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Background/objectives There are growing concerns about the safety and efficacy of psychotropic medications in Alzheimer's disease (AD). We sought to examine associations between psychotropic medication exposure and longitudinal change in cognitive, functional, and neuropsychiatric outcomes in a large clinical AD cohort. Design Longitudinal observational study. Setting National Alzheimer's Disease Coordinating Center combining data from 39 Alzheimer's disease centers. Participants 8,034 participants with AD dementia. Measurements Mini-Mental State Exam (MMSE), Clinical Dementia Rating Scale-Sum of Boxes (CDR-SB), and Neuropsychiatric Inventory Questionnaire (NPI-Q) Total. Probability of exposure to medication (the propensity score, PS) calculated via logistic regression. Medication classes included all antipsychotics (atypical vs conventional), antidepressants (Selective Serotonin Reuptake Inhibitor [SSRI] vs non-SSRI), and benzodiazepines. Participants treated with a medication class were matched with participants not treated with that class with the closest-matched PS. The effect of medication treatment was assessed using linear mixed-effects models. Results Participants had a mean (SD) age of 75.5 (9.8) years, and mean (SD) scores of MMSE 21.3 (5.7), CDR-SB 5.5 (3.4), and NPI-Q Total 4.5 (4.4). Mean duration of follow-up was 2.9-3.3 years depending on medication class. Non-SSRI antidepressant use was associated with better CDR-SB (2-year difference in change-DIC: -0.38 [-0.61, -0.15], P = .001). Atypical antipsychotic use was associated with greater decline on MMSE (DIC: -0.91 [-1.54, -0.28] P = .005) and CDR-SB scores (DIC: 0.50 [0.14, 0.86], P = .006). Notably, no drug class was associated with better NPI-Q scores. Conclusions Use of atypical antipsychotics was associated with poorer cognition and function, and no drug class was associated with improvement in neuropsychiatric symptoms.

Prevalence of Alzheimer's disease (AD) is higher for women, possibly influenced by sex-dependent effects of the estrogen. We examined the association between estrogen and cognitive decline in over 2,000 older adult women in a 12-year population-based study in Cache County, Utah.The baseline sample included 2,114 women (mean age = 74.94 y, SD = 6.71) who were dementia-free at baseline and completed a women's health questionnaire, asking questions regarding reproductive history and hormone therapy (HT). Endogenous estrogen exposure (EEE) was calculated taking the reproductive window (age at menarche to age at menopause), adjusted for pregnancy and breastfeeding. HT variables included duration of use, HT type (unopposed; opposed), and time of HT initiation. A modified version of the Mini-Mental State Examination (3MS) was administered at four triennial waves to assess cognitive status. Linear mixed-effects models examined the relationship between estrogen exposure and 3MS score over time.EEE was positively associated with cognitive status (β = 0.03, P = 0.054). In addition, longer duration of HT use was positively associated with cognitive status (β = 0.02, P = 0.046) and interacted with age; older women had greater benefit compared with younger women. The timing of HT initiation was significantly associated with 3MS (β = 0.55, P = 0.048), with higher scores for women who initiated HT within 5 years of menopause compared with those initiating HT 6-or-more years later.Our results suggest that longer EEE and HT use, especially in older women, are associated with higher cognitive status in late life.

Objective Closer caregiver-care recipient (CG-CR) relationships are associated with better cognitive and functional abilities, activities of daily living (in persons with dementia), and lower informal care costs. Methods Due to the difficulty in treating neuropsychiatric symptoms (NPSs) and their detrimental effects on caregivers and care recipients, we examined whether closeness of CG-CR relationships was associated with overall NPS severity or with specific NPS symptom domains in care recipients. In a longitudinal population-based study in Cache County, Utah, the 12-item Neuropsychiatric Inventory (NPI-12) was assessed in 300 CG-CR dyads. Caregivers reported current relationship closeness using the Whitlatch Relationship Closeness Scale. Linear mixed models examined associations between CG-CR closeness and NPI-12 total score or selected symptom domains over time (observation period: 2002–2012). Results In unadjusted linear mixed models, higher closeness scores were associated with a five-point lower NPI-12 score and a one-point lesser increase in NPI-12 per year. NPI scores also showed lower affective cluster scores (two points) and lesser increase in psychosis cluster (approximately 0.5 points per year) and agitation/aggression (0.16 points per year) for each unit increase in closeness. When controlling for NPI caregiver distress, associations between closeness and NPSs diminished to a 0.5-point lesser increase in total NPI-12 score per year. Adjusted models for NPI domains/clusters showed −0.32 points per year for the psychosis cluster, −0.11 points per year for agitation/aggression, and −0.67 overall for the affective cluster. Conclusion Higher CG-CR closeness, a potentially modifiable factor, is associated with lower NPS severity and may provide a target for intervention.

Introduction Severity of dementia and neuropsychiatric symptoms contribute to increasing informal care costs. We examined which neuropsychiatric symptoms subdomains (NPS-SD) were associated with informal costs in a population-based sample. Methods Dementia progression and informal costs (2015 dollars) were estimated from the Cache County Dementia Progression Study. Overall NPS and specific NPS-SD were assessed with the Neuropsychiatric Inventory. Generalized Estimating Equations (GEE with gamma-distribution/log-link) modeled the relationship between NPS-SDs and informal cost trajectories. Results Two hundred eighty participants (52.1% female; age M = 85.67, SD = 5.60) exhibited an adjusted cost increase of 5.6% (P = .005), 6.4% (P, Highlights • Specific neuropsychiatric symptoms/areas affect informal costs of dementia care differently over time; some have little to no impact. • Agitation/aggression, affective, and psychosis increase persons with dementia informal costs of dementia care over time. • Apathy increases rate of change in informal costs of dementia care over time.

Neurotrophins, including nerve-growth factor and brain-derived neurotrophic factor, have been implicated in Alzheimer's disease (AD). Associations between AD and neurotrophin signaling genes have been inconsistent, with few studies examining sex differences in risk. We examined four single-nucleotide polymorphisms (SNPs) involved in neurotrophin signaling (rs6265, rs56164415, rs2289656, rs2072446) and risk for AD by sex in a population-based sample of older adults. Three thousand four hundred and ninety-nine individuals without dementia at baseline [mean (standard deviation) age = 74.64 (6.84), 58% female] underwent dementia screening and assessment over four triennial waves. Cox regression was used to examine time to AD or right censoring for each SNP. Female carriers of the minor T allele for rs2072446 and rs56164415 had a 60% (hazard ratio [HR] = 1.60, 95% confidence interval [CI] = 1.02-2.51) and 93% (HR = 1.93, 95% CI = 1.30-2.84) higher hazard for AD, respectively, than male noncarriers of the T allele. Furthermore, male carriers of the T allele of rs2072446 had a 61% lower hazard (HR = 0.39, 95% CI = 0.14-1.06) than male noncarriers at trend-level significance (p = .07). The association between certain neurotrophin gene polymorphisms and AD differs by sex and may explain inconsistent findings in the literature.

The 2018-2019 Professional Affairs Committee examined the potential roles and needs of clinical educators (faculty and preceptors) in leading transformation in pharmacy practice. The committee was charged to (1) discuss the potential roles and responsibilities of faculty and preceptors leading transformation and enhanced patient care services in pharmacy practice; (2) describe factors, including clinician well-being and resilience, which may influence faculty and preceptor involvement in practice transformation and the enhancement of patient care services; and (3) recommend how the efforts and successes of faculty and preceptors involved in pharmacy practice transformation can be replicated and recognized as well as identify the types of continuing professional development (CPD) that should be available to enable the influence and implementation of patient care services. This report provides a framework for addressing the committee charges by examining the roles of advocacy, collaboration, continuing professional development, and clinician resilience and well-being. The committee provides a revision to a current AACP policy regarding continuing professional development as well as several recommendations to AACP and suggestions to colleges and schools of pharmacy pertaining to the committee charges.

Research indicates that lifestyle and genetic factors influence the course of cognitive impairment in aging, but their interactions have not been well-examined. This study examined the relationship between physical activity and genotypes related to brain-derived neurotrophic factor (BDNF) in predicting cognitive performance in a sample of older adults with up to 12 years of follow-up. Physical activity levels (sedentary, light, and moderate/vigorous) were determined for the sample of 3,591 participants (57% female) without dementia. The genotypes examined included BDNF gene single nucleotide polymorphisms (SNPs) (rs6265 and rs56164415) and receptor gene SNPs (NTRK2 rs2289656 and NGFR rs2072446). Cognition was assessed triennially using the Modified Mini-Mental State Exam. Unadjusted linear mixed models indicated that sedentary (β = −5.05) and light (β = −2.41) groups performed worse than moderate–vigorous (p < .001). Addition of interaction effects showed significant differences in rate of decline between activity levels, particularly among males (p = .006). A three-way interaction with sex, NGFR SNP rs2072446, and physical activity suggested that the C/C allele was associated with better cognitive performance among males engaging in light activity only (p = .004). Physical activity and sex, but not BDNF-related SNPs, predicted rate of cognitive decline in older adults, while NGFR rs2072446 may modify main effects.

Closer caregiver-care recipient (CG-CR) relationships have been associated with lower informal care costs and better cognitive and functional outcomes in persons with dementia. Considering difficulties in treating neuropsychiatric symptoms (NPS) and their significant detrimental effects on caregivers and care-recipients in dementia, we examined whether closer CG-CR relationships were associated with severity of overall NPS and specific subdomains in dementia. NPS were assessed by the Neuropsychiatric Inventory-12 (NPI-12) in 252 CG-CR dyads in the Dementia Progression Study a longitudinal-population based study in Cache County Utah. Caregivers reported on relationship closeness using the Whitlach Relationship Scale. Linear mixed models examined the association between NPI-12 total score and symptom subdomains with CG-CR closeness (time-varying) in separate models. When controlling for caregiver burden, kin relationship, and dementia severity, each increasing unit of closeness was associated with an approximate 3-point lower NPI-12 score (b=-2.73, p=.002), and an approximate 1-point slower increase in NPI total score per year (b=-0.92, p=0.046). In NPI subdomains, closer relationships were associated with lower affective domain scores (b=-0.15, p

This study examined warfarin usage for elderly Medicare beneficiaries with atrial fibrillation (AF) who suffered traumatic brain injury (TBI), hip fracture, or torso injuries. Using the 5% Chronic Condition Data Warehouse administrative claims data, this study included fee-for-service Medicare beneficiaries who had a single injury hospitalization (TBI, hip fracture, or major torso injury) between 1/1/2007 and 12/31/2009, with complete Medicare Parts A, B (no Medicare Advantage), and D coverage 6 months before injury, and who were aged 66 years or older and diagnosed with AF at least 1 year before injury. About 45% of the AF patients were using warfarin before TBI or torso injury, and 35% before hip fracture. After injury, there was a dramatic and persistent decrease in warfarin use in TBI and torso injury groups (30% for TBI and 37% for torso injury at 12 months after injury). Warfarin usage in hip fracture patients also dropped after injury but returned to pre-injury level within 4 months. TBI and torso injury lead to significant decreases in warfarin usage in elderly AF patients. Further research is needed to understand reasons for the pattern and to develop evidence-based management strategies in the post-acute setting.

Objectives: To assess the effectiveness of medications used in the management of Alzheimer's disease and related dementias (ADRD) on cognition and activity of daily living (ADL) trajectories and to determine whether sex modifies these effects. Design: Two-year (2007�2008) longitudinal study. Setting: Medicare enrollment and claims data linked to the Minimum Dataset 2.0. Participants: Older nursing home (NH) residents with newly diagnosed ADRD (n = 18,950). Measurements: Exposures included four medication classes: antidementia medications (ADMs), antipsychotics, antidepressants, and mood stabilizers. Outcomes included ADLs and cognition (Cognitive Performance Scale (CPS)). Marginal structural models were employed to account for time-dependent confounding. Results: The mean age was 83.6, and 76% of the sample was female. Baseline use of ADMs was 15%, antidepressants was 40%, antipsychotics was 13%, and mood stabilizers was 3%. Mean baseline ADL and CPS scores were 16.6 and 2.1, respectively. ADM use was not associated with change in ADLs over time but was associated with a slower CPS decline (slope difference: -0.09 points/year, 99% confidence interval (CI) = -0.14 to -0.03). Antidepressant use was associated with slower declines in ADL (slope difference: -0.36 points/year, 99% CI = -0.58 to -0.14) and CPS (slope difference: -0.12 points/year, 99% CI = -0.17 to -0.08). Sex modified the effect of both antipsychotic and mood stabilizer use on ADLs; female users declined most quickly. Antipsychotic use was associated with slower CPS decline (slope difference: -0.11 points/year, 99% CI = -0.17 to -0.06), whereas mood stabilizer use had no effect. Conclusion: Despite the observed statistically significantly slower declines in cognition with ADMs, antidepressants, and antipsychotics and the slower ADL decline found with antidepressants, it is unlikely that these benefits are of clinical significance.

Background Despite well-documented evidence regarding antipsychotic use in older adults residing in nursing homes (NHs), there is a lack of evidence-based use and quality benchmarks for other psychopharmacological medications (PPMs), including antidepressants, anxiolytics, and sedative-hypnotics. Objective To estimate the prevalence and patterns of use of PPMs and to measure the quality of PPM use. Methods Using a 5% random sample of 2007 Medicare claims data linked to the Minimum Data Set 2.0, this cross-sectional study identified a nationally representative sample of 69,832 NH residents with ≥3 months of institutionalization. This study measured 1-year prevalence and quality of PPM use, as assessed by indication, dose, and duration of use defined and operationalized according to the current Centers for Medicare and Medicaid Services Unnecessary Medication Guidance for Surveyors and relevant practice guidelines. Results Over two-thirds of residents (72.1%, n =50,349) used ≥1 PPM in 2007, with the highest prevalence seen in antidepressants (59.4%), and the lowest in anxiolytics (8.9%). Almost two-thirds (61.0%) of PPM users used ≥2 PPM classes. Compared to other PPM therapeutic classes, antipsychotic users had greatest evidence of guideline adequate use by indication (95.8%) and dose (78.7%). In addition, longer duration of adequate treatment was observed among antipsychotic users (mean = 208 days, standard deviation [SD] = 118) as compared to anxiolytic (mean = 159 days, SD = 118) and sedative-hypnotic users (mean = 183 days, SD = 117). Conclusions This study found that PPM use remains highly prevalent among long-stay Medicare NH residents. While antipsychotic use remained high (31.5%), little antipsychotic use was deemed inadequate by indication. However, the 1-year prevalence of use, dose, and duration of use of other PPMs remain high and potentially inadequate. Practitioners and policy-makers should heed both the high use and lower prescribing quality of antidepressants, anxiolytics, and sedative-hypnotics in NH residents.

Objectives: To estimate the effects of depression diagnosis and antidepressant treatment on 2-year all-cause mortality in Medicare beneficiaries with chronic obstructive pulmonary disease (COPD) and determine whether Social Security Disability Insurance (SSDI) eligibility modifies these relationships. Design: Retrospective cohort study. Setting: A 5% random sample of Medicare beneficiaries aged 65 and older in stand-alone Part D plans in 2006 to 2008. Participants: Beneficiaries diagnosed with COPD and continuously enrolled in Medicare Parts A, B, and D (N = 75,699). Measurements: Depression diagnosis was assessed at baseline (2006). Evidence of antidepressant treatment was measured across time. Covariates included baseline characteristics, comorbidities, and disease severity. Survival analyses using Cox proportional hazards models estimated 2-year mortality associated with depression diagnosis or antidepressant treatment (in beneficiaries with depression). Interaction terms of SSDI eligibility with baseline depression and time-dependent antidepressant treatment were tested. Results: More than one-fifth (21.6%) of beneficiaries with COPD had a depression diagnosis at baseline, and 82.1% of those received antidepressants. Nearly one-sixth (16.3%) of the sample were SSDI eligible. Baseline depression heightened risk of death (hazard ratio = 1.13, 95% confidence interval = 1.09�1.18) in beneficiaries who were not eligible for SSDI. In beneficiaries with depression, the association between antidepressant treatment and lower mortality was different according to SSDI eligibility status. Conclusion: Social Security Disability Insurance eligibility modifies the effects of depression and antidepressant treatment on mortality in Medicare beneficiaries with COPD. These data suggest that clinicians should identify and treat depression in individuals with COPD, but further studies are needed to determine the effect of these interventions.

Objective: Depression is a significant comorbidity in patients with chronic obstructive pulmonary disease (COPD). Although comorbid depression is associated with low use and poor adherence to medications treating other chronic conditions, evidence of the relationship between depression and COPD management is limited. This study estimated the association between depression and COPD maintenance medication (MM) adherence among patients with COPD. Methods:This cross-sectional study used a 5% random sample of 2006–2007 Chronic Condition Warehouse data. Medicare beneficiaries enrolled in Parts A, B, and D plans with diagnosed COPD who survived through 2006 were included (n=74,863). COPD MM adherence was measured as medication discontinuation and proportion of days covered (PDC). Depression was identified through the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. Multivariable models with modified generalized estimating equations were used to estimate adjusted association between depression diagnosis and medication adherence, controlling for sociodemographics, comorbidities, and disease severity. Results:Among the sample, about one third (33.6%) had diagnosed depression. More than half (61.8%) of beneficiaries with COPD filled at least one COPD MM prescription. Depressed beneficiaries had a higher likelihood of using COPD MM than non-depressed beneficiaries (adjusted prevalence ratios [PR]=1.02;95% confidenceintervals [CI]=1.01, 1.03).Among COPD MMusers,depressedbeneficiaries were more likely to discontinue medications (PR=1.09; 95% CI=1.04, 1.14) and less likely to exhibit PDC ≥0.80 (PR=0.89; 95% CI=0.86, 0.92) than non-depressed beneficiaries. Conclusions: Depression is prevalent in Medicare beneficiaries with COPD and independently associated with lower COPD MM adherence. Interventions to improve medication adherence for COPD patients may consider management of comorbidities such as depression. Copyright #2013John Wiley & Sons, Ltd.

Objectives: To assess the effect of exposure to evidence-based medication after hospital discharge for Medicare beneficiaries with acute myocardial infarction (AMI). Design: A discrete-time hazard model was used to estimate time to outcome associated with exposure to four drug classes (angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin-II receptor blockers (ARBs), beta-blockers (BBs), statins, and clopidogrel) used for post-AMI secondary prevention of cardiovascular events and mortality. Setting: Medicare administrative data for a 5% random sample of beneficiaries. Participants: Medicare beneficiaries (N = 9,538) hospitalized for an AMI between April 1, 2006, and December 31, 2007, who survived for at least 30 days after discharge. The cohort was followed until death or December 31, 2008. Measurements: Time-varying exposure was measured as proportion of days covered (PDC) for each quarter during the follow-up period. PDC was classified into five categories (0�0.2, 0.2�0.4, 0.4�0.6, 0.6�0.8, 0.8�1.0). Outcomes were mortality and a composite outcome of death or post-AMI hospitalization. Results: Over a median follow-up of 18 months, mean PDC rates ranged from 0.37 (clopidogrel) to 0.50 (statins). When comparing the highest versus lowest categories of exposure, the hazard of the composite outcome was significantly lower for all drug classes except BBs (statins, adjusted hazard ratio (aHR) = 0.71, ACEIs/ARBs, aHR = 0.81, clopidogrel, aHR = 0.85, BBs, aHR = 0.93). All four drug classes were significantly associated with reductions in mortality; the magnitude of effect for the mortality outcome was largest for statins and smallest for BBs. Age modified the effect of statins on mortality. Conclusion: Use of evidence-based medications for secondary prevention after AMI is suboptimal in the Medicare population, and low exposure rates are associated with significantly higher risk for subsequent hospitalization and death.

Chronic kidney disease is a high-risk condition for a variety of adverse safety events, yet little is known about differential rates of safety events across racial groups with decreased kidney function. We sought to examine the incidence of an array of disease-specific adverse safety events in black versus nonblack patients with decreased estimated glomerular filtration rate (eGFR).Retrospective observational study of a national US Veterans Affairs cohort.Veterans with eGFR60 mL/min/1.73 m(2) and one or more hospitalization during federal fiscal year 2005 (n = 70,154).Self-reported race/ethnicity dichotomized as black or nonblack.Hospital discharge coding for Agency for Healthcare Research and Quality (AHRQ) patient safety indicators (PSIs), laboratory records for detection of hyperkalemia and hypoglycemia, and pharmacy records to determine dosing of 4 selected medications.Relationship between race and disease-specific patient safety events.Black veterans were more likely than nonblack veterans to experience one type of safety event (33% vs 32%, respectively) and multiple types of safety events (32% vs 23%, respectively; both P0.001). After adjustment, black veterans were 11% and 36% more likely to have at least one episode of hyperkalemia and hypoglycemia, respectively, than nonblack veterans, but were 14% less likely to experience a medication error (all P0.001). There was no association between the occurrence of AHRQ PSIs and race after adjustment.Use of administrative data has a risk of imprecision in coding; Veterans Affairs cohort may limit generalizability.Black veterans with decreased eGFR are more likely to experience a broad array of safety events than nonblacks with decreased eGFR, with a preponderance of metabolic disturbances rather than medication errors or AHRQ PSIs. The differential safety phenotype in blacks versus nonblacks may have implications for preventive strategies to improve patient safety in an integrated health care system.

Objectives Hypertensive patients often are prescribed multiple medications for their hypertension as well as for other chronic conditions. Poor adherence has been both positively and negatively associated with increasing numbers of medications or required daily doses. We sought to determine whether adherence with antihypertensive drugs changes in response to a change in non-antihypertensive pill burden. Methods This retrospective cohort analysis used 2006–2007 US MarketScan Medicare Supplemental and Coordination of Benefits administrative data. The study sample comprised 471 359 beneficiaries diagnosed with hypertension. We measured monthly proportion of days covered (PDC) with antihypertensive medications and average number of daily doses with non-antihypertensive drugs (pill burden). We assessed the effect of changes in pill burden on subsequent changes in antihypertensive PDC using difference equations with sensitivity tests for the sign and magnitude of monthly change in pill burden and the presence of physician visits. Key findings Changes in monthly non-antihypertensive pill burden had essentially no impact on antihypertensive adherence rates for Medicare beneficiaries in retiree health plans. A monthly addition of one non-antihypertensive pill/day resulted in a statistically significant reduction in the following month's antihypertensive medication PDC of approximately one percentage point (−0.98). Similar results were obtained in a 3-month lag model (−0.88). These findings were insensitive to changes in model parameters. Conclusions while physicians should pay close attention to individual factors that may affect their patients' adherence to antihypertensive medications, our findings indicate that changes in medications used to treat concomitant diseases should have little short-term impact on antihypertensive adherence.

Background Medication reconciliation has been recognized as an important process in care transitions to prevent adverse health outcomes. Because older adults have multiple comorbid conditions and use multiple medications, they are more likely to experience complicated transitions between acute and long-term care settings. Hence, it is important to develop effective interventions to protect older adults at transition points of care. Objective To systematically review the literature and evaluate studies performing medication reconciliation interventions in patients transferred to and from long-term care settings. Methods The literature search focused on studies that evaluated an intervention involving medication reconciliation in patients transferred to and/or from long-term care settings, such as nursing homes, skilled nursing facilities, residential care facilities, assisted living facilities, homes for the aged, and hospice care. A search was conducted on Ovid MEDLINE (1950-August 2010), Ovid HealthSTAR (1966-August 2010), Cumulative Index to Nursing and Allied Health Literature (1982-August 2010), PubMed (1980-August 2010), The Cochrane Database of Systematic Reviews (2005-August 2010), the Agency for Healthcare Research and Quality website, and reference lists of relevant articles were hand-searched. Two reviewers screened the titles and abstracts for potentially relevant studies. Data abstraction from the included articles was performed independently by 4 reviewers. Results Seven studies met the inclusion criteria. Four studies were performed in the United States, whereas 3 studies were performed in other countries. A clinical pharmacist proved to be useful in providing medication reconciliation interventions by adopting specialized responsibilities such as serving as a transition pharmacist coordinator or working through a call center. Although improvement in the outcome(s) examined was shown in all of the studies, there were study design flaws. Conclusion There is a need for well-designed studies demonstrating the effectiveness of medication reconciliation interventions in long-term care settings. Future studies should focus on employing appropriate methods so that their interventions can be evaluated more effectively.

Introduction and Committee Charges The Bylaws of the American Association of Colleges of Pharmacy (AACP) state that the Academic Affairs Committee shall consider: the intellectual, social, and personal aspects of pharmaceutical education. It is expected to identify practices, procedures, and

Introduction Identifying factors associated with lower dementia care costs is essential. We examined whether two caregiver factors were associated with lower costs of informal care. Methods A total of 271 care dyads of the Cache County Dementia Study were included. Estimates of informal costs were based on caregiver reports of time spent in care-related activities and inflation-adjusted 2012 Utah median hourly wages. Caregiver coping and emotional closeness with the care-recipient were assessed using the Ways of Coping Checklist–Revised and Relationship Closeness Scale, respectively. Results Higher closeness was associated with 24% lower costs (expβ = 0.763 [95% confidence interval: 0.583–0.999]) in linear mixed models controlling for demographics and baseline dementia severity and duration. Problem-focused coping was not associated with informal costs ( P = .354). Discussion Caregiver closeness, a potentially modifiable factor, predicted lower dementia informal care costs over time. Future studies examining the care environment in closer dyads may identify specific care-related behaviors or strategies that are associated with lower costs.

Older adults with dementia are vulnerable to the central deteriorating effects of drugs with anticholinergic properties (DAPs). These effects include falls and confusion and may exacerbate dementia-related symptoms. Many individuals with dementia also receive acetylcholinesterase inhibitors (AChEIs), indicated for mild to moderate Alzheimer’s disease. AChEIs have opposing effects to DAPs and, consequently, concomitant use of DAPs and AChEIs may further impair cognition among patients with dementia. Our objectives were to (1) evaluate the anticholinergic burden among nursing home (NH) residents with dementia; (2) characterize trends in use of DAPs and concomitant use of DAPs and AChEIs among NH residents with dementia; and (3) identify factors associated with the use of DAPs and concomitant use of DAPs and AChEIs. We conducted a retrospective analysis of Medicare data from 2007 to 2008 linked to the Minimum Data Set. During the study period, 53,805 (77 %) NH residents with dementia used at least one DAP each month. Sixty-seven percent of residents with dementia used Anticholinergic Cognitive Burden Scale (ACBS) level 1 DAPs, 3 % used level 2 DAPs, and 31 % used level 3 DAPs. Thirteen percent of NH residents with dementia concomitantly used ACBS levels 2 or 3 DAPs and AChEIs. This study sheds new light on the prevalence of DAP use and concomitant use of DAPs and AChEIs among NH residents with dementia. Clinicians should consider alternatives with lower anticholinergic effects, particularly in patients already taking DAPs.

RESULTS Medicare beneficiaries with traumatic brain injury were predominantly female (64%) and white (92%), with a mean (SD) age of 81.3 (7.3) years, and 82% had atrial fibrillation. Over the 12 months following hospital discharge, 55% received warfarin during 1 or more 30-day periods. We examined the lagged effect of warfarin use on outcomes in the following period. Warfarin use in the prior period was associated with decreased risk of thrombotic events (relative risk [RR], 0.77 [95% CI, 0.67-0.88]) and increased risk of hemorrhagic events (RR, 1.51 [95% CI, 1.29-1.78]). Warfarin use in the prior period was associated with decreased risk of hemorrhagic or ischemic stroke (RR, 0.83 [95% CI, 0.72-0.96]).

Objective Following traumatic brain injury (TBI), older adults are at an increased risk of hemorrhagic and thromboembolic events, but it is unclear whether the increased risk continues after hospital discharge. We estimated incidence rates of hemorrhagic and ischemic stroke following hospital discharge for TBI among adults 65 years or older and compared them with pre-TBI rates. Participants A total of 16 936 Medicare beneficiaries 65 years or older with a diagnosis of TBI in any position on an inpatient claim between June 1, 2006, and December 31, 2009, who survived to hospital discharge. Design Retrospective analysis of a random 5% sample of Medicare claims data. Main measures Hemorrhagic stroke was defined as ICD-9 (International Classification of Diseases, Ninth Revision) codes 430.xx-432.xx. Ischemic stroke was defined as ICD-9 codes 433.xx-435.xx, 437.0x, and 437.1x. Results There was a 6-fold increase in the rate of hemorrhagic stroke following TBI compared with the pre-TBI period (adjusted rate ratio, 6.5; 95% confidence interval, 5.3-7.8), controlling for age and sex. A smaller increase in the rate of ischemic stroke was observed (adjusted rate ratio, 1.3; 95% CI, 1.2-1.4). Conclusion Future studies should investigate causes of increased stroke risk post-TBI as well as effective treatment options to reduce stroke risk and improve outcomes post-TBI among older adults.

Background Dementia costs are critical for influencing healthcare policy, but limited longitudinal information exists. We examined longitudinal informal care costs of dementia in a population-based sample. Methods Data from the Cache County Study included dementia onset, duration, and severity assessed by the Mini-Mental State Examination (MMSE), Clinical Dementia Rating Scale (CDR), and Neuropsychiatric Inventory (NPI). Informal costs of daily care (COC) was estimated based on median Utah wages. Mixed models estimated the relationship between severity and longitudinal COC in separate models for MMSE and CDR. Results Two hundred and eighty-seven subjects (53% female, mean (standard deviation) age was 82.3 (5.9) years) participated. Overall COC increased by 18% per year. COC was 6% lower per MMSE-point increase and compared with very mild dementia, COC increased over twofold for mild, fivefold for moderate, and sixfold for severe dementia on the CDR. Conclusions Greater dementia severity predicted higher costs. Disease management strategies addressing dementia progression may curb costs.

Summary Background and objectives The Agency for Healthcare and Research Quality patient safety indicators track adverse safety events in hospitalized patients but overlook safety incidents specific to CKD. This study considers candidate CKD-pertinent patient safety indicators and compares them with the Agency for Healthcare and Research Quality patient safety indicators. Design, setting, participants, & measurements Using a national Veterans Health Administration database of hospitalized veterans from fiscal year 2005, 247,160 hospitalized veterans with prehospitalization measures of renal function were retrospectively examined for proposed CKD patient safety indicators versus Agency for Healthcare and Research Quality patient safety indicators using International Classification of Diseases, Ninth Revision diagnosis codes. Candidate CKD-pertinent patient safety indicators included in-hospital acute kidney failure; in-hospital congestive heart failure (and related diagnostic codes); electrolyte disturbances; and medication errors, poisoning, and intoxication. Patients with a prehospital estimated GFR 2 (CKD group) were compared with a non-CKD group. For CKD patient safety indicators, hospitalizations were excluded if the admitting condition was a potential cause of the secondary condition. Regression methods were used to present adjusted rates in study groups of interest. Results The CKD patient safety indicators were generally more common than the Agency for Healthcare and Research Quality patient safety indicators in all groups, tended to occur in different patients than those patients who experienced Agency for Healthcare and Research Quality patient safety indicators, and were more common in the CKD group than the non-CKD group, except for hypoglycemia, hypokalemia, and hyponatremia. The adjusted composite CKD patient safety indicators rate (per 1000 patient-hospitalizations) was 398.0 (95% confidence interval, 391.2 to 405.0) for patients in the CKD group and 250.0 (95% confidence interval, 247.4 to 252.7) for patients in the non-CKD group. The prevalence ratio of CKD patient safety indicators to Agency for Healthcare and Research Quality patient safety indicators was 23.4 (95% confidence interval, 21.9 to 25.0). Conclusion The candidate CKD patient safety indicators that occur in hospitalized patients are distinct from the Agency for Healthcare and Research Quality patient safety indicators and tend to be more common in CKD than non-CKD patients. These measures have the potential to serve as sentinel tools for identifying patients with CKD who warrant examination for disease-pertinent safety events.

Objectives: To describe population-based use of cognitive-enhancing and psychopharmacological medications across care settings in Medicare beneficiaries with dementia. Design: One-year (2008) cross-sectional study. Setting: Medicare administrative claims from a 5% random sample. Participants: Medicare beneficiaries with dementia aged 65 and older with continuous Medicare Parts A, B, and D coverage and alive throughout 2008. To ascertain dementia, one or more medical claims with a dementia International Classification of Diseases, Ninth Revision, Clinical Modification code was required before 2008, and an additional claim was required in 2008 to confirm active disease. Measurements: Use of medications commonly prescribed in managing dementia (cognitive enhancers, antidepressants, antipsychotics, and mood stabilizers) was assessed using three measures: annual prevalence of use, consistency of use, and count of psychopharmacological medication classes. Care setting was determined using the number of months of nursing home (NH) residency: no NH (0 months), partial NH (1�11 months), and full NH (12 months). Results: Community-dwellers represented 41.3% of the cohort, whereas 42.4% and 16.3% resided partially and fully in a NH, respectively. Annual prevalence of use was 57.1% for cognitive enhancers, 56.4% for antidepressants, 34.0% for antipsychotics, and 8.8% for mood stabilizers. Cognitive enhancer use was significantly lower in those with any NH stay (partial NH vs no NH, adjusted prevalence ratio (APR) = 0.84, 99% confidence interval (CI) = 0.83�0.86; full NH vs no NH, APR = 0.83, 99% CI = 0.81�0.85). In contrast, those with any NH residence had significantly higher use of all psychopharmacological medication classes than community-dwellers. More than half the cohort had consistent medication regimens during 2008 (64.8%). The number of psychopharmacological medication classes used increased with increasing NH stay duration. Conclusion: This population-based study documents significant differences in medication use for managing dementia between care settings and substantial use of psychopharmacological medications in older adults with dementia.

Backgrounds Over 50% of antibiotics prescriptions are for outpatients with acute respiratory infections (ARI). Many of them are not needed and thus contribute both avoidable adverse events and pressures toward the development of bacterial resistance. Could a clinical decision support system (CDSS), interposed at the time of electronic prescription, adjust antibiotics utilization toward consensus treatment guidelines for ARI? Methods This is a retrospective comparison of pre- (2002) and post-intervention (2003–2006) periods at two comprehensive health care systems (intervention and control). The intervention was a CDSS that targeted fluoroquinolone and azithromycin; other antibiotics remained unrestricted. 7000 outpatients visits flagged by an ARI case-finding algorithm were reviewed for congruence with the guidelines (antibiotic prescribed-when-warranted or not-prescribed-when-unwarranted). Results 3831 patients satisfied the case definitions for one or more ARI: pneumonia (537), bronchitis (2931), sinusitis (717) and non-specific ARI (145). All patients with pneumonia received antibiotics. The relative risk (RR) of congruent prescribing was 2.57 (95% CI = (1.865 to 3.540) in favor of the intervention site for the antibiotics targeted by the CDSS; congruence did not change for other antibiotics (adjusted RR = 1.18 (95% CI = (0.691 to 2.011)). The proportion of unwarranted prescriptions of the targeted antibiotics decreased from 22% to 3%, pre vs. post-intervention (p

Our objective was to determine how patient demographics and outpatient referrals to specialized dementia (DEM) or mental health (MH) clinics influence receipt of anti-dementia (AD), antidepressant (ADEP), antipsychotic (APSY) and sedative-hypnotic (SEDH) medications among veterans with dementia. Retrospective, cross-sectional observational study. Veterans Affairs Maryland Health Care System (VAMHCS). Veterans aged ≥ 60 years with Alzheimer's or related dementia diagnosis after 1999 with minimum of one-year follow-up or death were included. Retrospective analysis of VAMHCS electronic medical records were used to determine predictors of AD, ADEP, APSY, and SEDH prescribing using logistic regression models that examined visits to DEM or MH clinics, patient age, follow-up time, race/ethnicity and marital status. Among 1209 veterans with average follow-up of 3.2 (SD 1.9) years, 36% percent had MH visits, 38% had DEM visits and 19% visited both clinics. DEM visits were associated with AD and ADEP but not APSY medication receipt (OR(AD:DEM) = 1.47, 95% CI = (1.052, 2.051); OR(ADEP:DEM) = 1.66, 95% CI = (1.193, 2.302); OR(APSY:DEM) = 1.35, 95% CI = (0.941, 1.929)). MH visit was associated with ADEP and APSY medication receipt (OR(AD:MH)/ = 1.16, 95% CI = (0.821, 1.631); OR(ADEP:MH) = 2.83, 95% CI = (2.005, 4.005); OR (APSY:MH) = 4.41, 95% CI = (3.109, 6.255)). In the VAMHCS dementia population, visits to DEM or MH specialty clinics increase the odds of receiving AD, ADEP, and APSY medications.

Author(s): Rattinger, Gail; Bero, Lisa | Abstract: BackgroundWhen a sponsor funds a study of two competing drugs in a head-to-head comparison, the results and conclusions are likely to favor the sponsor's drug. Thiazolidinediones, oral medications used for the treatment of type 2 diabetes, are one of the most costly choices of oral anti-diabetic medications, yet they do not demonstrate clinically relevant differences in achieving lower glycosylated hemoglobin levels compared to other oral antidiabetic drugs. Our aim is to examine associations between research funding source, study design characteristics aimed at reducing bias, and other factors with the results and conclusions of randomized controlled trials (RCTs) of thiazolidinediones compared to other oral hypoglycemic agents.Methods and findingsThis is a cross-sectional study of 61 published RCTs comparing a thiazolidinedione (glitazone) to another anti-diabetic drug or placebo for treatment of type 2 diabetes. Data on study design characteristics, funding source, author's financial ties, results for primary outcomes, and author conclusions were extracted. Univariate logistic regression identified associations between independent variables and results and conclusions that favored the glitazone. Of the RCTs, 59% (36/61) were funded by industry, 39% (24/61) did not disclose any funding. Common study design weaknesses included inadequate blinding and lack of concealment of allocation. Trials that reported favorable glycemic control results for the glitazone were more likely to have adequate blinding (OR (95% CI) = 5.42 (1.46, 21.19), p = 0.008) and have a corresponding author with financial ties to the glitazone manufacturer (OR (95% CI) = 4.12 (1.05, 19.53); p = 0.04). Trials with conclusions favoring the glitazone were less likely to be funded by a comparator drug company than a glitazone company (OR (95% CI) = 0.026 (0, 0.40), p = 0.003) and less likely to be published in journals with higher impact factors (OR (95% CI) = 0.79 (0.62, 0.97), p = 0.011). One limitation of our study is that we categorized studies as funded by industry based on each article's disclosure which could underestimate the number of industry sponsored studies and personal ties of investigators. Additionally, our study did not include any head-to-head comparisons of one glitazone to another.ConclusionsPublished RCT comparisons of glitazones with other anti-diabetic drugs or placebo are predominantly industry supported and this support, as well as the financial ties of study authors, appears to be associated with favorable findings.

Background: Intensive lipid-lowering therapy reduces cardiovascular (CV) event rates more than moderate therapy. Currently available generic statins cost less but provide less risk reduction. Objective: Our goal was to calculate the incremental cost-effectiveness ratio (ICER) comparing an intensive atorvastatin-based regimen versus usual care, defined as prevalent statin therapy used at the time of the Aggressive Lipid-Lowering Initiation Abates New Cardiac Events (ALLIANCE) study—a trial of usual community practice that was conducted among patients enrolled in managed-care plans. Methods: A 7-year cost model incorporated patient-level CV event rates and mortality data from the ALLIANCE study. To address the managed-care perspective, costs for clinical end points were estimated from administrative claims data for equivalent events. Direct medical costs included drugs, acute events, and a maximum of 36 months of follow-up costs. Average wholesale pricing was used for drug costs. Differences in patient copayments were incorporated and a 3 % discount factor was applied. Scenario analyses explored 3- and 5-year time frames, varying discount rates, drug costs, and copayment assumptions. Results: The baseline ICER using all events examined in the ALLIANCE study and a 7-year time frame was US $10,344 (year-2007 value) per event avoided. Over 7 years, the number needed to treat to avoid a clinical end point was 11 patients. Using a realworld economic model that considered atorvastatin becoming generic in 3 years, starting patients on branded and converting them to generic atorvastatin would be a cost-saving strategy compared with current generic statin use. Conclusions: Intensive lipid-lowering using atorvastatin increased prescription drug costs of treating CV disease patients but reduced CV events. Medical cost offsets associated with reduced events, based on data from the ALLIANCE study, resulted in ICERs within accepted cost-effectiveness ranges comparing atorvastatin with a generic statin. Atorvastatin-based regimens produced cost savings from a managed-care perspective when the anticipated impact of the generic availability of atorvastatin was modeled.

Many pharmacy schools have increased the amount of economics coursework to which pharmacy students are exposed in their prepharmacy and pharmacy curriculums. Students obtain competencies aimed at understanding the basic concepts of microeconomic theory, such as supply and demand. However, pharmacy students often have trouble applying these principles to real world pharmaceuticals or healthcare markets. Our objective is to make economics more relevant for pharmacy students. Specifically, we detail and provide pharmacy-relevant examples of the effects of monopoly power, barriers to marketplace entry, regulatory environment, third party insurance, information asymmetry and unanticipated changes in the marketplace on the supply and demand for pharmaceuticals and healthcare services.

radical~-'Mn(CO)~(P(n-Bu)~)~, 'Mn(CO)3(P(i-Bu)3)2, 'Mn(CO)3(P(i-Pr)3)2, and 'MII(CO),(P(O-~-P~)~)~. Anisotropic g shifts and metal hyperfine and phosphorus superhyperfine spin Hamiltonian parameters are reported and compared to values reported in the literature for 'Mn(CO)5. It is thus possible to examine some of the effects of varying ligand, geometry, and electronic parameters upon the characteristics of the EPR spectra obtained and upon the unpaired spin density localized in the manganese 3d9 and 4s metal orbitals and delocalized onto the phosphorus ligands. An LCAO-MO perturbation treatment of g and A values for these square-pyramidal d7 systems yields reasonable estimates of the distribution of unpaired spin density, upper and lower limits of core polarization, and the energy difference, AE, between the ground state and d?r excited state. of metal-centered organometallic species in hydride abstraction,8-lo electron transfers,11-13 ligand substituti~ns,~~~-~~~~l~-'~ atom transfer^?^^^'^ and oxidative additions/reductive elimination~.~J~ Because of rapid radical recombination it is difficult to prepare persistent zerovalent manganese-centered radicals: consequently, few examples are found in the literature?,l0 Persistent Mn(C0)3L2 metal-centered radicals have been generated, where the ligand, L, is either a tertiary phosphine or pho~phite.~J~J~ These species are isoelectronic with the pentacyanocobaltate radical anion, CO(CN)~~-, a well-characterized radical,6 and with the unsub- stituted manganese(0) pentacarbonyl radical.21v22 This paper presents a characterization via multifrequency EPR spectroscopy of a series of 'Mn(CO),L, radicals. We chose to study 'Mn- (CO)~(P(~-BU)~I~ , 'Mn(CO)dP(i-Bu)31,, 'Mn(CO)3(p(i-pr)312, and 'Mn(C0)3(P(O-i-Pr)3), in order to examine the effects of varying steric and electronic parameter~~~,~~ upon the charac- teristics of the EPR spectra obtained and upon the unpaired spin density localized in the manganese 3d,z and 4s metal orbitals and delocalized onto the phosphorus ligands. Anisotropic g shifts and metal hyperfine and phosphorus superhyperfine spin Hamiltonian parameters are reported and compared to values reported for 'Mn(C0)5.21 An LCAO-MO perturbation treatment of g and A values for these square-pyramidal d7 systems yields reasonable estimates of the distribution of unpaired spin density, upper and lower limits of core polarization, and the energy difference, AE, between the ground state and da excited state. A less detailed study of 'Mn(C0)3L2 radicals has previously appeared.25