A burden of proof study on alcohol consumption and ischemic heart disease.

Cohort and case-control data have suggested an association between low to moderate alcohol consumption and decreased risk of ischemic heart disease (IHD), yet results from Mendelian randomization (MR) studies designed to reduce bias have shown either no or a harmful association. Here we conducted an updated systematic review and re-evaluated existing cohort, case-control, and MR data using the burden of proof meta-analytical framework. Cohort and case-control data show low to moderate alcohol consumption is associated with decreased IHD risk - specifically, intake is inversely related to IHD and myocardial infarction morbidity in both sexes and IHD mortality in males - while pooled MR data show no association, confirming that self-reported versus genetically predicted alcohol use data yield conflicting findings about the alcohol-IHD relationship. Our results highlight the need to advance MR methodologies and emulate randomized trials using large observational databases to obtain more definitive answers to this critical public health question.

Estimating health spending associated with chronic multimorbidity in 2018: An observational study among adults in the United States.

BACKGROUND: The rise in health spending in the United States and the prevalence of multimorbidity-having more than one chronic condition-are interlinked but not well understood. Multimorbidity is believed to have an impact on an individual's health spending, but how having one specific additional condition impacts spending is not well established. Moreover, most studies estimating spending for single diseases rarely adjust for multimorbidity. Having more accurate estimates of spending associated with each disease and different combinations could aid policymakers in designing prevention policies to more effectively reduce national health spending. This study explores the relationship between multimorbidity and spending from two distinct perspectives: (1) quantifying spending on different disease combinations; and (2) assessing how spending on a single diseases changes when we consider the contribution of multimorbidity (i.e., additional/reduced spending that could be attributed in the presence of other chronic conditions). METHODS AND FINDINGS: We used data on private claims from Truven Health MarketScan Research Database, with 16,288,894 unique enrollees ages 18 to 64 from the US, and their annual inpatient and outpatient diagnoses and spending from 2018. We selected conditions that have an average duration of greater than one year among all Global Burden of Disease causes. We used penalized linear regression with stochastic gradient descent approach to assess relationship between spending and multimorbidity, including all possible disease combinations with two or three different conditions (dyads and triads) and for each condition after multimorbidity adjustment. We decomposed the change in multimorbidity-adjusted spending by the type of combination (single, dyads, and triads) and multimorbidity disease category. We defined 63 chronic conditions and observed that 56.2% of the study population had at least two chronic conditions. Approximately 60.1% of disease combinations had super-additive spending (e.g., spending for the combination was significantly greater than the sum of the individual diseases), 15.7% had additive spending, and 23.6% had sub-additive spending (e.g., spending for the combination was significantly less than the sum of the individual diseases). Relatively frequent disease combinations (higher observed prevalence) with high estimated spending were combinations that included endocrine, metabolic, blood, and immune disorders (EMBI disorders), chronic kidney disease, anemias, and blood cancers. When looking at multimorbidity-adjusted spending for single diseases, the following had the highest spending per treated patient and were among those with high observed prevalence: chronic kidney disease ($14,376 [12,291,16,670]), cirrhosis ($6,465 [6,090,6,930]), ischemic heart disease (IHD)-related heart conditions ($6,029 [5,529,6,529]), and inflammatory bowel disease ($4,697 [4,594,4,813]). Relative to unadjusted single-disease spending estimates, 50 conditions had higher spending after adjusting for multimorbidity, 7 had less than 5% difference, and 6 had lower spending after adjustment. CONCLUSIONS: We consistently found chronic kidney disease and IHD to be associated with high spending per treated case, high observed prevalence, and contributing the most to spending when in combination with other chronic conditions. In the midst of a surging health spending globally, and especially in the US, pinpointing high-prevalence, high-spending conditions and disease combinations, as especially conditions that are associated with larger super-additive spending, could help policymakers, insurers, and providers prioritize and design interventions to improve treatment effectiveness and reduce spending.

The Burden of Proof studies: assessing the evidence of risk.

Exposure to risks throughout life results in a wide variety of outcomes. Objectively judging the relative impact of these risks on personal and population health is fundamental to individual survival and societal prosperity. Existing mechanisms to quantify and rank the magnitude of these myriad effects and the uncertainty in their estimation are largely subjective, leaving room for interpretation that can fuel academic controversy and add to confusion when communicating risk. We present a new suite of meta-analyses-termed the Burden of Proof studies-designed specifically to help evaluate these methodological issues objectively and quantitatively. Through this data-driven approach that complements existing systems, including GRADE and Cochrane Reviews, we aim to aggregate evidence across multiple studies and enable a quantitative comparison of risk-outcome pairs. We introduce the burden of proof risk function (BPRF), which estimates the level of risk closest to the null hypothesis that is consistent with available data. Here we illustrate the BPRF methodology for the evaluation of four exemplar risk-outcome pairs: smoking and lung cancer, systolic blood pressure and ischemic heart disease, vegetable consumption and ischemic heart disease, and unprocessed red meat consumption and ischemic heart disease. The strength of evidence for each relationship is assessed by computing and summarizing the BPRF, and then translating the summary to a simple star rating. The Burden of Proof methodology provides a consistent way to understand, evaluate and summarize evidence of risk across different risk-outcome pairs, and informs risk analysis conducted as part of the Global Burden of Diseases, Injuries, and Risk Factors Study.