Immortal time in observational studies can bias the results in favour of the treatment group, but it is not difficult to identify and avoid

Use of interrupted time series methods in drug utilization research has increased, particularly in recent years. Despite methodological recommendations, there is large variation in reporting of analytic methods. Developing methodological and reporting standards for interrupted time series analysis is important to improve its application in drug utilization research, and we provide recommendations for consideration.

These agents may have dual cardiopulmonary protective properties, thereby substantially altering prognosis of patients with COPD. These findings need confirmation in randomized clinical trials.

ARDIOVASCULAR DISEASE IS AN important cause of morbidity and mortality among persons with type 2 diabetes mellitus. 1-3 The thiazolidinediones (TZDs), rosiglitazone and pioglitazone, are oral hypoglycemic agents that have been shown to improve glycemic control and may act to slow the progression of beta cell failure. 4 While improved glycemic control has been linked to better clinical outcomes in diabetes 5-7 and TZDs have been suggested as having potential cardiovascular benefits, 8-11 recent concerns have arisen regarding adverse cardiac effects of these drugs. Use of TZDs is associated with weight gain and edema, 12 and evidence suggests that both rosiglitazone and pioglitazone increase the risk of congestive heart failure (CHF). 8,10,13-19 A recent boxed warning for CHF was added for these agents recommending against the use of TZDs in persons with preexisting CHF. 20 Two meta-analyses have also suggested that rosiglitazone may be associated with an increased risk of acute myocardial infarction (AMI) and death. 18,21 These findings prompted a hearing by a US Food and Drug Administration advisory panel regarding the safety of rosiglitazone; however, the panel voted against removing rosiglitazone from the market because of insufficient data. 22 Most studies to date far have examined adverse cardiovascular outcomes associated with TZDs among clinical trial samples. However, the extent to which these adverse effects apply to real-world populations is less clear. In addition, older persons are traditionally underrepresented in clinical

Conventional nonsteroidal antiinflammatory drugs (NSAIDs) are associated with acute renal failure, but cyclooxygenase-2 inhibitors have not been comparatively evaluated. The authors conducted a nested case-control study to assess the association between exposure to NSAIDs, including cyclooxygenase-2 inhibitors, and hospitalization for acute renal failure. They identified 121,722 new NSAID users older than age 65 years from the administrative health care databases of Quebec, Canada, in 1999-2002. Data for 4,228 cases and 84,540 controls matched on age and follow-up time were analyzed by using conditional logistic regression, adjusted for sex, age, health status, health care utilization measures, exposure to contrast agents, and nephrotoxic medications. The risk of acute renal failure for all NSAIDs combined was highest within 30 days of treatment initiation (adjusted rate ratio (RR) = 2.05, 95% confidence interval (CI): 1.61, 2.60) and receded thereafter. The association with acute renal failure within 30 days of therapy initiation was comparable for rofecoxib (RR = 2.31, 95% CI: 1.73, 3.08), naproxen (RR = 2.42, 95% CI: 1.52, 3.85), and nonselective, non-naproxen NSAIDs (RR = 2.30, 95% CI: 1.60, 3.32) but was borderline lower for celecoxib (RR =1.54, 95% CI: 1.14, 2.09; test for interaction comparing celecoxib with rofecoxib, p = 0.057). There was a significant association for both selective and nonselective NSAIDs with acute renal failure, but confirmatory studies are required.

Background: Cyclooxygenase-2 (COX-2) selective inhibitors have been marketed since 1999 as safer alternatives to nonsteroidal anti-inflammatory drugs (NSAIDs). Debate about their cardiac safety has culminated in the recent withdrawal of rofecoxib. Additional studies are needed to better understand this risk and to determine whether this safety concern represents a class effect. Objective: To assess the influence of various NSAIDs on the risk for a first myocardial infarction (MI).

Our study found higher vertebral fracture incidence among GC initiators, yet a relative decline in fracture incidence with longer exposure. Our findings suggest that fracture incidence among oral GC users may be more common than previously estimated. Optimizing GC-induced osteoporosis management during early exposure to GC is essential to prevent fractures.

Research CMAJ, February 3, 2015, 187(2) E75