Articles: human.
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Randomized Controlled Trial
Effects of Sub-Anesthetic Oro-Mucosal Dexmedetomidine on Sleep in Humans: A Randomized, Controlled Pharmacokinetics-Pharmacodynamics Study.
The locus coeruleus noradrenergic system may provide a potential new target for pharmacologic insomnia treatment, particularly in patients suffering from elevated distress. The selective α 2 -noradrenergic agonist dexmedetomidine attenuates locus coeruleus activity in subanesthetic doses, yet no adequate nonparental delivery systems of dexmedetomidine are currently available. To examine the feasibility of oromucosal dexmedetomidine administration, the authors developed two distinct-one sublingual and one buccal-oromucosal, fast-disintegrating dexmedetomidine formulas tailored for self-administration. Here, the authors established the formulas' pharmacokinetic and pharmacodynamic profiles. ⋯ The favorable pharmacokinetic and pharmacodynamic profile of oromucosal dexmedetomidine delivery warrants further dose-finding and clinical studies to establish the exact roles of α 2 receptor agonism in pharmacologic sleep enhancement and as a possible novel mechanism to alleviate stress-related insomnia.
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Spatial repellent products are used for prevention of insect bites, and a body of evidence exists on spatial repellent entomological efficacy. A new option for vector control, spatial repellent products are designed to release active ingredient into the air for disruption of human-vector contact thereby reducing human exposure to mosquito-borne pathogens. Clinical trials have shown spatial repellent epidemiological efficacy against Aedes-borne viruses but inconclusive outcomes against malaria. We aimed to show and quantify the protective efficacy of spatial repellents in reducing malaria infection incidence in Busia County, Kenya. ⋯ This study was funded by Unitaid to the University of Notre Dame.
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Randomized Controlled Trial Multicenter Study
Guselkumab in patients with moderately to severely active ulcerative colitis (QUASAR): phase 3 double-blind, randomised, placebo-controlled induction and maintenance studies.
Interleukin-23 inhibition is effective in treating ulcerative colitis. Guselkumab is a dual-acting, human IgG1, interleukin-23p19 subunit inhibitor that potently neutralises interleukin-23 and can bind to CD64. We aimed to evaluate the efficacy and safety of guselkumab as induction and maintenance therapy in patients with ulcerative colitis. ⋯ Janssen Research and Development.
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Randomized Controlled Trial Multicenter Study
Safety and efficacy of intravenous recombinant human prourokinase for acute ischaemic stroke within 4·5 h after stroke onset (PROST-2): a phase 3, open-label, non-inferiority, randomised controlled trial.
Intra-arterial prourokinase has been shown to be a promising thrombolytic agent in patients with acute ischaemic stroke. Given the global shortage of thrombolytics, we aimed to assess the non-inferiority of intravenous recombinant human prourokinase compared with alteplase in patients with acute ischaemic stroke who were ineligible for or who refused endovascular thrombectomy. ⋯ For the Chinese translation of the abstract see Supplementary Materials section.
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Randomized Controlled Trial Multicenter Study
Ponsegromab for the Treatment of Cancer Cachexia.
Cachexia is a common complication of cancer and is associated with an increased risk of death. The level of growth differentiation factor 15 (GDF-15), a circulating cytokine, is elevated in cancer cachexia. In a small, open-label, phase 1b study involving patients with cancer cachexia, ponsegromab, a humanized monoclonal antibody inhibiting GDF-15, was associated with improved weight, appetite, and physical activity, along with suppressed serum GDF-15 levels. ⋯ Among patients with cancer cachexia and elevated GDF-15 levels, the inhibition of GDF-15 with ponsegromab resulted in increased weight gain and overall activity level and reduced cachexia symptoms, findings that confirmed the role of GDF-15 as a driver of cachexia. (Funded by Pfizer; ClinicalTrials.gov number, NCT05546476.).