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Abstract Background Hip fracture surgery under general or spinal anesthesia is a common procedure for older adults in the United States (US). Although spinal or general anesthesia can be appropriate for many patients, and the choice between anesthesia types is preference-sensitive, shared decision-making is not consistently used by anesthesiologists counseling patients on anesthesia for this procedure. We designed an Option Grid™-style conversation aid, My Anesthesia Choice─Hip Fracture, to promote shared decision making in this interaction. This study will refine the aid and evaluate its implementation and effectiveness in clinical practice. Methods The study will be conducted over 2 phases: qualitative interviews with relevant clinicians and patients to refine the aid, followed by a stepped wedge cluster randomized trial of the intervention at 6 settings in the US. Primary outcomes will include the percentage of eligible patients who receive the intervention (intervention reach) and the change in quality of patient/clinician communication (intervention effectiveness). Secondary outcomes addressing other RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) domains will also be collected. Outcomes will be compared between baseline data and an active implementation period and then compared between the active implementation period and a sustainment period. Implementation strategies are guided by three constructs from the Practical, Robust Implementation and Sustainability Model (PRISM): intervention, recipients, and implementation and sustainability infrastructure. Discussion This is a novel, large-scale trial evaluating and implementing a shared decision-making conversation aid for anesthesia choices. Strong buy-in from site leads and expert advisors will support both the success of implementation and the future dissemination of results and the intervention. Results from this study will inform the broader implementation of this aid for patients with hip fractures and can lead to the development and implementation of similar conversation aids for other anesthesia choices. Trial registration ClinicalTrials.gov, NCT06438640

Introduction Physical frailty is associated with increased mortality and poor quality of life (QoL) before and after liver transplantation (LT). Evidence is lacking on how to tailor exercise and behavioural techniques in this patient population.Methods and analysis Home-based EXercise and motivAtional programme before and after Liver Transplantation (EXALT) is a phase 2b, open-label, two-centre randomised controlled clinical trial designed to investigate whether a remotely monitored ‘home-based exercise and theory-based motivation support programme (HBEP)’ before and after LT improves QoL in LT recipients. Adult patients awaiting a primary LT will be assessed for eligibility at two LT centres (Birmingham, Royal Free London). Participants will be randomly assigned (1:1) to receive either an HBEP while on the LT waiting list through to 24 weeks after LT (Intervention) or a patient exercise advice leaflet (Control). Using a standard method of difference in means (two-sided significance level 0.05; power 0.90) and accounting for a 35% attrition/withdrawal rate, a minimum of 133 patients will be randomised to each treatment group. The primary outcome measure will be assessed using intention-to-treat analysis of the difference in the Physical Component Score of Short form-36 version 2.0 health-related QoL questionnaire between the groups at 24 weeks post-LT.Ethics and dissemination The protocol was approved by the South Central-Hampshire A National Research Ethics Committee. Recruitment into the EXALT trial started in May 2022 and is due to end in June 2024, with 217/266 patients randomised to date. The intervention follow-up is due to finish in May 2026. The findings of this trial will be disseminated through peer-reviewed publications, conferences and social media.Trial registration number ISRCTN13476586.

Abstract. Background:. Despite the recent emphasis on promoting international collaborations within orthopaedic surgery, criteria for determining the strengths of such partnerships has not been established. The purpose of this study was to evaluate orthopaedic experts' perceptions of the most valuable characteristics of international academic partnerships. Methods:. This study was conducted using a modified Delphi methodology. Experts were identified through the Consortium of Orthopaedic Academic Traumatologists (COACT). Responses were collected from February to September 2022. Three rounds of surveys listing possible topics on a 5-point Likert scale were used to develop consensus among a group of experts. Consensus criteria for topic inclusion in the final scale was determined as a rating of “strongly agree” or “agree” by ≥70% of the participants in the third survey. Results:. The Round 1 survey was distributed to 96 invited participants within the COACT network, of which 50 experts (52.1%) completed the first survey. Consensus was reached on 54 topics organized into the following 5 categories: Research, Advocacy/Leadership, Training/Surgical Skills, Education/Knowledge Exchange, and Sustainability and Safety (RATES Criteria). Conclusions:. Determining the most valuable characteristics of successful international academic partnerships can lead to more sustainable, mutually beneficial collaborations. The criteria identified in this study can provide the foundation for developing new partnerships and assessing existing ones.

Research question Is withholding anticoagulation for patients with isolated or incidental subsegmental pulmonary embolism clinically and cost-effective compared with full anticoagulation for 3 months? Background There has been an increase in the diagnosis of subsegmental pulmonary embolism since the advent of computed tomography pulmonary angiogram to investigate patients with suspected pulmonary embolism. Subsegmental pulmonary embolism is not often detectable with older nuclear medicine-based diagnostic imaging for ventilation/perfusion mismatch. The case fatality of pulmonary embolism has reduced as subsegmental pulmonary embolism diagnoses from computed tomography pulmonary angiogram have increased. There is growing equipoise about the optimal treatment for patients with subsegmental pulmonary embolism, given that full anticoagulation has significant risks of bleeding and subsegmental pulmonary embolism was not often diagnosed previously with ventilation/perfusion scanning and therefore most likely left predominantly untreated prior to the introduction of computed tomography pulmonary angiogram scanning. Objectives Determine whether withholding anticoagulation for isolated or incidental subsegmental pulmonary embolism (i.e. subsegmental pulmonary embolism with no coexisting deep-vein thrombosis) reduces the harms of recurrent thromboembolism and major bleeding compared with 3 months of full anticoagulation at 3, 6 and 12 months. Determine the rate of complications of anticoagulation therapy (predominantly bleeding) in patients with isolated subsegmental pulmonary embolism. Determine whether not treating isolated subsegmental pulmonary embolism is acceptable to clinicians and patients. Determine the reclassification rate of subsegmental pulmonary embolism diagnoses made by general reporting radiologists when reviewed by specialist respiratory radiologists and develop a set of rules to improve general radiologists’ diagnoses of subsegmental pulmonary embolism. Assess cost-effectiveness of not treating patients with isolated subsegmental pulmonary embolism with anticoagulation, taking a health service perspective. Methods Prospective individually randomised open controlled trial with blinded end-point committee assessment for outcomes, powered for non-inferiority for recurrent venous thromboembolism and for superiority for bleeding events. An internal pilot phase is included for feasibility and acceptability of no anticoagulation. We planned to recruit 1466 patients from at least 50 acute hospital sites. Allowing for a dropout rate of 15%, this would have given us 90% power to detect a reduction in major and clinically relevant non-major bleeding from 7.3% in the anticoagulation arm to 3% in the intervention arm. We were powered to determine that a strategy of no anticoagulation was non-inferior to anticoagulation with an upper margin of a 2.3% increase in recurrent venous thromboembolism from an expected rate of 2% in those who receive full anticoagulation. We also planned to undertake a study comparing acute reporting radiologists’ diagnoses of subsegmental pulmonary embolism from all computed tomography pulmonary angiograms with specialist respiratory radiologists. This would have allowed us to determine safety in the pilot study (i.e. patients with pulmonary embolism that was in fact larger than subsegmental would have been identified) and develop guidance for subsegmental pulmonary embolism diagnosis for general radiologists. Patients with lived experience of thrombosis contributed to all aspects of the trial design and were part of the Trial Management Group. Progress of study The STOPAPE trial was stopped prematurely due to a low recruitment rate in the wake of the COVID pandemic and prioritisation of recovery of the National Institute for Health and Care Research research portfolio. There are no outcome data available for this trial. Separate NIHR Library publications will detail the linked qualitative study examining the views of patients and clinicians around withholding anticoagulation for isolated subsegmental pulmonary embolism as well as presenting all collected data of recruited patients. Funding This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR128073. A plain language summary of this research article is available on the NIHR Journals Library Website https://doi.org/10.3310/HRCW7937. Plain language summary Pulmonary embolism is a potentially serious condition, whereby blood clots cause a blockage of the blood supply to the lungs. The diagnosis of pulmonary embolism is made with a scan of the lungs, by showing areas where blood cannot get through the vessels easily due to blood clots. The treatment of pulmonary embolism includes anticoagulant medication (‘blood thinners’) that is taken over months and includes warfarin, an injectable form of heparin and directly acting oral anticoagulants. These medications work by preventing new clots from forming while the body’s own mechanisms break down the clots. As the scanning technology for pulmonary embolism has become more sensitive, smaller clots are being diagnosed. However, small pulmonary embolisms may not cause any symptoms and may be found incidentally on scans performed for other reasons. In these situations, it is unclear whether treatment is required for the pulmonary embolism. These clots in smaller blood vessels away from the centre of the lungs (subsegmental pulmonary embolism) may be removed by the body’s own mechanisms for dissolving clots without needing medications. Anticoagulant medication can cause side effects in some patients such as bleeding. For the anticoagulant medication to be appropriate in these smaller pulmonary embolisms, the benefits from preventing future blood clots (pulmonary embolism and deep-vein thrombosis) would need to outweigh the potential risks from the medication side effects. The STOPAPE study aimed to answer this question by testing whether we can safely withhold anticoagulation from patients diagnosed with subsegmental pulmonary embolism. Although we aimed to enrol 1466 patients in the trial with half getting usual care of anticoagulation and half getting no anticoagulation, we could not recruit patients quickly enough to the trial and, as a result, we could not continue with the STOPAPE study. This study protocol is published to help future research teams that wish to answer this research question.

Introduction Aortic stenosis (AS) is common affecting >13% of adults over the age of 75 years. In people who develop symptoms, without valve replacement, prognosis is dismal with mortality as high as 50% at 1 year. In asymptomatic patients, the timing of valve intervention is less well defined and a strategy of watchful waiting is recommended. Many, however, may develop symptoms and attribute this to age related decline, rather than worsening AS. Timely intervention in asymptomatic severe AS is critical, since delayed intervention often results in poor outcomes. Proactive surveillance of symptoms, quality of life and functional capacity should enable timely identification of people who will benefit from aortic valve replacement. There are no data however, to support the clinical and cost effectiveness of such an approach in a healthcare setting in the UK. The aim of this pilot trial is to test the feasibility of a full-scale randomised controlled trial (RCT) to determine the utility of proactive surveillance in people with asymptomatic severe AS to guide the timing of intervention.Methods and analysis APRAISE-AS is a multi-centre, non-blinded, two-arm, parallel group randomised controlled trial of up to 66 participants aged >18 years with asymptomatic severe AS. Participants will be randomised to either standard care or standard care supplemented with the APRAISE-AS intervention. Primary outcomes will capture; adherence to and participant acceptability of the intervention, recruitment and retention rates, and completeness of data collection. The findings will be used to inform the sample size and most appropriate outcome measure(s) for a full-scale RCT and health economic evaluation.Ethics and dissemination Ethical approval was granted by the Black Country REC, reference: 22/WM/0214. Results will be submitted for publication in peer-reviewed journals and disseminated at local, regional and national meetings where appropriate.Trial registration number ISRCTN19413194 registered on 14.07.2023.

Background Renin–angiotensin system inhibitors, both angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, slow progression of mild and moderate chronic kidney disease. However, some evidence suggests that discontinuation of renin–angiotensin system inhibitors in patients with advanced chronic kidney disease might increase estimated glomerular filtration rate or slow its decline. Objective To test the hypothesis that stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, or a combination of both, compared with continuing these treatments, improves or stabilises kidney function in patients with progressive stages 4 or 5 chronic kidney disease based on assessment of kidney function using the modification of diet in renal disease four-variable estimated glomerular filtration rate at 3 years, follow-up. Setting Thirty-seven UK hospitals with kidney services. Design An investigator-led multicentre open-label, randomised controlled trial of 411 participants with advanced (stage 4 or 5) progressive chronic kidney disease. Participants Adult patients with advanced (estimated glomerular filtration rate < 30 ml/minute/1.73 m2) and progressive chronic kidney disease who were receiving either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, or a combination of both. Interventions Participants were randomised in a 1 : 1 ratio using a centralised internet-based system to either discontinue renin–angiotensin system inhibitors (n = 206) or continue renin–angiotensin system inhibitors (n = 205). Main outcome measures The primary outcome was the estimated glomerular filtration rate at 3 years; measurements of estimated glomerular filtration rate made after commencing kidney replacement therapy were excluded. Secondary outcomes included development of end-stage kidney disease or starting kidney replacement therapy, a composite of either a > 50% decline in estimated glomerular filtration rate or commencement of kidney replacement therapy (including end-stage kidney disease), cystatin C, hospitalisations, blood pressure, exercise capacity and quality of life. Cardiovascular events, death and safety were recorded. Results At 3 years, the least-squares mean (± standard error) estimated glomerular filtration rate was 12.6 ± 0.7 ml/minute/1.73 m2 in the discontinuation group and 13.3 ± 0.6 ml/minute/1.73 m2 in the continuation group [difference −0.7, 95% confidence interval (−2.5 to 1.0; p = 0.42)] with a negative value favouring the continuation group. The treatment effect did not differ (heterogeneity) when data were analysed by the pre-specified subgroups. End-stage kidney disease or kidney replacement therapy occurred in 128 (62%) and 115 (56%) participants randomised to the discontinue and continue renin–angiotensin system inhibitor groups, respectively (hazard ratio 1.28, 95% confidence interval 0.99 to 1.65). The numbers of cardiovascular events and deaths observed were similar for those randomised to discontinue (108 events and 20 deaths) or continue (88 events and 22 deaths) renin–angiotensin system inhibitors. Limitations Non-white ethnic backgrounds were poorly represented, limiting the generalisability of our findings. The open-label nature of the trial may have affected clinical care and subjective end points, such as quality of life and exercise capacity. We only included patients who were receiving renin–angiotensin system inhibitors at the time of randomisation, thus excluding those who had already discontinued these agents. Conclusions Discontinuing renin–angiotensin system inhibitors in advanced and progressive chronic kidney disease does not cause a clinically relevant change in estimated glomerular filtration rate or difference in its long-term decline. Future work Future work should focus on updating clinical guidelines. Further analyses, in addition to the prespecified analyses, may be undertaken if new estimated glomerular filtration rate equations are introduced into clinical practice. Subgroup analysis by kidney disease aetiology and gender may be undertaken to look for potential differences in outcome in specific groups. Trial registration This trial is registered as STOP ACEi EudraCT Number, 2013-003798-82; ISRCTN62869767. Funding This award was funded by the Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 11/30/07), a Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR) partnership. This is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 5. See the NIHR Funding and Awards website for further award information. Plain language summary Drugs called angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, together known as renin–angiotensin system inhibitors, are used to treat high blood pressure, slow worsening kidney function and lower the risk of kidney failure (known as end-stage kidney disease which requires treatment with dialysis or kidney transplantation) in patients with early chronic kidney disease. However, we did not know if patients treated with renin–angiotensin system inhibitors and who have progressed to more advanced chronic kidney disease (stage 4 or 5) should stop or continue renin–angiotensin system inhibitors. To determine whether stopping renin–angiotensin system inhibitors in people with advanced chronic kidney disease leads to an improvement or stabilisation of kidney function required a study comparing the outcomes of people who had had these drugs stopped with a group who continued these drugs (the STOP-angiotensin-converting enzyme inhibitors trial). We recruited 411 participants with advanced chronic kidney disease who were receiving renin–angiotensin system inhibitors from 37 kidney units in the UK, and randomly (like flipping a coin) allocated them to either stop or continue renin–angiotensin system inhibitors. We then compared kidney function between the two groups at 3 years. We also assessed whether stopping or continuing renin–angiotensin system inhibitors had an influence on the development of end-stage kidney disease or need for kidney replacement therapy, the number of hospitalisations, blood pressure, quality of life and physical function. We collected data on safety outcomes including death and heart-related events (such as heart attacks). The results of the trial showed no difference in kidney function at 3 years. The number of participants requiring dialysis, or a kidney transplant was also similar, as was the quality of life and physical function between the groups. Deaths and the number of heart events were similar in both groups. This research suggests that there is no benefit in stopping renin–angiotensin system inhibitors in patients with advanced chronic kidney disease. Scientific summary Background Renin–angiotensin system (RAS) inhibitors, both angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB), slow the progression of mild and moderate chronic kidney disease (CKD). However, some evidence suggests that discontinuation of RAS inhibitors in patients with advanced CKD might increase estimated glomerular filtration rate (eGFR) or slow its decline. Primary objective To test the hypothesis that discontinuing ACEi or ARB treatment, or a combination of both, compared with continuing on these treatments, improves or stabilises kidney function in patients with progressive stage 4 or stage 5 CKD based on assessment of kidney function using the modification of diet in renal disease (MDRD) four-variable eGFR at 3 years follow-up. Secondary objectives To test whether in each of the randomised groups. Clinical outcomes The number of participants starting kidney replacement therapy (KRT) (dialysis or transplantation) or sustaining a > 50% decline in eGFR differs. There is a difference in the time taken to reach end-stage kidney disease (ESKD) or need for KRT. Hospitalisation rates from any cause are different. Participant quality of life and well-being [measured using the kidney disease quality of life (KDQoL)-SF™ v1.3 questionnaire] differs. Participant physical function (measured using the 6-minute walk test) differs. Withdrawal of these treatments does not cause excess harm [e.g. increased cardiovascular (CV) events such as heart failure, hypertension, myocardial infarction, stroke] and is not associated with an increase in adverse effects. Participant survival in each group is similar. Blood pressure (BP) control is the same. Cystatin-C levels differ. Mechanistic outcomes There is a change in urine protein excretion [urinary protein-to-creatinine ratio (uPCR)]. Discontinuation of ACEi/ARB affects haemoglobin concentration. Discontinuation of ACEi/ARB affects the requirement for erythropoietin stimulating agents. Methods An investigator-initiated, multicentre, open-label randomised trial where people with advanced and progressive CKD (eGFR < 30 ml/minute/1.73 m2) were randomised to either discontinue or continue RAS inhibitors, and then followed up every 3 months for 3 years. Patients underwent screening at 39 centres in the UK. Adults (≥ 18 years of age) with stage 4 or stage 5 CKD (eGFR, < 30 ml/minute/1.73 m2 of body-surface area) were eligible to participate in the trial if they were not receiving dialysis and had not undergone kidney transplantation. All eligible patients were required to have had a decrease of more than 2 ml/minute/1.73 m2 per year in the eGFR during the previous 2 years and to have been receiving treatment with an ACEi, an ARB, or both for more than 6 months. We calculated the eGFR using the four-variable equation used in the MDRD study, as updated in 2005 (MDRD175). Exclusion criteria included uncontrolled hypertension or a history of myocardial infarction or stroke within the previous 3 months. All the patients provided written informed consent. Patients were randomly assigned in a 1 : 1 ratio to either discontinue or continue RAS inhibitors. Randomisation used a centralised internet-based system with minimisation to ensure balance between groups for the following variables: age (< 65 or ≥ 65 years), eGFR (< 15 or ≥ 15 ml/minute/1.73 m2), diabetes (type 1, type 2, or none), mean arterial pressure (< 100 or ≥ 100 mmHg) and proteinuria [protein-to-creatinine ratio (PCR), < 100 or ≥ 100 mg/mmol]. In the group that discontinued RAS inhibitor, any guideline-recommended antihypertensive agent other than a RAS inhibitor could be used to control BP. In the group that continued RAS inhibitors, the responsible clinician chose the agent and dose of the RAS inhibitor and could combine it with any other guideline-recommended antihypertensive agent. The primary outcome was the eGFR at 3 years as calculated according to the MDRD175 four-variable equation. Secondary outcome measures included the time until the development of ESKD or initiation of KRT; a composite of a decrease of more than 50% in the eGFR, the development of ESKD, or the initiation of KRT; hospitalisation for any cause; measures of cystatin C and BP; quality of life (as measured on the KDQoL 36-Item Short Form Survey, version 1.3); exercise capacity (as assessed by the 6-minute walk test); and CV events and death. At the time of this report, the transfer and processing of samples for cystatin C measurement had not yet occurred, so the results are not provided here. Secondary mechanistic outcomes included measures of haemoglobin and urinary protein excretion (PCR). The trial aimed to recruit 410 patients (205 patients in each trial group) which would provide 80% power to determine a minimum relevant between-group difference in the eGFR of 5 ml/minute/1.73 m2 (alpha level of 0.05), assuming an attrition rate of 20%. This difference represents an effect size of 0.31, with a standard deviation of 16 ml/minute/1.73 m2. The analyses were based on the intention-to-treat principle and were adjusted for the minimisation variables and baseline values. A repeated-measures, mixed-effects linear regression model was used to estimate the between-group difference in eGFR at 3 years. Any measurements of eGFR that were made after patients had initiated dialysis or undergone kidney transplantation were excluded from the primary analysis. To examine the effect of data that were not missing at random, we performed sensitivity analyses by fitting pattern-mixture and joint models for the primary outcome. We also repeated analyses for the primary outcome with the use of two other four-variable equations for the eGFR calculation: the Chronic Kidney Disease Epidemiology Collaboration 2009 equation and the MDRD186 equation. Continuously distributed secondary outcomes, such as BP, were analysed using the same methods as per the primary analysis, but data were not censored at the time of initiation of KRT. Categorical (dichotomous) secondary outcomes were analysed with the use of a Poisson regression model with robust standard errors (SEs) to estimate the relative risk (RR) and 95% confidence interval (CI). A Cox proportional-hazards model was used to calculate hazard ratios (HRs) and 95% CIs for time-to-event outcomes, such as the development of ESKD or the initiation of KRT. Categorical safety outcome measures (i.e. hospitalisation and serious adverse events) were summarised as the percentage of patients with these events. Data collection for kidney outcomes did not distinguish between ESKD and kidney-replacement outcomes (i.e. both outcomes used the same end-point code), although investigators could note the specific outcome. Prespecified subgroup analyses were performed only for the primary outcome according to the minimisation variables. Time and subgroup were included in the model to allow for the possibility of differential changes over time within subgroups, time according to subgroup and the three-way interaction among the variables of treatment, time and subgroup. Although all data were included in the regression models for the subgroup analyses, only estimates of differences at 3 years are presented. All analyses were performed with the use of SAS software, version 9.4 (SAS Institute), and Stata software, version 17 (StataCorp). Results At 3 years, among the 411 patients who underwent randomisation, the least-squares mean (LS-Mean) (±SE) eGFR was 12.6 ± 0.7 ml/minute/1.73 m2 in the discontinuation group and 13.3 ± 0.6 ml/minute/1.73 m2 in the continuation group (difference −0.7, 95% (CI −2.5 to 1.0; p = 0.42) with a negative value favouring the continuation group. End-stage kidney disease or the initiation of KRT occurred in 128 patients (62%) in the discontinuation group and in 115 patients (56%) in the continuation group (HR 1.28, 95% CI 0.99 to 1.65). The number of patients with > 50% decline in eGFR or need to start KRT (including ESKD) was 140/206 (68%) in the discontinue RAS inhibitor group compared to 127/202 (63%) in the continue RAS inhibitor group; RR 1.07, 95% CI 0.94 to 1.22. The number of hospitalisations were similar between the groups; 414 in the stop RAS inhibitor group versus 413 in the continue RAS inhibitor group. The difference in LS-Mean at 3 years for systolic BP was 0 mmHg, 95% CI −4 to 5 mmHg. The results were similar for diastolic BP; 0 mmHg, 95% CI −2 to 3 mmHg. Adverse events were similar in both the discontinuation group and continuation group with respect to CV events (108 vs. 88) and deaths (20 vs. 22). Conclusions Our STOP-ACEi trial showed that discontinuing RAS inhibitors for patients with advanced and progressive CKD does not lead to a clinically relevant change in eGFR or difference in the rate of long-term decline in eGFR, overall or in pre-specified subgroups by age, severity of CKD, diabetes, proteinuria or BP. Numerically more patients who discontinued RAS inhibitors had progression to ESKD or need for KRT, so a larger trial might have shown an advantage to continuing with RAS inhibition. The rate of CV events and death was similar. Systolic and diastolic BP and proteinuria were greater over the first year of follow-up in those randomised to discontinue RAS inhibitors but there was little difference, thereafter, reflecting initiation of antihypertensive agents other than RAS inhibitors. No differences in quality of life or exercise capacity were observed for those who discontinued or continued RAS inhibitors. Our trial lacked sufficient power to investigate the effect of withdrawing RAS inhibitors on CV events or mortality. However, because our trial suggests that there is no advantage in discontinuing RAS inhibitors from the perspective of kidney function, there is little rationale to conduct a larger randomised trial to investigate CV safety. Future work Future work should initially focus on updating clinical guidelines in the UK and potentially worldwide. Further analyses, in addition to the prespecified analyses, may be undertaken if new eGFR equations are introduced into routine clinical practice such as the National Institute for Health and Care Excellence recommended removal of black ethnicity correction factor from the eGFR equation. Consideration of subgroup analysis by aetiology of kidney disease and gender will be considered to look for any potential differences in outcome in specific groups which might warrant future studies. Trial registration This trial is registered as STOP ACEi EudraCT Number, 2013-003798-82; ISTRCTN62869767. Funding This award was funded by the Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 11/30/07), a Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR) partnership. This is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 5. See the NIHR Funding and Awards website for further award information.

Idiopathic sudden sensorineural hearing loss (ISSNHL) is the rapid onset of reduced hearing due to loss of function of the inner ear or hearing nerve of unknown aetiology. Evidence supports improved hearing recovery with early steroid treatment, via oral, intravenous, intratympanic or a combination of routes. The STARFISH trial aims to identify the most clinically and cost-effective route of administration of steroids as first-line treatment for ISSNHL. STARFISH is a pragmatic, multicentre, assessor-blinded, three-arm intervention, superiority randomised controlled trial (1:1:1) with an internal pilot (ISRCTN10535105, IRAS 1004878). 525 participants with ISSNHL will be recruited from approximately 75 UK Ear, Nose and Throat units. STARFISH will recruit adults with sensorineural hearing loss averaging 30dBHL or greater across three contiguous frequencies (confirmed via pure tone audiogram), with onset over a ≤3-day period, within four weeks of randomisation. Participants will be randomised to 1) oral prednisolone 1mg/Kg/day up to 60mg/day for 7 days; 2) intratympanic dexamethasone: three intratympanic injections 3.3mg/ml or 3.8mg/ml spaced 7±2 days apart; or 3) combined oral and intratympanic steroids. The primary outcome will be absolute improvement in pure tone audiogram average at 12-weeks following randomisation (0.5, 1.0, 2.0 and 4.0kHz). Secondary outcomes at 6 and 12 weeks will include: Speech, Spatial and Qualities of hearing scale, high frequency pure tone average thresholds (4.0, 6.0 and 8.0kHz), Arthur Boothroyd speech test, Vestibular Rehabilitation Benefit Questionnaire, Tinnitus Functional Index, adverse events and optional weekly online speech and pure tone hearing tests. A health economic assessment will be performed, and presented in terms of incremental cost effectiveness ratios, and cost per quality-adjusted life-year. Primary analyses will be by intention-to-treat. Oral prednisolone will be the reference. For the primary outcome, the difference between group means and 97.5% confidence intervals at each time-point will be estimated via a repeated measures mixed-effects linear regression model.

Humanitarian crises create opportunities for both in-person and remote aid. Durable, complex, and team-based care may leverage a telemedicine approach for comprehensive support within a conflict zone. Barriers and enablers are detailed, as is the need for mission expansion due to initial program success. Adapting a telemedicine program initially designed for critical care during the severe acute respiratory syndrome coronavirus 2 pandemic offers a solution to data transfer and data analysis issues. Staffing efforts and grouped elements of patient care detail the kinds of remote aid that are achievable. A multiprofessional team-based approach (clinical, administrative, nongovernmental organization, government) can provide comprehensive consultation addressing surgical planning, critical care management, infection and infection control management, and patient transfer for complex care. Operational and network security create parallel concerns relevant to avoid geolocation and network intrusion during consultation. Deliberate approaches to address cultural differences that influence relational dynamics are also essential for mission success.

Key Clinical Message Cortical venous thrombosis is a rare but severe complication of TBM that requires a high index of suspicion for early diagnosis. The treatment of CVT in TBM is based on anticoagulant therapy, which is known to improve the outcomes of the patients. Abstract The case report describes an 18‐year‐old male in India with symptoms of tubercular meningitis complicated by cortical venous thrombosis. Tubercular meningitis is a rare but severe form of meningitis caused by tuberculosis bacteria and is a significant public health concern in India. The patient presented to the emergency department with a history of fever, headache, and vomiting for the past month, with a positive Mycobacterium tuberculosis test. The patient was started on standard antitubercular therapy and was diagnosed with cortical venous thrombosis via an MRI scan. Treatment included antitubercular therapy, anticoagulation therapy, dexamethasone, and antiemetic drugs. The patient's symptoms improved over 2 weeks of therapy. The case highlights the importance of early detection, treatment, and prevention strategies, such as the National Tuberculosis elimination program, in controlling the spread of tuberculosis in India. It also emphasizes the importance of close monitoring for complications in patients with tubercular meningitis, such as cortical venous thrombosis, which can be life‐threatening.

Background:. Few evidence-based suggestions are available to help applicants and mentors improve reapplication outcomes. We sought to provide program directors' (PDs) perspectives on actionable steps to improve reapplicants' chances for a match. Methods:. The PDs were asked to rank positions unmatched applicants can pursue, steps these applicants can take for the next application cycle, and reasons why reapplicants do not match. Results:. Responses from 66 of 123 PDs were received (53.6% response rate). Obtaining new recommendation letters and rotating with orthopaedics were the highest 20 ranked steps unmatched applicants can take. No curriculum vitae (CV) improvement, poor interview, and poor letters of recommendation were the most important reasons hindering applicants from matching when reapplying. Conclusions:. Steps reapplicants could prioritize include obtaining new recommendation letters, rotating in orthopaedics, and producing new research items. CV strengthening and improving interview skills address the 2 main reasons why unmatched applicants failed in subsequent attempts. Level of Evidence:. Level IV

Summary:. At the 2021 annual meeting of the Orthopaedic Trauma Association, the Basic Science Focus Forum hosted its first ever debate-style symposium focused on biomechanics and fracture repair. The 3 subjects of debate were “Mechanics versus Biology—Which is ‘More Important’ to Consider?” “Locked Plate versus Forward Dynamization versus Reverse Dynamization—Which Way Should I Go?” and “Sawbones versus Cadaver Models—What Should I Believe Most?” These debates were held because fracture healing is a highly organized synergistic response between biological factors and the local mechanical environment. Multiple studies have demonstrated that both factors play roles in governing bone healing responses, and the causal relationships between the 2 remain unclear. The lack of clarity in this space has led to a spectrum of research with the common goal of helping surgeons make good decisions. Before reading further, the reader should understand that the questions posed in the debate titles are unanswerable and might represent a false choice. Instead, the reader should appreciate that the debates were held to gain a more thorough understanding of these topics based on the current state of the art of experimental and clinical studies, by using an engaging and thought-provoking format.

Background: Diabetes is an endocrinopathy and rare in the case of SARS-CoV-2, the virus primarily involves the lungs by its affinity to Angiotensin Converting enzyme(ACE-2) receptors, associated symptoms include Nausea, Vomiting, and Breathlessness. Case Presentation: We present the case of a 41-year-old male with pneumonia-like symptoms and a positive nasal swab RT-PCR test with Imaging studies highly suggestive of CO RADS-5 Progressive stage, the patient was immediately admitted to the Intensive care unit (ICU), and the treatment was started with Medical Oxygen, Intravenous Normal Saline Tablet Doxycycline, and Tablet Ivermectin as per the guidelines, he was admitted for 21 days. After 3 weeks the patient comes for a routine checkup and was found to have an elevated Fasting glucose level of 121 mg/dl (normal reference range 80-100mg/dl) further workup for diabetes revealed that he was a non-diabetic on the previous visit 2 months ago, he also had an increase in weight during this time. With the Body Mass Index(BMI) now being 30.2 from the previous 28.4 (Reference range >30 is obese), the pro-inflammatory cytokines like C-reactive protein were 111.6 (normal 0-6), and elevation in D-Dimer which is a fibrin degradation product was elevated to 1048ng/dl ( normal range 0-500 ng/dl) other measures for the increase in blood sugar also showed elevation as seen in table 1. Discussion: There have been many hypotheses to find a causal relationship between both Diabetes and Covid-19 like the use of Dexamethasone or that the virus produces proinflammatory cytokines like Interleukin-6(IL-6) that lead to impaired signaling and decreased lipolysis or that there is a direct action on the ACE 2 found in the pancreas by the virus and maybe the least looked upon factor being lockdown leading to sedentary life, no exercises and increase in consumption of fatty foods, whichever may be the case it could very well be a multifactorial cause with many of these ideas involved. Conclusion: In this case, the association may be with decreased physical activity and an increase in Lipolysis or the proinflammatory states as seen by the increase in the C-reactive protein and Interleukin-6 levels. Table: Parameter Values before COVID Values after Covid Reference range Total WBC 4900 11,400 4000-10000/cu.mm Platelet count 200000 450000 140000-440000/cu.mm C-reactive protein 1.55 111.6 0-6 D-Dimer 0.4 1048 0-500 ng/dl Interleukin (IL-6) - 97.42

Background: Anti-neutrophil cytoplasm antibody-associated vasculitis is a multisystem, autoimmune disease that causes organ failure and death. Physical removal of pathogenic autoantibodies by plasma exchange is recommended for severe presentations, along with high-dose glucocorticoids, but glucocorticoid toxicity contributes to morbidity and mortality. The lack of a robust evidence base to guide the use of plasma exchange and glucocorticoid dosing contributes to variation in practice and suboptimal outcomes. Objectives: We aimed to determine the clinical efficacy of plasma exchange in addition to immunosuppressive therapy and glucocorticoids with respect to death and end-stage renal disease in patients with severe anti-neutrophil cytoplasm antibody-associated vasculitis. We also aimed to determine whether or not a reduced-dose glucocorticoid regimen was non-inferior to a standard-dose regimen with respect to death and end-stage renal disease. Design: This was an international, multicentre, open-label, randomised controlled trial. Patients were randomised in a two-by-two factorial design to receive either adjunctive plasma exchange or no plasma exchange, and either a reduced or a standard glucocorticoid dosing regimen. All patients received immunosuppressive induction therapy with cyclophosphamide or rituximab. Setting: Ninety-five hospitals in Europe, North America, Australia/New Zealand and Japan participated. Participants: Participants were aged ≥ 16 years with a diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis, and either proteinase 3 anti-neutrophil cytoplasm antibody or myeloperoxidase anti-neutrophil cytoplasm antibody positivity, and a glomerular filtration rate of

Abstract. Objectives:. Current surgical fracture treatment paradigms, which use rigid metallic constructs to heal bones, provide reasonable clinical outcomes; however, they do not leverage recent advances in our understanding of bone healing and mechanotransduction throughout bone healing. The objective of this review was to investigate the efficacy and potential clinical applicability of surgical techniques and implants that deliberately introduce interfragmentary motion throughout the healing process. Methods:. The authors searched PubMed and Google Scholar databases for articles reporting on fracture repair using dynamic locking plates, dynamized surgical techniques, and reverse dynamization. Data collection also included assessment of additively manufactured (AM) implants that provide dynamic mechanical behaviors. Results:. Forty articles were included for final review. It was found that accelerated rates of fracture healing can be achieved with staged 2-part surgeries or dynamic implant designs. Temporal dynamization, where static fixation of bones is followed by the introduction of micromotion and controlled loading, has been shown to improve callus volume and accelerate the healing response. Reverse dynamization, where micromotion is encouraged during early callus formation and arrested later, may represent a significant advance for the treatment of critical defect injuries. Advances in AM techniques will likely provide the ability to create high-resolution implants capable of dynamized and reverse dynamized modalities. Conclusions:. There is no one-size-fits-all approach to optimization of fracture healing. However, it has been clearly demonstrated that fracture treatment can be enhanced by systematically altering the construct stiffness throughout the different phases of healing, which may be achieved with AM implant designs.

Background: Most children with steroid-sensitive nephrotic syndrome have relapses that are triggered by upper respiratory tract infections. Four small trials, mostly in children already taking maintenance corticosteroid in countries of different upper respiratory tract infection epidemiology, showed that giving daily low-dose prednisone/prednisolone for 5–7 days during an upper respiratory tract infection reduces the risk of relapse. Objectives: To determine if these findings were replicated in a large UK population of children with relapsing steroid-sensitive nephrotic syndrome on different background medication or none. Design: A randomised double-blind placebo-controlled trial, including a cost-effectiveness analysis. Setting: A total of 122 UK paediatric departments, of which 91 recruited patients. Participants: A total of 365 children with relapsing steroid-sensitive nephrotic syndrome (mean age 7.6 ± 3.5 years) were randomised (1 : 1) according to a minimisation algorithm based on background treatment. Eighty children completed 12 months of follow-up without an upper respiratory tract infection. Thirty-two children were withdrawn from the trial (14 prior to an upper respiratory tract infection), leaving a modified intention-to-treat analysis population of 271 children (134 and 137 children in the prednisolone and placebo arms, respectively). Interventions: At the start of an upper respiratory tract infection, children received 6 days of prednisolone (15 mg/m2) or an equivalent dose of placebo. Main outcome measures: The primary outcome was the incidence of first upper respiratory tract infection-related relapse following any upper respiratory tract infection over 12 months. The secondary outcomes were the overall rate of relapse, changes in background treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, change in Achenbach Child Behaviour Checklist score and quality of life. Analysis was by intention-to-treat principle. The cost-effectiveness analysis used trial data and a decision-analytic model to estimate quality-adjusted life-years and costs at 1 year, which were then extrapolated over 16 years. Results: There were 384 upper respiratory tract infections and 82 upper respiratory tract infection-related relapses in the prednisolone arm, and 407 upper respiratory tract infections and 82 upper respiratory tract infection-related relapses in the placebo arm. The number of patients experiencing an upper respiratory tract infection-related relapse was 56 (42.7%) and 58 (44.3%) in the prednisolone and placebo arms, respectively (adjusted risk difference –0.024, 95% confidence interval –0.14 to 0.09; p = 0.70). There was no evidence that the treatment effect differed when data were analysed according to background treatment. There were no significant differences in secondary outcomes between treatment arms. Giving daily prednisolone at the time of an upper respiratory tract infection was associated with increased quality-adjusted life-years (0.9427 vs. 0.9424) and decreased average costs (£252 vs. £254), when compared with standard care. The cost saving was driven by background therapy and hospitalisations after relapse. The finding was robust to sensitivity analysis. Limitations: A larger number of children than expected did not have an upper respiratory tract infection and the sample size attrition rate was adjusted accordingly during the trial. Conclusions: The clinical analysis indicated that giving 6 days of daily low-dose prednisolone at the time of an upper respiratory tract infection does not reduce the risk of relapse of steroid-sensitive nephrotic syndrome in UK children. However, there was an economic benefit from costs associated with background therapy and relapse, and the health-related quality-of-life impact of having a relapse. Future work: Further work is needed to investigate the clinical and health economic impact of relapses, interethnic differences in treatment response, the effect of different corticosteroid regimens in treating relapses, and the pathogenesis of individual viral infections and their effect on steroid-sensitive nephrotic syndrome. Trial registration: Current Controlled Trials ISRCTN10900733 and EudraCT 2012-003476-39. 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. 3. See the NIHR Journals Library website for further project information.

Abstract Background In cluster randomized crossover (CRXO) trials, groups of participants (i.e., clusters) are randomly allocated to receive a sequence of interventions over time (i.e., cluster periods). CRXO trials are becoming more comment when they are feasible, as they require fewer clusters than parallel group cluster randomized trials. However, CRXO trials have not been frequently used in orthopedic fracture trials and represent a novel methodological application within the field. To disseminate the early knowledge gained from our experience initiating two cluster randomized crossover trials, we describe our process for the identification and selection of the orthopedic practices (i.e., clusters) participating in the PREP-IT program and present data to describe their key characteristics. Methods The PREP-IT program comprises two ongoing pragmatic cluster randomized crossover trials (Aqueous-PREP and PREPARE) which compare the effect of iodophor versus chlorhexidine solutions on surgical site infection and unplanned fracture-related reoperations in patients undergoing operative fracture management. We describe the process we used to identify and select orthopedic practices (clusters) for the PREP-IT trials, along with their characteristics. Results We identified 58 potential orthopedic practices for inclusion in the PREP-IT trials. After screening each practice for eligibility, we selected 30 practices for participation and randomized each to a sequence of interventions (15 for Aqueous-PREP and 20 for PREPARE). The majority of orthopedic practices included in the Aqueous-PREP and PREPARE trials were situated in level I trauma centers (100% and 87%, respectively). Orthopedic practices in the Aqueous-PREP trial operatively treated a median of 149 open fracture patients per year, included a median of 11 orthopedic surgeons, and had access to a median of 5 infection preventionists. Orthopedic practices in the PREPARE trial treated a median of 142 open fracture and 1090 closed fracture patients per year, included a median of 7.5 orthopedic surgeons, and had access to a median of 6 infection preventionists. Conclusions The PREP-IT trials provide an example of how to follow the reporting standards for cluster randomized crossover trials by providing a clear definition of the cluster unit, a thorough description of the cluster identification and selection process, and sufficient description of key cluster characteristics. Trial registration Both trials are registered at ClinicalTrials.gov (A-PREP: NCT03385304 December 28, 2017, and PREPARE: NCT03523962 May 14, 2018).

Introduction: Cluster randomized crossover trials are often faced with a dilemma when selecting an optimal model of consent, as the traditional model of obtaining informed consent from participant's before initiating any trial related activities may not be suitable. We describe our experience of engaging patient advisors to identify an optimal model of consent for the PREP-IT trials. This paper also examines surrogate measures of success for the selected model of consent. Methods: The PREP-IT program consists of two multi-center cluster randomized crossover trials that engaged patient advisors to determine an optimal model of consent. Patient advisors and stakeholders met regularly and reached consensus on decisions related to the trial design including the model for consent. Patient advisors provided valuable insight on how key decisions on trial design and conduct would be received by participants and the impact these decisions will have. Results: Patient advisors, together with stakeholders, reviewed the pros and cons and the requirements for the traditional model of consent, deferred consent, and waiver of consent. Collectively, they agreed upon a deferred consent model, in which patients may be approached for consent after their fracture surgery and prior to data collection. The consent rate in PREP-IT is 80.7%, and 0.67% of participants have withdrawn consent for participation. Discussion: Involvement of patient advisors in the development of an optimal model of consent has been successful. Engagement of patient advisors is recommended for other large trials where the traditional model of consent may not be optimal.

Background: Chronic inflammation caused by ulcerative colitis (UC) causes a pro-neoplastic drive in the inflamed colon, leading to a markedly greater risk of invasive malignancy compared to the general population. Despite surveillance protocols, 50% of cases proceed to cancer before neoplasia is detected. The Enhanced Neoplasia Detection and Cancer Prevention in Chronic Colitis (ENDCaP-C) trial is an observational multi-centre test accuracy study to ascertain the role of molecular markers in improving the detection of dysplasia. We aimed to validate previously identified biomarkers of neoplasia in a retrospective cohort and create predictive models for later validation in a prospective cohort. Methods: A retrospective analysis using bisulphite pyrosequencing of an 11 marker panel (SFRP1, SFRP2, SRP4, SRP5, WIF1, TUBB6, SOX7, APC1A, APC2, MINT1, RUNX3) in samples from 35 patients with cancer, 78 with dysplasia and 343 without neoplasia undergoing surveillance for UC associated neoplasia across 6 medical centres. Predictive models for UC associated cancer/dysplasia were created in the setting of neoplastic and non-neoplastic mucosa. Findings: For neoplastic mucosa a five marker panel (SFRP2, SFRP4, WIF1, APC1A, APC2) was accurate in detecting pre-cancerous and invasive neoplasia (AUC = 0.83; 95% CI: 0.79, 0.88), and dysplasia (AUC = 0.88; (0.84, 0.91). For non-neoplastic mucosa a four marker panel (APC1A, SFRP4, SFRP5, SOX7) had modest accuracy (AUC = 0.68; 95% CI: 0.62,0.73) in predicting associated bowel neoplasia through the methylation signature of distant non-neoplastic colonic mucosa. Interpretation: This multiplex methylation marker panel is accurate in the detection of ulcerative colitis associated dysplasia and neoplasia and is currently being validated in a prospective clinical trial. Funding: The ENDCAP-C study was funded by the National Institute for Health Research Efficacy and Mechanism Evaluation (EME) Programme (11/100/29).

Introduction: Pragmatic trials in comparative effectiveness research assess the effects of different treatment, therapeutic, or healthcare options in clinical practice. They are characterized by broad eligibility criteria and large sample sizes, which can lead to an unmanageable number of participants, increasing the risk of bias and affecting the integrity of the trial. We describe the development of a sampling strategy tool and its use in the PREPARE trial to circumvent the challenge of unmanageable work flow. Methods: Given the broad eligibility criteria and high fracture volume at participating clinical sites in the PREPARE trial, a pragmatic sampling strategy was needed. Using data from PREPARE, descriptive statistics were used to describe the use of the sampling strategy across clinical sites. A Chi-square test was performed to explore whether use of the sampling strategy was associated with a reduction in the number of missed eligible patients. Results: 7 of 20 clinical sites (35%) elected to adopt a sampling strategy. There were 1539 patients excluded due to the use of the sampling strategy, which represents 30% of all excluded patients and 20% of all patients screened for participation. Use of the sampling strategy was associated with lower odds of missed eligible patients (297/4545 (6.5%) versus 341/3200 (10.7%) p

Abstract. Objectives:. The aim of this study was to determine the educational value of a national virtual fracture conference implemented during the COVID-19 disruption of resident education. Design:. Survey study. Setting:. National virtual conference administered by the Orthopaedic Trauma Association. Participants:. Attendees of virtual fracture conference. Intervention:. Participation at a national virtual fracture conference. Main outcome measure:. Surveys of perception of quality and value of virtual conferences relative to in-person conferences. Results:. Ninety-six percent of participants rated the virtual fracture conference as similar or improved educational quality relative to conventional in-person fracture conference. Participants also felt they learned as much (35%) or more (57%) at each virtual fracture conference compared to the amount learned in-person. The quality of interpersonal interactions at both the resident–faculty level and faculty–faculty level was also perceived to be overall superior to those at participants’ own institutions. Learners felt they were more likely to engage the primary literature as well. Overall, 100% of participants were likely to recommend virtual conference to their colleagues and 100% recommended continuing this conference even after COVID-19 issues resolve. Conclusions:. We found that learners find significant educational value in a national virtual fracture conference compared to in-person fracture conferences at their own institution. COVID-19 has proven to be a disruptor not only in health care but in medical education as well, accelerating our adoption of innovative and novel resident didactics. Level of Evidence:. Therapeutic Level III.

Background: Chronic ulcerative colitis is a large bowel inflammatory condition associated with increased colorectal cancer risk over time, resulting in 1000 colectomies per year in the UK. Despite intensive colonoscopic surveillance, 50% of cases progress to invasive cancer before detection. Detecting early (precancer) molecular changes by analysing biopsies from routine colonoscopy should increase neoplasia detection. Objectives: To establish a deoxyribonucleic acid (DNA) marker panel associated with early neoplastic changes in ulcerative colitis patients. To develop the DNA methylation test for high-throughput analysis within the NHS. To prospectively evaluate the test within the existing colonoscopy surveillance programme. Design: Module 1 analysed 569 stored biopsies from neoplastic and non-neoplastic sites/patients using pyrosequencing for 11 genes that were previously reported to have altered promoter methylation associated with colitis-associated neoplasia. Classifiers were constructed to predict neoplasia based on gene combinations. Module 2 translated analysis to a NHS laboratory, assessing next-generation sequencing to increase speed and reduce cost. Module 3 applied the molecular classifiers within a prospective diagnostic accuracy study, in the existing ulcerative colitis surveillance programme. Comparisons were made between baseline and reference colonoscopies undertaken in a stratified patient sample 6–12 months later. Setting: Thirty-one UK hospitals. Participants: Patients with chronic ulcerative colitis, either for at least 10 years and extensive disease, or with primary sclerosing cholangitis. Interventions: An optimised DNA methylation classifier tested on routine mucosal biopsies taken during colonoscopy. Main outcome: Identifying ulcerative colitis patients with neoplasia. Results: Module 1 selected five genes with specificity for neoplasia. The optimism-adjusted area under the receiver operating characteristic curve for neoplasia was 0.83 (95% confidence interval 0.79 to 0.88). Precancerous neoplasia showed a higher area under the receiver operating characteristic curve of 0.88 (95% confidence interval 0.84 to 0.92). Background mucosa had poorer discrimination (optimism-adjusted area under the receiver operating characteristic curve was 0.68, 95% confidence interval 0.62 to 0.73). Module 2 was unable to develop a robust next-generation sequencing assay because of the low amplification rates across all genes. In module 3, 818 patients underwent a baseline colonoscopy. The methylation assay (testing non-neoplastic mucosa) was compared with pathology assessments for neoplasia and showed a diagnostic odds ratio of 2.37 (95% confidence interval 1.46 to 3.82; p = 0.0002). The probability of dysplasia increased from 11.1% before testing to 17.7% after testing (95% confidence interval 13.0% to 23.2%), with a positive methylation result suggesting added value in neoplasia detection. To determine added value above colonoscopy alone, a second (reference) colonoscopy was performed in 193 patients without neoplasia. Although the test showed an increased number of patients with neoplasia associated with primary methylation changes, this failed to reach statistical significance (diagnostic odds ratio 3.93; 95% confidence interval 0.82 to 24.75; p = 0.09). Limitations: Since the inception of ENDCaP-C, technology has advanced to allow whole-genome or methylome testing to be performed. Conclusions: Methylation testing for chronic ulcerative colitis patients cannot be recommended based on this study. However, following up this cohort will reveal further neoplastic changes, indicating whether or not this test may be identifying a population at risk of future neoplasia and informing future surveillance programmes. Trial registration: Current Controlled Trials ISRCTN81826545. Funding: This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership, and will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 1. See the NIHR Journals Library website for further project information.

Category: Midfoot/Forefoot; Bunion Introduction/Purpose: Hyperpronation of the 1st metatarsal in hallux valgus (HV) is poorly understood by conventional weightbearing radiography. We aimed to evaluate this parameter using weightbearing computed tomography (WBCT) and understand its association with other standard measurements. Methods: Retrospective evaluation of WBCT and weightbearing radiographs (WBXR) was performed for 20 patients with hallux valgus (HV) feet and 20 controls with no such deformity. Axial CT images of both groups were compared for 1st metatarsal pronation angle (α angle) and tibial sesamoid subluxation (TSS) grades. The hallux valgus angle (HVA), first-second intermetatarsal angle (IMA), 1st metatarsal-medial cuneiform angle (MMCA), Meary’s angle, and calcaneal pitch (CP) angle of the study and control groups were compared on both WBXR and the corresponding 2D images of WBCT. All the measurements were independently studied by a dedicated musculoskeletal radiology fellow. Results: HV group demonstrated significantly higher values for TSS grade (p < 0.001) but not for α angle (p = 0.19) compared to controls. Pearson’s correlations of the α angle, in the HV group, revealed no significant linear relationship with TSS grades, IMA and MMCA, and only a moderate positive correlation with HVA as per WBXR (r = 0.38, p = 0.014) but not by WBCT (p = 0.084). Also, α angle performed within the range of a chance (AUC 0.64, 95% CI: 0.49 to 0.66) when measured by receiver operating characteristic (ROC) curves. Conclusion: The α angle - a measure of abnormal hyperpronation of the 1st metatarsal - is an independent factor that may co- exist with other parameters in HV, but in isolation has limited diagnostic utility. ‘Abnormal’ α angles may even be observed in individuals without HV deformity. An increase in the HVA, IMA, MMCA or TSS grade is not necessarily associated with a similar increase in the α angle and hence, the severity of HV deformity may not be judged on this parameter alone. The WBCT is a reliable method to assess hyperpronation and guide physicians during surgical management.

Background: Controversy continues regarding appropriate indications for posterior malleolus fracture fixation in unstable rotational trimalleolar ankle injuries, with limited data comparing gait in operatively treated trimalleolar ankle fractures vs control populations. The purpose of this study was to evaluate the effect of trimalleolar ankle fracture fixation on gait parameters in the early postoperative period as compared to a healthy control population. Methods: Adult patients having undergone operative treatment of isolated trimalleolar ankle fractures were eligible for inclusion. A total of 10 patients met the inclusion criteria and participated in the analysis. Patients were evaluated using standard parameters of human gait 6 months after their index procedures, with gait values compared to a population of 17 non–age-matched healthy control subjects in addition to literature values of healthy populations of younger and older subjects. Results: Significant differences were noted between the spatiotemporal gait parameters of healthy control subjects and patients who had undergone operative treatment of trimalleolar ankle fractures. However, within the fracture group itself, no differences were found between patients with or without posterior malleolar fixation for any of the tested gait parameters. When patients were compared to literature values of younger and older healthy control populations, they were found to have gait patterns more similar to older rather than younger individuals. Conclusion: Operative fixation of trimalleolar ankle fracture does not restore normal gait function in the early postoperative period. Fixation of the posterior malleolus in particular also does not appear to improve gait characteristics. Patients who undergo surgery for these injuries demonstrate gait patterns similar to those of healthy older adults. Level of Evidence: Level II, Therapeutic (prospective cohort study).

Background: Surgical specialties face unique challenges caused by SARS-COV-2 (COVID-19). These disruptions will call on clinicians to have greater consideration for non-operative treatment options to help manage patient symptoms and provide therapeutic care in lieu of the traditional surgical management course of action. This study aimed to summarize the current guidance on elective surgery during the COVID-19 pandemic, assess how this guidance may impact orthopaedic care, and review any recommendations for non-operative management in light of elective surgery disruptions. Methods: A systematic search was conducted, and included guidance were categorized as either “Selective Postponement” or “Complete Postponement” of elective surgery. Selective postponement was considered as guidance that suggested elective cases should be evaluated on a case-by-case basis, whereas complete postponement suggested that all elective procedures be postponed until after the pandemic, with no case-by-case consideration. In addition, any statements regarding conservative/non-operative management were summarized when provided by included reports. Results: A total of 11 reports from nine different health organizations were included in this review. There were seven (63.6%) guidance reports that suggested a complete postponement of non-elective surgical procedures, whereas four (36.4%) reports suggested the use of selective postponement of these procedures. The guidance trends shifted from selective to complete elective surgery postponement occurred throughout the month of March. The general guidance provided by these reports was to have an increased consideration for non-operative treatment options whenever possible and safe. As elective surgery begins to re-open, non-operative management will play a key role in managing the surgical backlog caused by the elective surgery shutdown. Conclusion: Global guidance from major medical associations are in agreement that elective surgical procedures require postponement in order to minimize the risk of COVID-19 spread, as well as increase available hospital resources for managing the influx of COVID-19 patients. It is imperative that clinicians and patients consider non-operative, conservative treatment options in order to manage conditions and symptoms until surgical management options become available again, and to manage the increased surgical waitlists caused by the elective surgery shutdowns.

An amendment to this paper has been published and can be accessed via the original article.

Communicating service-specific practice patterns, guidelines, and provider information to a new team of learners that rotate frequently can be challenging. Leveraging individual and healthcare electronic resources, a mobile device platform was implemented into a newly revised resident onboarding process. We hypothesized that offering an easy-to-use mobile application would improve communication across multiple disciplines as well as improve provider experiences when transitioning to a new rotation. A mobile platform was created and deployed to assist with enhancing communication within a trauma service and its resident onboarding process. The platform had resource materials such as: divisional policies, Clinical Practice Guidelines (CMGs), and onboarding manuals along with allowing for the posting of divisional events, a divisional directory that linked to direct dialing, text or email messaging, as well as on-call schedules. A mixed-methods study, including an anonymous survey, aimed at providing information on team member's impressions and usage of the mobile application was performed. Usage statistics over a 3-month period were analyzed on those providers who completed the survey. After rotation on the trauma service, trainees were asked to complete an anonymous, online survey addressing both the experience with, as well as the utility of, the mobile app. Thirty of the 37 (81%) residents and medical students completed the survey. Twenty-five (83%) trainees stated that this was their first experience rotating on the trauma service and 6 (20%) were from outside of the health system. According to those surveyed, the most useful function of the app were access to the directory (15, 50%), the divisional calendar (4, 13.3%), and the on-call schedules (3, 10%). Overall, the app was felt to be easy to use (27, 90%) and was accessed an average of 7 times per day (1–50, SD 9.67). Over half the survey respondents felt that the mobile app was helpful in completing their everyday tasks (16, 53.3%). Fifteen (50%) of the respondents stated that the app made the transition to the trauma service easier. Twenty-five (83.3%) stated it was valuable knowing about departmental events and announcements, and 17 (56.7%) felt more connected to the division. The evolution of mobile technology is rapidly becoming fundamental in medical education and training. We found that integrating a service-specific mobile application improved the learner's experience when transitioning to a new service and was a valuable onboarding instrument.Level of evidence IV.