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Träfflista för sökning "WFRF:(Clarke Philip M) srt2:(2020-2021)"

Sökning: WFRF:(Clarke Philip M) > (2020-2021)

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1.
  • Kitchen, Philip, et al. (författare)
  • Targeting Aquaporin-4 Subcellular Localization to Treat Central Nervous System Edema
  • 2020
  • Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 181:4, s. 19-799
  • Tidskriftsartikel (refereegranskat)abstract
    • Swelling of the brain or spinal cord (CNS edema) affects millions of people every year. All potential pharmacological interventions have failed in clinical trials, meaning that symptom management is the only treatment option. The water channel protein aquaporin-4 (AQP4) is expressed in astrocytes and mediates water flux across the blood-brain and blood-spinal cord barriers. Here we show that AQP4 cell-surface abundance increases in response to hypoxia-induced cell swelling in a calmodulin-dependent manner. Calmodulin directly binds the AQP4 carboxyl terminus, causing a specific conformational change and driving AQP4 cell-surface localization. Inhibition of calmodulin in a rat spinal cord injury model with the licensed drug trifluoperazine inhibited AQP4 localization to the blood-spinal cord barrier, ablated CNS edema, and led to accelerated functional recovery compared with untreated animals. We propose that targeting the mechanism of calmodulin-mediated cell-surface localization of AQP4 is a viable strategy for development of CNS edema therapies.
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2.
  • Bunzli, Samantha, et al. (författare)
  • Placebo Surgery Controlled Trials : Do They Achieve What They Set Out To Do? A Systematic Review
  • 2021
  • Ingår i: Annals of Surgery. - 1528-1140. ; 273:6, s. 1102-1107
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To explore whether placebo surgery controlled trials achieve what they set out to do by investigating discrepancy between projected and actual design aspects of trials identified through systematic review methods. SUMMARY BACKGROUND: Interest in placebo surgery controlled trials is growing in response to concerns regarding unnecessary surgery and the societal cost of low-value healthcare. As questions about the justifiability of using placebo controls in surgery have been addressed, attention is now being paid to more practical concerns. METHODS: Six databases were searched from inception - May 2020 (MEDLINE, Embase, Emcare, APA PsycInfo, CINAHL, Cochrane Library). Placebo surgery controlled trials with a published protocol were included. Three authors extracted "projected" design aspects from protocols and "actual" design aspects from main findings papers. Absolute and relative difference between projected and actual design aspects were presented for each trial. Trials were grouped according to whether they met their target sample size ("completed") and were concluded in a timely fashion. Pairs of authors assessed risk of bias. RESULTS: Of 24 trials with data available to analyse; 3 were completed and concluded within target timeframe; 10 were completed and concluded outside the target timeline; 4 were completed without clear target timeframes; 2 were incomplete and concluded within the target framework; 5 were incomplete and concluded outside the target timeline. Trials which reached the recruitment target underestimated trial duration by 88% and number of recruitment sites by 87%. CONCLUSIONS: Trialists need to factor additional time and sites into future placebo surgery controlled trials. A robust reporting framework of projected and actual trial design is imperative for trialists to learn from their predecessors. REVIEW REGISTRATION: PROSPERO (CRD42019133296).
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3.
  • Shadbolt, Cade, et al. (författare)
  • The Surgeon's Role in the Opioid Crisis : A Narrative Review and Call to Action
  • 2020
  • Ingår i: Frontiers in surgery. - : Frontiers Media SA. - 2296-875X. ; 7
  • Forskningsöversikt (refereegranskat)abstract
    • Over the past two decades, there has been a sharp rise in the use of prescription opioids. In several countries, most notably the United States, opioid-related harm has been deemed a public health crisis. As surgeons are among the most prolific prescribers of opioids, growing attention is now being paid to the role that opioids play in surgical care. While opioids may sometimes be necessary to provide patients with adequate relief from acute pain after major surgery, the impact of opioids on the quality and safety of surgical care calls for greater scrutiny. This narrative review summarizes the available evidence on rates of persistent postsurgical opioid use and highlights the need to target known risk factors for persistent postoperative use before patients present for surgery. We draw attention to the mounting evidence that preoperative opioid exposure places patients at risk of persistent postoperative use, while also contributing to an increased risk of several other adverse clinical outcomes. By discussing the prevalence of excess opioid prescribing following surgery and highlighting significant variations in prescribing practices between countries, we note that there is a pressing need to optimize postoperative prescribing practices. Guided by the available evidence, we call for specific actions to be taken to address important research gaps and alleviate the harms associated with opioid use among surgical patients.
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  • Resultat 1-4 av 4

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