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ID PMID Title PublicationDate abstract
26676186 Manipulation under Anesthesia for Stiffness after Total Knee Arthroplasty. 2015 Dec PURPOSE: This study evaluated the incidence of manipulation under anesthesia (MUA) for stiffness after total knee arthroplasty (TKA) and the degree of joint motion recovery after MUA. MATERIALS AND METHODS: A total of 4,449 TKAs (2,973 patients) were performed between March 2000 and August 2014. Cases that underwent MUA for stiffness after TKA were reviewed. TKAs were performed using the conventional procedure in 329 cases and using the minimally invasive procedure in 4,120 cases. The preoperative range of joint motion, timing of manipulation, diagnosis and the range of joint motion before and after MUA were retrospectively investigated. RESULTS: MUA was carried out in 22 cases (16 patients), resulting in the incidence of 0.5%. The incidence after the conventional procedure was 1.2% and 0.4% after the minimally invasive procedure. In the manipulated knees, the preoperative range of motion (ROM) was 102.5°±26.7°, and the preoperative diagnosis was osteoarthritis in 19 cases, rheumatoid arthritis in two, and infection sequela in one. MUA was performed 4.7±3.0 weeks after TKA. The average ROM was 64.5°±13.5° before manipulation. At an average of 64.3±41.3 months after manipulation, the ROM was recovered to 113.4°±31.2°, which was an additional 49.9° improvement in flexion. CONCLUSIONS: The satisfactory recovery of joint movement was achieved when MUA for stiffness was performed relatively early after TKA.
26633290 Targeting GM-CSF in inflammatory diseases. 2016 Jan Granulocyte-macrophage colony stimulating factor (GM-CSF) is a growth factor first identified as an inducer of differentiation and proliferation of granulocytes and macrophages derived from haematopoietic progenitor cells. Later studies have shown that GM-CSF is involved in a wide range of biological processes in both innate and adaptive immunity, with its production being tightly linked to the response to danger signals. Given that the functions of GM-CSF span multiple tissues and biological processes, this cytokine has shown potential as a new and important therapeutic target in several autoimmune and inflammatory disorders - particularly in rheumatoid arthritis. Indeed, GM-CSF was one of the first cytokines detected in human synovial fluid from inflamed joints. Therapies that target GM-CSF or its receptor have been tested in preclinical studies with promising results, further supporting the potential of targeting the GM-CSF pathway. In this Review, we discuss our expanding view of the biology of GM-CSF, outline what has been learnt about GM-CSF from studies of animal models and human diseases, and summarize the results of early phase clinical trials evaluating GM-CSF antagonism in inflammatory disorders.
26610159 Pharmacological effects of berberine and its derivatives: a patent update. 2016 INTRODUCTION: A number of plant-derived agents are used in many therapeutic areas. Berberine, an important protoberberine alkaloid, is present in a number of medicinal plants that have been widely used in traditional Chinese medicine for hundreds of years. Modern research has shown that berberine and its derivatives display several pharmacological effects through various mechanisms. AREAS COVERED: This review discusses recent and mostly Chinese patents that report the synthesis of berberine, berberine derivatives and berberine salts, and methods of preparation for formulations (traditional Chinese medicine) containing herbal components rich in berberine, along with their applications. The review covers several therapeutic effects of berberine, its derivatives and pharmaceutical formulations against cancer, obesity, diabetes, inflammation, atherosclerosis, Alzheimer's disease, rheumatoid arthritis and cardiovascular diseases. In addition, the mechanisms underlying the pharmacological effects are discussed. EXPERT OPINION: Modification of the functional groups of berberine has a significant effect on the pharmacological activity. However, studies on altering the atoms and size of the berberine skeleton are rare. Thus, it may be beneficial to initiate a drug development program focused on inserting heterocyclic rings of different sizes into berberine. Furthermore, structural modification to improve the safety, efficacy and selectivity is necessary to promote the use of berberine-based drugs in clinical settings.
26535596 RheuMetric A Physician Checklist to Record Patient Levels of Inflammation, Damage and Dist 2015 Jul BACKGROUND: A physician global estimate of patient status (DOCGL) was designed to quantitate inflammatory activity but may be influenced by the presence of damage and distress. Therefore, three additional 0 to 10 visual analog scales (VAS) have been developed on a RheuMetric checklist to record physician estimates of inflammation (DOCINF), damage (DOCDAM), and distress (DOCSTR) (such as fibromyalgia and somatization). We analyzed patient scores on a multidimensional health assessment questionnaire (MDHAQ) and four RheuMetric physician estimates inpatients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), osteoarthritis (OA), and fibromyalgia (FM). METHODS: All patients with all diagnoses seen by Rush University Medical Center rheumatologists complete an MDHAQ and have four RheuMetric 0 to 10 VAS estimates for DOCGL, DOCINF, DOCDAM, and DOCSTR assigned by the rheumatologist at each visit. A random visit of 205 patients with RA (N = 50), OA (N = 67), SLE (N = 66), and FM (N = 32) was analyzed for mean MDHAQ scores, RheuMetric estimates, and Spearman correlations. RESULTS: Mean MDHAQ scores and DOCGL were highest for FM, followed by OA, RA, and SLE. Highest estimates and highest correlations with DOCGL were seen for DOCINF in RA, for DOCDAM in OA, and for DOCSTR in FM. DOCDAM estimates were higher than DOCINF in RA and SLE, suggesting that damage may be as severe a clinical problem as inflammation. DOCGL was correlated significantly with patient global estimate (PATGL) in RA, SLE, and OA, but not in FM. CONCLUSIONS: Physician estimates for inflammation, damage,and distress differ in different rheumatic diagnoses. Many patients have inflammation and damage or distress, or all three problems, reflecting challenges of rheumatology care.
26516588 Prevention of fostamatinib-induced blood pressure elevation by antihypertensive agents. 2015 Oct Fostamatinib is a tyrosine kinase inhibitor with activity against spleen tyrosine kinase which has completed clinical trials for patients with rheumatoid arthritis. In clinical studies fostamatinib treatment was associated with a small elevation of systemic arterial blood pressure (BP), a similar finding to that seen with other kinase inhibitors, especially those that inhibit VEGFR2 signaling. We have investigated the link between fostamatinib-induced blood pressure elevation and plasma levels of the fostamatinib-active metabolite R940406 in conscious rats and found the time course of the BP effect correlated closely with changes in R940406 plasma concentration, indicating a direct pharmacological relationship. Free plasma levels of R940406 produced in these studies (up to 346 nmol/L) span the clinically observed mean peak free plasma concentration of 49 nmol/L. We have demonstrated that the blood pressure elevation induced by fostamatinib dosing can be successfully controlled by a variety of methods, notably simple drug withdrawal or codosing with a range of standard antihypertensive agents such as atenolol, captopril, and nifedipine. These findings support potential methods of maintaining patient safety while on fostamatinib therapy. Furthermore, we have demonstrated, using nifedipine as an example agent, that this blood pressure control was not achieved by reduction in plasma exposure of R940406, suggesting that potential benefits from the pharmacology of the investigational drug can be maintained while blood pressure control is managed by use of standard comedications.
26458569 [A case of anti-PL7 antibody positive myositis and a clinical and pathological review of t 2015 A 52-year-old woman was admitted to our hospital with muscle pain and an elevated creatine kinase level. She had experienced wrist pain at onset seven years ago. The initial possible diagnoses were rheumatoid arthritis and adult-onset Still disease. The patient received corticosteroid and immunosuppressant therapy but experienced deterioration of symptoms. The symptoms of muscle pain and mild creatine kinase elevation emerged four years prior to her visit. Further elevation of creatine kinase was observed for three months before her visit despite adjusting the immunosuppressant dose. On admission, she presented with muscle moderate weakness of the trunk and extremities and pain of the shoulder and medial thigh muscles. Elevation of muscle enzymes and inflammatory response were also detected, and the anti-PL7 antibody was positive. Muscle biopsy from biceps brachii revealed necrotizing myopathy with necrotic and regenerated muscle fibers. The final diagnosis was anti-PL7 antibody positive myositis. The patient was treated with a higher dose of prednisolone and an adequate dose of tacrolimus. Following this treatment, the symptoms were improved. Anti-ARS (aminoacyl t-RNA synthetase) antibodies such as anti-PL7 antibody are useful in diagnosis and for prognostic prediction. Further investigation of patients with anti-ARS antibodies positive myositis is required.
26360624 Estimation of the symptoms for GERD by GerdQ in the patients with rheumatic diseases. 2016 OBJECTIVE: Gastroesophageal reflux disease (GERD) is one of the most common comorbidity in many diseases, but the frequency in rheumatic disease has not been well understood. METHODS: We investigated the prevalence of GERD by GerdQ in 530 rheumatic patients [systematic lupus erythematosus (SLE; n = 120), rheumatoid arthritis (RA; n = 117), polymyalgia rheumatica (PMR; n = 40), dermatomyositis and polymyositis (PM/DM; n = 38), systemic scleroderma (SSc; n = 37), mixed connective tissue disease (MCTD; n = 18), Behçet disease (BD; n = 17), adult onset still disease (AOSD; n = 14), and other rheumatic diseases (n = 129)]. RESULTS: The mean GerdQ scores of patients was 6.2 ± 1.8, respectively, and no significant differences were observed between all patients. However, the GERD prevalence in SSc and BD was increased compared to that in SLE, RA, PMR, PM/DM, MCTD, and AOSD. In no medication of proton pump inhibitors (PPIs), a significant increase in the risk of GERD symptoms was 2.5 times compared with that in the medication of PPIs in all patients by multivariable regression analysis. On the other hand, there were no increased risks of GERD symptoms with corticosteroids. CONCLUSION: In rheumatic diseases, GerdQ would be the useful tool of diagnosis GERD, regardless whether the patients complain or not about gastrointestinal (GI) symptoms.
26311941 Effect of the application of a metatarsal bar on pressure in the metatarsal bones of the f 2015 Jul [Purpose] The aim of this study was to determine the effect of application of a metatarsal bar on the pressure in the metatarsal bones of the foot using a foot analysis system (pressure on the forefoot, midfoot, and rearfoot). [Subjects and Methods] Forty female university students in their twenties were selected for this study, and an experiment was conducted with them as the subjects, before and after application of a metatarsal bar. The static foot regions were divided into the forefoot, midfoot, and rearfoot, and then the maximum, average, and low pressures exerted at each region were measured, along with the static foot pressure distribution ratio. 1) Static foot pressure: The tips of both feet were aligned to match the vertical and horizontal lines of the foot pressure measuring plate. The subjects were told to look toward the front and not to wear shoes. 2) Distribution ratio: The distribution ratio was measured in four regions (front, back, left, and right) using the same method as used for static foot pressure measurement. [Results] The results of this study showed that the maximum, average, and minimum static pressures in the forefoot were significantly decreased. The minimum static pressure in the midfoot was significantly increased, and the pressure in the other parts was significantly decreased. The maximum and average static pressures in the rearfoot were also significantly decreased. [Conclusion] As reduction of foot pressure with a metatarsal bar results in lowering of the arch and an increased contact surface, the foot pressure was dispersed. These results suggest that wearing shoes with a bar that can decrease the foot pressure is therapeutically helpful for patients with a diabetic foot lesion or rheumatoid arthritis.
26181315 In vitro anti-denaturation and anti-hyaluronidase activities of extracts and galactolipids 2016 The in vitro anti-denaturation and anti-hyaluronidase activities of Impatiens parviflora extracts and isolated galactolipids (MGDG-1, DGDG-1) were investigated. This is the first report on these compounds in I. parviflora. All extracts showed anti-hyaluronidase activity, but only methanolic extract from fresh leaves exhibited significant activity against heat-induced denaturation of BSA in a dose-dependent manner. At 500 μg/mL, the extract and the reference drug showed 79.05% and 99.81% inhibition of protein denaturation, respectively. These results indicate that fresh leaves of I. parviflora may be beneficial in inflammatory conditions, especially those associated with protein denaturation, such as rheumatoid arthritis. The study revealed that only MGDG-1 showed weak activity in anti-denaturation assay but both galactolipids were potent inhibitors of hyaluronidase. MGDG-1 completely inhibited the enzyme activity at the concentration of 127.9 μg/mL. These results indicate the potential of galactolipids in the treatment of diseases associated with the loss of hyaluronic acid.
26167058 Rheumatological disorder (RD) in Indian women above 40 years of age: A cross-sectional WHO 2015 Apr AIM AND OBJECTIVE: To evaluate rheumatological profile among Indian women above 40 years. MATERIALS AND METHODS: A cross-sectional survey was carried out for a period of one year using pre-validated questionnaire of COPCORD/WHO-ILAR. Those who complain of pain, tenderness, stiffness or swelling were subjected to clinical evaluation and diagnosis was established using the ACR's criteria for various RDs. RESULTS: Mean age of the patients was 55.06 ± 6.82 years, mean age at menopause was 47.30 ± 2.50 years and the mean time since menopause was 9.077 ± 5.43 years. Among the total population evaluated (N = 130), 37.69% women presented with RD and 37.06% women among the menopausal women had RD with the most common being low backache (16.92%), followed by osteoarthritis (12.30%), fibromyalgia (3.84%) and rheumatoid arthritis (2.30%). The most common site involved was knee (9.23%) followed by lumbar spine (8.46%), hip (3.07%) and other sites (16.92%) such as neck, upper back, hand joints, shoulder, thighs, etc. Study failed to show any statistical correlation with any socio-demographic or other parameters of interest with RD. HAQ-DI (Health Assessment Questionnaire Disability Index) was found to be highly significant (P < 0.000) in 13.84% women when correlated with RD. CONCLUSION: The prevalence of RD is substantially high among Indian women above 40 years demanding attention of health care providers.
26089933 In Vitro and In Vivo Antitumor Effects of n-Butanol Extracts of Pterocephalus hookeri on H 2015 Pterocephalus hookeri is a widely applied Tibetan medicinal prescription for treatment of diseases such as flu, rheumatoid arthritis, and enteritis in China. It has been reported that Pterocephalus hookeri has anti-inflammatory and analgesic actions. However, the antitumor activity of Pterocephalus hookeri remains unknown. In the present study, we demonstrate that n-butanol extracts of Pterocephalus hookeri (YSC-ZDC) has a strong antitumor activity against hepatoma carcinoma cell in vitro and in vivo. YSC-ZDC inhibited proliferation of all cancer cell lines and significantly inhibited Hep3B cells proliferation in a dose- and time-dependant manner. Transmission electron microscopy, hoechst 33258 staining, and flow cytometry analysis revealed that YSC-ZDC induced apoptosis in Hep3B cells. YSC-ZDC treatment dramatically inhibited PDK1 and Akt phosphorylation in Hep3B cells. Moreover, YSC-ZDC increased Bax expression and inhibited Bcl-2 expression. In addition, YSC-ZDC inhibited growth hepatoma xenografts in vivo with no effect on body weight and spleen index. Consistent with results in vitro, YSC-ZDC increased Bax expression and inhibited Bcl-2 expression in tumor tissue. Taken together, this study shows YSC-ZDC with an antitumor activity both in vitro and in vivo. Its mechanism underlying is related to blocking of the Akt pathway and regulation of Bcl-2 family proteins expression.
26059064 T-cell plasticity in inflammatory skin diseases--the good, the bad, and the chameleons. 2015 Jul According to the concept of T-cell plasticity, peripheral T cells - once differentiated into a specific T cell subset - may, in response to new environmental cues or signaling alterations, adopt the phenotype of a different helper cell subset with regard to cytokine production and regulatory functions. In a variety of T cell-mediated inflammatory disorders, such as rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and psoriasis, T-cell plasticity - in particular the conversion of regulatory T cells (Tregs) to IL-17-producing inflammatory cells - has recently been described as key pathomechanism contributing to the aggravation of inflammatory symptoms and disease chronification. Apart from psoriasis, the phenomenon of immune cell plasticity may also have a role in other inflammatory conditions of the skin showing a T cell component and/or an IL-17-mediated pathology, such as lichen planus, lupus erythematosus, blistering diseases, allergic disorders, and others. This review summarizes the basic molecular mechanisms regulating T-cell fate decisions and plasticity in inflamed skin and in other lymphoid organs. Moreover, it explores the effect of established targeted therapies as well as alternative concepts with a focus on how to prevent the unwanted conversion of "helpful" T cells and other beneficial immune cells to pathological inflammatory vermin.
25984660 Autoimmune myelofibrosis and systemic lupus erythematosus in a middle-aged male presenting 2015 May Autoimmune myelofibrosis is a distinct clinicopathologic entity that occasionally occurs with autoimmune disorders such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. Most cases of autoimmune myelofibrosis have been reported in female patients with a known history of SLE. We report a case of a middle-aged male patient with an unusual presentation of SLE and autoimmune myelofibrosis who presented only with severe anemia initially and was later diagnosed with SLE and autoimmune myelofibrosis. The patient's condition improved dramatically after treatment with corticosteroids.SLE and autoimmune myelofibrosis is a rare but potentially devastating condition. Anemia maybe the only presenting symptom in addition to bone marrow fibrosis and careful clinical and laboratory assessment is imperative. Corticosteroids maybe useful and spare patients from bone marrow transplantation.
25913139 Revisiting the role of mast cells in autoimmunity. 2015 Sep Beside their well known role in allergy, mast cells (MCs) are capable to sense multiple signals and have therefore the potential to be involved in many immune responses. MCs are actively present in the target tissues of some autoimmune disorders, suggesting a possible function in the manifestation of such diseases. This idea is strengthened by the evidence that KIT-dependent MC-deficient mice are protected from disease in many mouse models of autoimmunity, including multiple sclerosis, rheumatoid arthritis and autoimmune skin blistering diseases. Thus, the essential role of MCs in autoimmunity not only significantly extends the knowledge of MCs in the immune response but also provides novel therapeutic targets for the treatment of such diseases. However, recent studies using a new generation of KIT-independent MC-deficient strains could not confirm an essential participation of MCs in autoimmune diseases. Therefore, it is necessary to clarify the observed discrepancies and to elucidate the role of MCs in autoimmune diseases. Here, we review the impact of MCs on the development of autoimmune diseases with focus on the controversial effects of MC deficiency in different mouse models of autoimmune diseases. We also try to clarify contradictory findings in mouse studies to finally elucidate the role of MCs in autoimmunity.
25698589 Auranofin: repurposing an old drug for a golden new age. 2015 Mar Drug discovery, development and registration is an expensive and time-consuming process associated with a high failure rate [Pessetto et al. (Mol Cancer Ther 12:1299-1309, 2013), Woodcock and Woosley (Annu Rev Med 59:1-12, 2008)]. Drug 'repurposing' is the identification of new therapeutic purposes for already approved drugs and is more affordable and achievable than novel drug discovery [Pessetto et al. (Mol Cancer Ther 12:1299-1309, 2013)]. Auranofin is a drug that is approved for the treatment of rheumatoid arthritis but is being investigated for potential therapeutic application in a number of other diseases including cancer, neurodegenerative disorders, HIV/AIDS, parasitic infections and bacterial infections [Tejman-Yarden et al. (Antimicrob Agents Chemother 57:2029-2035, 2013)]. The main mechanism of action of auranofin is through the inhibition of reduction/oxidation (redox) enzymes that are essential for maintaining intracellular levels of reactive oxygen species. Inhibition of these enzymes leads to cellular oxidative stress and intrinsic apoptosis [Pessetto et al. (Mol Cancer Ther 12:1299-1309, 2013), Fan et al. (Cell Death Dis 5:e1191, 2014), Fiskus et al. (Cancer Res 74:2520-2532, 2014), Marzano et al. (Free Radic Biol Med 42:872-881, 2007)]. Drugs such as auranofin that have already been approved for human use [Tejman-Yarden et al. (Antimicrob Agents Chemother 57:2029-2035, 2013)] can be brought into clinical use for other diseases relatively quickly and for a fraction of the cost of new drugs.
25376167 Pharmacokinetics and penetration into synovial fluid of systemical and electroporation adm 2015 Jun Sinomenine is an anti-rheumatoid arthritis (RA) drug derived from the Sinomenium acutum. The major site of RA treatment is within the synovial compartment. However, the pharmacokinetic and penetration into synovial fluid (SF) of sinomenine have not been reported. In our study, the pharmacokinetics and penetration into SF of systemic and electroporation administered sinomenine were investigated by microdialysis incorporated with HPLC-MS/MS. Sinomenine went into plasma and SF more rapidly with higher peak concentration (Cmax ) by intramuscular injection compared with oral administration. The area under the concentration-time graph (AUC0-∞ ) of intramuscularly injected sinomenine was 1,403,294.75 ± 125,534.567 ng min/mL in plasma and 456,116.37 ± 62,648.36 ng min/mL in SF, which were equivalent with those for an oral dose. These results indicated that equal amounts of sinomenine could penetrate into SF by the two administration routes, and the permeation ratios were approximately 1:3. The AUC0-∞ and Cmax were lower with electroporation compared with systemic administration, but the CSF /CPlasma (concentration of sinomenine in SF vs that of plasma) at 90, 120, 150, 180, 240 and 480 min by electroporation was 3- to 10-fold higher relative to systemic administration. This illustrated that sinomenine can be targeted into joints by electroporation, and electroporation is a potential technique for sinomenine's transdermal delivery.
26369575 Influence of past breast feeding on pattern and severity of presentation of juvenile idiop 2016 Apr This analysis aimed to study the influence of breast feeding on the pattern and severity of juvenile idiopathic arthritis (JIA) at presentation. The association between ever versus never breast feeding and disease severity at onset was compared in 923 children with JIA recruited to the UK Childhood Arthritis Prospective Study at first presentation to rheumatology. Fifty six per cent of children were ever breast fed (median 3.7 months). Breastfed children reported a lower median age at onset, a lower Childhood Health Assessment Questionnaire (CHAQ), a measure of disease severity, lower parent general evaluation scores and lower pain at presentation. There was a trend towards a higher proportion of breastfed children with rheumatoid factor-negative polyarthritis, but lesser enthesitis-related and psoriatic arthritis. There was a statistically significant inverse association between breast feeding and high CHAQ, even after adjusting for differences in socioeconomic status (adjusted OR 0.61 (95% CI 0.39 to 0.95)). Further work to understand the reasons behind these associations is required.
25862150 Risk of incident chronic kidney disease and end-stage renal disease in patients with psori 2015 Jun BACKGROUND: Psoriasis is a chronic inflammatory dermatosis that has been associated with various cardiovascular and metabolic comorbidities, including myocardial infarction, stroke, and diabetes mellitus. Recently, there are studies reporting the association of psoriasis with renal diseases. OBJECTIVE: To evaluate the risk of incident chronic kidney disease (CKD) and end-stage renal disease (ESRD) in people with psoriasis. METHODS: We used the Taiwan's National Health Insurance Research Database to conduct a nationwide population-based cohort study to assess the risk of incident CKD and ESRD in people with psoriasis and to further evaluate the respective risk estimates in those with mild and severe psoriasis based on treatment patterns. RESULTS: A total of 4633 psoriatic patients and 922,534 nonpsoriatic controls were included. Severe psoriasis, but not mild psoriasis, was an independent risk factor of incident CKD and ESRD (adjusted hazard ratio being 1.90 (95% confidence interval 1.33-2.70) and 2.97 (95% confidence interval 1.72-5.11), respectively) after adjustment for potential confounders including age, gender, comorbidities, and used of nonsteroidal anti-inflammatory drugs (NSAIDs). Severe psoriasis remained an independent risk factor of incident CKD and ESRD after various sensitivity analyses after adjusting for the presence of osteoarthritis and/or rheumatoid arthritis, use of methotrexate and/or cyclosporine, and chronic use of NSAIDs for at least 2 months. Psoriatic arthritis was an effect modifier for CKD and ESRD. CONCLUSIONS: The associations of severe psoriasis with CKD and ESRD should be recognized. Assessment of renal function and avoidance of long-term use of nephrotoxic drugs shall be implemented in the integrative care for patients with severe psoriasis.
27159835 American College of Rheumatology White Paper on Performance Outcome Measures in Rheumatolo 2016 Oct OBJECTIVE: To highlight the opportunities and challenges of developing and implementing performance outcome measures in rheumatology for accountability purposes. METHODS: We constructed a hypothetical performance outcome measure to demonstrate the benefits and challenges of designing quality measures that assess patient outcomes. We defined the data source, measure cohort, reporting period, period at risk, measure outcome, outcome attribution, risk adjustment, reliability and validity, and reporting approach. We discussed outcome measure challenges specific to rheumatology and to fields where patients have predominantly chronic, complex, ambulatory care-sensitive conditions. RESULTS: Our hypothetical outcome measure was a measure of rheumatoid arthritis disease activity intended for evaluating Accountable Care Organization performance. We summarized the components, benefits, challenges, and tradeoffs between feasibility and usability. We highlighted how different measure applications, such as for rapid cycle quality improvement efforts versus pay for performance programs, require different approaches to measure development and testing. We provided a summary table of key take-home points for clinicians and policymakers. CONCLUSION: Performance outcome measures are coming to rheumatology, and the most effective and meaningful measures can only be created through the close collaboration of patients, providers, measure developers, and policymakers. This study provides an overview of key issues and is intended to stimulate a productive dialogue between patients, practitioners, insurers, and government agencies regarding optimal performance outcome measure development.
26088004 Risk of liver injury among methotrexate users: A meta-analysis of randomised controlled tr 2015 Oct OBJECTIVE: Methotrexate is an effective treatment for a variety of inflammatory diseases. Robust evidence on the risk of serious liver injury is lacking. The aim of this study was to evaluate the relative risk and severity of liver disease among patients treated with methotrexate. METHODS: We searched PubMed and the Cochrane Central Register of Controlled Trials from 1 January 1990 to 24 April 2014 for double-blind randomised controlled trials of methotrexate versus comparator agents in adults with rheumatoid arthritis, psoriasis, psoriatic arthritis or inflammatory bowel disease. Studies with less than 100 subjects or of less than 24 weeks' duration were excluded. Two investigators independently searched both the databases. All authors reviewed the selected studies. We compared relative risk (RR) differences using the Mantel-Haenszel random effects method to assess total liver adverse events, minor liver enzyme abnormalities (≤ 3 ULN), major liver enzyme abnormalities (>3 ULN or treatment withdrawal) and a composite outcome of liver failure, fibrosis, cirrhosis or death. RESULTS: A total of 32 studies with 13,177 participants met our inclusion criteria. Methotrexate was associated with an increased risk of total adverse liver events, RR = 2.19 (95% CI: 1.73-2.77, I(2) = 68%), as well as minor and major liver enzyme abnormalities, RR = 2.16 (95% CI: 1.67-2.79, I(2) = 68%) and RR = 2.63 (95% CI: 1.90-3.64, I(2) = 10%), respectively. Patients treated with methotrexate were not at increased risk of liver failure, cirrhosis or death, RR = 0.12 (95% CI: 0.01-1.09, I(2) = 0%). CONCLUSION: Our study found an increased risk of elevated transaminases but not liver failure, cirrhosis or death with methotrexate compared to other agents. We were unable to assess long-term liver toxicity due to the short duration of included clinical trials.