A paradigm change to inform fibromyalgia research priorities by engaging patients and health care professionals.

Background: Research objectives should be focused toward advancing knowledge that has meaningful impact on health. However, research agendas are mostly driven by the health care community, with limited input from patients. Aims: In this study, prioirities of uncertainties for the management of fibromyalgia (FM) that could propel future research were identified by a defined process using the James Lind Alliance Priority Setting Partnership (JLA-PSP) methodology. Methods: As a first step, a survey was distributed across Canada that engaged patients, caregivers, and health care professionals to provide narrative input to eight open-ended questions regarding FM care. Responses were thematically condensed and synthesized into an initial list of 43 uncertainties used to guide a comprehensive literature search. Questions already effectively addressed in the literature were excluded, leaving 25 uncertainties that were ranked during a one-day consensus workshop. Results: Three broad themes emerged: the value of personalized targeted treatment and subgrouping of patients; the efficacy of various self-management strategies and educational initiatives; and identification of the ideal health care setting to provide FM care. Opioids and cannabinoids were the only specific pharmacologic interventions ranked as needing further research. Conclusions: The prioritized questions highlight the importance of recognizing the heterogeneity of FM symptoms, the need for a personalized treatment approach, and a better understanding of the value of self-management strategies. This is the first study that uses an established and transparent methodology to engage all FM stakeholders to help inform researchers and funding bodies of clinically relevant research priorities.

Contexte: Les objectifs en matière de recherche devraient se concentrer sur l'avancement des connaissances qui ont des effets significatifs sur la santé. Toutefois, les programmes de recherche sont surtout définis par le milieu des soins de santé, tandis que la contribution des patients demeure limitée.Objectifs: Dans cette étude, les incertitudes prioritaires pour la prise en charge de la fibromylagie, qui pourraient donner lieu à de futures études, ont été déterminées selon un processus fondé sur la méthodologie du Partenariat d'établissement des priorités de la James Lind Alliance.Méthodes: Comme première étape, une enquête a été distribuée partout au Canada auprès de patients, de prestataires de soins et de professionnels de la santé afin d'obtenir leurs réponses sous forme narrative à huit questions ouvertes concernant les soins relatifs à la fibromyalgie. Les réponses ont été regroupées par thèmes et résumées dans une liste initiale de 43 incertitudes qui a été utilisée pour orienter une recherche exhaustive de la littérature. Les questions déjà abordées de manière efficace dans la littérature ont été exclues, tandis que les 25 incertitudes restantes ont été classées dans le cadre d'un atelier de recherche de consensus d'une journée.Résultats: Trois grands thèmes se sont démarqués : l'utilité des traitements ciblés personnalisés et de la division des patients en sous-groupes; l'efficacité de diverses stratégies d'auto-prises en charge et initiatives éducatives; et la détermination du cadre de soins de santé idéal pour dispenser les soins relatifs à la fibromyalgie.Conclusions: Les questions priorisées soulignent l'importance de reconnaître l'hétérogénéité des symptômes de la fibromyalgie, la nécessité d'une approche de traitement personnalisé et une meilleure compréhension de l'utilité des stratégies d'auto-prise en charge. Il s'agit de la première étude à utiliser une méthodologie établie et transparente pour impliquer toutes les parties concernées par la fibromyalgie pour aider à faire connaître aux chercheurs et aux agences de financement les priorités pertinentes sur le plan clinique.

Impact of disease activity and treatment of comorbidities on the risk of myocardial infarction in rheumatoid arthritis.

BACKGROUND: The aim was to estimate the impact of individual risk factors and treatment with various disease-modifying antirheumatic drugs (DMARDs) on the incidence of myocardial infarction (MI) in patients with rheumatoid arthritis (RA). METHODS: We analysed data from 11,285 patients with RA, enrolled in the prospective cohort study RABBIT, at the start of biologic (b) or conventional synthetic (cs) DMARDs. A nested case-control study was conducted, defining patients with MI during follow-up as cases. Cases were matched 1:1 to control patients based on age, sex, year of enrolment and five cardiovascular (CV) comorbidities. Generalized linear models were applied (Poisson regression with a random component, conditional logistic regression). RESULTS: In total, 112 patients developed an MI during follow-up. At baseline, during the first 6 months of follow-up and prior to the MI, inflammation markers (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) but not 28-joint-count disease activity score (DAS28) were significantly higher in MI cases compared to matched controls and the remaining cohort. Baseline treatment with DMARDs was similar across all groups. During follow-up bDMARD treatment was significantly more often discontinued or switched in MI cases. CV comorbidities were significantly less often treated in MI cases vs. matched controls (36 % vs. 17 %, p < 0.01). In the adjusted regression model, we found a strong association between higher CRP and MI (OR for log-transformed CRP at follow-up: 1.47, 95 % CI 1.00; 2.16). Furthermore, treatment with prednisone ≥10 mg/day (OR 1.93, 95 % CI 0.57; 5.85), TNF inhibitors (OR 0.91, 95 % CI 0.40; 2.10) or other bDMARDs (OR 0.85, 95 % CI 0.27; 2.72) was not associated with higher MI risk. CONCLUSIONS: CRP was associated with risk of MI. Our results underline the importance of tight disease control taking not only global disease activity, but also CRP as an individual marker into account. It seems irrelevant with which class of (biologic or conventional) DMARD effective control of disease activity is achieved. However, in some patients the available treatment options were insufficient or insufficiently used - regarding DMARDs to treat RA as well as regarding the treatment of CV comorbidities.

An overlapping phenotype of Osteogenesis imperfecta and Ehlers-Danlos syndrome due to a heterozygous mutation in COL1A1 and biallelic missense variants in TNXB identified by whole exome sequencing.

Osteogenesis imperfecta (OI) and Ehlers-Danlos syndrome (EDS) are variable genetic disorders that overlap in different ways [Cole 1993; Grahame 1999]. Here, we describe a boy presenting with severe muscular hypotonia, multiple fractures, and joint hyperflexibility, features that are compatible with mild OI and hypermobility type EDS, respectively. By whole exome sequencing, we identified both a COL1A1 mutation (c.4006-1G > A) inherited from the patient's mildly affected mother and biallelic missense variants in TNXB (p.Val1213Ile, p.Gly2592Ser). Analysis of cDNA showed that the COL1A1 splice site mutation led to intron retention causing a frameshift (p.Phe1336Valfs*72). Type 1 collagen secretion by the patient's skin fibroblasts was reduced. Immunostaining of a muscle biopsy obtained from the patient revealed a clear reduction of tenascin-X in the extracellular matrix compared to a healthy control. These findings imply that the combination of the COL1A1 mutation with the TNXB variants might cause the patient's unique phenotype.

Anaphylaxis to etanercept in two children with juvenile idiopathic arthritis.

Anti-tumor necrosis factor α (TNFα) medications have revolutionized the care of children and adults with chronic arthritis. They are quick acting, highly effective, and remarkably safe, particularly in children with juvenile idiopathic arthritis (JIA). Anti-TNFα agents come in 2 basic varieties: monoclonal antibodies to TNFα (e.g., infliximab, adalimumab) and a fusion protein containing a TNF receptor (etanercept). Although hypersensitivity reactions are not uncommon with some of the TNFα antibodies (e.g., infliximab), there are only rare reports of anaphylaxis to subcutaneous injections of etanercept in adults with rheumatoid arthritis. Herein, we report 2 cases of anaphylaxis in children with JIA after etanercept injections. Although rare, pediatricians need to be aware of this potentially dangerous occurrence.

The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment.

RA is known to be associated with an increased risk of serious infection. Even more than 50 years ago, observational studies showed a greater than 2-fold increased risk of serious infection in RA. This was reinforced by various subsequent cohort studies. The elevated susceptibility of patients with RA can be explained by the pathobiology of the disease itself, the impact of chronic comorbid conditions, as well as sequelae of immunosuppressive treatment. It has been suggested that premature ageing of the immune system in RA contributes to weakened protection against infectious organisms. In addition, chronic comorbid conditions such as diabetes or chronic lung or kidney disease, disease-related functional disability, as well as lifestyle factors such as smoking, increase the risk in individual patients. For a long time glucocorticoids (GCs) have been used as potent immunosuppressive drugs in RA. There is evidence that they increase the risk of serious infections up to 4-fold in a dose-dependent manner. TNF-α inhibitors increase the serious infection risk up to 2-fold. They have, however, the potential to outweigh their risk when higher GC doses can be tapered down. If patients need higher dosages of GCs in addition to treatment with biologic agents, their risk of infection is substantial. This combination should be used carefully and, if possible, avoided in patients with additional risk factors such as older age or comorbid conditions.