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Pharmacogenetic interventions to improve outcomes in patients with multimorbidity or prescribed polypharmacy: a systematic review.

ABSTRACT: Conventional medicines optimisation interventions in people with multimorbidity and polypharmacy are complex and yet limited; a more holistic and integrated approach to healthcare delivery is required. Pharmacogenetics has potential as a component of medicines optimisation. Studies involving multi-medicine pharmacogenetics in adults with multimorbidity or polypharmacy, reporting on outcomes derived from relevant core outcome sets, were included in this systematic review. Narrative synthesis was undertaken to summarise the data; meta-analysis was inappropriate due to study heterogeneity. Fifteen studies of diverse design and variable quality were included. A small, randomised study involving pharmacist-led medicines optimisation, including pharmacogenetics, suggests this approach could have significant benefits for patients and health systems. However, due to study design heterogeneity and the quality of the included studies, it is difficult to draw generalisable conclusions. Further pragmatic, robust pharmacogenetics studies in diverse, real-world patient populations, are required to establish the benefit of multi-medicine pharmacogenetic screening on patient outcomes.

SUBMITTER: O'Shea J

PROVIDER: S-EPMC8975737 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Pharmacogenetic interventions to improve outcomes in patients with multimorbidity or prescribed polypharmacy: a systematic review.

O'Shea Joseph J Ledwidge Mark M Gallagher Joseph J Keenan Catherine C Ryan Cristín C

The pharmacogenomics journal 20220222 2

Conventional medicines optimisation interventions in people with multimorbidity and polypharmacy are complex and yet limited; a more holistic and integrated approach to healthcare delivery is required. Pharmacogenetics has potential as a component of medicines optimisation. Studies involving multi-medicine pharmacogenetics in adults with multimorbidity or polypharmacy, reporting on outcomes derived from relevant core outcome sets, were included in this systematic review. Narrative synthesis was ...[more]

PMID: 35194175

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Project description:BackgroundTreatment complexity rises in line with the number of drugs, single doses, and administration methods, thereby threatening patient adherence. Patients with multimorbidity often need flexible, individualised treatment regimens, but alterations during the course of treatment may further increase complexity. The objective of our study was to explore medication changes in older patients with multimorbidity and polypharmacy in general practice.MethodsWe retrospectively analysed data from the cluster-randomised PRIMUM trial (PRIoritisation of MUltimedication in Multimorbidity) conducted in 72 general practices. We developed an algorithm for active pharmaceutical ingredients (API), strength, dosage, and administration method to assess changes in physician-reported medication data during two intervals (baseline to six-months: ∆1; six- to nine-months: ∆2), analysed them descriptively at prescription and patient levels, and checked for intervention effects.ResultsOf 502 patients (median age 72 years, 52% female), 464 completed the study. Changes occurred in 98.6% of patients (changes were 19% more likely in the intervention group): API changes during ∆1 and ∆2 occurred in 414 (82.5%) and 338 (67.3%) of patients, dosage alterations in 372 (74.1%) and 296 (59.2%), and changes in API strength in 158 (31.5%) and 138 (27.5%) respectively. Administration method changed in 79 (16%) of patients in both ∆1 and ∆2. Simvastatin, metformin and aspirin were most frequently subject to alterations.ConclusionMedication regimens in older patients with multimorbidity and polypharmacy changed frequently. These are mostly due to discontinuations and dosage alterations, followed by additions and restarts. These findings cast doubt on the effectiveness of cross-sectional assessments of medication and support longitudinal assessments where possible.Trial registration1. Prospective registration: Trial registration number: NCT01171339 ; Name of registry: ClinicalTrials.gov; Date of registration: July 27, 2010; Date of enrolment of the first participant to the trial: August 12, 2010. 2. Peer reviewed trial registration: Trial registration number: ISRCTN99526053 ; Name of registry: Controlled Trials; Date of registration: August 31, 2010; Date of enrolment of the first participant to the trial: August 12, 2010.

Project description:BackgroundMultimorbidity, defined as the co-existence of two or more chronic conditions, presents significant challenges to patients, healthcare providers and health systems. Despite this, there is ongoing uncertainty about the most effective ways to manage patients with multimorbidity. This review updated and narrowed the focus of a previous Cochrane review and aimed to determine the effectiveness of interventions designed to improve outcomes in people with multimorbidity in primary care and community settings, compared to usual care.MethodsWe searched eight databases and two trials registers up to 9 September 2019. Two review authors independently screened potentially eligible titles and selected studies, extracted data, evaluated study quality and judged the certainty of the evidence (GRADE). Interventions were grouped by their predominant focus into care-coordination/self-management support, self-management support and medicines management. Main outcomes were health-related quality of life (HRQoL) and mental health. Meta-analyses were conducted, where possible, but the synthesis was predominantly narrative.ResultsWe included 16 RCTs with 4753 participants, the majority being older adults with at least three conditions. There were eight care-coordination/self-management support studies, four self-management support studies and four medicines management studies. There was little or no evidence of an effect on primary outcomes of HRQoL (MD 0.03, 95% CI -0.01 to 0.07, I2 = 39%) and mental health or on secondary outcomes with a small number of studies reporting that care coordination may improve patient experience of care and self-management support may improve patient health behaviours. Overall, the certainty of the evidence was graded as low due to significant variation in study participants and interventions.ConclusionsThere are remaining uncertainties about the effectiveness of interventions for people with multimorbidity, despite the growing number of RCTs conducted in this area. Our findings suggest that future research should consider patient experience of care, optimising medicines management and targeted patient health behaviours such as exercise.

Project description:ObjectivesThe aim of this study was to demonstrate the existence of systematic associations in drug prescription that lead to the establishment of patterns of polypharmacy, and the clinical interpretation of the associations found in each pattern.MethodsA cross-sectional study was conducted based on information obtained from electronic medical records and the primary care pharmacy database in 2008. An exploratory factor analysis of drug dispensing information regarding 79,089 adult patients was performed to identify the patterns of polypharmacy. The analysis was stratified by age and sex.ResultsSeven patterns of polypharmacy were identified, which may be classified depending on the type of disease they are intended to treat: cardiovascular, depression-anxiety, acute respiratory infection (ARI), chronic obstructive pulmonary disease (COPD), rhinitis-asthma, pain, and menopause. Some of these patterns revealed a clear clinical consistency and included drugs that are prescribed together for the same clinical indication (i.e., ARI and COPD patterns). Other patterns were more complex but also clinically consistent: in the cardiovascular pattern, drugs for the treatment of known risk factors-such as hypertension or dyslipidemia-were combined with other medications for the treatment of diabetes or established cardiovascular pathology (e.g., antiplatelet agents). Almost all of the patterns included drugs for preventing or treating potential side effects of other drugs in the same pattern.ConclusionsThe present study demonstrated the existence of non-random associations in drug prescription, resulting in patterns of polypharmacy that are sound from the pharmacological and clinical viewpoints and that exist in a significant proportion of the population. This finding necessitates future longitudinal studies to confirm some of the proposed causal associations. The information discovered would further the development and/or adaptation of clinical patient guidelines to patients with multimorbidity who are taking multiple drugs.

Project description:BackgroundChronic disease patients who are the greatest users of healthcare services are often referred to as high-need, high-cost (HNHC). Payers, providers, and policymakers in the United States are interested in identifying interventions that can modify or reduce preventable healthcare use among these patients, without adversely impacting their quality of care and health. We systematically reviewed the evidence on the effectiveness of complex interventions designed to change the healthcare of HNHC patients, modifying cost and utilization, as well as clinical/functional, and social risk factor outcomes.MethodsWe searched 8 electronic databases (January 2000 to March 2021) and selected non-profit organization and government agency websites for randomized controlled trials and observational studies with comparison groups that targeted HNHC patients. Two investigators independently screened each study and abstracted data into structured forms. Study quality was assessed using standard risk of bias tools. Random-effects meta-analysis was conducted for outcomes reported by at least 3 comparable samples.ResultsForty studies met our inclusion criteria. Interventions were heterogenous and classified into 7 categories, reflecting the predominant service location/modality (home, primary care, ambulatory intensive caring unit [aICU], emergency department [ED], community, telephonic/mail, and system-level). Home-, primary care-, and ED-based interventions resulted in reductions in high-cost healthcare services (ED and hospital use). ED-based interventions also resulted in greater use of primary care. Primary care- and ED-based interventions reduced costs. System-level transformation interventions did not reduce costs.DiscussionWe found limited evidence of intervention effectiveness in relation to cost and use, and additional evidence is needed to strengthen our confidence in the findings. Few studies reported patient clinical/functional or social risk factor outcomes (e.g., homelessness) or sufficient details for determining why individual interventions work, for whom, and when. Future evaluations could provide additional insights, by including intermediate process outcomes and patients' experiences, in assessing the impact of these complex interventions.Prospero registration numberCRD42020161179.

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Pharmacogenetic interventions to improve outcomes in patients with multimorbidity or prescribed polypharmacy: a systematic review.

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Pharmacogenetic interventions to improve outcomes in patients with multimorbidity or prescribed polypharmacy: a systematic review.

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