Rehabilitation for ankle fractures in adults.

BACKGROUND: Ankle fracture is one of the most common lower limb fractures. Whilst immobilisation of the ankle can support and protect the fracture site during early healing, this also increases the risk of ankle weakness, stiffness, and residual pain. Rehabilitation aims to address the after-effects of this injury, to improve ankle function and quality of life. Approaches are wide-ranging and include strategies to improve ankle joint movement, muscle strength, or both. This is an update of a Cochrane review last published in 2012. OBJECTIVES: To assess the effects of rehabilitation interventions following surgical or non-surgical management of ankle fractures in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, three other databases, and two clinical trials registers in May 2022, and conducted additional searches of CENTRAL, MEDLINE, and Embase in March 2023. We also searched reference lists of included studies and relevant systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing any rehabilitation intervention delivered to adults with ankle fracture. Interventions could have been given during or after the initial fracture management period (typically the first six weeks after injury), which may or may not have included surgical fixation. We excluded participants with multi-trauma, pathological fracture, or with established complications secondary to ankle fracture. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We collected data for five outcomes: activity limitation (ankle function), health-related quality of life (HRQoL), participant satisfaction with treatment, pain, and adverse events (we focused on re-operation, defined as unplanned return to theatre). We report the findings up to six months after injury. MAIN RESULTS: We included 53 studies (45 RCTs, 8 quasi-RCTs) with 4489 adults with ankle fracture. In most studies, orthopaedic management included surgical fixation but was non-surgical in five studies, and either surgical or non-surgical in six studies. Here, we summarise the findings for three common rehabilitation comparisons; these included the most data and were the most clinically relevant. Because of different intervention approaches, we sometimes included a study in more than one comparison. Data for other less common comparisons were also available but often included few participants and were imprecise. All studies were unavoidably at high risk of performance and detection bias. We downgraded the certainty of all evidence for this reason. We also downgraded for imprecision and when we noted inconsistencies between studies that precluded meta-analysis of data. Early (within 3 weeks of surgery) versus delayed weight-bearing (12 studies, 1403 participants) Early weight-bearing probably leads to better ankle function (mean difference (MD) 3.56, 95% confidence interval (CI) 1.35 to 5.78; 5 studies, 890 participants; moderate-certainty evidence); however, this does not include a clinically meaningful difference. Early weight-bearing may offer little or no difference to HRQoL compared to delayed weight-bearing (standardised mean difference (SMD) 0.15, 95% CI -0.01 to 0.30; 5 studies, 739 participants; low-certainty evidence); when translated to the EQ-5D scale (a commonly-used HRQoL questionnaire), any small difference was not clinically important. We were unsure whether there were any differences in participant satisfaction or pain because these outcomes had very low-certainty evidence. For adverse events, there may be little or no difference in re-operation (risk ratio (RR) 0.50, 95% CI 0.09 to 2.68; 7 studies, 1007 participants; low-certainty evidence). Removable versus non-removable ankle support (25 studies, 2206 participants) Following surgery, using a removable ankle support may lead to better ankle function (MD 6.39, 95% CI 1.69 to 11.09; 6 studies, 677 participants; low-certainty evidence). This effect included both a clinically important and unimportant difference. There is probably an improvement in HRQoL with a removable ankle support, although this difference included both a clinically important and unimportant difference when translated to the EQ-5D scale (SMD 0.30, 95% CI 0.11 to 0.50; 3 studies, 477 participants; moderate-certainty evidence). No studies reported participant satisfaction. We were unsure of the effects on pain because of very low-certainty evidence (1 study, 29 participants). There may be little or no difference in re-operations (RR 1.20, 95% CI 0.39 to 3.71; 6 studies, 624 participants; low-certainty evidence). Following non-surgical management, there may be little or no difference between removable and non-removable ankle supports in ankle function (MD 1.08, 95% CI -3.18 to 5.34; 3 studies, 399 participants), and HRQoL (SMD -0.04, 95% CI -0.24 to 0.15; 3 studies, 397 participants); low-certainty evidence. No studies reported participant satisfaction. We were unsure of the effects on pain (2 studies, 167 participants), or re-operation because of very low-certainty evidence (1 study, 305 participants). Physical therapy interventions versus usual care or other physical therapy interventions (9 studies, 857 participants) Types of interventions included the use of active controlled motion, a spring-loaded ankle trainer, an antigravity treadmill, and variations of enhanced physiotherapy (e.g. additional stretching, joint mobilisation, neuromuscular exercises), delivered during or after the initial fracture management period. We were unable to pool data because of the differences in the design of interventions and their usual care comparators. Studies often included very few participants. The certainty of the evidence for all outcomes in this comparison was very low, and therefore we were unsure of the effectiveness of these therapies. No studies in this comparison reported re-operation. AUTHORS' CONCLUSIONS: Early weight-bearing may improve outcomes in the first six months after surgery for ankle fracture, but the difference is likely to be small and may not always be clinically important. A removable ankle support may also provide a better outcome, but again, the difference may not always be clinically important. It is likely that neither approach increases the re-operation risk. We assume that the findings for these comparisons are applicable to people with closed ankle fractures, and that satisfactory fracture stabilisation had been achieved with surgery. For people who have non-surgical treatment, there is no evidence that either a removable or non-removable ankle support may be superior. We were uncertain whether any physical therapy interventions were more effective than usual care or other physical therapy interventions. We encourage investigators of future studies on rehabilitation interventions for ankle fracture to use a core outcome set.

The FAME trial study protocol: In younger adults with unstable ankle fractures treated with close contact casting, is ankle function not worse than those treated with surgical intervention?

Aims: Ankle fracture is one of the most common musculoskeletal injuries sustained in the UK. Many patients experience pain and physical impairment, with the consequences of the fracture and its management lasting for several months or even years. The broad aim of ankle fracture treatment is to maintain the alignment of the joint while the fracture heals, and to reduce the risks of problems, such as stiffness. More severe injuries to the ankle are routinely treated surgically. However, even with advances in surgery, there remains a risk of complications; for patients experiencing these, the associated loss of function and quality of life (Qol) is considerable. Non-surgical treatment is an alternative to surgery and involves applying a cast carefully shaped to the patient's ankle to correct and maintain alignment of the joint with the key benefit being a reduction in the frequency of common complications of surgery. The main potential risk of non-surgical treatment is a loss of alignment with a consequent reduction in ankle function. This study aims to determine whether ankle function, four months after treatment, in patients with unstable ankle fractures treated with close contact casting is not worse than in those treated with surgical intervention, which is the current standard of care. Methods: This trial is a pragmatic, multicentre, randomized non-inferiority clinical trial with an embedded pilot, and with 12 months clinical follow-up and parallel economic analysis. A surveillance study using routinely collected data will be performed annually to five years post-treatment. Adult patients, aged 60 years and younger, with unstable ankle fractures will be identified in daily trauma meetings and fracture clinics and approached for recruitment prior to their treatment. Treatments will be performed in trauma units across the UK by a wide range of surgeons. Details of the surgical treatment, including how the operation is done, implant choice, and the recovery programme afterwards, will be at the discretion of the treating surgeon. The non-surgical treatment will be close-contact casting performed under anaesthetic, a technique which has gained in popularity since the publication of the Ankle Injury Management (AIM) trial. In all, 890 participants (445 per group) will be randomly allocated to surgical or non-surgical treatment. Data regarding ankle function, QoL, complications, and healthcare-related costs will be collected at eight weeks, four and 12 months, and then annually for five years following treatment. The primary outcome measure is patient-reported ankle function at four months from treatment. Anticipated impact: The 12-month results will be presented and published internationally. This is anticipated to be the only pragmatic trial reporting outcomes comparing surgical with non-surgical treatment in unstable ankle fractures in younger adults (aged 60 years and younger), and, as such, will inform the National Institute for Health and Care Excellence (NICE) 'non-complex fracture' recommendations at their scheduled update in 2024. A report of long-term outcomes at five years will be produced by January 2027.

The true pelvic volume change with various corrective osteotomy techniques for exstrophy-epispadias complex spectrum: the value of computer-assisted virtual surgery.

Pelvic osteotomies are essential to approximate widened symphysis pubis in the exstrophy-epispadias complex, yet it is unknown which osteotomy type has the greatest effect on pelvic volume. We therefore used virtual surgery to study pelvic volume change with anterior, oblique, and posterior iliac osteotomies. Preoperative CT scans of two cloacal and one classic bladder exstrophy patients were used. Simulations were free-hand or constrained to keep minimal strain in the sacrospinous SSL and sacrotuberous STL ligaments. Changes in inter-pubic distance, pelvic volume, SSL and STL strains were measured. Mean pelvic volume decreased by 10% with free hand compared to 23% with constrained simulations ( P  = 0.171) and decreased by 7% with posterior, 17% with diagonal and 26% with horizontal osteotomies ( P  = 0.193). SSL and STL were strained by 20% and 26%, respectively, with free-hand simulations. A statistically significant moderate positive correlation was found between the decrease in inter-pubic distance and reduction in pelvic volume (r = 0.6, P  = 0.004). Mean pelvic volume decreased 0.05, 0.37 and 0.62% for each mm of pubic symphysis approximation with posterior, diagonal and horizontal osteotomies, respectively. Differences in effect on pelvic volume were identified between the osteotomies using virtual surgery which predicted residual diastasis in actual cloacal exstrophy surgical reconstructions. Oblique osteotomies are a compromise, avoiding difficulties with posterior osteotomies and excessive pelvic volume reduction with horizontal osteotomies. Understanding how osteotomy type affects pelvic morphology with virtual surgery may be an effective adjunct to pre-operative planning in exstrophy spectrum.

Bladder Neck Surgery is not Routinely Needed to Achieve Urinary Continence in Patients with Primary Epispadias.

BACKGROUND: This study aims at investigating the continence outcome in primary epispadias patients treated at a tertiary center. The authors hypothesized that additional continence procedures following primary epispadias repair is not routinely needed. METHODS: Patients treated for primary epispadias at the authors' institution between 2007 and 2019 and toilet trained, were identified from a prospective maintained database. Males underwent chordee correction, urethroplasty and glanuloplasty. Females underwent genitoplasty with reduction urethroplasty. If continence was not achieved by 4-5 years of age, pelvic floor muscle (PFM) biofeedback therapy was performed. Other continent procedures were discussed with family/patient if still incontinent. PRIMARY OUTCOME: urinary continence. SECONDARY OUTCOMES: PFM biofeedback therapy, continence surgery, hydronephrosis. Type of epispadias, age at repair and follow-up presented as median was also reported. RESULTS: Thirty-three patients (29 males) were included. Twelve had penopubic epispadias, 13 glanular/penile, 4 duplicated urethra, 4 females. Median age at repair: 2 years (IQR 1-3), at follow-up: 8 years (IQR 6-10). Daytime continence: 100 % in penile/glanular; 33 % in penopubic and 75 % in duplicated urethra. Nighttime continence: respectively 92 %, 50 % and 100 %. 24 % of males were intermittently incontinent. All patients except one voided urethrally. One patient underwent bladder neck closure, ileocystoplasty and Mitrofanoff. One girl achieved daytime continence, 2 were intermittently incontinent, one continuously incontinent. All were enuretic. 38 % of boys and 100 % of girls had biofeedback therapy. None had hydronephrosis/renal impairment. CONCLUSIONS: Most children with primary epispadias can achieve social urinary continence spontaneously or with the support of PFM biofeedback therapy. Other continence procedures should be reserved for patients who do not attain satisfactory continence. LEVEL OF EVIDENCE: Treatment study - level IV.

Pain with neuropathic characteristics after surgically treated lower limb fractures: Cost analysis and pain medication use.

Introduction: Neuropathic pain is prevalent among people after lower limb fracture surgery and is associated with lower health-related quality of life and greater disability. This study estimates the financial cost and pain medication use associated with neuropathic pain in this group. Methods: A secondary analysis using pain data collected over six postoperative months from participants randomised in the Wound Healing in Surgery for Trauma (WHiST) trial. Pain states were classified as pain-free, chronic non-neuropathic pain (NNP) or chronic neuropathic pain (NP). Cost associated with each pain state from a UK National Health Service (NHS) and personal social services (PSS) perspective were estimated by multivariate models based on multiple imputed data. Pain medication usage was analysed by pain state. Results: A total of 934 participants who provided either 3- or 6-months pain data were included. Compared to participants with NP, those with NNP (adjusted mean difference -£730, p = 0.38, 95% CI -2368 to 908) or were pain-free (adjusted mean difference -£716, p = 0.53, 95% CI -2929 to 1497) had lower costs from the NHS and PSS perspective in the first three postoperative months. Over the first three postoperative months, almost a third of participants with NP were prescribed opioids and 8% were prescribed NP medications. Similar trends were observed by 6 months postoperatively. Conclusion: This study found healthcare costs were higher amongst those with chronic NP compared to those who were pain-free or had chronic NNP. Opioids, rather than neuropathic pain medications, were commonly prescribed for NP over the first six postoperative months, contrary to clinical guidelines.

Experience of patients and physiotherapists within the AFTER pilot randomised trial of two rehabilitation interventions for people aged 50 years and over post ankle fracture: a qualitative study.

OBJECTIVES: To explore patient and staff experience of best-practice rehabilitation advice (one session of face-to-face self-management advice with up to two additional optional sessions) compared with progressive functional exercise (up to six sessions of face-to-face physiotherapy) after ankle fracture. DESIGN: The study drew on phenomenology using interviews and a focus group. SETTING: Participants were from three NHS Trusts in England, UK. PARTICIPANTS: A purposive sample of 20 patients with ankle (malleolar) fractures from the Ankle Fracture Treatment: Enhancing Rehabilitation-pilot trial (now completed) were interviewed (median 50 min) from May 2019 to January 2020. They were 6 months post injury, over 50 years of age, (median 66, 12 females) and had received surgical or non-surgical treatment (seven internal fixation surgery, seven close contact casting, six walking boot). A focus group of five physiotherapists who had provided the study interventions (2.5 hours) was undertaken. RESULTS: The findings show the acceptability of both interventions through the themes, 'being helped' (for patients) and 'developing expertise' (for staff) with subthemes of choosing and progressing. Progressive exercise added value with a perceived increase in strength, motion, ability to undertake activities and continued use of the workbook. Both staff and patients valued physiotherapy expertise demonstrated through interpersonal skills, advice, individualised exercise plans and active monitoring of progression. Best practice advice was particularly helpful in the early stages of recovery and with the use of mobility aids. CONCLUSION: Both interventions were acceptable but progressive exercise was highly valued by patients. Developing expertise through experiential learning enabled staff to facilitate progression. Adjustments to the workbook and the addition of exercises for continued recovery in the best practice advice would enhance a future study. Research during treatment provision may provide further insights into the challenges of facilitating progression of exercise. TRIAL REGISTRATION: ISRCTN16612336; AFTER-pilot trial).

Urethral Plate Grafting for Deficient Urethral Plate in Exstrophy: An Alternative Method to Augment Urethral Plate.

INTRODUCTION: Short urethral plate remains a challenge in exstrophy management. We report our experience with urethral plate grafting in cases of exstrophy with deficient urethral plate. METHODS: Among the exstrophy patients treated at the authors' institutions (2018-2022), those with a short urethral plate were prospectively included. A short urethral plate was defined as a distance between the verumontanum and the base of the glans of less than 10 mm. Urethral plate grafting was performed electively before the exstrophy closure. The urethral plate was divided just distal to verumontanum, and a thin inner preputial or para-exstrophy skin graft was harvested and deployed to cover the defect. Exstrophy closure was subsequently performed. The following parameters were recorded: age at grafting, type of graft and age at exstrophy closure. Reported outcomes include success of closure, complications, and follow up. RESULTS: Six male patients were included in the study: 3 classic bladder exstrophy (CBE) and 3 cloacal exstrophy (CE). Median age at grafting was 9 (3-18) months. Inner preputial grafts were utilized in the 3 CBE patients, and para-exstrophy skin grafts were used for the 3 CE patients. There was no graft loss, and longer and wide urethral plate was seen in all cases. Median time to bladder exstrophy closure was 3 (3-13) months after grafting. CONCLUSION: Pre-closure urethral plate grafting represents a safe and effective option for exstrophy patients with a short or inadequate urethral plate.

'It Makes Me Feel Old': Understanding the Experience of Recovery From Ankle Fracture at 6 Months in People Aged 50 Years and Over.

Ankle fracture is a common injury, and depending on injury severity, treatment may be a support boot, cast or surgery. Older people, particularly those with severe injuries who are asked to restrict weight bearing, struggle with early recovery. To elicit older peoples' experience of recovery 6 months after injury, we drew on a phenomenological approach using interviews. Findings revealed that getting on with life was a way of accepting what it feels like to 'be vulnerable', needing to 'be safe' while determinedly working hard to 'be myself'. Being vulnerable identified endurance of inactivity, loneliness and dependency in the non-weight bearing period of recovery, followed by a struggle to weight bear while lacking confidence and being fearful of falling and causing further damage. Being safe conveyed fragility where sensations, pain and stiffness acted as bodily reminders of injury. Lack of function and awareness of danger led to carefulness where planning or curtailing of activities ensured their safety. Being myself showed a determination to push away from a disrupted self-identify of being older or disabled while being challenged by the continuous process of learning to be more mobile. A lack of readiness for old age created a drive to age well. Despite loss of ability, participants hoped to regain their pre-injury way of living. This study challenges practice that disregards the hard work required to recover from ankle fracture. As comorbidity increases with age, failure to consider this aspect may contribute to frailty in this group of older people.

A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy.

Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.

Barrier-Forming Potential of Epithelial Cells from the Exstrophic Bladder.

Bladder exstrophy (BEX) is a rare developmental abnormality resulting in an open, exposed bladder plate. Although normal bladder urothelium is a mitotically quiescent barrier epithelium, histologic studies of BEX epithelia report squamous and proliferative changes that can persist beyond surgical closure. The current study examined whether patient-derived BEX epithelial cells in vitro were capable of generating a barrier-forming epithelium under permissive conditions. Epithelial cells isolated from 11 BEX samples, classified histologically as transitional (n = 6) or squamous (n = 5), were propagated in vitro. In conditions conducive to differentiated tight barrier formation by normal human urothelial cell cultures, 8 of 11 BEX lines developed transepithelial electrical resistances of more than 1000 Ω.cm2, with 3 squamous lines failing to generate tight barriers. An inverse relationship was found between expression of squamous KRT14 transcript and barrier development. Transcriptional drivers of urothelial differentiation PPARG, GATA3, and FOXA1 showed reduced expression in squamous BEX cultures. These findings implicate developmental interruption of urothelial transcriptional programming in the spectrum of transitional to squamous epithelial phenotypes found in BEX. Assessment of BEX epithelial phenotype may inform management and treatment strategies, for which distinction between reversible versus intractably squamous epithelium could identify patients at risk of medical complications or those who are most appropriate for reconstructive tissue engineering strategies.

Is an individually tailored programme of intense leg resistance and dynamic exercise acceptable to adults with an acute lateral patellar dislocation? A feasibility study.

BACKGROUND: Lateral patellar dislocations mainly affect active teenagers and young adults. To help people recover, non-surgical exercise-based treatment is often recommended but the optimal exercise-based treatment is unknown. Currently, treatment outcomes after this injury are variable. Common problems include recurrent dislocation, reduced activity levels, and later surgery. A programme of intense leg resistance exercises, and dynamic exercises related to participants' activity-related goals, has rationale, but has not been previously reported. In line with the Medical Research Council guidance, this study aimed to assess the acceptability of a novel evidence-based exercise programme for adults after acute lateral patellar dislocation and the feasibility of future research evaluating this treatment. METHODS: A single-group prospective study was conducted at the John Radcliffe Hospital, Oxford, UK. Participants were 16 years or older with an acute first-time or recurrent lateral patellar dislocation. Participants received up to six face-to-face, one-to-one, physiotherapy sessions, over a maximum of 3 months, and performed intensive home exercises independently at least three times per week. Strategies to increase exercise adherence were used. Primary objectives were to determine the number of eligible patients, the recruitment rate (proportion of eligible patients that provided written informed consent), participant adherence to scheduled physiotherapy sessions and self-reported adherence to prescribed exercise, and intervention acceptability to participants measured by attrition and a study-specific questionnaire. Data were analysed using descriptive statistics. RESULTS: Fifteen of 22 (68%) patients with a lateral patellar dislocation were eligible. All eligible (100%) were recruited. Two of 15 (13%) participants provided no outcome data, 2/15 (13%) provided partial outcome data, and 11/15 (73%) provided all outcome data. Questionnaire responses demonstrated high intervention acceptability to participants. Participants attended 56/66 (85%) physiotherapy sessions and 10/11 (91%) participants reported they 'always' or 'often' completed the prescribed exercise. One participant redislocated their patella; another experienced knee pain or swelling lasting more than one week after home exercise on three occasions. CONCLUSION: The intervention appeared acceptable to adults after acute lateral patellar dislocation, and a future randomised pilot trial is feasible. This future pilot trial should estimate attrition with increased precision over a longer duration and assess participants' willingness to be randomised to different treatments across multiple centres. TRIAL REGISTRATION: ClinicalTrials.gov NCT03798483 , registered on January 10, 2019.

The place of retroperitoneoscopic hemi-nephroureterectomy for duplex kidney in children; risk of damage to the remnant moiety and strategies to reduce the risk.

OBJECTIVE: To analyse the outcomes of retroperitoneoscopic upper and lower moiety hemi-nephroureterectomy (HNU) and to assess the different variables that may have an impact on outcome; remnant moiety damage, morbidity and the need for secondary surgery. METHODS: Prospectively recorded data of retroperitoneoscopic HNU's performed by a single surgeon from 2005 to 2018 were analysed. Patients were split into 2 groups according to moiety affected (UMHNU and LMHNU). Clinical presentation, underlying pathology, remnant moiety DRF on renal scintigraphy, and need for further surgery were recorded. Detailed operation notes were studied regards to renal vasculature, degree of dilatation, inflammatory changes and operative difficulties encountered. Renal loss was defined as remnant moiety DRF <10% post-operatively. Change in DRF was assessed regards to the moiety, pathology and age at surgery (<1 year, 1-2 years and ≥2 years). UMHNU group was further sub-divided into 3 subgroups: ureteroceles, ectopic ureters and 'other' pathology. Statistical analysis was performed using Fishers Exact test; findings were considered statistically significant at p < 0.05. RESULTS: 78 operations met the inclusion criteria on 75 patients (3 bilateral). There were no conversions to open, and 67% were performed as day-case procedures (53/78 patients). In 91.2% (71/78) patients the procedure was definitive in resolving pathology and symptoms. 7 patients needed further procedures after HNU, 5 for ureterocele/ureteric stump. Overall, there was remnant moiety renal loss in 5.1% (4/78) patients, all with UM surgery (3 ectopic ureters and 1 ureterocele). All 4 operations were recorded prospectively as 'difficult operations' due to grossly dilated UM ureter/pelvis measuring >2 cm in diameter. 2 patients had a thinned out lower moiety (LM) sitting on top of the UM renal pelvis like a pancake with all vessels stretched over this dilated pelvis/ureter causing difficulty in accurate identification. There was intra-operative concern about some damage to LM vessels in 3 patients. Age <1year was also related to increased renal loss (2/8 patients <1 year, 1/25 patients 1-2 years, 1/45 patients ≥2 years of age P = 0.005). CONCLUSION: Retroperitoneoscopic LMHNU is a safe and definitive procedure with rapid recovery and minimal scarring. UMHNU has higher rates of remnant moiety loss due to more complex renal pathology, but remains a safe, successful operation on the majority of patients. Renal damage was also related to age <1year (p = 0.005) and re-operation risk after UMHNU correlated to the presence of ureterocele (p = 0.003).

Progressive exercise compared with best practice advice, with or without corticosteroid injection, for the treatment of patients with rotator cuff disorders (GRASP): a multicentre, pragmatic, 2 × 2 factorial, randomised controlled trial.

BACKGROUND: Corticosteroid injections and physiotherapy exercise programmes are commonly used to treat rotator cuff disorders but the treatments' effectiveness is uncertain. We aimed to compare the clinical effectiveness and cost-effectiveness of a progressive exercise programme with a single session of best practice physiotherapy advice, with or without corticosteroid injection, in adults with a rotator cuff disorder. METHODS: In this pragmatic, multicentre, superiority, randomised controlled trial (2 × 2 factorial), we recruited patients from 20 UK National Health Service trusts. We included patients aged 18 years or older with a rotator cuff disorder (new episode within the past 6 months). Patients were excluded if they had a history of significant shoulder trauma (eg, dislocation, fracture, or full-thickness tear requiring surgery), neurological disease affecting the shoulder, other shoulder conditions (eg, inflammatory arthritis, frozen shoulder, or glenohumeral joint instability), received corticosteroid injection or physiotherapy for shoulder pain in the past 6 months, or were being considered for surgery. Patients were randomly assigned (centralised computer-generated system, 1:1:1:1) to progressive exercise (≤6 sessions), best practice advice (one session), corticosteroid injection then progressive exercise, or corticosteroid injection then best practice advice. The primary outcome was the Shoulder Pain and Disability Index (SPADI) score over 12 months, analysed on an intention-to-treat basis (statistical significance set at 1%). The trial was registered with the International Standard Randomised Controlled Trial Register, ISRCTN16539266, and EuDRACT, 2016-002991-28. FINDINGS: Between March 10, 2017, and May 2, 2019, we screened 2287 patients. 708 patients were randomly assigned to progressive exercise (n=174), best practice advice (n=174), corticosteroid injection then progressive exercise (n=182), or corticosteroid injection then best practice advice (n=178). Over 12 months, SPADI data were available for 166 (95%) patients in the progressive exercise group, 164 (94%) in the best practice advice group, 177 (97%) in the corticosteroid injection then progressive exercise group, and 175 (98%) in the corticosteroid injection then best practice advice group. We found no evidence of a difference in SPADI score between progressive exercise and best practice advice when analysed over 12 months (adjusted mean difference -0·66 [99% CI -4·52 to 3·20]). We also found no evidence of a difference between corticosteroid injection compared with no injection when analysed over 12 months (-1·11 [-4·47 to 2·26]). No serious adverse events were reported. INTERPRETATION: Progressive exercise was not superior to a best practice advice session with a physiotherapist in improving shoulder pain and function. Subacromial corticosteroid injection provided no long-term benefit in patients with rotator cuff disorders. FUNDING: UK National Institute for Health Research Technology Assessment Programme.

Objectively quantified lower limb strength recovery in people treated surgically or non-surgically after patellar dislocation: A systematic review.

OBJECTIVE: Synthesize evidence on objectively quantified lower limb strength recovery in people treated surgically or non-surgically after patellar dislocation. METHODS: MEDLINE, EMBASE, Cochrane Library, SPORTDiscus, PEDro, AMED and CINAHL databases were last searched on July 30th, 2020 for randomized controlled trials and observational studies that objectively quantified lower limb strength in people (any age or sex) treated surgically or non-surgically after patellar dislocation. RESULTS: 24 studies were included (877 participants, median age 20.7). All assessed knee extension strength, 11 knee flexion strength, three hip abduction strength, two hip external rotation strength, and one hip flexion, extension, adduction, and internal rotation strength. One randomized controlled trial judged at high risk of bias and two cohort studies with methodological limitations compared lower limb strength recovery between surgically and non-surgically treated people, with conflicting findings. After surgery, median long-term (>8 months) knee extension strength was 82.5% (IQR 78.5-88.2; 13 studies) of the unaffected leg and knee flexion strength was 91.5% (IQR 90.7-96.9; five studies). After non-surgical treatment, median long-term knee extension strength was 86% (IQR 79.3-87.4; four studies) and mean flexion strength ranged from 95.2 to 96.7% (two studies). Mean hip strength was always >90% (two studies). Two redislocations during eccentric isokinetic knee testing and knee pain during isokinetic knee extension testing were reported as adverse events. CONCLUSIONS: Available evidence indicates that after patellar dislocation, knee extension strength deficits in the affected limb are frequently observed and can persist long term, but this remains uncertain due to the limitations of relevant included studies. Whether lower limb strength recovery differs between people treated surgically and those treated non-surgically after patellar dislocation also remains uncertain. TRIAL REGISTRATION: (PROSPERO CRD42019139533).

Chronic pain with neuropathic characteristics after surgery for major trauma to the lower limb: prevalence, predictors, and association with pain severity, disability, and quality of life in the UK WHiST trial.

AIMS: To identify the prevalence of neuropathic pain after lower limb fracture surgery, assess associations with pain severity, quality of life and disability, and determine baseline predictors of chronic neuropathic pain at three and at six months post-injury. METHODS: Secondary analysis of a UK multicentre randomized controlled trial (Wound Healing in Surgery for Trauma; WHiST) dataset including adults aged 16 years or over following surgery for lower limb major trauma. The trial recruited 1,547 participants from 24 trauma centres. Neuropathic pain was measured at three and six months using the Doleur Neuropathique Questionnaire (DN4); 701 participants provided a DN4 score at three months and 781 at six months. Overall, 933 participants provided DN4 for at least one time point. Physical disability (Disability Rating Index (DRI) 0 to 100) and health-related quality-of-life (EuroQol five-dimension five-level; EQ-5D-5L) were measured. Candidate predictors of neuropathic pain included sex, age, BMI, injury mechanism, concurrent injury, diabetes, smoking, alcohol, analgaesia use pre-injury, index surgery location, fixation type, Injury Severity Score, open injury, and wound care. RESULTS: The median age of the participants was 51 years (interquartile range 35 to 64). At three and six months post-injury respectively, 32% (222/702) and 30% (234/787) had neuropathic pain, 56% (396/702) and 53% (413/787) had chronic pain without neuropathic characteristics, and the remainder were pain-free. Pain severity was higher among those with neuropathic pain. Linear regression analyses found that those with neuropathic pain at six months post-injury had more physical disability (DRI adjusted mean difference 11.49 (95% confidence interval (CI) 7.84 to 15.14; p < 0.001) and poorer quality of life (EQ-5D utility -0.15 (95% CI -0.19 to -0.11); p < 0.001) compared to those without neuropathic characteristics. Logistic regression identified that prognostic factors of younger age, current smoker, below knee fracture, concurrent injuries, and regular analgaesia pre-injury were associated with higher odds of post-injury neuropathic pain. CONCLUSION: Pain with neuropathic characteristics is common after lower limb fracture surgery and persists to six months post-injury. Persistent neuropathic pain is associated with substantially poorer recovery. Further attention to identify neuropathic pain post-lower limb injury, predicting patients at risk, and targeting interventions, is indicated. Cite this article: Bone Joint J 2021;103-B(6):1047-1054.

The findings of a surgical hip fracture trial were generalizable to the UK national hip fracture database.

OBJECTIVE: To estimate the generalizability of treatment effects observed in a randomized trial of hip fracture surgery implants to a broader population of people undergoing hip surgery in the United Kingdom. STUDY DESIGN AND SETTING: In 2018, the WHiTE-3 trial (n = 958) demonstrated that a modular hemiarthroplasty implant conferred no additional benefit over the traditional monoblock implant for quality of life and length of hospital stay. We compared and weighted the trial sample against two target populations: WHiTE-cohort (n = 2,457) and UK-National Hip Fracture Database (NHFD, n = 190,894), and re-estimate expected treatment effects for the target populations. RESULTS: Despite differences in baseline characteristics of the trial sample and target populations, the re-estimated treatment effects were comparable. For quality of life, the differences between the trial estimate and WHiTE-cohort and NHFD estimates were 0.01 points on the EuroQol (EQ5D). For length of stay, the difference between the trial estimate and WHiTE-cohort was 0.50 days; and the difference between the trial estimate and NHFD estimate was -0.47 days. CONCLUSION: This generalizability analysis of the WHiTE-3 trial found that the inferences from the trial can be generalized to a wider population of individuals in the UK NHFD and the WHiTE-cohort who met the inclusion criteria for WHiTE-3.

Intravesical gentamicin instillation for the treatment and prevention of urinary tract infections in complex paediatric urology patients: evidence for safety and efficacy.

BACKGROUND: Little has been reported to date on the instillation of antimicrobials directly into the bladder in children. Children with complex urinary tract anomalies struggle frequently with recurrent urinary tract infections (UTI), with frequent emergence of antibiotic resistance. Gentamicin bladder instillation to treat and prevent UTI was described in children since 2006. OBJECTIVE: We adopted gentamicin bladder instillation in 2016 and evaluate herein our intermediate-term experience with it. STUDY DESIGN AND METHODS: This study is a retrospective review of a prospectively initiated database and a clinical audit of our practice. The gentamicin bladder instillation was employed in 24 cases. A treatment regime was initiated for symptomatic documented UTI when resistance patterns precluded an oral alternative (14 cases), avoiding hospitalisation for parenteral antibiotics. A prophylaxis regime (19 cases-including 9 of the 14 who received an initial treatment regime) followed at least one breakthrough UTI while receiving oral prophylactic antibiotics. Two instillation volumes (8 mg gentamicin in 20 mL 0.9% NaCl or 20 mg gentamicin in 50 mL 0.9% NaCl) were used to suit different bladder capacities. The irrigation is given twice a day for 7 days in the treatment regime or once a day, every other day, in the prophylactic regime. Gentamicin serum levels (all cases) and audiology/audiometry testing (17/24 cases) were checked to assess the safety of this method. RESULTS: The median age when either the treatment course or prophylaxis regime was started was 3.8 years. The treatment regime was 86% successful (12/14) to suppress an acute UTI. The mean duration of prophylaxis was 252 days (median: 256 days). The percentage of patients on the prophylactic regime who had no breakthrough UTI was 58%. No serum gentamicin was detectable secondary to the intravesical instillation. No attributable cases of sensorineural hearing loss were detected. Gentamicin resistance emerged in one case (4.16%). DISCUSSION: Intravesical administration was feasible via various routes for a spectrum of complex lower urinary tract abnormalities (see Summary Figure). Concerns regarding systemic absorption, nephrotoxicity or ototoxicity were investigated and safety ensured. Limitations include being a small series of non-identical pathologies, albeit categorically similar and being a single-arm study, however, statistical significance was proven descriptively and analytically. CONCLUSION: In selected cases and with the appropriate specialist support and logistics, intravesical gentamicin instillation is well-tolerated and safe to treat and/or prevent urinary tract infections in pateints with complex bladder conditions and lower urinary tract pathologies.

Progressive exercise compared with best practice advice, with or without corticosteroid injection, for the treatment of rotator cuff disorders: statistical analysis plan for the Getting it Right: Addressing Shoulder Pain (GRASP) 2 × 2 factorial multicentre randomised controlled trial.

BACKGROUND: The Getting it Right: Addressing Shoulder Pain (GRASP) trial assesses the clinical and cost-effectiveness of individually tailored, progressive exercise compared with best practice advice, with or without corticosteroid injection, in adults with a rotator cuff disorder. This article describes the statistical analysis plan for the GRASP randomised controlled trial. METHODS/DESIGN: GRASP is a multicentre randomised controlled trial using a 2 × 2 factorial design. Adults aged ≥ 18 years with a new episode of shoulder pain related to a rotator cuff disorder, not currently receiving physiotherapy or being considered for surgery, are randomised (centralised computer-generated 1:1:1:1 allocation ratio) to one of four interventions: (1) progressive exercise (up to 6 physiotherapy sessions), (2) best practice advice (one physiotherapy session), (3) subacromial corticosteroid injection then progressive exercise and (4) subacromial corticosteroid injection then best practice advice. The primary outcome is the mean difference in Shoulder Pain and Disability Index (SPADI) total score over 12 months. Secondary outcomes are as follows: pain and function SPADI subdomains, health-related quality of life (EuroQol EQ-5D-5L), sleep disturbance, return to activity, global impression of change, health resource use, out-of-pocket expenses and work disability. Here, we describe in detail the following: sample size calculation, descriptive statistics of the primary and secondary outcomes, statistical models used for the analysis of the main outcomes, handling of missing data, planned sensitivity and subgroup analyses. This pre-specified statistical analysis plan was written and submitted without prior knowledge of the trial results. DISCUSSION: Publication of the statistical analysis plan for the GRASP trial aims to reduce the risk of outcome reporting bias and increase transparency of the data analysis. Any deviations or changes to the current SAP will be described and justified in the final study report and any results publications. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number ISRCTN16539266 . Registered on 14 June 2016. EudraCT number 2016-002991-28. Registered on 12 June 2016.

SLC20A1 Is Involved in Urinary Tract and Urorectal Development.

Previous studies in developing Xenopus and zebrafish reported that the phosphate transporter slc20a1a is expressed in pronephric kidneys. The recent identification of SLC20A1 as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role of SLC20A1 in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish ortholog slc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detected SLC20A1 in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequenced SLC20A1 in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelic de novo variants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novel de novo variant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact of SLC20A1 variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggest SLC20A1 is involved in urinary tract and urorectal development and implicate SLC20A1 as a disease-gene for BEEC.

Implications of the Ankle Injury Management (AIM) trial: close contact casting or surgery for older adults with an unstable ankle fracture?

The Ankle Injury Management (AIM) trial was a pragmatic equivalence randomized controlled trial conducted at 24 hospitals in the United Kingdom that recruited 620 patients aged more than 60 years with an unstable ankle fracture. The trial compared the usual care pathway of early management with open reduction and internal fixation with initially attempting non-surgical management using close contact casting (CCC). CCC is a minimally padded cast applied by an orthopaedic surgeon after closed reduction in the operating theatre. The intervention groups had equivalent functional outcomes at six months and longer-term follow-up. However, potential barriers to using CCC as an initial form of treatment for these patients have been identified. In this report, the results of the AIM trial are summarized and the key issues are discussed in order to further the debate about the role of CCC. Evidence from the AIM trial supports surgeons considering conservative management by CCC as a treatment option for these patients. The longer-term follow-up emphasized that patients treated with CCC need careful monitoring in the weeks after its application to monitor maintenance of reduction. Cite this article: Bone Joint J 2019;101-B:1472-1475.