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Objectives: To reliably quantify the radiographic severity of COVID-19 pneumonia with the Radiographic Assessment of Lung Edema (RALE) score on clinical chest X-rays among inpatients and examine the prognostic value of baseline RALE scores on COVID-19 clinical outcomes., Setting: Hospitalised patients with COVID-19 in dedicated wards and intensive care units from two different hospital systems., Participants: 425 patients with COVID-19 in a discovery data set and 415 patients in a validation data set., Primary and Secondary Outcomes: We measured inter-rater reliability for RALE score annotations by different reviewers and examined for associations of consensus RALE scores with the level of respiratory support, demographics, physiologic variables, applied therapies, plasma host-response biomarkers, SARS-CoV-2 RNA load and clinical outcomes., Results: Inter-rater agreement for RALE scores improved from fair to excellent following reviewer training and feedback (intraclass correlation coefficient of 0.85 vs 0.93, respectively). In the discovery cohort, the required level of respiratory support at the time of CXR acquisition (supplemental oxygen or non-invasive ventilation (n=178); invasive-mechanical ventilation (n=234), extracorporeal membrane oxygenation (n=13)) was significantly associated with RALE scores (median (IQR): 20.0 (14.1-26.7), 26.0 (20.5-34.0) and 44.5 (34.5-48.0), respectively, p<0.0001). Among invasively ventilated patients, RALE scores were significantly associated with worse respiratory mechanics (plateau and driving pressure) and gas exchange metrics (PaO2/FiO2 and ventilatory ratio), as well as higher plasma levels of IL-6, soluble receptor of advanced glycation end-products and soluble tumour necrosis factor receptor 1 (p<0.05). RALE scores were independently associated with 90-day survival in a multivariate Cox proportional hazards model (adjusted HR 1.04 (1.02-1.07), p=0.002). We replicated the significant associations of RALE scores with baseline disease severity and mortality in the independent validation data set., Conclusions: With a reproducible method to measure radiographic severity in COVID-19, we found significant associations with clinical and physiologic severity, host inflammation and clinical outcomes. The incorporation of radiographic severity assessments in clinical decision-making may provide important guidance for prognostication and treatment allocation in COVID-19., Competing Interests: Competing interests: Dr. Kitsios has received research funding from Karius, Inc. Dr. McVerry receives research funding from Bayer Pharmaceuticals, Inc. All other authors disclosed no conflict of interest, (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This case report describes an overdose on kratom, and elicits the potential dangers of overdose on the regulated dietary supplement. A young male presented to the emergency department intubated after being found unresponsive. He was found by his family to be unarousable and agonal breathing with minimal response to naloxone administered by Emergency Medical Services (EMS). Urine toxicology and blood alcohol content were negative. Physical exam was significant for tachycardia, hypotension, and pinpoint pupils with sluggish reactivity to light. Laboratory studies were significant for elevated liver enzymes, blood urea nitrogen, creatinine, lipase, amylase, troponins, and lactic acid. Family members revealed that the patient consumed kratom, which he obtained through an e-commerce business, and had consumed over 500 grams the previous day. Urine sample for kratom on day 3 tested positive with levels of more than 500 ng/dL. The patient received supportive care and, by day 10, pupillary reflexes returned to normal and he was extubated by day 14. Most of the medications/drugs labelled under herbal supplements by the U.S. Food and Drug Administration (FDA) are not regulated and can be purchased over the counter. The safety and side-effect profile of kratom is not well-studied, especially in an overdose scenario.