Graded exercise therapy compared to activity management for paediatric chronic fatigue syndrome/myalgic encephalomyelitis: pragmatic randomized controlled trial.

The MAGENTA pragmatic parallel groups randomized controlled trial compared graded exercise therapy (GET) with activity management (AM) in treating paediatric myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). Children aged 8-17 years with mild/moderate ME/CFS and presenting to NHS specialist paediatric services were allocated at random to either individualised flexible treatment focussing on physical activity (GET, 123 participants) or on managing cognitive, school and social activity (AM, 118 participants) delivered by NHS therapists. The primary outcome was the self-reported short-form 36 physical function subscale (SF-36-PFS) after 6 months, with higher scores indicating better functioning. After 6 months, data were available for 201 (83%) participants who received a mean of 3.9 (GET) or 4.6 (AM) treatment sessions. Comparing participants with measured outcomes in their allocated groups, the mean SF-36-PFS score changed from 54.8 (standard deviation 23.7) to 55.7 (23.3) for GET and from 55.5 (23.1) to 57.7 (26.0) for AM giving an adjusted difference in means of -2.02 (95% confidence interval -7.75, 2.70). One hundred thirty-five participants completed the mean SF-36-PFS at 12 months, and whilst further improvement was observed, the difference between the study groups remained consistent with chance. The two study groups showed similar changes on most of the secondary outcome measures: Chalder Fatigue, Hospital Anxiety and Depression Scale: Depression, proportion of full-time school attended, a visual analogue pain scale, participant-rated change and accelerometer measured physical activity, whether at the 6-month or 12-month assessment. There was an isolated finding of some evidence of an improvement in anxiety in those allocated to GET, as measured by the Hospital Anxiety and Depression Scale at 6 months, with the 12-month assessment, and the Spence Children's Anxiety scale being aligned with that finding. There was weak evidence of a greater risk of deterioration with GET (27%) than with AM (17%; p = 0.069). At conventional UK cost per QALY thresholds, the probability that GET is more cost-effective than AM ranged from 18 to 21%. Whilst completion of the SF-36-PFS, Chalder Fatigue Scale and EQ-5D-Y was good at the 6-month assessment point, it was less satisfactory for other measures, and for all measures at the 12-month assessment.  Conclusion: There was no evidence that GET was more effective or cost-effective than AM in this setting, with very limited improvement in either study group evident by the 6-month or 12-month assessment points.  Trial registration: The study protocol was registered at www.isrctn.com (3rd September 2015; ISRCTN 23962803) before the start of enrolment to the initial feasibility phase.

Randomised pilot and feasibility trial of a group intervention for men who perpetrate intimate partner violence against women.

BACKGROUND: There is a need for robust evidence on the effectiveness and cost-effectiveness of domestic abuse perpetrator programmes in reducing abusive behaviour and improving wellbeing for victim/survivors. While any randomised controlled trial can present difficulties in terms of recruitment and retention, conducting such a trial with domestic abuse perpetrators is particularly challenging. This paper reports the pilot and feasibility trial of a voluntary domestic abuse perpetrator group programme in the United Kingdom. METHODS: This was a pragmatic individually randomised pilot and feasibility trial with an integrated qualitative study in one site (covering three local-authority areas) in England. Male perpetrators were randomised to either the intervention or usual care. The intervention was a 23-week group programme for male perpetrators in heterosexual relationships, with an average of three one-to-one sessions, and one-to-one support for female current- or ex-partners delivered by third sector organisations. There was no active control treatment for men, and partners of control men were signposted towards domestic abuse support services. Data were collected at three-monthly intervals for nine months from male and female participants. The main objectives assessed were recruitment, randomisation, retention, data completeness, fidelity to the intervention model, and acceptability of the trial design. RESULTS: This study recruited 36 men (22 randomly allocated to attend the intervention group programme, 14 to usual care), and 15 current- or ex-partners (39% of eligible partners). Retention and completeness of data were high: 67% of male (24/36), and 80% (12/15) of female participants completed the self-reported questionnaire at nine months. A framework for assessing fidelity to the intervention was developed. In interviews, men who completed all or most of the intervention gave positive feedback and reported changes in their own behaviour. Partners were also largely supportive of the trial and were positive about the intervention. Participants who were not allocated to the intervention group reported feeling disappointed but understood the rationale for the trial. CONCLUSIONS: It was feasible to recruit, randomise and retain male perpetrators and female victim/survivors of abuse and collect self-reported outcome data. Participants were engaged in the intervention and reported positive benefits. The trial design was seen as acceptable. TRIAL REGISTRATION: ISRCTN71797549, submitted 03/08/2017, retrospectively registered 27/05/2022.

Developing an online, searchable database to systematically map and organise current literature on retention research (ORRCA2).

BACKGROUND: Addressing recruitment and retention challenges in trials is a key priority for methods research, but navigating the literature is difficult and time-consuming. In 2016, ORRCA (www.orrca.org.uk) launched a free, searchable database of recruitment research that has been widely accessed and used to support the update of systematic reviews and the selection of recruitment strategies for clinical trials. ORRCA2 aims to create a similar database to map the growing volume and importance of retention research. METHODS: Searches of Medline (Ovid), CINAHL, PsycINFO, Scopus, Web of Science Core Collection and the Cochrane Library, restricted to English language and publications up to the end of 2017. Hand searches of key systematic reviews were undertaken and randomised evaluations of recruitment interventions within the ORRCA database on 1 October 2020 were also reviewed for any secondary retention outcomes. Records were screened by title and abstract before obtaining the full text of potentially relevant articles. Studies reporting or evaluating strategies, methods and study designs to improve retention within healthcare research were eligible. Case reports describing retention challenges or successes and studies evaluating participant reported reasons for withdrawal or losses were also included. Studies assessing adherence to treatments, attendance at appointments outside of research and statistical analysis methods for missing data were excluded. Eligible articles were categorised into one of the following evidence types: randomised evaluations, non-randomised evaluations, application of retention strategies without evaluation and observations of factors affecting retention. Articles were also mapped against a retention domain framework. Additional data were extracted on research outcomes, methods and host study context. RESULTS: Of the 72,904 abstracts screened, 4,364 full texts were obtained, and 1,167 articles were eligible. Of these, 165 (14%) were randomised evaluations, 99 (8%) non-randomised evaluations, 319 (27%) strategies without evaluation and 584 (50%) observations of factors affecting retention. Eighty-four percent (n = 979) of studies assessed the numbers of participants retained, 27% (n = 317) assessed demographic differences between retained and lost participants, while only 4% (n = 44) assessed the cost of retention strategies. The most frequently reported domains within the 165 studies categorised as 'randomised evaluations of retention strategies' were participant monetary incentives (32%), participant reminders and prompts (30%), questionnaire design (30%) and data collection location and method (26%). CONCLUSION: ORRCA2 builds on the success of ORRCA extending the database to organise the growing volume of retention research. Less than 15% of articles were randomised evaluations of retention strategies. Mapping of the literature highlights several areas for future research such as the role of research sites, clinical staff and study design in enhancing retention. Future studies should also include cost-benefit analysis of retention strategies.

Driving in Parkinson's disease: a retrospective study of driving and mobility assessments.

BACKGROUND: To guide decision-making about driving ability, some patients with Parkinson's disease (PD) undergo specialist driving assessment. However, decisions about driving safety in most patients need to be made without this definitive test. There is no consensus on what predicts unsafe driving in PD nor a validated prediction tool to guide clinician decision-making and the need to refer for further assessment. OBJECTIVES: To describe the characteristics of patients with PD assessed at a Driving Mobility Centre and investigate factors that predict driving assessment outcome. METHODS: Retrospective cohort study of patients with PD assessed between 2012 and 2016. Descriptive analyses and logistic models to determine factors predicting a negative outcome. RESULTS: There were 86 assessments of patients with PD. The mean age was 70 years (±9.2), 86% were male, median disease duration 7 years (interquartile range 5-12.5 years) and 59% were referred by the Driver and Vehicle Licensing Agency. In total, 62% had a negative 'not drive' outcome. The Rookwood Driving Battery (RDB), depth of vision deficit, usual driving frequency, age, duration license held and response time were all predictors in univariable analysis. The RDB was the best predictor of assessment failure, conditional on other variables in a backward stepwise model (odds ratio 1.29; 95% confidence interval 1.05, 1.60; P = 0.015). CONCLUSIONS: This is the first study to describe patients with PD undergoing driving assessments in the UK. In this population, RDB performance was the best predictor of outcome. Future prospective studies are required to better determine predictors of driving ability to guide development of prediction tools for implementation into clinical practice.

Recruiting Adolescents With Chronic Fatigue Syndrome/Myalgic Encephalomyelitis to Internet-Delivered Therapy: Internal Pilot Within a Randomized Controlled Trial.

BACKGROUND: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) in adolescents is common and disabling. Teenagers in the United Kingdom are more likely to recover if they access specialist care, but most do not have access to a local specialist CFS/ME service. Delivering treatment remotely via the internet could improve access to treatment. OBJECTIVE: This study aims to assess (1) the feasibility of recruitment and retention into a trial of internet-delivered specialist treatment for adolescents with CFS/ME and (2) the acceptability of trial processes and 2 web-based treatments (to inform continuation to full trial). METHODS: This study is an internal pilot for the initial 12 months of a full randomized controlled trial (RCT), with integrated qualitative methods (analysis of recruitment consultations and participant and clinician interviews). Recruitment and treatment were delivered remotely from a specialist pediatric CFS/ME treatment service within a hospital in South West United Kingdom. Adolescents (aged 11-17 years) from across the United Kingdom with a diagnosis of CFS/ME and no access to local specialist treatment were referred by their general practitioner to the treatment center. Eligibility assessment and recruitment were conducted via remote methods (telephone and on the web), and participants were randomized (via a computer-automated system) to 1 of 2 web-based treatments. The trial intervention was Fatigue in Teenagers on the InterNET in the National Health Service, a web-based modular CFS/ME-specific cognitive behavioral therapy program (designed to be used by young people and their parents or caregivers) supported by individualized clinical psychologist electronic consultations (regular, scheduled therapeutic message exchanges between participants and therapist within the platform). The comparator was Skype-delivered activity management with a CFS/ME clinician (mainly a physiotherapist or occupational therapist). Both treatments were intended to last for up to 6 months. The primary outcomes were (1) the number of participants recruited (per out-of-area referrals received between November 1, 2016, to October 31, 2017) and the proportion providing 6-month outcome data (web-based self-report questionnaire assessing functioning) and (2) the qualitative outcomes indicating the acceptability of trial processes and treatments. RESULTS: A total of 89 out of 150 (59.3% of potentially eligible referrals) young people and their parents or caregivers were recruited, with 75 out of 89 (84.2%) providing 6-month outcome data. Overall, web-based treatment was acceptable; however, participants and clinicians described both the advantages and disadvantages of remote methods. No serious adverse events were reported. CONCLUSIONS: Recruiting young people (and their parents or caregivers) into an RCT of web-based treatment via remote methods is feasible and acceptable. Delivering specialist treatment at home via the internet is feasible and acceptable, although some families prefer to travel across the United Kingdom for face-to-face treatment. TRIAL REGISTRATION: ISRCTN 18020851; http://www.isrctn.com/ISRCTN18020851. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s13063-018-2500-3.

Management of multimorbidity using a patient-centred care model: a pragmatic cluster-randomised trial of the 3D approach.

BACKGROUND: The management of people with multiple chronic conditions challenges health-care systems designed around single conditions. There is international consensus that care for multimorbidity should be patient-centred, focus on quality of life, and promote self-management towards agreed goals. However, there is little evidence about the effectiveness of this approach. Our hypothesis was that the patient-centred, so-called 3D approach (based on dimensions of health, depression, and drugs) for patients with multimorbidity would improve their health-related quality of life, which is the ultimate aim of the 3D intervention. METHODS: We did this pragmatic cluster-randomised trial in general practices in England and Scotland. Practices were randomly allocated to continue usual care (17 practices) or to provide 6-monthly comprehensive 3D reviews, incorporating patient-centred strategies that reflected international consensus on best care (16 practices). Randomisation was computer-generated, stratified by area, and minimised by practice deprivation and list size. Adults with three or more chronic conditions were recruited. The primary outcome was quality of life (assessed with EQ-5D-5L) after 15 months' follow-up. Participants were not masked to group assignment, but analysis of outcomes was blinded. We analysed the primary outcome in the intention-to-treat population, with missing data being multiply imputed. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN06180958. FINDINGS: Between May 20, 2015, and Dec 31, 2015, we recruited 1546 patients from 33 practices and randomly assigned them to receive the intervention (n=797) or usual care (n=749). In our intention-to-treat analysis, there was no difference between trial groups in the primary outcome of quality of life (adjusted difference in mean EQ-5D-5L 0·00, 95% CI -0·02 to 0·02; p=0·93). 78 patients died, and the deaths were not considered as related to the intervention. INTERPRETATION: To our knowledge, this trial is the largest investigation of the international consensus about optimal management of multimorbidity. The 3D intervention did not improve patients' quality of life. FUNDING: National Institute for Health Research.

Evaluation of an intervention to promote walking during the commute to work: a cluster randomised controlled trial.

BACKGROUND: Opportunities for working adults to accumulate recommended physical activity levels (at least 150 min of moderate intensity physical activity in bouts of at least 10 min throughout the week) may include the commute to work. Systematic reviews of interventions to increase active transport suggest studies have tended to be of poor quality, relying on self-report and lacking robust statistical analyses. METHODS: We conducted a multi-centre parallel-arm cluster randomised controlled trial, in workplaces in south-west England and south Wales, to assess the effectiveness of a behavioural intervention to increase walking during the commute. Workplace-based Walk to Work promoters were trained to implement a 10-week intervention incorporating key behavioural change techniques: providing information; encouraging intention formation; identifying barriers and solutions; goal setting; self-monitoring; providing general encouragement; identifying social support; reviewing goals, and; relapse prevention. Physical activity outcomes were objectively measured using accelerometers and GPS receivers at baseline and 12-month follow-up. The primary outcome was daily minutes of moderate to vigorous physical activity (MVPA). Secondary outcomes included overall levels of physical activity and modal shift (from private car to walking). Cost-consequences analysis included employer, employee and health service costs and outcomes. RESULTS: Six hundred fifty-four participants were recruited across 87 workplaces: 10 micro (5-9 employees); 35 small (10-49); 22 medium (50-250); 20 large (250+). The majority of participants lived more than two kilometres from their place of work (89%) and travelled to work by car (65%). At 12-month follow-up, 84 workplaces (41 intervention, 43 control) and 477 employees (73% of those originally recruited) took part in data collection activities. There was no evidence of an intervention effect on MVPA or overall physical activity at 12-month follow-up. The intervention cost on average £181.97 per workplace and £24.19 per participating employee. CONCLUSIONS: The intervention, focusing primarily on individual behaviour change, was insufficient to change travel behaviour. Our findings contribute to the argument that attention should be directed towards a whole systems approach, focusing on interactions between the correlates of travel behaviour. TRIAL REGISTRATION: ISRCTN15009100 . Prospectively registered. (Date assigned: 10/12/2014).

Defining the minimally clinically important difference of the SF-36 physical function subscale for paediatric CFS/ME: triangulation using three different methods.

BACKGROUND: Defining the minimally clinically important difference (MCID) is important for the design and analysis of clinical trials and ensures that findings are clinically meaningful. Studies in adult populations have investigated the MCID of The Short Form 36 physical function sub-scale (SF-36-PFS). However, to our knowledge no studies have defined the MCID of the SF-36-PFS in a paediatric population. We aimed to triangulate findings from distribution, anchor and qualitative methods to identify the MCID of the SF-36-PFS for children and adolescents with CFS/ME. METHODS: Quantitative methods: We analysed routinely-collected data from a specialist paediatric CFS/ME service in South-West England using: 1) the anchor method, based on Clinical Global Impression (CGI) outcomes at 6 months' follow-up; 2) the distribution method, based on the standard deviation of baseline SF-36-PFS scores. Qualitative methods: Young people (aged 12-17 years) and parents were asked to complete the SF-36-PFS, marking each question twice: once for where they would currently rate themselves/their child and a second time to show what they felt would be the smallest amount of change for them/their child to feel treatment had made a difference. Semi-structured interviews were designed to explore what factors were deemed important to patients and to what extent an improvement was considered satisfactory. We thematically analysed qualitative interviews from 21 children and their parents. RESULTS: Quantitative results: Six-month follow-up data were available for 198 children with a mean age of 14 years. Most were female (74%, 146/198) and 95% gave their ethnicity as "White British". Half the standard deviation of the baseline SF-36-PFS scores was 11.0. "A little better" on the CGI equated to a mean difference on the SF-36-PFS from baseline to 6-month follow-up of 9.0. Qualitative results: Twenty-one children with CFS/ME participated: 16 females (76.2%) with a mean age of 14.4 years. Twenty mothers and two fathers were also interviewed. The median minimal improvement in the SF-36-PFS was 10. Participants indicated that small changes in physical function can lead to important improvements in valued social and family function. Patients and parents were positive about improvement even in the presence of persisting symptoms. Triangulation: The MCID based on the mean score from the three methods was 10. CONCLUSIONS: Converging evidence indicates future studies in paediatric CFS/ME should use an MCID of 10 on the SF-36-PFS.

Further development and validation of the Multimorbidity Treatment Burden Questionnaire (MTBQ).

OBJECTIVES: To undertake further psychometric testing of the Multimorbidity Treatment Burden Questionnaire (MTBQ) and examine whether reversing the scale reduced floor effects. DESIGN: Survey. SETTING: UK primary care. PARTICIPANTS: Adults (≥18 years) with three or more long-term conditions randomly selected from four general practices and invited by post. MEASURES: Baseline survey: sociodemographics, MTBQ (original or version with scale reversed), Treatment Burden Questionnaire (TBQ), four questions (from QQ-10) on ease of completing the questionnaires. Follow-up survey (1-4 weeks after baseline): MTBQ, TBQ and QQ-10. Anonymous data collected from electronic GP records: consultations (preceding 12 months) and long-term conditions. The proportion of missing data and distribution of responses were examined for the original and reversed versions of the MTBQ and the TBQ. Intraclass correlation coefficient (ICC) and Spearman's rank correlation (Rs) assessed test-retest reliability and construct validity, respectively. Ease of completing the MTBQ and TBQ was compared. Interpretability was assessed by grouping global MTBQ scores into 0 and tertiles (>0). RESULTS: 244 adults completed the baseline survey (consent rate 31%, mean age 70 years) and 225 completed the follow-up survey. Reversing the scale did not reduce floor effects or data skewness. The global MTBQ scores had good test-retest reliability (ICC for agreement at baseline and follow-up 0.765, 95% CI 0.702 to 0.816). Global MTBQ score was correlated with global TBQ score (Rs 0.77, p<0.001), weakly correlated with number of consultations (Rs 0.17, p=0.010), and number of different general practitioners consulted (Rs 0.23, p<0.001), but not correlated with number of long-term conditions (Rs -0.063, p=0.330). Most participants agreed that both the MTBQ and TBQ were easy to complete and included aspects they were concerned about. CONCLUSION: This study demonstrates test-retest reliability and ease of completion of the MTBQ and builds on a previous study demonstrating good content validity, construct validity and internal consistency reliability of the questionnaire.

Conservative management versus invasive management of significant traumatic pneumothoraces in the emergency department (the CoMiTED trial): a study protocol for a randomised non-inferiority trial.

INTRODUCTION: Traumatic pneumothoraces are present in one of five victims of severe trauma. Current guidelines advise chest drain insertion for most traumatic pneumothoraces, although very small pneumothoraces can be managed with observation at the treating clinician's discretion. There remains a large proportion of patients in whom there is clinical uncertainty as to whether an immediate chest drain is required, with no robust evidence to inform practice. Chest drains carry a high risk of complications such as bleeding and infection. The default to invasive treatment may be causing potentially avoidable pain, distress and complications. We are evaluating the clinical and cost-effectiveness of an initial conservative approach to the management of patients with traumatic pneumothoraces. METHODS AND ANALYSIS: The CoMiTED (Conservative Management in Traumatic Pneumothoraces in the Emergency Department) trial is a multicentre, pragmatic parallel group, individually randomised controlled non-inferiority trial to establish whether initial conservative management of significant traumatic pneumothoraces is non-inferior to invasive management in terms of subsequent emergency pleural interventions, complications, pain, breathlessness and quality of life. We aim to recruit 750 patients from at least 40 UK National Health Service hospitals. Patients allocated to the control (invasive management) group will have a chest drain inserted in the emergency department. For those in the intervention (initial conservative management) group, the treating clinician will be advised to manage the participant without chest drain insertion and undertake observation. The primary outcome is a binary measure of the need for one or more subsequent emergency pleural interventions within 30 days of randomisation. Secondary outcomes include complications, cost-effectiveness, patient-reported quality of life and patient and clinician views of the two treatment options; participants are followed up for 6 months. ETHICS AND DISSEMINATION: This trial received approval from the Wales Research Ethics Committee 4 (reference: 22/WA/0118) and the Health Research Authority. Results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN35574247.

Investigating the factors associated with meaningful improvement on the SF-36-PFS and exploring the appropriateness of this measure for young people with ME/CFS accessing an NHS specialist service: a prospective cohort study.

OBJECTIVES: Paediatric myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is relatively common and disabling, but little is known about the factors associated with outcome. We aimed to describe the number and characteristics of young people reaching the 10-point minimal clinically important difference (MCID) of SF-36-Physical Function Subscale (SF-36-PFS) and to investigate factors associated with reaching the MCID. DESIGN: Prospective observational cohort study. SETTING: A specialist UK National Health Service ME/CFS service, Southwest England; recruitment between March 2014 and August 2015. PARTICIPANTS: 193 eligible patients with ME/CFS aged 8-17 years reported baseline data. 124 (65%) and 121 (63%) with outcome data at 6 and 12 months, respectively. OUTCOME MEASURES: SF-36-PFS (primary outcome). Chalder Fatigue Questionnaire, school attendance, visual analogue pain scale, Hospital Anxiety and Depression Scale, Spence Young People Anxiety Scale, Clinical Global Impression scale and EQ-5D-Y (secondary). RESULTS: At 6 months 48/120 (40%) had reached the MCID for SF-36-PFS. This had increased to 63/117 (54%) at 12 months. On the Clinical Global Impressions, 77% and 79% reported feeling either a little better, much better or very much better. Those with worse SF-36-PFS at baseline assessment were more likely to achieve the MCID for SF-36-PFS at 6 months (odds ratio 0.97, 95% confidence interval 0.96 to 0.99, p value 0.003), but there was weaker evidence of effect at 12 months (OR 0.98, 95% CI 0.97 to 1.00, p value 0.038). No other factors at baseline were associated with the odds of reaching the MCID at 6 months. However, at 12 months, there was strong evidence of an effect of pain on MCID (OR 0.97, 95% CI 0.95 to 0.99, p value 0.001) and SF-36-PFS on MCID (OR 0.96, 95% CI 0.94 to 0.98, p value 0.001). CONCLUSIONS: 40% and 54% of young people reached the MCID at 6 and 12 months, respectively. No factors at assessment (other than SF-36-PFS at 6 months, and pain and SF-36-PFS at 12 months) are associated with MCID of SF-36-PFS at either 6 or 12 months. Further work is needed to explore the most appropriate outcome measure for capturing clinical meaningful improvement for young people with ME/CFS.

Informed consent in randomised controlled trials: further development and evaluation of the participatory and informed consent (PIC) measure.

BACKGROUND: Informed consent is an accepted ethical and legal prerequisite for trial participation, yet there is no standardised method of assessing patient understanding for informed consent. The participatory and informed consent (PIC) measure was developed for application to recruitment discussions to evaluate recruiter information provision and evidence of patient understanding. Preliminary evaluation of the PIC indicated the need to improve inter-rater and intra-rater reliability ratings and conduct further psychometric evaluation. This paper describes the assessment, revision and evaluation of the PIC within the context of OPTiMISE, a pragmatic primary care-based trial. METHODS: This study used multiple methods across two phases. In phase one, one researcher applied the existing PIC measure to 18 audio-recorded recruitment discussions from the OPTiMISE study and made detailed observational notes about any uncertainties in application. Appointments were sampled to be maximally diverse for patient gender, study centre, recruiter and before and after an intervention to optimise information provision. Application uncertainties were reviewed by the study team, revisions made and a coding manual developed and agreed. In phase two, the coding manual was used to develop tailored guidelines for applying the PIC to appointments within the OPTiMISE trial. Two researchers then assessed 27 further appointments, purposively sampled as above, to evaluate inter-rater and intra-rater reliability, content validity and feasibility. RESULTS: Application of the PIC to 18 audio-recorded OPTiMISE recruitment discussions resulted in harmonisation of the scales rating recruiter information provision and evidence of patient understanding, minor amendments to clarify wording and the development of detailed generic coding guidelines for applying the measure within any trial. Application of the revised measure using these guidelines to 27 further recruitment discussions showed good feasibility (time to complete), content validity (completion rate) and reliability (inter- and intra-rater) of the measure. CONCLUSION: The PIC provides a means to evaluate the content of information provided by recruiters, patient participation in recruitment discussions and, to some extent, evidence of patient understanding. Future work will use the measure to evaluate recruiter information provision and evidence of patient understanding both across and within trials.

Participant retention in paediatric randomised controlled trials published in six major journals 2015-2019: systematic review and meta-analysis.

BACKGROUND: The factors which influence participant retention in paediatric randomised controlled trials are under-researched. Retention may be more challenging due to child developmental stages, involving additional participants, and proxy-reporting of outcomes. This systematic review and meta-analysis explores the factors which may influence retention in paediatric trials. METHODS: Using the MEDLINE database, paediatric randomised controlled trials published between 2015 and 2019 were identified from six general and specialist high-impact factor medical journals. The review outcome was participant retention for each reviewed trial's primary outcome. Context (e.g. population, disease) and design (e.g. length of trial) factors were extracted. Retention was examined for each context and design factor in turn, with evidence for an association being determined by a univariate random-effects meta-regression analysis. RESULTS: Ninety-four trials were included, and the median total retention was 0.92 (inter-quartile range 0.83 to 0.98). Higher estimates of retention were seen for trials with five or more follow-up assessments before the primary outcome, those less than 6 months between randomisation and primary outcome, and those that used an inactive data collection method. Trials involving children aged 11 and over had the higher estimated retention compared with those involving younger children. Those trials which did not involve other participants also had higher retention, than those where they were involved. There was also evidence that a trial which used an active or placebo control treatment had higher estimated retention, than treatment-as-usual. Retention increased if at least one engagement method was used. Unlike reviews of trials including all ages of participants, we did not find any association between retention and the number of treatment groups, size of trial, or type of treatment. CONCLUSIONS: Published paediatric RCTs rarely report the use of specific modifiable factors that improve retention. Including multiple, regular follow-ups with participants before the primary outcome may reduce attrition. Retention may be highest when the primary outcome is collected up to 6 months after a participant is recruited. Our findings suggest that qualitative research into improving retention when trials involve multiple participants such as young people, and their caregivers or teachers would be worthwhile. Those designing paediatric trials also need to consider the use of appropriate engagement methods. RESEARCH ON RESEARCH (ROR) REGISTRY: https://ror-hub.org/study/2561.

The effectiveness and cost-effectiveness of a group domestic abuse perpetrator programme: protocol for a randomised controlled trial.

BACKGROUND: In contrast to evidence for interventions supporting victim/survivors of domestic violence and abuse (DVA), the effectiveness of perpetrator programmes for reduction of abuse is uncertain. This study aims to estimate the effectiveness and cost-effectiveness of a perpetrator programme for men. METHODS: Pragmatic two-group individually randomised controlled trial (RCT) with embedded process and economic evaluation. Five centres in southwest England and South Wales aim to recruit 316 (reduced from original target of 366) male domestic abuse perpetrators. These will be randomised 2:1 to a community-based domestic abuse perpetrator programme (DAPP) or usual care comparator with 12-month follow-up. Female partners/ex-partners will be invited to join the study. The intervention for men comprises 23 weekly sessions of a group programme delivered in voluntary sector domestic abuse services. The intervention for female partners/ex-partners is one-to-one support from a safety worker. Men allocated to usual care receive no intervention; however, they are free to access other services. Their partners/ex-partners will be signposted to support services. Data is collected at baseline, and 4, 8 and 12 months' follow-up. The primary outcome is men's self-reported abusive behaviour measured by the Abusive Behaviour Inventory (ABI-29) at 12 months. Secondary measures include physical and mental health status and resource use alongside the abuse measure ABI (ABI-R) for partners/ex-partners and criminal justice contact for men. A mixed methods process evaluation and qualitative study will explore mechanisms of effectiveness, judge fidelity to the intervention model using interviews and group observations. The economic evaluation, over a 1-year time horizon from three perspectives (health and social care, public sector and society), will employ a cost-consequences framework reporting costs alongside economic outcomes (Quality-Adjusted Life Years derived from EQ-5D-5L, SF-12 and CHU-9D, and ICECAP-A) as well as the primary and other secondary outcomes. DISCUSSION: This trial will provide evidence of the (cost)effectiveness of a DAPP. The embedded process evaluation will further insights in the experiences and contexts of participants and their journey through a perpetrator programme, and the study will seek to address the omission in other studies of economic evaluations. TRIAL REGISTRATION: ISRCTN15804282, April 1, 2019.

Using a checklist within simulation improves trainees' confidence on ward rounds.

Ward rounds are integral to maintaining patient safety in everyday clinical care. Junior doctors are often expected to conduct independent rounds on graduation, but many feel ill-equipped to do so. We developed a safety checklist and simulation sessions to improve junior-led ward round practice at one district general hospital. We found that embedding a checklist within simulation is an effective way to teach ward round skills and increase confidence among undergraduate and postgraduate medical trainees.

Who should we ask about mental health symptoms in adolescents with CFS/ME? Parent-child agreement on the revised children's anxiety and depression scale.

BACKGROUND: One in three adolescents with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) have mental health problems. Multi-informant perspectives are key to psychological assessment. Understanding parent-child agreement is crucial to accurate diagnosis, particularly where severe fatigue limits self-report. METHODS: Agreement on the revised children's anxiety and depression scale (RCADs) was assessed between parents and children with CFS/ME (n = 93) using Bland-Altman plots, cross tabulations and regression analyses. RESULTS: Diagnostic thresholds were met more frequently based on child-report. Parent- and child-report had similar sensitivity and specificity on RCADS compared to gold-standard diagnostic interviews. Regression analysis found similar accuracy between both reports. For anxiety diagnoses, odds ratio (OR) for child-report was 1.10 (CI = 1.06-1.14), and 1.10 (CI = 1.05-1.14) for parent-report. For depression, OR for child report was 1.26 (CI = 1.11-1.43), while for parent-report is was 1.25 (CI = 1.10-1.41). For total score, OR for child-report was 1.10 (CI = 1.05-1.13) while OR for parent-report was 1.09 (CI = 1.05-1.13). CONCLUSIONS: Reasonable agreement was observed between parent- and child-report of mental health symptoms in paediatric CFS/ME. While parent-report can facilitate psychological evaluation in CFS/ME, this is not a substitute for a child's own report.

The Association Between Frailty and Parkinson's Disease in the ReSPOnD Trial.

BACKGROUND: Frailty and Parkinson's disease (PD) are both highly prevalent in older people, but few studies have studied frailty in people with Parkinson's. Identifying frailty in this population is vital, to target new interventions to those who would most benefit. METHODS: Data were collected as part of the double-blind randomised controlled rivastigmine to stabilise gait ReSPonD trial in 130 people with Hoehn and Yahr 2-3, idiopathic PD who had fallen in the year prior to enrolment. Individuals were assessed at baseline and followed up at eight months, including determination of frailty status. RESULTS: 120 patients attended for follow-up. At follow-up, the mean (SD) age was 70.2 years (8.0), MDS-UPDRS total score 91.5 (29.1), and MDS-UPDRS motor score (Part III) 42.7 (14.8). Median disease duration was 9.2 years (IQR 4.6 to 13.1), Geriatric Depression Score 4 (IQR 2 to 6). Using the Fried frailty criteria, 31 (26%) were frail and 70 (58%) pre-frail. In univariable analysis, being female, higher depression score, and MDS-UPDRS score were associated with greater frailty. Using ordinal regression, in the multivariable model, being female (odds ratio [OR] 3.10, 95%CI 1.53 to 6.26, p=.002), higher total MDS-UPDRS score (OR 2.02, 95%CI 1.42 to 2.87, p<.0001) and higher depression (OR 1.47, 95%CI 1.05 to 2.06, p=.03) were associated with higher number of frailty markers. CONCLUSION: There was a high prevalence (84%) of pre-frail and frail individuals in patients participating in this RCT. Future research should determine the optimum tool to assess frailty in this at-risk population, and delineate the association between Parkinson's, frailty, and health outcomes.

Improving outcomes for primary school children at risk of cerebral visual impairment (the CVI project): protocol of a feasibility study for a cluster-randomised controlled trial and health economic evaluation.

INTRODUCTION: Cerebral visual impairment (CVI) refers to a spectrum of brain-related vision problems. CVI is associated with poor educational and mental health outcomes. An intervention has been developed to help children with CVI, involving input from clinicians, teachers and parents. The effectiveness of this intervention needs to be evaluated. This study aims to guide any refinements to the intervention or the design of a future cluster-randomised trial that may be needed. METHODS AND ANALYSIS: This study will include all methods anticipated for a future cluster-randomised controlled trial. Eight primary schools will be recruited and randomised to receive the intervention or carry on with usual practice. The intervention will comprise an information pack for schools and access to a local paediatric ophthalmology clinic (who are prepared to assess them for CVI), for up to 5% of participating children. Outcome assessments will be carried out at baseline (before randomisation) and after 4-5 months of intervention period. Assessments will include children's self-reported quality of life, their learning ability and behaviour as reported by teachers, and family functioning reported by parents. Cost data will include service use, family expenditure on additional support (eg, private appointments and administration) and school spending and resource used in helping children with special educational needs or disability. A process evaluation (PE) will collect additional data relating to the implementation of the intervention and the trial processes, in the school and clinic settings. The protocol for the PE will be reported separately. ETHICS AND DISSEMINATION: Ethical permission was obtained from the University of Bristol Faculty of Health Sciences Ethical Committee. The results will inform the design of a future trial to assess the effectiveness and cost-effectiveness of the intervention and will be shared with participants, CVI-support groups and peer-viewed journals. TRIAL REGISTRATION NUMBER: ISRCTN13762177; Pre-results.

The impact of vaso-occlusive crises and disease severity on quality of life and productivity among patients with sickle cell disease in the US.

AIM: Sickle cell disease (SCD) is a lifelong blood disorder affecting approximately 100,000 individuals in the United States (US). A number of new treatments have recently become available to improve SCD clinical outcomes, but it is unclear how treatment innovations that reduce disease severity could affect patients' humanistic and economic outcomes. METHODS AND MATERIALS: To answer this question, an online survey of US adult residents with a self-reported SCD diagnosis was conducted. Humanistic outcomes based on health-related quality of life (HRQoL)) were assessed during and outside of vaso-occlusive crises (VOCs). Economic outcomes were measured by annual household income and whether the respondent received disability insurance. RESULTS: Among the 301 respondents completing the survey, average age was 34.4 years and 73.4% were female. Average HRQoL, measured using health utilities, were 0.311 (95% CI: 0.286, 0.337) during a VOC and 0.738 (0.720, 0.756) not during a VOC. The likelihood of claiming disability insurance was correlated with more frequent VOCs (0 VOCs: 12% vs. ≥4 VOCs: 47%, p = .002) and disease severity (Severity Class II: 16% vs. Severity Class III: 39%, p = .03). There was a weak relationship between VOC frequency and household income (0 VOCs: $47,488 vs. ≥4 VOCs: $34,569, p = .06) and no evidence of a relationship between disease severity class and income (Severity Class II: $42,443 vs. Severity Class III: $36,842, p = .29). CONCLUSION: In conclusion, disease severity, strongly predicted worse self-reported HRQoL, moderately predicted increased likelihood of collecting disability insurance, and weakly predicted lower household income levels.