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Background: Perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS) are common complications after noncardiac surgery. Inflammation has been implicated in the pathogenesis of both disorders. The COP-AF trial tests the hypothesis that colchicine reduces the incidence of perioperative AF and MINS in patients undergoing major noncardiac thoracic surgery. Design: The 'COlchicine for the Prevention of Perioperative Atrial Fibrillation' (COP-AF) trial is an international, blinded, randomized trial that compares colchicine to placebo in patients aged at least 55 years and undergoing major noncardiac thoracic surgery with general anesthesia. Exclusion criteria include a history of AF and a contraindication to colchicine (e.g., severe renal dysfunction). Oral colchicine at a dose of 0.5 mg or matching placebo is given within 4 hours before surgery. Thereafter, patients receive colchicine 0.5 mg or placebo twice daily for a total of 10 days. The two independent co-primary outcomes are clinically important perioperative AF (including atrial flutter) and MINS during 14 days of follow-up. The main safety outcomes are sepsis or infection and non-infectious diarrhea. We aim to enroll 3,200 patients from approximately 40 sites across 11 countries to have at least 80% power for the independent evaluation of the two co-primary outcomes. Summary: COP-AF is a large randomized and blinded trial designed to determine whether colchicine reduces the risk of perioperative AF or MINS in patients who have major noncardiac thoracic surgery. Population Health Research Institute

Introduction: In clinical trials, event adjudication is a process to review and confirm the accuracy of outcomes reported by site investigators. Despite efforts to automate the communication between a clinical-data-and-coordination center and an event adjudication committee, the review and confirmation of outcomes, as the core function of the process, still fully rely on human labor. To address this issue, we present an automated event adjudication system and its application in two randomized controlled trials. Methods: Centrally executed by a clinical-data-and-coordination center, the automated event adjudication system automatedly assessed and classified outcomes in a clinical data management system. By checking clinically predefined criteria, the automated event adjudication system either confirmed or unconfirmed an outcome and automatedly updated its status in the database. It also served as a management tool to assist staff to oversee the process of event adjudication. The system has been applied in: (1) the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial and (2) the New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS) trial. The automated event adjudication system first screened outcomes reported on a case report form and confirmed those with data matched to preset definitions. For selected primary efficacy, secondary, and safety outcomes, the unconfirmed cases were referred to a human event adjudication committee for a final decision. In the New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source (NAVIGATE ESUS) trial, human adjudicators were given priority to review cases, while the automated event adjudication system took the lead in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial. Results: Outcomes that were adjudicated in a hybrid model are discussed here. The COMPASS automated event adjudication system adjudicated 3283 primary efficacy outcomes and confirmed 1652 (50.3%): 132 (21.1%) strokes, 522 (53%) myocardial infarctions, and 998 (59.7%) causes of deaths. The NAVIGATE ESUS one adjudicated 737 cases of selected outcomes and confirmed 383 (52%): 219 (51.5%) strokes, 34 (42.5%) myocardial infarctions, 73 (54.9%) causes of deaths, and 57 (57.6%) major bleedings. After one deducts the time needed for migrating the system to a new study, the automated event adjudication system helped to reduce the time required for human review from approximately 1303 to 716.5 h for the Cardiovascular Outcomes for People Using Anticoagulation Strategies trial and from 387 to 196 h for the New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus Aspirin to prevenT Embolism in Embolic Stroke of Undetermined Source trial. Conclusion: The automated event adjudication system in combination with human adjudicators provides a streamlined and efficient approach to event adjudication in clinical trials. To immediately apply automated event adjudication, one can first consider the automated event adjudication system and involve human assistance for cases unconfirmed by the former.

ImportanceIn patients with multivessel coronary artery disease (CAD) presenting with ST-segment elevation myocardial infarction (STEMI), complete revascularization reduces major cardiovascular events compared with culprit lesion–only percutaneous coronary intervention (PCI). Whether complete revascularization also improves angina-related health status is unknown.ObjectiveTo determine whether complete revascularization improves angina status in patients with STEMI and multivessel CAD.Design, Setting, and ParticipantsThis secondary analysis of a randomized, multinational, open label trial of patient-reported outcomes took place in 140 primary PCI centers in 31 countries. Patients presenting with STEMI and multivessel CAD were randomized between February 1, 2013, and March 6, 2017. Analysis took place between July 2021 and December 2021.InterventionsFollowing PCI of the culprit lesion, patients with STEMI and multivessel CAD were randomized to receive either complete revascularization with additional PCI of angiographically significant nonculprit lesions or to no further revascularization.Main Outcomes and MeasuresSeattle Angina Questionnaire Angina Frequency (SAQ-AF) score (range, 0 [daily angina] to 100 [no angina]) and the proportion of angina-free individuals by study end.ResultsOf 4041 patients, 2016 were randomized to complete revascularization and 2025 to culprit lesion–only PCI. The mean (SD) age of patients was 62 (10.7) years, and 3225 (80%) were male. The mean (SD) SAQ-AF score increased from 87.1 (17.8) points at baseline to 97.1 (9.7) points at a median follow-up of 3 years in the complete revascularization group (score change, 9.9 [95% CI, 9.0-10.8]; P P P = .006). Overall, 1457 patients (87.5%) were free of angina (SAQ-AF score, 100) in the complete revascularization group compared with 1376 patients (84.3%) in the culprit lesion–only group (absolute difference, 3.2% [95% CI, 0.7%-5.7%]; P = .01). This benefit was observed mainly in patients with nonculprit lesion stenosis severity of 80% or more (absolute difference, 4.7%; interaction P = .02).Conclusions and RelevanceIn patients with STEMI and multivessel CAD, complete revascularization resulted in a slightly greater proportion of patients being angina-free compared with a culprit lesion–only strategy. This modest incremental improvement in health status is in addition to the established benefit of complete revascularization in reducing cardiovascular events.

Influenza increases the risk of cardiovascular events and deaths. We aimed to see whether influenza vaccination reduces death and vascular events in patients with heart failure.We did a pragmatic, randomised, double-blind, placebo-controlled trial in 30 centres (mostly hospitals affliated with universities or a research institute) in ten countries in Asia, the Middle East, and Africa (7 in India, 4 in Philippines, 4 in Nigeria, 6 in China, 1 in Zambia, 2 in Mozambique, 3 in Saudi Arabia, 1 in Kenya, 1 in Uganda, and 1 in Zambia). Participants (aged ≥18 years; 52·1% female; not disaggregated by race or ethnicity) with heart failure (New York Heart Association class II, III, or IV) were randomly assigned (1:1) by a centralised web-based system with block randomisation stratified by site, to receive 0·5 ml intramuscularly once a year for up to 3 years of either inactivated standard dose influenza vaccine or placebo (saline). We excluded people who had received influenza vaccine in 2 of the previous 3 years, and those likely to require valve repair or replacement. Those who administered assigned treatments were not masked and had no further role in the study. Investigators, study coordinators, outcome adjudicators, and participants were masked to group assignment. The first of two co-primary outcomes was a first-event composite for cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, and the second was a recurrent-events composite for cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for heart failure. Outcomes were assessed every 6 months in the intention-to-treat population. Secondary outcomes were all-cause death, cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, all-cause hospitalisation, hospitalisation for heart failure, and pneumonia, both overall and during periods of peak influenza exposure. This study is registered with ClinicalTrials.gov, NCT02762851.Between June 2, 2015, and Nov 21, 2021, we enrolled 5129 participants and randomly assigned (1:1) 2560 (50·0%) to influenza vaccine and 2569 (50·0%) to placebo. The first co-primary outcome occurred in 380 (14·8%) of 2560 participants in the vaccine group and 410 (16·0%) of 2569 participants in the placebo group (hazard ratio [HR] 0·93 [95% CI 0·81-1·07]; p=0·30). The second co-primary outcome occurred in 754 (29·5%) of 2560 participants in the vaccine group and 819 (31·9%) of 2569 participants in the placebo group; HR 0·92 [95% CI 0·84-1·02]; p=0·12). The secondary outcomes of all-cause hospitalisations (HR 0·84 [95% CI 0·74-0·97]; p=0·013) and pneumonia (HR 0·58 [0·42-0·80]; p=0·0006) were significantly reduced in the vaccine group compared with in the placebo group but there was no significant difference between groups for all-cause death, cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for heart failure. In a prespecified analysis, in which events were limited to periods of peak influenza circulation, the first co-primary outcome, and the secondary outcomes of all-cause death, cardiovasular death, and pneumonia were significantly lower in the vaccinated group than in the placebo group, whereas the second co-primary outcome and the secondary outcomes of non-fatal myocardial infarction, non-fatal stroke, all-cause hospitalisation, and hospitalisation for heart failure were not significantly lower.Although the prespecified co-primary outcomes during the entire period of observation were not statistically significant, the reduction during the peak influenza circulating period suggests that there is likely to be a clinical benefit of giving influenza vaccine, given the clear reduction in pneumonia, a moderate reduction in hospitalisations, and a reduction in cardiovascular events and deaths during periods of peak circulation of influenza. Taken in conjunction with previous trials and the observational studies, the collective data suggest benefit.UK Joint Global Health Trials Scheme and Canadian Institutes for Health Research Foundation.

Bleeding is the most common adverse event in those with cardiovascular (CV) disease receiving antithrombotic therapy, and it most commonly occurs in the gastrointestinal (GI) tract. Clinicians often dismiss bleeding as an adverse event that is reversible with effective antithrombotic therapy, but bleeding is associated with substantial morbidity and mortality, most likely mediated through an increased risk of CV events. Reducing the burden of bleeding requires knowledge of the potentially modifiable risk factors for bleeding and the potentially modifiable risk factors for adverse outcomes after bleeding.INTERBLEED is an international, multicentre, 2-component, observational study, with an incident case-control study examining the risk factors for GI bleeding, and a prospective cohort study of risk factors for CV events after GI bleeding. Cases either have CV disease and present to the hospital with GI bleeding or develop GI bleeding during hospitalization. Controls have CV disease, but no history of GI bleeding. We use a questionnaire to obtain detailed information on known and potential risk factors for GI bleeding and for CV events and outcomes after bleeding. We obtain CV and anthropometric measurements, perform functional and cognitive assessments, and follow participants at 3 months and 12 months.As of April 1, 2022, the study is ongoing in 10 countries at 31 centres and has recruited 2407 cases and 1478 controls.Knowledge of risk factors for bleeding, and risk factors for CV events and functional decline after bleeding, will help develop strategies to prevent bleeding and subsequent complications.L’hémorragie est l’effet indésirable le plus fréquent chez les patients atteints de maladies cardiovasculaires (CV) qui reçoivent un traitement antithrombotique, et elle survient le plus souvent dans le tractus gastro-intestinal (GI). Les cliniciens considèrent souvent l’hémorragie comme une simple manifestation indésirable réversible par un traitement antithrombotique efficace, mais une morbidité et une mortalité considérables y sont associées, probablement en raison d’un risque accru d’événements CV. Une réduction du fardeau de l’hémorragie nécessite une connaissance des facteurs de risque potentiellement modifiables tant de l’hémorragie que des événements indésirables qui surviennent après l’hémorragie.INTERBLEED est une étude internationale, observationnelle et multicentrique à deux volets; le premier volet est une étude cas-témoins incidents visant à examiner les facteurs de risque d’hémorragie GI, alors que le second volet est une étude de cohorte prospective visant à examiner les facteurs de risque d’événements CV après une hémorragie GI. Les cas sont des patients atteints de maladies CV qui consultent les services hospitaliers pour une hémorragie GI ou qui présentent une hémorragie GI en cours d’hospitalisation. Les témoins sont des patients atteints de maladies CV, mais sans antécédents d’hémorragie GI. Un questionnaire est utilisé pour obtenir des renseignements détaillés au sujet de facteurs de risque connus et potentiels d’hémorragie GI et d’événements CV et d’autres résultats de santé après une hémorragie. Des mesures cardiovasculaires et anthropométriques ainsi que des évaluations fonctionnelles et cognitives sont réalisées, et les participants sont revus après trois mois et 12 mois.En date du 1La connaissance des facteurs de risque d’hémorragie, ainsi que des facteurs de risque d’événements CV et de déclin fonctionnel à la suite d’une hémorragie, aidera à mettre en place des stratégies pour prévenir les hémorragies et les complications qui peuvent en découler.

Background and Aims: Disorders of gut-brain interaction (DGBI) are a group of chronic illnesses that are crucial to public health because they are widespread, influence patients‘ quality of life and functional level, and exert a major socioeconomic impact. We assessed the national prevalence of all 22 DGBI, the percentage of respondents satisfying diagnostic criteria for at least one DGBI, and the impact on the disease burden in Romania using data from the Rome Foundation Global Epidemiology Study. Methods: Data were collected through an anonymous, nationwide, and secure online survey, which evaluated the prevalence of any DGBI as well as over 22 different DGBI. The Rome IV diagnostic questionnaire and an in-depth supplemental questionnaire were included in the survey, which was completed through the Internet with numerous built-in quality-assurance measures. Results: The survey was completed by 2,049 participants (mean age 42.29±13.11 years) with a representative national distribution. Diagnostic criteria for any DGBI were met in 40.1% of the subjects, while 28.6% met criteria for only one DGBI (no overlap), and 11.5% met criteria for DGBIs in two, three, or four overlapping gastrointestinal anatomical regions. Females had a substantially higher predominance of DGBI than males. Psychosocial characteristics (such as quality of life, somatization, and concern about digestive problems) and healthcare utilization (such as physician visits and medication use) were associated with having any DGBI. Conclusions: We provide the first comprehensive evaluation of the prevalence and burden of DGBI in Romania using the Rome IV criteria. The burden of DGBI in Romania is substantial, with 40.1% of the 2,049 participants meeting diagnostic criteria for any DGBI. These findings demonstrate the importance of patient care, and the need for training and future research.

In case-control studies, odds ratios (OR) are calculated from 2 × 2 tables and in some instances, we observe small cell counts or zero counts in one of the cells. The corrections to calculate the ORs in the presence of empty cells are available in literature. Some of these include Yates continuity correction and Agresti and Coull correction. However, the available methods provided different corrections and the situations where each could be applied are not very apparent. Therefore, the current research proposes an iterative algorithm of estimating an exact (optimum) correction factor for the respective sample size. This was evaluated by simulating data with varying proportions and sample sizes. The estimated correction factor was considered after obtaining the bias, standard error of odds ratio, root mean square error and the coverage probability. Also, we have presented a linear function to identify the exact correction factor using sample size and proportion.

Early in the COVID-19 pandemic, the South Asian community in the Greater Toronto Area (GTA) was identified as having risk factors for exposure and specific barriers to accessing testing and reliable health information, rendering them particularly vulnerable to SARS-CoV-2 infection. We sought to investigate the burden of SARS-CoV-2 infection among South Asian people in the GTA, and to characterize the demographic characteristics, risk perceptions and trusted sources of health information in this group.We conducted a cross-sectional analysis from the baseline assessment of participants in a prospective cohort study. Participants from the GTA were enrolled from Apr. 14 to July 28, 2021. Seropositivity for antispike and antinucleocapsid antibodies was determined from dried blood spots, and estimates of seropositivity were age and sex standardized to the South Asian population in Ontario. Demographic characteristics, risk perceptions and sources of COVID-19 information were collected via questionnaire and reported descriptively.Among the 916 South Asian participants enrolled (mean age 41 yr), the age- and sex-standardized seropositivity was 23.6% (95% confidence interval 20.8%-26.4%). Of the 693 respondents to the questionnaire, 228 (32.9%) identified as essential workers, and 125 (19.1%) reported living in a multigenerational household. A total of 288 (49.4%) perceived that they were at high COVID-19 risk owing to their geographic location, and 149 (34.3%) owing to their type of employment. The top 3 most trusted sources of information related to COVID-19 included health care providers and public health, traditional media sources and social media.By the third wave of the COVID-19 pandemic, about one-quarter of a sample of South Asian individuals in Ontario had serologic evidence of prior SARS-CoV-2 infection. Insight into factors that put certain populations at risk can help future pandemic planning and disease control efforts.

BACKGROUND AND AIMS: Conditions such as irritable bowel syndrome (IBS), functional dyspepsia, and functional constipation are among the prevalent gastrointestinal (GI) disorders classified as disorders of gut-brain interaction (DGBI), which can adversely affect the lives of sufferers. This study aimed to assess the degree and consequences of overlapping DGBI in a large population-based global scale. METHODS: Internet survey data from 54,127 adults (49.1% women) in 26 countries were analyzed by 4 GI anatomic regions (esophageal, gastroduodenal, bowel, and anorectal). The number of DGBI-affected GI regions was assessed, including associations with sex, age, disease severity, quality of life, psychosocial variables, and health care utilization. RESULTS: A total of 40.3% of surveyed individuals met Rome IV criteria for a DGBI. The percentages with 1-4 DGBI-affected GI regions were 68.3%, 22.3%, 7.1%, and 2.3%, respectively. The IBS symptom severity score increased significantly from 1 (207.6) to 4 (291.6) regions, as did non-GI symptom reporting (somatization), anxiety and depression, concerns and embarrassment about bowel function, doctor visits, medications, and abdominal surgeries (all P < .0001). Quality of life decreased with increasing number of DGBI regions (P < .0001). In a logistic mixed model, non-GI symptoms (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.08-1.10), being very vs not concerned (OR, 2.55; 95% CI, 2.27-2.90), being very vs not embarrassed about bowel function (OR, 1.20; 95% CI, 1.08-1.33), and mean number of doctor visits (OR, 1.23; 95% CI, 1.115-1.32) were most strongly associated with number of DGBI regions. CONCLUSIONS: DGBI in multiple anatomic GI regions is associated with increased psychological comorbidity, health care utilization, and IBS severity. Physician awareness of overlap could improve quality of care, prevent unnecessary interventions, and yield more positive health outcomes. ispartof: CLINICAL GASTROENTEROLOGY AND HEPATOLOGY vol:20 issue:5 pages:E945-E956 ispartof: location:United States status: published

BACKGROUND: Previous epidemiologic studies in Sweden have only covered some of the disorders of gut-brain interaction (DGBI) and are not representative of the general population. This study aimed to define the prevalence and impact of DGBI in Sweden. METHODS: We used Swedish data from the Rome Foundation Global Epidemiology Study which include information on DGBI diagnoses, psychological distress, quality of life (QoL), healthcare utilization, and the impact of stress on GI symptoms. KEY RESULTS: The prevalence of having any DGBI was 39.1% (95% CI 37.0-41.2); esophageal disorders 6.1% (5.1-7.3), gastroduodenal disorders 10.7% (9.3-12.0), bowel disorders 31.6% (29.6-33.6), and anorectal disorders 6.0% (5.1-7.2). Subjects with a DGBI more commonly reported anxiety and/or depression, reduced mental and physical QoL, and more frequent doctor visits due to health problems. Subjects with a DGBI reported bothersome gastrointestinal (GI) symptoms to a greater extent and more than 1/3 had visited a doctor due to GI problems and of those 1/3 had seen multiple doctors. Prescription medications were available among 36.4% (31.0-42.0) who had bothersome GI symptoms and a DGBI, with sufficient symptom relief in 73.2% (64.0-81.1). Psychological factors and eating were reported to worsen GI symptoms and stress during the last month was greater in subjects with a DGBI. CONCLUSIONS AND INFERENCES: DGBI prevalence and its impact in Sweden is in line with global data, including increased healthcare utilization. GI symptoms are commonly affected by psychological factors and eating, and a high proportion of those on prescription medication report sufficient GI symptom relief. ispartof: NEUROGASTROENTEROLOGY AND MOTILITY vol:35 issue:6 ispartof: location:England status: accepted

BACKGROUND: The Rome Foundation carried out a worldwide epidemiology study on DGBI according to the Rome IV criteria in 33 countries, including Belgium. DGBI prevalence varied between continents and countries, but prevalence differences within language groups in a single country have not yet been described. METHODS: We analyzed the prevalence rates of 18 DGBI and their psychosocial impact in Belgium in the French and Dutch language groups. KEY RESULTS: DGBI prevalence was similar in the French-speaking and Dutch-speaking population. Having one or more DGBI was negatively associated with psychosocial well-being. The scores for depression were lower in the Dutch-speaking participants with one or more DGBI compared to the French-speaking participants. Interestingly, we also found significantly lower scores in the general Dutch-speaking versus the French-speaking population for depression and non-gastrointesinal somatic symptoms, and higher global physical health and mental health quality-of-life component scores. In the Dutch-speaking group, medication use for gastric acid was lower, but use of prescribed analgesics was more common. Nevertheless, the use of non-prescribed pain medication was higher in the French-speaking group. Anxiety and sleep medication use was also higher in the latter group. CONCLUSIONS & INTERFERENCES: The results of this first in-depth analysis of Rome IV DGBI in Belgium show a higher prevalence for some DGBI in the French-speaking cohort, and a larger associated disease burden. These differences between language/culture groups in the same country support the psychosocial pathophysiological model of DGBI. ispartof: NEUROGASTROENTEROLOGY AND MOTILITY vol:35 issue:6 ispartof: location:England status: accepted

Objective To estimate the association between Social Determinants of Health (structural and intermediate) and caries indicators in Chile's Metropolitan Region preschool children. Methods A multilevel cross-sectional study of Social Determinants of Health (SDH) and caries in children aged 1 to 6 years in Chile's Metropolitan Region was conducted in 2014–2015, with three levels: district, school and child. Caries were assessed by the dmft-index and the prevalence of untreated caries. The structural determinants analyzed were Community Human Development Index (CHDI), urban/rural location, school type, caregiver's education and family income. Poisson multilevel regression models were fit. Results The sample size was 2,275 children from 40 schools in 13 districts. While the highest CHDI district had an untreated caries prevalence of 17.1% (12.3–22.7%), in the most disadvantaged district it was 53.9% (95% CI 46.0–61.6%). As family income increased, the probability of untreated caries prevalence decreased (PR = 0.9 95% CI 0.8–1.0). Rural districts had an average dmft-index of 7.3 (95% CI 7.2–7.4), while in urban districts, it was 4.4 (95% CI 4.3–4.5). Higher probabilities of untreated caries prevalence (PR = 3.0 95% CI 2.3–3.9) were observed in rural children. Greater probabilities of untreated caries prevalence (PR = 1.3 95% CI 1.1–1.6) and prevalence of caries experience (PR = 1.3 95% CI 1.1–1.5) were observed in children whose caregivers had a secondary educational level. Conclusions A strong association was observed between the social determinants of health, specifically the structural ones, and the caries indicators studied in children of the Metropolitan Region of Chile. There were notable differences in caries between districts according to social advantage. Rurality and caregiver's education were the most consistent predictors.

Altres ajuts: acords transformatius de la UAB Altres ajuts: JP-B was funded by a FONDECYT Grant 1212037 from the Chilean National Agency of Research and Development (ANID). GU contribution to this paper was supported by a CONICYT grant (MEC80170060), government of Chile. Funding information Overlap of primary studies among systematic reviews (SRs) is one of the main methodological challenges when conducting overviews. If not assessed properly, overlapped primary studies may mislead findings, since they may have a major influence either in qualitative analyses or in statistical weight. Moreover, overlapping SRs may represent the existence of duplicated efforts. Matrices of evidence and the calculation of the overall corrected covered area (CCA) are appropriate methods to address this issue, but they seem to be not comprehensive enough. In this article we present Graphical Representation of Overlap for OVErviews (GROOVE), an easy-to-use tool for overview authors. Starting from a matrix of evidence, GROOVE provides the number of included primary studies and SRs included in the matrix; the absolute number of overlapped and non-overlapped primary studies; and an overall CCA assessment. The tool also provides a detailed CCA assessment for each possible pair of SRs (or "nodes"), with a graphical and easy-to-read representation of these results. Additionally, it includes an advanced optional usage, incorporating structural missingness in the matrix. In this article, we show the details about how to use GROOVE, what results it achieves and how the tool obtains these results. GROOVE is intended to improve the overlap assessment by making it easier, faster, and more friendly for both authors and readers. The tool is freely available at http://doi.org/10.17605/OSF.IO/U2MS4 and https://es.cochrane.org/es/groovetool.

Communicating statistics in health risk communication is a fundamental part of managing public health emergencies. Effective communication requires careful planning and the anticipation of possible information demands from the population. The information should be clear, relevant, easy to understand, timely, accurate and precise, allowing the public to make informed decisions about protective behaviours. COVID-19, being a new disease, with little known about its characteristics and effects, has challenged governments and healthcare systems in all countries. This article discusses the statistical issues involved, and the experiences of risk communication in four countries – Canada, Chile, Ecuador and England. These countries have communicated risks differently, partly because of their different healthcare systems, as well as socioeconomic, cultural and political realities. During a pandemic, health authorities and governments must step up to the challenge of communicating statistical information under pressure and with urgency, when little is known about the disease, the situation is dynamic and evolving, and the general public is gripped with fear and anxiety. This is in addition to the existing challenges relating to the generation of data of different quality by diverse sources, and a public with varying levels of statistical literacy. From a statistical perspective, communiqués about risks and numbers should convey the uncertainty there is about the information, the inherent variabilities in the system, the precision and accuracy of estimates and the assumptions behind projections. Complex technical concepts, such as ‘flattening the curve’, ‘range in risk estimates’ and ‘projected trends,’ should be explained.

BackgroundCardiovascular disease (CVD) is a leading cause of death globally. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), compared in the ONTARGET trial, each prevent CVD. However, trial populations may not be representative of the general population.MethodsUsing trial replication methods within routine-care data, we explored replicability of the ONTARGET trial. For people prescribed an ACEi and/or an ARB in the UK Clinical Practice Research Datalink CPRD GOLD from 1/1/2001-31/7/2019, we applied trial criteria and propensity-score methods to create an ONTARGET trial-eligible cohort. Comparing ARB to ACEi, using Cox-proportional hazards models, we estimated hazard ratios for the primary composite trial outcome (cardiovascular death, myocardial infarction, stroke, or hospitalisation for heart failure), as well as secondary outcomes. As the pre-specified criteria were met confirming trial replicability, we then explored treatment effect heterogeneity of ACEi and ARB among three trial-underrepresented subgroups: females, those aged ≥75 years and those with chronic kidney disease.FindingsIn the trial-eligible population (n=137,155), results for the primary outcome met pre-specified criteria for similarity to the ONTARGET trial and demonstrated similar effects of ARB and ACEi, (HR 0.97 [95% CI: 0.93, 1.01]). When extending to trial-underrepresented groups, similar treatment effects of ARB and ACEi were observed by sex (P=0.09), age (P=0.70) and chronic kidney disease status (P=0.10).InterpretationWe were able to replicate the results of the ONTARGET trial using routinely-collected healthcare data. Results suggest that trial findings were generalisable to population subgroups underrepresented in the trial.FundingGlaxoSmithKlineResearch in ContextEvidence before this studyTrial replication is an important methodology increasingly used to validate findings from observational studies against target trials. Unlike many naïve observational comparisons, a previous study demonstrated replicability of the ONTARGET trial using United States insurance claims data. However, it is unknown whether trial replicability can be extended to UK routinely-collected healthcare data. In addition, little work has been done to extend findings of comparative effectiveness among trial-underrepresented subgroups such as women, the elderly and those with chronic kidney disease despite high rates of prescribing of ACE Inhibitors and angiotensin receptor blockers among these groups in routine-care.Added value of this studyWith access to the individual patient data from the ONTARGET study and using propensity-score methods to address confounding, we demonstrated trial replicability using routinely-collected primary care data, representative of a large proportion of the UK population. We were then able to leverage the large sample size of the trial-eligible cohort to extend findings to trial-underrepresented groups and demonstrated similar comparative effectiveness for subgroups of patients treated with ARB and ACEi among women, those aged ≥75 years and those with chronic kidney disease.Implications of all the available evidenceOur findings support similar effectiveness for cardiovascular and renal outcomes for patients receiving an ARB compared to an ACEi in a trial-eligible cohort and subgroups for which there is currently a lack of evidence of treatment effectiveness. Trial-replication methodology can be used to provide evidence for populations underrepresented in clinical trials.

There is controversy on whether to use incremental monetary net benefit (INMB) or incremental cost-effectiveness ratio (ICER) in health economic evaluations alongside randomized controlled trials. We studied the impact of restricted mean survival time (RMST) on the long-term projection of INMB and ICER. We analyzed the unbiasedness and efficiency of ICER and INMB by (1) deriving the metrics' expected values and variances based on theoretical probability distributions, (2) simulating their 15-year post-trial projections based on between-arm-RMST-gained through a 2 × 4 × 2 factorial experiment of Markov 2-state microsimulations. Simulations and comparison were run on the data from the Cardiovascular Outcomes for People Using Anticoagulation Strategies Study (COMPASS). Our simulation findings using RMST showed that ICER was more efficient than INMB, regardless of disease populations, time horizon, modeling choices, and underlying probability distributions of incremental mean cost and effect. ICER had a small variance and thus showed its robustness to the choices of models. INMB is unbiased, while ICER is biased-but-remediable. INMB’s variance varies with a willingness-to-pay (WTP) threshold value quadratically while ICER’s variance varies with incremental-mean-cost quadratically. A simple and naïve model can sufficiently estimate ICER. Future metrics are expected to be health-economic-meaningful, unambiguous, unbiased, efficient, and statistical-inference-friendly.

The relative roles of school context and individual student factors are of special interest to educators in measuring academic performance. Little is known about the effect of school violence on a student's academic performance and well-being. The aims of this study were to examine the effects of three types of school violence (direct violence, discrimination, and cyberbullying) on students' academic performance in standardized tests of mathematics, reading and history, and to identify individual student factors that contribute to reducing the negative effect of exposure to violence at school. We used 10th grade Chilean student data from the representative cross-sectional test of the Education Quality Measurement System (SIMCE in Spanish) from 2015. Multilevel linear models, adjusted for gender, incorporated other school and environmental contextual factors, as well as individual student factors. The results show that school violence in its three forms had a negative effect on academic performance. Student self-efficacy, educational expectations and satisfaction with interpersonal relations with their teachers, were important in reducing the negative effect of exposure to violence. The implications for the school are discussed.

Aims The Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial demonstrated that rivaroxaban 2.5 mg BID with aspirin 100 mg was more effective than aspirin 100 mg daily alone for the prevention of cardiovascular (CV) death, stroke, or myocardial infarction in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD). We aimed to examine the cost-effectiveness of rivaroxaban using patient-level data from the COMPASS trial. Methods and results We performed an in-trial analysis and extrapolated our results for 33 years using a two-state Markov model with a 1-year cycle length. Hospitalization events, procedures, and study drugs were documented for patients. We applied country-specific (Canada, France, and Germany) direct healthcare system costs (in USD) to healthcare resources consumed by patients. Average cost per patient during the trial (mean follow-up of 23 months), quality-adjusted life years (QALYs), and lifetime cost-effectiveness were calculated. Costs of events and procedures were reduced with rivaroxaban 2.5 mg BID with aspirin. The addition of rivaroxaban 2.5 mg BID increased total costs for the combination group. Over a lifetime horizon (in trial +33 years), rivaroxaban plus aspirin was associated with 1.17 QALYs gained, yielding an incremental cost-effectiveness ratio (ICER) of $3946/QALY, $9962/QALY, and $10 264/QALY in Canada, France, and Germany, respectively. PAD and polyvascular disease subgroups had lower ICERs. Conclusion Rivaroxaban 2.5 mg twice daily plus aspirin compared with aspirin alone reduces direct healthcare costs. After acquisition costs of rivaroxaban, the lifetime cost-effectiveness of 2.5 mg twice daily plus aspirin is highly cost-effective in Canada, France, and Germany. (COMPASS ClinicalTrials.gov identifier: NCT01776424)

IntroductionSouth Asians are more likely to develop gestational diabetes mellitus (GDM) than white Europeans. Diet and lifestyle modifications may prevent GDM and reduce undesirable outcomes in both the mother and offspring. Our study seeks to evaluate the effectiveness and participant acceptability of a culturally tailored, personalised nutrition intervention on the glucose area under the curve (AUC) after a 2-hour 75 g oral glucose tolerance test (OGTT) in pregnant women of South Asian ancestry with GDM risk factors.Methods and analysisA total of 190 South Asian pregnant women with at least 2 of the following GDM risk factors—prepregnancy body mass index>23, age>29, poor-quality diet, family history of type 2 diabetes in a first-degree relative or GDM in a previous pregnancy will be enrolled during gestational weeks 12–18, and randomly assigned in a 1:1 ratio to: (1) usual care, plus weekly text messages to encourage walking and paper handouts or (2) a personalised nutrition plan developed and delivered by a culturally congruent dietitian and health coach; and FitBit to track steps. The intervention lasts 6–16 weeks, depending on week of recruitment. The primary outcome is the glucose AUC from a three-sample 75 g OGTT 24–28 weeks’ gestation. The secondary outcome is GDM diagnosis, based on Born-in-Bradford criteria (fasting glucose>5.2 mmol/L or 2 hours post load>7.2 mmol/L).Ethics and disseminationThe study has been approved by the Hamilton Integrated Research Ethics Board (HiREB #10942). Findings will be disseminated among academics and policy-makers through scientific publications along with community-orientated strategies.Trial registration numberNCT03607799.

The ultimate objective of research on injuries is to generate knowledge that could be used to reduce trauma and injuries worldwide. Knowledge is generated from interpreting and contextualizing info...

Objective To evaluate the power of responder analyses in a randomized controlled trial. Study design and setting Simulations were based on the Chronic Kidney Disease Antidepressant Sertraline Trial (CAST), which compared sertraline to placebo for the treatment of depression in kidney disease. Baseline disease severity, placebo response, effect size, and the proportion of responders were varied across 72 scenarios. Power was assessed using a t-test for change scores, and the chi-square test for dichotomized outcomes of the minimal important difference (MID), improvement and remission in 10,000 datasets with a fixed sample size of 193. Results The t-test had >80% power except for scenarios with the lowest sertraline effect size. The chi-square test using the MID had 80% power only at higher effect sizes and/or when the proportion of responders was highest at 0.5. The chi-square test for improvement had marginal power increases compared to the t-test (4/72 scenarios = 5.6%) and that for remission did not outperform the t-test in any scenario. Conclusions The t-test outperforms the chi-square test for dichotomized outcomes regardless of baseline disease severity, placebo response, effect size and the proportion of responders to the intervention.

ObjectiveThe aim was to determine the effects of chronic intermittent hypobaric hypoxia (CIHH) on prostate-specific antigen (PSA) levels in Chilean miners who work at different altitudes.MethodsA cross-sectional study was conducted between April and July 2019. Miners from five mines (N=338) at different altitudes were evaluated. We recorded sociodemographic, working and altitude information. Haemoglobin oxygen saturation (SaO2) and haemoglobin (Hb) were measured in situ, while PSA and testosterone were analysed at a low level. Linear mixed-effect models were used to evaluate the association between PSA level and two CIHH exposures: composite CIHH (with four descriptors) and ChileStd-CIHH (CIHH Chilean standard; based on the Chilean technical guide for occupational exposure to CIHH). All models were adjusted by age, body mass index and day of the work the samples were taken.ResultsHighest and lowest PSA levels were found in mines ≥3000 m above sea level (mine 3: median=0.75, IQR=−0.45; mine 4: median=0.46, IQR=−0.35). In the multilevel models, the wider altitude difference between mining operation and camp showed lower PSA levels (model D: βPSA=−0.93 ng/mL, βlogPSA=−0.07, p2, Hb and testosterone. The descriptors of composite CIHH explained better PSA variations than ChileStd-CIHH (model D: marginal R2=0.090 vs model A: marginal R2=0.016).ConclusionsOccupational health regulations and high altitude medicine should consider these results as initial evidence on the inclusion of new descriptors for CIHH and the possible effect of this exposure on PSA levels in this male-dominated occupational sector.

Forty percent of individuals globally meet Rome IV criteria for a disorder of gut-brain interaction (DGBI). The global burden of pain across these disorders has not been characterized.Our study included 54,127 respondents from the 26 Internet survey countries. Prescription pain medication usage was selected as the proxy for pain. The associations between prescription pain medications and the environmental, sociodemographic, psychosocial, and DGBI diagnosis variables were investigated using the multivariate generalized robust Poisson regression model.Respondents with DGBI used prescription pain medications at higher rates than those without a DGBI diagnosis with pooled prevalence rate of 14.8% (95% confidence interval [CI], 14.4-15.3%), varying by country from 6.8% to 25.7%. The pooled prevalence ratio of prescription pain medication usage in respondents with and without DGBI was 2.2 (95% CI: 2.1-2.4). Factors associated with higher prevalence of pain medication usage among respondents with a DGBI diagnosis included living in a small community, increased anxiety, depression or somatization, increased stress concern or embarrassment about bowel functioning and having more than one anatomic DGBI diagnosis.14.8% of patients globally with at least one diagnosis of DGBI were on prescription pain medications with wide geographic variation, about twice as many as their counterparts without a diagnosis of DGBI. Environmental, sociodemographic, and individual factors may influence clinicians to consider personalized, multimodal approaches to address pain in patients with DGBI.

The large number of patients worldwide infected with the SARS-CoV-2 virus has overwhelmed health-care systems globally. The Anti-Coronavirus Therapies (ACT) outpatient trial aimed to evaluate anti-inflammatory therapy with colchicine and antithrombotic therapy with aspirin for prevention of disease progression in community patients with COVID-19.The ACT outpatient, open-label, 2 × 2 factorial, randomised, controlled trial, was done at 48 clinical sites in 11 countries. Patients in the community aged 30 years and older with symptomatic, laboratory confirmed COVID-19 who were within 7 days of diagnosis and at high risk of disease progression were randomly assigned (1:1) to receive colchicine 0·6 mg twice daily for 3 days and then 0·6 mg once daily for 25 days versus usual care, and in a second (1:1) randomisation to receive aspirin 100 mg once daily for 28 days versus usual care. Investigators and patients were not masked to treatment allocation. The primary outcome was assessed at 45 days in the intention-to-treat population; for the colchicine randomisation it was hospitalisation or death, and for the aspirin randomisation it was major thrombosis, hospitalisation, or death. The ACT outpatient trial is registered at ClinicalTrials.gov, NCT04324463 and is ongoing.Between Aug 27, 2020, and Feb 10, 2022, 3917 patients were randomly assigned to colchicine or control and to aspirin or control; after excluding 36 patients due to administrative reasons 3881 individuals were included in the analysis (n=1939 colchicine vs n=1942 control; n=1945 aspirin vs 1936 control). Follow-up was more than 99% complete. Overall event rates were 5 (0·1%) of 3881 for major thrombosis, 123 (3·2%) of 3881 for hospitalisation, and 23 (0·6%) of 3881 for death; 66 (3·4%) of 1939 patients allocated to colchicine and 65 (3·3%) of 1942 patients allocated to control experienced hospitalisation or death (hazard ratio [HR] 1·02, 95% CI 0·72-1·43, p=0·93); and 59 (3·0%) of 1945 of patients allocated to aspirin and 73 (3·8%) of 1936 patients allocated to control experienced major thrombosis, hospitalisation, or death (HR 0·80, 95% CI 0·57-1·13, p=0·21). Results for the primary outcome were consistent in all prespecified subgroups, including according to baseline vaccination status, timing of randomisation in relation to onset of symptoms (post-hoc analysis), and timing of enrolment according to the phase of the pandemic (post-hoc analysis). There were more serious adverse events with colchicine than with control (34 patients [1·8%] of 1939 vs 27 [1·4%] of 1942) but none in either group that led to discontinuation of study interventions. There was no increase in serious adverse events with aspirin versus control (31 [1·6%] vs 31 [1·6%]) and none that led to discontinuation of study interventions.The results provide no support for the use of colchicine or aspirin to prevent disease progression or death in outpatients with COVID-19.Canadian Institutes for Health Research, Bayer, Population Health Research Institute, Hamilton Health Sciences Research Institute, and Thistledown Foundation.For the Portuguese, Russian and Spanish translations of the abstract see Supplementary Materials section.

This study, using the database from the Rome Foundation Global Epidemiology Survey, aimed to assess the differences in quality of life overall, and by age and sex, across individual disorders of gut-brain interaction (DGBI), gastrointestinal anatomical region(s), and number of overlapping DGBI.Data were collected via the internet in 26 countries, using the Rome IV diagnostic questionnaire and a supplemental questionnaire including the Patient-Reported Outcomes Measurement Information Systems Global-10 quality of life measure. Factorial ANOVAs were used to explore physical and mental quality of life, adjusting for multiple comparisons.Among the 54,127 respondents, quality of life deteriorated significantly with increasing number of overlapping DGBI, with respondents reporting two or more DGBI having significantly poorer quality of life than those with only one DGBI or those without any DGBI. Males with DGBI reported better quality of life than females, and those aged ≥65 years old reported better quality of life than those65 years. Age, sex, number of overlapping DGBI, somatization, anxiety, depression, and functional experiences (concern, embarrassment, or stress associated with bowel functioning) relating to DGBI, were significant predictors of poorer physical and mental quality of life.This study is the most comprehensive assessment of quality of life to date in adults living with a DGBI. It provides a representative picture of DGBI impact on adults in the global adult population, and highlights the significant detrimental impact of living with a DGBI on quality of life.

This systematic review aimed to summarize reports of the incidence and long-term recurrence of new-onset atrial fibrillation (AF) associated with non-cardiac surgery. We searched CENTRAL, MEDLINE and EMBASE from inception to November 2019. We included studies that reported on the incidence of new-onset perioperative AF during hospitalization for non-cardiac surgery and/or AF recurrence in such patients following discharge. Reviewers screened articles and abstracted data independently and in duplicate. We assessed study quality by appraising methodology for collecting AF history, incident AF during hospitalization, and AF recurrence after discharge. From 39,233 citations screened, 346 studies that enrolled a total of 5,829,758 patients met eligibility criteria. Only 27 studies used prospective, continuous inpatient electrocardiographic (ECG) monitoring to detect incident AF. Overall, the incidence of postoperative AF during hospitalization ranged from 0.004 to 50.3%, with a median [interquartile range] of 8.7 [3.8–15.0]%. Atrial fibrillation incidence varied with type of surgery. Prospective studies using continuous ECG monitoring reported significantly higher incidences of AF than those that did not (13.9% vs 1.9%, respectively; P < 0.001). A total of 13 studies (25,726 patients) with follow-up up to 5.4 years reported on AF recurrence following hospital discharge; only one study used a prospective systematic monitoring protocol. Recurrence rates ranged from 0 to 37.3%. Rates of AF incidence first detected following non-cardiac surgery and long-term AF recurrence vary markedly. Differences in the intensity of ECG monitoring and type of surgery may account for this variation. PROSPERO (CRD42017068055); registered 1 September 2017.

The level of clustering and the adjustment by cluster-robust standard errors have yet to be widely considered and reported in cross-sectional studies of tuberculosis (TB) in prisons. In two cross-sectional studies of people deprived of liberty (PDL) in Medellin, we evaluated the impact of adjustment versus failure to adjust by clustering on prevalence ratio (PR) and 95% confidence interval (CI). We used log-binomial regression, Poisson regression, generalized estimating equations (GEE), and mixed-effects regression models. We used cluster-robust standard errors and bias-corrected standard errors. The odds ratio (OR) was 20% higher than the PR when the TB prevalence was >10% in at least one of the exposure factors. When there are three levels of clusters (city, prison, and courtyard), the cluster that had the strongest effect was the courtyard, and the 95% CI estimated with GEE and mixed-effect models were narrower than those estimated with Poisson and binomial models. Exposure factors lost their significance when we used bias-corrected standard errors due to the smaller number of clusters. Tuberculosis transmission dynamics in prisons dictate a strong cluster effect that needs to be considered and adjusted for. The omission of cluster structure and bias-corrected by the small number of clusters can lead to wrong inferences.

Violence against women has been recognized by the United Nations as a fundamental violation of women’s human rights. Although there is a good amount of research on physical violence, very little on psychological abuse from Indian researchers. In India too, domestic violence is prevalent in all sections of the community. The objectives of the study are to find the prevalence of psychological abuse in different stratum in India and the risk factors of psychological violence. A cross-sectional study based on 9938 women in rural, urban, and urban non-slum sites across India was conducted in 1998–1999. Logistic regression was done to find the risk factors of psychological violence. Despite the limitations of the 9426 women responded psychological violence, 3306 (35.1%) (95%CI: 23.1, 47.0) reported any psychological abuse in the past 1 year. The women who had lower education, from lower socioeconomic status (SES) and whose mothers-in-law not satisfied with dowry had higher risk for psychological abuse. There was a synergistic effect in psychological abuse if the woman is from low SES and the husband is an alcoholic and the risk is 7.4 times higher as compared to women who did not have both. However, alcoholism had significant independent effect when this was interacted with satisfaction of dowry. We suggest that the families should avoid asking and giving dowries. Besides these, the newly married women should be counseled to handle the conflicts at the family level so that the physical and psychological abuses can be avoided.

Introducción: el objetivo fue diseñar un estudio comunitario randomizado controlado multi-componente y evaluar su efecto en la prevención de obesidad en escolares del departamento de Caaguazú, Paraguay.Material y métodos: Diseño: ensayo comunitario randomizado controlado. Lugar: 16 escuelas públicas y privadas del área urbana y rural del Departamento de Caaguazú, Paraguay. Participantes e intervención: 16 escuelas serán asignadas aleatoriamente a dos grupos. Grupo intervención, recibirán un programa de educación nutricional y actividad física en el entorno escolar durante 6 meses. Grupo control, recibirán 3 charlas educativas en el mismo periodo. Medición de las principales variables: primaria (espesor de pliegues cutáneos), secundarias (z índice de masa corporal, conocimientos nutricionales, consumo de frutas y verduras, nivel de actividad física) y variables demográficas (sexo, edad, zona de residencia). Todas las variables serán medidas en la línea base y al final del estudio, utilizando herramientas calibradas, cuestionarios validados y protocolos de procedimiento. Análisis: se utilizará estadística descriptiva, además de los test t Student y chi2 para establecer diferencias. Se correrán modelos de regresión lineal y logística crudos y ajustados.Ética y diseminación: el protocolo de estudio ha sido evaluado y aprobado por el Comité de Ética en Investigación de la Universidad Nacional de Caaguazú. Se utilizarán consentimientos informados institucionales (escuelas) e individuales (padres) y asentimiento de los niños.

BACKGROUND/OBJECTIVES: The global epidemiology of gastroparesis is unknown. The European UEG and European Society for Neurogastroenterology and motility consensus defines Gastroparesis as a condition characterized by delayed gastric emptying in the absence of mechanical obstruction, with a symptom pattern of nausea and/or vomiting and overlapping postprandial distress syndrome (PDS). Real-world evidence of this gastroparesis-like symptom pattern is a crucial step in understanding the epidemiology of gastroparesis. METHODS: In the Rome Foundation Global Epidemiology Study, 54,127 respondents from 26 countries completed the Rome IV Diagnostic Questionnaire and variables associated with disorders of gut-brain interaction via Internet. We selected subjects with gastroparesis-like symptoms (GPLS) (nausea and/or vomiting ≥1 day/week and simultaneous PDS). Patients reporting organic gastrointestinal disease, or fulfilling criteria for self-induced vomiting, cyclic vomiting or cannabinoid hyperemesis syndrome were excluded. We determined prevalence, associated comorbidities, quality of life (QoL) (PROMIS Global-10), symptoms of anxiety and depression (PHQ-4), somatic symptoms (PHQ-12), and healthcare utilization. RESULTS: The global prevalence of GPLS was 0.9% overall and 1.3% among diabetic individuals. Subjects with GPLS showed frequent overlapping of epigastric pain syndrome and irritable bowel syndrome. Subjects with GPLS had significantly lower body mass index, QoL, more non-gastrointestinal somatic complaints, symptoms of anxiety and depression, higher medication usage and doctor visits in the overall and diabetic population, compared to subjects without these symptoms. CONCLUSIONS: GPLS are common worldwide and more common in diabetic patients. The symptom complex is associated with multiple aspects of illness and an increased healthcare consumption. ispartof: UNITED EUROPEAN GASTROENTEROLOGY JOURNAL vol:10 issue:8 pages:888-897 ispartof: location:England status: published

Matias F Martinez,1,2 Enzo Alveal,1 Tomas G Soto,1,3 Eva I Bustamante,4 Fernanda Ávila,5 Shrikant I Bangdiwala,6,7 Ivonne Flores,4 Claudia Benavides,4 Ricardo Morales,4 Nelson M Varela,1,2 Luis A Quiñones1,2 1Laboratory of Chemical Carcinogenesis and Pharmacogenetics (CQF), Department of Basic and Clinical Oncology (DOBC), Faculty of Medicine, University of Chile, Santiago, Chile; 2Latin American Network for the Implementation and Validation of Pharmacogenomic Clinical Guidelines (RELIVAF-CYTED), Madrid, Spain; 3Departamento De Ciencias Básicas Santiago, Facultad De Ciencias, Universidad Santo Tomás, Santiago, Chile; 4Cancer Institute Arturo López Pérez Foundation, Santiago, Chile; 5Infectology Section, Medicine Department, Clinical Hospital of the University of Chile, Santiago, Chile; 6Population Health Research Institute, McMaster University, Hamilton, ON, Canada; 7Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, CanadaCorrespondence: Luis A Quiñones; Nelson M VarelaLaboratory of Chemical Carcinogenesis and Pharmacogenetics (CQF), Department of Basic and Clinical Oncology (DBOC), Faculty of Medicine, University of Chile, Santiago, ChileTel +56-2-29770741; Tel +56-2-29770743Email lquinone@med.uchile.cl; nvarela@med.uchile.clPurpose: Neutropenia is a common event in patients undergoing cytotoxic chemotherapy for the treatment of a hematological malignancy. Some polymorphisms, as IL-6 − 572C>G (rs1800796), IL-1β − 31 G>A (rs1143627), and CARD8 304T>A (rs2043211), in genes related to the inflammatory process, could affect the level of absolute neutrophil count (ANC) after chemotherapy. Since an efficient inflammatory process enhances neutrophil survival, we hypothesize that these polymorphisms are associated with ANC.Patients and Methods: We carried out a prospective cohort study in two hospitals in Santiago, Chile. The patients included were adults diagnosed with acute myeloblastic leukemia, acute lymphoblastic leukemia, or non-Hodgkin’s lymphoma, undergoing cytotoxic chemotherapy. We use a multilevel linear regression model to test our hypothesis. The best model was selected using the Akaike’s information criterion (AIC).Results: We analyzed 1726 hemograms and ANCs from 172 hospitalizations from 32 patients. The results show that CC and CG genotypes of IL-6 − 572 C>G polymorphism are associated with higher ANCs compared with the GG genotype (Ln (ANC) ∼ 0.81 IC95% 0.02– 1.55). Similarly, TT and AT genotypes of CARD8 304T>A polymorphism were related to higher ANCs compared with AA (Ln (ANC) ∼ 0.95 IC95% 0.02– 1.82). IL-1β genetic polymorphism had no statistically significant association with ANC.Conclusion: IL-6 rs1800796 − 572C>G and CARD8 rs2043211 304T>A polymorphisms are associated with the absolute neutrophil count in patients undergoing cytotoxic chemotherapy for treatment of hematological malignancies. Our findings might be useful to improve the safety of chemotherapy through predictive ANC models.Keywords: pharmacogenetics, neutropenia, hematological neoplasms, leukemia, lymphoma, interleukin-6, CARD8 protein

ObjectiveTo investigate the behavior of restricted mean survival time (RMST) and designs of a two-state Markov microsimulation model through a 2 × 4 × 2 full factorial experiment.MethodBy projecting patient-wise 15-year-post-trial survival, we estimated life-year-gained between an intervention and a control group using data from the Cardiovascular Outcomes for People Using Anticoagulation Strategies Study (COMPASS). Projections considered either in-trial events or post-trial medications. They were compared based on three factors: (i) choice of probability of death, (ii) lengths of cycle, and (iii) usage of half-a-cycle age correction. Three-way analysis of variance and post-hoc Tukey's Honest Significant Difference test compared means among factors.ResultsWhen both in-trial events and post-trial study medications were considered, monthly, quarterly, or semiannually were not different from one other in projected life-year-gained. However, the annual one was different from the others: mean and 95 percent confidence interval 252.2 (190.5–313.9) days monthly, 251.8 (192.0–311.6) quarterly, 249.1 (189.7–308.5) semiannually, and 240.8 (178.5–303.1) annually. The other two factors also impacted life-year-gained: background probability (269.1 [260.3–277.9] days projected with REACH-based-probabilities, 227.7 [212.6–242.8] with a USA life table); half-a-cycle age correction (245.5 [199.0–292] with correction and 251.4 [209.1–293.7] without correction). When not considering post-trial medications, only the choice of probability of death appeared to impact life-year-gained.ConclusionFor a large trial or cohort, to optimally project life-year-gained, one should consider using (i) annual projections, (ii) life table probabilities, (iii) in-trial events, and (iv) post-trial medication use.

The international literature and public policy actions in education have positioned the school environment as a significant component of academic performance and the well-being of the entire educat...

Background The association of nuts with cardiovascular disease and deaths has been investigated mostly in Europe, the USA, and East Asia, with few data available from other regions of the world or from low- and middle-income countries. Objective To assess the association of nuts with mortality and cardiovascular disease (CVD). Methods The Prospective Urban Rural Epidemiology study is a large multinational prospective cohort study of adults aged 35–70 y from 16 low-, middle-, and high-income countries on 5 continents. Nut intake (tree nuts and ground nuts) was measured at the baseline visit, using country-specific validated FFQs. The primary outcome was a composite of mortality or major cardiovascular event [nonfatal myocardial infarction (MI), stroke, or heart failure]. Results We followed 124,329 participants (age = 50.7 y, SD = 10.2; 41.5% male) for a median of 9.5 y. We recorded 10,928 composite events [deaths (n = 8,662) or major cardiovascular events (n = 5,979)]. Higher nut intake (>120 g per wk compared with

Background Delirium is common after cardiac surgery and is associated with adverse outcomes. Perioperative benzodiazepine use is associated with delirium and is common during cardiac surgery, which may increase the risk of postoperative delirium. We undertook a pilot study to inform the feasibility of a large randomised cluster crossover trial examining whether an institutional policy of restricted benzodiazepine administration during cardiac surgery (compared with liberal administration) would reduce delirium. Methods We conducted a two-centre, pilot, randomised cluster crossover trial with four 4 week crossover periods. Each centre was randomised to a policy of restricted or liberal use, and then alternated between the two policies during the remaining three periods. Our feasibility outcomes were adherence to each policy (goal ≥80%) and outcome assessment (one delirium assessment per day in the ICU in ≥90% of participants). We also evaluated the incidence of intraoperative awareness in one site using serial Brice questionnaires. Results Of 800 patients undergoing cardiac surgery during the trial period, 127/800 (15.9%) had delirium. Of these, 355/389 (91.3%) received benzodiazepines during the liberal benzodiazepine periods and 363/411 (88.3%) did not receive benzodiazepines during the restricted benzodiazepine periods. Amongst the 800 patients, 740 (92.5%) had ≥1 postoperative delirium assessment per day in the ICU. Of 521 patients screened for intraoperative awareness, one patient (0.2%), managed during the restricted benzodiazepine period (but who received benzodiazepine), experienced intraoperative awareness. Conclusions This pilot study demonstrates the feasibility of a large, multicentre, randomised, cluster crossover trial examining whether an institutional policy of restricted vs liberal benzodiazepine use during cardiac surgery will reduce postoperative delirium. Clinical trial registration NCT03053869.

Background Air pollution contains a mixture of different pollutants from multiple sources. However, the interaction of these pollutants with other environmental exposures, as well as their harmful effects on children under five in tropical countries, is not well known. Objective This study aims to characterize the external exposome (ambient and indoor exposures) and its contribution to clinical respiratory and early biological effects in children. Materials and methods A cohort study will be conducted on children under five (n = 500) with a one-year follow-up. Enrolled children will be followed monthly (phone call) and at months 6 and 12 (in person) post-enrolment with upper and lower Acute Respiratory Infections (ARI) examinations, asthma development, asthma control, and genotoxic damage. The asthma diagnosis will be pediatric pulmonologist-based and a standardized protocol will be used. Exposure, effect, and susceptibility biomarkers will be measured on buccal cells samples. For environmental exposures PM2.5 will be sampled, and questionnaires, geographic information, dispersion models and Land Use Regression models for PM2.5 and NO2 will be used. Different statistical methods that include Bayesian and machine learning techniques will be used for the ambient and indoor exposures-and outcomes. This study was approved by the ethics committee at Universidad Pontificia Bolivariana. Expected study outcomes/findings To estimate i) The toxic effect of particulate matter transcending the approach based on pollutant concentration levels; ii) The risk of developing an upper and lower ARI, based on different exposure windows; iii) A baseline of early biological damage in children under five, and describe its progression after a one-year follow-up; and iv) How physical and chemical PM2.5 characteristics influence toxicity and children’s health.

Introduction In epidemiology, generalized linear models are the main statistical methods used to explore associations. However, the use of other methods such as Structural Equation Modelling (SEM) is gradually increasing. Objective The aim of the study was to illustrate the use of SEM in the assessment of salivary cortisol concentration in infants as a biomarker of perinatal exposure to inorganic arsenic. Material and methods This was a cohort study of pregnant women recruited from public health care centres in Arica, Chile, in 2013. Socio-demographic information and urine samples to assess inorganic arsenic were collected during the second trimester of pregnancy. Saliva samples were collected to assess cortisol in infants between 18–24 months of age. Four linear regression models (LRMs) and two SEMs were run to estimate the effect of prenatal exposure to inorganic arsenic on cortisol concentration in infants. Results According to LRMs and SEMs, prenatal exposure to inorganic arsenic and salivary cortisol were not associated. However, the association between maternal cortisol and cortisol in infants was statistically significant in all models; for each increase in standard deviation of the covariate Ln(maternal cortisol), the outcome Ln(cortisol in infant) increased by 0.49 units of variance in both SEMs. Conclusions LRMs and SEMs were useful to assess the effect of prenatal exposure to inorganic arsenic on cortisol in infants. However, SEM allowed the adjustment of estimations by an estimated latent that obtained the information about income, occupation, education and ethnicity in a more comprehensive way than achieved by LRM.

Black women typically lose small amounts of weight in behavioral weight loss interventions, partially due to low engagement in physical activity. Culturally relevant enhancement of the physical activity component may improve weight loss. This study compared the effectiveness of a culturally-relevant, physical activity-enhanced behavioral weight loss intervention to a standard behavioral weight loss intervention in Black women (n = 85) over 6 months. The study was conducted in two cohorts from March 2016 to February 2017 at the University of North Carolina at Chapel Hill. Participants had an average age of 48.30 ± 11.02 years with an average body mass index of 36.46 ± 4.50 kg/m2. Standard and enhanced groups' weight change (-2.83 kg and -2.08 kg, respectively) and change in physical activity (43.93 min/ week and 15.29 min/week, respectively) did not differ between groups. Significantly more standard group participants lost 5% of baseline weight compared to enhanced group participants. This study produced typical weight loss results in Black women. Behavioral weight loss treatment remains moderately effective for Black women. Strategies to increase attendance and self-monitoring, and the inclusion of cultural contexts to weight-related behaviors are needed to improve outcomes.

OBJECTIVE Diabetes is a major risk factor for renal function decline and failure. The availability of multiplex panels of biochemical markers provides the opportunity to identify novel biomarkers that can better predict changes in renal function than routinely available clinical markers. RESEARCH DESIGN AND METHODS The concentration of 239 biochemical markers was measured in stored serum from participants in the biomarker substudy of Outcome Reduction With Initial Glargine Intervention (ORIGIN) trial. Repeated-measures mixed-effects models were used to compute the annual change in eGFR (measured as mL/min/1.73 m2/year) for the 7,482 participants with a recorded baseline and follow-up eGFR. Linear regression models using forward selection were used to identify the independent biomarker determinants of the annual change in eGFR after accounting for baseline HbA1c, baseline eGFR, and routinely measured clinical risk factors. The incidence of the composite renal outcome (i.e., renal replacement therapy, renal death, renal failure, albuminuria progression, doubling of serum creatinine) and death within each fourth of change in eGFR predicted from these models was also estimated. RESULTS During 6.2 years of median follow-up, the median annual change in eGFR was −0.18 mL/min/1.73 m2/year. Fifteen biomarkers independently predicted eGFR decline after accounting for cardiovascular risk factors, as did 12 of these plus 1 additional biomarker after accounting for renal risk factors. Every 0.1 mL/min/1.73 m2 predicted annual fall in eGFR predicted a 13% (95% CI 12, 14%) higher mortality. CONCLUSIONS Adding up to 16 biomarkers to routinely measured clinical risk factors improves the prediction of annual change in eGFR in people with dysglycemia.

Background Atrial fibrillation (AF) is often detected for the first time in patients hospitalized for medical illness or non-cardiovascular surgery. AF occurring transiently with stress (AFOTS) describes this manifestation of AF, which may either be the result of a non-cardiac stressor, or existing paroxysmal AF that was not previously detected. Current estimates of AFOTS incidence are imprecise: ranging from 1 to 44%, owing to the marked heterogeneity in patient populations, identification and methods used to detect AFOTS. Methods The prospective, two-centre epidemiological AFOTS Incidence study will enroll 250 consecutive participants without a history of AF but with at increased risk of AF (Age ≥ 65 or >50 with one risk factor for AF) admitted to intensive care units (ICUs) for medical illness or non-cardiac surgery. Upon admission, participants will wear an ECG patch monitor that will remain in place for 14 days, or until discharge from hospital. Patients' consent to participation is deferred for up to 72 h after admission. The primary endpoint is the incidence of AF lasting ≥30 s. The study is powered to detect an AF incidence of 17% ± 5%. Results We conducted a vanguard feasibility study, and 55 participants have completed participation. The median duration of monitoring was seven days. AF was detected by the clinical team in 8 participants (14%; 95% Confidence Interval 7–26%). Conclusions The AFOTS Incidence study will employ a systematic and highly sensitive protocol for detecting AFOTS in medical illness and non-cardiac surgery ICU patients. This study is feasible and will provide a reliable estimate of the true incidence of AFOTS in this population.