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Background Headaches are a leading cause of years lived with disability. For some people, headaches become chronic and disabling, with treatment options being primarily pharmaceutical. Non-pharmacological alternative treatment approaches are worthy of exploration. Aim To develop and test an educational and supportive self-management intervention for people with chronic headaches. Objectives To develop and evaluate a brief diagnostic interview to support diagnosis for people with chronic headaches, and then to develop and pilot an education and self-management support intervention for the management of common chronic headache disorders (the CHESS intervention). To select the most appropriate outcome measures for a randomised controlled trial of the CHESS intervention, and then to conduct a randomised controlled trial and economic evaluation of the CHESS intervention with an embedded process evaluation. Design Developmental and feasibility studies followed by a randomised controlled trial. Setting General practice and community settings in the Midlands and London, UK. Participants For our feasibility work, 14 general practices recruited 131 people with chronic headaches (headaches on ≥15 days per month for >3 months). People with chronic headaches and expert clinicians developed a telephone classification interview for chronic headache that we validated with 107 feasibility study participants. We piloted the CHESS intervention with 13 participants and refined the content and structure based on their feedback. People with chronic headaches contributed to the decisions about our primary outcome and a core outcome set for chronic and episodic migraine. For the randomised controlled trial, we recruited adults with chronic migraine or chronic tension-type headache and episodic migraine, with or without medication overuse headache, from general practices and via self-referral. Our main analyses were on people with migraine. Interventions The CHESS intervention consisted of two 1-day group sessions focused on education and self-management to promote behaviour change and support learning strategies to manage chronic headaches. This was followed by a one-to-one nurse consultation and telephone support. The control intervention consisted of feedback from classification interviews, headache management leaflet and a relaxation compact disc. Main outcome measures The primary outcome was headache-related quality of life measured using the Headache Impact Test-6 at 12 months. The secondary outcomes included the Chronic Headache Quality of Life Questionnaire; headache days, duration and severity; EuroQol-5 Dimensions, five-level version; Short Form Questionnaire-12 items; Hospital Anxiety and Depression Scale; and Pain Self-Efficacy Questionnaire scores. We followed up participants at 4, 8 and 12 months. Results Between April 2017 and March 2019, we randomised 736 participants from 164 general practices. Nine participants (1%) had chronic tension-type headache only. Our main analyses were on the remaining 727 participants with migraine (376 in the intervention arm and 351 in the usual-care arm). Baseline characteristics were well matched. For the primary outcome we had analysable data from 579 participants (80%) at 12 months. There was no between-group difference in the Headache Impact Test-6 at 12 months, (adjusted mean difference –0.3, 95% confidence interval –1.23 to 0.67; p = 0.56). The limits of the 95% confidence interval effectively exclude the possibility of the intervention having a worthwhile benefit. At 4 months there was a difference favouring the CHESS self-management programme on the Headache Impact Test-6 (adjusted mean difference –1.0, 95% confidence interval –1.91 to –0.006; p = 0.049). However, the self-management group also reported 1.5 (95% confidence interval 0.48 to 2.56) more headache days in the previous 28 days. Apart from improved pain self-efficacy at 4 and 12 months, there were few other statistically significant between-group differences in the secondary outcomes. The CHESS intervention generated 0.031 (95% confidence interval –0.005 to 0.063) additional quality-adjusted life-years and increased NHS and Personal Social Services costs by £268 (95% confidence interval £176 to £377), on average, generating an incremental cost-effectiveness ratio of £8617 with an 83% chance of being cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life-year. The CHESS intervention was well received and fidelity was good. No process-related issues were identified that would explain why the intervention was ineffective. Limitations Only 288 out of 376 (77%) of those randomised to the CHESS intervention attended one or more of the intervention sessions. Conclusions This short, non-pharmacological, educational self-management intervention is unlikely to be effective for the treatment of people with chronic headaches and migraine. Future work There is a need to develop and test more sustained non-pharmacological interventions for people with chronic headache disorders. Patient and public involvement Substantial patient and public involvement went into the design, conduct and interpretation of the CHESS programme. This helped direct the research and ensured that the patient voice was embedded in our work. Trial registration This trial is registered as ISRCTN79708100. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 11, No. 2. See the NIHR Journals Library website for further information. Plain language summary What did we want to find out? We wanted to find out if an education and self-management support programme for people with frequent headaches made these people feel better. What did we do? We first made sure that we could find people with frequent headaches, from general practice, who would want to take part in our study. We then trained nurses to do telephone interviews to find out what sort of headaches people had. We looked at previous research and then, together with people with frequent headaches, designed a group education and self-management programme. It was run by a nurse and another health professional over 2 days, followed by a one-to-one session and telephone support with a nurse. We worked with people with frequent headaches and health professionals specialising in headaches to agree how best to measure how headaches affect people’s quality of life. We then tested our self-management programme. We recruited 736 people with frequent headaches, of whom 727 had migraine. Using a computer, we allocated them at random either to attend the self-management programme or to receive a relaxation compact disc. Everyone was told their headache type. We asked participants to tell us about their headaches and headache quality of life after 4 months, 8 months and 12 months. What did we find? Our main results are for the 727 people with migraine. Our support programme did not help people in our study with frequent migraines to live better. There were also no important differences in the number of headaches people had each month or the amount of prescribed or over-the-counter medication they took for their headaches. What does this mean? Our short 2-day programme did not appear to improve headache-related quality of life or reduce the number of headache days. Other ways of helping people manage their chronic headaches are needed. Scientific summary Background Headaches are second to low back pain as a global cause of years lived with disability. Headaches are the most common neurological disorder treated in primary care. They account for around 3% of general practitioner consultations. Seventy per cent of people with headaches seen by their general practitioner do not get a formal diagnosis. For some people headaches become a chronic disabling disorder. There is a need for more non-pharmacological treatments to help those living with headache disorders. Our overarching aim was to develop and test a supportive education and self-management group intervention, implementable in primary care, for people with chronic headaches. Objectives The objectives of the programme were to: •develop and test strategies for recruiting people with chronic headaches from primary care [work package (WP) 1] •develop and evaluate a brief classification interview to support diagnosis for people with chronic headaches (WP2) •develop and pilot an education and self-management support intervention for the management of common chronic headache disorders [the Chronic Headache Education and Self-management Study (CHESS) intervention] (WP3) •select the most appropriate outcome measures for a randomised controlled trial of the CHESS intervention package (WP4) •run a multicentre randomised controlled trial, including an economic evaluation, of the CHESS intervention package (WP5). Methods and results We used an epidemiological definition of chronic headaches: headaches on ≥15 days per month for >3 months. Phase 1 of our work, WPs 1–4, consisted of interlinked systematic reviews and a feasibility study. Feasibility study (work package 1) Fourteen general practices in the West Midlands recruited 131 people with chronic headaches by writing to people with recorded consultations for headaches and prescriptions for migraine-specific drugs (triptans and pizotifen). Eligibility was confirmed by a telephone call by the study team. This group was our sampling frame for WPs 2–4. Classification interview (work package 2) We wanted to identify the population of interest for the main trial but also to feel confident that those who had other headache types not suitable for our trial were appropriately identified and referred for relevant support. We first reviewed the literature on diagnostic tools and found 38 papers validating 30 tools. We did not find any tools that were suitable for our proposed trial. We therefore organised a consensus meeting to inform our thinking on the content of a new classification tool. This was attended by neurologists with a specialist interest in headaches, general neurologists, headache specialist nurses, general practitioners with a specialist interest in headaches and people with chronic headaches. We established what we needed to know from a person to: •exclude secondary headaches •exclude primary headaches other than chronic migraine and tension-type headache •distinguish between chronic tension-type headache and chronic migraine •identify medication overuse headache. We used this information to develop a classification logic model for use in a nurse-delivered classification interview. A research nurse and a doctor, with expertise in headaches, from the National Migraine Centre then independently interviewed 107 participants. We found a high level of agreement between the nurse and specialist. Over 90% of study participants were classified as having chronic migraine. Intervention development (work package 3) Three systematic reviews informed our intervention development. Using a meta-ethnographic approach our systematic review of the lived experience of chronic headaches (n = 4 studies) we found three overarching themes: •headache as a driver of behaviour •the spectre of headache •strained relationships. In our systematic review of prognostic factors in chronic headache (n = 27 studies), we found moderate evidence for depression and anxiety, poor sleep, stress, medication overuse and poor self-efficacy predicting a poor outcome. We found inconclusive evidence for treatment expectations, age and age at onset, body mass index, employment and headache features predicting a poor outcome. In our systematic review of the effectiveness, style and content of self-management interventions for chronic headache (n = 16 studies) we found beneficial effects of the interventions compared with usual care in pain intensity, headache-related disability and quality of life. Interventions including either education or mindfulness components, and delivered in a group format, showed greater reductions in pain intensity than interventions without these features. A greater beneficial effect on mood was observed in interventions that included a cognitive–behavioural approach component than in those without this. We interviewed seven people living with chronic headaches recruited through our charity partners. We found that participants had tried a range of therapies and interventions, some of which were helpful and others less so. Access to education and peer support was deemed positive, as was learning new skills such as relaxation, mindfulness and stress management. We then presented our findings to 18 people from clinical, academic and lay backgrounds at an intervention development day to agree the structure and content of our new intervention. We agreed on a modular group intervention for 8–10 people delivered by a nurse and a layperson with chronic headaches. It should include educational material, self-management material and medication advice, and include a digital versatile disc (DVD) suitable to share with friends and family. We included a single face-to-face session and up to 8 weeks of telephone support with a specially trained nurse. After piloting with 13 participants, we identified that it was difficult for lay facilitators to commit to the sessions because of the unpredictable nature of their headaches. We therefore changed to using allied health professionals as the second facilitator. The final format was two group days followed by a one-to-one session with a nurse to discuss medication, lifestyle factors and goal-setting, followed by up to 8 weeks of telephone support (individually negotiated). Clinical effectiveness and cost-effectiveness measures (work package 4) In our systematic review of patient-reported outcomes (46 studies evaluating 23 patient measures) we found that for a ‘headache’ population only the Headache Impact Test-6 (HIT-6) had acceptable evidence for its validity and reliability for use in our trial. The Migraine-Specific Quality of Life Questionnaire (MSQ v2.1) had relevance to our population. We modified this measure, changing the focus of each item from ‘migraine’ to ‘headache’ to produce the Chronic Headache Quality of Life Questionnaire (CHQLQ) and did a mixed-methods comparative evaluation of the CHQLQ and HIT-6. Both the CHQLQ and the HIT-6 were well completed, had good psychometric properties and were relevant to the experience of headache. The CHQLQ captured the wide-ranging impact of chronic headache, in particular the emotional impact, to a greater extent than the HIT-6. As this work was not complete before starting the main trial, we set HIT-6 as the primary outcome for the trial and the CHQLQ as a secondary outcome. We developed three questions to capture headache frequency, duration and severity for use in a smartphone application (app) or in a paper diary. Eight feasibility participants tested the app over 11 weeks. Feedback was positive but completion rates varied. We included the app as part of the main trial. From our work on outcome measures we identified the need for a core outcome set for migraine. This work took place after the design of the randomised controlled trial had been finalised. We identified >50 domains from our systematic reviews and our qualitative work. We did a modified, three-round electronic Delphi study with patients and professionals to identify which domains were most important. At a consensus day, when the aim was to ratify the core domains, a two-domain core outcome set was agreed for chronic and episodic migraine: 1.migraine-specific pain – to be assessed with an 11-point numerical pain rating scale, and frequency as the number of headache/migraine days over a specified period 2.migraine-specific quality of life to be assessed with the Migraine Functional Impact Questionnaire (MFIQ). Professor Underwood, the chief investigator for this study, is a director and shareholder of Clinvivo Ltd, who provided the Delphi platform. He recused himself from any discussions related to the choice of Delphi platform for this study. Phase 2: randomised controlled trial, work package 5 Phase 2 of the programme was a randomised controlled trial to evaluate the clinical effectiveness and cost-effectiveness of the CHESS intervention package. We identified people with chronic headaches from general practice records. Self-referral to the trial was also possible. We included adults with migraine or tension-type headache with or without medication overuse headache. People who appeared eligible after an initial telephone call were asked to provide consent and baseline measures. This was followed by a classification interview with a research nurse to confirm eligibility and identify people with suspected non-eligible headaches. After the feasibility study we specified that if at least 85% of our participants had migraine our primary analysis would just be on the population with migraine, with sample size inflated, if necessary, to ensure adequate statistical power for this analysis. The randomisation allocation ratio was 1 : 1.07 in favour of the intervention group to account for clustering in one arm. Randomisation was done using minimisation, stratifying by geographical locality (Midlands and Greater London) and headache type [definite chronic migraine, probable chronic migraine (i.e. episodic migraine plus chronic tension-type headache) and chronic tension-type headache only, with or without medication overuse headache]. Our primary outcome was the HIT-6 score at 1 year. We used the Migraine-Specific Quality of Life Questionnaire as the secondary headache disability outcome. We did follow-ups at 4, 8 and 12 months. The sample size was based on testing the clinical effectiveness in the migraine population excluding participants with just tension-type headache (n = 689 participants: relaxation arm, n = 689; self-management arm, n = 356) provided 90% power to detect a between-group difference of 2 points (standard deviation 6.87 points, from the feasibility study) in HIT-6 score at 12 months for those with migraine using a two-sided test and a 5% significance level with a 20% loss to follow-up. Some over-run on sample size was expected to allow all groups to be adequately populated. We did a within-trial health economic analysis. Between April 2017 and March 2019, staff at 164 general practices in the Midlands and London wrote to 31,026 people and we randomised 736 people, 727 (99%) with migraine: 54% (396/727) had chronic migraine and 56% (407/727) medication overuse headache. Despite reporting chronic headache when eligibility for the study was determined, after receiving informed consent at baseline, 38% (274/727) reported < 15 headache days in the preceding 4 weeks. Unless otherwise stated, analyses were on the 727 participants with migraine. Baseline characteristics were well matched. The first session was attended by 286 out of 376 (76%) intervention participants; 259 (69%) reached the minimum adherence (day 1, and the one-to-one session) and 216 (58%) achieved full adherence to the programme. There was no between-group difference in HIT-6 scores at 12 months [adjusted mean difference –0.3 points, 95% confidence interval (CI) –1.23 to 0.67 points; p = 0.56]. The limits of this 95% CI excluded our target (worthwhile) effect size of 2.0 points and the smaller minimally clinically important difference of 1.5 points suggested by others for studies of episodic migraine. At 4 months there was a difference favouring the CHESS self-management programme (adjusted mean difference –1.0 points; 95% CI –1.91 to –0.006 points; p = 0.049). There were few differences in secondary outcomes. The self-management group had 1.5 (95% CI 0.48 to 2.56; p = 0.004) more headache days over the preceding 28 days at 4 months. They also had improved pain self-efficacy scores at 4 and 12 months. Use of acute drugs, including both prescribed and over-the-counter drugs, and prophylactic drugs was unchanged over time with no between-group differences. Using electronic/paper diary data the difference over 12 months in number of headache days was 0.2 days (95% CI –0.11 to 0.46 days; p = 0.234), difference in duration of each headache was 0.4 hours (95% CI –0.47 to 1.28 hours; p = 0.361) and difference in average headache severity on a 0–10 scale was 0.2 (95% CI –0.08 to 0.46; p = 0.163). We found no subgroup effects. Our complier-average causal effect and sensitivity analyses were not materially different. There were seven adverse events: two in the standard-care arm and five in the self-management arm. The CHESS intervention generated 0.031 (95% CI –0.005 to 0.063) additional quality-adjusted life-years (QALYs) and increased NHS and Personal Social Services costs by £268 (95% CI £176 to £377), generating an incremental cost-effectiveness ratio of £8617 with an 83% chance of being cost-effective at a willingness to pay of £20,000 per QALY gained. Our process evaluation, including all 736 participants, showed that we recruited a nationally representative population including people from practices based in all 10 deciles of the Index of Multiple Deprivation; 18% of participants were from minority ethnic groups. Intervention fidelity was good, with adherence being slightly better than competence [adherence 83% (interquartile range 67–100%); competence 70% (interquartile range 50–90%)]. We carried out semistructured interviews with a purposive sample of 26 study participants. Most participants described gaining some new knowledge or insight about their headaches from the intervention they received, and a few changed medication. Some felt more confident to manage their headaches, but many did not. CHESS was well received by participants, facilitators and general practitioners. Participants enjoyed interacting with others and valued the opportunity to talk, share and discuss their chronic headache experiences with others in a similar situation in a safe knowledgeable space. Patient and public involvement There has been substantial patient and public involvement in the design, conduct and interpretation of the CHESS programme. Throughout the programme we worked closely with three UK migraine charities and a lay advisory group to help direct the research and ensure that the patient voice was embedded in our work. Conclusions Over the duration of the CHESS programme, we have advanced our understanding of the challenges of living with chronic headaches and made some progress in developing the methodology for running randomised controlled trials of complex interventions for people living with chronic headaches. Our data effectively excluded the possibility that this short intervention is effective for the treatment of chronic migraine or chronic tension-type headache and episodic migraine. Although there was no effect on our chosen headache-specific outcomes, we have not excluded the possibility that it produces a worthwhile QALY gain, as measured by the EuroQol-5 Dimensions, five-level version. The health burden of chronic headache disorders, principally chronic migraine, is debilitating. Those living with the condition warrant support to optimise their care planning according to their needs and the latest knowledge about treatment and management. Further advances in this field must be driven by new theoretically and/or biologically informed intervention models. Research recommendations •New work to better understand the health impact of chronic headache disorders and to identify modifiable risk factors for a poor outcome. •Development and testing of new non-pharmacological interventions for a tightly phenotyped group with chronic migraine. •Research is needed to support improved classification of headache disorders in primary care to allow better targeting of the available drug treatments of proven effectiveness, and reduce medication overuse. Trial registration This trial is registered as ISRCTN79708100. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 11, No. 2. See the NIHR Journals Library website for further project information.

Background: Between 2015 and 2019 the Chronic Headache Education and Self-management Study (CHESS) developed and tested a supportive self-management approach that aimed to improve outcomes for people with chronic migraine or chronic tension type headache with/without episodic migraine. However, a paucity of qualitative research which explored the lived experiences of people with chronic headache was evidenced. In response, we undertook to explore the experiences of living with chronic headaches of people who participated in the CHESS study. Methods: We adopted qualitative methodologies, inviting participants in the CHESS study to participate in semi-structured interviews. In phase 1 (feasibility study), a thematic analysis was conducted. In phase 2 (main CHESS trial), interviews were informed by topic guides developed from our learning from the phase 1 interviews. Pen portrait methodology and thematic analysis was employed allowing us to explore the data longitudinally. Results: Phase 1, 15 interviews (10 female) age range 29 to 69 years (median 47 years) revealed the complexities of living with chronic headache. Six overarching themes were identified including the emotional impact and the nature of their headaches. Phase 2, included 66 interviews (26 participants; median age group 50s (range 20s-60s); 20 females. 14 were interviewed at three points in time (baseline, 4 and 12 months) Through an iterative process four overlapping categories of headache impact emerged from the data and were agreed: i) 'I will not let headaches rule my life'; ii) 'Headaches rule my life'; iii) 'Headaches out of control—something needs to change'; and iv) 'Headaches controlled—not ruling my life'. One of these categories was assigned to each pen portrait at each timepoint. The remaining 12 participants were interviewed at two time points during a year; pen portraits were again produced. Analysis revealed that the headache impact categories developed above held true in this sample also providing some validation of the categories. Conclusions: These data give an insight into the complexities of living with chronic headache. Chronic headache is unpredictable, permeating all aspects of an individual's life; even when an individual feels that their headache is controlled and not interfering, this situation can rapidly change. It shows us that more work needs to be done both medically and societally to help people living with this often-hidden condition. Trial registration: ISRCTN79708100 [ABSTRACT FROM AUTHOR]

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

Key Points: Question: Among patients with chronic pain, does a multicomponent intervention consisting of group meetings, education, individual support, and skill-based learning reduce opioid use and improve pain interference with daily activities compared with usual care? Findings: In this multicentered, randomized clinical trial that included 608 participants with chronic pain due to nonmalignant causes from primary care settings in the UK, at 12-month follow-up, 29% of people in the intervention group, compared with 7% in the usual care group, discontinued opioids, but there were no statistically significant differences in pain interference with daily life activities between the 2 groups at 12 months. Meaning: Among patients with chronic pain due to nonmalignant causes, a group-based educational intervention significantly reduced opioid use had no effect on perceived pain compared with usual care. Importance: Opioid use for chronic nonmalignant pain can be harmful. Objective: To test whether a multicomponent, group-based, self-management intervention reduced opioid use and improved pain-related disability compared with usual care. Design, Setting, and Participants: Multicentered, randomized clinical trial of 608 adults taking strong opioids (buprenorphine, dipipanone, morphine, diamorphine, fentanyl, hydromorphone, methadone, oxycodone, papaveretum, pentazocine, pethidine, tapentadol, and tramadol) to treat chronic nonmalignant pain. The study was conducted in 191 primary care centers in England between May 17, 2017, and January 30, 2019. Final follow-up occurred March 18, 2020. Intervention: Participants were randomized 1:1 to either usual care or 3-day–long group sessions that emphasized skill-based learning and education, supplemented by 1-on-1 support delivered by a nurse and lay person for 12 months. Main Outcomes and Measures: The 2 primary outcomes were Patient-Reported Outcomes Measurement Information System Pain Interference Short Form 8a (PROMIS-PI-SF-8a) score (T-score range, 40.7-77; 77 indicates worst pain interference; minimal clinically important difference, 3.5) and the proportion of participants who discontinued opioids at 12 months, measured by self-report. Results: Of 608 participants randomized (mean age, 61 years; 362 female [60%]; median daily morphine equivalent dose, 46 mg [IQR, 25 to 79]), 440 (72%) completed 12-month follow-up. There was no statistically significant difference in PROMIS-PI-SF-8a scores between the 2 groups at 12-month follow-up (−4.1 in the intervention and −3.17 in the usual care groups; between-group difference: mean difference, −0.52 [95% CI, −1.94 to 0.89]; P =.15). At 12 months, opioid discontinuation occurred in 65 of 225 participants (29%) in the intervention group and 15 of 208 participants (7%) in the usual care group (odds ratio, 5.55 [95% CI, 2.80 to 10.99]; absolute difference, 21.7% [95% CI, 14.8% to 28.6%]; P <.001). Serious adverse events occurred in 8% (25/305) of the participants in the intervention group and 5% (16/303) of the participants in the usual care group. The most common serious adverse events were gastrointestinal (2% in the intervention group and 0% in the usual care group) and locomotor/musculoskeletal (2% in the intervention group and 1% in the usual care group). Four people (1%) in the intervention group received additional medical care for possible or probable symptoms of opioid withdrawal (shortness of breath, hot flushes, fever and pain, small intestinal bleed, and an overdose suicide attempt). Conclusions and Relevance: In people with chronic pain due to nonmalignant causes, compared with usual care, a group-based educational intervention that included group and individual support and skill-based learning significantly reduced patient-reported use of opioids, but had no effect on perceived pain interference with daily life activities. Trial Registration: isrctn.org Identifier: ISRCTN49470934 This randomized clinical trial compares the efficacy of a multicomponent, group-based, self-management intervention vs usual care in reducing opioid use and improving pain-related disability in patients taking strong opioids to treat chronic pain from nonmalignant causes. [ABSTRACT FROM AUTHOR]

Background: The Chronic Headache Education and Self-Management Study (CHESS) multicentre randomised trial evaluated the impact a group education and self-management support intervention with a best usual care plus relaxation control for people living with chronic headache disorders (tension type headaches or chronic migraine, with or without medication overuse headache). Here we report the process evaluation exploring potential explanations for the lack of positive effects from the CHESS intervention. Methods: The CHESS trial included 736 (380 intervention: 356 control) people across the Midlands and London UK. We used a mixed methods approach. Our extensive process evaluation looked at context, reach, recruitment, dose delivered, dose received, fidelity and experiences of participating in the trial, and included participants and trial staff. We also looked for evidence in our qualitative data to investigate whether the original causal assumptions underpinning the intervention were realised. Results: The CHESS trial reached out to a large diverse population and recruited a representative sample. Few people with chronic tension type headaches without migraine were identified and recruited. The expected 'dose'of the intervention was delivered to participants and intervention fidelity was high. Attendance ("dose received") fell below expectation, although 261/380 (69%) received at least at least the pre-identified minimum dose. Intervention participants generally enjoyed being in the groups but there was little evidence to support the causal assumptions underpinning the intervention were realised. Conclusions: From a process evaluation perspective despite our extensive data collection and analysis, we do not have a clear understanding of why the trial outcome was negative as the intervention was delivered as planned. However, the lack of evidence that the intervention causal assumptions brought about the planned behaviour change may provide some insight. Our data suggests only modest changes in managing headache behaviours and some disparity in how participants engaged with components of the intervention within the timeframe of the study. Moving forwards, we need a better understanding of how those who live with chronic headache can be helped to manage this disabling condition more effectively over time. Trial registration: ISRCTN79708100. [ABSTRACT FROM AUTHOR]

Objectives To determine whether a pre-existing smartphone app to teach mindfulness meditation is acceptable to women with chronic pelvic pain (CPP) and can be integrated into clinical practice within the National Health Service (NHS) CPP pathways, and to inform the design of a potential randomised clinical trial. Design A prestudy patient and public involvement (PPI) group to collect feedback on the acceptability of the existing app and study design was followed by a three-arm randomised feasibility trial. In addition, we undertook interviews and focus groups with patients and staff to explore app usability and acceptability. We also obtained participant comments on the research process, such as acceptability of the study questionnaires. Setting Two gynaecology clinics within Barts Health NHS, London, UK. Participants Patients with CPP lasting ≥6 months with access to smartphone or personal computer and understanding of basic English. Intervention The intervention was mindfulness meditation content plus additional pain module delivered by a smartphone app. Active controls received muscle relaxation content from the same app. Passive (waiting list) controls received usual care. Main outcome measures Themes on user feedback, app usability and integration, and reasons for using/not using the app. Results The use of the app was low in both active groups. Patients in the prestudy PPI group, all volunteers, were enthusiastic about the app (convenience, content, portability, flexibility, ease of use). Women contributing to the interview or focus group data (n=14), from a ‘real world’ clinic (some not regular app users), were less positive, citing as barriers lack of opportunities/motivation to use the app and lack of familiarity and capabilities with technology. Staff (n=7) were concerned about the potential need for extra support for them and for the patients, and considered the app needed organisational backing and peer acceptance. Conclusion The opinions of prestudy PPI volunteers meeting in their private time may not represent those of patients recruited at a routine clinic appointment. It may be more successful to codesign/codevelop an app with typical users than to adapt existing apps for use in real-world clinical populations. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the feasibility of a randomised trial of a modified, pre-existing, mindfulness meditation smartphone app for women with chronic pelvic pain. Design Three arm randomised feasibility trial. Setting Women were recruited at two gynaecology clinics in the UK. Interventions were delivered via smartphone or computer at a location of participants choosing. Participants Women were eligible for the study if they were over 18, had been experiencing organic or non-organic chronic pelvic pain for 6 months or more, and had access to a computer or smartphone. 90 women were randomised. Interventions Daily mindfulness meditation delivered by smartphone app, an active control app which delivered muscle relaxation techniques, and usual care without app. Interventions were delivered over 60 days. Primary and secondary outcome measures Outcomes included length of recruitment, follow-up rates, adherence to the app interventions, and clinical outcomes measured at baseline, two, three and 6 months. Results The target sample size was recruited in 145 days. Adherence to the app interventions was extremely low (mean app use 1.8 days mindfulness meditation group, 7.0 days active control). Fifty-seven (63%) women completed 6-month follow-up, and 75 (83%) women completed at least one postrandomisation follow-up. The 95% CIs for clinical outcomes were consistent with no benefit from the mindfulness meditation app; for example, mean differences in pain acceptance scores at 60 days (higher scores are better) were −2.3 (mindfulness meditation vs usual care, 95% CI: −6.6 to 2.0) and −4.0 (mindfulness meditation vs active control, 95% CI: −8.1 to 0.1). Conclusions Despite high recruitment and adequate follow-up rates, demonstrating feasibility, the extremely low adherence suggests a definitive randomised trial of the mindfulness meditation app used in this study is not warranted. Future research should focus on improving patient engagement. [ABSTRACT FROM AUTHOR]

Background: Bioelectrical impedance analysis (BIA) is a potentially valuable method for assessing lean mass and body fat levels in children from different ethnic groups. We examined the need for ethnic- and gender-specific equations for estimating fat free mass (FFM) from BIA in children from different ethnic groups and examined their effects on the assessment of ethnic differences in body fat. Methods: Cross-sectional study of children aged 8–10 years in London Primary schools including 325 South Asians, 250 black African-Caribbeans and 289 white Europeans with measurements of height, weight and arm-leg impedance (Z; Bodystat 1500). Total body water was estimated from deuterium dilution and converted to FFM. Multilevel models were used to derive three types of equation {A: FFM = linear combination(height+weight+Z); B: FFM = linear combination(height2/Z); C: FFM = linear combination(height2/Z+weight)}. Results: Ethnicity and gender were important predictors of FFM and improved model fit in all equations. The models of best fit were ethnicity and gender specific versions of equation A, followed by equation C; these provided accurate assessments of ethnic differences in FFM and FM. In contrast, the use of generic equations led to underestimation of both the negative South Asian-white European FFM difference and the positive black African-Caribbean-white European FFM difference (by 0.53 kg and by 0.73 kg respectively for equation A). The use of generic equations underestimated the positive South Asian-white European difference in fat mass (FM) and overestimated the positive black African-Caribbean-white European difference in FM (by 4.7% and 10.1% respectively for equation A). Consistent results were observed when the equations were applied to a large external data set. Conclusions: Ethnic- and gender-specific equations for predicting FFM from BIA provide better estimates of ethnic differences in FFM and FM in children, while generic equations can misrepresent these ethnic differences. [ABSTRACT FROM AUTHOR]

Background: Pregnant women with epilepsy on antiepileptic drugs (AEDs) may experience a reduction in serum AED levels. This has the potential to worsen seizure control., Objective: To determine if, in pregnant women with epilepsy on AEDs, additional therapeutic drug monitoring reduces seizure deterioration compared with clinical features monitoring after a reduction in serum AED levels., Design: A double-blind, randomised trial nested within a cohort study was conducted and a qualitative study of acceptability of the two strategies was undertaken. Stratified block randomisation with a 1 : 1 allocation method was carried out., Setting: Fifty obstetric and epilepsy clinics in secondary and tertiary care units in the UK., Participants: Pregnant women with epilepsy on one or more of the following AEDs: lamotrigine, carbamazepine, phenytoin or levetiracetam. Women with a ≥ 25% decrease in serum AED level from baseline were randomised to therapeutic drug monitoring or clinical features monitoring strategies., Interventions: In the therapeutic drug monitoring group, clinicians had access to clinical findings and monthly serum AED levels to guide AED dosage adjustment for seizure control. In the clinical features monitoring group, AED dosage adjustment was based only on clinical features., Main Outcome Measures: Primary outcome - seizure deterioration, defined as time to first seizure and to all seizures after randomisation per woman until 6 weeks post partum. Secondary outcomes - pregnancy complications in mother and offspring, maternal quality of life, seizure rates in cohorts with stable serum AED level, AED dose exposure and adverse events related to AEDs., Analysis: Analysis of time to first and to all seizures after randomisation was performed using a Cox proportional hazards model, and multivariate failure time analysis by the Andersen-Gill model. The effects were reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Secondary outcomes were reported as mean differences (MDs) or odds ratios., Results: A total of 130 women were randomised to the therapeutic drug monitoring group and 133 to the clinical features monitoring group; 294 women did not have a reduction in serum AED level. A total of 127 women in the therapeutic drug monitoring group and 130 women in the clinical features monitoring group (98% of complete data) were included in the primary analysis. There were no significant differences in the time to first seizure (HR 0.82, 95% CI 0.55 to 1.2) or timing of all seizures after randomisation (HR 1.3, 95% CI 0.7 to 2.5) between both trial groups. In comparison with the group with stable serum AED levels, there were no significant increases in seizures in the clinical features monitoring (odds ratio 0.93, 95% CI 0.56 to 1.5) or therapeutic drug monitoring group (odds ratio 0.93, 95% CI 0.56 to 1.5) associated with a reduction in serum AED levels. Maternal and neonatal outcomes were similar in both groups, except for higher cord blood levels of lamotrigine (MD 0.55 mg/l, 95% CI 0.11 to 1 mg/l) or levetiracetam (MD 7.8 mg/l, 95% CI 0.86 to 14.8 mg/l) in the therapeutic drug monitoring group than in the clinical features monitoring group. There were no differences between the groups on daily AED exposure or quality of life. An increase in exposure to lamotrigine, levetiracetam and carbamazepine significantly increased the cord blood levels of the AEDs, but not maternal or fetal complications. Women with epilepsy perceived the need for weighing up their increased vulnerability to seizures during pregnancy against the side effects of AEDs., Limitations: Fewer women than the original target were recruited., Conclusion: There is no evidence to suggest that regular monitoring of serum AED levels in pregnancy improves seizure control or affects maternal or fetal outcomes., Future Work Recommendations: Further evaluation of the risks of seizure deterioration for various threshold levels of reduction in AEDs and the long-term neurodevelopment of infants born to mothers in both randomised groups is needed. An individualised prediction model will help to identify those women who need close monitoring in pregnancy., Trial Registration: Current Controlled Trials ISRCTN01253916., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 22, No. 23. See the NIHR Journals Library website for further project information., Competing Interests: Manny Bagary reports personal fees from Eisai Co., Ltd, and personal fees from UCB Pharma outside the submitted work. Angela Pullen reports grants from GlaxoSmithKline plc., Cyberonics, Inc., Sanofi S.A., Desitin Pharma Ltd and UCB Pharma Ltd outside the submitted work. Sandra Eldridge is a member of the Health Technology Assessment Clinical Trials Board and National Institute for Health Research Clinical Trials Unit Support Funding.

Background: Female chronic pelvic pain (CPP) is defined as intermittent or constant pelvic or lower abdominal pain occurring in a woman for at least 6 months. Up to a quarter of women are estimated to be affected by CPP worldwide and it is responsible for one fifth of specialist gynecological referrals in the United Kingdom. Psychological interventions are commonly utilized. As waiting times and funding capacity impede access to face-to-face consultations, supported self-management (SSM) has emerged as a viable alternative. Mindfulness meditation is a potentially valuable SSM tool, and in the era of mobile technology, this can be delivered to the individual user via a smartphone app., Objective: To assess the feasibility of conducting a trial of a mindfulness meditation intervention delivered by a mobile phone app for patients with CPP. The main feasibility objectives were to assess patient recruitment and app adherence, to obtain information to be used in the sample size estimate of a future trial, and to receive feedback on usability of the app., Methods: Mindfulness Meditation for Women With Chronic Pelvic Pain (MEMPHIS) is a three-arm feasibility trial, that took place in two hospitals in the United Kingdom. Eligible participants were randomized in a 1:1:1 ratio to one of three treatment arms: (1) the intervention arm, consisting of a guided, spoken mindfulness meditation app; (2) an active control arm, consisting of a progressive muscle relaxation app; and (3) usual care (no app). Participants were followed-up for 6 months. Key feasibility outcomes included the time taken to recruit all patients for the study, adherence, and estimates to be used in the sample size calculation for a subsequent full-scale trial. Upon completion of the feasibility trial we will conduct focus groups to explore app usability and reasons for noncompliance., Results: Recruitment for MEMPHIS took place between May 2016 and September 2016. The study was closed March 2017 and the report was submitted to the NIHR on October 26, 2017., Conclusions: This feasibility trial will inform the design of a large multicentered trial to assess the clinical effectiveness of mindfulness meditation delivered via a smartphone app for the treatment of CPP., Trial Registration: ClinicalTrials.gov: NCT02721108; https://clinicaltrials.gov/ct2/show/NCT02721108 (Archived by WebCite at http://www.webcitation.org/6wLMAkuaU); BioMed Central: ISRCTN10925965; https://www.isrctn.com/ISRCTN10925965 (Archived by WebCite at http://www.webcitation.org/6wLMVLuys)., (©Elizabeth Ball, Sian Newton, Brennan C Kahan, Gordon Forbes, Neil Wright, Clara Cantalapiedra Calvete, Harry A L Gibson, Ewelina Rogozinska, Carol Rivas, Stephanie J C Taylor, Judy Birch, Julie Dodds. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 15.01.2018.)