PubMed Health⌕ Search

Biomedical subjects

Arthur Kavanaugh

Publications and source records attributed to Arthur Kavanaugh.

36 records · Page 2Linked to original sources
PubMed2005

A randomized, blinded, parallel group, placebo controlled pilot study evaluating the effect of PVAC treatment in patients with diffuse systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is a disorder characterized by progressive thickening of the skin; there is no effective therapy. PVAC, a potential therapeutic agent derived from delipidated, deglycolipidated Mycobacterium vaccae, has shown effects on cutaneous disease in animal models of SSc. We evaluated the safety and possible biologic effect of intradermal injections of PVAC in patients with diffuse SSc. METHODS: Eighteen patients enrolled in this double blind, placebo controlled, randomized, 24 week pilot study. All patients met criteria for diffuse SSc without evidence of significant renal dysfunction, pulmonary fibrosis, pulmonary hypertension, or congestive heart failure. Patients received 8 intradermal injections of 15 microg PVAC, 50 microg PVAC, or placebo at 3 week intervals. The primary efficacy endpoint was the change in Modified Rodnan Skin Score (MRSS) at Week 24. Each of the active drug arms was compared to placebo. RESULTS: Baseline demographic and disease characteristics were similar across the 3 treatment groups. The median age was 48 years and 14 of 18 (78%) patients were female. The regimens were well tolerated with no reported serious adverse events; however, grade 1 or 2 injection site reactions occurred in the majority of patients receiving PVAC. The MRSS improved by 20.6% in the 15 microg PVAC arm, while it worsened by 29.8% in the placebo arm and by 16.7% in the 50 microg arm. Change in physician and patient global assessments followed similar trends. CONCLUSION: In this pilot study, use of PVAC in patients with SSc appeared safe and was associated with a trend toward improved skin scores in the 15 microg treatment group. Additional evaluation of this therapeutic approach is warranted.

Adult↗
PubMed2004

Consideration of the risk and treatment of tuberculosis in patients who have rheumatoid arthritis and receive biologic treatments.

Evidence supports the association of tuberculosis (TB) with tumor necrosis factor inhibitor therapy in patients who have rheumatoid arthritis. There seem to be differential risks of TB with the currently available inhibitors. Screening for latent TB infection with purified protein derivative is indicated for patients who are being considered for treatment; it seems to be effective in reducing the occurrence of TB in treated patients.

Antirheumatic Agents↗
PubMed2004

Nutrient intake and diet quality in patients with systemic lupus erythematosus on a culturally sensitive cholesterol lowering dietary program.

OBJECTIVE: To evaluate the effect of a culturally sensitive cholesterol lowering dietary program on energy, protein, fiber, vitamin and mineral intake, diet quality, and hemoglobin levels in patients with systemic lupus erythematosus (SLE). METHODS: Seventeen patients with SLE were randomized to a Step II diet intervention group or a control group for 12 weeks. The diet intervention was made up of weekly group sessions during the first 6 weeks followed by telephone counseling every 2 weeks for the last 6 weeks. Food intake was assessed by 3-day food record at baseline, 6, and 12 weeks. Diet quality was assessed by expressing the nutrients as a percentage of the Dietary Reference Intakes of the US National Academy of Sciences, or as a percentage of the nutrient guidelines by the National Cholesterol Education Program, Adult Treatment Panel III. Between- and within-group changes in nutrient intakes were assessed by repeated measures ANOVA. RESULTS: The changes in nutrient intakes were not significantly different between the groups for any of the nonfat nutrients except vitamin B12 (p = 0.05), which decreased in the diet group and increased in the control group. Within-group analysis showed a significant reduction (p = 0.0003 to 0.02) in the diet group in energy and sodium intake at 6 and 12 weeks and B12 intake at 12 weeks compared to the respective baseline values (28-32%, 37-41%, and 43%, respectively). Sodium intake decreased to 66-71% of the total sodium allowance (< 2400 mg per day) in the diet group. The intervention was successful in maintaining adequate intakes or even increasing intakes of most nutrients except B12, dietary fiber, folate, calcium, and iron, which were slightly higher or below 67% of the Dietary Reference Intakes or other dietary guidelines. Anemia, as assessed by hemoglobin levels, was present throughout the study and did not correlate with iron intake. CONCLUSION: This culturally sensitive cholesterol reducing diet program was successful in decreasing sodium intake and maintaining adequate intakes of most nutrients except B12, dietary fiber, iron, calcium, and folate. Future intervention studies in patients with SLE need to pay special attention to these nutrients and the presence of anemia.

Adult↗
PubMed2004

A web-compatible instrument for measuring self-reported disease activity in arthritis.

OBJECTIVE: To describe a Web-based computer health assessment survey for patients with rheumatoid arthritis (RA) and to evaluate the survey in comparison with current paper versions. METHODS: Utilizing data from a study on RA, we compared results from 43 patients attending a university-based clinic who were each given a paper and a demonstration computer version of a patient self-assessment questionnaire including multiple-choice questions from a multi-dimensional Health Assessment Questionnaire (HAQ); visual analog scales (VAS) for pain, fatigue, and global disease severity; and a tender and swollen joint count reporting tool. Patients were given optional followup surveys to determine their opinion of the computer program. RESULTS: High correlations (intraclass correlation coefficient > 0.9) were seen across methods for the 10-item HAQ and psychological distress scores and the VAS scores for pain and global disease severity. Moderate correlation was observed for the self-efficacy scores, the VAS scores for fatigue, and tender joint counts. The data also revealed a small shift in the mean scores for the HAQ and self-efficacy questions, with patients reporting slightly higher scores on the computer instrument. Overall, patient opinions of the uniquely designed joint count tool were good, with 71% of responding patients answering favorably. CONCLUSION: Web-based computer versions of patient self-assessment surveys in RA are comparable to paper versions, and their use in clinics or over the Internet could dramatically facilitate the ability of physicians to monitor patients' health.

Adolescent↗
PubMed2004

Functional status and radiographic joint damage are associated with health economic outcomes in patients with rheumatoid arthritis.

OBJECTIVE: This analysis examines the relationship between the functional and radiographic measures of disease activity and the employment status in patients with rheumatoid arthritis (RA). We also assessed the influence of improvement in physical function on employability, healthcare costs, and quality of life, utilizing data collected in the ATTRACT trial. METHODS: During the ATTRACT trial, the Health Assessment Questionnaire (HAQ) disability index, radiographic damage measured by the van der Heijde modified Sharp (vdH-Sharp) score, employment status, healthcare resource utilization, and quality of life measured by Medical Outcomes Survey Short Form-36 were assessed at baseline and again periodically through Week 54. Clinically important improvement was defined as an improvement in the HAQ of > or = 0.25 from baseline to Week 54. RESULTS: There was a significant association at baseline between functional status and the percentages of patients employed. Increased radiographic joint damage was associated with lower full-time employment rate, with patients in the 2 highest quartiles (vdH-Sharp score > 51.5) of radiographic damage having lower rates of full-time employment than those with less damage. During the ATTRACT trial, patients who achieved a clinically important improvement in HAQ scores had a significant improvement in their employability (21% vs 3%; p < 0.001), in their time lost from work (7 vs 30 days; p = 0.012), in their total/direct medical costs (7093/6791 US dollars vs 11,712/10,039 US dollars; p < 0.001), and in their quality of life (p < 0.001) compared with those who did not demonstrate this improvement. CONCLUSION: Functional disability and radiographic joint damage are correlated with employment in patients with RA. Clinically important improvement in HAQ scores is associated with substantial health economic and quality of life benefits for patients with RA.

Arthritis, Rheumatoid↗
PubMed2004

Combination leflunomide and methotrexate (MTX) therapy for patients with active rheumatoid arthritis failing MTX monotherapy: open-label extension of a randomized, double-blind, placebo controlled trial.

OBJECTIVE: To obtain additional safety and efficacy data on leflunomide (LEF) treatment in combination with methotrexate (MTX) therapy in an open-label extension study in patients with rheumatoid arthritis (RA). METHODS: Following a 24 week, randomized, double-blind trial of adding placebo (PLA) or LEF to stable MTX therapy, patients could enter a 24 week extension. Subjects randomized to LEF and MTX continued treatment [(LEF/LEF) + MTX]. Subjects randomized to PLA and MTX switched to LEF (10 mg/day, no loading dose) and MTX [(PLA/LEF) + MTX]. The double-blind regarding initial randomization was maintained. RESULTS: For subjects in the extension phase, American College of Rheumatology 20% (ACR20) responder rates for the (LEF/LEF) + MTX group were maintained from Week 24 (57/96, 59.4%) to Week 48 (53/96, 55.2%). ACR20 responder rates improved in patients switched to LEF from PLA at Week 24 [(PLA/LEF) + MTX] from 25.0% (24/96) at Week 24 to 57.3% (55/96) at Week 48. Patients in the extension who switched from PLA to LEF without a loading dose exhibited a lower incidence of elevated transaminases compared to patients initially randomized to LEF. Diarrhea and nausea were less frequent during the open-label extension in patients who did not receive a LEF loading dose. CONCLUSION: Response to therapy was maintained to 48 weeks of treatment in patients who continued to receive LEF and MTX during the extension. Importantly, ACR20 response rates after 24 weeks of LEF therapy were similar between patients switched from PLA to LEF without loading dose, and those who received a loading does of LEF (100 mg/day x 2 days) at randomization. Fewer adverse events were reported in patients switched to LEF without a loading dose.

Antirheumatic Agents↗
PubMed2003

Quantitative biomarker analysis of synovial gene expression by real-time PCR.

Synovial biomarker analysis in rheumatoid arthritis can be used to evaluate drug effect in clinical trials of novel therapeutic agents. Previous studies of synovial gene expression for these studies have mainly relied on histological methods including immunohistochemistry and in situ hybridization. To increase the reliability of mRNA measurements on small synovial tissue samples, we developed and validated real time quantitative PCR (Q-PCR) methods on biopsy specimens. RNA was isolated from synovial tissue and cDNA was prepared. Cell-based standards were prepared from mitogen-stimulated peripheral blood mononuclear cells. Real time PCR was performed using TaqMan chemistry to quantify gene expression relative to the cell-based standard. Application of the cellular standard curve method markedly reduced intra- and inter-assay variability and corrected amplification efficiency errors compared with the C(t) method. The inter-assay coefficient of variation was less than 25% over time. Q-PCR methods were validated by demonstrating increased expression of IL-1beta and IL-6 expression in rheumatoid arthritis synovial samples compared with osteoarthritis synovium. Based on determinations of sampling error and coefficient of variation, twofold differences in gene expression in serial biopsies can be detected by assaying approximately six synovial tissue biopsies from 8 to 10 patients. These data indicate that Q-PCR is a reliable method for determining relative gene expression in small synovial tissue specimens. The technique can potentially be used in serial biopsy studies to provide insights into mechanism of action and therapeutic effect of new anti-inflammatory agents.

Anti-Inflammatory Agents↗
PubMed2003

Secondary immune deficiencies associated with biological therapeutics.

Biological therapeutics have been utilized in the past several years for the treatment of various autoimmune, cardiovascular, and neoplastic conditions. As these agents target both pathologic and physiologic components of inflammatory and immune systems, the scientific community has been challenged to identify potential secondary immune deficiencies associated with their use. This article will focus on biological agents used for the treatment of rheumatoid arthritis, including tumor necrosis factor-a inhibitors, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4 Ig), rituximab, and interleukin-1 receptor agonist (IL-1Ra). Both clinical and in vitro studies have been done to explore the potential immunomodulatory and immunosuppressive effects of these agents.

Abatacept↗
PubMed2003

Pharmacological treatment of established rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic, inflammatory condition of unknown aetiology that affects about 1% of the general population. Although the optimal care of RA patients requires various modalities, pharmacotherapy remains the cornerstone of treatment for established RA. The current therapeutic model encourages a step-up approach that safely incorporates several currently available classes of agents: non-steroidal anti-inflammatory drugs, selective cyclo-oxygenase-2 inhibitors, glucocorticoids, disease-modifying anti-rheumatic drugs, and biological agents (tumour necrosis factor-alpha inhibitors and interleukin-1 receptor antagonist). Non-steroidal anti-inflammatory drugs, selective cyclo-oxygenase-2 inhibitors and glucocorticoids, which offer a quick onset of symptom relief, are used mainly as adjunctive therapies. Disease-modifying anti-rheumatic drugs and biologicals have been successful in altering disease outcome and slowing radiographic progression. The indications, efficacy and safety of these agents in clinical trials and practice are reviewed in this chapter.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Allele and antigen-specific treatment of rheumatoid arthritis: a double blind, placebo controlled phase 1 trial.

OBJECTIVE: Human cartilage glycoprotein 39 (HC gp-39) appears to be a relevant autoantigen in patients with rheumatoid arthritis (RA). Administration of major histocompatibility complex (MHC) Class II complexed antigens without requisite costimulatory signals can induce immunologic tolerance. We evaluated the safety, pharmacokinetics, and preliminary efficacy of AG4263 in patients with RA. AG4263 is a soluble complex of native HLA-DR4 (beta*0401) complexed to Org 36601, a 13-mer peptide derived from HC gp-39 (also referred to as CDP263). METHODS: Thirty-one HLA-DRB1*0401 positive patients with persistent RA disease activity despite concurrent methotrexate were randomized to 7 infusions of AG4263 (n = 24) or placebo (n = 7) over 6 weeks. The initial dose of 0.5 micro g/kg was escalated in subsequent cohorts to a maximum of 150 micro g/kg. Safety analyses included recording of adverse events and measurement of CD4/CD8 counts, reactivity to recall antigens, and development of antibodies to HLA-DR4. Efficacy was assessed using the Paulus 20 criteria. RESULTS: Treatment was well tolerated, with injection site reaction the most common adverse event. There was no loss of reactivity to recall antigens, change in cell counts, or antibodies to HLA-DR. The mean half-life of AG4263 was 12.5 h. Some evidence of clinical response was seen; responses were more common among patients receiving the highest doses of AG4263 and among those with baseline T cell reactivity to CDP263. CONCLUSION: AG4263 was safe, well tolerated, and without evidence of generalized immune suppression. Along with the observed trend toward clinical efficacy, the results suggest that this therapeutic approach warrants further investigation in patients with RA.

Aged↗
PubMed2003

Reading and interpreting economic evaluations in rheumatoid arthritis: an assessment of selected instruments for critical appraisal.

OBJECTIVE: To describe and compare the relative attributes (reliability, ease of use, applicability, and relevance) of different assessment tools for economic analyses as they pertain to rheumatoid arthritis (RA) literature. METHODS: An expert panel, comprising rheumatology researchers and clinicians, operationalized 2 economic appraisal instruments and applied them to 11 articles used for analysis. Each expert reviewed 3 articles, with each article independently reviewed by a pair of experts. A summary score for each article per appraisal instrument was calculated by dividing the number of items that received a "positive" response by the total number of items in the appraisal instrument. RESULTS: Scores for each article were similar across reviewers and appraisal instruments. CONCLUSION: There is a need for a more comprehensive approach for evaluating this rapidly growing body of economic literature that is not only valid and reliable, but also easy to apply and understand. Although consistency between reviewers was good on both guidelines, inter-guideline discrepancies were noted and reviewers reported some difficulty in using the operationalized format.

Arthritis, Rheumatoid↗
PubMed2002

Estimating the cost-effectiveness of 54 weeks of infliximab for rheumatoid arthritis.

PURPOSE: To estimate the cost-effectiveness of infliximab plus methotrexate for active, refractory rheumatoid arthritis. METHODS: We projected the 54-week results from a randomized controlled trial of infliximab into lifetime economic and clinical outcomes using a Markov computer simulation model. Direct and indirect costs, quality of life, and disability estimates were based on trial results; Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS) database outcomes; and published data. Results were discounted using the standard 3% rate. Because most well-accepted medical therapies have cost-effectiveness ratios below $50,000 to $100,000 per quality-adjusted life-year (QALY) gained, results below this range were considered to be "cost-effective." RESULTS: At 3 mg/kg, each infliximab infusion would cost $1393. When compared with methotrexate alone, 54 weeks of infliximab plus methotrexate decreased the likelihood of having advanced disability from 23% to 11% at the end of 54 weeks, which projected to a lifetime marginal cost-effectiveness ratio of $30,500 per discounted QALY gained, considering only direct medical costs. When applying a societal perspective and including indirect or productivity costs, the marginal cost-effectiveness ratio for infliximab was $9100 per discounted QALY gained. The results remained relatively unchanged with variation of model estimates over a broad range of values. CONCLUSIONS: Infliximab plus methotrexate for 54 weeks for rheumatoid arthritis should be cost-effective with its clinical benefit providing good value for the drug cost, especially when including productivity losses. Although infliximab beyond 54 weeks will likely be cost-effective, the economic and clinical benefit remains uncertain and will depend on long-term results of clinical trials.

Adult↗
PubMed2002

The relationship of serum infliximab concentrations to clinical improvement in rheumatoid arthritis: results from ATTRACT, a multicenter, randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To investigate the relationship between serum concentrations of infliximab, a monoclonal anti-tumor necrosis factor alpha antibody, and clinical improvement from infliximab therapy for rheumatoid arthritis (RA). METHODS: Multiple blood samples were obtained from each of 428 subjects with active RA who were enrolled in a multicenter, randomized, double-blind, placebo-controlled trial (ATTRACT [Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy]) evaluating the clinical efficacy and safety of infliximab therapy. Serum levels of infliximab were measured by enzyme-linked immunosorbent assay. Dose-response trends were analyzed using generalized logistic regression techniques. Pharmacokinetic modeling was used to predict the serum concentrations of infliximab after simulated infusions using doses and dosing intervals not evaluated in the trial. RESULTS: At week 54, 26% of the subjects receiving 3 mg/kg infliximab every 8 weeks had undetectable trough serum levels of infliximab, a significantly greater proportion than in the other 3 treatment groups (P < 0.001). Increased magnitude of American College of Rheumatology (ACR) response (measured by the ACR-N, a continuous measure of clinical improvement derived from the ACR 20% response criteria) and greater reduction from baseline in serum C-reactive protein level were both associated with higher trough serum concentrations of infliximab (P < 0.001), as was less progression of radiographic joint damage (P = 0.004), providing support for a dose-response relationship. Pharmacokinetic models predicted that decreasing the dosing interval from 8 weeks to 6 weeks would yield higher trough serum levels of infliximab than increasing the dose by 100 mg. CONCLUSION: These results suggest that some patients with RA may benefit from infliximab given at higher doses than 3 mg/kg or more frequently than every 8 weeks.

Antibodies, Monoclonal↗
PubMed2002

Effect of a culturally sensitive cholesterol lowering diet program on lipid and lipoproteins, body weight, nutrient intakes, and quality of life in patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate the effect of a culturally sensitive cholesterol lowering diet program on lipid and lipoproteins, body weight, nutrient intakes, and quality of life (QOL) in patients with systemic lupus erythematosus (SLE). METHOD: Seventeen patients with SLE were randomized to a Step 2 diet intervention group or a control group for 12 weeks. The diet intervention was made up of weekly group sessions during the first 6 weeks followed by telephone counseling every 2 weeks for the last 6 weeks. Data on fasting lipid and lipoproteins, body weight, food intake (3 day food record), and QOL were collected at baseline, 6 weeks, and 12 weeks. Program acceptability was assessed in the diet group at 6 weeks. RESULTS: The intervention was found to be highly acceptable and culturally sensitive. The changes in nutrient intakes at 6 and 12 weeks in the diet group were -49% and -33%, respectively, for cholesterol, -44% and -32%, respectively, for percentage calories from fat, and -46% and -32%, respectively, for percentage calories from saturated fat. The corresponding figures in the control group were +22% and -8% for cholesterol, +9% and +6% for percentage calories from fat, and +5% and +7% for percentage calories from saturated fat. The treatment by time interaction was significant for all the dietary variables (p = 0.0003 to 0.02). QOL was reported to improve by 15-17% in the diet group and decrease by 4-6% in the control group, and the treatment by time interaction was significant (p = 0.05). The changes in the physiological variables at 6 and 12 weeks in the diet group were -10% and -6%, respectively, for total cholesterol, -10% and -2%, respectively, for low density lipoprotein (LDL) cholesterol, -11% and -4%, respectively, for high density lipoprotein (HDL) cholesterol, -25% and -34%, respectively, for very low density lipoprotein (VLDL) cholesterol, -8% and -24%, respectively, for triglycerides, and -2% and -5%, respectively, for body weight. The corresponding figures in the control group were -5% and -3% for total cholesterol, -6% and -5% for LDL cholesterol, 0% and +12% for HDL cholesterol, +4% and -8% for VLDL cholesterol, -6% and -15% for triglycerides, and -5% and -6% for body weight. The treatment by time interaction was significant for HDL cholesterol (p = 0.04). A significant reduction was seen in the diet group for total cholesterol at 6 and 12 weeks, LDL and HDL cholesterol at 6 weeks, and body weight at 12 weeks (p = 0.0002 to 0.01). CONCLUSION: This culturally sensitive cholesterol reducing diet program was highly accepted and effective in changing the diet and QOL of patients with SLE. The effect on serum lipids, lipoproteins, and body weight, however, was modest. A larger randomized study with a longer intervention period is necessary to test the effectiveness of a cholesterol-lowering diet on lipids and lipoproteins in patients with SLE.

Adult↗
PubMedDate not supplied

Anakinra (interleukin-1 receptor antagonist) has positive effects on function and quality of life in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) has severe and lasting effects on quality of life. This review (1) describes the disease progression, disability, and joint destruction that seriously alter a patient's quality of life, and (2) explains how the interleukin-1 receptor antagonist (IL-1Ra), anakinra, retards the progress of disease, thereby improving outcomes. Relevant articles were reviewed with a focus on RA, anakinra, and functional and quality-of-life outcomes. In randomized, controlled trials, the IL-1Ra anakinra provided meaningful benefits for patients with active RA, such as decreased signs and symptoms of disease, slower radiographic disease progression, reduced disability, and improved health-related quality of life. The biologic agent, anakinra, provides to patients with RA a valuable treatment option that has a positive impact on both function and quality of life.

Antirheumatic Agents↗
PubMedDate not supplied

Rheumatoid arthritis in dermatology.

Rheumatoid arthritis (RA) is a chronic progressive disorder characterized by symmetric inflammatory arthritis in association with systemic symptoms. Although considered a "joint disease," RA is associated with involvement in diverse organ systems, including the skin. Common manifestations include Raynaud phenomenon, rheumatoid nodules, and rheumatoid vasculitis. As with other extra-articular manifestations, dermatologic involvement tends to occur in patients with more severe RA. In addition to manifestations related to the disease, there are also sundry dermatologic reactions related to the medications used to treat RA. Understanding the etiology and therapy for cutaneous manifestations of RA will help optimize patient care.

Antirheumatic Agents↗