Identifying prescribing cascades in Alzheimer's disease and related dementias: The calcium channel blocker-diuretic prescribing cascade.

PURPOSE: Prescribing cascades occur when a physician prescribes a new drug to address the side-effect of another drug. Persons with Alzheimer's disease and related dementias (ADRD) are at increased risk for prescribing cascades. Our objective was to develop an approach to estimating the proportion of calcium channel blocker-diuretic (CCB-diuretic) prescribing cascades among persons with ADRD in two U.S. health plans. METHODS: We identified patients aged ≥50 on January 1, 2017, dispensed a drug to treat ADRD in the 365-days prior to/on cohort entry date. Patients had medical/pharmacy coverage for 1 year before and through cohort entry. We excluded individuals with an institutional stay encounter in the 45 days prior to cohort entry and censored patients based on: disenrollment from coverage, death, or end of data. We identified incident and prevalent CCB use in the 183-days following cohort entry, and identified subsequent incident diuretic use among incident and prevalent CCB-users within 365-days from cohort entry. RESULTS: There were 121 538 eligible patients. Approximately 62% were female, with a mean age of 79.5 (SD ±8.6). Overall 2.1% of the cohort experienced a prevalent CCB-diuretic prescribing cascade with 1586 incident diuretic-users among 36 462 prevalent CCB-users (4.3%, 95% CI 4.1-4.6%]); and there were161 incident diuretic-users among 3304 incident CCB-users (4.9%, 95% CI 4.2-5.7%) (incident CCB-diuretic cascade). CONCLUSIONS: We describe an approach to identify prescribing cascades in persons with ADRD, which can be used to assess the proportion of prescribing cascades in large cohorts. We determined the proportion of CCB-diuretic prescribing cascades was low.

Correction to: The AGING Initiative experience: a call for sustained support for team science networks.

After publication of the original article [1], it came to the authors' attention that a funding source was omitted. This Correction article shows the updated Funding section.

The AGING Initiative experience: a call for sustained support for team science networks.

Team science, defined as collaborative research efforts that leverage the expertise of diverse disciplines, is recognised as a critical means to address complex healthcare challenges, but the practical implementation of team science can be difficult. Our objective is to describe the barriers, solutions and lessons learned from our team science experience as applied to the complex and growing challenge of multiple chronic conditions (MCC). MCC is the presence of two or more chronic conditions that have a collective adverse effect on health status, function or quality of life, and that require complex healthcare management, decision-making or coordination. Due to the increasing impact on the United States society, MCC research has been identified as a high priority research area by multiple federal agencies. In response to this need, two national research entities, the Healthcare Systems Research Network (HCSRN) and the Claude D. Pepper Older Americans Independence Centers (OAIC), formed the Advancing Geriatrics Infrastructure and Network Growth (AGING) Initiative to build nationwide capacity for MCC team science. This article describes the structure, lessons learned and initial outcomes of the AGING Initiative. We call for funding mechanisms to sustain infrastructures that have demonstrated success in fostering team science and innovation in translating findings to policy change necessary to solve complex problems in healthcare.

The geriatrics research instrument library: A resource for guiding instrument selection for researchers studying older adults with multiple chronic conditions.

Background: After the passage of the 21st Century Cures Act in the U.S., the Inclusion Across the Lifespan policy eliminates upper-age limits for research participation unless risk justified. Broader inclusion will necessitate the use of reliable instruments in research that characterize the health status and function of older adults with multiple chronic conditions. As there is a plethora of such instruments, the Geriatrics Research Instrument Library (GRIL) was developed as freely available online resource of data collection instruments commonly used in gerontological research. GRIL has been revised and updated by the Advancing Geriatrics Infrastructure and Network Growth (AGING) Initiative, a joint endeavor of the Health Care Systems Research Network (HCSRN) and the Older Americans Independence Centers (OAICs). Methods: Extensive PubMed literature searches and domain expert feedback were utilized to inventory and update GRIL through the addition of instruments and compiling of instrument metadata. GRIL is hosted on the National Institute on Aging OAIC Coordinating Center website with a platform utilizing Microsoft Structured Query Language (SQL) and an Adobe ColdFusion application server. Tracking statistics are collected using Google Analytics. Results: Presently, GRIL includes 175 instruments across 18 domains, including instrument metadata such as instrument description, copyright information, completion time estimates, keywords, available translations, and a link and reference to the original manuscript describing the instrument. The GRIL website includes user-friendly features such as mobile platforming and resource links. Conclusions: GRIL provides a user-friendly public resource that facilitates clinical researchers in efficiently selecting appropriate instruments to measure clinical outcomes relevant to older adults across a full range of domains.

Antidopaminergic-Antiparkinsonian Medication Prescribing Cascade in Persons with Alzheimer's Disease.

OBJECTIVES: Persons living with Alzheimer's disease (AD) may be at increased risk for prescribing cascades due to greater multimorbidity, polypharmacy, and the need for more complex care. Our objective was to assess the proportion of the antidopaminergic-antiparkinsonian medication prescribing cascades among persons living with Alzheimer's disease. SETTING: Two large administrative claims databases in the United States. PARTICIPANTS: We identified patients aged ≥50 on January 1, 2017, who were dispensed a drug used to treat Alzheimer's disease for at least 1 day in the 365 days prior to or on cohort entry date and who had medical and pharmacy coverage in the 365 days prior to the cohort entry date. We excluded individuals with a recent institutional stay. We identified incident antidopaminergic (antipsychotic/metoclopramide) use in the 183 days following cohort entry and identified subsequent incident antiparkinsonian drug use within 8 to 365 days. RESULTS: There were 121,538 patients with Alzheimer's disease eligible for inclusion. Approximately 62% were women with a mean age of 79.5 (SD ± 8.6). The mean number of drugs dispensed was 9.2 (SD ± 4.9). There were 36 incident antiparkinsonian users among 4,534 incident antipsychotic/metoclopramide users (0.8%). CONCLUSION: We determined that the proportion of antidopaminergic-antiparkinsonian medication prescribing cascades, widely considered as high-priority, was low. Our approach can be used to assess the proportion of prescribing cascades in populations considered to be at high risk and to prioritize system-level interventional efforts to improve medication safety in these patients.

Effect of a Multifaceted Clinical Pharmacist Intervention on Medication Safety After Hospitalization in Persons Prescribed High-risk Medications: A Randomized Clinical Trial.

Importance: The National Action Plan for Adverse Drug Event (ADE) Prevention identified 3 high-priority, high-risk drug classes as targets for reducing the risk of drug-related injuries: anticoagulants, diabetes agents, and opioids. Objective: To determine whether a multifaceted clinical pharmacist intervention improves medication safety for patients who are discharged from the hospital and prescribed medications within 1 or more of these high-risk drug classes. Design, Setting, and Participants: This randomized clinical trial was conducted at a large multidisciplinary group practice in Massachusetts and included patients 50 years or older who were discharged from the hospital and prescribed at least 1 high-risk medication. Participants were enrolled into the trial from June 2016 through September 2018. Interventions: The pharmacist-directed intervention included an in-home assessment by a clinical pharmacist, evidence-based educational resources, communication with the primary care team, and telephone follow-up. Participants in the control group were provided educational materials via mail. Main Outcomes and Measures: The study assessed 2 outcomes over a 45-day posthospital discharge period: (1) adverse drug-related incidents and (2) a subset defined as clinically important medication errors, which included preventable or ameliorable ADEs and potential ADEs (ie, medication-related errors that may not yet have caused injury to a patient, but have the potential to cause future harm if not addressed). Clinically important medication errors were the primary study outcome. Results: There were 361 participants (mean [SD] age, 68.7 [9.3] years; 177 women [49.0%]; 319 White [88.4%] and 8 Black individuals [2.2%]). Of these, 180 (49.9%) were randomly assigned to the intervention group and 181 (50.1%) to the control group. Among all participants, 100 (27.7%) experienced 1 or more adverse drug-related incidents, and 65 (18%) experienced 1 or more clinically important medication errors. There were 81 adverse drug-related incidents identified in the intervention group and 72 in the control group. There were 44 clinically important medication errors in the intervention group and 45 in the control group. The intervention did not significantly alter the per-patient rate of adverse drug-related incidents (unadjusted incidence rate ratio, 1.13; 95% CI, 0.83-1.56) or clinically important medication errors (unadjusted incidence rate ratio, 0.99; 95% CI, 0.65-1.49). Conclusions and Relevance: In this randomized clinical trial, there was not an observed lower rate of adverse drug-related incidents or clinically important medication errors during the posthospitalization period that was associated with a clinical pharmacist intervention. However, there were study recruitment challenges and lower than expected numbers of events among the study population. Trial Registration: ClinicalTrials.gov Identifier: NCT02781662.

Recruitment Challenges for Low-Risk Health System Intervention Trials in Older Adults: A Case Study.

OBJECTIVE: To assess factors associated with trial participation in the context of a low-risk intervention intended to reduce adverse drug events in recently hospitalized older adults. DESIGN: Mixed methods: analysis of data collected during enrollment efforts and focus groups. SETTING: A large, multispecialty group practice. PARTICIPANTS: Individuals 50 years and older, recently discharged from the hospital and prescribed at least one high-risk medication, were eligible for the trial. Enrollees, decliners, and their caregivers were eligible to participate in focus groups. MEASUREMENTS: Reasons for declining to participate during the initial invitation as well as reasons for not providing consent were recorded. Focus groups were conducted with eligible individuals to explore reasons for enrolling or declining. We conducted multivariable logistic regression to compare characteristics (including sex, age, healthcare proxy, number and type of medications, visiting nurse services, reason for admission, and length of hospital stay) of those who enrolled with those who did not enroll. RESULTS: Of 3,606 individuals determined eligible, 3,147 (87%) declined, 98 (3%) verbally consented to participate but did not complete written consent, and 361 (10%) provided written consent and were considered enrolled. Individuals 80 year and older (odds ratio (OR) = 0.44; 95% confidence interval (CI) = 0.30-0.65) and those with visiting nurse services (OR = 0.64; 95% CI = 0.48-0.85) were least likely to enroll. Among those who provided a reason for declining (2,473), the most common was the belief they did not need additional medication assistance (18%). Another 332 (11%) declined because they were receiving visiting nurse services. CONCLUSION: Recruiting older adults recently discharged from the hospital to participate in trials of low-risk, system-level interventions is challenging and may underenroll the oldest individuals and those potentially at the highest risk for adverse events, limiting generalizability of study findings. Alternative study designs may be more effective than individually randomized trials in assessing low-risk, system-level interventions.

Prescribing cascades in persons with Alzheimer's disease: engaging patients, caregivers, and providers in a qualitative evaluation of print educational materials.

INTRODUCTION: Prescribing cascades occur when the side effect of a drug is misinterpreted as a new medical condition, and a second drug is prescribed to address the side effect. Persons with Alzheimer's disease (AD) are at increased risk of prescribing cascades due to greater multimorbidity, polypharmacy, and complexity of care. The objective of this study was to evaluate educational materials about prescribing cascades in persons with AD, and elicit input on their use in a future trial. METHODS: We interviewed community-dwelling adults with either an AD diagnosis or a prescription drug used to treat AD (n = 12), caregivers of patients meeting the same criteria (n = 14), and providers (n = 15). We coded interview transcripts and organized themes according to the communication-human information processing model. We revised the materials based on the interviews, and surveyed participating caregivers and providers for their reactions to the revised materials. RESULTS: Analysis of patients', caregivers', and providers' comments suggest: (a) Providers had conflicting views about the messaging of materials; (b) Caregivers were likely to read letters addressed to patients; (c) Providers were likely to ignore letters, but were receptive to patient/caregiver-initiated conversations; (d) Patients and caregivers had difficulty understanding prescribing cascades; (e) Providers worried that mailed materials would undermine trust; (f) Participants had mixed views on how materials might affect the clinical encounter; (g) Participants felt that materials would improve patient/caregiver engagement. When surveyed, most providers found the revised materials informative and actionable, and most caregivers found them understandable and useful. CONCLUSIONS: This evaluation of educational materials about prescribing cascades in patients with AD provides strong support for engaging caregivers to communicate with providers about prescribing cascades. By giving patients and caregivers a basic description of the prescribing cascade concept, our educational materials may help them prepare for a conversation with the provider, who can then tailor the discussion of the possible cascade to the specific needs of the individual patient and caregiver. However, evidence on whether materials can stimulate such conversations awaits testing in a future trial. LAY SUMMARY: Patient, caregiver and provider thoughts on educational materials about prescribing and medication safety Prescribing cascades occur when the side effect of a medication is misinterpreted as a new medical condition, and a second medication is prescribed to treat the side effect. Persons with Alzheimer's disease (AD) are at increased risk of prescribing cascades because they often have more medical conditions, more medications, and more complex care. The goal of this study was to evaluate mailed educational materials about prescribing cascades in persons with AD, and get input on their use in a future study. We interviewed 12 adults with AD, or prescribed a medication to treat AD, 14 caregivers of persons with AD, and 15 providers. We reviewed the interview transcripts to identify important findings about our educational materials. We edited the materials based on the interviews, and sent participating caregivers and providers a questionnaire to get their reactions to the new materials. Important findings from the interviews suggest: (a) Providers had conflicting views about the recommendations given; (b) Caregivers were likely to read letters addressed to patients; (c) Providers were likely to ignore letters, but were receptive to patients/caregivers introducing the topic; (d) Patients and caregivers had difficulty understanding prescribing cascades; (e) Providers worried mailed materials would undermine trust; (f) Participants had mixed views on how materials might affect a doctor's appointment; (g) Participants felt strongly that materials would improve patient/caregiver engagement. When surveyed, almost all providers found the revised materials informative and actionable; and most caregivers found them understandable and useful. These findings provide strong support for engaging caregivers to communicate with providers about prescribing cascades. The educational materials may help patients and caregivers prepare for a conversation with the provider, who can then tailor the discussion of the possible cascade to the specific needs of the individual patient and caregiver. However, evidence on whether materials can stimulate such conversations awaits testing in a future study.

Diagnostic Algorithms for Cardiovascular Death in Administrative Claims Databases: A Systematic Review.

INTRODUCTION: Valid algorithms for identification of cardiovascular (CV) deaths allow researchers to reliably assess the CV safety of medications, which is of importance to regulatory science, patient safety, and public health. OBJECTIVE: The aim was to conduct a systematic review of algorithms to identify CV death in administrative health plan claims databases. METHODS: We searched MEDLINE, EMBASE, and Cochrane Library for English-language studies published between January 1, 2012 and October 17, 2017. We examined references in systematic reviews to identify earlier studies. Selection included any observational study using electronic health care data to evaluate the sensitivity, specificity, positive predictive value (PPV), or negative predictive value (NPV) of algorithms for CV death (sudden cardiac death [SCD], myocardial infarction [MI]-related death, or stroke-related death) among adults aged ≥ 18 years in the United States. Data were extracted by two independent reviewers, with disagreements resolved through further discussion and consensus. The Quality Assessment of Diagnostic Accuracy Studies-2 instrument was used to assess the risk of bias. RESULTS: Five studies (n = 4 on SCD, n = 1 on MI- and stroke-related death) were included after a review of 2053 citations. All studies reported algorithm PPVs, with incomplete reporting on other accuracy parameters. One study was at low risk of bias, three studies were at moderate risk of bias, and one study was at unclear risk of bias. Two studies identified community-occurring SCD: one identified events using International Classification of Disease, Ninth Revision (ICD-9) codes on death certificates and other criteria from medical claims (PPV = 86.8%) and the other identified events resulting in hospital presentation using first-listed ICD-9 codes on emergency department or inpatient medical claims (PPV = 92.3%). Two studies used death certificates alone to identify SCD (PPV = 27% and 32%, respectively). One study used medical claims to identify CV death (PPV = 36.4%), coronary heart disease mortality (PPV = 28.3%), and stroke mortality (PPV = 34.5%). CONCLUSION: Two existing algorithms based on medical claims diagnoses with or without death certificates can accurately identify SCD to support pharmacoepidemiologic studies. Developing valid algorithms identifying MI- and stroke-related death should be a research priority. PROSPERO 2017 CRD42017078745.

Research Priorities to Advance the Health and Health Care of Older Adults with Multiple Chronic Conditions.

OBJECTIVES: To prioritize research topics relevant to the care of the growing population of older adults with multiple chronic conditions (MCCs). DESIGN: Survey of experts in MCC practice, research, and policy. Topics were derived from white papers, funding announcements, or funded research projects relating to older adults with MCCs. SETTING: Survey conducted through the Health Care Systems Research Network (HCSRN) and Claude D. Pepper Older Americans Independence Centers (OAICs) Advancing Geriatrics Infrastructure and Network Growth Initiative, a joint endeavor of the HCSRN and OAICs. PARTICIPANTS: Individuals affiliated with the HCSRN or OAICs and national MCC experts, including individuals affiliated with funding agencies having MCC-related grant portfolios. MEASUREMENTS: A "top box" methodology was used, counting the number of respondents selecting the top response on a 5-point Likert scale and dividing by the total number of responses to calculate a top box percentage for each of 37 topics. RESULTS: The highest-ranked research topics relevant to the health and healthcare of older adults with MCCs were health-related quality of life in older adults with MCCs; development of assessment tools (to assess, e.g., symptom burden, quality of life, function); interactions between medications, disease processes, and health outcomes; disability; implementation of novel (and scalable) models of care; association between clusters of chronic conditions and clinical, financial, and social outcomes; role of caregivers; symptom burden; shared decision-making to enhance care planning; and tools to improve clinical decision-making. CONCLUSION: Study findings serve to inform the development of a comprehensive research agenda to address the challenges relating to the care of this "high-need, high-cost" population and the healthcare delivery systems responsible for serving it.