Deprescribing

Medicines have adverse effects and the use of multiple medicines, polypharmacy, can be associated with poorer outcomes. Health professionals need to recognise when medicines should be ceased and how to deprescribe. Deprescribing could be considered when there is polypharmacy, adverse drug reactions, ineffective treatment, falls or when treatment goals have changed. If patients are slowly weaned off their medicines, withdrawal and rebound syndromes are usually not serious. A cautious approach to deprescribing includes two principles - stop one drug at a time and wean doses slowly over weeks and months

A call for the appropriate application of clinical pharmacological principles in the search for safe and efficacious COVID-19 (SARS-COV-2) treatments.

Syndrome Coronavirus 2 (SARS-CoV-2) has led to remarkable efforts by the scientific communities internationally to identify potential pharmacological treatments through the rapid initiation of clinical trials of novel and/or re-purposed regulatory authorityapproved therapies. We greatly welcome the significant global effort to safely expedite trials. However, we are concerned that many studies have not been of high quality to generate clinically meaningful data to enable effective translation to clinical practice. Identifying the “right” drug (or drug combinations) is only the first step. Applying core clinical pharmacology principles at all stages of research will help identify the right dose, the right patient, and the right treatment protocol. We hope that by setting out the principles outlined in this statement, efforts to find a safe and efficacious treatment for COVID-19 will have the best chance of success

Pain, Complex Chronic Conditions and Potential Inappropriate Medication in People with Dementia. Lessons Learnt for Pain Treatment Plans Utilizing Data from the Veteran Health Administration

Alzheimer’s disease and related dementias (ADRD), pain and chronic complex conditions (CCC) often co-occur leading to polypharmacy and with potential inappropriate medications (PIMs) use, are important risk factors for adverse drug reactions and hospitalizations in older adults. Many US veterans are at high risk for persistent pain due to age, injury or medical illness. Concerns about inadequate treatment of pain—accompanied by evidence about the analgesic efficacy of opioids—has led to an increase in the use of opioid medications to treat chronic pain in the Veterans Health Administration (VHA) and other healthcare systems. This study aims to investigate the relationship between receipt of pain medications and centrally (CNS) acting PIMs among veterans diagnosed with dementia, pain intensity, and CCC 90-days prior to hospitalization. The final analytic sample included 96,224 (81.7%) eligible older veterans from outpatient visits between October 2012–30 September 2013. We hypothesized that veterans with ADRD, and severe pain intensity may receive inappropriate pain management and CNS-acting PIMs. Seventy percent of the veterans, and especially people with ADRD, reported severe pain intensity. One in three veterans with ADRD and severe pain intensity have an increased likelihood for CNS-acting PIMs, and/or opioids. Regular assessment and re-assessment of pain among older persons with CCC, patient-centered tapering or discontinuation of opioids, alternatives to CNS-acting PIMs, and use of non-pharmacological approaches should be considered.publishedVersio

High risk prescribing in older adults: Prevalence, clinical and economic implications and potential for intervention at the population level

Background: High risk prescribing can compromise independent wellbeing and quality of life in older adults. The aims of this project are to determine the prevalence, risk factors, clinical consequences, and costs of high risk prescribing, and to assess the impact of interventions on high risk prescribing in older people. Methods. The proposed project will utilise data from the 45 and Up Study, a large scale cohort of 267,153 men and women aged 45 and over recruited during 2006-2009 from the state of New South Wales, Australia linked to a range of administrative health datasets. High risk prescribing will be assessed using three indicators: polypharmacy (use of five or more medicines); Beers Criteria (an explicit measure of potentially inappropriate medication use); and Drug Burden Index (a pharmacologic dose-dependent measure of cumulative exposure to anticholinergic and sedative medicines). Individual risk factors from the 45 and Up Study questionnaire, and health system characteristics from health datasets that are associated with the likelihood of high risk prescribing will be identified. The main outcome measures will include hospitalisation (first admission to hospital, total days in hospital, cause-specific hospitalisation); admission to institutionalised care; all-cause mortality, and, where possible, cause-specific mortality. Economic costs to the health care system and implications of high risk prescribing will be also investigated. In addition, changes in high risk prescribing will be evaluated in relation to certain routine medicines-related interventions. The statistical analysis will be conducted using standard pharmaco-epidemiological methods including descriptive analysis, univariate and multivariate regression analysis, controlling for relevant confounding factors, using a number of different approaches. Discussion. The availability of large-scale data is useful to identify opportunities for improving prescribing, and health in older adults. The size of the 45 and Up Study, along with linkage to health databases provides an important opportunity to investigate the relationship between high risk prescribing and adverse outcomes in a real-world population of older adults. © 2013 Gnjidic et al.; licensee BioMed Central Ltd

Anticholinergic drug burden tools/scales and adverse outcomes in different clinical settings: a systematic review of reviews

Background: Cumulative anticholinergic exposure (anticholinergic burden) has been linked to a number of adverse outcomes. To conduct research in this area, an agreed approach to describing anticholinergic burden is needed. Objective: This review set out to identify anticholinergic burden scales, to describe their rationale, the settings in which they have been used and the outcomes associated with them. Methods: A search was performed using the Healthcare Databases Advanced Search of MEDLINE, EMBASE, Cochrane, CINAHL and PsycINFO from inception to October 2016 to identify systematic reviews describing anticholinergic burden scales or tools. Abstracts and titles were reviewed to determine eligibility for review with eligible articles read in full. The final selection of reviews was critically appraised using the ROBIS tool and pre-defined data were extracted; the primary data of interest were the anticholinergic burden scales or tools used. Results: Five reviews were identified for analysis containing a total of 62 original articles. Eighteen anticholinergic burden scales or tools were identified with variation in their derivation, content and how they quantified the anticholinergic activity of medications. The Drug Burden Index was the most commonly used scale or tool in community and database studies, while the Anticholinergic Risk Scale was used more frequently in care homes and hospital settings. The association between anticholinergic burden and clinical outcomes varied by index and study. Falls and hospitalisation were consistently found to be associated with anticholinergic burden. Mortality, delirium, physical function and cognition were not consistently associated. Conclusions: Anticholinergic burden scales vary in their rationale, use and association with outcomes. This review showed that the concept of anticholinergic burden has been variably defined and inconsistently described using a number of indices with different content and scoring. The association between adverse outcomes and anticholinergic burden varies between scores and has not been conclusively established

Patterns of high-risk prescribing and other factors in relation to receipt of a home medicines review: A prospective cohort investigation among adults aged 45 years and over in Australia

© Author(s) (or their employer(s)) 2019. Objectives: To quantify the relationship between home medicines review (HMR) receipt in older adults and sociodemographic, medication-related and health factors. Design: Prospective cohort analysis. Settings, participants, measurements: Questionnaire data from a population-based cohort study of individuals aged ≥45 years, Sydney, Australia were linked with primary healthcare data, medication and hospitalisation data, to ascertain factors associated with HMR receipt during the period July 2009-June 2014. Medication-related factors included exposure to five and more medications (polypharmacy), narrow therapeutic index medicines, potentially inappropriate prescribing defined using Beers Criteria medicines, and anticholinergic and sedative drugs, defined using the Drug Burden Index (DBI). Poisson and Cox regression models were used to evaluate HMR receipt in relation to sociodemographic, behavioural and health characteristics, and time-varying factors including medication use and hospitalisations. Primary outcome: HMR receipt during the 5-year study period. Results: Over 5 years of follow-up, 4.7% (n=6115) of 131 483 participants received at least one HMR. Five-year HMR receipt was: 1.5% in people using <5 medications at baseline, 6.8% with 5-9 medications, 12.7% with ≥10 medications, 8.8% using Narrow Therapeutic Index medicines, 6.8% using Beers Criteria potentially inappropriate medicines and 7.4% using DBI medicines. Age-sex stratified HRs for HMR receipt were 6.07 (95% CI: 5.58 to 6.59) and 12.46 (11.42 to 13.59) for concurrent use of 5-9 and ≥10 versus <5 medications, respectively. The age-sex adjusted rate ratio for HMR receipt was 2.65 (2.51 to 2.80) with poor versus good self-reported health; this association was attenuated substantially following additional adjustment for polypharmacy. Conclusions: HMR was common in individuals using multiple medications, a formal indication for general practitioner referral and, to a lesser extent, with poorer health and other markers of high-risk prescribing. Despite this, HMR use over a 5-year period was generally below 10%, even in high-risk groups, suggesting substantial potential for improvement in uptake and targeting

Trajectories of long-term exposure to anticholinergic and sedative drugs: A latent class growth analysis

Introduction: A variety of drugs, which are frequently prescribed to older people, have anticholinergic and sedative effects whereby they may impair cognitive and physical function. Although substantial inter-individual variation in anticholinergic and sedative exposure has been documented, little is known about subpopulations with distinct trajectories of exposure. Methods: Data from the Longitudinal Aging Study Amsterdam (LASA), an ongoing Dutch population-based cohort study, collected over 20 years (1992-2012) at seven occasions, were analyzed. On each occasion, cumulative anticholinergic and sedative exposure was quantified with the Drug Burden Index, a linear additive pharmacological dose-response model. The most likely number of trajectories were empirically derived with Latent Class Growth Analysis using "Goodness of fit" statistics. Trajectories were then compared on physical and cognitive function. Results: A total of 763 participants completed all follow-ups (61% women; mean age 83, ±6). "Goodness of fit" statistics (Bayesian In-formation Criterion = 22916, Bootstrapped Likelihood Ratio Test of 3 vs. 2 classes = 514.12

Quantifying cumulative anticholinergic and sedative drug load among US Medicare Beneficiaries

Purpose: Medications with anticholinergic and sedative properties are widely used among older adults despite strong evidence of harm. The drug burden index (DBI), a pharmacological screening tool, measures these properties across drug classes, and higher DBI drug exposure (DBI > 1) has been associated with certain physical function-related adverse events. Our aim was to quantify mean daily DBI drug exposure among older adults in the United States (US). Methods: We screened medications for DBI properties and operationalized the DBI for US Medicare claims. We then conducted a retrospective cohort study of a 20% random, nationwide sample of 4 137 384 fee-for-service Medicare beneficiaries aged 66+ years (134 757 039 person-months) from January 2013 to December 2016. We measured the monthly distribution based on mean daily DBI, categorized as (a) >0 vs 0 (any use) and (b) 0, 0 2, and examined temporal trends. We described patient-level factors (eg, demographics, healthcare use) associated with high (>2) vs low (0 2. Predictors of high monthly DBI drug exposure (DBI > 2) included certain indicators of increased healthcare use (eg, high number of drug claims), white race, younger age, frailty, and a psychosis diagnosis code. Conclusions: The predictors of high DBI drug exposure can inform discussions between patients and providers about medication appropriateness and potential de-prescribing. Future Medicare-based studies should assess the association between the DBI and adverse events. © 2020 John Wiley & Sons Lt

Effects of anticholinergic and sedative medication use on fractures: A self-controlled design study

Background/Objectives: Unintentional falls are a leading cause of injury for older adults, and evidence is needed to understand modifiable risk factors. We evaluated 1-year fall-related fracture risk and whether dispensing of medications with anticholinergic/sedating properties is temporally associated with an increased odds of these fractures. Design: A retrospective cohort study with nested self-controlled analyses conducted between January 1, 2014, and December 31, 2016. Setting: Twenty percent nationwide, random sample of US Medicare beneficiaries. Participants: New users of medications with anticholinergic/sedating properties who were 66+ years old and had Medicare Parts A, B, and D coverage but no claims for medications with anticholinergic/sedating properties in the year before initiation were eligible. Measurements: We followed new users of medications with anticholinergic/sedating properties until first non-vertebral, fall-related fracture (primary outcome), Medicare disenrollment, death, or end of study data. We estimated the 1-year risk with corresponding 95% confidence intervals (CIs) of first fracture after new use. We applied the self-controlled case-crossover and case-time-control designs to estimate odds ratios (ORs) and 95% CIs by comparing anticholinergic and/or sedating medication exposure (any vs. none) during a 14-day hazard period preceding the fracture to exposure to these medications during an earlier 14-day control period. Results: A total of 1,097,989 Medicare beneficiaries initiated medications with anticholinergic/sedating properties in the study period. The 1-year cumulative incidence of fall-related fracture, accounting for death as a competing risk, was 5.0% (95% CI: 5.0%–5.0%). Using the case-crossover design (n = 41,889), the adjusted OR for the association between anticholinergic/sedating medications and fractures was 1.03 (95% CI: 0.99, 1.08). Accounting for the noted temporal trend using the case-time-control design (n = 209,395), the adjusted OR was 1.60 (95% CI: 1.52, 1.69). Conclusion: Use of anticholinergic/sedating medication was temporally associated with an increased odds of fall-related fractures. Patients and their healthcare providers should consider pharmacologic and non-pharmacologic treatments for the target condition that are safer

Toward optimal implementation of cancer prevention and control programs in public health: A study protocol on mis-implementation

Abstract Background Much of the cancer burden in the USA is preventable, through application of existing knowledge. State-level funders and public health practitioners are in ideal positions to affect programs and policies related to cancer control. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. Greater attention to mis-implementation should lead to use of effective interventions and more efficient expenditure of resources, which in the long term, will lead to more positive cancer outcomes. Methods This is a three-phase study that takes a comprehensive approach, leading to the elucidation of tactics for addressing mis-implementation. Phase 1: We assess the extent to which mis-implementation is occurring among state cancer control programs in public health. This initial phase will involve a survey of 800 practitioners representing all states. The programs represented will span the full continuum of cancer control, from primary prevention to survivorship. Phase 2: Using data from phase 1 to identify organizations in which mis-implementation is particularly high or low, the team will conduct eight comparative case studies to get a richer understanding of mis-implementation and to understand contextual differences. These case studies will highlight lessons learned about mis-implementation and identify hypothesized drivers. Phase 3: Agent-based modeling will be used to identify dynamic interactions between individual capacity, organizational capacity, use of evidence, funding, and external factors driving mis-implementation. The team will then translate and disseminate findings from phases 1 to 3 to practitioners and practice-related stakeholders to support the reduction of mis-implementation. Discussion This study is innovative and significant because it will (1) be the first to refine and further develop reliable and valid measures of mis-implementation of public health programs; (2) bring together a strong, transdisciplinary team with significant expertise in practice-based research; (3) use agent-based modeling to address cancer control implementation; and (4) use a participatory, evidence-based, stakeholder-driven approach that will identify key leverage points for addressing mis-implementation among state public health programs. This research is expected to provide replicable computational simulation models that can identify leverage points and public health system dynamics to reduce mis-implementation in cancer control and may be of interest to other health areas