Hydroxychloroquine-induced inverse psoriasis.

A 65-year-old woman presented to our rheumatology clinic with pain and swelling of multiple joints of her hands. After a thorough evaluation, she was diagnosed with rheumatoid arthritis and was started on hydroxychloroquine therapy. A week later, she presented to our clinic with an acute condition and reported that after taking hydroxychloroquine for a few days she developed multiple rashes, most prominent at skin folds around her breasts, neck, axillae and buttocks. The rashes were characteristic of inverse psoriasis. Hydroxychloroquine was discontinued and the patient was started on methotrexate therapy that resulted in resolution of her rashes in a week.

Golimumab in patients with active rheumatoid arthritis after treatment with tumor necrosis factor α inhibitors: findings with up to five years of treatment in the multicenter, randomized, double-blind, placebo-controlled, phase 3 GO-AFTER study.

INTRODUCTION: The aim of this study was to assess long-term golimumab therapy in rheumatoid arthritis (RA) patients who discontinued previous tumor necrosis factor-α (TNF)-inhibitor(s). METHODS: Patients enrolled into this multicenter, randomized, double-blind, placebo-controlled study of active RA (≥4 tender, ≥4 swollen joints) received placebo (Group 1) or golimumab 50 mg (Group 2) or 100 mg (Group 3) injections every 4 weeks. Patients in Groups 1 and 2 with inadequate response at week 16 escaped to golimumab 50 and 100 mg, respectively. At week 24, Group 1 patients crossed-over to golimumab 50 mg, Group 2 continued golimumab 50/100 mg per escape status, and Group 3 maintained dosing. During the long-term-extension (LTE), golimumab 50 mg could be increased to 100 mg, and 100 mg could be decreased to 50 mg. Data through 5 years are reported for all patients (safety) and patients using methotrexate (efficacy, intention-to-treat (ITT) analysis with last-observation-carried-forward for missing data and non-responder imputation for unsatisfactory efficacy discontinuations). RESULTS: In total, 459 of 461 randomized patients received the study agent, 304 of whom were methotrexate-treated and included in efficacy analyses. Through week 256, the proportions of methotrexate-treated patients achieving American-College-of-Rheumatology (ACR) responses were 37.6% to 47.0% for ACR20, 21.4% to 35.0% for ACR50, and 7.8% to 17.0% for ACR70 response across randomized groups. Golimumab safety through week 268 was generally consistent with that at week 24 and week 160 and other anti-TNF agents. CONCLUSIONS: In some patients with active RA discontinuing previous TNF-antagonist therapy, golimumab safety and efficacy, assessed conservatively with ITT analyses, was confirmed through 5 years. TRIAL REGISTRATION: Clinicaltrials.gov NCT00299546 . Registered 03 March 2006.

The effect of golimumab on haemoglobin levels in patients with rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis.

OBJECTIVE: To evaluate the effect of golimumab on haemoglobin levels in patients with RA, PsA or AS. METHODS: Secondary analysis was performed on integrated data from five randomized controlled studies: three RA, one PsA and one AS (2303 patients total). Golimumab 50 or 100 mg was injected s.c. every 4 weeks with or without MTX. Control groups received placebo injections plus MTX or background therapy. Patients with haemoglobin levels below the age- and sex-specific normal ranges were considered to have anaemia. Ferritin levels were used to distinguish anaemia of mixed aetiology (≥ 15 and <60 ng/ml) and anaemia of inflammation (≥ 60 ng/ml). Changes from baseline to weeks 14 and 24 in haemoglobin level were compared between treatment groups using an analysis of variance on the van der Waerden normal scores. RESULTS: At baseline, 21% of RA patients, 9% of PsA patients and 15% of AS patients had anaemia. Of these, 24%, 57% and 25%, respectively, had anaemia of inflammation. The median increase from baseline to week 14 in the haemoglobin level of anaemic patients was 0.3 g/dl in the control group and 0.9 g/dl in the golimumab group (P < 0.001). Haemoglobin levels improved within the subgroups of patients with anaemia of mixed aetiology (control, 0.4 g/dl vs golimumab, 0.7 g/dl) (P = 0.305) and with anaemia of inflammation (0.2 vs 1.4 g/dl, respectively) (P < 0.001). CONCLUSION: Compared with the control group, patients receiving golimumab treatment had significantly improved haemoglobin levels, particularly among patients with anaemia of inflammation.

Tanezumab reduces osteoarthritic hip pain: results of a randomized, double-blind, placebo-controlled phase III trial.

OBJECTIVE: To compare the efficacy of tanezumab versus placebo for reducing pain and improving physical function in patients with osteoarthritis (OA) of the hip. METHODS: This was a 32-week, randomized, double-blind, placebo-controlled, phase III trial. Patients with baseline Western Ontario and McMaster Universities OA Index (WOMAC) Pain and Physical Function subscale scores of ≥5 and ≥4, respectively, and patient's global assessment of OA as "fair," "poor," or "very poor" were treated at baseline and weeks 8 and 16. Coprimary efficacy end points were change from baseline to week 16 in WOMAC Pain and Physical Function subscales and patient's global assessment, analyzed using analysis of covariance. Adverse events (AEs) were monitored throughout. RESULTS: Patients (n = 621) were randomized 1:1:1:1 to treatment with intravenous tanezumab 2.5 mg, 5 mg, or 10 mg or placebo. Each tanezumab group showed significant improvement for the 3 coprimary end points versus placebo (P ≤ 0.001 for all). AE incidence ranged from 55% to 58% across tanezumab groups versus 44% for placebo. Safety findings were similar to those previously reported. The tanezumab OA clinical program was temporarily placed on hold because of AEs leading to joint replacement. Total joint replacements were reported in 8 patients: 1 in the 10 mg, 2 in the 5 mg, 2 in the 2.5 mg, and 3 in the placebo group. A total of 9 joints were replaced (8 hips [7 index joints] and 1 shoulder). CONCLUSION: Our findings indicate that tanezumab provides superior pain relief and improvement in physical function and patient's global assessment versus placebo in patients with painful hip OA, and is generally well tolerated.

Markers of inflammation and bone remodelling associated with improvement in clinical response measures in psoriatic arthritis patients treated with golimumab.

OBJECTIVE: To determine serum biomarker associations with clinical response to golimumab treatment in patients with psoriatic arthritis (PsA). METHODS: GO-REVEAL was a randomised, placebo-controlled study of golimumab in patients with active PsA. Samples were collected from 100 patients at baseline, week 4 and week 14, and analysed for serum-based biomarkers and protein profiling (total 92 markers); data were correlated with clinical measures at week 14. RESULTS: Serum levels of a subset of proteins (apolipoprotein C III, ENRAGE, IL-16, myeloperoxidase, vascular endothelial growth factor, pyridinoline, matrix metalloproteinase 3, C-reactive protein (CRP), carcinoembryonic antigen, intercellular adhesion molecule 1 and macrophage inflammatory protein 1α) at baseline or week 4 were strongly associated with American College of Rheumatology 20% improvement (ACR20) response and/or disease activity score in 28 joints (DAS28) at week 14. A smaller subset of proteins was significantly associated with a 75% improvement in the psoriasis area and severity index score (PASI75) at week 14, (adiponectin, apolipoprotein CIII, serum glutamic oxaloacetic transaminase, and tumour necrosis factor α). Subsets of proteins were identified as potentially predictive of clinical response for each of the clinical measures, and the power of these biomarker panels to predict clinical response to golimumab treatment was stronger than for CRP alone. CONCLUSIONS: This analysis provides insight into several panels of markers that may have utility in identifying PsA patients likely to have ACR20, DAS28, or PASI75 responses following golimumab treatment.

Tanezumab reduces osteoarthritic knee pain: results of a randomized, double-blind, placebo-controlled phase III trial.

UNLABELLED: The objective of this study was to compare the analgesic efficacy of tanezumab versus placebo in patients with osteoarthritis (OA) of the knee. This was a 32-week, randomized, double-blind, placebo-controlled phase III trial (NCT00733902). The patient criteria included diagnosis of OA; Western Ontario and McMaster Universities OA Index (WOMAC) Pain and Physical Function subscale scores of ≥5 and ≥4, respectively; Patient's Global Assessment of Osteoarthritis (PGA) ≥3; and failure of nonopiate pain medications or candidacy for invasive interventions. Patients received 3 intravenous doses of tanezumab (2.5, 5, or 10 mg) or placebo. The co-primary efficacy end points were changes in WOMAC subscales and PGA at week 16. Adverse events were monitored throughout. Overall, 690 patients (61% female) were randomized and treated. Those treated with tanezumab showed significant improvement in the 3 co-primary end points (P ≤ .015 for all). The incidence of adverse events was 55 to 60% for tanezumab-treated patients versus 48% for placebo-treated patients. Joint replacement was reported in 4 patients, 1 in each treatment group; a total of 5 joints were replaced (1 index knee and 4 hips). The tanezumab OA clinical program is currently on clinical hold due to potential adverse reactions leading to joint replacement. PERSPECTIVE: This is the first phase III randomized, controlled trial to demonstrate that nerve growth factor blockade by tanezumab has superior analgesic efficacy in OA of the knee compared with placebo. Tanezumab was well tolerated, and reports of worsening OA and/or joint replacement were evenly distributed across the treatment groups.

Effect of golimumab on patient-reported outcomes in rheumatoid arthritis: results from the GO-FORWARD study.

OBJECTIVE: To evaluate the effect of golimumab on physical function, general health, and fatigue in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) therapy. METHODS: In the multicenter, randomized, placebo-controlled GO-FORWARD study, 444 adults with active RA despite MTX received subcutaneous placebo + MTX (crossover to golimumab 50 mg at Week 24), golimumab 100 mg + placebo, golimumab 50 mg + MTX, or golimumab 100 mg + MTX every 4 weeks. Physical function and general health were assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI) and Physical and Mental Component Summary (PCS, MCS) scores of the Medical Outcomes Study Short Form-36 questionnaire (SF-36), respectively, through Week 52. Fatigue was measured through Week 24 using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire. RESULTS: Mean improvements from baseline in HAQ-DI, SF-36 PCS, and FACIT-Fatigue scores (Weeks 14 and 24) were significantly greater for golimumab 50 mg + MTX and 100 mg + MTX versus placebo + MTX. Significantly greater proportions of patients treated with golimumab + MTX achieved clinically meaningful improvements from baseline to Weeks 14 and 24 in HAQ-DI, PCS, and FACIT-Fatigue scores. Mean improvements in SF-36 PCS (Week 14), MCS (Week 24), and FACIT-Fatigue (Weeks 14 and 24) scores were significantly greater for golimumab 100 mg + placebo versus placebo + MTX. Mean improvements from baseline in HAQ-DI, SF-36 PCS, and MCS scores through Week 24 were sustained through Week 52. CONCLUSION: Patients with active RA despite MTX had significant improvement in physical function, general health, and fatigue following golimumab + MTX therapy; improvements in physical function and general health were maintained through Week 52. (Clinical Trials Registration NCT00264550).

Golimumab in patients with active rheumatoid arthritis who have previous experience with tumour necrosis factor inhibitors: results of a long-term extension of the randomised, double-blind, placebo-controlled GO-AFTER study through week 160.

OBJECTIVE: The aim of this study was to assess long-term golimumab therapy in patients with rheumatoid arthritis (RA) who discontinued previous tumour necrosis factor alpha (TNFα) inhibitor(s) for any reason. METHODS: Results through week 24 of this multicentre, randomised, double-blind, placebo-controlled study of active RA (≥4 tender, ≥4 swollen joints) were previously reported. Patients received placebo (Group 1), 50 mg golimumab (Group 2) or 100 mg golimumab (Group 3) subcutaneous injections every 4 weeks. Patients from Groups 1 and 2 with <20% improvement in tender/swollen joints at week 16 early escaped to golimumab 50 mg and 100 mg, respectively. At week 24, Group 1 patients crossed over to golimumab 50 mg, Group 2 continued golimumab 50/100 mg per escape status and Group 3 maintained dosing. Data through week 160 are reported. RESULTS: 459 of the 461 randomised patients were treated; 236/459 (51%) continued treatment through week 160. From week 24 to week 100, ACR20 (≥20% improvement in American College of Rheumatology criteria) response and ≥0.25 unit HAQ (Health Assessment Questionnaire) improvement were sustained in 70-73% and 75-81% of responding patients, respectively. Overall at week 160, 63%, 67% and 57% of patients achieved ACR20 response and 59%, 65% and 64% had HAQ improvement ≥0.25 unit in Groups 1, 2 and 3, respectively. Adjusted for follow-up duration, adverse event incidences (95% CI) per 100 patient-years among patients treated with golimumab 50 mg and 100 mg were 4.70 (2.63 to 7.75) and 8.07 (6.02 to 10.58) for serious infection, 0.95 (0.20 to 2.77) and 2.04 (1.09 to 3.49) for malignancy and 0.00 (0.00 to 0.94) and 0.62 (0.17 to 1.59) for death, respectively. CONCLUSION: In patients with active RA who discontinued previous TNF-antagonist treatment, golimumab 50 and 100 mg injections every 4 weeks yielded sustained improvements in signs/symptoms and physical function in ∼57-67% of patients who continued treatment. Golimumab safety was consistent with other anti-TNF agents, although definitive conclusions regarding long-term safety require further monitoring.

Tolerability of NGX-4010, a capsaicin 8% patch, in conjunction with three topical anesthetic formulations for the treatment of neuropathic pain.

BACKGROUND: The objective of this study was to assess the safety, tolerability, and preliminary efficacy of NGX-4010, a capsaicin 8% patch, following pretreatment with three different topical anesthetics in patients with peripheral neuropathic pain. METHODS: This open-label, multicenter study enrolled 117 patients with post-herpetic neuralgia, HIV-associated distal sensory polyneuropathy, or painful diabetic neuropathy. Patients received pretreatment with one of three lidocaine 4%-based topical anesthetics (L.M.X.4(®) [Ferndale Laboratories Inc, Ferndale, MI], Topicaine(®) Gel [Estela Basso, Jupiter, FL], or Betacaine Enhanced Gel 4 [Tiberius Inc, Tampa, FL]) for 60 minutes followed by a single 60- or 90-minute NGX-4010 application, and were followed for 12 weeks. Tolerability and safety measures included "pain now" Numeric Pain Rating Scale (NPRS) scores, dermal assessments, medication use for treatment-related pain, adverse events (AEs), clinical laboratory parameters, physical examinations, and vital signs. The primary efficacy variable was the percentage change in mean NPRS scores for "average pain for the past 24 hours" from baseline to weeks 2 through 12. RESULTS: Treatment with NGX-4010 following pretreatment with any of the three topical anesthetics was generally safe and well tolerated. Nearly all patients completed ≥90% of the planned NGX-4010 application duration. The most common treatment-related AEs, application-site burning and application-site pain, were transient, mostly mild or moderate, and could be adequately managed by local cooling or short-acting oral opioid analgesics. Although slightly more patients used medication for treatment-related discomfort following pretreatment with Topicaine compared with L.M.X.4 or Betacaine, there were no statistical differences between the topical anesthetics. Neuropathic pain reduction from baseline to weeks 2 through 12 was approximately 30% and was similar among the topical anesthetics; the proportion of responders ranged from 45% to 50%. CONCLUSION: Treatment with NGX-4010 following pretreatment with any of the three topical anesthetics was generally safe and well tolerated; no significant differences in the parameters measured were noted between the pretreatment groups.

Efficacy, safety, and tolerability of NGX-4010, capsaicin 8% patch, in an open-label study of patients with peripheral neuropathic pain.

AIMS: To assess efficacy, safety, and tolerability of NGX-4010, capsaicin 8% patch, in patients with peripheral neuropathic pain. METHODS: This open-label, uncontrolled, 12-week study enrolled 25 patients with postherpetic neuralgia (PHN), one with HIV-distal sensory polyneuropathy, and 91 with painful diabetic neuropathy (PDN). Patients received pre-treatment with one of three 4% lidocaine topical anesthetics (L.M.X.4¹, Topicaine Gel², or Betacaine Enhanced Gel 4³) followed by a single 60- or 90-min NGX-4010 application. The primary efficacy variable was the percentage change in Numeric Pain Rating Scale scores from baseline to Weeks 2-12. Adverse events (AEs), laboratory parameters, vital signs, neurosensory examinations, dermal assessments, treatment-related pain scores, and medication use for treatment-related pain were collected. RESULTS: PDN and PHN patients achieved a 31% and 28% mean pain decrease from baseline during Weeks 2-12, respectively, and 47% and 44%, respectively, were responders (≥30% pain decrease). Mild or moderate treatment-site-related burning and pain were the most common AEs and there was no evidence of impaired neurosensory function. CONCLUSIONS: NGX-4010 in conjunction with any of the three topical anesthetics tested was generally safe and well tolerated and reduced pain over a 12-week period in patients with PDN and PHN.

Golimumab in patients with active rheumatoid arthritis after treatment with tumour necrosis factor alpha inhibitors (GO-AFTER study): a multicentre, randomised, double-blind, placebo-controlled, phase III trial.

BACKGROUND: Tumour necrosis factor alpha (TNFalpha) inhibitors are frequently used to treat rheumatoid arthritis, but whether use of a different TNFalpha inhibitor can improve patient response is unknown. We assess the efficacy and safety of the TNFalpha inhibitor golimumab in patients with active rheumatoid arthritis who had previously received one or more TNFalpha inhibitors. METHODS: 461 patients with active rheumatoid arthritis from 82 sites in 10 countries were randomly allocated by interactive voice response system, stratified by study site and methotrexate use, to receive subcutaneous injections of placebo (n=155), 50 mg golimumab (n=153), or 100 mg golimumab (n=153) every 4 weeks between Feb 21, 2006, and Sept 26, 2007. Allocation was double-blind. Eligible patients had been treated with at least one dose of a TNFalpha inhibitor previously. Patients continued stable doses of methotrexate, sulfasalazine, hydroxychloroquine, oral corticosteroids, and non-steroidal anti-inflammatory drugs. The primary endpoint was achievement at week 14 of 20% or higher improvement in American College of Rheumatology criteria for assessment of rheumatoid arthritis (ACR20). At week 16, patients who had less than 20% improvement in tender and swollen joint counts were given rescue therapy and changed treatment from placebo to 50 mg golimumab, or from 50 mg to 100 mg golimumab. Drug efficacy was assessed by intention to treat and safety was assessed according to the study drug given. This study is registered with ClinicalTrials.gov, number NCT00299546. FINDINGS: Patients had discontinued previous TNFalpha inhibitors because of lack of effectiveness (269 [58%] patients) or reasons unrelated to effectiveness (246 [53%] patients), such as intolerance and accessibility issues. Patients had active disease, which was indicated by a median of 14.0 (IQR 9.0-22.0) swollen and 26.0 (16.0-41.0) tender joints for the whole group. 28 (18%) patients on placebo, 54 (35%) patients on 50 mg golimumab (odds ratio 2.5 [95% CI 1.5-4.2], p=0.0006), and 58 (38%) patients on 100 mg golimumab (2.8 [1.6-4.7], p=0.0001) achieved ACR20 at week 14. Two patients were never treated, and 57 patients did not complete the study because of adverse events, unsatisfactory treatment effect, loss to follow-up, death, or other reasons. 155 patients on placebo, 153 on 50 mg golimumab, and 153 on 100 mg golimumab were assessed for drug efficacy. For weeks 1-16, serious adverse events were recorded in 11 (7%) patients on placebo, 8 (5%) on 50 mg golimumab, and 4 (3%) on 100 mg golimumab. For weeks 1-24, after some patients were given rescue therapy, serious adverse events were recorded in 15 (10%) patients on placebo, 14 (5%) on 50 mg golimumab, and 8 (4%) on 100 mg golimumab. INTERPRETATION: Golimumab reduced the signs and symptoms of rheumatoid arthritis in patients with active disease who had previously received one or more TNFalpha inhibitors. FUNDING: Centocor Research and Development and Schering-Plough Research Institute.

Treatment of rheumatoid arthritis with a Syk kinase inhibitor: a twelve-week, randomized, placebo-controlled trial.

OBJECTIVE: Spleen tyrosine kinase (Syk) has been identified as an important modulator of immune signaling in B cells and cells bearing Fcgamma-activating receptors. R788, a prodrug of active metabolite R406, has been shown to be an inhibitor of Syk kinase, active in a variety of in vitro and in vivo models, suggesting potential activity in the treatment of rheumatoid arthritis (RA). METHODS: We enrolled 189 patients with active RA despite methotrexate therapy in a 3-month, multicenter, ascending-dose, double-blind, placebo-controlled trial. The primary end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12. RESULTS: Twice-daily oral doses of 100 mg and 150 mg of R788 were significantly superior to placebo or twice-daily oral doses of 50 mg at week 12 (ACR20 achieved in 65% and 72% versus 38% and 32% of patients, respectively [P < 0.01]). ACR50 (achieved in 49% and 57% versus 19% and 17% of patients, respectively) and ACR70 (achieved in 33% and 40% versus 4% and 2% of patients, respectively) scores showed a similar pattern. Clinical effect was noted as early as 1 week after initiation of therapy. Reductions in serum interleukin-6 and matrix metalloproteinase 3 levels also occurred as early as week 1 in the groups receiving 100 mg and 150 mg R788. The major adverse effects were gastrointestinal side effects (predominantly diarrhea) and neutropenia (<1,500/mm3), both of which were dose related. CONCLUSION: These results indicate that an inhibitor of Syk kinase produces significant clinical benefits at 12 weeks in a population of patients with active RA receiving methotrexate therapy. Syk kinase may be an important new therapeutic target in RA and related autoimmune conditions.

Evaluation of the comparative efficacy of etoricoxib and ibuprofen for treatment of patients with osteoarthritis: A randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To directly compare the efficacy and safety of etoricoxib, 30 mg once daily, ibuprofen, 800 mg 3 times daily, and placebo for treatment of osteoarthritis (OA) of the hip and knee. PATIENTS AND METHODS: A randomized, double-blind, placebo-controlled trial of patients with OA of the knee or hip was performed between February 2003 and November 2003 in 61 medical centers in the United States. Qualified patients aged 40 to 89 years were randomized to receive placebo, etoricoxib, 30 mg once daily, or ibuprofen, 800 mg 3 times daily, for 12 weeks. Primary efficacy end points Included the Western Ontario and McMaster Universities Osteoarthritis Index pain and physical function subscales and Patient Global Assessment of Disease Status. Response to treatment was assessed by the time-weighted average change from baseline over 12 weeks. RESULTS: In 528 patients, baseline values for the 3 primary end points ranged from 67.78 to 72.60 mm (0-100 mm visual analog scale). Near-maximal efficacy was achieved by week 2 with both active treatments and sustained over the course of the trial. During the 12-week period, least squares mean changes in the primary end points (Western Ontario and McMaster Universities Osteoarthritis Index and Patient Global Assessment of Disease Status subscales) ranged from -16.53 to -13.55 mm, -27.89 to -23.68 mm, and -26.53 to -22.97 mm in the placebo, etoricoxib, and Ibuprofen groups, respectively. Both etoricoxib and ibuprofen were more effective (P<.001) than placebo for all primary end points. Etoricoxib and ibuprofen treatment responses for the primary end points were determined to be comparable with use of prespecified comparability criteria. Results for all other efficacy end points were consistent with responses observed for the primary end points. Etoricoxib and ibuprofen generally were well tolerated. CONCLUSION: For patients with OA, treatment with etoricoxib, 30 mg/d, is well tolerated and provides sustained clinical effectiveness that is superior to placebo and comparable to ibuprofen, 2400 mg/d.

Management of postmenopausal osteoporosis.

Postmenopausal osteoporosis is associated with significant morbidity, mortality, reduction in quality of life, and increasing health care costs. It is estimated that 1.5 million women in the United States have one or more osteoporosis-related fractures annually. Fractures may occur at any site, but vertebral fractures are the most common. Longitudinal studies have demonstrated a decreased life expectancy associated with both vertebral and nonvertebral fractures. Once an initial fracture occurs, there is a fivefold increased risk of a second fracture within 1 year. The management of osteoporosis today incorporates multiple modalities of therapy. In addition to early detection, patient education, exercise, and nutritional supplementation, multiple therapeutic agents should be implemented early in an attempt to prevent initial and subsequent fractures. This article reviews currently approved modalities of therapy for the prevention and treatment of postmenopausal osteoporosis.

Increasing resident research in a military internal medicine program.

The internal medicine residents from our training program rarely participated in scholarly activity prior to 1994. In an attempt to increase the quality and quantity of resident research, we initiated a research program that included: (1) a mandatory research project, (2) 2 months of dedicated research time, (3) appointment of a research director, (4) lectures on the critical appraisal of medical literature and research design, (5) technical support, (6) faculty mentoring, (7) a research meeting and competition involving five residency programs, and (8) military achievement awards. From 1994 to 1999, our house staff has had 134 research presentations and 21 manuscripts accepted for publication in peer-reviewed journals. Ninety percent of our residents presented at least one project at a scientific meeting by completion of their training between 1996 and 1999. Resident scholarly activity is significantly enhanced by a structured research program, an opportunity to present at a scientific meeting, and award recognition.

Ethnic variation in the clinical manifestations of rheumatoid arthritis: role of HLA-DRB1 alleles.

OBJECTIVE: To assess the extent of ethnic variation in the clinical expression of rheumatoid arthritis (RA) and the role of HLA-DRB1 alleles in this variation. METHODS: We assessed consecutive RA patients for joint findings, subcutaneous nodules, laboratory and radiographic findings, and treatment. We typed HLA-DRB1 alleles to identify those that contain the shared epitope (SE). We adjusted ethnic comparisons for age and sex, and tested for ethnic heterogeneity in the effect of the SE. RESULTS: We studied 777 RA patients, 498 of whom were women (64%), 432 were Hispanic (56%), 272 were non-Hispanic white (NHW; 35%), 53 were African American (AA; 7%), and 20 were Asian (3%). Compared with NHW, Hispanics had significantly more tender joints (17 versus 11), more swollen joints (8 versus 7), more frequent rheumatoid factor (RF) positivity (93% versus 84%), higher erythrocyte sedimentation rate (ESR; 45 versus 36 mm/hr), and a lower number of lifetime disease-modifying antirheumatic drugs (1.9 versus 2.5). AA were older at onset (46 versus 44 years), had less frequent subcutaneous nodules (18% versus 28%), and higher ESR (42 versus 36 mm/hour) than did NHW. Hispanics and AA were more likely than NHW to be null for the SE (odds ratio [OR] = 4.59 for AA; and OR = 1.61 for Hispanics), and less likely to have 2 SE-carrying alleles (OR = 0.59 for Hispanics and OR = 0.25 for AA). The number of SE copies was associated with subcutaneous nodules, ESR, RF, and radiographic changes. Ethnic heterogeneity in the effect of the SE was modest. CONCLUSIONS: There is ethnic variation in the clinical expression of RA and in both the frequency and types of SE-carrying HLA-DRB1 alleles. Some ethnic variation in clinical findings is associated with differences in SE frequency. However, we found that the effect of the SE on the clinical features of RA varies little between ethnic groups.

Internuclear ophthalmoplegia (INO): an unusual presentation of neuropsychiatric lupus erythematosus.

BACKGROUND AND PURPOSE: INO in SLE is uncommon, affecting < 5% of hospitalized SLE patients. A MEDLINE search 1966-2001 revealed only 22 reported cases. INO also rarely presents with diplopia. We report such a case. CASE REPORT: A 35 year old woman with long standing SLE developed the abrupt onset of diplopia, vertigo and ataxia. Physical examination was remarkable only for the neurologic examination with a left INO and abnormal cerebellar testing. Treatment with corticosteroids and intravenous cyclophosphamide resulted in resolution of her cerebellar and ocular symptoms.

Heterogeneity between men and women in the influence of the HLA-DRB1 shared epitope on the clinical expression of rheumatoid arthritis.

OBJECTIVE: To test the hypothesis that the influence of the HLA-DRB1 shared epitope (SE) on the clinical manifestations of rheumatoid arthritis (RA) differs between men and women. METHODS: We assessed 777 consecutive RA patients for age at disease onset, articular manifestations, subcutaneous nodules, laboratory and radiographic findings, and treatment received. We typed HLA-DRB1 alleles by polymerase chain reaction-sequence-specific primer amplification and categorized the number of SE-containing alleles. We used regression models to adjust comparisons between the sexes for age and clustering by recruitment center, and included SE x sex interaction terms to look for heterogeneity between men and women in the effect of the SE. RESULTS: Among the 777 RA patients, 548 (71%) were women. Men and women differed significantly in the adjusted frequency of SE positivity (women 71.4% versus men 78.4%; P < or = 0.001). The SE was associated with a younger age at symptom onset and RA diagnosis among men, but not among women. The SE likewise had a significant adverse effect on joint tenderness, swelling, and deformity among men only. The SE was associated with a higher erythrocyte sedimentation rate in women and more frequent positivity for rheumatoid factor among both men and women. CONCLUSION: There is heterogeneity between men and women in the effect of the SE on RA susceptibility and clinical expression. Further research is needed to understand the mechanism of this heterogeneity.

Validation of the Diesse Mini-Ves erythrocyte sedimentation rate (ESR) analyzer using the Westergren ESR method in patients with systemic inflammatory conditions.

The Diesse Mini-Ves (DMV) erythrocyte sedimentation rate (ESR) analyzer was designed to improve efficiency in determining the ESR. We compared the Westergren ESR method with the 4-sample DMV ESR analyzer for performance and clinical correlation. This prospective observational study, conducted at a 450-bed tertiary medical center, evaluated 291 paired samples from subjects with various systemic inflammatory conditions. Linear regression analysis revealed a statistically significant correlation between the 2 methods. Satisfactory precision of the DMV analyzer was obtained for high and mid-range ESR values. The 4-sample DMV ESR analyzer was precise and comparable in results to the Westergren ESR method. This DMV ESR analyzer is now used at our medical center based on quality control improvements that include a faster, safer, and more standardized ESR method. Hospital or office-based clinical laboratories should consider using the 4-sample DMV ESR analyzer in place of the Westergren method.