Browse

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

ID PMID Title PublicationDate abstract
20861148 Detection and evaluation of a drug safety signal concerning pancreatic cancer: lessons fro 2011 Jan OBJECTIVES: A high incidence of pancreatic cancer (PCa) in patients exposed to was observed in the German biologics register. To evaluate this possible safety signal, a concerted analysis with the national biologics registers in the UK and Sweden was performed. METHODS: Patients with enrolled in the British Society of Rheumatology Biologics Register (BSRBR), the Swedish Rheumatology Register (SRR) or the German Biologics Register [Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT)] were analysed. The patients were exposed to biologic or conventional DMARDs. Outcomes were obtained from physician reports, health authorities and via linkage to national cancer and death registers. Age- and gender-standardized incidence ratios (SIRs) of PCa were calculated based on the expected rates available from the individual national cancer registers. RESULTS: Data from 5126 (Germany), 16 930 (UK) and 19 351 (Sweden) RA patients were available for the analysis. The highly discrepant prescription rates of LEF in the respective countries resulted in 11 343 (Germany), 30 787 (UK) and 2518 (S) patient-years of exposure to LEF. Compared with the general population, the incidence of PCa in patients ever exposed to LEF corresponded to a SIR of 3.1 (95% CI 1.3, 6.5) in Germany, 1.05 (95% CI 0.5, 2.1) in the UK and 1.8 (95% CI 0.1, 10.2) in Sweden. CONCLUSION: The results of the replication analyses do not support the hypothesis of an increased risk of PCa in patients exposed to treatment with LEF. However, they do not completely rule out concerns, and therefore further verification in other data sets is recommended.
19479851 Impaired differentiation and cytotoxicity of natural killer cells in systemic lupus erythe 2009 Jun OBJECTIVE: To determine the cytotoxicity of natural killer (NK) cells and the level of differentiation of hematopoietic stem cells (HSCs) into NK cells in systemic lupus erythematosus (SLE). METHODS: Patients with SLE (n=108), rheumatoid arthritis (RA; n=90), Behçet's disease (n=39), or ankylosing spondylitis (n=41) and healthy control subjects (n=173) were enrolled in the study. NK cell levels, NK cell cytotoxicities, and lymphokine-activated killer (LAK) activities against K562 cells were measured by flow cytometry. Gene expression was assessed by reverse transcription-polymerase chain reaction. NK cells were differentiated from peripheral blood and bone marrow HSCs in vitro. RESULTS: Percentages and absolute numbers of NK cells, cytotoxicities, and LAK activities were significantly lower in the peripheral blood of SLE and RA patients than in that of healthy controls. In particular, this NK cell deficiency was more prominent in patients with lupus nephritis and those with thrombocytopenia. Notably, purified NK cells derived from SLE patients, but not RA patients, were found to have lower cytotoxicities and LAK activities than those from healthy controls. This defect of NK cells in SLE patients was found to be related to lower numbers of NK precursors and to the down-regulation of perforin and granzyme in NK cells. The proliferative capacity of HSCs, the percentages of NK cells differentiated from HSCs, and NK cell cytotoxicities were significantly lower in SLE patients. CONCLUSION: In SLE patients, circulating levels of NK cells were diminished and their cytotoxicities were impaired. Furthermore, the differentiation of HSCs into NK cells was found to be defective. These abnormalities possibly contribute to immune system dysregulation in SLE.
20498202 Inducible costimulator (ICOS) blockade inhibits accumulation of polyfunctional T helper 1/ 2010 Aug OBJECTIVES: Inducible costimulator (ICOS) and its ligand (ICOSL) regulate T and B cell responses. Glucose-6-phosphate isomerase (G6PI)-induced arthritis requires T and B lymphocytes. It was hypothesised that blocking ICOS/ICOSL interactions ameliorates G6PI-induced arthritis and reduces G6PI-specific B and T lymphocyte responses. METHODS: DBA/1 mice were injected with a blocking, non-depleting anti-ICOSL monoclonal antibodies (mAbs) during the induction or effector phase of G6PI-induced arthritis. G6PI-specific antibody responses were measured by ELISA. G6PI-specific T helper (Th) cell responses were assayed by polychromatic flow cytometry. RESULTS: Transient blockade of ICOS/ICOSL interactions profoundly reduced the severity of G6PI-induced arthritis. ELISA and proliferation assays showed no clear ex vivo correlates of protection. Polychromatic flow cytometry revealed two major findings: the absolute number of G6PI-specific Th cells was markedly diminished in secondary lymphatic organs from mice with blocked ICOS/ICOSL interactions. Within the pool of G6PI-specific Th cells the frequency of interleukin 17 (IL17), interferon gamma or tumour necrosis factor alpha producers or polyfunctional Th cells (expressing two or more of these cytokines) was higher in treated than in control mice. CONCLUSIONS: ICOS costimulation is not mandatory for the differentiation of Th1 or Th17 cells. Instead, the lack of ICOS costimulation results in reduced survival of G6PI-specific Th cells irrespective of their functional differentiation. This study demonstrates that a thorough examination of the quantity and the quality of antigen-specific immune responses is useful to determine ex vivo correlates of efficacy for immunomodulating treatments.
20808167 Tumor necrosis factor-alpha antagonist-induced sarcoidosis. 2010 Sep Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Tumor necrosis factor (TNF)-alpha is an important player in granuloma formation, and recent clinical trials have investigated the efficacy of TNF-alpha inhibitors in sarcoidosis. Paradoxically, there are several case reports in the medical literature describing the development of sarcoidosis in patients treated with TNF-alpha inhibitors. We describe 3 cases of TNF-alpha antagonist-induced sarcoidosis: 1 case of pulmonary, ocular and cutaneous sarcoidosis developing in a patient receiving infliximab for erosive rheumatoid arthritis, 1 case of etanercept-induced sarcoidosis in a patient with seronegative rheumatoid arthritis, and 1 case of sarcoidosis developing in a patient receiving etanercept for erosive rheumatoid arthritis. We also provide a brief discussion on the role of TNF alpha in granuloma formation and implications in the use of TNF-alpha antagonists in autoimmune disease.
19567623 Lack of association with rheumatoid arthritis of selected polymorphisms in 4 candidate gen 2009 Aug OBJECTIVE: To investigate associations with rheumatoid arthritis (RA) of single-nucleotide polymorphisms (SNP) in 4 candidate genes, complement factor H (CFH), CD209 or DC-SIGN, eotaxin-3, and the MHC class II Transactivator (MHC2TA) genes. These SNP have been reported as important for RA (eotaxin-3 and MHC2TA) or for other immune-mediated diseases (CFH and CD209). METHODS: Genotypes for the 7 selected SNP were obtained from 1587 patients with RA and 1570 controls of Spanish ancestry. Analyses were carried out after stratification for sex, erosions, rheumatoid factor, shared epitope, anti-cyclic citrullinated peptide antibodies, and the R620W PTPN22 SNP. RESULTS: None of the comparisons between patients with RA and controls or between the different strata of patients according to disease features was significant. CONCLUSION: None of the SNP in CFH and CD209 showed evidence of association with RA. We did not replicate the association of eotaxin-3 with RA described in Koreans, or that of the MHC2T SNP.
20044851 Public health interventions for arthritis: expanding the toolbox of evidence-based interve 2009 Dec BACKGROUND: Since 1999, the Centers for Disease Control and Prevention's (CDC) Arthritis Program has worked to improve the quality of life for people with arthritis, in part by funding state health departments to disseminate physical activity (PA) and self-management education (SME) interventions. Initially, only one SME and two PA interventions were considered evidence-based and appropriate for people with arthritis. The purposes of this article are to describe the processes and criteria used to screen new or existing intervention programs and report the results of that screening, including an updated list of recommended intervention programs. METHODS: A series of three sets of screening criteria was created in consultation with subject matter experts: arthritis appropriateness, adequacy of the evidence base, and implementability as a public health intervention. Screening interventions were categorized as Recommended, Promising Practices, Watch List, Future Possibility, or Unlikely to Meet criteria based on how well the intervention met the screening criteria. RESULTS: A total of 15 packaged PA interventions and six SME interventions were screened. Three PA and three SME interventions met all three sets of criteria and were added to the list of recommended public health interventions for use by CDC-funded state arthritis programs. An additional two SME interventions are developing the infrastructure for public health dissemination and were categorized as Promising Practices, and six PA interventions have evaluations underway and are on the Watch List. CONCLUSIONS: The CDC Arthritis Program identified arthritis-appropriate interventions that can be used effectively and efficiently in public health settings to improve the quality of life of people with arthritis. The screening criteria used offer a guide to intervention developers on necessary characteristics of interventions for use in public health settings. The expanded menu of interventions is beneficial to clinical care and public health professionals and, ultimately, to people with arthritis.
19384869 Functional TLR9 modulates bone marrow B cells from rheumatoid arthritis patients. 2009 May TLR9 recognizes unmethylated CpG-rich, pathogen-derived DNA sequences and represents the component of the innate immune system that heavily influences adaptive immunity and may contribute to the immunological disturbances in rheumatoid arthritis (RA). Accumulating data indicate that BM of RA patients participates in the pathogenesis of this disease as a site of proinflammatory cytokines overproduction and lymphocytes activation. Here, we investigated the functionality of TLR9 and its role in the modulation of RA BM B-cell functions. We report that BM B cells isolated from RA patients express TLR9 at the mRNA and protein levels acquired at the stage of preB/immature B-cell maturation. Stimulation of BM CD20(+) B cells by CpG-containing oligodeoxynucleotide-enhanced expression of activation markers (CD86 and CD54) triggered IL-6 and TNF-alpha secretion and cell proliferation. Significantly higher levels of eubacterial DNA encoding 16S-rRNA were found in BM samples from RA than osteoarthritis patients. Moreover, RA BM B cells exerted higher expression of CD86 than their osteoarthritis counterparts, suggesting their in situ activation via TLR9. Thus, our data indicate that TLR9 may participate in direct activation and proliferation of B cells in BM, and therefore could play a role in the pathogenesis of RA.
19054822 Malignancies in the rheumatoid arthritis abatacept clinical development programme: an epid 2009 Dec OBJECTIVE: To provide context for the malignancy experience in the rheumatoid arthritis (RA) abatacept clinical development programme (CDP) by performing comparisons with similar RA patients and the general population. METHODS: Malignancy outcomes included total malignancy (excluding non-melanoma skin cancer (NMSC)), breast, colorectal, lung cancers and lymphoma. Comparisons were made between the observed incidence in patients within the abatacept CDP and RA patients on disease-modifying antirheumatic drugs (DMARD) identified from five data sources: the population-based British Columbia RA Cohort, the Norfolk Arthritis Register, the National Data Bank for Rheumatic Diseases, the Sweden Early RA Register and the General Practice Research Database. Age and sex-adjusted incidence rates (IR) and standardised incidence ratios (SIR) were used to compare events in the abatacept trials with the RA DMARD cohorts and the general population. RESULTS: A total of 4134 RA patients treated with abatacept in seven trials and 41,529 DMARD-treated RA patients in the five observational cohorts was identified for study inclusion. In the abatacept-treated patients, the 51 malignancies (excluding NMSC), seven cases of breast, two cases of colorectal, 13 cases of lung cancer and five cases of lymphoma observed were not greater than the range of expected cases from the five RA cohorts. The SIR comparing RA patients with the general population were consistent with those reported in the literature. CONCLUSIONS: The IR of total malignancy (excluding NMSC), breast, colorectal, lung cancers and lymphoma in the abatacept CDP were consistent with those in a comparable RA population. These data suggest no new safety signals with respect to malignancies, which will continue to be monitored.
18987779 A case of peripheral neuropathy and skin ulcer in a patient with rheumatoid arthritis afte 2009 We report a case of peripheral neuropathy and skin ulcer in a patient with rheumatoid arthritis (RA) who received tocilizumab. A 65-year-old woman with a 20-year history of RA participated in a tocilizumab clinical trial. She received a single dose of 8 mg/kg tocilizumab intravenously. The following day the patient started to experience numbness and purpura in all four extremities. The purpura of her left lower limb became necrotic, and a skin ulcer appeared 3 weeks later. Steroid-pulse treatment was initiated 12 weeks after tocilizumab administration, with the result that the numbness improved, and the skin ulcers showed complete epithelialization.
19283441 A significantly impaired natural killer cell activity due to a low activity on a per-cell 2009 To elucidate the characterization of peripheral natural killer (NK) cells in patients with rheumatoid arthritis (RA), we investigated the NK cell activity, the expression of NK cell activating receptors and intracellular molecules. The NK activity was analyzed in 27 RA patients, 22 primary Sjögren's syndrome (SS) patients, and 15 healthy individuals using the (51)Chrominium release assay. The expression of NK cell activating receptors (NKG2D, CD244, CD2, and CD16) and intracellular molecules (granzyme B, perforin, and TCR zeta chain) in CD3-CD56+ cells were characterized by flow cytometry. The serum cytokine levels (IL-6, TNFalpha, and IL-18) were measured using ELISA. Both the NK cell activity and the activity on a per-cell basis were observed to significantly decrease in the RA patients in comparison to the controls. The expression of NKG2D and CD244 also significantly decreased in both the RA and primary SS patients, whereas the significant decrease in the CD16 expression was only observed in the RA patients. The titer of the serum IL-6, TNFalpha, and IL-18 was significantly higher in the RA patients than in the controls. These data suggest that a low NK activity on a per-cell basis might therefore contribute to an impaired NK activity in the patients with RA.
19676055 Detection of parent-of-origin effects using general pedigree data. 2010 Feb Genomic imprinting is an important epigenetic factor in complex traits study, which has generally been examined by testing for parent-of-origin effects of alleles. For a diallelic marker locus, the parental-asymmetry test (PAT) based on case-parents trios and its extensions to incomplete nuclear families (1-PAT and C-PAT) are simple and powerful for detecting parent-of-origin effects. However, these methods are suitable only for nuclear families and thus are not amenable to general pedigree data. Use of data from extended pedigrees, if available, may lead to more powerful methods than randomly selecting one two-generation nuclear family from each pedigree. In this study, we extend PAT to accommodate general pedigree data by proposing the pedigree PAT (PPAT) statistic, which uses all informative family trios from pedigrees. To fully utilize pedigrees with some missing genotypes, we further develop the Monte Carlo (MC) PPAT (MCPPAT) statistic based on MC sampling and estimation. Extensive simulations were carried out to evaluate the performance of the proposed methods. Under the assumption that the pedigrees and their associated affection patterns are randomly drawn from a population of pedigrees with at least one affected offspring, we demonstrated that MCPPAT is a valid test for parent-of-origin effects in the presence of association. Further, MCPPAT is much more powerful compared to PAT for trios or even PPAT for all informative family trios from the same pedigrees if there is missing data. Application of the proposed methods to a rheumatoid arthritis dataset further demonstrates the advantage of MCPPAT.
19165558 Hemophagocytic syndrome in elderly patients with underlying autoimmune diseases. 2009 Apr In patients with autoimmune disease-associated hemophagocytic syndrome (AAHS), the clinical features may differ from hemophagocytic syndrome (HPS) of other etiologies, and new criteria for AAHS have been proposed. Since bone marrow (BM) circumstances are changed according to aging, here we reviewed retrospectively our cases with AAHS in elderly patients, including two systemic lupus erythematosus (SLE), three Evans syndrome, one rheumatoid arthritis (RA), one Hashimoto thyroiditis, and one autoimmune pancreatitis. Although only two SLE patients were diagnosed as HPS by the classical criteria, the remaining patients except one RA met the criteria for AAHS. Seven patients except one SLE patient showed good response to therapy and demonstrated positive autoantibodies to blood cells, lower serum ferritin levels, and increased erythroblastic islands in the BM. We consider the diagnosis of AAHS should be carefully made when macrophages phagocytosing blood cells are observed in BM smear without hyperferritinemia in elderly patients with autoimmune diseases.
19415460 Discoidin domain receptor 2 is associated with the increased expression of matrix metallop 2009 Oct Regulation of matrix metalloproteinase-13 (MMP-13) by collagen matrix in the synovial fibroblasts of rheumatoid arthritis (RA) is critical event in the progressive joint destruction. Our previous study indicated that a collagen receptor, discoidin receptor 2 (DDR2), was highly expressed in the synovial fibroblasts of RA. However, the functional role of DDR2 in the regulation of MMP-13 production in synovial fibroblasts has not been elucidated. In this study, we initially demonstrated that the DDR2 and MMP-13 proteins are both highly expressed in the synovial lining layer of RA. MMP-13 mRNA and protein in synovial fibroblasts of RA were preferentially induced by collagen type II compared with MMP-1. Furthermore, stable overexpression of wild type DDR2 in murine synoviocytes dramatically augments the production of MMP-13. The activation of DDR2 also mediates the up-regulation of MMP-13 promoter activity in 293T cells. Inhibitor specific for extracellular signal-regulated kinase mitogen-activated protein kinase (ERK MAPK) cascade was shown to decrease MMP-13 level induced by collagen II in RA synovial fibroblasts and DDR2-induced MMP-13 promoter activity. Runx2 and activator protein-1 (AP-1) binding sites in MMP-13 promoter region are required for DDR2-induced transcription. The data in this study suggest that DDR2-mediated MMP-13 induction by collagen matrix in synovial fibroblasts of RA contributed to articular cartilage destruction.
19019888 Long-term safety and efficacy of tocilizumab, an anti-IL-6 receptor monoclonal antibody, i 2009 Oct OBJECTIVES: To evaluate the safety and efficacy of 5-year, long-term tocilizumab monotherapy for patients with rheumatoid arthritis. METHODS: In an open-label, long-term extension trial following an initial 3-month randomised phase II trial, 143 of the 163 patients who participated in the initial blinded study received tocilizumab monotherapy (8 mg/kg) every 4 weeks. Concomitant therapy with non-steroidal anti-inflammatory drugs and/or oral prednisolone (10 mg daily maximum) was permitted. All patients were evaluated with American College of Rheumatology (ACR) improvement criteria, disease activity score (DAS) in 28 joints, and the European League Against Rheumatism response, as well as for safety issues. RESULTS: 143 patients were enrolled in the open-label, long-term extension trial and 94 (66%) patients had completed 5 years as of March 2007. 32 patients (22%) withdrew from the study due to adverse events and one patient (0.7%) due to unsatisfactory response. 14 patients withdrew because of the patient's request or other reasons. The serious adverse event rate was 27.5 events per 100 patient-years, with 5.7 serious infections per 100 patient-years, based on a total tocilizumab exposure of 612 patient-years. Of the 88 patients receiving corticosteroids at baseline, 78 (88.6%) were able to decrease their corticosteroid dose and 28 (31.8%) discontinued corticosteroids. At 5 years, 79/94 (84.0%), 65/94 (69.1%) and 41/94 (43.6%) of the patients achieved ACR20, ACR50, and ACR70 improvement criteria, respectively. Remission defined as DAS28 less than 2.6 was achieved in 52/94 (55.3%) of the patients. CONCLUSION: In this 5-year extension study, tocilizumab demonstrated sustained long-term efficacy and a generally good safety profile.
20079321 [Adalimumab plus methotrexate for the treatment of rheumatoid arthritis: a multi-center ra 2009 Nov OBJECTIVE: To investigate the efficacy and safety of adalimumab plus methotrexate (MTX) for the treatment of rheumatoid arthritis (RA). METHODS: This is a multi-center, randomized, double-blind, parallel-group, and placebo-controlled clinical study, included a total of 302 cases of active rheumatoid arthritis, randomized into three groups of observation: 40 mg adalimumab (121 cases), 80 mg adalimumab (121 cases), or placebo (60 cases). Upon enrollment, all subjects had been previously treated with MTX for at least 3 months, and their doses of drug had remained stable for at least 28 days. The double-blind phase lasted for 12 weeks, during which the subjects were administered with adalimumab or placebo subcutaneously every other week. Then the subjects entered into another 12 weeks of open-label study, which included subcutaneous injection of 40 mg adalimumab every other week. In both the double-blind and the open-label periods, all subjects were maintained concomitantly with MTX that had already been used before this study. The primary efficacy variables were evaluated on basis of American College of Rheumatology (ACR)20 response rate at week 12. The secondary efficacy variables included: ACR20 response rate at week 24; ACR50 and ACR70 response rates at weeks 12 and 24; and changes at weeks 12 and 24 compared with baseline observations for tender and swollen joint counts, as well as the assessment of pain with visual analog scale (VAS), the physician's and the patient's global assessment of disease activity (VAS), and the analysis on health assessment questionnaire (HAQ) and health related quality of life (HRQL) measured by Short Form-36 (SF-36); The safety variables mainly included adverse events (AE). RESULT: During the double-blind period, subjects treated with 40 mg of adalimumab, 57.0% achieved ACR20 response at week 12 (P = 0.004 versus placebo), and subjects treated with 80 mg of adalimumab, 51.2% achieved ACR20 response at week 12 (P = 0.026 versus placebo), and only 35.0% of subjects treated with placebo achieved ACR20 response at week 12. On the other hand, 32.2% of subjects receiving 40 mg of adalimumab achieved ACR50 response (P = 0.009 versus placebo), and 15.7% achieved ACR70 response (P = 0.007 versus placebo) at week 12. Subjects treated with 40 mg of adalimumab got a better result versus placebo at week 12 for tender joint count, swollen joint count, and improvement in C-reactive protein; and subjects treated with 80 mg of adalimumab were also seen an amelioration versus placebo at week 12 for swollen joint count, and improvement in C-reactive protein; all of these findings were statistically significant in differences. During the open-label period all subjects received 40 mg of adalimumab, and response rates for ACR20, ACR50, and ACR70 in the two treatment groups of 40 mg and 80 mg adalimumab were maintained or improved from week 12 to week 24 (being 73.1%, 40.3% and 17.6% respectively for 40 mg group; 71.1%, 39.5% and 17.5% respectively for 80 mg group); while response in the original placebo group (being 67.8%, 44.1% and 18.6%) increased during the 12-week open-label period to match that of the original adalimumab treatment groups. While for changes in tender and swollen joint counts, VAS, HAQ, SF-36, a significant improvement was seen at week 24 when compared with baseline and week 12 values. Throughout the double-blind and open-label period, adverse events reported in >/= 5% of subjects at least possibly associated with the study drug were upper respiratory tract infection, nasopharyngitis, and injection site itching, mostly being mild to moderate in severity. There were 3 cases of tuberculosis reported during this study. And 3 cases of serious adverse event (SAE) were reported among the adalimumab subjects during the double-blind period, which were determined as unrelated or probably unrelated to the study drug. And 8 cases (2.7%) of SAE were seen among the adalimumab subjects during the open-label period, 3 of which were at least possibly unrelated with the study drug. All SAEs reported were consistent to those seen in other adalimumab trials. No other unexpected safety signals were reported. CONCLUSION: Adalimumab plus MTX is better than single MTX in efficacy for the treatment of RA. Being generally safe and well tolerated, adalimumab plus MTX can significantly increase the response rate, continuously reduce the arthritic signs, symptoms and the inflammatory factors in patients, and also be helpful for reducing disabilities and improving the global quality of life for the patients.
19238514 Plasminogen activator inhibitor-1 C/G polymorphism in relation to plasma levels in rheumat 2009 Sep Plasminogen activator inhibitor type 1 (PAI-1) is an inhibitor of plasmin production. Plasmin can directly or indirectly to degrade cartilage and bone matrix. The PAI-1 HindIII polymorphism has been associated with high PAI-1 plasma levels in myocardial infarction patients and control populations. Furthermore, it has been associated with the angiographic extent of coronary artery disease, but their involvement in other diseases is still uncertain. Here, we assessed the relationship between PAI-1 HindIII polymorphism and PAI-1 plasma levels in rheumatoid arthritis (RA). One hundred and twenty-five RA patients and 132 control subjects (CS) were included. Genotypes were identified by the polymerase chain reaction-restriction fragment length polymorphism technique and PAI-1 plasma levels were quantified using an ELISA kit. Not significant differences in genotype and allele frequencies between both studied groups were observed (P > 0.05). RA patients showed lower PAI-1 plasma levels (18.92 +/- 12.94 ng/ml) than CS (23.68 +/- 23.38 ng/ml), without significant difference (P = 0.299). However, in RA patients the C/G genotype carriers showed higher PAI-1 plasma levels (23.00 +/- 13.81 ng/ml) with respect to C/C (16.77 +/- 11.97 ng/ml) and G/G (10.47 +/- 7.07 ng/ml) genotype carriers (P = 0.036). The PAI-1 HindIII polymorphism was not associated with RA susceptibility. However, the C/G genotype is associated with high PAI-1 plasma levels in RA patients.
19648298 Do rheumatoid arthritis patients have a higher risk for sleep apnea? 2009 Sep OBJECTIVE: Patients with rheumatoid arthritis (RA) have an increased risk for developing cardiovascular disease (CVD) compared to subjects in the general population. The development of CVD has also been linked to chronic sleep apnea. The purpose of this study was to examine the risk for sleep apnea in patients with RA compared to subjects without RA. METHODS: We recruited RA patients and non-RA subjects who were age and sex matched from the same population. These persons completed the Berlin Sleep Questionnaire, which evaluated their level of risk (high or low) for sleep apnea. In addition, there were 3 subscales evaluating snoring, fatigue, and relevant comorbidities [i.e., high blood pressure and obesity [body mass index (BMI) > or = 30 kg/m(2))]. Chi-squared tests were used for comparisons. RESULTS: The study population consisted of 164 patients with RA and 328 patients without RA. Age, sex and BMI were similar for both groups. There was no difference in snoring (p = 0.31) or in the comorbidities subscale (p = 0.37). However, RA patients reported more fatigue (38%) than subjects without RA (13%; p < 0.001). Overall, the risk for sleep apnea was significantly higher for the RA patients (50%) than the non-RA subjects (31%; p < 0.001). CONCLUSION: Patients with RA may be at a higher risk for sleep apnea compared to non-RA subjects. This apparent risk difference may be attributed to reports of fatigue in RA patients, which may be associated with sleep apnea or RA disease itself.
20149304 Patient and physician perception of the infusion process of the biologic agents abatacept, 2009 Nov OBJECTIVES: To assess the process related to each infusible biologic used in rheumatoid arthritis (RA) with regard to patient and physician engagement in the infusion process, ancillary services required, and participant preferences. METHODS: This was a cross-sectional survey of patients with RA and their physicians. Biologic-naïve patients with RA starting abatacept, infliximab, or rituximab were included. Both patients and physicians completed detailed questionnaires related to the infusion and satisfaction with the process. RESULTS: A total of 205 patients were enrolled: abatacept (n=102), infliximab (n=74), rituximab (n=29). Patients were primarily female (75%), Caucasian (85%), with a mean age of 58 years. Patients had a mean disease duration of approximately 8 years and had typically failed multiple DMARDs. Rituximab required the most pre-infusion preparation and the longest infusion time. Abatacept was associated with a shorter mean infusion time (42 minutes) than infliximab (131 minutes; p<0.0001) or rituximab (274 minutes; p<0.0001) and required less time away from work/home (p=0.01 and p<0.0001, respectively). Abatacept patients reported significantly less discomfort than rituximab patients (p=0.03), while discomfort was similar between abatacept and infliximab. From the physicians' perspective, compared to infliximab and rituximab abatacept was very easy to administer (57% vs. 27% and 5%, respectively), caused no pain/discomfort (52% vs. 42% and 31%), and had very infrequent infusion reactions (75% vs. 30% and 44%). CONCLUSION: The process involved in infusion administration, as perceived by both the patient and physician, seems to differ across the three infusible biologic agents and may have an impact on the decision-making process regarding which infusible biologic to use.
21125300 Endoscopic transnasal resection of the odontoid: case series and clinical course. 2011 Apr The transoral route is the gold standard for odontoid resection. Results are satisfying though surgery can be challenging for patients and surgeons due to its invasiveness. A less invasive transnasal approach could provide a sufficient extent of resection with less collateral damage. The technique of transnasal endoscopic odontoid resection is demonstrated by a case series of three patients. A fully endoscopic transnasal odontoid resection was conducted by use of CT-based neuronavigation. A complete odontoid resection succeeded in all patients. Symptoms such as dysarthria, swallowing disturbance, salivary retention, myelopathic gait disturbances, neck pain, and tetraparesis improved in all patients markedly. Transnasal endoscopic odontoid resection is a feasible alternative to the transoral technique. It leaves the oropharynx intact, which could result in lower approach related complications especially in patients with bulbar symptoms.
19920097 An open-source, self-explanatory touch screen in routine care. Validity of filling in the 2010 Jan OBJECTIVE: The Danish DANBIO registry has developed open-source software for touch screens in the waiting room. The objective was to assess the validity of outcomes from self-explanatory patient questionnaires on touch screen in comparison with the traditional paper form in routine clinical care. METHODS: Fifty-two AS patients and 59 RA patients completed Visual Analogue Scales (VASs) for pain, fatigue and global health, and Bath measures on Ankylosing Spondylitis Disease Activity Index (BASDAI) and Function Index (BASFI) (AS patients) or HAQs (RA patients) on touch screen and paper form in random order with a 1-h interval. Intra-class correlation coefficients (ICCs), 95% CIs and smallest detectable differences (SDDs) were calculated. RESULTS: ICC ranged from 0.922 to 0.988 (P < 0.001). The mean differences (95% CI) were: BASDAI [-0.5 (-14.5, 13.5) mm]; BASFI [-1.1 (-10.6, 8.4) mm]; Item 5 [-1.7 (-23.6, 20.2) mm] and Item 6 [-0.7 (-14.7, 13.3) mm] from BASDAI; HAQ score [0.023 (-0.183, 0.229)]. For VAS -0.4 to -2.8 mm (no significance for all except VAS global and VAS fatigue in RA). SDD for BASDAI was 14.0 mm; BASFI 9.5 mm; Item 5 21.8 mm; Item 6 14.0 mm; HAQ 0.206; VAS 11.1-18.8 mm. CONCLUSIONS: Self-explanatory touch screens based on the DANBIO open-source system generates valid results in AS and RA patients on completion of BASDAI, BASFI, HAQ and VAS scores for pain, fatigue and global health when compared with the traditional paper form. Implementation of touch screens in clinical practice is feasible and patients need no instruction.