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ID PMID Title PublicationDate abstract
19248103 Biomarkers of inflammation and development of rheumatoid arthritis in women from two prosp 2009 Mar OBJECTIVE: To examine the association of biomarkers of inflammation with preclinical rheumatoid arthritis (RA). METHODS: A nested case-control study was performed using samples from 2 large, prospectively studied cohorts of women (the Women's Health Study [WHS] and the Nurses' Health Study [NHS]). Blood samples obtained prior to symptom onset in women who later developed RA were selected as incident RA cases, and 3 controls per case were randomly chosen, matched for age, menopausal status, postmenopausal hormone use, and day, time, and fasting status at the time of collection. Plasma was tested for levels of interleukin-6 (IL-6), soluble tumor necrosis factor receptor II (sTNFRII) (as a proxy for TNFalpha), and high-sensitivity C-reactive protein. Relationships between biomarkers and RA were assessed using conditional logistic regression models, adjusting for age, body mass index, smoking habits, ethnicity, and reproductive factors. RESULTS: In 93 incident cases in the NHS and 77 incident cases in the WHS, the mean time between blood collection and the onset of RA symptoms was 5.2 years (range 0.3-12 years). Median IL-6 and sTNFRII levels were significantly higher in preclinical RA cases compared with matched controls in the NHS (P = 0.03 and P = 0.003, respectively) though not in the WHS. Pooled analysis of the NHS and WHS cohorts demonstrated significant association of sTNFRII with RA (relative risk 2.0 [95% confidence interval 1.1-3.6], P for trend = 0.004), and a modest association of IL-6 with RA (relative risk 1.4 [95% confidence interval 0.8-2.5], P for trend = 0.06). CONCLUSION: Levels of sTNFRII, a biomarker typically associated with active RA, were elevated up to 12 years prior to the development of RA symptoms and were positively associated with incident RA in these nested case-control studies. Studies with repeated assessments of biomarkers prior to RA development may provide further insight into the timing of biomarker elevation in preclinical RA.
20191579 Is the incidence of rheumatoid arthritis rising?: results from Olmsted County, Minnesota, 2010 Jun OBJECTIVE: To examine trends in the incidence and prevalence of rheumatoid arthritis (RA) from 1995 to 2007. METHODS: To augment our preexisting inception cohort of patients with RA (1955-1994), we assembled a population-based incidence cohort of individuals >or=18 years of age who first fulfilled the American College of Rheumatology 1987 criteria for the classification of RA between January 1, 1995 and December 31, 2007 and a cohort of patients with prevalent RA on January 1, 2005. Incidence and prevalence rates were estimated and were age-and sex-adjusted to the white population in the US in 2000. Trends in incidence rates were examined using Poisson regression methods. RESULTS: The 1995-2007 incidence cohort comprised 466 patients (mean age 55.6 years), 69% of whom were female and 66% of whom were rheumatoid factor positive. The overall age- and sex-adjusted annual RA incidence was 40.9/100,000 population. The age-adjusted incidence in women was 53.1/100,000 population (versus 27.7/100,000 population in men). During the period of time from 1995 to 2007, the incidence of RA increased moderately in women (P = 0.02) but not in men (P = 0.74). The increase was similar among all age groups. The overall age- and sex-adjusted prevalence on January 1, 2005 was 0.72% (95% confidence interval [95% CI] 0.66, 0.77), which is an increase when compared with a prevalence of 0.62% (95% CI 0.55, 0.69) in 1995 (P < 0.001). Applying the prevalence on January 1, 2005 to the US population in 2005 showed that an estimated 1.5 million US adults were affected by RA. This is an increase from the previously reported 1.3 million adults with RA in the US. CONCLUSION: The incidence of RA in women appears to have increased during the period of time from 1995 to 2007. The reasons for this recent increase are unknown, but environmental factors may play a role. A corresponding increase in the prevalence of RA was also observed.
20457282 MicroRNAs in Sjögren's syndrome as a prototypic autoimmune disease. 2010 Jul MicroRNAs are endogenous non-coding RNAs, approximately 22 nucleotides in length. They regulate gene expression and are important in a wide range of physiological and pathological processes. MicroRNA expression is tightly regulated during hematopoiesis and lymphoid cell differentiation and disruption of the entire microRNA network or selected microRNAs may lead to dysregulated immune responses. Abnormalities in microRNA expression related to inflammatory cytokines, Th-17 and regulatory T cells as well as B cells have been described in several autoimmune diseases. Sjogren's syndrome is characterized by features of systemic autoimmunity and chronic inflammation and dysfunction in exocrine organs. Its clinical characteristics along with the relatively easy access to the target tissue and its product makes Sjögren's syndrome appealing to study many aspects of microRNAs in a systemic autoimmune disease, such as their potential as diagnostic or prognostic biomarkers and their role in pathogenesis of autoimmunity, inflammation or organ dysfunction. Encouraging preliminary data from pilot studies in Sjogren's syndrome demonstrate the potential of microRNAs as putative diagnostic and prognostic biomarker candidates which should be tested in larger more definite studies. Combining the comparison of microRNA expression profiles between various clinical subsets of Sjögren's syndrome with bioinformatic modeling tools may predict formerly unsuspected pathways which may contribute to the disease process and lead to the generation of testable novel hypothesis of pathogenesis.
19886983 ACR70-disease activity score remission achievement from switches between all the available 2009 INTRODUCTION: The aim of our analysis was to compare the gaining of a major response (disease activity score [DAS] remission or American College of Rheumatology 70% improvement criteria [ACR70]) by switching between all the available biological therapies in rheumatoid arthritis. METHODS: A systematic review was performed including studies, published before December 2008, in which a second biological agent was used and clinical outcomes were evaluated after a first biological failure. RESULTS: Nine articles were included. Switching from etanercept and/or infliximab to adalimumab is effective with an ACR70 response ranging from 5% to 33%. Rituximab may be slightly more effective than switching to a second anti-tumor necrosis factor-alpha (anti-TNFalpha), reaching an ACR70 or DAS remission response in 12% and 9%, respectively. Clinical trials confirmed the efficacy in switching to abatacept (gain of effect 10.2%). Tocilizumab allows DAS28 (DAS using 28 joint counts) remission in 30.1% but ACR70 only in 12.4% of patients refractory to anti-TNFalpha. CONCLUSIONS: The efficacy of a second biological agent, irrespective of the mode of action, in reaching an ACR70 or DAS remission after a first biologic is observed from 5% to 15% and from 9% to 15.4%, respectively (except in two studies).
21109521 Changes in expression of membrane TNF, NF-{kappa}B activation and neutrophil apoptosis dur 2011 Mar BACKGROUND: Tumour necrosis factor (TNF) is central to the pathophysiological process of rheumatoid arthritis (RA), whether as soluble cytokine or membrane-expressed pro-TNF (mTNF). OBJECTIVES: To determine whether neutrophils, which can express TNF, are activated in the blood of patients with RA compared with healthy controls. To investigate, by focusing on mTNF expression, if the functions of RA neutrophils change in response to therapeutic TNF inhibition. METHODS: TNF was measured by flow cytometry and qPCR in neutrophils from 20 patients with RA before and after the start of TNF inhibitor therapy. Apoptosis was measured by morphology, and western blotting of pro- and antiapoptotic proteins in cell lysates. Nuclear factor κB (NF-κB) activation was determined by western blotting of phosphorylated NF-κB (p65). RESULTS: Before treatment RA neutrophils exhibited increased TNF mRNA expression, elevated mTNF levels and NF-κB activity compared with controls. They also underwent delayed apoptosis as shown by altered expression of anti- and proapoptotic proteins, such as Mcl-1 and caspases. Neutrophil TNF expression returned to baseline levels during successful treatment with anti-TNF biological agents, and there was a close correlation between clinical disease improvement and changes in neutrophil function. CONCLUSIONS: Neutrophils express elevated levels of TNF in RA and the transcription factor, NF-κB, a target of TNF, is activated. This mechanism could lead to a self-sustained inflammatory process. These data point to an important role of neutrophils in the abnormal TNF signalling pathways activated in RA and provide new evidence that neutrophils actively contribute to altered cytokine signalling in inflammatory diseases.
19447767 Safety of medium- to long-term glucocorticoid therapy in rheumatoid arthritis: a meta-anal 2009 Jul OBJECTIVE: Several randomized controlled trials (RCTs) and meta-analyses have confirmed clinical efficacy of glucocorticoids in RA. Concerns regarding safety associated with medium- to long-term use in RA have limited their use in clinical practice. In this meta-analysis, we assessed the toxicity related to medium- to long-term (defined as 1 year or longer) glucocorticoid therapy in RA. METHODS: MEDLINE, EMBASE and CINAHL databases were searched for RCTs of glucocorticoids in RA. RCTs fulfilling the following criteria were included: double-blinded, placebo-controlled, lasted 1 year or longer, used prednisolone (or equivalent) and in English. Toxicity was assessed by number of the patients withdrawn for adverse events (AEs), and the numbers of serious adverse events (SAEs) and AEs. RCTs were compared by meta-analysis using odd ratios (OR) with 95% CIs. RESULTS: Six RCTs with total of 689 patients met the inclusion criteria. All RCTs lasted >or=2 years. All studies allowed concomitant use of NSAIDs and DMARDs. Toxicity of glucocorticoid therapy based on number of patients withdrawn was limited (OR = 1.09; 95% CI 0.52, 2.25). Using number of AEs per patient-year (OR = 1.19; 95% CI 0.91, 1.57) and SAEs (OR = 1.06; 95% CI 0.67, 1.67) produced similar results. Efficacy/toxicity ratio was good for glucocorticoid therapy (number needed to harm/number needed to treat = 0.25). CONCLUSION: Medium- to long-term glucocorticoid therapy in RA is associated with limited toxicity compared to placebo.
19293160 Patient-reported outcomes improve with etanercept plus methotrexate in active early rheuma 2010 Jan OBJECTIVES: To compare the effects of etanercept (ETN) 50 mg once weekly plus methotrexate (MTX) versus MTX alone on patient-reported outcomes (PROs) and the relationship between remission and PRO improvement. METHODS: In this double-blind, randomised clinical trial (COMET), PROs included: the Health Assessment Questionnaire (HAQ), EuroQoL health status, fatigue and pain visual analogue scales, Hospital Anxiety and Depression Scale, and Medical Outcomes Short-Form-36. Mean changes from baseline were analysed by analysis of covariance using the last observation carried forward method. Results from week 52 are presented. RESULTS: Most PROs demonstrated significantly greater improvements with ETN+MTX than MTX alone, including physical functioning, pain, fatigue and overall health status. A significantly greater improvement in HAQ score was observed in the ETN+MTX than the MTX group (-1.02 vs -0.72; p<0.001) and a greater proportion reached the minimal clinically important difference of 0.22 (88% vs 78%; p<0.006). The relationship between PRO score and clinical status indicated that improvement was greatest among patients achieving remission. CONCLUSIONS: Early treatment with ETN+MTX leads to significantly greater improvements in multiple dimensions of PROs than MTX alone. The close relationship between disease activity and PRO improvement suggests that early treatment, with remission as a goal, should maximise the chance of restoring normal functioning and HRQoL.
18336869 Carotid intima-media thickness predicts the development of cardiovascular events in patien 2009 Apr OBJECTIVE: To establish whether carotid intima-media wall thickness (IMT) may be a good predictor for the development of cardiovascular (CV) events in patients with rheumatoid arthritis (RA). METHODS: A series of 47 RA patients who at the time of recruitment did not have traditional CV risk factors or CV disease were assessed by carotid ultrasonography. Carotid IMT and carotid plaques were measured in the right common carotid artery. Then, a prospective assessment of the CV outcome was performed over a 5-year period. Logistic regression models and receiver operating characteristic curves were performed to evaluate the ability of different variables to predict CV events. RESULTS: Carotid IMT was greater in RA patients who over the extended follow-up experienced CV events (1.01 +/- 0.16 mm) compared with the remaining RA patients who did not have CV complications (0.74 +/- 0.12 mm) (P < 0.001). Also, carotid IMT categorized in quartiles was strongly associated with CV events. In this regard, none of the patients with carotid IMT less than 0.77 mm had CV events. However, 6 of the 10 patients with carotid IMT greater than 0.91 mm experienced CV events (P value for the trend <0.001). Carotid IMT yielded a high predictive power for the development of CV events over the 5-year follow-up period. The area under the receiver operating characteristic curve was 0.93 for a model that only included carotid IMT and 0.90 for carotid plaque. CONCLUSIONS: The results from the present study support the use of carotid ultrasonography as a predictor of CV events in RA.
20675755 The use of patient-reported outcome measures and patient satisfaction ratings to assess ou 2010 Aug We have compared the outcome of hemiarthroplasty of the shoulder in three distinct diagnostic groups, using survival analysis as used by the United Kingdom national joint registers, patient-reported outcome measures (PROMs) as recommended by Darzi in the 2008 NHS review, and transition and satisfaction questions. A total of 72 hemiarthroplasties, 19 for primary osteoarthritis (OA) with an intact rotator cuff, 22 for OA with a torn rotator cuff, and 31 for rheumatoid arthritis (RA), were followed up for between three and eight years. All the patients survived, with no revisions or dislocations and no significant radiological evidence of loosening. The mean new Oxford shoulder score (minimum/worst 0, maximum/best 48) improved significantly for all groups (p < 0.001), in the OA group with an intact rotator cuff from 21.4 to 38.8 (effect size 2.9), in the OA group with a torn rotator cuff from 13.3 to 27.2 (effect size 2.1) and in the RA group from 13.7 to 28.0 (effect size 3.1). By this assessment, and for the survival analysis, there was no significant difference between the groups. However, when ratings using the patient satisfaction questions were analysed, eight (29.6%) of the RA group were 'disappointed', compared with one (9.1%) of the OA group with cuff intact and one (7.7%) of the OA group with cuff torn. All patients in the OA group with cuff torn indicated that they would undergo the operation again, compared to ten (90.9%) in the OA group with cuff intact and 20 (76.9%) in the RA group. The use of revision rates alone does not fully represent outcome after hemiarthroplasty of the shoulder. Data from PROMs provides more information about change in pain and the ability to undertake activities and perform tasks. The additional use of satisfaction ratings shows that both the rates of revision surgery and PROMs need careful interpretation in the context of patient expectations.
20425744 Avascular necrosis of femoral head associated with connective tissue disease in Nigerians: 2009 Jul BACKGROUND: Avascular Necrosis (AVN) or osteonecrosis has been frequently reported among Nigerians with sickle cell disease. Other known aetiologies include connective tissue diseases, alcohol, fat embolism, juvenile arthritis and pregnancy. Connective tissue disease (CTD) are uncommonly reported among Nigerians. OBJECTIVE: To report the cases of three Nigerian female patients with radiological evidence of AVN associated with connective tissue diseases and inflammatory arthritis who presented to a rheumatology hospital in Lagos, Nigeria. METHODS: The first patient was a 36-year-old woman who was initially diagnosed as systemic lupus erythematosus (SLE). After four years of treatment, she presented with intense pain in the left hip, which on radiograph showed AVN. She was initially treated with NSAIDS and narcotic analgesics. She eventually had a left hip replacement. The second patient was a 44-year-old female, who had presented seven years earlier with features of SLE. She had attended the clinic irregularly. She later developed pain in both hips and shortening of left lower limb over the preceding three years. Radiographs confirmed AVN. She was treated with analgesics. The third patient was an 18-year-old female undergraduate who had rheumatoid arthritis (RA) and later developed bilateral hip pain which on radiograph showed bilateral AVN. She was placed on analgesics and then referred for orthopaedic surgery. CONCLUSION: Osteonecrosis may be associated with connective tissue diseases. A high index of suspicion is needed for the diagnosis, especially in SLE and RA patients with prolonged hip pain not responding to immunosuppressive.
20127607 [Interpretation of elevated serum troponin levels in end stage renal disease - case 2/2010 2010 Feb HISTORY AND ADMISSION FINDINGS: We report on a female patient with rheumatoid arthritis and end-stage renal-disease following AA-amyloidosis who presented with chest pain to the emergency department. INVESTIGATIONS: ECG showed no signs of ischemia, echocardiography revealed a concentric left ventricular hypertrophy with increased texture. Serum concentration of troponin I was mildly elevated whereas creatine kinase (CK)/ CK-MB were normal. DIAGNOSIS, TREATMENT AND COURSE: The chief complaints resolved spontaneously and there was no change in the serum troponin-I and CK/CK-MB concentrations. Coronary heart disease was ruled out by angiography and cardiac involvement of the underlying AA-amyloidosis was diagnosed. After one month, the patient suffered from a syncope complicated by a pelvic ring fracture with hemorrhagic shock and declined chronic dialysis treatment. CONCLUSION: Patients with end-stage renal disease may exhibit a persisting elevation of serum troponin concentration reflecting the high burden of cardiovascular disease. Myocardial infarction can be distinguished by the lack of increase in serial tests.
19648944 A case of cervical spine meningioma following etanercept use in a patient with RA. 2009 Aug BACKGROUND: A 70-year-old female with active rheumatoid arthritis (RA) was administered etanercept to treat active disease that persisted despite therapy with conventional DMARDs. After 18 months of etanercept therapy, her RA symptoms had improved; however, she developed quadriparesis. She presented to a specialist rheumatology clinic with weakness and numbness in her arms and legs; she also had difficulty in standing up and walking. INVESTIGATIONS: Physical examination, neurological examination, nerve conduction studies, measurement of serum inflammatory markers and autoantibodies, MRI of the cranium and cervical spine, and X-rays of the chest and hands. DIAGNOSIS: The patient underwent neurosurgery to resect a 1 x 2 cm mass in the cervical spine at C6-C7. Histopathologic examination of the excised mass revealed it to be a meningioma. MANAGEMENT: Etanercept was discontinued because of a possible association between the drug and development of meningioma; however, shortly afterwards the patient experienced a flare of RA symptoms. High-dose NSAIDs and prednisolone were administered, but the patient died because of gastric perforation. To our knowledge, this is the first report in the literature of meningioma developing following use of tumor necrosis factor inhibitor therapy, and the first to suggest a cause-effect relationship.
20435931 Treatment of autoimmune arthritis using RNA interference-modulated dendritic cells. 2010 Jun 1 Dendritic cells (DCs) have a dual ability to either stimulate or suppress immunity, which is primarily associated with the expression of costimulatory molecules. Ag-loaded DCs have shown encouraging clinical results for treating cancer and infectious diseases; however, the use of these cells as a means of suppressing immune responses is only recently being explored. Here, we describe the induction of RNA interference through administering short interfering RNA (siRNA) as a means of specifically generating tolerogenic DCs. Knockdown of CD40, CD80, and CD86, prior to loading DCs with the arthritogenic Ag collagen II, led to a population of cells that could effectively suppress onset of collagen-induced arthritis. Maximum benefits were observed when all three genes were concurrently silenced. Disease suppression was associated with inhibition of collagen II-specific Ab production and suppression of T cell recall responses. Downregulation of IL-2, IFN-gamma, TNF-alpha, and IL-17 and increased FoxP3(+) cells with regulatory activity were observed in collagen-induced arthritis mice treated with siRNA-transfected DCs. Collectively, these data support the use of ex vivo gene manipulation in DCs using siRNA to generate tailor-made tolerogenic vaccines for treating autoimmunity.
20807848 Metacarpophalangeal joints in rheumatoid arthritis: delayed gadolinium-enhanced MR imaging 2010 Nov PURPOSE: To evaluate the feasibility of delayed gadolinium-enhanced magnetic resonance (MR) imaging of the cartilage of metacarpophalangeal (MCP) joints in patients with rheumatoid arthritis (RA) compared with that in control subjects. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Thirty-one MCP joints in 10 patients with RA (mean age, 59 years; range, 35-77 years) and six healthy volunteers (mean age, 51 years; range, 30-71 years) were examined with delayed gadolinium-enhanced MR imaging of cartilage. Sagittal images of the second and third MCP joints (hereafter, MCP II and MCP III) were acquired with a three-dimensional dual-flip-angle gradient-echo sequence at 3.0 T. B(1) field inhomogeneity-corrected T1 maps were calculated, and delayed gadolinium-enhanced MR imaging of cartilage values for phalangeal and metacarpal cartilage were determined. In addition, cartilage thickness was measured. A nonparametric Mann-Whitney U test was used to assess differences between groups. RESULTS: Phalangeal and metacarpal delayed gadolinium-enhanced MR imaging of cartilage values in patients with RA (MCP II: 388 msec ± 105 [standard deviation] and 342 msec ± 79, respectively; MCP III: 409 msec ± 96 and 371 msec ± 89, respectively) were significantly lower than in control subjects (MCP II: 598 msec ± 62 and 560 msec ± 51, respectively; MCP III: 586 msec ± 57 and 561 msec ± 80, respectively). Cartilage thickness of both joints was comparable in patients with RA (MCP II: 1.28 mm ± 0.50, MCP III: 1.17 mm ± 0.24) and control subjects (MCP II: 1.42 mm ± 0.33, MCP III: 1.18 mm ± 0.26). CONCLUSION: Delayed gadolinium-enhanced MR imaging of cartilage of the MCP joints is feasible at 3.0 T. Delayed gadolinium-enhanced MR imaging of cartilage may help to assess cartilage degeneration in morphologically normal-appearing MCP II and III cartilage in patients with RA.
20533540 CTLA-4Ig blocks the development and progression of citrullinated fibrinogen-induced arthri 2010 Oct OBJECTIVE: To assess the role of T cells in the mouse model of citrullinated human fibrinogen-induced rheumatoid arthritis (RA) using CTLA-4Ig, an agent that blocks T cell costimulation, which is required for T cell activation. METHODS: Humanized HLA-DRβ1*0401-transgenic (DR4-Tg) mice were immunized with Cit-human fibrinogen to induce arthritis. Prior to, and at the onset or peak of, arthritis, the DR4-Tg mice were treated with CTLA-4Ig or control human IgG1 or were left untreated. Arthritis development and progression were monitored by measuring ankle swelling with calipers and by assessing histopathologic changes. The immune responses to the citrullinated antigens and the corresponding unmodified antigens, as well as the arthritogenicity of lymphocytes from these mice, were examined. The latter was performed using lymphocyte transfers from CTLA-4Ig-treated or control mice via intraperitoneal injection into naive DR4-Tg mice. Recipient mice also received an intraarticular injection of Cit-human fibrinogen, unmodified human fibrinogen, or vehicle. RESULTS: CTLA-4Ig-treated, but not human IgG1-treated, arthritic mice had significantly reduced ankle swelling and pathologic joint damage. Treatment with CTLA-4Ig, but not human IgG1, suppressed Cit-human fibrinogen-induced T cell activation, including citrulline-specific T cell activation, when given prior to disease onset. Transfer of splenic lymphocytes from untreated or human IgG1-treated arthritic mice caused arthritis in recipients, and this occurred when Cit-human fibrinogen, but not unmodified fibrinogen, was deposited into the joint. Splenocytes from CTLA-4Ig-treated mice were unable to transfer arthritis. CONCLUSION: Activated citrulline-specific T cells play a direct role in the development and progression of arthritis in this model of Cit-human fibrinogen-induced RA.
20033495 Combined surface and volume processing for fused joint segmentation. 2010 May PURPOSE: Segmentation of rheumatoid joints from CT images is a complicated task. The pathological state of the joint results in a non-uniform density of the bone tissue, with holes and irregularities complicating the segmentation process. For the specific case of the shoulder joint, existing segmentation techniques often fail and lead to poor results. This paper describes a novel method for the segmentation of these joints. METHODS: Given a rough surface model of the shoulder, a loop that encircles the joint is extracted by calculating the minimum curvature of the surface model. The intersection points of this loop with the separate CT-slices are connected by means of a path search algorithm. Inaccurate sections are corrected by iteratively applying a Hough transform to the segmentation result. RESULTS: As a qualitative measure we calculated the Dice coefficient and Hausdorff distances of the automatic segmentations and expert manual segmentations of CT-scans of ten severely deteriorated shoulder joints. For the humerus and scapula the median Dice coefficient was 98.9% with an interquartile range (IQR) of 95.8-99.4 and 98.5% (IQR 98.3-99.2%), respectively. The median Hausdorff distances were 3.06 mm (IQR 2.30-4.14) and 3.92 mm (IQR 1.96 -5.92 mm), respectively. CONCLUSION: The routine satisfies the criterion of our particular application to accurately segment the shoulder joint in under 2 min. We conclude that combining surface curvature, limited user interaction and iterative refinement via a Hough transform forms a satisfactory approach for the segmentation of severely damaged arthritic shoulder joints.
20183464 An overview of practical approaches for handling missing data in clinical trials. 2009 Nov For a variety of reasons including poorly designed case report forms (CRFs), incomplete or invalid CRF data entries, and premature treatment or study discontinuations, missing data is a common phenomenon in controlled clinical trials. With the widely accepted use of the intent-to-treat (ITT) analysis dataset as the primary analysis dataset for the analysis of controlled clinical trial data, the presence of missing data could lead to complicated data analysis strategies and subsequently to controversy in the interpretation of trial results. In this article, we review the mechanisms of missing data and some common approaches to analyzing missing data with an emphasis on study dropouts. We discuss the importance of understanding the reasons for study dropouts with ways to assess the mechanisms of missingness. Finally, we discuss the results of a comparative Monte Carlo investigation of the performance characteristics of commonly utilized statistical methods for the analysis of clinical trial data with dropouts. The methods investigated include the mixed effects model for repeated measurements (MMRM), weighted and unweighted generalized estimating equations (GEE) method for the available case data, multiple-imputation-based GEE (MI-GEE), complete case (CC) analysis of covariance (ANCOVA), and last observation carried forward (LOCF) ANCOVA. Simulation experiments for the repeated measures model with missing at random (MAR) dropout, under varying dropout rates and intrasubject correlation, show that the LOCF, ANCOVA, and weighted GEE methods perform poorly in terms of percent relative bias for estimating a difference in means effect, while the MI-GEE and weighted GEE methods both have less power for rejecting a zero difference in means hypothesis.
21106403 Radial nerve palsy after humeral revision in total elbow arthroplasty. 2011 Mar HYPOTHESIS: The Mayo Clinic database was queried for all humeral component revision elbow arthroplasties complicated by radial nerve palsy. MATERIALS AND METHODS: Multiple variables were analyzed to determine their impact on patient outcomes. RESULTS: Of 258 humeral component revisions, 7 (2.7%) were complicated by radial nerve palsy. The mean follow-up was 84 months (range, 24-233 months). Only 3 of 7 patients (43%) regained function. There was no recovery in 4 out of the 5 patients in whom power instruments or ultrasound was used for cement removal. Two of three patients who underwent exposure of the radial nerve had return of function at most recent follow-up. CONCLUSIONS: Radial nerve palsy is an uncommon complication after humeral revision in total elbow arthroplasty but is not necessarily associated with full recovery. Return of function is less likely when power instruments or ultrasound is used for cement removal. Formal exposure and protection of the radial nerve are predictive of recovery.
20722019 Changes in glycosylated hemoglobin after initiation of hydroxychloroquine or methotrexate 2010 Dec OBJECTIVE: Prior research demonstrates that hydroxychloroquine (HCQ) lowers glycosylated hemoglobin (HbA(1c) ) in diabetes patients without rheumatic disease. We examined medical records of patients with diabetes mellitus (DM) and concomitant rheumatic illness to measure changes in HbA(1c) after starting HCQ or methotrexate (MTX). METHODS: We used electronic medical records to identify patients beginning treatment with either HCQ or MTX who had a diagnosis of DM (or a pretreatment HbA(1c) value of ≥7%) and at least 1 HbA(1c) measurement both before and within 12 months after initiation of treatment. Using a structured medical record abstraction, we examined rheumatic disease diagnosis, cumulative steroid use, duration (months) between drug initiation and lowest HbA(1c) value, a change in DM medication, body mass index (BMI), age, and sex. Adjusted linear regression models determined changes in HbA(1c) from pretreatment values to the lowest posttreatment values within 12 months. RESULTS: We identified 45 patients taking HCQ and 37 patients taking MTX who met the inclusion criteria. Rheumatoid arthritis had been diagnosed in approximately half of the patients in each group. Age, sex, and mean pretreatment HbA(1c) levels were similar across groups. The mean BMI of those taking HCQ (35.4 kg/m(2) ) was slightly higher than that of those taking MTX (32.2 kg/m(2) ) (P = 0.13). Glucocorticoid use appeared more common in those taking MTX (46%) than in those taking HCQ (29%) (P = 0.17). The mean reduction in HbA(1c) from pretreatment values to the lowest posttreatment values was 0.66% (95% confidence interval [95% CI] 0.26, 1.05) in those taking HCQ compared with 0.11% (95% CI -0.18, 0.40) in those taking MTX. In fully adjusted analyses, the reduction in HbA(1c) among those taking HCQ was 0.54% greater than the reduction among those taking MTX (P = 0.041). CONCLUSION: HCQ initiation was associated with a significantly greater reduction in HbA(1c) as compared with MTX initiation among diabetes patients with rheumatic disease.
20595268 A prospective study of periodontal disease and risk of rheumatoid arthritis. 2010 Sep OBJECTIVE: To test for an association between periodontal disease (PD) and incident rheumatoid arthritis (RA) in a large prospective cohort. METHODS: We conducted a prospective analysis of history of periodontal surgery, tooth loss, and risk of RA among 81,132 women in the Nurses' Health Study prospective cohort. Periodontal surgery and tooth loss were used as proxies for history of PD. There were 292 incident RA cases diagnosed from 1992 to 2004. Information on periodontal surgery and tooth loss in the past 2 years was collected by questionnaire in 1992. Cox proportional hazards models were used to assess relationships between periodontal surgery, tooth loss, and risk of RA adjusting for age, smoking, number of natural teeth, body mass index, parity, breastfeeding, postmenopausal status, postmenopausal hormone use, father's occupation, and alcohol intake. RESULTS: Compared with those who reported no history of periodontal surgery or tooth loss, women with periodontal surgery or tooth loss did not have a significantly elevated risk of RA in multivariable-adjusted models (RR 1.24, 95% CI 0.83, 1.83; and RR 1.18, 95% CI 0.47, 2.95, respectively). In analyses stratified by ever and never-smokers, ever-smokers with periodontal surgery had an increased risk that was also nonsignificant. Those with severe PD (both history of periodontal surgery and tooth loss) did not have a significant increased risk. CONCLUSION: In this large cohort of American women, there was no evidence of an increased risk of later-onset RA among those with a history of periodontal surgery and/or tooth loss.