Remdesivir for the treatment of patients in hospital with COVID-19 in Canada: a randomized controlled trial.

BACKGROUND: The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems. METHODS: We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation. RESULTS: Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (n = 634) or standard of care (n = 648). Of these, 15 withdrew consent or were still in hospital, for a total sample of 1267 patients. Among patients assigned to receive remdesivir, in-hospital mortality was 18.7%, compared with 22.6% in the standard-of-care arm (relative risk [RR] 0.83 (95% confidence interval [CI] 0.67 to 1.03), and 60-day mortality was 24.8% and 28.2%, respectively (95% CI 0.72 to 1.07). For patients not mechanically ventilated at baseline, the need for mechanical ventilation was 8.0% in those assigned remdesivir, and 15.0% in those receiving standard of care (RR 0.53, 95% CI 0.38 to 0.75). Mean oxygen-free and ventilator-free days at day 28 were 15.9 (± standard deviation [SD] 10.5) and 21.4 (± SD 11.3) in those receiving remdesivir and 14.2 (± SD 11) and 19.5 (± SD 12.3) in those receiving standard of care (p = 0.006 and 0.007, respectively). There was no difference in safety events of new dialysis, change in creatinine, or new hepatic dysfunction between the 2 groups. INTERPRETATION: Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation. Trial registration: ClinicalTrials.gov, no. NCT04330690.

Diagnostic precision of mentally estimated home blood pressure means.

CONTEXT: Paper home blood pressure (HBP) charts are commonly brought to physicians at office visits. The precision and accuracy of mental calculations of blood pressure (BP) means are not known. METHODS: A total of 109 hypertensive patients were instructed to measure and record their HBP for 1 week and to bring their paper charts to their office visit. Study section 1: HBP means were calculated electronically and compared to corresponding in-office BP estimates made by physicians. Study section 2: 100 randomly ordered HBP charts were re-examined repetitively by 11 evaluators. Each evaluator estimated BP means four times in 5, 15, 30, and 60 s (random order) allocated for the task. BP means and diagnostic performance (determination of therapeutic systolic and diastolic BP goals attained or not) were compared between physician estimates and electronically calculated results. RESULTS: Overall, electronically and mentally calculated BP means were not different. Individual analysis showed that 83% of in-office physician estimates were within a 5-mmHg systolic BP range. There was diagnostic disagreement in 15% of cases. Performance improved consistently when the time allocated for BP estimation was increased from 5 to 15 s and from 15 to 30 s, but not when it exceeded 30 s. CONCLUSION: Mentally calculating HBP means from paper charts can cause a number of diagnostic errors. Chart evaluation exceeding 30 s does not significantly improve accuracy. BP-measuring devices with modern analytical capacities could be useful to physicians.

Quantification of the External Validity of Randomized Controlled Trials Supporting Clinical Care Guidelines: The Case of Thromboprophylaxis.

BACKGROUND: Clinical guidelines are based on the results of several randomized controlled trials. However, due to the stringent exclusion criteria of these trials, their external validity may be low. We aimed to evaluate the external validity of the randomized controlled trials cited in the American College of Chest Physicians guidelines for the use of pharmacological thromboprophylaxis in hospitalized medical patients. METHODS: We conducted a cross-sectional, chart-review study of a random sample of patients admitted between July 1, 2013 and June 30, 2014 to the Internal Medicine ward of a large Canadian teaching university hospital. We identified the proportion of our population presenting exclusion criteria used in the randomized controlled trials cited in support of clinical care guidelines on thromboprophylaxis in the medical setting. RESULTS: Nine trials were identified for a total of 28,793 included patients following 23 distinct exclusion criteria. We included 429 patients. Median age was 65 years (interquartile ratio 51-77 years), and 236 (55%) were males. Of those not already anticoagulated at admission (n = 351), between 26% and 67% (weighted average, 51%) of our population presented at least one exclusion criterion, making them ineligible to be enrolled in randomized controlled trials. When restricting our population to patients with an indication for thromboprophylaxis based on a Padua risk score at admission ≥4, 21% to 76% (weighted average 55%) were ineligible to be enrolled in individual trials. CONCLUSIONS: Our cross-sectional study illustrates that the external validity of randomized controlled trials cited in the guidelines was low in our population, and lower when applying the risk-stratification tool recommended by guidelines. This can bias the clinicians toward treating patients that were not represented in the supporting evidence.

Recurrent arterial and venous thromboemboli as initial presentation of acute promyelocytic leukemia.

We report a case of a 52-year-old Caucasian woman diagnosed with a synchronic arterial and venous thrombosis as an initial presentation of an acute promyelocytic leukemia (APL). After the diagnosis, the patient was treated with all trans-retinoic acid and arsenic chemotherapy concomitant to systemic anticoagulation. This treatment regimen led to a complete remission and absence of relapse of the thrombosis or APL during the follow-up. To our knowledge, this presentation is the second case in the literature. We use this opportunity to emphasize the importance of performing a complete medical evaluation in cases of unusual thromboembolic events.

Lack of Clinical Benefit of Thromboprophylaxis in Patients Hospitalized in a Medical Unit Over a 10-year Span.

BACKGROUND: Thromboprophylaxis for hospitalized patients with a high risk of venous thromboembolic events (VTEs) is strongly recommended but is not universally applied on medical units. Outside of randomized trials, there is minimal evidence that the usual medications reduce the incidence of clinically significant VTE. METHODS: We conducted a retrospective cohort study including all patients admitted into a teaching medical unit during years 2001-2002, 2003-2004, 2005-2006, 2007-2008 and 2009-2010. Inclusion criteria for the analysis were having one or more risk factors for a VTE and no contraindication to thromboprophylaxis. RESULTS: Of 2,369 patients reviewed, 1,302 satisfied the inclusion criteria. Between years 2001-2002 and 2009-2010, the proportion of patients receiving thromboprophylaxis increased from 29.2% to 76.4% (P < 0.0001) and the duration of thromboprophylaxis increased from 63% of hospital stay to 84% (P = 0.004). There was no statistically significant association between the number of risk factors and the rate of thromboprophylaxis. Overall, only 32 patients suffered from a VTE with no decrease in VTE incidence between years 2001-2002 and 2009-2010. A total of 107 patients had a bleeding event, and there was no statistically significant change in the incidence of bleeding during our study period. CONCLUSIONS: In our medical units, we found a statistically significant increase in the use of the thromboprophylaxis practice. However, this was not associated with any statistically significant impact on the VTE incidence. This suggests that patients given thromboprophylaxis could be better selected.

Extracorporeal membrane oxygenation in diffuse alveolar hemorrhage secondary to systemic lupus erythematosus.

Diffuse alveolar hemorrhage (DAH) is a rare and potentially deadly complication of systemic lupus erythematosus (SLE). We report two adult cases where extracorporeal membrane oxygenation (ECMO) was used as rescue therapy for severe respiratory failure in this setting. We discuss the risk related to coagulation disturbance and the need for the circuit anticoagulation in this particular setting. We also briefly discuss the clinical problem of lack of knowledge on the bioavailability of the immunosuppressive treatment with the use of ECMO. We think that ECMO should be used as rescue therapy in patients with DAH caused by SLE, but strategies for anticoagulation require further precision.