Central and peripheral mechanisms of pain in fibromyalgia: scoping review protocol.

Fibromyalgia is characterised by widespread musculoskeletal pain, which may present with fatigue, depression, anxiety, sleep and cognitive disturbances. It is the second most prevalent rheumatic disease. An accurate diagnosis is challenging, since its symptoms may resemble diverse conditions such as carpal tunnel syndrome, Raynaud syndrome, Sjögren syndrome, amongst others. Neuropathic pain and autonomic dysfunction in fibromyalgia suggest the involvement of the nervous system. Ion channels, neurotransmitters and neuromodulators may play a role. Small fibre neuropathy (SFN) may also cause chronic widespread pain. SFN may occur in 50% of fibromyalgia patients, but its role in the disease is unknown. Despite several efforts to synthesise the evidence on the mechanisms for pain in fibromyalgia, there are few studies applying an integrative perspective of neurochemical, immunological, and neuroanatomical characteristics, and their relevance to the disease. This protocol aims to clarify the mechanisms of the central and peripheral nervous system associated with pain in fibromyalgia. We will retrieve published studies from Web of Science, MEDLINE, Scopus, EBSCOhost, Ovid and Google Scholar. All clinical studies or experimental models of fibromyalgia reporting imaging, neurophysiological, anatomical, structural, neurochemical, or immunological characteristics of the central or peripheral nervous systems associated with pain will be included. Exclusion criteria will eliminate studies evaluating pain without a standardised measure, studies written in languages different from Spanish or English that could not be appropriately translated, and studies whose full-text files could not be retrieved after all efforts made. A narrative synthesis will be performed.

Adherence to literature search reporting guidelines in leading rheumatology journals' systematic reviews: umbrella review protocol.

Literature searches are important components of systematic reviews. They are not only informative of the retrieval process, but they also set the data to be analyzed and influence additional components of systematic reviews. Despite the available guidelines, several studies have shown that the quality of reporting in systematic reviews is deficient in several medical fields. Systematic reviews may not comply completely with those guidelines despite explicitly stating they do. This protocol intends to answer to what extent systematic reviews published in rheumatology journals have complied with the PRISMA's search strategy guidelines published in 2009. The objective of the study is to analyze the compliance with the PRISMA (2009) search strategy guidelines among systematic reviews published in leading rheumatology journals. Inclusion criteria for this umbrella review protocol are systematic reviews (with or without meta-analyses) that mention having followed the PRISMA statement (2009) in their methods section, and published in journals listed in the Rheumatology category of the Journal of Citations Report 2020. Exclusion criteria are articles published before 2009; retraction letters, notes, expressions of concern; systematic reviews using PRISMA 2020. Databases to be consulted are Web of Science, PubMed and Scopus, from inception to present. Data summaries will be presented in graphs, figures, tables and network maps. A narrative synthesis will be described. This protocol complies with guidelines such as PRISMA 2020, PRISMA-A, PRISMA-P, PRISMA-S, PRESS, and JBI Manual for evidence synthesis, as long as it is suitable for umbrella review protocols. Articles in any language will be considered.

Advances in imaging technologies for the assessment of peripheral neuropathies in rheumatoid arthritis.

Peripheral neuropathy in patients with rheumatoid arthritis is associated with a maladaptive autoimmune response that may cause chronic pain and disability. Nerve conduction studies are the routine method performed when rheumatologists presume its presence. However, this approach is invasive, may not reveal subtle malfunctions in the early stages of the disease, and does not expose abnormalities in structures surrounding the nerves and muscles, limiting the possibility of a timely diagnosis. This work aims to present a narrative review of new technologies for the clinical assessment of peripheral neuropathy in Rheumatoid Arthritis. Through a bibliographic search carried out in five repositories, from 1990 to 2020, we identified three technologies that could detect peripheral nerve lesions and perform quantitative evaluations: (1) magnetic resonance neurography, (2) functional magnetic resonance imaging, and (3) high-resolution ultrasonography of peripheral nerves. We found these tools can overcome the main constraints imposed by the previous electrophysiologic methods, enabling early diagnosis.

Central Nervous System Mechanisms of Nausea in Gastroparesis: An fMRI-Based Case-Control Study.

BACKGROUND/AIMS: Nausea is a major complaint of gastroparesis (GP), and the pathophysiology of this condition is poorly understood. Therefore, this study utilized fMRI to investigate the possible central nervous system (CNS) mechanisms of nausea in 10 GP patients versus 8 healthy controls (HCs). METHODS: Nausea severity was assessed on a 0-10 scale and presented as mean ± SD. Nausea was increased from baseline utilizing up to 30 min of visual stimulation (VS). Functional network connectivity was measured with fMRI at baseline and after 30 min of VS. fMRI data were preprocessed using statistical parametric mapping software. Thirty-four independent components were identified as meaningful resting-state networks (RSNs) by group independent component analysis. The Functional Network Connectivity (FNC) among 5 RSNs considered important in CNS nausea mechanisms was calculated as the Pearson's pairwise correlation. RESULTS: Baseline nausea score in GP patients was 2.7 ± 2.0 and increased to 7.0 ± 1.5 after stimulation (P < 0.01). In HCs nausea scores did not increase from baseline after stimulus (0.3 ± 0.5). When comparing GP patients to HCs after VS, a significant reduction (P < 0.001) in bilateral insula network connectivity compared to the right insula network was detected. No significant differences in connectivity were noted among the other RSNs. Additionally, the average gray matter volume was non-significantly reduced in the insula in GP patients compared to HC. CONCLUSIONS: The insula connectivity network is impaired in nauseated GP patients. This phenomenon could explain the susceptibility of GP patients to nausea or may have resulted from a state of chronic nausea.

Barriers towards effective pharmacovigilance systems of biosimilars in rheumatology: A Latin American survey.

PURPOSE: This review summarises the current status of regulatory guidelines for the approval of biosimilars in Latin America and highlights the main barriers to effective pharmacovigilance in this region. We also report results from a survey of Latin American rheumatologists assessing their understanding of prescribing biosimilars and the pharmacovigilance of these drugs. METHODS: We reviewed the current guidelines for the regulatory approval of biosimilars and barriers to effective pharmacovigilance in Latin American countries. Rheumatologists attending the II Pan-American League of Rheumatology Associations PANLAR Review Course (Biosimilars update) in Lima, Peru were asked to complete a short survey to determine their knowledge of biosimilars. RESULTS: Many Latin American countries continue to lag behind Europe and the United States in establishing regulatory guidance and effective pharmacovigilance systems for biosimilars. Results from our survey also highlight a lack of awareness regarding the availability of biosimilars, their nomenclature, automatic substitution, and reporting adverse drug reactions because of these drugs. CONCLUSIONS: The main barriers to effective pharmacovigilance in Latin America are the lack of consensus on the interchangeability of reference biologics and biosimilars, and the need for more suitably trained personnel to carry out effective postmarketing pharmacovigilance of biosimilars. Inconsistencies in biosimilar nomenclature make it difficult to adequately trace drugs and record adverse drug reactions associated with their use, creating a barrier to the global pharmacovigilance of biologics.

Mexican rheumatology: where do we stand?

The aim of this review was to provide an overall overview of the past, present, and future situations and main challenges that are facing Mexican Rheumatology as a medical subspecialty in the context of their national healthcare system, where a deficit of workforce at the national level coexists with a shortage of specialists in the less-developed southern states of the country and a great surplus of professionals within large metropolitan areas. We also analyzed the prevalence and burden of Rheumatic and Musculoskeletal Diseases (RMDs), the structural composition and distribution of Mexican Rheumatology, and the clinical profile of the Mexican Rheumatologist. Last, we examined comorbidities, education and training programs and one scenario for Mexican Rheumatology wherein the principal main threats and opportunities are determined.

Pan-American League of Associations for Rheumatology-Central American, Caribbean and Andean Rheumatology Association Consensus-Conference Endorsements and Recommendations on the Diagnosis and Treatment of Chikungunya-Related Inflammatory Arthropathies in Latin America.

BACKGROUND/OBJECTIVE: Although mortality rates related with chikungunya (CHIK) outbreaks in Latin America's (LA's) dengue-endemic rural and new urban regions are low, dealing with symptoms and sequelae can both produce a significant burden of disease and diminish quality of life-from many months to years-after the acute phase of the infection, with a significant impact on public and individual health.The aim of this work was to establish Pan-American League of Associations for Rheumatology-Central American, Caribbean and Andean Rheumatology Association (ACCAR) consensus-conference endorsements and recommendations on the diagnosis and treatment of CHIK-related inflammatory arthropathies transmitted by Aedes aegypti and Aedes albopictus in LA. METHODS: Based on the Consensus Development Conference format, a panel of ACCAR rheumatologist voting members (n = 10) took part in this Pan-American League of Associations for Rheumatology initiative. Experts voted from a previous content analysis of the medical literature on CHIK, 4 subsequent topic conferences, and a workshop. Consensus represents the majority agreement (≥80%) achieved for each recommendation. RESULTS: The experts' panel reached 4 overarching principles: (1) CHIK virus (CHIKV) is a re-emergent virus transmitted by 2 species of mosquitoes: A. aegypti and A. albopictus; (2) CHIKV caused massive outbreaks in LA; (3) chronic CHIKV infection produces an inflammatory joint disease that, in some cases, can last for several months to years, and (4) currently, there are no vaccines or antivirals licensed for CHIKV infections. RECOMMENDATIONS: Pan-American League of Associations for Rheumatology-ACCAR achieved 13 endorsements and recommendations on CHIK categorized in 3 groups: (1) epidemiology and clinical manifestations, (2) diagnosis, and (3) treatment, representing the consensus agreement from the panel's members.

Ultrasound of sacroiliac joints in spondyloarthritis: a systematic review.

Ultrasound (US) is an accessible imaging technique with a possible role to diagnose active sacroiliitis, so this technique is projected as a promising diagnostic tool for the diagnosis of SpA. We analyse the available evidence about the use of US as a diagnostic tool in sacroiliitis in patients with SpA, by a systemic review of the literature fulfilling OMERACT criteria. A systematic literature search for original articles was carried out using four databases (Medline, Embase, Scopus and Web of Science). Data from studies were included only if participants had SpA and a US examination of sacroiliac joint (SIJ) was performed. The methodological quality of the studies was assessed using QUADAS-2 tool. Thirteen studies were included. All studies were observational, prospective and cross-sectional. In most articles (76.9%), the main US finding compatible with sacroiliitis evaluated was the presence of vascularisation (Doppler signals) with measurements of the resistive index (RI). The sensitivity and specificity analysis were performed in seven studies (58.8%) and were good, with a median of 90 and 89.2%, respectively. The studies showed a positive to moderate a strong correlation between the US and the gold standard but this was optimal only in four studies. In general, the agreement was good in all studies (≥ 0.80). The methods of evaluation of sacroiliitis vary between the studies included. To date, there is not enough evidence to support the use of ultrasound as a diagnostic method for sacroiliitis but it has potential to identify structural lesions at SIJ's level.

Case Reports and Consent for Publishing in Rheumatology Journals: A Latin American Perspective.

Case reports have a long-standing tradition in the current rheumatology literature. We aimed to present the main points of view regarding the importance, meaning, and barriers of consent for publishing under the comprehensive protection of patients' rights within this genre. We encourage Latin American editors and authors of rheumatology journals to adopt the best ethical practices in the field, avoiding security and legal liabilities from a regional perspective.

Disability in Mexico: a comparative analysis between descriptive models and historical periods using a timeline.

Some interpretations frequently argue that three Disability Models (DM) (Charity, Medical/Rehabilitation, and Social) correspond to historical periods in terms of chronological succession. These views permeate a priori within major official documents on the subject in Mexico. This paper intends to test whether this association is plausible by applying a timeline method. A document search was made with inclusion and exclusion criteria in databases to select representative studies with which to depict milestones in the timelines for each period. The following is demonstrated: 1) models should be considered as categories of analysis and not as historical periods, in that the prevalence of elements of the three models is present to date, and 2) the association between disability models and historical periods results in teleological interpretations of the history of disability in Mexico.

Defining Quality of Rheumatologic Care: Mexico.

We present an overview of rheumatology practices in Mexico, describing the national health care system as segmented and fragmentary, with a population separated into 3 main categories, according to employment-based coverage and income level: (1) private sector, (2) Social Security System, and (3) public insurance subsector.The rheumatology practice in the public and private sectors are described. We estimate that between 85%-90% of Mexican rheumatologists have a mixed (public and private)-type practice. Payments to rheumatologists are not currently affected by quality and value metrics, with low penetrance of electronic health records. Recent changes and challenges to health insurance coverage are illustrated.

PANLAR Presidency, First Self-Assessment Report 2014-2016: Challenges, Opportunities, and Results.

We present here the first PANLAR Presidency Self-Assessment Report 2014-2016, emphasizing the challenges, opportunities, and results achieved in terms of (1) governance, (2) education and scientific research, (3) finance, and (4) communications throughout this tenure. The main result must be understood as a strategic planning exercise that strengthened institutional responsibility in policies, decisions, and actions, thanks to the teamwork of Latin America's National Rheumatology Societies, the PANLAR Executive Committee, and PANLAR Board Members.

Threats to scholarly research integrity arising from paper mills: a rapid scoping review.

"Paper mills" are unethical outsourcing agencies proficient in fabricating fraudulent manuscripts submitted to scholarly journals. In earlier years, the activity of such companies involved plagiarism, but their processes have gained complexity, involving the fabrication of images and fake results. The objective of this study is to examine the main features of retracted paper mills' articles registered in the Retraction Watch database, from inception to the present, analyzing the number of articles per year, their number of citations, and their authorship network. Eligibility criteria for inclusion: retracted articles in any language due to paper mill activity. Retraction letters, notes, and notices, for exclusion. We collected the associated citations and the journals' impact factors of the retracted papers from Web of Science (Clarivate) and performed a data network analysis using VOSviewer software. This scoping review complies with PRISMA 2020 statement and main extensions. After a thorough analysis of the data, we identified 325 retracted articles due to suspected operations published in 31 journals (with a mean impact factor of 3.1). These retractions have produced 3708 citations. Nearly all retracted papers have come from China. Journal's impact factor lower than 7, life sciences journals, cancer, and molecular biology topics were common among retracted studies. The rapid increase of retractions is highly challenging. Paper mills damage scientific research integrity, exacerbating fraud, plagiarism, fake images, and simulated results. Rheumatologists should be fully aware of this growing phenomenon.

Update of the current role of ultrasound in asymptomatic hyperuricemia. A systematic literature review.

Ultrasound (US) is a recognized imaging modality for the assessment of gout. Recently it is being explored for its potential role in the evaluation of subjects with asymptomatic hyperuricemia (AH). Preliminary reports demonstrated the presence of monosodium urate (MSU)-crystal deposits including aggregates, double contour sign and/or tophi in both intra-articular and periarticular tissues of AH individuals. Although these results are exciting, the value and potential application of US in AH remain to be clearly delineated. In this systematic literature review, we aim to summarise the recent publications regarding the role of US in the assessment of AH. We analyzed possible application of US in the daily clinical practice and its future clinical and research potential in the evaluation of AH individuals.

Therapeutic Potential of Ultrasound Neuromodulation in Decreasing Neuropathic Pain: Clinical and Experimental Evidence.

BACKGROUND: For more than seven decades, ultrasound has been used as an imaging and diagnostic tool. Today, new technologies, such as focused ultrasound (FUS) neuromodulation, have revealed some innovative, potential applications. However, those applications have been barely studied to deal with neuropathic pain (NP), a cluster of chronic pain syndromes with a restricted response to conventional pharmaceuticals. OBJECTIVE: To analyze the therapeutic potential of low-intensity (LIFUS) and high-intensity (HIFUS) FUS for managing NP. METHODS: We performed a narrative review, including clinical and experimental ultrasound neuromodulation studies published in three main database repositories. DISCUSSION: Evidence shows that FUS may influence several mechanisms relevant for neuropathic pain management such as modulation of ion channels, glutamatergic neurotransmission, cerebral blood flow, inflammation and neurotoxicity, neuronal morphology and survival, nerve regeneration, and remyelination. Some experimental models have shown that LIFUS may reduce allodynia after peripheral nerve damage. At the same time, a few clinical studies support its beneficial effect on reducing pain in nerve compression syndromes. In turn, Thalamic HIFUS ablation can reduce NP from several etiologies with minor side-effects, but some neurological sequelae might be permanent. HIFUS is also useful in lowering non-neuropathic pain in several disorders. CONCLUSION: Although an emerging set of studies brings new evidence on the therapeutic potential of both LIFUS and HIFUS for managing NP with minor side-effects, we need more controlled clinical trials to conclude about its safety and efficacy.

Quantifying Potential Cost-Savings Through an Alternative Imaging-Based Diagnostic Process in Presumptive Seronegative Rheumatoid Arthritis.

BACKGROUND: Seronegative rheumatoid arthritis (SRA) is a condition that is not well understood and difficult to confirm by a conventional diagnostic process. We aimed to quantify the potential cost-savings of an alternative diagnostic process (ADP) imaging-based, for patients with presumptive SRA from everyday clinical practice. METHODS: We performed a retrospective analysis for patients with presumptive SRA who tested negative for both rheumatoid factor and anti-cyclic citrullinated peptide antibodies, through an ADP imaging-based, that is a standard clinical practice in our center. After we confirmed the diagnosis of SRA or reclassified patients in terms of another proper diagnosis, we estimate direct costs in two scenarios: a conventional and ADP. We compared the cost of RA treatment during the first year against the cost of the most misdiagnosed treatment (osteoarthritis) found after applying the ADP to determine potential cost-savings. RESULTS: We included 440 patients with a presumptive diagnosis of SRA. According to the imaging-based ADP, SRA was confirmed in 106/440 (24.1%), unspecified RA in 9/440 (2.0%), and osteoarthritis in 325/440 (73.9%) of those patients. Although the costs of conventional diagnosis per patient is lower than those of ADP ($59,20 USD vs $269,57 USD), we found a potential drug cost-savings of $1,570,775.20 US Dollars after 1 year of correct treatment. CONCLUSION: An alternative diagnosis process, including X-rays, US and MRI imaging, and clinical and blood-test assessment, not only increased diagnostic certainty in patients referred for evaluation of presumptive SRA but also suggested a potential cost-savings in pharmacological treatments avoided in misdiagnosed patients.

Computer-aided diagnosis in rheumatic diseases using ultrasound: an overview.

Clinical evaluation of rheumatic and musculoskeletal diseases through images is a challenge for the beginner rheumatologist since image diagnosis is an expert task with a long learning curve. The aim of this work was to present a narrative review on the main ultrasound computer-aided diagnosis systems that may help clinicians thanks to the progress made in the application of artificial intelligence techniques. We performed a literature review searching for original articles in seven repositories, from 1970 to 2019, and identified 11 main methods currently used in ultrasound computer-aided diagnosis systems. Also, we found that rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, and idiopathic inflammatory myopathies are the four musculoskeletal and rheumatic diseases most studied that use these innovative systems, with an overall accuracy of > 75%.

Clinical Outcomes of Patients with Rheumatoid Arthritis Treated in a Disease Management Program: Real-World Results.

BACKGROUND: Care models can affect the clinical outcome of patients with rheumatic and musculoskeletal diseases. OBJECTIVE: We aimed to compare how an innovative model of a rheumatoid arthritis disease-management program can improve the clinical outcomes of patients compared to a conventional assessment approach. METHODS: We performed a retrospective analysis of real-world data from clinical records of a cohort of 5078 patients diagnosed with rheumatoid arthritis who were followed up at the Center of Excellence in Rheumatoid Arthritis vs the clinical outcomes reported in the Colombian National Registry of Rheumatoid Arthritis. RESULTS: We found significant differences in the diagnosis and follow-up between the specialized Center program and the usual care reported by the Colombian National Registry (p<0.005), including the evaluation of rheumatoid factor, Anti-citrullinated antibodies Disease Activity Score, Health Assessment Questionnaire, number of visits to the rheumatologist, and clinical outcomes measured by the level of disease activity. In addition, when comparing the Center's clinical outcomes - from baseline to the last follow-up, we found an improvement in the level of disease activity, with patients classified in remission increasing from 20.8% to 58.5% (p<0.005), and a reduction in those with high disease activity from 18% to 4.7% (p<0.005). CONCLUSION: Real-world evidence showed that patients with rheumatoid arthritis who underwent follow-up under an innovative disease-management model improved their clinical outcomes compared with those patients in a conventional assessment program. These results could suggest a way of improving health policies for patients with rheumatoid arthritis.

Hypouricemia: what the practicing rheumatologist should know about this condition.

We presented an update in the field of hypouricemia, which is defined as a serum urate concentration of < 2 mg/dL (119 µmol/L), for the practicing rheumatologist, who usually is the consulting physician in cases of disorders of urate metabolism. We performed a narrative review through a literature search for original and review articles in the field of human hypouricemia published between January 1950 and July 2018. We divided the etiology of hypouricemia into two main categories: those associated with a decrease in urate production and those promoting the elimination of urate via the kidneys. The most common conditions associated with these categories are discussed. Furthermore, the etiology of hypouricemia may be associated with certain medications prescribed by the practicing rheumatologists, such as the following: urate-lowering drugs (allopurinol and febuxostat); recombinant uricase (pegloticase); uricosuric agents (probenecid, benzbromarone); urate transporter URAT1 inhibitor (lesinurad); angiotensin II receptor blocker (losartan); fenofibrate; high-dose trimethoprim-sulfamethoxazole; some NSAID; and high-dose salicylate therapy. The rheumatologist is considered an expert in the metabolism of urate and its associated pathological conditions. Therefore, specialists must recognize hypouricemia as a biomarker of various pathological and potentially harmful conditions, highlighting the importance of conducting a deeper clinical investigation to reach a more accurate diagnosis and treatment.

Challenges for social media editors in rheumatology journals: an outlook.

Social media has become a key component of contemporary medicine, and the rheumatology subspecialty is not an exemption. We found that just six of the 40 key peer-reviewed rheumatology journals have found it sensible to incorporate the new appointment of a Social Media Editor-or a similar designation-into their Editorial Boards. We propose that the role of a social media editor is a trinomial: not only a technological work to promote digital engagement but also an activity of ethical guidance and a cultural challenge dealing with worldwide cultural and mindset diversity.