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International audience; Background: Renin-angiotensin aldosterone system inhibitors (RAASi) are commonly used among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection (COVID-19). We evaluated whether continuation versus discontinuation of RAASi were associated with short term clinical or biochemical outcomes. Methods: The RAAS-COVID-19 trial was a randomized, open label study in adult patients previously treated with RAASi who are hospitalized with COVID-19 (NCT04508985). Participants were randomized 1:1 to discontinue or continue RAASi. The primary outcome was a global rank score calculated from baseline to day 7 (or discharge) incorporating clinical events and biomarker changes. Global rank scores were compared between groups using the Wilcoxon test statistic and the negative binomial test (using incident rate ratio [IRR]) and the intention-totreat principle. Results: Overall, 46 participants were enrolled; 21 participants were randomized to discontinue RAASi and 25 to continue. Patients' mean age was 71.5 years and 43.5% were female. Discontinuation of RAASi, versus continuation, resulted in a non-statistically different mean global rank score (discontinuation 6 [standard deviation [SD] 6.3] vs continuation 3.8 (SD 2.5); p= 0.60). The negative binomial analysis identified that discontinuation increased the risk of adverse outcomes (IRR 1.67 [95% CI 1.06 to 2.62]; p=0.027); RAASi discontinuation increased brain natriuretic peptide (BNP) levels (% change from baseline: +16.7% vs.-27.5%; p= 0.024) and the incidence of acute heart failure (33% vs. 4.2%, p=0.016). Conclusion: RAASi continuation in participants hospitalized with COVID-19 appears safe; discontinuation increased BNP levels and may increase risk of acute heart failure; where possible, RAASi should be continued.

The Thrombolysis in Myocardial Infarction Risk Score for Heart Failure (HF) in Diabetes (TRS-HFThe TRS-HFIn total, HF hospitalization occurred in 193 (3.6%) patients. Based on the TRS-HFThe TRS-HF

No abstract available.

Background The Thrombolysis in Myocardial Infarction Risk Score for Heart Failure in Diabetes (TRS-HFDM ) risk stratifies patients with type 2 diabetes mellitus (T2DM) and high cardiovascular risk for heart failure (HF) hospitalization. The utility of TRS-HFDM in risk stratification for HF outcomes requires further validation. Materials and methods We used data from the control group of The Action to Control Cardiovascular Risk in Diabetes Study Group (ACCORD) trial (n=5123; mean follow up 4.8 years). The TRS-HFDM includes: prior HF (2 points), atrial fibrillation (1 point), coronary artery disease (1 point), estimated glomerular filtration rate 300 mg/g; 2 point and 30-300 mg/g; 1 point). We evaluated discrimination (Harrell C index) and calibration (Nam-D Agostino calibration statistic) of TRS-HFDM for time to HF hospitalization or death due to HF. Results The mean age of participants was 62.8±6.6 years, and 38% were female. The prevalence of TRS-HFDM for 0, 1, 2, 3 and 4+ were 42.1%, 34.9%, 14.6%, 6.0%, and 2.5% respectively. Increasing TRS-HFDM corresponded to an increasing HF risk: 1.3/1000 person years (PY) (TRS-HFDM : 0) to 64.7/1000 PY (TRS-HFDM : 4+). TRS-HFDM demonstrated robust discrimination for HF outcomes (C-index 0.78). Furthermore, the score was well calibrated for HF outcomes (calibration statistic p=0.13). Similar results were seen in participants without baseline HF (C-index 0.75). Conclusion The TRS-HFDM discriminates for HF specific risk among people with T2DM. Using the TRS-HFDM to identify those who maximally benefit from therapies that reduce HF risk warrants evaluation. This article is protected by copyright. All rights reserved.

Objectives: In this study, we hypothesized that replacing conventional milk, which contains A1 and A2 β-casein proteins, with milk that contains only A2 β-casein in the diet of dairy or milk-intolerant preschoolers (age 5 to 6 years) would result in reduced gastrointestinal symptoms associated with milk intolerance, and that this would correspond with cognitive improvements. Methods: This randomized, double-blind, crossover study aimed to compare the effects of 5 days’ consumption of conventional milk versus milk containing only A2 β-casein on gastrointestinal symptoms, as assessed via visual analog scales, average stool frequency and consistency, and serum inflammatory and immune biomarkers in healthy preschoolers with mild-to-moderate milk intolerance. The study also aimed to compare changes in the cognitive behavior of preschoolers, based on Subtle Cognitive Impairment Test scores. Results: Subjects who consumed milk containing only A2 β-casein had significantly less severe gastrointestinal symptoms as measured by visual analog scales, reduced stool frequency, and improvements in stool consistency, compared with subjects consuming conventional milk. There were significant increases from baseline in serum interleukin-4, immunoglobulins G, E, and G1, and beta-casomorphin-7 coupled to lower glutathione levels, in subjects consuming conventional milk compared with milk containing only A2 β-casein. Subtle Cognitive Impairment Test analysis showed significant improvements in test accuracy after consumption of milk containing only A2 β-casein. There were no severe adverse events related to consumption of either milk product. Conclusions: Replacing conventional milk with milk containing only A2 β-casein reduced gastrointestinal symptoms associated with milk intolerance in Chinese preschool children, with corresponding improvements in aspects of cognitive performance.

Purpose We assessed the validity of postsurgery venous thromboembolism (VTE) diagnoses identified from administrative databases and compared Bayesian and multiple imputation (MI) approaches in correcting for outcome misclassification in logistic regression models. Methods Sensitivity and specificity of postsurgery VTE among patients undergoing total hip or knee replacement (THR/TKR) were assessed against chart review in six Montreal hospitals in 2009 to 2010. Administrative data on all THR/TKR Quebec patients in 2009 to 2010 were obtained. The performance of Bayesian external, Bayesian internal, and MI approaches to correct the odds ratio (OR) of postsurgery VTE in tertiary versus community hospitals was assessed using simulations. Bayesian external approach used prior information from external sources, while Bayesian internal and MI approaches used chart review. Results In total, 17 319 patients were included, 2136 in participating hospitals, among whom 75 had VTE in administrative data versus 81 in chart review. VTE sensitivity was 0.59 (95% confidence interval, 0.48-0.69) and specificity was 0.99 (0.98-0.99), overall. The adjusted OR of VTE in tertiary versus community hospitals was 1.35 (1.12-1.64) using administrative data, 1.45 (0.97-2.19) when MI was used for misclassification correction, and 1.53 (0.83-2.87) and 1.57 (0.39-5.24) when Bayesian internal and external approaches were used, respectively. In simulations, all three approaches reduced the OR bias and had appropriate coverage for both nondifferential and differential misclassification. Conclusion VTE identified from administrative data had low sensitivity and high specificity. The Bayesian external approach was useful to reduce outcome misclassification bias in logistic regression; however, it required accurate specification of the misclassification properties and should be used with caution.

Outcome misclassification may occur in observational studies using administrative databases. We evaluated a two-step multiple imputation approach based on complementary internal validation data obtained from two subsamples of study participants to reduce bias in hazard ratio (HR) estimates in Cox regressions.We illustrated this approach using data from a surveyed sample of 6247 individuals in a study of statin-diabetes association in Quebec. We corrected diabetes status and onset assessed from health administrative data against self-reported diabetes and/or elevated fasting blood glucose (FBG) assessed in subsamples. The association between statin use and new onset diabetes was evaluated using administrative data and the corrected data. By simulation, we assessed the performance of this method varying the true HR, sensitivity, specificity, and the size of validation subsamples.The adjusted HR of new onset diabetes among statin users versus non-users was 1.61 (95% confidence interval: 1.09-2.38) using administrative data only, 1.49 (0.95-2.34) when diabetes status and onset were corrected based on self-report and undiagnosed diabetes (FBG ≥ 7 mmol/L), and 1.36 (0.92-2.01) when corrected for self-report and undiagnosed diabetes/impaired FBG (≥ 6 mmol/L). In simulations, the multiple imputation approach yielded less biased HR estimates and appropriate coverage for both non-differential and differential misclassification. Large variations in the corrected HR estimates were observed using validation subsamples with low participation proportion. The bias correction was sometimes outweighed by the uncertainty introduced by the unknown time of event occurrence.Multiple imputation is useful to correct for outcome misclassification in time-to-event analyses if complementary validation data are available from subsamples. Copyright © 2017 John WileySons, Ltd.

International audience; Background: Dietary fibers have been associated with a reduction in appetite and energy intake. Although a few studies suggest that nonviscous fibers can exert such effects, likely through colonic fermentation, limited data are available. Objective: The objective of this study was to determine whether alpha-galacto-oligosaccharides (alpha-GOSs), fermentable soluble fibers extracted from legumes, could reduce appetite, food intake, and inflammation in overweight subjects. Methods: In 2 single-center, double-blind, randomized, placebo-controlled trials, 88 overweight adults [50% men and 50% women; 18-60 y old; body mass index (in kg/m(2)): 25-28] were supplemented for 14 d with tea that contained alpha-GOSs with different alpha-GOS dosages (6, 12, or 18 g alpha-GOSs/d), formulas (12 g alpha-GOSs/d with > 80% of molecules with a degree of polymerization of 2, 3, or 4), or a control substance (glucose syrup). Appetite scores (5 appetite dimensions were assessed on visual analog scales during a preload test meal), food intake (test meal and 24-h food recall), and inflammatory markers [plasma lipopolysaccharide (LPS) and C-reactive protein (CRP)] were evaluated at day 0 (baseline) and day 15. Results: Changes in appetite scores from day 0 to day 15 were significantly higher after alpha-GOS intake, with areas under the curve for the satiety score of + 121 +/- 108, +218 +/- 218, and +306 +/- 205 score . min for 6, 12, and 18 g alpha-GOSs/d, respectively, and -5 +/- 64 score . min for the control group. We observed dose-dependent effects that did not vary by alpha-GOS composition. The administration of 6, 12, or 18 g alpha-GOSs/d significantly and dose-dependently increased the change in energy intake from day 0 to day 15 during a test meal (-13 +/- 19, -26 +/- 22, and -32 +/- 22 kcal, respectively; +6 +/- 21 kcal for the control group). Reductions in energy intake during lunch and dinner were also higher in the alpha-GOS groups in the dose-effect study. At day 15, LPS was dose-dependently reduced without an association with alpha-GOS composition (0.16 +/- 0.02, 0.12 +/- 0.08, and 0.08 +/- 0.05 EU/mL for 6, 12, and 18 g alpha-GOSs/d, respectively, and 0.06 +/- 0.04 EU/mL for the control group) and CRP was significantly lower in the alpha-GOS groups than in the control group in the formulation-effect study. Conclusions: Consumption of alpha-GOSs for 14 d dose-dependently reduced appetite, food intake, and inflammation in overweight adults with no impact of alpha-GOS composition. Consequently, alpha-GOSs appear to promote long-term weight loss and mitigate metabolic disorders.

Probiotics are known to reduce antibiotic associated diarrhea (AAD) and Clostridium difficile associated diarrhea (CDAD) risk in a strain-specific manner. The aim of this study was to determine the dose-response effect of a four strain probiotic combination (HOWARU(®) Restore) on the incidence of AAD and CDAD and severity of gastrointestinal symptoms in adult in-patients requiring antibiotic therapy. Patients (n=503) were randomized among three study groups: HOWARU(®) Restore probiotic 1.70×10(10) CFU (high-dose, n=168), HOWARU(®) Restore probiotic 4.17×10(9) CFU (low-dose, n=168), or placebo (n=167). Subjects were stratified by gender, age, and duration of antibiotic treatment. Study products were administered daily up to 7 days after the final antibiotic dose. The primary endpoint of the study was the incidence of AAD. Secondary endpoints included incidence of CDAD, diarrhea duration, stools per day, bloody stools, fever, abdominal cramping, and bloating. A significant dose-response effect on AAD was observed with incidences of 12.5, 19.6, and 24.6% with high-dose, low-dose, and placebo, respectively (p=0.02). CDAD was the same in both probiotic groups (1.8%) but different from the placebo group (4.8%; p=0.04). Incidences of fever, abdominal pain, and bloating were lower with increasing probiotic dose. The number of daily liquid stools and average duration of diarrhea decreased with higher probiotic dosage. The tested four strain probiotic combination appears to lower the risk of AAD, CDAD, and gastrointestinal symptoms in a dose-dependent manner in adult in-patients.