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Background: Although randomized controlled trials (RCTs) have suggested a non-significant increased risk of stroke among proton pump inhibitor (PPI) users, the association has not been confirmed. We evaluated the association between regular use of PPIs and incident stroke and identified population groups at high net risk. Methods: This is a prospective analysis of 492,479 participants free of stroke from the UK biobank. Incident stroke was identified through linkage to hospital admission and death registries using the International Classification of Diseases (ICD)-10 codes (I60, I61, I63, and I64). We evaluated hazard ratios (HRs) adjusting for demographic factors, lifestyle habits, prevalent comorbidities, concomitant use of medications, and indications of PPIs. We assessed the risk differences (RDs) according to the baseline Framingham Stroke Risk Score. In the meta-analysis, we searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (from 1988 to 1 June 2020) for randomized trials comparing PPIs with other interventions, placebo, or no treatment on stroke risk. Results were combined using a fix-effect meta-analysis (Mantel-Haenszel method). Results: We documented 5182 incident strokes over 3,935,030 person-years of follow-up. Regular PPI users had a 16% higher risk of stroke than non-users (HR 1.16, 95% CI 1.06 to 1.27). The estimated effect was similar to our meta-analysis of nine RCTs (case/participants 371/26,642; RR 1.22, 95% CI 1.00 to 1.50; quality of evidence: moderate). The absolute effect of PPI use on stroke increased with the baseline Framingham Stroke Risk Score, with an RD of 1.34‰, 3.32‰, 4.83‰, and 6.28‰ over 5 years for the lowest, quartile 2, quartile 3, and the highest quartile, respectively. Conclusions: Regular use of PPIs was associated with an increased risk of stroke, with a higher absolute risk observed in individuals with high baseline stroke risk. Physicians should therefore exercise caution when prescribing PPIs. An assessment of the underlying stoke risk is recommended for individualized use of PPIs. [ABSTRACT FROM AUTHOR]

• Metabolic abnormalities, individually or combined, might increase the risk of IBD. • Individuals with high genetic risk and poor metabolic status have a higher risk of IBD. • Maintaining ideal metabolic status can reduce IBD risk regardless of genetic stratums. Metabolic disorders exhibit strong inflammatory underpinnings and vice versa. This study aimed to investigate the association between metabolic health status, genetic predisposition, and the risk of inflammatory bowel disease (IBD), and to explore the potential benefits of maintaining ideal metabolic status for individuals with a predetermined genetic risk of IBD. This population-based prospective study included 385,820 unrelated European descent participants from the UK Biobank. Using multivariable Cox regression, we assessed the relationship of metabolic phenotypes with risk of IBD and its subtypes. We also developed a polygenic risk score to examine how metabolic health status interacted with genetic risk in relation to IBD risk. During the follow-up period of 4,328,895 person-years, 2,044 newly-diagnosed IBD cases were identified. Higher genetic risk and an increasing number of abnormal metabolic phenotypes were associated with elevated IBD risk (p-trend <0.001). Individuals with high genetic risk and poor metabolic health had a significantly higher risk of IBD (HR=4.56, 95 % CI=3.27–6.36) compared to those with low genetic risk and ideal metabolic health. These results remained consistent for IBD subtypes. Maintaining ideal metabolic status reduced IBD risk within each genetic risk category and jointly decreased subsequent risk by 40 % in high genetic risk individuals. Our study reveals a combined impact of poor metabolic health and genetic risk on IBD incidence. Those with low genetic risk and optimal metabolic health exhibit the lowest IBD risk, offering insights into potential management strategies for individuals at predefined genetic risk. [ABSTRACT FROM AUTHOR]

Summary: Aim: Hospitalized heart failure (HF) patients have a poor prognosis postdischarge. We determined whether renin‐angiotensin system inhibitors (RASI) and β‐blockers dispensed to patients within 60 days post‐HF hospital discharge are associated with improved 1‐year survival. Methods: A retrospective population‐based study was conducted in 4897 seniors, aged 65‐84 years, alive at 60 days postindex HF hospitalization in Western Australia over 2003‐2008. Dispensing of RASI and β‐blocker dispensing was identified from the Pharmaceutical Benefits Scheme claims database linked to hospital admission and death records. Results: At 1‐year posthospital discharge, the all‐cause mortality and all‐cause death or HF rehospitalization rate was 13.5% (n = 663) and 24.4% (n = 1193), respectively. Postdischarge RASI and β‐blocker were dispensed in 77.4% and 53.0% of patients, respectively. Their use was associated with a lower inverse probability treatment weighted (IPTW) HR for 1‐year mortality of 0.70, 95% CI 0.61‐0.81 and 0.79, 95% CI 0.68‐0.92, respectively (both P < 0.0001), with a survival advantage most evident in the subgroup (70.1%) of patients with ischemic HF. In the overall cohort, these therapies were also associated with reduced IPTW HRs for all‐cause death or HF rehospitalization (both P < 0.005) but not for HF rehospitalization exclusively. Use of a β‐blocker was associated with a reduced IPTW HR for HF rehospitalization in the ischemic HF subgroup only. Conclusions: In a cohort of senior patients hospitalized with HF, dispensing of a RASI or β‐blocker within 60 days postdischarge is associated with a 1‐year survival benefit. Early postdischarge support programs after recent HF hospitalization should include measures to optimize adherence to evidence‐based medications. [ABSTRACT FROM AUTHOR]