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The rapidly developing fields of gene and cell therapy allow us a platform to repair or replace defective genes or introduce a missing gene. AAV and lentivirus are common viral vectors used in gene therapy to deliver a DNA payload to a tissue of interest. Recently, self-replicating RNA-based vaccines and therapies are also becoming increasingly popular for gene therapy after the success of SARS-CoV-2 vaccines. Cell therapy is the transplantation of human cells without or with ex vivo modification utilizing CAR-T and stem cell technology. Because PCR allows us to detect transgenes with high sensitivity, we can leverage this technology to quantify the efficacy of a therapy and long-term expression in vivo using both qPCR and RT-qPCR, respectively. PCR provides information that is used to justify first in human dose, toxicological evaluations, efficacy through PK/PD relationships, monitor persistency and shedding as well as biomarker and gene expression quantitation. As evaluation of safety endpoints is critical to drug development, PCR is imperative in the field of clinical pharmacology discovery.

Objectives: The aim of this study was to estimate the costs of primary hip and knee replacement in individuals with osteoarthritis up to 2 years post-surgery, compare costs before and after the surgery, and identify predictors of hospital costs. Methods: Patients aged 18 years or over with primary planned hip or knee replacements and osteoarthritis in England between 2008 and 2016 were identified from the National Joint Registry and linked with Hospital Episode Statistics data containing inpatient episodes. Primary care data linked with hospital outpatient records were also used to identify patients aged 18 years or over with primary hip or knee replacements between 2008 and 2016. All healthcare resource use was valued using 2016/17 costs and non-parametric censoring methods were used to estimate total 1-year and 2-year costs. Results: We identified 854,866 individuals undergoing hip or knee replacement. The mean censor-adjusted 1-year hospitalisation costs for hip and knee replacement were £7,827 (95% CI £7,813 to £7,842) and £7,805 (95% CI £7,790 to £7,818), respectively. Complications and revisions were associated with up to a three-fold increase in 1-year hospitalisation costs. The censor-adjusted 2-year costs were £9,258 (95 % CI £9,233 to £9,280) and £9,452 (95%CI £9,430 to £9,475) for hip and knee replacement. Adding primary and outpatient care, the mean total hip and knee replacement 2-year costs were £11,987 and £12,578, respectively. Conclusions: There are significant costs following joint replacement. Revisions and complications accounted for considerable costs and there is a significant incentive to identify best approaches to reduce these.

Aims Using bilateral internal thoracic arteries (BITAs) for coronary artery bypass grafting (CABG) has been suggested to improve survival compared to CABG using single internal thoracic arteries (SITAs) for patients with advanced coronary artery disease. We used data from the Arterial Revascularization Trial (ART) to assess long-term cost-effectiveness of BITA grafting compared to SITA grafting from an English health system perspective. Methods and results Resource use, healthcare costs, and quality-adjusted life years (QALYs) were assessed across 10 years of follow-up from an intention-to-treat perspective. Missing data were addressed using multiple imputation. Incremental cost-effectiveness ratios were calculated with uncertainty characterized using non-parametric bootstrapping. Results were extrapolated beyond 10 years using Gompertz functions for survival and linear models for total cost and utility. Total mean costs at 10 years of follow-up were £17 594 in the BITA arm and £16 462 in the SITA arm [mean difference £1133 95% confidence interval (CI) £239 to £2026, P = 0.015]. Total mean QALYs at 10 years were 6.54 in the BITA arm and 6.57 in the SITA arm (adjusted mean difference −0.01 95% CI −0.2 to 0.1, P = 0.883). At 10 years, BITA grafting had a 33% probability of being cost-effective compared to SITA, assuming a cost-effectiveness threshold of £20 000. Lifetime extrapolation increased the probability of BITA being cost-effective to 51%. Conclusions BITA grafting has significantly higher costs but similar quality-adjusted survival at 10 years compared to SITA grafting. Extrapolation suggests this could change over lifetime.

One approach to improve the utility of adeno-associated virus (AAV)-based gene therapy is to engineer the AAV capsid to (i) overcome poor transport through tissue barriers and (ii) redirect the broadly tropic AAV to disease-relevant cell types. Peptide- or protein-domain insertions into AAV surface loops can achieve both engineering goals by introducing a new interaction surface on the AAV capsid. However, we understand little about the impact of insertions on capsid structure and the extent to which engineered inserts depend on a specific capsid context to function. Here, we examine insert-capsid interactions for the engineered variant AAV9-PHP.B. The 7-amino-acid peptide insert in AAV9-PHP.B facilitates transport across the murine blood-brain barrier via binding to the receptor Ly6a. When transferred to AAV1, the engineered peptide does not bind Ly6a. Comparative structural analysis of AAV1-PHP.B and AAV9-PHP.B revealed that the inserted 7-amino-acid loop is highly flexible and has remarkably little impact on the surrounding capsid conformation. Our work demonstrates that Ly6a binding requires interactions with both the PHP.B peptide and specific residues from the AAV9 HVR VIII region. An AAV1-based vector that incorporates a larger region of AAV9-PHP.B-including the 7-amino-acid loop and adjacent HVR VIII amino acids-can bind to Ly6a and localize to brain tissue. However, unlike AAV9-PHP.B, this AAV1-based vector does not penetrate the blood-brain barrier. Here we discuss the implications for AAV capsid engineering and the transfer of engineered activities between serotypes. IMPORTANCE Targeting AAV vectors to specific cellular receptors is a promising strategy for enhancing expression in target cells or tissues while reducing off-target transgene expression. The AAV9-PHP.B/Ly6a interaction provides a model system with a robust biological readout that can be interrogated to better understand the biology of AAV vectors' interactions with target receptors. In this work, we analyzed the sequence and structural features required to successfully transfer the Ly6a receptor-binding epitope from AAV9-PHP.B to another capsid of clinical interest, AAV1. We found that AAV1- and AAV9-based vectors targeted to the same receptor exhibited different brain-transduction profiles. Our work suggests that, in addition to attachment-receptor binding, the capsid context in which this binding occurs is important for a vector's performance.

Purpose: Preventing CLABSI events in the dialysis inpatient population represents significant challenges. Bacteremia associated with lines or grafts are common health-associated infections that lead to adverse patient outcomes. Dialysis patients represent a much higher infection risk due to health frequency needs, more frequent hospitalizations, multiple comorbidity issues, fistula functionality, and multiple attempts for line access leading to additional complications, costs, morbidity, and mortality. Methods: An observational study was conducted including central line device days, CLABSI events, and possible confounding variables in admitted dialysis patients. All CLABSI data were identified according to the Centers for Disease Control and Prevention's National Healthcare Safety Network's definitions for CLABSIs. The intervention involved the removal of 70% alcohol swabs and alcohol hub disinfecting caps, then replacing with swabs containing 3.15% chlorhexidine gluconate/70% alcohol for central line hub disinfection and vascular graft access skin disinfection. Results: The 5-year preintervention period (2008–2012) involved 7568 central line days, 11 CLABSI events, and a 1.45 per 1000 device day rate. The 6-month trial period involved 1559 central line days and no CLABSI events. The 5-year postimplementation period (2013–2017) involved 9787 central line days, 5 CLABSI events, and a 0.51 per 1000 device day rate. The postimplementation period represented a statistically significant (P value=0.0493) reduction with 65% fewer CLABSI events compared with the preimplementation period. Limitations: A limitation was variations in scrub time and dry time during central venous catheter hub access. While we were comparing 2 products, behavioral practices using these 2 products were possible influencers and represent a possible confounding variable. Conclusions: This study found that using alcohol with chlorhexidine gluconate prior to accessing central line hubs and vascular grafts allows for reduction in CLABSI events and sustains statistically significant lower CLABSI rates in the inpatient dialysis population. HIGHLIGHTS Using alcohol with chlorhexidine gluconate (CHG) before accessing central line hubs helps reduce central line-associated bloodstream infection (CLABSI) events Using alcohol with CHG before accessing vascular grafts helps reduce CLABSI events A statistically significant reduction (65%) in CLABSI events occurred after use. Statistically significant lower CLABSI rates are sustainable with use of alcohol with CHG

AIMS It has been recommended that the percentage of high-grade (HG) Gleason patterns 4 and 5 should be quantified in prostate cancer. However, this has not been assessed in a cohort using prostate cancer death as an outcome, and there is debate as to whether the biopsy with the 'worst' percentage of HG disease or an 'overall' percentage of HG disease should be reported. Such data may assist in active surveillance decisions. METHODS AND RESULTS Men with clinically localised prostate cancer diagnosed by needle biopsy from 1990 to 2003 were included. The endpoint was prostate cancer death. Clinical variables included Gleason score (GS), prostate-specific antigen level, age, clinical stage, and disease extent. Deaths were divided into those from prostate cancer and those from other causes, according to World Health Organization criteria. Nine hundred and eighty-eight biopsy cases were centrally reviewed according to criteria agreed at the Chicago International Society of Urological Pathology conference in 2014. Cores were given individual GSs and Grade Groups (GGs), and a percentage of each grade was given for each core. Both the worst percentage of HG disease seen in a biopsy series and overall percentage of HG disease were calculated. The overall percentage of HG disease was highly significant, with a hazard ratio of 4.45 for the interquartile range (95% confidence interval 3.30-6.01, P

ObjectivesTo assess cost-effectiveness of enhanced recovery pathways following total hip and knee arthroplasties. Secondary objectives were to report on quality of studies and identify research gaps for future work.DesignSystematic review of cost–utility analyses.Data sourcesOvid MEDLINE, Embase, the National Health Service Economic Evaluations Database and EconLit, January 2000 to August 2019.Eligibility criteriaEnglish-language peer-reviewed cost–utility analyses of enhanced recovery pathways, or components of one, compared with usual care, in patients having total hip or knee arthroplasties for osteoarthritis.Data extraction and synthesisData extracted by three reviewers with disagreements resolved by a fourth. Study quality assessed using the Consensus on Health Economic Criteria list, the International Society for Pharmacoeconomics and Outcomes Research and Assessment of the Validation Status of Health-Economic decision models tools; for trial-based studies the Cochrane Collaboration’s tool to assess risk of bias. No quantitative synthesis was undertaken.ResultsWe identified 17 studies: five trial-based and 12 model-based studies. Two analyses evaluated entire enhanced recovery pathways and reported them to be cost-effective compared with usual care. Ten pathway components were more effective and cost-saving compared with usual care, three were cost-effective, and two were not cost-effective. We had concerns around risk of bias for all included studies, particularly regarding the short time horizon of the trials and lack of reporting of model validation.ConclusionsConsistent results supported enhanced recovery pathways as a whole, prophylactic systemic antibiotics, antibiotic-impregnated cement and conventional ventilation for infection prevention. No other interventions were subject of more than one study. We found ample scope for future cost-effectiveness studies, particularly analyses of entire recovery pathways and comparison of incremental changes within pathways. A key limitation is that standard practices have changed over the period covered by the included studies.PROSPERO registration numberCRD42017059473.

ObjectivesEffects of the UK Department of Health’s national Enhanced Recovery After Surgery (ERAS) Programme on outcomes after primary hip replacement.DesignNatural experimental study using interrupted time series to assess the changes in trends before, during and after ERAS implementation (April 2009 to March 2011).SettingSurgeries in the UK National Joint Registry were linked with Hospital Episode Statistics containing inpatient episodes from National Health Service trusts in England and patient reported outcome measures.ParticipantsPatients aged ≥18 years from 2008 to 2016.Main outcome measuresRegression coefficients of monthly means of length of hospital stay, bed day cost, change in Oxford Hip Scores (OHS) 6 months post-surgery, complications 6 months post-surgery and revision rates 5 years post-surgery.Results438 921 primary hip replacements were identified. Hospital stays shortened from 5.6 days in April 2008 to 3.6 in December 2016. There were also improvements in bed day costs (£7573 in April 2008 to £5239 in December 2016), positive change in self-reported OHS from baseline to 6 months post-surgery (17.7 points in April 2008 to 22.9 points in December 2016), complication rates (4.1% in April 2008 to 1.7% March 2016) and 5 year revision rates (5.9 per 1000 implant-years (95% CI 4.8 to 7.2) in April 2008 to 2.9 (95% CI 2.2 to 3.9) in December 2011). The positive trends in all outcomes started before ERAS was implemented and continued during and after the programme.ConclusionsPatient outcomes after hip replacement have improved over the last decade. A national ERAS programme maintained this improvement but did not alter the existing rate of change.

Background There is limited evidence concerning the effectiveness of enhanced recovery programmes in hip and knee replacement surgery, particularly when applied nationwide across a health-care system. Objectives To determine the effect of hospital organisation, surgical factors and the enhanced recovery after surgery pathway on patient outcomes and NHS costs of hip and knee replacement. Design (1) Statistical analysis of national linked data to explore geographical variations in patient outcomes of surgery. (2) A natural experimental study to determine clinical effectiveness of enhanced recovery after surgery. (3) A qualitative study to identify barriers to, and facilitators of, change. (4) Health economics analysis to establish NHS costs and cost-effectiveness. Setting Data from the National Joint Registry, linked to English Hospital Episode Statistics and patient-reported outcome measures in both the geographical variation and natural experiment studies, together with the economic evaluation. The ethnographic study took place in four hospitals in a region of England. Participants Qualitative study – 38 health professionals working in hip and knee replacement services in secondary care and 37 patients receiving hip or knee replacement. Interventions Natural experiment – implementation of enhanced recovery after surgery at each hospital between 2009 and 2011. Enhanced recovery after surgery is a complex intervention focusing on several areas of patients’ care pathways through surgery: preoperatively (patient is in best possible condition for surgery), perioperatively (patient has best possible management during and after operation) and postoperatively (patient experiences best rehabilitation). Main outcome measures Patient-reported pain and function (Oxford Hip Score/Oxford Knee Score); 6-month complications; length of stay; bed-day costs; and revision surgery within 5 years. Results Geographical study – there are potentially unwarranted variations in patient outcomes of hip and knee replacement surgery. This variation cannot be explained by differences in patients, case mix, surgical or hospital organisational factors. Qualitative – successful implementation depends on empowering patients to work towards their recovery, providing post-discharge support and promoting successful multidisciplinary team working. Care processes were negotiated between patients and health-care professionals. ‘Good care’ remains an aspiration, particularly in the post-discharge period. Natural experiment – length of stay has declined substantially, pain and function have improved, revision rates are in decline and complication rates remain stable. The introduction of a national enhanced recovery after surgery programme maintained improvement, but did not alter the rate of change already under way. Health economics – costs are high in the year of joint replacement and remain higher in the subsequent year after surgery. There is a strong economic incentive to identify ways of reducing revisions and complications following joint replacement. Published cost-effectiveness evidence supports enhanced recovery pathways as a whole. Limitations Short duration of follow-up data prior to enhanced recovery after surgery implementation and missing data, particularly for hospital organisation factors. Conclusion No evidence was found to show that enhanced recovery after surgery had a substantial impact on longer-term downwards trends in costs and length of stay. Trends of improving outcomes were seen across all age groups, in those with and without comorbidity, and had begun prior to the formal enhanced recovery after surgery roll-out. Reductions in length of stay have been achieved without adversely affecting patient outcomes, yet, substantial variation remains in outcomes between hospital trusts. Future work There is still work to be done to reduce and understand unwarranted variations in outcome between individual hospitals. Study registration This study is registered as PROSPERO CRD42017059473. 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. 8, No. 4. See the NIHR Journals Library website for further project information.

BackgroundThe use of bilateral internal thoracic arteries (BITA) for coronary artery bypass grafting (CABG) may improve survival compared with CABG using single internal thoracic arteries (SITA). We assessed the long-term costs of BITA compared with SITA.MethodsBetween June 2004 and December 2007, 3102 patients from 28 hospitals in seven countries were randomised to CABG surgery using BITA (n=1548) or SITA (n=1554). Detailed resource use data were collected from the initial hospital episode and annually up to 5 years. The associated costs of this resource use were assessed from a UK perspective with 5 year totals calculated for each trial arm and pre-selected patient subgroups.ResultsTotal costs increased by approximately £1000 annually in each arm, with no significant annual difference between trial arms. Cumulative costs per patient at 5-year follow-up remained significantly higher in the BITA group (£18 629) compared with the SITA group (£17 480; mean cost difference £1149, 95% CI £330 to £1968, p=0.006) due to the higher costs of the initial procedure. There were no significant differences between the trial arms in the cost associated with healthcare contacts, medication use or serious adverse events.ConclusionsHigher index costs for BITA were still present at 5-year follow-up mainly driven by the higher initial cost with no subsequent difference emerging between 1 year and 5 years of follow-up. The overall cost-effectiveness of the two procedures, to be assessed at the primary endpoint of the 10-year follow-up, will depend on composite differences in costs and quality-adjusted survival.Trial registration numberISRCTN46552265

Objective We aimed to test whether a national Enhanced Recovery After Surgery (ERAS) Programme in total knee replacement (TKR) had an impact on patient outcomes. Design Natural-experiment (April 2008–December 2016). Interrupted time-series regression assessed impact on trends before-during-after ERAS implementation. Setting Primary operations from the UK National Joint Registry (NJR) were linked with Hospital Episode Statistics (HES) data which contains inpatient episodes undertaken in National Health Service (NHS) trusts in England, and Patient Reported Outcome Measures (PROMs). Participants Patients undergoing primary planned TKR aged ≥18 years. Intervention ERAS implementation (April 2009–March 2011). Outcomes Regression coefficients of monthly means of Length of stay (LOS), bed day costs, change in Oxford knee scores (OKS) 6-months after surgery, complications (at 6 months), and rates of revision surgeries (at 5 years). Results 486,579 primary TKRs were identified. Overall LOS and bed-day costs decreased from 5.8 days to 3.7 and from £7607 to £5276, from April 2008 to December 2016. Oxford knee score (OKS) change improved from 15.1 points in April 2008 to 17.1 points in December 2016. Complications decreased from 4.1 % in April 2008 to 1.7 % in March 2016. 5-year revision rates remained stable at 4.8 per 1000 implants years in April 2008 and December 2011. After ERAS, declining trends in LOS and bed costs slowed down; OKS improved, complications remained stable, and revisions slightly increased. Conclusions Different secular trends in outcomes for patients having TKR have been observed over the last decade. Although patient outcomes are better than a decade ago ERAS did not improve them at national level.

IntroductionHip and knee replacement represents a significant burden to the UK healthcare system. ‘Enhanced recovery’ pathways have been introduced in the National Health Service (NHS) for patients undergoing hip and knee replacement, with the aim of improving outcomes and timely recovery after surgery. To support policymaking, there is a need to evaluate the cost-effectiveness of enhanced recovery pathways across jurisdictions. Our aim is to systematically summarise the published cost-effectiveness evidence on enhanced recovery in hip and knee replacement, both as a whole and for each of the various components of enhanced recovery pathways.Methods and analysisA systematic review will be conducted using MEDLINE, EMBASE, Econlit and the National Health Service Economic Evaluations Database. Separate search strategies were developed for each database including terms relating to hip and knee replacement/arthroplasty, economic evaluations, decision modelling and quality of life measures.We will extract peer-reviewed studies published between 2000 and 2017 reporting economic evaluations of preoperative, perioperative or postoperative enhanced recovery interventions within hip or knee replacement. Economic evaluations alongside cohort studies or based on decision models will be included. Only studies with patients undergoing elective replacement surgery of the hip or knee will be included. Data will be extracted using a predefined pro forma following best practice guidelines for economic evaluation, decision modelling and model validation.Our primary outcome will be the cost-effectiveness of enhanced recovery (entire pathway and individual components) in terms of incremental cost per quality-adjusted life year. A narrative synthesis of all studies will be presented, focussing on cost-effectiveness results, study design, quality and validation status.Ethics and disseminationThis systematic review is exempted from ethics approval because the work is carried out on published documents. The results of the review will be disseminated in a peer-reviewed academic journal and at conferences.PROSPERO registration numberCRD42017059473.

ObjectivesThrough the National Health Service (NHS) Bowel Cancer Screening Programme (BCSP), men and women in England aged between 60 and 74 years are invited for colorectal cancer (CRC) screening every 2 years using the guaiac faecal occult blood test (gFOBT). The aim of this analysis was to estimate the cost–utility of the faecal immunochemical test for haemoglobin (FIT) compared with gFOBT for a cohort beginning screening aged 60 years at a range of FIT positivity thresholds.DesignWe constructed a cohort-based Markov state transition model of CRC disease progression and screening. Screening uptake, detection, adverse event, mortality and cost data were taken from BCSP data and national sources, including a recent large pilot study of FIT screening in the BCSP.ResultsOur results suggest that FIT is cost-effective compared with gFOBT at all thresholds, resulting in cost savings and quality-adjusted life years (QALYs) gained over a lifetime time horizon. FIT was cost-saving (pConclusionsThis is the first published economic analysis of FIT screening in England using data directly comparing FIT with gFOBT in the NHS BSCP. These results for a cohort starting screening aged 60 years suggest that FIT is highly cost-effective at all thresholds considered. Further modelling is needed to estimate economic outcomes for screening across all age cohorts simultaneously.

Aims A trial-based comparison of the use of resources, costs and quality of life outcomes of arthroscopic and open surgical management for rotator cuff tears in the United Kingdom NHS was performed using data from the United Kingdom Rotator Cuff Study (UKUFF) randomised controlled trial. Patients and Methods Using data from 273 patients, healthcare-related use of resources, costs and quality-adjusted life years (QALYs) were estimated at 12 months and 24 months after surgery on an intention-to-treat basis with adjustment for covariates. Uncertainty about the incremental cost-effectiveness ratio for arthroscopic versus open management at 24 months of follow-up was incorporated using bootstrapping. Multiple imputation methods were used to deal with missing data. Results There were no significant differences between the arthroscopic and open groups in terms of total mean use and cost of resources or QALYs at any time post-operatively. Open management dominated arthroscopic management in 59.8% of bootstrapped cost and effect differences. The probability that arthroscopic management was cost-effective compared with open management at a willingness-to-pay threshold of £20 000 per QALY gained was 20.9%. Conclusion There was no significant overall difference in the use or cost of resources or quality of life between arthroscopic and open management in the trial. There was uncertainty about which strategy was most cost-effective. Cite this article: Bone Joint J 2016;98-B:1648–55.

The purpose of this study was to examine the level of agreement between a portable SpO2 device and the clinical gold standard SaO2 in intermediate care patients.

BackgroundUncertainty exists regarding the best management of patients with degenerative tears of the rotator cuff.ObjectiveTo evaluate the clinical effectiveness and cost-effectiveness of arthroscopic and open rotator cuff repair in patients aged ≥ 50 years with degenerative rotator cuff tendon tears.DesignTwo parallel-group randomised controlled trial.SettingNineteen teaching and district general hospitals in the UK.ParticipantsPatients (n = 273) aged ≥ 50 years with degenerative rotator cuff tendon tears.InterventionsArthroscopic surgery and open rotator cuff repair, with surgeons using their usual and preferred method of arthroscopic or open repair. Follow-up was by telephone questionnaire at 2 and 8 weeks after surgery and by postal questionnaire at 8, 12 and 24 months after randomisation.Main outcome measuresThe Oxford Shoulder Score (OSS) at 24 months was the primary outcome measure. Magnetic resonance imaging evaluation of the shoulder was made at 12 months after surgery to assess the integrity of the repair.ResultsThe mean OSS improved from 26.3 [standard deviation (SD) 8.2] at baseline to 41.7 (SD 7.9) at 24 months for arthroscopic surgery and from 25.0 (SD 8.0) at baseline to 41.5 (SD 7.9) at 24 months for open surgery. When effect sizes are shown for the intervention, a negative sign indicates that an open procedure is favoured. For the intention-to-treat analysis, there was no statistical difference between the groups, the difference in OSS score at 24 months was –0.76 [95% confidence interval (CI) –2.75 to 1.22;p = 0.452] and the CI excluded the predetermined clinically important difference in the OSS of 3 points. There was also no statistical difference when the groups were compared per protocol (difference in OSS score –0.46, 95% CI –5.30 to 4.39;p = 0.854). The questionnaire response rate was > 86%. At 8 months, 77% of participants reported that shoulder problems were much or slightly better, and at 24 months this increased to 85%. There were no significant differences in mean cost between the arthroscopic group and the open repair group for any of the component resource-use categories, nor for the total follow-up costs at 24 months. The overall treatment cost at 2 years was £2567 (SD £176) for arthroscopic surgery and £2699 (SD £149) for open surgery, according to intention-to-treat analysis. For the per-protocol analysis there was a significant difference in total initial procedure-related costs between the arthroscopic group and the open repair group, with arthroscopic repair being more costly by £371 (95% CI £135 to £607). Total quality-adjusted life-years accrued at 24 months averaged 1.34 (SD 0.05) in the arthroscopic repair group and 1.35 (SD 0.05) in the open repair group, a non-significant difference of 0.01 (95% CI –0.11 to 0.10). The rate of re-tear was not significantly different across the randomised groups (46.4% and 38.6% for arthroscopic and open surgery, respectively). The participants with tears that were impossible to repair had the lowest OSSs, the participants with re-tears had slightly higher OSSs and the participants with healed repairs had the most improved OSSs. These findings were the same when analysed per protocol.ConclusionIn patients aged > 50 years with a degenerative rotator cuff tear there is no difference in clinical effectiveness or cost-effectiveness between open repair and arthroscopic repair at 2 years for the primary outcome (OSS) and all other prespecified secondary outcomes. Future work should explore new methods to improve tendon healing and reduce the high rate of re-tears observed in this trial.Trial registrationCurrent Controlled Trials ISRCTN97804283.FundingThis project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 19, No. 80. See the NIHR Journals Library website for further project information.