Why asthma still kills: The national review of asthma deaths (NRAD)

Advancements in drug treatments, applied research and the development of evidence-based clinical guidelines have contributed to the reduction of deaths from asthma over the past 50 years.Previous confidential enquiries have suggested that avoidable factors play a part in as many as threequarters of cases of asthma death. These studies have often been small, conducted locally and undertaken at a considerable time after death. The National Review of Asthma Deaths (NRAD), reported here, is the first national investigation of asthma deaths in the UK and the largest study worldwide to date. Work on the NRAD was undertaken over a 3-year period and was one element of the Department of Health inEngland’s Respiratory Programme. The primary aim of the NRAD was to understand the circumstances surrounding asthma deaths in the UK in order to identify avoidable factors and make recommendations to improve care and reduce the number of deaths.Asthma deaths occurring between February 2012 and January 2013 were identified through the Office for National Statistics (ONS) for England and Wales, the Northern Ireland Statistics and Research Agency(NISRA) and the National Records of Scotland (NRS). Extensive information about each death was sought from multiple sources, including primary, secondary and tertiary care, as well as ambulance, paramedic and out-of-hours care providers. 374 local coordinators were appointed in 297 hospitals across the NHS to collect and submit information to the project team, and 174 expert clinical assessors were recruited from primary, secondary and tertiary care throughout the UK to join expert panels that reviewed data. Each assessor participated in one or more expert panels, during which all information gathered on each death, including post-mortem reports, was reviewed by two assessors in detail, and this was followed by discussion and a consensus agreement of avoidable factors and recommendations by the whole panel.Data were available for analysis on 195 people who were thought to have died from asthma during the review period and the key findings relate to this group. Denominators vary according to where data were missing

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Improvement in neonatal intensive care unit care: a cluster randomised controlled trial of active dissemination of information.

BACKGROUND: Research findings are not rapidly or fully implemented into policies and practice in care. OBJECTIVES: To assess whether an 'active' strategy was more likely to lead to changes in policy and practice in preterm baby care than traditional information dissemination. DESIGN: Cluster randomised trial. PARTICIPANTS: 180 neonatal units (87 active, 93 control) in England; clinicians from active arm units; babies born <27 weeks gestation. CONTROL ARM: Dissemination of research report; slides; information about newborn care position statement. ACTIVE ARM: As above plus offer to become 'regional 'champion' (attend two workshops, support clinicians to implement research evidence regionally), or attend one workshop, promote implementation of research evidence locally. MAIN OUTCOME MEASURES: timing of surfactant administration; admission temperature; staffing of resuscitation team present at birth. RESULTS: 48/87 Lead clinicians in the active arm attended one or both workshops. There was no evidence of difference in post-intervention policies between trial arms. Practice outcomes based on babies in the active (169) and control arms (186), in 45 and 49 neonatal units respectively, showed active arm babies were more likely to have been given surfactant on labour ward (RR=1.30; 95% CI 0.99 to 1.70); p=0.06); to have a higher temperature on admission to neonatal intensive care unit (mean difference=0.29(o)C; 95% CI 0.22 to 0.55; p=0.03); and to have had the baby's trunk delivered into a plastic bag (RR=1.27; 95% CI 1.01 to 1.60; p=0.04) than the control group. The effect on having an 'ideal' resuscitation team at birth was in the same direction of benefit for the active arm (RR=1.18; 95% CI 0.97 to 1.43; p=0.09). The costs of the intervention were modest. CONCLUSIONS: This is the first trial to evaluate methods for transferring information from neonatal research into local policies and practice in England. An active approach to research dissemination is both feasible and cost-effective. TRIAL REGISTRATION: Current controlled trials ISRCTN89683698

The BLISS cluster randomised controlled trial of the effect of 'active dissemination of information' on standards of care for premature babies in England (BEADI) study protocol [ISRCTN89683698].

BACKGROUND: Gaps between research knowledge and practice have been consistently reported. Traditional ways of communicating information have limited impact on practice changes. Strategies to disseminate information need to be more interactive and based on techniques reported in systematic reviews of implementation of changes. There is a need for clarification as to which dissemination strategies work best to translate evidence into practice in neonatal units across England. The objective of this trial is to assess whether an innovative active strategy for the dissemination of neonatal research findings, recommendations, and national neonatal guidelines is more likely to lead to changes in policy and practice than the traditional (more passive) forms of dissemination in England. METHODS/DESIGN: Cluster randomised controlled trial of all neonatal units in England (randomised by hospital, n = 182 and stratified by neonatal regional networks and neonatal units level of care) to assess the relative effectiveness of active dissemination strategies on changes in local policies and practices. Participants will be mainly consultant lead clinicians in each unit. The intervention will be multifaceted using: audit and feedback; educational meetings for local staff (evidence-based lectures on selected topics, interactive workshop to examine current practice and draw up plans for change); and quality improvement and organisational changes methods. Policies and practice outcomes for the babies involved will be collected before and after the intervention. Outcomes will assess all premature babies born in England during a three month period for timing of surfactant administration at birth, temperature control at birth, and resuscitation team (qualification and numbers) present at birth

CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label,parallel-group, multicentre trial

Background The benefi t of CT coronary angiography (CTCA) in patients presenting with stable chest pain has not been systematically studied. We aimed to assess the eff ect of CTCA on the diagnosis, management, and outcome of patients referred to the cardiology clinic with suspected angina due to coronary heart disease. Methods In this prospective open-label, parallel-group, multicentre trial, we recruited patients aged 18–75 years referred for the assessment of suspected angina due to coronary heart disease from 12 cardiology chest pain clinics across Scotland. We randomly assigned (1:1) participants to standard care plus CTCA or standard care alone. Randomisation was done with a web-based service to ensure allocation concealment. The primary endpoint was certainty of the diagnosis of angina secondary to coronary heart disease at 6 weeks. All analyses were intention to treat, and patients were analysed in the group they were allocated to, irrespective of compliance with scanning. This study is registered with ClinicalTrials.gov, number NCT01149590. Findings Between Nov 18, 2010, and Sept 24, 2014, we randomly assigned 4146 (42%) of 9849 patients who had been referred for assessment of suspected angina due to coronary heart disease. 47% of participants had a baseline clinic diagnosis of coronary heart disease and 36% had angina due to coronary heart disease. At 6 weeks, CTCA reclassifi ed the diagnosis of coronary heart disease in 558 (27%) patients and the diagnosis of angina due to coronary heart disease in 481 (23%) patients (standard care 22 [1%] and 23 [1%]; p<0·0001). Although both the certainty (relative risk [RR] 2·56, 95% CI 2·33–2·79; p<0·0001) and frequency of coronary heart disease increased (1·09, 1·02–1·17; p=0·0172), the certainty increased (1·79, 1·62–1·96; p<0·0001) and frequency seemed to decrease (0·93, 0·85–1·02; p=0·1289) for the diagnosis of angina due to coronary heart disease. This changed planned investigations (15% vs 1%; p<0·0001) and treatments (23% vs 5%; p<0·0001) but did not aff ect 6-week symptom severity or subsequent admittances to hospital for chest pain. After 1·7 years, CTCA was associated with a 38% reduction in fatal and nonfatal myocardial infarction (26 vs 42, HR 0·62, 95% CI 0·38–1·01; p=0·0527), but this was not signifi cant. Interpretation In patients with suspected angina due to coronary heart disease, CTCA clarifi es the diagnosis, enables targeting of interventions, and might reduce the future risk of myocardial infarction. Funding The Chief Scientist Offi ce of the Scottish Government Health and Social Care Directorates funded the trial with supplementary awards from Edinburgh and Lothian’s Health Foundation Trust and the Heart Diseases Research Fund