Managing chronic widespread pain in primary care : a qualitative study of patient perspectives and implications for treatment delivery

Funding The MUSICIAN trial was supported by an award from Arthritis Research UK, Chesterfield, UK. Grant number: 17292. The funding body approved the design of the study. They played no role in the collection, analysis, and interpretation of data or the writing of the manuscript.Peer reviewedPublisher PD

Treatment expectations but not preference affect outcome in a trial of CBT and exercise for pain

The following are members of the MUSICIAN study team: Gary Macfarlane (Principal Investigator), John McBeth (Investigator), Deborah Symmons (Investigator), Karina Lovell (investigator), Philip Keeley (Investigator), Phil Hannaford (Investigator), Chrysa Gkazinou (Trial manager), Marcus Beasley (Research Assistant), Elizabeth Jones (PhD student), Gordon Prescott (Statistician), and Steve Woby (Investigator). We are grateful to the practices and patients in Aberdeen city and Cheshire, which participated in the study: Carden medical centre, Elmbank medical practice, Great Western Road medical practice, Garthdee medical group, Readesmoor medical group practice, Lawton House surgery, Bollington medical practice, Park Lane surgery. The Scottish Primary Care Research Network facilitated access to patient information at the practices in Aberdeen city. Charlie Stockton was the study manager and Ashraf El-Metwally an Investigator during the setting up and for part of the conduct of the study. John Norrie was originally an investigator of the MUSICIAN study while Director of the Centre for Health Care Randomised Trials (CHART) at the University of Aberdeen. We are grateful for the input of members of the Health Services Research Unit (HSRU) at The University of Aberdeen in the conduct of the study: Alison MacDonald and Gladys McPherson. We are grateful to the project assistants who worked on the survey: Dev Acharya, Jennifer Bannister, Flora Joyce, Michelle Rein., Karen Kane, and Rowan Jasper. Alison Littlewood was responsible for study management at the Cheshire site. Finally, we thank the independent members of the trial steering committee (Professor Matthew Hotopf, Professor Tracey Howe, Professor Martin Underwood) and data monitoring committee (Dr. Marwan Bukhari, Professor Hazel Inskip, Dr. Chris Edwards). Funding details The study was funded by Arthritis Research UK, grant number 17292.Peer reviewedPublisher PD

Improving outcome for people with chronic widespread pain and fibromyalgia

Chronic widespread pain is characteristic of fibromyalgia, a condition which also includes features such as cognitive dysfunction, sleep problems, fatigue and mood disorders. The lack of objective measures of the disorder has proved challenging in terms of diagnostic criteria, and thus timely diagnosis and access to effective management. Although there is a perception that the aetiology of the condition is not known and that there is no effective treatment, this is not the case. Over the past decades understanding of the pathophysiology and aetiology of the condition has improved and management that results in improved symptoms for many patients, has been identified. This thesis addresses important components in relation to improving outcome for patients with chronic widespread pain and fibromyalgia. The thesis focuses on three areas (over seven published manuscripts): effective management for persons with chronic widespread pain and fibromyalgia; investigating excess mortality in people with chronic widespread pain; Identifying and managing fibromyalgia when it occurs in the context of inflammatory arthritis. It includes seven manuscripts. The results of the manuscripts show that there is good evidence for the non-pharmacologic therapies of exercise and a cognitive behaviour informed approach to managing people with chronic widespread pain/fibromyalgia, that the excess mortality in such patients could be addressed by focussing on lifestyle factors (diet and exercise). When fibromyalgia occurs in the context of axial spondyloarthritis, such patients do (as a group) respond to biologic therapy but that specific aspects of their conditions (high somatic symptom burden) predict non-response and the likely need for additional (non-pharmacologic approaches) to management

BayesGmed : An R-package for Bayesian Causal Mediation Analysis

3 figures. A missing appendix sections added and a text about prior specification added in section 4Preprin

Genetic variation in the hypothalamic–pituitary–adrenal stress axis influences susceptibility to musculoskeletal pain: results from the EPIFUND study

<b>Objectives</b> To determine if genetic variation in genes in the hypothalamic–pituitary–adrenal (HPA) axis, the primary stress response system, influences susceptibility to developing musculoskeletal pain.<p></p> <b>Methods</b> Pain and comorbidity data was collected at three time points in a prospective population-based cohort study. Pairwise tagging single nucleotide polymorphisms (SNPs) were selected and genotyped for seven genes. Genetic association analysis was carried out using zero-inflated negative binomial regression to test for association between SNPs and the maximum number of pain sites across the three time points in participants reporting pain, reported as proportional changes with 95% CIs. SNPs were also tested for association with chronic widespread pain (CWP) using logistic regression reporting odds ratios and 95% CI.<p></p> <b>Results</b> A total of 75 SNPs were successfully genotyped in 994 participants including 164 cases with persistent CWP and 172 pain-free controls. Multiple SNPs in SERPINA6 were associated with the maximum number of pain sites; for example, each copy of the T allele of rs941601 was associated with having 16% (proportional change=1.16, 95% CI 1.04 to 1.28, p=0.006) more pain sites compared to participants with the CC genotype. SERPINA6 gene SNPs were also associated with CWP. Significant associations between the maximum number of pain sites and SNPs in the CRHBP and POMC genes were also observed and a SNP in MC2R was also associated with CWP. Associations between SNPs and comorbidity of poor sleep quality and depression explained some of the associations observed.<p></p> <b>Conclusions</b> Genetic variation in HPA axis genes was associated with musculoskeletal pain; however, some of the associations were explained by comorbidities. Replication of these findings is required in independent cohorts

Scotland Registry for Ankylosing Spondylitis (SIRAS) – Protocol

Funding SIRAS was funded by unrestricted grants from Pfizer and AbbVie. The project was reviewed by both companies, during the award process, for Scientific merit, to ensure that the design did not compromise patient safety, and to assess the global regulatory implications and any impact on regulatory strategy.Publisher PD

Lessons from experiences of accessing healthcare during the pandemic for remobilising rheumatology services : a national mixed methods study

Acknowledgements We are grateful to our patient partner Inga Wood for help with designing the interview schedule and for commenting on the manuscript and Lynne Laidlaw for help with designing the questionnaire. The authors do not report any conflicts of interest. GJM conceived the idea for the study and all authors were involved in the detailed planning. LM, KS, and RH conducted the qualitative analysis with input from JP. MB and GJ undertook the questionnaire analysis. LM and RH integrated quantitative and qualitative findings, and KS, JP and GJM contributed to interpretation of findings. RH and LM drafted the manuscript and all authors contributed important intellectual content via written comments. Funding This work was supported by Versus Arthritis [Grant No: 20748] and the British Society for Rheumatology. The funding for the original studies included were from Versus Arthritis (MAmMOTH) and the British Society for Rheumatology (BSRBR-AS and BSR-PsA). LM is supported by the MRC/Versus Arthritis Centre for Musculoskeletal Health and Work [Grant No: 20665].Peer reviewedPublisher PD

Do genetic predictors of pain sensitivity associate with persistent widespread pain?

Genetic risk factors for pain sensitivity may also play a role in susceptibility to chronic pain disorders, in which subjects have low pain thresholds. The aim of this study was to determine if proposed functional single nucleotide polymorphisms (SNPs) in the GTP cyclohydrolase (GCH1) and μ opioid receptor (OPRM1) genes previously associated with pain sensitivity affect susceptibility to chronic widespread pain (CWP). Pain data was collected using body manikins via questionnaire at three time-points over a four year period from subjects aged 25-65 in the North-West of England as part of a population based cohort study, EPIFUND. CWP was defined at each time point using standard criteria. Three SNPs forming a proposed "pain-protective" haplotype in GCH1 (rs10483639, rs3783641 and rs8007267) and two SNPs in OPRM1 (rs1777971 (A118G) and rs563649) were genotyped in cases with persistent CWP (CWP present at ≥2 time-points) and controls who were pain-free at all time-points. The expectation-maximisation algorithm was used to estimate haplotype frequencies. The frequency of the "pain-protective" (CAT - C allele of rs10483639, A allele of rs3783641 and T allele of rs8007267) haplotype was compared to the frequency of the other haplotypes between cases and controls using the χ2 test. Allele frequencies and carriage of the minor allele was compared between cases and controls using χ2 tests for the OPRM1 SNPs. The frequency of the proposed GCH1 "pain-protective" haplotype (CAT) did not significantly differ between cases and controls and no significant associations were observed between the OPRM1 SNPs and CWP. In conclusion, there was no evidence of association between proposed functional SNPs, previously reported to influence pain sensitivity, in GCH1 and OPRM1 with CWP. Further evidence of null association in large independent cohorts is required to truly exclude these SNPs as genetic risk factors for CWP

Hypothalamic-pituitary-adrenal stress axis function and the relationship with chronic widespread pain and its antecedents

In clinic studies, altered hypothalamic-pituitary-adrenal (HPA) axis function has been associated with fibromyalgia, a syndrome characterised by chronic widespread body pain. These results may be explained by the associated high rates of psychological distress and somatisation. We address the hypothesis that the latter, rather than the pain, might explain the HPA results. A population study ascertained pain and psychological status in subjects aged 25 to 65 years. Random samples were selected from the following three groups: satisfying criteria for chronic widespread pain; free of chronic widespread pain but with strong evidence of somatisation ('at risk'); and a reference group. HPA axis function was assessed from measuring early morning and evening salivary cortisol levels, and serum cortisol after physical (pain pressure threshold exam) and chemical (overnight 0.25 mg dexamethasone suppression test) stressors. The relationship between HPA function with pain and the various psychosocial scales assessed was modelled using appropriate regression analyses, adjusted for age and gender. In all 131 persons with chronic widespread pain (participation rate 74%), 267 'at risk' (58%) and 56 controls (70%) were studied. Those in the chronic widespread pain and 'at risk' groups were, respectively, 3.1 (95% CI (1.3, 7.3)) and 1.8 (0.8, 4.0) times more likely to have a saliva cortisol score in the lowest third. None of the psychosocial factors measured were, however, associated with saliva cortisol scores. Further, those in the chronic widespread pain (1.9 (0.8, 4.7)) and 'at risk' (1.6 (0.7, 3.6)) groups were also more likely to have the highest serum cortisol scores. High post-stress serum cortisol was related to high levels of psychological distress (p = 0.05, 95% CI (0.02, 0.08)). After adjusting for levels of psychological distress, the association between chronic widespread pain and post-stress cortisol scores remained, albeit slightly attenuated. This is the first population study to demonstrate that those with established, and those psychologically at risk of, chronic widespread pain demonstrate abnormalities of HPA axis function, which are more marked in the former group. Although some aspects of the altered function are related to the psychosocial factors measured, we conclude that the occurrence of HPA abnormality in persons with chronic widespread pain is not fully explained by the accompanying psychological stress

The associated features of multiple somatic symptom complexes

We are grateful to the participants in the project and to the General Practitioners and their teams who facilitated it. The study would have been impossible without the work of our research assistants: Judy Jackson, Alison Littlewood and Ian Davies. The study was funded by the UK Medical Research Council. The UK MRC had no role in study design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.Peer reviewedPostprin