Compared with prescription of pioglitazone, prescription of rosiglitazone was associated with an increased risk of stroke, heart failure, and all-cause mortality and an increased risk of the composite of AMI, stroke, heart failure, or all-cause mortality in patients 65 years or older.

Context Although tumor necrosis factor alpha (TNF-α) antagonists are increasingly used in place of non-biologic comparator medications, their safety profile remains incomplete. Objectives To determine whether initiation of TNF-α antagonists compared with non-biologic comparators is associated with an increased risk of serious infections. Design, setting and patients Within a US multi-institutional collaboration, we assembled retrospective cohorts (1998–2007) of patients with rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis, psoriatic arthritis or ankylosing spondylitis (PsO-PsA-AS) combining data from Kaiser Permanente Northern California, New Jersey and Pennsylvania Pharmaceutical Assistance programs, Tennessee Medicaid and National Medicaid/Medicare. TNF-α antagonists and non-biologic regimens were compared in disease specific-propensity score (PS) matched cohorts using Cox regression models with non-biologics as reference. Baseline glucocorticoid use was evaluated as a separate covariate. Main outcome measure Infections requiring hospitalization (serious infections) during the first 12 months after initiation of TNF-α antagonists or non-biologic regimens. Results Study cohorts included 10484 RA, 2323 IBD and 3213 PsO-PsA-AS PS-matched pairs using TNF-α antagonists and comparator medications. Overall, we identified 1171 serious infections, most of which (53%) were pneumonia and skin and soft tissue infections. Among RA patients, serious infection hospitalization rates were 8.16 (TNF-α antagonists) and 7.78 (comparator regimens) per 100 person-years (adjusted hazard ratio [aHR]: 1.07 (95% CI: 0.93–1.23)). Among IBD patients, rates were 10.91 and 9.60 per 100 person-years (aHR: 1.13, (0.85–1.50)). Among PsO-PsA-AS patients, rates were 5.41 and 5.19 per 100 person-years (aHR: 1.10, (0.80–1.53)). Among RA patients, infliximab was associated with a significant increase in serious infections compared with etanercept and adalimumab (aHRs: 1.27 (1.08–1.49) and 1.23 (1.02–1.48)). Baseline glucocorticoid use was associated with a dose-dependent increase in infections. Conclusions Among patients with autoimmune diseases, compared to treatment with non-biologic regimens, initiation of TNF-α antagonists was not associated with an increased risk of hospitalizations for serious infections.

The association of drinking water arsenic and mortality outcome was investigated in a cohort of residents from Millard County, Utah. Median drinking water arsenic concentrations for selected study towns ranged from 14 to 166 ppb and were from public and private samples collected and analyzed under the auspices of the State of Utah Department of Environmental Quality, Division of Drinking Water. Cohort members were assembled using historical documents of the Church of Jesus Christ of Latter-day Saints. Standard mortality ratios (SMRs) were calculated. Using residence history and median drinking water arsenic concentration, a matrix for cumulative arsenic exposure was created. Without regard to specific exposure levels, statistically significant findings include increased mortality from hypertensive heart disease [SMR = 2.20; 95% confidence interval (CI), 1.36-3.36], nephritis and nephrosis (SMR = 1.72; CI, 1.13-2.50), and prostate cancer (SMR = 1.45; CI, 1.07-1. 91) among cohort males. Among cohort females, statistically significant increased mortality was found for hypertensive heart disease (SMR = 1.73; CI, 1.11-2.58) and for the category of all other heart disease, which includes pulmonary heart disease, pericarditis, and other diseases of the pericardium (SMR = 1.43; CI, 1.11-1.80). SMR analysis by low, medium, and high arsenic exposure groups hinted at a dose relationship for prostate cancer. Although the SMRs by exposure category were elevated for hypertensive heart disease for both males and females, the increases were not sequential from low to high groups. Because the relationship between health effects and exposure to drinking water arsenic is not well established in U.S. populations, further evaluation of effects in low-exposure populations is warranted.

In the last 5 years, regulatory agencies and drug monitoring centres have been developing computerised data-mining methods to better identify reporting relationships in spontaneous reporting databases that could signal possible adverse drug reactions. At present, there are no guidelines or standards for the use of these methods in routine pharmaco-vigilance. In 2003, a group of statisticians, pharmaco-epidemiologists and pharmaco-vigilance professionals from the pharmaceutical industry and the US FDA formed the Pharmaceutical Research and Manufacturers of America-FDA Collaborative Working Group on Safety Evaluation Tools to review best practices for the use of these methods.In this paper, we provide an overview of: (i) the statistical and operational attributes of several currently used methods and their strengths and limitations; (ii) information about the characteristics of various postmarketing safety databases with which these tools can be deployed; (iii) analytical considerations for using safety data-mining methods and interpreting the results; and (iv) points to consider in integration of safety data mining with traditional pharmaco-vigilance methods. Perspectives from both the FDA and the industry are provided. Data mining is a potentially useful adjunct to traditional pharmaco-vigilance methods. The results of data mining should be viewed as hypothesis generating and should be evaluated in the context of other relevant data. The availability of a publicly accessible global safety database, which is updated on a frequent basis, would further enhance detection and communication about safety issues.