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Objective: The aim of this study was to apply sequence analysis (SA) to phenotype healthcare patterns of adult patients with musculoskeletal (MSK) conditions using primary care electronic health records and to investigate the association between these healthcare patterns and post-consultation patient's self-reported outcome., Methods: Data from the Multi-level Integrated Data for musculoskeletal health intelligence and ActionS (MIDAS) programme conducted in North Staffordshire and Stoke-on-Trent, UK was utilised. The study included patients aged ≥18 years who consulted primary care for MSK conditions between September 2021 and July 2022. SA was employed to categorise patients with similar healthcare patterns in primary care in the five years prior to their index consultation in respect to consultations, analgesic prescriptions, imaging, physiotherapy, and secondary care referrals. Association of socio-demographic characteristics and self-reported outcome with clusters were determined., Results: In total, 1,875 patients consulting primary care for MSK conditions were available for analysis. SA identified five clusters of prior healthcare patterns among patients with MSK conditions, including "increasing consultation and analgesia" (5.60%), "low consultation and healthcare use" (57.39%), "high consultation and healthcare use" (8.32%), "low consultation but high analgesia" (13.01%), and "low consultation but moderate healthcare use" (15.68%). Patients in the "high consultation and healthcare use" group were predominantly female, older, obese, had more comorbidities and lived in the most deprived areas compared to those in the "low consultation and healthcare use" group. Additionally, self-reported outcome varied significantly between clusters, with patients in the "high consultation and healthcare use" group reporting worse self- reported outcome., Conclusion: This analysis identified five distinct clusters of healthcare patterns for patients with MSK conditions in primary care and observed substantial variations in patient's self-reported outcome and socio-demographic profiles across these different groups of patients., (This article is protected by copyright. All rights reserved.)

Objectives: To identify, appraise, and synthesize common themes from quality indicator (QI) sets designed for the assessment, management, and rehabilitation of musculoskeletal (MSK) conditions in primary and community care contexts., Data Sources: A systematic search was performed on six databases (MEDLINE, EMBASE, AMED, Web of Sciences Core Collection, The Cochrane Library, and The Health Management Information Consortium), public repositories, and the websites of organizations involved in the reporting of MSK QIs., Study Selection: Potential QI sources were screened for relevance using an a priori criteria. After the screening of 1493 titles, abstracts, 71 articles were reviewed independently by two authors, of which 25 met our criteria and were therefore included within the review., Data Extraction: The development of the QI sets was appraised using the AIRE instrument. Key characteristics of QI sets were extracted and tabulated. Nine out of 25 QI sets had "high" developmental methodology quality. A total of 410 QIs were identified from 25 QI sets., Data Synthesis: A narrative synthesis was undertaken to identify common themes among QIs. Themes were mapped against improvement drivers mentioned in recent British primary/community MSK care policy directives. Finally, "Draft Indicators" were synthesized from common themes identified. Eleven overarching themes were synthesized: policy and governance; optimizing access and provision of care; staffing and spending; optimizing assessment and diagnosis; optimizing patient education and self-management; pharmacology and injection guideline adherence; optimizing personalized care; optimizing imaging, investigations, and referral; public health management relevant to MSK conditions; optimizing patient experience; and optimizing patient outcomes., Conclusions: This review has identified common themes among QIs that focus on optimizing assessment, investigations, and treatment decisions for the primary/community care of MSK conditions. This work represents a valuable resource to commissioners, service managers, and clinicians internationally who resource, monitor, manage, assess, and rehabilitate individuals with MSK conditions., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Background: Abbreviation use in clinical and academic cardiology is widespread, yet there are few guidelines regulating the creation and utilization of abbreviations. Inconsistent abbreviations can introduce ambiguity and pose challenges to practice and research., Objectives: The authors aimed to analyze how abbreviations are created and utilized in general cardiology and cardiac imaging society guidelines in order to assess whether ambiguities and discrepancies exist between societies., Methods: Abbreviation data were collected from 7 national and international societies of general cardiology and cardiac imaging over a 6-year span (2018-2023). Data were linguistically coded for abbreviation type, unique occurrence, meaning or sense count, and frequency of discrepancy between societies., Results: Among a total of 5,394 abbreviation tokens, there were 1,782 unique entries. Among the unique entries, 227 (12.7%) had 2 or more associated meanings (senses), and thus were potentially ambiguous. Cardiac societies differed from each other, and also internally, in their use of abbreviations, with the European Society of Cardiology representing the highest frequency of discrepant abbreviation usage (14.5%)., Conclusions: More than 12.7% of abbreviations in cardiology society guidelines had 2 or more corresponding meanings, potentially increasing the risks of miscommunication and misrepresentation. We call on cardiology and cardiac imaging societies to define and publish best practices regarding abbreviation creation and utilization., Competing Interests: This research did not receive any specific grant funding from any public or private sources. Dr Hill is a consultant for Philips Healthcare. Dr Mitchell reports author textbook chapters with Elsevier and contracted research grants from W. L. Gore & Associates to University of Wisconsin-Madison, consulting Acoustic Range Estimates. Dr Rigolin owns stock ownership in Amgen, Edwards, Intuitive Surgical, Organon, Rednivia, Regeneron, AstraZeneca, Bristol Myers Squibb, Merck/Schering-Plough, Pfizer, and Viatris. Dr Strom received research grants from the National Heart, Lung, and Blood Institute (1R01HL169517) and National Institute of Aging (1R01AG063937), Anumana, Philips Healthcare, EVERSANA Lifesciences, and Bracco Diagnostics; reports consulting for Bracco Diagnostics, Edwards Lifesciences, Philips Healthcare, General Electric Healthcare, and EVERSANA, and is a scientific advisory board member for Ultromics, HeartSciences, Bristol Myers Squibb, and EchoIQ. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The content of this manuscript is solely the responsibility of the authors and does not necessarily reflect the official views of the NHLBI, NIH, or the United States Department of Health and Human Services., (© 2025 The Authors.)

Abstract: There have been at least 7 separate randomised controlled trials published between 2011 and 2023 that have examined primary care for nonspecific low back pain informed by the STarT Back approach to stratified care based on risk prediction, compared with care not informed by this approach. The results, across 4 countries, have been contrasting-some demonstrating effectiveness and/or efficiency of this approach, others finding no benefits over comparison interventions. This review considers possible explanations for the differences, particularly whether this is related to poor predictive performance of the STarT Back risk-prediction tool or to variable degrees of success in implementing the whole STarT Back approach (subgrouping and matching treatments to predicted risk of poor outcomes) in different healthcare systems. The review concludes that although there is room for improving and expanding the predictive value of the STarT Back tool, its performance in allocating individuals to their appropriate risk categories cannot alone explain the variation in results of the trials to date. Rather, the learning thus far suggests that challenges in implementing stratified care in clinical practice and in changing professional practice largely explain the contrasting trial results. The review makes recommendations for future research, including greater focus on studying facilitators of implementation of stratified care and developing better treatments for patients with nonspecific low back pain at high risk of poor outcomes., (Copyright © 2024 International Association for the Study of Pain.)

Abstract: We developed the SupportPrim PT clinical decision support system (CDSS) using the artificial intelligence method case-based reasoning to support personalised musculoskeletal pain management. The aim of this study was to evaluate the effectiveness of the CDSS for patients in physiotherapy practice. A cluster randomised controlled trial was conducted in primary care in Norway. We randomised 44 physiotherapists to (1) use the CDSS alongside usual care or (2) usual care alone. The CDSS provided personalised treatment recommendations based on a case base of 105 patients with positive outcomes. During the trial, the case-based reasoning system did not have an active learning capability; therefore, the case base size remained the same throughout the study. We included 724 patients presenting with neck, shoulder, back, hip, knee, or complex pain (CDSS; n = 358, usual care; n = 366). Primary outcomes were assessed with multilevel logistic regression using self-reported Global Perceived Effect (GPE) and Patient-Specific Functional Scale (PSFS). At 12 weeks, 165/298 (55.4%) patients in the intervention group and 176/321 (54.8%) in the control group reported improvement in GPE (odds ratio, 1.18; confidence interval, 0.50-2.78). For PSFS, 173/290 (59.7%) patients in the intervention group and 218/310 (70.3%) in the control group reported clinically important improvement in function (odds ratio, 0.41; confidence interval, 0.20-0.85). No significant between-group differences were found for GPE. For PSFS, there was a significant difference favouring the control group, but this was less than the prespecified difference of 15%. We identified several study limitations and recommend further investigation into artificial intelligence applications for managing musculoskeletal pain., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Dark photons that kinetically mix with the Standard Model photon give rise to new spectral anisotropies (patchy dark screening) in the cosmic microwave background (CMB) due to conversion of photons to dark photons within large-scale structure. We utilize predictions for this patchy dark screening signal to provide the tightest constraints to date on the dark photon kinetic mixing parameter [ϵ≲4.5×10^{-8} (95% confidence level)] over the mass range 10^{-13}  eV≲m_{A^{'}}≲10^{-11}  eV, almost an order of magnitude stronger than previous limits, by applying state-of-the-art component separation techniques to the cross-correlation of Planck CMB and unWISE galaxy survey data.

Purpose: The societal response and constraints of the COVID-19 pandemic reinforced ableism for disabled people who were yet again treated as an afterthought in society. Systemic ableism impacted their well-being, access, and ability to be active members of their community. Disabled experiences and voices must be heard and amplified to improve preparedness and address ableism. Disability Twitter is one avenue where the disability community can collectively listen and support one another. These voices can and should be used to influence policy and practice. This study used Disability Twitter to represent and honor the experiences of the disability community, using the COVID-19 pandemic as a moment in time., Research Method/design: Qualitative thematic analysis of U.S.-based Twitter posts was conducted using retrospective social media posts. A total of 238 initial tweets from January 1, 2020 and September 30, 2022 were analyzed by the research team., Results: Five themes were observed including ableism, devaluation, worthiness, act of reclaiming, and emotion. Disabled people reported instances of ableism, devaluation, and victimization by individuals, systems, and government entities throughout the pandemic. Disabled individuals utilized Twitter to share their collective experiences, urging society to address and respond to the needs of the disability community., Conclusions: Using social media to center the perspectives of the disability community can invoke system-wide change and inform policies. Implications for combating systemic ableism and promoting allyship for clinical professionals, research scholars, and educators are provided. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Men with high-risk localized prostate cancer exhibit high rates of post-surgical recurrence. In these patients, androgen deprivation therapy (ADT) is immunomodulatory, however increased infiltration of regulatory T cells (Tregs) may limit the antitumor immune effects of ADT. We designed a neoadjuvant clinical trial to test whether BMS-986218 - a next-generation non-fucosylated anti-CTLA-4 antibody engineered for enhanced antibody-dependent cellular cytotoxicity or phagocytosis (ADCC/P) - depletes intratumoral Tregs and augments the response to ADT. In this single-center, two-arm, open-label study, 24 men with high-risk localized prostate cancer were randomized to receive a single dose of ADT with or without two pre-operative doses of BMS-986218 (anti-CTLA4-NF) prior to radical prostatectomy. Treatment was well tolerated and feasible in the neoadjuvant setting. A secondary clinical outcome was the rate of disease recurrence, which was lower than predicted in both arms. Mechanistically, anti-CTLA4-NF reduced ADT-induced Treg accumulation through engagement of CD16a/ FCGR3A on tumor macrophages, and depth of Treg depletion was quantitatively associated with clinical outcome. Increased intratumoral dendritic cell (DC) frequencies also associated with lack of recurrence, and pre-clinical data suggest ADCC/P-competent anti-CTLA-4 antibodies elicit activation and expansion of tumor DCs. Patients receiving anti-CTLA4-NF also exhibited phenotypic signatures of enhanced antitumor T cell priming. In total, this study provides the first-in-human evidence of Treg depletion by glycoengineered antibodies targeting CTLA-4 in humans and their potential in combination with ADT in prostate cancer patients with high-risk of recurrence., Competing Interests: Conflicts of Interest: C.G.D is a co-inventor on patents licensed from Johns Hopkins University to BMS and Janssen. He is currently a paid employee of JnJ Innovative Medicine. A.C. is founder, equity holder, consultant, and director of DarwinHealth Inc., which has licensed IP related to these algorithms from Columbia University. Columbia University is an equity holder in DarwinHealth Inc.

Purpose: To develop and validate prediction models for the risk of future work absence and level of presenteeism, in adults seeking primary healthcare with musculoskeletal disorders (MSD)., Methods: Six studies from the West-Midlands/Northwest regions of England, recruiting adults consulting primary care with MSD were included for model development and internal-external cross-validation (IECV). The primary outcome was any work absence within 6 months of their consultation. Secondary outcomes included 6-month presenteeism and 12-month work absence. Ten candidate predictors were included: age; sex; multisite pain; baseline pain score; pain duration; job type; anxiety/depression; comorbidities; absence in the previous 6 months; and baseline presenteeism., Results: For the 6-month absence model, 2179 participants (215 absences) were available across five studies. Calibration was promising, although varied across studies, with a pooled calibration slope of 0.93 (95% CI: 0.41-1.46) on IECV. On average, the model discriminated well between those with work absence within 6 months, and those without (IECV-pooled C-statistic 0.76, 95% CI: 0.66-0.86). The 6-month presenteeism model, while well calibrated on average, showed some individual-level variation in predictive accuracy, and the 12-month absence model was poorly calibrated due to the small available size for model development., Conclusions: The developed models predict 6-month work absence and presenteeism with reasonable accuracy, on average, in adults consulting with MSD. The model to predict 12-month absence was poorly calibrated and is not yet ready for use in practice. This information may support shared decision-making and targeting occupational health interventions at those with a higher risk of absence or presenteeism in the 6 months following consultation. Further external validation is needed before the models' use can be recommended or their impact on patients can be fully assessed., (© 2024. The Author(s).)

The STarT MSK tool was developed to enable risk stratification of patients with common musculoskeletal (MSK) pain conditions and help identify individuals who may require more targeted interventions or closer monitoring in primary care settings, however, its validity in U.S.-based outpatient physical therapy settings has not been investigated. The 10-item Keele STarT MSK risk stratification tool was tested for construct (convergent and discriminant) and predictive validity using a multicenter, prospective cohort study design. Participants (n = 141) receiving physical therapy for MSK pain of the back, neck, shoulder, hip, knee, or multisite regions completed intake questionnaires including the Keele STarT MSK tool, Functional Comorbidity Index (FCI), Optimal Screening for Prediction of Referral and Outcome Review-of-Systems and Optimal Screening for Prediction of Referral and Outcome Yellow Flag tools. Pain intensity, pain interference, and health-related quality of life (Medical Outcomes Study 8-item Short-Form Health Survey (SF-8) physical [PCS] and mental [MCS] component summary scores) were measured at 2- and 6-month follow-up. Participants were classified as STarT MSK tool low (44%), medium (39%), and high (17%) risk. Follow-up rates were 70.2% (2 months) and 49.6% (6 months). For convergent validity, fair relationships were observed between the STarT MSK tool and FCI and SF-8 MCS (r = .35-.37) while moderate-to-good relationships (r = .51-.72) were observed for 7 other clinical measures. For discriminant validity, STarT MSK tool risk-dependent relationships were observed for Optimal Screening for Prediction of Referral and Outcome Review-of-Systems, Optimal Screening for Prediction of Referral and Outcome Yellow Flag, pain interference, and SF-8 PCS (low < medium < high; P < .01) and FCI, pain intensity, and SF-8 MCS (low < medium-or-high; P < .01). For predictive validity, intake STarT MSK tool scores explained additional variability in pain intensity (11.2%, 20.0%), pain interference (7.5%, 14.1%), and SF-8 PCS (8.2%, 12.8%) scores at 2 and 6 months, respectively. This study contributes to the existing literature by providing additional evidence of STarT MSK tool cross-sectional construct validity and longitudinal predictive validity. PERSPECTIVE: This study presents STarT MSK risk stratification tool validity findings from a U.S. outpatient physical therapy sample. The STarT MSK tool has the potential to help physical therapists identify individuals presenting with the most common MSK pain conditions who may require more targeted interventions or closer monitoring., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Low back pain is prevalent and a leading cause of disability. We aimed to determine the clinical and cost-effectiveness of an accessible, scalable internet intervention for supporting behavioural self-management (SupportBack)., Methods: Participants in UK primary care with low back pain without serious spinal pathology were randomly assigned 1:1:1 using computer algorithms stratified by disability level and telephone-support centre to usual care, usual care and SupportBack, or usual care and SupportBack with physiotherapist telephone-support (three brief calls). The primary outcome was low back pain-related disability (Roland Morris Disability Questionnaire [RMDQ] score) at 6 weeks, 3 months, 6 months, and 12 months using a repeated measures model, analysed by intention to treat using 97·5% CIs. A parallel economic evaluation from a health services perspective was used to estimate cost-effectiveness. People with lived experience of low back pain were involved in this trial from the outset. This completed trial was registered with ISRCTN, ISRCTN14736486., Findings: Between Nov 29, 2018, and Jan 12, 2021, 825 participants were randomly assigned (274 to usual care, 275 to SupportBack only, 276 to SupportBack with telephone-support). Participants had a mean age of 54 (SD 15), 479 (58%) of 821 were women and 342 (42%) were men, and 591 (92%) of 641 were White. Follow-up rates were 687 (83%) at 6 weeks, 598 (73%) at 3 months, 589 (72%) at 6 months, and 652 (79%) at 12 months. For the primary analysis, 736 participants were analysed (249 usual care, 245 SupportBack, and 242 SupportBack with telephone support). At a significance level of 0·025, there was no difference in RMDQ over 12 months with SupportBack versus usual care (adjusted mean difference -0·5 [97·5% CI -1·2 to 0·2]; p=0·085) or SupportBack with telephone-support versus usual care (-0·6 [-1·2 to 0·1]; p=0·048). There were no treatment-related serious adverse events. The economic evaluation showed that the SupportBack group dominated usual care, being both more effective and less costly. Both interventions were likely to be cost-effective at a threshold of £20 000 per quality adjusted life year compared with usual care., Interpretation: The SupportBack internet interventions did not significantly reduce low back pain-related disability over 12 months compared with usual care. They were likely to be cost-effective and safe. Clinical effectiveness, cost-effectiveness, and safety should be considered together when determining whether to apply these interventions in clinical practice., Funding: National Institute for Health and Care Research Health Technology Assessment (16/111/78)., Competing Interests: Declaration of interests LCR reports an educational grant from Pfizer held by their institute; consulting fees from the Musculoskeletal Association of Chartered Physiotherapists; and meeting support from Eurospine. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: This study evaluated the hypothesis that vascular aging (VA) reduces ventricular contractile function and mechanical efficiency (ME) using the left ventricular pressure-volume (PV) construct., Methods: A previously published in-silico computational model (CM) was modified to evaluate the hypothesis in two phases. In phase I, the CM included five settings of aortic compliance ( C A ) from normal to stiff, studied at a heart rate of 80 bpm, and phase II included the normal to stiff C A settings evaluated at 60, 100, and 140 bpm. The PV construct provided steady-state and transient data through a simulated vena caval occlusion (VCO). The steady-state data included left ventricular volumes (EDV and ESV), stroke work (SW), and VCO provided the PV area (PVA) data in addition to the three measures of contractile state (CS): end-systolic pressure-volume relationship (ESPVR), dP/dt max -EDV and preload recruitable stroke work (PRSW). Finally, ME was calculated with the SW/PVA parameter., Results: In phase I, EDV and ESV increased, as did SW and PVA. The impact on the CS parameters demonstrated a small decrease in ESPVR, no change in dP/dt max -EDV, and a large increase in PRSW. ME decreased from 71.5 to 60.8%, respectively. In phase II, at the normal and stiff C A settings, across the heart rates studied, EDV and ESV decreased, ESPVR and dP/dt max -EDV increased and PRSW decreased. ME decreased from 76.4 to 62.6% at the normal C A and 65.8 to 53.2% at the stiff C A ., Discussion: The CM generated new insights regarding how the VA process impacts the contractile state of the myocardium and ME., Competing Interests: The 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., (© 2024 Mulligan, Thrash, Mitrev, Folk, Exarchakis, Ewert and Hill.)

Objectives: To explore the acceptability of an optimised physiotherapy (OPTimisE) intervention for people with lateral elbow tendinopathy (LET) and feasibility of comparing it to usual care in a randomised controlled trial., Design: Semistructured interviews, analysed using thematic analysis and mapped onto the COM-B model of behaviour change., Setting: Conducted as part of the OPTimisE Pilot & Feasibility randomised controlled trial within physiotherapy departments in the United Kingdom National Health Service., Participants: 17 patients with LET (purposively sampled to provide representativeness based on age, sex, ethnicity, deprivation index and treatment allocation) and all 8 physiotherapists involved as treating clinicians or site principal investigators., Results: Four themes were identified. First, participants reported the OPTimisE intervention as acceptable. Second, differences between the OPTimisE intervention and usual care were identified, including the use of an orthosis, holistic advice/education including modifiable risk factors, forearm stretches, general upper body strengthening and a more prescriptive exercise-dosing regimen. Third, participants provided feedback related to the trial resources, which were viewed positively, but identified language translation as a need. Fourth, feedback related to trial processes identified the need for changes to outcome collection and reduction of administrative burden. From the perspective of adopting the OPTimisE intervention, we found evidence that participants were able to change their behaviour. Considering the findings through the lens of the COM-B model, the intervention is likely to be deliverable in practice and the trial can be delivered at scale with some additional support for physiotherapists., Conclusions: Overall, the OPTimisE intervention was found to be different to usual care and acceptable to patients and physiotherapists. The study highlighted the need to refine trial processes and resources prior to a full-scale trial, to reduce administrative burden, increase support for physiotherapists, improve return rate of outcome questionnaires and provide language translation., Trial Registration Number: ISRCTN database 19 July 2021. https://www.isrctn.com/ISRCTN64444585., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Globally, back pain is the leading cause of years of disability. In the United Kingdom, over 20 million people live with musculoskeletal (MSK) pain, with low back pain being one of the most common causes. National strategies promote self-management and the use of digital technologies to empower populations., Aims: To evaluate the uptake and impact of providing the SelfSTart approach (STarT Back and SelfBACK App) when delivered by a First Contact Physiotherapist (FCP) to people presenting with low back pain in primary care., Methods: Patients presenting with a new episode of low back pain underwent routine assessment and completion of a STarT Back questionnaire. Patients with low/medium scores were offered the SelfBACK App. A control population was provided by the MIDAS-GP study. Patient Experience, outcome measures, healthcare utilisation and retention were captured through the app and clinical systems (EMIS). Interviews with five FCPs explored the experiences of using the SelfSTart approach., Results: SelfSTarT was taken up by almost half (48%) of those to whom it was offered. Compared to MIDAS-GP, users were more likely to be younger, male, in work, and with higher health literacy. SelfSTarT users reported significant improved experiences relating to receiving an agreed care plan and receiving sufficient information. There were no significant differences in treatments offered. FCPs were positive about the app and felt it had value but wanted feedback on patient progress. They recognised that a digital solution would not be suitable for all., Conclusion: This approach offers an opportunity to empower and support self-management, using robustly evaluated digital technology., (© 2024 The Authors. Musculoskeletal Care published by John Wiley & Sons Ltd.)

Background: The OPTimisE intervention was developed to address uncertainty regarding the most effective physiotherapy treatment strategy for people with Lateral Elbow Tendinopathy (LET)., Objectives: To assess the feasibility of conducting a fully-powered randomised controlled trial (RCT) evaluating whether the OPTimisE intervention is superior to usual physiotherapy treatment for adults with LET., Design: A mixed-methods multi-centred, parallel pilot and feasibility RCT, conducted in three outpatient physiotherapy departments in the UK., Method: Patients were independently randomised 1:1 in mixed blocks, stratified by site, to the OPTimisE intervention or usual care. Outcomes were assessed using pre-defined feasibility progression criteria., Results: 50 patients were randomised (22 Female, 28 Male), mean age 48 years (range 27-75). Consent rate was 71% (50/70), fidelity to intervention 89% (16/18), attendance rate in the OPTimisE group 82% (55/67) vs 85% (56/66) in usual care, outcome measure completion 81% (39/48) at six-month follow-up. There were no related adverse events. Patients and physiotherapists reported that the OPTimisE intervention was acceptable but suggested improvements to the trial design. 49 patients were recruited from physiotherapy referrals vs one from primary care records. Outcome measure return rates were higher when completed online (74%) compared to postal questionnaire (50%). Exploratory analysis showed improvements in both groups over time., Conclusions: It is methodologically feasible to conduct a fully powered RCT comparing the clinical and cost-effectiveness of the OPTimisE intervention versus usual physiotherapy treatment. Considering the similar improvements observed in both groups, careful consideration is needed regarding the priority research question to be addressed in future research., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare. This paper presents independent research funded by the National Institute for Health and Care Research (NIHR) and Chartered Society of Physiotherapy Charitable Trust. The views expressed are those of the author(s) and not necessarily those of Chartered Society of Physiotherapy Charitable Trust, the NHS, the NIHR or the Department of Health and Social Care., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Mean arterial pressure and cardiac output provide insufficient guidance for the management of intraoperative hypotension (IOH). In silico models offer additional insights into acute changes in hemodynamic parameters that may be encountered during IOH. A computational model (CM) generated parameters quantifying ventricular-vascular coupling, and pressure-volume construct across levels of aortic compliance (C A ). We studied how a loss from normal-to-stiff C A impacts critical care metrics of hemodynamics during vascular occlusion. Pulse pressure (PP), end-systolic pressure (P es ), arterial compliance (Art-ca), arterial elastance (Art-ea), and dynamic arterial elastance (Eadyn), along mechanical efficiency (ME) were measured at five levels of C A . A loss in C A impacted all variables. During steady-state conditions, PP, P es , and stroke work increased significantly as C A decreased. Art-ca decreased and Art-ea increased similarly; Eadyn increased and ME decreased. During a decrease in preload across all C A levels, arterial dynamics measures remained linear. The CM demonstrated that a loss in C A impacts measures of arterial dynamics during steady-state and transient conditions and the model demonstrates that critical care metrics are sensitive to changes in C A . While Art-ca and Art-ea were sensitive to changes in preload, Eadyn did not change., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Endoplasmic reticulum (ER) retention of misfolded glycoproteins is mediated by the ER-localized eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). The enzyme recognizes a misfolded glycoprotein and flags it for ER retention by re-glucosylating one of its N-linked glycans. In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease, even if the mutant glycoprotein retains activity ("responsive mutant"). Using confocal laser scanning microscopy, we investigated here the subcellular localization of the human Trop-2-Q118E, E227K and L186P mutants, which cause gelatinous drop-like corneal dystrophy (GDLD). Compared with the wild-type Trop-2, which is correctly localized at the plasma membrane, these Trop-2 mutants are retained in the ER. We studied fluorescent chimeras of the Trop-2 Q118E, E227K and L186P mutants in mammalian cells harboring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 genes. The membrane localization of the Trop-2 Q118E, E227K and L186P mutants was successfully rescued in UGGT1 -/- cells. UGGT1 also efficiently reglucosylated Trop-2-Q118E-EYFP in cellula. The study supports the hypothesis that UGGT1 modulation would constitute a novel therapeutic strategy for the treatment of pathological conditions associated to misfolded membrane glycoproteins (whenever the mutation impairs but does not abrogate function), and it encourages the testing of modulators of ER glycoprotein folding quality control as broad-spectrum rescue-of-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants., (© 2024 The Authors. Traffic published by John Wiley & Sons Ltd.)

Current cosmological data exhibit discordance between indirect and some direct inferences of the present-day expansion rate H&#95;{0}. Early dark energy (EDE), which briefly increases the cosmic expansion rate prior to recombination, is a leading scenario for resolving this "Hubble tension" while preserving a good fit to cosmic microwave background (CMB) data. However, this comes at the cost of changes in parameters that affect structure formation in the late-time universe, including the spectral index of scalar perturbations n&#95;{s}. Here, we present the first constraints on axionlike EDE using data from the Lyman-α forest, i.e., absorption lines imprinted in background quasar spectra by neutral hydrogen gas along the line of sight. We consider two independent measurements of the one-dimensional Lyα forest flux power spectrum from the Sloan Digital Sky Survey (SDSS eBOSS) and from the MIKE/HIRES and X-Shooter spectrographs. We combine these with a baseline dataset comprised of Planck CMB data and baryon acoustic oscillation (BAO) measurements. Combining the eBOSS Lyα data with the CMB and BAO dataset reduces the 95% confidence level (C.L.) upper bound on the maximum fractional contribution of EDE to the cosmic energy budget f&#95;{EDE} from 0.07 to 0.03 and constrains H&#95;{0}=67.9&#95;{-0.4}^{+0.4}  km/s/Mpc (68% C.L.), with maximum a posteriori value H&#95;{0}=67.9  km/s/Mpc. Similar results are obtained for the MIKE/HIRES and X-Shooter Lyα data. Our Lyα-based EDE constraints yield H&#95;{0} values that are in >4σ tension with the SH0ES distance-ladder measurement and are driven by the preference of the Lyα forest data for n&#95;{s} values lower than those required by EDE cosmologies that fit Planck CMB data. Taken at face value, the Lyα forest severely constrains canonical EDE models that could resolve the Hubble tension.

Objective: The purpose of this study was to develop and externally validate multivariable prediction models for future pain intensity outcomes to inform targeted interventions for patients with neck or low back pain in primary care settings., Methods: Model development data were obtained from a group of 679 adults with neck or low back pain who consulted a participating United Kingdom general practice. Predictors included self-report items regarding pain severity and impact from the STarT MSK Tool. Pain intensity at 2 and 6 months was modeled separately for continuous and dichotomized outcomes using linear and logistic regression, respectively. External validation of all models was conducted in a separate group of 586 patients recruited from a similar population with patients' predictor information collected both at point of consultation and 2 to 4 weeks later using self-report questionnaires. Calibration and discrimination of the models were assessed separately using STarT MSK Tool data from both time points to assess differences in predictive performance., Results: Pain intensity and patients reporting their condition would last a long time contributed most to predictions of future pain intensity conditional on other variables. On external validation, models were reasonably well calibrated on average when using tool measurements taken 2 to 4 weeks after consultation (calibration slope = 0.848 [95% CI = 0.767 to 0.928] for 2-month pain intensity score), but performance was poor using point-of-consultation tool data (calibration slope for 2-month pain intensity score of 0.650 [95% CI = 0.549 to 0.750])., Conclusion: Model predictive accuracy was good when predictors were measured 2 to 4 weeks after primary care consultation, but poor when measured at the point of consultation. Future research will explore whether additional, nonmodifiable predictors improve point-of-consultation predictive performance., Impact: External validation demonstrated that these individualized prediction models were not sufficiently accurate to recommend their use in clinical practice. Further research is required to improve performance through inclusion of additional nonmodifiable risk factors., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Physical Therapy Association.)

Misfolded glycoprotein recognition and endoplasmic reticulum (ER) retention are mediated by the ER glycoprotein folding quality control (ERQC) checkpoint enzyme, UDP-glucose glycoprotein glucosyltransferase (UGGT). UGGT modulation is a promising strategy for broad-spectrum antivirals, rescue-of-secretion therapy in rare disease caused by responsive mutations in glycoprotein genes, and many cancers, but to date no selective UGGT inhibitors are known. The small molecule 5-[(morpholin-4-yl)methyl]quinolin-8-ol (5M-8OH-Q) binds a Ct UGGT GT24 "WY" conserved surface motif conserved across UGGTs but not present in other GT24 family glycosyltransferases. 5M-8OH-Q has a 47 μM binding affinity for Ct UGGT GT24 in vitro as measured by ligand-enhanced fluorescence. In cellula , 5M-8OH-Q inhibits both human UGGT isoforms at concentrations higher than 750 μM. 5M-8OH-Q binding to Ct UGGT GT24 appears to be mutually exclusive to M5-9 glycan binding in an in vitro competition experiment. A medicinal program based on 5M-8OH-Q will yield the next generation of UGGT inhibitors., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)

Background: Patient Reported Outcome Measures (PROMs) evaluate health status from a patient perspective. They can be used to support care at a patient level but also collectively to review quality of care across care providers. Vast amounts of patients with musculoskeletal (MSK) conditions present to General Practice (GP) primary care practitioners each year. Variation in patient outcomes in this setting however has not been reported., Objective: To identify variation in patient outcomes measured using the musculoskeletal health questionnaire (MSK-HQ) PROM for adults presenting to 20 GP practices in the UK with MSK conditions., Methods: A secondary analysis of the STarT MSK cluster randomised controlled trial dataset. A standardised case-mix adjustment model, adjusting for condition complexity co-variates, was used to calculate predicted 6-month follow-up MSK-HQ scores, and used to compare adjusted and un-adjusted health gain (n = 868). Patient MSK-HQ change outcomes were aggregated to practice level and boxplots used to display outlier GP practices for un-adjusted and adjusted outcomes., Results: Substantial variation in patient outcomes was seen across the 20 practices, even after case-mix adjustment, with mean change in MSK-HQ scores ranging from 6 to 12 points. Boxplots displaying un-adjusted outcomes showed one negative GP practice outlier and two positive outliers. However, the boxplots displaying case-mix adjusted outcomes showed no negative outliers, with two practices remaining as positive outliers, and one practice additionally becoming a positive outlier., Conclusion: This study showed a two-fold GP practice variation in patient outcomes measured using the MSK-HQ PROM. To our knowledge it is the first study to demonstrate that (a) a standardised case-mix adjustment method can be used to fairly compare patient health outcome variation in GP care, and (b) that case-mix adjustment changes benchmarking findings with regards to provider performance and outlier identification. This has important implications for identifying best practice exemplars and thereby helping to improve the quality of MSK primary care in the future., (© 2023 The Authors. Musculoskeletal Care published by John Wiley & Sons Ltd.)

Agile rf sources are a common requirement for control systems in quantum science and technology platforms. The direct digital synthesizer (DDS) often fills this role by allowing programmable control of the rf signals. Due to limitations of the DDS architecture, implementing an agile rf source requires rapid and precisely-timed programming of discrete updates that restrict the source's agility. Here, we describe a microcontroller-based interface that exploits the DDS's internal linear sweep accumulator to perform both sequential linear sweeps and standard discrete updates at the ∼10μs scale. This allows updates to the swept parameter as fast as every 8 ns with greatly reduced communication and memory overhead. We demonstrate the utility of this system by using it as the reference of an optical phase-locked loop to implement rapid, adjustable laser frequency sweeps in a Rydberg electromagnetically induced transparency spectroscopy measurement., (© 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).)

Objectives: To explore the lived experience of people with lateral elbow tendinopathy (LET) and its impact on everyday life., Design: Qualitative semi-structured interviews, analysed using thematic analysis., Setting: Conducted as part of the mixed-methods OPTimisE pilot and feasibility randomised controlled trial of outpatient physiotherapy patients in the UK., Participants: 17 participants with LET, purposively sampled from the trial to provide representativeness based on age, sex, ethnicity, deprivation index and treatment allocation., Results: Four themes were identified from the participants' responses: (1) cause of onset-typically symptoms were attributed to: sudden changes in activity, repetitive work or compensating for other musculoskeletal conditions; (2) impact on everyday life-which included substantial impacts on quality-of-life, particularly due to pain disturbing sleep and difficulties performing daily tasks (related to work and hobbies) due to pain, although most reported being able to persevere with work; (3) self-help and understanding of the condition-with uncertainty about the appropriateness and potential harm of online advice and confusion from the diagnostic term 'Tennis Elbow' that non-sporting individuals struggled to relate to; (4) healthcare experiences-the treatments received were highly variable and often perceived as ineffectual., Conclusions: For the first time, the lived experience of people from a range of backgrounds suffering from LET has been explored. Findings suggest that people frequently related the cause to a specific activity. They reported substantial impacts on daily tasks, sleep, work and hobbies. People also reported hesitancy to trust online information without formal healthcare advice, were confused by the common label of 'Tennis Elbow', and perceived the wide array of healthcare treatment options they had received to offer false hope and be largely ineffective. This study provides stimulus for clinicians to consider the advice and treatment provided, and whether the messages conveyed reflect the favourable natural history of the condition., Trial Registration Number: ISRCTN64444585., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Musculoskeletal disorders (MSDs) are a common reason for seeking primary health care. The STarT Musculoskeletal (MSK) tool is designed to stratify patients suffering from MSDs to risk groups, based on prognostic factors., Aim: The aim was to translate and cross-culturally adapt the STarT MSK tool in a Swedish primary health care context through testing of reliability and construct validity., Methods: We included consecutive patients with MSDs seeking primary care (n = 99). The STarT MSK was translated using international recommendations. Construct validity was investigated by correlation analysis (Spearmans Rho) with the following reference instruments: the Örebro Musculoskeletal Pain Questionnaire (ÖMPQ), the EuroQol 5-dimension (EQ-5D) and the Musculoskeletal Health Questionnaire (MSKHQ). Reliability was tested using test-retest (Intra Class Correlation, ICC 2.1 ) (n = 31). Known-groups validity was calculated with a difference of 10% between risk groups based on how the participants had answered., Results: The STarT MSK was successfully translated into Swedish. The participants were grouped into low risk (n = 28), medium risk (n = 60) and high risk (n = 11). The construct validity showed a moderate to high correlation with the ÖMPQ (r = .61), EQ-5D (r = .59) and MSK-HQ (r = .56). All separate items except item 2 and 9 correlated according to predefined hypotheses. Test-retest demonstrated an excellent reliability for the total score (ICC 2.1 0.85) (n = 31). The STarT MSK tool was able to differentiate by 10% between the risk groups, based on how the participants had answered., Conclusion: The STarT MSK has been successfully translated and adapted into Swedish and shows acceptable measurement properties regarding test-retest reliability and aspects of validity and seems to be able to discriminate between the proposed risk groups. The tool can therefore be useful in a Swedish primary health care context. A future study needs to determine the tools predictive validity and to investigate if stratification to risk groups leads to a faster recovery and to lower health care costs., (© 2023. The Author(s).)

Background: Video and computer games are popular activities, with 72% of adolescents aged 13 to 17 years reporting video game use on either a computer, game console, or portable device. Despite high levels of video and computer game use in adolescence, relatively little scientific literature exists examining the association and effects of video and computer games on adolescents., Objective: The objective of this study was to examine the prevalence of video and computer game use among US adolescents and rates of positive screens for obesity, diabetes, high blood pressure (BP), and high cholesterol., Methods: A secondary data analysis was conducted using the National Longitudinal Study of Adolescent to Adult Health (Add Health) data, including adolescents aged 12 to 19 years between 1994 and 2018., Results: Respondents (n=4190) who played the most video and computer games had a significantly (P=.02) higher BMI and were more likely to self-report having at least one of the evaluated metabolic disorders: obesity (BMI >30 kg/m 2 ), diabetes, high BP (BP >140/90), and high cholesterol (>240). With increased video or computer game use, there was a statistically significant increase in high BP rates in each quartile, with those with more frequent use also having higher rates of high BP. A similar trend was observed for diabetes, though the association did not reach statistical significance. No significant association was observed between video or computer game use and diagnoses of dyslipidemia, eating disorders, or depression., Conclusions: Frequency of video and computer game use is associated with obesity, diabetes, high BP, and high cholesterol in adolescents aged 12 to 19 years. Adolescents who play the most video and computer games have a significantly higher BMI. They are more likely to have at least one of the evaluated metabolic disorders: diabetes, high BP, or high cholesterol. Public health interventions designed to target modifiable disease states through health promotion and self-management may support the health of adolescents aged 12 to 19 years. Video and computer games can integrate health promotion interventions in gameplay. This is an important area for future research as video and computer games are integrated into the lives of adolescents., (©Stephanie R Lebby, Sangeetha Shyam, Amutha Ramadas, Andrew R Bohm, Julia C Hill, Karen L Fortuna, Stephanie R Zoltick. Originally published in JMIR Pediatrics and Parenting (https://pediatrics.jmir.org), 06.07.2023.)

We present measurements of the cross section and double-helicity asymmetry A&#95;{LL} of direct-photon production in p[over →]+p[over →] collisions at sqrt[s]=510  GeV. The measurements have been performed at midrapidity (|η|<0.25) with the PHENIX detector at the Relativistic Heavy Ion Collider. At relativistic energies, direct photons are dominantly produced from the initial quark-gluon hard scattering and do not interact via the strong force at leading order. Therefore, at sqrt[s]=510  GeV, where leading-order-effects dominate, these measurements provide clean and direct access to the gluon helicity in the polarized proton in the gluon-momentum-fraction range 0.02

Objectives: The aim of this study was to describe and compare health economic outcomes [health-care utilization and costs, work outcomes, and health-related quality of life (EQ-5D-5L)] in patients classified into different levels-of-risk subgroups by the Keele STarT MSK Tool., Methods: Data on health-care utilization, costs and EQ-5D-5L were collected from a health-care perspective within a primary care prospective observational cohort study. Patients presenting with one (or more) of the five most common musculoskeletal pain presentations were included: back, neck, shoulder, knee or multi-site pain. Participants at low, medium and high risk of persistent disabling pain were compared in relation to mean health-care utilization and costs, health-related quality of life, and employment status. Regression analysis was used to estimate costs., Results: Over 6 months, the mean (s.d.) total health-care (National Health Service and private) costs associated with the low, medium, and high-risk subgroups were £132.92 (167.88), £279.32 (462.98) and £476.07 (716.44), respectively. Mean health-related quality of life over the 6-month period was lower and more people changed their employment status in the high-risk subgroup compared with the medium- and low-risk subgroups., Conclusions: This study demonstrates that subgroups of people with different levels of risk for poor musculoskeletal pain outcomes also have different levels of health-care utilization, health-care costs, health-related quality of life, and work outcomes. The findings show that the STarT MSK Tool not only identifies those at risk of a poorer outcome, but also those who will have more health-care visits and incur higher costs., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Endoplasmic reticulum (ER) retention of mis-folded glycoproteins is mediated by the ERlocalised eukaryotic glycoprotein secretion checkpoint, UDP-glucose glycoprotein glucosyl-transferase (UGGT). The enzyme recognises a mis-folded glycoprotein and flags it for ER retention by reglucosylating one of its N-linked glycans. In the background of a congenital mutation in a secreted glycoprotein gene, UGGT-mediated ER retention can cause rare disease even if the mutant glycoprotein retains activity ("responsive mutant"). Here, we investigated the subcellular localisation of the human Trop-2 Q118E variant, which causes gelatinous droplike corneal dystrophy (GDLD). Compared with the wild type Trop-2, which is correctly localised at the plasma membrane, the Trop-2-Q118E variant is found to be heavily retained in the ER. Using Trop-2-Q118E, we tested UGGT modulation as a rescue-of-secretion therapeutic strategy for congenital rare disease caused by responsive mutations in genes encoding secreted glycoproteins. We investigated secretion of a EYFP-fusion of Trop-2-Q118E by confocal laser scanning microscopy. As a limiting case of UGGT inhibition, mammalian cells harbouring CRISPR/Cas9-mediated inhibition of the UGGT1 and/or UGGT2 gene expressions were used. The membrane localisation of the Trop-2-Q118E-EYFP mutant was successfully rescued in UGGT1 -/- and UGGT1/2 -/- cells. UGGT1 also efficiently reglucosylated Trop-2-Q118E-EYFP in cellula . The study supports the hypothesis that UGGT1 modulation constitutes a novel therapeutic strategy for the treatment of Trop-2-Q118E associated GDLD, and it encourages the testing of modulators of ER glycoprotein folding Quality Control (ERQC) as broad-spectrum rescueof-secretion drugs in rare diseases caused by responsive secreted glycoprotein mutants.

Background: With respect to survivorship following total knee arthroplasty (TKA), joint registries consistently demonstrate higher revision rates for both genders in those aged less than 55 years. The present study analyzed the survivorship of 500 cementless TKAs performed in this age group in a high-volume primary joint unit where cementless TKA has traditionally been used for the majority of patients., Methods: This was a retrospective review of 500 consecutive TKAs performed in patients aged less than 55 years between March 1994 and April 2017. The primary outcome measures for the study were survivorship and all-cause revisions. Secondary outcome measures included nonrevision procedures, clinical, functional, and radiological outcomes., Results: An all-cause survival rate of 98.4% and an aseptic survival rate of 99.2% at a median time of 10.7 years (interquartile range 7.3-14.9, range 0.2-27.7) were found. Four patents were revised for infection, 2 for stiffness, 1 for aseptic loosening of the tibial component, and 1 for a patella that was resurfaced for anterior knee pain. Thirty four patients (6.8%) had a nonrevision procedure with manipulation under anesthetic accounting for 27. On a multivariate analysis, preoperative range of motion and female gender were negatively associated with postoperative range of motion (P < .001 and P = .003, respectively). Sixty seven patients (17.3%) had radioluscent lines and on a multivariate analysis, there were no significant predictors of radiolucent lines., Conclusion: Cementless TKA in the young patient can achieve excellent clinical and functional outcomes. At a median of 10.7 years, aseptic revision rates are exceptionally low at 0.8% for the entire cohort., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Musculoskeletal disorders represented 149 million years lived with disability world-wide in 2019 and are the main cause of years lived with disability worldwide. Current treatment recommendations are based on "one-size fits all" principle, which does not take into account the large degree of biopsychosocial heterogeneity in this group of patients. To compensate for this, we developed a stratified care computerized clinical decision support system for general practice based on patient biopsychosocial phenotypes; furthermore, we added personalized treatment recommendations based on specific patient factors to the system. In this study protocol, we describe the randomized controlled trial for evaluating the effectiveness of computerized clinical decision support system for stratified care for patients with common musculoskeletal pain complaints in general practice. The aim of this study is to test the effect of a computerized clinical decision support system for stratified care in general practice on subjective patient outcome variables compared to current care., Methods: We will perform a cluster-randomized controlled trial with 44 general practitioners including 748 patients seeking their general practitioner due to pain in the neck, back, shoulder, hip, knee, or multisite. The intervention group will use the computerized clinical decision support system, while the control group will provide current care for their patients. The primary outcomes assessed at 3 months are global perceived effect and clinically important improvement in function measured by the Patient-Specific Function Scale (PSFS), while secondary outcomes include change in pain intensity measured by the Numeric Rating Scale (0-10), health-related quality of life (EQ-5D), general musculoskeletal health (MSK-HQ), number of treatments, use of painkillers, sick-leave grading and duration, referral to secondary care, and use of imaging., Discussion: The use of biopsychosocial profile to stratify patients and implement it in a computerized clinical decision support system for general practitioners is a novel method of providing decision support for this patient group. The study aim to recruit patients from May 2022 to March 2023, and the first results from the study will be available late 2023., Trial Registration: The trial is registered in ISRCTN 11th of May 2022: 14,067,965., (© 2023. The Author(s).)

Complex astrophysical systems often exhibit low-scatter relations between observable properties (e.g., luminosity, velocity dispersion, oscillation period). These scaling relations illuminate the underlying physics, and can provide observational tools for estimating masses and distances. Machine learning can provide a fast and systematic way to search for new scaling relations (or for simple extensions to existing relations) in abstract high-dimensional parameter spaces. We use a machine learning tool called symbolic regression (SR), which models patterns in a dataset in the form of analytic equations. We focus on the Sunyaev-Zeldovich flux-cluster mass relation ( Y SZ - M ), the scatter in which affects inference of cosmological parameters from cluster abundance data. Using SR on the data from the IllustrisTNG hydrodynamical simulation, we find a new proxy for cluster mass which combines Y SZ and concentration of ionized gas ( c gas ): M ∝ Y conc 3/5 ≡ Y SZ 3/5 (1 - A c gas ). Y conc reduces the scatter in the predicted M by ∼20 - 30% for large clusters ( M ≳ 10 14 h -1 M ⊙ ), as compared to using just Y SZ . We show that the dependence on c gas is linked to cores of clusters exhibiting larger scatter than their outskirts. Finally, we test Y conc on clusters from CAMELS simulations and show that Y conc is robust against variations in cosmology, subgrid physics, and cosmic variance. Our results and methodology can be useful for accurate multiwavelength cluster mass estimation from upcoming CMB and X-ray surveys like ACT, SO, eROSITA and CMB-S4.

Introduction: High quality data on service performance is essential in healthcare to evidence efficacy, efficiency, and value. There remains a paucity of publicly reported data in community and primary care musculoskeletal (MSK) services. There is also a lack of guidance on which metrics MSK services should be collecting and reporting, and how this data could be used to directly improve patient outcomes, experiences, and value., Method: A narrative review of the evidence around benchmarking MSK services was undertaken with a focus on how to develop routine data collection within community/primary care settings, and how to develop benchmarking capabilities for the future, looking towards a national MSK audit. This evidence was triangulated with the findings from recent MSK data studies undertaken by the authors and emerging UK policy and guidance in this area., Recommendations: To enable MSK benchmarking services need to collect consistent, standardised outcomes and, therefore, we have developed a recommendation on a minimum MSK 'core outcome set' of Patient Reported Outcome Measures (PROMs) and Patient Reported Experience Measures (PREMs) (PROMs: MSK-HQ, NPRS, WPAI; PREMs: National MSK PREM). In addition, we make recommendations on the use of a standardised evidence-based method for case-mix adjustment and outlier identification (using the following baseline demographics and clinical factors; age, sex, ethnicity, pain site, comorbidities, duration of symptoms, previous surgery, previous pain episodes), alongside considerations on how this data should be integrated and reported within NHS systems., Conclusions: Capturing high quality MSK data in a standardised, consistent, and sustainable way is a significant challenge. Policy holders, commissioners, managers, and clinicians need to be realistic with expectations, and take time to explore barriers to implementation including, funding, digital infrastructure/intra-operability, data sharing/governance, digital literacy, and local/national leadership. Next steps include developing a national MSK audit programme to provide a benchmarking model to support continuous improvements in care quality for patients living with MSK conditions., (© 2022 John Wiley & Sons Ltd.)

Background: The STarT MSK cluster randomised controlled trial (RCT) investigated the clinical- and cost-effectiveness of risk-based stratified primary care versus usual care for patients with back, neck, shoulder, knee or multi-site pain. Trial quantitative results showed risk-based stratified care was not superior to usual care for patients' clinical outcomes, but the intervention led to some changes in GP clinical decision-making. This paper reports a linked qualitative study exploring how risk-based stratified care was perceived and used in the trial, from the perspectives of clinicians and patients., Methods: Semi-structured interviews were conducted with 27 patients, and focus groups and interviews with 20 clinicians (GPs and physiotherapists) in the intervention arm of the trial. Data were analysed thematically and findings explored using Normalisation Process Theory (NPT) and the COM-B model., Main Findings: Risk-based stratified care (subgrouping and matching treatments) was found to have 'coherence' (i.e. made sense) to several clinicians and patients, in that it was well-integrated in practice, and supported clinical decision-making. However, for some GPs stratified care was less 'meaningful', as the risk-stratification tool did not fit with usual ways of consulting and added to already time-pressured consultations. GPs reported giving more patients written information/advice due to easier access to electronic information leaflets through the trial template and were motivated to refer patients to physiotherapy as they believed the trial resulted in faster physiotherapy access (although this was not the case). Patients and clinicians reported that risk-based stratified care influenced conversations in the consultation, prompting greater attention to psychosocial factors, and facilitating negotiation of treatment options. Physiotherapists saw benefits in receiving information about patients' risk subgroup on referral forms., Conclusion: These findings provide context for interpreting some of the trial outcomes, particularly in relation to changes in clinical decision-making when risk-based stratified care was used. Findings also indicate potential reasons for lack of GP engagement with risk-based stratified care. Positive outcomes were identified that were not captured in the quantitative data, specifically that risk-based stratified care positively influenced some GP-patient conversations and facilitated negotiation of treatment options., Trial Registration: ISRCTN15366334 (26/04/2016)., (© 2022. The Author(s).)

Pericytes are essential components of small blood vessels and are found in human aortic vasa vasorum. Prior work uncovered lower vasa vasorum density and decreased levels of pro-angiogenic growth factors in adventitial specimens of human ascending thoracic aortic aneurysm. We hypothesized that adventitial extracellular matrix (ECM) from normal aorta promotes pericyte function by increasing pericyte contractile function through mechanisms deficient in ECM derived from aneurysmal aortic adventitia. ECM biomaterials were prepared as lyophilized particulates from decellularized adventitial specimens of human and porcine aorta. Immortalized human aortic adventitia-derived pericytes were cultured within Type I collagen gels in the presence or absence of human or porcine adventitial ECMs. Cell contractility index was quantified by measuring the gel area immediately following gelation and after 48 h of culture. Normal human and porcine adventitial ECM increased contractility of pericytes when compared with pericytes cultured in absence of adventitial ECM. In contrast, aneurysm-derived human adventitial ECM failed to promote pericyte contractility. Pharmacological inhibition of TGFβR1 and antibody blockade of α 2 β 1 integrin independently decreased porcine adventitial ECM-induced pericyte contractility. By increasing pericyte contractility, adventitial ECM may improve microvascular function and thus represents a candidate biomaterial for less invasive and preventative treatment of human ascending aortic disease., (© 2022 Wiley Periodicals LLC.)

High-power, narrow-linewidth light sources in the visible and UV spectra are in growing demand, particularly as quantum information and sensing research proliferates. Vertical external-cavity surface-emitting lasers (VECSELs) with intra-cavity frequency conversion are emerging as an attractive platform to fill these needs. Using such a device, we demonstrate 3.5 MHz full-width half-maximum Rydberg-state spectroscopy via electromagnetically induced transparency (EIT). The laser's 690 mW of output power at a wavelength of 475 nm enables large Rabi frequencies and strong signal-to-noise ratio in shorter measurement times. In addition, we characterize the frequency stability of the VECSEL using the delayed self-heterodyne technique and direct comparison with a commercial external-cavity diode laser (ECDL). We measure the pre-doubled light's Lorentzian linewidth to be 2π × 5.3(2) kHz, and the total linewidth to be 2π × 23(2) kHz. These measurements provide evidence that intra-cavity frequency-doubled VECSELs can perform precision spectroscopy at and below the MHz level, and are a promising tool for contemporary, and future, quantum technologies.

Objective: Previous research has found that college students experience both positive and negative outcomes after a hookup. The present study examined the role that hookup motives and sex play in determining the overall positivity and negativity of the experience. Participants: College students ( N  = 156) completed an online survey about their most recent hookup. Method: The survey assessed hookup motivations and outcomes. Results: Lower coping motives and higher social-sexual, relationship-seeking, and enhancement motives predicted more positive outcomes. Higher coping motives and lower social-sexual, conformity, and enhancement motives predicted more negative outcomes. For men, positive outcomes were correlated with weaker enhancement motives, while negative outcomes were correlated with more enhancement motives. For women, higher levels of positive outcomes were positively correlated with enhancement, social-sexual, and relationship-seeking motives, while negative outcomes were negatively correlated with social-sexual, enhancement, and coping motives. Conclusions: The results of this study have implications for risk prevention and future research.

Objectives: We hypothesized that expression and activity of nitric oxide synthase-3 enzyme (Nos3) in bicuspid aortic valve (BAV) aortopathy are related to tissue layer and Nos3 genotype., Methods: Gene expression of Nos3 and platelet and endothelial cell adhesion molecule-1 (Pecam1) and NOS activity were measured in intima-containing media and adventitial specimens of ascending aortic tissue. The presence of 2 Nos3 single-nucleotide polymorphisms (SNPs; -786T/C and 894G/T) was determined for non-aneurysmal (NA) and aneurysmal patients with BAV (n = 40, 89, respectively); patients with tricuspid aortic valve (TAV) and aneurysm (n = 151); and NA patients with TAV (n = 100)., Results: Elevated Nos3 relative to Pecam1 and reduced Pecam1 relative to a housekeeping gene were observed within intima-containing aortic specimens from BAV patients when compared with TAV patients. Lower Nos3 in the adventitia of aneurysmal specimens was noted when compared with specimens of NA aorta, independent of valve morphology. NOS activity was similar among cohorts in media/intima and decreased in the diseased adventitia, relative to control patients. Aneurysmal BAV patients exhibited an under-representation of the wild-type genotype for -786 SNP. No differences in genotype distribution were noted for 894 SNP. Primary intimal endothelial cells from patients with at least 1 C allele at -786 SNP exhibited lower Nos3 when compared with wild-type cells., Conclusions: These findings of differential Nos3 in media/intima versus adventitia depending on valve morphology or aneurysm reveal new information regarding aneurysmal pathophysiology and support our ongoing assertion that there are distinct mechanisms giving rise to ascending aortopathy in BAV and TAV patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Aims: Traditional methods of determining femoral head centre (FHC) during total hip arthroplasty (THA) rely on measuring the distance from a fixed point on the femur or using a calliper. The aim of this experiment was to investigate how accurately a simple circular ring could locate FHC., Methods: 144 consecutively available femoral heads (FHs) were collected from patients undergoing THA. Each FH was orientated and mounted on a Sawbone, to create a model of its position on a proximal femur. The ring was applied to the posterior aspect of the FH and a head-centre pin (HCP) was then drilled into the FH and the ring removed, leaving the HCP in place.Each FH was then photographed normal to the axis of the HCP. A MATLAB analysis program then assessed the accuracy of the ring in locating FHC., Results: Mean location accuracy for FHC was 1.77 (range 0.07-5.83) mm with 97.2% within 4 mm and all but 1 within 5 mm., Conclusions: This ring device located FHC to within 4 mm in 97% of a series of osteoarthritic FHs. This indicates that the posterior aspect of the FH maintains its sphericity late into the osteoarthritic process. Having a simple FHC location device during THA would be of value to control leg length and offset when using the posterior approach.

Background: Physiotherapy is recommended for people with tennis elbow, but whilst a wide array of treatments is available, the optimal approach remains uncertain. We have therefore recently developed an optimised physiotherapy treatment package for tennis elbow based on a synthesis of the evidence, patient input and clinical consensus. It consists of detailed advice and education, a structured progressive exercise programme and provision of a counter-force elbow brace. Here, we report the protocol for our multicentre pilot and feasibility randomised controlled trial (RCT) designed to (a) examine the feasibility of our optimised physiotherapy treatment package and (b) to pilot trial processes for a future fully powered RCT to test clinical and cost-effectiveness compared with usual physiotherapy treatment., Methods: A multicentre pilot and feasibility RCT will be conducted across three sites in England, recruiting up to 50 patients (or for a maximum of 12 months). Participants with tennis elbow, identified from physiotherapy clinic waiting lists and general practice surgeries, will be randomly allocated to receive the optimised physiotherapy treatment package or usual physiotherapy care. Analysis will focus on feasibility measures including consent rate, intervention fidelity, follow-up rate and outcome completion rate. A nested qualitative study will explore the acceptability of the study processes and patient and physiotherapist experiences of the new optimised intervention., Discussion: This study will determine the feasibility of a new optimised physiotherapy treatment package for people with tennis elbow and pilot the processes for a future fully powered RCT. In the longer term, this treatment package may provide superior clinical outcomes for patients, in terms of pain and quality of life, and be more cost-effective for the health service., Trial Registration: Registered with the ISRCTN database 19/7/2021, https://www.isrctn.com/ISRCTN64444585., (© 2022. The Author(s).)

Background: Low back pain (LBP) is one of the most common reasons for primary care visits and is the leading contributor to years lived with disability worldwide. The purpose of this study was to understand the perspectives of patients and primary care team members related to their experiences with a new physiotherapist-led primary care model for LBP., Methods: We conducted an interpretive description qualitative study. Data were collected using a combination of semi-structured interviews and focus group discussions and analyzed using thematic analysis. Participants included adults (> 18 years of age) with LBP and primary care team members who participated in a physiotherapist-led primary care model for LBP in Kingston, Ontario, Canada., Results: We conducted 18 semi-structured interviews with patients with LBP (10 women; median age of 52) as well as three focus group discussions with a total of 20 primary care team members representing three teams. Four themes (each with sub-themes) were constructed: 1) enhanced primary care delivery for LBP (improved access and engagement in physiotherapy care, improved communication and care integration between the physiotherapist and primary care team, less inappropriate use of healthcare resources); 2) positive patient experiences and perceived outcomes with the new model of care (physiotherapist built therapeutic alliance, physiotherapist provided comprehensive care, improved confidence in managing LBP, decreased impact of pain on daily life); 3) positive primary care team experiences with the new model of care (physiotherapist fit well within the primary care team, physiotherapist provided expertise on LBP for the primary care team, satisfaction in being able to offer a needed service for patients); and 4) challenges implementing the new model of care (challenges with prompt access to physiotherapy care, challenges making the physiotherapist the first contact for LBP, and opportunities to optimize communication between the physiotherapist and primary care team)., Conclusions: A new physiotherapist-led primary care model for LBP was described by patients and primary care team members as contributing to positive experiences and perceived outcomes for patients, primary care team members, and potentially the health system more broadly. Results suggest that this model of care may be a viable approach to support integrated and guideline adherent management of LBP in primary care settings., (© 2022. The Author(s).)

Background: Risk-based stratified care shows clinical effectiveness and cost-effectiveness versus usual primary care for non-specific low back pain but is untested for other common musculoskeletal disorders. We aimed to test the clinical effectiveness and cost-effectiveness of point-of-care risk stratification (using Keele's STarT MSK Tool and risk-matched treatments) versus usual care for the five most common musculoskeletal presentations (back, neck, knee, shoulder, and multi-site pain)., Methods: In this cluster-randomised, controlled trial in UK primary care with embedded qualitative and health economic studies we recruited patients from 24 general practices in the West Midlands region of England. Eligible patients were those aged 18 years or older whose general practitioner (GP) confirmed a consultation for a musculoskeletal presentation. General practices that consented to participate via a representative of the cluster were randomly assigned (1:1) to intervention or usual care, using stratified block randomisation. Researchers involved in data collection, outcome data entry, and statistical analysis were masked at both the cluster and individual participant level. Participating patients were told the study was examining GP treatment of common aches and pains and were not aware they were in a randomised trial. GPs in practices allocated to the intervention group were supported to deliver risk-based stratified care using a bespoke computer-based template, including the risk-stratification tool, and risk-matched treatment options for patients at low, medium, or high risk of poor disability or pain outcomes. There were 15 risk-matched treatment options. In the usual care group, patients with musculoskeletal pain consulting their GP received treatment as usual, typically including advice and education, medication, referral for investigations or tests, or referral to other services. The primary outcome was time-averaged pain intensity over 6 months. All analyses were done by intention to treat. The trial is registered with ISRCTN, ISRCTN15366334., Results: Between May 1, 2018, and April 30, 2019, 104 GPs from 24 practices (12 per study group) identified 2494 patients with musculoskeletal pain. 1211 (49%) participants consented to questionnaires (534 in the intervention group and 677 in the usual care group), with 1070 (88%) completing the follow-up questionnaire at 6 months. We found no significant difference in time-averaged pain intensity (mean(SD) mean 4·4 [SD 2·3] in the intervention group vs 4·6 [2·5] in the control group; adjusted mean difference -0·16, 95% CI -0·65 to 0·34) or in standardised function score (mean -0·06 [SD 0·94] in the intervention group vs 0·05 [1·04]; adjusted mean difference -0·07, 95% CI -0·22 to 0·08). No serious adverse events or adverse events were reported. Risk stratification received positive patient and clinician feedback., Interpretation: Risk stratification for patients in primary care with common musculoskeletal presentations did not lead to significant improvements in pain or function, although some aspects of GP decision making were affected, and GP and patients had positive experiences. The costs of risk-based stratified care were similar to usual care, and such a strategy only offers marginal changes in cost-effectiveness outcomes. The clinical implications from this trial are largely inconclusive., Funding: National Institute for Health Research., Competing Interests: JCH, NEF, ML, KMD, JP, DvdW, CM, and EMH report grants from the National Institute for Health and Care Research. All other authors declare no competing interests. This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research scheme (grant number RP-PG-1211-20010); and Versus Arthritis through a Centre of Excellence grant (grant reference 20202). Nadine Foster is a NIHR Senior Investigator and was supported through an NIHR Research Professorship (NIHRRP-011-015). The views expressed in this publication are those of the authors and not necessarily those of the UK National Health Service, the NIHR, or the Department of Health and Social Care. Funders of the study had no role in the design of the study, data collection, analysis and interpretation of data, or in writing the manuscript., (© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)

Aims: Tranexamic acid (TXA) is now commonly used in major surgical operations including orthopaedics. The TRAC-24 randomized control trial (RCT) aimed to assess if an additional 24 hours of TXA postoperatively in primary total hip (THA) and total knee arthroplasty (TKA) reduced blood loss. Contrary to other orthopaedic studies to date, this trial included high-risk patients. This paper presents the results of a cost analysis undertaken alongside this RCT., Methods: TRAC-24 was a prospective RCT on patients undergoing TKA and THA. Three groups were included: Group 1 received 1 g intravenous (IV) TXA perioperatively and an additional 24-hour postoperative oral regime, Group 2 received only the perioperative dose, and Group 3 did not receive TXA. Cost analysis was performed out to day 90., Results: Group 1 was associated with the lowest mean total costs, followed by Group 2 and then Group 3. The differences between Groups 1 and 3 (-£797.77 (95% confidence interval -1,478.22 to -117.32) were statistically significant. Extended oral dosing reduced costs for patients undergoing THA but not TKA. The reduced costs in Groups 1 and 2 resulted from reduced length of stay, readmission rates, emergency department attendances, and blood transfusions., Conclusion: This study demonstrated significant cost savings when using TXA in primary THA or TKA. Extended oral dosing reduced costs further in THA but not TKA. Cite this article: Bone Jt Open  2022;3(7):536-542.

Background: The STarT-MSK-Tool is an adaptation of the well established STarT-Back-Tool, used to risk-stratify patients with a wider range of musculoskeletal presentations., Objective: To formally translate and cross-culturally adapt the Keele STarT-MSK risk stratification tool into German (STarT-MSKG) and to establish its reliability and validity., Methods: A formal, multi-step, forward and backward translation approach was used. To assess validity patients aged ≥18 years, with acute, subacute or chronic musculoskeletal presentations in the lumbar spine, hip, knee, shoulder, or neck were included. The prospective cohort was used with initial data collected electronically at the point-of-consultation. Retest and 6-month follow-up questionnaires were sent by email. Test-retest reliability, construct validity, discriminative ability, predictive ability and floor or ceiling effects were analysed using intraclass correlation coefficient, and comparisons with a reference standard (Orebro-Musculoskeletal-Pain-Questionnaire: OMPQ) using correlations, ROC-curves and regression models., Results: The participants' (n = 287) mean age was 47 (SD = 15.8) years, 51% were female, with 48.8% at low, 43.6% at medium, and 7.7% at high risk. With ICC = 0.75 (95% CI 0.69; 0.81) test-retest-reliability was good. Construct validity was good with correlations for the STarT-MSKG-Tool against the OMPQ-Tool of rs = 0.74 (95% CI 0.68, 0.79). The ability of the tool [comparison OMPQ] to predict 6-month pain and disability was acceptable with AUC = 0.77 (95% CI 0.71, 0.83) [OMPQ = 0.74] and 0.76 (95% CI 0.69, 0.82) [OMPQ = 0.72] respectively. However, the explained variance (linear/logistic regression) for predicting 6-month pain (21% [OMPQ = 17%]/logistic = 29%) and disability (linear = 20%:[OMPQ = 19%]/logistic = 26%), whilst being comparable to the existing OMPQ reference standard, fell short of the a priori target of ≥30%., Conclusions: The German version of the STarT-MSK-Tool is a valid instrument for use across multiple musculoskeletal conditions and is availabe for use in clinical practice. Comparison with the OMPQ suggests it is a good alternative., Competing Interests: The authors have declared that no competing interests exist.

Racial and language minority groups in the U.S. are at a higher risk for morbidity and mortality from colorectal cancer (CRC), partially due to lower screening rates. This is a retrospective cohort study comparing successful multi-target stool DNA test (mt-sDNA) test completion among patients with limited English proficiency (LEP) and English proficient (EP) patients, from 2015 to 2018. Patients with LEP were frequency matched to EP patients by age at a 3:1 ratio. The percentage of mt-sDNA tests without useful results was 53% among patients with LEP compared to 29% among EP patients (p < 0.0001). The median number of days from order placement to test completion was 62.5 among patients with LEP compared to 33 for EP patients (p = 0.003). This study demonstrates a significant disparity in CRC screening completion using the mt-sDNA test among populations with LEP, which may widen existing disparities in CRC mortality., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose Musculoskeletal (MSK) pain is a common cause of work absence. The recent SWAP (Study of Work And Pain) randomised controlled trial (RCT) found that a brief vocational advice service for primary care patients with MSK pain led to fewer days' work absence and provided good return-on-investment. The I-SWAP (Implementation of the Study of Work And Pain) initiative aimed to deliver an implementation test-bed of the SWAP vocational advice intervention with First Contact Practitioners (FCP). This entailed adapting the SWAP vocational advice training to fit the FCP role. This qualitative investigation explored the implementation potential of FCPs delivering vocational advice for patients with MSK pain. Methods Semi-structured interviews and focus groups were conducted with 10 FCPs and 5 GPs. Data were analysed thematically and findings explored using Normalisation Process Theory (NPT). Results I-SWAP achieved a degree of 'coherence' (i.e. made sense), with both FCPs and GPs feeling FCPs were well-placed to discuss work issues with these patients. However, for many of the FCPs, addressing or modifying psychosocial and occupational barriers to return-to-work was not considered feasible within FCP consultations, and improving physical function was prioritised. Concerns were also raised that employers would not act on FCPs' recommendations regarding return-to-work. Conclusion FCPs appear well-placed to discuss work issues with MSK patients, and signpost/refer to other services; however, because they often only see patients once they are less suited to deliver other aspects of vocational advice. Future research is needed to explore how best to provide vocational advice in primary care settings., (© 2021. The Author(s).)

Objectives: Stratified care using prognostic models to estimate the risk profiles of patients has been increasing. A refined version of the popular STarT Back tool, the Keele STarT MSK tool, is a newly developed model for matched treatment across a wide range of musculoskeletal pain presentations. The aim of this study was to translate and culturally adapt the Keele STarT MSK tool into Norwegian, examine its construct validity and assess the representativeness of the included sample., Methods: The Keele STarT MSK tool was formally translated into Norwegian following a multistep approach of forward and backward translation. A pre-final version was tested in 42 patients. Minor changes were implemented. To assess its construct validity, an online survey was conducted among workers aged 18-67 years who were on sick leave (>4 weeks) due to musculoskeletal disorders. Construct validity was evaluated in terms of convergent and discriminant validity using Pearson's correlation coefficient, and known-group validity by comparing risk subgroups as suggested by the COSMIN checklist. The representativeness of the sample was assessed by comparing demographic and sick leave information of participants to eligible non-participants (n=168,137)., Results: A representative sample of 549 workers participated in the validity assessment; 74 participants (13.5%) were categorised as low risk, 314 (57.2%) as medium risk and 161 (29.3%) as high risk. The construct validity was found sufficient, with 90.9% and 75.0% of the pre-defined hypotheses confirmed for convergent and discriminant validity, and known-group validity, respectively. Floor or ceiling effects were not found., Conclusions: The Keele STarT MSK tool was successfully translated into Norwegian. The construct validity of the tool was acceptable in a representative cohort of workers on sick leave as a result of musculoskeletal pain. However, the analyses raised concerns as to whether one of the questions captures the construct it is intended to measure., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Objectives: There are a wide range of physiotherapy treatment options for people with lateral elbow tendinopathy (LET); however, previous studies have reported inconsistent approaches to treatment and a lack of evidence demonstrating clinical effectiveness. This study aimed to combine the best available research evidence with stakeholder perspectives to develop key components of an optimised physiotherapist-led treatment protocol for testing in a future randomised controlled trial (RCT)., Design: Online consensus groups using nominal group technique (NGT), a systematic approach to building consensus using structured multistage meetings., Setting: UK National Health Service (NHS)., Participants: 10 physiotherapists with special interest in LET, 2 physiotherapy service managers and 3 patients who had experienced LET., Interventions: Two consensus groups were conducted; the first meeting focused on agreeing the types of interventions to be included in the optimised treatment protocol; the second meeting focused on specific details of intervention delivery. Participants were sent an evidence summary of available treatments for LET prior to the first meeting. All treatment options were discussed before anonymous voting and ranking of priority. Consensus for inclusion of each treatment option was set at ≥70% based on OMERACT guidelines. Options with 30%-69% agreement were discussed again, and a second vote was held, allowing for a change of opinion., Results: The optimised physiotherapist-led treatment package included: advice and education, exercise therapy and orthotics. Specific components for each of these interventions were also agreed such as: condition-specific advice, health-promotion advice, exercise types, exercise into 'acceptable' levels of pain, exercise dosage and type of orthoses. Other treatment options including electrotherapy, acupuncture and manual therapy were excluded., Conclusion: An optimised physiotherapist-led treatment protocol for people with LET was successfully developed using an online NGT consensus approach. This intervention is now ready for testing in a future pilot/feasibility RCT to contribute much needed evidence about the treatment of LET., Trial Registration Number: This is the pre-cursor to the OPTimisE Pilot and Feasibility Randomised Controlled Trial. Registration: https://www.isrctn.com/ISRCTN64444585., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objective: First Contact Physiotherapy (FCP) is a primary care model where expert musculoskeletal (MSK) physiotherapists undertake the first patient consultation, to enhance MSK-patient care and free-up GP capacity. The authors report the quantitative findings from the FCP National Evaluation (Phase 3) which evaluated the FCP model against success criteria., Design and Setting: A mixed-methods 24-month service evaluation involving 40 FCP sites and 240 FCPs across England., Methods: An online platform collected patient-reported experience and outcomes following the FCP consultation and at 1, 2 and 3-months follow-up. These included the Keele STarT MSK Tool, pain intensity (0-10 NRS scale), Musculoskeletal Health Questionnaire (MSK-HQ, range 0-56), and Friends-and-Family Test., Results: Over 13 months, 2825 patients were invited by email and 24% (n=680) completed their initial questionnaire. Their mean age was 56.2 (SD 14.9), 61% were female, ethnicity was 97% white, mean pain intensity was 6.1 (SD 2.13) and mean MSK-HQ score was 33.8 (SD 9.5). At 3-months follow-up (n=370) there was a 2.8 (CI 2.5 to 3.1) mean pain intensity reduction from baseline, a mean 7.1 (6.0 to 8.2) score improvement in MSK-HQ and 64% reporting overall improvement (much better/better) since seeing the FCP. One of the six success criteria was not met; 29% of those in employment reported receiving specific work advice from the FCP (target ≥75%)., Conclusion: Ahead of the planned scale-up of the FCP primary care model across the UK, this evaluation provides useful data on patients who access this service, their short-term clinical outcomes and whether key success criteria are being met., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)