N-Acetylcysteine (NAC) is a frequently used "antioxidant" in vitro, but the concentrations applied rarely correlate with those encountered with oral dosing in vivo. Here, we investigated the in vitro antioxidant and antiplatelet properties of NAC at concentrations (10-100 microM) that are achievable in plasma with tolerable oral dosing. The impact of NAC pretreatment (2 hours) on aggregation of platelets from healthy volunteers in response to thrombin and adenosine diphosphate and on platelet-derived nitric oxide (NO) was examined. NAC was found to be a weak reducing agent and a poor antioxidant compared with glutathione (reduced form) (GSH). However, platelets treated with NAC showed enhanced antioxidant activity and depression of reactive oxygen species generation associated with increases in intraplatelet GSH levels. An approximately 2-fold increase in NO synthase-derived nitrite was observed with 10 microM NAC treatment, but the effect was not concentration dependent. Finally, NAC significantly reduced both thrombin-induced and adenosine diphosphate-induced platelet aggregation. NAC should be considered a weak antioxidant that requires prior conversion to GSH to convey antioxidant and antithrombotic benefit at therapeutically relevant concentrations. Our results suggest that NAC might be an effective antiplatelet agent in conditions where increased oxidative stress contributes to heightened risk of thrombosis but only if the intraplatelet machinery to convert it to GSH is functional.
ObjectivesExplore what ‘good’ patient and family involvement in healthcare adverse event reviews may involve.DesignData was collected using semi-structured telephone interviews. Interview transcripts were analysed using an inductive thematic approach.SettingNHS Scotland.Participants19 interviews were conducted with patients who had experienced an adverse event during the provision of their healthcare or their family member.ResultsFour key themes were derived from these interviews: trauma, communication, learning and litigation.ConclusionsThere are many advantages of actively involving patients and their families in adverse event reviews. An open, collaborative, person-centred approach which listens to, and involves, patients and their families is perceived to lead to improved outcomes. For the patient and their family, it can help with reconciliation following a traumatic event and help restore their faith in the healthcare system. For the health service, listening and involving people will likely enhance learning with subsequent improvements in healthcare provision with reduction in risk of similar events occurring for other patients. This study suggests eight recommendations for involving patients and families in adverse event reviews using the APICCTHS model (table 3) which includes an apology, person-centred inclusive communication, closing the loop, timeliness, putting patients and families at the heart of the review with appropriate support for staff involved. Communicating in a compassionate manner could also decrease litigation claims following an adverse event.
BackgroundPlatelet hyperaggregability is a pro-thrombotic feature of type-2 diabetes, associated with low levels of the antioxidant glutathione (GSH). Clinical delivery of N-acetylcysteine (NAC), a biosynthetic precursor of GSH, may help redress a GSH shortfall in platelets, thereby reducing thrombotic risk in type-2 diabetes patients. We investigated the effect of NAC in vitro, at concentrations attainable with tolerable oral dosing, on platelet GSH concentrations and aggregation propensity in blood from patients with type-2 diabetes.MethodsBlood samples (n = 13) were incubated (2 h, 37°C) with NAC (10-100 micromolar) in vitro. Platelet aggregation in response to thrombin and ADP (whole blood aggregometry) was assessed, together with platelet GSH concentration (reduced and oxidized), antioxidant status, reactive oxygen species (ROS) generation, and plasma NOx (a surrogate measure of platelet-derived nitric oxide; NO).ResultsAt therapeutically relevant concentrations (10-100 micromolar), NAC increased intraplatelet GSH levels, enhanced the antioxidant effects of platelets, and reduced ROS generation in blood from type-2 diabetes patients. Critically, NAC inhibited thrombin- and ADP-induced platelet aggregation in vitro. Plasma NOx was enhanced by 30 micromolar NAC.ConclusionsOur results suggest that NAC reduces thrombotic propensity in type-2 diabetes patients by increasing platelet antioxidant status as a result of elevated GSH synthesis, thereby lowering platelet-derived ROS. This may increase bioavailability of protective NO in a narrow therapeutic range. Therefore, NAC might represent an alternative or additional therapy to aspirin that could reduce thrombotic risk in type-2 diabetes.
AIMSPrescribing errors are common and inadequate preparation of prescribers appears to contribute. A junior doctor-led prescribing tutorial programme has been developed for Edinburgh final year medical students to increase exposure to common prescribing tasks. The aim of this study was to assess the impact of these tutorials on students and tutors. METHODSOne hundred and ninety-six tutorials were delivered to 183 students during 2010-2011. Each student completed a questionnaire after tutorial attendance which explored their previous prescribing experiences and the perceived benefits of tutorial attendance. Tutors completed a questionnaire which evaluated their teaching experiences and the impact on their prescribing practice. Student tutorial attendance was compared with end-of-year examination performance using linear regression analysis. RESULTSThe students reported increased confidence in their prescribing knowledge and skills after attending tutorials. Students who attended more tutorials also tended to perform better in end-of-year examinations (Drug prescribing: r = 0.16, P = 0.015; Fluid prescribing: r = 0.18, P = 0.007). Tutors considered that participation enhanced their own prescribing knowledge and skills. Although they were occasionally unable to address student uncertainties, 80% of tutors reported frequently correcting misconceptions and deficits in student knowledge. Ninety-five percent of students expressed a preference for prescribing training delivered by junior doctors over more senior doctors.
ObjectivesExplore what ‘good’ patient and family involvement in healthcare adverse event reviews may involve.DesignData was collected using semi-structured telephone interviews. Interview transcripts were analysed using an inductive thematic approach.SettingNHS Scotland.Participants19 interviews were conducted with patients who had experienced an adverse event during the provision of their healthcare, or their family member.ResultsFour key themes were derived from these interviews: trauma, communication, learning and litigation.ConclusionsFindings suggest there are many advantages of actively involving patients and their families in adverse event reviews. An open, collaborative, person-centred approach which listens to, and involves, patients and their families is perceived to lead to improved outcomes for all. For the patient and their family, it can help with reconciliation following a traumatic event and help restore their faith in the healthcare system. For the health service, listening and involving people will likely enhance learning with subsequent improvements in healthcare provision with reduction in risk of similar events occurring for other patients. Communicating in a compassionate manner could also decrease litigation claims following an adverse event. Overall, having personalised conversations and a streamlined review process, with open engagement to enhance learning, was important to most participants in this study.
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