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.

Pre-existing musculoskeletal pain and its association with mortality in newly diagnosed co-morbid conditions: an electronic health record cohort study.

Objective: Musculoskeletal pain is a common risk factor for co-morbid conditions and might increase the risk of poor outcomes. The objective was to determine whether patients with pre-existing musculoskeletal pain have an increased risk for mortality following a new diagnosis of a co-morbid condition. Methods: Patients aged ≥45 years with a new diagnosis of acute coronary syndrome (ACS), stroke, cancer, dementia or pneumonia recorded in a UK electronic primary care database linked to hospital and mortality records were examined. The association of mortality with musculoskeletal pain (inflammatory conditions, OA and regional pain) was determined. Results: The sample size varied from 128 649 (stroke) to 406 289 (cancer) by cohort, with 22-31% having pre-existing musculoskeletal conditions. In the ACS cohort, there was a higher rate of mortality for all musculoskeletal types. There were also higher unadjusted mortality rates in patients with inflammatory arthritis compared with those without musculoskeletal pain in the stroke, cancer and dementia cohorts and for patients with OA in the stroke and cancer cohorts. After adjustment for the number of prescribed medications and age, the increased risk of mortality remained only for patients with inflammatory arthritis in the ACS cohort (adjusted hazard ratio = 1.07; 95% CI 1.03, 1.10). Conclusion: Older adults with inflammatory arthritis and OA have increased risk of mortality when they develop a new condition, which seems to be related to the prescription of multiple medicines. Pre-existing musculoskeletal pain is an indicator of a complex patient who is at risk of poorer outcomes at the onset of new illnesses.

Estimating the direct healthcare utilization and cost of musculoskeletal pain among people with comorbidity: a retrospective electronic health record study.

OBJECTIVE: To investigate the impact of pre-existing painful musculoskeletal conditions on healthcare utilization and costs among patients with five common conditions: acute coronary syndrome (ACS), stroke, cancer, dementia and pneumonia. METHODS: Using primary and secondary care services data from electronic health records, a negative binomial regression model was used to compare resource use while a two-part model was used to compare costs across the five conditions, between those with and without a pre-existing musculoskeletal pain. RESULTS: The study included 760,792 patients (144,870 with ACS, 121,208 with stroke, 231,702 with cancer, 134,638 with dementia, and 128,374 with pneumonia) in the complete case analysis. Pre-existing musculoskeletal pain had an incident rate ratio of above one for most healthcare resources over the follow-up period and an adjusted additional mean cumulative total healthcare costs per patient of £674.59 (95%CI 570.30 to 778.87) for ACS; £613.34 (95%CI 496.87 to 729.82) for stroke; £459.26 (95%CI 376.60 to 541.91) for cancer; and £766.23 (95%CI 655.06 to 877.39) for dementia over five years after diagnosis; and £200.85 (95%CI 104.16 to 297.55) for pneumonia over one year after diagnosis compared to those without musculoskeletal pain. CONCLUSION: This study highlights that individuals with painful musculoskeletal conditions have higher healthcare utiliszation and costs than those without painful musculoskeletal conditions. Given the high occurrence of musculoskeletal pain in patients with other conditions, effective management strategies are needed to reduce the burden on healthcare resources.

CARE: Protocol of a randomised trial evaluating the feasibility of preoperative intentional weight loss to support postoperative recovery in patients with excess weight and colorectal cancer.

AIM: Excess weight increases the risk of morbidity following colorectal cancer surgery. Weight loss may improve morbidity, but it is uncertain whether patients can follow an intensive weight loss intervention while waiting for surgery and there are concerns about muscle mass loss. The aim of this trial is to assess the feasibility of intentional weight loss in this setting and determine progression to a definitive trial. METHODS: CARE is a prospectively registered, multicentre, feasibility, parallel, randomised controlled trial with embedded evaluation and optimisation of the recruitment process. Participants with excess weight awaiting curative colorectal resection for cancer are randomised 1:1 to care as usual or a low-energy nutritionally-replete total diet replacement programme with weekly remote behavioural support by a dietitian. Progression criteria will be based on the recruitment, engagement, adherence, and retention rates. Data will be collected on the 30-day postoperative morbidity, the typical primary outcome of prehabilitation trials. Secondary outcomes will include, among others, length of hospital stay, health-related quality of life, and body composition. Qualitative interviews will be used to understand patients' experiences of and attitudes towards trial participation and intervention engagement and adherence. CONCLUSION: CARE will evaluate the feasibility of intensive intentional weight loss as prehabilitation before colorectal cancer surgery. The results will determine the planning of a definitive trial.

Musculoskeletal pain and its impact on prognosis following acute coronary syndrome or stroke: A linked electronic health record cohort study.

OBJECTIVE: Musculoskeletal painful conditions are a risk factor for cardiovascular disease (CVD), but less is known about whether musculoskeletal pain also worsens prognosis from CVD. The objective was to determine whether patients with musculoskeletal pain have poorer prognosis following acute coronary syndrome (ACS) or stroke. METHODS: The study utilised UK electronic primary care records (CPRD Aurum) with linkage to hospital and mortality records. Patients aged ≥45 years admitted to hospital with incident ACS/stroke were categorised by healthcare use for musculoskeletal pain (inflammatory conditions, osteoarthritis [OA], and regional pain) based on primary care consultations in the prior 24 months. Outcomes included mortality, length of stay, readmission and management of index condition (ACS/stroke). RESULTS: There were 171,670 patients with incident ACS and 138,512 with stroke; 30% consulted for musculoskeletal pain prior to ACS/stroke and these patients had more comorbidity than those without musculoskeletal pain. Rates of mortality and readmission, and length of stay were higher in those with musculoskeletal pain, particularly OA and inflammatory conditions, in ACS. Readmission was also higher for patients with musculoskeletal pain in stroke. However, increased risks associated with musculoskeletal pain did not remain after adjustment for age and polypharmacy. Inflammatory conditions were associated with increased likelihood of prescriptions for dual anti-platelets (ACS only) and anti-coagulants. CONCLUSIONS: Patients with musculoskeletal pain have higher rates of poor outcome from ACS which relates to being older but also increased polypharmacy. The high rates of comorbidity including polypharmacy highlight the complexity of patients with musculoskeletal pain who have new onset ACS/stroke.

Arthroscopic hip surgery compared with personalised hip therapy in people over 16 years old with femoroacetabular impingement syndrome: UK FASHIoN RCT.

BACKGROUND: Femoroacetabular impingement syndrome is an important cause of hip pain in young adults. It can be treated by arthroscopic hip surgery or with physiotherapist-led conservative care. OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of hip arthroscopy with best conservative care. DESIGN: The UK FASHIoN (full trial of arthroscopic surgery for hip impingement compared with non-operative care) trial was a pragmatic, multicentre, randomised controlled trial that was carried out at 23 NHS hospitals. PARTICIPANTS: Participants were included if they had femoroacetabular impingement, were aged ≥ 16 years old, had hip pain with radiographic features of cam or pincer morphology (but no osteoarthritis) and were believed to be likely to benefit from hip arthroscopy. INTERVENTION: Participants were randomly allocated (1 : 1) to receive hip arthroscopy followed by postoperative physiotherapy, or personalised hip therapy (i.e. an individualised physiotherapist-led programme of conservative care). Randomisation was stratified by impingement type and recruiting centre using a central telephone randomisation service. Outcome assessment and analysis were masked. MAIN OUTCOME MEASURE: The primary outcome was hip-related quality of life, measured by the patient-reported International Hip Outcome Tool (iHOT-33) 12 months after randomisation, and analysed by intention to treat. RESULTS: Between July 2012 and July 2016, 648 eligible patients were identified and 348 participants were recruited. In total, 171 participants were allocated to receive hip arthroscopy and 177 participants were allocated to receive personalised hip therapy. Three further patients were excluded from the trial after randomisation because they did not meet the eligibility criteria. Follow-up at the primary outcome assessment was 92% (N = 319; hip arthroscopy, n = 157; personalised hip therapy, n = 162). At 12 months, mean International Hip Outcome Tool (iHOT-33) score had improved from 39.2 (standard deviation 20.9) points to 58.8 (standard deviation 27.2) points for participants in the hip arthroscopy group, and from 35.6 (standard deviation 18.2) points to 49.7 (standard deviation 25.5) points for participants in personalised hip therapy group. In the primary analysis, the mean difference in International Hip Outcome Tool scores, adjusted for impingement type, sex, baseline International Hip Outcome Tool score and centre, was 6.8 (95% confidence interval 1.7 to 12.0) points in favour of hip arthroscopy (p = 0.0093). This estimate of treatment effect exceeded the minimum clinically important difference (6.1 points). Five (83%) of six serious adverse events in the hip arthroscopy group were related to treatment and one serious adverse event in the personalised hip therapy group was not. Thirty-eight (24%) personalised hip therapy patients chose to have hip arthroscopy between 1 and 3 years after randomisation. Nineteen (12%) hip arthroscopy patients had a revision arthroscopy. Eleven (7%) personalised hip therapy patients and three (2%) hip arthroscopy patients had a hip replacement within 3 years. LIMITATIONS: Study participants and treating clinicians were not blinded to the intervention arm. Delays were encountered in participants accessing treatment, particularly surgery. Follow-up lasted for 3 years. CONCLUSION: Hip arthroscopy and personalised hip therapy both improved hip-related quality of life for patients with femoroacetabular impingement syndrome. Hip arthroscopy led to a greater improvement in quality of life than personalised hip therapy, and this difference was clinically significant at 12 months. This study does not demonstrate cost-effectiveness of hip arthroscopy compared with personalised hip therapy within the first 12 months. Further follow-up will reveal whether or not the clinical benefits of hip arthroscopy are maintained and whether or not it is cost-effective in the long term. TRIAL REGISTRATION: Current Controlled Trials ISRCTN64081839. 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. 26, No. 16. See the NIHR Journals Library website for further project information.

In some people, the ball and the socket of the hip joint develop so that they do not fit together properly. This is called hip impingement, and is an important cause of hip and groin pain in young and middle-aged adults. Treatments include physiotherapy and surgery. Physiotherapy typically involves a programme of 6­10 outpatient consultations that aim to strengthen the muscles around the hip: we called this personalised hip therapy. Surgery can be carried out by a keyhole operation, called a hip arthroscopy, which aims to reshape the hip to prevent impingement. Surgery is normally followed by some physiotherapy. We performed a research study to compare the results of hip arthroscopy and personalised hip therapy in people with hip impingement. A total of 348 people with painful hip impingement in 23 hospitals in the UK agreed to take part. About half were treated with hip arthroscopy and half with personalised hip therapy. We used questionnaires to ask participants about pain in the hip and their ability to do everyday things at 6 months and 1 year after entering the study. At 2 and 3 years, we asked if patients required any additional treatments. We found that both groups improved, but those treated with hip arthroscopy improved a moderate amount more than those treated with personalised hip therapy. However, these improvements were not cost-effective compared with personalised hip therapy at 1 year. We need to see whether or not this difference continues after several years, but the results, so far, suggest that if a person has painful hip impingement, then hip arthroscopy offers greater improvements than personalised hip therapy.

Extracorporeal Life Support for Refractory Cardiac Arrest: A 10-Year Comparative Analysis.

BACKGROUND: Cardiopulmonary resuscitation of cardiac arrest has poor outcomes. Extracorporeal life support (ECLS) could represent a salvage option. This study aimed to analyze the outcomes of ECLS used for refractory cardiac arrest. METHODS: In this observational analysis, patients were divided into an in-hospital cardiac arrest group (IHCA) and an out-of-hospital (OHCA) cardiac arrest group. The primary end point was survival to hospital discharge with good neurologic outcome. Both groups were compared after propensity score matching. Risk factors were searched with multivariate analyses. RESULTS: From January 2007 to December 2016, study investigators performed 131 ECLS procedures (IHCA, n = 45, 34.4%; OHCA, n = 86, 65.6%). The mean age of patients was 43.2 years, and 71.8% were male. Baseline characteristics were comparable between both groups except mean no-flow duration (0.2 minutes vs 2.5 minutes; p < 0.001) and low-flow duration (46.9 minutes vs 85.3 minutes; p < 0.001), which were significantly shorter in the IHCA group. A total of 103 (82.4%) patients died during ECLS (IHCA, 79.1% vs OHCA, 84.1%; p = 0.479). The complication rate during ECLS was comparable between both groups. Twenty (16%) patients were successfully weaned from ECLS (IHCA, 18.6% vs OHCA, 14.6%; p = 0.565) after a mean support period of 6.7 days. Survival to hospital discharge with good neurologic outcome was not different between the two matched groups (odds ratioOHCA vs IHCA 1.3; 95% confidence interval, 0.023 to 74.902; p = 0.9). Presence of shockable rhythm was associated with a better outcome (odds ratioshockable vs nonshockable 6.674; 95% confidence interval, 1.078 to 41.336; p = 0.044). CONCLUSIONS: Patients in the IHCA and OHCA groups experienced the same survival with good neurologic outcome after ECLS support. A better selection of patients with IHCA is mandatory to avoid futile support.

Hip arthroscopy versus best conservative care for the treatment of femoroacetabular impingement syndrome (UK FASHIoN): a multicentre randomised controlled trial.

BACKGROUND: Femoroacetabular impingement syndrome is an important cause of hip pain in young adults. It can be treated by arthroscopic hip surgery, including reshaping the hip, or with physiotherapist-led conservative care. We aimed to compare the clinical effectiveness of hip arthroscopy with best conservative care. METHODS: UK FASHIoN is a pragmatic, multicentre, assessor-blinded randomised controlled trial, done at 23 National Health Service hospitals in the UK. We enrolled patients with femoroacetabular impingement syndrome who presented at these hospitals. Eligible patients were at least 16 years old, had hip pain with radiographic features of cam or pincer morphology but no osteoarthritis, and were believed to be likely to benefit from hip arthroscopy. Patients with bilateral femoroacetabular impingement syndrome were eligible; only the most symptomatic hip was randomly assigned to treatment and followed-up. Participants were randomly allocated (1:1) to receive hip arthroscopy or personalised hip therapy (an individualised, supervised, and progressive physiotherapist-led programme of conservative care). Randomisation was stratified by impingement type and recruiting centre and was done by research staff at each hospital, using a central telephone randomisation service. Patients and treating clinicians were not masked to treatment allocation, but researchers who collected the outcome assessments and analysed the results were masked. The primary outcome was hip-related quality of life, as measured by the patient-reported International Hip Outcome Tool (iHOT-33) 12 months after randomisation, and analysed in all eligible participants who were allocated to treatment (the intention-to-treat population). This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN64081839, and is closed to recruitment. FINDINGS: Between July 20, 2012, and July 15, 2016, we identified 648 eligible patients and recruited 348 participants: 171 participants were allocated to receive hip arthroscopy and 177 to receive personalised hip therapy. Three further patients were excluded from the trial after randomisation because they did not meet the eligibility criteria. Follow-up at the primary outcome assessment was 92% (319 of 348 participants). At 12 months after randomisation, mean iHOT-33 scores had improved from 39·2 (SD 20·9) to 58·8 (27·2) for participants in the hip arthroscopy group, and from 35·6 (18·2) to 49·7 (25·5) in the personalised hip therapy group. In the primary analysis, the mean difference in iHOT-33 scores, adjusted for impingement type, sex, baseline iHOT-33 score, and centre, was 6·8 (95% CI 1·7-12·0) in favour of hip arthroscopy (p=0·0093). This estimate of treatment effect exceeded the minimum clinically important difference (6·1 points). There were 147 patient-reported adverse events (in 100 [72%] of 138 patients) in the hip arthroscopy group) versus 102 events (in 88 [60%] of 146 patients) in the personalised hip therapy group, with muscle soreness being the most common of these (58 [42%] vs 69 [47%]). There were seven serious adverse events reported by participating hospitals. Five (83%) of six serious adverse events in the hip arthroscopy group were related to treatment, and the one in the personalised hip therapy group was not. There were no treatment-related deaths, but one patient in the hip arthroscopy group developed a hip joint infection after surgery. INTERPRETATION: Hip arthroscopy and personalised hip therapy both improved hip-related quality of life for patients with femoroacetabular impingement syndrome. Hip arthroscopy led to a greater improvement than did personalised hip therapy, and this difference was clinically significant. Further follow-up will reveal whether the clinical benefits of hip arthroscopy are maintained and whether it is cost effective in the long term. FUNDING: The Health Technology Assessment Programme of the National Institute of Health Research.

Systematic Review and Meta-Analysis of Response Rates and Diagnostic Yield of Screening for Type 2 Diabetes and Those at High Risk of Diabetes.

BACKGROUND: Screening for type 2 diabetes (T2DM) and individuals at risk of diabetes has been advocated, yet information on the response rate and diagnostic yield of different screening strategies are lacking. METHODS: Studies (from 1998 to March/2015) were identified through Medline, Embase and the Cochrane library and included if they used oral glucose tolerance test (OGTT) and WHO-1998 diagnostic criteria for screening in a community setting. Studies were one-step strategy if participants were invited directly for OGTT and two, three/four step if participants were screened at one or more levels prior to invitation to OGTT. The response rate and diagnostic yield were pooled using Bayesian random-effect meta-analyses. FINDINGS: 47 studies (422754 participants); 29 one-step, 11 two-step and seven three/four-step were identified. Pooled response rate (95% Credible Interval) for invitation to OGTT was 65.5% (53.7, 75.6), 63.1% (44.0, 76.8), and 85.4% (76.4, 93.3) in one, two and three/four-step studies respectively. T2DM yield was 6.6% (5.3, 7.8), 13.1% (4.3, 30.9) and 27.9% (8.6, 66.3) for one, two and three/four-step strategies respectively. The number needed to invite to the OGTT to detect one case of T2DM was 15, 7.6 and 3.6 in one, two, and three/four-step strategies. In two step strategies, there was no difference between the response or yield rates whether the first step was blood test or risk-score. There was evidence of substantial heterogeneity in rates across study populations but this was not explained by the method of invitation, study location (rural versus urban) and developmental index of the country in which the study was performed. CONCLUSIONS: Irrespective of the invitation method, developmental status of the countries and or rural/urban location, using a multi-step strategy increases the initial response rate to the invitation to screening for diabetes and reduces the number needed to have the final diagnostic test (OGTT in this study) for a definite diagnosis.

Extending methods for investigating the relationship between treatment effect and baseline risk from pairwise meta-analysis to network meta-analysis.

Baseline risk is a proxy for unmeasured but important patient-level characteristics, which may be modifiers of treatment effect, and is a potential source of heterogeneity in meta-analysis. Models adjusting for baseline risk have been developed for pairwise meta-analysis using the observed event rate in the placebo arm and taking into account the measurement error in the covariate to ensure that an unbiased estimate of the relationship is obtained. Our objective is to extend these methods to network meta-analysis where it is of interest to adjust for baseline imbalances in the non-intervention group event rate to reduce both heterogeneity and possibly inconsistency. This objective is complicated in network meta-analysis by this covariate being sometimes missing, because of the fact that not all studies in a network may have a non-active intervention arm. A random-effects meta-regression model allowing for inclusion of multi-arm trials and trials without a 'non-intervention' arm is developed. Analyses are conducted within a Bayesian framework using the WinBUGS software. The method is illustrated using two examples: (i) interventions to promote functional smoke alarm ownership by households with children and (ii) analgesics to reduce post-operative morphine consumption following a major surgery. The results showed no evidence of baseline effect in the smoke alarm example, but the analgesics example shows that the adjustment can greatly reduce heterogeneity and improve overall model fit.