Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
30415433 Correction to: Sam68 Promotes Invasion, Migration, and Proliferation of Fibroblast-like Sy 2019 Apr Unfortunately the author name, Rongqing Qin, was wrongly spelt as Rongqin Qin in the original version. It has been updated and the complete corrected author group is given below.
30824460 Hydroxychloroquine-induced inverse psoriasis. 2019 Feb 28 A 65-year-old woman presented to our rheumatology clinic with pain and swelling of multiple joints of her hands. After a thorough evaluation, she was diagnosed with rheumatoid arthritis and was started on hydroxychloroquine therapy. A week later, she presented to our clinic with an acute condition and reported that after taking hydroxychloroquine for a few days she developed multiple rashes, most prominent at skin folds around her breasts, neck, axillae and buttocks. The rashes were characteristic of inverse psoriasis. Hydroxychloroquine was discontinued and the patient was started on methotrexate therapy that resulted in resolution of her rashes in a week.
31885649 The Effect of Acupoint Application of Sinomenine for Rheumatoid Arthritis Measured by Micr 2019 OBJECTIVE: This study aimed to investigate the treatment effects of acupoint application of sinomenine in rheumatoid arthritis (RA). RA models were constructed using male New Zealand rabbits. METHODS: The rabbits were randomly divided into a blank control group and four experimental groups as follows: ST 36 group (acupoint application of sinomenine at Zusanli); GB 34 group (acupoint application of sinomenine at Yanglingquan); knee-joint group (application directly at the site of the knee joint); and oral administration group (sinomenine administered by gavage). In all rabbits, microdialysis was applied at the knee joint to obtain samples. Pharmacokinetic (PK) and pharmacodynamic (PD) parameters were measured by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and the PK/PD models were established according to the parameters derived. RESULTS: Sinomenine concentration was in the range of 0.832-208 ng/mL, and the peak area showed a good linear relationship with the regression equation of y = 539.64x + 953.81; r = 0.9998. Moreover, good specificity and precision were obtained for the LC-MS/MS method of sinomenine evaluation in the microdialysate samples. The PK analysis showed that the sinomenine effect time was longer in the ST 36 group (area under the time-concentration curve (AUC): 12683.81 h·ng/ml and T (max): 6.21 h) than in the other groups. Arginine and citrulline were selected as the indices for PD, and in the analysis of parameters for PK/PD, the highest value of E (max) and the lowest value of k (e0) were obtained in the ST 36 group. CONCLUSION: Acupoint application of sinomenine at ST 36 has potential for use in patients with RA by enabling enhanced and prolonged treatment effects.
31600905 Periodontal Pathogens as Risk Factors of Cardiovascular Diseases, Diabetes, Rheumatoid Art 2019 Oct 9 Cardiovascular diseases, chronic obstructive pulmonary diseases, diabetes, rheumatoid arthritis, and cancer are the most common noncommunicable diseases (NCDs). These NCDs share risk factors with periodontal disease (PD), a preventable risk factor linked to lifestyle. The discussion regarding the association between these chronic diseases is more complex. There is still a significant knowledge gap particularly of the causal relationship between PD and NCDs. In this paper, we present fundamental knowledge of the mechanisms and roles of putative periodontal bacteria to gather several hypotheses, evidence that clinical studies thus far have not produced. Although the causal hypotheses are not yet clearly established on a biological basis, prevention and prophylactic measures are recommended to prevent even the possibility of such potential risk factors.
31512536 Medical cannabis and cannabinoids in rheumatology: where are we now? 2019 Oct Introduction: Clinicians involved in pain management can finally include cannabis or cannabis-related products in their therapeutic armamentarium as a growing number of countries have approved them for pain relief. Despite the several benefits attributed to analgesic, anti-inflammatory and immunomodulatory properties of cannabinoids, there are still significant areas of uncertainty concerning their use in many fields of medicine. The biosynthesis and inactivation of cannabinoids are regulated by a complex signaling system of cannabinoid receptors, endocannabinoids (the endogenous ligands of cannabinoid receptors) and enzymes, with a variety of interactions with neuroendocrinological and immunological systems. Areas covered: A review of studies carried out during clinical development of cannabis and cannabis medical products in systemic rheumatic diseases was performed, highlighting the aspects that we believe to be relevant to clinical practice. Expert opinion: The growing public opinion, pushing toward the legalization of the use of cannabis in chronic pain and various rheumatological conditions, makes it necessary to have educational programs that modify the concerns and widespread preconceptions related to this topic in the medical community by increasing confidence. More extensive basic and clinical research on the mechanisms and clinical utility of cannabis and derivatives in various diseases and their long-term side effects is necessary.
31057960 A Comparative Study of Interleukin 6, Inflammatory Markers, Ferritin, and Hematological Pr 2019 BACKGROUND: Interleukin-6 (IL-6) proinflammatory cytokine is associated with the pathogenesis of rheumatoid arthritis and development of anemia in it. This is a comparative study of inflammatory and hematological parameters in RA patients with anemia of chronic disease (ACD) and iron deficiency anemia (IDA). It aimed to demonstrate the changes in serum level of IL-6, ferritin level, and hematological parameters in different groups of patients with RA and to find out the potential correlation between serum level of IL-6 and ferritin level and the relationship between serum level of IL-6 and iron status. METHODS: The study included 89 patients from both sexes divided into four groups (group 1: 30 iron deficiency anemia (IDA), 59 RA; group 2: 20 RA-COMBI; group 3: 23 RA-ACD; and group 4: 16 nonanemic RA). These different groups were compared with a healthy group of 50 healthy individuals. Different blood parameters (WBC, RBC, HGB, HCT, MCV, and MCH) have been evaluated. Serum concentrations of IL-6, hsCRP, anti-CCP, and ferritin were measured in all patients and healthy individual using enzyme-linked immunosorbent assay ELISA. RESULTS: There were significant changes in most of blood parameters between the groups, and there was a significant increase in the levels of IL-6 among RA patients. This increase was highly significant among RA-ACD patients in particular, and this elevation has been directly correlated with clinical indices of disease activity such as hsCRP, ESR, anti-CCP, and ferritin. There was an inverse relationship between ferritin and all iron status parameter, such as RBC, HGB, and haematocrit. CONCLUSION: IL-6 and ferritin level estimation may be workable tests to differentiate the patients with IDA and ACD in RA.
31001268 Feto-Maternal Microchimerism: The Pre-eclampsia Conundrum. 2019 Feto-maternal microchimerism (FMM) involves bidirectional cross-placental trafficking during pregnancy, leading to a micro-chimeric state that can persist for decades. In this manner a pregnant woman will harbor cells from her mother, as well as, cells from her child. Historically, eclampsia, a severe disorder of pregnancy provided the basis for FMM following the detection of trophoblast cells in the lungs of deceased women. Bi-directional cell trafficking between mother and fetus is also altered in pre-eclampsia and has been suggested to contribute to the underlying etiology. FMM has been implicated in tolerance promotion, remission of auto-inflammatory disorders during pregnancy, or the development of autoimmune conditions post-partum. The underlying mechanism whereby the host immune system is modulated is unclear but appears to involve HLA class II molecules, in that incompatibility between mother and fetus promotes remission of rheumatoid arthritis, whereas feto-maternal HLA compatibility may assist in the post-partum initiation of scleroderma. Couples having a high degree of HLA class II compatibility have an increased risk for pre-eclampsia, while the occurrence of scleroderma and rheumatoid arthritis is greater in pre-eclamptic cases than in women with normal pregnancies, suggesting a long term autoimmune predisposition. Since pregnant women with pre-eclampsia exhibit significantly lower levels of maternally-derived micro-chimerism, the question arises whether pre-eclampsia and post-partum development of autoimmune conditions occur due to the failure of the grandmothers cells to adequately regulate an inappropriate micro-chimeric constellation.
31648042 Cannabinoids in the treatment of rheumatic diseases: Pros and cons. 2019 Dec Medical cannabis is being increasingly used in the treatment of rheumatic diseases because, despite the paucity of evidence regarding its safety and efficacy, a growing number of countries are legalising its use for medical purposes in response to social pressure. Cannabinoids may be useful in the management of rheumatic disorders for two broad reasons: their anti-inflammatory and immunomodulatory activity, and their effects on pain and associated symptoms. It is interesting to note that, although a wide range of medications are available for the treatment of inflammation, including an ever-lengthening list of biological medications, the same is not true of the treatment of chronic pain, a cardinal symptom of many rheumatological disorders. The publication of systematic reviews (SR) concerning the use of cannabis-based medicines for chronic pain (with and without meta-analyses) is outpacing that of randomised controlled trials. Furthermore, narrative reviews of public institution are largely based on these SRs, which often reach different conclusions regarding the efficacy and safety of cannabis-based medicines because of the lack of high-quality evidence of efficacy and the presence of indications that they may be harmful for patients. Societal safety concerns about medical cannabis (e.g. driving risks, workplace safety and pediatric intoxication) must always be borne in mind, and will probably not be addressed by clinical studies. Medical cannabis and cannabis-based medicines have often been legalised as therapeutic products by legislative bodies without going through the usual process of regulatory approval founded on the results of traditional evidence-based studies. This review discusses the advantages and limitations of using cannabis to treat rheumatic conditions.
31686403 Assessing the Importance of Factors Associated with Cost-Related Nonadherence to Medicatio 2019 Dec BACKGROUND: Prescription drug costs have been rising rapidly in the USA, contributing to the persistent problem of cost-related medication nonadherence (CRN) among older Medicare beneficiaries. Given the importance of CRN and the negative outcomes associated with it, it is important to examine the factors that affect CRN. This study aims to estimate the factors influencing CRN among older Medicare beneficiaries and to rank their relative contribution in explaining CRN. METHODS: We used a 2015 Medicare Current Beneficiary Survey linked to Medicare claims data to identify older Medicare beneficiaries aged 65 years and over. Multivariate logistic regression was performed to identify factors associated with CRN. Factors included in the regression analyses were based on a conceptual framework adapted from Piette et al., including main effects (financial factors and regimen complexity) and contextual factors (sociodemographic, lifestyle and health factors). Dominance analysis was conducted to determine their relative importance in predicting CRN. RESULTS: Our study sample included 4427 older Medicare beneficiaries, 13.43% of whom reported CRN. For main effects, drug coverage and regimen complexity were significantly associated with CRN. Compared to beneficiaries with public coverage, those with private drug coverage were less likely to report CRN while those without drug coverage were more likely to report CRN. Having more than two monthly prescriptions was also associated with higher CRN. Significant contextual factors included age, activities of daily living limitations, perceived health status, cancer, rheumatoid arthritis, non-rheumatoid arthritis, depression, and lung disease. Dominance analysis showed drug coverage was the most influential factor in explaining CRN, after which age, ADL limitations, and depression ranked in sequence. CONCLUSIONS: These findings can help policy makers understand the relative importance of factors affecting CRN and identify the most important areas for intervention to improve CRN.
30959928 The Importance of the Knee Joint Meniscal Fibrocartilages as Stabilizing Weight Bearing St 2019 Apr 6 The aim of this study was to review aspects of the pathobiology of the meniscus in health and disease and show how degeneration of the meniscus can contribute to deleterious changes in other knee joint components. The menisci, distinctive semilunar weight bearing fibrocartilages, provide knee joint stability, co-ordinating functional contributions from articular cartilage, ligaments/tendons, synovium, subchondral bone and infra-patellar fat pad during knee joint articulation. The meniscus contains metabolically active cell populations responsive to growth factors, chemokines and inflammatory cytokines such as interleukin-1 and tumour necrosis factor-alpha, resulting in the synthesis of matrix metalloproteases and A Disintegrin and Metalloprotease with ThromboSpondin type 1 repeats (ADAMTS)-4 and 5 which can degrade structural glycoproteins and proteoglycans leading to function-limiting changes in meniscal and other knee joint tissues. Such degradative changes are hall-marks of osteoarthritis (OA). No drugs are currently approved that change the natural course of OA and translate to long-term, clinically relevant benefits. For any pharmaceutical therapeutic intervention in OA to be effective, disease modifying drugs will have to be developed which actively modulate the many different cell types present in the knee to provide a global therapeutic. Many individual and combinatorial approaches are being developed to treat or replace degenerate menisci using 3D printing, bioscaffolds and hydrogel delivery systems for therapeutic drugs, growth factors and replacement progenitor cell populations recognising the central role the menisci play in knee joint health.
31816595 Social phobia in immune-mediated inflammatory diseases. 2020 Jan OBJECTIVE: Immune-mediated inflammatory diseases (IMID) such as multiple sclerosis (MS), inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) are associated with a high prevalence of psychiatric comorbidity but little is known about the prevalence of social phobia in IMID, or the factors associated with social phobia. We aimed to determine the prevalence of social phobia in MS, IBD and RA, and the factors associated with social phobia in these IMID. METHODS: We obtained data from the enrollment visit of a cohort study in IMID of whom 654 participants were eligible for this analysis (MS: 254, IBD: 247, RA: 153). Each participant underwent a semi-structured psychiatric interview which identified depression and anxiety disorders including social phobia (lifetime and current), an assessment of disease activity, and reported sociodemographic information. RESULTS: Overall, 12.8% of participants had a lifetime diagnosis of social phobia (MS: 10.2%, IBD: 13.0%, RA: 17.0%). Social phobia was associated with younger age (OR 0.98; 0.97-1.00), having a high school education or less (OR 1.78; 1.08-2.91), comorbid major depressive disorder (OR 2.79; 1.63-4.78) and comorbid generalized anxiety disorder (OR 2.56; 1.30-5.05). Persons with RA had increased odds of having social phobia as compared to persons with MS (OR 2.26; 1.14-4.48) but not IBD. CONCLUSION: Persons with IMIDs have a relatively high lifetime prevalence of social phobia, exceeding that reported for the Canadian general population. Strategies aimed at early detection, and effective clinical management of social phobia in IMID are warranted.
30832414 Superiority of a Treat-to-Target Strategy over Conventional Treatment with Fixed csDMARD a 2019 Mar 3 BACKGROUND: Treatment of rheumatoid arthritis (RA) includes the use of conventional (cs), biologic (b) disease-modifying anti-rheumatic drugs (DMARDs) and oral, intramuscularly, intravenous, or intraarticular (IA) glucocorticoids (GCs). In this paper, we analysed whether a treat-to-target (T2T) strategy optimizing csDMARD, oral, and IA-GC treatment as an adjunct new therapy to a new certolizumab pegol (CZP) therapy improves the effectivity in RA patients. METHODS: 43 patients with active RA (≥6 tender, ≥6 swollen joints, ESR ≥ 20 mm/h or CRP ≥ 7mg/L) despite csDMARD treatment for ≥ 3 months and naïve to bDMARDs were randomized to CZP (200 mg/2 weeks after loading with 400 mg at weeks 0⁻2⁻4) plus a treat-to-target strategy (T2T, n = 21), or to CZP added to the established csDMARD therapy (fixed regimen, n = 22). The T2T strategy consisted of changing the baseline csDMARD therapy (1) SC-methotrexate (dose: 15 ≥ 20 ≥ 25 mg/week, depending on the initial dose) ≥ leflunomide (20 mg/d) ≥ sulphasalazine (2 × 1000 mg/d) plus (2) oral GCs (prednisolone 20⁻15⁻12.5⁻10⁻7.5⁻5⁻2.5⁻0 mg/d tapered every five days) and (3) injections of ≤5 affected joints with triamcinolone. DMARD modification and an addition of oral GCs were initiated, depending on the achievement of low disease activity (DAS 28 < 3.2). The primary objective was defined as the ACR 50 response at week 24. RESULTS: ACR 50 was achieved in 76.2% of the T2T, as compared to 36.4% of the fixed regimen patients (p = 0.020). ACR 20 and 70 responses were achieved in 90.5% and 71.4% of the T2T patients and 59.1% and 27.3% of the fixed regimen patients, respectively (p = 0.045 and p = 0.010, respectively). The adverse event rate was similar for both groups (T2T n = 51; fixed regimen n = 55). CONCLUSION: Treat-to-target management with the optimization of csDMARDs, oral, and IA-GCs of RA patients in parallel to a newly established CZP treatment was safe and efficacious in comparison to a fixed regimen of csDMARDs background therapy.
28935290 Objectives and methodology of BIOBADASER phase iii. 2019 Jul OBJECTIVE: Describe the objectives, methods and results of the first year of the new version of the Spanish registry of adverse events involving biological therapies and synthetic drugs with an identifiable target in rheumatic diseases (BIOBADASER III). METHODOLOGY: Multicenter prospective registry of patients with rheumatic inflammatory diseases being treated with biological drugs or synthetic drugs with an identifiable target in rheumatology departments in Spain. The main objective of BIOBADASER Phase III is the registry and analysis of adverse events; moreover, a secondary objective was added consisting of assessing the effectiveness by means of the registry of activity indexes. Patients in the registry are evaluated at least once every year and whenever they experience an adverse event or a change in treatment. The collection of data for phase iii began on 17 December 2015. RESULTS: During the first year, 35 centers participated. The number of patients included in this new phase in December 2016 was 2,664. The mean age was 53.7 years and the median duration of treatment was 8.1 years. In all, 40.4% of the patients were diagnosed with rheumatoid arthritis. The most frequent adverse events were infections and infestations. CONCLUSIONS: BIOBADASER Phase III has been launched to adapt to a changing pharmacological environment, with the introduction of biosimilars and small molecules in the treatment of rheumatic diseases. This new stage is adapted to the changes in the reporting of adverse events and now includes information related to activity scores.
31382369 Formulation Strategies for Folate-Targeted Liposomes and Their Biomedical Applications. 2019 Aug 2 The folate receptor (FR) is a tumor-associated antigen that can bind with folic acid (FA) and its conjugates with high affinity and ingests the bound molecules inside the cell via the endocytic mechanism. A wide variety of payloads can be delivered to FR-overexpressed cells using folate as the ligand, ranging from small drug molecules to large DNA-containing macromolecules. A broad range of folate attached liposomes have been proven to be highly effective as the targeted delivery system. For the rational design of folate-targeted liposomes, an intense conceptual understanding combining chemical and biomedical points of view is necessary because of the interdisciplinary nature of the field. The fabrication of the folate-conjugated liposomes basically involves the attachment of FA with phospholipids, cholesterol or peptides before liposomal formulation. The present review aims to provide detailed information about the design and fabrication of folate-conjugated liposomes using FA attached uncleavable/cleavable phospholipids, cholesterol or peptides. Advances in the area of folate-targeted liposomes and their biomedical applications have also been discussed.
30856027 Tumor necrosis factor receptor-2 (TNFR2): an overview of an emerging drug target. 2019 Apr Tumor necrosis factor (TNF) receptor 2 (TNFR2) is one of two receptors of the cytokines, TNF and lymphotoxin-α. TNFR1 is a strong inducer of proinflammatory activities. TNFR2 has proinflammatory effects too, but it also elicits strong anti-inflammatory activities and has protective effects on oligodendrocytes, cardiomyocytes, and keratinocytes. The protective and anti-inflammatory effects of TNFR2 may explain why TNF inhibitors failed to be effective in diseases such as heart failure or multiple sclerosis, where TNF has been strongly implicated as a driving force. Stimulatory and inhibitory TNFR2 targeting hence attracts considerable interest for the treatment of autoimmune diseases and cancer. Areas covered: Based on a brief description of the pathophysiological importance of the TNF-TNFR1/2 system, we discuss the potential applications of TNFR2 targeting therapies. We also debate TNFR2 activation as a way forward in the search for TNFR2-specific agents. Expert opinion: The use of TNFR2 to target regulatory T-cells is attractive, but this approach is just one amongst many suitable targets. With respect to its preference for Treg stimulation and protection of non-immune cells, TNFR2 is more unique and thus offers opportunities for translational success.
31568819 A systematic review on Piper longum L.: Bridging traditional knowledge and pharmacological 2020 Jan 30 ETHNOPHARMACOLOGICAL RELEVANCE: Piper longum, commonly referred as 'Pippali', has found its traditional use in India, Malaysia, Singapore and other South Asian countries as an analgesic, carminative, anti-diarrhoeic, immunostimulant, post childbirth to check postpartum hemorrhage and to treat asthma, insomnia, dementia, epilepsy, diabetes, rheumatoid arthritis, asthma, spleen disorder, puerperal fever, leprosy etc. AIM OF THE REVIEW: This review offers essential data focusing on the traditional use, phytochemistry and pharmacological profile of Piper longum thereby identifying research gaps and future opportunities for investigation on this plant. MATERIALS AND METHODS: This systematic survey was accomplished as per the PRISMA guidelines. The information was collected from books, and electronic search (PubMed, Science Direct, Lilca and Scielo) during 1967-2019. RESULTS: Many phytochemicals have been identified till date, including alkaloids as its major secondary metabolites (piperine and piperlongumine), essential oil, flavonoids and steroids. These exhibit a wide range of activities including anti-inflammatory, analgesic, anti-oxidant, anti-microbial, anti-cancer, anti-parkinsonian, anti-stress, nootropic, anti-epileptic, anti-hyperglycemic, hepatoprotective, anti-hyperlipidemic, anti-platelet, anti-angiogenic, immunomodulatory, anti-arthritic, anti-ulcer, anti-asthmatic, anthelmintic action, anti-amebic, anti-fungal, mosquito larvicidal and anti-snake venom. CONCLUSION: Amongst various activities, bioscientific clarification in relation to its ethnopharmacological perspective has been evidenced mainly for anti-amebic, anthelminthic, anti-tumor and anti-diabetic activity. However, despite traditional claims, insufficient scientific validation for the treatment of insomnia, dementia, epilepsy, rheumatoid arthritis, asthma, spleen disorder, puerperal fever and leprosy, necessitate future investigations in this direction. It is also essential and critical to generate toxicological data and pharmacokinetics on human subjects so as to confirm its conceivable bio-active components in the body.
30963011 A Case of Rheumatoid Arthritis Presenting with Renal Thrombotic Microangiopathy Probably d 2019 A 51-year-old woman with rheumatoid arthritis presented with mild hypertension 20 months after tacrolimus treatment and developing proteinuria 24 months after the treatment. Tacrolimus was discontinued 27 months after the treatment, followed by heavy proteinuria, accelerated hypertension, and deteriorating renal function without ocular fundus lesions as a clinical sign of malignant hypertension. Renal biopsy revealed malignant nephrosclerosis characterized by subacute and chronic thrombotic microangiopathy (TMA), involving small arteries, arterioles, and glomeruli. Focal segmental glomerulosclerosis, probably secondary to chronic TMA, was identified as a cause of heavy proteinuria. The zonal tubulointerstitial injury caused by subacute TMA may have mainly contributed to deteriorating renal function. The presence of nodular hyalinosis in arteriolar walls was indicative of tacrolimus-associated nephrotoxicity. Together with other antihypertensive drugs, administration of aliskiren stabilized renal function with reducing proteinuria. Owing to the preexisting proteinuria prior to severe hypertension and the complex renal histopathology, we postulated that chronic TMA, which was initially triggered by tacrolimus, was aggravated by severe hypertension, resulting in overt renal TMA.
30687959 Population based study: atopy and autoimmune diseases are associated with functional dyspe 2019 Mar BACKGROUND: The pathogenesis of functional GI disorders (FGIDs) is uncertain. However, underlying immune activation and psychological distress has been documented in irritable bowel syndrome (IBS) and functional dyspepsia (FD). Epidemiological data from the UK suggest that FGIDs are linked to atopy and certain autoimmune diseases but this has not been confirmed. AIM: To test if allergic or autoimmune diseases are independently associated with FGIDs, irrespective of psychological distress in a large population based study. METHODS: A total of 3542 people (mean age 57.9 years and 52.7% females) randomly selected from the Australian population, returned a mail survey (response rate = 43%). The survey asked about a physician diagnosis of autoimmune disease (scleroderma, psoriasis, rheumatoid arthritis and diabetes mellitus) or allergic conditions (asthma, food, pollen and/or animal allergy). The questionnaire assessed psychological distress and Rome III criteria for FD and IBS. RESULTS: Asthma, food, pollen and animal allergies, psoriasis and rheumatoid arthritis were univariately significantly associated with IBS and FD. Food allergy (OR = 1.66; 95% CI = 1.15-2.40, P = 0.007), psoriasis (OR = 1.81; 95% CI = 1.19-2.74, P = 0.006) and rheumatoid arthritis (OR = 1.68; 95% CI = 1.15-2.4, P = 0.007) were independent risk factors for IBS, controlling for age, gender and psychological distress. In FD, asthma (OR = 1.32; 95% CI = 1.04-1.68, P = 0.025) and food allergy (OR = 1.78; 95% CI = 1.28-2.49, P = 0.001) were independent predictors, controlling for age, sex and psychological distress. CONCLUSIONS: There is evidence that both atopic and autoimmune diseases are risk factors for FGIDs, independent of psychological distress, differing in IBS and FD. This provides evidence that different peripheral pathways may be involved in the pathogenesis of certain FGIDs.
31543508 Rheuma SPACE - Standard Practice Aiming Clinical Excellence: description of the methodolog 2019 Sep 8 BACKGROUND: Quality of care is a key component of the right to health, and the route to equity and dignity. The aim of the project Rheuma SPACE - Standard Practice Aiming Clinical Excellence was to develop a set of quality indicators focused in rheumatoid arthritis care and apply them to rheumatology departments of the Portuguese National Health Service in order to benchmark the care for these patients. This article details the methodology that was applied. METHODOLOGY: This was a single country, three-phase project, each phase comprising multiple steps. The first step defined quality indicators and the excellence quality model to be used. It involved a literature search for international benchmarking of quality of care initiatives and indicators, followed by a pre-selection of an initial set of indicators. The set of indicators was latter on narrowed after an online Delphi round with all Portuguese rheumatologists and two consensus meetings involving the study task force. A set of 26 quality indicators was defined, within the three classic Donabedian dimensions of healthcare quality: Structure (9), Processes (11), and Outcomes (6). These indicators cover eleven domains of quality of care: personnel and organizational structure, training and research, facilities, equipment and information technology, budgeting and financial resources, access to care, clinical records, patient communication, multidisciplinary management, clinical outcomes, and patient and personnel satisfaction. Decision on quality and excellence thresholds for each of the 26 quality indicators was agreed upon a consensus meeting gathering principal investigators of the eight Rheumatology Departments that decided to participate, task force core set members and invited representatives of all Portuguese Departments/Units. Rheumatoid arthritis was the chosen disease model of the project based on the reliability of the outcomes to be measured in the context of this condition. The second step was the assessment of the participating Rheumatology Departments. During eighteen months, research teams applied the 26 quality indicators to their own Departments. The third step comprised data analysis and the elaboration of individual Rheumatology Department reports and of a global public report. RESULTS: Eight Departments, comprising 80 specialists, 20 residents and 30 nurses, covering 5.904.080 inhabitants, underwent quality evaluation. More than one thousand patients (1,325) and 113 health professionals' surveys were analysed, as well as data from 570 clinical records and 3,927 medical appointments on rheumatoid arthritis patients. DISCUSSION: 26 quality indicators were used for the first evaluation of Portuguese Rheumatology Departments, turning Rheuma SPACE into a pioneer project. Data analysis and benchmarking will be the subject of a further publication.
30959419 PI3K activity in dendritic cells exerts paradoxical effects during autoimmune inflammation 2019 Jul The peripheral activation of autoreactive T cells and subsequent central nervous system (CNS) immune cell infiltration are key events relevant for experimental autoimmune encephalomyelitis (EAE), a commonly employed multiple sclerosis (MS) model, influenced by T(H)1 and T(H)17 mediated immunity. The phosphoinositide-3-kinase (PI3K)-AKT kinase pathway modulates outcome during EAE, with direct actions of PI3K on adaptive immunity implicated in deleterious and effects on antigen presenting cells involved in beneficial responses during EAE. Here, by genetically deleting the regulatory subunit of Class Ia PI3K, p85α, in selective myeloid cells, we aimed to resolve the impact of PI3K in EAE. While genetically deleting PI3K in LysM expressing cells exerted unremarkable effects, attenuating PI3K function in CD11c(+) dendritic cells (DCs), promoted secretion of pathogenic EAE promoting cytokines, particularly skewing T(H)1 and T(H)17 immunity, while notably, improving health in EAE. Neutralizing IFN-γ activity using blocking antibodies revealed a prolonged T(H)1 response was critical for the decreased disease of these animals. Thus, PI3K-AKT signaling in DCs acts in a paradoxical manner. While attenuating EAE associated T(H)1 and T(H)17 responses, it impairs health during autoimmune inflammation.