Objectively measured disturbed sleep was consistently related to poorer cognition, whereas total sleep time was not. This finding may suggest that it is disturbance of sleep rather than quantity that affects cognition.

Among patients without known risk factors for iron deficiency, gastric acid inhibitor use for ≥2 years was associated with an increased subsequent risk of iron deficiency. The risk increased with increasing potency of acid inhibition and decreased after medication discontinuation.

Sleep parameters from actigraphy corresponded reasonably well to PSG in this population, with the PIM mode of actigraphy correlating highest. Those with poor sleep quality had the largest measurement error between the 2 procedures.

Background: Prior studies have suggested that insomnia and self-reported poor sleep are associated with increased risk of falls. However, no previous study, to our knowledge, has tested the independent associations of objectively estimated characteristics of sleep and risk of falls, accounting for the use of commonly prescribed treatments for insomnia. Methods: Study subjects were participants in the Study of Osteoporotic Fractures. In 2978 primarily community-dwelling women 70 years and older (mean age, 84 years), sleep and daytime inactivity were estimated using wrist actigraphy data collected for a minimum of 3 consecutive 24-hour periods (mean duration, 86.3 hours). Fall frequency during the subsequent year was ascertained by a triannual questionnaire. Use of medications was obtained by examiner interview. Results: In multivariate-adjusted models, relative to those with "normal" nighttime sleep duration (Ͼ7 to 8 hours per night), the odds of having 2 or more falls in the subsequent year was elevated for women who slept 5 hours or less per night (odds ratio, 1.52; 95% confidence interval, 1.03-2.24). This association was not explained by the use of benzodiazepines. Indexes of sleep fragmentation were also associated with an increased risk of falls. For example, women with poor sleep efficiency (Ͻ70% of time in bed spent sleeping) had 1.36-fold increased odds of falling compared with others (odds ratio, 1.36; 95% confidence interval, 1.07-1.74). Conclusion: Short nighttime sleep duration and increased sleep fragmentation are associated with increased risk of falls in older women, independent of benzodiazepine use and other risk factors for falls.

itamin B 12 deficiency is relatively common, especially among older adults; it has potentially serious medical complications if undiagnosed. Left untreated, vitamin B 12 deficiency can lead to dementia, neurologic damage, anemia, and other complications, which may be irreversible. According to data from the National Health and Nutrition Examination Survey, 3.2% of adults older than 50 years are estimated to have low serum vitamin B 12 levels. 1 Other studies have reported prevalence rates of 5% to 15%, although these may be underestimates of the true prevalence in some population subgroups. 2,3 Thus, identifying modifiable risk factors for vitamin B 12 deficiency is of significant public health importance. Acid inhibitors are among the most commonly used pharmaceuticals in the United States. In 2012, 14.9 million patients received 157 million prescriptions for proton pump inhibitors (PPIs); thus, use of PPIs could theoretically increase the population's risk of vitamin B 12 deficiency. 4 Gastric acid is required to cleave vitamin B 12 from ingested dietary proteins for the essential vitamins to be absorbed, and it is produced by the same cells that produce intrinsic factor, a compound required for vitamin B 12 absorption. 5 Thus, PPIs and histamine 2 receptor antagonists (H 2 RAs), which suppress the production of gastric acid, may lead to malabsorption of vitamin B 12. IMPORTANCE Proton pump inhibitors (PPIs) and histamine 2 receptor antagonists (H 2 RAs) suppress the production of gastric acid and thus may lead to malabsorption of vitamin B 12. However, few data exist regarding the associations between long-term exposure to these medications and vitamin B 12 deficiency in large population-based studies. OBJECTIVE To study the association between use of PPIs and H 2 RAs and vitamin B 12 deficiency in a community-based setting in the United States. DESIGN, SETTING, AND PATIENTS We evaluated the association between vitamin B 12 deficiency and prior use of acid-suppressing medication using a case-control study within the Kaiser Permanente Northern California population. We compared 25 956 patients having incident diagnoses of vitamin B 12 deficiency between January 1997 and June 2011 with 184 199 patients without B 12 deficiency. Exposures and outcomes were ascertained via electronic pharmacy, laboratory, and diagnostic databases. MAIN OUTCOMES AND MEASURES Risk of vitamin B 12 deficiency was estimated using odds ratios (ORs) from conditional logistic regression. RESULTS Among patients with incident diagnoses of vitamin B 12 deficiency, 3120 (12.0%) were dispensed a 2 or more years' supply of PPIs, 1087 (4.2%) were dispensed a 2 or more years' supply of H 2 RAs (without any PPI use), and 21 749 (83.8%) had not received prescriptions for either PPIs or H 2 RAs. Among patients without vitamin B 12 deficiency, 13 210 (7.2%) were dispensed a 2 or more years' supply of PPIs, 5897 (3.2%) were dispensed a 2 or more years' supply of H 2 RAs (without any PPI use), and 165 092 (89.6%) had not received prescriptions for eithe...

INTRODUCTION: Proton pump inhibitors (PPIs) are commonly used for gastrointestinal disorders; given they increase the systemic levels of gastrin, a trophic hormone, there is a concern about their carcinogenicity. This study evaluated the association between PPI use and gastrointestinal cancers. METHODS: We performed a nested case-control study in a large, community-based integrated healthcare setting. Cases were adults with gastric (n = 1,233), colorectal (n = 18,595), liver (n = 2,329), or pancreatic cancers (n = 567). Each case was matched with up to 10 controls by age, sex, race/ethnicity, medical facility, and enrollment duration. The primary exposure was defined as ≥2-year cumulative PPI supply. Data were obtained from pharmacy, cancer registry, and electronic medical record databases. Associations were evaluated using conditional logistic regression and adjusted for multiple confounders. We also evaluated the cancer risks separately by PPI dose, duration of use, and dose and duration. RESULTS: PPI use of ≥2-years was not associated with the risks of gastric (odds ratio [OR]: 1.07, 95% confidence interval [CI]: 0.81–1.42), colorectal (OR: 1.05, 95% CI: 0.99–1.12), liver (OR: 1.14, 95% CI: 0.91–1.43), or pancreatic cancers (OR: 1.22, 95% CI: 0.89–1.67), compared to non-users. In exploratory analyses, elevated cancer risks were primarily restricted to those with ≥10 years of PPI use, but no consistent associations were found for increasing PPI dose and/or duration of use. DISCUSSION: PPI use of ≥2 years was not associated with increased risks of gastrointestinal cancers. The cancer risks associated with PPI use of ≥10 years requires further study.

As genome sequencing technology advances, research is needed to guide decision-making about what results can or should be offered to patients in different clinical settings. We conducted three focus groups with individuals who had prior preconception genetic testing experience to explore perceived advantages and disadvantages of genome sequencing for preconception carrier screening, compared to usual care. Using a discussion guide, a trained qualitative moderator facilitated the audio-recorded focus groups. Sixteen individuals participated. Thematic analysis of transcripts started with a grounded approach and subsequently focused on participants’ perceptions of the value of genetic information. Analysis uncovered two orientations toward genomic preconception carrier screening: “certain” individuals desiring all possible screening information; and “hesitant” individuals who were more cautious about its value. Participants revealed valuable information about barriers to screening: fear/anxiety about results; concerns about the method of returning results; concerns about screening necessity; and concerns about partner participation. All participants recommended offering choice to patients to enhance the value of screening and reduce barriers. Overall, two groups of likely users of genome sequencing for preconception carrier screening demonstrated different perceptions of the advantages or disadvantages of screening, suggesting tailored approaches to education, consent, and counseling may be warranted with each group.Electronic supplementary materialThe online version of this article (doi:10.1007/s10897-015-9851-7) contains supplementary material, which is available to authorized users.

Background and Aims Medications are a major cause of acute liver failure (ALF) in the US, but no population-based studies have evaluated the incidence of ALF from drug-induced liver injury. We aimed to determine the incidence and outcomes of drug-induced ALF in an integrated healthcare system that approximates a population-based cohort. Methods We performed a retrospective cohort study using data from the Kaiser Permanente Northern California (KPNC) healthcare system between January 1, 2004 and December 31, 2010. We included all KPNC members ≥18 y old with ≥6 months of membership and hospitalization for potential ALF. The primary outcome was drug-induced ALF (defined as coagulopathy and hepatic encephalopathy without underlying chronic liver disease), determined by hepatologists who reviewed medical records of all KPNC members with inpatient diagnostic and laboratory criteria suggesting potential ALF. Results Among 5,484,224 KPNC members between 2004 and 2010, 669 had inpatient diagnostic and laboratory criteria indicating potential ALF. After medical record review, 62 (9.3%) were categorized as having definite or possible ALF, and 32 (51.6%) had a drug-induced etiology (27 definite, 5 possible). Acetaminophen was implicated in 18 events (56.3%), dietary/herbal supplements in 6 (18.8%), antimicrobials in 2 (6.3%), and miscellaneous medications in 6 (18.8%). One patient with acetaminophen-induced ALF died (5.6%; .06 events/1,000,000 person-years) compared to 3 patients with non-acetaminophen induced ALF (21.4%; .18/1,000,000 person-years). Overall, 6 patients (18.8%) underwent liver transplantation, and 22 patients (68.8%) were discharged without transplantation. The incidence rates of any definite drug-induced ALF and acetaminophen-induced ALF were 1.61 events/1,000,000 person-years (95% confidence interval, 1.06–2.35) events and 1.02 events/1,000,000 person-years (95% confidence interval, 0.59–1.63), respectively. Conclusions Drug-induced ALF is uncommon, but over-the-counter products and dietary/herbal supplements are its most common causes.