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The 7Be(d, p)8Be∗ reaction was measured in inverse kinematics at a beam energy of 11 MeV/u using the ISOLDE Solenoidal Spectrometer, in order to identify and characterise high-excitation states in 8Be. The spin-parities of many of the states in the 16−20 MeV region can be explained as being particle-hole excitations within a two-centre shell model. The present experiment aims to elucidate the spin parities of higher excited states, > 20 MeV, to assess their candidacy as rotational excitations of the aforementioned particlehole states. The beam intensity in this experiment was measured using a downstream Micron S1 double-sided silicon strip detector to pick up elastically scattered deuterons. The focus of this paper is to present methods for calculating the beam intensity, which is key for extracting the spectroscopic factors of the measured states. Preliminary excitation spectra are also presented.

Introduction: Combination use of atogepant and onabotulinumtoxinA has the potential to be more effective than either alone for the preventive treatment of chronic migraine (CM) due to their complementary mechanisms of action. This analysis collected real-world data to evaluate the safety, tolerability, and effectiveness of adding atogepant to onabotulinumtoxinA as a combination preventive treatment for CM., Methods: This retrospective, longitudinal, multicenter chart review included adults with CM who received ≥ 2 consecutive cycles of onabotulinumtoxinA before ≥ 1 month of onabotulinumtoxinA and atogepant combination treatment. Charts at atogepant prescription (index date) and two subsequent onabotulinumtoxinA treatment visits (~ 3 and ~ 6 months post-index) were reviewed for change from baseline in monthly headache days (MHDs), ≥ 50% reduction in MHDs, discontinuation rates, and adverse events (AEs)., Results: Of the 55 charts that met safety analysis criteria, 31 had data on headache days at index and first post-index visit and were eligible for effectiveness analysis (mean age 46.7 years, 94.5% female). For those with data available prior to onabotulinumtoxinA treatment (n = 25), the mean MHD was 24.0 days, reduced by 8.15 days after onabotulinumtoxinA treatment. After atogepant was added, MHD was incrementally reduced by 4.53 days and 8.75 days from index date to the first (N = 31) and second (N = 23) post-index onabotulinumtoxinA treatment visit, respectively. A ≥ 50% reduction in MHDs was achieved by 45.2% of patients ~ 3 months post-index. Atogepant and onabotulinumtoxinA were discontinued by 16.1% and 6.5% of patients, respectively. In the safety population, 32.7% of patients experienced ≥ 1 AE. No serious AEs were reported., Conclusions: This real-world study of patients with CM demonstrated that adding atogepant to onabotulinumtoxinA as a combination preventive treatment for CM was effective by providing an additional reduction in MHDs over ~ 3 and ~ 6 months of combination treatment. Safety results were consistent with the known safety profiles of onabotulinumtoxinA and atogepant, with no new safety signals identified., (© 2024. The Author(s).)

Background: Skin conditions can have a psychological impact on a child and their caregivers, however, support is not equally distributed between geographical regions in the United Kingdom (UK)., Objectives: This study aimed to investigate the experience of National Health Service (NHS) healthcare professionals (HCPs) of addressing the psychological needs of children with skin conditions and their families, and gain expert opinion as to how services need to further develop., Design: HCPs were recruited to a qualitative study with an advert posted on social media., Methods: Fifteen HCPs took part in interviews, including dermatologists ( n  = 4), dermatology nurse consultants/specialists ( n  = 4), clinical psychologists ( n  = 4), liaison psychiatrists ( n  = 2), and a children's psychological well-being practitioner ( n  = 1)., Results: Thematic analysis revealed children often presented with anxiety, depression, self-harm and suicidal ideation. The impact on caregivers was equally profound. There were differences in service provision across the UK and all HCPs recognised the urgent need for psychological support to be integrated into standard care. Participants described how a range of interventions are typically required including cognitive behavioural therapy (CBT), and systemic approaches, as well as mindfulness/third-wave approaches. Barriers to the delivery of psychological services were associated with a lack of funding and training opportunities for core and specialist staff alike. However, in some instances, participants had overcome these challenges to be able to deliver unique services., Conclusions: There exist several barriers to providing paediatric psychological interventions, and many locations across the UK remain vulnerable as a result of continuing lack of national guidelines for the provision of psychological services., Competing Interests: O.H is a Patient Associate Editor for the British Journal of Dermatology. A.R.T is an Associate Editor for the British Journal of Dermatology and has received research support or/and honorarium in the last 12 months from Sanofi, Pfizer, and UCB. He is also a Trustee to the charity Changing Faces and a member of scientific advisor board of The Vitiligo Society., (© 2024 The Authors. Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p < 5 × 10 -8 ), of which two have not been previously reported in any ancestry group. We integrated fine-mapped loci with epigenomic and transcriptomic resources to highlight potential effector genes relevant to kidney physiology and disease, and reveal key regulatory elements and pathways involved in renal function and development. We demonstrate the varying but increased predictive power offered by a multi-ancestry polygenic score for eGFR and highlight the importance of population diversity in GWASs and multi-omics resources to enhance opportunities for clinical translation for all., Competing Interests: Declaration of interests P.N. reports investigator-initiated research grants from Allelica, Apple, Amgen, Boston Scientific, Genentech/Roche, and Novartis, personal fees from Allelica, Apple, AstraZeneca, Blackstone Life Sciences, Eli Lilly & Co, Foresite Labs, Genentech/Roche, GV, HeartFlow, Magnet Biomedicine, and Novartis, scientific advisory board membership of Esperion Therapeutics, Preciseli, and TenSixteen Bio, scientific co-founder of TenSixteen Bio, equity in MyOme, Preciseli, and TenSixteen Bio, and spousal employment at Vertex Pharmaceuticals, all unrelated to the present work. M.B.L. has received speaker and advisory fees from Otsuka, Reata, Bayer, and Sanofi Genzyme. G.P. has received speaker and advisory fees from Amgen, Bayer, Novartis, and Sanofi, and has received research grants from Bayer and Sanofi. L.M.R. is a consultant for the TOPMed Administrative Coordinating Center (through Westat)., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This systematic review aimed to identify and appraise studies investigating the efficacy of mindfulness-based interventions (MBIs) for improving depression, anxiety and parental stress in families affected by childhood physical illnesses, as well as feasibility and acceptability., Methods: Embase, PsycINFO, Scopus, Medline, and PubMed were searched between February 2 and 17, 2021, and updated on August 5, 2022. Studies investigating MBIs with children and adolescents (<18 years) with physical health conditions were included, and results are presented with narrative synthesis., Results: Eighteen studies met eligibility criteria. Studies included children and adolescents with chronic pain, headaches, cancer, heart conditions, esophageal atresia, inflammatory bowel disease, and polycystic ovary syndrome. Most studies reported mindfulness was feasible and acceptable, although findings for different health conditions were mixed. Some studies encountered difficulties with attrition, resulting in findings being underpowered., Conclusions: MBIs show promise for improving anxiety and depression in children with physical health conditions, but there is limited support for reducing stress in the family unit. A potential direction for future research might be the inclusion of parents. However, because of the heterogeneity of studies included in this review, findings must be cautiously interpreted., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Pediatric Psychology.)

Psoriasis is a chronic inflammatory skin condition, which can be affected by stress. Living with psoriasis can trigger negative emotions, which may influence quality of life. The present study explored the lived experiences of people with psoriasis with attention to the potential role of anger in the onset and progression of the chronic skin condition. Semi-structured qualitative interviews were conducted with 12 participants ( n  = 5 females, n  = 7 males) recruited from an advert on a patient charity social media platform. Data were transcribed and analysed using thematic analysis. Four key themes were identified: (1) anger at the self and others, (2) the impact of anger on psoriasis: angry skin, (3) shared experiences of distress and (4) moving past anger to affirmation. Findings suggest that anger can have a perceived impact on psoriasis through contributing to sensory symptoms and unhelpful coping cycles, and points to a need for enhanced treatment with more psychological support. The findings also highlight the continued stigma which exists for those living with visible skin conditions and how this may sustain anger for those individuals. Future research could usefully focus on developing targeted psychosocial interventions to promote healthy emotional coping., Competing Interests: The authors report no conflict of interest., (© 2022 The Authors. Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: OnabotulinumtoxinA and calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) target different migraine pathways, therefore, combination treatment may provide additional effectiveness for the preventive treatment of chronic migraine (CM) than either treatment alone. The objective of this study was to collect real-world data to improve the understanding of the safety, tolerability, and effectiveness of adding a CGRP mAb to onabotulinumtoxinA treatment for the preventive treatment of CM. Methods: This was a retrospective, longitudinal study conducted using data extracted from a single clinical site's electronic medical records (EMR) of adult patients (≥18 years) with CM treated with ≥2 consecutive cycles of onabotulinumtoxinA before ≥1 month of continuous onabotulinumtoxinA and CGRP mAb (erenumab, fremanezumab, or galcanezumab) combination treatment. Safety was evaluated by the rate of adverse events (AE) and serious adverse events (SAE). The proportion of patients who discontinued either onabotulinumtoxinA, a CGRP mAb, or combination treatment, and the reason for discontinuation, if available, was collected. The effectiveness of combination preventive treatment was assessed by the reduction in monthly headache days (MHD). Outcome data were extracted from EMR at the first CGRP mAb prescription (index) and up to four assessments at ~3, 6, 9, and 12 months post-index. The final analyses were based on measures consistently reported in the EMR. Results: EMR were collected for 192 patients, of which 148 met eligibility criteria and were included for analysis. Erenumab was prescribed to 56.7% of patients, fremanezumab to 42.6%, and galcanezumab to 0.7%. Mean (standard deviation [SD]) MHD were 20.4 (6.6) prior to onabotulinumtoxinA treatment and 14.0 (6.9) prior to the addition of a CGRP mAb (baseline). After real-world addition of a CGRP mAb, there were significant reductions in MHD at the first assessment (~3 months) (mean -2.6 days/month, 95% CI -3.7, -1.4) and at all subsequent visits. After ~12 months of continuous combination treatment, MHD were reduced by 4.6 days/month (95% CI -6.7, -2.5) and 34.9% of patients achieved ≥50% MHD reduction from index. AEs were reported by 18 patients (12.2%), with the most common being constipation ( n = 8, 5.4% [onabotulinumtoxinA plus erenumab only]) and injection site reactions ( n = 5, 3.4%). No SAEs were reported. Overall, 90 patients (60.8%) discontinued one or both treatments. The most common reason for discontinuing either treatment was lack of insurance coverage (40%); few (~14%) patients discontinued a CGRP mAb and none discontinued onabotulinumtoxinA due to safety/tolerability. Conclusion: In this real-world study, onabotulinumtoxinA was effective at reducing MHD and the addition of a CGRP mAb was safe, well-tolerated and associated with incremental and clinically meaningful reductions in MHD for those who stayed on the combination treatment. No new safety signals were identified. Of those who discontinued, the majority reported lack of insurance coverage as a reason. Prospective real-world and controlled trials are needed to further evaluate the safety and potential benefits of this combination treatment paradigm for people with CM., Competing Interests: LM has received personal compensation for consulting, serving on a scientific advisory board, speaking, research affiliation, or other activities with Alder Pharmaceuticals, Allergan (now AbbVie Inc.), Amgen, Avanir, Biohaven, Boston Biomedical Inc., CellDex, DelMar Pharmaceuticals, electroCore, Novartis, Orbis Pharmaceuticals, Promius, Teva Pharmaceuticals, and Jushi; he has financial interest in Jushi. NS has served as speaker and/or advisory board member for Allergan (now AbbVie Inc.), Amgen, Avanir, Biohaven, Currax, Depomed, Egalet, GammaCore, Eli Lilly, Lundbeck, Pernix, Promius, Supernus, and Teva. JM has served as a speaker and/or received research support from Allergan (now AbbVie Inc.), Amgen/Novartis, Avanir, Biohaven, Eli Lilly, Lundbeck, Theranica, Amneal and Teva. OH is an employee of ICON plc. AT and AA are full-time employees of AbbVie Inc., and may hold AbbVie stock. The authors declare that this study received funding from Allergan, an AbbVie Company. Employees of AbbVie participated in the research, interpretation of data, review of the manuscript, and the decision to submit for publication., (Copyright © 2022 Mechtler, Saikali, McVige, Hughes, Traut and Adams.)

Many complex systems operating far from the equilibrium exhibit stochastic dynamics that can be described by a Langevin equation. Inferring Langevin equations from data can reveal how transient dynamics of such systems give rise to their function. However, dynamics are often inaccessible directly and can be only gleaned through a stochastic observation process, which makes the inference challenging. Here we present a non-parametric framework for inferring the Langevin equation, which explicitly models the stochastic observation process and non-stationary latent dynamics. The framework accounts for the non-equilibrium initial and final states of the observed system and for the possibility that the system's dynamics define the duration of observations. Omitting any of these non-stationary components results in incorrect inference, in which erroneous features arise in the dynamics due to non-stationary data distribution. We illustrate the framework using models of neural dynamics underlying decision making in the brain., (© 2021. The Author(s).)

Exopolysaccharide (EPS) is a bacterial extracellular carbohydrate moiety which has been associated with immunomodulatory activity and host protective effects of several gut commensal bacteria. Bifidobacterium breve are early colonizers of the human gastrointestinal tract (GIT) but the role of EPS in mediating their effects on the host has not been investigated for many strains. Here, we characterized EPS production by a panel of human B. breve isolates and investigated the effect of EPS status on host immune responses using human and murine cell culture-based assay systems. We report that B. breve EPS production is heterogenous across strains and that immune responses in human THP-1 monocytes are strain-specific, but not EPS status-specific. Using wild type and isogenic EPS deficient mutants of B. breve strains UCC2003 and JCM7017 we show that EPS had strain-specific divergent effects on cytokine responses from murine bone marrow derived macrophages (BMDMs) and dendritic cells (BMDCs). The B. breve UCC2003 EPS negative (EPS - ) strain increased expression of cytokine genes ( Tnfa, Il6, Il12a , and Il23a ) relative to untreated BMDCs and BMDCs treated with wild type strain. B. breve UCC2003 and JCM7017 EPS - strains increased expression of dendritic cell (DC) activation and maturation marker genes ( Cd80, Cd83 , and Cd86 ) relative to untreated BMDCs. Consistent with this, BMDCs co-cultured with B. breve UCC2003 and JCM7017 EPS - strains engineered to express OVA antigen activated OVA-specific OT-II CD4 + T-cells in a co-culture antigen-presentation assay while EPS proficient strains did not. Collectively, these data indicate that B. breve EPS proficient strains use EPS to prevent maturation of DCs and activation of antigen specific CD4 + T cells responses to B. breve . This study identifies a new immunomodulatory role for B. breve EPS and suggests it may be important for immune evasion of adaptive immunity by B. breve and contribute to host-microbe mutualism., Competing Interests: OH is employed by the company Luminex Corporation which manufactures the Amnis ImageStream flow cytometer used in this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hickey, Stamou, Udayan, Ramón-Vázquez, Esteban-Torres, Bottacini, Woznicki, Hughes, Melgar, Ventura, Van Sinderen, Rossini and Nally.)

Background: Whilst competence in the management of a wide range of urological emergencies is a requirement for certification in urology, many conditions are uncommon and exposure during training may be limited. This prospective observational study sought to evaluate the feasibility and effectiveness of a standardised cadaveric emergency urology simulation course aimed at improving operative confidence and competence prior to independent on-call practice in the United Kingdom., Methods: A two-day cadaveric emergency urology simulation course supported by the British Association of Urological Surgeons (BAUS) was implemented at two pilot centres. All delegates that undertook one of the initial series of courses were invited to complete online pre- and post-course questionnaires relating to prior operative experience, documented competence and perceived confidence in being able to perform specific emergency procedures independently. Primary outcome was a self-reported 'confidence score' selected from a linear numeric scale ranging from 1 (not at all confident to perform a given procedure independently) to 10 (fully confident). Statistical analysis was undertaken using SPSS Statistics for Mac Version 25 and the paired student's t-test used to compare mean pre- and post-course scores., Results: One hundred and four delegates undertook the course during the study period. Of these, 85 (81.7%) completed the pre-course survey and 67 (64.4%) completed the post-course survey, with 61 (58.7%) completing both. The greatest proportion of respondents were Speciality Trainees in Urology of ST5 level or higher (equivalent of Resident/Fellows with 4 or more years of surgical training; n = 31, 36.5%). Delegates reported variable pre-course exposure, with most experience reported in loin approach to the kidney (median 10) and least in exploration and packing of a transurethral resection cavity and emergency nephrectomy (median 0). Following course completion, a statistically significant increase in confidence score was observed for each procedure, with the greatest increases seen for shunt for priapism (4.87 to 8.80, p < 0.001), ureteric reimplantation (3.52 to 7.33, p < 0.001) and primary ureteric anastomosis (3.90 to 7.49, p < 0.001)., Conclusions: A standardised high fidelity cadaveric simulation course is feasible and significantly improves the confidence of trainees in performing a wide range of emergency procedures to which exposure is currently limited.

Objectives: Active surveillance (AS) enables men with low risk, localised prostate cancer (PCa) to avoid radical treatment unless progression occurs; lack of reliable AS protocols to determine progression leaves uncertainties for men and clinicians. This study investigated men's strategies for coping with the uncertainties of active monitoring (AM, a surveillance strategy within the Prostate testing for cancer and Treatment, ProtecT trial) over the longer term and implications for optimising supportive care., Design: Longitudinal serial in-depth qualitative interviews every 2-3 years for a median 7 (range 6-14) years following diagnosis., Setting: Four centres within the UK Protect trial., Participants: Purposive sample of 20 men with localised PCa: median age at diagnosis 64 years (range 52-68); 15 (75%) had low-risk PCa; 12 randomly allocated to, 8 choosing AM. Eleven men continued with AM throughout the study period (median 7 years). Nine received radical treatment after a median 4 years (range 0.8-13.8 years)., Intervention: AM: 3-monthly serum prostate-specific antigen (PSA)-level assessment (year 1), 6-12 monthly thereafter; increase in PSA ≥50% during previous 12 months or patient/clinician concern triggered review., Main Outcomes: Thematic analysis of 73 interviews identified strategies to accommodate uncertainty and anxiety of living with untreated cancer; implications for patient care., Results: Men sought clarity, control or reassurance, with contextual factors mediating individual responses. Trust in the clinical team was critical for men in balancing anxiety and facilitating successful management change/continued monitoring. Only men from ProtecT were included; men outside ProtecT may have different experiences., Conclusion: Men looked to clinicians for clarity, control and reassurance. Where provided, men felt comfortable continuing AM or having radical treatments when indicated. Clinicians build patient trust by clearly describing uncertainties, allowing patients control wherever possible and being aware of how context influences individual responses. Insights indicate need for supportive services to build trust and patient engagement over the long term., Trial Registration Number: ISRCTN20141297; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: There is limited evidence relating to the cost-effectiveness of treatments for localised prostate cancer., Methods: The cost-effectiveness of active monitoring, surgery, and radiotherapy was evaluated within the Prostate Testing for Cancer and Treatment (ProtecT) randomised controlled trial from a UK NHS perspective at 10 years' median follow-up. Prostate cancer resource-use collected from hospital records and trial participants was valued using UK reference-costs. QALYs (quality-adjusted-life-years) were calculated from patient-reported EQ-5D-3L measurements. Adjusted mean costs, QALYs, and incremental cost-effectiveness ratios were calculated; cost-effectiveness acceptability curves and sensitivity analyses addressed uncertainty; subgroup analyses considered age and disease-risk., Results: Adjusted mean QALYs were similar between groups: 6.89 (active monitoring), 7.09 (radiotherapy), and 6.91 (surgery). Active monitoring had lower adjusted mean costs (£5913) than radiotherapy (£7361) and surgery (£7519). Radiotherapy was the most likely (58% probability) cost-effective option at the UK NICE willingness-to-pay threshold (£20,000 per QALY). Subgroup analyses confirmed radiotherapy was cost-effective for older men and intermediate/high-risk disease groups; active monitoring was more likely to be the cost-effective option for younger men and low-risk groups., Conclusions: Longer follow-up and modelling are required to determine the most cost-effective treatment for localised prostate cancer over a man's lifetime., Trial Registration: Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).

Background: Prostate cancer is the most common cancer among men in the UK. Prostate-specific antigen testing followed by biopsy leads to overdetection, overtreatment as well as undertreatment of the disease. Evidence of treatment effectiveness has lacked because of the paucity of randomised controlled trials comparing conventional treatments., Objectives: To evaluate the effectiveness of conventional treatments for localised prostate cancer (active monitoring, radical prostatectomy and radical radiotherapy) in men aged 50-69 years., Design: A prospective, multicentre prostate-specific antigen testing programme followed by a randomised trial of treatment, with a comprehensive cohort follow-up., Setting: Prostate-specific antigen testing in primary care and treatment in nine urology departments in the UK., Participants: Between 2001 and 2009, 228,966 men aged 50-69 years received an invitation to attend an appointment for information about the Prostate testing for cancer and Treatment (ProtecT) study and a prostate-specific antigen test; 82,429 men were tested, 2664 were diagnosed with localised prostate cancer, 1643 agreed to randomisation to active monitoring ( n  = 545), radical prostatectomy ( n  = 553) or radical radiotherapy ( n  = 545) and 997 chose a treatment., Interventions: The interventions were active monitoring, radical prostatectomy and radical radiotherapy., Trial Primary Outcome Measure: Definite or probable disease-specific mortality at the 10-year median follow-up in randomised participants., Secondary Outcome Measures: Overall mortality, metastases, disease progression, treatment complications, resource utilisation and patient-reported outcomes., Results: There were no statistically significant differences between the groups for 17 prostate cancer-specific ( p  = 0.48) and 169 all-cause ( p  = 0.87) deaths. Eight men died of prostate cancer in the active monitoring group (1.5 per 1000 person-years, 95% confidence interval 0.7 to 3.0); five died of prostate cancer in the radical prostatectomy group (0.9 per 1000 person-years, 95% confidence interval 0.4 to 2.2 per 1000 person years) and four died of prostate cancer in the radical radiotherapy group (0.7 per 1000 person-years, 95% confidence interval 0.3 to 2.0 per 1000 person years). More men developed metastases in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring, n  = 33 (6.3 per 1000 person-years, 95% confidence interval 4.5 to 8.8); radical prostatectomy, n  = 13 (2.4 per 1000 person-years, 95% confidence interval 1.4 to 4.2 per 1000 person years); and radical radiotherapy, n  = 16 (3.0 per 1000 person-years, 95% confidence interval 1.9 to 4.9 per 1000 person-years; p  = 0.004). There were higher rates of disease progression in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring ( n  = 112; 22.9 per 1000 person-years, 95% confidence interval 19.0 to 27.5 per 1000 person years); radical prostatectomy ( n  = 46; 8.9 per 1000 person-years, 95% confidence interval 6.7 to 11.9 per 1000 person-years); and radical radiotherapy ( n  = 46; 9.0 per 1000 person-years, 95% confidence interval 6.7 to 12.0 per 1000 person years; p  < 0.001). Radical prostatectomy had the greatest impact on sexual function/urinary continence and remained worse than radical radiotherapy and active monitoring. Radical radiotherapy's impact on sexual function was greatest at 6 months, but recovered somewhat in the majority of participants. Sexual and urinary function gradually declined in the active monitoring group. Bowel function was worse with radical radiotherapy at 6 months, but it recovered with the exception of bloody stools. Urinary voiding and nocturia worsened in the radical radiotherapy group at 6 months but recovered. Condition-specific quality-of-life effects mirrored functional changes. No differences in anxiety/depression or generic or cancer-related quality of life were found. At the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year, the probabilities that each arm was the most cost-effective option were 58% (radical radiotherapy), 32% (active monitoring) and 10% (radical prostatectomy)., Limitations: A single prostate-specific antigen test and transrectal ultrasound biopsies were used. There were very few non-white men in the trial. The majority of men had low- and intermediate-risk disease. Longer follow-up is needed., Conclusions: At a median follow-up point of 10 years, prostate cancer-specific mortality was low, irrespective of the assigned treatment. Radical prostatectomy and radical radiotherapy reduced disease progression and metastases, but with side effects. Further work is needed to follow up participants at a median of 15 years., Trial Registration: Current Controlled Trials ISRCTN20141297., Funding: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 24, No. 37. See the National Institute for Health Research Journals Library website for further project information., Competing Interests: Malcolm Mason reports personal fees from Sanofi (Paris, France), Bayer (Leverkusen, Germany) and Janssen Pharmaceutica (Beerse, Belgium) outside the submitted work. Derek Rosario reports grants from Bayer and personal fees from Ferring Pharmaceuticals (Saint-Prex, Switzerland) outside the submitted work. Jane Blazeby was a member of the following during the project: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Clinical Trials and Evaluation Committee (2009–2013), HTA NIHR Obesity (2010–2012), Commissioning Board for HTA Surgery Themed Call Board and the NIHR Clinical Trials Unit (CTU) Standing Advisory Committee (2015–2019). Jenny Donovan was a member of the following during the project: HTA Commissioning Board (2006–12), Rapid Trials and Add-on Studies Board (2012), NIHR Senior Investigator panel (2009–12) and NIHR Health Services and Delivery Research board (Deputy Chairperson) (2010–11). Freddie C Hamdy was a member of the following during the project: HTA Commissioning Board (2007–12) and HTA Surgery Themed Call Board (2012–13). J Athene Lane was a member of the following during the project: CTUs funded by NIHR (2017 to present). Chris Metcalfe was a member of the following during the project: CTUs funded by NIHR (2010 to present). Tim Peters was a member of the following during the project: HTA Medicines for Children Themed Call (2005–6) and NIHR CTU Standing Advisory Committee (2008–14). John Staffurth reports support for travel to conferences and attendance on an advisory board from Bayer. Emma L Turner reports grants from Cancer Research UK (London, UK) during the conduct of the study.

Objective: Adequate resources are required to rapidly diagnose and treat pediatric musculoskeletal infection (MSKI). The workload MSKI consults contribute to pediatric orthopaedic services is unknown as prior epidemiologic studies are variable and negative work-ups are not included in national discharge databases. The hypothesis was tested that MSKI consults constitute a substantial volume of total consultations for pediatric orthopaedic services across the United States., Study Design: Eighteen institutions from the Children's ORthopaedic Trauma and Infection Consortium for Evidence-based Study (CORTICES) group retrospectively reviewed a minimum of 1 year of hospital data, reporting the total number of surgeons, total consultations, and MSKI-related consultations. Consultations were classified by the location of consultation (emergency department or inpatient). Culture positivity rate and pathogens were also reported., Results: 87,449 total orthopaedic consultations and 7,814 MSKI-related consultations performed by 229 pediatric orthopaedic surgeons were reviewed. There was an average of 13 orthopaedic surgeons per site each performing an average of 154 consultations per year. On average, 9% of consultations were MSKI related and 37% of these consults yielded positive cultures. Finally, a weak inverse monotonic relationship was noted between percent culture positivity and percent of total orthopedic consults for MSKI., Conclusion: At large, academic pediatric tertiary care centers, pediatric orthopaedic services consult on an average of ~3,000 'rule-out' MSKI cases annually. These patients account for nearly 1 in 10 orthopaedic consultations, of which 1 in 3 are culture positive. Considering that 2 in 3 consultations were culture negative, estimating resources required for pediatric orthopaedic consult services to work up and treat children based on culture positive administrative discharge data underestimates clinical need. Finally, ascertainment bias must be considered when comparing differences in culture rates from different institution's pediatric orthopaedics services, given the variability in when orthopaedic physicians become involved in a MSKI workup., Competing Interests: Funding for the creation of this database was provided by the Pediatric Orthopaedic Society of North America (POSNA) through a directed research. Many members of the CORTICES are likewise active members of POSNA. The CORTICES Group has no other competing interests.