The magnitude of the suspected increase in risk of acute interstitial nephritis among proton pump inhibitor users is uncertain. Here, we conducted a nested case-control study using routinely collected national health and drug dispensing data in New Zealand to estimate the relative and absolute risks of acute interstitial nephritis resulting in hospitalization or death in users of proton pump inhibitors. The cohort included 572,661 patients without a history of interstitial nephritis or other renal diseases who started a new episode of proton pump inhibitor use between 2005 and 2009. Cases had a first diagnosis after cohort entry of acute interstitial nephritis confirmed by hospital discharge letter or death record, and renal histology (definite, 46 patients), or discharge letter or death record only (probable, 26 patients). Ten controls, matched by birth year and sex, were randomly selected for each case. In the case-control analysis based on definite cases and their controls, the unadjusted matched odds ratio (95% confidence interval) for current versus past use of proton pump inhibitors was 5.16 (2.21–12.05). The estimate was similar when all cases (definite and probable) and their corresponding controls were analyzed, and when potential confounders were added to the models. The crude incidence rates and confidence intervals per 100,000 person-years were 11.98 (9.11–15.47) and 1.68 (0.91–2.86) for current and past use, respectively. Thus, current use of a proton pump inhibitor was associated with a significantly increased risk of acute interstitial nephritis, relative to past use.

These findings contribute to emerging evidence that the combined oral contraceptive containing drospirenone carries a higher risk of venous thromboembolism than do formulations containing levonorgestrel.

Our results for conventional antipsychotics are consistent with previous studies of non-fatal venous thromboembolism. The finding for antidepressants needs to be replicated in other studies.

FRS, for the Million Women Study CollaboratorsBackground-Obesity and surgery are known risk factors for venous thromboembolism (VTE), but there is limited information about the independent effects of obesity on the incidence of postoperative VTE. We linked questionnaire data from the Million Women Study with hospital admission and death records to examine the risk of VTE in relation to body mass index (BMI) both in the absence of surgery and in the first 12 weeks following an operation. Methods and Results-Overall, 1 170 495 women (mean age, 56.1 years) recruited in 1996 to 2001 through the National Health Service Breast Screening Programme in England and Scotland were followed for an average of 6 years, during which time 6438 were admitted to hospital or died of VTE. The adjusted relative risks of VTE increased progressively with increasing BMI and women with a BMI Ն35 kg/m 2 were 3-4 times as likely to develop VTE as those with a BMI 22.5 to 24.9 (relative risk 3.45 [95% CI 3.09 -3.86]). Overweight and obese women were more likely than lean women to be admitted for surgery and also to develop postoperative VTE. During a 12-week period without surgery, the incidence rates of VTE per 1000 women with a BMI Ͻ25 and Ն25 were 0.10 (0.09 -0.10) and 0.19 (0.18 -0.20); the corresponding rates in the 12 weeks following day and inpatient surgery were, respectively, about 4 and 40 times higher. Conclusions-VTE risk increases with increasing BMI and the associated excess risk is much greater after surgery than without surgery. (Circulation. 2012;125:1897-1904.)

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