Advice only versus advice and a physiotherapy programme for acute traumatic anterior shoulder dislocation: the ARTISAN RCT.

Background: The extra benefit of a programme of physiotherapy in addition to advice alone, following first-time traumatic shoulder dislocation, is uncertain. We compared the clinical and cost-effectiveness of a single session of advice with a single session of advice and a programme of physiotherapy. Objective: The primary objective was to quantify and draw inferences about observed differences in the Oxford Shoulder Instability Score between the trial treatment groups 6 months post randomisation, in adults with a first-time traumatic shoulder dislocation. Design: A pragmatic, multicentre, superiority, randomised controlled trial with embedded qualitative study. Setting: Forty-one hospitals in the UK NHS. Participants: Adults with a radiologically confirmed first-time traumatic anterior shoulder dislocation, being managed non-operatively. People with neurovascular complications or bilateral dislocations, and those unable to adhere to trial procedures or unable to attend physiotherapy within 6 weeks of injury, or who had previously been randomised, were excluded. Interventions: All participants received the same initial shoulder examination followed by advice to aid self-management, lasting up to 1 hour and administered by a physiotherapist (control). Participants randomised to receive an additional programme of physiotherapy were offered sessions lasting for up to 30 minutes, over a maximum duration of 4 months from the date of randomisation (intervention). Main outcome measures: The primary outcome measure was the Oxford Shoulder Instability Score. This is a self-completed outcome measure containing 12 questions (0-4 points each), with possible scores from 0 (worst function) to 48 (best function). Measurements were collected at 6 weeks, 3 months, 6 months and 12 months by postal questionnaire; 6 months was the primary outcome time point. The primary health outcome for economic evaluation was the quality-adjusted life-year, in accordance with National Institute of Health and Care Excellence guidelines. Results: Between 14 November 2018 and 14 March 2022, 482 participants were randomised to advice (n = 240) or advice and a programme of physiotherapy (n = 242). Participants were 34% female, with a mean age of 45 years, and treatment arms were balanced at baseline. There was not a statistically significant difference in the primary outcome between advice only and advice plus a programme of physiotherapy at 6 months for the primary intention-to-treat adjusted analysis (favours physiotherapy: 1.5, 95% confidence interval -0.3 to 3.5) or at earlier 3-month and 6-week time points on the Oxford Shoulder Instability Score (0-48; higher scores indicate better function). The probability of physiotherapy being cost-effective at a willingness-to-pay threshold of £30,000 was 0.95. Conclusions: We found little difference in the primary outcome or other secondary outcomes. Advice with additional physiotherapy sessions was found likely to be cost-effective. However, small imprecise incremental costs and quality-adjusted life-years raise questions on whether it is the best use of scarce physiotherapy resources given current service demands. Limitations: Loss to follow-up was 27%; however, the observed standard deviation was much smaller than anticipated. These changes in parameters reduced the number of participants required to observe the planned target difference of four points. Our post hoc sensitivity analysis, accounting for missing data, gives similar results. Future work: Further research should be directed towards optimising self-management strategies. Study registration: This study is registered as ISRCTN63184243. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/167/56) and is published in full in Health Technology Assessment; Vol. 28, No. 22. See the NIHR Funding and Awards website for further award information.

The shoulder dislocates (comes out of its socket joint) when the upper end of the arm bone is forced out during an injury. This common problem occurs mostly in men in their 20s and women aged over 80. After the bone is put back in its socket, most people are managed with physiotherapy. In the United Kingdom, once the bone is back in its socket, there is a range of physiotherapy provision: some hospitals offer advice, and some offer advice and a course of additional physiotherapy sessions. We compared advice alone to advice and physiotherapy for people who had a shoulder that had come out of its joint for the first time. Physiotherapy advice and additional sessions included education about the injury and exercises to move and strengthen the shoulder. When we started this project, this was the first time these two treatments had been compared. Our aim was to compare what activities the two groups could do 6 months after injury via a questionnaire. We also compared quality of life and the cost of rehabilitation at 6 weeks, 3 months, 6 months and 12 months after injury. Adults with a shoulder out of its joint and who were not having surgery were asked to take part. All adults who were eligible and consented to take part were assigned, by chance, to either a single session of advice or the same session followed by physiotherapy. Between 14 November 2018 and 14 March 2022 we collected data on 482 people, from 41 NHS sites across the UK. We found at 6 months there was little evidence that additional physiotherapy was better, when compared to advice alone. Cost-effectiveness analysis (comparing changes in costs and quality of life) suggests additional physiotherapy might provide value for money. However, the changes involved are small and uncertain.

What recovery domains are important following a total knee replacement? A qualitative, interview-based study.

OBJECTIVES: To explore people's views of recovery from total knee replacement (TKR) and which recovery domains they felt were important. DESIGN: Semi-structured interviews exploring the views of individuals about to undergo or who have undergone TKR. A constant-comparative approach with thematic analysis was used to identify themes. The process of sampling, collecting data and analysis were continuous and iterative throughout the study, with interviews ceasing once thematic saturation was achieved. SETTING: Tertiary care centre. PARTICIPANTS: A purposive sample was used to account for variables including pre, early or late postoperative status. RESULTS: 12 participants were interviewed, 4 who were preoperative, 4 early postoperative and 4 late postoperative. Themes of pain, function, fear of complications, awareness of the artificial knee joint and return to work were identified. Subthemes of balancing acute and chronic pain were identified. CONCLUSIONS: The results of this interview-based study identify pain and function, in particular mobility, that were universally important to those undergoing TKR. Surgeons should consider exploring these domains when taking informed consent to enhance shared decision-making. Researchers should consider these recovery domains when designing interventional studies.

Does pain self-efficacy predict, moderate or mediate outcomes in people with chronic headache; an exploratory analysis of the CHESS trial.

BACKGROUND: Chronic headache disorders are disabling. The CHESS trial studied the effects of a short non-pharmacological intervention of education with self-management support for people affected by migraine and/or tension type headache for at least 15 days per month for at least three months. There were no statistically significant effects on the Headache Impact Test-6 (HIT-6) at 12-months. However, we observed improvement in pain self-efficacy questionnaire (PSEQ) and short-term HIT-6. We explored the impact of the CHESS intervention on PSEQ, and subsequently, on the HIT-6 and chronic headache quality of life questionnaire (CH-QLQ) at four, eighth and 12 months. METHODS: We included all 736 participants from the CHESS trial. We used simple linear regression models to explore the change of HIT-6 and CH-QLQ with treatment and PSEQ at baseline (predictor analysis), and the interaction between treatment and baseline PSEQ (moderator analysis). We considered the change of PSEQ from baseline to four months as a mediator in the mediation analysis. RESULTS: Baseline PSEQ neither predicted nor moderated outcomes. The prediction effect on change of HIT-6 from baseline to 12 months was 0.01 (95% CI, -0.03 to 0.04) and the interaction (moderation) effect was -0.07 (95% CI, -0.15 to 0.002). However, the change of PSEQ from baseline to 4-month mediated the HIT-6 (baseline to 8-, and 12-month) and all components of CH-QLQ (baseline to 8-, and 12-month). The CHESS intervention improved the mediated variable, PSEQ, by 2.34 (95% CI, 0.484 to 4.187) units and this corresponds to an increase of 0.21 (95% CI, 0.03 to 0.45) units in HIT-6 at 12-months. The largest mediated effect was observed on the CH-QLQ Emotional Function, an increase of 1.12 (95% CI, 0.22 to 2.20). CONCLUSIONS: PSEQ was not an effective predictor of outcome. However, change of short-term PSEQ mediated all outcomes, albeit minimally. Future behavioural therapy for chronic headache may need to consider how to achieve larger, and more sustained increases level of self-efficacy than that achieved within the CHESS trial. TRIAL REGISTRATION: ISRCTN79708100.

Waste not, want not: call to action for spinal manipulative therapy researchers.

BACKGROUND: Research waste is defined as research outcomes with no or minimal societal benefits. It is a widespread problem in the healthcare field. Four primary sources of research waste have been defined: (1) irrelevant or low priority research questions, (2) poor design or methodology, (3) lack of publication, and (4) biased or inadequate reporting. This commentary, which was developed by a multidisciplinary group of researchers with spinal manipulative therapy (SMT) research expertise, discusses waste in SMT research and provides suggestions to improve future research. MAIN TEXT: This commentary examines common sources of waste in SMT research, focusing on design and methodological issues, by drawing on prior research and examples from clinical and mechanistic SMT studies. Clinical research is dominated by small studies and studies with a high risk of bias. This problem is compounded by systematic reviews that pool heterogenous data from varying populations, settings, and application of SMT. Research focusing on the mechanisms of SMT often fails to address the clinical relevance of mechanisms, relies on very short follow-up periods, and has inadequate control for contextual factors. CONCLUSIONS: This call to action is directed to researchers in the field of SMT. It is critical that the SMT research community act to improve the way research is designed, conducted, and disseminated. We present specific key action points and resources, which should enhance the quality and usefulness of future SMT research.

Developing an international consensus Reporting guideline for intervention Fidelity in Non-Drug, non-surgical trials: The ReFiND protocol.

BACKGROUND: Inadequate reporting of fidelity to interventions in trials limits the transparency and interpretation of trial findings. Despite this, most trials of non-drug, non-surgical interventions lack comprehensive reporting of fidelity. If fidelity is poorly reported, it is unclear which intervention components were tested or implemented within the trial, which also hinders research reproducibility. This protocol describes the development process of a reporting guideline for fidelity of non-drug, non-surgical interventions (ReFiND) in the context of trials. METHODS: The ReFiND guideline will be developed in six stages. Stage one: a guideline development group has been formed to oversee the guideline methodology. Stage two: a scoping review will be conducted to identify and summarize existing guidance documents on the fidelity of non-drug, non-surgical interventions. Stage three: a Delphi study will be conducted to reach consensus on reporting items. Stage four: a consensus meeting will be held to consolidate the reporting items and discuss the wording and structure of the guideline. Stage five: a guidance statement, an elaboration and explanation document, and a reporting checklist will be developed. Stage six: different strategies will be used to disseminate and implement the ReFiND guideline. DISCUSSION: The ReFiND guideline will provide a set of items developed through international consensus to improve the reporting of intervention fidelity in trials of non-drug, non-surgical interventions. This reporting guideline will enhance transparency and reproducibility in future non-drug, non-surgical intervention research.

Adverse and serious adverse events incidence of pharmacological interventions for managing chronic and episodic migraine in adults: a systematic review.

Background: Migraine is the second most common prevalent disorder worldwide and is a top cause of disability with a substantial economic burden. Many preventive migraine medications have notable side effects that affect different body organs. Method: We systematically searched for published randomised controlled trials (RCTs) using terms for migraine/headache and preventive medications. Using eligibility criteria, two reviewers independently assessed the articles. Cochrane risk-of-bias tool was applied to assess the quality of the studies. Data were classified by system organ class (SOC). Results: Thirty-two RCTs with 21 780 participants met the eligibility criteria for the incidence of adverse events (AEs). Additionally, 33 RCTs with 22 615 participants were included to synthesise the incidence of serious AEs (SAEs). The percentage of attributed AEs and SAEs to each SOC for 10 preventive drugs with different dosing regimens was calculated. Amitriptyline and topiramate had a higher incidence of nervous system disorders; Topiramate was also associated with a higher incidence of psychiatric disorders. All drugs showed a certain incidence of infections and infestations, with Onabotulinumtoxin A (BTA) having the lowest rate. BTA had a higher incidence of musculoskeletal disorders than the other drugs. Calcitonin gene-related peptide (CGRP) monoclonal antibodies (MAbs) such as fremanezumab and galcanezumab were linked to more general disorders and administration site conditions than other drugs. Conclusion: Notably, the observed harm to SOCs varies among these preventive drugs. We suggest conducting head-to-head RCTs to evaluate the safety profile of oral medications, BTA, and CGRP MAbs in episodic and/or chronic migraine populations. PROSPERO registration number: CRD42021265993.

Clinical effectiveness of an online supervised group physical and mental health rehabilitation programme for adults with post-covid-19 condition (REGAIN study): multicentre randomised controlled trial.

OBJECTIVE: To evaluate whether a structured online supervised group physical and mental health rehabilitation programme can improve health related quality of life compared with usual care in adults with post-covid-19 condition (long covid). DESIGN: Pragmatic, multicentre, parallel group, superiority randomised controlled trial. SETTING: England and Wales, with home based interventions delivered remotely online from a single trial hub. PARTICIPANTS: 585 adults (26-86 years) discharged from NHS hospitals at least three months previously after covid-19 and with ongoing physical and/or mental health sequelae (post-covid-19 condition), randomised (1:1.03) to receive the Rehabilitation Exercise and psycholoGical support After covid-19 InfectioN (REGAIN) intervention (n=298) or usual care (n=287). INTERVENTIONS: Best practice usual care was a single online session of advice and support with a trained practitioner. The REGAIN intervention was delivered online over eight weeks and consisted of weekly home based, live, supervised, group exercise and psychological support sessions. MAIN OUTCOME MEASURES: The primary outcome was health related quality of life using the patient reported outcomes measurement information system (PROMIS) preference (PROPr) score at three months. Secondary outcomes, measured at three, six, and 12 months, included PROMIS subscores (depression, fatigue, sleep disturbance, pain interference, physical function, social roles/activities, and cognitive function), severity of post-traumatic stress disorder, general health, and adverse events. RESULTS: Between January 2021 and July 2022, 39 697 people were invited to take part in the study and 725 were contacted and eligible. 585 participants were randomised. Mean age was 56 (standard deviation (SD) 12) years, 52% were female participants, mean health related quality of life PROMIS-PROPr score was 0.20 (SD 0.17), and mean time from hospital discharge was 323 (SD 144) days. Compared with usual care, the REGAIN intervention led to improvements in health related quality of life (adjusted mean difference in PROPr score 0.03 (95% confidence interval 0.01 to 0.05), P=0.02) at three months, driven predominantly by greater improvements in the PROMIS subscores for depression (1.39 (0.06 to 2.71), P=0.04), fatigue (2.50 (1.19 to 3.81), P<0.001), and pain interference (1.80 (0.50 to 3.11), P=0.01). Effects were sustained at 12 months (0.03 (0.01 to 0.06), P=0.02). Of 21 serious adverse events, only one was possibly related to the REGAIN intervention. In the intervention group, 141 (47%) participants fully adhered to the programme, 117 (39%) partially adhered, and 40 (13%) did not receive the intervention. CONCLUSIONS: In adults with post-covid-19 condition, an online, home based, supervised, group physical and mental health rehabilitation programme was clinically effective at improving health related quality of life at three and 12 months compared with usual care. TRIAL REGISTRATION: ISRCTN registry ISRCTN11466448.

Acute rehabilitation following traumatic anterior shoulder dislocation (ARTISAN): pragmatic, multicentre, randomised controlled trial.

OBJECTIVE: To assess the effects of an additional programme of physiotherapy in adults with a first-time traumatic shoulder dislocation compared with single session of advice, supporting materials, and option to self-refer to physiotherapy. DESIGN: Pragmatic, multicentre, randomised controlled trial (ARTISAN). SETTING AND PARTICIPANTS: Trauma research teams at 41 UK NHS Trust sites screened adults with a first time traumatic anterior shoulder dislocation confirmed radiologically, being managed non-operatively. People were excluded if they presented with both shoulders dislocated, had a neurovascular complication, or were considered for surgical management. INTERVENTIONS: One session of advice, supporting materials, and option to self-refer to physiotherapy (n=240) was assessed against the same advice and supporting materials and an additional programme of physiotherapy (n=242). Analyses were on an intention-to-treat basis with secondary per protocol analyses. MAIN OUTCOME MEASURES: The primary outcome was the Oxford shoulder instability score (a single composite measure of shoulder function), measured six months after treatment allocation. Secondary outcomes included the QuickDASH, EQ-5D-5L, and complications. RESULTS: 482 participants were recruited from 40 sites in the UK. 354 (73%) participants completed the primary outcome score (n=180 allocated to advice only, n=174 allocated to advice and physiotherapy). Participants were mostly male (66%), with a mean age of 45 years. No significant difference was noted between advice compared with advice and a programme of physiotherapy at six months for the primary intention-to-treat adjusted analysis (between group difference favouring physiotherapy 1.5 (95% confidence interval -0.3 to 3.5)) or at earlier three month and six week timepoints. Complication profiles were similar across the two groups (P>0.05). CONCLUSIONS: An additional programme of current physiotherapy is not superior to advice, supporting materials, and the option to self-refer to physiotherapy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN63184243.

A tailored psychological intervention for anxiety and depression management in people with chronic obstructive pulmonary disease: TANDEM RCT and process evaluation.

Background: People with chronic obstructive pulmonary disease have high levels of anxiety and depression, which is associated with increased morbidity and poor uptake of effective treatments, such as pulmonary rehabilitation. Cognitive-behavioural therapy improves mental health of people with long-term conditions and could potentially increase uptake of pulmonary rehabilitation, enabling synergies that could enhance the mental health of people with chronic obstructive pulmonary disease. Aim: Our aim was to develop and evaluate the clinical effectiveness and cost effectiveness of a tailored cognitive-behavioural approach intervention, which links into, and optimises the benefits of, routine pulmonary rehabilitation. Design: We carried out a pragmatic multicentre randomised controlled trial using a 1.25 : 1 ratio (intervention : control) with a parallel process evaluation, including assessment of fidelity. Setting: Twelve NHS trusts and five Clinical Commissioning Groups in England were recruited into the study. The intervention was delivered in participant's own home or at a local NHS facility, and by telephone. Participants: Between July 2017 and March 2020 we recruited adults with moderate/very severe chronic obstructive pulmonary disease and mild/moderate anxiety and/or depression, meeting eligibility criteria for assessment for pulmonary rehabilitation. Carers of participants were invited to participate. Intervention: The cognitive-behavioural approach intervention (i.e. six to eight 40- to 60-minute sessions plus telephone support throughout pulmonary rehabilitation) was delivered by 31 trained respiratory healthcare professionals to participants prior to commencing pulmonary rehabilitation. Usual care included routine pulmonary rehabilitation referral. Main outcome measures: Co-primary outcomes were Hospital Anxiety and Depression Scale - anxiety and Hospital Anxiety and Depression Scale - depression at 6 months post randomisation. Secondary outcomes at 6 and 12 months included health-related quality of life, smoking status, uptake of pulmonary rehabilitation and healthcare use. Results: We analysed results from 423 randomised participants (intervention, n = 242; control, n = 181). Forty-three carers participated. Follow-up at 6 and 12 months was 93% and 82%, respectively. Despite good fidelity for intervention delivery, mean between-group differences in Hospital Anxiety and Depression Scale at 6 months ruled out clinically important effects (Hospital Anxiety and Depression Scale - anxiety mean difference -0.60, 95% confidence interval -1.40 to 0.21; Hospital Anxiety and Depression Scale - depression mean difference -0.66, 95% confidence interval -1.39 to 0.07), with similar results at 12 months. There were no between-group differences in any of the secondary outcomes. Sensitivity analyses did not alter these conclusions. More adverse events were reported for intervention participants than for control participants, but none related to the trial. The intervention did not generate quality-of-life improvements to justify the additional cost (adjusted mean difference £770.24, 95% confidence interval -£27.91 to £1568.39) to the NHS. The intervention was well received and many participants described positive affects on their quality of life. Facilitators highlighted the complexity of participants' lives and considered the intervention to be of potential valuable; however, the intervention would be difficult to integrate within routine clinical services. Our well-powered trial delivered a theoretically designed intervention with good fidelity. The respiratory-experienced facilitators were trained to deliver a low-intensity cognitive-behavioural approach intervention, but high-intensity cognitive-behavioural therapy might have been more effective. Our broad inclusion criteria specified objectively assessed anxiety and/or depression, but participants were likely to favour talking therapies. Randomisation was concealed and blinding of outcome assessment was breached in only 15 participants. Conclusions: The tailored cognitive-behavioural approach intervention delivered with fidelity by trained respiratory healthcare professionals to people with chronic obstructive pulmonary disease was neither clinically effective nor cost-effective. Alternative approaches that are integrated with routine long-term condition care are needed to address the unmet, complex clinical and psychosocial needs of this group of patients. Trial registration: This trial is registered as ISRCTN59537391. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/146/02) and is published in full in Health Technology Assessment; Vol. 28, No. 1. See the NIHR Funding and Awards website for further award information.

People with long-standing lung problems, such as chronic obstructive pulmonary disease, often also have anxiety and depression, which further reduces their quality of life. Two existing treatments could help. Pulmonary rehabilitation (a programme of exercise and education) improves both the physical and mental health of people with chronic obstructive pulmonary disease. Cognitive­behavioural therapy (a talking therapy) may reduce anxiety and depression. The TANDEM [Tailored intervention for Anxiety and Depression Management in chronic obstructive pulmonary disease (COPD)] intervention linked these two treatments by providing talking therapy based on cognitive­behavioural therapy during the waiting time following referral for pulmonary rehabilitation. The TANDEM treatment was delivered by respiratory healthcare professionals (e.g. nurses or physiotherapists) trained to deliver the talking therapy in six to eight weekly sessions. The sessions were conducted in the participant's home (or another convenient location), with brief telephone support during the pulmonary rehabilitation. Of 423 participants recruited to the study, 242 participants received TANDEM talking therapy and 181 participants received usual care (including a referral to pulmonary rehabilitation). We measured mental health, quality of life, social life, attendance at pulmonary rehabilitation and healthcare use in both groups at 6 and 12 months. Forty-three carers joined the study and we assessed their mental well-being. We interviewed patients, carers and health professionals to find out their views and experience of the TANDEM treatment. We also examined whether or not the TANDEM treatment was good value for money. The TANDEM treatment did not improve the mental or the physical health of people with chronic obstructive pulmonary disease. In addition, the TANDEM treatment cost the NHS an extra £770 per patient, which was not good value for money. The TANDEM treatment was well received, and many participants told us how it had helped them. Heath-care professionals noted how participants did not just have chronic obstructive pulmonary disease, but were coping with many physical, mental and social problems. The TANDEM intervention was not effective and, therefore, other strategies will be needed to help people with chronic obstructive pulmonary disease and mental health problems live with their condition.

Robotic trials in arthroplasty surgery.

Total hip and knee arthroplasty (THA, TKA) are largely successful procedures; however, both have variable outcomes, resulting in some patients being dissatisfied with the outcome. Surgeons are turning to technologies such as robotic-assisted surgery in an attempt to improve outcomes. Robust studies are needed to find out if these innovations are really benefitting patients. The Robotic Arthroplasty Clinical and Cost Effectiveness Randomised Controlled Trials (RACER) trials are multicentre, patient-blinded randomized controlled trials. The patients have primary osteoarthritis of the hip or knee. The operation is Mako-assisted THA or TKA and the control groups have operations using conventional instruments. The primary clinical outcome is the Forgotten Joint Score at 12 months, and there is a built-in analysis of cost-effectiveness. Secondary outcomes include early pain, the alignment of the components, and medium- to long-term outcomes. This annotation outlines the need to assess these technologies and discusses the design and challenges when conducting such trials, including surgical workflows, isolating the effect of the operation, blinding, and assessing the learning curve. Finally, the future of robotic surgery is discussed, including the need to contemporaneously introduce and evaluate such technologies.

GPs' views on emergency care treatment plans: an online survey.

BACKGROUND: A holistic approach to emergency care treatment planning is needed to ensure that patients' preferences are considered should their clinical condition deteriorate. To address this, emergency care and treatment plans (ECTPs) have been introduced. Little is known about their use in general practice. AIM: To find out GPs' experiences of, and views on, using ECTPs. DESIGN & SETTING: Online survey of GPs practising in England. METHOD: A total of 841 GPs were surveyed using the monthly online survey provided by medeConnect, a market research company. RESULTS: Forty-one per cent of responders' practices used Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) plans for ECTP, 8% used other ECTPs, and 51% used Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) forms. GPs were the predominant professional group completing ECTPs in the community. There was broad support for a wider range of community-based health and social care professionals being able to complete ECTPs. There was no system for reviewing ECTPs in 20% of responders' practices. When compared with using a DNACPR form, GPs using a ReSPECT form for ECTP were more comfortable having conversations about emergency care treatment with patients (odds ratio [OR] = 1.72, 95% confidence interval [CI] = 1.1 to 2.69) and family members (OR =1.85, 95% CI = 1.19 to 2.87). CONCLUSION: The potential benefits and challenges of widening the pool of health and social care professionals initiating and/or completing the ECTP process needs consideration. ReSPECT plans appear to make GPs more comfortable with ECTP discussions, supporting their implementation. Practice-based systems for reviewing ECTP decisions should be strengthened.

Opioid analgesics for nociceptive cancer pain: A comprehensive review.

Pain is one of the most burdensome symptoms in people with cancer, and opioid analgesics are considered the mainstay of cancer pain management. For this review, the authors evaluated the efficacy and toxicities of opioid analgesics compared with placebo, other opioids, nonopioid analgesics, and nonpharmacologic treatments for background cancer pain (continuous and relatively constant pain present at rest), and breakthrough cancer pain (transient exacerbation of pain despite stable and adequately controlled background pain). They found a paucity of placebo-controlled trials for background cancer pain, although tapentadol or codeine may be more efficacious than placebo (moderate-certainty to low-certainty evidence). Nonsteroidal anti-inflammatory drugs including aspirin, piroxicam, diclofenac, ketorolac, and the antidepressant medicine imipramine, may be at least as efficacious as opioids for moderate-to-severe background cancer pain. For breakthrough cancer pain, oral transmucosal, buccal, sublingual, or intranasal fentanyl preparations were identified as more efficacious than placebo but were more commonly associated with toxicities, including constipation and nausea. Despite being recommended worldwide for the treatment of cancer pain, morphine was generally not superior to other opioids, nor did it have a more favorable toxicity profile. The interpretation of study results, however, was complicated by the heterogeneity in the study populations evaluated. Given the limited quality and quantity of research, there is a need to reappraise the clinical utility of opioids in people with cancer pain, particularly those who are not at the end of life, and to further explore the effects of opioids on immune system function and quality of life in these individuals.

What's important for recovery after a total knee replacement? A systematic review of mixed methods studies.

BACKGROUND: Understanding how patients perceive and prioritise various aspects of recovery following total knee replacement, including pain, function and return to activity, will help clinicians in pre-operative consultations by ensuring they effectively address patient concerns and managing their expectations. AIMS: The aim of this study is to identify aspects of recovery that are important to people after a total knee replacement. METHODS: Studies were identified from Medline, Embase, PsycInfo, Cochrane Library and Web of Science. This mixed methods review included all original study types (quantitative, qualitative, discrete choice experiments and mixed methods design). Reviews and non-peer-reviewed publications were excluded. Studies with participants (age ≥ 18 years) who had a primary TKR for osteoarthritis were included. Studies of people with unicompartmental knee, patella-femoral or revision knee replacement were excluded. Recovery attributes were extracted from individual papers and grouped into recovery themes. RESULTS: A total of 23 studies with 8404 participants and 18 recovery themes were developed. The most frequently identified overarching theme was pain, followed by activities of daily living, mobility (walking), recreational activities, specific functional movements of the knee, use of walking aids, sexual activity and range of motion of the knee. Medical complications were an infrequently reported theme, however, was deemed to be high importance. CONCLUSIONS: Reducing pain, returning of activities and daily living and mobility are the three most frequently reported recovery domains for people after TKR. Clinicians should be aware of recovery themes, to ensure they are explored sufficiently when consenting for a TKR. Future research should aim to determine the relative importance of these attributes compared to each other. Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021253699.

Preconceptual administration of doxycycline in women with recurrent miscarriage and chronic endometritis: protocol for the Chronic Endometritis and Recurrent Miscarriage (CERM) trial, a multicentre, double-blind, placebo-controlled, adaptive randomised trial with an embedded translational substudy.

INTRODUCTION: Recurrent miscarriage is a common condition with a substantial associated morbidity. A hypothesised cause of recurrent miscarriage is chronic endometritis (CE). The aetiology of CE remains uncertain. An association between CE and recurrent miscarriage has been shown. This study will aim to determine if preconceptual administration of doxycycline, in women with recurrent miscarriages, and CE, reduces first trimester miscarriages, increasing live births. METHODS AND ANALYSIS: Chronic Endometritis and Recurrent Miscarriage is a multicentre, double-blind adaptive trial with an embedded translational substudy. Women with a history of two or more consecutive first trimester losses with evidence of CE on endometrial biopsy (defined as ≥5 CD138 positive cells per 10 mm2) will be randomised to oral doxycycline or placebo for 14 days. A subset will be recruited to a mechanistic substudy in which microbial swabs and preintervention/postintervention endometrial samples will be collected. Up to 3062 women recruited from 29 National Health Service (NHS) hospital sites across the UK are expected to be screened with up to 1500 women randomised in a 1:1 ratio. Women with a negative endometrial biopsy (defined as <5 CD138 positive cells per 10 mm2) will also be followed up to test validity of the tool. The primary outcome is live births plus pregnancies ≥24 + 0 weeks gestation at the end of the trial, in the first or subsequent pregnancy. Secondary clinical outcomes will also be assessed. Exploratory outcomes will assess the effect of doxycycline treatment on the endometrial microbiota, the differentiation capacity of the endometrium and the senescent profile of the endometrium with CE. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the NHS Research Ethics Committee Northwest-Haydock (19/NW/0462). Written informed consent will be gained from all participants. The results will be published in an open-access peer-reviewed journal and reported in the National Institute for Health and Care Research journals library. TRIAL REGISTRATION NUMBER: ISRCTN23947730.

Clinical effectiveness of pharmacological interventions for managing chronic migraine in adults: a systematic review and network meta-analysis.

BACKGROUND: Chronic migraine can be a profoundly disabling disorder that may be treated with preventive medications. However, uncertainty remains as to which preventive medication is the most effective. We present a network meta-analysis to determine the effectiveness and rank of preventive drugs for chronic migraine in adults. METHODS: We identified, reviewed, and extracted data from randomised controlled trials (RCTs) of preventive drugs for chronic migraine with at least 200 participants. Data were analysed using network meta-analysis. FINDINGS: We included 12 RCTs of six medications (Eptinezumab, Erenumab, Fremanezumab, Galcanezumab, Onabotulinumtoxin A, and Topiramate) compared to placebo or each other. All drugs effectively reduced monthly headache and migraine days compared with placebo. The most effective drug for monthly headache days was Eptinezumab 300mg, with a mean difference of -2.46 days, 95% Credible Interval (CrI): -3.23 to -1.69. On the Surface Under the Cumulative Ranking Area (SUCRA) analysis, the probability that Eptinezumab 300mg was ranked highest was 0.82. For monthly migraine days, the most effective medication was Fremanezumab-monthly, with a mean difference: -2.77 days, 95% CrI: -3.36 to -2.17, and 0.98 probability of being ranked the highest. All included drugs, except Topiramate, improved headache-related quality of life. No eligible studies were identified for the other common preventive oral medications such as Amitriptyline, Candesartan, and Propranolol. The main reasons were that the studies did not define chronic migraine, were undertaken before the definition of chronic migraine, or were too small. INTERPRETATION: All six medications were more effective than the placebo on monthly headache and migraine days. The absolute differences in the number of headache/migraine days are, at best, modest. No evidence was found to determine the relative effectiveness of the six included drugs with other oral preventive medications. REGISTRATION: PROSPERO (number CRD42021265990).

Competing treatments for migraine: a headache for decision-makers.

BACKGROUND: Migraine is the world's second most common disabling disorder, affecting 15% of UK adults and costing the UK over £1.5 billion per year. Several costly new drugs have been approved by National Institute for Health and Care Excellence. AIM: To assess the cost-effectiveness of drugs used to treat adults with chronic migraine. METHODS: We did a systematic review of placebo-controlled trials of preventive drugs for chronic migraine. We then assessed the cost-effectiveness of the currently prescribable drugs included in the review: Onabotulinum toxin A (BTA), Eptinezumab (100mg or 300mg), Fremanezumab (monthly or quarterly dose), Galcanezumab or Topiramate, each compared to placebo, and we evaluated them jointly. We developed a Markov (state-transition) model with a three-month cycle length to estimate the costs and quality-adjusted life years (QALYs) for the different medications from a UK NHS and Personal Social Services perspective. We used a two-year time horizon with a starting age of 30 years for the patient cohort. We estimated transition probabilities based on monthly headache days using a network meta-analysis (NMA) developed by us, and from published literature. We obtained costs from published sources and applied discount rates of 3.5% to both costs and outcomes. RESULTS: Deterministic results suggest Topiramate was the least costly option and generated slightly more QALYs than the placebo, whereas Eptinezumab 300mg was the more costly option and generated the most QALYs. After excluding dominated options, the incremental cost-effectiveness ratio (ICER) between BTA and Topiramate was £68,000 per QALY gained and the ICER between Eptinezumab 300mg and BTA was not within plausible cost-effectiveness thresholds. The cost-effectiveness acceptability frontier showed that Topiramate is the most cost-effective medication for any amount the decision maker is willing-to-pay per QALY. CONCLUSIONS: Among the various prophylactic medications for managing chronic migraine, only Topiramate was within typical cost-effectiveness threshold ranges. Further research is needed, ideally an economic evaluation alongside a randomised trial, to compare these newer, expensive CGRP MAbs with the cheaper oral medications.

'It was a joint plan we worked out together'. How the I-WOTCH programme enabled people with chronic non-malignant pain to taper their opioids: a process evaluation.

BACKGROUND: The Improving the Wellbeing of people with Opioid Treated CHronic pain (I-WOTCH) randomised controlled trial found that a group-based educational intervention to support people using strong opioids for chronic non-malignant pain helped a significant proportion of people to stop or decrease opioid use with no increase in pain-related disability. We report a linked process evaluation of the group-based intervention evaluated in comparison to a usual-care control group that received a self-help booklet and relaxation CD. METHODS: We interviewed 18 intervention facilitators, and 20 intervention and 20 control participants who had chronic non-malignant pain and were recruited from general (family) practices in the UK. Quantitative data included change mechanism questions on the trial questionnaires which explored motivation, expectations and self-efficacy. Fidelity was assessed by listening to a sample of audio-recorded group sessions and nurse consultations. Quantitative and qualitative data were integrated using 'follow a thread' and a mixed-methods matrix. FINDINGS: Four overarching themes emerged: (1) the right time to taper, (2) the backdrop of a life with chronic pain, (3) needing support and (4) the benefits of being in a group. Delivery fidelity was good, adherence (83%) and competence (79%) across a range of intervention groups. Staff delivering the intervention found three typical responses to the intervention: resistance, open to trying and feeling it was not the right time. The group experience was important to those in the intervention arm. It provided people with a forum in which to learn about the current thinking about opioid usage and its effects. It also gave them examples of how feasible or personally relevant coming off opioids might be. CONCLUSION: The process evaluation data showed that the I-WOTCH intervention was well delivered, well received and useful for most interviewees. Being 'the right time' to taper and having support throughout tapering, emerged as important factors within the context of living with chronic pain. TRIAL REGISTRATION NUMBER: ISRCTN49470934.

Comparison of different statistical models for the analysis of fracture events: findings from the Prevention of Falls Injury Trial (PreFIT).

BACKGROUND: Fractures are rare events and can occur because of a fall. Fracture counts are distinct from other count data in that these data are positively skewed, inflated by excess zero counts, and events can recur over time. Analytical methods used to assess fracture data and account for these characteristics are limited in the literature. METHODS: Commonly used models for count data include Poisson regression, negative binomial regression, hurdle regression, and zero-inflated regression models. In this paper, we compare four alternative statistical models to fit fracture counts using data from a large UK based clinical trial evaluating the clinical and cost-effectiveness of alternative falls prevention interventions in older people (Prevention of Falls Injury Trial; PreFIT). RESULTS: The values of Akaike information criterion and Bayesian information criterion, the goodness-of-fit statistics, were the lowest for negative binomial model. The likelihood ratio test of no dispersion in the data showed strong evidence of dispersion (chi-square = 225.68, p-value < 0.001). This indicates that the negative binomial model fits the data better compared to the Poisson regression model. We also compared the standard negative binomial regression and mixed effects negative binomial models. The LR test showed no gain in fitting the data using mixed effects negative binomial model (chi-square = 1.67, p-value = 0.098) compared to standard negative binomial model. CONCLUSIONS: The negative binomial regression model was the most appropriate and optimal fit model for fracture count analyses. TRIAL REGISTRATION: The PreFIT trial was registered as ISRCTN71002650.

UK robotic arthroplasty clinical and cost effectiveness randomised controlled trial for hips (RACER-Hip): a study protocol.

INTRODUCTION: The number of robotic-assisted hip replacement procedures has expanded globally with the intended aim of improving outcomes. Intraoperative robotic-arm systems add additional costs to total hip replacement (THR) surgery but may improve surgical precision and could contribute to diminished pain and improved function. Additionally, these systems may reduce the need for expensive revision surgery. Surgery with conventional instruments may be just as successful, quick and affordable. There is timely demand for a robust evaluation of this technology. METHODS AND ANALYSIS: The Robotic Arthroplasty Clinical and cost Effectiveness Randomised controlled trial for Hips (RACER-Hip) is a multicentre (minimum of six UK sites), participant-assessor blinded, randomised controlled trial. 378 participants with hip osteoarthritis requiring THR will be randomised (1:1) to receive robotic-assisted THR, or THR using conventional surgical instruments. The primary outcome is the Forgotten Joint Score at 12 months post-randomisation; a patient-reported outcome measure assessing participants' awareness of their joint when undertaking daily activities. Secondary outcomes will be collected post-operatively (pain, blood loss and opioid usage) and at 3, 6, 12, 24 months, then 5 and 10 years postrandomisation (including function, pain, health-related quality of life, reoperations and satisfaction). Allocation concealment will be accomplished using a computer-based randomisation procedure on the day of surgery. Blinding methods include the use of sham incisions for marker clusters and blinded operation notes. The primary analysis will adhere to the intention-to-treat principle. Results will adhere to Consolidated Standards of Reporting Trials statements. ETHICS AND DISSEMINATION: The trial was approved by an ethics committee (Solihull Research Ethics Committee, 30 June 2021, IRAS: 295831). Participants will provide informed consent before agreeing to participate. Results will be disseminated using peer-reviewed journal publications, presentations at international conferences and through the use of social media. We will develop plans to disseminate to patients and public with our patient partners. TRIAL REGISTRATION NUMBER: ISRCTN13374625.