Distribution by Scientific Domains

Kinds of Followup

  • median followup

  • Terms modified by Followup

  • followup study

  • Selected Abstracts

    Selection Criteria for Emergency Medicine Residency Applicants

    Joseph T. Crane MD
    Abstract: Objectives: To determine the criteria used by emergency medicine (EM) residency selection committees to select their residents, to determine whether there is a consensus among residency programs, to inform programs of areas of possible inconsistency, and to better educate applicants pursuing careers in EM. Methods: A questionnaire consisting of 20 items based on the current Electronic Residency Application Service (ERAS) guidelines was mailed to the program directors of all 118 EM residencies in existence in February 1998. The program directors were instructed to rank each item on a five-point scale (5 = most important, 1 = least important) as to its importance in the selection of residents. Followup was done in the form of e-mail and facsimile. Results: The overall response rate was 79.7%, with 94 of 118 programs responding. Items ranking as most important (4.0-5.0) in the selection process included: EM rotation grade (mean ± SD = 4.79 ± 0.50), interview (4.62 ± 0.63), clinical grades (4.36 ± 0.70), and recommendations (4.11 ± 0.85). Moderate emphasis (3.0-4.0) was placed on: elective done at program director's institution (3.75 ± 1.25), U.S. Medical Licensing Examination (USMLE) step II (3.34 ± 0.93), interest expressed in program director's institution (3.30 ± 1.19), USMLE step I (3.28 ± 0.86), and awards/achievements (3.16 ± 0.88). Less emphasis (<3.0) was placed on Alpha Omega Alpha Honor Society (AOA) status (3.01 ± 1.09), medical school attended (3.00 ± 0.85), extracurricular activities (2.99 ± 0.87), basic science grades (2.88 ± 0.93), publications (2.87 ± 0.99), and personal statement (2.75 ± 0.96). Items most agreed upon by respondents (lowest standard deviation, SD) included EM rotation grade (SD 0.50), interview (SD 0.63), and clinical grades (SD 0.70). Of the 94 respondents, 37 (39.4%) replied they had minimum requirements for USMLE step I (195.11 ± 13.10), while 30 (31.9%) replied they had minimum requirements for USMLE step II (194.27 ± 14.96). Open-ended responses to "other" were related to personal characteristics, career/goals, and medical school performance. Conclusions: The selection criteria with the highest mean values as reported by the program directors were EM rotation grade, interview, clinical grades, and recommendations. Criteria showing the most consistency (lowest SD) included EM rotation grade, interview, and clinical grades. Results are compared with those from previous multispecialty studies. [source]

    Posttraumatic stress symptoms, PTSD, and risk factors among lower Manhattan residents 2,3 years after the September 11, 2001 terrorist attacks

    Laura DiGrande
    Manhattan residents living near the World Trade Center may have been particularly vulnerable to posttraumatic stress disorder (PTSD) after the September 11, 2001 (9/11) terrorist attacks. In 2003,2004, the authors administered the PTSD Checklist to 11,037 adults who lived south of Canal Street in New York City on 9/11. The prevalence of probable PTSD was 12.6% and associated with older age, female gender, Hispanic ethnicity, low education and income, and divorce. Injury, witnessing horror, and dust cloud exposure on 9/11 increased risk for chronic PTSD. Postdisaster risk factors included evacuation and rescue and recovery work. The results indicate that PTSD is a continued health problem in the local community. The relationship between socioeconomic status and PTSD suggests services must target marginalized populations. Followup is necessary on the course and long-term consequences of PTSD. [source]

    Effectiveness of rituximab treatment in primary Sjögren's syndrome: A randomized, double-blind, placebo-controlled trial,

    ARTHRITIS & RHEUMATISM, Issue 4 2010
    J. M. Meijer
    Objective To study the efficacy and safety of B cell depletion with rituximab, a chimeric murine/human anti-CD20 monoclonal antibody, in patients with primary Sjögren's syndrome (SS) in a double-blind, randomized, placebo-controlled trial. Methods Patients with active primary SS, as determined by the revised American,European Consensus Group criteria, and a rate of stimulated whole saliva secretion of ,0.15 ml/minute were treated with either rituximab (1,000 mg) or placebo infusions on days 1 and 15. Patients were assigned randomly to a treatment group in a ratio of 2:1 (rituximab:placebo). Followup was conducted at 5, 12, 24, 36, and 48 weeks. The primary end point was the stimulated whole saliva flow rate, while secondary end points included functional, laboratory, and subjective variables. Results Thirty patients with primary SS (29 female) were randomly allocated to a treatment group. The mean ± SD age of the patients receiving rituximab was 43 ± 11 years and the disease duration was 63 ± 50 months, while patients in the placebo group were age 43 ± 17 years and had a disease duration of 67 ± 63 months. In the rituximab group, significant improvements, in terms of the mean change from baseline compared with that in the placebo group, were found for the primary end point of the stimulated whole saliva flow rate (P = 0.038 versus placebo) and also for various laboratory parameters (B cell and rheumatoid factor [RF] levels), subjective parameters (Multidimensional Fatigue Inventory [MFI] scores and visual analog scale [VAS] scores for sicca symptoms), and extraglandular manifestations. Moreover, in comparison with baseline values, rituximab treatment significantly improved the stimulated whole saliva flow rate (P = 0.004) and several other variables (e.g., B cell and RF levels, unstimulated whole saliva flow rate, lacrimal gland function on the lissamine green test, MFI scores, Short Form 36 health survey scores, and VAS scores for sicca symptoms). One patient in the rituximab group developed mild serum sickness,like disease. Conclusion These results indicate that rituximab is an effective and safe treatment strategy for patients with primary SS. [source]

    "A Large Object with a Small Museum": A Narrative Analysis of Tlotlo's Experience of an Astronomy Science Center

    Anthony Lelliott
    We illustrate the power of narrative in illuminating the importance of the student's perspective in understanding the conditions for learning in a museum setting. Using principles of narrative presentation, the paper describes Tlotlo's thinking throughout his participation in a school visit to the visitors' center at a radio telescope. The paper discusses six features of the visit: student misconceptions; inadequate preparation and followup; memories and imaginings; enjoyment; discussing the visit afterwards; and socioeconomic constraints on visits. These features are examined within the context of a developing country: both confirming previous research on school visits and providing new insights into how such visits can be interpreted. The significance of narrative analysis for science center educators is discussed and suggested as appropriate for current research in museums. [source]

    Physical activity and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

    Nina Føns Johnsen
    Abstract The evidence concerning the possible association between physical activity and the risk of prostate cancer is inconsistent and additional data are needed. We examined the association between risk of prostate cancer and physical activity at work and in leisure time in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. In our study, including 127,923 men aged 20,97 years from 8 European countries, 2,458 cases of prostate cancer were identified during 8.5 years of followup. Using the Cox proportional hazards model, we investigated the associations between prostate cancer incidence rate and occupational activity and leisure time activity in terms of participation in sports, cycling, walking and gardening; a metabolic equivalent (MET) score based on weekly time spent on the 4 activities; and a physical activity index. MET hours per week of leisure time activity, higher score in the physical activity index, participation in any of the 4 leisure time activities, and the number of leisure time activities in which the participants were active were not associated with prostate cancer incidence. However, higher level of occupational physical activity was associated with lower risk of advanced stage prostate cancer (ptrend = 0.024). In conclusion, our data support the hypothesis of an inverse association between advanced prostate cancer risk and occupational physical activity, but we found no support for an association between prostate cancer risk and leisure time physical activity. © 2009 UICC [source]

    Abstracts: In vitro/in vivo and analytical evaluation of sunless tanning formulations containing different rheology modifiers

    O. V. Dueva-Koganov
    pp. 73,83 In vitro data suggest that different in vivo performances are expected for two dihydroxyacetone (DHA)-containing formulations with similar concentrations of DHA and excipients but different commercially available rheology modifiers: one with a cationic polymer-based rheology modifier (blend) [dimethylacrylamide/ethyltrimonium chloride methacrylate copolymer (and) propylene glycol dicaprylate/dicaprate (and) PPG-1 trideceth-6 (and) C10-11 isoparaffin]; and the other with a polyacrylamide-based rheology modifier (blend) [polyacrylamide (and) C13-14 isoparaffin (and) laureth-7]. Both rheology modifiers (blends) contained comparable levels of polymers and were used at 3% w/w (as supplied). Differences in color development were illustrated in vitro with respect to the yellow/red and lightness/chroma parameters, which were confirmed in the followup in vivo studies. The test article with the cationic polymer-based rheology modifier produced a more natural sunless tan, comparable to a desirable sun-induced tan, for all panelists, one that was more uniform and lasted longer compared with the sunless tan generated by the test article with the polyacrylamide-based rheology modifier. A method for HPLC analysis of DHA in sunless tanning formulations was established and utilized to confirm concentrations of DHA in test articles. [source]

    Outcomes of eating disorders: A systematic review of the literature,

    Nancy D. Berkman PhD
    Abstract Objective: The RTI International-University of North Carolina at Chapel Hill Evidence-based Practice Center systematically reviewed evidence on factors associated with outcomes among individuals with anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) and whether outcomes differed by sociodemographic characteristics. Method: We searched electronic databases including MEDLINE and reviewed studies published from 1980 to September, 2005, in all languages against a priori inclusion/exclusion criteria and focused on eating, psychiatric or psychological, or biomarker outcomes. Results: At followup, individuals with AN were more likely than comparisons to be depressed, have Asperger's syndrome and autism spectrum disorders, and suffer from anxiety disorders including obsessive-compulsive disorders. Mortality risk was significantly higher than what would be expected in the population and the risk of suicide was particularly pronounced. The only consistent factor across studies relating to worse BN outcomes was depression. A substantial proportion of individuals continue to suffer from eating disorders over time but BN was not associated with increased mortality risk. Data were insufficient to draw conclusions concerning factors associated with BED outcomes. Across disorders, little to no data were available to compare results based on sociodemographic characteristics. Conclusion: The strength of the bodies of literature was moderate for factors associated with AN and BN outcomes and weak for BED. © 2007 by Wiley Periodicals, Inc. Int J Eat Disord 2007 [source]

    Treatment of a Myasthenic Dog with Mycophenolate Mofetil

    C.W. Dewey DVM, DACVIM (Neurology), DACVS
    Summary A ten-year-old, male castrated Springer Spaniel was presented for dysphagia, ptyalism, and regurgitation. Evidence of megaesophagus and mild aspiration pneumonia were apparent on thoracic radiographs. A diagnosis of focal acquired myasthenia gravis was suspected and subsequently confirmed with a positive serum acetylcholine (ACh) receptor antibody concentration (3.87 nM/L). A gastrostomy tube was placed shortly after presentation; food and drugs (including azathioprine) were administered through the tube. After transient improvement, the dog suddenly deteriorated clinically, experiencing frequent episodes of regurgitation and developing severe aspiration pneumonia. Mycophenolate mofetil (MMF), a novel immunosuppressive drug with relative specificity for lymphocytes, was instituted every twelve hours via the gastrostomy tube. Within four days of beginning MMF therapy, both clinical evidence of pharyngeal/esophageal dysfunction and radiographic evidence of megaesophagus had resolved. Initially, clinical side-effects of combined MMF/AZA administration were not apparent, but the patient experienced several vomiting episodes during the third week of treatment. The vomiting resolved after decreasing the dose of both drugs. The patient made a full recovery, and a one-month follow-up ACh receptor antibody concentration was normal (0.26 nM/L). After one month of combination therapy, the patient was weaned off of AZA and maintained on MMF as the sole immunosuppressive drug. The dog was subsequently weaned off of MMF on two occasions. Mycophenolate mofetil was reinstituted after the first discontinuation due to the development of profound appendicular muscle weakness two days after stopping MMF; the weakness resolved within 24 hours of reinstituting MMF. A positive ACh receptor antibody concentration (0.89 nM/L) after the second MMF weaning prompted the second reinstitution of MMF. Two months following this second MMF reinstitution, the dog was again serologically negative (0.51 nM/L) for myasthenia gravis. At the time of last followup, the dog remained in clinical remission eight months after initial presentation. The use of MMF to treat acquired myasthenia gravis in dogs has not been reported previously. The literature concerning MMF and its potential use in treating patients with autoimmune diseases is discussed. [source]

    Two-Micron All-Sky Survey J01542930+0053266: a new eclipsing M dwarf binary system

    A. C. Becker
    ABSTRACT We report on Two-Micron All-Sky Survey (2MASS) J01542930+0053266, a faint eclipsing system composed of two M dwarfs. The variability of this system was originally discovered during a pilot study of the 2MASS Calibration Point Source Working Data base. Additional photometry from the Sloan Digital Sky Survey yields an eight-passband light curve from which we derive an orbital period of 2.639 0157 ± 0.000 0016 d. Spectroscopic followup confirms our photometric classification of the system, which is likely composed of M0 and M1 dwarfs. Radial velocity measurements allow us to derive the masses (M1= 0.66 ± 0.03 M,; M2= 0.62 ± 0.03 M,) and radii (R1= 0.64 ± 0.08 R,; R2= 0.61 ± 0.09 R,) of the components, which are consistent with empirical mass,radius relationships for low-mass stars in binary systems. We perform Monte Carlo simulations of the light curves which allow us to uncover complicated degeneracies between the system parameters. Both stars show evidence of H, emission, something not common in early-type M dwarfs. This suggests that binarity may influence the magnetic activity properties of low-mass stars; activity in the binary may persist long after the dynamos in their isolated counterparts have decayed, yielding a new potential foreground of flaring activity for next generation variability surveys. [source]

    Mixed chimerism and graft failure following conditioning with the fludarabine and cyclophosphamide nonablative regimen; Conversion to full donor chimerism

    Anand P. Jillella
    Abstract Twenty-one patients with hematologic malignancies were treated with the fludarabine (120,125 mg/m2) and cyclophosphamide (120 mg/kg) nonmyeloablative conditioning regimen. Graft versus host disease (GVHD) and graft rejection prophylaxis was with tacrolimus and mycophenolate mofetil. Thirteen of the 21 patients (62%) had mixed chimerism (,,90% donor cells) at day 60 and 11 (52%) of these patients had mixed chimerism which persisted until day 100. Immunosuppression was discontinued in 12 of 13 patients and two of them converted to full chimerism by day 100. Eight patients received a donor lymphocyte infusion (DLI) and five of them converted to full donor chimerism with DLI alone. Two patients were given GM-CSF in addition to a DLI with conversion to full donor chimerism. Three patients (14%) had graft failure requiring a second transplant using fludarabine (125 mg/m2) and melphalan (140 mg/m2). With a median followup of 2.8 years, 15 patients are alive,one with disease and 14 with no disease. Two patients died of acute GVHD, one of chronic GVHD, and three due to progressive disease. We conclude that the nonmyeloablative fludarabine/cyclophosphamide regimen results in a significant incidence of mixed chimerism and graft rejection but is well tolerated. We suggest a more intense regimen, such as fludarabine and melphalan, be used in patients with a high risk of early disease progression to establish early engraftment and graft versus tumor effect. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc. [source]

    Mortality in a cohort of Danish patients with fibromyalgia: Increased frequency of suicide

    ARTHRITIS & RHEUMATISM, Issue 10 2010
    Lene Dreyer
    Objective A previous study demonstrated an association between self-reported widespread body pain and increased mortality. The aim of this study was to analyze whether fibromyalgia (FM) and FM-like symptoms are related to increased mortality. Methods From hospital records, we identified 1,361 patients referred during the period 1984,1999 because of the suspicion of FM. The cases were reviewed by reviewers who were blinded to the outcome. The cohort was followed up for a total of 5,295 person-years at risk and was linked to the Danish Mortality Register. Using the number of years at risk and sex-, age-, and calendar-specific mortality rates from the general population, cause-specific standardized mortality ratios [SMRs] were calculated. Results We observed no overall increased mortality among patients with FM. Among the 1,269 female patients, the SMRs (95% confidence intervals [95% CIs]) for an increased risk of death from suicide, liver cirrhosis/biliary tract disease, and cerebrovascular disease were 10.5 (95% CI 4.5,20.7), 6.4 (95% CI 2.3,13.9), and 3.1 (95% CI 1.1,6.8), respectively. The suicide risk was increased at the time of diagnosis and remained increased after 5 years. Patients meeting the American College of Rheumatology criteria for FM and patients with possible FM had the same cause-specific mortality pattern. No increased cause-specific mortality was observed in the 84 male patients. Conclusion The causes of a markedly increased rate of suicide among female patients with FM are at present unknown but may be related to increased rates of lifetime depression, anxiety, and psychiatric disorders. Risk factors for suicide should be sought at the time of the diagnosis of FM and at followup. The results also suggest that risk factors for liver disease and cerebrovascular disease should be evaluated in patients with FM. [source]

    Anti,apolipoprotein A-1 IgG predicts major cardiovascular events in patients with rheumatoid arthritis

    ARTHRITIS & RHEUMATISM, Issue 9 2010
    Nicolas Vuilleumier
    Objective To determine whether anti,apolipoprotein A-1 (anti,Apo A-1) IgG are associated with major cardiovascular events in patients with rheumatoid arthritis (RA). Methods We determined anti,Apo A-1 IgG levels and the concentrations of cytokines, oxidized low-density lipoprotein (LDL), and matrix metalloproteinase 1 (MMP-1) MMP-2, MMP-3, and MMP-9 in sera from 133 patients with RA who did not have cardiovascular disease at baseline, all of whom were longitudinally followed up over a median period of 9 years. A major cardiovascular event was defined as a fatal or nonfatal stroke or acute coronary syndrome. The proinflammatory effects of anti,Apo A-1 IgG were assessed on human macrophages in vitro. Results During followup, the overall incidence of major cardiovascular events was 15% (20 of 133 patients). At baseline, anti,Apo A-1 IgG positivity was 17% and was associated with a higher incidence of major cardiovascular events (adjusted hazard ratio 4.2, 95% confidence interval 1.5,12.1). Patients who experienced a subsequent major cardiovascular event had higher circulating levels of anti,Apo A-1 IgG at baseline compared with those who did not have a major cardiovascular event. Receiver operating curve analysis showed that anti,Apo A-1 IgG was the strongest of all tested biomarkers for the prediction of a subsequent major cardiovascular event, with an area under the curve value of 0.73 (P = 0.0008). At the predefined and previously validated cutoff levels, the specificity and sensitivity of anti,Apo A-1 IgG to predict major cardiovascular events were 50% and 90%, respectively. Anti,Apo A-1 IgG positivity was associated with higher median circulating levels of interleukin-8 (IL-8), oxidized LDL, and MMP-9 and higher proMMP-9 activity as assessed by zymography. On human macrophages, anti,Apo A-1 IgG induced a significant dose-dependent increase in IL-8 and MMP-9 levels and proMMP-9 activity. Conclusion Anti,Apo A-1 IgG is an independent predictor of major cardiovascular events in RA, possibly by affecting vulnerability to atherosclerotic plaque. [source]

    Long-term remission after cessation of interferon-, treatment in patients with severe uveitis due to Behçet's disease

    ARTHRITIS & RHEUMATISM, Issue 9 2010
    Christoph M. E. Deuter
    Objective To retrospectively assess the development of visual acuity and the frequency and duration of relapse-free periods in patients who were treated with interferon-, (IFN,) for severe uveitis due to Behçet's disease (BD) and who completed a followup period of ,2 years. Methods IFN alfa-2a was administered at an initial dosage of 6 million IU per day, then tapered to a maintenance dosage of 3 million IU twice per week, and finally discontinued, if possible. In case of a relapse, IFN treatment was repeated. Visual acuity at the end of followup was compared with visual acuity when ocular disease was in remission. Results Of 53 patients (96 eyes), 52 (98.1%) responded to IFN. In 47 patients (88.7%), IFN could be discontinued when the disease was in remission. Twenty of these 47 (42.6%) needed a second treatment course during a median followup of 6.0 years (range 2.0,12.6 years). Visual acuity improved or remained unchanged in 91 eyes (94.8%). Ocular disease was still in remission in 50% of the patients 45.9 months after cessation of the first IFN course. The relapse rate tended to be lower in women than in men. The BD activity score decreased significantly during followup, but long-term remission of nonocular BD manifestations was not achieved. However, since local treatments were sufficient, no systemic treatment was administered. Conclusion Our findings indicate that IFN, induces long-lasting remission in patients with severe ocular BD, resulting in a notable improvement in visual prognosis. [source]

    Mortality in Behçet's disease

    ARTHRITIS & RHEUMATISM, Issue 9 2010
    D. Saadoun
    Objective To report the long-term mortality in patients with Behçet's disease (BD). Methods A cohort of 817 patients fulfilling the international criteria for BD from a single center in France were analyzed for causes of death, the standardized mortality ratio (SMR), and the factors associated with mortality. Results Among the 817 patients with BD, 41 (5%) died after a median followup of 7.7 years, of whom 95.1% were male. The mean ± SD age at death was 34.8 ± 11.9 years. Main causes of death included major vessel disease (mainly, arterial aneurysm and Budd-Chiari syndrome) (43.9%), cancer and malignant hemopathy (14.6%), central nervous system involvement (12.2%), and sepsis (12.2%). The mortality rate at 1 year and 5 years was 1.2% and 3.3%, respectively. There was an increased mortality among patients ages 15,24 years (SMR 2.99, 95% confidence interval [95% CI] 1.54,5.39) and those ages 25,34 years (SMR 2.90, 95% CI 1.80,4.49) as compared with age-and sex-matched healthy controls. The mortality decreased in patients older than age 35 years (SMR 1.23, 95% CI 0.75,1.92). In multivariate analyses, male sex (hazard ratio [HR] 4.94, 95% CI 1.53,16.43), arterial involvement (HR 2.51, 95% CI 1.07,5.90), and a high number of BD flares (HR 2.37, 95% CI 1.09,5.14) were independently associated with the risk of mortality. Conclusion The overall mortality in our BD cohort was 5% after a median followup of 7.7 years. Male sex, arterial involvement, and the number of flares were associated with mortality in BD. [source]

    Adalimumab in severe and acute sciatica: A multicenter, randomized, double-blind, placebo-controlled trial,

    ARTHRITIS & RHEUMATISM, Issue 8 2010
    Stéphane Genevay
    Objective Based on several experimental results and on a preliminary study, a trial was undertaken to assess the efficacy of adalimumab, a tumor necrosis factor , inhibitor, in patients with radicular pain due to lumbar disc herniation. Methods A multicenter, double-blind, randomized controlled trial was conducted between May 2005 and December 2007 in Switzerland. Patients with acute (duration of <12 weeks) and severe (Oswestry Disability Index score of >50) radicular leg pain and imaging-confirmed lumbar disc herniation were randomized to receive as adjuvant therapy either 2 subcutaneous injections of adalimumab (40 mg) at 7-day intervals or matching placebo. The primary outcome was the score for leg pain, based on a visual analog scale (0,100 mm), which was recorded every day for 10 days and at 6 weeks and 6 months. Results Of the 265 patients screened, 61 were enrolled; 31 patients were assigned to receive adalimumab, and 4 patients in the placebo group were lost to followup. Over time, the course of leg pain was more favorable in the adalimumab group than in the placebo group (P = 0.002). However, the effect size was relatively small, and at the last followup visit the difference was 13.8 (95% confidence interval ,11.5, 39.0). Compared with patients in the placebo group, approximately twice as many patients in the adalimumab group fulfilled the criteria for "responders" and for "low residual disease impact" (P < 0.05), and fewer surgical discectomies were performed (6 versus 13 in the placebo group; P = 0.04). Conclusion The addition of a short course of adalimumab to the treatment regimen of patients experiencing acute and severe sciatica resulted in a small decrease in leg pain and in significantly fewer surgical procedures. [source]

    The effect of alcohol on radiographic progression in rheumatoid arthritis

    ARTHRITIS & RHEUMATISM, Issue 5 2010
    M. J. Nissen
    Objective Alcohol consumption reduces the risk of development of rheumatoid arthritis (RA) and significantly attenuates the development of erosive arthritis in animal models. It remains unknown whether alcohol consumption influences joint damage progression in RA. This study was undertaken to compare the rates of radiographic damage progression in alcohol drinkers and nondrinkers in a large prospective cohort of patients with RA. Methods All patients in the population-based Swiss Clinical Quality Management in RA registry database with at least 2 sequential radiographs were included. Joint erosions were assessed in 38 joints in the hands and feet using a validated scoring method. The rate of progression of erosions was analyzed using multivariate regression models for longitudinal data and was adjusted for potential confounders. Results The study included 2,908 patients with RA with a mean of 4 sequential radiographs and 3.9 years of followup. A trend toward reduced radiographic progression existed in drinkers compared with nondrinkers, with a mean rate of erosive progression of 0.99% (95% confidence interval [95% CI] 0.89,1.09) and 1.13% (95% CI 1.01,1.26) at 1 year, respectively. Alcohol consumption displayed a J-shaped dose-response effect, with a more favorable evolution in occasional consumers (P = 0.01) and daily consumers (P = 0.001) as compared with nondrinkers, while heavy drinkers demonstrated worse radiographic evolution (P = 0.0001). We found significant effect modification by sex, with male drinkers displaying significantly less erosive progression compared with male nondrinkers (mean 0.86% [95% CI 0.70,1.03] versus 1.35% [95% CI 1.02,1.67]; P = 0.007). Conclusion Our findings indicate a trend toward reduced radiographic progression in alcohol drinkers compared with nondrinkers, specifically in occasional and daily alcohol consumers. In particular, male patients with RA who consume alcohol demonstrate less radiographic progression than do male nondrinkers. [source]

    Epidemiology of gout in women: Fifty-two,year followup of a prospective cohort

    ARTHRITIS & RHEUMATISM, Issue 4 2010
    Vidula Bhole
    Objective Despite the recent doubling of the incidence of gout among women and its substantial prevalence particularly in the aging female population, the risk factors for gout among women remain unknown. We undertook this study to evaluate purported risk factors for incident gout among women and to compare them with those among men. Methods Using prospective data from the Framingham Heart Study, we examined over a 52-year period (1950,2002) the relationship between purported risk factors and the incidence of gout in 2,476 women and 1,951 men. Results We documented 304 incident cases of gout, 104 of them among women. The incidence rates of gout for women per 1,000 person-years according to serum uric acid levels of <5.0, 5.0,5.9, 6.0,6.9, 7.0,7.9, and ,8.0 mg/dl were 0.8, 2.5, 4.2, 13.1, and 27.3, respectively (P for trend < 0.0001). The magnitude of this association was lower than that among men (P for interaction = 0.0002). Multivariate relative risks conferred by increasing age (per 5 years), obesity (body mass index ,30 kg/m2), alcohol intake (,7 ounces of pure alcohol/week), hypertension, and diuretic use were 1.24, 2.74, 3.10, 1.82, and 2.39, respectively (all P < 0.05), for women. Conclusion These prospective data with long-term followup provide evidence that higher levels of serum uric acid increase the risk of gout in a graded manner among women, but the rate of increase is lower than that among men. Increasing age, obesity, alcohol consumption, hypertension, and diuretic use were associated with the risk of incident gout among women. [source]

    Antimalarial treatment may have a time-dependent effect on lupus survival: Data from a multinational Latin American inception cohort

    ARTHRITIS & RHEUMATISM, Issue 3 2010
    Samuel K. Shinjo
    Objective To evaluate the beneficial effect of antimalarial treatment on lupus survival in a large, multiethnic, international longitudinal inception cohort. Methods Socioeconomic and demographic characteristics, clinical manifestations, classification criteria, laboratory findings, and treatment variables were examined in patients with systemic lupus erythematosus (SLE) from the Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL) cohort. The diagnosis of SLE, according to the American College of Rheumatology criteria, was assessed within 2 years of cohort entry. Cause of death was classified as active disease, infection, cardiovascular complications, thrombosis, malignancy, or other cause. Patients were subdivided by antimalarial use, grouped according to those who had received antimalarial drugs for at least 6 consecutive months (user) and those who had received antimalarial drugs for <6 consecutive months or who had never received antimalarial drugs (nonuser). Results Of the 1,480 patients included in the GLADEL cohort, 1,141 (77%) were considered antimalarial users, with a mean duration of drug exposure of 48.5 months (range 6,98 months). Death occurred in 89 patients (6.0%). A lower mortality rate was observed in antimalarial users compared with nonusers (4.4% versus 11.5%; P< 0.001). Seventy patients (6.1%) had received antimalarial drugs for 6,11 months, 146 (12.8%) for 1,2 years, and 925 (81.1%) for >2 years. Mortality rates among users by duration of antimalarial treatment (per 1,000 person-months of followup) were 3.85 (95% confidence interval [95% CI] 1.41,8.37), 2.7 (95% CI 1.41,4.76), and 0.54 (95% CI 0.37,0.77), respectively, while for nonusers, the mortality rate was 3.07 (95% CI 2.18,4.20) (P for trend < 0.001). After adjustment for potential confounders in a Cox regression model, antimalarial use was associated with a 38% reduction in the mortality rate (hazard ratio 0.62, 95% CI 0.39,0.99). Conclusion Antimalarial drugs were shown to have a protective effect, possibly in a time-dependent manner, on SLE survival. These results suggest that the use of antimalarial treatment should be recommended for patients with lupus. [source]

    Clinical features and outcomes in 348 patients with polyarteritis nodosa: A systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French vasculitis study group database

    ARTHRITIS & RHEUMATISM, Issue 2 2010
    Christian Pagnoux
    Objective Previous studies of polyarteritis nodosa (PAN) included patients with microscopic polyangiitis, because these entities were not distinguished prior to the Chapel Hill Consensus Conference (CHCC). This study was undertaken to describe the main characteristics of and long-term outcomes in patients with well-characterized PAN diagnoses. Methods We conducted a systematic retrospective study of 348 patients who were diagnosed as having PAN between March 1963 and October 2005, were registered in the French Vasculitis Study Group database, and satisfied the American College of Rheumatology and CHCC criteria. Patient characteristics and outcomes were analyzed and compared according to hepatitis B virus (HBV) status. Results At diagnosis, the mean ± SD age was 51.2 ± 17.3 years. The most frequent findings were general symptoms (93.1%), neurologic manifestations (79%), skin involvement (49.7%), abdominal pain (35.6%), and hypertension (34.8%); 66.2% had renal artery microaneurysms; 70.1% had histologically proven PAN. Patients with HBV-related PAN (n = 123) had more frequent peripheral neuropathy, abdominal pain, cardiomyopathy, orchitis, and hypertension compared with patients with non,HBV-related PAN (n = 225). During a mean ± SD followup of 68.3 ± 63.5 months, 76 patients (21.8%) relapsed (63 with non,HBV-related PAN [28%] versus 13 with HBV-related PAN [10.6%]; P < 0.001); 86 patients (24.7%) died (44 with non,HBV-related PAN [19.6%] versus 42 with HBV-related PAN [34.1%]; P = 0.003). Five-year relapse-free survival rates were 59.4% (95% confidence interval [95% CI] 52.6,67.0) versus 67.0% (95% CI 58.5,76.8) for non,HBV-related PAN and HBV-related PAN, respectively. Multivariate analysis retained age >65 years, hypertension, and gastrointestinal manifestations requiring surgery or at least consultation with a surgeon as independent predictors of death, whereas patients with cutaneous manifestations or non,HBV-related PAN had a higher risk of relapse. Conclusion Our findings indicate that the rate of mortality from PAN remains high, especially for the elderly, and relapses do occur, particularly in patients with non,HBV-related PAN with cutaneous manifestations. [source]

    Rapid and sustained improvement in bone and cartilage turnover markers with the anti,interleukin-6 receptor inhibitor tocilizumab plus methotrexate in rheumatoid arthritis patients with an inadequate response to methotrexate: Results from a substudy of the multicenter double-blind, placebo-controlled trial of tocilizumab in inadequate responders to methotrexate alone,

    ARTHRITIS & RHEUMATISM, Issue 1 2010
    Patrick Garnero
    Objective To investigate the effects of tocilizumab (TCZ) added to a stable dosage of methotrexate (MTX) on biochemical markers of bone and cartilage metabolism in patients in the multicenter double-blind, placebo-controlled OPTION (Tocilizumab Pivotal Trial in Methotrexate Inadequate Responders) study who have moderate-to-severe rheumatoid arthritis (RA) and an inadequate response to MTX. Methods Included in this study were 416 of the 623 patients with active RA enrolled in the OPTION study. Patients were randomized to receive TCZ (4 mg/kg or 8 mg/kg) or placebo intravenously every 4 weeks, with MTX continued at the stable prestudy doses (10,25 mg for 20 weeks, with a final followup at week 24). Serum biochemical markers of bone formation (osteocalcin, N-terminal propeptide of type I collagen [PINP]), bone resorption (C-terminal crosslinking telopeptide of type I collagen [CTX-I] and C-terminal crosslinking telopeptide of type I collagen generated by matrix metalloproteinases [ICTP]), cartilage metabolism (N-terminal propeptide of type IIA collagen [PIIANP]), collagen helical peptide [HELIX-II]), and matrix metalloproteinase 3 (MMP-3) were measured at baseline and at weeks 4, 16, and 24. Results TCZ induced marked dose-dependent reductions in PIIANP, HELIX-II, and MMP-3 levels at week 4 that were maintained until week 24, an effect associated with increased levels of bone formation markers that were significant as compared with placebo only for PINP and only at 4 weeks (P < 0.01 for both TCZ doses). TCZ induced significant decreases in the bone degradation markers CTX-I and ICTP, providing initial evidence of a beneficial effect on bone turnover. TCZ-treated patients who met the American College of Rheumatology 50% improvement criteria (achieved an ACR50 response) or achieved clinical remission (as determined by a Disease Activity Score in 28 joints <2.6) at week 24 had greater reductions in ICTP, HELIX-II, and MMP-3 levels as compared with ACR50 nonresponders. Conclusion TCZ combined with MTX reduces systemic bone resorption, cartilage turnover, and proteolytic enzyme MMP-3 levels, which provides evidence of a limitation of joint damage and possible beneficial effects on skeletal structure in patients with established moderate-to-severe RA. [source]

    Lymphopenia is a risk factor in the progression of carotid intima-media thickness in juvenile-onset systemic lupus erythematosus

    ARTHRITIS & RHEUMATISM, Issue 12 2009
    Yu-Lin Huang
    Objective To characterize the atherosclerotic risk factors in the progression of subclinical atherosclerosis in patients with juvenile-onset systemic lupus erythematosus (SLE). Methods This was a longitudinal study of 76 patients with juvenile-onset SLE. Carotid arteries were evaluated using ultrasonography at baseline and at followup visits at 6-month intervals over the 6-year study period. Clinical and laboratory parameters, disease activity, treatment, and traditional risk factors for atherosclerosis were evaluated. Data were analyzed using generalized estimating equations. Results The mean ± SD age of the patients at baseline was 15.01 ± 3.48 years and the mean ± SD disease duration was 2.65 ± 2.5 years. The mean ± SD duration of followup was 3.74 ± 1.24 years. The mean ± SD intima-media thickness (IMT) of the common carotid arteries differed significantly between the patient and control (n = 38) groups (0.63 ± 0.08 mm versus 0.54 ± 0.06 mm; P < 0.001). The presence of lymphopenia at diagnosis and at baseline and higher levels of serum creatinine and C-reactive protein at baseline were positively associated with progression of carotid IMT (P = 0.006, P = 0.043, P = 0.037, and P = 0.049, respectively). In multivariate analysis, only lymphopenia at baseline and at diagnosis were consistently associated with progression of IMT (P = 0.012 and P = 0.045, respectively). Conclusion In patients with juvenile-onset SLE, some nontraditional risk factors for the progression of subclinical atherosclerosis were identified. Lymphopenia was the only independent risk factor for the progression of IMT. The pathogenic mechanisms warrant further investigation. [source]

    Cancer risk in patients with rheumatoid arthritis treated with anti,tumor necrosis factor , therapies: Does the risk change with the time since start of treatment?

    ARTHRITIS & RHEUMATISM, Issue 11 2009
    Johan Askling
    Objective To determine the short-term and medium-term risks of cancer in patients receiving anti,tumor necrosis factor , (anti-TNF,) therapies that have proven effective in the treatment of chronic inflammatory conditions. Methods By linking together data from the Swedish Biologics Register, Swedish registers of RA, and the Swedish Cancer Register, we identified and analyzed for cancer occurrence a national cohort of 6,366 patients with RA who first started anti-TNF therapy between January 1999 and July 2006. As comparators, we used a national biologics-naive RA cohort (n = 61,160), a cohort of RA patients newly starting methotrexate (n = 5,989), a cohort of RA patients newly starting disease-modifying antirheumatic drug combination therapy (n = 1,838), and the general population of Sweden. Relative risks (RRs) were estimated using Cox regression analyses, examining overall RR as well as RR by time since the first start of anti-TNF therapy, by the duration of active anti-TNF therapy, and by the anti-TNF agent received. Results During 25,693 person-years of followup in 6,366 patients newly starting anti-TNF, 240 first cancers occurred, yielding an RR of 1.00 (95% confidence interval 0.86,1.15) versus the biologics-naive RA cohort, and similar RRs versus the other 2 RA comparators. RRs did not increase with increasing time since the start of anti-TNF therapy, nor with the cumulative duration of active anti-TNF therapy. During the first year following the first treatment start, but not thereafter, dissimilar cancer risks for adalimumab, etanercept, and infliximab were observed. Conclusion During the first 6 years after the start of anti-TNF therapy in routine care, no overall elevation of cancer risk and no increase with followup time were observed. [source]

    Epitope-specific immunotherapy of rheumatoid arthritis: Clinical responsiveness occurs with immune deviation and relies on the expression of a cluster of molecules associated with T cell tolerance in a double-blind, placebo-controlled, pilot phase II trial,

    ARTHRITIS & RHEUMATISM, Issue 11 2009
    Eva C. Koffeman
    Objective Induction of immune tolerance to maintain clinical control with a minimal drug regimen is a current research focus in rheumatoid arthritis (RA). Accordingly, we are developing a tolerization approach to dnaJP1, a peptide part of a pathogenic mechanism that contributes to autoimmune inflammation in RA. We undertook this study to test 2 hypotheses: 1) that mucosal induction of immune tolerance to dnaJP1 would lead to a qualitative change from a proinflammatory phenotype to a more tolerogenic functional phenotype, and 2) that immune deviation of responses to an inflammatory epitope might translate into clinical improvement. Methods One hundred sixty patients with active RA and with immunologic reactivity to dnaJP1 were enrolled in a pilot phase II trial. They received oral doses of 25 mg of dnaJP1 or placebo daily for 6 months. Results The dnaJP1 peptide was safe and well-tolerated. In response to treatment with dnaJP1, there was a significant reduction in the percentage of T cells producing tumor necrosis factor , and a corresponding trend toward an increased percentage of T cells producing interleukin-10. Coexpression of a cluster of molecules (programmed death 1 and its ligands) associated with T cell regulation was also found to be a prerequisite for successful tolerization in clinical responders. Analysis of the primary efficacy end point (meeting the American College of Rheumatology 20% improvement criteria at least once on day 112, 140, or 168) showed a difference between treatment groups that became significant in post hoc analysis using generalized estimating equations. Differences in clinical responses were also found between treatment groups on day 140 and at followup. Post hoc analysis showed that the combination of dnaJP1 and hydroxychloroquine (HCQ) was superior to the combination of HCQ and placebo. Conclusion Tolerization to dnaJP1 leads to immune deviation and a trend toward clinical efficacy. Susceptibility to treatment relies on the coexpression of molecules that can down-regulate adaptive immunity. [source]

    Integrated cardiac and vascular assessment in Takayasu arteritis by cardiovascular magnetic resonance

    ARTHRITIS & RHEUMATISM, Issue 11 2009
    Niall G. Keenan
    Objective This study was undertaken to evaluate the value of cardiovascular magnetic resonance (CMR) in the assessment of patients with Takayasu arteritis (TA). Methods Sixteen patients with TA and 2 populations comprising 110 normal volunteers were prospectively recruited. All patients with TA underwent a CMR protocol including measurement of carotid artery wall volume, assessment of left ventricular (LV) volumes and function, and late gadolinium enhancement for the detection of myocardial scarring. Results Carotid artery wall volume, total vessel volume, and the wall:outer wall ratio were elevated in TA patients compared with controls (wall volume 1,045 mm3 in TA patients versus 640 mm3 in controls, P < 0.001; total vessel volume 2,268 mm3 in TA patients versus 2,037 mm3 in controls, P < 0.05; wall:outer wall ratio 48% in TA patients versus 32% in controls, P < 0.001). The lumen volume was reduced in TA (1,224 mm3 versus 1,398 mm3 in controls, P < 0.05). In TA, LV function was more dynamic, with reduced end-systolic volume (mean ± 95% confidence interval ejection fraction 74 ± 3% versus 67 ± 1% in controls, P < 0.001; LV end-systolic volume 19 ± 4 ml/m2 versus 25 ± 1 ml/m2 in controls, P < 0.001). Myocardial late gadolinium enhancement was present in 4 (27%) of 15 patients, indicating previously unrecognized myocardial damage. Conclusion Our findings indicate that an integrated method of cardiovascular assessment by CMR in TA not only provides good delineation of vessel wall thickening, but has also demonstrated dynamic ventricular function, myocardial scarring, and silent myocardial infarction. CMR has benefits compared with other approaches for the assessment and followup of patients with TA, and has potential to identify patients most at risk of complications, allowing early preventative therapy. [source]

    Prevalence of and screening for serious spinal pathology in patients presenting to primary care settings with acute low back pain

    ARTHRITIS & RHEUMATISM, Issue 10 2009
    Nicholas Henschke
    Objective To determine the prevalence of serious pathology in patients presenting to primary care settings with acute low back pain, and to evaluate the diagnostic accuracy of recommended "red flag" screening questions. Methods An inception cohort of 1,172 consecutive patients receiving primary care for acute low back pain was recruited from primary care clinics in Sydney, Australia. At the initial consultation, clinicians recorded responses to 25 red flag questions and then provided an initial diagnosis. The reference standard was a 12-month followup supplemented with a specialist review of a random subsample of participants. Results There were 11 cases (0.9%) of serious pathology, including 8 cases of fracture. Despite the low prevalence of serious pathology, most patients (80.4%) had at least 1 red flag (median 2, interquartile range 1,3). Only 3 of the red flags for fracture recommended for use in clinical guidelines were informative: prolonged use of corticosteroids, age >70 years, and significant trauma. Clinicians identified 5 of the 11 cases of serious pathology at the initial consultation and made 6 false-positive diagnoses. The status of a diagnostic prediction rule containing 4 features (female sex, age >70 years, significant trauma, and prolonged use of corticosteroids) was moderately associated with the presence of fracture (the area under the curve for the rule score was 0.834 [95% confidence interval 0.654,1.014]; P = 0.001). Conclusion In patients presenting to a primary care provider with back pain, previously undiagnosed serious pathology is rare. The most common serious pathology observed was vertebral fracture. Approximately half of the cases of serious pathology were identified at the initial consultation. Some red flags have very high false-positive rates, indicating that, when used in isolation, they have little diagnostic value in the primary care setting. [source]

    18F-fluorodeoxyglucose,positron emission tomography scanning is more useful in followup than in the initial assessment of patients with Erdheim-Chester disease

    ARTHRITIS & RHEUMATISM, Issue 10 2009
    Laurent Arnaud
    Objective Erdheim-Chester disease (ECD) is a rare form of non,Langerhans' cell histiocytosis. The aim of this study was to assess the value of whole-body scanning with 18F-fluorodeoxyglucose,positron emission tomography (FDG-PET) in a large cohort of ECD patients from a single center. Methods We retrospectively reviewed all PET scans performed on 31 patients with ECD who were referred to our department between 2005 and 2008. PET images were reviewed by 2 independent nuclear medicine specialist physicians and were compared with other imaging modalities performed within 15 days of each PET scan. Results Thirty-one patients (10 women and 21 men; median age 59.5 years) underwent a total of 65 PET scans. Twenty-three patients (74%) were untreated at the time of the initial PET scan, whereas 30 of the 34 followup PET scans (88%) were performed in patients who were undergoing immunomodulatory therapy. Comparison of the initial and followup PET scans with other imaging modalities revealed that the sensitivity of PET scanning varied greatly among the different organs studied (range 4.3,100%), while the specificity remained high (range 69.2,100%). Followup PET scans were particularly helpful in assessing central nervous system (CNS) involvement, since the PET scan was able to detect an early therapeutic response of CNS lesions, even before magnetic resonance imaging showed a decrease in their size. PET scanning was also very helpful in evaluating the cardiovascular system, which is a major prognostic factor in ECD, by assessing the heart and the entire vascular tree during a single session. Conclusion The results of our large, single-center, retrospective study suggest that the findings of a FDG-PET scan may be interesting in the initial assessment of patients with ECD, but its greater contribution is in followup of these patients. [source]

    Urinary CD4+ effector memory T cells reflect renal disease activity in antineutrophil cytoplasmic antibody,associated vasculitis

    ARTHRITIS & RHEUMATISM, Issue 9 2009
    Wayel H. Abdulahad
    Objective Numbers of circulating CD4+ effector memory T cells are proportionally increased in patients with proteinase 3 antineutrophil cytoplasmic antibody,associated vasculitis (AAV) whose disease is in remission and are decreased during active disease, which presumably reflects their migration toward sites of inflammation. Since renal infiltrating cells may appear in urine, we investigated the presence of CD4+ effector memory T cells in urinary sediment as a reflection of renal disease activity in AAV. Methods CD4+ effector memory (CD45RO+CCR7,CD3+CD4+) T cells were quantitated in the urine and peripheral blood of patients with AAV with renal involvement (n = 33), patients with AAV without renal involvement (n = 18), patients with AAV whose disease was in remission (n = 29), and patients with active disease (n = 22), using 4-color flow cytometric analysis. Numbers and percentages of urine CD4+ effector memory T cells in 12 patients with AAV with active renal disease were obtained over several weeks of followup during remission induction. Results A notable increase in urine CD4+ effector memory T cell numbers was observed in patients with active renal AAV compared with patients whose disease was in remission and patients with active disease without renal involvement. The increase in these cells in the urine of patients with active renal AAV was accompanied by a reciprocal decrease in these cells in peripheral blood. Results from followup analysis showed a clear reduction in urine CD4+ effector memory T cells following treatment. Moreover, a negative correlation was observed between percentages of circulating and urine CD4+ effector memory T cells, consistent with their migration toward sites of inflammation. Conclusion Our findings indicate that the presence of CD4+ effector memory T cells in urine reflects renal involvement in AAV. Flow cytometric analysis of these cells in urine may contribute to assessing renal disease activity in patients with AAV. [source]

    Value of anti,modified citrullinated vimentin and third-generation anti,cyclic citrullinated peptide compared with second-generation anti,cyclic citrullinated peptide and rheumatoid factor in predicting disease outcome in undifferentiated arthritis and rheumatoid arthritis

    ARTHRITIS & RHEUMATISM, Issue 8 2009
    Michael P. M. van der Linden
    Objective Autoantibodies such as rheumatoid factor (RF) and anti,citrullinated protein autoantibodies (ACPAs) determined by testing with second-generation anti,cyclic citrullinated peptide (anti,CCP-2) are frequently measured in clinical practice because of their association with disease outcome in undifferentiated arthritis (UA) and rheumatoid arthritis (RA). Recently, 2 new ACPA tests were developed: third-generation anti-CCP (anti,CCP-3) and anti,modified citrullinated vimentin (anti-MCV) autoantibody tests. To facilitate the decision on which autoantibody to test in daily practice, this study evaluated the capability of these autoantibodies and combinations of them to predict 3 outcome measures: progression from UA to RA, the rate of joint destruction in RA, and the chance of achieving sustained disease-modifying antirheumatic drug (DMARD),free remission in RA. Methods Patients with UA (n = 625) were studied for whether UA progressed to RA after 1 year. Patients with RA (n = 687) were studied for whether sustained DMARD-free remission was achieved and for the rate of joint destruction during a median followup of 5 years. Positive predictive values (PPVs) for RA development and for associations with the disease course in RA were compared between single tests (anti,CCP-2, anti,CCP-3, anti-MCV, and RF) and between combinations of these tests. Results Among the single tests performed in patients with UA, anti,CCP-2 tended to have the highest PPV for RA development (67.1%), but the 95% confidence intervals of the other tests overlapped. Among the single tests in patients with RA, all 4 tests showed comparable associations with the rate of joint destruction and with the achievement of remission. In both ACPA-positive and ACPA-negative RA, the presence of RF was not associated with more joint destruction. For all outcome measures, performing combinations of 2 or 3 autoantibody tests did not increase the predictive accuracy compared with performing a single test. Conclusion For clinical practice, a single autoantibody test is sufficient for risk estimation in UA and RA. [source]

    Association of a single-nucleotide polymorphism in CD40 with the rate of joint destruction in rheumatoid arthritis

    ARTHRITIS & RHEUMATISM, Issue 8 2009
    Michael P. M. van der Linden
    Objective The severity of joint destruction in rheumatoid arthritis (RA) is highly variable from patient to patient and is influenced by genetic factors. Genome-wide association studies have enormously boosted the field of the genetics of RA susceptibility, but risk loci for RA severity remain poorly defined. A recent meta-analysis of genome-wide association studies identified 6 genetic regions for susceptibility to autoantibody-positive RA: CD40, KIF5A/PIP4K2C, CDK6, CCL21, PRKCQ, and MMEL1/TNFRSF14. The purpose of this study was to investigate whether these newly described genetic regions are associated with the rate of joint destruction. Methods RA patients enrolled in the Leiden Early Arthritis Clinic were studied (n = 563). Yearly radiographs were scored using the Sharp/van der Heijde method (median followup 5 years; maximum followup 9 years). The rate of joint destruction between genotype groups was compared using a linear mixed model, correcting for age, sex, and treatment strategies. A total of 393 anti,citrullinated protein antibody (ACPA),positive RA patients from the North American Rheumatoid Arthritis Consortium (NARAC) who had radiographic data available were used for the replication study. Results The TT and CC/CG genotypes of 2 single-nucleotide polymorphisms, rs4810485 (CD40) and rs42041 (CDK6), respectively, were associated with a higher rate of joint destruction in ACPA-positive RA patients (P = 0.003 and P = 0.012, respectively), with rs4810485 being significant after Bonferroni correction for multiple testing. The association of the CD40 minor allele with the rate of radiographic progression was replicated in the NARAC cohort (P = 0.021). Conclusion A polymorphism in the CD40 locus is associated with the rate of joint destruction in patients with ACPA-positive RA. Our findings provide one of the first non,HLA-related genetic severity factors that has been replicated. [source]

    Efficacy and tolerability of rituximab with or without PEGylated interferon alfa-2b plus ribavirin in severe hepatitis C virus,related vasculitis: A long-term followup study of thirty-two patients

    ARTHRITIS & RHEUMATISM, Issue 8 2009
    Benjamin Terrier
    Objective To report on the long-term followup of a cohort of patients with hepatitis C virus (HCV),related vasculitis treated with rituximab with or without PEGylated interferon alfa-2b (PEG,IFN alfa-2b) plus ribavirin. Methods The study group comprised 32 HCV RNA,positive patients with HCV-related vasculitis: 20 patients were treated with rituximab and PEG,IFN alfa-2b (9 of whom had not previously received antiviral treatment and 11 of whom had experienced disease resistance to or relapse with antiviral treatment), and 12 antiviral-intolerant patients were treated with rituximab alone. Results Treatment with rituximab and PEG,IFN alfa-2b plus ribavirin induced a complete clinical response and a partial clinical response in 80% and 15% of patients, respectively, a complete immunologic response and a partial immunologic response in 67% and 33% of patients, respectively, and a sustained virologic response in 55% of patients. Treatment with rituximab alone induced a complete clinical response and a partial clinical response in 58% and 9% of patients, respectively, and a complete immunologic response and a partial immunologic response in 46% and 36% of patients, respectively. B cell depletion was achieved in 96% of patients, and B cell recovery began after a median delay of 12 months. After a mean ± SD followup period of 23 ± 12 months, 22% of patients experienced a clinical relapse, and 34% of patients experienced an immunologic relapse. All relapses were associated with the absence of virologic control, and 78% of relapses were associated with B cell recovery. Six patients were re-treated with rituximab. All 6 of these patients had a complete clinical response, 50% had a complete immunologic response, and 50% had a partial immunologic response. Rituximab was well tolerated overall. Conclusion Rituximab is an effective treatment of severe and/or refractory HCV-related vasculitis. Relapses were consistently associated with the absence of virologic control. The clinical and immunologic efficacy of rituximab after repeated infusion appeared to be the same as that observed after induction therapy. [source]