Additional file 1: of CONFIRM: a double-blind, placebo-controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial

SPIRIT Checklist. (DOC 121 kb

Increasing specialist intensity at weekends to improve outcomes for patients undergoing emergency hospital admission: the HiSLAC two-phase mixed-methods study

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’.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.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.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.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.Observational research, variable survey response rates and subjective assessments of care quality were compensated for by using a difference-in-difference analysis over time.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 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.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. Background Objectives Design Methods Results Limitations Conclusions Future work Funding</p

Additional file 1: of Catheter Ablation versus Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation (CASA-AF): study protocol for a randomised controlled trial

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Catheter Ablation Versus Thoracoscopic Surgical Ablation in Long Standing Persistent Atrial Fibrillation: CASA-AF Randomised Controlled Trial

AimsLong-standing persistent atrial fibrillation (LSPAF) is challenging to treat with suboptimal catheter ablation (CA) outcomes. Thoracoscopic surgical ablation (SA) has shown promising efficacy in atrial fibrillation (AF). This multicentre randomized controlled trial tested whether SA was superior to CA as the first interventional strategy in de novo LSPAF.Methods and resultsWe randomized 120 LSPAF patients to SA or CA. All patients underwent predetermined lesion sets and implantable loop recorder insertion. Primary outcome was single procedure freedom from AF/atrial tachycardia (AT) ≥30 s without anti-arrhythmic drugs at 12 months. Secondary outcomes included clinical success (≥75% reduction in AF/AT burden); procedure-related serious adverse events; changes in patients’ symptoms and quality-of-life scores; and cost-effectiveness. At 12 months, freedom from AF/AT was recorded in 26% (14/54) of patients in SA vs. 28% (17/60) in the CA group [OR 1.128, 95% CI (0.46–2.83), P = 0.83]. Reduction in AF/AT burden ≥75% was recorded in 67% (36/54) vs. 77% (46/60) [OR 1.13, 95% CI (0.67–4.08), P = 0.3] in SA and CA groups, respectively. Procedure-related serious adverse events within 30 days of intervention were reported in 15% (8/55) of patients in SA vs. 10% (6/60) in CA, P = 0.46. One death was reported after SA. Improvements in AF symptoms were greater following CA. Over 12 months, SA was more expensive and provided fewer quality-adjusted life-years (QALYs) compared with CA (0.78 vs. 0.85, P = 0.02).ConclusionSingle procedure thoracoscopic SA is not superior to CA in treating LSPAF. Catheter ablation provided greater improvements in symptoms and accrued significantly more QALYs during follow-up than SA.Clinical Trial RegistrationISRCTN18250790 and ClinicalTrials.gov: NCT02755688</div