Biomedical subjects

Kenneth C Kalunian

Publications and source records attributed to Kenneth C Kalunian.

11 recordsLinked to original sources

PubMed2007

The modified Nail Psoriasis Severity Index: validation of an instrument to assess psoriatic nail involvement in patients with psoriatic arthritis.

OBJECTIVE: Patients with psoriasis and psoriatic arthritis (PsA) commonly have nail involvement. There is no validated psoriatic nail assessment tool. Recently, investigators developed the Nail Psoriasis Severity Index (NAPSI). Beginning with NAPSI, our goal was to validate a psoriatic nail assessment tool for use in clinical trials, and investigate correlations between nail and other PsA features. METHODS: Fingernails of 29 patients with PsA were photographed and scored. Clinical data were collected. Using the original NAPSI, analysis revealed high interrater variability of nail scores. Twenty patients' photographs were regraded using the modified NAPSI (mNAPSI). RESULTS: The mNAPSI scores had excellent interrater reliability (Cronbach's alpha 0.98). Nail scores and physicians' global nail severity visual analog scores showed good inter- and intrarater correlations (Spearman's rho 0.85 and 0.90-0.99, respectively; p < 0.01). Several clinical measures correlated with nail scores. CONCLUSION: The mNAPSI demonstrated excellent interrater reliability and construct validity, and may be a valuable tool.

Adult↗

PubMed2005

Combined oral contraceptives in women with systemic lupus erythematosus.

BACKGROUND: Oral contraceptives are rarely prescribed for women with systemic lupus erythematosus, because of concern about potential negative side effects. In this double-blind, randomized, noninferiority trial, we prospectively evaluated the effect of oral contraceptives on lupus activity in premenopausal women with systemic lupus erythematosus. METHODS: A total of 183 women with inactive (76 percent) or stable active (24 percent) systemic lupus erythematosus at 15 U.S. sites were randomly assigned to receive either oral contraceptives (triphasic ethinyl estradiol at a dose of 35 microg plus norethindrone at a dose of 0.5 to 1 mg for 12 cycles of 28 days each; 91 women) or placebo (92 women) and were evaluated at months 1, 2, 3, 6, 9, and 12. Subjects were excluded if they had moderate or high levels of anticardiolipin antibodies, lupus anticoagulant, or a history of thrombosis. RESULTS: The primary end point, a severe lupus flare, occurred in 7 of 91 subjects receiving oral contraceptives (7.7 percent) as compared with 7 of 92 subjects receiving placebo (7.6 percent). The 12-month rates of severe flare were similar: 0.084 for the group receiving oral contraceptives and 0.087 for the placebo group (P=0.95; upper limit of the one-sided 95 percent confidence interval for this difference, 0.069, which is within the prespecified 9 percent margin for noninferiority). Rates of mild or moderate flares were 1.40 flares per person-year for subjects receiving oral contraceptives and 1.44 flares per person-year for subjects receiving placebo (relative risk, 0.98; P=0.86). In the group that was randomized to receive oral contraceptives, there was one deep venous thrombosis and one clotted graft; in the placebo group, there was one deep venous thrombosis, one ocular thrombosis, one superficial thrombophlebitis, and one death (after cessation of the trial). CONCLUSIONS: Our study indicates that oral contraceptives do not increase the risk of flare among women with systemic lupus erythematosus whose disease is stable.

Adolescent↗

PubMed2005

The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus: a randomized trial.

BACKGROUND: There is concern that exogenous female hormones may worsen disease activity in women with systemic lupus erythematosus (SLE). OBJECTIVE: To evaluate the effect of hormone replacement therapy (HRT) on disease activity in postmenopausal women with SLE. DESIGN: Randomized, double-blind, placebo-controlled noninferiority trial conducted from March 1996 to June 2002. SETTING: 16 university-affiliated rheumatology clinics or practices in 11 U.S. states. PATIENTS: 351 menopausal patients (mean age, 50 years) with inactive (81.5%) or stable-active (18.5%) SLE. INTERVENTIONS: 12 months of treatment with active drug (0.625 mg of conjugated estrogen daily, plus 5 mg of medroxyprogesterone for 12 days per month) or placebo. The 12-month follow-up rate was 82% for the HRT group and 87% for the placebo group. MEASUREMENTS: The primary end point was occurrence of a severe flare as defined by Safety of Estrogens in Lupus Erythematosus, National Assessment-Systemic Lupus Erythematosus Disease Activity Index composite. RESULTS: Severe flare was rare in both treatment groups: The 12-month severe flare rate was 0.081 for the HRT group and 0.049 for the placebo group, yielding an estimated difference of 0.033 (P = 0.23). The upper limit of the 1-sided 95% CI for the treatment difference was 0.078, within the prespecified margin of 9% for noninferiority. Mild to moderate flares were significantly increased in the HRT group: 1.14 flares/person-year for HRT and 0.86 flare/person-year for placebo (relative risk, 1.34; P = 0.01). The probability of any type of flare by 12 months was 0.64 for the HRT group and 0.51 for the placebo group (P = 0.01). In the HRT group, there were 1 death, 1 stroke, 2 cases of deep venous thrombosis, and 1 case of thrombosis in an arteriovenous graft; in the placebo group, 1 patient developed deep venous thrombosis. LIMITATIONS: Findings are not generalizable to women with high-titer anticardiolipin antibodies, lupus anticoagulant, or previous thrombosis. CONCLUSIONS: Adding a short course of HRT is associated with a small risk for increasing the natural flare rate of lupus. Most of these flares are mild to moderate. The benefits of HRT can be balanced against the risk for flare because HRT did not significantly increase the risk for severe flare compared with placebo.

Adolescent↗

PubMed2005

Calcium-containing crystals and osteoarthritis: implications for the clinician.

The clinical implication of articular deposits of calcium-containing crystals (specifically of calcium pyrophosphate dihydrate and hydroxyapatite) in osteoarthritis is unknown. Recent longitudinal studies have suggested that in some instances calcium crystals are direct participants in cartilage damage, while in other situations they are merely markers of joint damage. Better understanding of the mechanisms of crystal formation, especially in relation to inorganic pyrophosphate regulation, has lead to potential avenues for therapeutic intervention. The current treatment of osteoarthritis associated with calcium-containing crystals should involve nonsteroidal anti-inflammatory drugs, intra-articular steroids, and in resistant cases, joint irrigation can be considered. While preliminary studies suggest the possibility of favorable benefits from colchicine and hydroxycholorquine in this osteoarthritis disease subset, more rigorous studies need to be conducted to establish their roles.

Antirheumatic Agents↗

PubMed2005

New developments in osteoarthritis.

Osteoarthritis (OA) has been a frustrating disease for both the patient and the physician. Its current impact on society is tremendous, and rivals that of ischemic heart disease in many regards. As the baby boomers reach late adulthood and the obesity epidemic rages on, OA will assume an even greater impact on society. The current OA armamentarium only reduces pain and perhaps improves function, and has no impact on the disease incidence or progression. Thus, the challenge for researchers to develop disease-modifying OA drugs becomes an issue of paramount importance. Several advances in our understanding of OA pathophysiology have provided a glimpse of optimism that disease modification is a real possibility. Appreciation of the local factors involved in OA progression as well as the inflammatory nature in a subset of patients has led to different treatment strategies based on predominant phenotype. Further understanding of the initiating events in cartilage destruction, the relationship between the different pathologic influences, and the role of the chondrocyte in maintaining extracellular matrix homeostasis will be necessary to reveal potential targets of therapy.

Acetaminophen↗

PubMed2005

Validation of American College of Rheumatology classification criteria for knee osteoarthritis using arthroscopically defined cartilage damage scores.

OBJECTIVE: To validate the ability of the American College of Rheumatology (ACR) clinical classification criteria and the ACR clinical plus radiographic classification criteria for osteoarthritis of the knee to predict articular cartilage damage. METHODS: Ninety subjects with knee osteoarthritis (OA) who were enrolled in a prospective study determining the therapeutic efficacy of arthroscopic irrigation were characterized as to whether they fulfilled the ACR clinical classification criteria or the ACR clinical plus radiographic classification criteria. Ten rheumatoid arthritis (RA) patients were included as controls. Cartilage damage was defined using the ACR/Knee Arthroscopy Osteoarthritis Scale (ACR/KAOS) system, which is a validated outcome instrument for knee OA based on arthroscopic visualization. Mean values of the damage scores in each group were calculated and compared by t-test to determine statistical significance between the 3 groups. RESULTS: The mean ACR/KAOS score for the 10 RA patients was 1.8 [SD 1.22; range 0 to 4]. Of the 90 OA patients who underwent arthroscopy, only 73 patients had sufficient videotape to make an accurate assessment by the blinded assessor. The mean ACR/KAOS score for the 6 OA patients who fulfilled only the ACR clinical classification was 17.4 [SD 11.3; range 5 to 34.3] and the mean ACR/KAOS score for the 67 patients who fulfilled the ACR clinical plus radiographic classification criteria was 42.0 [SD 29.1; range 5.1 to 118.4]. These differences were statistically significant (RA versus OA clinical P=0.02; RA versus OA clinical+radiographic P<or=0.01). Nonparametric multivariate analysis did not reveal significant correlations between ACR/KAOS scores and WOMAC global scores (r=0.11, P=0.39), patient VAS (r=0.29, P=0.022), and age (r=0.29, P=0.08). CONCLUSIONS: The ACR clinical and clinical plus radiographic criteria for OA of the knee accurately predict cartilage damage as assessed by arthroscopy. Furthermore, the ACR clinical classification criteria identify OA patients with cartilage damage before any radiographic change, while the ACR clinical plus radiographic classification criteria identify OA patients with more severe cartilage damage. RELEVANCE: The ACR classification criteria correlates well with articular cartilage damage in patients with OA.

Adult↗

PubMed2004

Effects of prasterone on disease activity and symptoms in women with active systemic lupus erythematosus.

OBJECTIVE: To determine whether prasterone administration results in improvement or stabilization of systemic lupus erythematosus (SLE) disease activity and its symptoms. METHODS: Women with active SLE were treated with prasterone 200 mg/day plus standard SLE treatments or with placebo plus standard SLE treatments for up to 12 months in this randomized, double-blind investigation conducted at 27 centers. Standard SLE treatments included prednisone (</=10 mg/day), antimalarials, and immunosuppressive agents; dosages were required to be stable for >/=6 weeks prior to enrollment and remain unchanged during protocol treatment. Responders were patients who experienced no clinical deterioration and had improvement or stabilization over the duration of the study in 2 disease activity measures (the SLE Disease Activity Index [SLEDAI] and the Systemic Lupus Activity Measure) and 2 quality of life measures (patient's global assessment and the Krupp Fatigue Severity Scale). RESULTS: A total of 381 women with SLE were enrolled. Among patients with clinically active disease at baseline (SLEDAI score >2), 86 of 147 in the prasterone group (58.5%) demonstrated improvement or stabilization without clinical deterioration, as compared with 65 of 146 in the placebo group (44.5%) (P = 0.017). Acne and hirsutism were reported in 33% and 16%, respectively, of the prasterone group and in 14% and 2%, respectively, of the placebo group (P < 0.05 for both comparisons). However, most cases of acne and hirsutism were mild and did not require withdrawal from therapy. Myalgias and oral stomatitis were reported less frequently in the prasterone group (22% and 15%, respectively) than in the placebo group (36% and 23%, respectively) (P < 0.05 for both comparisons). Serum levels of high-density lipoprotein cholesterol, triglycerides, and C3 complement significantly decreased, while levels of testosterone and, to a lesser extent, estradiol increased in the prasterone group. CONCLUSION: In adult women with active SLE, administration of prasterone at a dosage of 200 mg/day improved or stabilized signs and symptoms of disease and was generally well tolerated.

Adjuvants, Immunologic↗

PubMed2004

Defining response in systemic lupus erythematosus: a study by the Systemic Lupus International Collaborating Clinics group.

OBJECTIVE: In a preliminary attempt to develop a drug responder index for patients with systemic lupus erythematosus (SLE), 2 validated disease activity instruments were studied for their responsiveness and compared to a physician visual analog scale (VAS) assessment of disease activity. We attempted to determine whether these validated instruments were useful components in characterizing response in the setting of a clinical trial. METHODS: Eighty paper patients were assessed using the British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Disease Activity Index (SLEDAI) and by physician's assessment of global activity. The cases were arranged in random order and divided into groups of 20 patients and each group was assessed by 20 lupus experts; change in disease activity was recorded at 3 and 6 months compared to baseline using a physician VAS. RESULTS: Four different lupus experts assessed disease activity in all 80 patients at baseline and 3 and 6 months after initiation of therapy using the BILAG and SLEDAI instruments. BILAG and SLEDAI scores correlated well over time; however, in a regression analysis where average physician VAS were chosen as the outcome variable, a significant amount of variation in the average physician VAS not related to the SLEDAI and BILAG scores was noted. CONCLUSION: The physician VAS may be too blunt to assess response in SLE, because even among experienced lupus assessors, there were considerable differences in what influenced scoring decisions.

Adult↗

PubMed2002

Familiality and co-occurrence of clinical features of systemic lupus erythematosus.

OBJECTIVE: To evaluate familiality of 15 clinical and laboratory features in systemic lupus erythematosus (SLE)-affected sibpairs, and to estimate correlations with the age at SLE diagnosis in affected sibpairs and parent-offspring pairs. METHODS: Concordance rates and sibling risk ratios were used as indicators of familiality for 15 manifestations of SLE. Pearson's correlations and paired t-tests were used to compare the age at SLE diagnosis in affected sibpairs and in parent-offspring pairs. RESULTS: Increased sibling risk ratios (1.9-3.9) for thrombocytopenia, discoid rash, neurologic disorder (defined as seizure or psychosis), and hemolytic anemia were observed in 159 SLE-affected sibpairs. Among these clinical features, paired expression of hemolytic anemia plus thrombocytopenia and hemolytic anemia plus neurologic disorder appeared to be more frequent in 709 SLE patients than would be expected by chance (P < 0.00001 and P < 0.007, respectively). The ratio of the presence of both hemolytic anemia and neurologic disorder was approximately 13 times higher in the younger affected sib than in the older affected sib (P < 0.02). Familiality of patient age at SLE diagnosis, as observed by relative correlations, was greater in 125 affected sibpairs (r = 0.67, P < 0.0001) than in 37 affected parent-offspring pairs (r = 0.47, P = 0.003). The median +/- SD age at SLE diagnosis was significantly lower in offspring (21.5 +/- 10.1 years) than in their parents (41.6 +/- 15.8 years) (P < 0.0001) but was not different in sibpairs. The combined non-Caucasian sibpairs had a younger mean age at SLE diagnosis compared with Caucasian sibpairs (P = 0.014). CONCLUSION: Evidence for familiality of thrombocytopenia, discoid rash, neurologic disorder, hemolytic anemia, and co-occurring neurologic disorder plus hemolytic anemia in SLE was observed in 159 affected sibpairs. Familiality of the age at SLE diagnosis in relative pairs suggests that shared genes and/or shared environmental exposures impact disease susceptibility. Shared immediate environmental triggers appear less compelling, because the average time between dates of diagnosis was 11 years in parent-offspring pairs and 7.5 years in affected sibpairs. The significantly earlier age at disease diagnosis in offspring compared with their parents suggests that some forms of anticipation might play a role in susceptibility to SLE. Stratifying families by subphenotypes that are familial may reduce heterogeneity and facilitate identification of genetic risk factors for SLE.

Age of Onset↗

PubMed2002

Linkage and interaction of loci on 1q23 and 16q12 may contribute to susceptibility to systemic lupus erythematosus.

OBJECTIVE: Six recent genome scans of different systemic lupus erythematosus (SLE) multiplex family cohorts showed multiple putative susceptibility loci. In the present study, we examined 4 previously identified loci to replicate findings of significant linkage to 1q23 and 16q12, and to support findings of suggestive linkage to 14q21-23 and 20p12 in a cohort of 115 multiethnic nuclear families containing 145 SLE-affected sibpairs. METHODS: Model-free, multipoint linkage analyses (SIBPAL2, SAGE version 4.0) and exclusion mapping (GeneHunter) were performed. RESULTS: Linkages to 1q23 (peak at D1S2675, mean allele sharing [MAS] 0.56; P = 0.003) and to 16q12 (peaks between D16S753 and D16S757, MAS 0.57; P = 0.003) were confirmed, but linkage evidence at 20p12 was weak and inconsistent (MAS 0.52-0.56; from P = 0.005 to P not significant). Evidence for linkage to 1q23 and 16q12 was stronger in 68 non-Caucasian affected sibpairs than in 77 Caucasian affected sibpairs. Exclusion mapping ruled out linkage at 14q21-23 (lambda(s) [sib recurrence risk or genotypic risk ratio] = 1.8). Because the pericentromeric region of chromosome 16 has been identified by genome scans in several autoimmune diseases, we postulated that it might harbor an autoimmune modifier gene. To explore this possibility, we tested for an interaction between 16q12 and 1q23, and between 16q12 and 20p12. Haplotype sharing at 1q23 increased concomitantly with increased haplotype sharing at 16q12 (P = 0.008 by nonparametric Jonckheere-Terpstra exact statistical test). No evidence supporting an interaction between 16q12 and 20p12 was observed. Analysis of sibpairs sharing 2 alleles at 16q12 also showed increased allele sharing at 1q23 (MAS from 0.56 to 0.65). CONCLUSION: These data support the presence of SLE susceptibility genes at 1q23 and 16q12, particularly in non-Caucasians. The skewed distribution of haplotypes suggests that genetic interaction of these two loci may affect SLE susceptibility.

Adolescent↗

PubMed2002

Treatment of systemic lupus erythematosus by inhibition of T cell costimulation with anti-CD154: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the safety and efficacy of a humanized monoclonal antibody against CD154 (IDEC-131) in patients with active systemic lupus erythematosus (SLE). METHODS: In this phase II, double-blind, placebo-controlled, multiple-center, multiple-dose study, 85 patients with mild-to-moderately active SLE were randomized to receive 6 infusions of IDEC-131, ranging from 2.5 mg/kg to 10.0 mg/kg, or placebo over 16 weeks. Efficacy was assessed at week 20, primarily by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and secondarily, by multiple measures of disease activity. Safety was assessed through week 28 by clinical and laboratory evaluation. Immunogenicity studies were also performed. RESULTS: SLEDAI scores improved from the baseline levels of disease activity in all groups, including the placebo group. However, these scores were not statistically different among the IDEC-131 treatment and placebo groups at week 20. Evaluations of secondary variables did not indicate significant differences between the IDEC-131 treatment and placebo groups. The type and frequency of adverse events were similar between the IDEC-131 and placebo groups. CONCLUSION: IDEC-131 administered at doses ranging 2.5-10.0 mg/kg over 16 weeks was safe and well tolerated in patients with SLE. Efficacy of the drug compared with placebo was not demonstrated. There were statistically significant improvements from baseline in all groups, including the placebo group.

Adult↗