Aims: Inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale that warrants urgent investigation of its therapeutic potential in patients with COVID-19. UFH has antiviral effects and prevents the SARS-CoV-2 virus' entry into mammalian cells. In addition, UFH has significant anti-inflammatory and anticoagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis. Methods: The INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP) metatrial is a prospective individual patient data analysis of on-going randomised controlled trials and early phase studies. Individual studies are being conducted in multiple countries. Participating studies randomise adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome for the metatrial is intubation (or death, for patients who died before intubation) at day 28. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time-to-event analyses. Individual studies may have additional outcomes.Analysis: We use a Bayesian approach to monitoring, followed by analysing individual patient data, outcomes and adverse events. All analyses will follow the intention-to-PI Statement: The authors confirm that the PI for this paper is Professor Frank M.P. van Haren and that he has direct responsibility for the described metatrial. Metatrial Combined Protocol and Statistical Analysis Plan date and version: 14 December 2020, INHALE-HEP metatrial version 2.0.

Objectives: Patients with cannabinoid hyperemesis syndrome (CHS) present frequently to the emergency department. Previous case studies suggest dramatic symptomatic improvement with topical capsaicin treatment. This exploratory study examined the potential effectiveness of topical capsaicin in patients with nausea and vomiting due to a suspected CHS exacerbation. Methods: This was a double-blind, randomized placebo-controlled pilot trial. Adults who presented with vomiting suspected to be from CHS were eligible for enrollment. We excluded pregnant women and those with resolution of symptoms. Following randomization, topical 0.1% capsaicin or placebo cream was applied to the anterior abdomen in a uniform manner. The primary outcome was the severity of nausea on a visual analog scale (VAS) of 0 to 10 cm assessed at 30 minutes. Secondary outcomes were adverse events, occurrence of posttreatment vomiting, nausea by VAS at 60 minutes, and hospital admission. Results: This pilot trial enrolled 30 patients, 17 in the capsaicin arm and 13 in the placebo arm. One patient in the capsaicin arm did not tolerate treatment due to skin irritation. Mean AE SD nausea severity at 30 minutes was 4.1 AE 2.3 cm in the capsaicin arm and 6.1 AE 3.3 cm in the placebo arm (difference = À2.0 cm, 95% confidence interval [CI] = 0.2 to À4.2 cm). At 60 minutes, mean AE SD nausea severity was 3.2 AE 3.2 cm versus 6.4 AE 2.8 cm (difference = À3.2 cm, 95% CI = À0.9 to À5.4 cm). The percent reduction in nausea at 60 minutes from baseline was 46.0% in the capsaicin arm and 24.9% in the placebo arm (difference = 21.1%, 95% CI = À5.6% to 47.9%). A higher proportion of capsaicin group patients (29.4% vs. 0%) had complete resolution of nausea (relative risk = 3.4, 95% CI = 1.6 to 7.1). Conclusion: In this pilot trial, the application of topical capsaicin cream was associated with a significant reduction in nausea at 60 minutes but not at 30 minutes and provided more complete relief of nausea. C annabinoid hyperemesis syndrome (CHS), thought to be a variant of cyclic vomiting syndrome (CVS), is characterized by the chronic use of cannabis, intractable nausea, recurrent vomiting episodes, and diffuse abdominal pain. Duration and quantification of cannabis use is variable and minimally involves weekly use. 1-4 One particular unique feature of this syndrome, which differentiates it from

Aims: To determine the safety and efficacy-potential of inhaled nebulised unfractionated heparin (UFH) in the treatment of hospitalised patients with COVID-19.Methods: Retrospective, uncontrolled multicentre single-arm case series of hospitalised patients with laboratory-confirmed COVID-19, treated with inhaled nebulised UFH (5000 IU q8h, 10 000 IU q4h, or 25 000 IU q6h) for 6 ± 3 (mean ± standard deviation) days. Outcomes were activated partial thromboplastin time (APTT) before treatment (baseline) and highest-level during treatment (peak), and adverse events including bleeding. Exploratory efficacy outcomes were oxygenation, assessed by ratio of oxygen saturation to fraction of inspired oxygen (FiO 2 ) and FiO 2 , and the World Health Organisation modified ordinal clinical scale.Results: There were 98 patients included. In patients on stable prophylactic or therapeutic systemic anticoagulant therapy but not receiving therapeutic UFH infusion, APTT levels increased from baseline of 34 ± 10 seconds to a peak of 38 ± 11 seconds (P < .0001). In 3 patients on therapeutic UFH infusion, APTT levels did not significantly increase from baseline of 72 ± 20 to a peak of 84 ± 28 seconds (P = .17). Two patients had serious adverse events: bleeding gastric ulcer requiring transfusion and thigh haematoma; both were on therapeutic anticoagulation. Minor bleeding occurred in 16 patients, 13 of whom were on therapeutic anticoagulation.The oxygen saturation/FiO 2 ratio and the FiO 2 worsened before and improved after commencement of inhaled UFH (change in slope, P < .001). Conclusion:Inhaled nebulised UFH in hospitalised patients with COVID-19 was safe.Although statistically significant, inhaled nebulised UFH did not produce a clinically relevant increase in APTT (peak values in the normal range). Urgent randomisedThe authors confirm that the PI for this paper is Professor Frank M.P. van Haren and that he has direct responsibility for the described case-series.

Lean methodology was successfully used to reduce time to antibiotic administration, which led to improved compliance with the newly implemented sepsis CMS core measure.

Trace elements are essential for many physiologic processes. In recent years, supplementation has been studied for a variety of indications, including glycemic control, wound healing, antioxidant effect, and anemia. Critical illness, especially states such as burns, traumas, and septic shock, is associated with inflammatory and oxidative stress, immune dysfunction, and malnutrition. In these patients, enteral and parenteral nutrition or pharmaceutical supplementation is used to provide essential macronutrients, including trace elements. The purpose of this review is to describe trace element supplementation, including iron, copper, chromium, manganese, selenium, and zinc, and highlight their mechanism, pharmacology, outcome data, and adverse effects.