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      Multimorbidity patterns, polypharmacy and their association with liver and kidney abnormalities in people over 65 years of age: a longitudinal study

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          Abstract

          Background

          The implementation of individual clinical practice guidelines in patients with multimorbidity often results in polypharmacy. Our aim was to analyse medication use according to longitudinal multimorbidity patterns (MP) and determine during a 5-year period (2012–16) which MP are associated with abnormal liver and kidney function in primary care patients over 65 years of age living in Catalonia.

          Methods

          Design: Longitudinal study (years 2012 to 2016) based on the electronic health records contained in Information System for Research in Primary Care database of the Catalan Institute of Health (SIDIAP). Variables: age, sex, MP, medication and polypharmacy (drug exposure obtained from the Pharmacy Invoice Registry). Medicines were classified in accordance with the Anatomical Therapeutic Chemical Classification System (ATC). Glomerular filtration rate was used to determine abnormal kidney function, and serum levels of alkaline phosphatase, alanine transaminase and gamma-glutamyl transpeptidase were used to diagnose abnormal liver function. Statistics: For medication use in MP, we calculated annual mean packages of each drug in each MP, and observed/expected ratios were obtained by dividing mean packages in the cluster by mean packages of the same drug in the overall population. Logistic regression models were fitted to estimate the association between MP at baseline and abnormal kidney and liver function tests during follow up.

          Results

          Nine hundred sixteen thousand six hundred nineteen patients were included, and 743,827 completed the follow up. We identified one polypharmacy profile per MP, and concluded that the most prescribed drugs in each pattern corresponded to the diseases overrepresented in that specific MP. The median of drugs ranged from 3 (Cluster 1 - Non-Specific) to 8 (Cluster 10 - Multisystem Pattern). Abnormal kidney function was most commonly observed in the Cluster 4 - Cardio-Circulatory and Renal (Odds Ratio [OR] 2.19; Confidence interval [CI] 95% 2.15–2.23) and Cluster 3 - Minority Metabolic Autoimmune-Inflammatory (OR 2.16; CI 95% 2.12–2.20) MP. A higher risk of abnormal liver function was observed in the Cluster 8 - Digestive (OR 3.39; CI 95% 3.30–3.49), and Cluster 4 - Cardio-Circulatory and Renal (OR 1.96; CI 95% 1.91–2.02) MP.

          Conclusions

          A higher risk of abnormal kidney and liver function was observed in specific MP. The long-term characterisation of MP and polypharmacy illustrates the burden of chronic multimorbidity and polypharmacy in the elderly population.

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          Most cited references21

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          Polypharmacy in elderly patients.

          Polypharmacy (ie, the use of multiple medications and/or the administration of more medications than are clinically indicated, representing unnecessary drug use) is common among the elderly. The goal of this research was to provide a description of observational studies examining the epidemiology of polypharmacy and to review randomized controlled studies that have been published in the past 2 decades designed to reduce polypharmacy in older adults. Materials for this review were gathered from a search of the MEDLINE database (1986-June 2007) and International Pharmaceutical Abstracts (1986-June 2007) to identify articles in people aged >65 years. We used a combination of the following search terms: polypharmacy, multiple medications, polymedicine, elderly, geriatric, and aged. A manual search of the reference lists from identified articles and the authors' article files, book chapters, and recent reviews was conducted to identify additional articles. From these, the authors identified those studies that measured polypharmacy. The literature review found that polypharmacy continues to increase and is a known risk factor for important morbidity and mortality. There are few rigorously designed intervention studies that have been shown to reduce unnecessary polypharmacy in older adults. The literature review identified 5 articles, which are included here. All studies showed an improvement in polypharmacy. Many studies have found that various numbers of medications are associated with negative health outcomes, but more research is needed to further delineate the consequences associated with unnecessary drug use in elderly patients. Health care professionals should be aware of the risks and fully evaluate all medications at each patient visit to prevent polypharmacy from occurring.
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            Interventions to improve the appropriate use of polypharmacy in older people: a Cochrane systematic review

            Objective To summarise the findings of an updated Cochrane review of interventions aimed at improving the appropriate use of polypharmacy in older people. Design Cochrane systematic review. Multiple electronic databases were searched including MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (from inception to November 2013). Hand searching of references was also performed. Randomised controlled trials (RCTs), controlled clinical trials, controlled before-and-after studies and interrupted time series analyses reporting on interventions targeting appropriate polypharmacy in older people in any healthcare setting were included if they used a validated measure of prescribing appropriateness. Evidence quality was assessed using the Cochrane risk of bias tool and GRADE (Grades of Recommendation, Assessment, Development and Evaluation). Setting All healthcare settings. Participants Older people (≥65 years) with ≥1 long-term condition who were receiving polypharmacy (≥4 regular medicines). Primary and secondary outcome measures Primary outcomes were the change in prevalence of appropriate polypharmacy and hospital admissions. Medication-related problems (eg, adverse drug reactions), medication adherence and quality of life were included as secondary outcomes. Results 12 studies were included: 8 RCTs, 2 cluster RCTs and 2 controlled before-and-after studies. 1 study involved computerised decision support and 11 comprised pharmaceutical care approaches across various settings. Appropriateness was measured using validated tools, including the Medication Appropriateness Index, Beers’ criteria and Screening Tool of Older Person's Prescriptions (STOPP)/ Screening Tool to Alert doctors to Right Treatment (START). The interventions demonstrated a reduction in inappropriate prescribing. Evidence of effect on hospital admissions and medication-related problems was conflicting. No differences in health-related quality of life were reported. Conclusions The included interventions demonstrated improvements in appropriate polypharmacy based on reductions in inappropriate prescribing. However, it remains unclear if interventions resulted in clinically significant improvements (eg, in terms of hospital admissions). Future intervention studies would benefit from available guidance on intervention development, evaluation and reporting to facilitate replication in clinical practice.
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              The epidemiology of polypharmacy in older adults: register-based prospective cohort study

              Objective Polypharmacy is the concomitant use of several drugs by a single person, and it increases the risk of adverse drug-related events in older adults. Little is known about the epidemiology of polypharmacy at the population level. We aimed to measure the prevalence and incidence of polypharmacy and to investigate the associated factors. Methods A prospective cohort study was conducted using register data with national coverage in Sweden. A total of 1,742,336 individuals aged ≥65 years at baseline (November 1, 2010) were included and followed until death or the end of the study (December 20, 2013). Results On average, individuals were exposed to 4.6 (SD =4.0) drugs at baseline. The prevalence of polypharmacy (5+ drugs) was 44.0%, and the prevalence of excessive polypharmacy (10+ drugs) was 11.7%. The incidence rate of polypharmacy among individuals without polypharmacy at baseline was 19.9 per 100 person-years, ranging from 16.8% in individuals aged 65–74 years to 33.2% in those aged ≥95 years (adjusted hazard ratio [HR] =1.49, 95% confidence interval [CI] 1.42–1.56). The incidence rate of excessive polypharmacy was 8.0 per 100 person-years. Older adults using multi-dose dispensing were at significantly higher risk of developing incident polypharmacy compared with those receiving ordinary prescriptions (HR =1.51, 95% CI 1.47–1.55). When adjusting for confounders, living in nursing home was found to be associated with lower risks of incident polypharmacy and incident excessive polypharmacy (HR =0.79 and HR =0.86, p<0.001, respectively). Conclusion The prevalence and incidence of polypharmacy are high among older adults in Sweden. Interventions aimed at reducing the prevalence of polypharmacy should also target potential incident polypharmacy users as they are the ones who fuel future polypharmacy.
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                Author and article information

                Contributors
                aroso@idiapjgol.org
                cviolan@idiapjgol.org
                Journal
                BMC Geriatr
                BMC Geriatr
                BMC Geriatrics
                BioMed Central (London )
                1471-2318
                12 June 2020
                12 June 2020
                2020
                : 20
                : 206
                Affiliations
                [1 ]GRID grid.22061.37, ISNI 0000 0000 9127 6969, Àrea del Medicament i Servei de Farmàcia, Gerencia Territorial de Barcelona, , Institut Català de la Salut, ; Barcelona, Spain
                [2 ]Fundació Institut Universitari per a la recerca a l’Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
                [3 ]GRID grid.7080.f, Universitat Autònoma de Barcelona, ; Cerdanyola del Vallès, Bellaterra, Spain
                [4 ]GRID grid.440820.a, Department of Psychiatry, , Vic University Hospital, ; Vic, Spain
                [5 ]GRID grid.22061.37, ISNI 0000 0000 9127 6969, Àrea de Serveis Assistencials. Servei Català de la Salut, ; Barcelona, Spain
                Author information
                http://orcid.org/0000-0003-3309-5360
                Article
                1580
                10.1186/s12877-020-01580-1
                7291454
                32532213
                7dfd50ea-2c4d-4f3f-8a72-824e44417a1d
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 11 December 2019
                : 7 May 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004587, Instituto de Salud Carlos III;
                Award ID: PI16/00639
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100010552, Departament de Salut, Generalitat de Catalunya;
                Award ID: SLT002/16/00058
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100002943, Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya;
                Award ID: SGR 578
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Geriatric medicine
                multimorbidity,epidemiology,polypharmacy,primary health care,ageing,longitudinal study

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