Shelly L. Gray

Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: results from the Women's Health Initiative.

BACKGROUND Proton pump inhibitor (PPI) medications have been inconsistently shown to be associated with osteoporotic fractures. We examined the association of PPI use with bone outcomes (fracture, bone mineral density [BMD]). METHODS This prospective analysis included 161 806 postmenopausal women 50 to 79 years old, without history of hip fracture, enrolled in the Womens Health Initiative (WHI) Observational Study and Clinical Trials with a mean (SD) follow-up of 7.8 (1.6) years. Analyses were conducted for 130 487 women with complete information. Medication information was taken directly from drug containers during in-person interviews (baseline, year 3). The main outcome measures were self-reported fractures (hip [adjudicated], clinical spine, forearm or wrist, and total fractures) and for a subsample (3 densitometry sites), 3-year change in BMD. RESULTS During 1 005 126 person-years of follow-up, 1500 hip fractures, 4881 forearm or wrist fractures, 2315 clinical spine fractures, and 21 247 total fractures occurred. The multivariate-adjusted hazard ratios for current PPI use were 1.00 (95% confidence interval [CI], 0.71-1.40) for hip fracture, 1.47 (95% CI, 1.18-1.82) for clinical spine fracture, 1.26 (95% CI, 1.05-1.51) for forearm or wrist fracture, and 1.25 (95% CI, 1.15-1.36) for total fractures. The BMD measurements did not vary between PPI users and nonusers at baseline. Use of PPIs was associated with only a marginal effect on 3-year BMD change at the hip (P = .05) but not at other sites. CONCLUSION Use of PPIs was not associated with hip fractures but was modestly associated with clinical spine, forearm or wrist, and total fractures.

Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study

IMPORTANCE Many medications have anticholinergic effects. In general, anticholinergic-induced cognitive impairment is considered reversible on discontinuation of anticholinergic therapy. However, a few studies suggest that anticholinergics may be associated with an increased risk for dementia. OBJECTIVE To examine whether cumulative anticholinergic use is associated with a higher risk for incident dementia. DESIGN, SETTING, AND PARTICIPANTS Prospective population-based cohort study using data from the Adult Changes in Thought study in Group Health, an integrated health care delivery system in Seattle, Washington. We included 3434 participants 65 years or older with no dementia at study entry. Initial recruitment occurred from 1994 through 1996 and from 2000 through 2003. Beginning in 2004, continuous replacement for deaths occurred. All participants were followed up every 2 years. Data through September 30, 2012, were included in these analyses. EXPOSURES Computerized pharmacy dispensing data were used to ascertain cumulative anticholinergic exposure, which was defined as the total standardized daily doses (TSDDs) dispensed in the past 10 years. The most recent 12 months of use was excluded to avoid use related to prodromal symptoms. Cumulative exposure was updated as participants were followed up over time. MAIN OUTCOMES AND MEASURES Incident dementia and Alzheimer disease using standard diagnostic criteria. Statistical analysis used Cox proportional hazards regression models adjusted for demographic characteristics, health behaviors, and health status, including comorbidities. RESULTS The most common anticholinergic classes used were tricyclic antidepressants, first-generation antihistamines, and bladder antimuscarinics. During a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia (637 of these [79.9%] developed Alzheimer disease). A 10-year cumulative dose-response relationship was observed for dementia and Alzheimer disease (test for trend, P < .001). For dementia, adjusted hazard ratios for cumulative anticholinergic use compared with nonuse were 0.92 (95% CI, 0.74-1.16) for TSDDs of 1 to 90; 1.19 (95% CI, 0.94-1.51) for TSDDs of 91 to 365; 1.23 (95% CI, 0.94-1.62) for TSDDs of 366 to 1095; and 1.54 (95% CI, 1.21-1.96) for TSDDs greater than 1095. A similar pattern of results was noted for Alzheimer disease. Results were robust in secondary, sensitivity, and post hoc analyses. CONCLUSIONS AND RELEVANCE Higher cumulative anticholinergic use is associated with an increased risk for dementia. Efforts to increase awareness among health care professionals and older adults about this potential medication-related risk are important to minimize anticholinergic use over time.

Medication Adherence in Elderly Patients Receiving Home Health Services following Hospital Discharge

OBJECTIVE: To assess prevalence and risk factors for medication under- and overadherence in a two-week period following hospital discharge in adults ⩾ 65 years. DESIGN: Prospective, cohort study. SETTING: Three home healthcare agencies in Madison, Wisconsin, and surrounding vicinity. PARTICIPANTS: One hundred forty-seven older participants taking three or more medications who were hospitalized for medical illness, received home nursing after discharge, and completed the two-week interview. MEASUREMENTS: The main outcome measures were having at least one medication with less than 70% adherence (underadherence) and having at least one medication with more than 120% adherence (overadherence) based on pill counts. RESULTS: Forty-five (30.6%) participants were underadherent and 27 (18.4%) participants were overadherent with at least one medication. In a multivariate model, underadherence was predicted by poor cognition (OR 2.5; 95% CI 1.02 to 6.10) and higher medication use (OR 1.16; 95% CI 1.03 to 1.31, for each 1-unit increase in number of medications). Both poor cognition and low education were significantly associated with overadherence in univariate analysis; however, neither variable was significant once included in the multivariate model. CONCLUSIONS: Under- and overadherence to medications is common after hospital discharge. Poor cognition and a greater number of medications were associated with underadherence. Poor cognition and lower education were markers for overadherence; however, further study is needed to determine whether these are independent predictors. Patients who have impaired cognition or are taking a greater number of medications after hospitalization may benefit from targeted interventions to monitor and improve medication compliance.

Drug-induced cognition disorders in the elderly: incidence, prevention and management.

The aetiology of cognitive impairment is multifactorial; however, drugs are an important cause of delirium and dementia. Several factors may increase the risk of drug-induced cognition disorders in the elderly including imbalances in neurotransmitters (e.g. acetylcholine), age-related alterations in pharmacokinetics and pharmacodynamics, and high levels of medication use.Nearly any drug can cause cognitive impairment in susceptible individuals; however, certain classes are more commonly implicated. Benzodiazepines, opioids, anticholinergics, and tricyclic antidepressants are probably the worst offenders. Older antihypertensive agents (reserpine, clonidine) have negative effects on cognition; however, large clinical trials in the elderly indicate that commonly used agents [e.g. thiazide diuretics, calcium antagonists (amiodipine, diltiazem) ACE inhibitors (captopril, enalapril) and β-blockers (atenolol)] have minimal effects on cognition. Newer antidepressants such as selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) and reversible inhibitors of monoamine oxidase A have not been shown to have negative effects on cognition. Although some drugs have shown low risk for causing cognition disorders in research studies, risk may be increased in frail older adults taking several medications and each case should be reviewed carefully.Identification of drug-induced cognitive impairment is crucial to early detection and resolution of symptoms. Preventive strategies directed at avoiding high risk medications when possible, appropriately adjusting doses based on agerelated changes and close follow-up may prevent these conditions.

Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) may prevent Alzheimer dementia (AD). Methods: We analyzed the association of prior NSAID exposure with incident dementia and AD in the Adult Changes in Thought population-based cohort aged ≥65 years (median 74.8) at enrollment. Participants were members of Group Health, which provided computerized pharmacy dispensing records from 1977 onward. We studied 2,736 dementia-free enrollees with extensive prior pharmacy data, following them biennially for up to 12 years to identify dementia and AD. Cox proportional hazards regression assessed association of dementia or AD with NSAID use graded in standard daily doses (SDD) dispensed over 2 years (e.g., heavy use = 500+ SDD), with some analyses also adding consecutive biennial self-reports of NSAID use. Results: Pharmacy records identified 351 participants (12.8%) with history of heavy NSAID use at enrollment. Another 107 became heavy users during follow-up. Some 476 individuals developed incident dementia, 356 with AD (median onset ages 83.5 and 83.8 years). Contrary to the hypothesis that NSAIDs protect against AD, pharmacy-defined heavy NSAID users showed increased incidence of dementia and AD, with adjusted hazard ratios of 1.66 (95% confidence interval, 1.24–2.24) and 1.57 (95% confidence interval, 1.10–2.23). Addition of self-reported exposure data did not alter these results. Conclusions: These findings differ from those of other studies with younger cohorts. The results observed elsewhere may reflect delayed onset of Alzheimer dementia (AD) in nonsteroidal anti-inflammatory drug (NSAID) users. Conceivably, such delay could result in increased AD incidence in late old age. The relation of NSAID use and AD pathogenesis needs further investigation. ACT = Adult Changes in Thought; AD = Alzheimer dementia; ADL = activities of daily living; aHR = adjusted hazard ratio; CI = confidence interval; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; GH = Group Health; HR = hazard ratio; NSAID = nonsteroidal anti-inflammatory drug; OR = odds ratio; SDD = standard daily dose.

Adverse Drug Events in Elderly Patients Receiving Home Health Services following Hospital Discharge

OBJECTIVE: To assess incidence, healthcare consequences, and identify risk factors for adverse drug events (ADEs) in elderly patients receiving home health services during the month following hospital discharge. METHODS: This was a prospective cohort study of three home health agencies in Madison, Wisconsin, and its surrounding area. The sample consisted of 256 participants aged •65 years who were hospitalized for medical illness, received home nursing after discharge, and completed the one-month interview. The main outcome measure was self-reported ADEs (possible, probable, or definite) during the month following hospital discharge. RESULTS: Incidence of ADEs was 20%. Fifty-two participants (20.3%) reported 64 ADEs: 23 possible, 37 probable, and four definite. The most common ADEs involved the gastrointestinal tract (31.3%) and the central nervous system (31.3%). Of 53 ADEs reported to providers, 59% of the drugs were discontinued or altered. One ADE resulted in hospitalization. In logistic regression, female gender (OR = 2.26; 95% CI 1.06 to 4.77) and the interaction between number of new medications and cognition were significantly associated with ADEs. The risk of an event increased with the number of new medications at discharge; however, risk was elevated primarily for participants with lower cognition. CONCLUSIONS: ADEs were common during the month following hospital discharge, were more frequent in women, and often resulted in medication changes. Individuals at particular risk were those with lower cognition who were discharged with several new medications.

Caring for Poorly Controlled Diabetes Mellitus: A Randomized Pharmacist Intervention

BACKGROUND: There is limited information from randomized controlled studies about the influence of pharmacist interventions on diabetes control. OBJECTIVE: To evaluate the effect of a pharmacist intervention on improving diabetes control; secondary endpoints were medication appropriateness and self-reported adherence. METHODS: A randomized, controlled, multi-clinic trial was conducted in the University of Washington Medicine Neighborhood Clinics. Seventy-seven subjects, ⩾18 years old with a hemoglobin (Hb) A1c ⩾9% at baseline and taking at least one oral diabetes medication, were randomized to receive a pharmacist intervention (n = 43) or usual care (n = 34) for 6 months followed by a 6-month usual-care observation period for both groups. Subjects met with a clinical pharmacist to establish and initiate a diabetes care plan followed by weekly visits or telephone calls to facilitate diabetes management and adherence. HbA1c, medication appropriateness, and self-reported adherence were assessed at baseline, 6 months, and 12 months. RESULTS: The mean HbA1c did not differ between groups over the 12-month period (p = 0.61). A reduction in HbA1c was noted for both groups over time compared with baseline (p = 0.001); however, control subjects relied more heavily on provider visits. Medication appropriateness was not improved for diabetes medications (p = 0.65). Self-reported adherence was not significantly improved by the intervention. CONCLUSIONS: This pharmacist intervention did not significantly improve diabetes control, but did allow for similar HbA1c control with fewer physician visits. Medication appropriateness and self-reported adherence compared with usual care in individuals with poorly controlled diabetes were not changed.

Barriers to Medication Adherence in Poorly Controlled Diabetes Mellitus

PURPOSE The purpose of this study is to characterize the adherence and medication management barriers for adults with poorly controlled type 2 diabetes mellitus (DM) (those with A1c 9% or above) and to identify specific adherence characteristics associated with poor diabetes control. METHODS This was a cross-sectional analysis of baseline data from a randomized, controlled diabetes intervention conducted in University of Washington (UW) Medicine Clinics in the greater Seattle, Washington, area. The goal of the original study was to evaluate the effect of a pharmacist intervention on improving diabetes control over 12 months. Evaluation measures for medication adherence included self-reported adherence and medication management challenges using the Morisky question format and difficulty with taking medications for each diabetes medication based on the Brief Medication Questionnaire. Specific adherence characteristics associated with poor diabetes control (A1c >9%) were identified using multivariate regression analysis. RESULTS Seventy-seven subjects (mean A1c, 10.4%; mean duration of DM, 7 years) were studied. The most common adherence challenges included paying for medications (34%), remembering doses (31%), reading prescription labels (21%), and obtaining refills (21%). Taking more than 2 doses of DM medication daily (beta = .78, SE = 0.32, P = .02) and difficulty reading the DM medication prescription label (beta = .76, SE = 0.37, P = .04) were significantly associated with higher hemoglobin A1c. Self-reported adherence was not related to A1c control. CONCLUSIONS In this study, we identified 2 factors that were associated with poorer A1c control. These findings highlight the importance of identifying potential challenges to medication adherence for those with DM and providing support to minimize or resolve these barriers to control.

Benzodiazepine Use and Physical Disability in Community‐Dwelling Older Adults

OBJECTIVES: To determine whether benzodiazepine use is associated with incident disability in mobility and activities of daily living (ADLs) in older individuals.

Antioxidant vitamin supplement use and risk of dementia or Alzheimer's disease in older adults

OBJECTIVES: To examine whether use of vitamins C or E alone or in combination was associated with lower incidence of dementia or Alzheimers disease (AD).