Browse

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

ID PMID Title PublicationDate abstract
21120343 [Situation of lawsuits concerning the access to medical products by the Health Department 2010 Nov This study describes the situation of lawsuits concerning the access to medical products by the Health Department of Santa Catarina State (SES/SC), Brazil, during the years of 2003 and 2004. The variables considered were: declared illnesses, medicines demanded, prescription origin, possible alternatives therapeutics in the Santa Catarina State Register of Essential Medicines (Resme), the medicines registration at the National Health Surveillance Agency (Anvisa) and total expenditure. 622 lawsuits were filed. Total expenditure was R$ 11,333,750,00 (Brazilian Reais). Private health care was the source of 56% of the prescriptions. Hepatitis C and rheumatoid arthritis were the most commonly diseases involved. About 40% of requested drugs were on the Resme. 6.2% of required drugs were approved in Brazil after 2000. PEG-Interferon and Infliximab were responsible for 46% of total expenditure. There were still some cases of drugs or indications not registered at Anvisa. These results indicate the need to reassess the list of medicines regularly provided by the SES/SC, and also to improve accessibility to (and information concerning) Programs of medicines distribution. These measures may potentially reduce the number of lawsuits filed against the State.
21098742 Pregnancy outcomes after maternal exposure to rituximab. 2011 Feb 3 Rituximab is a chimeric anti-CD20 monoclonal B cell-depleting antibody indicated for certain hematologic malignancies and active rheumatoid arthritis with inadequate response to tumor necrosis factor antagonists. Despite counseling to avoid pregnancy, women may inadvertently become pregnant during or after rituximab treatment. Using the rituximab global drug safety database, we identified 231 pregnancies associated with maternal rituximab exposure. Maternal indications included lymphoma, autoimmune cytopenias, and other autoimmune diseases. Most cases were confounded by concomitant use of potentially teratogenic medications and severe underlying disease. Of 153 pregnancies with known outcomes, 90 resulted in live births. Twenty-two infants were born prematurely; with one neonatal death at 6 weeks. Eleven neonates had hematologic abnormalities; none had corresponding infections. Four neonatal infections were reported (fever, bronchiolitis, cytomegalovirus hepatitis, and chorioamnionitis). Two congenital malformations were identified: clubfoot in one twin, and cardiac malformation in a singleton birth. One maternal death from pre-existing autoimmune thrombocytopenia occurred. Although few congenital malformations or neonatal infections were seen among exposed neonates, women should continue to be counseled to avoid pregnancy for ≤ 12 months after rituximab exposure; however, inadvertent pregnancy does occasionally occur. Practitioners are encouraged to report complete information to regulatory authorities for all pregnancies with suspected or known exposure to rituximab.
21542548 2010 Nov PURPOSE: We compared the effectiveness and harms of oral or topical nonsteroidal antiinflammatory drugs (NSAIDs) in the treatment of chronic pain from osteoarthritis, rheumatoid arthritis, soft tissue pain, back pain, and ankylosing spondylitis. DATA SOURCES: We searched Ovid MEDLINE(®) and the Cochrane Library and the Database of Abstracts of Reviews of Effects through May 2010. For additional data we also hand searched reference lists, US Food and Drug Administration medical and statistical reviews and dossiers submitted by pharmaceutical companies. REVIEW METHODS: Study selection, data abstraction, validity assessment, grading the strength of the evidence, and data synthesis were all carried out according to standard Drug Effectiveness Review Project review methods. RESULTS AND CONCLUSIONS: For pain relief, no significant short-term (< 6 months) differences were found among oral NSAIDs, topical NSAIDs, or between oral and topical NSAID. For serious harms, celecoxib does not appear to be associated with higher risk of cardiovascular events and is gastroprotective in the short term compared with nonselective NSAIDs. These findings vary by subgroup, depending on age, recent history of gastrointestinal bleeding, and concomitant use of antiulcer medication. Nonselective NSAIDs were associated with similar increased risks of serious gastrointestinal events, and all but naproxen were associated with similar increased risk of serious cardiovascular events, but the partially selective NSAID nabumetone was gastroprotective compared with nonselective NSAIDs. Compared with oral NSAIDs, topical diclofenac was gastroprotective but had higher risk of application site dryness. Application site reactions and withdrawals due to adverse events were higher with diclofenac 1.5% topical solution but not with diclofenac 1.0% topical gel compared with placebo.
20852572 Metabolic syndrome, inflammation and atherosclerosis - the role of adipokines in health an 2009 Oct Cardiovascular (CV) events are among the leading causes of morbidity and mortality in patients with inflammatory rheumatic diseases. It has been hypothesized that, in addition to the traditional CV risk factors, inflammation is a major contributor to atherogenesis. Metabolic syndrome (MetS) stands for a cluster of risk factors associated with insulin resistance and increased abdominal fat. Inflammation and MetS are intimately linked. Inflammatory biomarkers are frequently elevated in people with MetS and, conversely, the prevalence of MetS is higher in patients with chronic inflammatory rheumatic diseases, such as Rheumatoid Arthritis and Systemic Lupus Erythematosus. Inflammatory cytokines impair insulin sensitivity and can induce an adverse lipoprotein profile as seen in MetS. Furthermore, the presence of MetS correlates with increased subclinical atherosclerosis, major adverse CV events and death, making an important contribution to the CV burden in inflammatory diseases. Adipose tissue has recently emerged as an active organ that produces and secretes numerous mediators - adipokines - particularly relevant in energy homeostasis, inflammation, immune regulation and angiogenesis. These mediators arise as a potential link between MetS, inflammation and atherogenesis. Understanding the complex regulation and function of adipokines in health and disease is a priority since it may lead to new preventive and therapeutic interventions aiming to decrease CV risk.
20805369 Polymorphisms at 16p13 are associated with systemic lupus erythematosus in the Chinese pop 2011 Jan BACKGROUND: Chromosomal region 16p13 has been reported to harbour variants associated with several autoimmune diseases, including type I diabetes, rheumatoid arthritis and multiple sclerosis. OBJECTIVE: To test whether variants in the 16p13 region are also associated with systemic lupus erythematosus (SLE) by performing a candidate locus study in the Chinese Han population. METHODS: Tag single nucleotide polymorphisms (SNPs) encompassing 50 kb upstream and downstream of the 250 kb linkage disequilibrium block, previously implicated in several autoimmune diseases, were analysed in 1047 patients with SLE and 1205 controls. The SNP showing the strongest association with SLE was then replicated in an independent cohort of 1643 cases and 5930 controls. RESULTS AND CONCLUSIONS: The association between SNP rs12599402 and SLE reached the genome-wide significance level (p<5 × 10⁻⁸). The SNP was likely to tag the same functional variant as previously reported in European populations. The results suggested that the chromosomal region at 16p13 contains common susceptibility genes for different immune-mediated disorders.
27713349 Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke. 2010 Jul 8 Cannabis contains the psychoactive component delta⁸-tetrahydrocannabinol (delta⁸-THC), and the non-psychoactive components cannabidiol (CBD), cannabinol, and cannabigerol. It is well-known that delta⁸-THC and other cannabinoid CB₁ receptor agonists are neuroprotective during global and focal ischemic injury. Additionally, delta⁸-THC also mediates psychological effects through the activation of the CB₁ receptor in the central nervous system. In addition to the CB₁ receptor agonists, cannabis also contains therapeutically active components which are CB₁ receptor independent. Of the CB₁ receptor-independent cannabis, the most important is CBD. In the past five years, an increasing number of publications have focused on the discovery of the anti-inflammatory, anti-oxidant, and neuroprotective effects of CBD. In particular, CBD exerts positive pharmacological effects in ischemic stroke and other chronic diseases, including Parkinson's disease, Alzheimer's disease, and rheumatoid arthritis. The cerebroprotective action of CBD is CB₁ receptor-independent, long-lasting, and has potent anti-oxidant activity. Importantly, CBD use does not lead to tolerance. In this review, we will discuss the therapeutic possibility of CBD as a cerebroprotective agent, highlighting recent pharmacological advances, novel mechanisms, and therapeutic time window of CBD in ischemic stroke.
20550512 Recent patents on immunoregulatory DNA vaccines for autoimmune diseases and allograft reje 2010 Jun The goal of immunoregulatory DNA vaccination is the antigen- and tissue-specific suppression of pathological inflammation that underlies immune-mediated inflammatory disorders like autoimmune diseases and allograft rejection. Recent patents and patent applications have applied immunoregulatory DNA vaccines in rodent model systems and human clinical trials using plasmid DNA coding for autoantigens such as insulin and glutamic acid decarboxylase for type 1 diabetes, myelin-associated proteins for multiple sclerosis, and heat-sock protein 60 for rheumatoid arthritis. In these cases, the objective is to induce a homeostatic-like regulatory immune response to suppress pathological inflammation. In addition, patent applications have disclosed the use of DNA vaccines encoding the pro-inflammatory MIF cytokine and the CD25 IL-2 receptor subunit to interfere with the inflammatory process. Approaches have also been taken to improve DNA vaccination efficacy, including covalent modification of plasmid DNA, engineering secretion of vaccine-encoded antigen, and co-delivery of DNA coding for anti-inflammatory cytokines, a mutant co-stimulatory molecule, a growth factor, or a pro-apoptotic protein. Furthermore, a patent application has disclosed the use of a DNA vaccine previously shown to treat successfully an autoimmune disease to prolong allograft survival. Taken together, these patents and patent applications indicate a promising bench-to-bedside potential for immunoregulatory DNA vaccination applied to autoimmune diseases and allograft rejection.
20511601 Patient-held medical records for patients with chronic disease: a systematic review. 2010 Oct OBJECTIVES: To determine whether in patients with chronic disease a patient-held medical record (PHR), compared to usual care, improves clinical care, patient outcomes or satisfaction. DESIGN: Systematic review. DATA SOURCES: Databases searched were All EBM (The Cochrane Database of Systematic Reviews, DARE CENTRAL), Medline, CINAHL and EMBASE from 1980 to 16 February 2009. STUDY SELECTION: Two reviewers assessed comparative studies that compared paper-based PHR to usual care for inclusion using a priori study selection criteria. STUDIES REVIEWED: Four hundred and eighty-one articles were reviewed by title and abstract. Full text was retrieved for 120 articles. Fourteen studies met the inclusion and exclusion criteria and were appraised using a priori criteria for methodological quality. RESULTS: Fourteen studies were included in diabetes, oncology, mental health, rheumatoid arthritis, stroke and palliative care. The studies used a variety of designs of PHR and compared this with usual care. PHR were implemented with varying degrees of patient and staff support and education, mainly for six months or less. Outcomes included attitudes on the usefulness of PHR, the quality of information exchange, process indicators, and clinical and physiological indicators. The effectiveness of PHRs is generally of low or very low quality, with the majority of studies having a high risk of bias. These studies do not demonstrate a significant benefit of introducing PHR. CONCLUSIONS: There is no clear benefit of implementing a PHR, and due to medium to high risk of bias these findings should be interpreted with caution. More high quality studies are needed to evaluate properly the effectiveness of PHRs in chronic disease populations.
20306464 Characterizing the clinical practice and professional behaviour of rheumatology nurse spec 2010 Sep BACKGROUND: There is a need to characterize the practice of nurse specialists, for several reasons: to identify the skills and knowledge required for the role, to safeguard the role and to facilitate appropriate remuneration of activities. OBJECTIVE: To develop an instrument, which characterizes the clinical and professional activities of rheumatology nurse specialists (RNSs). METHODS: A questionnaire was produced, informed by the Nursing and Midwifery Council (NMC), to assess competencies in advanced nursing practice and completed by senior clinical rheumatology nurses in the UK undertaking an MSc in rheumatology nursing. Consenting respondents were also interviewed, to enable triangulation of the data. RESULTS: A 38-item questionnaire was produced. It comprised four sections: clinical activities, non-patient-based activities, professional behaviour and perceived confidence in a number of areas of practice. Thirteen nurses completed the questionnaire and seven of these took part in a telephone interview. All RNSs were engaged in the follow-up care of patients with rheumatoid arthritis, providing education, psychological support, monitoring and changing of drug treatments, and referrals to other health professionals. The RNSs produced guidelines, conducted audits and provided mentorship. They had low levels of confidence in seeing new patients, presenting the results of an audit at a conference, and writing a business case. CONCLUSIONS: We have begun the process of developing a questionnaire that can identify the clinical activities, perceived self-competence and professional behaviour of RNSs. This method of characterizing advanced nursing practice offers potential as a model for nurse specialists in other disciplines. Further work is required to validate the questionnaire on a large cohort of RNSs.
20192154 Pigmented villonodular synovitis of the elbow treated with the Tsuge wide joint exposure t 2010 Feb Pigmented villonodular synovitis (PVNS) is a benign, locally aggressive disease of the synovium; its cause remains unclear. The most frequently involved joint is the knee, followed by the hip, ankle, wrist, and shoulder. Pigmented villonodular synovitis of the elbow joint is rare. Synovectomy is currently believed to be the best treatment for PVNS. Open or arthroscopic synovectomy is usually selected. During synovectomy for PVNS, the possibility of local recurrence after surgery must be considered. The recurrence rate after synovectomy of any joint for PVNS is approximately 40%. Therefore, surgical treatment for PVNS of the elbow requires sufficient removal of the lesion. For good functional results, prevention of postoperative joint stiffness is also necessary. This article describes a case of a 29-year-old woman with PVNS of the right elbow who was treated by total synovectomy using the Tsuge technique. Tsuge reported a new surgical technique for debridement arthroplasty using a posterolateral approach to the elbow in 1987. He has also reported using this procedure during arthroplasty for posttraumatic stiff elbow and for synovectomy in rheumatoid arthritis. This approach permits easy dislocation of the elbow and provides a good view of the whole joint. Although the recurrence rate of PVNS of the elbow is high, our patient has retained good elbow function with no evidence of local recurrence at 30 months postoperatively.
20173394 TNF in host resistance to tuberculosis infection. 2010 TNF is essential to control Mycobacterium tuberculosis infection and cannot be replaced by other proinflammatory cytokines. Overproduction of TNF may cause immunopathology, while defective TNF production results in uncontrolled infection. The critical role of TNF in the control of tuberculosis has been illustrated recently by primary and reactivation of latent infection in some patients under pharmacological anti-TNF therapy for rheumatoid arthritis or Crohn's disease. In this review, we discuss results of recent studies aimed at better understanding of molecular, cellular and kinetic aspects of TNF-mediated regulation of host-mycobacteria interactions. In particular, recent data using either mutant mice expressing solely membrane TNF or specific inhibitor sparing membrane TNF demonstrated that membrane TNF is sufficient to control acute M. tuberculosis infection. This is opening the way to selective TNF neutralization that might retain the desired anti-inflammatory effect but reduce the infectious risk.
20146942 Vitamin D and autoimmune rheumatologic disorders. 2010 May Vitamin D levels depend on many variables, including sun exposure, age, ethnicity, body mass index, use of medications and supplements. A much higher oral vitamin D intake than the current guidelines is necessary to maintain adequate circulating 25(OH)D levels in the absence of UVB radiation of the skin. In addition to the traditional known metabolic activities, vitamin D has been shown to modulate the immune system, and its deficiency has been linked to the development of several autoimmune disorders including type 1 diabetes and multiple sclerosis. Experimental use of vitamin D has revealed a novel role in the immunopathogenesis of autoimmune diseases. Disorders such as systemic lupus erythematosus, rheumatoid arthritis, Behçet's, polymyositis/dermatomyositis and systemic scleroderma have all been associated to some extent to vitamin D deficiency. If vitamin D deficiency occurs at a higher rate in patients with autoimmune disorders, then appropriate supplementation may be indicated.
20103766 Induction of neutrophil degranulation by S100A9 via a MAPK-dependent mechanism. 2010 May S100A9 is a proinflammatory protein, expressed abundantly in the cytosol of neutrophils and monocytes. High extracellular S100A9 concentrations have been correlated with chronic inflammatory diseases such as rheumatoid arthritis and Crohn's disease, as well as with phagocyte extravasation. This study tested the hypothesis that S100A9 induces degranulation in human neutrophils. S100A9 was found to up-regulate the surface expression of CD35 and CD66b, proteins contained in secretory vesicles and specific/gelatinase granules, respectively. In addition, gelatinase and albumin, stored, respectively, in specific/gelatinase granules and secretory vesicles, were detected in the supernatants of neutrophils stimulated with S100A9. In contrast, stimulation with S100A9 had no effect on CD63 expression or MPO secretion, two proteins contained in azurophilic granules. S100A9 induced the phosphorylation of the MAPKs, ERK1/2, p38, and JNK. Inhibition of p38 and JNK but not ERK1/2, with specific inhibitors (SB203580, JNKII, and PD98059, respectively), blocked neutrophil degranulation induced by S100A9. Taken together, these results support the hypothesis and clearly indicate that S100A9 induces the degranulation of secretory and specific/gelatinase granules but not of azurophilic granules in a process involving p38 and JNK and further support its classification as a DAMP.
20072943 Combination of anti-angiogenic therapy and virotherapy: arming oncolytic viruses with anti 2009 Dec Angiogenesis is essential for development and tissue repair, and is controlled by a balance of inhibitors and promoters. Overactive angiogenesis promotes tumor progression and other chronic disorders, including diabetic retinopathy and rheumatoid arthritis. The discovery of angiogenesis inhibitors has resulted in a promising therapeutic approach to these diseases. However, the benefits of anti-angiogenic drugs have been modest, stimulating interest in developing more effective approaches by combining anti-angiogenic therapy with other therapeutics. Oncolytic virotherapies are attractive therapeutics for cancer, but virotherapy alone has had similar problems to anti-angiogenic therapy, with few examples of clinical efficacy. This review summarizes the progress of the emerging field of combinations of anti-angiogenic therapy and virotherapy, and highlights future challenges in experimental and translational research that need to be addressed in order for these therapeutics to advance into the clinic.
20065996 HDL and immunomodulation: an emerging role of HDL against atherosclerosis. 2010 Mar Changes in plasma lipoprotein profiles, particularly low levels of high-density lipoprotein (HDL) cholesterol, are associated with several inflammatory and immune diseases, including atherosclerosis and rheumatoid arthritis, implying the potential link between HDL and immunity. Accumulating evidence suggests that HDL possesses anti-inflammatory effects and has an important function in host defense as part of the innate immune system. In addition, HDL inhibits the ability of antigen-presenting cells (APCs) to stimulate T cells. It is subsequently discovered that HDL or HDL-associated platelet-activating factor-acetylhydrolase can restore the emigratory process of monocyte-derived dendritic cells and thus result in resolution of inflammatory reactions in atherosclerotic plaques. Lipid rafts in plasma membrane are the key structure responsible for the immunomodulation effects of HDL, the remarkable ability of HDL to regulate innate and adaptive immune responses extends our understanding of its atheroprotective role, and provides new therapeutic approaches to atherosclerosis and other inflammatory conditions.
22312219 Improving health outcomes with better patient understanding and education. 2010 A central plank of health care reform is an expanded role for educated consumers interacting with responsive health care teams. However, for individuals to realize the benefits of health education also requires a high level of engagement. Population studies have documented a gap between expectations and the actual performance of behaviours related to participation in health care and prevention. Interventions to improve self-care have shown improvements in self-efficacy, patient satisfaction, coping skills, and perceptions of social support. Significant clinical benefits have been seen from trials of self-management or lifestyle interventions across conditions such as diabetes, coronary heart disease, heart failure and rheumatoid arthritis. However, the focus of many studies has been on short-term outcomes rather that long term effects. There is also some evidence that participation in patient education programs is not spread evenly across socio economic groups. This review considers three other issues that may be important in increasing the public health impact of patient education. The first is health literacy, which is the capacity to seek, understand and act on health information. Although health literacy involves an individual's competencies, the health system has a primary responsibility in setting the parameters of the health interaction and the style, content and mode of information. Secondly, much patient education work has focused on factors such as attitudes and beliefs. That small changes in physical environments can have large effects on behavior and can be utilized in self-management and chronic disease research. Choice architecture involves reconfiguring the context or physical environment in a way that makes it more likely that people will choose certain behaviours. Thirdly, better means of evaluating the impact of programs on public health is needed. The Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework has been promoted as one such potential approach.
20001666 Spleen tyrosine kinase: an Src family of non-receptor kinase has multiple functions and re 2010 Feb Spleen tyrosine kinase (Syk) is involved in the development and function of B and T cells, the Fc receptor-mediated degranulation of basophils and mast cells. Recent work has assigned important roles for Syk in the aberrant function of T cells in patients with systemic lupus erythematosus (SLE), osteoclasts, and urate crystal-induced neutrophil stimulation. Preclinical and early clinical studies have urged Syk inhibition for the treatment of patients with rheumatoid arthritis, whereas ex vivo experiments and preclinical studies point to a therapeutic potential of Syk inhibition in patients with SLE and crystal-induced arthritides.
19962623 The HAQ compared with the MDHAQ: "keep it simple, stupid" (KISS), with feasibility and cli 2009 Nov The health assessment questionnaire (HAQ) is the questionnaire most widely used to assess and monitor patients with rheumatic diseases. The HAQ includes 20 activities grouped into 8 categories of 2 or 3 (and queries the use of "aids and devices" and "help from another person" to perform these activities), and visual analog scales (VAS) for pain and patient global estimate of status. Use of the HAQ in usual care over the years has led to several modifications to develop a multidimensional HAQ (MDHAQ). The MDHAQ includes 10 activities, one from each category of the HAQ plus 2 complex activities-walk 2 miles or 3 km-all on one side of a page for easy "eyeball" review by a clinician; pain, global and fatigue VAS with 21 circles rather than 10-cm lines for ease of scoring; recent medical history; review of systems; a query about exercise; and scoring templates for the 3 rheumatoid arthritis (RA) Core Data Set patient-reported measures-physical function, pain, and global estimate-for a routine assessment of patient index data (RAPID3) composite score. Both the HAQ and MDHAQ involve 2 sides of one sheet of paper, and are completed by patients in 5 to 10 minutes. The HAQ requires 42 seconds to score, compared with 5 to 10 seconds for RAPID3 on the MDHAQ.
19930834 Expression and activation of proline-rich tyrosine kinase 2 (PYK2) in peripheral blood mon 2009 Sep This study analysed the expression and activation of proline-rich tyrosine kinase 2 (PYK2) in peripheral blood mononuclear cells (PBMCs) from 36 systemic lupus erythematosus (SLE) patients and explored whether activation of PYK2 correlates with disease activity or organ damage in SLE. Samples from 19 patients with rheumatoid arthritis (RA) and 15 healthy individuals were included as controls. There was a significant increase in both total PYK2 protein and its activated/phosphorylated form in PBMCs from patients with SLE, particularly in those with the complication of World Health Organization class IV lupus nephritis. There was a clear correlation between the activation of PYK2 and the level of serum complement, but no relationship was found between the activation of PYK2 and SLE Disease Activity Index (SLEDAI). As previous studies have shown that PYK2 provides important signals during the activation of lymphocytes, PYK2 could be a major contributor to the complex autoimmune pathogenesis of SLE.
19890635 Necrotizing fasciitis in a patient with overlap syndrome of systemic sclerosis and systemi 2011 Jul Necrotizing fasciitis (NF) is an uncommon destructive disease and fatal infection of the subcutaneous tissue. The literature includes a limited number of NF cases in rheumatic disease such as rheumatoid arthritis and systemic lupus erythematosus (SLE). We report a 40-year-old patient who had complicated with NF during treatment with corticosteroid and azathioprine for overlap syndrome of systemic sclerosis and SLE. She underwent urgent surgical debridement and internal drainage with antibiotics and had complete recovery from NF. To our knowledge, this is the first case of NF developed in a patient of overlap syndrome with diffuse type of systemic sclerosis and SLE and suggests that NF can be a very rare cutaneous manifestation of this disease.