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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 ± SD nausea severity at 30 minutes was 4.1 ± 2.3 cm in the capsaicin arm and 6.1 ± 3.3 cm in the placebo arm (difference = -2.0 cm, 95% confidence interval [CI] = 0.2 to -4.2 cm). At 60 minutes, mean ± SD nausea severity was 3.2 ± 3.2 cm versus 6.4 ± 2.8 cm (difference = -3.2 cm, 95% CI = -0.9 to -5.4 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 = -5.6% 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.

The INHALE-HEP meta-trial is a prospective collaborative individual participant data meta-analysis of randomised controlled trials and early phase studies, to evaluate whether inhaled nebulised UFH in hospitalised patients with COVID-19 who do not require immediate invasive mechanical ventilation, significantly reduces intubation (or death, for patients who died before intubation) at day 28 compared to standard care alone. Objective: In keeping with best practice and with the published protocol, a pre-specified statistical analysis plan has been described and made public before completion of patient recruitment and data collection into the INHALE-HEP meta-trial. Methods: Our statistical analysis plan was designed by the INHALE-HEP executive committee and statisticians and approved by the INHALE-HEP steering committee. We reviewed the data collected as specified in the meta-trial protocol and collected in individual contributing studies. We present information pertaining to data collection, pre-specified subgroups, and study outcomes. Primary and secondary outcomes are defined, and additional subgroup analyses of pre-defined variables are described. Results: We have described our methods for presenting the trial profile and baseline characteristics, as well as our Bayesian approach to monitoring and meta-analysing individual patient data, outcomes and adverse events. All analyses will follow the intention-to-treat principle, considering all participants in the treatment group to which they were assigned, except for cases lost to follow-up or withdrawn. Conclusion: To minimise analytical bias, we have developed a statistical analysis plan and made this available to the public domain before completion of patient recruitment and data collection into the INHALE-HEP meta-trial.

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‐treat principle, considering all participants in the treatment group to which they were assigned, except for cases lost to follow‐up or withdrawn.Trial registration, ethics and dissemination: the metatrial is registered at ClinicalTrials.gov ID NCT04635241. Each contributing study is individually registered and has received approval of the relevant ethics committee or institutional review board. Results of this study will be shared with the World Health Organisation, published in scientific journals and presented at scientific meetings.

Introduction Inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale and warrants urgent investigation of its therapeutic potential for 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 anti-coagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis. Methods and intervention This meta-trial is a prospective collaborative individual patient data meta-analysis of randomised controlled trials and early phase studies. Individual studies are conducted in multiple countries. Adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, are randomised to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome is intubation (or death, for patients who died before intubation) at day 28, assessed in a time-to-event analysis. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time-to-event analyses. Individual studies may have specific outcome measures in addition to the core set. Ethics and dissemination: The meta-trial is registered at ClinicalTrials.gov, ID NCT04635241. Results of this study will be shared with the WHO, published in scientific journals and presented at scientific meetings.

Purpose Results of a study to apply lean methodology to an inpatient pharmacy workflow to optimize timely administration of Centers for Medicare and Medicaid Services (CMS)–approved antibiotics for patients with severe sepsis or septic shock are presented. Methods This quasi-experimental study was conducted at an 802-bed institution using lean methodology to assess the inpatient pharmacy workflow for dispensing antibiotics to adult patients. The preintervention and postintervention phases occurred from February to September, 2015, and from October 2015 to May 2016, respectively. Patients were included if they were hospitalized with an intensive care department 9 or 10 code for severe sepsis or septic shock, had an order for a CMS-approved antibiotic, and met clinical criteria for severe sepsis or septic shock. Patients were excluded if they received first-dose antibiotics in the emergency department. The primary outcome was time from CMS-approved antibiotic order entry to medication administration. Secondary outcomes included timeliness of individual workflow dispensing parameters, patient outcomes, and compliance with the newly implemented workflow. Results A total of 102 patients were included, 54 in the preintervention and 48 in the postintervention group. Baseline demographics between the groups were similar. There was a significant reduction in the median time from order entry to antibiotic administration by 40 minutes (preintervention phase 120 minutes versus postintervention phase 80 minutes, p = 0.014). Time from order verification to administration was significantly reduced. There was no difference in other secondary outcomes. Conclusion 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.