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A recent systematic review and meta-analysis of RCTs of early vs late tracheostomy in mechanically ventilated patients suggest that early tracheostomy reduces the duration of ICU stay and mechanical ventilation, but does not reduce short-term mortality or ventilator-associated pneumonia (VAP). Meta-analysis of randomised trials is typically performed using a frequentist approach, and although reporting confidence intervals, interpretation is usually based on statistical significance. To provide a robust basis for clinical decision-making, we completed the search used from the previous review and analysed the data using Bayesian methods to estimate posterior probabilities of the effect of early tracheostomy on clinical outcomes.The search was completed for RCTS comparing early vs late tracheostomy in the databases PubMed, EMBASE, and Cochrane library in June 2022. Effect estimates and 95% confidence intervals were calculated for the outcomes short-term mortality, VAP, duration of ICU stay, and mechanical ventilation. A Bayesian meta-analysis was performed with uninformative priors. Risk ratios (RRs) and standardised mean differences (SMDs) with 95% credible intervals were reported alongside posterior probabilities for any benefit (RR1; SMD0), a small benefit (number needed to treat, 200; SMD-0.5), or modest benefit (number needed to treat, 100; SMD-1).Nineteen RCTs with 3508 patients were included. Comparing patients with early vs late tracheostomy, the posterior probabilities for any benefit, small benefit, and modest benefit, respectively, were: 99%, 99%, and 99% for short-term mortality; 94%, 78%, and 51% for VAP; 97%, 43%, and 1% for duration of mechanical ventilation; and 97%, 75%, and 27% and for length of ICU stay.Bayesian meta-analysis suggests a high probability that early tracheostomy compared with delayed tracheostomy has at least some benefit across all clinical outcomes considered.

Health service delivery interventions include a range of hospital ‘quality improvement’ initiatives and broader health system policies. These interventions act through multiple causal pathways to affect patient outcomes and they present distinct challenges for evaluation. In this article, we propose an empirical approach to estimating the effect of service delivery interventions on patient length of stay considering three principle issues: (i) informative censoring of discharge times due to mortality; (ii) post-treatment selection bias if the intervention affects patient admission probabilities; and (iii) decomposition into direct and indirect pathways mediated by quality. We propose a Bayesian structural survival model framework in which results from a subsample in which required assumptions hold, including conditional independence of the intervention, can be applied to the whole sample. We evaluate a policy of increasing specialist intensity in hospitals at the weekend in England and Wales to inform a cost-minimisation analysis. Using data on adverse events from a case note review, we compare various specifications of a structural model that allows for observations of hospital quality. We find that the policy was not implemented as intended but would have likely been cost saving, that this conclusion is sensitive to model specification, and that the direct effect accounts for almost all of the total effect rather than any improvement in hospital quality.

Background NHS England’s 7-day services policy comprised 10 standards to improve access to quality health care across all days of the week. Six standards targeted hospital specialists on the assumption that their absence caused the higher mortality associated with weekend hospital admission: the ‘weekend effect’. The High-intensity Specialist-Led Acute Care (HiSLAC) collaboration investigated this using the implementation of 7-day services as a ‘natural experiment’. Objectives The objectives were to determine whether or not increasing specialist intensity at weekends improves outcomes for patients undergoing emergency hospital admission, and to explore mechanisms and cost-effectiveness. Design This was a two-phase mixed-methods observational study. Year 1 focused on developing the methodology. Years 2–5 included longitudinal research using quantitative and qualitative methods, and health economics. Methods A Bayesian systematic literature review from 2000 to 2017 quantified the weekend effect. Specialist intensity measured over 5 years used self-reported annual point prevalence surveys of all specialists in English acute hospital trusts, expressed as the weekend-to-weekday ratio of specialist hours per 10 emergency admissions. Hospital Episode Statistics from 2007 to 2018 provided trends in weekend-to-weekday mortality ratios. Mechanisms for the weekend effect were explored qualitatively through focus groups and on-site observations by qualitative researchers, and a two-epoch case record review across 20 trusts. Case-mix differences were examined in a single trust. Health economics modelling estimated costs and outcomes associated with increased specialist provision. Results Of 141 acute trusts, 115 submitted data to the survey, and 20 contributed 4000 case records for review and participated in qualitative research (involving interviews, and observations using elements of an ethnographic approach). Emergency department attendances and admissions have increased every year, outstripping the increase in specialist numbers; numbers of beds and lengths of stay have decreased. The reduction in mortality has plateaued; the proportion of patients dying after discharge from hospital has increased. Specialist hours increased between 2012/13 and 2017/18. Weekend specialist intensity is half that of weekdays, but there is no relationship with admission mortality. Patients admitted on weekends are sicker (they have more comorbid disease and more of them require palliative care); adjustment for severity of acute illness annuls the weekend effect. In-hospital care processes are slightly more efficient at weekends; care quality (errors, adverse events, global quality) is as good at weekends as on weekdays and has improved with time. Qualitative researcher assessments of hospital weekend quality concurred with case record reviewers at trust level. General practitioner referrals at weekends are one-third of those during weekdays and have declined further with time. Limitations Observational research, variable survey response rates and subjective assessments of care quality were compensated for by using a difference-in-difference analysis over time. Conclusions Hospital care is improving. The weekend effect is associated with factors in the community that precede hospital admission. Post-discharge mortality is increasing. Policy-makers should focus their efforts on improving acute and emergency care on a ‘whole-system’ 7-day approach that integrates social, community and secondary health care. Future work Future work should evaluate the role of doctors in hospital and community emergency care and investigate pathways to emergency admission and quality of care following hospital discharge. Funding This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 9, No. 13. See the NIHR Journals Library website for further project information.

The study Bion J, Aldridge C, Beet C, et al. Increasing specialist intensity at weekends to improve outcomes for patients undergoing emergency hospital admission: the HiSLAC two-phase mixed-methods study. HSDR 2021;9:13. To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/hospital-emergency-care-is-as-good-at-the-weekend-as-on-weekdays/

Background: Dysregulated inflammation is associated with poor outcomes in COVID-19. We aimed to assess the efficacy of namilumab (a granulocyte-macrophage colony stimulating factor inhibitor) and infliximab (a tumour necrosis factor inhibitor) in hospitalised patients with COVID-19, to prioritise agents for phase 3 trials. Methods: In this randomised, multicentre, multi-arm, multistage, parallel-group, open-label, adaptive, phase 2, proof-of-concept trial (CATALYST), we recruited patients (aged ≥16 years) admitted to hospital with COVID-19 pneumonia and C-reactive protein (CRP) concentrations of 40 mg/L or greater, at nine hospitals in the UK. Participants were randomly assigned with equal probability to usual care or usual care plus a single intravenous dose of namilumab (150 mg) or infliximab (5 mg/kg). Randomisation was stratified by care location within the hospital (ward vs intensive care unit [ICU]). Patients and investigators were not masked to treatment allocation. The primary endpoint was improvement in inflammation, measured by CRP concentration over time, analysed using Bayesian multilevel models. This trial is now complete and is registered with ISRCTN, 40580903. Findings: Between June 15, 2020, and Feb 18, 2021, we screened 299 patients and 146 were enrolled and randomly assigned to usual care (n=54), namilumab (n=57), or infliximab (n=35). For the primary outcome, 45 patients in the usual care group were compared with 52 in the namilumab group, and 29 in the usual care group were compared with 28 in the infliximab group. The probabilities that the interventions were superior to usual care alone in reducing CRP concentration over time were 97% for namilumab and 15% for infliximab; the point estimates for treatment–time interactions were –0·09 (95% CI –0·19 to 0·00) for namilumab and 0·06 (–0·05 to 0·17) for infliximab. 134 adverse events occurred in 30 (55%) of 55 patients in the namilumab group compared with 145 in 29 (54%) of 54 in the usual care group. 102 adverse events occurred in 20 (69%) of 29 patients in the infliximab group compared with 112 in 17 (50%) of 34 in the usual care group. Death occurred in six (11%) patients in the namilumab group compared with ten (19%) in the usual care group, and in four (14%) in the infliximab group compared with five (15%) in the usual care group. Interpretation: Namilumab, but not infliximab, showed proof-of-concept evidence for reduction in inflammation—as measured by CRP concentration—in hospitalised patients with COVID-19 pneumonia. Namilumab should be prioritised for further investigation in COVID-19.

Introduction Severe SARS-CoV-2 infection is associated with a dysregulated immune response. Inflammatory monocytes and macrophages are crucial, promoting injurious, proinflammatory sequelae. Immunomodulation is, therefore, an attractive therapeutic strategy and we sought to test licensed and novel candidate drugs. Methods and analysis The CATALYST trial is a multiarm, open-label, multicentre, phase II platform trial designed to identify candidate novel treatments to improve outcomes of patients hospitalised with COVID-19 compared with usual care. Treatments with evidence of biomarker improvements will be put forward for larger-scale testing by current national phase III platform trials. Hospitalised patients >16 years with a clinical picture strongly suggestive of SARS-CoV-2 pneumonia (confirmed by chest X-ray or CT scan, with or without a positive reverse transcription PCR assay) and a C reactive protein (CRP) ≥40 mg/L are eligible. The primary outcome measure is CRP, measured serially from admission to day 14, hospital discharge or death. Secondary outcomes include the WHO Clinical Progression Improvement Scale as a principal efficacy assessment. Ethics and dissemination The protocol was approved by the East Midlands-Nottingham 2 Research Ethics Committee (20/EM/0115) and given urgent public health status; initial approval was received on 5 May 2020, current protocol version (V.6.0) approval on 12 October 2020. The MHRA also approved all protocol versions. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications. Trial registration numbers EudraCT2020-001684-89,NCT40580903.

Background: Patients with co-morbidities are particularly vulnerable to severe COVID-19 disease. Critically ill patients with COVID-19 frequently experience severe tachycardias and avoidance of these is important in some co-morbidities, for instance cardiovascular disease. There is growing interest in beta blockade in critical illness as their use been associated with improved outcomes in a variety of conditions. We report the real-world use of heart rate management in patients during the first wave of the COVID-19 pandemic. As retrospective data are prone to an Immortal Time Bias, we created a Cohort Trial such as might be used for a future prospective trial and used Time Dependent Covariate Analysis for its analysis. Methods: Data for all PCR-proven COVID-19 patients ventilated in the Intensive Care Unit (ICU) were extracted from the hospital databases. To compensate for the risk of immortal time bias, we restricted analysis to 144 patients who achieved a heart rate (HR) of 90 beats per minute for more than 12 hours and were treated with norepinephrine. We recorded time from these ‘entry criteria’ to first beta blocker dose. Those patients who did not receive a beta blocker were given a nominal time to beta blocker beyond the censor day. Outcome was mortality censored at 28 days.Results: In the study group, 83/144 patients (57.6%) received a beta blocker. The median interval from entry criteria to beta blocker was 7.91 days (IQR 3.89, 13.15) and median duration of treatment was 7.00 days (IQR 4.00, 14.00). Twenty-four beta blocker patients (28.9%) died within 28 days compared with 29 (47.5%) who did not (adjusted OR 0.43; 95% CI 0.20-0.95, P=0.036). Cox Regression with time-dependent covariate analysis revealed there was an increased, but not significant, risk of death with beta blocker delay (Hazard Ratio 1.42 p=0.264). Mortality was also reduced for each day treated with beta blockade (adjusted Odds Ratio 0.76, 95% CI 0.64-0.91; P=0.002).Conclusions: In a retrospective analysis of critically ill ventilated patients with COVID-19 who developed a tachycardia >90 beats per minute and were treated with norepinephrine, beta blockade was associated with reduced mortality.

SummaryBackgroundDysregulated inflammation is associated with poor outcomes in Coronavirus disease 2019 (COVID-19). We assessed the efficacy of namilumab, a granulocyte-macrophage colony-stimulating factor inhibitor and infliximab, a tumour necrosis factor inhibitor in hospitalised patients with COVID-19 in order to prioritise agents for phase 3 trials.MethodsIn this randomised, multi-arm, parallel group, open label, adaptive phase 2 proof-of-concept trial (CATALYST) we recruited hospitalised patients ≥ 16 years with COVID-19 pneumonia and C-reactive protein (CRP) ≥ 40mg/L in nine UK hospitals. Participants were randomly allocated with equal probability to usual care, or usual care plus a single 150mg intravenous dose of namilumab (150mg) or infliximab (5mg/kg). Randomisation was stratified for ward versus ICU. The primary endpoint was improvement in inflammation in intervention arms compared to control as measured by CRP over time, analysed using Bayesian multi-level models. ISRCTN registry number 40580903.FindingsBetween 15thJune 2020 and 18thFebruary 2021 we randomised 146 participants: 54 to usual care, 57 to namilumab and 35 to infliximab. The probabilities that namilumab and infliximab were superior to usual care in reducing CRP over time were 97% and 15% respectively. Consistent effects were seen in ward and ICU patients and aligned with clinical outcomes, such that the probability of discharge (WHO levels 1-3) at day 28 was 47% and 64% for ICU and ward patients on usual care, versus 66% and 77% for patients treated with namilumab. 134 adverse events occurred in 30/55 (54.5%) namilumab patients compared to 145 in 29/54 (53.7%) usual care patients. 102 events occurred in 20/29 (69.0%) infliximab patients versus 112 events in 17/34 (50.0%) usual care patients.InterpretationNamilumab, but not infliximab, demonstrated proof-of-concept evidence for reduction in inflammation in hospitalised patients with COVID-19 pneumonia which was consistent with secondary clinical outcomes. Namilumab should be prioritised for further investigation in COVID-19.FundingMedical Research Council.

Background The degree to which elevated mortality associated with weekend or night-time hospital admissions reflects poorer quality of care (‘off-hours effect’) is a contentious issue. We examined if off-hours admissions for primary percutaneous coronary intervention (PPCI) were associated with higher adjusted mortality and estimated the extent to which potential differences in door-to-balloon (DTB) times—a key indicator of care quality for ST elevation myocardial infarction (STEMI) patients—could explain this association. Methods Nationwide registry-based prospective observational study using Myocardial Ischemia National Audit Project data in England. We examined how off-hours admissions and DTB times were associated with our primary outcome measure, 30-day mortality, using hierarchical logistic regression models that adjusted for STEMI patient risk factors. In-hospital mortality was assessed as a secondary outcome. Results From 76 648 records of patients undergoing PPCI between January 2007 and December 2012, we included 42 677 admissions in our analysis. Fifty-six per cent of admissions for PPCI occurred during off-hours. PPCI admissions during off-hours were associated with a higher likelihood of adjusted 30-day mortality (OR 1.13; 95% CI 1.01 to 1.25). The median DTB time was longer for off-hours admissions (45 min; IQR 30–68) than regular hours (38 min; IQR 27–58; p

Pharmacists working in community and primary care are increasingly developing advanced skills to provide enhanced services, particularly in dealing with minor acute illness. These services can potentially free-up primary care physicians’ time; however, it is not clear whether they are sufficiently cost effective to be recommended for wider provision in the UK. The aim of this study was to review published economic evaluations of enhanced pharmacy services in the community and primary care settings. We undertook a systematic review of economic evaluations of enhanced pharmacy services to inform NICE guidelines for emergency and acute care. The review protocol was developed and agreed with the guideline committee. The National Health Service Economic Evaluation Database, Health Technology Assessment Database, Health Economic Evaluations Database, MEDLINE and EMBASE were searched in December 2016 and the search was updated in March 2018. Studies were assessed for applicability and methodological quality using the NICE Economic Evaluation Checklist. Of 3124 records, 13 studies published in 14 papers were included. The studies were conducted in the UK, Spain, The Netherlands, Australia, Italy and Canada. Settings included community pharmacies, primary care/general practice surgeries and patients’ homes. Most of the studies were assessed as partially applicable with potentially serious limitations. Services provided in community and primary care settings were found to be either dominant or cost effective, at a £20,000 per quality-adjusted life-year threshold, compared with usual care. Those delivered in the patient’s home were not found to be cost effective. Advanced pharmacy services appear to be cost effective when delivered in community and primary care settings, but not in domiciliary settings. Expansion in the provision of these services in community and primary care can be recommended for wider implementation.

Objectives In various medical and surgical conditions, research has found that centers with higher patient volumes have better outcomes. This relationship has not previously been explored for status epilepticus. This study sought to examine whether centers that see higher volumes of patients with status epilepticus have lower in-hospital mortality than low-volume centers. Design Cohort study, using 2010-2015 data from the nationwide Case Mix Programme database of the U.K.'s Intensive Care National Audit and Research Centre. Setting Greater than 90% of ICUs in United Kingdom, Wales, and Northern Ireland. Patients Twenty-thousand nine-hundred twenty-two adult critical care admissions with a primary or secondary diagnosis of status epilepticus or prolonged seizure. Interventions Annual hospital status epilepticus admission volume. Measurements and main results We used multiple logistic regression to evaluate the association between hospital annual status epilepticus admission volume and in-hospital mortality. Hospital volume was modeled as a nonlinear variable using restricted cubic splines, and generalized estimating equations with robust SEs were used to account for clustering by institution. There were 2,462 in-hospital deaths (11.8%). There was no significant association between treatment volume and in-hospital mortality for status epilepticus (p = 0.54). This conclusion was unchanged across a number of subgroup and sensitivity analyses, although we lacked data on seizure duration and medication use. Secondary analyses suggest that many high-risk patients were already transferred from low- to high-volume centers. Conclusions We find no evidence that higher volume centers are associated with lower mortality in status epilepticus overall. It is likely that national guidelines and local pathways in the United Kingdom allow efficient patient transfer from smaller centers like district general hospitals to provide satisfactory patient care in status epilepticus. Future research using more granular data should explore this association for the subgroup of patients with refractory and superrefractory status epilepticus.

Improving the quality and safety of perioperative care is a global priority. The Enhanced Peri-Operative Care for High-risk patients (EPOCH) trial was a stepped-wedge cluster randomised trial of a quality improvement (QI) programme to improve 90-day survival for patients undergoing emergency abdominal surgery in 93 hospitals in the UK National Health Service.The aim of this process evaluation is to describe how the EPOCH intervention was planned, delivered and received, at both cluster and local hospital levels. The QI programme comprised of two interventions: a care pathway and a QI intervention to aid pathway implementation, focussed on stakeholder engagement, QI teamwork, data analysis and feedback and applying the model for improvement. Face-to-face training and online resources were provided to support senior clinicians in each hospital (QI leads) to lead improvement. For this evaluation, we collated programme activity data, administered an exit questionnaire to QI leads and collected ethnographic data in six hospitals. Qualitative data were analysed with thematic or comparative analysis; quantitative data were analysed using descriptive statistics.The EPOCH trial did not demonstrate any improvement in survival or length of hospital stay. Whilst the QI programme was delivered as planned at the cluster level, self-assessed intervention fidelity at the hospital level was variable. Seventy-seven of 93 hospitals responded to the exit questionnaire (60 from a single QI lead response on behalf of the team); 33 respondents described following the QI intervention closely (35%) and there were only 11 of 37 care pathway processes that 50% of respondents reported attempting to improve. Analysis of qualitative data suggests QI leads were often attempting to deliver the intervention in challenging contexts: the social aspects of change such as engaging colleagues were identified as important but often difficult and clinicians frequently attempted to lead change with limited time or organisational resources.Significant organisational challenges faced by QI leads shaped their choice of pathway components to focus on and implementation approaches taken. Adaptation causing loss of intervention fidelity was therefore due to rational choices made by those implementing change within constrained contexts. Future large-scale QI programmes will need to focus on dedicating local time and resources to improvement as well as on training to develop QI capabilities.ISRCTN80682973 https://doi.org/10.1186/ISRCTN80682973 Registered 27 February 2014 and Lancet protocol 13PRT/7655.

IntroductionSevere SARS-CoV-2 infection is associated with a dysregulated immune response. Inflammatory monocytes and macrophages are crucial, promoting injurious, pro-inflammatory sequelae. Immunomodulation is, therefore, an attractive therapeutic strategy and we sought to test licensed and novel candidate drugs.Methods and analysisThe CATALYST trial is a multi-arm, open-label, multi-centre, phase II platform trial designed to identify candidate novel treatments to improve outcomes of patients hospitalised with COVID-19 compared with usual care. Treatments with evidence of biomarker improvements will be put forward for larger-scale testing by current national phase III platform trials. Hospitalised patients >16 years with a clinical picture strongly suggestive of SARS-CoV-2 pneumonia (confirmed by chest X-ray or CT scan, with or without a positive reverse transcription polymerase chain reaction (RT-PCR) assay) and a C-Reactive Protein (CRP) ≥40 mg/L are eligible. The primary outcome measure is CRP, measured serially from admission to day 14, hospital discharge or death. Secondary outcomes include the WHO Clinical Progression Improvement Scale as a principal efficacy assessment.Ethics and disseminationThe protocol was approved by the East Midlands - Nottingham 2 Research Ethics Committee (20/EM/0115) and given Urgent Public Health status; initial approval was received on 05-May-2020, current protocol version (v6.0) approval on 12-Oct-2020. The MHRA also approved all protocol versions. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.Trial registration numberEudraCT Number: 2020-001684-89ISRCTN Number: 40580903Strengths and limitations of this trialCATALYST will provide a rapid readout on the safety and proof-of-concept of candidate novel treatmentsCATALYST will enable phase III trial resources to be focussed and allocated for agents with a high likelihood of successCATALYST uses Bayesian multi-level models to allow for nesting of repeated measures data, with factors for each individual patient and treatment arm, and allowing for non-linear responsesCATALYST is not designed to provide a definitive signal on clinical outcomes

There is a limited access to liver transplantation, however, many organs are discarded based on subjective assessment only. Here we report the VITTAL clinical trial (ClinicalTrials.gov number NCT02740608) outcomes, using normothermic machine perfusion (NMP) to objectively assess livers discarded by all UK centres meeting specific high-risk criteria. Thirty-one livers were enroled and assessed by viability criteria based on the lactate clearance to levels ≤2.5 mmol/L within 4 h. The viability was achieved by 22 (71%) organs, that were transplanted after a median preservation time of 18 h, with 100% 90-day survival. During the median follow up of 542 days, 4 (18%) patients developed biliary strictures requiring re-transplantation. This trial demonstrates that viability testing with NMP is feasible and in this study enabled successful transplantation of 71% of discarded livers, with 100% 90-day patient and graft survival; it does not seem to prevent non-anastomotic biliary strictures in livers donated after circulatory death with prolonged warm ischaemia. The shortage of viable donated livers limits patient access to liver transplantation. Here the authors report the use of normothermic machine perfusion to help identify viable organs from livers discarded based on current clinical criteria, which are then transplanted to recipients in a single-arm clinical trial.

BackgroundIn 2013, the English National Health Service launched the policy of 7-day services to improve care quality and outcomes for weekend emergency admissions.AimsTo determine whether the quality of care of emergency medical admissions is worse at weekends, and whether this has changed during implementation of 7-day services.MethodsUsing data from 20 acute hospital Trusts in England, we performed randomly selected structured case record reviews of patients admitted to hospital as emergencies at weekends and on weekdays between financial years 2012–2013 and 2016–2017. Senior doctor (‘specialist’) involvement was determined from annual point prevalence surveys. The primary outcome was the rate of clinical errors. Secondary outcomes included error-related adverse event rates, global quality of care and four indicators of good practice.ResultsSeventy-nine clinical reviewers reviewed 4000 admissions, 800 in duplicate. Errors, adverse events and care quality were not significantly different between weekend and weekday admissions, but all improved significantly between epochs, particularly errors most likely influenced by doctors (clinical assessment, diagnosis, treatment, prescribing and communication): error rate OR 0.78; 95% CI 0.70 to 0.87; adverse event OR 0.48, 95% CI 0.33 to 0.69; care quality OR 0.78, 95% CI 0.70 to 0.87; all adjusted for age, sex and ethnicity. Postadmission in-hospital care processes improved between epochs and were better for weekend admissions (vital signs with National Early Warning Score and timely specialist review). Preadmission processes in the community were suboptimal at weekends and deteriorated between epochs (fewer family doctor referrals, more patients with chronic disease or palliative care designation).Conclusions and implicationsHospital care quality of emergency medical admissions is not worse at weekends and has improved during implementation of the 7-day services policy. Causal pathways for the weekend effect may extend into the prehospital setting.

SUMMARY Background Bloodstream infections (BSIs) in patients in intensive care units (ICUs) are associated with increased morbidity, mortality and economic costs. Many BSIs are associated with central venous catheters (CVCs). The Infection in Critical Care Quality Improvement Programme (ICCQIP) was established to initiate surveillance of BSIs in English ICUs. Methods A web-based data capture system was launched on 1st May 2016 to collect all positive blood cultures (PBCs), patient-days and CVC-days. National Health Service (NHS) trusts in England were invited to participate in the surveillance programme. Data were linked to the antimicrobial resistance dataset maintained by Public Health England and to mortality data. Findings Between 1st May 2016 and 30th April 2017, 84 ICUs (72 adult ICUs, seven paediatric ICUs and five neonatal ICUs) based in 57 of 147 NHS trusts provided data. In total, 1474 PBCs were reported, with coagulase-negative staphylococci, Escherichia coli, Staphylococcus aureus and Enterococcus faecium being the most commonly reported organisms. The rates of BSI and ICU-associated CVC-BSI were 5.7, 1.5 and 1.3 per 1000 bed-days and 2.3, 1.0 and 1.5 per 1000 ICU-CVC-days in adult, paediatric and neonatal ICUs, respectively. There was wide variation in BSI and CVC-BSI rates within ICU types, particularly in adult ICUs (0–44.0 per 1000 bed-days and 0–18.3 per 1000 ICU-CVC-days). Conclusions While the overall rates of ICU-associated CVC-BSIs were lower than 2.5 per 1000 ICU-CVC-days across all age ranges, large differences were observed between ICUs, highlighting the importance of a national standardized surveillance system to identify opportunities for improvement. Data linkage provided clinically important information on resistance patterns and patient outcomes at no extra cost to participating trusts.

Conflicts of interest are a normal part of human social intercourse. They become problematic when there is a power differential between participants in the setting of relationships requiring a high degree of trust, as in healthcare. In this white paper we consider how these conflicts may be detected and mitigated. Following Medline search and reference chaining, we undertook a narrative review of the literature with iterative discussion. Conflicts of interest may be financial, professional or personal, and may operate at the level of the individual or the organisation. Unmanaged, they become a source of bias which places the interests of the professional or the organisation before those of the patient. Reported with increasing frequency, conflicts damage trust, harm patients, and defraud the health system. We make 15 recommendations for minimising conflicts of interest. Nationally funded open-access registries should be established to permit complete disclosure of financial, professional, and personal relationships with the potential for driving bias in research, clinical practice, or health management. Governance of disclosure should be the responsibility of employing organisations through annual staff appraisals, audited by national research integrity committees. Research fraud should incur suspension of the license to practice. Organisations should monitor staff perceptions of ethical climate to enhance awareness of staff behaviours and the potential for misconduct driven by academic pressures. Clear separation of advisory and voting roles is needed in best practice guideline panels. Professional societies and scientific journals should display conflict of interest policies for their own staff and officers as well as for speakers and authors. Undergraduates should not be exposed to pharmaceutical promotions masquerading as education. Undergraduate and postgraduate training programmes should include teaching about managing conflicts of interest and identifying research misconduct.

Much policy focus has been afforded to the role of “whistleblowers” in raising concerns about quality and safety of patient care in healthcare settings. However, most opportunities for personnel to identify and act on these concerns are likely to occur much further upstream, in the day-to-day mundane interactions of everyday work. Using qualitative data from over 900 h of ethnographic observation and 98 interviews across 19 English intensive care units (ICUs), we studied how personnel gave voice to concerns about patient safety or poor practice. We observed much low-level social control occurring as part of day-to-day functioning on the wards, with challenges and sanctions routinely used in an effort to prevent or address mistakes and norm violations. Pre-emptions were used to intervene when patients were at immediate risk, and included strategies such as gentle reminders, use of humour, and sharp words. Corrective interventions included education and evidence-based arguments, while sanctions that were applied when it appeared that a breach of safety had occurred included “quiet words”, bantering, public exposure or humiliation, scoldings and brutal reprimands. These forms of social control generally functioned effectively to maintain safe practice. But they were not consistently effective, and sometimes risked reinforcing norms and idiosyncratic behaviours that were not necessarily aligned with goals of patient safety and high-quality healthcare. Further, making challenges across professional boundaries or hierarchies was sometimes problematic. Our findings suggest that an emphasis on formal reporting or communication training as the solution to giving voice to safety concerns is simplistic; a more sophisticated understanding of social control is needed., Highlights • Most opportunities to raise safety concerns may arise in routine clinical work. • Informal strategies for raising concerns are multiple and often effective. • Use of strategies varies within and between professional groups and hierarchies. • Increased focus on effective use of informal strategies of social control is needed.

BACKGROUND: After a single-center trial and observational studies suggesting that early, goal-directed therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT. METHODS: We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding. After completion of the trials, we pooled data, excluding the protocol-based standard-therapy group from the ProCESS trial, and resolved residual differences. The primary outcome was 90-day mortality. Secondary outcomes included 1-year survival, organ support, and hospitalization costs. We tested for treatment-by-subgroup interactions for 16 patient characteristics and 6 care-delivery characteristics. RESULTS: We studied 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar for EGDT (462 of 1852 patients [24.9%]) and usual care (475 of 1871 patients [25.4%]); the adjusted odds ratio was 0.97 (95% confidence interval, 0.82 to 1.14; P=0.68). EGDT was associated with greater mean (±SD) use of intensive care (5.3±7.1 vs. 4.9±7.0 days, P=0.04) and cardiovascular support (1.9±3.7 vs. 1.6±2.9 days, P=0.01) than was usual care; other outcomes did not differ significantly, although average costs were higher with EGDT. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation. CONCLUSIONS: In this meta-analysis of individual patient data, EGDT did not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and hospital characteristics. (Funded by the National Institute of General Medical Sciences and others; PRISM ClinicalTrials.gov number, NCT02030158.)

Background Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Objectives The objectives were to assess whether or not the QI programme improves 90-day survival after emergency abdominal surgery; to assess effects on 180-day survival, hospital stay and hospital readmission; and to better understand these findings through an integrated process evaluation, ethnographic study and cost-effectiveness analysis. Design This was a stepped-wedge cluster randomised trial. Hospitals were organised into 15 geographical clusters, and commenced the QI programme in random order over 85 weeks. Analyses were performed on an intention-to-treat basis. The primary outcome was analysed using a mixed-effects parametric survival model, adjusting for time-related effects. Ethnographic and economics data were collected in six hospitals. The process evaluation included all hospitals. Setting The trial was set in acute surgical services of 93 NHS hospitals. Participants Patients aged ≥ 40 years who were undergoing emergency abdominal surgery were eligible. Intervention The intervention was a QI programme to implement an evidence-based care pathway. Main outcome measures The primary outcome measure was mortality within 90 days of surgery. Secondary outcomes were mortality within 180 days, length of hospital stay and hospital readmission within 180 days. The main economic measure was the quality-adjusted life-years. Data sources Data were obtained from the National Emergency Laparotomy Audit database; qualitative interviews and ethnographic observations; quality-of-life and NHS resource use data were collected via questionnaires. Results Of 15,873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 participants in the usual care group and 7374 in the QI group. The primary outcome occurred in 1393 participants in the usual care group (16%), compared with 1210 patients in the QI group (16%) [QI vs. usual care hazard ratio (HR) 1.11, 95% confidence interval (CI) 0.96 to 1.28]. No differences were found in mortality at 180 days or hospital readmission; there was a small increase in hospital stay in the QI group (HR for discharge 0.90, 95% CI 0.83 to 0.97). There were only modest improvements in care processes following QI implementation. The ethnographic study revealed good QI engagement, but limited time and resources to implement change, affecting which processes teams addressed, the rate of change and eventual success. In some sites, there were challenges around prioritising the intervention in busy environments and in obtaining senior engagement. The intervention is unlikely to be cost-effective at standard cost-effectiveness thresholds, but may be cost-effective over the lifetime horizon. Limitations Substantial delays were encountered in securing data access to national registries. Fewer patients than expected underwent surgery and the mortality rate was lower than anticipated. Conclusions There was no survival benefit from a QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. The modest impact of the intervention on process measures, despite good clinician engagement, may have been limited by the time and resources needed to improve patient care. Future work Future QI programmes must balance intervention complexity with the practical realities of NHS services to ensure that such programmes can be delivered with the resources available. Trial registration Current Controlled Trials ISRCTN80682973 and The Lancet protocol 13PRT/7655. Funding This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 7, No. 32. See the NIHR Journals Library website for further project information.

Background Patient and staff experiences provide important insights into care quality, but health systems have difficulty using these data to improve care. Little attention has been paid to understanding how patient experience feedback can act as a prompt to reflection in practice in the clinical setting. Objective We aimed to identify the ways in which different types of patient experience feedback act as a trigger or prompt for engagement in reflection in clinical practice in acute hospital settings and identify important considerations for enhancing the value of patient experience data for reflective learning. Methods We conducted an ethnographic study in eight acute care units in three NHS hospital trusts in England, including 140 hours of observations and 45 semi‐structured interviews with nursing, medical and managerial staff working in acute medical units and intensive care units. The data were analysed thematically. Findings We distinguished between formal patient experience data sources: data purposively collected and collated to capture the patient experience of care, generally at organizational level, including surveys, complaints and comments; and informal sources of feedback on the patient experience recognized by staff alongside the formal data. We also identified patient narratives as an ‘in between’ source of data. The impact of different types of patient feedback in triggering reflection primarily depended on the extent to which the feedback was experienced as personally relevant, meaningful and emotionally salient. Discussion Patient experience feedback is multi‐faceted, but our study suggests that all types of feedback could be harnessed more effectively to prompt reflection.

IntroductionPatient and staff experiences are strongly influenced by attitudes and behaviours, and provide important insights into care quality. Patient and staff feedback could be used more effectively to enhance behaviours and improve care through systematic integration with techniques for reflective learning. We aim to develop a reflective learning framework and toolkit for healthcare staff to improve patient, family and staff experience.Methods & analysisLocal project teams including staff and patients from the acute medical units (AMUs) and intensive care units (ICUs) of three National Health Service trusts will implement two experience surveys derived from existing instruments: a continuous patient and relative survey and an annual staff survey. Survey data will be supplemented by ethnographic interviews and observations in the workplace to evaluate barriers to and facilitators of reflective learning. Using facilitated iterative co-design, local project teams will supplement survey data with their experiences of healthcare to identify events, actions, activities and interventions which promote personal insight and empathy through reflective learning. Outputs will be collated by the central project team to develop a reflective learning framework and toolkit which will be fed back to the local groups for review, refinement and piloting. The development process will be mapped to a conceptual theory of reflective learning which combines psychological and pedagogical theories of learning, alongside theories of behaviour change based on capability, opportunity and motivation influencing behaviour. The output will be a locally-adaptable workplace-based toolkit providing guidance on using reflective learning to incorporate patient and staff experience in routine clinical activities.Ethics & disseminationThe PEARL project has received ethics approval from the London Brent Research Ethics Committee (REC Ref 16/LO/224). We propose a national cluster randomised step-wedge trial of the toolkit developed for large-scale evaluation of impact on patient outcomes.

Context Survival rates after severe injury are improving, but complication rates and outcomes are variable. Objective This cohort study addressed the lack of longitudinal data on the steroid response to major trauma and during recovery. Design We undertook a prospective, observational cohort study from time of injury to 6 months postinjury at a major UK trauma centre and a military rehabilitation unit, studying patients within 24 hours of major trauma (estimated New Injury Severity Score (NISS) > 15). Main outcome measures We measured adrenal and gonadal steroids in serum and 24-hour urine by mass spectrometry, assessed muscle loss by ultrasound and nitrogen excretion, and recorded clinical outcomes (ventilator days, length of hospital stay, opioid use, incidence of organ dysfunction, and sepsis); results were analyzed by generalized mixed-effect linear models. Findings We screened 996 multiple injured adults, approached 106, and recruited 95 eligible patients; 87 survived. We analyzed all male survivors Conclusion The catabolic response to severe injury was accompanied by acute and sustained androgen suppression. Whether androgen supplementation improves health outcomes after major trauma requires further investigation.

Background and objectivesA clinical trial in 93 National Health Service hospitals evaluated a quality improvement programme for emergency abdominal surgery, designed to improve mortality by improving the patient care pathway. Large variation was observed in implementation approaches, and the main trial result showed no mortality reduction. Our objective therefore was to evaluate whether trial participation led to care pathway implementation and to study the relationship between care pathway implementation and use of six recommended implementation strategies.MethodsWe performed a hospital-level time-series analysis using data from the Enhanced Peri-Operative Care for High-risk patients trial. Care pathway implementation was defined as achievement of >80% median reliability in 10 measured care processes. Mean monthly process performance was plotted on run charts. Process improvement was defined as an observed run chart signal, using probability-based ‘shift’ and ‘runs’ rules. A new median performance level was calculated after an observed signal.ResultsOf 93 participating hospitals, 80 provided sufficient data for analysis, generating 800 process measure charts from 20 305 patient admissions over 27 months. No hospital reliably implemented all 10 processes. Overall, only 279 of the 800 processes were improved (3 (2–5) per hospital) and 14/80 hospitals improved more than six processes. Mortality risk documented (57/80 (71%)), lactate measurement (42/80 (53%)) and cardiac output guided fluid therapy (32/80 (40%)) were most frequently improved. Consultant-led decision making (14/80 (18%)), consultant review before surgery (17/80 (21%)) and time to surgery (14/80 (18%)) were least frequently improved. In hospitals using ≥5 implementation strategies, 9/30 (30%) hospitals improved ≥6 care processes compared with 0/11 hospitals using ≤2 implementation strategies.ConclusionOnly a small number of hospitals improved more than half of the measured care processes, more often when at least five of six implementation strategies were used. In a longer term project, this understanding may have allowed us to adapt the intervention to be effective in more hospitals.

Background Patient experience is identified by NHS England as a key component in improving care quality. Although several indicators have been developed to measure patient experience and provide institutional benchmarks, comparatively little is known about the range of sources of information about patient experience within healthcare, or about how staff interpret and use experiential data to enhance knowledge and improve care. Aims To understand more clearly the breadth of patient experience data which is currently available and how it is being responded to by healthcare professionals to improve patient care. Methods We conducted ethnographic observations and interviews with a purposive sample of healthcare staff in Intensive Care Units and Acute Medical Units in three NHS hospital sites, involving over 100 hours of observations and 45 interviews. Results We identified a spectrum of types of information about patient experience, including written feedback from surveys and complaints; ‘bedside’ conversations or patients returning to speak about their experiences; and information received in a sensory way such as a hug, or gifts of chocolates or flowers. Some types of data were codified and used as intelligence within organisations to monitor and improve services, but much of the information about patient experience remained ‘below the line’: it was recognised by staff and used to shape their practice informally, but never entered the formal economy of data for improvement. Conclusions We suggest that, rather than trying to convert this ‘soft’ information into hard data that can be counted at an organisational level, there is value in recognising the different ways in which different types of information about the patient experience can be harnessed to drive improvement. Soft data can promote grass-roots improvement through reinforcing good practice and facilitating reflection.

ObjectiveTo determine whether the higher weekend admission mortality risk is attributable to increased severity of illness.DesignRetrospective analysis of 4 years weekend and weekday adult emergency admissions to a university teaching hospital in England.Outcome measures30-day postadmission weekend:weekday mortality ratios adjusted for severity of illness (baseline National Early Warning Score (NEWS)), routes of admission to hospital, transfer to the intensive care unit (ICU) and demographics.ResultsDespite similar emergency department daily attendance rates, fewer patients were admitted on weekends (mean admission rate 91/day vs 120/day) because of fewer general practitioner referrals. Weekend admissions were sicker than weekday (mean NEWS 1.8 vs 1.7, p=0.008), more likely to undergo transfer to ICU within 24 hours (4.2% vs 3.0%), spent longer in hospital (median 3 days vs 2 days) and less likely to experience same-day discharge (17.2% vs 21.9%) (all p values The crude 30-day postadmission mortality ratio for weekend admission (OR=1.13; 95% CI 1.08 to 1.19) was attenuated using standard adjustment (OR=1.11; 95% CI 1.05 to 1.17). In patients for whom NEWS values were available (90%), the crude OR (1.07; 95% CI 1.01 to 1.13) was not affected with standard adjustment. Adjustment using NEWS alone nullified the weekend effect (OR=1.02; 0.96–1.08).NEWS completion rates were higher on weekends (91.7%) than weekdays (89.5%). Missing NEWS was associated with direct transfer to intensive care bypassing electronic data capture. Missing NEWS in non-ICU weekend patients was associated with a higher mortality and fewer same-day discharges than weekdays.ConclusionsPatients admitted to hospital on weekends are sicker than those admitted on weekdays. The cause of the weekend effect may lie in community services.

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Background: Survival rates after severe injury are improving, but complication rates and outcomes are variable. This study addressed the lack of data on adrenal and gonadal steroid response during recovery from major trauma in relation to clinical outcomes, exploring potential targets for future intervention. Methods: We undertook a prospective, observational cohort study at a major UK trauma centre and a military rehabilitation unit, studying patients within 24 hours of major trauma (estimated New Injury Severity Score (NISS) >15) and at regular intervals for six months. We recorded clinical outcomes (ventilator days, length of hospital stay, organ dysfunction, sepsis), measured adrenal and gonadal steroids by tandem mass spectrometry, and assessed muscle loss by ultrasound and nitrogen excretion. Findings: We screened 996 multiply injured adults, approached 106, and recruited 95 eligible patients; 87 survived. We analysed all male survivors

Background The increased mortality risk associated with weekend admission to hospital (the ‘weekend effect’) has been reported across many health systems. More recently research has focused on causal mechanisms. Variations in the organisation and delivery of in-hospital care between weekends and weekdays have been identified, but this is not always to the detriment of weekend admissions, and the impact on mortality is uncertain. The insights of frontline staff and patients have been neglected. This article reports a qualitative study of patients and clinicians, to explore their views on quality and safety of care at weekends. Methods We conducted focus groups and interviews with clinicians and patients with experience of acute medical care, recruited from three UK hospital Trusts. We analysed the data using a thematic analysis approach, aided by the use of NVivo, to explore quality and safety of care at weekends. Results We held four focus groups and completed six in-depth interviews, with 19 clinicians and 12 patients. Four threats to quality and safety were identified as being more prominent at weekends, relating to i) the rescue and stabilisation of sick patients; ii) monitoring and responding to deterioration; iii) timely accurate management of the therapeutic pathway; iv) errors of omission and commission. Conclusions At weekends patients and staff are well aware of suboptimal staffing numbers, skill mix and access to resources at weekends, and identify that emergency admissions are prioritised over those already hospitalised. The consequences in terms of quality and safety and patient experience of care are undesirable. Our findings suggest the value of focusing on care processes and systems resilience over the weekends, and how these can be better supported, even in the limited resource environment that exists in many hospitals at weekends. Electronic supplementary material The online version of this article (10.1186/s12913-018-3833-z) contains supplementary material, which is available to authorized users.

Summary Background Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding National Institute for Health Research Health Services and Delivery Research Programme.

IntroductionIn 2013, a single-centre study reported the safe use of esmolol in patients with septic shock and tachycardia who required vasopressor therapy for more than 24 hours. Although not powered to detect a change in mortality, marked improvements were seen in survival (adjusted HR, 0.39; 95% CI, 0.26 to 0.59; pMethods and analysisSTRESS-L is a randomised, open-label, non-blinded clinical trial which is enrolling a total of 340 patients with septic shock as defined by Sepsis-3 consensus definition and a tachycardia (heart rate ≥95 beats per minute (bpm)) after vasopressor treatment of at least 24 hours. Standard randomisation (1:1 ratio) allocates patients to receive usual care (according to international standards) versus usual care and a continuous landiolol infusion to reduce the heart rate between 80 and 94 bpm. The primary endpoint is the mean Sequential Organ Failure Assessment score over 14 days from entry into the trial and while in intensive care unit. Results will inform current clinical practice guidelines.Ethics and disseminationThis trial has clinical trial authorisation from the UK competent authority, the Medicines and Healthcare products Regulatory Agency, and has been approved by the East of England-Essex Research Ethics Committee (reference: 17/EE/0368).The results of the trial will be reported first to trial collaborators. The main report will be drafted by the trial coordinating team, and the final version will be agreed by the Trial Steering Committee before submission for publication, on behalf of the collaboration.RegistrationThe trial is funded by the National Institute for Health Research Efficacy and Mechanism Evaluation (EME) (Project Number: EME-14/150/85) and registeredISRCTN12600919and EudraCT: 2017-001785-14.

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