The association between wealth and sleep medication use in a nationally-representative sample of older Medicare beneficiaries.

BACKGROUND: Sleep disorders are common among older adults, leading to high prevalence of over-the-counter and prescription sleep medication use. Socioeconomically disadvantaged individuals have higher prevalence of sleep disorders. Frequent use of sleep medications can increase the risk of falls. Little is known about the association between wealth and sleep medication use in older adults. METHODS: We conducted a cross-sectional analysis using a nationwide sample of 7603 Medicare beneficiaries (65+ years) from Round 1 (2011) of the National Health and Aging Trends Study. We measured self-reported wealth as the sum of assets (retirement savings, stocks/bonds, checking/savings accounts, business assets, and home value) minus liabilities (mortgage, credit card, and medical debt). Self-reported sleep medication use in the past month was categorized as frequent (5-7 nights/week), sometimes (1-4 nights/week), or never (0 night/week). We estimated differences in the prevalence of sleep medication use by quintiles of wealth using crude and adjusted binomial regression models. Individuals missing sleep medication information were excluded. RESULTS: Median wealth was $152 582 (IQR: $24 023-412 992). Sixteen percent reported frequent sleep medication use, 15% reported some use, and 70% reported no use. Frequent sleep medication use was more common in lower wealth quintiles (lowest: 20%, highest: 12%). Alternatively, some use was more common in higher wealth quintiles (lowest: 11%, highest: 18%). Results were similar after adjustment for demographic factors, anxiety, depression, and sleep disorders. CONCLUSIONS: In this study, less wealthy older adults had higher prevalence of frequent sleep medication use. This may lead to dependency or increased fall risk in this vulnerable population.

Generating synthetic data from administrative health records for drug safety and effectiveness studies.

Introduction: Administrative health records (AHRs) are used to conduct population-based post-market drug safety and comparative effectiveness studies to inform healthcare decision making. However, the cost of data extraction, and the challenges associated with privacy and securing approvals can make it challenging for researchers to conduct methodological research in a timely manner using real data. Generating synthetic AHRs that reasonably represent the real-world data are beneficial for developing analytic methods and training analysts to rapidly implement study protocols. We generated synthetic AHRs using two methods and compared these synthetic AHRs to real-world AHRs. We described the challenges associated with using synthetic AHRs for real-world study. Methods: The real-world AHRs comprised prescription drug records for individuals with healthcare insurance coverage in the Population Research Data Repository (PRDR) from Manitoba, Canada for the 10-year period from 2008 to 2017. Synthetic data were generated using the Observational Medical Dataset Simulator II (OSIM2) and a modification (ModOSIM). Synthetic and real-world data were described using frequencies and percentages. Agreement of prescription drug use measures in PRDR, OSIM2 and ModOSIM was estimated with the concordance coefficient. Results: The PRDR cohort included 169,586,633 drug records and 1,395 drug types for 1,604,734 individuals. Synthetic data for 1,000,000 individuals were generated using OSIM2 and ModOSIM. Sex and age group distributions were similar in the real-world and synthetic AHRs. However, there were significant differences in the number of drug records and number of unique drugs per person for OSIM2 and ModOSIM when compared with PRDR. For the average number of days of drug use, concordance with the PRDR was 16% (95% confidence interval [CI]: 12%-19%) for OSIM2 and 88% (95% CI: 87%-90%) for ModOSIM. Conclusions: ModOSIM data were more similar to PRDR than OSIM2 data on many measures. Synthetic AHRs consistent with those found in real-world settings can be generated using ModOSIM. Synthetic data will benefit rapid implementation of methodological studies and data analyst training.

Eventos adversos em uma unidade de internação psiquiátrica / Eventos adversos en una unidad de hospitalización psiquiátrica / Adverse events in a psychiatric hospitalization unit

RESUMO Objetivo descrever os eventos adversos presentes na internação psiquiátrica, analisando-os à luz da teoria do erro humano. Método pesquisa qualitativa, realizada em 2018 em um hospital psiquiátrico. Os dados foram coletados por entrevistas semiestruturadas com 15 profissionais de saúde da equipe multidisciplinar. A análise foi lexical por meio do software Alceste. Resultados evidenciaram-se eventos adversos medicamentosos por erros de administração ou por reações adversas a medicamentos, que produzem danos como impregnação, reações extrapiramidais associadas aos riscos de queda e broncoaspiração pela sonolência e/ou sedação. Outros danos relacionam-se à agressividade do paciente, que produz lesões corporais a si ou a outro, como durante uma tentativa de suicídio ou uso de violência como comportamento de fuga ou defesa. Considerações finais e implicações para a prática existem eventos adversos mais comuns nos ambientes de internação psiquiátrica que precisam ser de conhecimento da equipe de saúde mental porque demandam ações de mitigação por meio do fortalecimento dos sistemas de segurança do paciente. Os dados subsidiam ações para o fortalecimento dos sistemas de segurança nos ambientes de internação psiquiátrica e contribuem à reflexão do conceito de segurança do paciente na psiquiatria.

RESUMEN Objetivo describir los eventos adversos presentes en la hospitalización psiquiátrica, analizándolos a la luz de la teoría del error humano. Método investigación cualitativa, realizada en 2018 en un hospital psiquiátrico. Los datos se recolectaron a través de entrevistas semiestructuradas con 15 profesionales de la salud del equipo multidisciplinario. Se llevó a cabo el análisis léxico por medio del software Alceste. Resultados se evidenciaron eventos adversos por errores de administración o reacciones adversas al fármaco, que producen daños como impregnación y reacciones extrapiramidales asociadas al riesgo de caídas y broncoaspiración por somnolencia y / o sedación. Otros daños se relacionan con agresividad por parte del paciente, que produce daño corporal a sí mismo o a otro, como durante un intento de suicidio o uso de violencia como conducta de fuga o defensa. Conclusión e implicaciones para la práctica hay eventos adversos más comunes en entornos de hospitalización psiquiátrica que deben ser conocidos por el equipo de salud mental porque exigen acciones de mitigación a través del fortalecimiento de los sistemas de seguridad del paciente. Los datos reflejan la necesidad de implementar acciones para fortalecer los sistemas de seguridad en entornos de hospitalización psiquiátrica y contribuyen a la reflexión del concepto de seguridad del paciente en psiquiatría.

ABSTRACT Objective to describe the adverse events found in psychiatric hospitalization, analyzing them in the light of the human error theory. Method a qualitative research study, carried out in 2018 in a psychiatric hospital. The data were collected through semi-structured interviews with 15 health professionals from the multidisciplinary team. Analysis was of the lexical type using the Alceste software. Results adverse drug events were evidenced due to administration errors or adverse drug reactions, which produce harms such as impregnation and extrapyramidal reactions associated with the risks for falls and bronchoaspiration due to drowsiness and/or sedation. Other harms are related to the patient's aggressiveness, which produce bodily self-harm or harms to another person, such as during a suicide attempt or use of violence as an escape or defense behavior. Conclusion and implications for the practice some adverse events are more frequent in psychiatric hospitalization settings; such events need to be known by the mental health team, as they require mitigation actions through the strengthening of patient safety systems. The data subsidize actions for strengthening safety systems in psychiatric hospitalization settings and contribute to reflecting on the concept of patient safety in Psychiatry.

Mortality and concurrent use of opioids and hypnotics in older patients: A retrospective cohort study.

BACKGROUND: Benzodiazepine hypnotics and the related nonbenzodiazepine hypnotics (z-drugs) are among the most frequently prescribed medications for older adults. Both can depress respiration, which could have fatal cardiorespiratory effects, particularly among patients with concurrent opioid use. Trazodone, frequently prescribed in low doses for insomnia, has minimal respiratory effects, and, consequently, may be a safer hypnotic for older patients. Thus, for patients beginning treatment with benzodiazepine hypnotics or z-drugs, we compared deaths during periods of current hypnotic use, without or with concurrent opioids, to those for comparable patients receiving trazodone in doses up to 100 mg. METHODS AND FINDINGS: The retrospective cohort study in the United States included 400,924 Medicare beneficiaries 65 years of age or older without severe illness or evidence of substance use disorder initiating study hypnotic therapy from January 2014 through September 2015. Study endpoints were out-of-hospital (primary) and total mortality. Hazard ratios (HRs) were adjusted for demographic characteristics, psychiatric and neurologic disorders, cardiovascular and renal conditions, respiratory diseases, pain-related diagnoses and medications, measures of frailty, and medical care utilization in a time-dependent propensity score-stratified analysis. Patients without concurrent opioids had 32,388 person-years of current use, 260 (8.0/1,000 person-years) out-of-hospital and 418 (12.9/1,000) total deaths for benzodiazepines; 26,497 person-years,150 (5.7/1,000) out-of-hospital and 227 (8.6/1,000) total deaths for z-drugs; and 16,177 person-years,156 (9.6/1,000) out-of-hospital and 256 (15.8/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (respective HRs: 0.99 [95% confidence interval, 0.81 to 1.22, p = 0.954] and 0.95 [0.82 to 1.14, p = 0.513] and z-drugs (HRs: 0.96 [0.76 to 1.23], p = 0.767 and 0.87 [0.72 to 1.05], p = 0.153) did not differ significantly from that for trazodone. Patients with concurrent opioids had 4,278 person-years of current use, 90 (21.0/1,000) out-of-hospital and 127 (29.7/1,000) total deaths for benzodiazepines; 3,541 person-years, 40 (11.3/1,000) out-of-hospital and 64 (18.1/1,000) total deaths for z-drugs; and 2,347 person-years, 19 (8.1/1,000) out-of-hospital and 36 (15.3/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (HRs: 3.02 [1.83 to 4.97], p < 0.001 and 2.21 [1.52 to 3.20], p < 0.001) and z-drugs (HRs: 1.98 [1.14 to 3.44], p = 0.015 and 1.65 [1.09 to 2.49], p = 0.018) were significantly increased relative to trazodone; findings were similar with exclusion of overdose deaths or restriction to those with cardiovascular causes. Limitations included composition of the study cohort and potential confounding by unmeasured variables. CONCLUSIONS: In US Medicare beneficiaries 65 years of age or older without concurrent opioids who initiated treatment with benzodiazepine hypnotics, z-drugs, or low-dose trazodone, study hypnotics were not associated with mortality. With concurrent opioids, benzodiazepines and z-drugs were associated with increased out-of-hospital and total mortality. These findings indicate that the dangers of benzodiazepine-opioid coadministration go beyond the documented association with overdose death and suggest that in combination with opioids, the z-drugs may be more hazardous than previously thought.

Opioid deaths involving concurrent benzodiazepine use: Assessing risk factors through the analysis of prescription drug monitoring data and postmortem toxicology.

BACKGROUND: A high proportion of opioid drug deaths involve concurrent benzodiazepine use. To reduce the risk of drug overdose, various prescription drug monitoring programs have been implemented. This study examined the impact of concurrent benzodiazepine use on opioid-related deaths, and the utility of the Michigan Automated Prescription System (MAPS) in predicting risk of opioid death. METHODS: Wayne County Medical Examiner's Office cases from 2018 were examined in terms of MAPS data and MAPS-derived drug risk scores, as well as postmortem toxicology. Opioid death cases with concurrent benzodiazepine use were compared to non-drug deaths. RESULTS: For cases with a MAPS history for 6 months preceding death, the incidence of opioid prescriptions filled did not differ between groups. In contrast, significantly more opioid death cases had filled a benzodiazepine prescription; alprazolam prescription was the single best predictor of opioid drug death. Groups differed in MAPS-calculated drug risk scores, though these were less predictive of opioid death than some individual measures of prescription drug use. In terms of postmortem toxicology, fentanyl was the best discriminator between cohorts, with significant associations seen for morphine, benzodiazepine, or cocaine use. Similar results were obtained in the subset of subjects filling a prescription within a month of death, except that MAPS risk scores no longer predicted drug deaths. CONCLUSION: MAPS scores did not adequately predict risk of opioid-related death. Contrary to expectations, prescription opioid use was not correlated with opioid-related death, whereas concurrent use of opioids and benzodiazepines represented a highly significant risk factor.

Opioid Prescribing in the 2016 Medicare Fee-for-Service Population.

BACKGROUND AND OBJECTIVES: Opioid use and misuse are prevalent and remain a national crisis. This study identified beneficiary characteristics associated with filling opioid prescriptions, variation in opioid dosing, and opioid use with average daily doses (ADDs) equal to 120 morphine milligram equivalents (MMEs) or more in the 100% Medicare fee-for-service (FFS) population. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: In a cohort of FFS beneficiaries with 12 months of Medicare Part D coverage in 2016, we examined patient factors associated with filling an opioid prescription (n = 20,880,490) and variation in ADDs (n = 7,325,031) in a two-part model. Among those filling opioids, we also examined the probability of ADD equal to 120 MMEs or more via logistic regression. RESULTS: About 35% of FFS beneficiaries had one or more opioid prescription fills in 2016 and 1.5% had ADDs equal to 120 MMEs or more. Disability-eligible beneficiaries and beneficiaries with multiple chronic conditions were more likely to fill opioids, to have higher ADDs or were more likely to have ADD equal to 120 MMEs or more. Beneficiaries with chronic obstructive pulmonary disease (COPD) were more likely to fill opioids (odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.46-1.47), have higher ADDs (rate ratio = 1.06, 95% CI = 1.06-1.06) when filled and were more likely to have ADD equal to 120 MMEs or more (OR = 1.23, 95% CI = 1.21-1.24). Finally, black and Hispanic beneficiaries were less likely to fill opioids, had lower overall doses and were less likely to have ADDs equal to 120 MMEs or more compared to white beneficiaries. CONCLUSION: Several beneficiary subgroups have underappreciated risk of adverse events associated with ADD equal to 120 MMEs or more that may benefit from opioid optimization interventions that balance pain management and adverse event risk, especially beneficiaries with COPD who are at risk for respiratory depression.

Prescription of Colchicine with Other Dangerous Concomitant Medications: A Nation-Wide Survey Using the Japanese Claims Database.

The anti-inflammatory agent colchicine may cause toxic effects such as rhabdomyolysis, pancytopenia, and acute respiratory distress syndrome in cases of overdose and when patients have renal or liver impairment. As colchicine is a substrate for CYP3A4 and P-glycoprotein (P-gp), drug-drug interactions are important factors that cause fatal colchicine-related side effects. Thus, we conducted a nation-wide survey to determine the status of inappropriate colchicine prescriptions in Japan. Patients prescribed the regular use of colchicine from April 2014 to March 2017 were identified using the Japanese large health insurance claims database. As the primary endpoint, we evaluated the concomitant prescription proportions of strong CYP3A4 and/or P-gp inhibitors classified as "contraindications for co-administration" with colchicine in patients with renal or liver impairment. We defined these cases as "inappropriate colchicine prescriptions." Additionally, factors affecting inappropriate colchicine prescriptions were analyzed. Among the 3302 enrolled patients, 43 (1.30%) were inappropriately prescribed colchicine. Of these 43 patients, 11 had baseline renal and/or liver impairment. By multiple regression analysis, the primary diseases "gout" and "Behçet's disease" were extracted as independent factors for inappropriate colchicine prescriptions with odds ratios of 0.40 (95% confidence interval: 0.19-0.84) and 4.93 (95% confidence interval: 2.12-11.5), respectively. We found that approximately 1% of patients had important colchicine interactions. Particularly, Behçet's disease was a risk factor for inappropriate prescriptions, with approximately 25% of patients showing renal and/or liver impairment (classified as "contraindications for co-administration"). These findings may be useful for medical professionals who prescribe colchicine therapy.

Historical Evolution and Provider Awareness of Inactive Ingredients in Oral Medications.

PURPOSE: A multitude of different versions of the same medication with different inactive ingredients are currently available. It has not been quantified how this has evolved historically. Furthermore, it is unknown whether healthcare professionals consider the inactive ingredient portion when prescribing medications to patients. METHODS: We used data mining to track the number of available formulations for the same medication over time and correlate the number of available versions in 2019 to the number of manufacturers, the years since first approval, and the number of prescriptions. A focused survey among healthcare professionals was conducted to query their consideration of the inactive ingredient portion of a medication when writing prescriptions. RESULTS: The number of available versions of a single medication have dramatically increased in the last 40 years. The number of available, different versions of medications are largely determined by the number of manufacturers producing this medication. Healthcare providers commonly do not consider the inactive ingredient portion when prescribing a medication. CONCLUSIONS: A multitude of available versions of the same medications provides a potentially under-recognized opportunity to prescribe the most suitable formulation to a patient as a step towards personalized medicine and mitigate potential adverse events from inactive ingredients.

Geographic Variation in the Prevalence of High-Risk Medication Use Among Medicare Part D Beneficiaries by Hospital Referral Region.

BACKGROUND: Understanding geographic patterns of high-risk medication (HRM) prescribed and dispensed among older adults may help the Centers for Medicare & Medicaid Services and their partners develop and tailor prevention strategies. OBJECTIVE: To compare the geographic variation in the prevalence of HRM use among Medicare Part D beneficiaries from 2011 to 2013, for Medicare Advantage Prescription Drug (MA-PD) plans and stand-alone Prescription Drug Plans (PDPs). METHODS: This retrospective study used the data of a 5% national Medicare sample (2011-2013). Beneficiaries were included in the study if they were aged ≥ 65 years, continuously enrolled in MA-PDs or PDPs (~1.3 million each year), and had ≥ 2 prescriptions for the same HRM (e.g., amitriptyline) prescribed and dispensed during the year based on the Pharmacy Quality Alliance's (PQA) quality measures for HRM use. Multivariable logistic regression was used to estimate adjusted annual HRM use rates (i.e., adjusted predictions, average marginal predictions, or model-adjusted risk) across 306 Dartmouth Atlas of Health Care hospital referral regions (HRRs), controlling for sociodemographic, health-status, and access-to-care factors. RESULTS: Among eligible beneficiaries each year (1,161,076 in 2011, 1,237,653 in 2012, and 1,402,861 in 2013), nearly 40% were enrolled in MA-PD plans, whereas the remaining 60% were in PDP plans. The adjusted prevalence of HRM use significantly decreased among Medicare beneficiaries enrolled in MA-PD (13.1%-8.4%, P < 0.001) and PDP (16.2%-12.2%, P < 0.001) plans from 2011 to 2013. For MA-PD and PDP beneficiaries, HRM users were more likely to be (all P < 0.001) the following: female (MA-PD: 70.4% vs. 59.9%; PDP: 72.8% vs. 62.5%); White (MA-PD: 84.6% vs. 81.4%; PDP: 86.6% vs. 85.3%); with low-income subsidy or dual eligibility for Medicaid (MA-PD: 22.3% vs. 16.6%; PDP: 29.2% vs. 23.3%); and disabled (MA-PD: 15.6% vs. 8.7%; PDP: 15.4% vs. 8.5%) compared with non-HRM users in 2013. In 2013, significant geographic variation existed, with the ratios of 75th-25th percentiles of HRM use rates across HRRs as 1.42 for MA-PDs and 1.31 for PDPs. For MA-PDs, the top 5 HRRs with the highest HRM use rates in 2013 were Casper, WY (20.4%), Waco, TX (16.7%), Lubbock, TX (15.7%), Santa Barbara, CA (15.2%), and Temple, TX (15.1%); for PDPs, they were Lawton, OK (18.8%), Alexandria, LA (18.8%), Lake Charles, LA (18.6%), Oklahoma City, OK (18.0%), and Slidell, LA (18.0%). CONCLUSIONS: Substantial geographic variation exists in the prevalence of HRM use among older adults in Medicare, regardless of prescription drug plan. Areas with high prevalence of HRM use may benefit from targeted interventions (e.g., medication therapy management monitoring or alternative medication substitutions) to prevent potential adverse consequences. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose. This study was presented as a poster at the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) Asia Pacific Meeting; September 8-11, 2018; Tokyo, Japan.

"It is through shared conversation, that I understand"-Maori older adults' experiences of medicines and related services in Aotearoa New Zealand.

AIM: An understanding of patients' healthcare experiences and perceptions is essential for developing new health services. In Aotearoa New Zealand, inequities in health outcomes exist, with Maori experiencing worse health outcomes than non-Maori. This includes poorer access to, and quality of, prescribed medicines. This study aims to explore kaumatua (Maori older adults') experiences of medicines and medicine-related services in New Zealand. METHOD: This qualitative research applied kaupapa Maori theory and explored Maori older adults' experiences of medicines and medicine-related services in New Zealand. Ten kaumatua from Auckland, New Zealand participated in semi-structured interviews. Reflexive thematic analysis was used to analyse data. RESULTS: Three themes were generated: 1. diverse, multi-dimensional realities of medicine-taking for Maori with ageing; 2. medicines supply as a business transaction; and 3. self-determined agency of kaumatua supported by authentic healthcare partnerships. Kaumatua expressed their ability to retain power and control over their medicine therapy and their desire for this to occur within a supportive, authentic partnership model that involves them and their multiple healthcare providers. CONCLUSION: Maori older adults have the ability, desire and right to control their medicines journey in a way that is relevant to their experiences of medicines. They value support from authentic healthcare partnerships in enabling this.

Combined Pediatric and Adult Trials Submitted to the US Food and Drug Administration 2012-2018.

Despite legislation incentivizing and requiring drug companies to conduct pediatric clinical trials, there still is a 9-year delay in drug approval for pediatric labeling after the initial adult drug approval. The aim of this study was to review the experience of the US Food and Drug Administration (FDA) with combined pediatric and adult trials as a means for expediting pediatric approval and labeling. Combined pediatric and adult trials submitted to the FDA from 2012 to 2018 were reviewed. Only the publicly available labels and reviews were utilized for this analysis. Combined trials were identified for 72 products, with a total of 156 combined adult and pediatric trials. The therapeutic areas with the largest number of combined trials were in pulmonology for products reviewed under the Best Pharmaceuticals for Children Act (BPCA) and/or the Pediatric Research Equity Act (PREA), and hematology reviewed under the Orphan Drug Act (ODA). All drugs that utilized combined pediatric and adult clinical trials were approved simultaneously for both the adults and that part of the pediatric population. A separate pediatric subgroup efficacy analysis was reported in 57% and 48% of products under BPCA/PREA and the ODA, respectively, with a separate safety analysis in 48% and 38% of these products. When considering both BPCA/PREA and orphan drug studies, all the combined pediatric and adult trials allowed concurrent approval and labeling for part of the pediatric population at the time of the adult approval.

Toward digital-based interventions for medication adherence and safety.

INTRODUCTION: Adherence to the prescribed use of medications is a major problem for many patients. Whether intentional or unintentional, the failure to take medications as prescribed results in an array of health problems, hospitalizations, and increased health expenditures. AREAS COVERED: The paper reviews the different types of interventions to promote the appropriate use of medications from provider-based to digital-based interventions. These interventions often combine passive and interactive approaches and may include bio-surveillance/monitoring. Many studies have evaluated these interventions in a variety of conditions and patient population, demonstrating mixed outcomes. EXPERT OPINION: The complexity of the underlying causes of poor medication adherence may warrant personalized interventions that combine passive/interactive and personal/digital options. Enriching patient trials may enable observation of larger effect sizes.

Association of Medicare Part D Benzodiazepine Coverage Expansion With Changes in Fall-Related Injuries and Overdoses Among Medicare Advantage Beneficiaries.

Importance: Benzodiazepines, which are associated with safety-related harms for older adults, were not covered when the US Medicare Part D prescription drug benefit began. Coverage was extended to benzodiazepines in 2013. Objective: To examine whether the expansion of benzodiazepine coverage among Medicare Advantage (MA) beneficiaries was associated with increases in fall-related injuries or overdoses among older adults. Design, Setting, and Participants: This ecological study used interrupted time-series with comparison-series analyses of MA claims data from 4 635 312 age-eligible MA beneficiaries and 940 629 commercially insured individuals (comparison group) stratified by age (65-69, 70-74, 75-79, and ≥80 years) to separately compare trends in fall-related injury and overdose before (January 1, 2010, to December 31, 2012) and after (January 1, 2013, to December 31, 2015) coverage expansion for benzodiazepines. Data analysis was performed from September 1, 2018, to August 31, 2019. Exposures: Expansion of benzodiazepine coverage in Medicare Part D in 2013. Main Outcomes and Measures: Monthly rate of fall-related injury and overdose. Results: In 2012 (the year before the policy change), women constituted 57.5% of the MA group and 47.4% of the comparison group. A total of 25.8% of individuals in the MA group were aged 65 to 69 years, and 29.3% were 80 years or older (mean [SD], 75.1 [6.4] years); 56.7% of individuals in the comparison group were aged 65 to 69 years, and 15.1% were 80 years or older (mean [SD] age, 70.9 [6.5] years). In the MA group, 4 635 312 individuals contributed 156 754 749 person-months from 2010 through 2015; in the comparison group, 940 629 individuals contributed 25 104 534 person-months. After coverage of benzodiazepines began, the rate (ie, slope) of fall-related injury among MA beneficiaries increased from before to after coverage among all age groups. Compared with the comparison group, the increase in rate was statistically significant for those 80 years or older (rate changes for the MA vs comparison groups: 0.12 [95% CI, 0.07 to 0.17] vs -0.01 [95% CI, -0.11 to 0.10]; P = .04 for interaction). The overdose trend changed from decreasing to increasing among MA beneficiaries after coverage for all age groups, with a statistically significant increase compared with the comparison group among those aged 65 to 69 years (rate changes for the MA vs comparison groups: 0.23 [95% CI, 0.17 to 0.30] vs 0.02 [95% CI, -0.06 to 0.11]; P < .001 for interaction) and among those 80 years or older (rate changes for the MA vs comparison groups: 0.07 [95% CI, 0.00 to 0.14] vs -0.20 [95% CI, -0.35 to -0.05]; P = .002 for interaction). Results among MA beneficiaries were consistent when stratified by sex and when limited to those prescribed opioids. Conclusions and Relevance: Medicare's expansion of benzodiazepine coverage may have been associated with increases in the rates of overdose among adults ages 65 to 69 years and in the rates of overdose and fall-related injury among those 80 years or older.

Impact of pharmacist-led multidisciplinary medication review on the safety and medication cost of the elderly people living in a nursing home: a before-after study.

Objectives: Adverse drug events (ADE) are a common cause of morbidity and mortality in elderly patients. In this study, we assessed the impact of multidisciplinary medication review (MMR) for nursing home residents on patient safety and costs incurred by the hospital and the national health service. Methods: Medical files of residents were retrospectively assessed for medications prescribed in the previous six months. A pharmacist reviewed the prescriptions and suggested modifications to the patient's medical team. Patients were followed for six months. Trivalle's ADE geriatric risk score was calculated before and after MMR, as were number of potentially inappropriate medications, and economic impact from the perspective of the health care system and the nursing home. Results: Forty-nine patients were recruited. ADE score dropped one risk level (median score of 4 before versus 1 after, p < 0.0001). The number of patients taking at least one potentially inappropriate medication decreased from 30.6% before to 6.1% after MMR (p = 0.005). A mean saving of €232 per patient was made from the nursing home perspective following MMR (p = 0.008). Conclusion: The MMR reduced the iatrogenic drug risk for elderly residents and costs from the nursing home perspective, particularly drug expenditure.

Predicting Opioid Overdose Deaths Using Prescription Drug Monitoring Program Data.

INTRODUCTION: Prescription Drug Monitoring Program data can provide insights into a patient's likelihood of an opioid overdose, yet clinicians and public health officials lack indicators to identify individuals at highest risk accurately. A predictive model was developed and validated using Prescription Drug Monitoring Program prescription histories to identify those at risk for fatal overdose because of any opioid or illicit opioids. METHODS: From December 2018 to July 2019, a retrospective cohort analysis was performed on Maryland residents aged 18-80 years with a filled opioid prescription (n=565,175) from January to June 2016. Fatal opioid overdoses were identified from the Office of the Chief Medical Examiner and were linked at the person-level with Prescription Drug Monitoring Program data. Split-half technique was used to develop and validate a multivariate logistic regression with a 6-month lookback period and assessed model calibration and discrimination. RESULTS: Predictors of any opioid-related fatal overdose included male sex, age 65-80 years, Medicaid, Medicare, 1 or more long-acting opioid fills, 1 or more buprenorphine fills, 2 to 3 and 4 or more short-acting schedule II opioid fills, opioid days' supply ≥91 days, average morphine milligram equivalent daily dose, 2 or more benzodiazepine fills, and 1 or more muscle relaxant fills. Model discrimination for the validation cohort was good (area under the curve: any, 0.81; illicit, 0.77). CONCLUSIONS: A model for predicting fatal opioid overdoses was developed using Prescription Drug Monitoring Program data. Given the recent national epidemic of deaths involving heroin and fentanyl, it is noteworthy that the model performed equally well in identifying those at risk for overdose deaths from both illicit and prescription opioids.

Medicare Prescription Drug Plan Formulary Restrictions After Postmarket FDA Black Box Warnings.

BACKGROUND: The boxed warning (also known as "black box warning") is one of the FDA's strongest safety actions for pharmaceuticals. After the FDA issues black box warnings for drugs, prescribing changes have been inconsistent. Formulary management may provide an opportunity to restrict access to drugs with serious safety concerns. OBJECTIVE: To examine Medicare prescription drug plan formulary changes after new FDA postmarket black box warnings and major updates to preexisting black box warnings. METHODS: In this cohort study, we identified each drug that received a new FDA postmarket black box warning or a major update to a preexisting black box warning from January 2008 through June 2015 and examined its formulary coverage. The main outcome measure was the proportion of Medicare prescription drug plan formularies providing unrestrictive coverage immediately before the black box warning, at least 1 year after the warning and at least 2 years after the warning. Unrestrictive formulary coverage was defined as coverage of a drug without prior authorization or step-therapy requirements. RESULTS: Of 101 new black box warnings and major updates to preexisting warnings affecting 68 unique drug formulations, the mean percentage of formularies providing unrestrictive coverage changed from 65.4% (95% CI = 59.6%-71.2%) prewarning; 62.6% (95% CI = 56.3%-68.9%, P = 0.04) at least 1 year postwarning; and 61.9% (95% CI = 55.4%-68.5%, P = 0.10) at least 2 years postwarning. CONCLUSIONS: The mean percentage of Medicare prescription drug plan formularies providing unrestrictive coverage decreased modestly by approximately 3 percentage points after drugs received postmarket FDA black box warnings. Formulary restrictions may present an underused mechanism to reduce use of potentially unsafe medications. DISCLOSURES: This study was supported by a student research grant received by Solotke and provided by the Yale School of Medicine Office of Student Research under National Institutes of Health training grant award T35DK104689. Karaca-Mandic, Shah, and Ross acknowledge support from Agency for Healthcare Research and Quality (AHRQ) grant R01 HS025164, which studies factors associated with de-adoption of drug therapies shown to be ineffective or unsafe. The content of this study is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors assume full responsibility for the accuracy and completeness of the ideas presented. Ross has received support from the following: the U.S. Food and Drug Administration (FDA) as part of the Centers for Excellence in Regulatory Science and Innovation (CERSI) program; Johnson and Johnson through Yale University to develop methods of clinical trial data sharing; Medtronic and the FDA to develop methods for postmarket surveillance of medical devices; the Blue Cross Blue Shield Association to better understand medical technology evaluation; the Centers for Medicare & Medicaid Services (CMS) to develop and maintain performance measures that are used for public reporting; the AHRQ to examine community predictors of health care quality; and the Laura and John Arnold Foundation, which established the Collaboration for Research Integrity and Transparency at Yale University. Shah has received support from the FDA as part of the CERSI program. In addition, he has received support through the Mayo Clinic from CMS, AHRQ, National Science Foundation, and Patient-centered Outcomes Research Institute. Karaca-Mandic has provided consulting services to Precision Health Economics and Tactile Medical for work unrelated to this manuscript. Dhruva and Solotke have no conflicts of interest to report.

Do dissonant ad visuals cause consumers to discount prescription drug side effects?

In most video-based advertising, visuals reinforce the ads' verbal messages. This use of redundant images, however, is often not the case in television commercials for prescription drugs. These ads frequently employ dissonant visuals, or pleasant images, during the narration of the drugs' negative side effects. This visual-verbal inconsistency could adversely impact consumers' interpretation and decision-making about the drugs. Through an empirical investigation, this study found that consumers attribute significantly more positive affect and lower risk to prescription drug ads that employ dissonant visuals versus redundant ones. Such findings challenge the ethicality of these pervasive and influential health messages.

Fixed-dose combinations banned in India: is it the right decision? An eye-opening review.

Introduction: Fixed-dose combination (FDC) medicines contain more than one approved active pharmaceutical ingredient (API), are manufactured as a fixed-dose and packed in a single dosage form. FDCs have been drawing attention from the pharmaceutical industries because of the government's ban on 328 irrational FDCs in September 2018. The Drug Technical Advisory Board (DTAB) recommended that 'there is no therapeutic justification' for the active ingredients in the banned FDCs and accordingly these combinations 'may involve a risk to human beings'. Areas covered: The review illustrates the present status of FDCs, its regulatory framework, approvals in India and discusses the substantive cause behind the ban on FDCs in India. Expert opinion: The expert stress to establish a robust regulatory system for the approval of FDCs in India. The pharmaceutical industries should not perceive the ban against irrational FDCs as an impediment; rather, they should view as an opportunity to establish a stronger healthcare system. The current review is an eye-opener for the section of people who consider that the ban on FDCs is irrational. However, the ban on 328 FDCs may prove a landmark decision for the development of stronger healthcare policy in India.