46 research outputs found

    HIV-1 Tat immunization restores immune homeostasis and attacks the HAART-resistant blood HIV DNA: results of a randomized phase II exploratory clinical trial

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    Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

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    Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

    Behavior change interventions and policies influencing primary healthcare professionals’ practice—an overview of reviews

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    A core outcome set for pre‐eclampsia research: an international consensus development study

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    Objective To develop a core outcome set for pre‐eclampsia. Design Consensus development study. Setting International. Population Two hundred and eight‐one healthcare professionals, 41 researchers and 110 patients, representing 56 countries, participated. Methods Modified Delphi method and Modified Nominal Group Technique. Results A long‐list of 116 potential core outcomes was developed by combining the outcomes reported in 79 pre‐eclampsia trials with those derived from thematic analysis of 30 in‐depth interviews of women with lived experience of pre‐eclampsia. Forty‐seven consensus outcomes were identified from the Delphi process following which 14 maternal and eight offspring core outcomes were agreed at the consensus development meeting. Maternal core outcomes: death, eclampsia, stroke, cortical blindness, retinal detachment, pulmonary oedema, acute kidney injury, liver haematoma or rupture, abruption, postpartum haemorrhage, raised liver enzymes, low platelets, admission to intensive care required, and intubation and ventilation. Offspring core outcomes: stillbirth, gestational age at delivery, birthweight, small‐for‐gestational‐age, neonatal mortality, seizures, admission to neonatal unit required and respiratory support. Conclusions The core outcome set for pre‐eclampsia should underpin future randomised trials and systematic reviews. Such implementation should ensure that future research holds the necessary reach and relevance to inform clinical practice, enhance women's care and improve the outcomes of pregnant women and their babies

    Structure of the activation domain of the GM-CSF/IL-3/IL-5 receptor common b-chain bound to an antagonist

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    Heterodimeric cytokine receptors generally consist of a major cytokine-binding subunit and a signaling subunit. The latter can transduce signals by more than 1 cytokine, as exemplified by the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and IL-6 receptor systems. However, often the signaling subunits in isolation are unable to bind cytokines, a fact that has made it more difficult to obtain structural definition of their ligand-binding sites. This report details the crystal structure of the ligand-binding domain of the GM-CSF/IL-3/IL-5 receptor beta-chain (beta(c)) signaling subunit in complex with the Fab fragment of the antagonistic monoclonal antibody, BION-1. This is the first single antagonist of all 3 known eosinophil-producing cytokines, and it is therefore capable of regulating eosinophil-related diseases such as asthma. The structure reveals a fibronectin type III domain, and the antagonist-binding site involves major contributions from the loop between the B and C strands and overlaps the cytokine-binding site. Furthermore, tyrosine(421) (Tyr(421)), a key residue involved in receptor activation, lies in the neighboring loop between the F and G strands, although it is not immediately adjacent to the cytokine-binding residues in the B-C loop. Interestingly, functional experiments using receptors mutated across these loops demonstrate that they are cooperatively involved in full receptor activation. The experiments, however, reveal subtle differences between the B-C loop and Tyr(421), which is suggestive of distinct functional roles. The elucidation of the structure of the ligand-binding domain of beta(c) also suggests how different cytokines recognize a single receptor subunit, which may have implications for homologous receptor systems. (Blood. 2000;95:2491-2498)Jamie Rossjohn, William J. McKinstry, Joanna M. Woodcock, Barbara J. McClure, Timothy R. Hercus, Michael W. Parker, Angel F. Lopez, and Christopher J. Bagle

    Design and implementation characteristics of research training for rural health professionals: a qualitative descriptive study

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    Abstract Background Research capacity and capability of rural health professionals is essential to the delivery of evidence-based care and for informing strategies to address rural health inequities. Effective implementation of research education and training is fundamental to building rural health professional research capacity and capability. A lack of overarching guidance to inform the delivery of research education and training in rural health services can contribute to gaps in capacity-building approaches. The aim of this study was to identify characteristics of the design and implementation of current research training for rural health professionals in Victoria, Australia, to inform a future model for rural health professional research capacity and capability building. Methods A qualitative descriptive study was undertaken. Key informants, with extensive knowledge of research education and training in rural health services in Victoria, were invited to participate in semi-structured telephone interviews via snowballing recruitment methods. Interview transcripts were analysed inductively, with themes and codes mapped to the domains of the Consolidated Framework for Implementation Research. Results Of the 40 key informants approached, 20 agreed to participate including 11 regional health service managers, five rural health academics and four university managers. Participants suggested that research training varied in quality and relevance to rural health professionals. Training costs and lack of tailoring to the rural context were key barriers, whereas experiential learning and flexible modes of delivery enabled training uptake. Health service and government policies, structures, and processes both enabled or stifled implementation opportunities, with rural health professional networks from different regions offering capacity for research training development, and government departmental structures hampering training coordination. Tension between research activities and clinical practice, and health professional knowledge and beliefs, shaped the delivery of training programs. Strategically planned and evaluated research training programs and education via co-design with rural health professionals and use of research champions were strongly recommended by participants. Conclusions To optimise research training for rural health professionals and increase the quality and quantity of relevant rural health research, a systematically planned, implemented, and resourced region-wide research training model is required
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