Early versus delayed weight-bearing following operatively treated ankle fracture (WAX): a non-inferiority, multicentre, randomised controlled trial.

BACKGROUND: After surgery for a broken ankle, patients are usually instructed to avoid walking for 6 weeks (delayed weight-bearing). Walking 2 weeks after surgery (early weight-bearing) might be a safe and preferable rehabilitation strategy. This study aimed to determine the clinical and cost effectiveness of an early weight-bearing strategy compared with a delayed weight-bearing strategy. METHODS: This was a pragmatic, multicentre, randomised, non-inferiority trial including 561 participants (aged ≥18 years) who received acute surgery for an unstable ankle fracture in 23 UK National Health Service (NHS) hospitals who were assigned to either a delayed weight-bearing (n=280) or an early weight-bearing rehabilitation strategy (n=281). Patients treated with a hindfoot nail, those who did not have protective ankle sensation (eg, peripheral neuropathy), did not have the capacity to consent, or did not have the ability to adhere to trial procedures were excluded. Neither participants nor clinicians were masked to the treatment. The primary outcome was ankle function measured using the Olerud and Molander Ankle Score (OMAS) at 4 months after randomisation, in the per-protocol population. The pre-specified non-inferiority OMAS margin was -6 points and superiority testing was included in the intention-to-treat population in the event of non-inferiority. The trial was prospectively registered with ISRCTN Registry, ISRCTN12883981, and the trial is closed to new participants. FINDINGS: Primary outcome data were collected from 480 (86%) of 561 participants. Recruitment was conducted between Jan 13, 2020, and Oct 29, 2021. At 4 months after randomisation, the mean OMAS score was 65·9 in the early weight-bearing and 61·2 in the delayed weight-bearing group and adjusted mean difference was 4·47 (95% CI 0·58 to 8·37, p=0·024; superiority testing adjusted difference 4·42, 95% CI 0·53 to 8·32, p=0·026) in favour of early weight-bearing. 46 (16%) participants in the early weight-bearing group and 39 (14%) in the delayed weight-bearing group had one or more complications (adjusted odds ratio 1·18, 95% CI 0·80 to 1·75, p=0·40). The mean costs from the perspective of the NHS and personal social services in the early and delayed weight-bearing groups were £725 and £785, respectively (mean difference -£60 [95% CI -342 to 232]). The probability that early weight-bearing is cost-effective exceeded 80%. INTERPRETATION: An early weight-bearing strategy was found to be clinically non-inferior and highly likely to be cost-effective compared with the current standard of care (delayed weight-bearing). FUNDING: National Institute for Health and Care Research (NIHR), NIHR Barts Biomedical Research Centre, and NIHR Applied Research Collaboration Oxford and Thames Valley.

A protocol for the conduct of a multicentre, prospective, randomized superiority trial of surgical versus non-surgical interventions for humeral shaft fractures.

Aims: Fractures of the humeral shaft represent 3% to 5% of all fractures. The most common treatment for isolated humeral diaphysis fractures in the UK is non-operative using functional bracing, which carries a low risk of complications, but is associated with a longer healing time and a greater risk of nonunion than surgery. There is an increasing trend to surgical treatment, which may lead to quicker functional recovery and lower rates of fracture nonunion than functional bracing. However, surgery carries inherent risk, including infection, bleeding, and nerve damage. The aim of this trial is to evaluate the clinical and cost-effectiveness of functional bracing compared to surgical fixation for the treatment of humeral shaft fractures. Methods: The HUmeral SHaft (HUSH) fracture study is a multicentre, prospective randomized superiority trial of surgical versus non-surgical interventions for humeral shaft fractures in adult patients. Participants will be randomized to receive either functional bracing or surgery. With 334 participants, the trial will have 90% power to detect a clinically important difference for the Disabilities of the Arm, Shoulder and Hand questionnaire score, assuming 20% loss to follow-up. Secondary outcomes will include function, pain, quality of life, complications, cost-effectiveness, time off work, and ability to drive. Discussion: The results of this trial will provide evidence regarding clinical and cost-effectiveness between surgical and non-surgical treatment of humeral shaft fractures. Ethical approval has been obtained from East of England - Cambridge Central Research Ethics Committee. Publication is anticipated to occur in 2024.

Protocol for Surgery or Cast of the EpicoNdyle in Children's Elbows (SCIENCE).

Aims: The management of fractures of the medial epicondyle is one of the greatest controversies in paediatric fracture care, with uncertainty concerning the need for surgery. The British Society of Children's Orthopaedic Surgery prioritized this as their most important research question in paediatric trauma. This is the protocol for a randomized controlled, multicentre, prospective superiority trial of operative fixation versus nonoperative treatment for displaced medial epicondyle fractures: the Surgery or Cast of the EpicoNdyle in Children's Elbows (SCIENCE) trial. Methods: Children aged seven to 15 years old inclusive, who have sustained a displaced fracture of the medial epicondyle, are eligible to take part. Baseline function using the Patient-Reported Outcomes Measurement Information System (PROMIS) upper limb score, pain measured using the Wong Baker FACES pain scale, and quality of life (QoL) assessed with the EuroQol five-dimension questionnaire for younger patients (EQ-5D-Y) will be collected. Each patient will be randomly allocated (1:1, stratified using a minimization algorithm by centre and initial elbow dislocation status (i.e. dislocated or not-dislocated at presentation to the emergency department)) to either a regimen of the operative fixation or non-surgical treatment. Outcomes: At six weeks, and three, six, and 12 months, data on function, pain, sports/music participation, QoL, immobilization, and analgesia will be collected. These will also be repeated annually until the child reaches the age of 16 years. Four weeks after injury, the main outcomes plus data on complications, resource use, and school absence will be collected. The primary outcome is the PROMIS upper limb score at 12 months post-randomization. All data will be obtained through electronic questionnaires completed by the participants and/or parents/guardians. The NHS number of participants will be stored to enable future data linkage to sources of routinely collected data (i.e. Hospital Episode Statistics).

Service availability and readiness for hip fracture care in low- and middle-income countries in South and Southeast Asia.

Aims: The aim of this study was to describe the current pathways of care for patients with a fracture of the hip in five low- and middle-income countries (LMIC) in South Asia (Nepal and Sri Lanka) and Southeast Asia (Malaysia, Thailand, and the Philippines). Methods: The World Health Organization Service Availability and Readiness Assessment tool was used to collect data on the care of hip fractures in Malaysia, Thailand, the Philippines, Sri Lanka, and Nepal. Respondents were asked to provide details about the current pathway of care for patients with hip fracture, including pre-hospital transport, time to admission, time to surgery, and time to weightbearing, along with healthcare professionals involved at different stages of care, information on discharge, and patient follow-up. Results: Responses were received from 98 representative hospitals across the five countries. Most hospitals were publicly funded. There was consistency in clinical pathways of care within country, but considerable variation between countries. Patients mostly travel to hospital via ambulance (both publicly- and privately-funded) or private transport, with only half arriving at hospital within 12 hours of their injury. Access to surgery was variable and time to surgery ranged between one day and more than five days. The majority of hospitals mobilized patients on the first or second day after surgery, but there was notable variation in postoperative weightbearing protocols. Senior medical input was variable and specialist orthogeriatric expertise was unavailable in most hospitals. Conclusion: This study provides the first step in mapping care pathways for patients with hip fracture in LMIC in South Asia. The previous lack of data in these countries hampers efforts to identify quality standards (key performance indicators) that are relevant to each different healthcare system.

Randomised controlled trial comparing intraoperative cell salvage and autotransfusion with standard care in the treatment of hip fractures: a protocol for the WHITE 9 study.

INTRODUCTION: People who sustain a hip fracture are typically elderly, frail and require urgent surgery. Hip fracture and the urgent surgery is associated with acute blood loss, compounding patients' pre-existing comorbidities including anaemia. Approximately 30% of patients require a donor blood transfusion in the perioperative period. Donor blood transfusions are associated with increased rates of infections, allergic reactions and longer lengths of stay. Furthermore, there is a substantial cost associated with the use of donor blood. Cell salvage and autotransfusion is a technique that recovers, washes and transfuses blood lost during surgery back to the patient. The objective of this study is to determine the clinical and cost effectiveness of intraoperative cell salvage, compared with standard care, in improving health related quality-of-life of patients undergoing hip fracture surgery. METHODS AND ANALYSIS: Multicentre, parallel group, two-arm, randomised controlled trial. Patients aged 60 years and older with a hip fracture treated with surgery are eligible. Participants will be randomly allocated on a 1:1 basis to either undergo cell salvage and autotransfusion or they will follow the standard care pathway. Otherwise, all care will be in accordance with the National Institute for Health and Care Excellence guidance. A minimum of 1128 patients will be recruited to obtain 90% power to detect a 0.075-point difference in the primary endpoint: EuroQol-5D-5L HRQoL at 4 months post injury. Secondary outcomes will include complications, postoperative delirium, residential status, mobility, allogenic blood use, mortality and resource use. ETHICS AND DISSEMINATION: NHS ethical approval was provided on 14 August 2019 (19/WA/0197) and the trial registered (ISRCTN15945622). After the conclusion of this trial, a manuscript will be prepared for peer-review publication. Results will be disseminated in lay form to participants and the public. TRIAL REGISTRATION NUMBER: ISRCTN15945622.

The British Orthopaedic Surgery Surveillance study: Perthes' disease: the epidemiology and two-year outcomes from a prospective cohort in Great Britain.

AIMS: The aim of this study was to evaluate the epidemiology and treatment of Perthes' disease of the hip. METHODS: This was an anonymized comprehensive cohort study of Perthes' disease, with a nested consented cohort. A total of 143 of 144 hospitals treating children's hip disease in the UK participated over an 18-month period. Cases were cross-checked using a secondary independent reporting network of trainee surgeons to minimize those missing. Clinician-reported outcomes were collected until two years. Patient-reported outcome measures (PROMs) were collected for a subset of participants. RESULTS: Overall, 371 children (396 hips) were newly affected by Perthes' disease arising from 63 hospitals, with a median of two patients (interquartile range 1.0 to 5.5) per hospital. The annual incidence was 2.48 patients (95% confidence interval (CI) 2.20 to 2.76) per 100,000 zero- to 14-year-olds. Of these, 117 hips (36.4%) were treated surgically. There was considerable variation in the treatment strategy, and an optimized decision tree identified joint stiffness and age above eight years as the key determinants for containment surgery. A total of 348 hips (88.5%) had outcomes to two years, of which 227 were in the late reossification stage for which a hip shape outcome (Stulberg grade) was assigned. The independent predictors of a poorer radiological outcome were female sex (odds ratio (OR) 2.27 (95% CI 1.19 to 4.35)), age above six years (OR 2.62 (95% CI (1.30 to 5.28)), and over 50% radiological collapse at inclusion (OR 2.19 (95% CI 0.99 to 4.83)). Surgery had no effect on radiological outcomes (OR 1.03 (95% CI 0.55 to 1.96)). PROMs indicated the marked effect of the disease on the child, which persisted at two years. CONCLUSION: Despite the frequency of containment surgery, we found no evidence of improved outcomes. There appears to be a sufficient case volume and community equipoise among surgeons to embark on a randomized clinical trial to definitively investigate the effectiveness of containment surgery. Cite this article: Bone Joint J 2022;104-B(4):510-518.

The British Orthopaedic Surgery Surveillance study: slipped capital femoral epiphysis: the epidemiology and two-year outcomes from a prospective cohort in Great Britain.

AIMS: The aim of this study was to inform the epidemiology and treatment of slipped capital femoral epiphysis (SCFE). METHODS: This was an anonymized comprehensive cohort study, with a nested consented cohort, following the the Idea, Development, Exploration, Assessment, Long-term study (IDEAL) framework. A total of 143 of 144 hospitals treating SCFE in Great Britain participated over an 18-month period. Patients were cross-checked against national administrative data and potential missing patients were identified. Clinician-reported outcomes were collected until two years. Patient-reported outcome measures (PROMs) were collected for a subset of participants. RESULTS: A total of 486 children (513 hips) were newly affected, with a median of two patients (interquartile range 0 to 4) per hospital. The annual incidence was 3.34 (95% confidence interval (CI) 3.01 to 3.67) per 100,000 six- to 18-year-olds. Time to diagnosis in stable disease was increased in severe deformity. There was considerable variation in surgical strategy among those unable to walk at diagnosis (66 urgent surgery vs 43 surgery after interval delay), those with severe radiological deformity (34 fixation with deformity correction vs 36 without correction) and those with unaffected opposite hips (120 prophylactic fixation vs 286 no fixation). Independent risk factors for avascular necrosis (AVN) were the inability of the child to walk at presentation to hospital (adjusted odds ratio (aOR) 4.4 (95% CI 1.7 to 11.4)) and surgical technique of open reduction and internal fixation (aOR 7.5 (95% CI 2.4 to 23.2)). Overall, 33 unaffected untreated opposite hips (11.5%) were treated for SCFE by two-year follow-up. Age was the only independent risk factor for contralateral SCFE, with age under 12.5 years the optimal cut-off to define 'at risk'. Of hips treated with prophylactic fixation, none had SCFE, though complications included femoral fracture, AVN, and revision surgery. PROMs demonstrated the marked impact on quality of life on the child because of SCFE. CONCLUSION: The experience of individual hospitals is limited and mechanisms to consolidate learning may enhance care. Diagnostic delays were common and radiological severity worsened with increasing time to diagnosis. There was unexplained variation in treatment, some of which exposes children to significant risks that should be evaluated through randomized controlled trials. Cite this article: Bone Joint J 2022;104-B(4):519-528.

A protocol for a nationwide multicentre, prospective surveillance cohort and nested-consented cohort to determine the incidence and clinical outcomes of slipped capital femoral epiphysis.

AIMS: Slipped capital femoral epiphysis (SCFE) is one of the most common hip diseases of adolescence that can cause marked disability, yet there is little robust evidence to guide treatment. Fundamental aspects of the disease, such as frequency, are unknown and consequently the desire of clinicians to undertake robust intervention studies is somewhat prohibited by a lack of fundamental knowledge. METHODS: The study is an anonymized nationwide comprehensive cohort study with nested consented within the mechanism of the British Orthopaedic Surgery Surveillance (BOSS) Study. All relevant hospitals treating SCFE in England, Scotland, and Wales will contribute anonymized case details. Potential missing cases will be cross-checked against two independent external sources of data (the national administrative data and independent trainee data). Patients will be invited to enrich the data collected by supplementing anonymized case data with patient-reported outcome measures. In line with recommendations of the IDEAL Collaboration, the study will primarily seek to determine incidence, describe case mix and variations in surgical interventions, and explore the relationships between baseline factors (patients and types of interventions) and two-year outcomes. DISCUSSION: This is the first disease to be investigated using the BOSS Study infrastructure. It provides a robust method to determine the disease frequency, and a large unbiased sample of cases from which treatment strategies can be investigated. It may form the basis for definitive robust intervention studies or, where these are demonstrated not to be feasible, this may be the most robust cohort study.

The BOSS Study. Determining the incidence and clinical outcomes of uncommon conditions and events in orthopaedic surgery.

INTRODUCTION: There is widespread variation in the management of rare orthopaedic disease, in a large part owing to uncertainty. No individual surgeon or hospital is typically equipped to amass sufficient numbers of cases to draw robust conclusions from the information available to them. The programme of research will establish the British Orthopaedic Surgery Surveillance (BOSS) Study; a nationwide reporting structure for rare disease in orthopaedic surgery. METHODS: The BOSS Study is a series of nationwide observational cohort studies of pre-specified orthopaedic disease. All relevant hospitals treating the disease are invited to contribute anonymised case details. Data will be collected digitally through REDCap, with an additional bespoke software solution used to regularly confirm case ascertainment, prompt follow-up reminders and identify potential missing cases from external sources of information (i.e. national administrative data). With their consent, patients will be invited to enrich the data collected by supplementing anonymised case data with patient reported outcomes.The study will primarily seek to calculate the incidence of the rare diseases under investigation, with 95% confidence intervals. Descriptive statistics will be used to describe the case mix, treatment variations and outcomes. Inferential statistical analysis may be used to analyze associations between presentation factors and outcomes. Types of analyses will be contingent on the disease under investigation. DISCUSSION: This study builds upon other national rare disease supporting structures, particularly those in obstetrics and paediatric surgery. It is particularly focused on addressing the evidence base for quality and safety of surgery, and the design is influenced by the specifications of the IDEAL collaboration for the development of surgical research.

Individualised screening for diabetic retinopathy: the ISDR study-rationale, design and methodology for a randomised controlled trial comparing annual and individualised risk-based variable-interval screening.

INTRODUCTION: Currently, all people with diabetes (PWD) aged 12 years and over in the UK are invited for screening for diabetic retinopathy (DR) annually. Resources are not increasing despite a 5% increase in the numbers of PWD nationwide each year. We describe the rationale, design and methodology for a randomised controlled trial (RCT) evaluating the safety, acceptability and cost-effectiveness of personalised variable-interval risk-based screening for DR. This is the first randomised trial of personalised screening for DR and the largest ophthalmic RCT in the UK. METHODS AND ANALYSIS: PWD attending seven screening clinics in the Liverpool Diabetic Eye Screening Programme were recruited into a single site RCT with a 1:1 allocation to individualised risk-based variable-interval or annual screening intervals. A risk calculation engine developed for the trial estimates the probability that an individual will develop referable disease (screen positive DR) within the next 6, 12 or 24 months using demographic, retinopathy and systemic risk factor data from primary care and screening programme records. Dynamic, secure, real-time data connections have been developed. The primary outcome is attendance for follow-up screening. We will test for equivalence in attendance rates between the two arms. Secondary outcomes are rates and severity of DR, visual outcomes, cost-effectiveness and health-related quality of life. The required sample size was 4460 PWD. Recruitment is complete, and the trial is in follow-up. ETHICS AND DISSEMINATION: Ethical approval was obtained from National Research Ethics Service Committee North West - Preston, reference 14/NW/0034. Results will be presented at international meetings and published in peer-reviewed journals. This pragmatic RCT will inform screening policy in the UK and elsewhere. TRIAL REGISTRATION NUMBER: ISRCTN87561257; Pre-results.

A software program to assist coding of prelinguistic vocalizations in real time.

Numerous studies have confirmed that prelinguistic utterances are precursors to speech, and there is ample evidence that, for example, frequency of canonical syllables and syllable inventory size correlate with speech and language measures at older ages. Traditionally, prelinguistic utterances have been assessed by phonetic transcription which is difficult and time-consuming in infants. Recently, a more time-efficient methodology to assess prelinguistic utterances in real time, called naturalistic listening, was developed (Ramsdell et al., 2012). In a large international NIDCR-funded randomized controlled trial, Timing of Primary Surgery for with Cleft Palate (TOPS), including many coders, a software program (TimeStamper) was developed to assist in coding of prelinguistic vocalizations in real time, to ensure consistency of the coding procedures. Coders upload a video (or audio) file and watch and listen to the recording in real time without any possibility of pausing or taking notes. In real time, the coder registers each speech-like syllable as canonical or non-canonical. TimeStamper automatically calculates the percentage of canonical syllables of all syllables registered (canonical babbling ratio). At the end of a recording, TimeStamper assists in assessing presence/absence of canonical babbling and syllable inventory size. The software is presented and instructions for free access are provided.