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Interleukin 6 is involved in the pathogenesis of rheumatoid arthritis via its broad effects on immune and inflammatory responses. Our aim was to assess the therapeutic effects of blocking interleukin 6 by inhibition of the interleukin-6 receptor with tocilizumab in patients with rheumatoid arthritis. In this double-blind, randomised, placebo-controlled, parallel group phase III study, 623 patients with moderate to severe active rheumatoid arthritis were randomly assigned with an interactive voice response system, stratified by site with a randomisation list provided by the study sponsor, to receive tocilizumab 8 mg/kg (n=205), tocilizumab 4 mg/kg (214), or placebo (204) intravenously every 4 weeks, with methotrexate at stable pre-study doses (10–25 mg/week). Rescue therapy with tocilizumab 8 mg/kg was offered at week 16 to patients with less than 20% improvement in both swollen and tender joint counts. The primary endpoint was the proportion of patients with 20% improvement in signs and symptoms of rheumatoid arthritis according to American College of Rheumatology criteria (ACR20 response) at week 24. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00106548. The intention-to-treat analysis population consisted of 622 patients: one patient in the 4 mg/kg group did not receive study treatment and was thus excluded. At 24 weeks, ACR20 responses were seen in more patients receiving tocilizumab than in those receiving placebo (120 [59%] patients in the 8 mg/kg group, 102 [48%] in the 4 mg/kg group, 54 [26%] in the placebo group; odds ratio 4·0 [95% CI 2·6–6·1], p<0·0001 for 8 mg/kg vs placebo; and 2·6 [1·7–3·9], p<0·0001 for 4 mg/kg vs placebo). More people receiving tocilizumab than those receiving placebo had at least one adverse event (143 [69%] in the 8 mg/kg group; 151 [71%] in the 4 mg/kg group; 129 [63%] in the placebo group). The most common serious adverse events were serious infections or infestations, reported by six patients in the 8 mg/kg group, three in the 4 mg/kg group, and two in the placebo group. Tocilizumab could be an effective therapeutic approach in patients with moderate to severe active rheumatoid arthritis. F Hoffmann-La Roche, Chugai Pharmaceutical.

[...]the foundation for translating such scientific advances into clinical use lies in healthcare professionals. [...]integrating clinical practice and teaching with scientific research is essential and has profound implications for healthcare quality and societal advancement (1). Evidence-based medical practice and translational research form the bedrock of translating scientific discoveries to clinical applications and fast-tracking the process of converting research findings into tangible benefits to improve public health (6–10). [...]it may hold little significance for most practitioners without an effective mechanism for translating and disseminating this knowledge. [...]research-oriented clinicians can individualize care, optimize therapeutic regimens, and apply innovative approaches, thus improving patient outcomes. 3.2 Innovation and breakthroughs Research developed by physicians fuels medical innovation due to clinical questions emanating from practical realities. [...]financial support enables them to build state-of-the-art research facilities and develop newer technologies with high-class clinical trials. [...]the more funding increases, the higher the chances of hiring and retaining renowned researchers, which improves the institution's research performance. 4 Consequences of physicians not engaging in research In high-income countries, undesirable outcomes may occur when physicians fail to engage in research.

Background To determine the burden of Rheumatoid Arthritis (RA) on patients’ work productivity and health related quality of life (HRQoL), and examine the influence of several exposure variables; to analyze the progression of RA over 1 year and its impact on work productivity and HRQoL. Methods International multicenter prospective survey including patients in 18 centers in Argentina, Brazil, Colombia and Mexico with diagnosis of RA and aged between 21-55 years. The following standard questionnaires were completed at baseline and throughout a 1-year follow-up: WPAI:RA, WALS, WLQ-25, EQ-5D-3 L and SF-36. Clinical and demographic variables were also collected through interview. Results The study enrolled 290 patients on baseline visit. Overall mean scores at baseline visit were: WPAI:RA (presenteeism) = 29.5% (SD = 28.8%); WPAI:RA (absenteeism) = 9.0% (SD = 23.2%); WPAI:RA (absenteeism and presenteeism) = 8.6% (SD = 22.6%); WALS = 9.0 (SD = 6.1); WLQ-25 = 7.0% (SD = 5.1%); SF-36 Physical Scale = 39.1 (SD = 10.3) and Mental Scale = 45.4 (SD = 11.3); EQ-5D-3 L VAS = 69.8 (SD = 20.4) and EQ-5D-3 L index = 0.67 (SD = 0.23). Higher educational levels were associated with better results in WLQ-25, while previous orthopedic surgeries reduced absenteeism results of WPAI:RA and work limitations in WLQ-25. Higher disease duration was associated with decreased HRQoL. Intensification of disease activity was associated with decreased work productivity and HRQoL, except in WLQ-25. In the longitudinal analysis, worsening in disease activity was associated with a decrease in both work productivity and HRQoL. Conclusions RA patients are dealing with workplace disabilities and limitations and loss in HRQoL, and multiple factors seems to be associated with this. Worsening of disease activity further decreased work productivity and HRQoL, stressing the importance of disease tight control.

Recent advances in gene expression analysis techniques and increased access to technologies such as microarrays, qPCR arrays, and next-generation sequencing, in the last decade, have led to increased awareness of the complexity of the inflammatory responses that lead to pathology. This finding is also the case for rheumatic diseases, importantly and specifically, rheumatoid arthritis (RA). The coincidence in major genetic and epigenetic regulatory events leading to RA’s inflammatory state is now well-recognized. Research groups have characterized the gene expression profile of early RA patients and identified a group of miRNAs that is particularly abundant in the early stages of the disease and miRNAs associated with treatment responses. In this perspective, we summarize the current state of RNA-based biomarker discovery and the context of technology adoption/implementation due to the COVID-19 pandemic. These advances have great potential for clinical application and could provide preclinical disease detection, follow-up, treatment targets, and biomarkers for treatment response monitoring.

Objectives To assess the quality and performance of manuscripts previously rejected by a rheumatology-focused journal. Methods This was a cross-sectional, audit-type, exploratory study of manuscripts submitted to Clinical Rheumatology (CLRH) and rejected by one associate editor in 2019. We used a 36-item quality assessment instrument (5-point ordinal scale, 1 being worst). Performance variables included whether a rejected manuscript was published in another PubMed-listed journal, impact factor of the publishing journal (Scimago), number of citations (Web of Science), and social media attention (Altmetrics). Exploratory variables included authors’ past publications, use of reporting guidelines, and text structure. Exploratory variables were assessed using non-parametric tests. Results In total, 165 manuscripts were rejected. Reporting guidelines were used in only five (4%) manuscripts. The mean overall quality rating was 2.48 ± 0.73, with 54% of manuscripts rated 2; 40–80% were rated < 3 on crucial items. Over a 26-month follow-up, 79 (48%) rejected manuscripts were published in other journals, mostly with lower impact factors; 70% of these had at least one citation, compared with 90.5% for manuscripts published in CLRH. Altmetrics was significantly lower for manuscripts published elsewhere than for those published in CLRH. As for text structure, the methods and results sections were shorter and the discussion longer than suggested. The corresponding authors’ past experience and text structure were not associated with quality or acceptance. Conclusions Research report quality is an area for improvement, mainly for items critical to explaining the research and findings. The use of reporting guidelines should be encouraged by journals. Key Points • The quality of research reports (in rejected manuscripts) is insufficient. • Guidelines for reporting are seldom used in rejected manuscripts. • A manuscript rejected by Clinical Rheumatology may subsequently be published in another journal with a lower impact factor and have fewer citations and less social media attention than accepted manuscripts.

Diversity is widely recognized as a driver of excellence and innovation. In recent years, women have become an increasingly significant part of the rheumatology workforce. We aimed to assess the gender representation of the leading rheumatology journals' editors and to explore whether editors' gender correlates with the gender of the first and last authors of published articles. We conducted a cross-sectional study and extracted editorial members of rheumatology journals in quartiles 1 to 3 (Clarivate Analytics) from each journal's website. We categorized editorial positions according to the level of influence in manuscript acceptance decision-making (levels I to III). The gender of editors and of the first and last authors in all 2019 original articles published in a sample of 15 rheumatology journals was assigned using a combination of digital gallery and manual searches. There were 2242 editors' names retrieved from 43 journals, 24 (26%) of the 94 editors at level I, 139 (36%) of 385 editors at level II, and 469 (27%) of 1763 at level III were female. The imbalance between journals was heterogeneous. Females were the first authors in 1342 (48%) and the last authors in 969 (35%) of the 2797 published articles. However, we found no significant correlation between editors' and authors' gender. Our data showed uneven gender representation on the editorial boards of most rheumatology journals, but we did not find any apparent vertical segregation or influence on publishing by gender. Our findings suggest that a generational transition may be occurring among authors.

Rheumatoid arthritis (RA) is an inflammatory debilitating disease that affects the joints in the early and productive phases of an individual's life. Several cytokines have been linked to the disease pathogenesis and are known to contribute to the inflammatory state characteristic of RA. The participation of type I interferon (IFN) in the pathogenesis of the disease has been already described as well as the identity of the genes that are regulated by this molecule, which are collectively known as the type I IFN signature. These genes have several functions associated with apoptosis, transcriptional regulation, protein degradation, Th2 cell induction, B cell proliferation, etc. This article evaluated the expression of several genes of the IFN signature in different stages of disease and their correlation with the levels of anticitrullinated protein antibodies (ACPA) anticarbamylated protein (Anti-CarP) antibodies. Samples from individuals with early and established RA, high-risk individuals (ACPA+ and ACPA-), and healthy controls were recruited at \"Unidad de Artritis y Rheumatismo\" (Rheumatism and Arthritis Unit) in Guadalajara Jalisco Mexico. Determinations of ACPA were made with Eurodiagnostica ACPA plus kit. Anti-CarP determinations were made according to previously described protocols. RNA was isolated, and purity and integrity were determined according to RNA integrity number >6. Gene expression analysis was made by RT-qPCR using specific primers for mRNAs of the type I IFN signature. Relative gene expression was calculated according to Livak and Schmitgen. Significant differences in gene expression were identified when comparing the different groups for and (  < 0.05), also when comparing established RA and ACPA- in both IFIT 1 and . An increased expression of was identified (  < 0.05), and a clear tendency toward increase was identified for . , and were found to be elevated in the chronic/established RA and early RA (  < 0.05). Significant correlations were identified for the IFN signature genes with the levels of ACPA and anti-CarP (  < 0.05). Our data confirm previous observations in the role of IFN signature and the pathogenesis of RA. Also, we provide evidence of an association between several genes of the IFN signature (that regulate Th2 cells and B cell proliferation) with the levels of anti-CarP antibodies and ACPA.

An open-label study was undertaken at multiple centers in Mexico to assess the impact of treatment with etoricoxib - a selective cyclo-oxygenase-2 (COX-2) inhibitor - on quality of life (QoL) and pain relief among patients with osteoarthritis (OA), rheumatoid arthritis (RA) or chronic low-back pain (CLBP). The study involved 191 adult patients (aged > 18years old) who had used non-selective non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of OA, RA or CLBP during the month prior to study enrolment. After discontinuation of prior therapy, patients were treated with etoricoxib 60 mg for OA and CLBP, or 90 mg for RA once daily for 2 weeks. Patient and physician questionnaires were used to collect information about drug treatments, patients' QoL (Short Form-8 Health Survey [SF-8™] and EQ-5D VAS), patients' pain assessment, and physicians' and patients' satisfaction with treatment at baseline and at follow-up visits. Relative to prior NSAID use, etoricoxib use was associated with improvements in all SF-8 QoL domains and component scores as well as in measures of pain and physical functioning. Current pain was reduced from 59.1 mm (0-100mm VAS) at baseline to 27.1 mm at follow-up and the physical component score of the SF-8 improved from 33.3 to 46.3 (on a scale from 0 to100). At follow-up, 91% of patients were satisfied with the pain control provided by etoricoxib compared with 34% who were satisfied with the pain control provided by previous NSAIDs. Among physicians, 93% reported satisfaction with the analgesic effect, 95% with the anti-inflammatory profile, and 82% with the side-effect profile of etoricoxib relative to pre-study NSAID treatment. During etoricoxib therapy, use of concomitant medications was reduced. The results of this study are limited due to the lack of a control group, the un-blinded design, and the small number of patients. Large naturalistic trials are needed to confirm the results.

ObjectivesThis is a demand-based infodemiology study using the Google Trends and AdWords tools to illustrate infodemiology’s potential use in rheumatology. The study investigates three questions in North American countries: (1) What terms associated with “rheumatology” and “arthritis” do people search for on Google? (2) What is the search volume for disease-modifying antirheumatic drugs (DMARDs)? and (3) What is the search volume for the term “arthritis” compared with for “hepatitis C” and “breast cancer”?MethodsWe conducted independent searches by country and search term for 2015–2017. Seventeen DMARDs were searched for 2015 through May 2018, with the turmeric remedy included for comparison. Data were exported to Excel for further analysis, adjusted by country population, and expressed as searches per 100,000 inhabitants (SpTh).ResultsThere were approximately 550 associated terms for “arthritis” in each country, and 5679 SpTh for DMARDs across the three countries. Searches for turmeric numbered slightly lower than for all DMARDs together in Canada and the USA, but were 70% higher in Mexico. Turmeric was also searched four times more than the most-searched biological DMARD in Canada and the USA, and 60 times more in Mexico. Arthritis was more commonly searched for in Canada than hepatitis C and breast cancer, but hepatitis C was highest in the USA and breast cancer in Mexico. Monthly trends did not show expected peaks associated with arthritis awareness campaigns.ConclusionInfodemiology provides preliminary information that could help in generating hypotheses, assessing health-care interventions, or even in providing patient-centered care.