species). Eggs of Stylogaster were only found on the two Tricyclea species: Tricycleafasciata (Macquart) and Tricyclea sp. A, which were also the most numerous flies in the sample as 44% of the calliphorids belonged to Tricyclea. In total, 133 specimens of Tricyclea were collected, of which 32 (24%) had Stylogaster eggs attached and a total of 48 Stylogaster eggs were counted (Table T.fasciata (N = 23) p = 1, T. sp. A (N = 9) p = 0.57) or between the two Tricyclea species (Fisher's Exact Test: (N = 32) p = 0.6). Stylogaster eggs were predominantly found attached to female Tricyclea, although this was non-significant  = 0.28, p = 0.6), with 21 (65.6%) females and 11 (34.4%) males of the total of 32 Tricyclea individuals collected with eggs attached. However, there is a marked difference at the species-level, where more females carry eggs in T.fasciata  = 3.85, p = 0.05), while more males carry eggs in T. sp. A, although the latter difference is non-significant  = 0.17, p = 0.7).From the flies attracted to the wounded millipedes, a total of 301 calliphorid flies belonging to three different genera were collected and examined: Stylogaster eggs were only found attached to the posterior part of the abdomen of both male and female carriers  and crickets  from the Nearctic and Afrotropics (Table Stylogaster species have been reared from crickets: the Nearctic S.biannulata (Say) and S.neglecta Williston  and one egg attached to an undetermined orthopteran. There has been some confusion about other records of eggs on crickets and cockroaches, i.e. Stylogaster eggs attached to cockroaches and crickets, as compared to the numerous records of eggs on calyptrate flies, could be due to a lack of coordinated search efforts, as suggested by the study of Stylogaster eggs and larvae were collected after targeted sampling. Another explanation could be that eggs have been overlooked or that eggs detach after some time, as one observation suggests  and eggs have also been found on a spider . Taking into consideration the different proportions of surface area for head (17.5%), thorax (54.1%) and abdomen (28.4%), Stylogaster eggs to be randomly distributed on the bodies of the flies, for example, from the muscid genera Dichaetomyia Malloch, Dimorphia Malloch and Pyrellina Malloch. This agrees reasonably well with our data compiled for Muscidae, where most eggs are placed on the thorax (62%), followed by the abdomen (19%) and head (15%)  with the micropylar end "irregularly broken open" and interpreted this as a hatched egg. If the larva hatches from the egg through the end facing away from the host, especially for eggs that are attached to the ventral part of the host, it would appear that there is a high risk that the emerging larva would fall off the host. That would support the hypothesis of the calyptrate flies functioning as egg-carriers rather than true hosts.It is not known how the ost Fig. . Some haost Fig. D2, as thost Fig. . This isost Fig. , and StuTricyclea Wulp found to be impaled by Stylogaster eggs in the present study have a remarkably similar – and notably high – rate of infection (23–24%)  species of Tricyclea were impaled, none of the four species of Hemigymnochaeta Corti was impaled (Table Hemigymnochaeta carrying eggs of Stylogaster (Table The two species of %) Table . This mate Table . Male crnfection 3–24%  have been reared from the refuse piles of the ant Paltothyreustarsatus (Fabricius) and T.semithoracica Villeneuve and T.perpendicularis Villeneuve have been observed ovipositing near the nests of driver ants (Dorylus Fabricius) , which is behaviour known from the millipede-associated species of the Nearctic flesh fly genus Spirobolomyia Townsend and probably the pantropical scuttle fly genus Myriophora Brown  (Table Species of rmitinae . Tricyclbricius) . The flira Brown , but notra Brown  and whic%) Table .Tricyclea have Stylogaster eggs predominantly inserted at the tip of the abdomen rather than distributed randomly as for other calyptrate flies, nor will it explain why, in the material studied here, species of Tricyclea are impaled, while those of Hemigymnochaeta are not.This will not, however, explain why the species of Stylogaster hosts, there seems to be no phylogenetic pattern in the position of Stylogaster with confirmed hosts. Stylogaster species that parasitise crickets are found in all three major Stylogaster groups and both in the Nearctic, Neotropics and Afrotropics  is higher than most of the other calyptrate observations. Second, the Stylogaster egg placement on the abdomen of Tricyclea is similar to that on the confirmed hosts of Stylogaster and not random as for most of the other calyptrates. Third, the morphologically very similar Hemigymnochaeta that were collected from the same site as the egg-carrying Tricyclea spp. had no Stylogaster eggs, which suggests targeted rather than indiscriminate oviposition.Stylogaster (Fig. Stylogaster females and, in particular, on how the larva hatches from the egg and enters its host.We are getting closer to understanding the biology of ter Fig. , but theStylogaster is a part of and the early evolution of Conopidae. For example, if host location is mainly by visual cues, looking for patterns or movement, as the observations of Stylogaster darting at moving hosts near army ants would indicate, then that would explain the association of Stylogaster with army ants and the eggs impaled in Neotropical Calodexia and, possibly, also why eggs are found predominantly in Afrotropical calyptrates with similarly-coloured abdomen.Answering these questions is crucial if we want to understand the complex biological interactions that DFA851C0-2DA7-5C3C-872B-ECADC8C4910610.3897/BDJ.8.e54808.suppl1Supplementary material 1Supplementary Table S1Data typemorphologicalBrief descriptionStylogaster eggs for each individual fly examined. The ID of the fly corresponds to the visual representation of this data in Fig. 2.Data on the placement and number of File: oo_411417.pdfhttps://binary.pensoft.net/file/411417Arn Rytter Jensen, Freja Odgaard, Pierfilippo Cerretti, Thomas Pape


We aimed to prospectively investigate the association between the DII and CVD risk in the large Korean Genome and Epidemiology Study_Health Examination (KoGES_HEXA) cohort comprised of 162,773 participants . A validated semi-quantitative food frequency questionnaire (SQ-FFQ) was used to calculate the DII score. Statistical analyses were performed by using a multivariable Cox proportional hazard model. During the mean follow-up of 7.4 years, 1111 cases of CVD were diagnosed. Higher DII score was associated with increased risk of CVD in men  and in women , although not significant for women. The risk of CVD was significantly higher in physically inactive men , obese men  and men who smoked , respectively. The risk of developing stroke was significantly higher for men , but not for women. A pro-inflammatory diet, as indicated by higher DII scores, was associated with increased risk of CVD and stroke among men.Recently, diets with higher inflammatory potentials based on the dietary inflammatory index (DII Diet has been known to play an important role in modulating chronic inflammation ,2,3. Chr®), a literature-derived tool, was developed to evaluate the inflammatory potential of an individual’s diet [The dietary inflammatory index  cohort.KoGES cohort data were used for the current study. The KoGES cohort is based on the general Korean population, and aimed to obtain information on the genetic, environmental, and lifestyle determinants . KoGES collects and examines biological data such as urine, blood, and genetic material as well as epidemiological survey data. KoGES includes several cohorts including the KoGES cardiovascular disease association study (CAVAS), KoGES Ansan and Ansung study, and the KoGES health examinee study (HEXA). These population-based cohorts include both men and women participants who were recruited by the National Health Examinee Registry, and were 40–79 years of age at baseline. Detailed information on KoGES cohorts can be found elsewhere . Among tA total of 173,343 participants were recruited at the baseline between 2004 and 2013 and were asked to attend follow-up visits between 2007 and 2016 (mean follow up = 7.4 years). All participants voluntarily signed an informed consent form before the study and the study protocol was officially approved by the Institutional Review Board of the National Cancer Center (IRB No. NCC2018-0164) as well as the IRBs of the institutions that had participated in KoGES. Data accumulated from the baseline to the first follow-up were used and person–years of exposure time were obtained from the baseline to the first follow-up. Data from participants who had CVD  at the baseline had missing data (=6296), were missing caloric intake , or had no energy data were excluded from the analyses. This resulted in a final sample size of 162,773. The outcome was defined as a diagnosis of CVD by a medical doctor, which was self-reported by the participants. A total of 1111 incident cases of overall CVD  were identified after fulfilling the exclusion criteria .For baseline recruitment, eligible participants were asked to volunteer through on-site invitation, mailed letters, telephone calls, media campaigns, or community leader-mediated conferences. For the interview, a questionnaire was administered by trained staff. Baseline assessment included a physical examination. Participants were invited to complete periodic follow-up surveys by mail and telephone calls. The information about sociodemographic characteristics, personal and family history, physical activity, physical examinations, clinical investigations, and semi-quantitative food frequency questionnaire (SQFFQ) were obtained at the baseline and follow-up examinations using a structured questionnaire ,31,32,33The participants’ dietary intakes were recorded at the baseline using a validated SQFFQ. Detailed information on the validity of the SQFFQ is available elsewhere . Based oDetails of the updated DII are available elsewhere . Brieflyp values were calculated for continuous and categorical variables using the Jonckheere–Terpstra test and Mantel–Haenszel Chi-square test, respectively. The association between the baseline DII and newly diagnosed CVD  were analyzed by using the multivariable Cox’s proportional hazard model. To confirm the assumption of proportional risk, all of the models were evaluated and deemed to be consistent with a model that included time-dependent covariates. The model was adjusted for sex ; energy intake (continuous), age (continuous), BMI (continuous), alcohol consumption ; physical activity  and smoke . Stratified analyses were carried out by physical activity and BMI. The hazard ratios (HRs) were calculated with 95% confidence intervals (CIs), and the two-sided probability values were judged to be statistically significant if p < 0.05. We assessed heterogeneity between subgroups (men and women) using a likelihood ratio test comparing Cox’s proportional hazard models with and without interaction terms for DII and gender. All of the statistical analyses were performed with SAS® 9.3 . p values < 0.05 were considered as statistically significant.The association between DII and the risk of CVD  were statistically analyzed. The DII levels were represented as quintiles, based on the cohort for whom there was no baseline CVD . Continuous and categorical variables were represented as the means with standard deviation and frequency/counts as percentages, respectively. The trends in p < 0.0001), while the mean energy intake decreased (p < 0.0001). The mean BMI of the participants with a lower DII score was higher when compared to the higher DII score (p < 0.0001). The percentage of participants in the lower DII score for education attainment was higher when compared to the higher DII score participants (p < 0.0001). Moreover, participants with higher DII scores relative to those with lower scores had a lower income, higher smoking rate, and exercised less regularly (p < 0.0001). The number of post-menopausal women participants increased, while the number of married people decreased as the DII increased, respectively (p < 0.0001). The number of never drinkers increased, while current drinkers decreased as the DII score increased (p < 0.0001).The baseline characteristics of the participants from the KoGES_HEXA cohort based on the DII quintiles are presented in p = 0.006) of developing overall CVD  at the baseline for pro-inflammatory quintile (=Q5), while setting the lowest DII as the reference (=Q1) after adjusting for confounding variables  , while the result was not significant among women . The p-heterogeneity between men and women indicated no significant difference by sex (p = 0.64).During the 7.4 years follow-up, a total of 1111 individuals (578 men and 533 women) developed CVD (842 cases of MI and 288 cases of stroke). Cox’s regression analysis exhibited significantly higher risk ( intake) . After sQuintile 5 vs. 1 1.55; 95% CI 0.99–2.44; p = 0.008) and for men ; however, no significant results were found for women.The Cox’s regression analysis showed no significant risk of developing MI for all participants, or for men and women separately, after adjusting for confounding variables  . The risQuintile 5 vs. 1 1.80; 95% CI 1.03–3.12; p = 0.03) when compared to the participants who participated regularly . However, we did not find any significant association between DII score and overall CVD in female participants after stratified by physical activity.2), a significant association was observed between the DII and risk of developing overall CVD . After stratification by smoking, the risk of overall CVD was significantly higher among all participants who smoked . When further stratified by gender, the risk of overall CVD was higher (p = 0.002) in male smokers .The risk of developing overall CVD increased, especially among physically inactive men, obese men, and smoking men. In obese men (BMI > 25 Kg/m2), cigarette smokers, and physically inactive. These findings indicate that the most pro-inflammatory diet (high DII score = Q5) had a higher risk of CVD compared to those with an anti-inflammatory diet (lowest DII score = Q1). Similar results were reported by Garcia-Arellano et al. [n = 124), and regional specificity, which might be associated with different culture and lifestyle factors, and therefore, cannot be generalized to the general population of Iran. In addition, their validated FFQ had fewer food items (65 items) compared with the FFQ used (106 items) in the present study. Therefore, it is likely that they missed some factors for estimation, which were predictive in our results.In this prospective cohort study, we aimed to investigate the prospective association between dietary inflammatory potential and the risk of CVD in the Korean population. We observed that the Korean participants who had higher DII scores were at 63% higher risk of developing overall CVD, which was attenuated after multivariable-adjustment . The association was stronger among males compared to females. The risk of overall CVD was higher among men who were overweight or obese (BMI > 25 Kg/mo et al. ,20 in tho et al.  reportedo et al. . The difo et al.  could beIt is important to note that stroke and myocardial infarction present a multifactorial pathogenesis, which also includes genetics in addition to lifestyle and diet. Episodes of stroke and myocardial infarction may occur across generations. However, in the present study, compared to individuals without a family history of CVDs with a higher DII, individuals with lower DII but with a family history of CVDs were not more likely to develop stroke.Based on the hypothesis that inflammation is associated an atherothrombotic outcomes , we woulTo our knowledge, this is the first report of a strong association between a more pro-inflammatory diet as measured by DII and stroke risk among men in a prospective study. Lower DII score not only reflects the anti-inflammatory potential of the diet, but that the diets are generally healthier . TherefoAnother interesting finding of our study is that a statistically significant association was found between the DII and CVD risk among participants who were physically inactive. When stratified further for gender, the risk of CVD for physically inactive men was significantly higher than for women. Several studies have demonstrated an inverse relationship between regular exercise and the risk of coronary heart disease, cardiac events, and death ,47,48. TThere is concern about the effect of the growing rate of overweight and obesity and their association with CVD, stroke, metabolic syndrome, type II diabetes mellitus, cancer, and hypertension . BMI hasSmoking is considered an important risk factor for the development of CVD like many other chronic diseases . We founsine qua non of external validity.This study has some limitations that need to be pointed out. First, the diagnosis of the diseases was self-reported by participants who may underestimate the incidence with some error. Second, we used an FFQ to record the food consumption for the past year; thus, an individual may misreport her/his food intake. Additionally, we lacked information on eight food parameters to calculate a DII score that could influence the results. Despite these limitations, there are certain strengths to this study. It is the first of its kind from an Asian country, which assesses the association of the inflammatory effect of diet in terms of DII score with CVD risk. This could be utilized for important clinical recommendations, especially those addressing the trend of worsening dietary patterns worldwide. Another strength of the current study includes its prospective design, which minimizes recall bias and reverse causation. Additionally, it was adjusted for several lifestyles, demographic factors, and dietary factors as confounders. Furthermore, the population-based nature of the study cohorts increased the external validity. Finally, this study included a much larger number of Korean adults and by using the KoGES_HEXA cohort database, it is a sample that has strong internal validity; a In conclusion, diets with pro-inflammatory effects, as estimated by the DII, were significantly associated with an increased risk of CVD in men; however, they were not significantly associated in women. Additionally, the association between DII and subtypes of CVD was significant only in stroke, not in MI. Physical activity, smoking, and BMI acted as mediators between DII and CVD risk. These findings suggest that inflammation is a connection between diet and CVD risk as well as the usefulness of the DII in estimating the inflammatory impact of diet. Furthermore, the results underline the importance of consuming a more anti-inflammatory diet as a strategy to lower the risk of CVD for public health recommendations and guidelines for dietary recommendations in clinical settings.


The expected negative correlations between READ and HSCL-25 and the positive correlations between RSE, self-efficacy, and SWL were supported. Furthermore, the results of the measurement invariance demonstrated that the originally proposed five-dimensional structure is equal in the German and Swiss samples, and it can be assumed that the same construct was assessed by excluding one item. The five-factor, 27-item solution is a valid and reliable self-report measure of protective factors between two German-speaking samples.The Resilience Scale for Adolescents (READ) is a highly rated scale for measuring protective factors of resilience. Even though the READ has been validated in several different cultural samples, no studies have validated the READ across samples in German from Switzerland and Germany. The purpose of this study was to explore the construct validity of the German READ version in two samples from two different countries and to test the measurement invariance between those two samples. A German sample ( According to the World Health Organization , half ofUntil the late 1970s, the concept of pathogenesis, pioneered and developed by rise above to overcome adversities . Secondly, most of these instruments do not cover all three introduced overarching categories of resilience , and they differ significantly and focus mainly on individual factors. Among the just mentioned scales, only the Youth Resiliency: Assessing Developmental Strengths (YR: ADS) measures dimensions apart from individual factors, such as family, community, and peers. Nevertheless, this scale includes 10 dimensions and 94 items, which might be too lengthy and extensive for certain research applications. Thirdly, some of these scales are in the early stages of development and all need further validation . It has been validated in different countries and with different samples  were conducted, with a sample of 421 adolescents aged 13–15 years, resulting in a 28-item, five-factor structure with acceptable model fit indices. The five factors of the READ comprised all three generally accepted higher categories of resilience, and the READ scale was organized into five factors, which are represented in the six factors of the RSA. The first overarching factor, positive individual factors, is represented by the three dimensions, Personal Competence, Social Competence, and Structured Style. The second and third overarching factors, social family support and supportive environment outside the family are covered by the subscales Family Cohesion and Social Resources.The READ  was devePersonal Competence factor includes factors that measure several individual aspects, such as self-esteem, self-efficacy, ability to uphold daily routines, or the ability to plan and organize. The Social Competence factor focuses mainly on excellent communication skills and flexibility in social matters. The Structured Style factor measures the preference of an individual to plan and structure their daily routines. The Family Cohesion factor measures family support and the family’s attitude toward life in times of adversity. Lastly, the Social Resources factor measures perceived access to a social environment outside the family, such a relatives and friends, and the availability of their support  in Mexico.Just like Criticizing the use of confirmatory factor analyses and exploratory factor analyses, There is only one study so far that could confirm the original structure by using a confirmatory factor analysis without any modifications . The stuThe construct validity of the READ has been supported by negative correlations with, on the one hand, depression  and anxiThe literature review has demonstrated several strengths in previous validations, such as sample sizes and age ranges. However, certain methodological weaknesses need to be addressed. There is a lack of correspondence between the results of the confirmatory factor analysis (CFA), exploratory factor analysis (EFA), and exploratory structure equation modeling (ESEM) because the factor analysis techniques may not be fully comparable . CFA is Previous validations have shown that there is not only a lack of methodological clarity but also a lack of a validated version of the READ in any German-speaking countries. German is the native language to more than 100 million people, mainly spoken in Central Europe . Even though these countries and regions share a common language, they differ in their cultural backgrounds and dialects . Some woTherefore, this study examines the psychometric properties and the factorial validity of the German READ in a German and Swiss sample of adolescents in seventh grade by conducting a multi-group factor analysis (MGCFA).Even though most studies have used exploratory approaches to validate the READ, (i)the German version of the READ is a reliable and valid instrument, and the five-factor structure of the READ is consistent with the model proposed by the developers  and the Furthermore, (ii)not only form invariance but also metric invariance can be expected, indicating the equivalence of factor loadings across the German and Swiss samples.However, the equivalence in residual variances was not expected or regarded as a requirement for a valid use of the READ within the German-speaking countries .Lastly, several studies e.g.,  have fou(iii)the READ correlates negatively with anxiety and depression but positively with self-esteem, self-efficacy, and satisfaction with life.Due to the rapid pace of globalization, the worldwide population diversity has increased and calls for a need to ensure that assessment tools function equivalently across contexts and that the same construct manifests similarly and, therefore, is measured similarly. Researchers and clinicians conduct more multinational and multicultural studies and have to adapt instruments for use in other languages and cultures . HoweverHowever, these cross-cultural studies vary according to the contexts , and eveSubstantive differences in the meaning of resilience and how resilience manifests across the two independent samples could restrict the generalizability of findings. This could be the result of differences in the scale locations or the starting points that different people use to scale their responses on the READ scale despite having the same values on the latent resilience construct. Measurement invariance examines whether the same construct has been measured in the same way across different people, contexts, and cultures . Measuren = 321), ranging from 11 to 16 years, was 12.74 (SD = 0.77), and 44.2% of the participants were female. Whereas, the mean age of the random sample in Switzerland (n = 349), ranging from 11 to 15 years, was 12.67 (SD = 0.69), and 45.6% of the participants were female (gender was not identified for seven participants).This cross-sectional sample is based on the National Centres of Competence in Research (NCCR) project On the Move—The Migration-Mobility Nexus Overcoming Inequalities with Education—School and Resilience, funded by the Swiss National Science Foundation (SNSF). Six hundred and seventy seventh graders from lower secondary education classes (ISCED 2) in Germany and Switzerland completed the German-speaking web-based survey of risk and protective factors of mental health. The mean age of the random sample in Germany , the Cantonal Bureau for Education in the Cantons of Aargau, Basel-City, and Solothurn, and the Ethics Committee  of the Faculty of Arts and Social Sciences of the University of Zürich endorsed the data collection. First, the students’ questionnaires were translated into seven languages . A first translator translated the questionnaire into the target language, and a second independent translator checked the translation via retranslation. In the end, they decided on a consensus questionnaire. For the present study, only German-speaking questionnaires have been considered, as German is also the primary language in the three participating Swiss cantons. Afterward, schools in rural and urban areas in the Federal State Baden-Württemberg and the Cantons of Aargau, Basel-City, and Solothurn were asked to participate in the study. The headmaster of each school and the teachers approved participation in the survey. All parents and students received information letters explaining the procedure, and participation and data collection was voluntary, anonymous, and confidential. Participants were free to withdraw at any point in the study. Written informed consent to participate in the study was provided by the students and by their legal guardians. Students were asked to fill out the web-based questionnaires individually at their convenience on tablets. Teachers helped to administer the surveys during a regular school session of 90 min. Those not present while the study was carried out were asked to participate later.Gender and age were collected as single-item indicators for demographical information.totally disagree) to 5 . Higher scores indicate higher levels of resilience  is a valid and reliable measurement for resilience.The READ  is a 28-silience . The scaNot bothered) to 4 (Extremely bothered), with a high internal consistency. One item was omitted  due to the participants’ age range.The Hopkins Symptom Checklist HSCL-25;  is a selStrongly disagree) to 4 (Strongly agree). Higher scores on the unidimensional high internal consistency scale  indicate a higher level of self-esteem  to 4 (Exactly true). The total score of the scale, which is available in 33 languages, is calculated by finding the overall sum. The total score ranges between 10 and 40, indicating more self-efficacy with a higher score.To measure general self-efficacy, Strongly disagree) to 7 (Strongly agree). A score of 20 represents a neutral point on the scale, whereas scores of 5–9 indicate extreme dissatisfaction, and scores of 31–35 indicate extreme satisfaction with life. According to The Satisfaction with Life Scale SWL;  is a briFor the confirmatory factor and measurement invariance analyses, Mplus version 8  was usedSecondly, configural, metric, and scalar invariance for the CFA model across the two national samples were examined . ConfiguThe Chi square-test statistics have disadvantages due to the sensitivity of the sample size , and a cz-value was calculated.Thirdly, reliability and validity were evaluated by using IBM SPSS Statistics, version 24 . Cronbacz-values of all measurement instruments and their subscales. The sum scores of the following scales and subscales were higher in Switzerland compared to the German sample: HSCL-25 Anxiety, RSE, READ total, Personal Competence, Social Competence, Social Competence, Structured Style, Family Cohesion, and Social Resources. Furthermore, both countries show mean scores in the HSCL-25 scale above the cut-off value for “caseness,” which is defined at 1.75 for the original English version ( version  and is w version .χ2(340) = 581.934, p < 0.001; RMSEA = 0.047 [90% CI = 0.041–0.054]; SRMR = 0.058 CFI = 0.876; TLI = 0.862), which was also the case for the Swiss sample (χ2(340) = 595.875, p < 0.001; RMSEA = 0.047 [90% CI = 0.040–0.053]; SRMR = 0.060 CFI = 0.882; TLI = 0.868).The original 28-item, five-factor model of the READ was tested through a confirmatory factor analysis (CFA) across the two independent samples. The results showed that the fit indices yielded a fit with room for improvement in the German sample (I am satisfied with my life up till now”). Therefore, it was removed, which resulted in acceptable fit indices for both samples: Germany (χ2(312) = 460.87, p < 0.001; RMSEA = 0.039 [90% CI = 0.031–0.046]; SRMR = 0.053 CFI = 0.918; TLI = 0.907), and Switzerland (χ2(311) = 491.237, p < 0.001; RMSEA = 0.041 [90% CI = 0.034–0.048]; SRMR = 0.057 CFI = 0.912; TLI = 0.900). Hence, these results confirm the original five-factor structure of the READ by excluding one item, consequently leaving a 27-item solution (M1a and M1b in After freely estimating the covariance of two (Germany) and three (Switzerland) error terms to the items 28–14 and 16–11, and 7–1, 15–5, and 8–2, respectively, the fit indices still showed room for improvement. They have been freely estimated due to statistical reasons and similar wording content of the items. The modification indices further demonstrated one problematic item: item 4 , self-efficacy (ranging from r = 0.29 to 0.54), and SWL (ranging from r = 0.20 to 0.59). The highest negative correlations were between HSCL-25 and the READ factors Personal Competence and Family Cohesion. The same subscale factors had the highest associations with RSE, self-efficacy, and SWL. In general, most of the correlations between all measurements were higher in the Swiss sample than in the German sample. However, testing for the significance of these correlations showed that only a few z-values were significant. The significant differences between the total READ scale and RSE , as well as the SWL , are higher in Switzerland than in Germany. The same applies for the subscale Social Competence and RSE , Structured Style and SWL , and Family Cohesion and SWL . The comparison of the correlations between the subscale Social Resources and age showed a significant z-value of −2.21 (p < 0.05), which was more negative for the German sample than for the Swiss sample.To validate the READ, all five factors of the 27-item version were correlated with several psychological variables to investigate its convergent validity see . As expeThe READ is an approved scale that continues to be used widely as a measure of protective factors of resilience e.g., . The pri“I am satisfied with my life up till now” seems to be a problematic item, and its exclusion was justified statistically by showing high cross-loadings with the Family Cohesion factor and high modification indices. However, the item was designed to measure Personal Competence and cannot be statistically or clearly allocated to this factor. It can only be assumed that being satisfied with your own life might be strongly influenced by the family in this specific age range. The argument is founded on research by The first finding of the presented study was the support for the five-factor structure of the READ, even though one item had to be removed, thus supporting configural invariance. Item four, which has typically loaded poorly or inconsistently in previous studies of the READ, has been excluded several times e.g., . “I am sThe most important test of invariance, metric invariance, was also supported, showing that the factor loadings are equal for both groups. Thus, participants in Germany and Switzerland understand the items similarly and, therefore, interpret the wording of the items equally; their scores on the scale are comparable. Thus, it allowed simple regression analyses to predict comparable changes in criterion-related outcome variables across the two samples. Even scalar invariance was confirmed and therefore demonstrated that participants with the same value on the latent construct have identical values on the observed variable in both countries. These results show that the comparisons across the German and Swiss sample are meaningful and valid, direct mean comparisons are possible, and it can be assumed the same construct was assessed.Structured Style is rather low. This factor was the weakest one in previous studies  would be of great benefit. As Germany and Switzerland are culturally similar  and the M = 1.75 (M = 1.85 (SD = 0.60), and in the Swiss sample M = 1.85 (SD = 0.61). In addition, the sum scores of the subscales indicated “caseness,” and no specific sample facing adversity was investigated. Therefore, it would be interesting to have a closer look at a specific subsample with HSCL-25 values above 1.75 to examine the psychometric properties and factorial validity of a sample truly facing adversities. Furthermore, adolescents could have been categorized into depress/non-depressed or anxious/non-anxious adolescents based on the HSCL-25 to verify the difference in the READ scores among these groups. Also finding out to see if resilience as measured through the READ negatively predicts the total score at the HSCL-25 over and above self-esteem and self-efficacy could be a further way of showing incremental validity of the READ.Secondly, according to M = 1.75 : in the Thirdly, self-report measures always bear the risk of social desirability, especially when carrying out a study in the classroom . To reduIn conclusion, the first cross-cultural validation of the READ with samples from Germany and Switzerland provides further evidence on the psychometric properties of the READ as a valuable tool for the assessment of protective factors of resilience. The five-factor, 27-item model resulted in a good fit for the German and Swiss samples and has the potential for future research. Participants from both countries understood and interpreted these items in a similar and comparable fashion, which allows prospective studies to investigate adolescents’ mental health. However, modifications indicate a need for further investigations, whether the findings of the existing latent structure are replicable in different samples, countries, and cultures.clarissa.janousch@fhnw.ch.The datasets presented in this article are not readily available because the raw data supporting the conclusions of this article will be made available by the authors after 2023 when the project and dissertations will be completed. Requests to access the datasets should be directed to Clarissa Janousch, The studies involving human participants were reviewed and approved by the Ministry of Baden-Württemberg (Germany), the Cantonal Bureau for Education in the Cantons of Aargau, Basel-City, and Solothurn; and Ethics Committee  of the Faculty of Arts and Social Sciences of the University of Zürich. Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.CJ collected the data, conducted the data analysis, wrote the first draft of the manuscript, and continuously revised and developed the final version based on the feedback received. FA, OH, and CH provided substantial feedback on the manuscript and data analysis. 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.


N = 1,028, 72% female) completed an online questionnaire. Gambling engagement data was collected for pre-lockdown via the Brief Problem Gambling Screen (BPGS) allowing participants to be classified as Non-Gamblers (NG), Non-Problem Gamblers (NPG) or Potential Problem Gamblers (PPG). The Depression, Stress, and Anxiety Scale (DASS21) was used to measure depression, stress, and anxiety scores both pre- and during-lockdown. Results indicate that depression, stress and anxiety has increased across the whole sample. Participants classified in the PPG group reported higher scores on each sub scale at both baseline and during lockdown. Increases were observed on each DASS21 subscale, for each gambler group, however despite variable significance and effect sizes, the magnitude of increases did not differ between groups. Lockdown has had a significant impact on mental health of participants; whilst depression stress and anxiety remain highest in potential problem gamblers, pre-lockdown gambler status did not affect changes in DASS21 scores.To combat the spread of COVID-19, the UK Government implemented a range of “lockdown” measures. Lockdown has necessarily changed the gambling habits of gamblers in the UK, and the impact of these measures on the mental health of gamblers is unknown. To understand the impact of lockdown on gamblers, in April 2020, after ~6 weeks of lockdown, participants ( The global COVID-19 pandemic has had a significant impact on the lives of people around the world. In the UK, government measures implemented to stop the spread of the virus resulted in much of society being in “lockdown” from late March, with measures only being eased in late June and early July. Lockdown impacted on individuals, families, and wider society from different perspectives; interestingly, some of these impacts may have led to changes in addictive behaviors due to reduced accessibility of substances, withdrawal, increased craving, removal of positive reinforcers, and reduced access to medical or psychological support  and was then shared to the online participant recruitment pool, Prolific Academic. Registered Prolific users were then able to respond to the study advert, and assuming eligibility, complete the study. Prolific Academic was chosen over other crowd-sourcing platforms as participants recruited from Prolific Academic have been found to be more naïve and less dishonest than those recruited from alternative platform Amazon's Mechanical Turk (MTurk), and to produce higher quality data than alternative crowd-sourcing platform CrowdFlower . Age did not differ significantly between males  and females  . All participants included in analyses were engaged in some level of measures to prevent the spread of COVID-19, either social distancing, social isolation, or social shielding. For convenience, the term social distancing is used henceforth to include all levels distancing measures. Participants were most commonly social distancing in a household with 2–3 other people (40.5%), and least commonly distancing alone (15%). Most were distancing with family (76.46%); 76.17% had been distancing for between 2 and 4 weeks, and 64.1% were employed, at the time of survey completion.Participants were recruited through Prolific Academic. To maximize responses, the only eligibility criteria specified was that participants were required to be a current UK resident, and were adhering to some measure of social distancing, therefore were affected by lockdown. Thirteen participants were excluded as they were not engaged in any form of social distancing, resulting in a final sample of 1,028 participants , medium (η2 = 0.06), or large (η2 = 0.14), , Non-Problem Gamblers, as defined by indicating past-year gambling but scoring zero on the BPGS  or Potential Problem Gamblers, as defined by scoring > 0 on the BPGS .Raw scores on the DASS21 were analyzed between groups using repeated measures ANOVA models. Positively skewed data were SQRT(+1) transformed prior to statistical comparison. Where transformations did not correct skewness, equivalent non-parametric tests were used. A standard alpha of 0.05 was used, however Bonferroni adjusted alpha values were adopted to correct for multiple comparisons, where appropriate. To report the magnitude of differences between groups, eta squared was reported as a measure of effect size. Effect sizes were reported as either small (η= 0.14), . Change p values . For subp < 0.001]. Analysis of adjusted z score residuals indicates significant decreases in the “normal” category (p < 0.001) and increases in the “extremely severe” category (p < 0.001). The omnibus model for anxiety was significant [p = 0.012]; post hoc tests did not indicate any category change distribution change significant at the adjusted alpha of 0.005, although the increase in “extremely severe” was significant at 0.05. The omnibus model for stress was significant [p < 0.001]; post hoc tests indicate a significant increase in the “extremely severe” category (p < 0.001).DASS scales showed significant increases between pre-lockdown and during-lockdown for depression, anxiety, and stress . For depWhen analyzing between gambler groups, DASS scale scores reported for pre- and during-lockdown were compared between groups. Data were analyzed in repeated measures ANOVAs with factors of Time (pre- and during-lockdown), and Group .F = 55.83, p < 0.001, η2 = 0.052]. Using a Bonferroni corrected alpha of 0.016, the NG and NPG groups reported significant increases in depression between pre- and during-lockdown . The PPG group reported an increase significant at 0.05, but not at the adjusted alpha , For depression, the repeated measures ANOVA model showed a significant main effect of Time . The PPG group reported higher depression scores than both the NG and NPG groups  for both pre- and during-lockdown. The NG and NPG groups did not differ from each other at either timepoint. The Time*Group interaction was not significant . The mean change score was calculated by subtracting scale score for pre-lockdown from the scale score for during-lockdown. Using a corrected alpha of 0.016, depression change scores did not significantly vary between any groups .The factor Group was also significant . All groups reported an increase in anxiety between pre- and during-lockdown. The increase was significant for the NPG group , but not the NG or PPG groups , For anxiety, the repeated measures ANOVA model showed a significant main effect of Time . The PPG group reported significantly higher anxiety scores than the NPG and NG groups  for both pre- and during-lockdown. The NG and NPG groups did not differ at either timepoint. The Time*Group interaction was not significant . The mean change score for anxiety did not differ between groups .The factor of Group was significant . All groups reported an increase in stress between pre- and during-lockdown. The increase was significant for the NG and NPG groups , but not for the PPG group , For stress, the repeated measures ANOVA model showed a significant main effect of Time . The PPG group reported higher stress scores than the NG group at both periods . The PPG group reported higher stress scores than the NPG group pre-lockdown , but not for during-lockdown . The NG and NPG group did not differ at either time period. The Time*Group interaction was not significant . The mean change score for stress did not differ between groups at the adjusted alpha level, although change scores between the NG and PPG groups  and the NPG and PPG groups  were significant at 0.05.The main effect of Group was also significant  to alloThe global COVID-19 pandemic and the subsequent Government response have created an unprecedented set of circumstances for the UK public. Several factors resulting from enforced lockdown are conducive to the development, maintenance, or relapse into gambling problems. This study sought to explore the initial change is depression, anxiety, and stress in gamblers and non-gamblers in the UK, in the first weeks of lockdown. Results indicate that depression, stress, and anxiety are increasing regardless of gambler status; however, the mere fact that increases are general across all groups, should not detract from the elevated levels of depression, stress, and anxiety experienced by those experiencing gambling harm. This study provides a foundation for assessing and measuring the continuing and longer-term impacts of COVID-19 on longer term depression, anxiety, and stress in gamblers in the UK.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the University Research Ethics Committee, University of East London. The patients/participants provided their written informed consent to participate in this study.SS was responsible for questionnaire design, data collection, and manuscript preparation. AR, HB-J, and JS were responsible for questionnaire design and manuscript preparation. All authors contributed to the article and approved the submitted version.http://www.kcl.ac.uk/ioppn/depts/addictions/people/hod.aspx. JS is a National Institute for Health Research (NIHR) Senior Investigator and is supported by the NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and King's College London.In the last 3 years, SS has received funding from the Society for the Study of Addiction (SSA), and the NIHR. He is currently employed at the NAC, part of the NIHR Biomedical Research Centre and declares no conflicts. AR has received funding from Santander, Public Health for Lincoln, The Royal Society, The Maurice and Jacqueline Bennett Charitable Trust, East Midlands RDS and internal University of Lincoln awards. She has no conflicts of interest. HB-J is the Director of The National Problem Gambling Clinic which receives funds from the National Health Service and GambleAware. She is Honorary Professor at University College London. Board member, International Society of Addiction Medicine, Board member of the International Society for the Study of Behavioural Addictions. President Elect of the Royal Society of Medicine Psychiatry Section. JS is a researcher and clinician who has worked with a range of governmental and non-governmental organizations, and with pharmaceutical and technology companies to seek to identify new or improved treatments from whom his employer (King's College London) has received honoraria, travel costs, and/or consultancy payments, but these do not have a relationship to the study and findings reported here. For a fuller account, see JS's web-page at:


Background: Screening echocardiograms can detect early-stage rheumatic heart disease (RHD), offering a chance to limit progression. Implementation of screening programs is challenging and requires further research. This is the first large-scale study assessing the risk of RHD among previous screen-negative children.Methods: This retrospective cohort study, conducted in Gulu, Uganda, performed school-based echo screening on children ages 5–18 years. Surveys were used to determine which children underwent initial screening 3–5 years prior. Age, gender, and disease severity were compared between cohorts. Relative risk (RR) of RHD was calculated for those with a prior screen-negative echo (exposed cohort) compared to those undergoing first screening (unexposed cohort).Results: Echo screening was completed in 75,708 children; 226 were excluded, leaving 1,582 in the exposed cohort and 73,900 in the unexposed cohort. Prevalence of new RHD was 0.6%  and 1% , in the exposed and unexposed cohorts, respectively. The RR of RHD was 0.64 , a nearly 40% reduced risk of RHD in those with a prior negative echo. There was no difference in age or gender between RHD cohorts. All cases in the exposed cohort were borderline/mild; 2.6% of cases in the unexposed cohort had moderate/severe disease.Conclusion: There was no statistical difference in RHD prevalence between previous screen-negative children and children with no prior echocardiogram, however, there was a trend toward decreased risk and severity. This information has important implications for the design of screening programs and the use of screening echocardiograms in endemic RHD regions. Rheumatic Heart Disease (RHD) is a common cause of cardiovascular morbidity and mortality in children and young adults globally. In 2017, the worldwide prevalence of RHD was over 39 million, with 249,000 RHD-related deaths . In addiOne key question is whether or not echo screening and early detection of disease will improve outcomes. An ongoing randomized control trial is designed to answer that question by evaluating the impact of Penicillin prophylaxis on RHD progression over time . In addition to studying the utility of screening, the optimal frequency and timing of screening has not been clearly delineated. Knowing the optimal frequency of screening would simultaneously cut unnecessary cost and use of resources, while minimizing the risk of disease progression between screening echos. Prior studies have evaluated small cohorts of children with mild or no RHD to evaluate progression over time, and have shown variable results –9. Our sThis retrospective cohort study was conducted in Gulu District, Uganda, located in Northern Uganda, with known endemic rates of RHD. The study enrolled children, ages 5 to 18 years, who attended primary and secondary schools in Gulu District. Initial screening echos were performed between 2013 and 2015 on 8,009 children, as part of three separate studies looking at the utility of hand-held echo to detect RHD –13. A seDuring the second screening, a short 4-question interview was conducted by members of the research team with each child to determine prior participation in echo screening. When children self-reported a prior echo screening, they were asked for their name, age, and prior school and class. This data was used to ensure adequacy of recall. All children with positive screening echos in the schools subsequently underwent a complete confirmatory echocardiogram, analogous to the process in the initial screening studies. World Heart Federation (WHF) criteria were used to confirm the diagnosis of RHD, evaluate valve morphology, and determine the severity of disease . Childret-tests, a sample size of 2,316 would be required in each group to detect a difference of 50% (1% in the exposed population), with an alpha of 0.05 and power (1-B) of 0.8  were determined with 95% confidence intervals (CI). Statistical significance was deduced when the 95% CI of a RR did not include one and p < 0.05.Statistical analysis was performed using SPSS statistical analysis software. Age, gender, and details of the initial screening echo (school name and class) were collected by in-person interviews for those in the exposed cohort, and for all participants with a positive screening echo. Median and interquartile range (IQR) were calculated for age in the exposed cohort and in those with RHD in both the exposed and unexposed cohorts. Within the exposure group, RHD and non-RHD groups were compared. Age was compared by independent This study was covered under an existing Institutional Review Board (IRB) through Mulago Hospital at Makerere University, as part of the National RHD Outreach Program (REC REF 2013-072).A total of 75,708 children underwent echo screening during the second echo screening period. Sixty-five children were excluded from the study: 36 were diagnosed with another form of heart disease , 5 were outside the study age range (<5 years or >18 years of age), and 24 had been previously diagnosed with RHD before the time of the initial screening echo . A totalp = 0.15). The relative risk reduction was 0.4, or a 40% reduced risk of newly diagnosed RHD in those who had a previously negative screening echo compared to those who had never been screened before. There was no difference in age or gender between those who developed RHD and those without RHD in the exposed cohort . There were 737 new cases of RHD in the unexposed cohort; a prevalence of 1% . The relative risk of developing RHD if a child had a prior negative screening echo compared to those with no prior screening echo was determined to be 0.64  had evidence of RHD at an average follow up of 3.5 years . After aIn a third study out of Fiji, Engelman et al. reported clinical outcomes for 70 screen-negative cases with a median of 7.4 years and found no deaths or RHD-related admissions , Mulago Hospital at Makerere University, as part of the National RHD Outreach Program (REC REF 2013-072). Written informed consent for participation was not provided by the participants' legal guardians/next of kin because: Echocardiographic screening was performed under the national RHD Outreach Program.MZ, CS, and AB prepared the written manuscript. MZ, AS, AD, J-LN, IO, AT, JR, EO, CS, and AB reviewed and edited the manuscript. AS, AD, J-LN, IO, JR, and EO contributed to data gathering. AS, AD, and AT contributed to data organization. MZ, CS, and AB contributed to data analysis. 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.