Coffee intake protects against symptomatic gallstone disease in the general population: a Mendelian randomization study.

BACKGROUND AND OBJECTIVES: Coffee intake is associated with low risk of symptomatic gallstone disease (GSD). We tested the hypothesis that high coffee intake causally protects against symptomatic GSD using a Mendelian randomization design. METHODS: First, we tested whether high coffee intake was associated with low risk of GSD in 104 493 individuals from the general population. Mean follow-up was 8 years (range: <1-13 years). Secondly, we tested whether two genetic variants near CYP1A1/A2 (rs2472297) and AHR (rs4410790), combined as an allele score, were associated with higher coffee intake measured as a continuous variable. Thirdly, we tested whether the allele score was associated with lower risk of GSD in 114 220 individuals including 7294 gallstone events. Mean follow-up was 38 years (range: <1-40 years). RESULTS: In observational analysis, those with coffee intake of >6 cups daily had 23% lower risk of GSD compared to individuals without coffee intake [hazard ratio (HR) = 0.77 (95% confidence interval: 0.61-0.94)]. In genetic analysis, there was a stepwise higher coffee intake of up to 41% (caffeine per day) in individuals with 4 (highest) versus 0 (lowest) coffee intake alleles (P for trend = 3 x 10-178 ) and a corresponding stepwise lower risk of GSD up to 19%[HR = 0.81 (0.69-0.96)]. The estimated observational odds ratio for GSD for a one cup per day higher coffee intake was 0.97 (0.96-0.98), equal to 3% lower risk. The corresponding genetic odds ratio was 0.89 (0.83-0.95), equal to 11% lower risk. CONCLUSION: High coffee intake is associated observationally with low risk of GSD, and with genetic evidence to support a causal relationship.

Red blood cell transfusion in surgery: an observational study of the trends in the USA from 2011 to 2016.

Guidelines recommend restrictive red blood cell transfusion strategies. We conducted an observational study to examine whether the rate of peri-operative red blood cell transfusion in the USA had declined during the period from 01 January 2011 to 31 December 2016. We included 4,273,168 patients from all surgical subspecialties. We examined parallel trends in rates of the following: pre-operative transfusion; prevalence of bleeding disorders and coagulopathy; and minimally invasive procedures. To account for changes in population and procedure characteristics, we performed multivariable logistic regression to assess whether the risk of receiving a transfusion had declined over the study period. Clinical outcomes included peri-operative myocardial infarction, stroke and all-cause mortality at 30 days. Peri-operative red blood cell transfusion rates declined from 37,040/441,255 (8.4%) in 2011 to 46,845/1,000,195 (4.6%) in 2016 (p < 0.001) across all subspecialties. Compared with 2011, the corresponding adjusted OR (95%CI) for red blood cell transfusion decreased gradually from 0.88 (0.86-0.90) in 2012 to 0.51 (0.50-0.51) in 2016 (p < 0.001). Pre-operative red blood cell transfusion rates and the prevalence of bleeding disorders decreased, whereas haematocrit levels and the proportion of minimally invasive procedures increased. Compared with 2011, the adjusted hazard ratios (95%CI) in 2012 and 2016 were 0.96 (0.90-1.02) and 1.05 (0.99-1.11) for myocardial infarction, 0.91 (0.83-0.99) and 0.99 (0.92-1.07) for stroke and 0.98 (0.94-1.02) and 0.99 (0.96-1.03) for all-cause mortality. Use of peri-operative red blood cell transfusion declined from 2011 to 2016. This was not associated with an increase in adverse clinical outcomes.