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ID PMID Title PublicationDate abstract
22931581 Ultrasound imaging for the rheumatologist XL. Sonographic assessment of the hip in rheumat 2012 Jul OBJECTIVES: The aim of the present study was to correlate clinical and laboratory data with those obtained by ultrasound (US) evaluation of the hip in a cohort of patients with rheumatoid arthritis (RA). METHODS: Fifty-two RA patients attending the Rheumatology Departments involved in the present study were enrolled. Demographic (age, gender), clinical (body mass index, disease duration, treatments, history or current hip pain, tenderness by internal or external hip rotation or palpation of the greater trochanteric region), laboratory (erythrosedimentation rate, C-reactive protein, rheumatoid factor and antibodies anti-citrullinated peptides) and clinimetric data (disease activity score 28 - DAS28, Health Assessment Questionnaire - HAQ, Lequesne index) were collected. All patients underwent an US examination of both hips according to international guidelines. RESULTS: A total of 100 hips were scanned in 52 patients with RA. Approximately half of the patients reported a history of hip pain, one fourth complained of current pain, and the physical examination (internal and/or external rotation and palpation of the greater trochanteric region) evocated pain up to 19% and 22% of the patients, respectively. US examination found signs of hip joint abnormalities in 42% of the patients; US changes indicative of hip joint inflammation and damage were detected respectively in 24% and 32% of the cases. No patient presented power Doppler signal in the hip joint. A significant correlation between US pathological findings at hip level was found with clinical data (current pain and evocated pain by internal or external hip rotation). Furthermore, US cartilage lesion correlated with age of the patient, and US bone erosions with the disease duration. No correlation was found between the sonographic assessment and laboratory data, DAS 28, and Lequesne index. CONCLUSIONS: US abnormalities at hip joint level obtained in the present study correlated with clinical findings, while no correlation was found with DAS28 or laboratory data. Further investigations are encouraged to clarify the US additional value at hip level in patients with RA.
22270468 Periarticular local anesthesia does not improve pain or mobility after THA. 2012 Jul BACKGROUND: Periarticular infiltration of local anesthetic, NSAIDs, and adrenaline have been reported to reduce postoperative pain, improve mobility, and reduce hospital stay for patients having THAs, but available studies have not determined whether local anesthetic infiltration alone achieves similar improvements. QUESTIONS: We therefore asked whether periarticular injection of a local anesthetic during THA reduced postoperative pain and opioid requirements and improved postoperative mobility. METHODS: We randomized 96 patients to either treatment (n = 50) or control groups (n = 46). Before wound closure, the treatment group received local infiltration of 160 mL of levobupivacaine with adrenaline. The control group received no local infiltration. We assessed postoperative morphine consumption and pain during the 24 hours after surgery. Mobilization was assessed 24 hours postoperatively with supine-to-sit and sit-to-stand transfers, timed 10-m walk test, and timed stair ascent and descent. Patients and assessing physiotherapists were blind to study status. RESULT: We observed no differences in postoperative morphine consumption, time to ascend and descend stairs, or ability to transfer between treatment and control groups. The treatment group reported more pain 7 to 12 hours postoperatively, but there were no differences in pain scores between groups at all other postoperative intervals. The treatment group showed increased postoperative walking speed greater than 6 m, but not greater than 10 m, compared with the control group. CONCLUSIONS: Periarticular infiltration of local anesthetic during THA did not reduce postoperative pain or length of hospital stay and did not improve early postoperative mobilization.
23972864 The effects of self-pain management on the intensity of pain and pain management methods i 2013 Sep The aims of this study were to investigate the effects of pain management education on the intensity of pain and frequency of utilization of pain management methods in two groups of patients with arthritis of different pathogenesis and clinical features, and to compare whether a significant difference existed between the two groups. The study was carried out between September 2007 and June 2008 on 30 female patients with gonarthrosis and 30 female patients with rheumatoid arthritis (RA) followed at the rheumatology outpatient clinic of a university hospital. Data on sociodemographic characteristics and those related with the illness were collected using a special survey. Each patient was given information about the features, causes, and treatment of the arthritis and how to cope with pain, emphasizing the importance of pain management methods. The intensity of pain and efficacy of pain management methods were assessed using the McGill Pain Questionnaire and the Pain Management Inventory at baseline and the second and sixth weeks after the education. The SPSS (v15.0) statistical package was used for statistical analysis. After education, significant improvements in pain intensity scores compared with baseline scores were observed in both groups (p < .05), and there was no significant difference between the RA and gonarthrosis groups. Among the various pain management methods, the education program led to significantly more utilization of massaging the painful area, exercising, and using complementary methods to control stress in both groups of patients, and there was no significant difference between the groups. In conclusion, the pain management education given in this study alleviated the intensity of pain and significantly increased the use of some pain management methods in both gonarthrosis and RA cases.
21553228 Associations between interleukin-10 polymorphisms and susceptibility to rheumatoid arthrit 2012 Jan The aim of this study was to determine whether the interleukin-10 (IL-10) polymorphisms confer susceptibility to rheumatoid arthritis (RA). A meta-analysis was conducted on the associations between the IL-10 -1082 G/A, -592 C/A, -892 C/T and IL-10.R polymorphisms and RA using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. A total of 16 studies (19 comparisons) involving 2647 RA patients and 3383 controls were considered in the meta-analysis. Meta-analysis of the IL-10 -1082 G/A polymorphism showed no association with RA in the study subjects, or in European or Asian subjects. However, meta-analysis of the -1082 G allele in 4 studies in Hardy-Weinberg equilibrium showed a significant association with RA (OR=1.217, 95% CI=1.027-1.442, P=0.0236). In contrast, meta-analysis of the C allele, the CC genotype, and of the CC versus the AA genotype of the IL-10 -592 C/A polymorphism showed significant associations with RA. The overall ORs of the associations between the C allele and RA were 0.684 and 0.758 (95% CI=0.494-0.946, P=0.022; 95% CI=0.475-1.210, P=0.045) in all study subjects and Asians. Meta-analysis of the CC+CT versus TT genotype and of the CC versus TT genotype of the IL-10 -892 C/T polymorphism revealed significant associations with RA. The overall OR of the association between the C allele carrier and RA was 0.552 (95% CI=0.375-0.812, P=0.003). No association was found between the IL10.R2 alleles and RA. This meta-analysis suggests that the IL-10 -592 C/A polymorphism confers susceptibility to RA in Asians and that the IL-10 -1082 G/A and -892 C/T polymorphisms are associated with RA susceptibility. These findings suggest the IL-10 genes confer susceptibility to RA.
21305507 Low frequency of primary lipid screening among medicare patients with rheumatoid arthritis 2011 May OBJECTIVE: Although studies have demonstrated suboptimal preventive care in RA patients, performance of primary lipid screening (i.e., testing before cardiovascular disease [CVD], CVD risk equivalents, or hyperlipidemia is evident) has not been systematically examined. The purpose of this study was to examine associations between primary lipid screening and visits to primary care providers (PCPs) and rheumatologists among a national sample of older RA patients. METHODS: This retrospective cohort study examined a 5% Medicare sample that included 3,298 RA patients without baseline CVD, diabetes mellitus, or hyperlipidemia, who were considered eligible for primary lipid screening during the years 2004-2006. The outcome was probability of lipid screening by the relative frequency of primary care and rheumatology visits, or seeing a PCP at least once each year. RESULTS: Primary lipid screening was performed in only 45% of RA patients. Overall, 65% of patients received both primary and rheumatology care, and 50% saw a rheumatologist as often as a PCP. Any primary care predicted more lipid screening than lone rheumatology care (26% [95% confidence interval (95% CI) 21-32]). As long as a PCP was involved, performance of lipid screening was similar regardless of the balance between primary and rheumatology visits (44-48% [95% CI 41-51]). Not seeing a PCP at least annually decreased screening by 22% (adjusted risk ratio 0.78 [95% CI 0.71-0.84]). CONCLUSION: Primary lipid screening was performed in fewer than half of eligible RA patients, highlighting a key target for CVD risk reduction efforts. Annual visits to a PCP improved lipid screening, although performance remained poor (51%). Half of RA patients saw their rheumatologist as often or more often than they saw a PCP, illustrating the need to study optimal partnerships between PCPs and rheumatologists for screening patients for CVD risks.
21459944 Challenges in diagnosing latent tuberculosis infection in patients treated with tumor necr 2011 Jul Reactivation of latent tuberculosis infection (LTBI) is well recognized as an adverse event associated with anti-tumor necrosis factor-α (anti-TNF-α) therapy. The strengths and weaknesses of current techniques for detecting LTBI in patients with chronic inflammatory diseases such as rheumatoid arthritis (RA) and psoriasis have not been fully examined. T cell hyporesponsiveness due to immunosuppression caused by illness or drugs, referred to as anergy, may produce false-negative tuberculin skin test (TST) and interferon-γ release assay (IGRA) results. The literature suggests that anergy may influence screening performance of TST and IGRA tests in candidates for anti-TNF-α therapy. Conversely, the potential for false-positive TST and IGRA results must be considered, as treatment for LTBI may be associated with significant morbidity. This review examines the reliability issues related to LTBI diagnostic testing and provides practical direction to help prevent LTBI reactivation and facilitate successful anti-TNF-α treatment.
21543514 Association of the PTPN22 R620W polymorphism with increased risk for SLE in the geneticall 2011 Apr Autoimmune diseases affect approximately 5% of the population, but much work remains to define the genetic risk factors and pathogenic mechanisms underlying these conditions. There is accumulating evidence that common genetic factors might predispose to multiple autoimmune disorders. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are complex autoimmune disorders with multiple susceptibility genes. The functional R620W (C1858T) polymorphism of the protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene, a member of the PTPs that negatively regulate T-cell activation, has been recently associated with susceptibility to various autoimmune diseases. The aim of this study was to assess whether the C1858T polymorphism of PTPN22 also confers increased risk for SLE and RA in the genetically homogeneous population of Crete. It was found that the minor T allele of the PTPN22 C1858T SNP was more common in SLE patients than in control individuals (odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.11 to 3.9, p = 0.017). No significant difference was observed in the frequency of this allele when RA patients were compared with controls (OR = 1.14, 95% CI = 0.65 to 1.9, p = 0.64). Although the PTPN22 1858 T allele is found at decreased frequency in Southern Europe, including Crete, an association was found between this allele and SLE in the population studied.
22488178 Prolyl hydroxylase domain enzyme 2 is the major player in regulating hypoxic responses in 2012 Sep OBJECTIVE: Rheumatoid arthritis (RA) is characterized by hypoxia and the expression of hypoxia-inducible transcription factors (HIFs), which coordinate cellular responses to hypoxia. The objective of this study was to analyze the expression and regulation of prolyl hydroxylase domain (PHD) enzymes and factor-inhibiting HIF-1α (FIH-1), which regulate cellular HIF levels, and to study the roles of these enzymes in RA fibroblast-like synoviocytes (RA FLS). METHODS: The expression of PHD and FIH and downstream target genes was assessed by quantitative polymerase chain reaction and Western blotting. A small interfering RNA (siRNA) approach and an in vitro endothelial cell angiogenesis assay were used to analyze the roles of HIF hydroxylases. RESULTS: In human RA FLS, knockdown of PHD-2, but not knockdown of PHD-1 or FIH-1, dramatically augmented HIF-1α expression, modestly increased HIF-2α protein expression under normoxic conditions, and up-regulated HIF-dependent gene expression. In contrast, silencing of PHD-3 up-regulated HIF-2α but reduced HIF-1α, thereby decreasing the expression of HIF-regulated genes. A similar effect of PHD-2 knockdown was observed in osteoarthritis FLS (OA FLS) but not in nondiseased primary human dermal fibroblasts. These findings correlated with the induction of in vitro angiogenesis by supernatants from RA FLS and OA FLS transfected with siPHD-2 but not by supernatants from nondiseased fibroblasts or from siPHD-3-transfected cells. CONCLUSION: Our data suggest that PHD-2 is the major hydroxylase regulating HIF levels and the expression of angiogenic genes in arthritic cells. PHD-2 appears to regulate responses relevant to arthritis via HIF-α, highlighting the major importance of this enzyme in hypoxia- and angiogenesis-dependent inflammatory diseases such as RA.
21384334 Impact of synthetic and biologic disease-modifying antirheumatic drugs on antibody respons 2011 Jun OBJECTIVE: To identify the determinants of antibody responses to adjuvanted split influenza A (H1N1) vaccines in patients with inflammatory rheumatic diseases. METHODS: One hundred seventy-three patients (82 with rheumatoid arthritis, 45 with spondylarthritis, and 46 with other inflammatory rheumatic diseases) and 138 control subjects were enrolled in this prospective single-center study. Controls received 1 dose of adjuvanted influenza A/09/H1N1 vaccine, and patients received 2 doses of the vaccine. Antibody responses were measured by hemagglutination inhibition assay before and 3-4 weeks after each dose. Geometric mean titers (GMTs) and rates of seroprotection (GMT≥40) were calculated. A comprehensive medical questionnaire was used to identify the determinants of vaccine responses and adverse events. RESULTS: Baseline influenza A/09/H1N1 antibody levels were low in patients and controls (seroprotection rates 14.8% and 14.2%, respectively). A significant response to dose 1 was observed in both groups. However, the GMT and the seroprotection rate remained significantly lower in patients (GMT 146 versus 340, seroprotection rate 74.6% versus 87%; both P<0.001). The second dose markedly increased antibody titers in patients, with achievement of a similar GMT and seroprotection rate as elicited with a single dose in healthy controls. By multivariate regression analysis, increasing age, use of disease-modifying antirheumatic drugs (DMARDs) (except hydroxychloroquine and sulfasalazine), and recent (within 3 months) B cell depletion treatment were identified as the main determinants of vaccine responses; tumor necrosis factor α antagonist treatment was not identified as a major determinant. Immunization was well tolerated, without any adverse effect on disease activity. CONCLUSION: DMARDs exert distinct influences on influenza vaccine responses in patients with inflammatory rheumatic diseases. Two doses of adjuvanted vaccine were necessary and sufficient to elicit responses in patients similar to those achieved with 1 dose in healthy controls.
20954191 Immune complexes containing citrullinated fibrinogen costimulate macrophages via Toll-like 2011 Jan OBJECTIVE: Rheumatoid arthritis (RA) is associated with the presence of anti-citrullinated protein antibodies (ACPAs). Nearly two-thirds of patients with ACPA-positive RA have immune complexes that contain citrullinated fibrinogen, and these citrullinated fibrinogen-containing immune complexes (cFb-IC) can exacerbate disease in murine models of RA; however, the exact role of such ACPA ICs in RA pathogenesis has remained elusive. We undertook the present study to investigate a novel mechanism by which ACPAs specifically targeting citrullinated fibrinogen may directly stimulate macrophage tumor necrosis factor (TNF) production. METHODS: Murine or human macrophages were stimulated with native fibrinogen (nFb), cFb, or in vitro-generated nFb-IC or cFb-IC, and TNF production was measured by enzyme-linked immunosorbent assay. ICs were generated with either polyclonal anti-Fb antibodies or pooled IgG from patients with ACPA-positive RA. To evaluate the role of the Toll-like receptor 4 (TLR-4)/myeloid differentiation protein (MyD88) pathway and the Fcγ receptor (FcγR) pathway in the induction of TNF by Fb and Fb-IC, parallel experiments were performed using 1) TLR-4-deficient or MyD88-deficient macrophages, and 2) inhibitors of TLR-4 or FcγR. RESULTS: Citrullinated Fb stimulated macrophage TNF production more potently than did native Fb. Incorporation of cFb into ICs augmented its ability to stimulate TNF production by macrophages. Stimulation of TNF by cFb was dependent on TLR-4 and MyD88, while stimulation by cFb-IC was dependent on both TLR-4/MyD88 and FcγR. CONCLUSION: We demonstrated that cFb-IC can costimulate macrophages via dual engagement of TLR-4 and FcγR, resulting in the synergistic induction of TNF production. Our findings suggest a potential role of citrullination in increasing the potency of an endogenous innate immune ligand and provide insight into the mechanism by which anticitrulline autoimmunity may contribute to the onset and propagation of inflammation in RA.
22820726 The Core Diseasome. 2012 Oct Large amounts of protein-protein interaction (PPI) data are available. The human PPI network currently contains over 56 000 interactions between 11 100 proteins. It has been demonstrated that the structure of this network is not random and that the same wiring patterns in it underlie the same biological processes and diseases. In this paper, we ask if there exists a subnetwork of the human PPI network such that its topology is the key to disease formation and hence should be the primary object of therapeutic intervention. We demonstrate that such a subnetwork exists and can be obtained purely computationally. In particular, by successively pruning the entire human PPI network, we are left with a "core" subnetwork that is not only topologically and functionally homogeneous, but is also enriched in disease genes, drug targets, and it contains genes that are known to drive disease formation. We call this subnetwork the Core Diseasome. Furthermore, we show that the topology of the Core Diseasome is unique in the human PPI network suggesting that it may be the wiring of this network that governs the mutagenesis that leads to disease. Explaining the mechanisms behind this phenomenon and exploiting them remains a challenge.
22104048 Abatacept mechanism of action: concordance with its clinical profile. 2012 Mar The double and simultaneous molecular interaction between antigen-presentig cells (APC) and T lymphocytes is essential for the optimal activation of the immunological response and requires the participation of two membrane receptor groups. Abatacept is a fusion protein that selectively modulates one of these two ways, by binding to CD80 and CD86 receptors on APC. In this way, the drug inhibits T cell activation, selectively blocking the specific interaction of CD80/CD86 receptors to CD28 and, therefore, inhibiting T cell proliferation and B cell immunological response. This pharmacological action results in the normalization of inflammatory mediators in rheumatoid arthritis patients and in a safe and efficacious clinical response. Abatacept in combination with methotrexate prevents the progression of joint damage and improves physical function in rheumatoid arthritis patients.
23155222 Individualised aerobic and resistance exercise training improves cardiorespiratory fitness 2013 Nov BACKGROUND AND OBJECTIVES: Low cardiorespiratory fitness (CRF) is a significant predictor of cardiovascular disease (CVD), and interventions aiming at increasing CRF are known to reduce CVD risk. The effects of such interventions on CVD risk have not been studied in patients with rheumatoid arthritis (RA). METHODS: 40 age, gender, body mass index (BMI) and disease duration matched RA patients were allocated to either an exercise (receiving 6 months individualised aerobic and resistance high intensity exercise intervention, three times per week), or control (receiving advice on exercise benefits and lifestyle changes) arm. Participants were assessed at baseline, 3 and 6 months for aerobic capacity (VO2max), individual CVD risk factors (blood pressure, lipids, insulin resistance, body composition), 10-year CVD event probability and RA characteristics (C-reactive protein (CRP), Disease Activity Score 28 (DAS28) and Health Assessment Questionnaire (HAQ)). RESULTS: There were no differences between groups at baseline in any of the assessed variables. VO2max (p=0.001), blood pressure (systolic: p<0.001; diastolic: p=0.003), triglycerides (p=0.030), high density lipoprotein (HDL; p=0.042), total cholesterol:HDL ratio (p=0.005), BMI (p=0.001), body fat (p=0.026), 10-year CVD event probability (p=0.012), CRP (p=0.042), DAS28 (p=0.008) and HAQ (p=0.003) were all significantly improved in the exercise versus the control group. The change in VO2max was the strongest predictor for the observed improvements in all of the assessed CVD risk factors and disease characteristics. CONCLUSIONS: Individualised aerobic and resistance exercise intervention can lead to significantly improved CRF, individual CVD risk factors, composite CVD risk, and disease activity and severity in RA patients.
22962438 Complement receptor type 1 (CR1, CD35) is a potent inhibitor of B-cell functions in rheuma 2013 Jan The involvement of B cells, complement activation and subsequent immune complex deposition has all been implicated in the pathogenesis of rheumatoid arthritis (RA). Although the reduced expression of complement receptor 1 (CR1, CD35) and 2 (CR2, CD21) on the B cells of RA patients has been known for a long time, their exact role in B-cell tolerance and autoimmunity is not yet fully understood. To get a deeper insight into the possible mechanisms, we studied the expression and function of CR1 and CR2 on various subsets of B cells of healthy donors and RA patients at various stages of the disease by FACS analysis, (3)H-thymidine incorporation and ELISA. We found that CD19(+)CD27(-) naive B cells up-regulate the expression of the inhibitory CR1 during differentiation to CD19(+)CD27(+) memory B cells both in healthy donors and in RA patients, whereas the expression of the activatory CR2 is down-regulated. This clearly demonstrates that the expression of these two antagonistic complement receptors is regulated differentially during the development of human B cells, a phenomenon which may influence the maintenance of peripheral B-cell tolerance. Our functional studies show that after clustering CR1 both by its natural ligand and To5 mAb, the inhibitory function of CD35 is maintained in RA patients, despite its significantly reduced expression compared with healthy individuals. Besides blocking B-cell receptor-induced proliferation, CR1 inhibits the differentiation of B cells to plasmablasts and their immunoglobulin production. Since the reduced expression of CR1 in RA patients does not affect its inhibitory function, this receptor might serve as a new target for therapeutical interventions.
21528357 Inhibition of inflammatory mediators and related signaling pathways by macrophage-stimulat 2011 Sep OBJECTIVE: To evaluate the mechanism of macrophage-stimulating protein (MSP)-mediated inhibition of inflammatory cytokine and chemokine production in rheumatoid arthritis synovial fibroblasts (RASF). MATERIALS AND METHODS: RASF were treated with different concentrations (0, 0.5, 1, 5 and 10 ng/ml) of MSP with or without 1 μg/mL lipopolysaccharide (LPS). The protein expressions of IL-1β, TNF-α, IL-18, MIP-1, MCP-1, RANTES and PGE(2) were analyzed by enzyme-linked immunosorbent assays (ELISA). The total nitric oxide (NO) concentration was determined using the Griess reaction. The protein expressions of iNOS, COX-2, NF-κB(p-p65), IKB-α, IKB-β, p-P38, p-Erk1/2 (P-P42/44) and p-AKT were detected by Western blotting. RESULTS: MSP markedly inhibited expression of inflammatory cytokines (IL-1β, TNF-α and IL-18), chemokines (MIP-1, MCP-1 and RANTES) and iNOS, NO, COX-2 and PGE(2) in RASF stimulated by LPS. MSP treatment decreased expressions of p-IκBα, p-IKBβ and p-P65 in RASF in a concentration-dependent manner. Expressions of p-AKT, p-p38 and p-Erk1/2 were also inhibited markedly in RASF stimulated by LPS after treatment with MSP in a concentration-dependent manner. CONCLUSION: MSP could inhibit the inflammatory cycle by suppressing inflammatory mediators and activation of NF-κB as well. The inhibitory effect of MSP on LPS-stimulated RASF may act through suppression of multiple signals such as the PI3K/AKT and/or MAPK pathways.
21560115 Genome-wide and species-wide dissection of the genetics of arthritis severity in heterogen 2011 Sep OBJECTIVE: Susceptibility to inflammatory arthritis is determined by a complex set of environmental and genetic factors, but only a portion of the genetic effect can be explained. Conventional genome-wide screens of arthritis models using crosses between inbred mice have been hampered by the low resolution of results and by the restricted range of natural genetic variation sampled. The aim of this study was to address these limitations by performing a genome-wide screen for determinants of arthritis severity using a genetically heterogeneous cohort of mice. METHODS: Heterogeneous stock (HS) mice derive from 8 founder inbred strains by serial intercrossing (n>60), resulting in fine-grained genetic variation. With a cohort of 570 HS mice, we performed a genome-wide screen for determinants of arthritis severity in the K/BxN serum-transfer model. RESULTS: We mapped regions on chromosomes 1, 2, 4, 6, 7, and 15 that contain quantitative trait loci influencing arthritis severity at a resolution of a few megabases. In several instances, these regions proved to contain 2 quantitative trait loci: the region on chromosome 2 included the C5 fraction of complement known to be required for K/BxN serum-transfer arthritis but also contained a second adjacent quantitative trait locus, for which an intriguing candidate is Ptgs1 (Cox1). Interesting candidates on chromosome 4 included the Padi family, encoding the peptidyl arginine deiminases responsible for citrulline protein modification; suggestively, Padi2 and Padi4 RNA expression was correlated with arthritis severity in HS mice. CONCLUSION: These results provide a broad overview of the genetic variation that controls the severity of K/BxN serum-transfer arthritis and suggest intriguing candidate genes for further study.
21903597 Association of paediatric inflammatory bowel disease with other immune-mediated diseases. 2011 Nov BACKGROUND: Associations between inflammatory bowel diseases (IBDs) and other immune-mediated diseases have been described in adult populations. Whether such associations exist in childhood-onset disease remains unknown. OBJECTIVES: The authors sought to evaluate whether paediatric IBD is associated with the occurrence of other immune-mediated diseases. STUDY DESIGN: The authors identified cases of Crohn's disease (CD) and ulcerative colitis (UC), ≤20 years of age, using administrative data from 87 health plans. Each case was matched to three controls, on the basis of age, gender, and geographical region. The authors used logistic regression to compare the prevalence of various immune-mediated diseases (identified by International Classification of Diseases, ninth revision codes) in cases versus controls. RESULTS: The study included 737 children with CD (1997 controls) and 488 with UC (1310 controls). CD was associated with a higher prevalence of rheumatoid arthritis (OR 15.7, 95% CI 4.6 to 53.7), lupus (OR 41.0, 95% CI 2.3 to 719.1) and hypothyroidism (OR 2.9, 95% CI 1.4 to 6.1), with a trend toward an increased prevalence of asthma, eczema, allergic rhinitis and diabetes. UC was associated with a higher prevalence of diabetes (OR 2.7, 95% CI 1.1 to 6.6), with a trend towards increased prevalence of asthma, eczema, allergic rhinitis, hypothyroidism, rheumatoid arthritis and lupus. DISCUSSION: Children with IBD, particularly CD, have an elevated risk for immune-mediated conditions. This comorbidity adds to the burden of paediatric IBD, and suggests common aetiologic mechanisms.
21120562 Effectiveness of radiation synovectomy with Yttrium-90 and Samarium-153 particulate hydrox 2011 Jan The aim of the present study was to investigate the long-term effectiveness of and tolerance to Yttrium-90 and Samarium-153-particulate hydroxyapatite radiation synovectomy in patients with rheumatoid arthritis (RA) and chronic knee synovitis. Eight-four patients (90 knees) with chronic knee synovitis and RA (according to the American College of Rheumatology criteria) participated in a controlled, double-blinded trial. Patients were randomized to receive an intra-articular injection with either 5 mCi Yttrium-90 plus 40 mg of triamcinolone hexacetonide (Y/TH Group), 15 mCi Samarium-153 hydroxyapatite plus 40 mg of triamcinolone hexacetonide (Sm/TH Group), or 40 mg triamcinolone hexacetonide alone (Control Group). Blinded examination at baseline, 1, 4, 12, 32, and 48 weeks post-intervention included a visual analog scale for joint pain and swelling, morning stiffness, range of motion, knee circumference, Likert scale, percentage of improvement, Stanford Health Assessment Questionnaire, Lequesne index, use of non-steroidal anti-inflammatory drugs and corticosteroids, events and adverse effects, calls to the physician, and hospital visits. There were three withdrawals prior to the injections. Regarding the pain, there was a significantly better response in the Y/TH Group versus the Sm/TH Group at T1 (p = 0.025) and versus TH alone at T48 (p = 0.026). The Sm/TH group had more adverse effects (p = 0.042), but these were mild and transitory. For the pain parameter alone, Yttrium-90 radiosynovectomy associated to TH proved superior to Samarium-153 hydroxyapatite radiosynovectomy associated to TH at T1 and to synovectomy with TH at T48. No other statistically significant inter-group differences were detected.
21831256 Indirect comparison of biological treatments in refractory rheumatoid arthritis. 2012 Jun WHAT IS KNOWN AND OBJECTIVE: A number of biological treatments are available for rheumatoid arthritis. They are effective some patients but their comparative efficacy is inadequately evaluated. Our aim was to compare the efficacy of adalimumab, etanercept, infliximab, abatacept, tocilizumab, golimumab and certolizumab pegol in rheumatoid arthritis, refractory to disease-modifying antirheumatic drugs (DMARDs), through a systematic review of published trials. METHODS: As there were no direct comparisons, we searched for studies with similar characteristics to identify trials with results suitable for indirect comparison. Randomized, placebo-controlled pivotal clinical trials, with reported American College of Rheumatology ACR50 data at 24/30 weeks as efficacy endpoint, approved clinical doses and patients resistant to DMARDs who had not previously received other biological treatments were included. ACR50 was defined as the primary endpoint for the indirect comparison, with ACR20 and ACR70 as secondary endpoints. When two or more trials on one same drug were available, and a combined analysis was performed when appropriate. In the indirect comparison, the Bucher adjusted method was used with etanercept as reference drug. In the equivalence study, the equivalence window was a response efficacy difference of 15% between the alternatives. RESULTS AND DISCUSSION: Ten trials were found suitable for detailed analysis. In the clinical trials, all the biological drugs were seen to be more effective than placebo. Indirect comparison based on the ACR50 efficacy criterion all biological treatments showed similar results within the defined equivalence Δ value. The absolute efficacy difference (reduction of absolute risk, RAR) versus etanercept being 2·6% with adalimumab, 14% with infliximab, 11·6% with abatacept, 3% with tocilizumab, 12·4% with golimumab and 6·5% with certolizumab pegol. WHAT IS NEW AND CONCLUSION: The biological drugs used in rheumatoid arthritis are no different in efficacy. Their therapeutic positioning depends on their relative safety and convenience profiles.
21975946 Variability of medial and posterior offset in patients with fourth-generation stemmed shou 2012 Mar PURPOSE: Most anthropometric data on the proximal humerus has been obtained from deceased healthy individuals with no deformities. Endoprostheses are implanted for primary and secondary osteoarthritis, rheumatoid arthritis,humeral-head necrosis, fracture sequelae and other humeral-head deformities. This indicates that pathologicoanatomical variability may be greater than previously assumed. We therefore investigated a group of patients with typical shoulder replacement diagnoses, including posttraumatic and rheumatic deformities. MATERIAL AND METHODS: One hundred and twenty-two patients with a double eccentrically adjustable shaft endoprosthesis served as a specific dimension gauge to determine in vivo the individual humeral-head rotation centres from the position of the adjustable prosthesis taper and the eccentric head. RESULTS: All prosthesis heads were positioned eccentrically.The entire adjustment range of the prosthesis of 12 mm medial/lateral and 6 mm dorsal/ventral was required. Mean values for effective offset were 5.84 mm mediolaterally[standard deviation (SD) 1.95, minimum +2, maximum +11]and 1.71 mm anteroposteriorly (SD 1.71, minimum −3,maximum 3 mm), averaging 5.16 mm (SD 1.76, minimum +2,maximum + 10). The posterior offset averaged 1.85 mm(SD 1.85, minimum −1, maximum + 6 mm). CONCLUSIONS: In summary, variability of the combined medial and dorsal offset of the humeral-head rotational centre determined in patients with typical underlying diagnoses in shoulder replacement was not greater than that recorded in the literature for healthy deceased patients.The range of deviation is substantial and shows the need for an adjustable prosthetic system.