Biomarker Driven Antifungal Stewardship (BioDriveAFS) in acute leukaemia-a multi-centre randomised controlled trial to assess clinical and cost effectiveness: a study protocol for a randomised controlled trial.

BACKGROUND: Acute leukaemias (AL) are life-threatening blood cancers that can be potentially cured with treatment involving myelosuppressive, multiagent, intensive chemotherapy (IC). However, such treatment is associated with a risk of serious infection, in particular invasive fungal infection (IFI) associated with prolonged neutropenia. Current practice guidelines recommend primary antifungal (AF) prophylaxis to be administered to high-risk patients to reduce IFI incidence. AFs are also used empirically to manage prolonged neutropenic fever. Current strategies lead to substantial overuse of AFs. Galactomannan (GM) and ß-D-glucan (BG) biomarkers are also used to diagnose IFI. Combining both biomarkers may enhance the predictability of IFI compared to administering each test alone. Currently, no large-scale randomised controlled trial (RCT) has directly compared a biomarker-based diagnostic screening strategy without AF prophylaxis to AF prophylaxis (without systematic biomarker testing). METHODS: BioDriveAFS is a multicentre, parallel, two-arm RCT of 404 participants from UK NHS Haematology departments. Participants will be allocated on a 1:1 basis to receive either a biomarker-based antifungal stewardship (AFS) strategy, or a prophylactic AF strategy, which includes existing standard of care (SoC). The co-primary outcomes will be AF exposure in the 12-month post randomisation and the patient-reported EQ-5D-5L measured at 12-month post randomisation. Secondary outcomes will include total AF exposure, probable/proven IFI, survival (all-cause mortality and IFI mortality), IFI treatment outcome, AF-associated adverse effects/events/complications, resource use, episodes of neutropenic fever requiring hospital admission or outpatient management, AF resistance in fungi (non-invasive and invasive) and a Desirability of Outcome Ranking. The trial will have an internal pilot phase during the first 9 months. A mixed methods process evaluation will be integrated in parallel to the internal pilot phase and full trial, aiming to robustly assess how the intervention is delivered. Cost-effectiveness analysis will also be performed. DISCUSSION: The BioDriveAFS trial aims to further the knowledge of strategies that will safely optimise AF use through comparison of the clinical and cost-effectiveness of a biomarker-led diagnostic strategy versus prophylactic AF to prevent and manage IFI within acute leukaemia. The evidence generated from the study will help inform global clinical practice and approaches within antifungal stewardship. TRIAL REGISTRATION: ISRCTN11633399. Registered 24/06/2022.

Smoking, nicotine and pregnancy 2 (SNAP2) trial: protocol for a randomised controlled trial of an intervention to improve adherence to nicotine replacement therapy during pregnancy.

INTRODUCTION: Smoking during pregnancy is harmful to unborn babies, infants and women. Nicotine replacement therapy (NRT) is offered as the usual stop-smoking support in the UK. However, this is often used in insufficient doses, intermittently or for too short a time to be effective. This randomised controlled trial (RCT) explores whether a bespoke intervention, delivered in pregnancy, improves adherence to NRT and is effective and cost-effective for promoting smoking cessation. METHODS AND ANALYSIS: A two-arm parallel-group RCT was conducted for pregnant women aged ≥16 years and who smoke ≥1 daily cigarette (pre-pregnancy smoked ≥5) and who agree to use NRT in an attempt to quit. Recruitment is from antenatal care settings and via social media adverts. Participants are randomised using blocked randomisation with varying block sizes, stratified by gestational age (<14 or ≥14 weeks) to receive: (1) usual care (UC) for stop smoking support or (2) UC plus an intervention to increase adherence to NRT, called 'Baby, Me and NRT' (BMN), comprising adherence counselling, automated tailored text messages, a leaflet and website. The primary outcome is biochemically validated smoking abstinence at or around childbirth, measured from 36 weeks gestation. Secondary outcomes include NRT adherence, other smoking measures and birth outcomes. Questionnaires collect follow-up data augmented by medical record information. We anticipate quit rates of 10% and 16% in the control and intervention groups, respectively (risk ratio=1.6). By recruiting 1320 participants, the trial should have 90% power (alpha=5%) to detect this intervention effect. An economic analysis will use the Economics of Smoking in Pregnancy model to determine cost-effectiveness. ETHICS AND DISSEMINATION: Ethics approval was granted by Bloomsbury National Health Service's Research Ethics Committee (21/LO/0123). Written informed consent will be obtained from all participants. Findings will be disseminated to the public, funders, relevant practice/policy representatives, researchers and participants. TRIAL REGISTRATION NUMBER: ISRCTN16830506. PROTOCOL VERSION: 5.0, 10 Oct 2023.

Surgical versus non-surgical management of lateral compression type-1 pelvic fracture in adults 60 years and older: the L1FE RCT.

Background: Lateral compression type-1 pelvic fractures are a common fragility fracture in older adults. Patients who do not mobilise due to ongoing pain are at greater risk of immobility-related complications. Standard treatment in the United Kingdom is provision of pain relief and early mobilisation, unlike fragility hip fractures, which are usually treated surgically based on evidence that early surgery is associated with better outcomes. Currently there is no evidence on whether patients with lateral compression type-1 fragility fractures would have a better recovery with surgery than non-surgical management. Objectives: To assess the clinical and cost effectiveness of surgical fixation with internal fixation device compared to non-surgical management of lateral compression type-1 fragility fractures in older adults. Design: Pragmatic, randomised controlled superiority trial, with 12-month internal pilot; target sample size was 600 participants. Participants were randomised between surgical and non-surgical management (1 : 1 allocation ratio). An economic evaluation was planned. Setting: UK Major Trauma Centres. Participants: Patients aged 60 years or older with a lateral compression type-1 pelvic fracture, arising from a low-energy fall and unable to mobilise independently to a distance of 3 m and back due to pelvic pain 72 hours after injury. Interventions: Internal fixation device surgical fixation and non-surgical management. Participants, surgeons and outcome assessors were not blinded to treatment allocation. Main outcome measures: Primary outcome - average patient health-related quality of life, over 6 months, assessed by the EuroQol-5 Dimensions, five-level version utility score. Secondary outcomes (over the 6 months following injury) - self-rated health, physical function, mental health, pain, delirium, displacement of pelvis, mortality, complications and adverse events, and resource use data for the economic evaluation. Results: The trial closed early, at the end of the internal pilot, due to low recruitment. The internal pilot was undertaken in two separate phases because of a pause in recruitment due to the coronavirus disease 2019 pandemic. The planned statistical and health economic analyses were not conducted. Outcome data were summarised descriptively. Eleven sites opened for recruitment for a combined total of 92 months. Three-hundred and sixteen patients were assessed for eligibility, of whom 43 were eligible (13.6%). The main reason for ineligibility was that the patient was able to mobilise independently to 3 m and back (n = 161). Of the 43 eligible participants, 36 (83.7%) were approached for consent, of whom 11 (30.6%) provided consent. The most common reason for eligible patients not consenting to take part was that they were unwilling to be randomised to a treatment (n = 10). There were 11 participants, 5 randomised to surgical management with internal fixation device and 6 to non-surgical management. The average age of participants was 83.0 years (interquartile range 76.0, 89.0) and the EuroQol-5 Dimensions, five-level version utility score at 6 months post randomisation (n = 8) was 0.32 (standard deviation 0.37). A limitation of the trial was that study objectives were not addressed due to poor recruitment. Conclusions: It was not feasible to recruit to this trial in the current context. Further research to understand the treatment and recovery pathways of this group of patients, along with their outcomes, would be needed prior to undertaking a future trial. Future work: Exploration of equipoise across different healthcare professional groups. Investigate longer-term patient outcomes. Trial registration: This trial is registered as ISRCTN16478561. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/167/57) and is published in full in Health Technology Assessment; Vol. 28, No. 15. See the NIHR Funding and Awards website for further award information.

When older adults with weak bones fall onto their side, they can fracture the pelvis in a certain way known as a 'lateral compression type-1 fracture'; this summary will use 'pelvic fracture'. Pelvic fractures can heal without surgery; patients are offered pain relief and encouraged to move as much as they can after the injury. Pelvic fractures can be painful, and some people are not able to get up and walk for weeks. These fractures can cause health problems such as chest infections, urinary tract infections, pressure sores and blood clots. To avoid these problems, we are trying to find treatments to help people recover sooner. Pelvic surgeons think patients may benefit from surgery with an internal fixation device (a bar and screws) to stabilise the pelvis; however, there can be risks and complications with any surgery. This study aimed to find out which treatment is better for patients and better value for money for the National Health Service. This required 600 people aged over 60, in hospital with a pelvic fracture and having difficulty walking to take part. Three hundred would receive surgery and 300 would receive non-surgical treatment. Over 6 months, participants would complete questionnaires, a walking assessment and have X-rays to check healing. The trial had a 12-month run-in period to see if enough people would take part. The trial closed early as we were unable to recruit sufficient people into the study. Fewer older patients with pelvic fractures were identified than expected, 51% were able to walk after a few days and therefore were not eligible to be included in the study. Of the patients, 13.6% were eligible and 30.6% of those consented to take part. Restrictions on visitors during the coronavirus disease 2019 pandemic made it difficult to discuss the study with patients' families and fewer patients were admitted to hospital where the study was taking place. The research question could not be answered by this study at the present time.

Examination of early treatment effects and related biases during the conduct of two UK-wide pragmatic orthopaedic surgical trials: ProFHER and UK FROST.

Early large treatment effects can arise in small studies, which lessen as more data accumulate. This study aimed to retrospectively examine whether early treatment effects occurred for two multicentre orthopaedic randomized controlled trials (RCTs) and explore biases related to this. Included RCTs were ProFHER (PROximal Fracture of the Humerus: Evaluation by Randomisation), a two-arm study of surgery versus non-surgical treatment for proximal humerus fractures, and UK FROST (United Kingdom Frozen Shoulder Trial), a three-arm study of two surgical and one non-surgical treatment for frozen shoulder. To determine whether early treatment effects were present, the primary outcome of Oxford Shoulder Score (OSS) was compared on forest plots for: the chief investigator's (CI) site to the remaining sites, the first five sites opened to the other sites, and patients grouped in quintiles by randomization date. Potential for bias was assessed by comparing mean age and proportion of patients with indicators of poor outcome between included and excluded/non-consenting participants. No bias in treatment effect was observed overall for the CI site, or the first five sites, compared with the remaining sites in either trial. An early treatment effect on the OSS was observed for the first quintile of participants recruited to ProFHER only (clinically relevant difference of seven points). Selection bias for age was observed in the ProFHER trial only, with slightly younger patients being recruited into the study. Both trials showed some selection bias for markers of poor prognosis, although these did not appear to change over time. No bias in treatment effects overall were found at the CI or early sites set-up. An early treatment effect was found in one of the two trials, which was likely a chance effect as this did not continue during the study. Selection bias was observed in both RCTs, however this was minimal and did not impact on outcome.

Reverse shoulder arthroplasty versus hemiarthroplasty versus non-surgical treatment for older adults with acute 3- or 4-part fractures of the proximal humerus: study protocol for a randomised controlled trial (PROFHER-2: PROximal Fracture of Humerus Evaluation by Randomisation - Trial Number 2).

BACKGROUND: Proximal humerus fractures (PHF) are common and painful injuries, with the majority resulting from falls from a standing height. As with other fragility fractures, its age-specific incidence is increasing. Surgical treatment with hemiarthroplasty (HA) and reverse shoulder arthroplasty (RSA) have been increasingly used for displaced 3- and 4-part fractures despite a lack of good quality evidence as to whether one type of arthroplasty is superior to the other, and whether surgery is better than non-surgical management. The PROFHER-2 trial has been designed as a pragmatic, multicentre randomised trial to compare the clinical and cost-effectiveness of RSA vs HA vs Non-Surgical (NS) treatment in patients with 3- and 4-part PHF. METHODS: Adults over 65 years of age presenting with acute radiographically confirmed 3- or 4-part fractures, with or without associated glenohumeral joint dislocation, who consent for trial participation will be recruited from around 40 National Health Service (NHS) Hospitals in the UK. Patients with polytrauma, open fractures, presence of axillary nerve palsy, pathological (other than osteoporotic) fractures, and those who are unable to adhere to trial procedures will be excluded. We will aim to recruit 380 participants (152 RSA, 152 HA, 76 NS) using 2:2:1 (HA:RSA:NS) randomisation for 3- or 4-part fractures without joint dislocation, and 1:1 (HA:RSA) randomisation for 3- or 4-part fracture dislocations. The primary outcome is the Oxford Shoulder Score at 24 months. Secondary outcomes include quality of life (EQ-5D-5L), pain, range of shoulder motion, fracture healing and implant position on X-rays, further procedures, and complications. Independent Trial Steering Committee and Data Monitoring Committee will oversee the trial conduct, including the reporting of adverse events and harms. DISCUSSION: The PROFHER-2 trial is designed to provide a robust answer to guide the treatment of patients aged 65 years or over who sustain 3- and 4-part proximal humeral fractures. The pragmatic design and recruitment from around 40 UK NHS hospitals will ensure immediate applicability and generalisability of the trial findings. The full trial results will be made available in a relevant open-access peer-reviewed journal. TRIAL REGISTRATION: ISRCTN76296703. Prospectively registered on 5th April 2018.

Lateral compression type 1 fracture fixation in the elderly (L1FE): study protocol for a randomised controlled trial (with internal pilot) comparing the effects of INFIX surgery and non-surgical management for treating patients with lateral compression type 1 (LC-1) fragility fractures.

BACKGROUND: Lateral compression type1 (LC-1) fragility fractures are a common, painful injury in older adults resulting in reduced mobility. The incidence of these fractures is increasing with the growing older adult population. The current standard of care is non-surgical management; however, patients with this injury are at risk of long-term immobility and related complications. INFIX is a pelvic fixation device used in younger patients with high-energy fractures. The device is fitted via a percutaneous technique with no external pin sites and has good purchase even in osteoporotic bone. It therefore has the potential to be well tolerated in patients with LC-1 fragility fractures. INFIX could improve patients' ability to mobilise and reduce the risk of immobility-related complications. However, there is a risk of complications related to surgery, and robust evidence is required on patient outcomes. This study will investigate the clinical and cost-effectiveness of surgical fixation with INFIX compared to non-surgical management of LC-1 fragility fractures in older adults. METHODS: A multi-centre randomised controlled trial of 600 patients allocated 1:1 to non-surgical management or INFIX surgery. The study will have a 12-month internal pilot to assess recruitment and trial feasibility. The primary outcome will be the patient quality of life over 6 months, measured by the patient-reported EQ-5D-5L. The secondary outcomes will include physical function, mental health, pain, delirium, imaging assessment, resource use, and complications. DISCUSSION: The L1FE study aims to compare the clinical and cost-effectiveness of surgical and non-surgical management of people aged 60 years and older with LC-1 fragility fractures. The trial is sufficiently powered and rigorously designed to inform future clinical and patient decision-making and allocation of NHS resources. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number Registry ISRCTN16478561. Registered on 8 April 2019.

Effect of financial voucher incentives provided with UK stop smoking services on the cessation of smoking in pregnant women (CPIT III): pragmatic, multicentre, single blinded, phase 3, randomised controlled trial.

OBJECTIVE: To examine effectiveness, cost effectiveness, generalisability, and acceptability of financial incentives for smoking cessation during pregnancy in addition to variously organised UK stop smoking services. DESIGN: Pragmatic, multicentre, single blinded, phase 3, randomised controlled trial (Cessation in Pregnancy Incentives Trial phase 3 (CPIT III)). SETTING: Seven UK stop smoking services provided in primary and secondary care facilities in Scotland, Northern Ireland, and England. PARTICIPANTS: 944 pregnant women (age ≥16 years) who self-reported as being smokers (at least one cigarette in the past week) when asked at first maternity visit, less than 24 weeks' gestation, and notified to the trial team by routine stop smoking services. INTERVENTIONS: Participants in the control group were offered the standard stop smoking services, which includes the offer of counselling by specially trained workers using withdrawal orientated therapy and the offer of free nicotine replacement therapy. The intervention was the offer of usual support from the stop smoking services and the addition of up to £400 ($440; €455) of LoveToShop financial voucher incentives for engaging with current stop smoking services or to stop smoking, or both, during pregnancy. MAIN OUTCOME MEASURES: Self-reported smoking cessation in late pregnancy (between 34 and 38 weeks' gestation) corroborated by saliva cotinine (and anabasine if using nicotine replacement products). Results were adjusted for age, smoking years, index of multiple deprivation, Fagerström score, before or after covid, and recruitment site. Secondary outcomes included point and continuous abstinence six months after expected date of delivery, engagement with stop smoking services, biochemically validated abstinence from smoking at four weeks after stop smoking date, birth weight of baby, cost effectiveness, generalisability documenting formats of stop smoking services, and acceptability to pregnant women and their carers. RESULTS: From 9 January 2018 to 4 April 2020, of 4032 women screened by stop smoking services, 944 people were randomly assigned to the intervention group (n=471) or the control group (n=470). Three people asked for their data to be removed. 126 (27%) of 471 participants stopped smoking from the intervention group and 58 (12%) of 470 from the control group (adjusted odds ratio 2.78 (1.94 to 3.97) P<0.001). Serious adverse events were miscarriages and other expected pregnancy events requiring hospital admission; all serious adverse events were unrelated to the intervention. Most people who stopped smoking from both groups relapsed after their baby was born. CONCLUSIONS: The offer of up to £400 of financial voucher incentives to stop smoking during pregnancy as an addition to current UK stop smoking services is highly effective. This bolt-on intervention supports new guidance from the UK National Institute for Health and Care Excellence, which includes the addition of financial incentives to support pregnant women to stop smoking. Continuing incentives to 12 months after birth is being examined to prevent relapse. TRIAL REGISTRATION: ISRCTN Registry ISRCTN15236311.

Scaling up Quality Improvement for Surgical Teams (QIST)-avoiding surgical site infection and anaemia at the time of surgery: a cluster randomised controlled trial of the effectiveness of quality improvement collaboratives to introduce change in the NHS.

BACKGROUND: The aim of this trial was to assess the effectiveness of quality improvement collaboratives to implement large-scale change in the National Health Service (NHS) in the UK, specifically for improving outcomes in patients undergoing primary, elective total hip or knee replacement. METHODS: We undertook a two-arm, cluster randomised controlled trial comparing the roll-out of two preoperative pathways: methicillin-sensitive Staphylococcus aureus (MSSA) decolonisation (infection arm) and anaemia screening and treatment (anaemia arm). NHS Trusts are public sector organisations that provide healthcare within a geographical area. NHS Trusts (n = 41) in England providing primary, elective total hip and knee replacements, but that did not have a preoperative anaemia screening or MSSA decolonisation pathway in place, were randomised to one of the two parallel collaboratives. Collaboratives took place from May 2018 to November 2019. Twenty-seven Trusts completed the trial (11 anaemia, 16 infection). Outcome data were collected for procedures performed between November 2018 and November 2019. Co-primary outcomes were perioperative blood transfusion (within 7 days of surgery) and deep surgical site infection (SSI) caused by MSSA (within 90 days post-surgery) for the anaemia and infection trial arms, respectively. Secondary outcomes were deep and superficial SSIs (any organism), length of hospital stay, critical care admissions and unplanned readmissions. Process measures included the proportion of eligible patients receiving each preoperative initiative. RESULTS: There were 19,254 procedures from 27 NHS Trusts included in the results (6324 from 11 Trusts in the anaemia arm, 12,930 from 16 Trusts in the infection arm). There were no improvements observed for blood transfusion (anaemia arm 183 (2.9%); infection arm 302 (2.3%) transfusions; adjusted odds ratio 1.20, 95% CI 0.52-2.75, p = 0.67) or MSSA deep SSI (anaemia arm 8 (0.13%); infection arm 18 (0.14%); adjusted odds ratio 1.01, 95% CI 0.42-2.46, p = 0.98). There were no significant improvements in any secondary outcome. This is despite process measures showing the preoperative pathways were implemented for 73.7% and 61.1% of eligible procedures in the infection and anaemia arms, respectively. CONCLUSIONS: Quality improvement collaboratives did not result in improved patient outcomes in this trial; however, there was some evidence they may support successful implementation of new preoperative pathways in the NHS. TRIAL REGISTRATION: Prospectively registered on 15 February 2018, ISRCTN11085475.

Bah humbug! Association between sending Christmas cards to trial participants and trial retention: randomised study within a trial conducted simultaneously across eight host trials.

OBJECTIVES: To determine the effectiveness of sending Christmas cards to participants in randomised controlled trials to increase retention rate at follow-ups, and to explore the feasibility of doing a study within a trial (SWAT) across multiple host trials simultaneously. DESIGN: Randomised SWAT conducted simultaneously across eight host trials. SETTING: Eight randomised controlled trials researching various areas including surgery and smoking cessation. PARTICIPANTS: 3223 trial participants who were still due at least one follow-up from their host randomised controlled trial. INTERVENTION: Participants were randomised (1:1, separately by each host trial) to either received a Christmas card in mid-December 2019 or to not receive a card. MAIN OUTCOME MEASURE: Proportion of participants completing their next follow-up (retention rate) within their host randomised controlled trial. RESULTS: 1469 participants (age 16-94 years; 70% (n=1033) female; 96% (813/847) white ethnicity) across the eight host randomised controlled trials were involved in the analysis (cut short owing to covid-19). No evidence was found of a difference in retention rate between the two arms for any of the host trials when analysed separately or when the results were combined (85.3% (639/749) for cards versus 85.4% (615/720) for no card; odds ratio 0.96, 95% confidence interval 0.71 to 1.29; P=0.77). No difference was observed when comparing just participants who were due a follow-up in the 30 days after receiving the card (odds ratio 0.96, 0.42 to 2.21). No evidence of a difference in time to complete the questionnaire was found (hazard ratio 1.01, 95% confidence interval 0.91 to 1.13; P=0.80). These results were robust to post hoc sensitivity analyses. The cost of this intervention was £0.76 (€0.91; $1.02) per participant, and it will have a carbon footprint of approximately 140 g CO2 equivalent per card. One benefit of this approach was the need to only submit one ethics application. CONCLUSIONS: Sending Christmas cards to participants in randomised controlled trials does not increase retention. Undertaking a SWAT within multiple randomised controlled trials at the same time is, however, possible. This approach should be used more often to build an evidence base to support selection of recruitment and retention strategies. Although no evidence of a boost to retention was found, embedding a SWAT in multiple host trials simultaneously has been shown to be possible. STUDY REGISTRATION: SWAT repository https://www.qub.ac.uk/sites/TheNorthernIrelandNetworkforTrialsMethodologyResearch/FileStore/Filetoupload,846275,en.pdf#search=SWAT%2082.

Surgery versus conservative management of stable thoracolumbar fracture: the PRESTO feasibility RCT.

BACKGROUND: There is informal consensus that simple compression fractures of the body of the thoracolumbar vertebrae between the 10th thoracic vertebra and the second lumbar vertebra without neurological complications can be managed conservatively and that obvious unstable fractures require surgical fixation. However, there is a zone of uncertainty about whether surgical or conservative management is best for stable fractures. OBJECTIVES: To assess the feasibility of a definitive randomised controlled trial comparing surgical fixation with initial conservative management of stable thoracolumbar fractures without spinal cord injury. DESIGN: External randomised feasibility study, qualitative study and national survey. SETTING: Three NHS hospitals. METHODS: A feasibility randomised controlled trial using block randomisation, stratified by centre and type of injury (high- or low-energy trauma) to allocate participants 1 : 1 to surgery or conservative treatment; a costing analysis; a national survey of spine surgeons; and a qualitative study with clinicians, recruiting staff and patients. PARTICIPANTS: Adults aged ≥ 16 years with a high- or low-energy fracture of the body of a thoracolumbar vertebra between the 10th thoracic vertebra and the second lumbar vertebra, confirmed by radiography, computerised tomography or magnetic resonance imaging, with at least one of the following: kyphotic angle > 20° on weight-bearing radiographs or > 15° on a supine radiograph or on computerised tomography; reduction in vertebral body height of 25%; a fracture line propagating through the posterior wall of the vertebra; involvement of two contiguous vertebrae; or injury to the posterior longitudinal ligament or annulus in addition to the body fracture. INTERVENTIONS: Surgical fixation: open spinal surgery (with or without spinal fusion) or minimally invasive stabilisation surgery. Conservative management: mobilisation with or without a brace. MAIN OUTCOME MEASURE: Recruitment rate (proportion of eligible participants randomised). RESULTS: Twelve patients were randomised (surgery, n = 8; conservative, n = 4). The proportion of eligible patients recruited was 0.43 (95% confidence interval 0.24 to 0.63) over a combined total of 30.7 recruitment months. Of 211 patients screened, 28 (13.3%) fulfilled the eligibility criteria. Patients in the qualitative study (n = 5) expressed strong preferences for surgical treatment, and identified provision of information about treatment and recovery and when and how they are approached for consent as important. Nineteen surgeons and site staff participated in the qualitative study. Key themes were the lack of clinical consensus regarding the implementation of the eligibility criteria in practice and what constitutes a stable fracture, alongside lack of equipoise regarding treatment. Based on the feasibility study eligibility criteria, 77% (50/65) and 70% (46/66) of surgeons participating in the survey were willing to randomise for high- and low-energy fractures, respectively. LIMITATIONS: Owing to the small number of participants, there is substantial uncertainty around the recruitment rate. CONCLUSIONS: A definitive trial is unlikely to be feasible currently, mainly because of the small number of patients meeting the eligibility criteria. The recruitment and follow-up rates were slightly lower than anticipated; however, there is room to increase these based on information gathered and the support within the surgical community for a future trial. FUTURE WORK: Development of consensus regarding the population of interest for a trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12094890. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 62. See the NIHR Journals Library website for further project information.

Fractures occurring in the mid- to low back region (or thoracolumbar fractures) are the most common back fractures. When the fracture is stable with no spinal nerve injury, there is uncertainty whether treatment with surgery or non-surgical treatment (e.g. stabilising the spine with a brace) results in the best outcome for patients. The Pragmatic Randomised Evaluation of Stable Thoracolumbar fracture treatment Outcomes (PRESTO) study aimed to explore whether or not it would be feasible to carry out a full-scale study to find out which of these two treatments works best. Adults aged ≥ 16 years being treated for these fractures in three hospitals were invited to take part in the study. Over the course of 1 year, we assessed how many patients were treated, the number who met the study entry criteria and the proportion of eligible patients who agreed to take part. Staff and patients were interviewed about the study processes and their experiences of taking part. Spine surgeons from around the UK were also asked to complete an online survey, which asked questions about the treatment of patients with this fracture. There were fewer patients than expected who met the study entry criteria and, of these, fewer patients who agreed to take part. There were differences among surgeons about the definition of a stable fracture, and we found that surgeons have strong views about whether or not surgery is appropriate when fractures are stable. We also found that more support would be required for the staff involved in inviting patients to take part in a bigger study, and that the format and content of information provided to patients needs to be improved. The findings of the PRESTO study showed that a large trial is unlikely to be successful at this time; however, we have provided important information for future research into the treatment of these fractures.

Dupuytren's interventions surgery versus collagenase (DISC) trial: study protocol for a pragmatic, two-arm parallel-group, non-inferiority randomised controlled trial.

BACKGROUND: Dupuytren's contracture is a fibro-proliferative disease of the hands affecting over 2 million UK adults, particularly the white, male population. Surgery is the traditional treatment; however, recent studies have indicated that an alternative to surgery-collagenase clostridium histolyticum (collagenase)-is better than a placebo in the treatment of Dupuytren's contracture. There is however no robust randomised controlled trial that provides a definitive answer on the clinical effectiveness of collagenase compared with limited fasciectomy surgery. Dupuytren's intervention surgery vs collagenase trial (DISC) trial was therefore designed to fill this evidence gap. METHODS/DESIGN: The DISC trial is a multi-centre pragmatic two-arm parallel-group, randomised controlled trial. Participants will be assigned 1:1 to receive either collagenase injection or surgery (limited fasciectomy). We aim to recruit 710 adult participants with Dupuytren's contracture. Potential participants will be identified in primary and secondary care, screened by a delegated clinician and if eligible and consenting, baseline data will be collected and randomisation completed. The primary outcome will be the self-reported patient evaluation measure assessed 1 year after treatment. Secondary outcome measures include the Unité Rhumatologique des Affections de la Main Scale, the Michigan Hand Questionnaire, EQ-5D-5L, resource use, further procedures, complications, recurrence, total active movement and extension deficit, and time to return to function. Given the limited evidence comparing recurrence rates following collagenase injection and limited fasciectomy, and the importance of a return to function as soon as possible for patients, the associated measures for each will be prioritised to allow treatment effectiveness in the context of these key elements to be assessed. An economic evaluation will assess the cost-effectiveness of treatments, and a qualitative sub-study will assess participants' experiences and preferences of the treatments. DISCUSSION: The DISC trial is the first randomised controlled trial, to our knowledge, to investigate the clinical and cost-effectiveness of collagenase compared to limited fasciectomy surgery for patients with Dupuytren's contracture. TRIAL REGISTRATION: Clinical.Trials.gov ISRCTN18254597 . Registered on April 11, 2017.

A multicentre, randomized, parallel group, superiority study to compare the clinical effectiveness and cost-effectiveness of external frame versus internal locking plate for complete articular pilon fracture fixation in adults.

AIMS: A pilon fracture is a severe ankle joint injury caused by high-energy trauma, typically affecting men of working age. Although relatively uncommon (5% to 7% of all tibial fractures), this injury causes among the worst functional and health outcomes of any skeletal injury, with a high risk of serious complications and long-term disability, and with devastating consequences on patients' quality of life and financial prospects. Robust evidence to guide treatment is currently lacking. This study aims to evaluate the clinical and cost-effectiveness of two surgical interventions that are most commonly used to treat pilon fractures. METHODS: A randomized controlled trial (RCT) of 334 adult patients diagnosed with a closed type C pilon fracture will be conducted. Internal locking plate fixation will be compared with external frame fixation. The primary outcome and endpoint will be the Disability Rating Index (a patient self-reported assessment of physical disability) at 12 months. This will also be measured at baseline, three, six, and 24 months after randomization. Secondary outcomes include the Olerud and Molander Ankle Score (OMAS), the five-level EuroQol five-dimenison score (EQ-5D-5L), complications (including bone healing), resource use, work impact, and patient treatment preference. The acceptability of the treatments and study design to patients and health care professionals will be explored through qualitative methods. DISCUSSION: The two treatments being compared are the most commonly used for this injury, however there is uncertainty over which is most clinically and cost-effective. The Articular Pilon Fracture (ACTIVE) Trial is a sufficiently powered and rigorously designed study to inform clinical decisions for the treatment of adults with this injury. Cite this article: Bone Jt Open 2021;2(3):150-163.

Surgical treatments compared with early structured physiotherapy in secondary care for adults with primary frozen shoulder: the UK FROST three-arm RCT.

BACKGROUND: Frozen shoulder causes pain and stiffness. It affects around 10% of people in their fifties and is slightly more common in women. Costly and invasive surgical interventions are used, without high-quality evidence that these are effective. OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of three treatments in secondary care for adults with frozen shoulder; to qualitatively explore the acceptability of these treatments to patients and health-care professionals; and to update a systematic review to explore the trial findings in the context of existing evidence for the three treatments. DESIGN: This was a pragmatic, parallel-group, multicentre, open-label, three-arm, randomised superiority trial with unequal allocation (2 : 2 : 1). An economic evaluation and a nested qualitative study were also carried out. SETTING: The orthopaedic departments of 35 hospitals across the UK were recruited from April 2015, with final follow-up in December 2018. PARTICIPANTS: Participants were adults (aged ≥ 18 years) with unilateral frozen shoulder, characterised by restriction of passive external rotation in the affected shoulder to < 50% of the opposite shoulder, and with plain radiographs excluding other pathology. INTERVENTIONS: The inventions were early structured physiotherapy with a steroid injection, manipulation under anaesthesia with a steroid injection and arthroscopic capsular release followed by manipulation. Both of the surgical interventions were followed with post-procedural physiotherapy. MAIN OUTCOME MEASURES: The primary outcome and end point was the Oxford Shoulder Score at 12 months post randomisation. A difference of 5 points between early structured physiotherapy and manipulation under anaesthesia or arthroscopic capsular release or of 4 points between manipulation under anaesthesia and arthroscopic capsular release was judged clinically important. RESULTS: The mean age of the 503 participants was 54 years; 319 were female (63%) and 150 had diabetes (30%). The primary analyses comprised 473 participants (94%). At the primary end point of 12 months, participants randomised to arthroscopic capsular release had, on average, a statistically significantly higher (better) Oxford Shoulder Score than those randomised to manipulation under anaesthesia (2.01 points, 95% confidence interval 0.10 to 3.91 points; p = 0.04) or early structured physiotherapy (3.06 points, 95% confidence interval 0.71 to 5.41 points; p = 0.01). Manipulation under anaesthesia did not result in statistically significantly better Oxford Shoulder Score than early structured physiotherapy (1.05 points, 95% confidence interval -1.28 to 3.39 points; p = 0.38). No differences were deemed of clinical importance. Serious adverse events were rare but occurred in participants randomised to surgery (arthroscopic capsular release,n = 8; manipulation under anaesthesia,n = 2). There was, however, one serious adverse event in a participant who received non-trial physiotherapy. The base-case economic analysis showed that manipulation under anaesthesia was more expensive than early structured physiotherapy, with slightly better utilities. The incremental cost-effectiveness ratio for manipulation under anaesthesia was £6984 per additional quality-adjusted life-year, and this intervention was probably 86% cost-effective at the threshold of £20,000 per quality-adjusted life-year. Arthroscopic capsular release was more costly than early structured physiotherapy and manipulation under anaesthesia, with no statistically significant benefit in utilities. Participants in the qualitative study wanted early medical help and a quicker pathway to resolve their shoulder problem. Nine studies were identified from the updated systematic review, including UK FROST, of which only two could be pooled, and found that arthroscopic capsular release was more effective than physiotherapy in the long-term shoulder functioning of patients, but not to the clinically important magnitude used in UK FROST. LIMITATIONS: Implementing physiotherapy to the trial standard in clinical practice might prove challenging but could avoid theatre use and post-procedural physiotherapy. There are potential confounding effects of waiting times in the trial. CONCLUSIONS: None of the three interventions was clearly superior. Early structured physiotherapy with a steroid injection is an accessible and low-cost option. Manipulation under anaesthesia is the most cost-effective option. Arthroscopic capsular release carries higher risks and higher costs. FUTURE WORK: Evaluation in a randomised controlled trial is recommended to address the increasing popularity of hydrodilatation despite the paucity of high-quality evidence. TRIAL REGISTRATION: Current Controlled Trials ISRCTN48804508. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 71. See the NIHR Journals Library website for further project information.

Frozen shoulder occurs when the soft tissue envelope around the shoulder joint becomes inflamed, scarred and contracted, making movement painful and stiff. It affects around 1 in 10 people and is more common in women. Most patients are treated in the community. Those who do not improve are offered treatments in hospital. This includes costly and invasive surgical options. It is unclear which treatment provides the best patient outcomes and is cost-effective. UK FROST (UK FROzen Shoulder Trial) comprised 503 patients (from 35 UK hospitals) who randomly received one of three commonly offered treatments for frozen shoulder: early physiotherapy to restore movement, including a steroid injection for pain reliefmanipulation under anaesthesia, to stretch and tear the tight capsule to restore movement, and a steroid injection followed by physiotherapyarthroscopic capsular release, which uses keyhole surgery, including manipulation, to restore movement, followed by physiotherapy with pain medication. No important differences were found between the three treatments in shoulder function or pain at 12 months. Fewer patients who received arthroscopic capsular release required further treatment, and patients who received arthroscopic capsular release had slightly better shoulder function and pain outcomes than those who received the manipulation procedure or early physiotherapy. This improvement, however, was unlikely to be of clinical benefit to patients. Arthroscopic capsular release had slightly higher risks and substantially higher costs. Six serious complications were reported in patients who received arthroscopic capsular release (mostly owing to co-existing health problems) and two were reported in patients who received manipulation under anaesthesia. Physiotherapy was the least expensive treatment, but patients who received manipulation under anaesthesia had slightly better general health than those who received physiotherapy. Early physiotherapy with steroid injection could be accessed quicker than the surgical alternatives. Manipulation under anaesthesia cost more than physiotherapy but provided the best value for money. Patients in the study wanted early access to medical help to improve their shoulder problems.

Surgical fixation compared with cast immobilisation for adults with a bicortical fracture of the scaphoid waist: the SWIFFT RCT.

BACKGROUND: Scaphoid fractures account for 90% of carpal fractures and occur predominantly in young men. Immediate surgical fixation of this fracture has increased. OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of surgical fixation with cast treatment and early fixation in adults with scaphoid waist fractures that fail to unite. DESIGN: Multicentre, pragmatic, open-label, parallel two-arm randomised controlled trial with an economic evaluation and a nested qualitative study. SETTING: Orthopaedic departments of 31 hospitals in England and Wales recruited from July 2013, with final follow-up in September 2017. PARTICIPANTS: Adults (aged ≥ 16 years) presenting within 2 weeks of injury with a clear, bicortical fracture of the scaphoid waist on plain radiographs. INTERVENTIONS: Early surgical fixation using Conformité Européenne-marked headless compression screws. Below-elbow cast immobilisation for 6-10 weeks and urgent fixation of confirmed non-union. MAIN OUTCOME MEASURES: The primary outcome and end point was the Patient-Rated Wrist Evaluation total score at 52 weeks, with a clinically relevant difference of 6 points. Secondary outcomes included Patient-Rated Wrist Evaluation pain and function subscales, Short Form questionnaire 12-items, bone union, range of movement, grip strength, complications and return to work. RESULTS: The mean age of 439 participants was 33 years; 363 participants were male (83%) and 269 participants had an undisplaced fracture (61%). The primary analysis was on 408 participants with valid Patient-Rated Wrist Evaluation outcome data for at least one post-randomisation time point (surgery, n = 203 of 219; cast, n = 205 of 220). There was no clinically relevant difference in the Patient-Rated Wrist Evaluation total score at 52 weeks: the mean score in the cast group was 14.0 (95% confidence interval 11.3 to 16.6) and in the surgery group was 11.9 (95% confidence interval 9.2 to 14.5), with an adjusted mean difference of -2.1 in favour of surgery (95% confidence interval -5.8 to 1.6; p = 0.27). The non-union rate was low (surgery group, n = 1; cast group, n = 4). Eight participants in the surgery group had a total of 11 reoperations and one participant in the cast group required a reoperation for non-union. The base-case economic analysis at 52 weeks found that surgery cost £1295 per patient more (95% confidence interval £1084 to £1504) than cast treatment. The base-case analysis of a lifetime-extrapolated model confirmed that the cast treatment pathway was more cost-effective. The nested qualitative study identified patients' desire to have a 'sense of recovering', which surgeons should address at the outset. LIMITATION: There were 17 participants who had initial cast treatment and surgery for confirmed non-union, which in 14 cases was within 6 months from randomisation and in three cases was after 6 months. Three of the four participants in the cast group who had a non-union at 52 weeks were not offered surgery. CONCLUSIONS: Adult patients with an undisplaced or minimally displaced scaphoid waist fracture should have cast immobilisation and suspected non-unions immediately confirmed and urgently fixed. Patients should be followed up at 5 years to investigate the effect of partial union, degenerative arthritis, malunion and screw problems on their quality of life. TRIAL REGISTRATION: Current Controlled Trials ISRCTN67901257. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 52. See the NIHR Journals Library website for further project information.

Fracture of the scaphoid bone (one of eight small bones in the wrist) is common in young active people. It is caused by a fall on the hand or the hand being suddenly forced backwards. The usual treatment is to rest the wrist in a plaster cast for 6­10 weeks and allow the broken bone to heal. In 1 in 10 cases in which the fracture is treated in a plaster cast, the bone does not heal and an operation is needed. In the operation, the broken bone is held still with a screw. In the last few years, it has become more common to fix the broken bone with a screw in the first few days after injury, instead of resting the wrist in a plaster cast. It is not clear if fixing the bone early with a screw, compared with resting the wrist in a cast, gives better outcomes for patients and if one treatment is better value for money for the NHS. In this study, 439 adult patients agreed either to have surgery to hold the broken scaphoid with a special screw or to have the wrist held still in a plaster cast (with surgery offered after 6 weeks to those who were still not healed). The decision about which treatment to use was made using randomisation, which is similar to tossing a coin. Patients reported their own wrist pain and function at 6, 12, 26 and 52 weeks. Information was also collected on general health, bone healing, grip strength and range of movement, complications from treatment and costs. No important differences were found in patients' wrist pain and function at 52 weeks. The bone did not heal properly in four patients in the surgery group or in nine patients in the plaster cast group at 52 weeks. For one of these patients in the surgery group and four of these patients in the plaster cast group, the bone did not join at all. Eight patients in the surgery group had further surgery following their initial operation to fix their wrist, and one patient in the cast group required repeated surgery because the bone did not join at all. The overall cost of treating with a plaster cast was lower than that of early surgery. Therefore, the findings of the study suggest that a plaster cast should be used initially and that the bone should be immediately fixed with a screw if it does not heal.

Management of adults with primary frozen shoulder in secondary care (UK FROST): a multicentre, pragmatic, three-arm, superiority randomised clinical trial.

BACKGROUND: Manipulation under anaesthesia and arthroscopic capsular release are costly and invasive treatments for frozen shoulder, but their effectiveness remains uncertain. We compared these two surgical interventions with early structured physiotherapy plus steroid injection. METHODS: In this multicentre, pragmatic, three-arm, superiority randomised trial, patients referred to secondary care for treatment of primary frozen shoulder were recruited from 35 hospital sites in the UK. Participants were adults (≥18 years) with unilateral frozen shoulder, characterised by restriction of passive external rotation (≥50%) in the affected shoulder. Participants were randomly assigned (2:2:1) to receive manipulation under anaesthesia, arthroscopic capsular release, or early structured physiotherapy. In manipulation under anaesthesia, the surgeon manipulated the affected shoulder to stretch and tear the tight capsule while the participant was under general anaesthesia, supplemented by a steroid injection. Arthroscopic capsular release, also done under general anaesthesia, involved surgically dividing the contracted anterior capsule in the rotator interval, followed by manipulation, with optional steroid injection. Both forms of surgery were followed by postprocedural physiotherapy. Early structured physiotherapy involved mobilisation techniques and a graduated home exercise programme supplemented by a steroid injection. Both early structured physiotherapy and postprocedural physiotherapy involved 12 sessions during up to 12 weeks. The primary outcome was the Oxford Shoulder Score (OSS; 0-48) at 12 months after randomisation, analysed by initial randomisation group. We sought a target difference of 5 OSS points between physiotherapy and either form of surgery, or 4 points between manipulation and capsular release. The trial registration is ISRCTN48804508. FINDINGS: Between April 1, 2015, and Dec 31, 2017, we screened 914 patients, of whom 503 (55%) were randomly assigned. At 12 months, OSS data were available for 189 (94%) of 201 participants assigned to manipulation (mean estimate 38·3 points, 95% CI 36·9 to 39·7), 191 (94%) of 203 participants assigned to capsular release (40·3 points, 38·9 to 41·7), and 93 (94%) of 99 participants assigned to physiotherapy (37·2 points, 35·3 to 39·2). The mean group differences were 2·01 points (0·10 to 3·91) between the capsular release and manipulation groups, 3·06 points (0·71 to 5·41) between capsular release and physiotherapy, and 1·05 points (-1·28 to 3·39) between manipulation and physiotherapy. Eight serious adverse events were reported with capsular release and two with manipulation. At a willingness-to-pay threshold of £20 000 per quality-adjusted life-year, manipulation under anaesthesia had the highest probability of being cost-effective (0·8632, compared with 0·1366 for physiotherapy and 0·0002 for capsular release). INTERPRETATION: All mean differences on the assessment of shoulder pain and function (OSS) at the primary endpoint of 12 months were less than the target differences. Therefore, none of the three interventions were clinically superior. Arthoscopic capsular release carried higher risks, and manipulation under anaesthesia was the most cost-effective. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Yorkshire Lung Screening Trial (YLST): protocol for a randomised controlled trial to evaluate invitation to community-based low-dose CT screening for lung cancer versus usual care in a targeted population at risk.

INTRODUCTION: Lung cancer is the world's leading cause of cancer death. Low-dose computed tomography (LDCT) screening reduced lung cancer mortality by 20% in the US National Lung Screening Trial. Here, we present the Yorkshire Lung Screening Trial (YLST), which will address key questions of relevance for screening implementation. METHODS AND ANALYSIS: Using a single-consent Zelen's design, ever-smokers aged 55-80 years registered with a general practice in Leeds will be randomised (1:1) to invitation to a telephone-based risk-assessment for a Lung Health Check or to usual care. The anticipated number randomised by household is 62 980 individuals. Responders at high risk will be invited for LDCT scanning for lung cancer on a mobile van in the community. There will be two rounds of screening at an interval of 2 years. Primary objectives are (1) measure participation rates, (2) compare the performance of PLCOM2012 (threshold ≥1.51%), Liverpool Lung Project (V.2) (threshold ≥5%) and US Preventive Services Task Force eligibility criteria for screening population selection and (3) assess lung cancer outcomes in the intervention and usual care arms. Secondary evaluations include health economics, quality of life, smoking rates according to intervention arm, screening programme performance with ancillary biomarker and smoking cessation studies. ETHICS AND DISSEMINATION: The study has been approved by the Greater Manchester West research ethics committee (18-NW-0012) and the Health Research Authority following review by the Confidentiality Advisory Group. The results will be disseminated through publication in peer-reviewed scientific journals, presentation at conferences and on the YLST website. TRIAL REGISTRATION NUMBERS: ISRCTN42704678 and NCT03750110.

Surgery versus cast immobilisation for adults with a bicortical fracture of the scaphoid waist (SWIFFT): a pragmatic, multicentre, open-label, randomised superiority trial.

BACKGROUND: Scaphoid fractures account for 90% of carpal fractures and occur predominantly in young men. The use of immediate surgical fixation to manage this type of fracture has increased, despite insufficient evidence of improved outcomes over non-surgical management. The SWIFFT trial compared the clinical effectiveness of surgical fixation with cast immobilisation and early fixation of fractures that fail to unite in adults with scaphoid waist fractures displaced by 2 mm or less. METHODS: This pragmatic, parallel-group, multicentre, open-label, two-arm, randomised superiority trial included adults (aged 16 years or older) who presented to orthopaedic departments of 31 hospitals in England and Wales with a clear bicortical fracture of the scaphoid waist on radiographs. An independent remote randomisation service used a computer-generated allocation sequence with randomly varying block sizes to randomly assign participants (1:1) to receive either early surgical fixation (surgery group) or below-elbow cast immobilisation followed by immediate fixation if non-union of the fracture was confirmed (cast immobilisation group). Randomisation was stratified by whether or not there was displacement of either a step or a gap of 1-2 mm inclusive on any radiographic view. The primary outcome was the total patient-rated wrist evaluation (PRWE) score at 52 weeks after randomisation, and it was analysed on an available case intention-to-treat basis. This trial is registered with the ISRCTN registry, ISRCTN67901257, and is no longer recruiting, but long-term follow-up is ongoing. FINDINGS: Between July 23, 2013, and July 26, 2016, 439 (42%) of 1047 assessed patients (mean age 33 years; 363 [83%] men) were randomly assigned to the surgery group (n=219) or to the cast immobilisation group (n=220). Of these, 408 (93%) participants were included in the primary analysis (203 participants in the surgery group and 205 participants in the cast immobilisation group). 16 participants in the surgery group and 15 participants in the cast immobilisation group were excluded because of either withdrawal, no response, or no follow-up data at 6, 12, 26, or 52 weeks. There was no significant difference in mean PRWE scores at 52 weeks between the surgery group (adjusted mean 11·9 [95% CI 9·2-14·5]) and the cast immobilisation group (14·0 [11·3 to 16·6]; adjusted mean difference -2·1 [95% CI -5·8 to 1·6], p=0·27). More participants in the surgery group (31 [14%] of 219 participants) had a potentially serious complication from surgery than in the cast immobilisation group (three [1%] of 220 participants), but fewer participants in the surgery group (five [2%]) had cast-related complications than in the cast immobilisation group (40 [18%]). The number of participants who had a medical complication was similar between the two groups (four [2%] in the surgery group and five [2%] in the cast immobilisation group). INTERPRETATION: Adult patients with scaphoid waist fractures displaced by 2 mm or less should have initial cast immobilisation, and any suspected non-unions should be confirmed and immediately fixed with surgery. This treatment strategy will help to avoid the risks of surgery and mostly limit the use of surgery to fixing fractures that fail to unite. FUNDING: National Institute for Health Research Health Technology Assessment Programme.

Scaling up Quality Improvement for Surgical Teams (QIST) - avoiding surgical site infection and anaemia at the time of surgery: protocol for a cluster randomised controlled trial.

BACKGROUND: Measures shown to improve outcomes for patients often fail to be adopted into routine practice in the NHS. The Institute for Health Improvement Breakthrough Series Collaborative (BSC) model is designed to support implementation at scale. This trial aims to assess the effectiveness and cost-effectiveness of quality improvement collaboratives (QICs) based on the BSC method for introducing service improvements at scale in the NHS. METHODS: Forty Trusts will be randomised (1:1) to introduce one of two protocols already shown to improve outcomes in patients undergoing elective total hip and knee replacement surgery. The intervention is improvement collaboratives based on the BSC model, a learning system that brings together a large number of teams to seek improvement focussed on a proven intervention. Collaboratives aim to deliver at scale, maximise local engagement and leadership and are designed to build capacity, enable learning and prepare for sustainability. Collaboratives involve Learning Sessions, Action Periods, and a summative congress. Trusts will be supported to introduce either: decolonisation for Methicillin Sensitive Staphylococcus aureus (MSSA) to reduce post-operative infection (QIST: Infection), or an anaemia optimisation programme to reduce peri-operative blood transfusions (QIST: Anaemia). Trusts will continue with their usual practice for whichever protocol they are not introducing. Anonymised data related to both infection and anaemia outcomes for patients undergoing hip or knee arthroplasty at all sites will mean that the two groups act as controls for each other. The primary outcome for the QIST: Infection collaborative is deep MSSA surgical site infection within 90 days of surgery, and for the QIST: Anaemia collaborative is blood transfusion within 7 days of surgery. Patient-level secondary outcomes include length of hospital stay and readmission, which will also inform the economic costings. Qualitative interviews will evaluate the support provided to teams. DISCUSSION: The scale of this trial brings considerable challenges and potential barriers to delivery. Anticipated challenges relate to recruiting and sustaining up to 40 organisations, each with its own culture and context. This complex project with multiple stakeholders across a large geographical area will be managed by experienced senior-level project leaders with a proven track record in advanced project management. The team should ensure effective project governance and communications. TRIAL REGISTRATION: ISRCTN, ISRCTN11085475. Prospectively registered on 15 February 2018.

The smoking cessation in pregnancy incentives trial (CPIT): study protocol for a phase III randomised controlled trial.

BACKGROUND: Eighty per cent of UK women have at least one baby, making pregnancy an opportunity to help women stop smoking before their health is irreparably compromised. Smoking cessation during pregnancy helps protect infants from miscarriage, still birth, low birth weight, asthma, attention deficit disorder and adult cardiovascular disease. UK national guidelines highlight lack of evidence for effectiveness of financial incentives to help pregnant smokers quit. This includes a research recommendation: within a UK context, are incentives an acceptable, effective and cost-effective way to help pregnant women who smoke to quit? METHODS: The Cessation in Pregnancy Incentives Trial (CPIT) III is a pragmatic, 42-month, multi-centre, parallel-group, individually randomised controlled superiority trial of the effect on smoking status of adding to usual Stop Smoking Services (SSS) support, the offer of up to £400 of financial voucher incentives, compared with usual support alone, to quit smoking during pregnancy. Participants (n = 940) are pregnant smokers (age > 16 years, < 24 weeks pregnant, English speaking), who consent via telephone to take part and are willing to be followed-up in late pregnancy and 6 months after birth. The primary outcome is cotinine/anabasine-validated abstinence from smoking in late pregnancy. Secondary outcomes include engagement with SSS, quit rates at 4 weeks from agreed quit date and 6 months after birth, and birth weight. Outcomes will be analysed by intention to treat, and regression models will be used to compare treatment effects on outcomes. A meta-analysis will include data from the feasibility study in Glasgow. An economic evaluation will assess cost-effectiveness from a UK NHS perspective. Process evaluation using a case-study approach will identify opportunities to improve recruitment and learning for future implementation. Research questions include: what is the therapeutic efficacy of incentives; are incentives cost-effective; and what are the potential facilitators and barriers to implementing incentives in different parts of the UK? DISCUSSION: This phase III trial in Scotland, England and Northern Ireland follows a successful phase II trial in Glasgow, UK. The participating sites have diverse SSS that represent most cessation services in the UK and serve demographically varied populations. If found to be acceptable and cost-effective, this trial could demonstrate that financial incentives are effective and transferable to most UK SSS for pregnant women. TRIAL REGISTRATION: Current Controlled Trials, ISRCTN15236311. Registered on 9 October 2017.

Does time to surgery affect patient-reported outcome in proximal humeral fractures? A subanalysis of the PROFHER randomized clinical trial.

AIMS: The aim of this study was to explore whether time to surgery affects functional outcome in displaced proximal humeral fractures. METHODS: A total of 250 patients presenting within three weeks of sustaining a displaced proximal humeral fracture involving the surgical neck were recruited at 32 acute NHS hospitals in the United Kingdom between September 2008 and April 2011. Of the 125 participants, 109 received surgery (fracture fixation or humeral head replacement) as per randomization. Data were included for 101 and 67 participants at six-month and five-year follow-up, respectively. Oxford Shoulder Scores (OSS) collected at six, 12, and 24 months and at three, four, and five years following randomization was plotted against time to surgery. Long-term recovery was explored by plotting six-month scores against five-year scores and agreement was illustrated with a Bland-Altman plot. RESULTS: The mean time from initial trauma to surgery was 10.5 days (1 to 33). Earlier surgical intervention did not improve OSS throughout follow-up, nor when stratified by participant age (< 65 years vs ≥ 65 years) and fracture severity (one- and two-part vs three- and four-part fractures). Participants managed later than reported international averages (three days in the United States and Germany, eight days in the United Kingdom) did not have worse outcomes. At five-year follow-up, 50 participants (76%) had the same or improved OSS compared with six months (six-month mean OSS 35.8 (SD 10.0); five-year mean OSS 40.1 (SD 9.1); r = 0.613). A Bland-Altman plot demonstrated a positive mean difference (3.3 OSS points (SD 7.92)) with wide 95% limits of agreement (-12.2 and 18.8 points). CONCLUSION: Timing of surgery did not affect OSS at any stage of follow-up, irrespective of age or fracture type. Most participants had maximum functional outcome at six months that was maintained at five years. These findings may help guide providers of trauma services on surgical prioritization. Cite this article: Bone Joint J 2020;102-B(1):33-41.