Validation of a next generation sequencing method for adventitious virus detection: Demonstration of sensitivity in multiple cell lines.

In the past few years NGS has become the technology of choice to replace animal-based virus safety methods and this has been strengthened by the recent revision to the ICHQ5A virus safety chapter. Here we describe the validation of an NGS method using an agnostic analysis to detect and identify RNA virus and actively replicating DNA virus contaminants in cell banks. We report the results of the validation of each step in the sequencing process that established quality criteria to ensure consistent sequencing data. Furthermore, the validation of the analysis algorithm designed to identify virus specific sequences is described along with steps undertaken to ensure the integrity of the sequencing data from generation to analysis. Lastly, the validated sequencing and analysis systems were used to establish a limit of detection (LOD) for model viruses in cells that are commonly used in biomanufacturing. The LOD from these studies ranged from 1E+03 to 1E+04 genome copies and were dependent on the virus type with little variability between the different cell types. Thus, the validation of the NGS method for adventitious agent testing and the establishment of a general LOD for cell-based samples provides a suitable alternative to traditional virus detection methods.

End of life decision making when home mechanical ventilation is used to sustain breathing in Motor Neurone Disease: patient and family perspectives.

BACKGROUND: Motor Neurone Disease (MND) leads to muscle weakening, affecting movement, speech, and breathing. Home mechanical ventilation, particularly non-invasive ventilation (NIV), is used to alleviate symptoms and support breathing in people living with MND. While home mechanical ventilation can alleviate symptoms and improve survival, it does not slow the progression of MND. This study addresses gaps in understanding end-of-life decision-making in those dependent on home mechanical ventilation, considering the perspectives of patients, family members, and bereaved families. METHODS: A UK-wide qualitative study using flexible interviews to explore the experiences of people living with MND (n = 16), their family members (n = 10), and bereaved family members (n = 36) about the use of home mechanical ventilation at the end of life. RESULTS: Some participants expressed a reluctance to discuss end-of-life decisions, often framed as a desire to "live for the day" due to the considerable uncertainty faced by those with MND. Participants who avoided end-of-life discussions often engaged in 'selective decision-making' related to personal planning, involving practical and emotional preparations. Many faced challenges in hypothesising about future decisions given the unpredictability of the disease, opting to make 'timely decisions' as and when needed. For those who became dependent on ventilation and did not want to discuss end of life, decisions were often 'defaulted' to others, especially once capacity was lost. 'Proactive decisions', including advance care planning and withdrawal of treatment, were found to empower some patients, providing a sense of control over the timing of their death. A significant proportion lacked a clear understanding of the dying process and available options. CONCLUSIONS: The study highlights the complexity and evolution of decision-making, often influenced by the dynamic and uncertain nature of MND. The study emphasises the need for a nuanced understanding of decision-making in the context of MND.

Application of immersive virtual reality mirror therapy for upper limb rehabilitation after stroke: a scoping review.

Mirror therapy is a commonly used rehabilitation intervention in post stroke upper limb rehabilitation. Despite many potential technological developments, mirror therapy is routinely delivered through the use of a static mirror or mirror box. This review aims to synthesise evidence on the application of immersive virtual reality mirror therapy (IVRMT) in poststroke upper limb rehabilitation. A scoping review was performed on relevant English studies published between 2013 to 2023. Literature search was undertaken on APA PsycInfo, CINAHL, Cochrane Library, MEDLINE, PubMed and Web of Science between August 5 and 17, 2023. Additional studies were included from Google Scholar and reference lists of identified articles. A total of 224 records were identified, of which 8 full-text articles were selected for review. All included studies were published between 2019 and 2023, and from high- and upper-middle-income nations. All the studies were experimental (n = 8). The total sample size in the studies was 259, most of whom were stroke patients with upper limb weakness (n = 184). This review identified three major themes and two sub-themes based on the contents of the studies conducted on the application of IVRMT: IVRMT's technical application, feasibility and impact on clinical outcomes (motor recovery and adverse events). IVRMT was concluded to be a safe and feasible approach to post-stroke upper limb rehabilitation, offering enhanced engagement and motor recovery. However, more methodologically robust studies should be conducted to advance this area of practice, and to include a uniform IVRMT intervention protocol, dose, and use of outcome measure.

Spatial Neglect: An Exploration of Clinical Assessment Behaviour in Stroke Rehabilitation.

OBJECTIVE: There is a large gap between evidence-based recommendations for spatial neglect assessment and clinical practice in stroke rehabilitation. We aimed to describe factors that may contribute to this gap, clinician perceptions of an ideal assessment tool, and potential implementation strategies to change clinical practice in this area. DESIGN: Qualitative focus group investigation. Focus group questions were mapped to the Theoretical Domains Framework and asked participants to describe their experiences and perceptions of spatial neglect assessment. SETTING: Online stroke rehabilitation educational bootcamp. PARTICIPANTS: A sample of 23 occupational therapists, three physiotherapists, and one orthoptist that attended the bootcamp. INTERVENTION: Prior to their focus group, participants watched an hour-long educational session about spatial neglect. MAIN MEASURES: A deductive analysis with the Theoretical Domains Framework was used to describe perceived determinants of clinical spatial neglect assessment. An inductive thematic analysis was used to describe perceptions of an ideal assessment tool and practice-change strategies in this area. RESULTS: Participants reported that their choice of spatial neglect assessment was influenced by a belief that it would positively impact the function of people with stroke. However, a lack of knowledge about spatial neglect assessment appeared to drive low clinical use of standardised functional assessments. Participants recommended open-source online education involving a multidisciplinary team, with live-skill practice for the implementation of spatial neglect assessment tools. CONCLUSIONS: Our results suggest that clinicians prefer functional assessments of spatial neglect, but multiple factors such as knowledge, training, and policy change are required to enable their translation to clinical practice.

Child restraint systems: Understanding confidence in proper use and addressing the need for education.

Objective: To quantify the extent of proper local child restraint system (CRS) use and to better understand changes to the level of self-reported confidence with increased CRS installations. With the goal being to improve safety for children travelling in personal vehicles across London, ON and the region. Methods: Public CRS clinics were initiated by Injury Prevention staff after they obtained the Child Passenger Safety Technician certification. Additionally, an online survey was commissioned targeting Ontario parents who had installed at least one CRS in the last five years. Results: From September 2018 to September 2019, 96 comprehensive CRS checks were performed, with 29% of systems found to be installed correctly. Survey results showed a high level of reported confidence with CRS installation (N = 514, 70% female, 43% one child). Parents who had installed only one CRS reported higher confidence in their first install, compared to parents who had installed two or more systems. Conclusions: The error rate with CRS installation and use seen in London, Ontario and the region, is similar to that reported in previous research. Survey results showed high levels of self-reported confidence in CRS use, especially for parents who have installed only one CRS. There presents a need to better understand the root cause of the discrepancy between level of confidence and proper CRS use and to expand our understanding of CRS knowledge retention and transferability to subsequent systems.

Physiotherapy management of atraumatic anterior sternoclavicular joint instability: A prospective case series.

Background: Atraumatic sternoclavicular joint (SCJ) instability is rare. Long-term outcomes are presented for patients managed with physiotherapy. A standardised method of assessment and treatment with a structured physiotherapy programme is also presented. Methods: Long-term outcome was analysed in this prospectively collected series (2011-2019) of patients who were assigned to a structured physiotherapy programme for atraumatic SCJ instability. Outcome-measures (subjective SCJ grading of joint stability (SSGS score), Oxford shoulder instability score (OSIS adapted for SCJ) and visual analogue scale (VAS) for pain) were collected at discharge and long-term follow up. Results: 26 patients (29 SCJ's) responded (return rate 81%). Mean follow-up was 5.1 years (range 0.9-8.3 years). 17/26 patients were hyperlax. 93% (27/29) of SCJs achieved a stable joint on SSGS score. Mean OSIS score at long-term follow up was 33.4 (range 3-48) and VAS 2.7 (range 0-9). 95% who were compliant with physiotherapy had a stable SCJ (mean OSIS 37.8 (SD 7.3) and VAS 1.6 (SD 2.1)). Those non-compliant, 90% were stable but had lower function (mean OSIS 25 (SD 14, p = 0.02) and more pain, VAS 4.9 (SD 2.9, p = 0.006). Conclusion: The structured physiotherapy programme is highly effective in treating patients with atraumatic SCJ instability. Compliance was essential in ensuring better outcomes.

Comparative effectiveness of guselkumab in psoriatic arthritis: updates to a systematic literature review and network meta-analysis.

OBJECTIVE: The IL-23 p19-subunit inhibitor guselkumab has been previously compared with other targeted therapies for PsA through network meta-analysis (NMA). The objective of this NMA update was to include new guselkumab COSMOS trial data, and two key comparators: the IL-23 inhibitor risankizumab and the Janus kinase (JAK) inhibitor upadacitinib. MATERIAL AND METHODS: A systematic literature review was conducted to identify randomized controlled trials up to February 2021. A hand-search identified newer agents up to July 2021. Bayesian NMAs were performed to compare treatments on ACR response, Psoriasis Area and Severity Index (PASI) response, modified van der Heijde-Sharp (vdH-S) score, and serious adverse events (SAEs). RESULTS: For ACR 20, guselkumab 100 mg every 8 weeks (Q8W) and every 4 weeks (Q4W) were comparable (i.e. overlap in credible intervals) to most other agents, including risankizumab, upadacitinib, subcutaneous TNF inhibitors and most IL-17A inhibitors. For PASI 90, guselkumab Q8W and Q4W were better than multiple agents, including subcutaneous TNF and JAK inhibitors. For vdH-S, guselkumab Q8W was similar to risankizumab, while guselkumab Q4W was better; both doses were comparable to most other agents. Most agents had comparable SAEs. CONCLUSIONS: Guselkumab demonstrates better skin efficacy than most other targeted PsA therapies, including upadacitinib. For vdH-S, both guselkumab doses are comparable to most treatments, with both doses ranking higher than most, including upadacitinib and risankizumab. Both guselkumab doses demonstrate comparable ACR responses to most other agents, including upadacitinib and risankizumab, and rank favourably in the network for SAEs.

Midterm results of chronic anterior instability of the sternoclavicular joint managed using a standardized treatment algorithm.

AIMS: There remains a lack of consensus regarding the management of chronic anterior sternoclavicular joint (SCJ) instability. This study aimed to assess whether a standardized treatment algorithm (incorporating physiotherapy and surgery and based on the presence of trauma) could successfully guide management and reduce the number needing surgery. METHODS: Patients with chronic anterior SCJ instability managed between April 2007 and April 2019 with a standardized treatment algorithm were divided into non-traumatic (offered physiotherapy) and traumatic (offered surgery) groups and evaluated at discharge. Subsequently, midterm outcomes were assessed via a postal questionnaire with a subjective SCJ stability score, Oxford Shoulder Instability Score (OSIS, adapted for the SCJ), and pain visual analogue scale (VAS), with analysis on an intention-to-treat basis. RESULTS: A total of 47 patients (50 SCJs, three bilateral) responded for 75% return rate. Of these, 31 SCJs were treated with physiotherapy and 19 with surgery. Overall, 96% (48/50) achieved a stable SCJ, with 60% (30/50) achieving unrestricted function. In terms of outcomes, 82% (41/50) recorded good-to-excellent OSIS scores (84% (26/31) physiotherapy, 79% (15/19) surgery), and 76% (38/50) reported low pain VAS scores at final follow-up. Complications of the total surgical cohort included a 19% (5/27) revision rate, 11% (3/27) frozen shoulder, and 4% (1/27) scar sensitivity. CONCLUSION: This is the largest midterm series reporting chronic anterior SCJ instability outcomes when managed according to a standardized treatment algorithm that emphasizes the importance of appropriate patient selection for either physiotherapy or surgery, based on a history of trauma. All but two patients achieved a stable SCJ, with stability maintained at a median of 70 months (11 to 116) for the physiotherapy group and 87 months (6 to 144) for the surgery group.Cite this article: Bone Jt Open 2022;3(10):815-825.

Exhaled gases and the potential for cross-infection via noninvasive ventilation machines.

Guidelines suggest that exhaled gases do not reach the outlet of noninvasive ventilators in clinical use. In this study, when tidal volumes exceeded 800 mL, exhaled gases did reach the ventilator, leading to a risk of cross-infection between users. https://bit.ly/3EdvtY6.

The management of displaced humeral shaft fractures - A survey of UK shoulder and elbow surgeons.

Introduction: Indications for surgical management of displaced humeral shaft fractures are not clearly established, leading to variations in practice. The aim of this study was to determine the scale of these variations in the UK practice to help design a future national trial. Methods: An online survey was sent to all surgeon members of British Elbow and Shoulder Society to help define humeral shaft fractures, fracture displacement as well as indications for operative and non-operative management. Patient and injury related factors considered important when managing humeral shaft fractures were investigated. Results: The survey achieved a response rate of 32% (104/327). There was a lack of consensus on definitions for humeral shaft fractures and fracture displacement. A functional brace was the most common form of non-operative treatment (63%). Majority immobilise humeral shaft fractures for 4-8 weeks or until callus are visible (62%) with a similar number considering operative treatment if adequate signs of healing are not present at around 12-16 weeks. Around half of our respondents exclusively use plates with variations in preference of approach and a minority (2%) exclusively use intra-medullary nails. Conclusion: The significant variation in management of displaced humeral shaft fractures in the UK suggests a clear need to evaluate clinical and cost effectiveness through a multi-centre randomised trial.

The Problematic Role of Materialistic Values in the Pursuit of Sustainable Well-Being.

Strong materialistic values help to maintain consumer capitalism, but they can have negative consequences for individual well-being, for social equity and for environmental sustainability. In this paper, we add to the existing literature on the adverse consequences of materialistic values by highlighting their negative association with engagement in attitudes and actions that support the achievement of sustainable well-being. To do this, we explore the links between materialistic values and attitudes towards sufficiency (consuming "just enough") as well as mindfulness (non-judgmental awareness of the present moment) and flow (total immersion in an activity), which have all been linked to increased well-being and more sustainable behaviours. We present results from three correlational studies that examine the association between materialistic values and sufficiency attitudes (Study 1, n = 310), a multi-faceted measure of mindfulness (Study 2, n = 468) and the tendency to experience flow (Study 3, n = 2000). Results show that materialistic values were negatively associated with sufficiency attitudes, mindfulness, and flow experiences. We conclude with practical considerations and suggest next steps for tackling the problematic aspects of materialism and encouraging the development of sustainable well-being.

Preventing facial pressure injuries among health care staff working in diverse COVID-19 care environments.

The aim of this study was to determine the impact of a specially designed care bundle on the development of facial pressure injuries among frontline health care workers wearing personal protective equipment (PPE) during the COVID-19 pandemic. This was a mixed methods study. First, a pre-posttest observational design was employed to evaluate the impact of the pre-piloted intervention, a care bundle including skin cleansing and hydration, protective material use, facemask selection and skin inspection, developed in line with international best practice guidelines. Data were collected using survey methodology. Frontline COVID-19 staff working in acute, community and ambulance services were invited to participate. Then, judgemental and volunteer sampling was used to select participants to undertake semi-structured interviews to elicit feedback on their perceptions of the care bundle. The sample included 120 acute hospital staff, 60 Ambulance staff, 24 Community Hub staff and 20 COVID-19 testing centre staff. A survey response rate of 61% was realised (n = 135/224). Of the participants, 32% (n = 43) had a facial pressure ulcer (FPI) pre-intervention and 13% (n = 18) developed an FPI while using the care bundle. The odds ratio (OR) was 0.33 (95% CI: 0.18 to 0.61; P = .0004), indicating a 77% reduction in the odds of FPI development with use of the care bundle. Analysis of the qualitative data from 22 interviews identified three key themes, the context for the care bundle, the ease of use of the care bundle and the care bundle as a solution to FPI development. The care bundle reduced the incidence of FPI among the participants and was found to be easy to use. Implementation of skin protection for frontline staff continues to be important given the persistently high incidence of COVID-19 and the ongoing need to wear PPE for protracted durations.

Early versus delayed repair of traumatic rotator cuff tears. Does timing matter on outcomes?

INTRODUCTION: The purpose of this study was to determine if delay (before or after 4 months) in repairing a symptomatic traumatic rotator cuff tear affected clinical outcome, re-rupture rates and use of interpositional dermal grafts. METHODS: This was a case matched (age + tear size) series of patients who underwent an early (≤ 4 months) or delayed (> 4 months) rotator cuff repair following a traumatic tear. If a direct repair could not be achieved a dermal interposition graft was used. Outcomes were collected at a median time of 30 months post-operatively using the Oxford, Constant and EQ5D scores. RESULTS: Twenty patients underwent rotator cuff repair within 4 months (1-4) of injury. Twenty age and cuff tear size-matched patients were identified who had undergone a delayed repair (4.1-24 months) after injury. We found no significant difference (p > 0.05) in patient reported outcomes scores between the early and delayed repair. [Oxford scores; Early 43(13-48), Delayed 45 (31-48); Constant scores; Early 73 (21-94), Delayed 73.5 (44-87); EQ5D; Early 0.75 (0.25-1), Delayed 0.77 (0.4-1)]. Time to full recovery was significantly longer (14 vs 33.8 months) for the delayed repair group (P > 0.05). When cuff tears were subdivided into < 3 cm tears or ≥ 3 cm tears, no significant difference outcome scores were founds. However, use of dermal interposition graft was 44% in delayed group for tears ≥ 3 cm. No grafts were used in early repair group. There was one symptomatic re-tear in our series which was in the early repair group. CONCLUSION: When compared to the delayed repair group, patients that underwent early repair of traumatic rotator cuff tears had shorter time of recovery, and less need for allograft augmentation for tears 3 cm or greater. However, at mid-term follow-up, this study found no difference in patient reported outcomes following early versus delayed repair of traumatic rotator cuff tears. LEVEL OF EVIDENCE: 3.

Joining the workforce during the COVID-19 pandemic: views of Allied Health Profession students.

In the United Kingdom, the onset of the COVID-19 pandemic placed great pressures on universities to ensure final year health care students completed their studies earlier than planned in order to join the National Health Service workforce. This study aimed to explore the anticipations and support needs of final year allied health profession students transitioning to practice during a pandemic. Final year university students across seven healthcare professions were asked to complete an online survey. Demographic data were analyzed by descriptive statistics and responses to open questions were explored using content analysis. Sixty participants completed the survey. Content analysis regarding students' anticipations, fears, and support needs identified the following themes: professional identity and growth; opportunities for improvement; preparedness for transition from university to the workplace, the workplace environment; COVID-19; support from lecturers; daily support within the workplace and innovative methods of support. Although the transition from student to practitioner continues to be a stressful period, only a minority of participants reported COVID-19 as an explicit stressor. However, as the effects of COVID-19 continue to evolve in the United Kingdom, universities and healthcare trusts must ensure adequate supports are in place for recent graduates navigating this transition during a healthcare crisis.

Floor and ceiling effects in the Oxford Shoulder Score : an analysis from the National Joint Registry.

AIMS: The main objective of this study was to examine whether the Oxford Shoulder Score (OSS) demonstrated floor or ceiling effects when used to measure outcomes following shoulder arthroplasty in a large national cohort. Secondary objectives were to assess its pain and function subscales, and to identify independent predictors for patients achieving a postoperative ceiling score following shoulder arthroplasty. METHODS: Secondary database analysis of the National Joint Registry (NJR), which included 48,270 patients undergoing shoulder arthroplasty, was conducted. The primary outcome measure was the OSS. Secondary outcome measures were the OSS-Function Component Subscale and OSS-Pain Component Subscale. Floor and ceiling effects were considered to be present if > 15% of patients scored either the lowest or highest possible score. Logistic regression analysis was used to identify independent predictors for scoring the highest possible OSS score postoperatively. RESULTS: Preoperatively, 1% of patients achieved the lowest possible OSS score (0) and 0.4% of patients achieved the highest possible score (48). Postoperatively, < 1% of patients achieved the lowest score at all timepoints, but the percentage achieving the highest score at six months was 8.3%, at three years 16.9%, and at five years 17%. Male patients, those aged between 60 and 89 years, and those undergoing an anatomical total shoulder arthroplasty (ATSA) were more likely to contribute to the ceiling effect seen in the OSS questionnaire. Pain and function subscales exhibited greater ceiling effects at three years and five years when compared with the overall OSS questionnaire. Logistic regression analysis showed that sex, procedure type, and preoperative OSS score were independent predictors for scoring the highest possible OSS at years. CONCLUSION: Based on NJR patient-reported outcome measures data, the OSS does not exhibit a ceiling effect at six months, but does at three years and five years, in part due to outcome scores of ATSA. Preoperative OSS, age, male sex, and ATSA are independent predictors of achieving a ceiling score. Cite this article: Bone Joint J 2021;103-B(11):1717-1724.

The Management of Distal Clavicle Fractures - A Survey of UK Shoulder and Elbow Surgeons.

Background Distal clavicle fractures (DCF) are a management challenge frequently encountered by shoulder surgeons. Despite an array of surgical fixation strategies, the indications and role of surgery are unclear, with there being no gold standard or consensus regarding their management. The aim of this study was to identify current United Kingdom (UK) clinical practices relating to DCFs and to inform a future randomised control trial (RCT). Methods An online survey was sent to the consultant surgeon members of the British Elbow and Shoulder Society (BESS). Questions covered respondent indications for surgical fixation, important factors considered for management of DCFs, fixation strategies, the volume of patients treated, and willingness to participate in the conduct of a randomized trial. Results The response rate was 84/327 (26%). 64-67% of respondents reported surgically managing DCFs classified as Neer type 2A, 2B and 5. The most important factors considered by surgeons when deciding between operative and nonoperative intervention were degree of displacement (90%), clinical assessment of impending open fracture (87%), and age of the patient (74%). For conservatively managed DCFs, the preferred length of complete immobilization was 2-4 weeks (46%), followed by 4-8 weeks (17%). 30% reported not immobilizing their patients at all. For operative intervention, the locking plate was the preferred fixation method by most respondents (68%), although there was no clear consensus regarding other fixation methods. Most surgeons (52%) reported treating a low volume of patients with DCFs (0-10) per year. 58% of respondents were willing to randomize patients to non-operative treatment in a multi-centre RCT, with a further 22% undecided. Finally, 68% (n=79) of respondents would consider being co-investigators in such a trial. Conclusion There is considerable heterogeneity in the management of patients with DCFs in the UK. The indications for surgery and the optimal surgical fixation method remain uncertain. There is a clear need for pragmatic multi-centre clinical research in this area.

Surgical treatments compared with early structured physiotherapy in secondary care for adults with primary frozen shoulder: the UK FROST three-arm RCT.

BACKGROUND: Frozen shoulder causes pain and stiffness. It affects around 10% of people in their fifties and is slightly more common in women. Costly and invasive surgical interventions are used, without high-quality evidence that these are effective. OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of three treatments in secondary care for adults with frozen shoulder; to qualitatively explore the acceptability of these treatments to patients and health-care professionals; and to update a systematic review to explore the trial findings in the context of existing evidence for the three treatments. DESIGN: This was a pragmatic, parallel-group, multicentre, open-label, three-arm, randomised superiority trial with unequal allocation (2 : 2 : 1). An economic evaluation and a nested qualitative study were also carried out. SETTING: The orthopaedic departments of 35 hospitals across the UK were recruited from April 2015, with final follow-up in December 2018. PARTICIPANTS: Participants were adults (aged ≥ 18 years) with unilateral frozen shoulder, characterised by restriction of passive external rotation in the affected shoulder to < 50% of the opposite shoulder, and with plain radiographs excluding other pathology. INTERVENTIONS: The inventions were early structured physiotherapy with a steroid injection, manipulation under anaesthesia with a steroid injection and arthroscopic capsular release followed by manipulation. Both of the surgical interventions were followed with post-procedural physiotherapy. MAIN OUTCOME MEASURES: The primary outcome and end point was the Oxford Shoulder Score at 12 months post randomisation. A difference of 5 points between early structured physiotherapy and manipulation under anaesthesia or arthroscopic capsular release or of 4 points between manipulation under anaesthesia and arthroscopic capsular release was judged clinically important. RESULTS: The mean age of the 503 participants was 54 years; 319 were female (63%) and 150 had diabetes (30%). The primary analyses comprised 473 participants (94%). At the primary end point of 12 months, participants randomised to arthroscopic capsular release had, on average, a statistically significantly higher (better) Oxford Shoulder Score than those randomised to manipulation under anaesthesia (2.01 points, 95% confidence interval 0.10 to 3.91 points; p = 0.04) or early structured physiotherapy (3.06 points, 95% confidence interval 0.71 to 5.41 points; p = 0.01). Manipulation under anaesthesia did not result in statistically significantly better Oxford Shoulder Score than early structured physiotherapy (1.05 points, 95% confidence interval -1.28 to 3.39 points; p = 0.38). No differences were deemed of clinical importance. Serious adverse events were rare but occurred in participants randomised to surgery (arthroscopic capsular release,n = 8; manipulation under anaesthesia,n = 2). There was, however, one serious adverse event in a participant who received non-trial physiotherapy. The base-case economic analysis showed that manipulation under anaesthesia was more expensive than early structured physiotherapy, with slightly better utilities. The incremental cost-effectiveness ratio for manipulation under anaesthesia was £6984 per additional quality-adjusted life-year, and this intervention was probably 86% cost-effective at the threshold of £20,000 per quality-adjusted life-year. Arthroscopic capsular release was more costly than early structured physiotherapy and manipulation under anaesthesia, with no statistically significant benefit in utilities. Participants in the qualitative study wanted early medical help and a quicker pathway to resolve their shoulder problem. Nine studies were identified from the updated systematic review, including UK FROST, of which only two could be pooled, and found that arthroscopic capsular release was more effective than physiotherapy in the long-term shoulder functioning of patients, but not to the clinically important magnitude used in UK FROST. LIMITATIONS: Implementing physiotherapy to the trial standard in clinical practice might prove challenging but could avoid theatre use and post-procedural physiotherapy. There are potential confounding effects of waiting times in the trial. CONCLUSIONS: None of the three interventions was clearly superior. Early structured physiotherapy with a steroid injection is an accessible and low-cost option. Manipulation under anaesthesia is the most cost-effective option. Arthroscopic capsular release carries higher risks and higher costs. FUTURE WORK: Evaluation in a randomised controlled trial is recommended to address the increasing popularity of hydrodilatation despite the paucity of high-quality evidence. TRIAL REGISTRATION: Current Controlled Trials ISRCTN48804508. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 71. See the NIHR Journals Library website for further project information.

Frozen shoulder occurs when the soft tissue envelope around the shoulder joint becomes inflamed, scarred and contracted, making movement painful and stiff. It affects around 1 in 10 people and is more common in women. Most patients are treated in the community. Those who do not improve are offered treatments in hospital. This includes costly and invasive surgical options. It is unclear which treatment provides the best patient outcomes and is cost-effective. UK FROST (UK FROzen Shoulder Trial) comprised 503 patients (from 35 UK hospitals) who randomly received one of three commonly offered treatments for frozen shoulder: early physiotherapy to restore movement, including a steroid injection for pain reliefmanipulation under anaesthesia, to stretch and tear the tight capsule to restore movement, and a steroid injection followed by physiotherapyarthroscopic capsular release, which uses keyhole surgery, including manipulation, to restore movement, followed by physiotherapy with pain medication. No important differences were found between the three treatments in shoulder function or pain at 12 months. Fewer patients who received arthroscopic capsular release required further treatment, and patients who received arthroscopic capsular release had slightly better shoulder function and pain outcomes than those who received the manipulation procedure or early physiotherapy. This improvement, however, was unlikely to be of clinical benefit to patients. Arthroscopic capsular release had slightly higher risks and substantially higher costs. Six serious complications were reported in patients who received arthroscopic capsular release (mostly owing to co-existing health problems) and two were reported in patients who received manipulation under anaesthesia. Physiotherapy was the least expensive treatment, but patients who received manipulation under anaesthesia had slightly better general health than those who received physiotherapy. Early physiotherapy with steroid injection could be accessed quicker than the surgical alternatives. Manipulation under anaesthesia cost more than physiotherapy but provided the best value for money. Patients in the study wanted early access to medical help to improve their shoulder problems.

Management of adults with primary frozen shoulder in secondary care (UK FROST): a multicentre, pragmatic, three-arm, superiority randomised clinical trial.

BACKGROUND: Manipulation under anaesthesia and arthroscopic capsular release are costly and invasive treatments for frozen shoulder, but their effectiveness remains uncertain. We compared these two surgical interventions with early structured physiotherapy plus steroid injection. METHODS: In this multicentre, pragmatic, three-arm, superiority randomised trial, patients referred to secondary care for treatment of primary frozen shoulder were recruited from 35 hospital sites in the UK. Participants were adults (≥18 years) with unilateral frozen shoulder, characterised by restriction of passive external rotation (≥50%) in the affected shoulder. Participants were randomly assigned (2:2:1) to receive manipulation under anaesthesia, arthroscopic capsular release, or early structured physiotherapy. In manipulation under anaesthesia, the surgeon manipulated the affected shoulder to stretch and tear the tight capsule while the participant was under general anaesthesia, supplemented by a steroid injection. Arthroscopic capsular release, also done under general anaesthesia, involved surgically dividing the contracted anterior capsule in the rotator interval, followed by manipulation, with optional steroid injection. Both forms of surgery were followed by postprocedural physiotherapy. Early structured physiotherapy involved mobilisation techniques and a graduated home exercise programme supplemented by a steroid injection. Both early structured physiotherapy and postprocedural physiotherapy involved 12 sessions during up to 12 weeks. The primary outcome was the Oxford Shoulder Score (OSS; 0-48) at 12 months after randomisation, analysed by initial randomisation group. We sought a target difference of 5 OSS points between physiotherapy and either form of surgery, or 4 points between manipulation and capsular release. The trial registration is ISRCTN48804508. FINDINGS: Between April 1, 2015, and Dec 31, 2017, we screened 914 patients, of whom 503 (55%) were randomly assigned. At 12 months, OSS data were available for 189 (94%) of 201 participants assigned to manipulation (mean estimate 38·3 points, 95% CI 36·9 to 39·7), 191 (94%) of 203 participants assigned to capsular release (40·3 points, 38·9 to 41·7), and 93 (94%) of 99 participants assigned to physiotherapy (37·2 points, 35·3 to 39·2). The mean group differences were 2·01 points (0·10 to 3·91) between the capsular release and manipulation groups, 3·06 points (0·71 to 5·41) between capsular release and physiotherapy, and 1·05 points (-1·28 to 3·39) between manipulation and physiotherapy. Eight serious adverse events were reported with capsular release and two with manipulation. At a willingness-to-pay threshold of £20 000 per quality-adjusted life-year, manipulation under anaesthesia had the highest probability of being cost-effective (0·8632, compared with 0·1366 for physiotherapy and 0·0002 for capsular release). INTERPRETATION: All mean differences on the assessment of shoulder pain and function (OSS) at the primary endpoint of 12 months were less than the target differences. Therefore, none of the three interventions were clinically superior. Arthoscopic capsular release carried higher risks, and manipulation under anaesthesia was the most cost-effective. FUNDING: The National Institute for Health Research Health Technology Assessment programme.