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Biomedical subjects

Daniel J Wallace

Publications and source records attributed to Daniel J Wallace.

At least 19 recordsLinked to original sources
PubMed2006

Development and validation of a preference weight multiattribute health outcome measure for rheumatoid arthritis.

OBJECTIVE: To develop and validate multiattribute measures for patients with rheumatoid arthritis (RA) to report health states and estimate preference weights. METHODS: Survey materials were mailed to 748 patients. Factor analysis, an item response theory-based model, and an internal consistency test were used to identify attributes and evaluate items. Two multiattribute preference weight functions (MAPWF) were constructed. Construct validity of the new measures was then tested. RESULTS: Four hundred eighty-seven patients returned the survey; 24 items on 6 health attributes were selected to form the new outcomes measure. Two MAPWF were derived with preference weights measured with time tradeoff and visual analog scales as dependent variables. All validity test results were statistically significant. CONCLUSION: Our results reveal that the new measures are reliable and valid in assessing health states and associated preference weights of patients with RA.

Activities of Daily Living↗
PubMed2006

Risk genotypes in folate-dependent enzymes and their association with methotrexate-related side effects in rheumatoid arthritis.

OBJECTIVE: Methotrexate (MTX) is an antifolate agent that is often associated with toxicity. This study investigated whether risk genotypes for folate-dependent enzymes are associated with the toxicity of MTX in patients with rheumatoid arthritis (RA). METHODS: Blood was collected for analysis in a muticenter, cross-sectional study of RA patients who had been receiving MTX for at least 1 month prior to enrollment, and side effects occurring at the time of a single study visit were recorded. Low-penetrance risk genotypes in methylenetetrahydrofolate reductase (MTHFR) 677TT, thymidylate synthase (TSER) *2/*2 (variable number of tandem repeats), amino imidazole ribonucleotide transformylase (ATIC) 347GG, and serine hydroxymethyltransferase (SHMT1) 1420CC were measured and summed to constitute the toxicogenetic index specific to each patient. Statistical analyses consisted of logistic regression models with clustered-center effects, and associations with risk genotypes were expressed as adjusted odds ratios (ORs). RESULTS: Among 214 patients enrolled at 4 study sites, a total of 67 patients (31%) presented with a side effect (gastrointestinal event, headache, lethargy, alopecia, cough, or dyspnea). Risk genotypes associated with side effects in the central nervous system were MTHFR 677TT (OR 3.3, P < 0.01) and SHMT1 1420CC (OR 2.4, P < 0.05). ATIC 347GG was associated with gastrointestinal side effects (OR 3.0, P < 0.01), while TSER*2/*2 (OR 5.4, P < 0.01) and SHMT1 1420CC (OR 3.2, P < 0.01) were associated with alopecia. The toxicogenetic index ranged from 0 to 3 (median 1). An index of 3 was associated with an approximately 7-fold higher likelihood of having a side effect compared with an index of 0 (P < 0.01). CONCLUSION: These data suggest that a composite index of the cumulative risk genotypes in folate-dependent enzymes may be an effective means of profiling RA patients who develop side effects to MTX.

Aged↗
PubMed2006

Proinflammatory high-density lipoprotein as a biomarker for atherosclerosis in patients with systemic lupus erythematosus and rheumatoid arthritis.

OBJECTIVE: Women with systemic lupus erythematosus (SLE) have a 7-50-fold increased risk of coronary artery disease (CAD). In the general population, oxidized low-density lipoprotein (ox-LDL) increases the risk for CAD. Normal high-density lipoproteins (HDLs) protect LDL from oxidation; proinflammatory HDLs do not. This study was undertaken to determine whether patients with SLE, who have chronic inflammation that causes oxidative damage, have more proinflammatory HDL and higher levels of ox-LDL, thus predisposing them to atherosclerosis. METHODS: One hundred fifty-four women with SLE, 48 women with rheumatoid arthritis (RA), and 72 healthy controls were studied. The ability of the patients' HDL to prevent oxidation of normal LDL was measured. Values >1.0 (the value assigned for LDL oxidation in the absence of HDL) after the addition of HDL indicated proinflammatory HDL. Plasma ox-LDL levels were measured as the amount of oxidation produced by the patient's LDL after the removal of HDL. RESULTS: SLE patients had more proinflammatory HDL (mean +/- SD score 1.02 +/- 0.57, versus 0.68 +/- 0.28 in controls [P < 0.0001] and 0.81 +/- 0.22 in RA patients [P = 0.001 versus SLE patients]). A higher proportion of SLE patients had proinflammatory HDL: 44.7% of SLE patients versus 4.1% of controls and 20.1% of RA patients had scores >1.0 (P < 0.006 between all groups). Levels of ox-LDL correlated with levels of proinflammatory HDL (r = 0.37, P < 0.001). SLE patients with CAD had significantly higher proinflammatory HDL scores than patients without CAD (P < 0.001). CONCLUSION: HDLs are proinflammatory in a significant proportion of SLE patients and are associated with elevated levels of ox-LDL. Abnormal HDLs impair the ability to prevent LDL oxidation and may predispose to atherosclerosis.

Adult↗
PubMed2006

Is there a role for cytokine based therapies in fibromyalgia.

Cytokines are glycoproteins that serve as chemical messengers between cells. They assist in the regulation of cell growth and repair and also have immune modulating properties. Cytokines play a role in diverse clinical processes and phenomena such as fatigue, fever, sleep, pain, stress and aching. A review of the fibromyalgia literature and related studies suggest that IL-1, IL-6 and IL-8 are dysregulated in the syndrome. Therapies directed against these cytokines may be of potential importance in the management of fibromyalgia.

Cytokines↗
PubMed2005

Mycophenolate mofetil or intravenous cyclophosphamide for lupus nephritis.

BACKGROUND: Since anecdotal series and small, prospective, controlled trials suggest that mycophenolate mofetil may be effective for treating lupus nephritis, larger trials are desirable. METHODS: We conducted a 24-week randomized, open-label, noninferiority trial comparing oral mycophenolate mofetil (initial dose, 1000 mg per day, increased to 3000 mg per day) with monthly intravenous cyclophosphamide (0.5 g per square meter of body-surface area, increased to 1.0 g per square meter) as induction therapy for active lupus nephritis. A change to the alternative regimen was allowed at 12 weeks in patients who did not have an early response. The study protocol specified adjunctive care and the use and tapering of corticosteroids. The primary end point was complete remission at 24 weeks (normalization of abnormal renal measurements and maintenance of baseline normal measurements). A secondary end point was partial remission at 24 weeks. RESULTS: Of 140 patients recruited, 71 were randomly assigned to receive mycophenolate mofetil and 69 were randomly assigned to receive cyclophosphamide. At 12 weeks, 56 patients receiving mycophenolate mofetil and 42 receiving cyclophosphamide had satisfactory early responses. In the intention-to-treat analysis, 16 of the 71 patients (22.5 percent) receiving mycophenolate mofetil and 4 of the 69 patients receiving cyclophosphamide (5.8 percent) had complete remission, for an absolute difference of 16.7 percentage points (95 percent confidence interval, 5.6 to 27.9 percentage points; P=0.005), meeting the prespecified criteria for noninferiority and demonstrating the superiority of mycophenolate mofetil to cyclophosphamide. Partial remission occurred in 21 of the 71 patients (29.6 percent) and 17 of the 69 patients (24.6 percent), respectively (P=0.51). Three patients assigned to cyclophosphamide died, two during protocol therapy. Fewer severe infections and hospitalizations but more diarrhea occurred among those receiving mycophenolate. CONCLUSIONS: In this 24-week trial, mycophenolate mofetil was more effective than intravenous cyclophosphamide in inducing remission of lupus nephritis and had a more favorable safety profile.

Administration, Oral↗
PubMed2005

Photoemission studies of polythiophene and polyphenyl films produced via surface polymerization by ion-assisted deposition.

Conducting polymer films are grown by mass-selected, hyperthermal thiophene ions coincident on a surface with a thermal beam of organic monomers of either alpha-terthiophene (3T) or p-terphenyl (3P) neutrals. Mass spectrometry and X-ray photoelectron spectroscopy previously verified polymerization of both 3T and 3P by 200 eV C(4)H(4)S(+) during surface polymerization by ion-assisted deposition (SPIAD). The electronic structure of these films are probed here by ultraviolet photoelectron spectroscopy (UPS) and polarized near-edge X-ray absorption fine structure spectroscopy (NEXAFS) and compared with similar spectra of evaporated films. The conducting polymer films formed by SPIAD display new valence band features resulting from a reduction in both their band gap and barrier to hole injection, which are calculated from the occupied and unoccupied valence band states measured by UPS and NEXAFS. These changes in film electronic structure result from an increase in the electron conjugation length and other changes in film structure induced by SPIAD.

Journal Article↗
PubMed2005

Sustained benefits of infliximab therapy for dermatologic and articular manifestations of psoriatic arthritis: results from the infliximab multinational psoriatic arthritis controlled trial (IMPACT).

OBJECTIVE: To investigate the efficacy and tolerability of infliximab therapy for the articular and dermatologic manifestations of active psoriatic arthritis (PsA). METHODS: One hundred four patients with PsA in whom prior therapy with at least 1 disease-modifying antirheumatic drug (DMARD) had failed were recruited into this investigator-initiated, multicenter, randomized, double-blind, placebo-controlled clinical trial. During the initial blinded portion of the study, patients received infusions of infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, and 14. After week 16, patients initially assigned to receive placebo crossed over to receive infliximab 5 mg/kg every 8 weeks through week 50, while patients initially randomized to infliximab continued to receive active treatment at the same dose through week 50. The primary efficacy outcome was achievement of the American College of Rheumatology 20% criteria for improvement in rheumatoid arthritis (ACR20) at week 16. Additional predefined clinical efficacy assessments included the Psoriasis Area and Severity Index (PASI) score, the ACR50 and ACR70 criteria, the Disease Activity Score in 28 joints, the Health Assessment Questionnaire, ratings of enthesitis and dactylitis, and the Psoriatic Arthritis Response Criteria score. RESULTS: The proportion of infliximab-treated patients who achieved an ACR20 response at week 16 (65%) was significantly higher than the proportion of placebo-treated patients who achieved this response (10%). In addition, 46% of infliximab-treated patients achieved an ACR50 response, and 29% achieved an ACR70 response; no placebo-treated patient achieved these end points. Among patients who had PASI scores of >/=2.5 at baseline, 68% of infliximab-treated patients achieved improvement of >/=75% in the PASI score at week 16 compared with none of the placebo-treated patients. Continued therapy with infliximab resulted in sustained improvement in articular and dermatologic manifestations of PsA through week 50. The incidence of adverse events was similar between the treatment groups. CONCLUSION: Therapy with infliximab at a dose of 5 mg/kg significantly improved the signs and symptoms of arthritis, psoriasis, dactylitis, and enthesitis in patients with active PsA that had been resistant to DMARD therapy. With continued infliximab treatment, benefits were sustained through 50 weeks. The benefit-to-risk ratio appeared favorable in this study population.

Adult↗
PubMed2005

Association analysis of the R620W polymorphism of protein tyrosine phosphatase PTPN22 in systemic lupus erythematosus families: increased T allele frequency in systemic lupus erythematosus patients with autoimmune thyroid disease.

OBJECTIVE: Recent case-control studies show associations of the minor T allele (of the C1858T single-nucleotide polymorphism corresponding to the R620W amino acid substitution) of PTPN22 with multiple autoimmune diseases, including systemic lupus erythematosus (SLE). We performed family-based association studies of this polymorphism in 4 independent cohorts containing SLE patients and their parents and/or other family members. METHODS: A total of 2,689 individuals from 902 independent Caucasian families with SLE were genotyped using polymerase chain reaction pyrosequencing (cohorts 1 and 2) and the Sequenom MassArray system (cohorts 3 and 4). The transmission disequilibrium test (TDT) and the pedigree disequilibrium test (PDT) were conducted to assess the evidence of association. RESULTS: The 1858 C > T allele frequencies of the parents showed no deviation from Hardy-Weinberg equilibrium within each cohort. No evidence of preferential transmission of the T allele from heterozygous parents to their affected offspring was observed in each of the 4 cohorts or in the combined sample. Consistent with the TDT result, the PDT analysis revealed no significant association between the T allele and SLE. In 54 of the 661 SLE patients (cohorts 1 and 3) with documented autoimmune thyroid disease, the T allele frequency was higher than in individuals with SLE alone (16.7% versus 8.5%; P = 0.008, odds ratio 2.16 [95% confidence interval 1.25-3.72]). CONCLUSION: The R620W polymorphism of the PTPN22 gene is not a major risk allele for SLE susceptibility in our sample of Caucasian individuals from northern America, the UK, or Finland, but it appears to be a risk factor for the concurrent autoimmune diseases of autoimmune thyroid disease and SLE.

Arginine↗
PubMed2005

Identification of polyclonal and monoclonal antibodies against tissue plasminogen activator in the antiphospholipid syndrome.

OBJECTIVE: To test the hypotheses that some plasmin-reactive anticardiolipin antibodies (aCL) may bind to tissue plasminogen activator (tPA) and that some of the tPA-reactive aCL may inhibit tPA activity. METHODS: We studied the reactivity of 8 patient-derived monoclonal aCL with tPA and examined the presence of IgG anti-tPA antibodies in patients with the antiphospholipid syndrome (APS). The effects of the reactive monoclonal aCL on the activity of tPA were also examined. RESULTS: Six patient-derived plasmin-reactive monoclonal aCL bound to tPA. Analysis of plasma samples revealed that 10 of 80 APS patients (12.5%) and 1 of 81 systemic lupus erythematosus patients (1.2%) had antibodies against fibrin-associated tPA, based on a cutoff value equal to the mean + 2SD of the level in 28 normal subjects. Of the 6 tPA-reactive monoclonal aCL, 2 of them (CL1 and CL15) inhibited tPA activity. CONCLUSION: Some of the plasmin-reactive aCL in APS patients may bind to tPA. Of the tPA-reactive aCL, some (such as CL1 and CL15) may inhibit tPA activity and, thus, may be prothrombotic in the host.

Adult↗
PubMed2005

Chronic inflammatory demyelinating polyneuropathy in patients with systemic lupus erythematosus: prognosis and outcome.

OBJECTIVES: To identify clinical characteristics, laboratory features, approaches to management, and predictors of outcome of chronic inflammatory demyelinating polyneuropathy (CIDP) in patients with systemic lupus erythematosus (SLE). METHODS: An analysis of 6 adults with the concurrent diagnosis of CIDP and SLE seen at a SLE Clinic from 1994 to 2004 with a review of 13 patients with SLE and CIDP reported in the medical literature from 1950 through 2004. RESULTS: Among our 6 patients with SLE and CIDP, 3 (50%) achieved a substantial clinical response to intravenous immunoglobulin (IVIg) and the remainder had a minimal response. The improved patients were more likely to have received treatment earlier (within 1 year of CIDP onset) and to respond faster (<1 to 3 months) than minimally improved patients. They tended to have CIDP features of weakness of all extremities, hyporeflexia of the upper extremities, and slowed nerve conduction velocity of the motor median nerve. Compared with minimal responders, responders had more serious internal organ manifestations and multiple autoantibodies associated with SLE. Review of the literature identified 13 previously reported CIDP patients with SLE. Many had neurological involvement of all extremities, nerve biopsies showing demyelination, and serious SLE internal organ manifestations. Most were treated with steroids, but the 1 treated with IVIg had similar characteristics to our subset of patients who improved with IVIg. CONCLUSIONS: CIDP is an uncommon, but not rare, manifestation of SLE. Certain characteristics including early CIDP diagnosis, involvement of all 4 extremities, hyporeflexia of the upper extremities, and slowed motor nerve conduction velocity of the median nerve in addition to SLE involvement of critical internal organs and the presence of multiple antibodies associated with SLE all appear to predict a good response to IVIg.

Adult↗
PubMed2005

Rapid prevention of vertebral fractures associated with osteoporosis.

Osteoporosis affects postmenopausal women and patients on glucocorticoid therapy. Fractures are the most devastating outcome. Patients who experience an osteoporotic vertebral fracture are at substantial risk of experiencing another within 1 year. Risk can be reduced rapidly with antiresorptives. Risedronate reduced the risk of vertebral fracture in patients with post-menopausal or glucocorticoid-induced osteoporosis after 1 year by up to 71% in prospective studies. In post hoc analyses, significant reductions in clinical vertebral fractures were demonstrated after 6 months with risedronate and 1 year with alendronate and raloxifene. Rapid reduction in fracture risk is achievable with the potent therapeutic agents available.

Aged↗
PubMed2005

Measuring preference weights for American college of rheumatology response criteria for patients with rheumatoid arthritis.

OBJECTIVE: To estimate weights for health states comprising American College of Rheumatology (ACR) response and different levels of adverse events associated with rheumatoid arthritis (RA) treatments. METHODS: A survey was mailed to 748 patients with RA from southern California. In addition to several questionnaires commonly used for patients with RA, patients were instructed to evaluate 10 hypothetical health states, in which they could have an ACR response and/or adverse events due to new treatments, with a visual analog scale (VAS). Patients also evaluated their current health with a VAS question and a time tradeoff (TTO) question. Linear extrapolation was used to derive 6 more health states. The Pearson correlation coefficient was used to validate VAS and TTO results. RESULTS: A total of 487 (65%) patients returned the survey. Among the 10 health states evaluated with VAS directly, the health state in which a patient has ACR70 with no adverse events had the highest VAS weight (0.84), followed by the one having an ACR50 response with no adverse events (0.80). Correlation coefficients ranged from 0.63 for the correlation between VAS and physical component summary to -0.18 between TTO and pain and tender joint count; the correlation coefficients were all statistically significant, indicating there was convergent validity of the VAS and that VAS functioned differently from TTO in how it measured weights. CONCLUSION: VAS weights for 16 ACR response health states of patients with RA were derived. These weights could be used for cost-utility analyses of interventions for patients with RA.

Aged↗
PubMed2004

Eligibility, utilization, and costs in a California Medicaid lupus population.

OBJECTIVE: To investigate whether ethnicity was associated with differences in Medicaid eligibility, health care utilization, and direct medical costs in a systemic lupus erythematosus (SLE) population. METHODS: A retrospective analysis of California Medicaid claims data was conducted on patients with SLE. Patient eligibility and month-by-month utilization and costs were computed and compared across ethnic groups. Descriptive statistics are presented. A mixed regression model on patient-level data was used to verify the trends of the aggregate data, controlling for covariates. A survival regression model on time to ineligibility was used to show eligibility patterns adjusted for covariates. RESULTS: Hispanic patients were less likely to have a lengthy eligibility period as compared with other cohorts (approximately 50% versus 70% eligible at month 36, respectively). As treatment progressed, Hispanics generated lower total costs than other cohorts. Results for inpatient frequency, prescription costs, and outpatient/physician/supply (Part B) costs followed similar patterns. Mixed regression model findings revealed that when adjusted for age, sex, and aid program, total costs for Hispanic patients decreased as the length of care increased, in contrast to other ethnic groups. The interaction between ethnicity and treatment progression measured by quarter was significant (P <0.0001), but ethnicity as a main effect was not (P=0.091). This suggests that differences in total costs are small initially, but as the followup period extends, Hispanic patients experience lower total costs as compared with other ethnic groups. CONCLUSION: These California Medicaid program data reinforce the importance of investigating treatment differences in ethnic groups with SLE.

Adolescent↗
PubMed2004

Fibromyalgia: the gastrointestinal link.

Patients with fibromyalgia (FM) frequently have gastrointestinal symptoms and signs. This article critically reviews the available literature and concludes the following: evidence that inflammatory bowel disease is associated with FM is contradictory, but should be looked for in patients taking concomitant steroids; patients diagnosed with celiac disease often have a history of FM or irritable bowel syndrome (IBS) that may or may not be present; reflux, nonulcer dyspepsia, and noncardiac chest pain are common in FM patients; medications used to manage pain, inflammation, and gastrointestinal complaints confound the management of FM; and IBS affects smooth muscles and the parasympathetic nervous system, while FM patients have complaints of striated muscles and dysfunction of the sympathetic nervous system. Of those patients with FM, 30% to 70% have concurrent IBS. Small intestinal bacterial overgrowth is associated with hyperalgesia and IBS-like complaints, is common in FM, and responds transiently to antimicrobial therapy.

Anti-Infective Agents↗