Research priorities for the management of broken bones of the upper limb in people over 50: A UK priority setting partnership with the James Lind Alliance

Objective. To determine research priorities for the management of broken bones of the upper limb in people over 50 which represent the shared priorities of patients, their families, carers and healthcare professionals. Design/setting. A national (UK) research priority-setting partnership. Participants. People aged 50 and over who have experienced a fracture of the upper limb; carers involved in their care; family and friends of patients; healthcare professionals involved in the treatment of these patients. Methods. Using a multiphase methodology in partnership with the James Lind Alliance over 15 months (September 2017 – December 2018), a national scoping survey asked respondents to submit their research uncertainties. These were amalgamated into a smaller number of research questions. The existing evidence was searched to ensure that the questions had not already been answered. A second national survey asked respondents to prioritise the research questions. A final shortlist of 25 questions was taken to a multistakeholder workshop where a consensus was reached on the top 10 priorities. Results. There were 1898 original uncertainties submitted by 328 respondents to the first survey. These original uncertainties were refined into 51 research questions of which 50 were judged to be true uncertainties following a review of the research evidence. There were 209 respondents to the second (interim prioritisation) survey. The top 10 priorities encompass a broad range of uncertainties in management and rehabilitation of upper limb fractures. Conclusions. The top 10 UK research priorities highlight uncertainties in how we assess outcomes, provide information, achieve pain control, rationalise surgical intervention, optimise rehabilitation and provide psychological support. The breadth of these research areas highlights the value of this methodology. This work should help to steer research in this area for the next 5-10 years and the challenge for researchers now is to refine and deliver answers to these research priorities

Translating Developmental Origins:Improving the Health of Women and Their Children Using a Sustainable Approach to Behaviour Change

Theories of the developmental origins of health and disease imply that optimising the growth and development of babies is an essential route to improving the health of populations. A key factor in the growth of babies is the nutritional status of their mothers. Since women from more disadvantaged backgrounds have poorer quality diets and the worst pregnancy outcomes, they need to be a particular focus. The behavioural sciences have made a substantial contribution to the development of interventions to support dietary changes in disadvantaged women. Translation of such interventions into routine practice is an ideal that is rarely achieved, however. This paper illustrates how re-orientating health and social care services towards an empowerment approach to behaviour change might underpin a new developmental focus to improving long-term health, using learning from a community-based intervention to improve the diets and lifestyles of disadvantaged women. The Southampton Initiative for Health aimed to improve the diets and lifestyles of women of child-bearing age through training health and social care practitioners in skills to support behaviour change. Analysis illustrates the necessary steps in mounting such an intervention: building trust; matching agendas and changing culture. The Southampton Initiative for Health demonstrates that developing sustainable; workable interventions and effective community partnerships; requires commitment beginning long before intervention delivery but is key to the translation of developmental origins research into improvements in human health

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Variations in achievement of evidence-based, high-impact quality indicators in general practice : An observational study

BACKGROUND: There are widely recognised variations in the delivery and outcomes of healthcare but an incomplete understanding of their causes. There is a growing interest in using routinely collected 'big data' in the evaluation of healthcare. We developed a set of evidence-based 'high impact' quality indicators (QIs) for primary care and examined variations in achievement of these indicators using routinely collected data in the United Kingdom (UK). METHODS: Cross-sectional analysis of routinely collected, electronic primary care data from a sample of general practices in West Yorkshire, UK (n = 89). The QIs covered aspects of care (including processes and intermediate clinical outcomes) in relation to diabetes, hypertension, atrial fibrillation, myocardial infarction, chronic kidney disease (CKD) and 'risky' prescribing combinations. Regression models explored the impact of practice and patient characteristics. Clustering within practice was accounted for by including a random intercept for practice. RESULTS: Median practice achievement of the QIs ranged from 43.2% (diabetes control) to 72.2% (blood pressure control in CKD). Considerable between-practice variation existed for all indicators: the difference between the highest and lowest performing practices was 26.3 percentage points for risky prescribing and 100 percentage points for anticoagulation in atrial fibrillation. Odds ratios associated with the random effects for practices emphasised this; there was a greater than ten-fold difference in the likelihood of achieving the hypertension indicator between the lowest and highest performing practices. Patient characteristics, in particular age, gender and comorbidity, were consistently but modestly associated with indicator achievement. Statistically significant practice characteristics were identified less frequently in adjusted models. CONCLUSIONS: Despite various policy and improvement initiatives, there are enduring inappropriate variations in the delivery of evidence-based care. Much of this variation is not explained by routinely collected patient or practice variables, and is likely to be attributable to differences in clinical and organisational behaviour

Abstracts from the NIHR INVOLVE Conference 2017

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International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication