Patient Outcomes After Delirium Screening and Incident Alzheimer's Disease or Related Dementias in Skilled Nursing Facilities.

BACKGROUND: The extent to which a positive delirium screening and new diagnosis of Alzheimer's disease or related dementias (ADRD) increases the risk for re-hospitalization, long-term nursing home placement, and death remains unknown. OBJECTIVE: To compare long-term outcomes among newly admitted skilled nursing facility (SNF) patients with delirium, incident ADRD, and both conditions. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of Medicare beneficiaries who entered a SNF from hospital with a minimum 14-day stay (n = 100,832) from 2015 to 2016. MAIN MEASURES: Return to home, hospital readmission, admission to a long-term care facility, or death. KEY RESULTS: Patients with delirium were as likely to be discharged home as patients diagnosed with ADRD (HR: 0.63, 95% CI: 0.59, 0.67; HR: 0.65, 95% CI: 0.64, 0.67). Patients with both delirium and ADRD were less likely to be discharged home (HR: 0.49, 95% CI: 0.47, 0.52) and showed increased risk of death (HR: 1.30, 95% CI: 1.17, 1.45). Patients with ADRD, regardless of delirium screening status, had increased risk for long-term nursing home care transfer (HR: 1.66, 95% CI: 1.63, 1.70; HR: 1.76, 95% CI: 1.69, 1.82). Patients with delirium and no ADRD showed increased risk of transfer to long-term nursing home care (HR: 1.25, 95% CI: 1.18, 1.33). The rate of deaths was higher among patients who screened positive for delirium without ADRD compared to the no delirium and no ADRD groups (HR: 2.35, 95% CI: 2.11, 2.61). CONCLUSION: A positive delirium screening increased risk of death and transfer to long-term care in the first 100 days after admission regardless of incident ADRD diagnosis. Patients with delirium and/or ADRD also are less likely to be discharged home. Our study builds on the evidence base that delirium is important to address in older adults as it is associated with negative outcomes.

Medication cost-reducing behaviors in older adults with atrial fibrillation: The SAGE-AF study.

BACKGROUND: As patient prices for many medications have risen steeply in the United States, patients may engage in cost-reducing behaviors (CRBs) such as asking for generic medications or purchasing medication from the Internet. OBJECTIVE: The objective of this study is to describe patterns of CRB, cost-related medication nonadherence, and spending less on basic needs to afford medications among older adults with atrial fibrillation (AF) and examine participant characteristics associated with CRB. METHODS: Data were from a prospective cohort study of older adults at least 65 years with AF and a high stroke risk (CHA2DS2VASc ≥ 2). CRB, cost-related medication nonadherence, and spending less on basic needs to afford medications were evaluated using validated measures. Chi-square and t tests were used to evaluate differences in characteristics across CRB, and statistically significant characteristics (P < 0.05) were entered into a multivariable logistic regression to examine factors associated with CRB. RESULTS: Among participants (N = 1224; mean age 76 years; 49% female), 69% reported engaging in CRB, 4% reported cost-related medication nonadherence, and 6% reported spending less on basic needs. Participants who were cognitively impaired (adjusted odds ratio 0.69 [95% CI 0.52-0.91]) and those who did not identify as non-Hispanic white (0.66 [0.46-0.95]) were less likely to engage in CRB. Participants who were married (1.88 [1.30-2.72]), had a household income of $20,000-$49,999 (1.52 [1.02-2.27]), had Medicare insurance (1.38 [1.04-1.83]), and had 4-6 comorbidities (1.43 [1.01-2.01]) had significantly higher odds of engaging in CRB. CONCLUSION: Although CRBs were common among older adults with AF, few reported cost-related medication nonadherence and spending less on basic needs. Patients with cognitive impairment may benefit from pharmacist intervention to provide support in CRB and patient assistance programs.

Association Between Perioperative Medication Use and Postoperative Delirium and Cognition in Older Adults Undergoing Elective Noncardiac Surgery.

BACKGROUND: Postoperative delirium is frequent in older adults and is associated with postoperative neurocognitive disorder (PND). Studies evaluating perioperative medication use and delirium have generally evaluated medications in aggregate and been poorly controlled; the association between perioperative medication use and PND remains unclear. We sought to evaluate the association between medication use and postoperative delirium and PND in older adults undergoing major elective surgery. METHODS: This is a secondary analysis of a prospective cohort study of adults ≥70 years without dementia undergoing major elective surgery. Patients were interviewed preoperatively to determine home medication use. Postoperatively, daily hospital use of 7 different medication classes listed in guidelines as risk factors for delirium was collected; administration before delirium was verified. While hospitalized, patients were assessed daily for delirium using the Confusion Assessment Method and a validated chart review method. Cognition was evaluated preoperatively and 1 month after surgery using a neurocognitive battery. The association between prehospital medication use and postoperative delirium was assessed using a generalized linear model with a log link function, controlling for age, sex, type of surgery, Charlson comorbidity index, and baseline cognition. The association between daily postoperative medication use (when class exposure ≥5%) and time to delirium was assessed using time-varying Cox models adjusted for age, sex, surgery type, Charlson comorbidity index, Acute Physiology and Chronic Health Evaluation (APACHE)-II score, and baseline cognition. Mediation analysis was utilized to evaluate the association between medication use, delirium, and cognitive change from baseline to 1 month. RESULTS: Among 560 patients enrolled, 134 (24%) developed delirium during hospitalization. The multivariable analyses revealed no significant association between prehospital benzodiazepine (relative risk [RR], 1.44; 95% confidence interval [CI], 0.85-2.44), beta-blocker (RR, 1.38; 95% CI, 0.94-2.05), NSAID (RR, 1.12; 95% CI, 0.77-1.62), opioid (RR, 1.22; 95% CI, 0.82-1.82), or statin (RR, 1.34; 95% CI, 0.92-1.95) exposure and delirium. Postoperative hospital benzodiazepine use (adjusted hazard ratio [aHR], 3.23; 95% CI, 2.10-4.99) was associated with greater delirium. Neither postoperative hospital antipsychotic (aHR, 1.48; 95% CI, 0.74-2.94) nor opioid (aHR, 0.82; 95% CI, 0.62-1.11) use before delirium was associated with delirium. Antipsychotic use (either presurgery or postsurgery) was associated with a 0.34 point (standard error, 0.16) decrease in general cognitive performance at 1 month through its effect on delirium (P = .03), despite no total effect being observed. CONCLUSIONS: Administration of benzodiazepines to older adults hospitalized after major surgery is associated with increased postoperative delirium. Association between inhospital, postoperative medication use and cognition at 1 month, independent of delirium, was not detected.

Opioid Use Increases the Risk of Delirium in Critically Ill Adults Independently of Pain.

Rationale: It is unclear whether opioid use increases the risk of ICU delirium. Prior studies have not accounted for confounding, including daily severity of illness, pain, and competing events that may preclude delirium detection.Objectives: To evaluate the association between ICU opioid exposure, opioid dose, and delirium occurrence.Methods: In consecutive adults admitted for more than 24 hours to the ICU, daily mental status was classified as awake without delirium, delirium, or unarousable. A first-order Markov model with multinomial logistic regression analysis considered four possible next-day outcomes (i.e., awake without delirium, delirium, unarousable, and ICU discharge or death) and 11 delirium-related covariables (baseline: admission type, age, sex, Acute Physiology and Chronic Health Evaluation IV score, and Charlson comorbidity score; daily: ICU day, modified Sequential Organ Failure Assessment, ventilation use, benzodiazepine use, and severe pain). This model was used to quantify the association between opioid use, opioid dose, and delirium occurrence the next day.Measurements and Main Results: The 4,075 adults had 26,250 ICU days; an opioid was administered on 57.0% (n = 14,975), severe pain occurred on 7.0% (n = 1,829), and delirium occurred on 23.5% (n = 6,176). Severe pain was inversely associated with a transition to delirium (odds ratio [OR] 0.72; 95% confidence interval [CI], 0.53-0.97). Any opioid administration in awake patients without delirium was associated with an increased risk for delirium the next day [OR, 1.45; 95% CI, 1.24-1.69]. Each daily 10-mg intravenous morphine-equivalent dose was associated with a 2.4% increased risk for delirium the next day.Conclusions: The receipt of an opioid in the ICU increases the odds of transitioning to delirium in a dose-dependent fashion.

Association Between Incident Delirium Treatment With Haloperidol and Mortality in Critically Ill Adults.

OBJECTIVES: Haloperidol is commonly administered in the ICU to reduce the burden of delirium and its related symptoms despite no clear evidence showing haloperidol helps to resolve delirium or improve survival. We evaluated the association between haloperidol, when used to treat incident ICU delirium and its symptoms, and mortality. DESIGN: Post hoc cohort analysis of a randomized, double-blind, placebo-controlled, delirium prevention trial. SETTING: Fourteen Dutch ICUs between July 2013 and December 2016. PATIENTS: One-thousand four-hundred ninety-five critically ill adults free from delirium at ICU admission having an expected ICU stay greater than or equal to 2 days. INTERVENTIONS: Patients received preventive haloperidol or placebo for up to 28 days until delirium occurrence, death, or ICU discharge. If delirium occurred, treatment with open-label IV haloperidol 2 mg tid (up to 5 mg tid per delirium symptoms) was administered at clinician discretion. MEASUREMENTS AND MAIN RESULTS: Patients were evaluated tid for delirium and coma for 28 days. Time-varying Cox hazards models were constructed for 28-day and 90-day mortality, controlling for study-arm, delirium and coma days, age, Acute Physiology and Chronic Health Evaluation-II score, sepsis, mechanical ventilation, and ICU length of stay. Among the 1,495 patients, 542 (36%) developed delirium within 28 days (median [interquartile range] with delirium 4 d [2-7 d]). A total of 477 of 542 (88%) received treatment haloperidol (2.1 mg [1.0-3.8 mg] daily) for 6 days (3-11 d). Each milligram of treatment haloperidol administered daily was associated with decreased mortality at 28 days (hazard ratio, 0.93; 95% CI, 0.91-0.95) and 90 days (hazard ratio, 0.97; 95% CI, 0.96-0.98). Treatment haloperidol administered later in the ICU course was less protective of death. Results were stable by prevention study-arm, predelirium haloperidol exposure, and haloperidol treatment protocol adherence. CONCLUSIONS: Treatment of incident delirium and its symptoms with haloperidol may be associated with a dose-dependent improvement in survival. Future randomized trials need to confirm these results.

Cost-related Medication Nonadherence and Its Risk Factors Among Medicare Beneficiaries.

BACKGROUND: Unaffordability of medications is a barrier to effective treatment. Cost-related nonadherence (CRN) is a crucial, widely used measure of medications access. OBJECTIVES: Our study examines the current national prevalence of and risk factors for CRN (eg, not filling, skipping or reducing doses) and companion measures in the US Medicare population. RESEARCH DESIGN: Survey-weighted analyses included logistic regression and trends 2006-2016. SUBJECTS: Main analyses used the 2016 Medicare Current Beneficiary Survey. Our study sample of 12,625 represented 56 million community-dwelling beneficiaries. MEASURES: Additional outcome measures were spending less on other necessities in order to pay for medicines and use of drug cost reduction strategies such as requesting generics. RESULTS: In 2016, 34.5% of enrollees under 65 years with disability and 14.4% of those 65 years and older did not take their medications as prescribed due to high costs; 19.4% and 4.7%, respectively, experienced going without other essentials to pay for medicines. Near-poor older beneficiaries with incomes $15-25K had 50% higher odds of CRN (vs. >$50K), but beneficiaries with incomes <$15K, more likely to be eligible for the Part D Low-Income Subsidy, did not have significantly higher risk. Three indicators of worse health (general health status, functional limits, and count of conditions) were all independently associated with higher risk of CRN. CONCLUSIONS: Changes in the risk profile for CRN since Part D reflect the effectiveness of targeted policies. The persistent prevalence of CRN and associated risks for sicker people in Medicare demonstrate the consequences of high cost-sharing for prescription fills.

Association between incident delirium and 28- and 90-day mortality in critically ill adults: a secondary analysis.

BACKGROUND: While delirium prevalence and duration are each associated with increased 30-day, 6-month, and 1-year mortality, the association between incident ICU delirium and mortality remains unclear. We evaluated the association between both incident ICU delirium and days spent with delirium in the 28 days after ICU admission and mortality within 28 and 90 days. METHODS: Secondary cohort analysis of a randomized, double-blind, placebo-controlled trial conducted among 1495 delirium-free, critically ill adults in 14 Dutch ICUs with an expected ICU stay ≥2 days where all delirium assessments were completed. In the 28 days after ICU admission, patients were evaluated for delirium and coma 3x daily; each day was coded as a delirium day [≥1 positive Confusion Assessment Method for the ICU (CAM-ICU)], a coma day [no delirium and ≥ 1 Richmond Agitation Sedation Scale (RASS) score ≤ - 4], or neither. Four Cox-regression models were constructed for 28-day mortality and 90-day mortality; each accounted for potential confounders (i.e., age, APACHE-II score, sepsis, use of mechanical ventilation, ICU length of stay, and haloperidol dose) and: 1) delirium occurrence, 2) days spent with delirium, 3) days spent in coma, and 4) days spent with delirium and/or coma. RESULTS: Among the 1495 patients, 28 day mortality was 17% and 90 day mortality was 21%. Neither incident delirium (28 day mortality hazard ratio [HR] = 1.02, 95%CI = 0.75-1.39; 90 day mortality HR = 1.05, 95%CI = 0.79-1.38) nor days spent with delirium (28 day mortality HR = 1.00, 95%CI = 0.95-1.05; 90 day mortality HR = 1.02, 95%CI = 0.98-1.07) were significantly associated with mortality. However, both days spent with coma (28 day mortality HR = 1.05, 95%CI = 1.02-1.08; 90 day mortality HR = 1.05, 95%CI = 1.02-1.08) and days spent with delirium or coma (28 day mortality HR = 1.03, 95%CI = 1.00-1.05; 90 day mortality HR = 1.03, 95%CI = 1.01-1.06) were significantly associated with mortality. CONCLUSIONS: This analysis suggests neither incident delirium nor days spent with delirium are associated with short-term mortality after ICU admission. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier NCT01785290 Registered 7 February 2013.

Nursing homes underreport antipsychotic prescribing.

Objective: Determine the accuracy of nursing home self-reported antipsychotic prescribing before and after implementation of a Medicare campaign to reduce use.Methods: Quasi-experimental study comparing trends in self-reported antipsychotic prescribing relative to claims-based prescribing. Setting is a nationwide sample of 11,912 facilities, 2011-2013. Participants are long-stay nursing home residents (n = 586,281) with prescribing data in Medicare Minimum Data Set 3.0 and Medicare Part D claims database. Verified with a pharmacy dispensing database. Main outcomes are the discrepancies in quarterly prevalence of antipsychotic prescribing between nursing home self-reports and claims data and the characteristics of facilities and residents where discrepancies were identified.Results: Nursing homes underreport their antipsychotic prescribing levels, on average, by 1 percentage point per quarter relative to Medicare Part D claims (0.013, 95% confidence interval (CI), 0.012-0.015; p<.001). After the Medicare campaign, the underreporting gap increased by another half a percentage point (0.004, 95% CI .003-.005; p = .012). Nursing home residents with dementia, Alzheimer's disease or bipolar disorders were at the highest risk for underreported antipsychotic prescribing before the campaign (Adjusted Odds ratio (AOR) 1.385, 95% CI: 1.330-1.444; AOR 1.234, 95% CI: 1.172-1.300; AOR 1.574, 95% CI: 1.444-1.716, respectively) and afterwards. After the launch of the Medicare campaign, underreported antipsychotic prescribing occurred most in for-profit nursing homes (AOR 1.088, 95% CI: 1.005-1.178) and facilities in the US South (AOR 1.262, 95% CI: 1.145-1.391). Agreement was high between claims and dispensing data (99.7%).Conclusion: Nursing homes did not identify up to 6,000 residents per calendar quarter as having received antipsychotics despite these prescriptions being paid by Medicare and dispensed by a pharmacy. Nursing home rates of antipsychotic prescribing from self-reported data may be biased.

Did Medicare Part D Affect National Trends in Health Outcomes or Hospitalizations? A Time-Series Analysis.

BACKGROUND: Medicare Part D increased economic access to medications, but its effect on population-level health outcomes and use of other medical services remains unclear. OBJECTIVE: To examine changes in health outcomes and medical services in the Medicare population after implementation of Part D. DESIGN: Population-level longitudinal time-series analysis with generalized linear models. SETTING: Community. PATIENTS: Nationally representative sample of Medicare beneficiaries (n = 56,293 [unweighted and unique]) from 2000 to 2010. MEASUREMENTS: Changes in self-reported health status, limitations in activities of daily living (ADLs) (ADLs and instrumental ADLs), emergency department visits and hospital admissions (prevalence, counts, and spending), and mortality. Medicare claims data were used for confirmatory analyses. RESULTS: Five years after Part D implementation, no clinically or statistically significant reductions in the prevalence of fair or poor health status or limitations in ADLs or instrumental ADLs, relative to historical trends, were detected. Compared with trends before Part D, no changes in emergency department visits, hospital admissions or days, inpatient costs, or mortality after Part D were seen. Confirmatory analyses were consistent. LIMITATIONS: Only total population-level outcomes were studied. Self-reported measures may lack sensitivity. CONCLUSION: Five years after implementation, and contrary to previous reports, no evidence was found of Part D's effect on a range of population-level health indicators among Medicare enrollees. Further, there was no clear evidence of gains in medical care efficiencies.

Approaches to Gradual Dose Reduction of Chronic Off-Label Antipsychotics Used for Behavioral and Psychological Symptoms of Dementia.

OBJECTIVE: Little is known about how to best taper antipsychotics used in patients with dementia. To address this gap, we reviewed published antipsychotic discontinuation trials to summarize what is known about tapering strategies for antipsychotics used with older adults with dementia. We further developed pharmacokinetic-based gradual dose reduction (GDR) protocols based on antipsychotic half-lives. DATA SOURCES: MEDLINE, EMBASE, and International Pharmaceutical Abstracts were searched up to October 2014 to identify intervention studies reporting the behavioral and psychological symptoms of dementia outcomes resulting from discontinued off-label use of antipsychotics in nursing facility populations. Recently published pharmacokinetic reviews and standard pharmacology texts were used to determine antipsychotic drug half-lives for the pharmacokinetic-based GDR protocols. STUDY SELECTION: For the review, studies with an intervention resulting in antipsychotic medication discontinuation or tapering were eligible, including randomized controlled trials and pre- and post-intervention studies. DATA EXTRACTION: When available, we extracted the protocols used for antipsychotic GDR from each study included in the review. DATA SYNTHESIS: We found that clinical trials used different approaches to antipsychotic discontinuation, including abrupt discontinuation, slow tapers (more than two weeks), and mixed strategies based on drug dosage. None of the published trials described an approach based on pharmacokinetic principles. We developed a two-stage GDR protocol for tapering antipsychotic medications based on the log dose-response relationship; each stage was designed to result in a 50% dose reduction prior to discontinuation. This pharmacologically based strategy for patients chronically prescribed antipsychotics resulted in recommendations for slow tapers. CONCLUSION: Our theoretically derived GDR recommendations suggest a different approach than previously published in clinical trials. Further study is needed to evaluate the effect of this approach on patients.

Persistent medication affordability problems among disabled Medicare beneficiaries after Part D, 2006-2011.

BACKGROUND: Disabled Americans who qualify for Medicare coverage typically have multiple chronic conditions, are highly dependent on effective drug therapy, and have limited financial resources, putting them at risk for cost-related medication nonadherence (CRN). Since 2006, the Part D benefit has helped Medicare beneficiaries afford medications. OBJECTIVE: To investigate recent national trends in medication affordability among this vulnerable population, stratified by morbidity burden. DESIGN AND SUBJECTS: We estimated annual rates of medication affordability among nonelderly disabled participants in a nationally representative survey (2006-2011, n=14,091 person-years) using multivariate logistic regression analyses. MEASURE: Survey-reported CRN and spending less on other basic needs to afford medicines. RESULTS: In the 6 years following Part D implementation, the proportion of disabled Medicare beneficiaries reporting CRN ranged from 31.6% to 35.6%, while the reported prevalence of spending less on other basic needs to afford medicines ranged from 17.7% to 21.8%. Across study years, those with multiple chronic conditions had consistently worse affordability problems. In 2011, the prevalence of CRN was 37.3% among disabled beneficiaries with ≥ 3 morbidities as compared with 28.1% among those with fewer morbidities; for spending less on basic needs, the prevalence was 25.4% versus 15.7%, respectively. There were no statistically detectable changes in either measure when comparing 2011 with 2007. CONCLUSIONS: Disabled Medicare beneficiaries continue to struggle to afford prescription medications. There is an urgent need for focused policy attention on this vulnerable population, which has inadequate financial access to drug treatments, despite having drug coverage under Medicare Part D.

Cognitive and functional change in skilled nursing facilities: Differences by delirium and Alzheimer's disease and related dementias.

BACKGROUND: Whether cognitive and functional recovery in skilled nursing facilities (SNF) following hospitalization differs by delirium and Alzheimer's disease related dementias (ADRD) has not been examined. OBJECTIVE: To compare change in cognition and function among short-stay SNF patients with delirium, ADRD, or both. DESIGN: Retrospective cohort study using claims data from 2011 to 2013. SETTING: Centers for Medicare and Medicaid certified SNFs. PARTICIPANTS: A total of 740,838 older adults newly admitted to a short-stay SNF without prevalent ADRD who had at least two assessments of cognition and function. MEASUREMENTS: Incident delirium was measured by the Minimum Data Set (MDS) Confusion Assessment Method and ICD-9 codes, and incident ADRD by ICD-9 codes and MDS diagnoses. Cognitive improvement was a better or maximum score on the MDS Brief Interview for Mental Status, and functional recovery was a better or maximum score on the MDS Activities of Daily Living Scale. RESULTS: Within 30 days of SNF admission, the rate of cognitive improvement in patients with both delirium/ADRD was half that of patients with neither delirium/ADRD (HR = 0.45, 95% CI:0.43, 0.46). The ADRD-only and delirium-only groups also were 43% less likely to have improved cognition or function compared to those with neither delirium/ADRD (HR = 0.57, 95% CI:0.56, 0.58 and HR = 0.57, 95% CI:0.55, 0.60, respectively). Functional improvement was less likely in patients with both delirium/ADRD, as well (HR = 0.85, 95% CI:0.83, 0.87). The ADRD only and delirium only groups were also less likely to improve in function (HR = 0.93, 95% CI:0.92, 0.94 and HR = 0.92, 95% CI:0.90, 0.93, respectively) compared to those with neither delirium/ADRD. CONCLUSIONS: Among older adults without dementia admitted to SNF for post-acute care following hospitalization, a positive screen for delirium and a new diagnosis of ADRD, within 7 days of SNF admission, were both significantly associated with worse cognitive and functional recovery. Patients with both delirium and new ADRD had the worst cognitive and functional recovery.

Reported racial discrimination, trust in physicians, and medication adherence among inner-city African Americans with hypertension.

OBJECTIVES: We sought to determine if reported racial discrimination was associated with medication nonadherence among African Americans with hypertension and if distrust of physicians was a contributing factor. METHODS: Data were obtained from the TRUST project conducted in Birmingham, Alabama, 2006 to 2008. All participants were African Americans diagnosed with hypertension and receiving care at an inner city, safety net setting. Three categories of increasing adherence were defined based on the Morisky Medication Adherence Scale. Trust in physicians was measured with the Hall General Trust Scale, and discrimination was measured with the Experiences of Discrimination Scale. Associations were quantified by ordinal logistic regression, adjusting for gender, age, education, and income. RESULTS: The analytic sample consisted of 227 African American men and 553 African American women, with a mean age of 53.7 ± 9.9 years. Mean discrimination scores decreased monotonically across increasing category of medication adherence (4.1, 3.6, 2.9; P = .025), though the opposite was found for trust scores (36.5, 38.5, 40.8; P < .001). Trust mediated 39% (95% confidence interval = 17%, 100%) of the association between discrimination and medication adherence. CONCLUSIONS: Within our sample of inner city African Americans with hypertension, racial discrimination was associated with lower medication adherence, and this association was partially mediated by trust in physicians. Patient, physician and system approaches to increase "earned" trust may enhance existing interventions for promoting medication adherence.

A critical review of methods to evaluate the impact of FDA regulatory actions.

PURPOSE: To conduct a synthesis of the literature on methods to evaluate the impacts of FDA regulatory actions and identify best practices for future evaluations. METHODS: We searched MEDLINE for manuscripts published between January 1948 and August 2011 that included terms related to FDA, regulatory actions, and empirical evaluation; the review additionally included FDA-identified literature. We used a modified Delphi method to identify preferred methodologies. We included studies with explicit methods to address threats to validity and identified designs and analytic methods with strong internal validity that have been applied to other policy evaluations. RESULTS: We included 18 studies out of 243 abstracts and papers screened. Overall, analytic rigor in prior evaluations of FDA regulatory actions varied considerably; less than a quarter of studies (22%) included control groups. Only 56% assessed changes in the use of substitute products/services, and 11% examined patient health outcomes. Among studies meeting minimal criteria of rigor, 50% found no impact or weak/modest impacts of FDA actions and 33% detected unintended consequences. Among those studies finding significant intended effects of FDA actions, all cited the importance of intensive communication efforts. There are preferred methods with strong internal validity that have yet to be applied to evaluations of FDA regulatory actions. CONCLUSIONS: Rigorous evaluations of the impact of FDA regulatory actions have been limited and infrequent. Several methods with strong internal validity are available to improve trustworthiness of future evaluations of FDA policies.

The incident user design in comparative effectiveness research.

Comparative effectiveness research includes cohort studies and registries of interventions. When investigators design such studies, how important is it to follow patients from the day they initiated treatment with the study interventions? Our article considers this question and related issues to start a dialogue on the value of the incident user design in comparative effectiveness research. By incident user design, we mean a study that sets the cohort's inception date according to patients' new use of an intervention. In contrast, most epidemiologic studies enroll patients who were currently or recently using an intervention when follow-up began. We take the incident user design as a reasonable default strategy because it reduces biases that can impact non-randomized studies, especially when investigators use healthcare databases. We review case studies where investigators have explored the consequences of designing a cohort study by restricting to incident users, but most of the discussion has been informed by expert opinion, not by systematic evidence.

Associations of state-level and county-level hate crimes with individual-level cardiovascular risk factors in a prospective cohort study of middle-aged Americans: the National Longitudinal Survey of Youths 1979.

BACKGROUND: There have been long-standing debates about the potential health consequences of hate crimes over and above other types of crimes. Besides the direct consequences for victims, less is known about whether hate crimes have spillover effects onto the health of local residents. METHODS: We drew data on cardiovascular disease risk factors from middle-aged Americans in the National Longitudinal Survey of Youths 1979 and on hate crimes from the FBI's Uniform Crime Reports. Employing multivariable logistic regression, we estimated the associations between changes in state/county-level all and group-specific hate crime rates from 2000 to 2006 and incident individual-level diabetes, hypertension, obesity and depressive symptoms from 2008 to 2016. All models controlled for individual-level sociodemographic factors and financial strain, county-level and state-level changes in the total crime rate, the percentage of non-Hispanic Black and Hispanic/Latino residents, and median household income, as well as state-level changes in the percentage of residents aged 65 years or older and the unemployment rate. RESULTS: 1-SD increases in state-level all and race/ethnicity-based hate crime rates were associated with 20% (OR 1.20, 95% CI 1.05 to 1.35) and 15% higher odds (OR 1.15, 95% CI 1.01 to 1.31) of incident diabetes, respectively. At the county level, a 1-SD increase in the all hate crime rate was linked to 8% higher odds (OR 1.08, 95% CI 1.00 to 1.16) of obesity, while a 1-SD increase in the race/ethnicity-based hate crime rate was associated with 8% higher odds (OR 1.08, 95% CI 1.01 to 1.15) of obesity and 9% higher odds (OR 1.09, 95% CI 1.02 to 1.17) of hypertension. We found no significant associations for depressive symptoms, and no interactions between race/ethnicity-based hate crime rates and individual-level race/ethnicity. CONCLUSION: Living in areas with higher hate crime rates may confer higher odds of hypertension, diabetes and obesity.

Psychoactive medication therapy and delirium screening in skilled nursing facilities.

BACKGROUND: A positive delirium screen at skilled-nursing facility (SNF) admission can trigger a simultaneous diagnosis of Alzheimer's Disease or related dementia (AD/ADRD) and lead to psychoactive medication treatment despite a lack of evidence supporting use. METHODS: This was a nationwide historical cohort study of 849,086 Medicare enrollees from 2011-2013 who were admitted to the SNF from a hospital without a history of dementia. Delirium was determined through positive Confusion Assessment Method screen and incident AD/ADRD through active diagnosis or claims. Cox proportional hazard models predicted the risk of receiving one of three psychoactive medications (i.e., antipsychotics, benzodiazepines, antiepileptics) within 7 days of SNF admission and within the entire SNF stay. RESULTS: Of 849,086 newly-admitted SNF patients (62.6% female, mean age 78), 6.1% had delirium (of which 35.4% received an incident diagnosis of AD/ADRD); 12.6% received antipsychotics, 30.4% benzodiazepines, and 5.8% antiepileptics. Within 7 days of admission, patients with delirium and incident dementia were more likely to receive an antipsychotic (relative risk [RR] 3.09; 95% confidence interval [CI] 2.99 to 3.20), or a benzodiazepine (RR 1.23; 95% CI 1.19 to 1.27) than patients without either condition. By the end of the SNF stay, patients with both delirium and incident dementia were more likely to receive an antipsychotic (RR 3.04; 95% CI 2.95 to 3.14) and benzodiazepine (RR 1.32; 95% CI 1.29 to 1.36) than patients without either condition. CONCLUSION: In this historical cohort, a positive delirium screen was associated with a higher risk of receiving psychoactive medication within 7 days of SNF admission, particularly in patients with an incident AD/ADRD diagnosis. Future research should examine strategies to reduce inappropriate psychoactive medication prescribing in older adults admitted with delirium to SNFs.

Medicare part D and changes in prescription drug use and cost burden: national estimates for the Medicare population, 2000 to 2007.

CONTEXT: The full effect of Medicare Part D, after the initial policy transition period and across the United States Medicare population, remains unclear. OBJECTIVE: To estimate nationally representative changes in prescription drug use and out-of-pocket drug costs 2 years after implementation of Part D. DESIGN, SETTING, AND PARTICIPANTS: We examined study outcomes over 8 years (2000 to 2007) and estimated changes after Part D, accounting for earlier trends. Our analyses used the community-dwelling sample of the Medicare Current Beneficiary Survey (unweighted unique n=38,798). Actual post-Part D outcomes were compared with projected values using 2000 to 2005 data. Subgroup analyses and standardization weights were used to address population-level shifts over time in health status and demographic characteristics. MAIN OUTCOME MEASURES: Annual prescription drug fills and out-of-pocket drug costs. RESULTS: We observed significant average per person increases of 1.8 prescription fills [95% confidence interval (CI), 1.1-2.5] in 2006 and 3.4 prescription fills (95% CI, 2.7-4.1) in 2007 above pre-Part D increases of 0.9 prescription fills per year. Average out-of-pocket drug costs decreased significantly by $143 (95% CI, -182.5--103.1) in 2006 and $148 (95% CI, -181.2--114.1) in 2007 above average pre-Part D increases of $12 per year. Prescription fills did not change for beneficiaries with fair to poor health until 2007 when large increases occurred (increases of 3.7 to 11.0 fills above pre-Part D trends). Significant reductions in OOP drug costs occurred in 2006 and persisted into 2007 across all groups except for sick and poor beneficiaries without Medicaid. CONCLUSIONS: After the transition year of 2006, the impact of Part D seemed larger and more consistent across the Medicare population. Of note, sick and poor beneficiaries experienced significant improvements in prescription drug use in 2007.

Adherence with tobramycin inhaled solution and health care utilization.

BACKGROUND: Adherence with tobramycin inhalation solution (TIS) during routine cystic fibrosis (CF) care may differ from recommended guidelines and affect health care utilization. METHODS: We analyzed 2001-2006 healthcare claims data from 45 large employers. Study subjects had diagnoses of CF and at least 1 prescription for TIS. We measured adherence as the number of TIS therapy cycles completed during the year and categorized overall adherence as: low ≤ 2 cycles, medium >2 to <4 cycles, and high ≥ 4 cycles per year. Interquartile ranges (IQR) were created for health care utilization and logistic regression analysis of hospitalization risk was conducted by TIS adherence categories. RESULTS: Among 804 individuals identified with CF and a prescription for TIS, only 7% (n = 54) received ≥ 4 cycles of TIS per year. High adherence with TIS was associated with a decreased risk of hospitalization when compared to individuals receiving ≤ 2 cycles (adjusted odds ratio 0.40; 95% confidence interval 0.19-0.84). High adherence with TIS was also associated with lower outpatient service costs (IQR: $2,159-$8444 vs. $2,410-$14,423) and higher outpatient prescription drug costs (IQR: $35,125-$60,969 vs. $10,353-$46,768). CONCLUSIONS: Use of TIS did not reflect recommended guidelines and may impact other health care utilization.

Socially-isolated neighborhoods and the risk of all-cause mortality among nursing home residents in the United States: A multilevel study.

The total number of Americans age 65 and older is expected to nearly double by 2060, and the number of Americans admitted to nursing homes is likewise anticipated to escalate. Studies have found living alone to be an important risk factor for mortality. Yet little is known about possible spillover health effects of living in a community where many elderly residents live alone. Even less is known about whether these risks persist after entering nursing homes. Our study population consisted of 874,162 US elderly adults newly admitted to nursing homes in 2011, as identified from the 3.0 Minimum Data Set. Data on these individuals were linked to Medicare claims and 2010 Census data. In this cohort study, we estimated multivariable-adjusted hazard ratios for the associations between the quartiles of county-level percentage of households with those age 65 or older living alone and the individual-level risks of all-cause mortality until December 31, 2013, controlling for county-, nursing home facility-, and individual-level factors. Older adults in counties belonging to the highest quartile of elderly single-occupancy households had a 8% higher risk of dying (HR = 1.08; 95% CI = 1.04-1.12, p < 0.001) after entering nursing homes compared to those in counties belonging to the lowest quartile. There was evidence of a linear trend (p for trend < 0.001). Should these findings be confirmed in future studies, it would suggest that living arrangements in elderly communities may have spillover health effects onto their residents. Programs and interventions that modify such living arrangements may yield more favorable health trajectories among older Americans, who are increasingly aging in place and at growing risk of entering nursing homes.