Computational issues in chemo-dynamical modelling of the formation and evolution of galaxies

Chemo-dynamical N-body simulations are an essential tool for understanding the formation and evolution of galaxies. As the number of observationally determined stellar abundances continues to climb, these simulations are able to provide new constraints on the early star formaton history and chemical evolution inside both the Milky Way and Local Group dwarf galaxies. Here, we aim to reproduce the low $\alpha$-element scatter observed in metal-poor stars. We first demonstrate that as stellar particles inside simulations drop below a mass threshold, increases in the resolution produce an unacceptably large scatter as one particle is no longer a good approximation of an entire stellar population. This threshold occurs at around $10^3\,\rm{M_\odot}$, a mass limit easily reached in current (and future) simulations. By simulating the Sextans and Fornax dwarf spheroidal galaxies we show that this increase in scatter at high resolutions arises from stochastic supernovae explosions. In order to reduce this scatter down to the observed value, we show the necessity of introducing a metal mixing scheme into particle-based simulations. The impact of the method used to inject the metals into the surrounding gas is also discussed. We finally summarise the best approach for accurately reproducing the scatter in simulations of both Local Group dwarf galaxies and in the Milky Way.Comment: 23 pages, 18 figures, accepted for publication in Astronomy and Astrophysic

Experiences of people taking opioid medication for chronic non-malignant pain : a qualitative evidence synthesis using meta-ethnography

Objective To review qualitative studies on the experience of taking opioid medication for chronic non-malignant pain (CNMP) or coming off them. Design This is a qualitative evidence synthesis using a seven-step approach from the methods of meta-ethnography. Data sources and eligibility criteria We searched selected databases—Medline, Embase, AMED, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, Web of Science and Scopus (Science Citation Index and Social Science Citation Index)—for qualitative studies which provide patients’ views of taking opioid medication for CNMP or of coming off them (June 2017, updated September 2018). Data extraction and synthesis Papers were quality appraised using the Critical Appraisal Skills Programme tool, and the GRADE-CERQual (Grading of Recommendations Assessment, Development and Evaluation working group - Confidence in Evidence from Reviews of Qualitative research) guidelines were applied. We identified concepts and iteratively abstracted these concepts into a line of argument. Results We screened 2994 unique citations and checked 153 full texts, and 31 met our review criteria. We identified five themes: (1) reluctant users with little choice; (2) understanding opioids: the good and the bad; (3) a therapeutic alliance: not always on the same page; (4) stigma: feeling scared and secretive but needing support; and (5) the challenge of tapering or withdrawal. A new overarching theme of ‘constantly balancing’ emerged from the data. Conclusions People taking opioids were constantly balancing tensions, not always wanting to take opioids, and weighing the pros and cons of opioids but feeling they had no choice because of the pain. They frequently felt stigmatised, were not always ‘on the same page’ as their healthcare professional and felt changes in opioid use were often challenging

A longitudinal, qualitative study exploring sustained adherence to a hand exercise programme for Rheumatoid Arthritis evaluated in the SARAH Trial

Purpose: This study explores the experience of participants taking part in a hand exercise programme for people with rheumatoid arthritis with a focus on adherence. The exercise programme was tested in a randomised controlled trial. This parallel qualitative study will inform future implementation into clinical practice. Method: Twenty-seven semi-structured interviews from 14 participants were undertaken at 2 time points (4 and 12 months after randomisation). We collected data of participants’ experiences over time. This was guided by an interview schedule. Interview data were analysed using interpretative phenomenological analysis which is informed by phenomenological and hermeneutic theory. We recruited participants from National Health Service rheumatology and therapy departments. Results: At 4 months, 11/14 participants reported continuing with the exercises. By 12 months, 7/13 participants still reported exercising. The ability to establish a routine determined whether participants adhered to the exercise programme. This was sometimes influenced by practical issues. We also identified facilitators and barriers to regular exercise in the themes of – the therapeutic encounter, perceived benefit of exercises, attitude of mind, confidence and unpredictability. Conclusions: Establishing a routine was an important step towards participants being able to exercise independently. Therapists provided participants with skills to continue to exercise while dealing with changes in symptoms and schedules. Potential barriers to long term exercise adherence need to be taken into account and addressed for successful implementation of this programme

Process evaluation protocol for the I-WOTCH study : an opioid tapering support programme for people with chronic non-malignant pain

Introduction The Improving the Wellbeing of people with Opioid Treated CHronic Pain (I-WOTCH) randomised controlled trial uses a multicomponent self-management intervention to help people taper their opioid use. This approach is not widely used and its efficacy is unknown. A process evaluation alongside the trial will help to assess how the intervention was delivered, looking at the dose of intervention received and the fidelity of the delivery. We will explore how the intervention may have brought about change through the experiences of the participants receiving and the staff delivering the intervention and whether there were contextual factors involved. Methods and analysis A mixed methods process evaluation will assess how the processes of the I-WOTCH intervention fared and whether these affected the outcomes. We will collect quantitative data, for example, group attendance analysed with statistical methods. Qualitative data, for example, from interviews and feedback forms will be analysed using framework analysis. We will use a ‘following a thread’ and a mixed methods matrix for the final integrated analysis. Ethics and dissemination The I-WOTCH trial and process evaluation were granted full ethics approval by Yorkshire and The Humber—South Yorkshire Research Ethics Committee on 13 September 2016 (16/YH/0325). All data were collected in accordance with data protection guidelines. Participants provided written informed consent for the main trial, and all interviewees provided additional written informed consent. The results of the process evaluation will be published and presented at conferences

Implementing a hybrid cognitive-behavioural therapy for pain-related insomnia in primary care : lessons learnt from a mixed-methods feasibility study

Objectives: To test the feasibility of implementing a brief but intensive hybrid cognitive behavioural therapy (Hybrid CBT) for pain-related insomnia. Design: Mixed-methods, with qualitative process evaluation on a two-arm randomised controlled feasibility trial. Setting: Primary care. Participants: Twenty-five adult patients with chronic pain and insomnia. Intervention: Hybrid CBT or self-help control intervention. Primary and secondary outcome measures: Primary outcomes measures were the Insomnia Severity Index and interference scale of the Brief Pain Inventory (BPI). Secondary outcomes measures were the present pain intensity rating from the BPI, Multidimensional Fatigue Inventory, Hospital Anxiety and Depression Scale and EQ-5D-5L. Results: Fourteen participants were randomised to receive Hybrid CBT, 11 to receive the self-help control treatment. Of the 14 in the Hybrid CBT group, 9 (64%) completed all four treatment sessions (4 discontinued due to poor health; 1 due to time constraints). Adherence to the self-help control treatment was not monitored. The total number of participants completing the 12-week and 24-week follow-ups were 12 (6 in each group; Hybrid CBT: 43%; self-help: 55%) and 10 (5 in each group; Hybrid CBT: 36%; self-help: 45%). Based on the data available, candidate outcome measures appeared to be sensitive to changes associated with interventions. Thematic analysis of pre-postintervention interview data revealed satisfaction with treatment content among those who completed the Hybrid CBT, whereas those in the self-help control treatment wanted more contact hours and therapist guidance. Other practical suggestions for improvement included shortening the duration of each treatment session, reducing the amount of assessment paperwork, and minimising the burden of sleep and pain monitoring. Conclusion: Important lessons were learnt with regard to the infrastructure required to achieve better patient adherence and retention. Based on the qualitative feedback provided by a subset of treatment completers, future trials should also consider lowering the intensity of treatment and streamlining the data collection procedure. Trial registration number: ISRCTN17294365

The lived experience of chronic headache : a systematic review and synthesis of the qualitative literature

Objective To systematically review the qualitative literature of the lived experience of people with a chronic headache disorder. Background Chronic headaches affect 3%–4% of the population. The most common chronic headache disorders are chronic migraine, chronic tension-type headache and medication overuse headache. We present a systematic review and meta-ethnographic synthesis of the lived experience of people with chronic headache. Methods We searched seven electronic databases, hand-searched nine journals and used a modified Critical Appraisal Skills Programme checklist to appraise study quality. Following thematic analysis we synthesised the data using a meta-ethnographic approach. Results We identified 3586 unique citations; full texts were examined for 86 studies and 4 were included in the review. Included studies differed in their foci: exploring, patient-centred outcomes, chronic headache as a socially invisible disease, psychological processes mediating impaired quality of life, and the process of medication overuse. Initial thematic analysis and subsequent synthesis gave three overarching themes: ‘headache as a driver of behaviour’ (directly and indirectly), ‘the spectre of headache’ and ‘strained relationships’. Conclusion This meta-synthesis of published qualitative evidence demonstrates that chronic headaches have a profound effect on people’s lives, showing similarities with other pain conditions. There were insufficient data to explore the similarities and differences between different chronic headache disorders

CHESS process evaluation results report

Executive Summary Purpose: The purpose of this report is to present the findings from the CHESS trial process evaluation. These results are being presented to the CHESS Chief Investigator and the CHESS team before the main trial outcomes are presented. These results will form the basis of the process evaluation interpretation of the CHESS outcome as well as a process evaluation paper. Background: This process evaluation is for the Chronic Headache Education and Self-management Study (CHESS) RCT, which is evaluating an education and self-management group behavioural intervention for people with chronic headache. Chronic headache is defined as headaches which are present for 15 or more days per month. The most common types are chronic migraine and chronic tension type and medication overuse headaches. Methods: Our process evaluation was guided by the MRC framework and explored components proposed by Steckler and Linnan including Context, Reach, Recruitment, Dose delivered, Dose receive, intervention fidelity and Implementation. We employed a mixed methods approach. Using both quantitative and qualitative data. Quantitatively we explored: Reach/context, recruitment, dose delivered, dose received and fidelity. In addition to this we included the experiences of both participants and intervention facilitators about their involvement in the trial. By bringing together both the qualitative and quantitative results where we explored both early implementation (4-months) and implementation overall; looking for facilitators and barriers. Results: Reach/Context results show that we reached a diverse population that was representative of national averages in terms of ethnic mix and levels of deprivation, with a good mix of rural and suburban areas. Recruitment proved to be consistent across the study with an average of 2% (31,020) of the populations from the 164 GP practices being identified as potential participants. The study team struggled to recruit all headache types and the study became predominantly populated with those reporting migraine. The research team identified 31,020 people from GP searches and contacted, of these 7% (2178) were interested in CHESS, but of these only 47% (1034) were eligible, 68% (706) were randomised. There is a slight trend towards better recruitment and randomisation in less deprived areas. The study team successfully delivered 42 (2-day) group sessions. A total of 380 participants were invited to attend the two-day group sessions and the 1-2-1 discussions with a nurse. 288 (76%) attended at least part of the two-day course. 92 (24%) were not exposed to the CHESS intervention at all. Of the 288 who did attend the group sessions 227 (79%) attended both days whilst 61 (21%) only attended day one. Of the 288 who took part in groups 261 (91%) had a one-to-one interaction with the nurse. Overall 380/261 (69%) achieved the predefined minimum dose (attended at least some of the course and the 1-2-1 discussion with the nurse). Only 217 (57%) fully adhered to the intervention. In terms of fidelity the intervention was delivered well with adherence being slightly better than competence. (Adherence 0.83% (0.67, 1.00) Competence 70% (0.50, 0.90)). Interviews with participants gave us an insight into the lives of people who live with chronic headache. 31 participated in the interview study covering both the intervention and control arms. Participants provided their thoughts and feelings about the interventions, both control and active, with generally favourable comments. A sample of participants (n = 117) who were in the intervention arm provided detailed feedback on the 2-day group session and the nurse 1-2-1. Results were generally positive with high levels of satisfaction with the course overall and the facilitators. Venues, relaxation and taster sessions and the mindfulness received less favourable satisfaction scores. Interviewees were largely positive about the group sessions with them generally liking the group format, however some sessions were more popular than others For example, the lifestyle session, stress and anxiety and sleep sessions and overall felt it were useful to raise awareness of how these may affect headaches. Whilst the Mindfulness and relaxation for headaches Taster activity and the managing setbacks session were not well liked. Comments on the 1-2-1 sessions again were generally positive. Focus groups with the facilitators offered provided views from their perspective. Fourteen interviewees contributed to a longitudinal examination of their experiences of the trial and its impact on their lives with chronic headache. These showed similarities and differences between the intervention and control arm participants. Again these interviews highlight the complexity of living with chronic headache. In the intervention arm participants described having made, or making, changes to their lives and headache management that could be attributed to CHESS. But equally there is evidence of similar improvements in control participants. Conclusion: The results of the PE, reveal that the CHESS study was well conducted and it reached out to a diverse population across different geographical settings. Recruitment was successful. However, the PE does highlight that this is a complex population that may be hard to reach. The intervention components (2-day course and 1-2-1 sessions) were delivered with fidelity and, in most cases, were well received. We have results that will help interpret the outcome results from the main trial and we are making a number of recommendations

Patient and public involvement in a UK National Institute for Health Research Programme Grant for Applied Research:Experiences from the Chronic Headache Education and Self-management Study (CHESS)

Background: Patient and public involvement (PPI) plays a crucial role in ensuring research is carried out in conjunction with the people that it will impact upon. In this article, we present our experiences and reflections from working collaboratively with patients and public through the lifetime of an National Institute for Health Research (NIHR) programme grant; the Chronic Headache Education and Self-management Study (CHESS) which took place between 2015 and 2020. PPI over the course of CHESS: We worked closely with three leading UK migraine charities and a lay advisory group throughout the programme. We followed NIHR standards and used the Guidance for Reporting Involvement of Patients and the Public checklist. We consulted our PPI contacts using a variety of methods depending on the phase of the study and the nature of the request. This included emails, discussions, and face-to-face contact. PPI members contributed throughout the study in the programme development, in the grant application, ethics documentation, and trial oversight. During the feasibility study; in supporting the development of a classification interview for chronic headache by participating in a headache classification conference, assessing the relevance, and acceptability of patient-reported outcome measures by helping to analyse cognitive interview data, and testing the smartphone application making suggestions on how best to present the summary of data collected for participants. Due to PPI contribution, the content and duration of the study intervention were adapted and a Delphi study with consensus meeting developed a core outcome set for migraine studies. Conclusions: The involvement of the public and patients in CHESS has allowed us to shape its overall design, intervention development, and establish a core outcome set for future migraine studies. We have reflected on many learning points for the future application of PPI

Dementia and physical activity (DAPA) trial of moderate to high intensity exercise training for people with dementia : randomised controlled trial

Objective: To estimate the effect of a moderate to high intensity aerobic and strength exercise training programme on cognitive impairment and other outcomes in people with mild to moderate dementia. Design: Multicentre, pragmatic, investigator masked, randomised controlled trial. Setting: National Health Service primary care, community and memory services, dementia research registers, and voluntary sector providers in 15 English regions. Participants: 494 people with dementia: 329 were assigned to an aerobic and strength exercise programme and 165 were assigned to usual care. Random allocation was 2:1 in favour of the exercise arm. Interventions: Usual care plus four months of supervised exercise and support for ongoing physical activity, or usual care only. Interventions were delivered in community gym facilities and NHS premises. Main outcome measures: The primary outcome was score on the Alzheimer’s disease assessment scale-cognitive subscale (ADAS-cog) at 12 months. Secondary outcomes included activities of daily living, neuropsychiatric symptoms, health related quality of life, and carer quality of life and burden. Physical fitness (including the six minute walk test) was measured in the exercise arm during the intervention. Results: The average age of participants was 77 (SD 7.9) years and 301/494 (61%) were men. By 12 months the mean ADAS-cog score had increased to 25.2 (SD 12.3) in the exercise arm and 23.8 (SD 10.4) in the usual care arm (adjusted between group difference −1.4, 95% confidence interval −2.6 to −0.2, P=0.03). This indicates greater cognitive impairment in the exercise group, although the average difference is small and clinical relevance uncertain. No differences were found in secondary outcomes or preplanned subgroup analyses by dementia type (Alzheimer’s disease or other), severity of cognitive impairment, sex, and mobility. Compliance with exercise was good. Over 65% of participants (214/329) attended more than three quarters of scheduled sessions. Six minute walking distance improved over six weeks (mean change 18.1 m, 95% confidence interval 11.6 m to 24.6 m). Conclusion: A moderate to high intensity aerobic and strength exercise training programme does not slow cognitive impairment in people with mild to moderate dementia. The exercise training programme improved physical fitness, but there were no noticeable improvements in other clinical outcomes