Search

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.

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.

BACKGROUND AND AIMS: The Rome Foundation Global Epidemiology Study (RFGES) assessed the prevalence, burden, and associated factors of Disorders of Gut-Brain Interaction (DGBI) in 33 countries around the world. Achieving worldwide sampling necessitated use of two different surveying methods: In-person household interviews (9 countries) and Internet surveys (26 countries). Two countries, China and Turkey, were surveyed with both methods. This paper examines the differences in the survey results with the two methods, as well as likely reasons for those differences. METHODS: The two RFGES survey methods are described in detail, and differences in DGBI findings summarized for household versus Internet surveys globally, and in more detail for China and Turkey. Logistic regression analysis was used to elucidate factors contributing to these differences. RESULTS: Overall, DGBI were only half as prevalent when assessed with household vs Internet surveys. Similar patterns of methodology-related DGBI differences were seen within both China and Turkey, but prevalence differences between the survey methods were dramatically larger in Turkey. No clear reasons for outcome differences by survey method were identified, although greater relative reduction in bowel and anorectal versus upper gastrointestinal disorders when household versus Internet surveying was used suggests an inhibiting influence of social sensitivity. CONCLUSIONS: The findings strongly indicate that besides affecting data quality, manpower needs and data collection time and costs, the choice of survey method is a substantial determinant of symptom reporting and DGBI prevalence outcomes. This has important implications for future DGBI research and epidemiological research more broadly. ispartof: NEUROGASTROENTEROLOGY AND MOTILITY vol:35 issue:6 ispartof: location:England status: accepted

BACKGROUND & AIMS: The Rome criteria are widely accepted for diagnosing disorders of gut-brain interaction, but their global applicability has been debated. This study aimed to evaluate the validity of the Rome IV criteria by factor analysis globally, across geographical regions, by sex, and by age groups. METHODS: Data were collected in 26 countries using the Rome IV questionnaire. Forty-nine ordinal variables were used in exploratory factor analysis (EFA) to identify clusters of inter-correlated variables (factors) within the data set. Confirmatory factor analysis with predefined factors of the disorders of gut-brain interaction was compared with the factors in the EFA. Analyses were performed globally, for each geographical region (North and Latin America, Western and Eastern Europe, Middle East, Asia), sex, and age groups (18-34, 35-49, 50-64, ≥65). RESULTS: A total of 54,127 people were included. The EFA identified 10 factors accounting for 57% of the variance: irritable bowel syndrome, constipation, diarrhea, upper gastrointestinal symptoms, globus, regurgitation/retching, chest pain, nausea/vomiting, and 2 right upper quadrant pain factors. Most factors had close correspondence to a Rome IV criteria diagnosis, but notably, functional dysphagia and heartburn symptoms were often included in the same factor and/or in upper gastrointestinal symptoms. Most factors were consistent across geographical regions, sex, and age groups, and compatible to the global results. All prespecified factors in the confirmatory analysis had a loading ≥0.4, indicating validity of the Rome IV criteria. CONCLUSIONS: The results indicate that the Rome IV criteria for irritable bowel syndrome, functional dyspepsia, functional constipation, globus, and biliary pain are globally valid and represent universal diagnostic entities that are similar across sex and age groups. ispartof: GASTROENTEROLOGY vol:164 issue:7 pages:1211-1222 ispartof: location:United States status: published

Functional constipation; Functional dyspepsia; Functional gastrointestinal disorders Estreñimiento funcional; Dispepsia funcional; Trastornos gastrointestinales funcionales Restrenyiment funcional; Dispèpsia funcional; Trastorns gastrointestinals funcionals Objective Many studies have been published on disorders of the gut–brain interaction (DGBI) in Asia and Western Europe, but no previous study has directly assessed the difference between the two regions. The aim was to compare the prevalence of DGBI in Asia and Western Europe. Methods We used data collected in a population-based Internet survey, the Rome Foundation Global Epidemiology Study, from countries in Western Europe (Belgium, France, Germany, Netherlands, Italy, Spain, Sweden, and the United Kingdom) and Asia (China, Japan, South Korea, and Singapore). We assessed DGBI diagnoses (Rome IV Adult Diagnostic Questionnaire), anxiety/depression (Patient Health Questionnaire-4, PHQ-4), non-GI somatic symptoms (PHQ-12), and access to and personal costs of doctor visits. Results The study included 9487 subjects in Asia and 16,314 in Western Europe. Overall, 38.0% had at least one DGBI; younger age, female sex, and higher scores on PHQ4 and PHQ12 were all associated with DGBI. The prevalence of having at least one DGBI was higher in Western Europe than in Asia (39.1% vs 36.1%, OR 1.14 [95% CI 1.08–1.20]). This difference was also observed for DGBI by anatomical regions, most prominently esophageal DGBI (OR 1.67 [1.48–1.88]). After adjustment, the difference in DGBI prevalence diminished and psychological (PHQ-4) and non-GI somatic symptoms (PHQ-12) had the greatest effect on the odds ratio estimates. Conclusion The prevalence of DGBI is generally higher in Western Europe compared to Asia. A considerable portion of the observed difference in prevalence rates seems to be explained by more severe psychological and non-GI somatic symptoms in Western Europe.

BACKGROUND: There are minimal epidemiological data comparing the burden of disorders of gut brain interaction (DGBI) in the UK with other countries. We compared the prevalence of DGBI in the UK with other countries that participated in the Rome Foundation Global Epidemiology Study (RFGES) online.METHODS: Participants from 26 countries completed the RFGES survey online including the Rome IV diagnostic questionnaire and an in-depth supplemental questionnaire with questions about dietary habits. UK sociodemographic and prevalence data were compared with the other 25 countries pooled together.KEY RESULTS: The proportion of participants with at least one DGBI was lower in UK participants compared with in the other 25 countries (37.6% 95% CI 35.5%-39.7% vs. 41.2%; 95% CI 40.8%-41.6%, p = 0.001). The UK prevalence of 14 of 22 Rome IV DGBI, including irritable bowel syndrome (4.3%) and functional dyspepsia (6.8%), was similar to the other countries. Fecal incontinence, opioid-induced constipation, chronic nausea and vomiting, and cannabinoid hyperemesis (p CONCLUSIONS AND INFERENCES: The prevalence and burden of DGBI is consistently high in the UK and in the rest of the world. Opioid prescribing, cultural, dietary, and lifestyle factors may contribute to differences in the prevalence of some DGBI between the UK and other countries.

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

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)