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      Association between Clinical Frailty Scale score and hospital mortality in adult patients with COVID-19 (COMET): an international, multicentre, retrospective, observational cohort study

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          Abstract

          Background

          During the COVID-19 pandemic, the scarcity of resources has necessitated triage of critical care for patients with the disease. In patients aged 65 years and older, triage decisions are regularly based on degree of frailty measured by the Clinical Frailty Scale (CFS). However, the CFS could also be useful in patients younger than 65 years. We aimed to examine the association between CFS score and hospital mortality and between CFS score and admission to intensive care in adult patients of all ages with COVID-19 across Europe.

          Methods

          This analysis was part of the COVID Medication (COMET) study, an international, multicentre, retrospective observational cohort study in 63 hospitals in 11 countries in Europe. Eligible patients were aged 18 years and older, had been admitted to hospital, and either tested positive by PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or were judged to have a high clinical likelihood of having SARS-CoV-2 infection by the local COVID-19 expert team. CFS was used to assess level of frailty: fit (CFS 1–3), mildly frail (CFS 4–5), or frail (CFS 6–9). The primary outcome was hospital mortality. The secondary outcome was admission to intensive care. Data were analysed using a multivariable binary logistic regression model adjusted for covariates (age, sex, number of drugs prescribed, and type of drug class as a proxy for comorbidities).

          Findings

          Between March 30 and July 15, 2020, 2434 patients (median age 68 years [IQR 55–77]; 1480 [61%] men, 954 [30%] women) had CFS scores available and were included in the analyses. In the total sample and in patients aged 65 years and older, frail patients and mildly frail patients had a significantly higher risk of hospital mortality than fit patients (total sample: CFS 6–9 vs CFS 1–3 odds ratio [OR] 2·71 [95% CI 2·04–3·60], p<0·0001 and CFS 4–5 vs CFS 1–3 OR 1·54 [1·16–2·06], p=0·0030; age ≥65 years: CFS 6–9 vs CFS 1–3 OR 2·90 [2·12–3·97], p<0·0001 and CFS 4–5 vs CFS 1–3 OR 1·64 [1·20–2·25], p=0·0020). In patients younger than 65 years, an increased hospital mortality risk was only observed in frail patients (CFS 6–9 vs CFS 1–3 OR 2·22 [1·08–4·57], p=0·030; CFS 4–5 vs CFS 1–3 OR 1·08 [0·48–2·39], p=0·86). Frail patients had a higher incidence of admission to intensive care than fit patients (CFS 6–9 vs CFS 1–3 OR 1·54 [1·21–1·97], p=0·0010), whereas mildly frail patients had a lower incidence than fit patients (CFS 4–5 vs CFS 1–3 OR 0·71 [0·55–0·92], p=0·0090). Among patients younger than 65 years, frail patients had an increased incidence of admission to intensive care (CFS 6–9 vs CFS 1–3 OR 2·96 [1·98–4·43], p<0·0001), whereas mildly frail patients had no significant difference in incidence compared with fit patients (CFS 4–5 vs CFS 1–3 OR 0·93 [0·63–1·38], p=0·72). Among patients aged 65 years and older, frail patients had no significant difference in the incidence of admission to intensive care compared with fit patients (CFS 6–9 vs CFS 1–3 OR 1·27 [0·92–1·75], p=0·14), whereas mildly frail patients had a lower incidence than fit patients (CFS 4–5 vs CFS 1–3 OR 0·66 [0·47–0·93], p=0·018).

          Interpretation

          The results of this study suggest that CFS score is a suitable risk marker for hospital mortality in adult patients with COVID-19. However, treatment decisions based on the CFS in patients younger than 65 years should be made with caution.

          Funding

          LOEY Foundation.

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          Most cited references28

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          World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.

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            Frailty in elderly people

            Frailty is the most problematic expression of population ageing. It is a state of vulnerability to poor resolution of homoeostasis after a stressor event and is a consequence of cumulative decline in many physiological systems during a lifetime. This cumulative decline depletes homoeostatic reserves until minor stressor events trigger disproportionate changes in health status. In landmark studies, investigators have developed valid models of frailty and these models have allowed epidemiological investigations that show the association between frailty and adverse health outcomes. We need to develop more efficient methods to detect frailty and measure its severity in routine clinical practice, especially methods that are useful for primary care. Such progress would greatly inform the appropriate selection of elderly people for invasive procedures or drug treatments and would be the basis for a shift in the care of frail elderly people towards more appropriate goal-directed care. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              A global clinical measure of fitness and frailty in elderly people.

              There is no single generally accepted clinical definition of frailty. Previously developed tools to assess frailty that have been shown to be predictive of death or need for entry into an institutional facility have not gained acceptance among practising clinicians. We aimed to develop a tool that would be both predictive and easy to use. We developed the 7-point Clinical Frailty Scale and applied it and other established tools that measure frailty to 2305 elderly patients who participated in the second stage of the Canadian Study of Health and Aging (CSHA). We followed this cohort prospectively; after 5 years, we determined the ability of the Clinical Frailty Scale to predict death or need for institutional care, and correlated the results with those obtained from other established tools. The CSHA Clinical Frailty Scale was highly correlated (r = 0.80) with the Frailty Index. Each 1-category increment of our scale significantly increased the medium-term risks of death (21.2% within about 70 mo, 95% confidence interval [CI] 12.5%-30.6%) and entry into an institution (23.9%, 95% CI 8.8%-41.2%) in multivariable models that adjusted for age, sex and education. Analyses of receiver operating characteristic curves showed that our Clinical Frailty Scale performed better than measures of cognition, function or comorbidity in assessing risk for death (area under the curve 0.77 for 18-month and 0.70 for 70-month mortality). Frailty is a valid and clinically important construct that is recognizable by physicians. Clinical judgments about frailty can yield useful predictive information.
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                Author and article information

                Journal
                Lancet Healthy Longev
                Lancet Healthy Longev
                The Lancet. Healthy Longevity
                The Author(s). Published by Elsevier Ltd.
                2666-7568
                9 February 2021
                9 February 2021
                Affiliations
                [a ]Department of Internal Medicine, University Medical Centre Rotterdam, Rotterdam, Netherlands
                [b ]Department of Cardiology, University Medical Centre Rotterdam, Rotterdam, Netherlands
                [c ]Department of Hospital Pharmacy, University Medical Centre Rotterdam, Rotterdam, Netherlands
                [d ]Department of Geriatrics, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands
                [e ]Department of Geriatrics, Amphia Hospital, Breda, Netherlands
                [f ]Digitalis Rx BV, Amsterdam, Netherlands
                [g ]Department of Gerontology and Geriatrics, Leiden University Medical Centre, Leiden, Netherlands
                Author notes
                [* ]Correspondence to: Prof Hugo van der Kuy, Department of Hospital Pharmacy, Erasmus MC, University Medical Centre Rotterdam, 3015 GD Rotterdam, Netherlands
                [†]

                Members are listed in the appendix (pp 9–10)

                Article
                S2666-7568(21)00006-4
                10.1016/S2666-7568(21)00006-4
                7906710
                33655235
                06604fb8-00a8-4b6e-b403-7a314ecd6d9a
                © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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