Browse

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

ID PMID Title PublicationDate abstract
23199057 Did Rubens' Delilah have Mondor's disease? 2013 Mar BACKGROUND: Rubens was a master of European Baroque painting and a practitioner of realism. A female model for his paintings of Samson and Delilah and the Three Graces has apparent right-sided breast abnormalities. METHOD AND RESULTS: Examination of the images shows persistent changes. The clinical scenario suggests Mondor's disease, possibly related to rheumatoid arthritis or chronic infection. DISCUSSION: Visible breast changes such as distortion, skin retraction and nipple deviation warrant concern and require investigation.
25182058 Current and future therapeutic targets of rheumatoid arthritis. 2011 Rheumatoid arthritis (RA) is a chronic systematic autoimmune disease which affects about 1% of the population world wide. This article aimed to identify current therapeutic targets for RA based on data from the literature and drug target related databases. Identified targets were further analysed using a powerful bioinformatics tool, PANTHER (Protein ANalysis THrough Evolutionary Relationships). Additionally, we explored future possible therapeutic targets for RA and discussed the possibility of discovering novel drugs with improved efficacy and reduced toxicity for RA treatment. Data on current clinical drugs for RA treatment were extracted from the US Food and Drugs Administration (FDA) website. Candidate targets of RA were extracted from three online databases: Drugbank, Therapeutic Target Database (TTD) and Potential Drug Target Database (PDTD). A total of 95 clinical protein targets for RA have been identified and were analysed using the PANTHER Classification System. According to the PANTHER analysis, most commonly involved pathways in current RA targeting includes inflammation mediated by chemokine and cytokine signalling pathways, angiogenesis, p53 pathway, de novo purine biosynthesis, T-cell activation, apoptosis signalling pathway and vascular endothelial growth factor (VEGF) receptor signalling pathway. Accordingly, current clinical agents for the treatment of RA mainly include corticosteroids, non-steriodal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs). In addition, a number of investigational targets for RA have been identified and many novel drugs for RA therapy are under investigation. Current approaches to handle RA aim to ameliorate inflammation, to relieve pain, and most importantly to protect the cartilage, joints and bones from further damage by blocking proinflammatory molecules and inhibit the production of matrix-degrading factors. New drugs for RA with improved efficacy and safety should be developed.
22786458 Dysfunctional endogenous analgesia during exercise in patients with chronic pain: to exerc 2012 Jul BACKGROUND: Exercise is an effective treatment for various chronic pain disorders, including fibromyalgia, chronic neck pain, osteoarthritis, rheumatoid arthritis, and chronic low back pain. Although the clinical benefits of exercise therapy in these populations are well established (i.e. evidence based), it is currently unclear whether exercise has positive effects on the processes involved in chronic pain (e.g. central pain modulation). OBJECTIVES: Reviewing the available evidence addressing the effects of exercise on central pain modulation in patients with chronic pain. METHODS: Narrative review. RESULTS: Exercise activates endogenous analgesia in healthy individuals. The increased pain threshold following exercise is due to the release of endogenous opioids and activation of (supra)spinal nociceptive inhibitory mechanisms orchestrated by the brain. Exercise triggers the release of beta-endorphins from the pituitary (peripherally) and the hypothalamus (centrally), which in turn enables analgesic effects by activating μ-opioid receptors peripherally and centrally, respectively. The hypothalamus, through its projections on the periaqueductal grey, has the capacity to activate descending nociceptive inhibitory mechanisms. However, several groups have shown dysfunctioning of endogenous analgesia in response to exercise in patients with chronic pain. Muscle contractions activate generalized endogenous analgesia in healthy, pain-free humans and patients with either osteoarthritis or rheumatoid arthritis, but result in increased generalised pain sensitivity in fibromyalgia patients. In patients having local muscular pain (e.g. shoulder myalgia), exercising non-painful muscles activates generalized endogenous analgesia. However, exercising painful muscles does not change pain sensitivity either in the exercising muscle or at distant locations. LIMITATIONS: The reviewed studies examined acute effects of exercise rather than long-term effects of exercise therapy. CONCLUSIONS: A dysfunctional response of patients with chronic pain and aberrations in central pain modulation to exercise has been shown, indicating that exercise therapy should be individually tailored with emphasis on prevention of symptom flares. The paper discusses the translation of these findings to rehabilitation practice together with future research avenues.
22655000 Determinants of Risk Infection During Therapy with Anti TNF-Alpha Blocking Agents in Rheum 2012 The use of TNF-alpha antagonists (infliximab, etanercept, adalimumab) has changed the course of many rheumatic diseases including rheumatoid arthritis (RA). Since their approval, some questions regarding their safety including infections have been observed. The aim of the study was to evaluate the changes in cytokines levels and cells subsets in patients with RA during anti TNF blocking agents treatment and the possible effect on infections' development. We evaluated in 89 RA patients [39 treated with etanercept (ETN), 29 with adalimumab (ADA) and 21 with infliximab (IFN)] at baseline and after 6 months the following parameters: procalcitonin, ESR, CRP, cytokines as TNF, IL-6, IL-10, IL-8 and the TNF/IL-10 ratio, and peripheral mononuclear cells as CD3+, CD3+/CD4+, CD3+/CD8+, CD19+, CD3- /CD16+/56+, CD14+HLADR+, CD20+, CD19+/CD38+. Peripheral mononuclear cells were detected by flow cytometric system Cytomics FC500 and cytokines circulating levels by a quantitative sandwich enzyme immunoassay technique (Human IL-8 Instant ELISAe Bioscience, Human IL-6 Instant ELISA e Bioscience, Human IL-10 Instant ELISAe Bioscience and Human TNF-a Quantikine immunoassay RD system). A lower reduction of CD14+HLADR+ in ADA group 54.6±10.4% vs ETA 48.4±15.7% vs INF 40.7±16.5%, p<0.039 was found. No differences in all three groups on peripheral mononuclear cells CD3+, CD3+/CD4+, CD3+/CD8+, CD19+, CD 20+, CD19+/CD38+, CD3-/CD16+/56+, and cytokine circulating levels were found. The number of infections at 6 months was: 10.3% in ADA group, 12.8% in ETN group and 19.04% in IFN group. A correlation was found between the reduction in CD14+HLADR+ cells and IFN treatment. Our data showed that the level of CD14+HLADR+ cells was reduced during therapy with IFN. ADA and ETN don't reduce lymphocyte populations and their subsets such as CD14+HLADR+ cells that play an important role host defence.
22069275 Evidence for the role of STAT4 as a general autoimmunity locus in the Korean population. 2011 Nov BACKGROUND: Recently, the association of a common STAT4 haplotype with type 1 diabetes (T1D) as well as rheumatoid arthritis has been documented in Caucasians and Koreans. STAT4 is involved in the signalling of interleukin-12 and γIFN, as well as interleukin-23. To discover genes affecting the susceptibility of common autoimmune diseases, we studied the association of polymorphisms in STAT4 with autoimmune thyroid disease (AITD) as well as T1D in the Korean population. SUBJECTS AND METHODS: Four single-nucleotide polymorphisms on the chromosome 2q (rs11889341, rs7574865, rs8179673, and rs10181656), which were found to associate with rheumatoid arthritis were examined for association in a Korean sample of 428 AITD, 418 T1D patients, and 1060 controls. RESULTS: The minor alleles of all four single-nucleotide polymorphisms and the reconstructed STAT4 haplotypes conferred significant degree of risk for AITD (p=10(-2) to 10(-4)). Although we found a weak association of rs11889341 with T1D (p<0.05), the same haplotypes were not associated with T1D susceptibility. When we stratified T1D patients according to the age of onset, the minor alleles of all four single-nucleotide polymorphisms and the same haplotypes showed significant association with the susceptibility of T1D in the early-onset subgroup (p<0.01), not in the late-onset subgroup. CONCLUSION: STAT4 alleles and the same haplotypes might influence cytokine signalling, and therefore the development of AITD as well as T1D. These results reinforce the influence of STAT4 gene as a general autoimmune gene.
23145356 "Now I see a brighter day": expectations and perceived benefits of an Iyengar yoga interve 2011 Jun 11 Rheumatoid arthritis (RA) is a chronic disease characterized by inflammation of joints and associated fatigue, deteriorated range of motion, and impaired psychosocial functioning. Young adults with RA are at a particular risk for compromised health-related quality of life, and there is a need for safe, effective complementary treatment in addition to traditional medical approaches. The aim of the present study was to use face-to-face participant interviews, conducted before and after an Iyengar yoga (IY) program, to examine mechanisms through which yoga may be beneficial to young adults with RA.This pilot study utilized a single-arm design where all participants received the intervention. Classes were taught twice per week (1.5 hours each) for 6 weeks by an IY teacher qualified in therapeutics. Interview themes included participants' baseline expectations about yoga and viewpoints as to how their functioning had been impacted by the IY intervention were examined. Five young adults with RA aged 24-31 years (mean = 28; 80% female) completed the yoga intervention. Participants consistently reported that yoga helped with energy, relaxation and mood and they discussed perceived mechanisms for how yoga impacted well-being. Mechanisms included physical changes such as range of motion and physiological awareness, and psychospiritual developments such as acceptance, coping, self-efficacy and mindfulness. Though the study is limited, participants' responses provide compelling evidence that IY for RA patients is an intervention worthy of further exploration. The mechanisms and outcomes reported by participants support a biopsychosocial model, which proposes that yoga benefits patients through both physiological and psychospiritual changes.
21120596 Anti-inflammatory and anti-oxidant properties of Curcuma longa (turmeric) versus Zingiber 2011 Aug Turmeric (rich in curcuminoids) and ginger (rich in gingerols and shogaols) rhizomes have been widely used as dietary spices and to treat different diseases in Ayurveda/Chinese medicine since antiquity. Here, we compared the anti-inflammatory/anti-oxidant activity of these two plants in rat adjuvant-induced arthritis (AIA). Both plants (at dose 200 mg/kg body weight) significantly suppressed (but with different degrees) the incidence and severity of arthritis by increasing/decreasing the production of anti-inflammatory/pro-inflammatory cytokines, respectively, and activating the anti-oxidant defence system. The anti-arthritic activity of turmeric exceeded that of ginger and indomethacin (a non-steroidal anti-inflammatory drug), especially when the treatment started from the day of arthritis induction. The percentage of disease recovery was 4.6-8.3% and 10.2% more in turmeric compared with ginger and indomethacin (P < 0.05), respectively. The present study proves the anti-inflammatory/anti-oxidant activity of turmeric over ginger and indomethacin, which may have beneficial effects against rheumatoid arthritis onset/progression as shown in AIA rat model.
23133648 Type II collagen induces peripheral tolerance in BALB/c mice via the generation of CD8+ T 2012 Antigens introduced into the anterior chamber (AC) of the eye induce a potent form of antigen-specific peripheral immune tolerance termed AC-associated immune deviation (ACAID), which prevents inflammatory immune responses and is characterized by impaired delayed-type hypersensitivity (DTH) responses. Type-II collagen (CII) is a fibrillar protein expressed exclusively in cartilage tissues. Although of its clinical relevance to Rheumatoid arthritis, aging, and osteoarthritis, there have been no studies to date to test if CII has the ability to induce ACAID. We hypothesized that ACAID could be generated via AC injection of CII in BALB/c mice. Using a DTH assay, the hypothesis was supported and led to another hypothesis that CII is capable of inducing specific immune tolerance via CD8(+) T regulatory cells (Tregs). Thus, we performed functional local adoptive transfer (LAT) assays to examine the regulatory roles of spleen cells, T cells, and CD8(+) T cells in the specific immune regulation induced by CII injection into the AC. Results indicated that CII induced ACAID when injected into the AC. Spleen cells of mice injected with CII in the AC significantly suppressed DTH responses. The T cell compartment of the spleen was capable of expressing this suppression. CD8(+) Tregs could solely express this CII-driven suppression and even exerted more noticeable suppression than spleen cells or splenic T cells. This study suggests a crucial role for CD8(+) Tregs in mediating CII-driven ACAID-mediated immune tolerance. This could have therapeutic implications in Rheumatoid arthritis, aging, osteoarthritis, and other diseases in which CII is involved.
23020731 Pathologic quantification of connective tissue disease-associated versus idiopathic usual 2012 Oct CONTEXT: Usual interstitial pneumonia (UIP) is a common chronic interstitial pneumonitis. It can occur idiopathically (I-UIP) or in the setting of systemic connective tissue disease (CTD-UIP). Some studies suggest that CTD-UIP has a better prognosis than I-UIP. The histologic differences between CTD-UIP and I-UIP are not clearly defined. OBJECTIVE: The purpose of this study was to evaluate histologic criteria that may differentiate CTD-UIP from I-UIP, including fibroblastic foci (FFs), lymphoid aggregates (LAs), and the presence of nonspecific interstitial pneumonia pattern. DESIGN: Thirty-five patients with histologic diagnoses of UIP were identified (27 biopsies [77%]; 8 explants [23%]). Biopsy slides were scanned and analyzed quantitatively for FF size, FF area, LA size, and LA area. Biopsy and explant slides were examined qualitatively for the presence of a nonspecific interstitial pneumonia pattern in areas away from UIP fibrosis. Results.-Of 27 biopsies, the number and size of FFs in CTD-UIP were smaller than they were in I-UIP. The number and size of LAs were larger in patients with rheumatoid arthritis than they were in patients with I-UIP. There was no interobserver variability among 3 pathologists using this quantitative system. Of 35 biopsies and explants, there was a higher prevalence of the nonspecific interstitial pneumonia pattern among patients with CTD-UIP than there was among patients with I-UIP (P = .005). CONCLUSIONS: Patients with CTD-UIP had fewer, smaller FFs than did patients with I-UIP, and patients with rheumatoid arthritis-UIP had more, larger LAs than did patients with I-UIP. Of importance, the coexistence of UIP and the nonspecific interstitial pneumonia patterns was one of the most salient features in distinguishing CTD-UIP from I-UIP because CTD-UIP demonstrated an increased prevalence of multilobar, cellular, nonspecific interstitial pneumonia patterns in areas away from the UIP fibrosis.
22768863 [Affinity optimization of an anti-hIL17A single-chain Fv antibody through error-prone PCR 2012 Jul AIM: To optimize antibody affinity of a humanized anti-hIL17A single-chain Fv (scFV) antibody through error-prone polymerase chain reaction (PCR) so as to develop a therapeutic humanized antibody for the treatment of rheumatoid arthritis (RA). METHODS: Variable regions of heavy chain and light chain were subjected to random mutation by error-prone PCR and a scFv library was constructed by overlapping PCR. The library was screened for improved mutants by the bacterial inner membrane display technique and flow cytometry (FCM). Real-time PCR was used to detect neutralization effects of the purified scFv antibody mutants on mRNA expressions of IL-6 and IL-8 in HeLa cells stimulated by hIL17A. RESULTS: We obtained five mutants with improved affinity. FCM revealed that the affinity of three clones was greatly enhanced as compared with the parent clone. All mutants retained binding specificity to hIL17A. Real-time PCR results showed that all five mutants could block hIL17A stimulation of HeLa cells to express IL-6 and IL-8, and the neutralization effects were positively related to mutant affinity. CONCLUSION: Error-prone PCR technique is a feasible method for antibody affinity optimization in vitro, which is able to improve the affinity and neutralization capacity of antibody on the basis of its unchanged antigen binding specificity. This study provides potential drug candidates aimed for the treatment of rheumatoid arthritis and an alternative method of optimizing antibody affinity in vitro.
22441388 Modulation of anti-tumor necrosis factor alpha (TNF-α) antibody secretion in mice immuniz 2012 May Tumor necrosis factor alpha (TNF-α) blockade is an effective treatment for patients with TNF-α-dependent chronic inflammatory diseases, such as rheumatoid arthritis, Crohn's disease, and psoriasis. TNF-α kinoid, a heterocomplex of human TNF-α and keyhole limpet hemocyanin (KLH) (TNF-K), is an active immunotherapy targeting TNF-α. Since the TNF-K approach is an active immunization, and patients receiving this therapy also receive immunosuppressant treatment, we evaluated the effect of some immunosuppressive drugs on the generation of anti-TNF-α antibodies produced during TNF-K treatment. BALB/c mice were injected intramuscularly with TNF-K in ISA 51 adjuvant. Mice were also injected intraperitoneally with one of the following: phosphate-buffered saline, cyclophosphamide, methylprednisolone, or methotrexate. Anti-TNF-α and anti-KLH antibody levels were assessed by enzyme-linked immunosorbent assay and the anti-TNF-α neutralizing capacity of sera by L929 bioassay. Our results showed that current treatments used in rheumatoid arthritis, such as methylprednisolone and methotrexate, do not significantly alter anti-TNF-α antibody production after TNF-K immunization. In contrast, the administration of cyclophosphamide (200 mg/kg) after immunization significantly reduced anti-TNF-α antibody titers and their neutralizing capacity.
22267889 Predictors of Medication Adherence in Patients with Rheumatoid Arthritis. 2011 Dec Medication adherence is a significant problem in patients with rheumatoid arthritis (RA), a prevalent autoimmune disease. Due to the equivocal results reported in the research, consistent predictors of medication adherence in patients with RA are undetermined. A cross-sectional descriptive, predictive study of 108 patients with RA was used to: 1) describe self-reported medication adherence to disease modifying anti-rheumatic drugs (DMARDs); 2) compare demographic (age, residence, marital status, employment status, years of education, and ethnicity) and clinical (duration of disease and number of medications) factors of adherent and non-adherent individuals; and 3) determine the predictive power of demographic and clinical factors for DMARD adherence using various cut-points (research-based, mean, and median) on a validated, self-report scale measuring medication adherence. Independent samples t-tests, Chi square analyses, and logistic regression modeling were used to analyze these data. Approximately 90% of the individuals with RA reported adherence with their prescribed DMARD prescriptions. The only demographic and clinical difference between the adherent and non-adherent group was ethnicity (p=0.04); nonwhite individuals reported significantly less adherence with their prescribed DMARDs when compared to white individuals. Logistic regression models identified ethnicity (OR= 3.34-10.1; p< 0.05) and the number of medications taken (OR=1.7; p< 0.05) as predictors of medication non-adherence. These data provide evidence that ethnicity and taking an increased number of prescribed medications are independent predictors of medication adherence in patients with RA. These findings confirm the presence of a health disparity and an area where further research is needed to optimize patient outcomes.
21848493 A mixed treatment comparison of the short-term efficacy of biologic disease modifying anti 2011 Oct BACKGROUND: The short-term efficacy of biological disease modifying anti-rheumatic drugs (bDMARDs) for the treatment of established moderate to severe rheumatoid arthritis (RA) has been demonstrated by various randomized placebo or active treatment controlled trials. However, there is a lack of direct comparison of these agents. SCOPE: To compare the short-term efficacy of nine bDMARDs - abatacept, adalimumab, anakinra, certolizumab, etanercept, golimumab, infliximab, rituximab and tocilizumab - in patients with established RA. FINDINGS: A systematic review was conducted to obtain all available efficacy data for each included bDMARD. Medline, EMBASE, and Cochrane clinical trials were searched for trials in patients with RA. Twenty-seven trials were retrieved from a systematic literature search and included in the meta-analysis. Mixed treatment comparison (MTC) techniques were used to perform indirect comparisons. Analyses were conducted to estimate the odds ratio of an ACR20, ACR50, and ACR70 response at approximately six months if treated with a bDMARD compared with placebo or methotrexate. Between-drug comparisons were also made. The analyses were performed including recommended doses only (as per the product information). All drugs except anakinra and golimumab demonstrated a statistically significant advantage compared to control treatment for ACR20 responses. The between-drug comparisons revealed a statistically significant advantage for certolizumab compared to most bDMARDs for ACR20, ACR50 and ACR70 response and for etanercept versus adalimumab and anakinra for ACR20 and ACR50 response, as well as a statistically significant advantage for tocilizumab versus anakinra for ACR50 response. CONCLUSION: The analyses, using MTC of efficacy of nine bDMARDs suggest that treatment with anakinra is inferior to other bDMARDs and that etanercept and certolizumab may be more effective than other bDMARDs. There are some limitations of our analyses due to MTC assumptions, variations in trial design and the fact that only ACR outcomes at six months were included.
21794822 [Influence of the physical therapy on the health and quality of life of the rheumatic pati 2011 Jul OBJECTIVE: To evaluate the effectiveness of a specific physical therapy treatment on stiffness, pain and quality of life (HRQL) in rheumatic patients. METHODS: Experimental, prospective, longitudinal and intervention study. It involved 29 individuals with a mean age (SD) of 54.16 (11,9) years, belonging to the Salmantina Association of Rheumatoid Arthritis Patients, randomized into 2 groups: treatment (GT) and control (GC). The study analyzed the time in minutes of morning stiffness, pain -using the Downie Scale- and CVRS through the Nottingham Health Profile (NHP) and the Health Questionnaire SF-36 (SF-36). It carries out an individual treatment that includes mainly physiotherapy manual techniques in one or two sessions per week for six months. RESULTS: The time of early morning stiffness showed a mean (SD) 21.38 (29.99) minutes (GC=20,38, GT=22.19), increasing in GC (26.82) and decreasing in GT (12,5). Pain presented at the beginning a mean (SD) 3.6 (2.03) points (GC=2,85, GT=4.22) decreasing in GT (3.68) and increasing in GC (3.45). There was an improvement of CVRS in the GT with decreased scores on four dimensions of NHP (pain, sleep, physical mobility and emotional reactions) and increases in SF-36 (physical problems, social function, pain, function physics). In any case the results were statistically significant. CONCLUSION: The study cannot conclude the effectiveness of physiotherapy in the treatment of rheumatoid arthritis although the results show a decrease of morning stiffness and pain and increased CVRS, which is clinically interesting.
21639923 A traditional Chinese medicine versus Western combination therapy in the treatment of rheu 2011 Jun 4 BACKGROUND: The common randomized controlled trial design has distinct limitations when applied to Chinese medicine, because Chinese medicine identifies and treats 'Chinese medicine patterns' rather than diagnosed diseases. Chinese medicine patterns are a group of associated symptoms, tongue appearances and pulse characteristics. These limitations could be overcome by developing new strategies to evaluate the effect of Chinese medicine. The idea behind pattern-based efficacy evaluations may optimize clinical trial design by identifying the responsiveness-related Chinese medicine patterns. METHODS/DESIGN: This is a two-stage multi-center trial of Chinese herbal medicine for the management of rheumatoid arthritis. The stage one trial is an open-label trial and aims to explore what groups of Chinese medicine information (such as symptoms) correlates with better efficacy, and the stage two trial is a randomized, controlled, double-blind, double-dummy clinical trial that incorporates the efficacy-related information identified in the stage-one trial into the inclusion criteria. DISCUSSION: The indication of a Chinese herbal formula is a specific Chinese medicine pattern and not a single disease and stratifying a disease into several patterns with a group of symptoms is a feasible procedure in clinical trials. This study is the first to investigate whether this approach in the design of Chinese herbal medicine trials can improve responses. TRIAL REGISTRATION: ChiCTR-TRC-10000989.
22950670 Lung adenocarcinoma with Lambert-Eaton myasthenic syndrome indicated by voltage-gated calc 2012 Sep 5 INTRODUCTION: Lambert-Eaton myasthenic syndrome is a rare disorder and it is known as a paraneoplastic neurological syndrome. Small cell lung cancer often accompanies this syndrome. Lambert-Eaton myasthenic syndrome associated with lung adenocarcinoma is extremely rare; there are only a few reported cases worldwide. CASE PRESENTATION: A 75-year-old Japanese man with a past history of chronic rheumatoid arthritis and Sjögren syndrome was diagnosed with Lambert-Eaton myasthenic syndrome by electromyography and serum anti-P/Q-type voltage-gated calcium channel antibody level preceding the diagnosis of lung cancer. A chest computed tomography to screen for malignant lesions revealed an abnormal shadow in the lung. Although a histopathological examination by bronchoscopic study could not reveal the malignancy, lung cancer was mostly suspected after the results of a chest computed tomography and [18F]-fluorodeoxyglucose positron emission tomography. An intraoperative diagnosis based on the frozen section obtained by tumor biopsy was adenocarcinoma so the patient underwent a lobectomy of the right lower lobe and lymph node dissection with video-assisted thoracoscopic surgery. The permanent pathological examination was the same as the frozen diagnosis (pT2aN1M0: Stage IIa: TNM staging 7th edition). Immunohistochemistry revealed that most of the cancer cells were positive for P/Q-type voltage-gated calcium channel. CONCLUSIONS: Our case is a rare combination of Lambert-Eaton myasthenic syndrome associated with lung adenocarcinoma, rheumatoid arthritis and Sjögren syndrome, and to the best of our knowledge it is the first report that indicates the presence of voltage-gated calcium channel in lung adenocarcinoma by immunostaining.
22889288 Reliability of the TekScan MatScan® system for the measurement of postural stability in o 2012 Aug 13 BACKGROUND: Postural stability can be measured in clinical and research settings using portable plantar pressure systems. People with rheumatoid arthritis (RA) have decreased postural stability compared to non-RA populations and impaired postural stability is associated with falls in people with RA. The purpose of this study was therefore to investigate the reliability of the TekScan MatScan® system in assessing postural stability in people with RA. METHODS: Twenty three participants with RA, mean (SD) age 69.74 (10.1) years, were assessed in barefoot double-limb quiet standing, with eyes open and eyes closed, for antero-posterior and medio-lateral postural sway values. Three repetitions, at a sampling frequency of 40 Hz, were recorded for each test condition to obtain a mean value. Measurements were repeated one hour later. Intraclass correlation coefficients (ICC) with 95% confidence intervals (CI) were calculated to determine between-session reliability. Measurement error was assessed through the calculation of the standard error of the measurement (SEM) and the smallest real difference (SRD). RESULTS: The system displayed good to excellent reliability for antero-posterior and medio-lateral sway, with eyes open and closed, as indicated by ICC values ranging from 0.84 to 0.92. Measurement error, as evidenced by the SEM, ranged from 1.27 to 2.35 mm. The degree of change required to exceed the expected trial to trial variability was relatively high, compared to mean values, with SRD ranging from 3.08 to 5.71 mm. CONCLUSIONS: The portability and ease of use of the TekScan MatScan® makes it a useful tool for the measurement of postural stability in clinical and research settings. The TekScan MatScan® system can reliably measure double-limb quiet standing in older people, aged 60 to 80 years, with RA.
23144258 Regional and temporal variation in the treatment of rheumatoid arthritis across the UK: a 2012 OBJECTIVES: To describe current disease-modifying antirheumatic drugs (DMARDs) prescription in rheumatoid arthritis (RA) with reference to best practice and to identify temporal and regional trends in the UK. DESIGN: Descriptive, register-based cohort study. PARTICIPANTS: Permanently registered patients aged ≥18 years with a recorded diagnosis of RA between 1 January 1995 and 31 March 2010 and matched controls. Participants with RA were identified through screening of all patients in the General Practice Research Database (GPRD) with a clinical or referral record for RA and at least 1 day of follow-up. SETTING: 639 general practices in the UK supplying data to the GPRD. MAIN OUTCOME MEASURES: Medication prescribing between 3 and 12 months of RA diagnosis by region and time period (1995-1999, 2000-2005 and 2006-April 2010). RESULTS: Of the 35 911 patients in the full RA cohort, 15 259 patients (42%) had incident RA. Analysis of prescribing in incident RA patients demonstrated that between 1995 (baseline) and 2010 there was a substantial increase in DMARD, and specifically methotrexate, prescribing across all regions with a less marked increase in combination DMARD prescribing. Taking 12-month prescribing as a snapshot: DMARD prescribing was 19-49% at baseline increasing to 45-74% by 2006-April 2010; methotrexate prescribing was 4-16% at baseline increasing to 32-60%; combination DMARD prescribing was 0-8% at baseline increasing to 3-17%. However, there was marked regional variation in the proportion of RA patients receiving DMARD regardless of time period. CONCLUSIONS: There has been a substantial increase in prescribing of DMARDs for RA since 1995; however, regional variation persists across the UK with relative undertreatment, according to established best practice. Improved implementation of evidence-based best clinical practice to facilitate removal of treatment variation is warranted. This may occur as a result of the implementation of published national guidance.
22931205 Formulation development and statistical optimization of chronotherapeutic tablets of indom 2013 Sep Chronotherapeutic drug delivery offers a new approach in the pharmacologic interventions design for the effective treatment in the diseases which follows circadian rhythm. In the present study chronotherapeutic tablets of indometacin was designed to match the timing of rheumatoid arthritis treatment with the intrinsic illness timing. The developed chronotherapeutic delivery system consists of a core tablet containing the active ingredient along with osmogents and other excipients, which was coated with a swellable polymer, hydroxyl propyl methyl cellulose by compression coating technique. The time controlled release was achieved by coating the entire system with a combination of pH-independent polymer, Eudragit RS 100 and Eudragit RL 100 (1:1). The optimization technique using Box-Behnken design was employed for the selection of the ideal formula. The optimization procedure was validated, and the observed value of the ideal batch was found to be similar with the predicted values within 5% of predicted error. The formulation when administered at bed time starts releasing the drug after a lag time of 4 h and provides sufficient plasma concentration after 6 h of normal sleep. Thus, the tablets can be successfully used for the chronotherapeutic drug delivery of indometacin in the treatment of rheumatoid arthritis.
22583466 Tails from the peak district: adjusted limited dependent variable mixture models of EQ-5D 2012 May OBJECTIVES: Health utility data generated by using the EuroQol five-dimensional (EQ-5D) questionnaire are right bounded at 1 with a substantial gap to the next set of observations, left bounded, and multimodal. These features present challenges to the estimation of the effect of clinical and socioeconomic characteristics on health utilities. Our objective was to develop and demonstrate an appropriate method for dealing with these features. METHODS: We developed a statistical model that incorporates an adjusted limited dependent variable approach to reflect the upper bound and the large gap in feasible EQ-5D questionnaire values. Further flexibility was then gained by adopting a mixture modeling framework to address the multimodality of the EQ-5D questionnaire distribution. We compared the performance of these approaches with that of those frequently adopted in the literature (linear and Tobit models) by using data from a clinical trial of patients with rheumatoid arthritis. RESULTS: We found that three latent classes are appropriate in estimating EQ-5D questionnaire values from function, pain, and sociodemographic factors. Superior performance of the adjusted limited dependent variable mixture model was achieved in terms of Akaike and Bayesian information criteria, root mean square error, and mean absolute error. Unlike other approaches, the adjusted limited dependent variable mixture model fits the data well at high EQ-5D questionnaire levels and cannot predict unfeasible EQ-5D questionnaire values. CONCLUSIONS: The distribution of the EQ-5D questionnaire is characterized by features that raise statistical challenges. It is well known that standard approaches do not perform well for this reason. This article developed an appropriate method to reflect these features by combining limited dependent variable and mixture modeling and demonstrated superior performance in a rheumatoid arthritis setting. Further refinement of the general framework and testing in other data sets are warranted. Analysis of utility data should apply methods that recognize the distributional features of the data.