Calcifediol treatment and COVID-19-related outcomes

Context COVID-19 is a major health problem because of saturation of intensive care units (ICU) and mortality. Vitamin D has emerged as a potential treatment able to reduce the disease severity. Objective To elucidate the effect of calcifediol [25OHD3] treatment on COVID-19-related outcomes. Design Observational cohort study from March to May, 2020. Setting Patients admitted to COVID-19 wards of Hospital del Mar, Barcelona, Spain. Patients A total of 930 patients with COVID-19 were included. Ninety-two were excluded due to previous calcifediol intake. Intervention Of the remaining 838, a total of 447 received calcifediol (532ug on day one plus 266ug on day 3, 7, 15, and 30) whereas 391 were not treated at the time of hospital admission (Intention-to-Treat). Of the latter, 53 patients were treated later during ICU admission and were allocated in the treated group in a second analysis. In healthy subjects, calcifediol is about 3.2-fold more potent on a weight basis than cholecalciferol. Main Outcome Measures ICU admission and mortality. Results ICU assistance was required by 102 (12.2%) participants. Out of 447 patients treated with calcifediol at admission, 20 (4.5%) required ICU, compared to 82 (21%) out of 391 non-treated (p-value<0.0001). Logistic regression of calcifediol treatment on ICU admission, adjusted by age, gender, linearized 25OHD levels at baseline, and comorbidities showed that treated patients had a reduced risk to require ICU (OR 0.13 [95% CI 0.07;0.23]). Overall mortality was 10%. In the Intention-to-Treat analysis, 21 (4.7%) out of 447 patients treated with calcifediol at admission died compared to 62 patients (15.9%) out of 391 non-treated (p=0.0001). Adjusted results showed a reduced mortality risk with an OR 0.21 [95% CI 0.10; 0.43]). In the second analysis, the obtained OR was 0.52 [95% CI 0.27;0.99]. Conclusions In patients hospitalized with COVID-19, calcifediol treatment significantly reduced ICU admission and mortality

Impact of age on the performance of the ESC 0/1h-algorithms for early diagnosis of myocardial infarction

Aims We aimed to evaluate the impact of age on the performance of the European Society of Cardiology (ESC) 0/1halgorithms and to derive and externally validate alternative cut-offs specific to older patients. Methods and results We prospectively enrolled patients presenting to the emergency department (ED) with symptoms suggestive of acute myocardial infarction in three large diagnostic studies. Final diagnoses were adjudicated by two independent cardiologists. High-sensitivity cardiac troponin (hs-cTn) T and I concentrations were measured at presentation and after 1 h. Patients were stratified according to age [<55 years (young), ≥55 to <70 years (middle-age), ≥70 years (old)]. Rule-out safety of the ESC hs-cTnT 0/1h-algorithm was very high in all age-strata: sensitivity 100% [95% confidence interval (95% CI) 94.9-100] in young, 99.3% (95% CI 96.0-99.9) in middle-age, and 99.3% (95% CI 97.5- 99.8) in old patients. Accuracy of rule-in decreased with age: specificity 97.0% (95% CI 95.8-97.9) in young, 96.1% (95% CI 94.5-97.2) in middle-age, and 92.7% (95% CI 90.7-94.3) in older patients. Triage efficacy decreased with increasing age (young 93%, middle-age 80%, old 55%, P < 0.001). Similar results were found for the ESC hs-cTnT 0/1h-algorithm. Alternative, slightly higher cut-off concentrations optimized for older patients maintained very high safety of rule-out, increased specificity of rule-in (P < 0.01), reduced overall efficacy for hs-cTnT (P < 0.01), while maintaining efficacy for hs-cTnI. Findings were confirmed in two validation cohorts (n = 2767). Conclusion While safety of the ESC 0/1h-algorithms remained very high, increasing age significantly reduced overall efficacy and the accuracy of rule-in. Alternative slightly higher cut-off concentrations may be considered for older patients, particularly if using hs-cTnI