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Background: We illustrate a method for stratum assignment in small cohort studies that avoids modeling assumptions. Methods: Off-the-shelf software (rgenoud) made stratum assignments to minimize a loss function built on within-stratum and populationadjusted Euclidean distances. Results: In 100 trials using simulated data of 300 records with a binary treatment and four dissimilar covariate treatment predictors, minimizing a loss based on Euclidean distance reduced covariate imbalance by a median of 99%. Stratification by propensity score and weighting records by the inverse of their probability of treatment reduced imbalance by 76%-89% and 83%-94%, respectively. Loss minimization applied to a cohort of 361 children undergoing immunotherapy achieved nearly complete elimination of covariate differences for important treatment predictors. Conclusion: With the availability of semiparametric stratumassignment algorithms, analysts can tailor loss functions to meet design goals. Here, a loss function that emphasized covariate balance performed well under limited testing. [ABSTRACT FROM AUTHOR]

Purpose: For observational cohort studies that employ matching by propensity scores (PS), preliminary stratification by consequential predictors of outcome better emulates stratified randomization and potentially reduces variance and bias through relaxed dependence on modeling assumptions. We assessed the impact of pre‐stratification in two real‐life examples. For both, prior evidence from placebo‐controlled randomized clinical trials (RCTs) suggested small or no risk reduction, but observational analysis suggested protection, presumably the result of confounding bias. Study Design and Setting: The study populations consisted of Medicare beneficiaries (2014‐18) with type 2 diabetes initiating either (i) empagliflozin versus dipeptidyl peptidase‐4 inhibitors (DPP‐4i) or (ii) empagliflozin versus glucagon‐like peptide‐1 receptor agonists (GLP‐1RA). The outcome was myocardial infarction or stroke. We estimated hazard ratios (HR) and rate differences (RD) after controlling for 143 pre‐exposure covariates via 1:1 PS matching after (1) PS estimation in the total cohort (total‐cohort PS‐matching) and (2) PS estimation separately by baseline cardiovascular disease (stratified PS matching). Results: Stratified PS matching resulted in HRs that exceeded those from total‐cohort PS‐matching by 13% and 9%, respectively, for the comparisons of empagliflozin to DPP‐4i and GLP‐1RA. Against both comparators, HRs and RDs after stratified PS matching were closer to the null, with slightly higher variances (2%–3%) than those after total‐cohort PS matching. Conclusion: Stratified PS matching produced effect estimates closer to the expected trial findings than total‐cohort PS matching. The price paid in increased variance was minimal. [ABSTRACT FROM AUTHOR]

Purpose: Azithromycin is a common first‐line antibiotic for respiratory infection; however, there is conflicting evidence regarding risk of cardiovascular death. We assessed cardiovascular and noncardiovascular mortality associated with azithromycin versus amoxicillin–clavulanate among US Veterans treated for nonear–nose–throat respiratory infection ("respiratory") or ear–nose–throat infection indication. Methods: Electronic health record data from the US Veterans Health Administration database were used to identify Veterans (30–74 years) with outpatient dispensings of oral azithromycin versus amoxicillin–clavulanate for respiratory or ear–nose–throat infection (January 01, 2000–December 31, 2014). Outcomes assessed were risk of cardiovascular death and noncardiovascular death within 1–5 and 6–10 days postdispensing. Inverse probability of treatment‐weighted proportional hazards models and binomial regression models were used to estimate hazard ratios (HRs) and compute risk differences (RD) per million courses of therapy. Cardiac death (subset of cardiovascular death) was assessed in sensitivity analyses. Results: There were 629 345 azithromycin and 168 429 amoxicillin–clavulanate dispensings for respiratory indications, 143 783 azithromycin, and 203 142 amoxicillin–clavulanate dispensings for ear–nose–throat indications. For respiratory indications, azithromycin was not associated with a significantly different risk of cardiovascular death versus amoxicillin–clavulanate within 1–5 days postdispensing (HR [95% confidence interval (CI)]: 1.12 [0.63, 2.00]; RD [95% CI]: 11 [−43, 64] deaths/million courses of therapy). No elevated risk for azithromycin was found for ear–nose–throat indications. Pooled results for both indications via meta‐analysis showed no association between antibiotics and cardiovascular mortality. There was no significant difference in risk of noncardiovascular or cardiac death between antibiotics postdispensing. Conclusion: Azithromycin was not associated with elevated risk of cardiovascular or noncardiovascular death versus amoxicillin–clavulanate among US Veterans. [ABSTRACT FROM AUTHOR]

A study to examine whether the use of Aprotinin during coronary-artery bypass grafting surgery can lead to in-hospital death is conducted. Results conclude that those patients that were administered Aprotinin on the day of surgery had a greater risk of mortality as compared to those who were not given Aprotinin.

A Canadian study shows that reference pricing of ACE inhibitors will not necessarily make patients stop using ACE inhibitors. Instead, they simply switch to a cheaper ACE inhibitor. Reference pricing means that a standard reimbursement fee is set for a class of drugs. If the drug is equal to or less than the fee, insurance will cover the entire fee. If it is more, the patient must pay the difference.