Senicapoc treatment in COVID-19 Patients with Severe Respiratory Insufficiency - A Randomized, Open-Label, Phase II Trial

BACKGROUND: The aim of the current study was to determine if treatment with senicapoc, improves the PaO(2)/FiO(2) ratio in patients with COVID‐19 and severe respiratory insufficiency. METHODS: Investigator‐initiated, randomized, open‐label, phase II trial in four intensive care units (ICU) in Denmark. We included patients aged ≥18 years and admitted to an ICU with severe respiratory insufficiency due to COVID‐19. The intervention consisted of 50 mg enteral senicapoc administered as soon as possible after randomization and again after 24 h. Patients in the control group received standard care only. The primary outcome was the PaO(2)/FiO(2) ratio at 72 h. RESULTS: Twenty patients were randomized to senicapoc and 26 patients to standard care. Important differences existed in patient characteristics at baseline, including more patients being on non‐invasive/invasive ventilation in the control group (54% vs. 35%). The median senicapoc concentration at 72 h was 62.1 ng/ml (IQR 46.7–71.2). The primary outcome, PaO(2)/FiO(2) ratio at 72 h, was significantly lower in the senicapoc group (mean 19.5 kPa, SD 6.6) than in the control group (mean 24.4 kPa, SD 9.2) (mean difference −5.1 kPa [95% CI −10.2, −0.04] p = .05). The 28‐day mortality in the senicapoc group was 2/20 (10%) compared with 6/26 (23%) in the control group (OR 0.36 95% CI 0.06–2.07, p = .26). CONCLUSIONS: Treatment with senicapoc resulted in a significantly lower PaO(2)/FiO(2) ratio at 72 h with no differences for other outcomes

Peripheral bone mineral density and different intensities of physical activity in children 6-8 years old: the Copenhagen School Child Intervention study

This study aimed to evaluate the association between objectively measured habitual physical activity and calcaneal and forearm bone mineral density (BMD, g/cm(2)), one mechanically more loaded and one less loaded skeletal region, in children aged 6-8 years. BMD was measured in 297 boys and 265 girls by peripheral dual-energy X-ray absorptiometry in the forearm and calcaneus. An accelerometer registered the level of physical activity during 4 days (2 weekdays and the weekend). Weight, height, and skinfold thickness were measured. In order to establish thresholds (count center dot min(-1)) for bone-stimulating physical activity, we evaluated different definitions of vigorous physical activity. The boys had 3.2% higher distal forearm bone mineral content (BMC, P < 0.001) and 4.5% higher distal forearm BMD (P < 0.001) than the girls. They also carried out 9.7% more daily physical activity and spent 14.6-19.0% more time in vigorous physical activity (all P < 0.05) compared to the girls. In contrast, the girls had 3.8% higher calcaneal BMC (P < 0.01) and 2.5% higher calcaneal BMD (P < 0.05) than the boys. Both calcaneal and forearm BMD were significantly related to total time of daily physical activity as well as with intense physical activity above all the chosen cut-off points (all P < 0.05). The beta value for mean count center dot min(-1) physical activity was significantly lower than that for all the chosen cut-off points of vigorous activity both for calcaneal and distal forearm BMD. This study suggests that both habitual daily physical activity and amount of vigorous physical activity in children aged 6-8 years are associated with appendicular BMD

A Metabolomics Study of Retrospective Forensic Data from Whole Blood Samples of Humans Exposed to 3,4-Methylenedioxymethamphetamine: A New Approach for Identifying Drug Metabolites and Changes in Metabolism Related to Drug Consumption

The illicit drug 3,4-methylenedioxymethamphetamine (MDMA) has profound physiological cerebral, cardiac, and hepatic effects that are reflected in the blood. Screening of blood for MDMA and other narcotics are routinely performed in forensics analysis using ultra-performance liquid chromatography with high-resolution time-of-flight mass spectrometry (UPLC–HR-TOFMS). The aim of this study was to investigate whether such UPLC–HR-TOFMS data collected over a two-year period could be used for untargeted metabolomics to determine MDMA metabolites as well as endogenous changes related to drug response and toxicology. Whole blood samples from living Danish drivers’ positive for MDMA in different concentrations were compared to negative control samples using various statistical methods. The untargeted identification of known MDMA metabolites was used to validate the methods. The results further revealed changes of several acylcarnitines, adenosine monophosphate, adenosine, inosine, thiomorpholine 3-carboxylate, tryptophan, <i>S</i>-adenosyl-l-homocysteine (SAH), and lysophospatidylcholine (lysoPC) species in response to MDMA. These endogenous metabolites could be implicated in an increased energy demand and mechanisms related to the serotonergic syndrome as well as drug induced neurotoxicity. The findings showed that it was possible to extract meaningful results from retrospective UPLC–HR-TOFMS screening data for metabolic profiling in relation to drug metabolism, endogenous physiological effects, and toxicology