BACKGROUND & AIMS Nonsteroidal Anti-inflammatory Drugs (NSAIDs), including aspirin, have been implicated in diverticular complications. We examined the influence of aspirin and NSAID use on risk of diverticulitis and diverticular bleeding in a large prospective cohort. METHODS We studied 47,210 US men in the Health Professionals Follow-up Study cohort who were 40–75 years old at baseline, in 1986. We assessed use of aspirin, non-aspirin NSAIDs, and other risk factors biennially. We identified men with diverticulitis or diverticular bleeding based on responses to biennial and supplemental questionnaires. RESULTS We documented 939 cases of diverticulitis and 256 cases of diverticular bleeding during a 22-year period of follow-up. After adjustment for risk factors, men who used aspirin regularly (≥2 times per week) had a multivariable relative risk (RR) of 1.25 (95% confidence interval [CI], 1.05–1.47) for diverticulitis and RR of 1.70 (95% CI, 1.21–2.39) for diverticular bleeding, compared with non-users of aspirin and NSAIDs. Use of aspirin at intermediate doses (2–5.9 standard, 325 mg, tablets per week) and frequency (4–6 days per week) were associated with the highest risk of bleeding (multivariable RR=2.32; 95% CI, 1.34–4.02, and multivariable RR=3.13; 95% CI, 1.82–5.38, respectively). Regular users of non-aspirin NSAIDs also had an increased risk of diverticulitis (multivariable RR=1.72; 95% CI, 1.40–2.11) and diverticular bleeding (multivariable RR=1.74; 95% CI, 1.15–2.64), compared with men who denied use of these medications. CONCLUSIONS Regular use of aspirin or NSAIDs is associated with an increased risk for diverticulitis and diverticular bleeding. Patients at risk of diverticular complications should carefully consider the potential risks and benefits of using these medications.

Objective Geographical variation in the incidence of Crohn’s disease (CD) and ulcerative colitis (UC) according to the latitude of residence has been reported in Europe. However, there are no comparable data in the USA. The incidence of CD and UC in relation to latitude was assessed in a geographically diverse population of women enrolled in two large prospective studies in the USA. Design A prospective study was undertaken of women enrolled in the Nurses’ Health Study I (NHS) in 1976 and in the NHS II in 1989. Information on state of residence at the time of birth, at age 15 years and age 30 years was collected in 1992 in NHS I and in 1993 in NHS II. Reported diagnoses of incident CD or UC to the end of 2003 were confirmed by medical record review. Cox proportional hazards models were used to calculate HRs and 95% CIs for risk of CD and UC. Results In both cohorts, among 175 912 women reporting their residence in 1992, 257 cases of CD and 313 cases of UC were documented over 3 428 376 person-years of follow-up. The incidence of CD and UC increased significantly with increasing latitude (ptrend<0.01), with residence at age 30 years more strongly associated with risk. Compared with women residing in northern latitudes at age 30, the multivariate-adjusted HR for women residing in southern latitudes was 0.48 (95% CI 0.30 to 0.77) for CD and 0.62 (95% CI 0.42 to 0.90) for UC. The effect of latitude of residence on risk of CD and UC did not vary according to smoking history (pinteraction=0.26 for CD and 0.99 for UC). Conclusion In a population of US women, increasing latitude of residence was associated with a higher incidence of CD and UC.

Background Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are anti-inflammatory but have been linked in some studies to Crohn disease (CD) and ulcerative colitis (UC). Objective To assess the association between aspirin and NSAID use and incident CD and UC. Design Prospective cohort study. Setting Nurses' Health Study I. Patients 76 795 U.S. women who provided biennially updated data about aspirin and NSAID use. Measurements Incident CD and UC between 1990 and 2008 (outcome) and NSAID and aspirin use (exposure). Results 123 incident cases of CD and 117 cases of UC occurred over 18 years and 1 295 317 person-years of follow-up. Compared with nonusers, women who used NSAIDs at least 15 days per month seemed to have increased risk for both CD (absolute difference in age-adjusted incidence, 6 cases per 100 000 person-years [95% CI, 0 to 13]; multivariate hazard ratio, 1.59 [CI, 0.99 to 2.56]) and UC (absolute difference, 7 cases per 100 000 person-years [CI, 1 to 12]; multivariate hazard ratio, 1.87 [CI, 1.16 to 2.99]). Less frequent NSAID use was not clearly associated with risk for CD or UC, and there was no clear association between aspirin use and disease. Limitations Cohort participants were exclusively women, most of whom were white. Aspirin and NSAID use were self-reported. Conclusion Frequent use of NSAIDs but not aspirin seemed to be associated with increased absolute incidence of CD and UC. The findings have more mechanistic than clinical implications, because the absolute incidence of CD or UC associated with NSAIDs was low and the increase in risk for CD or UC associated with NSAIDs is unlikely to alter the balance of more common and clinically significant risks and benefits associated with these agents. Primary Funding Source American Gastroenterological Association, IBD Working Group, Broad Medical Research Program, and National Institutes of Health.

Objective To examine the association between chronic use of proton pump inhibitors (PPIs) and risk of hip fracture.Design Prospective cohort study.Setting Nurses' Health Study, which originally recruited from the 11 most populous states in the US.Participants 79 899 postmenopausal women enrolled in the Nurses' Health Study who provided data on the use of PPIs and other risk factors biennially since 2000 and were followed up to 1 June 2008. Main outcome measure Incident hip fractureResults During 565 786 person years of follow-up, we documented 893 incident hip fractures. The absolute risk of hip fracture among regular users of PPIs was 2.02 events per 1000 person years, compared with 1.51 events per 1000 person years among non-users. Compared with non-users, the risk of hip fracture among women who regularly used PPIs for at least two years was 35% higher (age adjusted hazard ratio 1.35 (95% confidence interval 1.13 to 1.62)), with longer use associated with increasing risk (P trend <0.01). Adjustment for risk factors, including body mass index, physical activity, and intake of calcium did not materially alter this association (hazard ratio 1.36 (1.13 to 1.63)). These associations were also not changed after accounting for reasons for PPI use. The relation between PPI use and fracture differed by smoking history (P interaction =0.03). Among current and former smokers, PPI use was associated with greater than 50% increase in risk of fracture, with a multivariate hazard ratio for fracture of 1.51 (1.20 to 1.91). In contrast, among women who never smoked there was no association (multivariate hazard ratio 1.06 (0.77 to 1.46)). In a meta-analysis of these results with 10 prior studies, the pooled odds ratio of hip fracture associated with PPI use was 1.30 (1.25 to 1.36). ConclusionChronic use of PPIs is associated with increased risk of hip fracture, particularly among women with a history of smoking. IntroductionProton pump inhibitors (PPIs) are among the most commonly used drugs worldwide. 1 In the US, PPI use increased dramatically since 2003 after the Food and Drug Administration approved the drugs for "over the counter" use. Primarily used for the treatment of heartburn symptoms, gastroesophageal reflux, or peptic ulcer, PPIs antagonise hydrogen-potassium adenosine triphosphatase pumps located on gastric parietal cells, 2 thereby reducing acid production to a greater extent than histamine receptor-2 (H 2 ) blockers. 3 Although short term use of PPIs is generally well tolerated, concern has grown over potential association between long term use and bone fractures, especially of the hip, which are known to be associated with substantial morbidity and mortality. [4][5][6] PPIs may inhibit calcium absorption, 7 directly interfere with osteoclast function, 8 or induce hypergastrinaemia, resulting in reductions in bone mineral density related to hyperparathyroidism. 9 Several studies have investigated the association between PPI use and risk of hip fracture.3 10-17 Many of these studies have had important lim...