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Background Recruitment to surgical randomised controlled trials (RCTs) can be challenging. The Sunflower study is a large-scale multi-centre RCT that seeks to establish the clinical and cost effectiveness of pre-operative imaging versus expectant management in patients with symptomatic gallstones undergoing laparoscopic cholecystectomy at low or moderate risk of common bile duct stones. Trials such as Sunflower, with a large recruitment target, rely on teamworking. Recruitment can be optimised by embedding a QuinteT Recruitment Intervention (QRI). Additionally, engaging surgical trainees can contribute to successful recruitment, and the NIHR Associate Principal Investigator (API) scheme provides a framework to acknowledge their contributions. Methods This was a mixed-methods study that formed a component part of an embedded QRI for the Sunflower RCT. The aim of this study was to understand factors that supported and hindered the participation of surgical trainees in a large-scale RCT and their participation in the API scheme. It comprised semi-structured telephone interviews with consultant surgeons and surgical trainees involved in screening and recruitment of patients, and descriptive analysis of screening and recruitment data. Interviews were analysed thematically to explore the perspectives of—and roles undertaken by—surgical trainees. Results Interviews were undertaken with 34 clinicians (17 consultant surgeons, 17 surgical trainees) from 22 UK hospital trusts. Surgical trainees contributed to patient screening, approaches and randomisation, with a major contribution to the randomisation of patients from acute admissions. They were often encouraged to participate in the study by their centre principal investigator, and career development was a typical motivating factor for their participation in the study. The study was registered with the API scheme, and a majority of the trainees interviewed (n = 14) were participating in the scheme. Conclusion Surgical trainees can contribute substantial activity to a large-scale multi-centre RCT. Benefits of trainee engagement were identified for trainees themselves, for local sites and for the study as a whole. The API scheme provided a formal framework to acknowledge engagement. Ensuring that training and support for trainees are provided by the trial team is key to optimise success for all stakeholders.

Background: The major joint registries report better survivorship for ceramic on polyethylene over metal on polyethylene bearings in total hip arthroplasty and it is generally accepted that this is due to a lower polyethylene wear rate. We used evidence synthesis to compare survivorship, polyethylene wear rates and metal ion levels for metal-on-polyethylene (MoP) and ceramic-on-polyethylene (CoP) bearings. If wear rates are not dissimilar in vivo this difference in revision rate may have another cause. Modular junctions are a potential source of corrosion and it is postulated that this may result in higher revision rates. Methods: We performed a systematic review and meta-analysis comparing the survivorship of MoP and CoP bearings. Odds ratio (95% CI) of revision was calculated. Mean difference (MD) and 95% confidence intervals (CI) were used to compare secondary outcomes of polyethylene wear and metal ion levels. Meta-analysis was performed with a Mantel-Haenszel Random-Effects Model. Results: 6 randomised controlled trials were included. There was no statistically significant difference between MoP and CoP revision rate (OR 1.04; 95% CI, 0.37–2.90, I2 = 0%, p = 0.94), linear bearing wear (MD 0.00 mm; 95% CI, −0.05 –0.05, I2 = 98%, p = 0.90), nor volumetric bearing wear (MD 33.57 mm3; 95% CI, −215.56–282.70, I2 = 98%, p = 0.79). No studies evaluated metal ion levels. Conclusions: We found no evidence of a difference in revision rates nor linear and volumetric wear between MoP and CoP bearings in the randomised controlled trials currently available. Our study therefore does not advocate the additional cost associated with the use of ceramic heads in combination with polyethylene bearings in order to minimise revision rates. This contrasts the findings of in vitro studies and the major joint registries.

Prosthetic joint infection (PJI) after total ankle replacement (TAR) is a challenging complication, which often requires debridement and implant retention (DAIR) with or without polyethylene exchange, revision surgery, implantation of a cement spacer, conversion to arthrodesis, or even amputation. The optimum treatment for ankle PJI is not well established. We conducted a systematic review and meta-analysis to compare the clinical effectiveness of various treatment strategies for infected ankle prostheses. We searched MEDLINE, Embase, Web of Science, and the Cochrane Library up to December 2018 for studies evaluating the impact of treatment in patient populations with infected ankle prostheses following TAR. Binary data were pooled after arcsine transformation. Six citations comprising 17 observational design comparisons were included. The reinfection rates (95% confidence intervals) for DAIR with or without polyethylene exchange, 1-stage revision, 2-stage revision, cement spacer, and arthrodesis were 39.8% (24.4 to 56.1), 0.0% (0.0 to 78.7), 0.0% (0.0 to 8.5), 0.2% (0.0 to 17.9), and 13.6% (0.0 to 45.8), respectively. Rates of amputation for DAIR with or without polyethylene exchange and cement spacer were 5.6% (0.0 to 16.9) and 22.2% (6.3 to 54.7), respectively. Measures of function, pain, and satisfaction could not be compared because of limited data. One- and 2-stage revision strategies seem to be associated with the lowest reinfection rates, but these findings are based on limited data. Arthrodesis and DAIR with or without polyethylene exchange appear to be commonly used in treating infected ankle prosthesis, but are associated with poor infection control. Clear gaps exist in the literature, and further research is warranted to evaluate treatment strategies for infected ankle prosthesis.

BACKGROUND: Venous thromboembolism, a potential complication of total joint replacement, is associated with preventable mortality and morbidity and is likely to be influenced by host-related factors such as sociodemographic characteristics, body mass index, medical and surgical histories, as well as circulating biomarkers. We conducted a systematic review and meta-analysis to assess the associations between host-related factors and venous thromboembolism risk following total hip and knee replacements.METHODS: We searched MEDLINE, Embase, Web of Science, and Cochrane Library to March 2018 for longitudinal studies reporting these associations. Summary measures of association were relative risks (95% confidence intervals).RESULTS: We identified 89 studies with data on 14,763,963 joint replacements and 150,086 venous thromboembolism events. Comparing males to females, age ≥70 to CONCLUSIONS: Enhanced venous thromboembolism prophylaxis should be considered in those with nonmodifiable risk factors such as older black female knee replacement patients. Modifiable risk factors such as high body mass index and fluid & electrolyte imbalance should be addressed prior to elective surgery.SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2018: CRD42018089625.

Background: Millions of non-locking screws are manually tightened during surgery each year, but their insertion frequently results in overtightening and damage to the surrounding bone. We postulated that by calculating the torque limit of a screw hole, using bone and screw properties, the risk of overtightening during screw insertion could be reduced. Additionally, predicted maximum torque could be used to identify optimum screw torque, as a percentage of the maximum, based on applied compression and residual pullout strength. Methods: Longitudinal cross-sections were taken from juvenile bovine tibial diaphyses, a validated surrogate of human bone, and 3.5 mm cortical non-locking screws were inserted. Fifty-four samples were used to define the association between stripping torque and cortical thickness. The relationship derived enabled prediction of insertion torques representing 40 to 100% of the theoretical stripping torque (Tstr) for a further 170 samples. Screw-bone compression generated during insertion was measured, followed immediately by axial pullout testing. Findings: Screw-bone compression increased linearly with applied torque up to 80% of Tstr (R2 = 0.752, p < 0.001), but beyond this, no significant further compression was generated. After screw insertion, with all screw threads engaged, more tightening did not create any significant (R2 = 0.000, p = 0.498) increase in pullout strength. Interpretation: Increasing screw tightness beyond 80% of the maximum did not increase screw-bone compression. Variations in torques below Tstr, did not affect pullout forces of inserted screws. Further validation of these findings in human bone and creation of clinical guidelines based on this research approach should improve surgical outcomes and reduce operative costs.

Introduction Previous research suggests that patient-reported outcomes plateau by one year after total knee replacement (TKR). Analysis of trajectories to date has predominately been based on changes in median/mean scores over the first post-operative year, rather than variability in trajectory patterns over the longer-term. The aim was to evaluate variability in long-term pain and function trajectories after TKR. Hypothesis There will be variability in long-term pain and function trajectories after TKR. Patients and methods In all, 266 patients undergoing a Triathlon® TKR because of osteoarthritis were recruited from one orthopaedic centre. Participants completed the WOMAC Pain and Function scales preoperatively and then at 3 months, 1 year, 2 years, 3 years, 5 years and 7 years post-operative. Longitudinal analyses evaluated patterns of clinically meaningful change. Results Most patients had an improvement in pain and function during the first year post-operative; improvement was greatest in the first 3 months. By 1-year post-operative, 8% of patients had no change or a worsening of pain and 21% for function. Thereafter, approximately 15% of patients improved and 15% worsened between each assessment time. For those patients who had no change in symptoms from pre-operative to 1-year post-operative, one third had further improvement between 1 and 2 years post-operative. Discussion This study identified clinically meaningful variability in long-term outcomes after TKR, which could be discussed with patients to ensure they have realistic expectations of their outcome. Further research is needed to evaluate determinants of this variability and whether patients who will do poorly can be identified early in their recovery pathway. Level of evidence IV, prospective cohort study.

Summary Background Identifying prognostic factors for outcomes after joint replacement could improve the provision of stratified care. We investigated whether social support is a prognostic factor for improved patient-reported outcomes after total hip replacement or total knee replacement. Methods For this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO from inception to April 5, 2019. Cohort studies investigating the association between social support and patient-reported outcomes at 3 months or longer after total hip replacement or total knee replacement were eligible for inclusion. Patient-reported outcomes were pain, function, satisfaction, and general health, which were evaluated predominantly with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Oxford Knee Score, and 36-item short form health survey (SF-36) questionnaires. Data were extracted from published articles and results of relevant statistical analyses requested from authors where not available. Data were synthesised by use of meta-analysis and narrative synthesis. This study is registered on PROSPERO, CRD42016041485. Findings We identified 5810 articles, and 56 studies with data from 119 165 patients were included (13 in the meta-analysis, 43 in the narrative synthesis). In the meta-analysis, the presence of social support had a beneficial effect on the long-term postoperative WOMAC (2022 patients; mean difference 2·88 [95% CI 1·30 to 4·46]) and Oxford Knee Score (69 570 patients; 0·29 [0·12 to 0·45]) in the fixed-effects model. Social support measured by use of a validated questionnaire was found to be associated with WOMAC pain (671 patients; mean difference 0·04 [95% CI 0·00 to 0·08]) in the fixed-effects model but not with WOMAC function (671 patients; −0·01 [–0·12 to 0·11]) in the random-effects model. The presence of social support had a positive association with some SF-36 subscales but not others. For all outcomes, results of the narrative synthesis were inconsistent. Interpretation Social support appears to be a prognostic factor for some outcomes after joint replacement. The development and evaluation of complex interventions to improve social support and social integration is warranted in patients who have undergone joint replacement surgery. Funding NIHR Biomedical Research Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol.

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Background Lower urinary tract symptoms (LUTS) can relate to urinary storage or voiding. In men, the prevalence and severity of LUTS increases with age, with a significant impact on quality of life. The majority of men presenting with LUTS are managed by their general practitioner (GP) in the first instance, with conservative therapies recommended as the initial treatment. However, the provision of conservative therapies in primary care is variable and can be time and resource limited. GPs require practical resources to enhance patient engagement with such interventions. TRIUMPH aims to determine whether a standardised and manualised care intervention delivered in primary care achieves superior symptomatic outcome for LUTS versus usual care. Methods/design TRIUMPH is a two-arm, cluster randomised controlled trial (RCT) being conducted in 30 National Health Service (NHS) general practices in England. The TRIUMPH intervention comprises a standardised LUTS advice booklet developed for the trial with patient and healthcare professional (HCP) consultation. The booklet is delivered to patients by nurses/healthcare assistants following assessment of their urinary symptoms. Patients are directed to relevant sections of the booklet, providing the manualised element of the intervention. To encourage adherence, HCPs provide follow-up contacts over 12 weeks. Practices are randomised 1:1 to either deliver the TRIUMPH intervention or a usual care pathway. The patient-reported International Prostate Symptom Score (IPSS) at 12 months post consent is the primary outcome. Secondary outcomes include cost-effectiveness, patient-reported outcomes on LUTS, quality of life, and patient and HCP acceptability and experience of the intervention. Primary analyses will be conducted on an intention-to-treat basis. Discussion It is unclear whether conservative therapies for male LUTS are effectively delivered in primary care using current approaches. This can lead to men being inappropriately referred to secondary care or experiencing persistent symptoms. Primary care, therefore, holds the key to effective treatment for these men. The TRIUMPH intervention, through its standardised and manualised approach, has been developed to support GP practices in delivering effective conservative care. This pragmatic, cluster RCT should provide robust evidence in a primary-care setting to inform future guidelines. Trial registration ISCRTN registry, ID: ISRCTN11669964. Registered on 12 April 2018. Electronic supplementary material The online version of this article (10.1186/s13063-019-3648-1) contains supplementary material, which is available to authorized users.

OBJECTIVE: The Core Outcome Set-STAndards for Development (COS-STAD) contains 11 standards (12 criteria) that are deemed to be the minimum design recommendations for all core outcome set (COS) development projects. Cancer is currently the disease area with the highest number of published COSs and is a major cause of worldwide morbidity and mortality. The aim of this study was to provide a baseline of cancer COS standards.STUDY DESIGN AND SETTING: Systematic reviews of COSs have identified 307 published COS studies. Cancer COSs were eligible for inclusion. Two reviewers independently assessed each of the COSs against the 12 criteria.RESULTS: Forty-nine cancer COSs were included; none met all 12 criteria representing the 11 minimum standards assessed in this study (range = 4-11 criteria, median = 6 criteria). All studies met the four scope standards, eight (16%) met all three standards for stakeholders involved, and two (4%) met all four standards for consensus process standards.CONCLUSION: With the exception of "scope" specification, there is much need for improvement. Poor reporting often made it challenging to assess whether minimum standards were met. The consensus process criteria were most difficult to assess, particularly those that required an assessment of being a priori. This is the first application of COS-STAD criteria to studies that have developed COSs and provides a baseline of cancer COS standards of development.

Background Although delivering a chosen mode of anaesthesia for certain emergency surgery procedures is potentially beneficial to patients, it is a complex intervention to evaluate. This qualitative study explored clinician and patient perspectives about mode of anaesthesia for emergency surgery. Methods Snowball sampling was used to recruit participants from eight National Health Service Trusts that cover the following three emergency surgery settings: ruptured abdominal aortic aneurysms, hip fractures and inguinal hernias. A qualitative researcher conducted interviews with clinicians and patients. Thematic analysis was applied to the interview transcripts. Results Interviews were conducted with 21 anaesthetists, 21 surgeons, 14 operating theatre staff and 23 patients. There were two main themes. The first, impact of mode of anaesthesia in emergency surgery, had four subthemes assessing clinician and patient ideas about: context and the ‘best’ mode of anaesthesia; balance in choosing it over others; change and developments in anaesthesia; and the importance of mode of anaesthesia in emergency surgery. The second, tensions in decision‐making about mode of anaesthesia, comprised four subthemes: clinical autonomy and guidelines in anaesthesia; conforming to norms in mode of anaesthesia; the relationship between expertise, preference and patient involvement; and team dynamics in emergency surgery. The results highlight several interlinking factors affecting decision‐making, including expertise, preference, habit, practicalities, norms and policies. Conclusion There is variation in practice in choosing the mode of anaesthesia for surgery, alongside debate as to whether anaesthetic autonomy is necessary or results in a lack of willingness to change., Although delivering a chosen mode of anaesthesia for certain emergency surgery procedures is potentially beneficial to patients, it is a complex intervention to evaluate. Seventy‐nine interviews with clinicians and patients were analysed thematically to explore experiences of anaesthesia in emergency surgery. The results highlight several interlinking factors affecting decision‐making, including expertise, preference, habit, practicalities, norms and policies. General anaesthesia or not?

Importance Perioperative chemotherapy and surgery are a standard of care for operable gastroesophageal adenocarcinoma. Anti-HER2 therapy improves survival in patients with advanced HER2-positive disease. The safety and feasibility of adding lapatinib to perioperative chemotherapy should be assessed. Objectives To assess the safety of adding lapatinib to epirubicin, cisplatin, and capecitabine (ECX) chemotherapy and to establish a recommended dose regimen for a phase 3 trial. Design, Setting, and Participants Phase 2 randomized, open-label trial comparing standard ECX (sECX: 3 preoperative and 3 postoperative cycles of ECX with modified ECX plus lapatinib (mECX+L). This multicenter national trial was conducted in 29 centers in the United Kingdom in patients with histologically proven, HER2-positive, operable gastroesophageal adenocarcinoma. Registration forERBB/HER2testing took place from February 25, 2013, to April 19, 2016, and randomization took place between May 24, 2013, and April 21, 2016. Data were analyzed May 10, 2017, to May 25, 2017. Interventions Patients were randomized 1:1 open-label to sECX (3 preoperative and 3 postoperative cycles of 50 mg/m2of intravenous epirubicin on day 1, 60 mg/m2intravenous cisplatin on day 1, 1250 mg/m2 of oral capecitabine on days 1 through 21) or mECX+L (ECX plus lapatinib days 1 through 21 in each cycle and as 6 maintenance doses). The first 10 patients in the mECX+L arm were treated with 1000 mg/m2of capecitabine and 1250 mg of lapatinib per day, after which preoperative toxic effects were reviewed according to predefined criteria to determine doses for subsequent patients. Main Outcomes and Measures Proportion of patients experiencing grade 3 or 4 diarrhea with mECX+L. A rate of 20% or less was considered acceptable. No formal comparison between arms was planned. Results Between February 2013, and April 2016, 441 patients underwent central HER2 testing and 63 (14%) were classified as HER2 positive. Forty-six patients were randomized; 44 (24 sECX, 20 mECX+L) are included in this analysis. Two of the first 10 patients in the mECX+L arm reported preoperative grade 3 diarrhea; thus, no dose increase was made. The primary endpoint of preoperative grade 3 or 4 diarrhea rates were 0 of 24 in the sECX arm (0%) and 4 of 20 in the mECX+L arm (21%). One of 24 in the sECX arm and 3 of 20 in the mECX+L arm stopped preoperative treatment early, and for 4 of 19 in the mECX+L arm, lapatinib dose was reduced. Postoperative complication rates were similar in each arm. Conclusions and Relevance Administration of 1250 mg of lapatinib per day in combination with ECX chemotherapy was feasible with some increase in toxic effects, which did not compromise operative management. Trial Registration ISRCTN.org identifier:46020948; clinicaltrialsregister.eu identifier:2006-000811-12

Background Acute otitis media (AOM) is a common reason for primary care consultations and antibiotic prescribing in children. Options for improved pain control may influence antibiotic prescribing and consumption. Objective The Children’s Ear Pain Study (CEDAR) investigated whether or not providing anaesthetic–analgesic ear drops reduced antibiotic consumption in children with AOM. Secondary objectives included pain control and cost-effectiveness. Design A multicentre, randomised, parallel-group (two-group initially, then three-group) trial. Setting Primary care practices in England and Wales. Participants 1- to 10-year-old children presenting within 1 week of suspected AOM onset with ear pain during the preceding 24 hours and not requiring immediate antibiotics. Participating children were logged into the study and allocated using a remote randomisation service. Interventions Two-group trial – unblinded comparison of anaesthetic–analgesic ear drops versus usual care. Three-group trial – blinded comparison of anaesthetic–analgesic ear drops versus placebo ear drops and unblinded comparison with usual care. Main outcome measures The primary outcome measure was parent-reported antibiotic use by the child over 8 days following enrolment. Secondary measures included ear pain at day 2 and NHS and societal costs over 8 days. Results Owing to a delay in provision of the placebo drops, the recruitment period was shortened and most participants were randomly allocated to the two-group study (n = 74) rather than the three-group study (n = 32). Comparing active drops with usual care in the combined two-group and three-group studies, 1 out of 39 (3%) children allocated to the active drops group and 11 out of 38 (29%) children allocated to the usual-care group consumed antibiotics in the 8 days following enrolment [unadjusted odds ratio 0.09, 95% confidence interval (CI) 0.02 to 0.55; p = 0.009; adjusted for delayed prescribing odds ratio 0.15, 95% CI 0.03 to 0.87; p = 0.035]. A total of 43% (3/7) of patients in the placebo drops group consumed antibiotics by day 8, compared with 0% (0/10) of the three-group study active drops groups (p = 0.051). The economic analysis of NHS costs (£12.66 for active drops and £11.36 for usual care) leads to an estimated cost of £5.19 per antibiotic prescription avoided, but with a high degree of uncertainty. A reduction in ear pain at day 2 in the placebo group (n = 7) compared with the active drops group (n = 10) (adjusted difference in means 0.67, 95% CI –1.44 to 2.79; p = 0.51) is consistent with chance. No adverse events were reported in children receiving active drops. Limitations Estimated treatment effects are imprecise because the sample size target was not met. It is not clear if delayed prescriptions of an antibiotic were written prior to randomisation. Few children received placebo drops, which hindered the investigation of ear pain. Conclusions This study suggests that reduced antibiotic use can be achieved in children with AOM by combining a no or delayed antibiotic prescribing strategy with anaesthetic–analgesic ear drops. Whether or not the active drops relieved ear pain was not established. Future work The observed reduction in antibiotic consumption following the prescription of ear drops requires replication in a larger study. Future work should establish if the effect of ear drops is due to pain relief. Trial registration Current Controlled Trials ISRCTN09599764. 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. 23, No. 34. See the NIHR Journals Library website for further project information. Alastair D Hay was funded by a NIHR Research Professorship (funding identifier NIHR-RP-02-12-012).

Background: Vitamin E highly cross-linked polyethylene (HXLPE) was developed to reduce wear in total hip replacement (THR). This formal systematic review and meta-analysis aimed to provide independent synthesis of wear characteristics of Vitamin E treated HXLPE compared to HXPLE/UHMWPE. Secondary outcome measures were differences in revision rates and functional scores. Methods: We performed a formal systematic review as per PRISMA guidelines; literature searches were conducted on 14 November 2017 (MEDLINE, Embase on Ovid, and the Cochrane Library). We included randomised controlled trials, analyses of joint registries, and case-controlled studies of primary THR comparing cups with a vitamin E HXLPE bearing with bearing surfaces made from other types of polyethylene. Initial screening was performed by 2 independent assessors; disagreement resolved in discussion with a third reviewer. Studies were evaluated using the Cochrane risk of bias tool. Data extraction permitted meta-analysis. Results: 372 studies were identified on initial screening, 5 studies met the eligibility criteria. There was no significant heterogeneity between studies. There was variable risk of bias. At a mean of 35 (range 20–60) months, Vitamin E HXLPE had significant advantages over highly cross-linked polyethylene with regards total femoral head penetration ( p = 0.004). Given the RSA measurement errors this may not be clinically significant. There were neither significant differences in revision rates nor Harris Hip Scores ( p = 0.06). Conclusion: At a minimum of 3 years follow-up there was reduced total femoral head penetration for vitamin E HXLPE over HXLPE. This bearing surface does not, as yet, have clinically significant advantages in terms of revision rates or patient function over HXLPE.

Summary Limited uptake of minimally invasive surgery (MIS) of the aorta hinders assessment of its efficacy compared to median sternotomy (MS). The objective of this systematic review is to compare operative and perioperative outcomes for MIS versus MS. Online databases Medline, EMBASE, Cochrane Library and Web of Science were searched from inception until July 2018. Both randomized and observational studies of patients undergoing aortic root, ascending aorta or aortic arch surgery by MIS versus MS were eligible for inclusion. Primary outcomes were 30-day mortality, reoperation for bleeding, perioperative renal impairment and neurological events. Intraoperative and postoperative timing measures were also evaluated. Thirteen observational studies were included comparing 1101 MIS and 1405 MS patients. The overall quality of evidence was very low for all outcomes. Mortality and the incidence of stroke were similar between the 2 cohorts. Meta-analysis demonstrated increased length of cardiopulmonary bypass (CPB) time for patients undergoing MS [standardized mean difference 0.36, 95% confidence interval (CI) 0.15–0.58; P = 0.001]. Patients receiving MS spent more time in hospital (standardized mean difference 0.30, 95% CI 0.17–0.43; P

After practicing OPCAB for 25 years, I reflect on this experience and offer some insights that I hope will be of help to the surgical community, particularly to the young surgeons in training.

Background Many children do not meet the recommended level of daily physical activity, even with the widely acknowledged health benefits associated with being physically active. There is a need to establish factors related to physical activity in children so that public health interventions may be appropriately designed. We investigated the association between Pediatric Quality of Life Inventory (PedsQL), family expenditure on physical activity and objectively measured daily physical activity in 2–4-year-old children. Methods Cross-sectional study with a sample of 81 UK preschool children taking part in the NAPSACC UK feasibility randomized controlled trial. Descriptive statistics are presented. We undertook Student t-tests to establish differences in physical activity by gender, age, parental education and nursery versus non-nursery days. Mixed effects linear regressions were used to model the association between minutes spent physically activity, minutes spent in moderate-to-vigorous (MVPA) physical activity and PedsQL scores (physical and psychosocial) and family expenditure on physical activity. Results Most children (88.9%) did not engage in the recommended 180 min daily physical activity. There was mean (SD) of 141.9 (33.1) daily minutes of physically activity and 22.2 min per day (SD = 9.9) of MVPA. Boys and older children were more physically active. Children were more active on nursery days. There was no difference in physical activity by parental education. Half of the sample parents (50.6%) spent less than £9.00 weekly on their pre-schooler’s physical activity. Children within the highest tertile of PedsQL physical functioning scores had higher levels of MVPA (3.6, 95% CI: − 1.3–8.4, p-value 0.15), although confidence intervals crossed the null in the adjusted model. We found no evidence of an association between positive PedsQL psychosocial scores, or higher parental expenditure on physical activity, with the physical activity variables. Conclusions Children in this sample were not meeting the recommended 180 min of daily physical activity. The 2–4-year-olds were most active on nursery days. There is no evidence of an association between better PedsQL physical scores and higher levels of MVPA. There was no evidence of an association between expenditure on physical activity and time spent physically active. Further examination in larger representative datasets is needed. Electronic supplementary material The online version of this article (10.1186/s12889-019-7129-y) contains supplementary material, which is available to authorized users.

BackgroundLow participation in clinical trials is a major challenge to advancing clinical Alzheimer’s Disease (AD) research and care. Factors influencing recruitment to AD trials are not fully understood. AimsTo identify barriers to, and facilitators of, recruitment in a UK multi-centre, secondary care AD trial (Reducing pathology in Alzheimer’s Disease through Angiotensin TaRgeting (RADAR) trial) and implications for improving recruitment to AD trials.MethodsSemi-structured qualitative telephone interviews with a purposive sample of 17 trial site staff explored the RADAR trial recruitment pathway and views and experiences of recruitment. Interviews were analysed thematically. ResultsDiagnostic and care pathways hindered identifying patients with mild-moderate AD, with a lack of up-to-date patient records and data access problems affecting screening. Research is not routinely embedded in AD care but facilitated recruitment when it was. Clinicians’ and patients’ favourable view of the trial purpose facilitated recruitment, although the complexity of participant information sheets and requirement for study companion created challenges. ConclusionThese findings have important implications for the design of future AD trials and for planning how to best interface with clinical commitments to ensure sufficient and timely recruitment. Challenges to AD trial recruitment can occur at care pathway, clinician, and patient and companion levels. Recruitment can be facilitated by: improving diagnostic processes and systems for recording and sharing patient information, embedding research into routine patient care, collaborating with a range of services to identify and approach eligible patients, training and engaging trial staff, and providing patients with clear and concise study information.

Background: Prosthetic joint infection is a devastating complication of knee replacement. The risk of developing a prosthetic joint infection is affected by patient, surgical, and health-care system factors. Existing evidence is limited by heterogeneity in populations studied, short follow-up, inadequate power, and does not differentiate early prosthetic joint infection, most likely related to the intervention, from late infection, more likely to occur due to haematogenous bacterial spread. We aimed to assess the overall and time-specific associations of these factors with the risk of revision due to prosthetic joint infection following primary knee replacement. Methods: In this cohort study, we analysed primary knee replacements done between 2003 and 2013 in England and Wales and the procedures subsequently revised for prosthetic joint infection between 2003 and 2014. Data were obtained from the National Joint Registry linked to the Hospital Episode Statistics data in England and the Patient Episode Database for Wales. Each primary replacement was followed for a minimum of 12 months until the end of the observation period (Dec 31, 2014) or until the date of revision for prosthetic joint infection, revision for another indication, or death (whichever occurred first). We analysed the data using Poisson and piecewise exponential multilevel models to assess the associations between patient, surgical, and health-care system factors and risk of revision for prosthetic joint infection. Findings: Of 679 010 primary knee replacements done between 2003 and 2013 in England and Wales, 3659 were subsequently revised for an indication of prosthetic joint infection between 2003 and 2014, after a median follow-up of 4·6 years (IQR 2·6–6·9). Male sex (rate ratio [RR] for male vs female patients 1·8 [95% CI 1·7–2·0]), younger age (RR for age ≥80 years vs 2 vs 2 1·5 [1·3–1·6]), chronic pulmonary disease (RR 1·2 [1·1–1·3]), diabetes (RR 1·4 [1·2–1·5]), liver disease (RR 2·2 [1·6–2·9]), connective tissue and rheumatic diseases (RR 1·5 [1·3–1·7]), peripheral vascular disease (RR 1·4 [1·1–1·7]), surgery for trauma (RR 1·9 [1·4–2·6]), previous septic arthritis (RR 4·9 [2·7–7·6]) or inflammatory arthropathy (RR 1·4 [1·2–1·7]), operation under general anaesthesia (RR 1·1 [1·0–1·2]), requirement for tibial bone graft (RR 2·0 [1·3–2·7]), use of posterior stabilised fixed bearing prostheses (RR for posterior stabilised fixed bearing prostheses vs unconstrained fixed bearing prostheses 1·4 [1·3–1·5]) or constrained condylar prostheses (3·5 [2·5–4·7]) were associated with a higher risk of revision for prosthetic joint infection. However, uncemented total, patellofemoral, or unicondylar knee replacement (RR for uncemented vs cemented total knee replacement 0·7 [95% CI 0·6–0·8], RR for patellofemoral vs cemented total knee replacement 0·3 [0·2–0·5], and RR for unicondylar vs cemented total knee replacement 0·5 [0·5–0·6]) were associated with lower risk of revision for prosthetic joint infection. Most of these factors had time-specific effects, depending on the time period post-surgery. Interpretation: We have identified several risk factors for revision for prosthetic joint infection following knee replacement. Some of these factors are modifiable, and the use of targeted interventions or strategies could lead to a reduced risk of revision for prosthetic joint infection. Non-modifiable factors and the time-specific nature of the effects we have observed will allow clinicians to appropriately counsel patients preoperatively and tailor follow-up regimens. Funding: National Institute for Health Research.

Background RCTs in surgery are challenging owing to well established methodological issues. Well designed pilot and feasibility studies (PFS) may help overcome such issues to inform successful main trial design and conduct. This study aimed to analyse protocols of UK-funded studies to explore current use of PFS in surgery and identify areas for practice improvement. Methods PFS of surgical interventions funded by UK National Institute for Health Research programmes from 2005 to 2015 were identified, and original study protocols and associated publications sourced. Data extracted included study design characteristics, reasons for performing the work including perceived uncertainties around conducting a definitive main trial, and whether the studies had been published. Results Thirty-five surgical studies were identified, of which 29 were randomized, and over half (15 of 29) included additional methodological components (such as qualitative work examining recruitment, and participant surveys studying current interventions). Most studies focused on uncertainties around recruitment (32 of 35), with far fewer tackling uncertainties specific to surgery, such as intervention stability, implementation or delivery (10 of 35). Only half (19 of 35) had made their results available publicly, to date. Conclusion The full potential of pretrial work to inform and optimize definitive surgical studies is not being realized.

AimsThe aim of this study was to determine and compare the congruency of the articular surface contact area of the patellofemoral joint (PFJ) during both active and passive movement of the knee with the use of an MRI mapping technique in both the stable and unstable PFJ.Patients and MethodsA prospective case-control MRI imaging study of patients with a history of PFJ instability and a control group of volunteers without knee symptoms was performed. The PFJs were imaged with the use of an MRI scan during both passive and active movement from 0° through to 40° of flexion. The congruency through measurement of the contact surface area was mapped in 5-mm intervals on axial slices. In all, 40 patients were studied. The case group included 31 patients with symptomatic patellofemoral instability and the control group of nine asymptomatic volunteers. The ages were well matched between the case and control groups. The mean age was 25 years (16 to 42; sd 6.9) in the case group and 26 years (19 to 32; sd 5.1) in the control group. There were 19 female and 12 male patients in the case group.ResultsThe unstable PFJs were demonstrably less congruent than the stable PFJs throughout the range of knee movement. The greatest mean differences in congruency between unstable and stable PFJ’s were observed between 11° and 20° flexion (1.73 cm2vs 4.00 cm2; p < 0.005).ConclusionThe unstable PFJ is less congruent than the stable PFJ throughout the range of knee movement studied. This approach to mapping PFJ congruency produces a measurable outcome and will allow the assessment of pre- and postoperative results following surgical intervention. This may facilitate the design of new procedures for patients with PFJ instability. If a single axial series is to be obtained on MRI scan, the authors recommend 11° to 20° of tibiofemoral flexion, as this was shown to have the greatest difference in contact surface area between the case and control groups. Cite this article: Bone Joint J 2019;101-B:552–558.

Aims/hypothesis Previous studies have shown that diabetes mellitus destabilises the integrity of the microvasculature in different organs by damaging the interaction between pericytes and endothelial cells. In bone marrow, pericytes exert trophic functions on endothelial cells and haematopoietic cells through paracrine mechanisms. However, whether bone marrow pericytes are a target of diabetes-induced damage remains unknown. Here, we investigated whether type 2 diabetes can affect the abundance and function of bone marrow pericytes. Methods We conducted an observational clinical study comparing the abundance and molecular/functional characteristics of CD146+ pericytes isolated from the bone marrow of 25 individuals without diabetes and 14 individuals with uncomplicated type 2 diabetes, referring to our Musculoskeletal Research Unit for hip reconstructive surgery. Results Immunohistochemistry revealed that diabetes causes capillary rarefaction and compression of arteriole size in bone marrow, without changing CD146+ pericyte counts. These data were confirmed by flow cytometry on freshly isolated bone marrow cells. We then performed an extensive functional and molecular characterisation of immunosorted CD146+ pericytes. Type 2 diabetes caused a reduction in pericyte proliferation, viability, migration and capacity to support in vitro angiogenesis, while inducing apoptosis. AKT is a key regulator of the above functions and its phosphorylation state is reportedly reduced in the bone marrow endothelium of individuals with diabetes. Surprisingly, we could not find a difference in AKT phosphorylation (at either Ser473 or Thr308) in bone marrow pericytes from individuals with and without diabetes. Nonetheless, the angiocrine signalling reportedly associated with AKT was found to be significantly downregulated, with lower levels of fibroblast growth factor-2 (FGF2) and C-X-C motif chemokine ligand 12 (CXCL12), and activation of the angiogenesis inhibitor angiopoietin 2 (ANGPT2). Transfection with the adenoviral vector carrying the coding sequence for constitutively active myristoylated AKT rescued functional defects and angiocrine signalling in bone marrow pericytes from diabetic individuals. Furthermore, an ANGPT2 blocking antibody restored the capacity of pericytes to promote endothelial networking. Conclusions/interpretation This is the first demonstration of pericyte dysfunction in bone marrow of people with type 2 diabetes. An altered angiocrine signalling from pericytes may participate in bone marrow microvascular remodelling in individuals with diabetes. Electronic supplementary material The online version of this article (10.1007/s00125-019-4865-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Objective To establish current practice of the management of learning and clustering effects, by treating center and surgeon, in the design and analysis of randomized surgical trials. Study design and setting The need for more surgical randomized trials is well recognized, and in recent years conduct has grown. Rigorous design, conduct, and analyses of such studies is important. Two methodological challenges are clustering effects, by center or surgeon, and surgical learning on trial outcomes. Sixteen leading journals were searched for randomized trials published within a two-year period. Data were extracted on considerations for learning and clustering effects. Results A total of 247 eligible studies were identified. Trials accounted for learning with 2% using an expertise-based design and 39% accounting for expertise by predefining surgeon credentials. One study analyzed learning. Clustering, by site and surgeon, was commonly managed by stratifying randomization, although one-third of center and 40% of surgeon stratified trials did not also adjust analysis. Conclusion Considerations for surgical learning and clustering effects are often unclear. Methods are varied and demonstrate poor adherence to established reporting guidelines. It is recommended that researchers consider these issues on a trial-by-trial basis, and report methods or justify where not needed to inform interpretation of results.

Background: Prosthetic implants used in total hip replacements (THR) have a range of bearing surface combinations (metal-on-polyethylene, ceramic-on-polyethylene, ceramic-on-ceramic, and metal-on-metal), head sizes (small [

After more than thirty years, a hundred randomized studies and dozens of meta-analyses, there is still controversy on the results and benefits of off-pump coronary artery bypass grafting. The present review summarizes the most relevant evidence, the relation of outcomes with surgeon's and institution's experience, addresses regional variations in popularity of the technique, and the need for structural training.

OBJECTIVES: To compare the rates of deep infection, flap failure, and nonunion after temporary internal fixation (TIF) with temporary external fixation (ex-fix) in the management of Gustilo-Anderson type IIIB open tibia fractures.DESIGN: Retrospective comparative cohort study.SETTING: Level 1 trauma center.PATIENTS/PARTICIPANTS: Sixty-four consecutive patients with a Gustilo-Anderson type IIIB open diaphyseal tibia fracture (OTA/AO 42) were treated between May 2014 and May 2016. Forty-seven patients (TIF = 24; ex-fix = 23) met the inclusion criteria and underwent 2-stage reconstruction. Definitive fixation was with an intramedullary nail.INTERVENTION: Temporary fracture stabilization at the first-stage debridement was achieved with either TIF with a plate or ex-fix.MAIN OUTCOME MEASUREMENT: The main outcome measure was deep infection.RESULTS: There were 4 complications in the ex-fix group (3 infection and 1 nonunion) and 2 complications in the TIF group (1 infection and 1 flap failure). Multiple regression modeling revealed that infection (P = 0.610), nonunion (P = 0.918), and flap failure (P = 0.112) were not significantly associated with the mode of temporary fixation or other demographic and treatment variables. The odds ratio of patients treated with TIF developing an infection compared with those treated with an ex-fix was 0.29 (95% confidence interval, 0.03-3.01).CONCLUSIONS: TIF of type IIIB open diaphyseal tibial fractures seems to be a safe alternative to conventional external fixation.LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

INTRODUCTION: The terminology for nocturia and nocturnal lower urinary tract function is reviewed and updated in a clinically and practically-based consensus report.METHODS: This report has been created by a Working Group under the auspices and guidelines of the International Continence Society (ICS) Standardisation Steering Committee (SSC). All relevant definitions were updated on the basis of research over the last 16 years since the publication of the first nocturia standardization document in 2002. An extensive process of 16 rounds of internal and external reviews was involved to examine each definition exhaustively, with decision-making by collective opinion (consensus).RESULTS: A clinically-based terminology report for nocturia and nocturnal lower urinary tract function, encompassing five key definitions divided into signs and symptoms has been developed. Clarity and user-friendliness have been key aims to make it interpretable by healthcare professionals and allied healthcare practitioners involved in the care of individuals with nocturnal lower urinary tract function.CONCLUSION: A consensus-based terminology report for nocturia and nocturnal lower urinary tract function has been produced to aid clinical practice and research.

Foot complications are a common cause of hospital admission of people with diabetes and a frequent cause of amputation. Neuropathy and arterial disease make the foot particularly vulnerable, but infection is often the pathology precipitating presentation. Recognition of the patient at risk may prevent the development of foot complications, but if they do occur urgent treatment is required to prevent limb loss. The infected foot in a patient with diabetes is a surgical emergency. In addition to antibiotics, debridement and surgical drainage of infection should be considered within the first 24 hours. Once the foot is made safe, revascularization should be undertaken in those with significant arterial disease. Adoption of a multidisciplinary team approach to managing diabetic foot complications has resulted in reduction in major amputations in some European countries.

Background Several hundred core outcome set (COS) projects have been systematically identified to date which, if adopted, ensure that researchers measure and report those outcomes that are most likely to be relevant to users of their research. The uptake of a COS by COS users will depend in part on the transparency and robustness of the methods used in the COS development study, which would be increased by the use of a standardised protocol. This article describes the development of the COS-STAP (Core Outcome Set-STAndardised Protocol Items) Statement for the content of a COS development study protocol. Methods The COS-STAP Statement was developed following the Enhancing the Quality and Transparency Of Health Research (EQUATOR) Network’s methodological framework for guideline development. This included an initial item generation stage, a two-round Delphi survey involving more than 150 participants representing three stakeholder groups (COS developers, journal editors and patient and public involvement researchers interested in COS development), followed by a consensus meeting with eight voting participants. Results The COS-STAP Statement consists of a checklist of 13 items considered essential documentation in a protocol, outlining the scope of the COS, stakeholder involvement, COS development plans and consensus processes. Conclusions Journal editors and peer reviewers can use the guidance to assess the completeness of a COS development study protocol submitted for publication. By providing guidance for key content, the COS-STAP Statement will enhance the drafting of high-quality protocols and determine how the COS development study will be carried out. Electronic supplementary material The online version of this article (10.1186/s13063-019-3230-x) contains supplementary material, which is available to authorized users.

Aim: To compare the long-term clinical and radiological results of metal-on-polyethylene hybrid total hip replacement (THA) with metal-on-metal Birmingham hip resurfacing (BHR) in young, active patients. Patients and methods: From the 1st consecutive 63 hips in young, active patients who underwent BHR by the senior author, 54 (51 patients) were matched to patients who had undergone THA with regard to age, gender, body mass index and preoperative levels of activity. Radiologically, all hips were assessed for migration and osteolysis, THAs for polyethylene wear and BHRs for a pedestal sign. Patient-reported outcomes, mortality and revision rates were compared. Results: The mean follow-up of the patients with a hybrid THR was 19.9 years and for those with a BHR, 17.6 years. 13 patients with a hybrid THR and 5 with a BHR had died. 1 hybrid THR and 3 BHRs were lost to follow-up. The revision rate of the hybrid THRs was 14/54 and of the BHRs 6/54. Log rank comparison of Kaplan-Meier survival estimates demonstrated a significantly lower mortality in the BHR group ( p = 0.039; hazard ratio [HR] = 0.37 [95% CI, 0.15–0.95]) but a non-significant difference in revision rates ( p = 0.067; HR = 0.43 [95% CI, 0.18–1.06]). The BHRs recorded superior OHS ( p = 0.03), UCLA ( p = 0.0096), and EuroQol visual analogue scores ( p = 0.03). Significantly more BHRs had run, played sport and undertaken heavy manual labour in the month preceding follow-up. Conclusion: After 18 years, patients with BHRs remained more active with a lower mortality rate but demonstrated no significant difference in revision rates. Both groups demonstrated progressive radiological changes at long-term follow-up.

Background: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer–metabolite associations using two-sample Mendelian randomization (MR). Methods: The case–control portion of the study was conducted in nine UK centers with men ages 50–69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Results: Thirty-five metabolites were strongly associated with prostate cancer (P < 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal. Conclusions: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk. Impact: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.

Aims The aim of this study was to investigate the association between the type of operation used to treat a trochanteric fracture of the hip and 30-day mortality. Patients and Methods Data on 82 990 patients from the National Hip Fracture Database were analyzed using generalized linear models with incremental case-mix adjustment for patient, non-surgical and surgical characteristics, and socioeconomic factors. Results The use of short and long intramedullary nails was associated with an increase in 30-day mortality (adjusted odds ratio (OR) 1.125, 95% confidence interval (CI) 1.040 to 1.218; p = 0.004) compared with the use of sliding hip screws (12.5% increase). If this were causative, it would represent 98 excess deaths over the four-year period of the study and one excess death would be caused by treating 112 patients with an intramedullary nail rather than a sliding hip screw. Conclusion There is a 12.5% increase in the risk of 30-day mortality associated with the use of an intramedullary nail compared with a sliding hip screw in the treatment of a trochanteric fractures of the hip.

Introduction: in severe post prostatectomy stress urinary incontinence (SUI), urodynamics may not identify crucial parameters because of inadequate bladder filling. This study describes evaluation of cystometry and pressure flow study (PFS) in men where severe SUI during attempted filling necessitated application of a penile clamp to allow filling to reach cystometric capacity. Methods: we identified all men who had undergone prior radical prostatectomy from a database of patients attending for videourodynamic testing between 2012-2017. Symptom scores, bladder diary and free flow rate tests were retrieved. We evaluated the measurements of the subgroup of men with severe SUI for whom a Thomson-Walker compression clamp was utilised to enable full urodynamic evaluation. Results: 166 radical prostatectomy patients were identified. In 30 (18%), severe SUI led to incomplete filling cystometry, i.e. failure to reach cystometric capacity. Following application of the penile compression clamp, it was possible to achieve further filling in each case. Applying the clamp did not alter vesical filling or impede pressure recording. These men had a lower maximum urethral closure pressure (31.6 vs 46.5cmH2O; p

Objective Minimally invasive mitral valve repair may be associated with prolonged cardioplegic arrest times and ischemic reperfusion injury. Intravenous (propofol) and volatile (sevoflurane) anesthesia are used routinely during cardiac surgery and are thought to provide cardioprotection; however, the individual contribution of each regimen to cardioprotection is unknown. Therefore, the authors sought to compare the cardioprotective effects of propofol and sevoflurane anesthesia in patients undergoing minimally invasive mitral valve repair. Design A single-center single-blind randomized controlled trial. Setting A specialized regional cardiac surgery center in Italy. Participants The study enrolled 62 adults undergoing elective isolated minimally invasive mitral valve repair for degenerative disease. Exclusion criteria included secondary mitral regurgitation, previously treated coronary artery disease, diabetes mellitus, chronic renal failure requiring dialysis, atrial fibrillation, and documented allergy to either propofol or sevoflurane. Interventions All patients received video-assisted minimally invasive right minithoracotomy. Patients were randomized to receive propofol or sevoflurane anesthesia in a 1:1 ratio. Measurements and Main Results Cardiac troponin I release was measured over the first 72 hours postoperatively. Operative, cross-clamp, and total bypass times were similar between groups. Cardiac troponin I release was reduced nonsignificantly in the propofol group (p = 0.62), and peak troponin I release was correlated with cross-clamp time in both groups. There were no differences in terms of intraoperative lactate release and blood pH between groups. Conclusion Propofol and sevoflurane anesthesia were associated with similar degrees of myocardial injury, indicating comparable cardioprotection. Myocardial injury was related directly to the duration of cardioplegic arrest.

Significance: Keloid and hypertrophic scarring are common following acute wounds. However, the variability in scarring outcomes between individuals and in particular, the association between genetic factors and scarring, is not well understood. This scoping review aims to summarize the methodology used in studies of genetic influences on the development of keloid or hypertrophic scarring in adults and children after acute wounding. The objectives were to determine the study designs used, the characteristics of participants included, the tools used to assess scarring and the length of follow-up after wounding. Recent Advances: The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Medline, Excerpta Medica Database (EMBASE), Web of Science, Biosciences Information Service (BIOSIS), Prospective Register of Systematic Reviews (PROSPERO), The Human Genetic Epidemiology (HuGE) Navigator (database of genetic association studies), and the genome-wide association study Catalog were searched from January 2008 to April 2020. Cohort studies and case-control studies that examined the association between one or more genetic variations and the development of keloid or hypertrophic scarring were eligible for inclusion. A narrative synthesis that grouped studies by wound type was conducted. Critical Issues: Nine studies met the inclusion criteria (five in burns, four surgical wounds, and none in other types of acute wounds). Seven assessed hypertrophic scarring, one keloid scarring, and one both scar types. Seven studies used a prospective cohort design. All studies used subjective methods (clinician or patient observation) to assess scarring. There was considerable variation in how scar scales were operationalized. Future Directions: This review identified a small body of evidence on genetic susceptibility to scarring after acute wounding. Further studies are needed, and in a wide range of populations, including patients with wounds caused by trauma.

Objectives:Recruitment to pragmatic trials is often difficult, and little is known about factors associated with key participation and treatment decisions. These were explored in the Prostate cancer testing and Treatment (ProtecT) study. Study Design and Setting:Baseline sociodemographic, patient-reported outcome, clinical history, and prostate cancer biopsy data were collected for all patients eligible to take part in the ProtecT trial, in a comprehensive cohort design. Men who rejected randomization specified a preferred option and were followed up identically to the randomized cohort. Factors associated with participation decisions, patient preferences, and reasons for changing treatment were explored. Results:Of 2,664 men with clinically localized prostate cancer, 997 (37%) rejected randomization. Their treatment preferences and subsequent treatment choices/changes in both randomized and treatment choice cohorts were strongly associated with prostate cancer risk features: toward active monitoring for low-risk disease and toward radical options with higher risk prostate cancer. Among many factors measured, only a small number of weak associations were found for occupation groups and some patient symptoms. Similar percentages changed from the random allocation and initially stated preference. Conclusion:The comprehensive cohort design provided new insights into trial recruitment and participation decisions. Opportunities to improve recruitment by supporting recruiters with equipoise and patient preferences were identified.

Background Trial oversight is important for trial governance and conduct. Patients and/or lay members of the public are increasingly included in trial oversight committees, influenced by international patient and public involvement (PPI) initiatives to improve the quality and relevance of research. However, there is a lack of guidance on how to undertake PPI in trial oversight and tokenistic PPI remains an issue. This paper explores how PPI functions in existing trial oversight committees and provides recommendations to optimise PPI in future trials. This was part of a larger study investigating the role and function of oversight committees in trials facing challenges. Methods Using an ethnographic study design, we observed oversight meetings of eight UK trials and conducted semi-structured interviews with members of their trial steering committees (TSCs) and trial management groups (TMGs) including public contributors, trial sponsors and funders. Thematic analysis of data was undertaken, with findings integrated to provide a multi-perspective account of how PPI functions in trial oversight. Results Eight TSC and six TMG meetings from eight trials were observed, and 66 semi-structured interviews conducted with 52 purposively sampled oversight group members, including three public contributors. PPI was reported as beneficial in trial oversight, with public members contributing a patient voice and fulfilling a patient advocacy role. However, public contributors were not always active at oversight meetings and were sometimes felt to have a tokenistic role, with trialists reporting a lack of understanding of how to undertake PPI in trial oversight. To optimise PPI in trial oversight, the following areas were highlighted: the importance of planning effective strategies to recruit public contributors; considering the level of oversight and stage(s) of trial to include PPI; support for public contributors by the trial team between and during oversight meetings. Conclusions We present evidence-based recommendations to inform future PPI in trial oversight. Consideration should be given at trial design stage on how to recruit and involve public contributors within trial oversight, as well as support and mentorship for both public contributors and trialists (in how to undertake PPI effectively). Findings from this study further strengthen the evidence base on facilitating meaningful PPI within clinical trials.

Purpose: To explore the long-term impact of difficulty with kneeling and how healthcare services could be improved to help patients kneel after total knee replacement. Patients and methods: Telephone interviews were conducted with 56 patients who had extreme difficulty kneeling at 7–10 years after knee replacement. Patients were asked about reasons for difficulty kneeling, how it impacted upon their lives, and experiences of healthcare services. Responses were recorded on a standardized proforma and a descriptive content analysis performed. Results: Most people had difficulty kneeling because of pain or discomfort in the replaced knee. Many patients described how this limitation affected their daily lives, including housework, gardening, religious practices, leisure activities and getting up after a fall. Patients often adapted to these limitations by finding alternatives to kneeling, assistance from others or home adaptations. Many patients had accepted that they could not kneel, however some still expressed frustrated. Few patients had consulted with healthcare professionals about kneeling difficulties, and unmet needs included the provision of information about kneeling and post-operative physiotherapy. Interpretation: This study provides an initial insight into how difficulty kneeling after knee replacement impacts upon patientsand the need for better healthcare provision.Implications for rehabilitationRehabilitation professionals should be aware that many patients experience difficulty with kneeling after total knee replacement and that this has a long-term impact upon patients.There is a need for rehabilitation after knee replacement to address kneeling difficulties.It is suggested that this rehabilitation should be delivered early in the postoperative recovery phase and designed to address the multifactorial reasons that patients find kneeling problematic. Rehabilitation professionals should be aware that many patients experience difficulty with kneeling after total knee replacement and that this has a long-term impact upon patients. There is a need for rehabilitation after knee replacement to address kneeling difficulties. It is suggested that this rehabilitation should be delivered early in the postoperative recovery phase and designed to address the multifactorial reasons that patients find kneeling problematic.

BackgroundWe report functional outcomes at six years in patients with varying degrees of fatty infiltration and atrophy of the rotator cuff muscles who have undergone anatomic total shoulder replacement.MethodsA retrospective analysis of case notes and magnetic resonance imaging scans of patients undergoing total shoulder replacement for primary glenohumeral arthritis was performed. Patients were grouped based upon their pre-operative magnetic resonance imaging findings for fatty infiltration, muscle area and tendinopathy. Post-operative functional outcomes were assessed using the Oxford Shoulder Score and Quick Disabilities of the Arm, Shoulder and Hand score. Post-operative measurements were made for active shoulder movements.ResultsThirty-two patients were reviewed at a mean of 67 months following surgery. All patients demonstrated fatty infiltration on their pre-operative magnetic resonance imaging scan. Muscle atrophy was shown in 22 patients and 12 had tendinopathy. Multiple regression analysis showed no correlation between the Oxford Shoulder Score (p = 0.443), the Quick Disabilities of the Arm, Shoulder and Hand score (p = 0.419), forward flexion (p = 0.170), external rotation (p = 0.755) and any of the pre-operative independent variables.DiscussionThe degree of fatty infiltration, muscle atrophy and tendinopathy of the rotator cuff muscle on pre-operative magnetic resonance imaging scanning is not associated with functional outcome score or functional movement at medium-term follow-up following total shoulder replacement.Level of evidenceIV

Background. Multiple Sclerosis (MS) is a chronic neurological disorder caused by neurodegeneration within the central nervous system. It results in impaired physical, cognitive, and psychological functioning and can also lead to lower urinary tract symptoms including nocturia. While clinical trials have suggested an association between nocturia and melatonin secretion, to our knowledge, no qualitative research has been conducted on the experience of taking melatonin to treat nocturia in progressive MS within a clinical trial. Methods. 17 semistructured qualitative interviews were conducted as part of a double-blind, randomised, placebo controlled, crossover, clinical trial with consenting adults with MS. Interviews explored participants’ experiences of nocturia associated with MS and their experience of taking melatonin as a trial treatment for nocturia versus a placebo. Data was analysed using a thematic analysis. Results. Themes on the experience of nocturia revealed participants’ understandings of nocturia, the impact it had on their night, and increased daily fatigue. Themes on the intervention showed perceived improvements to nocturia, sleep, and energy and negative effects including lethargy, a lack of significant change, and physical side effects including vivid dreams. Conclusion. This qualitative exploration revealed an association between nocturia and increased levels of fatigue during the day by those with MS. However, perspectives towards the effectiveness of melatonin as a potential treatment varied as both placebo and melatonin were perceived as having very similar effects.

ObjectiveTo compare normothermic (35°C–36°C) versus hypothermic (28°C) cardiopulmonary bypass (CPB) in paediatric patients undergoing open heart surgery to test the hypothesis that normothermic CPB perfusion maintains the functional integrity of major organ systems leading to faster recovery.MethodsTwo single-centre, randomised controlled trials (known as Thermic-1 and Thermic-2, respectively) were carried out to compare the effectiveness and acceptability of normothermic versus hypothermic CPB in children with congenital heart disease undergoing open heart surgery. In both studies, the co-primary clinical outcomes were duration of inotropic support, intubation time and postoperative hospital stay.ResultsIn total, 200 participants were recruited; 59 to the Thermic-1 study and 141 to the Thermic-2 study. 98 patients received normothermic CPB and 102 patients received hypothermic CPB. There were no significant differences between the treatment groups for any of the co-primary outcomes: inotrope duration HR=1.01, 95% CI (0.72 to 1.41); intubation time HR=1.14, 95% CI (0.86 to 1.51); postoperative hospital stay HR=1.06, 95% CI (0.80 to 1.40). Differences favouring normothermia were found in urea nitrogen at 2 days geometric mean ratio (GMR)=0.86 95% CI (0.77 to 0.97); serum creatinine at 3 days GMR=0.89, 95% CI (0.81 to 0.98); urinary albumin at 48 hours GMR=0.32, 95% CI (0.14 to 0.74) and neutrophil gelatinase-associated lipocalin at 4 hours GMR=0.47, 95% CI (0.22 to 1.02), but not at other postoperative time points.ConclusionsNormothermic CPB is as safe and effective as hypothermic CPB and can be routinely adopted as a perfusion strategy in low-risk infants and children undergoing open heart surgery.Trial registration numberISRCTN93129502.

AIMS: To capture in-depth qualitative evidence regarding attitudes to and experiences of urodynamic testing among men with lower urinary tract symptoms (LUTS) at each end of the clinical pathway.METHODS: Semi-structured interview study conducted within the Urodynamics for Prostate Surgery: Randomized Evaluation of Assessment Methods (UPSTREAM) trial, which randomized men to a care pathway including urodynamics or routine non-invasive tests from 26 secondary care urology sites across England. Men were interviewed after assessments but prior to treatment, or after surgery for LUTS. Men were purposively sampled to include those who had urodynamics and those who did not, and diversity in demographic characteristics and symptom burden. Interviews were analyzed using inductive thematic analysis.RESULTS: Forty-one men participated (25 pre-treatment, 16 post-surgery), ages 52-89. The 16 men who had not previously experienced urodynamics said they would accept the test in their assessment, but some were apprehensive or wanted more information. The 25 men who had experienced urodynamics all found it acceptable, though some reported pain, infection, or embarrassment. Embarrassment was minimized by informing patients what the procedure would be like, and ensuring privacy. Urodynamics was valued for its perceived diagnostic insight. Information deficits were reported before, during, and after the test. How and when results were explained and the adequacy of explanations varied.CONCLUSIONS: Urodynamics is acceptable to men with LUTS and generally well-tolerated. To ensure patients are prepared and informed, good communication before and during the procedure is essential. Privacy should be prioritized, and test results discussed promptly and in sufficient detail. Staff require training and guidance in these areas.

BACKGROUND: Idiopathic pulmonary artery aneurysm is a rare anomaly with only a handful reports in the literature. It is often asymptomatic, while the first presentation could be severe hemoptysis or death. Surgical intervention needs to be planned carefully with a multidisciplinary team approach to secure optimal outcome. We hope to spread our experience with such cases and to encourage other surgeons worldwide to deal surgically with these cases when its indicated.CASE PRESENTATION: A 47 years old man presented to our institution after three episodes of hemoptysis, echo demonstrated good left ventricle (LV) systolic function, normal right ventricle (RV) size and function, Chest computed tomography (CT) revealed aneurysmal dilatation with pending rupture of the pulmonary artery trunk (4.5 cm), the left pulmonary artery (6 cm) and the right pulmonary artery (2.3 cm). The patient successfully underwent replacement of Pulmonary artery trunk, left pulmonary artery and right pulmonary artery by Wovex Prosthetic graft (28 mm). The patient discharged home on the eight postoperative day in good clinical condition .CONCLUSION: With this case report we wish to emphasize the need for a careful multidisciplinary approach given the complex and rare nature of the reported pathology.

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Background Dual antiplatelet therapy (DAPT) is the recommended preventative treatment for secondary ischaemic events, but increases the risk of bleeding, potentially affecting patients’ health-related quality-of-life (HRQoL). Varied utility decrements have been used in cost-effectiveness models assessing alternative DAPT regimens, but it is unclear which of these decrements are most appropriate. Therefore, we reviewed existing sources of utility decrements for bleeds in patients receiving DAPT and undertook primary research to estimate utility decrements through a patient elicitation exercise using vignettes and the EuroQol EQ-5D. Methods MEDLINE, PubMed and references of included studies were searched. Primary research and decision analytic modelling studies reporting utility decrements for bleeds related to DAPT were considered. For the primary research study, 21 participants completed an elicitation exercise involving vignettes describing minor and major bleeds and the EQ-5D-3 L and EQ-5D-5 L. Utility decrements were derived using linear regression and compared to existing estimates. Results Four hundred forty-two citations were screened, of which 12 studies were included for review. Reported utility decrements ranged from − 0.002 to − 0.03 for minor bleeds and − 0.007 to − 0.05 for major bleeds. Data sources used to estimate the decrements, however, lacked relevance to our population group and few studies adequately reported details of their measurement and valuation approaches. No study completely adhered to reimbursement agency requirements in the UK according to the National Institute for Health and Care Excellence reference case. Our primary research elicited utility decrements overlapped existing estimates, ranging from − 0.000848 to − 0.00828 for minor bleeds and − 0.0187 to − 0.0621 for major bleeds. However, the magnitude of difference depended on the instrument, estimation method and valuation approach applied. Conclusions Several sources of utility decrements for bleeds are available for use in cost-effectiveness analyses, but are of limited quality and relevance. Our elicitation exercise has derived utility decrements from a relevant patient population, based on standardised definitions of minor and major bleeding events, using a validated HRQoL instrument and have been valued using general population tariffs. We suggest that our utility decrements be used in future cost-effectiveness analyses of DAPT.

Background: The risk of prosthetic joint infection (PJI) is influenced by patient, surgical, and health-care factors. Existing evidence is based on short-term follow-up. It does not differentiate between factors associated with early onset caused by the primary intervention from those associated with later onset more likely to result from haematogenous spread. We aimed to assess the overall and time-specific associations of these factors with the risk of revision due to PJI after primary total hip replacement. Methods: We did a prospective observational cohort study analysing 623 253 primary hip procedures performed between April 1, 2003, and Dec 31, 2013, in England and Wales and recorded the number of procedures revised because of PJI. We investigated the associations between risk factors and risk of revision for PJI across the overall follow-up period using Poisson multilevel models. We reinvestigated the associations by post-operative time periods (0–3 months, 3–6 months, 6–12 months, 12–24 months, >24 months) using piece-wise exponential multilevel models with period-specific effects. Data were obtained from the National Joint Registry linked to the Hospital Episode Statistics data. Findings: 2705 primary procedures were subsequently revised for an indication of PJI between 2003 and 2014, after a median (IQR) follow up of 4·6 years (2·6–7·0). Among the factors associated with an increased revision due to PJI there were male sex (1462 [1·2‰] of 1 237 170 male-years vs 1243 [0·7‰] of 1 849 691 female-years; rate ratio [RR] 1·7 [95% CI 1·6–1·8]), younger age (739 [1·1‰] of 688 000 person-years 2 vs 272 [0·9‰] of 297 686 person-years with a BMI 2; 1·9 [1·7–2·2]), diabetes (245 [1·4‰] 178 381 person-years with diabetes vs 2120 [1·0‰] of 2 209 507 person-years without diabetes; 1·4 [1·2–1·5]), dementia (5 [10·1‰] of 497 person-years with dementia at 3 months vs 311 [2·6‰] of 120 850 person-years without dementia; 3·8 [1·2–7·8]), previous septic arthritis (22 [7·2‰] of 3055 person-years with previous infection vs 2683 [0·9‰] of 3 083 806 person-years without previous infection; 6·7 [4·2–9·8]), fractured neck of femur (66 [1·5‰] of 43 378 person-years operated for a fractured neck of femur vs 2639 [0·9‰] of 3 043 483 person-years without a fractured neck of femur; 1·8 [1·4–2·3]); and use of the lateral surgical approach (1334 [1·0‰] of 1 399 287 person-years for lateral vs 1242 [0·8 ‰] of 1 565 913 person-years for posterior; 1·3 [1·2–1·4]). Use of ceramic rather than metal bearings was associated with a decreased risk of revision for PJI (94 [0·4‰] of 239 512 person-years with ceramic-on-ceramic bearings vs 602 [0·5‰] of 1 114 239 peron-years with metal-on-polyethylene bearings at ≥24 months; RR 0·6 [0·4–0·7]; and 82 [0·4‰] of 190 884 person-years with ceramic-on-polyethyene bearings vs metal-on-polyethylene bearings at ≥24 months; 0·7 [0·5–0·9]). Most of these factors had time-specific effects. The risk of revision for PJI was marginally or not influenced by the grade of the operating surgeon, the absence of a consultant surgeon during surgey, and the volume of procedures performed by hospital or surgeon. Interpretation: Several modifiable and non-modifiable factors are associated with the risk of revision for PJI after primary hip replacement. Identification of modifiable factors, use of targeted interventions, and beneficial modulation of some of these factors could be effective in reducing the incidence of PJI. It is important for clinicians to consider non-modifiable factors and factors that exhibit time-specific effects on the risk of PJI to counsel patients appropriately preoperatively. Funding: National Institute for Health Research.

Background Venous thromboembolism (VTE) is an important cause of morbidity and a preventable cause of deaths following lower limb joint replacement. Risk prediction scores that help to predict individual VTE risk following lower limb joint replacement may inform the development of preventive strategies and guide treatment decisions. We aimed to systematically review the evidence on the development and/or validation of risk prediction scores for VTE following lower limb joint replacement. Methods Population-based studies that have developed and/or validated a risk prediction score for VTE following hip or knee replacement and randomised controlled trials (RCTs) that have evaluated the clinical impact of a score were searched for in MEDLINE, Embase, Web of Science, and The Cochrane Library to April 2018. Results Five observational cohort studies describing five risk scores were included. No RCTs were identified. The number of component variables in a single risk score ranged from 5 to 26. Three risk scores comprised 5–8 component variables. None of the studies reported calibration or discrimination statistics. Two risk scores were externally validated in single-institution cohorts and were reported to perform well. One study evaluated the general surgery Caprini risk score in primary hip and knee replacement patients and did not find it useful for VTE risk stratification. Conclusions Few VTE risk prediction scores in lower limb joint replacement exist and these have methodological issues, have been inadequately reported, not been sufficiently validated, and their impact on patient outcomes and decision making is unknown. Research is urgently warranted in the field. Systematic review registration: PROSPERO 2018: CRD42018088712.

Aims To test the significance of association between a validated index of detrusor contractility, vCE , the Watts Factor, and the Detrusor Contractility Parameter, t20-80 ; and to test whether t20-80 depends on outflow tract resistance as indicated by Bladder Outlet Obstruction Index (BOOI). Methods Thirty-seven pressure-flow traces from 20 male and 17 female patients were analyzed and forms of the Watts Factor, t20-80 and BOOI were compared with vCE . Results The Detrusor Contractility Parameter, t20-80 , is significantly associated with vCE for both women and men without a high degree of bladder outlet obstruction. The Watts Factor only had a significant association with vCE at the point of maximum flow in women. Conclusions The Detrusor Contractility Parameter (DCP) (t20-80 ), can be measured easily from the pressure flow curves of a urodynamic test. The Watts Factor at maximum urine flow, WFQmax , can be readily calculated, but is only applicable to women. In both women and men without a high degree of bladder outlet obstruction, DCP is better associated with true detrusor contractility than any Watts Factor analysis.

Orthopaedic research necessitates accurate and reliable models of human bone to enable biomechanical discoveries and translation into clinical scenarios. Juvenile bovine bone is postulated to be a potential model of normal human bone given its dimensions and comparatively reduced ethical restrictions. Demineralisation techniques can reduce bone density and alter bone properties, and methods to model osteoporotic bone using demineralised juvenile bovine bone are investigated. Juvenile bovine long bones were quantitatively CT scanned to assess bone density. Demineralisation using hydrochloric acid (0.6, 1.2 and 2.4 M) was performed to create different bone density models which underwent biomechanical validation for normal and osteoporotic bone models. All long bones were found to have comparable features to normal human bone including bone density (1.96 ± 0.08 gcm−3), screw insertion torque and pullout strength. Demineralisation significantly reduced bone density and pullout strength for all types, with 0.6 M hydrochloric acid creating reductions of 25% and 71% respectively. Juvenile bovine bone is inexpensive, easy to source and not subject to extensive ethical procedures. This study establishes for the first time, the use of its long bones as surrogates for both normal and osteoporotic human specimens and offers preliminary validation for its use in biomechanical testing.

Background and purpose — The impact of diabetes and glycemic control before joint replacement on clinical and patient-reported outcomes is unclear. We compared pain, function, complications, and length of hospital stay in diabetic and nondiabetic patients receiving primary total hip (THR) or knee replacement (TKR) and compared these outcomes in patients with poorly controlled versus well-controlled diabetes. Patients and methods — We conducted a prospective cohort study of patients undergoing primary THR (n = 300) or TKR (n = 287) for osteoarthritis. Self-reported diabetes and glycemic control (HbA1c ≤ or >7%) extracted from medical notes were used. Adjusted comparisons were performed with generalized linear models including body mass index (BMI) and comorbidities. Results — Diabetes prevalence was 11% (THR 8%; TKR 14%). Diabetic patients were more likely to have a higher BMI and greater number of comorbidities. The median length of hospital stay was 1 day longer in diabetic patients (p = 0.004), but this attenuated after adjustments for BMI and comorbidities (p = 0.3). Inpatient pain was greater for diabetic patients but attenuated following adjustment. The 12-month postoperative WOMAC subscales were similar by diabetes status following adjustment. There was little evidence of difference in outcomes according to glycemic control. Interpretation — The associations between diabetes and worse postoperative outcomes in patients undergoing THR or TKR for osteoarthritis appear to be predominantly due to associated obesity and comorbidities. In diabetic patients there is little evidence of association between postoperative outcome and preoperative glycemic control. The underlying mechanisms and causal pathways of obesity, diabetes, and multimorbidity that lead to worse outcomes after joint replacement are not well known.