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      Current evidence on the impact of medication optimization or pharmacological interventions on frailty or aspects of frailty: a systematic review of randomized controlled trials

      review-article
      1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 1 ,
      European Journal of Clinical Pharmacology
      Springer Berlin Heidelberg
      Frailty, Prefrailty, Polypharmacy, Medication optimization, Inappropriate drug treatment, Older people

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          Abstract

          Background

          Frailty and adverse drug effects are linked in the fact that polypharmacy is correlated with the severity of frailty; however, a causal relation has not been proven in older people with clinically manifest frailty.

          Methods

          A literature search was performed in Medline to detect prospective randomized controlled trials (RCTs) testing the effects of pharmacological interventions or medication optimization in older frail adults on comprehensive frailty scores or partial aspects of frailty that were published from January 1998 to October 2019.

          Results

          Twenty-five studies were identified, 4 on comprehensive frailty scores and 21 on aspects of frailty. Two trials on comprehensive frailty scores showed positive results on frailty although the contribution of medication review in a multidimensional approach was unclear. In the studies on aspects related to frailty, ten individual drug interventions showed improvement in physical performance, muscle strength or body composition utilizing alfacalcidol, teriparatide, piroxicam, testosterone, recombinant human chorionic gonadotropin, or capromorelin. There were no studies examining negative effects of drugs on frailty.

          Conclusion

          So far, data on a causal relationship between drugs and frailty are inconclusive or related to single-drug interventions on partial aspects of frailty. There is a clear need for RCTs on this topic that should be based on a comprehensive, internationally consistent and thus reproducible concept of frailty assessment.

          Electronic supplementary material

          The online version of this article (10.1007/s00228-020-02951-8) contains supplementary material, which is available to authorized users.

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          Most cited references54

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          Assessing the quality of reports of randomized clinical trials: is blinding necessary?

          It has been suggested that the quality of clinical trials should be assessed by blinded raters to limit the risk of introducing bias into meta-analyses and systematic reviews, and into the peer-review process. There is very little evidence in the literature to substantiate this. This study describes the development of an instrument to assess the quality of reports of randomized clinical trials (RCTs) in pain research and its use to determine the effect of rater blinding on the assessments of quality. A multidisciplinary panel of six judges produced an initial version of the instrument. Fourteen raters from three different backgrounds assessed the quality of 36 research reports in pain research, selected from three different samples. Seven were allocated randomly to perform the assessments under blind conditions. The final version of the instrument included three items. These items were scored consistently by all the raters regardless of background and could discriminate between reports from the different samples. Blind assessments produced significantly lower and more consistent scores than open assessments. The implications of this finding for systematic reviews, meta-analytic research and the peer-review process are discussed.
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            American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults

            (2019)
            The American Geriatrics Society (AGS) Beers Criteria® (AGS Beers Criteria®) for Potentially Inappropriate Medication (PIM) Use in Older Adults are widely used by clinicians, educators, researchers, healthcare administrators, and regulators. Since 2011, the AGS has been the steward of the criteria and has produced updates on a 3-year cycle. The AGS Beers Criteria® is an explicit list of PIMs that are typically best avoided by older adults in most circumstances or under specific situations, such as in certain diseases or conditions. For the 2019 update, an interdisciplinary expert panel reviewed the evidence published since the last update (2015) to determine if new criteria should be added or if existing criteria should be removed or undergo changes to their recommendation, rationale, level of evidence, or strength of recommendation. J Am Geriatr Soc 67:674-694, 2019.
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              Frailty: implications for clinical practice and public health

              Frailty is an emerging global health burden, with major implications for clinical practice and public health. The prevalence of frailty is expected to rise alongside rapid growth in the ageing population. The course of frailty is characterised by a decline in functioning across multiple physiological systems, accompanied by an increased vulnerability to stressors. Having frailty places a person at increased risk of adverse outcomes, including falls, hospitalisation, and mortality. Studies have shown a clear pattern of increased health-care costs and use associated with frailty. All older adults are at risk of developing frailty, although risk levels are substantially higher among those with comorbidities, low socioeconomic position, poor diet, and sedentary lifestyles. Lifestyle and clinical risk factors are potentially modifiable by specific interventions and preventive actions. The concept of frailty is increasingly being used in primary, acute, and specialist care. However, despite efforts over the past three decades, agreement on a standard instrument to identify frailty has not yet been achieved. In this Series paper, we provide an overview of the global impact and burden of frailty, the usefulness of the frailty concept in clinical practice, potential targets for frailty prevention, and directions that need to be explored in the future.
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                Author and article information

                Contributors
                martin.wehling@medma.uni-heidelberg.de
                Journal
                Eur J Clin Pharmacol
                Eur J Clin Pharmacol
                European Journal of Clinical Pharmacology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0031-6970
                1432-1041
                7 August 2020
                7 August 2020
                2021
                : 77
                : 1
                : 1-12
                Affiliations
                [1 ]GRID grid.7700.0, ISNI 0000 0001 2190 4373, Clinical Pharmacology Mannheim, Faculty of Medicine Mannheim, , Ruprecht-Karls-University of Heidelberg, ; Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
                [2 ]GRID grid.5342.0, ISNI 0000 0001 2069 7798, Section of Geriatrics, Department of Internal Medicine and Paediatrics, , Ghent University, ; Ghent, Belgium
                [3 ]GRID grid.418083.6, ISNI 0000 0001 2152 7926, Department of Geriatric Medicine, , INRCA Istituto Nazionale di Ricovero e Cura per Anziani, ; Ancona, Italy
                [4 ]GRID grid.416651.1, ISNI 0000 0000 9120 6856, Department of Cardiovascular, Endocrine-Metabolic Diseases and Aging, , Istituto Superiore di Sanità, ; Rome, Italy
                [5 ]GRID grid.411347.4, ISNI 0000 0000 9248 5770, Servicio de Geriatría. Hospital Universitario Ramón y Cajal (IRYCIS), ; Madrid, Spain
                [6 ]GRID grid.6582.9, ISNI 0000 0004 1936 9748, Department of Geriatrics, , University of Ulm and Geriatric Center Ulm/Alb-Donau, Agaplesion Bethesda Hospital, ; Alb-Donau, Ulm, Germany
                [7 ]GRID grid.5292.c, ISNI 0000 0001 2097 4740, Faculty of Industrial Design Engineering, , Delft University of Technology, ; Delft, Netherlands
                [8 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Institute of Pharmaceutical Science, , King’s College London, ; London, UK
                [9 ]GRID grid.5491.9, ISNI 0000 0004 1936 9297, Academic Geriatric Medicine, Faculty of Medicine, , Southampton University, ; Southampton, UK
                [10 ]GRID grid.414601.6, ISNI 0000 0000 8853 076X, Geriatric & Stroke Medicine, , Brighton and Sussex Medical School, ; Brighton, UK
                [11 ]GRID grid.7914.b, ISNI 0000 0004 1936 7443, Department of Clinical Science, , University of Bergen, ; Bergen, Norway
                [12 ]AZ Alma, Eeklo, Belgium
                [13 ]GRID grid.16008.3f, ISNI 0000 0001 2295 9843, University of Luxembourg, ; Esch-sur-Alzette, Luxembourg
                [14 ]GRID grid.9757.c, ISNI 0000 0004 0415 6205, Keele University, ; Newcastle under Lyme, UK
                [15 ]Department of Acute Geriatrics, Social Medical Center East, Vienna, Austria
                [16 ]GRID grid.83440.3b, ISNI 0000000121901201, School of Medicine, , University College Cork, ; Cambridge, UK
                [17 ]GRID grid.14013.37, ISNI 0000 0004 0640 0021, University of Iceland, Geriatrics K4, Landspítali University, ; Reykjavík, Iceland
                [18 ]GRID grid.7692.a, ISNI 0000000090126352, Geriatrics, Department of Geriatric Medicine and Expertise Centre Pharmacotherapy in Old Persons, , University Medical Center Utrecht, Utrecht University, ; Utrecht, The Netherlands
                [19 ]GRID grid.7872.a, ISNI 0000000123318773, Department of Medicine, , University College Cork, Cork University Hospital, ; Cork, Ireland
                [20 ]GRID grid.450697.9, ISNI 0000 0004 1757 8650, Department of Geriatric Care, Orthogeriatrics and Rehabilitation, , Galliera Hospital, ; Genoa, Italy
                [21 ]GRID grid.7644.1, ISNI 0000 0001 0120 3326, Department of Interdisciplinary Medicine, , University of Bari, ; Bari, Italy
                [22 ]Department of Public Health and Caring Sciences/Geriatrics, Uppsala, Sweden
                [23 ]GRID grid.410526.4, ISNI 0000 0001 0277 7938, Geriatric Department, , Hospital General Universitario Gregorio Marañón, ; Madrid, Spain
                [24 ]GRID grid.410526.4, ISNI 0000 0001 0277 7938, Instituto de Investigación Sanitaria Gregorio Marañón, ; Madrid, Spain
                [25 ]Consorcio de Investigación Biomédica en Red: Fragilidad y Envejecimiento Saludable, CIBERFES, Madrid, Spain
                [26 ]GRID grid.4795.f, ISNI 0000 0001 2157 7667, Medicine Department, Facultad de Medicina, , Universidad Complutense de Madrid, ; Madrid, Spain
                [27 ]GRID grid.414037.5, ISNI 0000 0004 0622 6211, Outpatient Geriatric Assessment Unit, , Henry Dunant Hospital Center, ; Athens, Greece
                [28 ]GRID grid.12380.38, ISNI 0000 0004 1754 9227, Department of General Medicine and Geriatric Medicine, , Free University, ; Amsterdam, The Netherlands
                [29 ]GRID grid.5645.2, ISNI 000000040459992X, Section of Geriatric Medicine, Department of Internal Medicine, Erasmus MC, , University Medical Center Rotterdam, ; Rotterdam, The Netherlands
                [30 ]GRID grid.416213.3, ISNI 0000 0004 0460 0556, Department of Geriatric Medicine, , Maasstad Hospital, ; Rotterdam, The Netherlands
                [31 ]GRID grid.421126.2, ISNI 0000 0001 0698 0044, Effective Prescribing and Therapeutics, , Scottish Government, ; Edinburgh, EH1 3DG UK
                [32 ]GRID grid.7700.0, ISNI 0000 0001 2190 4373, IV. Medical Department, Geriatrics, University Hospital Mannheim, , Heidelberg University, ; Mannheim, Germany
                [33 ]GRID grid.22254.33, ISNI 0000 0001 2205 0971, Geriatric Laboratory Palliative Medicine Department, , Poznan University of Medical Sciences, ; Poznan, Poland
                [34 ]GRID grid.22254.33, ISNI 0000 0001 2205 0971, Department of Palliative Medicine, , Poznan University of Medical Sciences, ; Poznan, Poland
                [35 ]GRID grid.499063.1, Palliative Medicine Unit, , University Hospital of Lord’s Transfiguration, ; Poznan, Poland
                [36 ]GRID grid.9983.b, ISNI 0000 0001 2181 4263, Department of Internal Medicine, Hospital Curry Cabral, , Centro Hospitalar Universitário de Lisboa Central, ; Lisbon, Portugal
                [37 ]GRID grid.435541.2, ISNI 0000 0000 9851 304X, Internal Medicine Department 7.2, , Hospital Curry Cabral - Centro Hospitalar Universitário Lisboa Central, EPE, ; Lisbon, Portugal
                [38 ]AGAPLESION Bethesda Clinic Ulm, Ulm, Germany
                [39 ]GRID grid.189504.1, ISNI 0000 0004 1936 7558, Dept. of Epidemiology, , Boston University School of Public Health, ; Boston, MA USA
                [40 ]GRID grid.503422.2, ISNI 0000 0001 2242 6780, CHU Lille, ULR 2694 - METRICS: Évaluation des technologies de santé et des pratiques médicales, , Univ. Lille, ; F-59000 Lille, France
                [41 ]GRID grid.12380.38, ISNI 0000 0004 1754 9227, Department of Geriatric Medicine, , Free University, ; Amsterdam, the Netherlands
                Author information
                http://orcid.org/0000-0003-1393-1691
                Article
                2951
                10.1007/s00228-020-02951-8
                8197722
                32770278
                a91ac0a5-fd98-4f21-bfcf-a1cd9b8900d0
                © The Author(s) 2020, corrected publication 2021

                Open Access This 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/.

                History
                : 24 March 2020
                : 30 June 2020
                Categories
                Review
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                © Springer-Verlag GmbH Germany, part of Springer Nature 2021

                Pharmacology & Pharmaceutical medicine
                frailty,prefrailty,polypharmacy,medication optimization,inappropriate drug treatment,older people

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