Lower urinary tract symptoms in men: the TRIUMPH cluster RCT.

Background: Conservative therapies are recommended as initial treatment for male lower urinary tract symptoms. However, there is a lack of evidence on effectiveness and uncertainty regarding approaches to delivery. Objective: The objective was to determine whether or not a standardised and manualised care intervention delivered in primary care achieves superior symptomatic outcome for lower urinary tract symptoms to usual care. Design: This was a two-arm cluster randomised controlled trial. Setting: The trial was set in 30 NHS general practice sites in England. Participants: Participants were adult men (aged ≥ 18 years) with bothersome lower urinary tract symptoms. Interventions: Sites were randomised 1 : 1 to deliver the TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions trial intervention or usual care to all participants. The TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions intervention comprised a standardised advice booklet developed for the trial from the British Association of Urological Surgeons' patient information sheets, with patient and expert input. Patients were directed to relevant sections by general practice or research nurses/healthcare assistants following urinary symptom assessment, providing the manualised element. The healthcare professional provided follow-up contacts over 12 weeks to support adherence to the intervention. Main outcome measures: The primary outcome was the validated patient-reported International Prostate Symptom Score 12 months post consent. Rather than the minimal clinically important difference of 3.0 points for overall International Prostate Symptom Score, the sample size aimed to detect a difference of 2.0 points, owing to the recognised clinical impact of individual symptoms. Results: A total of 1077 men consented to the study: 524 in sites randomised to the intervention arm (n = 17) and 553 in sites randomised to the control arm (n = 13). A difference in mean International Prostate Symptom Score at 12 months was found (adjusted mean difference of -1.81 points, 95% confidence interval -2.66 to -0.95 points), with a lower score in the intervention arm, indicating less severe symptoms. Secondary outcomes of patient-reported urinary symptoms, quality of life specific to lower urinary tract symptoms and perception of lower urinary tract symptoms all showed evidence of a difference between the arms favouring the intervention. No difference was seen between the arms in the proportion of urology referrals or adverse events. In qualitative interviews, participants welcomed the intervention, describing positive effects on their symptoms, as well as on their understanding of conservative care and their attitude towards the experience of lower urinary tract symptoms. The interviews highlighted that structured, in-depth self-management is insufficiently embedded within general practitioner consultations. From an NHS perspective, mean costs and quality-adjusted life-years were similar between trial arms. The intervention arm had slightly lower mean costs (adjusted mean difference of -£29.99, 95% confidence interval -£109.84 to £22.63) than the usual-care arm, and a small gain in quality-adjusted life-years (adjusted mean difference of 0.001, 95% confidence interval -0.011 to 0.014). Conclusions: The intervention showed a small, sustained benefit for men's lower urinary tract symptoms and quality of life across a range of outcome measures in a UK primary care setting. Qualitative data showed that men highly valued the intervention. Intervention costs were marginally lower than usual-care costs. Limitations of the study included that trial participants were unmasked, with limited diversity in ethnicity and deprivation level. Additional research is needed to assess the applicability of the intervention for a more ethnically diverse population.. Trial registration: This trial is registered as ISRCTN11669964. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/90/03) and is published in full in Health Technology Assessment; Vol. 28, No. 13. See the NIHR Funding and Awards website for further award information.

Urinary problems among men become more common with age. Nearly one-third of all men aged > 65 years experience some urinary symptoms, which can have a substantial effect on their daily lives. Symptoms include needing to pass urine more often, urgently or during the night, and difficulties in passing urine. Men are usually diagnosed and treated by their general practitioner, and should be offered advice on controlling their symptoms themselves (e.g. lifestyle changes and exercises) before trying tablets or surgery. However, it is not known how helpful such advice is, and how general practices can effectively provide it. Thirty general practices in the West of England and Wessex took part in the study. Practices were split into two groups, with each practice providing either the TReatIng Urinary symptoms in Men in Primary Health care using non-pharmacological and non-surgical interventions care package or the practice's usual care to all of its patients in the trial. The TReatIng Urinary symptoms in Men in Primary Healthcare using nonpharmacological and non-surgical interventions care package included a booklet of advice to help control urinary symptoms, with a nurse or healthcare assistant directing men to relevant sections according to their symptoms, and providing follow-up contacts. We mainly assessed the benefits of the TReatIng Urinary symptoms in Men in Primary Healthcare using nonpharmacological and non-surgical interventions care package, compared with usual care, by using a questionnaire on urinary symptoms completed by participants. A total of 1077 men with urinary symptoms that bothered them joined the study. The main result was that men reported greater improvement in urinary symptoms with the TRIUMPH care package than with usual care, 12 months after joining the study. We also found that men receiving the TRIUMPH care package had a slight improvement in quality of life and outlook on their urinary symptoms. There was no difference between the two groups in the number of patients referred to hospital for treatment, the type, number and severity of side effects or cost to the NHS. Overall, the TRIUMPH care package was more effective in treating men with urinary symptoms than usual care by their general practice.

Cost-effectiveness of a primary healthcare intervention to treat male lower urinary tract symptoms: the TRIUMPH cluster randomised controlled trial.

OBJECTIVES: To estimate the cost-effectiveness of a primary care intervention for male lower urinary tract symptoms (LUTS) compared with usual care. DESIGN: Economic evaluation alongside a cluster randomised controlled trial from a UK National Health Service (NHS) perspective with a 12-month time horizon. SETTING: Thirty NHS general practice sites in England. PARTICIPANTS: 1077 men aged 18 or older identified in primary care with bothersome LUTS. INTERVENTIONS: A standardised and manualised intervention for the treatment of bothersome LUTS was compared with usual care. The intervention group (n=524) received a standardised information booklet with guidance on conservative treatment for LUTS, urinary symptom assessment and follow-up contacts for 12 weeks. The usual care group (n=553) followed local guidelines between general practice sites. MEASURES: Resource use was obtained from electronic health records, trial staff and participants, and valued using UK reference costs. Quality-adjusted life-years (QALYs) were calculated from the EQ-5D-5L questionnaire. Adjusted mean differences in costs and QALYs and incremental net monetary benefit were estimated. RESULTS: 866 of 1077 (80.4%) participants had complete data and were included in the base-case analysis. Over the 12-month follow-up period, intervention and usual care arms had similar mean adjusted costs and QALYs. Mean differences were lower in the intervention arm for adjusted costs -£29.99 (95% CI -£109.84 to £22.63) while higher in the intervention arm for adjusted QALYs 0.001 (95% CI -0.011 to 0.014). The incremental net monetary benefit statistic was £48.01 (95% CI -£225.83 to £321.85) at the National Institute for Health and Care Excellence UK threshold of £20 000 per QALY. The cost-effectiveness acceptability curve showed a 63% probability of the intervention arm being cost-effective at this threshold. CONCLUSIONS: Costs and QALYs were similar between the two arms at 12 months follow-up. This indicates that the intervention can be implemented in general practice at neutral cost. TRIAL REGISTRATION NUMBER: ISRCTN11669964.

Treatment of lower urinary tract symptoms in men in primary care using a conservative intervention: cluster randomised controlled trial.

OBJECTIVE: To determine whether a standardised and manualised care intervention in men in primary care could achieve superior improvement of lower urinary tract symptoms (LUTS) compared with usual care. DESIGN: Cluster randomised controlled trial. SETTING: 30 National Health Service general practice sites in England. PARTICIPANTS: Sites were randomised 1:1 to the intervention and control arms. 1077 men (≥18 years) with bothersome LUTS recruited between June 2018 and August 2019: 524 were assigned to the intervention arm (n=17 sites) and 553 were assigned to the usual care arm (n=13 sites). INTERVENTION: Standardised information booklet developed with patient and expert input, providing guidance on conservative and lifestyle interventions for LUTS in men. After assessment of urinary symptoms (manualised element), general practice nurses and healthcare assistants or research nurses directed participants to relevant sections of the manual and provided contact over 12 weeks to assist with adherence. MAIN OUTCOME MEASURES: The primary outcome was patient reported International Prostate Symptom Score (IPSS) measured 12 months after participants had consented to take part in the study. The target reduction of 2.0 points on which the study was powered reflects the minimal clinically important difference where baseline IPSS is <20. Secondary outcomes were patient reported quality of life, urinary symptoms and perception of LUTS, hospital referrals, and adverse events. The primary intention-to-treat analysis included 887 participants (82% of those recruited) and used a mixed effects multilevel linear regression model adjusted for site level variables used in the randomisation and baseline scores. RESULTS: Participants in the intervention arm had a lower mean IPSS at 12 months (adjusted mean difference -1.81 points, 95% confidence interval -2.66 to -0.95) indicating less severe urinary symptoms than those in the usual care arm. LUTS specific quality of life, incontinence, and perception of LUTS also improved more in the intervention arm than usual care arm at 12 months. The proportion of urology referrals (intervention 7.3%, usual care 7.9%) and adverse events (intervention seven events, usual care eight events) were comparable between the arms. CONCLUSIONS: A standardised and manualised intervention in primary care showed a sustained reduction in LUTS in men at 12 months. The mean difference of -1.81 points (95% confidence interval -0.95 to -2.66) on the IPSS was less than the predefined target reduction of 2.0 points. TRIAL REGISTRATION: ISRCTN Registry ISRCTN11669964.

Comparison of lotions, creams, gels and ointments for the treatment of childhood eczema: the BEE RCT.

Background: Emollients are recommended for children with eczema (atopic eczema/dermatitis). A lack of head-to-head comparisons of the effectiveness and acceptability of the different types of emollients has resulted in a 'trial and error' approach to prescribing. Objective: To compare the effectiveness and acceptability of four commonly used types of emollients for the treatment of childhood eczema. Design: Four group, parallel, individually randomised, superiority randomised clinical trials with a nested qualitative study, completed in 2021. A purposeful sample of parents/children was interviewed at ≈ 4 and ≈ 16 weeks. Setting: Primary care (78 general practitioner surgeries) in England. Participants: Children aged between 6 months and 12 years with eczema, of at least mild severity, and with no known sensitivity to the study emollients or their constituents. Interventions: Study emollients sharing the same characteristics in the four types of lotion, cream, gel or ointment, alongside usual care, and allocated using a web-based randomisation system. Participants were unmasked and the researcher assessing the Eczema Area Severity Index scores was masked. Main outcome measures: The primary outcome was Patient-Oriented Eczema Measure scores over 16 weeks. The secondary outcomes were Patient-Oriented Eczema Measure scores over 52 weeks, Eczema Area Severity Index score at 16 weeks, quality of life (Atopic Dermatitis Quality of Life, Child Health Utility-9 Dimensions and EuroQol-5 Dimensions, five-level version, scores), Dermatitis Family Impact and satisfaction levels at 16 weeks. Results: A total of 550 children were randomised to receive lotion (analysed for primary outcome 131/allocated 137), cream (137/140), gel (130/135) or ointment (126/138). At baseline, 86.0% of participants were white and 46.4% were female. The median (interquartile range) age was 4 (2-8) years and the median Patient-Oriented Eczema Measure score was 9.3 (SD 5.5). There was no evidence of a difference in mean Patient-Oriented Eczema Measure scores over the first 16 weeks between emollient types (global p = 0.765): adjusted Patient-Oriented Eczema Measure pairwise differences - cream-lotion 0.42 (95% confidence interval -0.48 to 1.32), gel-lotion 0.17 (95% confidence interval -0.75 to 1.09), ointment-lotion -0.01 (95% confidence interval -0.93 to 0.91), gel-cream -0.25 (95% confidence interval -1.15 to 0.65), ointment-cream -0.43 (95% confidence interval -1.34 to 0.48) and ointment-gel -0.18 (95% confidence interval -1.11 to 0.75). There was no effect modification by parent expectation, age, disease severity or the application of UK diagnostic criteria, and no differences between groups in any of the secondary outcomes. Median weekly use of allocated emollient, non-allocated emollient and topical corticosteroids was similar across groups. Overall satisfaction was highest for lotions and gels. There was no difference in the number of adverse reactions and there were no significant adverse events. In the nested qualitative study (n = 44 parents, n = 25 children), opinions about the acceptability of creams and ointments varied most, yet problems with all types were reported. Effectiveness may be favoured over acceptability. Parents preferred pumps and bottles over tubs and reported improved knowledge about, and use of, emollients as a result of taking part in the trial. Limitations: Parents and clinicians were unmasked to allocation. The findings may not apply to non-study emollients of the same type or to children from more ethnically diverse backgrounds. Conclusions: The four emollient types were equally effective. Satisfaction with the same emollient types varies, with different parents/children favouring different ones. Users need to be able to choose from a range of emollient types to find one that suits them. Future work: Future work could focus on how best to support shared decision-making of different emollient types and evaluations of other paraffin-based, non-paraffin and 'novel' emollients. Trial registration: This trial is registered as ISRCTN84540529 and EudraCT 2017-000688-34. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (HTA 15/130/07) and will be published in full in Health Technology Assessment; Vol. 27, No. 19. See the NIHR Journals Library website for further project information.

One in five children in the UK have eczema, a long-term, itchy, dry skin condition. It can significantly affect both the child and their family. Most children are diagnosed and looked after by their family doctor (general practitioner) and are prescribed moisturisers (also called emollients) to relieve skin dryness and other creams (topical corticosteroids) to control flare-ups. However, there are many different types of emollients and, to our knowledge, limited research to show which is better. In the Best Emollients for Eczema clinical trial, we compared the four main types of moisturisers ­ lotions, creams, gels and ointments. These types vary in their consistency, from thin to thick. We recruited 550 children (most of whom were white and had moderate eczema) and randomly assigned them to use one of the four different types as their main moisturiser for 16 weeks. We found no difference in effectiveness. Parent-reported eczema symptoms, eczema severity and quality of life were the same for all the four types of moisturisers. However, overall satisfaction was highest for lotions and gels. Ointments may need to be used less and cause less stinging. We interviewed 44 parents and 25 children who took part. Opinions of all four types of moisturisers varied. What one family liked about a moisturiser was not necessarily the same for another and preferences were individual to each user. Sometimes there was a tension between how well a moisturiser worked (effectiveness) and how easy it was to use (acceptability). In these cases, effectiveness tended to decide whether or not parents kept using it. People found moisturisers in pumps and bottles easier to use than those in tubs. A number of participants valued the information they were given about how to use moisturisers. Our results suggest that the type of moisturiser matters less than finding one that suits the child and family.

PROTEUS Study: A Prospective Randomized Controlled Trial Evaluating the Use of Artificial Intelligence in Stress Echocardiography.

BACKGROUND: Stress echocardiography (SE) is one of the most commonly used diagnostic imaging tests for coronary artery disease (CAD) but requires clinicians to visually assess scans to identify patients who may benefit from invasive investigation and treatment. EchoGo Pro provides an automated interpretation of SE based on artificial intelligence (AI) image analysis. In reader studies, use of EchoGo Pro when making clinical decisions improves diagnostic accuracy and confidence. Prospective evaluation in real world practice is now important to understand the impact of EchoGo Pro on the patient pathway and outcome. METHODS: PROTEUS is a randomized, multicenter, 2-armed, noninferiority study aiming to recruit 2,500 participants from National Health Service (NHS) hospitals in the UK referred to SE clinics for investigation of suspected CAD. All participants will undergo a stress echocardiogram protocol as per local hospital policy. Participants will be randomized 1:1 to a control group, representing current practice, or an intervention group, in which clinicians will receive an AI image analysis report (EchoGo Pro, Ultromics Ltd, Oxford, UK) to use during image interpretation, indicating the likelihood of severe CAD. The primary outcome will be appropriateness of clinician decision to refer for coronary angiography. Secondary outcomes will assess other health impacts including appropriate use of other clinical management approaches, impact on variability in decision making, patient and clinician qualitative experience and a health economic analysis. DISCUSSION: This will be the first study to assess the impact of introducing an AI medical diagnostic aid into the standard care pathway of patients with suspected CAD being investigated with SE. TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT05028179, registered on 31 August 2021; ISRCTN: ISRCTN15113915; IRAS ref: 293515; REC ref: 21/NW/0199.

Artificial intelligence based left ventricular ejection fraction and global longitudinal strain in cardiac amyloidosis.

BACKGROUND: Assessment of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) plays a key role in the diagnosis of cardiac amyloidosis (CA). However, manual measurements are time consuming and prone to variability. We aimed to assess whether fully automated artificial intelligence (AI) calculation of LVEF and GLS provide similar estimates and can identify abnormalities in agreement with conventional manual methods, in patients with pre-clinical and clinical CA. METHODS: We identified 51 patients (age 80 ± 10 years, 53% male) with confirmed CA according to guidelines, who underwent echocardiography before and/or at the time of CA diagnosis (median (IQR) time between observations 3.87 (1.93, 5.44 years). LVEF and GLS were quantified from the apical 2- and 4-chamber views using both manual and fully automated methods (EchoGo Core 2.0, Ultromics). Inter-technique agreement was assessed using linear regression and Bland-Altman analyses and two-way ANOVA. The diagnostic accuracy and time for detecting abnormalities (defined as LVEF ≤ 50% and GLS ≥ -15.1%, respectively) using AI was assessed by comparisons to manual measurements as a reference. RESULTS: There were no significant differences in manual and automated LVEF and GLS values in either pre-CA (p = .791 and p = .105, respectively) or at diagnosis (p = .463 and p = .722). The two methods showed strong correlation on both the pre-CA (r = .78 and r = .83) and CA echoes (r = .74 and r = .80) for LVEF and GLS, respectively. The sensitivity and specificity of AI-derived indices for detecting abnormal LVEF were 83% and 86%, respectively, in the pre-CA echo and 70% and 79% at CA diagnosis. The sensitivity and specificity of AI-derived indices for detecting abnormal GLS was 82% and 86% in the pre-CA echo and 100% and 67% at the time of CA diagnosis. There was no significant difference in the relationship between LVEF (p = .99) and GLS (p = .19) and time to abnormality between the two methods. CONCLUSION: Fully automated AI-calculated LVEF and GLS are comparable to manual measurements in patients pre-CA and at the time of CA diagnosis. The widespread implementation of automated LVEF and GLS may allow for more rapid assessment in different disease states with comparable accuracy and reproducibility to manual methods.

Effectiveness and safety of lotion, cream, gel, and ointment emollients for childhood eczema: a pragmatic, randomised, phase 4, superiority trial.

BACKGROUND: To our knowledge, there are no trials comparing emollients commonly used for childhood eczema. We aimed to compare the clinical effectiveness and safety of the four main emollient types: lotions, creams, gels, and ointments. METHODS: We did a pragmatic, individually randomised, parallel group, phase 4 superiority trial in 77 general practice surgeries in England. Children aged between 6 months and 12 years with eczema (Patient Orientated Eczema Measure [POEM] score >2) were randomly assigned (1:1:1:1; stratified by centre and minimised by baseline POEM score and age, using a web-based system) to lotions, creams, gels, or ointments. Clinicians and parents were unmasked. The initial emollient prescription was for 500 g or 500 mL, to be applied twice daily and as required. Subsequent prescriptions were determined by the family. The primary outcome was parent-reported eczema severity over 16 weeks (weekly POEM), with analysis as randomly assigned regardless of adherence, adjusting for baseline and stratification variables. Safety was assessed in all randomly assigned participants. This trial was registered with the ISRCTN registry, ISRCTN84540529. FINDINGS: Between Jan 19, 2018, and Oct 31, 2019, 12 417 children were assessed for eligibility, 550 of whom were randomly assigned to a treatment group (137 to lotion, 140 to cream, 135 to gel, and 138 to ointment). The numbers of participants who contributed at least two POEM scores and were included in the primary analysis were 131 in the lotion group, 137 in the cream group, 130 in the gel group, and 126 in the ointment group. Baseline median age was 4 years (IQR 2-8); 255 (46%) participants were girls, 295 (54%) were boys; 473 (86%) participants were White; and the mean POEM score was 9·3 (SD 5·5). There was no difference in eczema severity between emollient types over 16 weeks (global p value=0·77), with adjusted POEM pairwise differences of: cream versus lotion 0·42 (95% CI -0·48 to 1·32), gel versus lotion 0·17 (-0·75 to 1·09), ointment versus lotion -0·01 (-0·93 to 0·91), gel versus cream -0·25 (-1·15 to 0·65), ointment versus cream -0·43 (-1·34 to 0·48), and ointment versus gel -0·18 (-1·11 to 0·75). This result remained unchanged following multiple imputation, sensitivity, and subgroup analyses. The total number of adverse events did not significantly differ between the treatment groups (lotions 49 [36%], creams 54 [39%], gels 54 [40%], and ointments 48 [35%]; p=0·79), although stinging was less common with ointments (12 [9%] of 138 participants) than lotions (28 [20%] of 137), creams (24 [17%] of 140), or gels (25 [19%] of 135). INTERPRETATION: We found no difference in effectiveness between the four main types of emollients for childhood eczema. Users need to be able to choose from a range of emollients to find one that they are more likely to use effectively. FUNDING: National Institute for Health and Care Research.

Cost-Effectiveness of Group-Based Outpatient Physical Therapy After Total Knee Replacement: Results From the Economic Evaluation Alongside the ARENA Multicenter Randomized Controlled Trial.

OBJECTIVE: To assess the cost-utility and cost-effectiveness of a group-based outpatient physical therapy intervention delivered 6 weeks after primary total knee replacement (TKR) compared with usual care, alongside the Activity-Orientated Rehabilitation Following Knee Arthroplasty (ARENA) multicenter, randomized, controlled trial. METHODS: The economic analyses were performed from the perspective of the health and social care payer. We collected resource use for health and social care and productivity losses and patient outcomes for 12 months after surgery to derive costs and quality-adjusted life years (QALYs). Results were expressed in incremental cost-effectiveness ratios (ICERs), and incremental net monetary benefit statistics (INMBs) for a society willingness-to-pay (WTP) threshold of £20,000 per QALY gained, with sensitivity analyses to model specification and perspective. RESULTS: The cost of the ARENA physical therapy classes was mean ± SD £179 ± 39 per patient. Treatment in the year following surgery cost was, on average, £1,739 (95% confidence interval [95% CI] -£742, £4,221) per patient in the intervention group (n = 89), which was an additional £346 (95% CI £38, £653) per patient compared with usual care (n = 91) (£1,393 [95% CI -£780, £3,568]). QALY benefits were 0.0506 higher (95% CI 0.009, 0.09) in the intervention group, corresponding to an additional 19 days in "perfect health." The ICER for the intervention group was £6,842 per QALY gained, and the INMB was £665 (95% CI £139, £1,191), with a 92% probability of being cost-effective, and no less than 73% in all sensitivity analysis scenarios. CONCLUSION: The addition of group-based outpatient physical therapy classes to usual care improves quality of life and is a cost-effective treatment option following TKR for a society WTP threshold of £20,000 per QALY gained.

The STAR care pathway for patients with pain at 3 months after total knee replacement: a multicentre, pragmatic, randomised, controlled trial.

BACKGROUND: Approximately 20% of people experience chronic pain after total knee replacement, but effective treatments are not available. We aimed to evaluate the clinical effectiveness and cost-effectiveness of a new care pathway for chronic pain after total knee replacement. METHODS: We did an unmasked, parallel group, pragmatic, superiority, randomised, controlled trial at eight UK National Health Service (NHS) hospitals. People with chronic pain at 3 months after total knee replacement surgery were randomly assigned (2:1) to the Support and Treatment After Replacement (STAR) care pathway plus usual care, or to usual care alone. The STAR intervention aimed to identify underlying causes of chronic pain and enable onward referrals for targeted treatment through a 3-month post-surgery assessment with an extended scope practitioner and telephone follow-up over 12 months. Co-primary outcomes were self-reported pain severity and pain interference in the replaced knee, assessed with the Brief Pain Inventory (BPI) pain severity and interference scales at 12 months (scored 0-10, best to worst) and analysed on an as-randomised basis. Resource use, collected from electronic hospital records and participants, was valued with UK reference costs. Quality-adjusted life-years (QALYs) were calculated from EQ-5D-5L responses. This trial is registered with ISRCTN, ISRCTN92545361. FINDINGS: Between Sept 6, 2016, and May 31, 2019, 363 participants were randomly assigned to receive the intervention plus usual care (n=242) or to receive usual care alone (n=121). Participants had a median age of 67 years (IQR 61 to 73), 217 (60%) of 363 were female, and 335 (92%) were White. 313 (86%) patients provided follow-up data at 12 months after randomisation (213 assigned to the intervention plus usual care and 100 assigned to usual care alone). At 12 months, the mean between-group difference in the BPI severity score was -0·65 (95% CI -1·17 to -0·13; p=0·014) and the mean between-group difference in the BPI interference score was -0·68 (-1·29 to -0·08; p=0·026), both favouring the intervention. From an NHS and personal social services perspective, the intervention was cost-effective (greater improvement with lower cost), with an incremental net monetary benefit of £1256 (95% CI 164 to 2348) at £20 000 per QALY threshold. One adverse reaction of participant distress was reported in the intervention group. INTERPRETATION: STAR is a clinically effective and cost-effective intervention to improve pain outcomes over 1 year for people with chronic pain at 3 months after total knee replacement surgery. FUNDING: National Institute for Health Research.

Screening to Identify Postoperative Pain and Cross-Sectional Associations Between Factors Identified in This Process With Pain and Function, Three Months After Total Knee Replacement.

OBJECTIVE: To describe the screening and recruitment process of a randomized trial and evaluate associations with knee pain and function 3 months after total knee replacement (TKR). METHODS: In order to screen for a multicenter trial, a total of 5,036 patients were sent the Oxford Knee Score (OKS) questionnaire 10 weeks post-TKR. Patients who reported pain in their replaced knee (score of ≤14 on the OKS pain component) completed a second OKS questionnaire 12 weeks post-TKR. Those patients who were still experiencing pain 12 weeks post-TKR completed a detailed questionnaire 13 weeks post-TKR. These data were used to characterize pain in a cross-sectional analysis. Multivariable regression was performed in order to identify factors associated with pain and function at 13 weeks post-TKR. RESULTS: We received OKS questionnaires from 3,058 of 5,063 TKR patients (60%), and 907 of the 3,058 (30%) reported pain in their replaced knee 10 weeks post-TKR. By 12 weeks, 179 of 553 patients (32%) reported improved pain (score of >14 on the OKS pain component). At 13 weeks, 192 of 363 patients (53%) who completed a detailed questionnaire reported neuropathic pain, 94 of 362 (26%) reported depression symptoms, and 95 of 363 (26%) anxiety symptoms. More severe pain at 13 weeks postoperatively was associated with poorer general health, poorer physical health, more pain worry, and lower satisfaction with surgery outcome. More severe functional limitation was associated with higher levels of depression, more pain worry, lower satisfaction with surgery outcome, and higher pain acceptance. CONCLUSION: Screening after TKR identified individuals with pain. We identified several potential targets (physical and mental health outcomes, acceptance of pain, and quality of life) for tailored intervention to improve outcomes for patients. Future trials of multidisciplinary interventions warranted.

Effectiveness and cost-effectiveness of the PLAN-A intervention, a peer led physical activity program for adolescent girls: results of a cluster randomised controlled trial.

BACKGROUND: Physical activity is associated with improved health. Girls are less active than boys. Pilot work showed that a peer-led physical activity intervention called PLAN-A was a promising method of increasing physical activity in secondary school age girls. This study examined the effectiveness and cost-effectiveness of the PLAN-A intervention. METHODS: We conducted a cluster randomised controlled trial with Year 9 (13-14 year old) girls recruited from 20 secondary schools. Schools were randomly assigned to the PLAN-A intervention or a non-intervention control group after baseline data collection. Girls nominated students to be peer leaders. The top 18 % of girls nominated by their peers in intervention schools received three days of training designed to prepare them to support physical activity. Data were collected at two time points, baseline (T0) and 5-6 months post-intervention (T1). Participants wore an accelerometer for seven days to assess the primary outcome of mean weekday minutes of moderate-to-vigorous physical activity (MVPA). Multivariable mixed effects linear regression was used to estimate differences in the primary outcome between the two arms on an Intention-to-Treat (ITT) basis. Resource use and quality of life were measured and a within trial economic evaluation from a public sector perspective was conducted. RESULTS: A total of 1558 girls were recruited to the study. At T0, girls in both arms engaged in an average of 51 min of MVPA per weekday. The adjusted mean difference in weekday MVPA at T1 was - 2.84 min per day (95 % CI = -5.94 to 0.25) indicating a slightly larger decline in weekday MVPA in the intervention group. Results were broadly consistent when repeated using a multiple imputation approach and for pre-specified secondary outcomes and sub-groups. The mean cost of the PLAN-A intervention was £2817 per school, equivalent to £31 per girl. Economic analyses indicated that PLAN-A did not lead to demonstrable cost-effectiveness in terms of cost per unit change in QALY. CONCLUSIONS: This study has shown that the PLAN-A intervention did not result in higher levels of weekday MVPA or associated secondary outcomes among Year 9 girls. The PLAN-A intervention should not be disseminated as a public health strategy. TRIAL REGISTRATION: ISRCTN14539759 -31 May, 2018.

Physical Activity and Psychosocial Characteristics of the Peer Supporters in the PLAN-A Study-A Latent Class Analysis.

PLAN-A is a cluster randomised controlled trial of a peer-led physical activity intervention which uses peer supporters to increase the physical activity of 13-14-year-old girls in the UK. This paper uses latent class analysis to identify classes in the whole study population and investigate how those selected as peer supporters in PLAN-A were drawn from different social groups. We identified five classes of girls, based on psychosocial variables (self-esteem, physical activity self-efficacy, motivation, physical activity values among friends and peer support for physical activity (PA) and physical activity behaviour variables (average minutes of weekday MVPA, sedentary time and screen viewing). Peer supporters were similar to the whole study population in terms of overall demographics, but were drawn unequally from the five classes. In addition, there was considerable variation in the distribution of peer supporters between schools. The selection of peer supporters is an integral component of peer-led interventions and should be explored and linked to underlying theory to understand the characteristics of those recruited. However, demographic representativeness is not necessarily the aim, and simple reporting of overall demographic comparisons may mask important differences within subgroups.

Continuity of care as a predictor of ongoing frequent attendance in primary care: a retrospective cohort study.

BACKGROUND: Frequent attenders (FAs) in primary care receive considerable resources with uncertain benefit. Only some FAs attend persistently. Modestly successful models have been built to predict persistent attendance. Nevertheless, an association between relational continuity of care and persistent frequent attendance remains unclear, and could be important considering both the UK government and Royal College of General Practitioner's (RCGP) aim of improving continuity. AIM: To identify predictive measures (including continuity) for persistent frequent attendance that may be modified in future interventions. DESIGN & SETTING: This is a retrospective cohort study sampling 35 926 adult patients registered in seven Bristol practices. METHOD: The top 3% (1227) of patients by frequency of GP consultations over 6 months were classed as FAs. Individual relational continuity was measured over the same period using the Usual Provider Continuity (UPC) index. Attendance change was calculated for the following 6 months. Multivariable logistic regression analysis was used to determine variables that predicted attendance change. RESULTS: FAs were on average 8.41 years older (difference 95% confidence interval [CI] = 7.33 to 9.50, P<0.001) and more likely to be female (65.36% versus 57.88%) than non-FAs. In total, 79.30% of FAs decreased attendance over the subsequent 6 months. No association was found between continuity and subsequent attendance. Increasing age was associated with maintained frequent attendance. CONCLUSION: Continuity does not predict change in frequent attendance. In addition to improving continuity, recent government policy is focused on increasing primary care access. If both aims are achieved it will be interesting to observe any effect on frequent attendance.

The content and conduct of GP consultations for dermatology problems: a cross-sectional study.

BACKGROUND: Skin complaints are common in primary care, and poor outcomes in long-term conditions are often due to low adherence to treatment. Shared decision making and self-management support may help, yet there is little understanding of patient involvement or the support provided by GPs. AIM: To describe the content of primary care consultations for skin problems, including shared decision making practice, delivery of self-management advice, and follow-up. DESIGN AND SETTING: Cross-sectional study of video-recorded UK adult GP consultations and linked data. METHOD: A coding tool was developed and applied to all consultations with skin problems. Shared decision making was assessed using the observer OPTION5 scale. RESULTS: A total of 45/318 consultations (14.2%) related to one or more skin problems, which were discussed alongside other problems in 71.1% (32/45) of consultations. Of the 100 different problems discussed in these consultations, 51 were dermatological. The mean amount of time spent on skin problems in the consultations was 4 minutes 16 seconds. Medication was recommended for 66.7% (34/51) of skin problems, with low shared decision making (mean OPTION5 score = 10.7). Self-management advice (verbal only) was given for 47.1% (24/51) of skin problems. Most skin problems (84.3%; 43/51) were not referred to secondary care; 32.6% (14/43) of the skin problems not referred were seen again in primary care within 12 weeks, of which 35.7% (5/14) follow-up appointments were not planned. CONCLUSION: In this study, skin problems were usually presented alongside other complaints and resulted in a medication recommendation. Shared decision making was uncommon and self-management advice not consistently given, with re-attendance for the same problem common. GPs' training should reflect how frequently skin problems are seen and seek to improve patient involvement in decision making and support self-management.

Observational Cost-Effectiveness Analysis Using Routine Data: Admission and Discharge Care Bundles for Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory disease, and accounts for a substantial proportion of unplanned hospital admissions. Care bundles for COPD are a set of standardised, evidence-based interventions that may improve outcomes in hospitalised COPD patients. We estimated the cost effectiveness of care bundles for acute exacerbations of COPD using routinely collected observational data. METHODS: Data were collected from implementation (n = 7) and comparator (n = 7) acute hospitals located in England and Wales. We conducted a difference-in-difference cost-effectiveness analysis using a secondary care (i.e. hospital) perspective to examine the effect on National Health Service (NHS) costs and 90-day mortality of implementing care bundles compared with usual care for patients admitted to hospital with an acute exacerbation of COPD. Adjusted models included as covariates patient age, sex, deprivation, ethnicity and seasonal effects and mixed effects for site. RESULTS: Outcomes and baseline characteristics of up to 12,532 patients were analysed using both complete case and multiply imputed models. Implementation of bundles varied. COPD care bundles were associated with slightly lower secondary care costs, but there was no evidence that they improved outcomes once adjustments were made for site and baseline covariates. Care bundles were unlikely to be cost effective for the NHS with an estimated net monetary benefit per 90-day death avoided from an adjusted multiply imputed model of -£1231 (95% confidence interval - £2428 to - £35) at a high cost-effectiveness threshold of £50,000 per 90-day death avoided. CONCLUSION AND RECOMMENDATIONS: Care bundles for COPD did not appear to be cost effective, although this finding may have been influenced by unmeasured variations in bundle implementation and other potential confounding factors.

Effect of Group-Based Outpatient Physical Therapy on Function After Total Knee Replacement: Results From a Multicenter Randomized Controlled Trial.

OBJECTIVE: To evaluate the long-term clinical effectiveness of a novel group-based outpatient physical therapy (PT) following total knee replacement (TKR). METHODS: In this 2-center, unblinded, superiority, randomized controlled trial, 180 patients on a waiting list for primary TKR due to osteoarthritis were randomized to a 6 session group-based outpatient PT intervention and usual care (n = 89) or usual care alone (n = 91). The primary outcome was patient-reported functional ability measured by the Lower Extremity Functional Scale at 12 months postoperative. Secondary outcomes included knee symptoms, depression, anxiety, and satisfaction. Questionnaires were completed preoperatively and at 3, 6, and 12 months postoperatively. RESULTS: The mean difference in function between groups was 4.47 (95% confidence interval [95% CI] 0.20, 8.75; P = 0.04) at 12 months postoperative, favoring the intervention. The mean difference in function between groups decreased over time, from 8.1 points at 3 months (95% CI 3.8, 12.4; P < 0.001) to 5.4 (95% CI 1.1, 9.8; P = 0.015) at 6 months postoperative. There were no clinically relevant differences in any secondary outcomes between groups, although patients in the intervention group were more likely to be satisfied with their PT. No serious adverse events related to the intervention were reported. CONCLUSION: Supplementing usual care with this group-based outpatient PT intervention led to improvements in function at 12 months after TKR, although the magnitude of the difference was below the minimum clinically important difference of 9 points. However, patient satisfaction was higher in the intervention group, and there was some evidence of clinically relevant improvements in function at 3 months.

Development of a tool for coding safety-netting behaviours in primary care: a mixed-methods study using existing UK consultation recordings.

BACKGROUND: Safety netting is recommended in a variety of clinical settings, yet there are no tools to record clinician safety-netting communication behaviours. AIM: To develop and assess the inter-rater reliability (IRR) of a coding tool designed to assess safety-netting communication behaviours in primary care consultations. DESIGN AND SETTING: A mixed-methods study using an existing dataset of video-and audio-recorded UK primary care consultations. METHOD: Key components that should be assessed in a coding tool were identified using the published literature and relevant guidelines. An iterative approach was utilised to continuously refine and generate new codes based on the application to real-life consultations. After the codebook had been generated, it was applied to 35 problems in 24 consultations independently by two coders. IRR scores were then calculated. RESULTS: The tool allows for the identification and quantification of the key elements of safety-netting advice including: who initiates the advice and at which stage of the consultation; the number of symptoms or conditions the patient is advised to look out for; what action patients should take and how urgently; as well as capturing how patients respond to such advice plus important contextual codes such as the communication of diagnostic uncertainty, the expected time course of an illness, and any follow-up plans. The final tool had substantial levels of IRR with the mean average agreement for the final tool being 88% (κ = 0.66). CONCLUSION: The authors have developed a novel tool that can reliably code the extent of clinician safety-netting communication behaviours.

Safety netting in routine primary care consultations: an observational study using video-recorded UK consultations.

BACKGROUND: Safety-netting advice is information shared with a patient or their carer designed to help them identify the need to seek further medical help if their condition fails to improve, changes, or if they have concerns about their health. AIM: To assess when and how safety-netting advice is delivered in routine GP consultations. DESIGN AND SETTING: This was an observational study using 318 recorded GP consultations with adult patients in the UK. METHOD: A safety-netting coding tool was applied to all consultations. Logistic regression for the presence or absence of safety-netting advice was compared between patient, clinician, and problem variables. RESULTS: A total of 390 episodes of safety-netting advice were observed in 205/318 (64.5%) consultations for 257/555 (46.3%) problems. Most advice was initiated by the GP (94.9%) and delivered in the treatment planning (52.1%) or closing (31.5%) consultation phases. Specific advice was delivered in almost half (47.2%) of episodes. Safety-netting advice was more likely to be present for problems that were acute (odds ratio [OR] 2.18, 95% confidence interval [CI] = 1.30 to 3.64), assessed first in the consultation (OR 2.94, 95% CI = 1.85 to 4.68) or assessed by GPs aged ≤49 years (OR 2.56, 95% CI = 1.45 to 4.51). Safety-netting advice was documented for only 109/242 (45.0%) problems. CONCLUSION: GPs appear to commonly give safety-netting advice, but the contingencies or actions required on the patient's part may not always be specific or documented. The likelihood of safety-netting advice being delivered may vary according to characteristics of the problem or the GP. How to assess safety-netting outcomes in terms of patient benefits and harms does warrant further exploration.

Best emollients for eczema (BEE) - comparing four types of emollients in children with eczema: protocol for randomised trial and nested qualitative study.

INTRODUCTION: Atopic dermatitis/eczema affects around 20% of children and is characterised by inflamed, dry, itchy skin. Guidelines recommend 'leave-on' emollients that are applied directly to the skin to add or trap moisture and used regularly, they can soothe, enhance the skin barrier and may prevent disease 'flares'. However, the suitability of the many different emollients varies between people and there is little evidence to help prescribers and parents and carers decide which type to try first. METHODS AND ANALYSIS: Design: pragmatic, multicentre, individually randomised, parallel group superiority trial of four types of emollient (lotions, creams, gel or ointments). SETTING: general practitioner surgeries in England. PARTICIPANTS: children aged over 6 months and less than 12 years with mild-to-severe eczema and no known sensitivity to study emollients. INTERVENTIONS: study-approved lotion, cream, gel or ointment as the only leave-on emollient for 16 weeks, with directions to apply twice daily and as required. Other treatments, such as topical corticosteroids, used as standard care. FOLLOW-UP: 52 weeks. PRIMARY OUTCOME: validated patient-orientated eczema measure measured weekly for 16 weeks. SECONDARY OUTCOMES: eczema signs (Eczema Area Severity Index) by masked researcher, treatment use, parent satisfaction, adverse events, child and family quality of life (Atopic Dermatitis Quality of Life, Child Health Utility 9D and Dermatitis Family Impact). SAMPLE SIZE: 520 participants (130 per group). ANALYSIS: intention-to-treat using linear mixed models for repeated measures.Nested qualitative study: audio-recording of sample of baseline appointments and up to 60 interviews with participants at 4 and 16 weeks, interviews to be transcribed and analysed thematically. ETHICS AND DISSEMINATION: Ethics approval granted by the NHS REC (South West - Central Bristol Research Ethics Committee 17/SW/0089). Findings will be presented at conferences, published in open-access peer-reviewed journals and the study website; and summaries shared with key stakeholders. TRIAL REGISTRATION NUMBER: ISRCTN84540529.

Action 3:30R: process evaluation of a cluster randomised feasibility study of a revised teaching assistant-led extracurricular physical activity intervention for 8 to 10 year olds.

BACKGROUND: Numerous interventions to increase children's physical activity levels are published, yet, few studies report indicators of external validity. Process evaluations are critical for assessing intervention implementation, sustainability and effectiveness. A mixed-methods process evaluation, using the RE-AIM framework, was conducted to evaluate the internal and external validity of Action 3:30R, a revised teaching assistant-led after-school intervention which aimed to increase physical activity in children aged 8-10 years and was underpinned by Self-determination Theory (SDT). METHODS: Data were collected and reported in line with the five components of RE-AIM (Reach, Effectiveness, Adoption, Implementation and Maintenance). Quantitative measures included logbooks, registers and self-reported teaching-efficacy, autonomy support, child enjoyment and perceived exertion questionnaires. Questionnaire data were collected at three points throughout the 15-week intervention. Observations by trained researchers were also conducted to assess fidelity to the intervention manual and its underpinning theory. Post-intervention focus groups with pupils and interviews with teaching assistants (TAs), school staff and external stakeholders explored the implementation and potential sustainability of Action 3:30R from stakeholders' perspectives. RESULTS: Action 3:30R appealed to a broad range of pupils, including girls and less-active pupils. The Action 3:30R TA training was implemented as intended and was perceived as valuable professional development. Releasing staff for training was a barrier in two of the six intervention schools, which were unable to deliver the intervention as a result. Pupils enjoyed the intervention, and the Action 3:30R core principles underpinned by SDT were implemented with high fidelity, as was the intervention itself. Scheduling conflicts with other clubs and lack of parental support were perceived as the main barriers to recruitment and attendance. Lack of space and season were cited as the main barriers affecting the quality of delivery. The study shows evidence of maintenance, as one intervention school decided to continue Action 3:30R beyond the study. Funding and continued TA training were suggested as factors which may affect the maintenance of Action 3:30R. CONCLUSIONS: Action 3:30R is an enjoyable, autonomy-supportive after-school programme, which engages a range of pupils and offers TAs valuable training. RE-AIM provided helpful structure and is recommended for intervention evaluations. TRIAL REGISTRATION: ISRCTN34001941 . Prospectively registered 01/12/2016.