Prone positioning of patients with moderate hypoxaemia due to covid-19: multicentre pragmatic randomised trial (COVID-PRONE).

OBJECTIVES: To assess the effectiveness of prone positioning to reduce the risk of death or respiratory failure in non-critically ill patients admitted to hospital with covid-19. DESIGN: Multicentre pragmatic randomised clinical trial. SETTING: 15 hospitals in Canada and the United States from May 2020 until May 2021. PARTICIPANTS: Eligible patients had a laboratory confirmed or a clinically highly suspected diagnosis of covid-19, needed supplemental oxygen (up to 50% fraction of inspired oxygen), and were able to independently lie prone with verbal instruction. Of the 570 patients who were assessed for eligibility, 257 were randomised and 248 were included in the analysis. INTERVENTION: Patients were randomised 1:1 to prone positioning (that is, instructing a patient to lie on their stomach while they are in bed) or standard of care (that is, no instruction to adopt prone position). MAIN OUTCOME MEASURES: The primary outcome was a composite of in-hospital death, mechanical ventilation, or worsening respiratory failure defined as needing at least 60% fraction of inspired oxygen for at least 24 hours. Secondary outcomes included the change in the ratio of oxygen saturation to fraction of inspired oxygen. RESULTS: The trial was stopped early on the basis of futility for the pre-specified primary outcome. The median time from hospital admission until randomisation was 1 day, the median age of patients was 56 (interquartile range 45-65) years, 89 (36%) patients were female, and 222 (90%) were receiving oxygen via nasal prongs at the time of randomisation. The median time spent prone in the first 72 hours was 6 (1.5-12.8) hours in total for the prone arm compared with 0 (0-2) hours in the control arm. The risk of the primary outcome was similar between the prone group (18 (14%) events) and the standard care group (17 (14%) events) (odds ratio 0.92, 95% confidence interval 0.44 to 1.92). The change in the ratio of oxygen saturation to fraction of inspired oxygen after 72 hours was similar for patients randomised to prone positioning and standard of care. CONCLUSION: Among non-critically ill patients with hypoxaemia who were admitted to hospital with covid-19, a multifaceted intervention to increase prone positioning did not improve outcomes. However, wide confidence intervals preclude definitively ruling out benefit or harm. Adherence to prone positioning was poor, despite multiple efforts to increase it. Subsequent trials of prone positioning should aim to develop strategies to improve adherence to awake prone positioning. STUDY REGISTRATION: ClinicalTrials.gov NCT04383613.

Preventable Diabetic Complications After a Cancer Diagnosis in Patients With Diabetes: A Population-Based Cohort Study.

BACKGROUND: A cancer diagnosis may disrupt diabetes management, increasing the risk of preventable complications. The objective was to determine whether a cancer diagnosis in patients with diabetes is associated with an increased risk of diabetic complications. METHODS: This retrospective cohort study using health care data from Ontario, Canada, included persons age 50 years or older diagnosed with diabetes from 2007 to 2011 and followed until 2014. We examined the effects of cancer as a time-varying covariate: breast cancer (in women), prostate cancer (in men), colorectal cancer, and other cancers (in men and women). Each cancer exposure was categorized as stage I-III, IV, or unknown, and by time since cancer diagnosis (0-1 year, >1-3 years, and >3 years). The primary outcome was hospital visits for diabetic emergencies. Secondary outcomes were hospital visits for skin and soft tissue infections and cardiovascular events. RESULTS: Of 817 060 patients with diabetes (mean age = 64.9 +/- 10.7 years), there were 9759 (1.2%) colorectal and 45 705 (5.6%) other cancers, 6714 (1.7%) breast cancers among 384 257 women and 10 331 (2.4%) prostate cancers among 432 803 men. For all cancers except stage I-III prostate cancer, rates of diabetic complications were significantly higher zero years to one year after diagnosis compared with no cancer (adjusted relative rates ranging from 1.26, 95% confidence interval [CI] = 1.08 to 1.49, to 4.07, 95% CI = 3.80 to 4.36); these differences were attenuated in the subsequent periods after cancer diagnosis. CONCLUSIONS: Patients with diabetes are at increased risk for preventable complications after a cancer diagnosis. Better diabetes care is needed during this vulnerable period.