Patient engagement in designing, conducting, and disseminating clinical pain research: IMMPACT recommended considerations.

ABSTRACT: In the traditional clinical research model, patients are typically involved only as participants. However, there has been a shift in recent years highlighting the value and contributions that patients bring as members of the research team, across the clinical research lifecycle. It is becoming increasingly evident that to develop research that is both meaningful to people who have the targeted condition and is feasible, there are important benefits of involving patients in the planning, conduct, and dissemination of research from its earliest stages. In fact, research funders and regulatory agencies are now explicitly encouraging, and sometimes requiring, that patients are engaged as partners in research. Although this approach has become commonplace in some fields of clinical research, it remains the exception in clinical pain research. As such, the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials convened a meeting with patient partners and international representatives from academia, patient advocacy groups, government regulatory agencies, research funding organizations, academic journals, and the biopharmaceutical industry to develop consensus recommendations for advancing patient engagement in all stages of clinical pain research in an effective and purposeful manner. This article summarizes the results of this meeting and offers considerations for meaningful and authentic engagement of patient partners in clinical pain research, including recommendations for representation, timing, continuous engagement, measurement, reporting, and research dissemination.

Rapid anti-myeloma activity by T cells expressing an anti-BCMA CAR with a human heavy-chain-only antigen-binding domain.

Multiple myeloma (MM) is a rarely curable malignancy of plasma cells. MM expresses B cell maturation antigen (BCMA). We developed a fully human anti-BCMA chimeric antigen receptor (CAR) with a heavy-chain-only antigen-recognition domain, a 4-1BB domain, and a CD3ζ domain. The CAR was designated FHVH33-CD8BBZ. We conducted the first-in-humans clinical trial of T cells expressing FHVH33-CD8BBZ (FHVH-T). Twenty-five patients with relapsed MM were treated. The stringent complete response rate (sCR) was 52%. Median progression-free survival (PFS) was 78 weeks. Of 24 evaluable patients, 6 (25%) had a maximum cytokine-release syndrome (CRS) grade of 3; no patients had CRS of greater than grade 3. Most anti-MM activity occurred within 2-4 weeks of FHVH-T infusion as shown by decreases in the rapidly changing MM markers serum free light chains, urine light chains, and bone marrow plasma cells. Blood CAR+ cell levels peaked during the time that MM elimination was occurring, between 7 and 15 days after FHVH-T infusion. C-C chemokine receptor type 7 (CCR7) expression on infusion CD4+ FHVH-T correlated with peak blood FHVH-T levels. Single-cell RNA sequencing revealed a shift toward more differentiated FHVH-T after infusion. Anti-CAR antibody responses were detected in 4 of 12 patients assessed. FHVH-T has powerful, rapid, and durable anti-MM activity.

Bringing the Walk with Ease Programme to the UK: a mixed-methods study to assess the relevance, acceptability, and feasibility of implementation for people with arthritis and musculoskeletal conditions.

Developed in the United States (US), Walk With Ease (WWE) is a popular evidence-based, 6-week community walking programme for adults with arthritis, delivered in either an instructor-led or self-directed format. While WWE has expanded into communities across the USA, it is relatively unknown in other countries across the globe. This study, in collaboration with community and patient partners, aimed to examine the relevance, acceptability and feasibility of introducing WWE into a UK context. After initial cultural adaptation, participants were recruited into the study. Eligible (≥18 years, doctor diagnosed arthritis (confirmed or self-report), self-reported joint symptoms in last 30 days, BMI ≥25 kg/m2, and <150 min/week of moderate/vigorous PA) and consented participants were randomized into two groups: WWE programme or usual care. A mixed-methods analysis approach integrated quantitative data (physical performance assessment; baseline and post-six week programme questionnaire) and qualitative data (narrative interviews exploring participants' pre- and post-WWE experiences and stakeholders' perceptions). Of 149 participants, the majority were women (70%) aged ≥60 years (76%). Among the 97 receiving the programme, 52 chose instructor-led; 45 chose self-directed. Participants found WWE relevant and acceptable-99% indicating they would recommend WWE to family/friends. Within both WWE formats, mixed differences representing improvement were observed at 6 weeks from baseline for physical performance and arthritis symptoms. Emergent themes included improved motivation, health, and social well-being. WWE is a relevant and acceptable walking programme with scope for wider implementation to support UK health and well-being policy strategies.

Walk With Ease (WWE) is a popular walking programme in the USA. It was specially designed for people living with arthritis and musculoskeletal conditions. Over 6-weeks, participants follow a guidebook and can choose to walk by themselves or with an instructor-led group. Research evidence has shown that WWE increases time spent being physically active and improves arthritis symptoms. We wanted to bring WWE across the pond to explore whether it would be well-received and possible to conduct in the UK. We worked with community and patient partners to make sure the WWE materials made sense for a British audience and trained walk leaders. We recruited participants and asked them to complete physical assessment tests, questionnaires, and interviews both before and after the 6-week walking programme. There were 149 participants who took part­most were older women­and 97 participants received the WWE programme. Almost all (99%) would recommend WWE to family and friends. They said, in the interviews, that the programme improved their motivation to be physically active, helped their mood, and social well-being. Their physical performance and arthritis symptoms also improved. WWE has great potential to improve health and well-being of people with arthritis in the UK.

Factors predicting the transition from acute to persistent pain in people with 'sciatica': the FORECAST longitudinal prognostic factor cohort study protocol.

INTRODUCTION: Sciatica is a common condition and is associated with higher levels of pain, disability, poorer quality of life, and increased use of health resources compared with low back pain alone. Although many patients recover, a third develop persistent sciatica symptoms. It remains unclear, why some patients develop persistent sciatica as none of the traditionally considered clinical parameters (eg, symptom severity, routine MRI) are consistent prognostic factors.The FORECAST study (factors predicting the transition from acute to persistent pain in people with 'sciatica') will take a different approach by exploring mechanism-based subgroups in patients with sciatica and investigate whether a mechanism-based approach can identify factors that predict pain persistence in patients with sciatica. METHODS AND ANALYSIS: We will perform a prospective longitudinal cohort study including 180 people with acute/subacute sciatica. N=168 healthy participants will provide normative data. A detailed set of variables will be assessed within 3 months after sciatica onset. This will include self-reported sensory and psychosocial profiles, quantitative sensory testing, blood inflammatory markers and advanced neuroimaging. We will determine outcome with the Sciatica Bothersomeness Index and a Numerical Pain Rating Scale for leg pain severity at 3 and 12 months.We will use principal component analysis followed by clustering methods to identify subgroups. Univariate associations and machine learning methods optimised for high dimensional small data sets will be used to identify the most powerful predictors and model selection/accuracy.The results will provide crucial information about the pathophysiological drivers of sciatica symptoms and may identify prognostic factors of pain persistence. ETHICS AND DISSEMINATION: The FORECAST study has received ethical approval (South Central Oxford C, 18/SC/0263). The dissemination strategy will be guided by our patient and public engagement activities and will include peer-reviewed publications, conference presentations, social media and podcasts. TRIAL REGISTRATION NUMBER: ISRCTN18170726; Pre-results.

Sex Difference in OA: Should We Blame Estrogen?

Osteoarthritis (OA) is a leading cause of chronic pain and disability, not only in the United States but also worldwide. The burden of OA is higher in women than in men. Estrogen as a possible explanation for observed sex differences in OA has not been definitively established. The purpose of this review was to summarize the results from studies of estrogen, estrogen depletion and treatment, and their impact on knee, hip, hand, and spine OA. We conducted a targeted review of the literature using PubMed. Although several studies show that hormone replacement therapy has the potential to be protective of OA for some joints, there are studies that showed no protective effect or even adverse effect. Taken together, the evidence for the protective effect of estrogen therapy depends on OA joint, OA outcome, and study design. Although this area has been studied for decades, more exclusively since the 1990s, there is a lack of high-quality experimental research in this topic. The lack of definitive conclusion on whether estrogen can play a role in the development in OA of either the knee, hip, spine, or hand is often in part due to the noncomparability of studies existing within the literature. Differences in diagnostic criteria, imaging modalities, populations studied, study designs, and outcome measures, as well as random error, have all contributed to inconclusive evidence. Future research on the role of estrogen in OA is needed, particularly as global demographic shifts in increasing overweight/obesity prevalence and ageing populations may contribute to widening OA-related health inequalities.

Determinants of healthy ageing: a systematic review of contemporary literature.

BACKGROUND: Healthy ageing frameworks have been highly explored. Our objective was to assess existing frameworks for healthy ageing and to identify commonly described factors that can potentially act as determinants of healthy ageing. METHODS: We carried out a systematic review by searching five electronic databases (EMBASE, MEDLINE, Cochrane, PsychINFO, and CINAHL) from January 2010 to November 2020 to capture contemporary evidence. Eligible studies needed to report a clear framework of healthy ageing in humans, within one or more of three domains (physical, mental/cognitive, social), in English. No restriction was placed on geographical location. Retrospective studies, studies that did not report a framework of healthy ageing, and studies with a focus on diagnostic measures were excluded. RESULTS: Of 3329 identified records, nine studies met our eligibility criteria and were included. Most of the studies were qualitative or cross sectional, and a majority were carried out in Asia, followed by North America, Australia, and Africa. The ten determinants identified for healthy ageing include physical activity, diet, self-awareness, outlook/attitude, life-long learning, faith, social support, financial security, community engagement, and independence. CONCLUSIONS: We identified ten determinants of healthy ageing proposed by the contemporary evidence base. There appears to be increasing acknowledgement of the instrumental role of social and mental/cognitive well-being as determinants of healthy ageing. The extent to which each determinant contributes to healthy ageing requires further evaluation.

Motor development in infancy and spine shape in early old age: Findings from a British birth cohort study.

Spine shape changes dramatically in early life, influenced by attainment of developmental milestones such as independent walking. Whether these associations persist across life is unknown. Therefore, we investigated associations between developmental milestones and spine shape, as determined using statistical shape models (SSMs) of lumbar spine from dual-energy X-ray absorptiometry scans in 1327 individuals (688 female) at 60 to 64 years in the MRC National Survey of Health and Development. Lumbar lordosis angle (L4 inferior endplate to T12 superior endplate) was measured using the two-line Cobb method. In analyses adjusted for sex, height, lean and fat mass, socioeconomic position, and birthweight, later walking age was associated with greater lordosis described by SSM1 (regression coefficient, 0.023; 95% CI, 0.000-0.047; P = .05) and direct angle measurement. Modest associations between walking age and less variation in anterior-posterior vertebral size caudally (SSM6) were also observed (0.021; 95% CI, -0.002 to 0.044; P = .07). Sex interactions showed that later walking was associated with larger relative vertebral anterior-posterior dimensions in men (SSM3; -0.043; 95% CI, -0.075 to 0.01; P = .01) but not women (0.018; 95% CI, -0.0007 to 0.043; P = .17). Similar associations were observed between age at independent standing and SSMs but there was little evidence of association between sitting age and spine shape. Unadjusted associations between walking age and SSMs 1 and 6 remained similar after adjustment for potential confounders and mediators. This suggests that these associations may be explained by altered mechanical loading of the spine during childhood growth, although other factors could contribute. Early life motor development, particularly walking, may have a lasting effect on the features of spine morphology with clinical significance.

AxSpA patients who also meet criteria for fibromyalgia: identifying distinct patient clusters using data from a UK national register (BSRBR-AS).

BACKGROUND: Around 1 in 8 patients with axial spondyloarthritis (axSpA) also meet criteria for fibromyalgia and such patients have considerable unmet need. Identifying effective therapy is important but to what extent fibromyalgia-like symptoms relate to axSpA disease severity has not been established. The aim of the current analysis was to determine whether distinct clusters of axSpA patients exist and if so to determine a) whether they differ in terms of prevalence of fibromyalgia and b) the features of patients in clusters with high prevalence. METHODS: The British Society for Rheumatology Biologics Register (BSRBR-AS) recruited axSpA patients from 83 centres 2012-2017. Clinical data, and information from patients was collected (including research criteria for fibromyalgia). Cluster analysis was undertaken using split samples for development and validation both in the whole population and the sub-group which met fibromyalgia criteria. RESULTS: One thousand three hundred thirty-eight participants were included of whom 23% met research criteria for fibromyalgia. Four clusters were identified. Two exhibited very high disease activity, one which was primarily axial (n = 347) and a smaller cluster (n = 32) with axial and peripheral disease, and in both groups more than half of members met criteria for fibromyalgia. The remaining two clusters (n = 437, n = 462) had overall less severe disease however the one which showed greater disease activity and poorer quality of life had a higher proportion meeting fibromyalgia criteria (16% v. 4%). Within those meeting fibromyalgia criteria there were three clusters. The two main groups were defined by level of symptom severity with a smaller third cluster noted to have high average swollen and tender joint counts and high levels of comorbidity. CONCLUSIONS: The major feature defining clusters with a high proportion of persons meeting criteria for fibromyalgia is high axSpA disease activity although clusters with features of fibromyalgia in the absence of high disease activity also show moderately high prevalence. Management may be most successful with pharmacologic therapy to target inflammation but enhanced by the concurrent use of non-pharmacologic therapy in such patients.

Nonpharmacologic Management of Orthostatic Hypotension in Older People: A Systematic Review. The SENATOR ONTOP Series.

OBJECTIVES: Nonpharmacologic therapies are often recommended as a first-line treatment for orthostatic hypotension (OH). However, the true effect of nonpharmacologic therapy remains unclear, particularly in the older population. We undertook a systematic review evaluating the efficacy of nonpharmacologic interventions in older people with OH to provide evidence-based recommendations. DESIGN: Systematic review of systematic reviews. SETTING AND PARTICIPANTS: MEDLINE, PubMed, EMBASE, and Cochrane Database of Systematic Reviews, CINHAL, and PsycINFO were searched up to June 2018. Two reviewers identified eligible systematic reviews from which primary studies were selected. We included both randomized and nonrandomized studies that evaluated any type of nonpharmacologic intervention and reported outcomes of change in postural drop in systolic blood pressure (SBP) and/or orthostatic symptoms measured using any validated instrument. The Cochrane risk of bias tool was used, with recommendations based on the GRADE approach. RESULTS: Eleven trials were included. Meta-analysis of lower limb compression showed a reduction in the postural drop in SBP of 9.83 mmHg [95% confidence interval (CI) -12.56, -7.11], whereas abdominal compression showed a larger reduction in postural drop in SBP of 12.30 mmHg (95% CI -18.20, -6.39). Compression therapy was also beneficial in reducing OH symptoms. However, the quality of the evidence for compression therapy was very poor. One study each was identified for sleeping with head-up (SHU), home-based resistance training (HBRT), and multicomponent intervention but did not significantly reduce postural SBP drop. Bolus water drinking was effective in 1 study but the study was of low quality. CONCLUSIONS/IMPLICATIONS: There is no high-quality evidence to recommend any of the nonpharmacologic therapies for the management of OH in older people. Yet, we make a weak recommendation for lower limb and abdominal compression therapy based on very low quality evidence. Large-scale trials are warranted in older people to substantiate the efficacy of nonpharmacologic therapies in OH.

Association between musculoskeletal pain with social isolation and loneliness: analysis of the English Longitudinal Study of Ageing.

INTRODUCTION: Musculoskeletal pain is a prevalent health challenge for all age groups worldwide, but most notably in older adults. Social isolation is the consequence of a decrease in social network size with a reduction in the number of social contacts. Loneliness is the psychological embodiment of social isolation and represents an individual's perception of dissatisfaction in the quality or quantity of their social contacts. This study aims to determine whether a relationship exists between musculoskeletal pain and social isolation and loneliness. METHODS: A cross-sectional analysis of the English Longitudinal Study of Ageing (ELSA) cohort was undertaken. ELSA is a nationally representative sample of the non-institutionalised population of individuals aged 50 years and over based in England. Data were gathered on social isolation through the ELSA Social Isolation Index, loneliness through the University of California, Los Angeles (UCLA) Loneliness Scale and musculoskeletal pain. Data for covariates included physical activity, depression score, socioeconomic status, access to transport and demographic characteristics. Logistic regression analyses were undertaken to determine the relationship between social isolation and loneliness with pain and the additional covariates. RESULTS: A total of 9299 participants were included in the analysis. This included 4125 (44.4%) males, with a mean age of 65.8 years. There was a significant association where social isolation was lower for those in pain (odd ratio (OR): 0.87; 95% confidence intervals (CI): 0.75 to 0.99), whereas the converse occurred for loneliness where this was higher for those in pain (OR: 1.15; 95% CI: 1.01 to 1.31). Age, occupation, physical activity and depression were all associated with increased social isolation and loneliness. CONCLUSION: People who experience chronic musculoskeletal pain are at greater risk of being lonely, but at less risk of being socially isolated. Health professionals should consider the wider implications of musculoskeletal pain on individuals, to reduce the risk of negative health implications associated with loneliness from impacting on individual's health and well-being.

Differences in long-term physical activity trajectories among individuals with chronic widespread pain: A secondary analysis of a randomized controlled trial.

BACKGROUND: Little is known about long-term physical activity (PA) maintenance in those with chronic widespread pain (CWP) following an exercise intervention. This study examined PA over time to identify the existence and characteristics of subgroups following distinct PA trajectories. METHODS: Data come from individuals with CWP who took part in a 2 × 2 factorial randomized controlled trial, receiving either exercise or both exercise and cognitive behavioural therapy treatment. Information, including self-report PA, was collected at baseline recruitment, immediately post-intervention, 3, 24 and 60+ month post-treatment. Analyses were conducted on 196 men and women with ≥ 3 PA data points. Group-based trajectory modelling was used to identify latent PA trajectory groups and baseline characteristics (e.g., demographics, pain, self-rated health, fatigue, coping-strategy use and kinesiophobia) of these groups. RESULTS: The best fitting model identified was one with three trajectories: "non-engagers" (n = 32), "maintainers" (n = 144) and "super-maintainers" (n = 20). Overall, mean baseline PA levels were significantly different between groups (non-engagers: 1.1; maintainers: 4.6; super-maintainers: 8.6, p < 0.001) and all other follow-up points. Non-engagers reported, on average, greater BMI, higher disabling chronic pain, poorer self-rated health, physical functioning, as well as greater use of passive coping strategies and lower use of active coping strategies. CONCLUSIONS: The majority of individuals with CWP receiving exercise as part of a trial were identified as long-term PA maintainers. Participants with poorer physical health and coping response to symptoms were identified as non-engagers. For optimal symptom management, a stratified approach may enhance initiation and long-term PA maintenance in individuals with CWP. SIGNIFICANCE: Chronic pain can be a major barrier to engaging in exercise, a popular self-management strategy. Our findings identify three distinct long-term physical activity trajectories for individuals receiving the same exercise intervention. This suggests an approach by health care providers which identifies individuals who would benefit from additional support to enhance initiation and long-term physical activity maintenance could deliver better outcomes for such patients.

Protocol for a multicentre randomised controlled parallel-group trial to compare the effectiveness of remotely delivered cognitive-behavioural and graded exercise interventions with usual care alone to lessen the impact of fatigue in inflammatory rheumatic diseases (LIFT).

INTRODUCTION: Fatigue remains pervasive, disabling and challenging to manage across all inflammatory rheumatic diseases (IRDs). Non-pharmacological interventions, specifically cognitive-behavioural approaches (CBAs) and graded exercise programmes designed to support and increase exercise, are valuable treatments which help patients with IRD to manage their fatigue. Yet, healthcare systems have encountered substantial barriers to the implementation of these therapeutic options. Lessening the Impact of Fatigue in Inflammatory Rheumatic Diseases: a Randomised Trial (LIFT) is designed to give insights into the effectiveness of a remotely delivered standardised intervention for a range of patients with IRD. It will also enable the exploration of putative moderating factors which may allow for the future triage of patients and to investigate the precise mediators of treatment effect in IRD-related fatigue. METHODS AND ANALYSIS: LIFT is a pragmatic, multicentre, three-arm randomised, controlled trial, which will test whether adapted CBA and personalised exercise programme interventions can individually reduce the impact and severity of fatigue. This will be conducted with up to 375 eligible patients diagnosed with IRD and interventions will be delivered by rheumatology healthcare professionals, using the telephone or internet-based audio/video calls. ETHICS APPROVAL AND DISSEMINATION: Ethical approval has been granted by Wales REC 7 (17/WA/0065). Results of this study will be disseminated through presentation at scientific conferences and in scientific journal. A lay summary of the results will be sent to participants. TRIAL REGISTRATION NUMBER: NCT03248518; Pre-results.

Age at Onset of Walking in Infancy Is Associated With Hip Shape in Early Old Age.

Bones' shapes and structures adapt to the muscle and reaction forces they experience during everyday movements. Onset of independent walking, at approximately 12 months, represents the first postnatal exposure of the lower limbs to the large forces associated with bipedal movements; accordingly, earlier walking is associated with greater bone strength. However, associations between early life loading and joint shape have not been explored. We therefore examined associations between walking age and hip shape at age 60 to 64 years in 1423 individuals (740 women) from the MRC National Survey of Health and Development, a nationally representative British birth cohort. Walking age in months was obtained from maternal interview at age 2 years. Ten modes of variation in hip shape (HM1 to HM10), described by statistical shape models, were ascertained from DXA images. In sex-adjusted analyses, earlier walking age was associated with higher HM1 and HM7 scores; these associations were maintained after further adjustment for height, body composition, and socioeconomic position. Earlier walking was also associated with lower HM2 scores in women only, and lower HM4 scores in men only. Taken together, this suggests that earlier walkers have proportionately larger (HM4) and flatter (HM1, HM4) femoral heads, wider (HM1, HM4, HM7) and flatter (HM1, HM7) femoral necks, a smaller neck-shaft angle (HM1, HM4), anteversion (HM2, HM7), and early development of osteophytes (HM1). These results suggest that age at onset of walking in infancy is associated with variations in hip shape in older age. Early walkers have a larger femoral head and neck and smaller neck-shaft angle; these features are associated with reduced hip fracture risk, but also represent an osteoarthritic-like phenotype. Unlike results of previous studies of walking age and bone mass, associations in this study were not affected by adjustment for lean mass, suggesting that associations may relate directly to skeletal loading in early life when joint shape changes rapidly. © 2018 American Society for Bone and Mineral Research.

Associations between back pain across adulthood and spine shape in early old age in a British birth cohort.

We aimed to examine whether back pain across adulthood was associated with spine shape at age 60-64 years. Data were from 1405 participants in the MRC National Survey of Health and Development, a nationally representative British birth cohort. Back pain was ascertained during nurse interviews at ages 36, 43, 53 and 60-64 years. Cumulative exposure to back pain was then derived by counting the number of ages at which back pain was reported. Statistical shape modelling was used to characterise thoracolumbar spine shape using lateral dual-energy x-ray absorptiometry images which were ascertained at age 60-64 years. Linear regression models were used to test associations of spine shape modes (SM) with: (1) cumulative exposure to back pain; (2) back pain reports during different periods of adulthood. After adjusting for sex, higher cumulative exposure to back pain across adulthood was associated with wedge-shaped L4-5 disc (lower SM4 scores) and smaller disc spaces (higher SM8 scores) in both sexes. In addition, reporting of back pain at ages 53 and/or 60-64 years was associated with smaller L4-5 disc space (lower SM6 scores) in men but not women. These findings suggest that back pain across adulthood may be associated with specific variations in spine shapes in early old age.

Influence of co-morbid fibromyalgia on disease activity measures and response to tumour necrosis factor inhibitors in axial spondyloarthritis: results from a UK national register.

Objective: To quantify the extent to which co-morbid FM is associated with higher disease activity, worse quality of life (QoL) and poorer response to TNF inhibitors (TNFis) in patients with axial SpA. Methods: A prospective study recruiting across 83 centres in the UK. Clinical information and patient-reported measures were available, including 2011 criteria for FM. Multivariable linear regression was used to model the effect of meeting the FM criteria on disease activity, QoL and response to TNFis. Results: A total of 1757 participants were eligible for analyses, of whom 22.1% met criteria for FM. Those with co-morbid FM criteria had higher disease activity [BASDAI average difference FM+ - FM- 1.04 (95% CI 0.75, 1.33)] and worse QoL [Ankylosing Spondylitis Quality of Life score difference 1.42 (95% CI 0.88, 1.96)] after adjusting for demographic, clinical and lifestyle factors. Among 291 participants who commenced biologic therapy, BASDAI scores in those with co-morbid FM were 2.0 higher at baseline but decreased to 1.1 higher at 12 months. There was no significant difference in the likelihood of meeting Assessment of SpondyloArthritis international Society 20 criteria at 12 months. Less improvement in disease activity and QoL over 3 months of TNFi therapy was most strongly related to high scores on the FM criteria symptom severity scale component. Conclusion: Fulfilling criteria for FM has a modest impact on the assessment of axial SpA disease activity and QoL and does not significantly influence response to biologic therapy. Those with a high symptom severity scale on FM assessment may benefit from additional specific management for FM.

Body mass index and waist circumference in early adulthood are associated with thoracolumbar spine shape at age 60-64: The Medical Research Council National Survey of Health and Development.

This study investigated associations between measures of adiposity from age 36 and spine shape at 60-64 years. Thoracolumbar spine shape was characterised using statistical shape modelling on lateral dual-energy x-ray absorptiometry images of the spine from 1529 participants of the MRC National Survey of Health and Development, acquired at age 60-64. Associations of spine shape modes with: 1) contemporaneous measures of total and central adiposity (body mass index (BMI), waist circumference (WC)) and body composition (android:gynoid fat mass ratio and lean and fat mass indices, calculated as whole body (excluding the head) lean or fat mass (kg) divided by height2 (m)2); 2) changes in total and central adiposity between age 36 and 60-64 and 3) age at onset of overweight, were tested using linear regression models. Four modes described 79% of the total variance in spine shape. In men, greater lean mass index was associated with a larger lordosis whereas greater fat mass index was associated with straighter spines. Greater current BMI was associated with a more uneven curvature in men and with larger anterior-posterior (a-p) vertebral diameters in both sexes. Greater WC and fat mass index were also associated with a-p diameter in both sexes. There was no clear evidence that gains in BMI and WC during earlier stages of adulthood were associated with spine shape but younger onset of overweight was associated with a more uneven spine and greater a-p diameter. In conclusion, sagittal spine shapes had different associations with total and central adiposity; earlier onset of overweight and prior measures of WC were particularly important.

Associations between body mass index across adult life and hip shapes at age 60 to 64: Evidence from the 1946 British birth cohort.

OBJECTIVE: To examine the associations of body mass index (BMI) across adulthood with hip shapes at age 60-64years. METHODS: Up to 1633 men and women from the MRC National Survey of Health and Development with repeat measures of BMI across adulthood and posterior-anterior dual-energy X-ray absorptiometry bone mineral density images of the proximal femur recorded at age 60-64 were included in analyses. Statistical shape modelling was applied to quantify independent variations in hip mode (HM), of which the first 6 were examined in relation to: i) BMI at each age of assessment; ii) BMI gain during different phases of adulthood; iii) age first overweight. RESULTS: Higher BMI at all ages (i.e. 15 to 60-64) and greater gains in BMI were associated with higher HM2 scores in both sexes (with positive HM2 values representing a shorter femoral neck and a wider and flatter femoral head). Similarly, younger age first overweight was associated with higher HM2 scores but only in men once current BMI was accounted for. In men, higher BMI at all ages was also associated with lower HM4 scores (with negative HM4 values representing a flatter femoral head, a wider neck and smaller neck shaft angle) but no associations with BMI gain or prolonged exposure to high BMI were found. Less consistent evidence of associations was found between BMI and the other four HMs. CONCLUSION: These results suggest that BMI across adulthood may be associated with specific variations in hip shapes in early old age.

Co-Occurrence and Characteristics of Patients With Axial Spondyloarthritis Who Meet Criteria for Fibromyalgia: Results From a UK National Register.

OBJECTIVE: To estimate the proportion of patients with axial spondyloarthritis (SpA) in a UK national biologics registry who met criteria for fibromyalgia (FM), and to delineate the characteristics of these patients. METHODS: Two cohorts of patients are prospectively recruited from across 83 centers in the UK for the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS). All patients are required to meet Assessment of SpondyloArthritis international Society (ASAS) criteria for axial SpA. Patients are either newly starting biologic therapy (biologics cohort) or are naive to treatment with biologic agents (non-biologics cohort) at the time of recruitment, and all patients are followed up prospectively. At recruitment and follow-up, clinical information and measurements are recorded while patients complete the 2011 research criteria for FM and assessments of the level of disease activity and work impact. RESULTS: Of the patients registered in the BSRBR-AS, 1,504 (68% male) were eligible for the current analysis, of whom 311 (20.7%) met the 2011 research criteria for FM. Prevalence of FM was similar between patients who fulfilled the modified New York criteria for AS (19.7%) and those who fulfilled ASAS imaging criteria but not the modified New York criteria (25.2%); however, among those who fulfilled only the ASAS clinical criteria, the prevalence of FM was lower (9.5%). Patients who met FM criteria reported significantly worse disease activity, function, global severity scores, and quality of life, and were more likely to have moderate or severe levels of mood disorder and clinically important fatigue. Patients who met FM criteria reported experiencing work impairment around half their working time. Meeting FM criteria was not related to elevated C-reactive protein levels or most extraspinal manifestations, but was associated with a higher likelihood of having received biologic therapy. CONCLUSION: Developing management approaches that would address the significant unmet clinical needs of the 1 in 5 patients with axial SpA who meet criteria for FM should be a research priority.

Is there role for vitamin D in the treatment of chronic pain?

Chronic pain is highly prevalent in the developed world, and levels of vitamin D are often lower among those with chronic pain conditions than those without. Supplementation of vitamin D has been investigated as a potential independent treatment for chronic pain. This paper presents an overview of the scientific evidence and provides recommendations for use of vitamin D in clinical practice with chronic pain patients.