Svanenorup8177

Azithromycin has rapidly been adopted as a repurposed drug for the treatment of COVID-19, despite the lack of high-quality evidence. In this review, we critically appraise the current pharmacological, preclinical and clinical data of azithromycin for treating COVID-19. Interest in azithromycin has been fuelled by favourable treatment outcomes in other viral pneumonias, a documented antiviral effect on SARS-CoV-2 in vitro and uncontrolled case series early in the pandemic. Its antiviral effects presumably result from interfering with receptor mediated binding, viral lysosomal escape, intracellular cell-signalling pathways and enhancing type I and III interferon expression. Its immunomodulatory effects may mitigate excessive inflammation and benefit tissue repair. Currently, in vivo reports on azithromycin in COVID-19 are conflicting and do not endorse its widespread use outside of clinical trials. They are, however, mostly retrospective and therefore inherently biased. The effect size of azithromycin may depend on when it is started. Also, extended follow-up is needed to assess benefits in the recovery phase. Safety data warrant monitoring of drug-drug interactions and subsequent cardiac adverse events, especially with hydroxychloroquine. More prospective data of large randomised controlled studies are expected and much-needed. Uniform reporting of results should be strongly encouraged to facilitate data pooling with the many ongoing initiatives.Nicotine has previously been shown to augment the antinociceptive effects of μ-opioid agonists in squirrel monkeys without producing a concomitant increase in behavioral disruption. The present studies were conducted to extend these findings by determining the ability of the nicotinic acetylcholine receptor (nAChR) agonist epibatidine and partial α4β2 nAChR agonist varenicline to selectively augment the antinociceptive effects of the μ-opioid receptor (MOR) full agonist fentanyl, the MOR partial agonist nalbuphine, and the κ-opioid receptor (KOR) agonist U69,593 in male squirrel monkeys. Results indicate that both nAChR ligands selectively increased the antinociceptive effects of nalbuphine and that epibatidine increased the antinociceptive effects of U69,593 without altering effects on operant behavior. However, neither epibatidine nor varenicline enhanced the antinociceptive effects of fentanyl, perhaps due to its high efficacy. The enhancement of nalbuphine's antinociceptive effects by epibatidine, but notα4β2 nAChR agonist varenicline can also augment the antinociceptive effects of nalbuphine, as well as those of a κ-opioid receptor agonist, without concomitantly exacerbating their behaviorally disruptive effects. These findings support the view that nAChR agonists and partial agonists may have potential as adjuvant therapies for opioid-based analgesics.Ethanol is a noncompetitive inhibitor of N-methyl-d-aspartate receptors (NMDARs) and acutely disrupts hippocampal synaptic plasticity and learning. SecinH3 cost In the present study, we examined the effects of oxysterol positive allosteric modulators (PAMs) of NMDARs on ethanol-mediated inhibition of NMDARs, block of long-term potentiation (LTP) and long-term depression (LTD) in rat hippocampal slices, and defects in one-trial learning in vivo. We found that 24S-hydroxycholesterol and a synthetic oxysterol analog, SGE-301, overcame effects of ethanol on NMDAR-mediated synaptic responses in the CA1 region but did not alter acute effects of ethanol on LTD; the synthetic oxysterol, however, overcame acute inhibition of LTP. In addition, both oxysterols overcame persistent effects of ethanol on LTP in vitro, and the synthetic analog reversed defects in one-trial inhibitory avoidance learning in vivo. These results indicate that effects of ethanol on both LTP and LTD arise by complex mechanisms beyond NMDAR antagonism and that oxysterol NMDAR PAMS may represent a novel approach for preventing and reversing acute ethanol-mediated changes in cognition. SIGNIFICANCE STATEMENT Ethanol acutely inhibits hippocampal NMDARs, LTP, and learning. This study found that certain oxysterols that are NMDAR-positive allosteric modulators can overcome the acute effects of ethanol on NMDARs, LTP, and learning. Oxysterols differ in their effects from agents that inhibit integrated cellular stress responses.

Review available evidence for impact of electronic health records (EHRs) on predefined patient safety outcomes in interventional studies to identify gaps in current knowledge and design interventions for future research.

Scoping review to map existing evidence and identify gaps for future research.

PubMed, the Cochrane Library, EMBASE, Trial registers.

Eligibility criteria We conducted a scoping review of bibliographic databases and the grey literature of randomised and non-randomised trials describing interventions targeting a list of fourteen predefined areas of safety. The search was limited to manuscripts published between January 2008 and December 2018 of studies in adult inpatient settings and complemented by a targeted search for studies using a sample of EHR vendors. Studies were categorised according to methodology, intervention characteristics and safety outcome.Results from identified studies were grouped around common themes of safety measures.

The search yielded 583 articles of which 24nd further research into suitable metrics and study designs.

Published evidence for EHR impact on safety outcomes from interventional studies is limited and does not permit firm conclusions regarding the full safety impact of EHRs or support recommendations about ideal design features. The review highlights the need for greater transparency in quality assurance of existing EHRs and further research into suitable metrics and study designs.

The COVID-19 pandemic represents a major societal challenge that requires large-scale behaviour change, widespread collective action and cooperation to reduce viral transmission. Existing literature indicates that several messaging approaches may be effective, including emphasising the benefits to the recipient, aligning with the recipient's moral values and focusing on protecting others. Current research suggests that prosocial public health messages that highlight behaviours linked to societal benefits (eg, protecting 'each other'), rather than focusing on behaviours that protect oneself (eg, protecting 'yourself'), may be a more effective method for communicating strategies related to infectious disease. To investigate this we will conduct a systematic review that will identify what messages and behaviour change techniques have the potential to optimise the effect on population behaviour in relation to reducing transmission of respiratory infections.

A systematic literature search of published and unpublished studies (including grey literature) in electronic databases will be conducted to identify those that meet our inclusion criteria.