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 incide...
Patients with amyotrophic lateral sclerosis (ALS) who are treated with the antiglutamatergic drug riluzole receive a fixed-dose regimen of 50 mg b.i.d. The drug has been shown to increase tracheostomy-free survival by 3-6 months. The pharmacokinetics of riluzole show a high interindividual variability. Riluzole serum concentrations are associated with side effects and ALS symptoms, but the effect of the actual blood level of riluzole on disease progression and survival is unknown. We measured trough and peak serum concentrations of riluzole in 160 patients with ALS, and estimated the area under the curve for one dosage interval (AUCi) using a Bayesian method. We then determined the association between riluzole AUCi and survival over a 5-year period, and between riluzole AUCi and disease progression, defined by the rates of decline of arm strength and vital lung capacity. No significant association was found between riluzole AUCi and survival or disease progression.
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