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ID PMID Title PublicationDate abstract
22374935 Portability of an algorithm to identify rheumatoid arthritis in electronic health records. 2012 Jun OBJECTIVES: Electronic health records (EHR) can allow for the generation of large cohorts of individuals with given diseases for clinical and genomic research. A rate-limiting step is the development of electronic phenotype selection algorithms to find such cohorts. This study evaluated the portability of a published phenotype algorithm to identify rheumatoid arthritis (RA) patients from EHR records at three institutions with different EHR systems. MATERIALS AND METHODS: Physicians reviewed charts from three institutions to identify patients with RA. Each institution compiled attributes from various sources in the EHR, including codified data and clinical narratives, which were searched using one of two natural language processing (NLP) systems. The performance of the published model was compared with locally retrained models. RESULTS: Applying the previously published model from Partners Healthcare to datasets from Northwestern and Vanderbilt Universities, the area under the receiver operating characteristic curve was found to be 92% for Northwestern and 95% for Vanderbilt, compared with 97% at Partners. Retraining the model improved the average sensitivity at a specificity of 97% to 72% from the original 65%. Both the original logistic regression models and locally retrained models were superior to simple billing code count thresholds. DISCUSSION: These results show that a previously published algorithm for RA is portable to two external hospitals using different EHR systems, different NLP systems, and different target NLP vocabularies. Retraining the algorithm primarily increased the sensitivity at each site. CONCLUSION: Electronic phenotype algorithms allow rapid identification of case populations in multiple sites with little retraining.
21181220 Th-17 associated cytokines in patients with reactive arthritis/undifferentiated spondyloar 2011 Jun We and others have previously shown that IL-17 is elevated in the synovial fluid of patients with reactive arthritis (ReA)/undifferentiated spondyloarthropathy (uSpA) having acute synovitis. Major source for IL-17 is Th17 cells, which differentiate from Th0 cells under the influence of TGF-β and IL-6, IL1-β and are maintained by IL-21 and 23. There is a paucity of data on these cytokines in ReA/uSpA. Thus, we measured the levels of Th-17 differentiating and maintaining cytokines in synovial fluid of patients with ReA and uSpA. Fifty patients with ReA/uSpA (ReA 24, uSpA 26), 19 patients with rheumatoid arthritis (RA) and 11 patients with osteoarthritis (OA) were included in the study. Synovial fluid (SF) were collected from knee joint and stored at -80°C until analysis. Cytokines were assayed using ELISA in SF specimens. The median IL-17A levels were significantly elevated in ReA (48.3 pg/ml) and uSpA (32.5 pg/ml) as compared to non-inflammatory OA controls (<7.8 pg/ml; p < 0.0001), while comparable to RA (57.9 pg/ml). Further, IL-6 median values were higher in ReA (25.2 ng/ml) and uSpA (13.6 ng/ml) as compared to OA (0.76 ng/ml; p < 0.0001), and comparable to RA (15.8 ng/ml). The median levels of IL-1β, IL-21 levels were elevated in ReA, uSpA and RA as compared to OA but were not statistically significant. TGF-β levels in ReA and uSpA were similar to OA but lower than in RA (4340 pg/ml; p < 0.05). IL-23 was not detectable in any synovial fluid sample. However, levels of these cytokines did not correlate with disease activity parameters. Significant positive correlation was observed between IL-17 and IL-1β (r = 0.38, p < 0.005), IL-17 and IL-6 (r = 0.659, p < 0.0001), and IL-1β and IL-6 (r = 0.391, p < 0.0001) in ReA and uSpA group. Inflammatory synovitis in ReA/uSpA is mediated by pro-inflammatory cytokines like IL-17, IL-6, IL-1β, and IL-21. However, IL-23 was not detectable in SF. Good correlation between IL-17, IL-6, and IL 1β suggest that either they are co-regulated or they regulate each other.
22610275 The multifaceted balance of TNF-α and type I/II interferon responses in SLE and RA: how m 2012 Nov Many cytokines are involved in the pathogenesis of autoimmune diseases and are recognized as relevant therapeutic targets to attenuate inflammation, such as tumor necrosis factor (TNF)-α in rheumatoid arthritis (RA) and interferon (IFN)-α/γ in systemic lupus erythematosus (SLE). To relate the transcriptional imprinting of cytokines in a cell type- and disease-specific manner, we generated gene expression profiles from peripheral monocytes of SLE and RA patients and compared them to in vitro-generated signatures induced by TNF-α, IFN-α2a, and IFN-γ. Monocytes from SLE and RA patients revealed disease-specific gene expression profiles. In vitro-generated signatures induced by IFN-α2a and IFN-γ showed similar profiles that only partially overlapped with those induced by TNF-α. Comparisons between disease-specific and in vitro-generated signatures identified cytokine-regulated genes in SLE and RA with qualitative and quantitative differences. The IFN responses in SLE and RA were found to be regulated in a STAT1-dependent and STAT1-independent manner, respectively. Similarly, genes recognized as TNF-α regulated were clearly distinguishable between RA and SLE patients. While the activity of SLE monocytes was mainly driven by IFN, the activity from RA monocytes showed a dominance of TNF-α that was characterized by STAT1 down-regulation. The responses to specific cytokines were revealed to be disease-dependent and reflected the interplay of cytokines within various inflammatory milieus. This study has demonstrated that monocytes from RA and SLE patients exhibit disease-specific gene expression profiles, which can be molecularly dissected when compared with in vitro-generated cytokine signatures. The results suggest that an assessment of cytokine-response status in monocytes may be helpful for improvement of diagnosis and selection of the best cytokine target for therapeutic intervention.
23395494 [Persistent aphthous mouth ulcers associated with tocilizumab: two cases]. 2013 Feb BACKGROUND: Tocilizumab, a humanized monoclonal antibody that blocks interleukin-6 receptor, is approved for use in rheumatological diseases. The most frequent adverse events reported are infections. We describe for the first time the occurrence of recurrent aphthous mouth ulcers in two patients on TCZ. PATIENTS AND METHODS: Two patients were treated with TCZ for rheumatological disease. A few weeks after administration of TCZ, they presented with multiple painful mouth ulcers that would not heal until TCZ had been withdrawn. In both cases, the oral ulcers resolved 6 to 7weeks after withdrawal of TCZ and readministration of the drug led to recurrence of oral ulcers within 10days in both patients. DISCUSSION: We describe for the first time the occurrence of aphthous mouth ulcers induced by TCZ. The causative role of TCZ was established by positive rechallenge. These cases were similar to a recently reported case of multiple intestinal aphthous ulcers occurring during TCZ treatment. Such mucosal side effects may be explained by similar inflammatory mechanisms but appear paradoxical because TCZ inhibits a pro-inflammatory cytokine, interleukin 6. TCZ treatment can be maintained if necessary, in combination with colchicine, as reported for one of our patients.
23211260 Prescription of antiviral therapy after herpes zoster in general practice: who receives th 2012 Dec BACKGROUND: Antivirals can accelerate rash healing during an acute zoster episode and can limit the severity and duration of pain. Their use within 7 days of rash onset is recommended among specific patient groups. AIM: To describe antiviral prescription patterns and patient characteristics associated with antiviral receipt after zoster diagnosis. DESIGN AND SETTING: Descriptive study and risk factor analysis using electronic healthcare records from UK general practice. METHOD: Incident adult zoster cases occurring between 2000 and 2011 were identified in the General Practice Research Database. Therapy records were searched for antiviral prescriptions of aciclovir, famciclovir, or valaciclovir within 7 days of zoster diagnosis. The proportion of incident zoster cases receiving antivirals was calculated and multivariable logistic regression used to assess associations between patient characteristics and antiviral use. RESULTS: Of 142 216 incident zoster cases 58.1% received an antiviral prescription. The majority (69.0%) were aciclovir. The proportion receiving antiviral prescriptions increased with age up to 65 years, then declined to 56.8% among patients aged ≥85 years. Being female and of higher socioeconomic status were associated with higher antiviral receipt. Antivirals were more commonly prescribed to immunosuppressed patients with herpes zoster (odds ratio 1.27; 95% CI = 1.22 to 1.33), however they were not given routinely to this patient group. CONCLUSION: Antiviral therapies for zoster are under-prescribed in UK general practice even among groups, such as immunosuppressed and older individuals, for whom guidelines recommend treatment. Patients may present too late to receive treatment or physicians may decide that antivirals are not essential treatment. Consideration could be given to reviewing the guidelines.
21414748 Cementless total hip arthroplasty with a metal-on-metal bearing in patients younger than 5 2011 Dec Total hip arthroplasty (THA) longevity is the primary concern in young patients. Metal-on-metal articulations were reintroduced to reduce polyethylene particle-induced osteolysis and improve survivorship; to date, based on issued reports, this strategy appears to have been successful. In this study, the authors investigated metal-on-metal articulation survivorship and osteolysis incidence in young patients (19-50 years old at index operations) and retrospectively reviewed cementless metal-on-metal THAs in 70 patients (78 hips) with a mean follow-up of 12.4 years. Metasul articulation was used with the Wagner acetabular component in all. Survivorship with revision for any cause was 98.7% (95% confidence interval, 98%-100%), and survivorship due to the development of osteolysis for any lesion was 97.5% (95% confidence interval, 95%-99%). Mean Harris hip score improved from 51 to 95 points at final follow-up. The findings of this study indicate that outcomes of cementless THA with a metal-on-metal bearing in young patients are satisfactory. However, longer-term studies in larger cohorts are required to determine whether metal-on-metal articulations are really a favorable option in young patients.
21210261 Heterotopic ossification after total hip arthroplasty: our experience. 2011 Apr Heterotopic ossification is a condition characterized by the presence of mature lamellar bone and often bone marrow in soft tissues surrounding a major joint. It represents a common complication after total hip arthroplasty (THA). The etiology and predisposing factors are not completely known, but some authors reported that the implant of a non-cemented prosthesis seems to be associated with a greater incidence of HO. Two hundred and two non-cemented total hip arthroplasties were performed between October 1997 and February 2002. The mean age was 70.2 years. The average follow-up for 181 hips included in the study was 96 months (range, 72-120 months). A standard lateral approach (Hardinge) was performed for the implant of a non-cemented femoral component and a non-cemented acetabular component. Radiographs were done before and after surgery, at 1, 4 and 12 months postop, then every year. The incidence of HO was assessed in the antero-posterior view at each interval and graded according to Brooker classification. Out of 181 implants, HO was observed in 52 hips (28,7%). Heterotopic bone was graded as class I in 32 (17.7%) hips, class II in 14 (7.73%) hips, class III in 6 (3,3%) hips and class IV in none (0%). The mean preoperative Harris hip score was 48; at the last follow-up, the mean postoperative score was preoperatively to a mean of 89 points (range, 76-97 points) in HO Hip and of 91 points (range, 78-100 points) in the other Hip. In our experience, non-cemented THA led to a higher incidence of class I and II HO according to Brooker Classification, the incidence of HO is comparable to the rates reported in recent studies about the HO finding after a non-cemented THA, the importance of clinical symptoms in the presence of HO is very low.
21541707 Previous fracture surgery is a major risk factor of infection after total knee arthroplast 2011 Dec PURPOSE: Total knee arthroplasty (TKA) has been proven to be the most effective treatment for patients with severe joint disease. Although infection is not a frequent complication, it is certainly one of the most dreaded. The purpose of this study was to identify factors associated with infection after TKA. METHODS: Between 1995 and 2006, 2,022 primary TKAs in 1,146 patients were evaluated. Flexible Nichidai Knee (FNK) was used as a prothesis in all subjects. Twenty-four patient-specific data items were collected via chart review for each patient. Revision arthroplasty procedures and infected knees were excluded. The medical records were reviewed to extract the following information: age, gender, body mass index (BMI), preoperative C-reactive protein (CRP), preoperative erythrocyte sedimentation rate (ESR), preoperative total protein (TP), duration of surgery, operative blood loss, total blood loss, duration of surgical drain, duration of antibiotic prophylaxis, primary diagnoses, smoking, diabetes mellitus, steroid or disease modifying anti-rheumatic drugs (DMARDs) therapy, previous operation around the knee joint, previous arthroscopic surgery, previous non-arthroscopic surgery, previous high tibial osteotomy (HTO) or open reduction internal fixation (ORIF), remnants of previous internal fixation material, bone graft, patella replacement, and bone cement. RESULTS: The median age of the patients at the time of primary TKA was 72 (range, 26-91) years. The median follow-up period after primary TKA was 42 (range, 6-145) months. During the study period, 17 infected knee arthroplasties in 17 patients were identified. Previous history of ORIF, male gender, remnants of previous internal fixation material, and BMI showed significant correlation with postoperative infection. CONCLUSION: This study identified previous history of fracture and remnants of internal fixation as major risk factors of infection after TKA. For clinical relevance, surgeons should be aware of potential infection when performing TKA in patients with these risk factors and patients should be informed of the potential risks.
22571392 Lambert-Eaton myasthenic syndrome following H1N1-influenza vaccination: a case report. 2012 Nov BACKGROUND: The outbreak of influenza A (H1N1) pandemic during the year 2009 led to the development of several vaccinations against H1N1 virus. In Finland, 2.6 million citizens were vaccinated during pandemic 2009 - 2010 with adjuvanted influenza vaccine, Pandemrix(®) . CLINICAL PRESENTATION: In this case report, we describe a patient with non-paraneoplastic Lambert-Eaton myasthenic syndrome following Pandemrix(®) vaccination. CONCLUSION: Development of various autoimmune diseases in genetically predisposed subjects following exposure to certain environmental factors, including vaccinations, is a well-known entity. Clinicians should be aware of the possibility of the induction of autoimmune diseases following vaccinations and actively ask the relevant clinical history in a newly diagnosed patient with an autoimmune disorder.
21676237 Predictors for pathologically confirmed aortitis after resection of the ascending aorta: a 2011 Jun 15 INTRODUCTION: Assessing the prevalence of, and predictors for, pathologically-confirmed inflammation of the aorta in Denmark, using a nationwide population-based study design. METHODS: We identified all adults with first-time surgery on the ascending aorta between January 1, 1997 and March 1, 2009 in Denmark. Presence of aortic inflammation was ascertained through linkage to a nationwide pathology registry. We used logistic regression to compute prevalence odds ratios (ORs) for sex, age at surgery, cardiovascular risk factors, cancer, connective tissue disease, and infectious diseases associated with the presence of aortitis. RESULTS: A total of 1,210 adults underwent resection of the ascending aorta, of who 610 (50.4%) had tissue submitted for pathological examination. Aortitis was found in 37 (6.1%) patients whose tissue was examined. Ten of the 37 patients were diagnosed with conditions known to be associated with aortitis or aortic aneurysm: five patients with temporal arteritis, one with Crohn's disease, one with rheumatoid arthritis, one with systemic lupus erythematosus, one with infectious aortitis, and one with Marfan's disease. Twenty-seven patients had idiopathic aortitis. Predictors of aortitis included history of connective tissue disease (adjusted OR 4.7, 95% confidence interval (CI) 1.6, 13.6), diabetes (OR 5.2, 95% CI 0.9, 29.7), advanced age (> 67 years OR 2.5, 95% CI 0.8, 7.6), and aortic valve pathology (OR 2.3, 95% CI 1.1, 4.9). CONCLUSIONS: Aortitis was present in 6.1% of adults in Denmark who had pathological examination after resection of the ascending aorta. Predictors of inflammation included connective tissue disease, diabetes, advanced age, and aortic valve pathology.
23264551 Monoclonal anti-citrullinated protein antibodies selected on citrullinated fibrinogen have 2013 Apr OBJECTIVE: ACPAs are thought to play a pathogenic role in RA. Because of their polyclonal nature it is difficult to study characteristics of ACPAs such as cross-reactivity or affinity. This study aimed to analyse the ACPA response at clonal level. METHODS: Citrullinated fibrinogen-specific B cells were isolated from blood derived from an RA patient by fluorescent automated cell sorting (FACS). Antigen specificity was verified by ELISA of culture supernatant. RNA of antigen-specific B cells was isolated and VH and VL chains were cloned and subsequently expressed as IgG1 antibodies. RESULTS: Two human recombinant antibodies were obtained that bind to citrullinated fibrinogen peptide (cFib). Both monoclonal antibodies originate from different naive B cells, undergo extensive somatic hypermutation and bind to cFib (but not to Fib) with moderate avidity. Furthermore, they show distinct cross-reactivity patterns towards other citrullinated peptides, suggesting that both antibodies have different primary targets. CONCLUSION: Together these data suggest that ACPAs are formed by antigen-driven maturation, and that multiple citrullinated antigens are involved in activating the B-cell response.
22047978 Ultrasound screening of periarticular soft tissue abnormality around metal-on-metal bearin 2012 Jun Although metal hypersensitivity or pseudotumors are concerns for metal-on-metal (MoM) bearings, detailed pathologies of patterns, severity, and incidence of periprosthetic soft tissue lesions are incompletely understood. We examined the potential of ultrasound for screening of periarticular soft tissue lesions around MoM bearings. Ultrasound examinations were conducted in 88 hips (79 patients) with MoM hip resurfacings or MoM total hip arthroplasties with a large femoral head. Four qualitative ultrasound patterns were shown, including normal pattern in 69 hips, joint-expansion pattern in 11 hips, cystic pattern in 5 hips, and mass pattern in 3 hips. Hips with the latter 3 abnormal patterns showed significantly higher frequency of clinical symptoms, without significant differences of sex, duration of implantation, head sizes, and cup abduction/anteversion angles, compared with hips with normal pattern. Ultrasound examination provides sensitive screening of soft tissue reactions around MoM bearings and may be useful in monitoring progression and defining treatment for periarticular soft tissue abnormalities.
21196185 Functional role of Akt in macrophage-mediated innate immunity. 2011 Jan 1 Akt (protein kinase B) is a serine/threonine protein kinase that regulates cell metabolism, survival and proliferation. Recent studies of the role of Akt in phagocytosis, intracellular bacterial infections, LPS tolerance, production of inflammatory cytokines and mediators, and migration during macrophage-mediated innate immunity strongly suggest a pivotal role for this enzyme in the functional activation of macrophages. Considering that a variety of inflammatory diseases, such as rheumatoid arthritis, atherosclerosis, diabetes, obesity, cancer and osteoporosis, are regulated by macrophage-mediated innate immunity, efforts should be more carefully focused on understanding the function of Akt in macrophage-mediated innate immunity. Although few studies have addressed this question, this review discusses recent findings that support an important role for Akt in macrophage-mediated innate immunity and underlines the need for trials to develop pharmaceutically useful drugs that target Akt for treatment of macrophage-mediated inflammatory diseases. The findings we review here suggest that a novel and safe Akt inhibitor with strong immunosuppressive and anti-inflammatory properties will be applied to various chronic inflammatory diseases in the near future.
21362765 Association of anti-modified citrullinated vimentin with subclinical atherosclerosis in ea 2011 May OBJECTIVE: To investigate anti-modified citrullinated vimentin (anti-MCV) in early rheumatoid arthritis (RA), including correlation with disease activity and cardiovascular risk factors, compared with anti-cyclic citrullinated peptides (anti-CCP3). METHODS: Anti-MCV and anti-CCP3 concentrations were measured in 100 patients with early RA and 100 healthy controls at baseline to determine sensitivity and specificity. Patients received methotrexate (MTX) 0.2 mg/kg/week plus prednisone 10 mg/day. Anti-MCV, anti-CCP3, rheumatoid factor (RF), Disease Activity Score for 28 joints (DAS-28), lipid profile, erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein assay (hsCRP), homeostasis model assessment for insulin resistance (HOMA-IR) index, tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and carotid intima-media thickness (cIMT) were measured before and after 12 months of treatment. RESULTS: The sensitivity and specificity for anti-MCV antibody were 75% and 90%, respectively, and for anti-CCP3 antibody 71% and 96%. Serum anti-MCV and serum anti-CCP3 levels at baseline were positively correlated with hsCRP, IL-6, HOMA-IR index, serum RF levels (p < 0.001), and cIMT (p < 0.05). Serum anti-MCV was positively correlated with serum anti-CCP3 levels. There were significant positive correlations between the percentage of changes of anti-MCV levels versus changes in DAS-28, ESR, hsCRP, atherogenic ratios (TC/HDL-C and LDL-C/HDL-C), apolipoprotein A-I, IL-6, TNF-α, HOMA-IR index, and cIMT. These correlations were not found between changes in anti-CCP3 levels compared to clinical, laboratory, and radiological variables. CONCLUSION: Anti-MCV was as sensitive as anti-CCP3 in diagnosing early RA. Anti-MCV testing appears to be useful for monitoring associated subclinical atherosclerosis in early RA.
23077958 [Contributions to the methodology of study in the functional assessment of temporomandibul 2012 Apr AIM: Dysfunctional syndrome of the temporomandibular joint through the complexity and variability of the symptoms may result in significant structural and functional changes leading from discomfort to disability and a negative impact on quality of life. MATERIALS AND METHODS: A prospective study was conducted between October 2009-December 2010, in 52 subjects diagnosed with rheumatoid arthritis and complaining of symptoms in the temporomandibular joint. The functional examination of the joint and muscle has included the assessment of the active range of motion, passive range of motion, resistance range of motions of the temporomandibular joint, dermatomes and the pain in the region of masseter, temporalis, median and lateral pterigoids, digastric, sternocleidomastoid and longus colli muscles. The ultrasound examination has included clinical aspects of alignment, shape, dynamics of the mandibular condyle, of the temporal fossa, aspects regarding the temporal and masseter muscles at rest and at contraction phases. RESULTS: The clinical examination highlighted the presence of pain at temporomandibular jointlevel for all tested pacients. The majority complained the pain from moderate to severe level. For the majorityof cases (59,60%) the pain stars spontaneously, during the day time (80,80%) and the night time (50,60%). Over 50% from the research cases complained cracks at the temporomandibular joint level released by a movement. At the oral and dental examination of the research group 55,8% from the tested pacients presented dental cavities toothless partially or totally duet o additionally overworking temporomandibular joint. The limitation of the range of motion is not the most important detected dysfunction, affecting approximately 30% of the cases that have been studied. Pain and spasm in a very large proportion are present in the masseter and temporal muscles regions. Atrophy is present in a lesser extent. The dysfunctional index shows an involvement of the temporomandibular joint, for over 45% of patients tested. The ultrasound examination revealed degenerative inflammatory lesions at a rate of 38.46%, inflammatory lesions at a rate of 28.85% and mixed lesions at a rate of 9.62%. CONCLUSIONS: The research regarding the clinical paraclinical and functional aspects of temporomandibular joint, permited to highlight the fact that rheumatic inflamatory and degenerative, pathology, characterises it self through a high index of morbidity and disability that lowers the life quality. Establishing a treatment plan involves customizing all clinical, functional and laboratory data.
21736751 Efficacy and safety of the human anti-IL-1β monoclonal antibody canakinumab in rheumatoid 2011 Jul 7 BACKGROUND: Canakinumab is a fully human anti-interleukin IL-1beta monoclonal antibody, being investigated for the treatment of rheumatoid arthritis (RA). This multicenter, phase II, randomized, double-blind, placebo-controlled, parallel-group, dose-finding study investigated the efficacy and safety of canakinumab in patients with active RA despite ongoing therapy at stable doses of methotrexate. METHODS: Patients were randomized to receive one of four regimens, in addition to methotrexate, for 12 weeks: canakinumab 150 mg subcutaneously (SC) every 4 weeks (q4wk), canakinumab 300 mg SC (2 injections of 150 mg SC) every 2 weeks, a 600 mg intravenous loading dose of canakinumab followed by 300 mg SC every 2 weeks', or placebo SC every 2 weeks. RESULTS: Among 274 patients with evaluable efficacy data, the percentage of responders according to American College of Rheumatology 50 criteria (the primary endpoint, based on a 28-joint count) was significantly higher with canakinumab 150 mg SC q4wk than with placebo (26.5% vs. 11.4%, respectively; p = 0.028). Compared to placebo, this dosage of canakinumab was also associated with significantly more favorable responses at week 12 with respect to secondary endpoints including the Disease Activity Score 28, scores on the Health Assessment Questionnaire and Functional Assessment of Chronic Illness Therapy-Fatigue, swollen 28-joint count, and patient's and physician's global assessments of disease activity. No safety concerns were raised with canakinumab therapy, particularly with regard to infections. Few injection-site reactions occurred. CONCLUSION: The addition of canakinumab 150 mg SC q4wk improves therapeutic responses among patients who have active RA despite stable treatment with methotrexate. TRIAL REGISTRATION: (ClinicalTrials.gov identifier: NCT00784628).
22332705 Tumor necrosis factor blocker dose escalation among biologic naïve rheumatoid arthritis p 2012 OBJECTIVE: This study uses real-world US managed-care claims data to estimate dose escalation rates over the first and second years of therapy among biologic naïve rheumatoid arthritis (RA) patients initiating tumor necrosis factor (TNF) blocker therapy with etanercept, adalimumab, or infliximab. METHODS: Non-elderly adult (age 18-65 years) RA patients initiating etanercept, adalimumab, or infliximab from July 1, 2005 to April 30, 2009, were identified using the MarketScan Commercial Database. National and regional dose-escalation patterns were evaluated 12 and 24 months after initiation. In the single-instance method, dose escalation was defined as having one average weekly dose 115%, 130%, or 150% greater than the initial average weekly dose. By the two-instances method, dose escalation was defined as having two consecutive claims with an average weekly dose 115% or 130% greater than the initial average weekly dose. RESULTS: A total of 2747 patients met the inclusion criteria (mean age 50 years [SD=10]; 74% female). More patients initiated etanercept (44%) than adalimumab (37%) or infliximab (20%). Using the single-instance method, dose escalation at 12 months ranges were 0.8-1.5% for etanercept, 10.8-12.5% for adalimumab, and 16.4-42.5% for infliximab; ranges at 24 months were 0.8-2.1% for etanercept, 14.3-17.5% for adalimumab, and 26.4-57.6% for infliximab. The two-instances method showed a similar relationship among the treatment cohorts at both 12 and 24 months, with lower dose-escalation rates for etanercept (0.8%, 0.8%) than adalimumab (8.7%, 13.3%) or infliximab (22.9%, 37.6%) at the 130% threshold (p<0.001). Dose-escalation rates for etanercept, adalimumab, and infliximab were consistent across US geographic regions. CONCLUSION: Patients initiating etanercept had lower rates of dose escalation than patients initiating adalimumab or infliximab in the first and second year following therapy initiation, as well as across US geographic regions. These results may not be generalizable to the entire US RA population.
21068104 Discontinuing treatment in patients with rheumatoid arthritis in sustained clinical remiss 2011 Feb OBJECTIVES: To determine the relapse rate after discontinuing treatment in patients with rheumatoid arthritis (RA) in sustained clinical remission, to identify predictors of a relapse and to evaluate treatment response after restarting treatment. METHODS: Five-year data from the BeSt study were used, in which 508 patients with recent-onset RA were randomised into four dynamic treatment strategies, aiming at a disease activity score (DAS) ≤ 2.4. When DAS was < 1.6 for ≥ 6 months, the last disease-modifying antirheumatic drug (DMARD) was tapered and discontinued. If DAS increased to ≥ 1.6, the last DMARD was immediately reintroduced. RESULTS: During a 5-year period, 115/508 patients (23%) achieved drug-free remission. Of these, 53 patients (46%) restarted treatment because the DAS was ≥ 1.6 after a median of 5 months, 59 patients (51%) remained in drug-free remission for a median duration of 23 months and 3 (3%) were lost to follow-up. In those who restarted treatment, mean (SD) DAS increased from 1.13 (0.73) at remission before tapering to 2.18 (0.65) at restart, reflecting an increase in all four components of DAS. Multivariable predictors for restarting treatment were anti-cyclic citrullinated peptide (anti-CCP), last DMARD sulfasalazine, low baseline Health Assessment Questionnaire score and high mean DAS until remission. Of the 53 patients who restarted treatment, 39 (74%) again achieved remission 3-6 months after the restart. The median (IQR) damage progression in those who restarted treatment during the year of DAS increase was 0 (0-1) Sharp-van der Heijde units. CONCLUSION: During 5 years DAS steered treatment, nearly 25% of patients with RA achieved drug-free remission; 46% restarted DMARD monotherapy because of a relapse, the majority of whom again achieved clinical remission within 3-6 months without showing radiological progression during the relapse.
20554264 [The mastoid osteoma, an incidental feature?]. 2011 Mar Osteoma in the mastoid is a rare benign osteogenic tumour that has been described in literature in only 137 cases. It usually appears in asymptomatic patients, although a few cases are described associated with clinical manifestations. We report three cases of mastoid osteoma: a pedunculated osteoma in the aditus ad antrum (associated with a cholesteatoma), a superficial osteoma of the mastoid surface and a sessile osteoma that progressed to the temporal lobe (associated with vertigo). A brief review of this rare entity is presented and a possible association between mastoid osteoma, cholesteatoma otitis and vertigo is posed.
22395477 Clinical and radiographic evaluation of total hip arthroplasties using porous tantalum mod 2013 Jan OBJECTIVES: Porous tantalum is a biomaterial newly applied for artificial joints. We present here 5-years follow-up report of a multicenter clinical trial of total hip arthroplasties (THA) with porous tantalum modular acetabular component (modular PTC). METHODS: Study participants received 82 hips in 79 cases, with 61.2 months follow-up on average. Age at operation was 60.9 years. Clinical results were evaluated using Merle d'Aubigne Postel score. Presence of implant loosening, periacetabular radiolucency, osteolysis, and gap filling were examined for radiographic results. RESULTS: Merle d'Aubigne Postel score improved from 10.0 to 16.4 points. All PTC were radiographically stable, with no evidence of progressive radiolucencies. Average polyethylene wear rate was 0.004 mm/year, with no periacetabular osteolysis. Fifteen hips (18.3%) showed a gap >1 mm; however, all showed bone filling within 12 months. PTC with oversized reaming was significantly less likely to have a gap. No implant failure was noted related to modularity. Resulting survival rate of modular PTC was 100% at 5 years. CONCLUSIONS: Modular PTC showed excellent results at 5-years of follow-up. Some hips showed periacetabular gaps, which were filled with bone within 1 year. Further follow-up was needed to determine long-term efficacy.