Landiolol and Organ Failure in Patients With Septic Shock: The STRESS-L Randomized Clinical Trial.

Importance: Patients with septic shock undergo adrenergic stress, which affects cardiac, immune, inflammatory, and metabolic pathways. ß-Blockade may attenuate the adverse effects of catecholamine exposure and has been associated with reduced mortality. Objectives: To assess the efficacy and safety of landiolol in patients with tachycardia and established septic shock requiring prolonged (>24 hours) vasopressor support. Design, Setting, and Participants: An open-label, multicenter, randomized trial involving 126 adults (≥18 years) with tachycardia (heart rate ≥95/min) and established septic shock treated for at least 24 hours with continuous norepinephrine (≥0.1 µg/kg/min) in 40 UK National Health Service intensive care units. The trial ran from April 2018 to December 2021, with early termination in December 2021 due to a signal of possible harm. Intervention: Sixty-three patients were randomized to receive standard care and 63 to receive landiolol infusion. Main Outcomes and Measures: The primary outcome was the mean Sequential Organ Failure Assessment (SOFA) score from randomization through 14 days. Secondary outcomes included mortality at days 28 and 90 and the number of adverse events in each group. Results: The trial was stopped prematurely on the advice of the independent data monitoring committee because it was unlikely to demonstrate benefit and because of possible harm. Of a planned 340 participants, 126 (37%) were enrolled (mean age, 55.6 years [95% CI, 52.7 to 58.5 years]; 58.7% male). The mean (SD) SOFA score in the landiolol group was 8.8 (3.9) compared with 8.1 (3.2) in the standard care group (mean difference [MD], 0.75 [95% CI, -0.49 to 2.0]; P = .24). Mortality at day 28 after randomization in the landiolol group was 37.1% (23 of 62) and 25.4% (16 of 63) in the standard care group (absolute difference, 11.7% [95% CI, -4.4% to 27.8%]; P = .16). Mortality at day 90 after randomization was 43.5% (27 of 62) in the landiolol group and 28.6% (18 of 63) in the standard care group (absolute difference, 15% [95% CI, -1.7% to 31.6%]; P = .08). There were no differences in the number of patients having at least one adverse event. Conclusion and Relevance: Among patients with septic shock with tachycardia and treated with norepinephrine for more than 24 hours, an infusion of landiolol did not reduce organ failure measured by the SOFA score over 14 days from randomization. These results do not support the use of landiolol for managing tachycardia among patients treated with norepinephrine for established septic shock. Trial Registration: EU Clinical Trials Register Eudra CT: 2017-001785-14; isrctn.org Identifier: ISRCTN12600919.

Bayesian analysis of a systematic review of early versus late tracheostomy in ICU patients.

BACKGROUND: 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. METHODS: 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 (RR<1; SMD<0), a small benefit (number needed to treat, 200; SMD<-0.5), or modest benefit (number needed to treat, 100; SMD<-1). RESULTS: 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. CONCLUSIONS: Bayesian meta-analysis suggests a high probability that early tracheostomy compared with delayed tracheostomy has at least some benefit across all clinical outcomes considered.

Emergency care in hospitals is as good at the weekend as on weekdays.

The studyBion 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/.

Namilumab or infliximab compared with standard of care in hospitalised patients with COVID-19 (CATALYST): a randomised, multicentre, multi-arm, multistage, open-label, adaptive, phase 2, proof-of-concept trial.

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. FUNDING: Medical Research Council.

CATALYST trial protocol: a multicentre, open-label, phase II, multiarm trial for an early and accelerated evaluation of the potential treatments for COVID-19 in hospitalised adults.

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, ISRCTN40580903.

A qualitative study of organisational response to national quality standards for 7-day services in English hospitals.

BACKGROUND: National standards are commonly used as an improvement strategy in healthcare, but organisations may respond in diverse and sometimes negative ways to external quality demands. This paper describes how a sample of NHS hospital trusts in England responded to the introduction of national standards for 7-day services (7DS), from an organisational behaviour perspective. METHODS: We conducted 43 semi-structured interviews with executive/director level and clinical staff, in eight NHS trusts that varied in size, location, and levels of specialist staffing at weekends. We explored approaches to implementing standards locally, and the impact of organisational culture and local context on organisational response. RESULTS: Senior staff in the majority of trusts described a focus on hitting targets and achieving compliance with the standards. Compliance-based responses were associated with a hierarchical organisational culture and focus on external performance. In a minority of trusts senior staff described mobilising commitment-based strategies. In these trusts senior staff reframed the external standards in terms of organisational values, and used co-operative strategies for achieving change. Trusts that took a commitment-based approach tended to be described as having a developmental organisational culture and a history of higher performance across the board. Audit data on 7DS showed improvement against standards for most trusts, but commitment-focused trusts were less likely to demonstrate improvements on the 7DS audit. The ability of trusts to respond to external standards was limited when they were under pressure due to a history of overall poor performance or resource limitations. CONCLUSIONS: National standards and audit for service-level improvement generate different types of response in different local settings. Approaches to driving improvement nationally need to be accompanied by resources and tailored support for improvement, taking into account local context and organisational culture.

Study into the reversal of septic shock with landiolol (beta blockade): STRESS-L Study protocol for a randomised trial.

INTRODUCTION: In 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; p<0.001). Beta blockers are one of the most studied groups of drugs but their effect in septic shock is poorly understood; proposed mechanisms include not only the modulation of cardiac function but also immunomodulation. METHODS AND ANALYSIS: STRESS-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 DISSEMINATION: This 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. REGISTRATION: The trial is funded by the National Institute for Health Research Efficacy and Mechanism Evaluation (EME) (Project Number: EME-14/150/85) and registered ISRCTN12600919 and EudraCT: 2017-001785-14.

Changes in weekend and weekday care quality of emergency medical admissions to 20 hospitals in England during implementation of the 7-day services national health policy.

BACKGROUND: In 2013, the English National Health Service launched the policy of 7-day services to improve care quality and outcomes for weekend emergency admissions. AIMS: To 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. METHODS: Using 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. RESULTS: Seventy-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 IMPLICATIONS: Hospital 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.

Transplantation of discarded livers following viability testing with normothermic machine perfusion.

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.

Mapping the Steroid Response to Major Trauma From Injury to Recovery: A Prospective Cohort Study.

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 <50 years not treated with steroids (N = 60; median age 27 [interquartile range 24-31] years; median NISS 34 [29-44]). Urinary nitrogen excretion and muscle loss peaked after 1 and 6 weeks, respectively. Serum testosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate decreased immediately after trauma and took 2, 4, and more than 6 months, respectively, to recover; opioid treatment delayed dehydroepiandrosterone recovery in a dose-dependent fashion. Androgens and precursors correlated with SOFA score and probability of sepsis. 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.

Reflection in practice: How can patient experience feedback trigger staff reflection in hospital acute care settings?

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.

Patient experience and reflective learning (PEARL): a mixed methods protocol for staff insight development in acute and intensive care medicine in the UK.

INTRODUCTION: Patient 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 & ANALYSIS: Local 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 & DISSEMINATION: The 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.

Cost Effectiveness of Advanced Pharmacy Services Provided in the Community and Primary Care Settings: A Systematic Review.

BACKGROUND: 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. OBJECTIVE: The aim of this study was to review published economic evaluations of enhanced pharmacy services in the community and primary care settings. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Magnitude and modifiers of the weekend effect in hospital admissions: a systematic review and meta-analysis.

OBJECTIVE: To examine the magnitude of the weekend effect, defined as differences in patient outcomes between weekend and weekday hospital admissions, and factors influencing it. DESIGN: A systematic review incorporating Bayesian meta-analyses and meta-regression. DATA SOURCES: We searched seven databases including MEDLINE and EMBASE from January 2000 to April 2015, and updated the MEDLINE search up to November 2017. Eligibility criteria: primary research studies published in peer-reviewed journals of unselected admissions (not focusing on specific conditions) investigating the weekend effect on mortality, adverse events, length of hospital stay (LoS) or patient satisfaction. RESULTS: For the systematic review, we included 68 studies (70 articles) covering over 640 million admissions. Of these, two-thirds were conducted in the UK (n=24) or USA (n=22). The pooled odds ratio (OR) for weekend mortality effect across admission types was 1.16 (95% credible interval 1.10 to 1.23). The weekend effect appeared greater for elective (1.70, 1.08 to 2.52) than emergency (1.11, 1.06 to 1.16) or maternity (1.06, 0.89 to 1.29) admissions. Further examination of the literature shows that these estimates are influenced by methodological, clinical and service factors: at weekends, fewer patients are admitted to hospital, those who are admitted are more severely ill and there are differences in care pathways before and after admission. Evidence regarding the weekend effect on adverse events and LoS is weak and inconsistent, and that on patient satisfaction is sparse. The overall quality of evidence for inferring weekend/weekday difference in hospital care quality from the observed weekend effect was rated as 'very low' based on the Grading of Recommendations, Assessment, Development and Evaluations framework. CONCLUSIONS: The weekend effect is unlikely to have a single cause, or to be a reliable indicator of care quality at weekends. Further work should focus on underlying mechanisms and examine care processes in both hospital and community. PROSPERO REGISTRATION NUMBER: CRD42016036487.

Methodological challenges in European ethics approvals for a genetic epidemiology study in critically ill patients: the GenOSept experience.

BACKGROUND: During the set-up phase of an international study of genetic influences on outcomes from sepsis, we aimed to characterise potential differences in ethics approval processes and outcomes in participating European countries. METHODS: Between 2005 and 2007 of the FP6-funded international Genetics Of Sepsis and Septic Shock (GenOSept) project, we asked national coordinators to complete a structured survey of research ethic committee (REC) approval structures and processes in their countries, and linked these data to outcomes. Survey findings were reconfirmed or modified in 2017. RESULTS: Eighteen countries participated in the study, recruiting 2257 patients from 160 ICUs. National practices differed widely in terms of composition of RECs, procedures and duration of the ethics approval process. Eight (44.4%) countries used a single centralised process for approval, seven (38.9%) required approval by an ethics committee in each participating hospital, and three (16.7%) required both. Outcomes of the application process differed widely between countries because of differences in national legislation, and differed within countries because of interpretation of the ethics of conducting research in patients lacking capacity. The RECs in four countries had no lay representation. The median time from submission to final decision was 1.5 (interquartile range 1-7) months; in nine (50%) approval was received within 1 month; six took over 6 months, and in one 24 months; had all countries been able to match the most efficient approvals processes, an additional 74 months of country or institution-level recruitment would have been available. In three countries, rejection of the application by some local RECs resulted in loss of centres; and one country rejected the application outright. CONCLUSIONS: The potential benefits of the single application portal offered by the European Clinical Trials Regulation will not be realised without harmonisation of research ethics committee practices as well as national legislation.

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial.

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.