Assessing the effects of distinct biologic therapies on rheumatoid arthritis pain by nociceptive, neuropathic and nociplastic pain components: a randomised feasibility study.

BACKGROUND: Pain management is a major unmet need in people with rheumatoid arthritis (RA). Although many patients are treated with disease modifying anti-rheumatic drugs (DMARDS), including biologic therapies, many people with RA continue to experience significant pain. We aimed to determine whether performing a comprehensive pain evaluation is feasible in people with active RA receiving conventional DMARDs and biologic therapies. METHODS: The BIORA-PAIN feasibility study was an open-label, randomised trial, which recruited participants suitable for treatment with biologic therapy. The primary feasibility outcomes were recruitment, randomisation and retention of eligible participants. All participants underwent pain assessment for nociceptive, neuropathic and nociplastic pain during the 12-month study period, with quarterly assessments for VAS (Visual Analogue Scale) pain, painDETECT and QST (quantitative sensory testing). This trial was registered in clinicaltrials.gov NCT04255134. RESULTS: During the study period, 93 participants were screened of whom 25 were eligible: 13 were randomised to adalimumab and 12 to abatacept. Participant recruitment was lower than expected due to the COVID-19 pandemic. Pain assessments were practical in the clinical trial setting. An improvement was observed for VAS pain from baseline over 12 months, with a mean (SEM) of 3.7 (0.82) in the abatacept group and 2.3 (1.1) in the adalimumab group. There was a reduction in painDETECT and improvement in QST measures in both treatment groups during the study. Participant feedback included that some of the questionnaire-based pain assessments were lengthy and overlapped in their content. Adverse events were similar in both groups. There was one death due to COVID-19. CONCLUSIONS: This first-ever feasibility study of a randomised controlled trial assessing distinct modalities of pain in RA met its progression criteria. This study demonstrates that it is feasible to recruit and assess participants with active RA for specific modalities of pain, including nociceptive, neuropathic and nociplastic elements. Our data suggests that it is possible to stratify people for RA based on pain features. The differences in pain outcomes between abatacept and adalimumab treated groups warrant further investigation. TRIAL REGISTRATION: NCT04255134, Registered on Feb 5, 2020.

Functional Outcomes of Congenital Scoliosis at a Mean 35-Year Follow-up Post In Situ Fusion. Revisiting Patients From the 2002 Goldberg et al Study.

BACKGROUND: The management of congenital scoliosis poses a significant challenge for treating surgeons. The aim of our study was to provide insight into the long-term clinical results of spinal fusion in congenital scoliosis. METHODS: We performed a retrospective review of the scoliosis database in our institution for the period 1976 until 2002 identifying 43 patients with congenital scoliosis who underwent spinal fusion. Patient demographics, diagnosis, levels fused, and radiographs were evaluated. Patients were evaluated for unplanned return to the operating room (UPROR) via SRS 22, EQ5D-5L, and Oswestry Disability Index (ODI). RESULTS: Of the 43 patients who fulfilled the inclusion criteria, 22 patients agreed to participate, 3 patients were known to be deceased and 18 patients were lost to follow-up or declined to participate and were excluded. The mean age of the respondents was 40.7 years (range, 30 to 47 y) with a mean follow-up from index surgery of 35 years (range, 20 to 44 y). At most recent follow-up, 12 patients (54%) underwent UPROR. The mean age at diagnosis was 3.4 years (range, birth to 11.5 y), and the mean age for first surgery was 5.8 years (range, 1 to 13 y). As regards radiologic follow-up; the mean number of levels fused was 5.2 (range, 2 to 12). Thoracic fusion was performed in 17 patients (77%). The mean T1 to T12 height at index surgery and maturity was 166 mm (range, 130 to 240 mm) and 202 mm (range, 125 to 270 mm), respectively. The mean functional scores at follow-up were SRS 22: 4.5 (range, 2.4 to 5), cumulative EQ5D-5L score 7.2 (range, 5 to 15), and ODI: 8% (range, 2 to 30%). All respondents completed high school, 10 patients (45%) completed university, and 2 patients were awarded doctorates. Currently, 17 patients (77%) are in paid employment. CONCLUSIONS: This report constitutes the largest series of patients treated by spinal arthrodesis for congenital scoliosis followed into maturity. We demonstrate the thorax continues to grow after index fusion, patient-reported outcomes were satisfactory with superior educational and employment rates and unplanned return to theatre is rare in adult life. LEVEL OF EVIDENCE: Therapeutic Level IV.

The Evaluation of Serum Metal Ion Levels and Metallosis in Graduated Patients With Magnetically Controlled Growing Rods.

BACKGROUND: Magnetically controlled growing rods (MCGR) aim to control curve progression while limiting surgical burden in children with early-onset scoliosis. Systemic and local distribution of metal debris has been documented in children with spinal implants. The aim of the study was to assess serum metal ion levels and local metal debris-related changes at the conclusion of MCGR treatment. METHODS: Between February 2019 and September 2022, all patients who had a conversion to definitive fusion at the completion of MCGR treatment in our institution were invited to participate in this study. Consenting patients had serum metal ion levels drawn (titanium, cobalt, and chromium) and histologic analyses of peri-implant tissue samples. RESULTS: We enrolled 24 children who underwent definitive fusion post-MCGR treatment for early-onset scoliosis. The average age at definitive fusion was 13.3 years (range: 11 to 17 y). The average length of MCGR treatment was 4.8 years (range: 1.5 to 6.8 y). At the end of the MCGR treatment, 23 (96%) patients had elevated serum metal ion levels. Mean serum titanium levels were 165.4 nmol/L (range: 30 to 390 nmol/L), mean serum cobalt levels were 4.6 nmol/L (range: 1.2 to 14 nmol/L), and mean serum chromium levels were 14 nmol/L (range: 2.4 to 30 nmol/L). Peri-implant soft tissue histologic analysis demonstrated local metal debris and foreign body reactions in all patients. CONCLUSIONS: At the completion of MCGR treatment, the majority of patients demonstrate elevated serum metal ion levels and local metal debris-related peri-implant soft tissue changes. Although there is no current literature to suggest these findings are harmful, further research as to the clinical significance is required. LEVEL OF EVIDENCE: Level IV.

Collagen-I influences the post-translational regulation, binding partners and role of Annexin A2 in breast cancer progression.

Introduction: The extracellular matrix (ECM) has been heavily implicated in the development and progression of cancer. We have previously shown that Annexin A2 is integral in the migration and invasion of breast cancer cells and in the clinical progression of ER-negative breast cancer, processes which are highly influenced by the surrounding tumor microenvironment and ECM. Methods: We investigated how modulations of the ECM may affect the role of Annexin A2 in MDA-MB-231 breast cancer cells using western blotting, immunofluorescent confocal microscopy and immuno-precipitation mass spectrometry techniques. Results: We have shown that the presence of collagen-I, the main constituent of the ECM, increases the post-translational phosphorylation of Annexin A2 and subsequently causes the translocation of Annexin A2 to the extracellular surface. In the presence of collagen-I, we identified fibronectin as a novel interactor of Annexin A2, using mass spectrometry analysis. We then demonstrated that reducing Annexin A2 expression decreases the degradation of fibronectin by cancer cells and this effect on fibronectin turnover is increased according to collagen-I abundance. Discussion: Our results suggest that Annexin A2's role in promoting cancer progression is mediated by collagen-I and Annexin A2 maybe a therapeutic target in the bi-directional cross-talk between cancer cells and ECM remodeling that supports metastatic cancer progression.

X-linked cerebral adrenoleukodystrophy.

A man in his 30s presented with a 6-month history of progressive left face, arm and leg weakness. Medical history included epilepsy and vitamin B12 deficiency. Three maternal second degree relatives died before the age of 7 from various neurological disorders. Examination revealed a mild left facial droop and weakness of the left shoulder, hip and ankle. Reflexes were symmetrical and tone was normal. Differential diagnosis included glioma, subacute infarction, lymphoma and demyelination. MRI brain showed an extensive right sided subcortical white matter lesion, with extension into the brainstem. The patient's weakness progressed over 3 months. Brain biopsy showed evidence of demyelination and gliosis. A pathological diagnosis of tumefactive multiple sclerosis was made, but also rare metabolic disorders such as X-linked adrenoleukodystrophy (X-ALD) were proposed. Serum very long-chain fatty acids were significantly elevated. Genetic testing showed a mutation in the ABCD1 gene, confirming a diagnosis of X-ALD.

Histone Deacetylase 6 Inhibition Exploits Selective Metabolic Vulnerabilities in LKB1 Mutant, KRAS Driven NSCLC.

INTRODUCTION: In KRAS-mutant NSCLC, co-occurring alterations in LKB1 confer a negative prognosis compared with other mutations such as TP53. LKB1 is a tumor suppressor that coordinates several signaling pathways in response to energetic stress. Our recent work on pharmacologic and genetic inhibition of histone deacetylase 6 (HDAC6) revealed the impaired activity of numerous enzymes involved in glycolysis. On the basis of these previous findings, we explored the therapeutic window for HDAC6 inhibition in metabolically-active KRAS-mutant lung tumors. METHODS: Using cell lines derived from mouse autochthonous tumors bearing the KRAS/LKB1 (KL) and KRAS/TP53 mutant genotypes to control for confounding germline and somatic mutations in human models, we characterize the metabolic phenotypes at baseline and in response to HDAC6 inhibition. The impact of HDAC6 inhibition was measured on cancer cell growth in vitro and on tumor growth in vivo. RESULTS: Surprisingly, KL-mutant cells revealed reduced levels of redox-sensitive cofactors at baseline. This is associated with increased sensitivity to pharmacologic HDAC6 inhibition with ACY-1215 and blunted ability to increase compensatory metabolism and buffer oxidative stress. Seeking synergistic metabolic combination treatments, we found enhanced cell killing and antitumor efficacy with glutaminase inhibition in KL lung cancer models in vitro and in vivo. CONCLUSIONS: Exploring the differential metabolism of KL and KRAS/TP53-mutant NSCLC, we identified decreased metabolic reserve in KL-mutant tumors. HDAC6 inhibition exploited a therapeutic window in KL NSCLC on the basis of a diminished ability to compensate for impaired glycolysis, nominating a novel strategy for the treatment of KRAS-mutant NSCLC with co-occurring LKB1 mutations.

Influence of Social Support, Financial Status, and Lifestyle on the Disparity Between Inflammation and Disability in Rheumatoid Arthritis.

OBJECTIVE: To investigate how social support, financial status, and lifestyle influence the development of excess disability in rheumatoid arthritis (RA). METHODS: Data were obtained from the Étude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR) cohort study of people with RA. A previous analysis identified groups with similar inflammation trajectories but markedly different disability over 10 years; those in the higher disability trajectory groups were defined as having "excess disability." Self-reported data regarding contextual factors (social support, financial situation, lifestyle) were obtained from participants, and they completed patient-reported outcome measures (pain, fatigue, anxiety, depression) at baseline. The direct effect of the contextual factors on excess disability and the effect mediated by patient-reported outcome measures were assessed using structural equation models. Findings were validated in 2 independent data sets (Norfolk Arthritis Register [NOAR], Early Rheumatoid Arthritis Network [ERAN]). RESULTS: Of 538 included ESPOIR participants (mean age ± SD 48.3 ± 12.2 years; 79.2% women), 200 participants (37.2%) were in the excess disability group. Less social support (ß = 0.17 [95% confidence interval (95% CI) 0.08, 0.26]), worse financial situation (ß = 0.24 [95% CI 0.14, 0.34]), less exercise (ß = 0.17 [95% CI 0.09-0.25]), and less education (ß = 0.15 [95% CI 0.06, 0.23]) were associated with excess disability group membership; smoking, alcohol consumption, and body mass index were not. Fatigue and depression mediated a small proportion of these effects. Similar results were seen in NOAR and ERAN. CONCLUSION: Greater emphasis is needed on the economic and social contexts of individuals with RA at presentation; these factors might influence disability over the following decade.

Does exercise therapy improve pulmonary function in patients with Adolescent Idiopathic Scoliosis?

INTRODUCTION: Exercise therapy is frequently used for treating patients with Adolescent Idiopathic Scoliosis (AIS) however no previous review has evaluated the effect of exercise therapy on pulmonary function in this population. OBJECTIVE: To systematically analyze the literature on the effect of exercise therapy on pulmonary function in patients with AIS. METHODS: A systematic electronic database search (CINAHL, Embase, Medline, Web of Science) was conducted. Manual searches of key reviews and studies were also conducted. Studies that included exercise-based interventions to improve pulmonary function in patients with AIS and reported pre- and post-intervention pulmonary function test scores were included. Test scores were compared using standardized mean difference (SMD) between intervention and control groups in randomized control trials (RCT) and mean ± SD between pre- and post-intervention in prospective intervention studies (PI). Methodological quality was assessed using a modified Downs and Black checklist. RESULTS: Fifteen studies met the inclusion criteria (six RCTs and nine PIs). Results indicated the positive effect of exercise-based therapy on lung volumes (FVC/VC) and FEV1 in patients with AIS. CONCLUSION: Exercise therapy has a positive effect on lung volumes in patients with AIS. The quality of many studies was only 'fair,' therefore more suitably powered higher level clinical trials are required.

EULAR points to consider for therapeutic drug monitoring of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases.

OBJECTIVE: To develop EULAR points-to-consider for therapeutic drug monitoring (TDM) of biopharmaceuticals in inflammatory rheumatic and musculoskeletal diseases (RMDs). METHODS: The points-to-consider were developed in accordance with EULAR standardised operation procedures by a multidisciplinary task force from eight European countries, based on a systematic literature review and expert consensus. Level of evidence and strength of the points-to-consider were determined, and mean levels of agreement among the task force were calculated using a 10-point rating scale. RESULTS: Six overarching principles and 13 points-to-consider were formulated. The level of agreement among the task force for the overarching principles and points-to-consider ranged from 8.4 to 9.9.The overarching principles define TDM and its subtypes, and reinforce the underlying pharmacokinetic/pharmacodynamic principles, which are relevant to all biopharmaceutical classes. The points-to-consider highlight the clinical utility of the measurement and interpretation of biopharmaceutical blood concentrations and antidrug antibodies in specific clinical scenarios, including factors that influence these parameters. In general, proactive use of TDM is not recommended but reactive TDM could be considered in certain clinical situations. An important factor limiting wider adoption of TDM is the lack of both high quality trials addressing effectiveness and safety of TDM and robust economic evaluation in patients with RMDs. Future research should focus on providing this evidence, as well as on further understanding of pharmacokinetic and pharmacodynamic characteristics of biopharmaceuticals. CONCLUSION: These points-to-consider are evidence-based and consensus-based statements for the use of TDM of biopharmaceuticals in inflammatory RMDs, addressing the clinical utility of TDM.

The Utility of Myositis Specific Antibodies in Clinical Practice.

BACKGROUND: Fifteen myositis-specific antibodies have been described and characterized over the past 40 years. Approximately two thirds of patients with idiopathic inflammatory myositis have a myositis-specific antibody and only rarely more than one. Assays to detect them are now widely available within clinical practice. CONTENT: We describe the original description and clinical phenotype of the myositis-specific antibodies, forming the antisynthetase syndrome group, anti-MDA-5 and rapidly progressive interstitial lung disease, anti-SRP/HMGCR and necrotizing myositis, anti-TIF-1γ/NXP-2 and malignancy, anti-SAE and esophageal disease, and anti-Mi-2 and classic dermatomyositis skin disease. SUMMARY: Clinical practice is likely to be refined, with diagnosis and classification of the idiopathic inflammatory myositides based primarily on myositis-specific antibody, rather than directed by muscle histology or the broader clinical characteristics of polymyositis and dermatomyositis. All patients newly presenting with idiopathic inflammatory myositis should be routinely screened for myositis-specific antibodies. A positive result will usefully provide diagnostic and prognostic information, guide selection of therapy, and prompt surveillance for potential organ involvement and other features, such as cancer, throughout the disease course.

Exploring the disparity between inflammation and disability in the 10-year outcomes of people with rheumatoid arthritis.

OBJECTIVES: To identify groups of people with RA with different disability trajectories over 10 years, despite comparable levels of inflammation. METHODS: Data for this analysis came from three European prospective cohort studies of people with RA [Norfolk Arthritis Register (NOAR), Early RA Network (ERAN), Étude et Suivi des Polyarthrites Indifférenciées Récentes (ESPOIR)]. Participants were assessed regularly over 8 (ERAN) to 10 (NOAR/ESPOIR) years. Inclusion criteria were: recruited after 1 January 2000, <24 months baseline symptom duration, and disability (HAQ) and inflammation [two-component DAS28 (DAS28-2C)] recorded at baseline and at one other follow-up. People in each cohort also completed patient-reported outcome measures at each assessment (pain, fatigue, depressive symptoms). Group-based trajectory models were used to identify distinct groups of people with similar HAQ and DAS28-2C trajectories over follow-up. RESULTS: This analysis included 2500 people with RA (NOAR: 1000, ESPOIR: 766, ERAN: 734). ESPOIR included more women and the participants were younger [mean (standard deviation) age: NOAR: 57.1 (14.6), ESPOIR: 47.6 (12.5), ERAN: 56.8 (13.8); women: NOAR: 63.9%, ESPOIR: 76.9%, ERAN: 69.1%). Within each cohort, two pairs of trajectories following the hypothesized pattern (comparable DAS28-2Cs but different HAQs) were identified. Higher pain, fatigue and depressive symptoms were associated with increased odds of being in the high HAQ trajectories. CONCLUSION: Excess disability is persistent in RA. Controlling inflammation may not be sufficient to alleviate disability in all people with RA, and effective pain, fatigue and mood management may be needed in some groups to improve long-term function.

Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies: incidence using different testing criteria, and case series.

OBJECTIVES: To estimate the incidence of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies utilising different testing criteria, and review the clinical details of a series of patients with associated autoimmune myopathy. METHODS: The incidence of anti-HMGCR antibodies in 2019 from 3 groups, South West London, Berkshire/Surrey and Southampton, were compared in the adult population. Anti-HMGCR antibodies were measured by commercial chemiluminescent and immunodot assays. The case notes of patients with anti-HMGCR antibodies were reviewed for the case series. RESULTS: The estimated incidence of anti-HMGCR antibodies in the first 2 groups was 1.94 per million adults per year, and in the third group 10.3 per million adults per year. In the first 2 groups the test criteria restricted analysis to specific clinician request for anti-HMGCR. In the third group test criteria included cases with less specific clinical features or a cytoplasmic indirect immunofluorescence anti-nuclear antibody pattern. The latter strategy had a positive predictive value of 66.1% for anti-HMGCR associated myopathy. A case series of 27 patients with anti-HMGCR antibodies revealed 19 with myopathy, oesophageal involvement in 26% and median peak CK 8000 IU/L. Response to treatment, including intravenous immunoglobulin, was good with CK normalising after median 5.5 months. In 8 cases there was no evidence of autoimmune muscle disease, 7 not statin exposed. CONCLUSIONS: Varying criteria result in a 5-fold difference in estimated incidence of anti-HMGCR antibodies, revealing positive cases without evidence of myopathy. Patients with anti-HMGCR myopathy respond well to immune suppression, supporting wider testing for these antibodies amongst patients with myopathy.

Does quality assured eLearning provide adequate preparation for robotic surgical skills; a prospective, randomized and multi-center study.

PURPOSE: In particular after the onset of the COVID-19 pandemic, there was a precipitous rush to implement virtual and online learning strategies in surgery and medicine. It is essential to understand whether this approach is sufficient and adequate to allow the development of robotic basic surgical skills. The main aim of the authors was to verify if the quality assured eLearning is sufficient to prepare individuals to perform a basic surgical robotic task. METHODS: A prospective, randomized and multi-center study was conducted in September 2020 in the ORSI Academy, International surgical robotic training center. Forty-seven participants, with no experience but a special interest in robotic surgery, were matched and randomized into four groups who underwent a didactic preparation with different formats before carrying out a robotic suturing and anastomosis task. Didactic preparation methods ranged from a complete eLearning path to peer-reviewed published manuscripts describing the suturing, knot tying and task assessment metrics. RESULTS: The primary outcome was the percentage of trainees who demonstrated the quantitatively defined proficiency benchmark after learning to complete an assisted but unaided robotic vesico-urethral anastomosis task. The quantitatively defined benchmark was based on the objectively assessed performance (i.e., procedure steps completed, errors and critical errors) of experienced robotic surgeons for a proficiency-based progression (PBP) training course. None of the trainees in this study demonstrated the proficiency benchmarks in completing the robotic surgery task. CONCLUSIONS: PBP-based e-learning methodology is an effective training method avoiding critical errors in the suturing and knotting task. Quality assured online learning is insufficient preparation for robotic suturing and knot tying anastomosis skills. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04541615.

Rituximab and intravenous immunoglobulin treatment in PM/Scl antibody-associated disease: case-based review.

Autoantibodies to the 75-kDa and 100-kDa subunits of the PM/Scl nucleolar protein complex are associated with an overlap syndrome, manifesting with clinical features of systemic sclerosis and idiopathic inflammatory myopathy. We describe the diverse clinical features in a series of 4 cases with anti-PM/Scl-75 and/or anti-PM/Scl-100 antibodies, including severe proximal muscle weakness, oesophageal dysfunction, respiratory weakness requiring mechanical ventilation, Raynaud's, calcinosis cutis, sclerodactyly and critical digital ischaemia. Despite the severity of striated and oesophageal muscle weakness, all patients responded very well to immune suppression, and calcinosis cutis in one case regressed substantially. We highlight the efficacy of Rituximab and intravenous immunoglobulin therapy (IVIg) in these cases, enabling return to normal muscle function within six months. Rituximab was preferentially chosen for cases with hyper-gammaglobulinemia and multiple autoantibodies in addition to anti-PM/Scl, and IVIg was utilised for cases where a rapid onset of effect was required, such as severe ventilator-dependent respiratory muscle weakness and oesophageal dysfunction.

Adolescents' Experiences of Idiopathic Scoliosis in the Presurgical Period: A Qualitative Study.

OBJECTIVE: Adolescent idiopathic scoliosis (AIS) is a sideways curvature of the spine that can progress severely during adolescent development and require surgical intervention. This qualitative study was conducted to explore the psychosocial experiences of adolescents with idiopathic scoliosis during the presurgical stage of treatment. METHODS: Fourteen adolescents with moderate-to-severe AIS aged 12-17 years participated in semistructured interviews and data were analyzed using inductive reflexive thematic analysis. RESULTS: Four key themes were generated from the analysis. "Proceeding with Caution" described adolescents' adaptation to the physical impact of their AIS, while "Am I Different?" encompassed adolescents' perceptions of their changing appearance and visibility of their condition. "An Emotional Journey" captured the rollercoaster of emotions from shock at diagnosis to the daunting realization of the severity of their condition, while knowing others with AIS could ease the emotional burden. Finally, adolescents' concerns and expectations about their prospective surgery were captured by the theme "No Pain, No Gain", whereby they were often keen to put surgery behind them. CONCLUSIONS: Understanding and addressing adolescents' psychosocial support needs as they manage the challenges associated with idiopathic scoliosis is a key component of promoting better outcomes among this patient group. Clinical implications and opportunities for support provision are discussed.

Large joints are progressively involved in rheumatoid arthritis irrespective of rheumatoid factor status-results from the early rheumatoid arthritis study.

This study aimed to examine the progression of large joint involvement from early to established RA in terms of range of movement (ROM) and time to joint surgery, according to the presence of rheumatoid factor (RF). We used a historical longitudinal cohort of early RA patients. Patients were deemed RF negative if all repeated assessments were negative. The rate of progression from normal to any loss of range of movement (ROM) from years 3 to 14 were modelled using generalized estimating equations, for elbows, wrists, hips, knees and ankle, adjusting for confounders. Time to joint surgery was analysed using multivariable Cox models. A total of 1458 patients were included (66% female, mean age 55 years) and 74% were RF-positive. The prevalence of any loss of ROM, from year 3 through to 14 was highest in the wrist followed by ankle, knee, elbow and hip. Odds of loss of ROM increased over time in all joint regions assessed, at around 7-13% per year from year 3 to 14. Time to surgery was similar according to RF-status for the wrist and ankle, but RF-positive cases had a lower hazard of surgery at the elbow (HR 0.37, 0.15-0.90), hip (HR 0.69, 0.48-0.99) and after 10 years at the knee (HR 0.41, 0.25-0.68). Large joints become progressively involved in RA, most frequently affecting the wrist followed by ankle, which is overlooked in composite disease activity indices. RF-negative and positive cases progressed similarly. Treat-to-target approaches should be followed irrespective of RF status.

Fatigue in early rheumatoid arthritis: data from the Early Rheumatoid Arthritis Network.

OBJECTIVES: Fatigue is a disabling symptom in people with RA. This study aims to describe the prevalence, risk factors and longitudinal course of fatigue in early RA. METHODS: Demographic, clinical, quality of life (QoL), comorbidities and laboratory data were from the Early RA Network (ERAN), a UK multicentre inception cohort of people with RA. Fatigue was measured using the vitality subscale of the 36-item Short Form Health Survey, where higher values represent better QoL. Baseline prevalences of fatigue classifications were age and sex standardized. Linear regression, hierarchical growth curve modelling and group-based trajectory modelling (GBTM) were utilized. RESULTS: At baseline (n = 1236, 67% female, mean age 57 years), the mean vitality was 41 (s.d. 11) and disease duration was 11 months (interquartile range 7-18). Age- and sex-standardized prevalence rates of fatigue and severe fatigue were 44% (95% CI 39, 50) and 19% (95% CI 15, 23), respectively. Fatigue changed little over 3 years and five measurement occasions ß = -0.13 (95% CI -0.23, -0.02). GBTM identified two subgroups, which we named 'Fatigue' (53%) and 'No-fatigue' (47%). Female sex, worse pain, mental health and functional ability were associated with greater fatigue and predicted Fatigue group membership (area under the receiver operating characteristics curve = 0.81). Objective measures of inflammation-swollen joint count and ESR-were not significantly associated with fatigue. CONCLUSIONS: Fatigue is prevalent and persistent in early RA. Diverse characteristics indicative of central mechanisms are associated with persistent fatigue. Management of fatigue might require interventions targeted at central mechanisms in addition to inflammatory disease modification. People who require such interventions might be identified at presentation with early RA.

Identifying the gaps in Irish cancer care: Patient, public and providers' perspectives.

BACKGROUND: The University of Limerick Cancer network (ULCaN) was established in 2019 with funding from the Health Research Institute at the University of Limerick in order to build a network between individuals in academia, primary and secondary care and the general public so that cancer services can be coordinated and more effective. The aim of this paper is to outline our experience of engaging with stakeholders to identify gaps in the cancer journey locally. METHODS: Four focus group discussions were conducted with patients; their carers; members of the public; and healthcare providers with 2 main aims: 1) to investigate gaps in cancer services; 2) to identify knowledge, attitudes and opportunities available to promote cancer research. The focus groups were audio recorded, transcribed and thematically analysed. RESULTS: 15 themes within the topics of cancer care, palliation, communication, clinical trials, diet and exercise and public and patient involvement in research and advocacy were identified. These include directing people to reliable information and navigating misinformation and stigma linked with cancer, promoting awareness of clinical trials and palliative care services and improving communication when multiple healthcare providers are involved. CONCLUSION: The need to make more coherent, efficient and integrated cancer research amongst local stakeholders was evident. Embedding patients and members of the public into ULCaN is an important deliverable for collaborative research.