Biomedical subjects

Weng Kee Wong

Publications and source records attributed to Weng Kee Wong.

14 recordsLinked to original sources

PubMed2006

Association of tumor necrosis factor alpha polymorphism, but not the shared epitope, with increased radiographic progression in a seropositive rheumatoid arthritis inception cohort.

OBJECTIVE: To determine whether the tumor necrosis factor alpha (TNFA) -308 guanine-to-adenosine polymorphism and/or the shared epitope (SE) is associated with radiographic damage in patients with early rheumatoid arthritis (RA). METHODS: The cohort consisted of 189 patients with early seropositive RA (median 5.6 months since symptom onset) who had active disease, no previous disease-modifying antirheumatic drug treatment, and >or=2 sets of scored radiographs of the hands/wrists and forefeet. TNFA -308 polymorphism was analyzed by polymerase chain reaction pyrosequencing. The SE was defined as presence of any 1 of the following HLA-DRB1 alleles: *0101, *0102, *0401, *0404, *0405, *0408, *0410, *1001, *1402, or *1406. Radiographic progression was assessed by the total Sharp score. RESULTS: Using a weighted least-squares regression analysis, patients with the -308 TNFA AA plus AG genotypes (n=49) had significantly higher rates of progression in erosion scores (median 0.84 versus 0.48 units/year), joint space narrowing (JSN) scores (0.42 versus 0.04), and total Sharp scores (1.70 versus 0.61) compared with patients with the TNFA GG genotype (n=140). Presence of the SE (n=137) was associated with significantly lower progression rates (per year) for total Sharp scores (median 0.9 versus 1.25 units/year) and JSN scores (0.04 versus 0.41), but not for erosion scores (0.50 versus 0.61) compared with patients without the SE (n=52). In a least-squares multiple linear regression model, the presence of the AA plus AG genotypes was associated with a significantly higher progression rate after adjusting for the presence of the SE, interaction between the SE and the AA plus AG genotypes, baseline log C-reactive protein level, Health Assessment Questionnaire Disability Index, total Sharp score, swollen joint count, and presence of osteophytes (osteoarthritis). There was a strong linkage disequilibrium between DRB1*0301 and TNFA polymorphism (D'=0.84, r2=0.45, P<0.001). CONCLUSION: This study showed an association between the TNFA -308 polymorphism and progression of radiographic damage in patients with early seropositive RA. This association appeared to be independent of the SE, but might be dependent on other genetic variants in linkage disequilibrium with the -308 TNFA A allele and DRB1*0301. Further studies should be conducted to validate these results in both longitudinal observational cohorts and randomized clinical trials.

Arthritis, Rheumatoid↗

PubMed2006

Efficacy of conventional and implant-supported mandibular resection prostheses: study overview and treatment outcomes.

STATEMENT OF PROBLEM: While surgical restoration of mandibular resections has advanced dramatically with free-flap techniques, oral function and patient perceptions of function, as well as treatment outcomes, often indicate significant impairment. PURPOSE: This longitudinal prospective study was designed to determine whether conventional prostheses (CP) or implant-supported prostheses (IP) and current surgical reconstructive procedures restore patients' oral functions and quality of life to their status prior to segmental mandibulectomy with immediate fibula free-flap reconstruction. Study design and implementation, characteristics of the study sample, treatment completion rates, and selected presurgical and postsurgical functional and perceptual outcomes are presented. MATERIAL AND METHODS: Forty-six subjects were enrolled. Longitudinal evaluations of medical and dental histories, oromaxillofacial examinations, questionnaires, and sensory and functional tests were planned before and after surgery and after CP and IP treatment. Sample characteristics are described with descriptive statistics and comparisons of subject responses to questionnaire items at entry and postsurgical intervals were made with Fisher exact tests (alpha=.05). RESULTS: Conventional prostheses were completed in 33 of 46 subjects, and 16 of 33 CP subjects were treated with IP. Reasons for noncompletion of IP were recurrent/metastatic disease (16), refusal of implant therapy (7), lost to follow-up (4), treatment with a reconstruction plate (1), excessive radiation at implant sites (1), and death (1). All 16 recurrences/metastases occurred within 13 months of surgery. Only 3 of the 58 implants placed in 17 participants were considered failures. One failed due to lack of integration 31 weeks following placement, and 2 were buried due to unacceptable positioning for prosthetic restoration during denture fabrication. The remaining 55 implants were successful at final evaluation, ranging from 58 to 123 weeks following implant placement (mean duration=78.9 +/- 16.0 weeks). CONCLUSIONS: While 72% (33/46) of the subjects enrolled were able and willing to complete treatment with CP, only 35% (16/46) completed IP treatment. Careful consideration must be given to selection of the type of prosthetic rehabilitation and the timing of implant placement if an IP is planned.

Adult↗

PubMed2006

Masticatory and swallowing threshold performances with conventional and implant-supported prostheses after mandibular fibula free-flap reconstruction.

STATEMENT OF PROBLEM: Significant strides in microvascular surgical techniques allow predictable restoration of bony and soft tissue orofacial defects. In combination with prosthetic rehabilitation, varying degrees of improvement in esthetics, speech intelligibility, and swallowing have been noted; however, the relative impact of conventional and implant-supported prostheses on restoration of masticatory function are not known. PURPOSE: The purpose of this study was to determine whether conventional or implant-supported dental prostheses and current surgical reconstructive procedures restore patients' masticatory function to presurgical levels. MATERIAL AND METHODS: Of the 46 subjects enrolled in this study, 23 (7 edentulous and 16 partially dentate) completed conventional prosthesis (CP) treatment and masticatory evaluation, and of these, 15 (3 edentulous and 12 partially dentate) completed treatment and evaluation with an implant-supported prosthesis (IP). Standardized masticatory performance tests with peanuts and carrots as the test food were made on the defect and nondefect sides. Tests of swallowing threshold performance were made with carrots as the test food. Statistical analysis included repeated-measures analysis of variance (ANOVA) with post hoc Tukey HSD tests (alpha=.05). RESULTS: Masticatory function at entry was markedly compromised. Further performance declines were noted following surgery (PS) on both the defect and nondefect sides. Restoration with CP and IP produced improvements (significant for defect side only, P<.05) in performance over the PS interval and were not significantly different from performances at entry prior to surgery. In addition, the performance on the defect side with the IP was significantly greater than the performance with the CP (P<.001). CONCLUSION: Impairment in masticatory ability remains following free-flap reconstruction prior to prosthetic rehabilitation. Both CP and IP may provide improved masticatory ability, permitting patients to regain the functional level they possessed prior to surgical intervention. The IP may contribute to greater support and stability of the prosthesis, resulting in increased use for mastication and superior performance on the defect side compared to the CP.

Bone Transplantation↗

PubMed2006

Bayesian optimal designs for a quantal dose-response study with potentially missing observations.

In a dose-response study, there are frequently multiple goals and not all planned observations are realized at the end of the study. Subjects drop out and the initial design can be quite different from the final design. Consequently, the final design can be inefficient. Single- and multiple-objective Bayesian optimal designs that account for potentially missing observations in quantal response models were recently proposed in Baek (2005). In this work, we investigate the efficiencies of the conventional optimal designs that do not incorporate potential missing information relative to our proposed designs. Furthermore, we examine the impact of restricted dose range on the resulting optimal designs. As an application, we used missing data information from a study by Yocum et al. (2003) to design a study for estimating dose levels of tacrolimus that will result in a certain percentage of rheumatoid arthritis patients having an ACR20 response at 6 months.

Algorithms↗

PubMed2006

Challenges in improving fitness: results of a community-based, randomized, controlled lifestyle change intervention.

OBJECTIVE: This study tested the efficacy of an 8-week culturally targeted nutrition and physical activity intervention on body composition. METHODS: A randomized, attention-controlled, two-group trial was conducted in a blackowned commercial gym with a sample of 366 predominantly healthy, obese African American women. A free 1-year membership to the study site gym was provided to participants in both groups. Data were collected at baseline, 2, 6, and 12 months. RESULTS: Sample retention at 1 year was 71%. Between-group longitudinal analysis including only participants with complete data revealed a trend toward weight stability in the intervention group at 2 months compared with controls (+0.05 kg/m(2), p = 0.75; +0.32 kg/m(2), p = 0.08, respectively), disappearing at 12 months (+1.37 kg/m(2), p = 0.0001; +1.02 kg/m(2), p = 0.001, respectively). Within-group analysis demonstrated that intervention and control participants' fitness (1-mile run-walk) improved by 1.9 minutes (p = 0.0001) and 2.3 minutes (p = 0.0001), respectively, at 12 months. Mixed model regression analyses demonstrated a significant main effect of the intervention on fitness (p = 0.0185) and a marginally significant effect on body mass index (BMI) (p = 0.057), at 2 months, disappearing by 6 months. By 12 months, however, the controls exhibited a significant advantage in waist circumference stability compared with intervention participants (+1.1 cm, p = 0.2763; +2.1 cm, p = 0.0002, respectively). CONCLUSIONS: The intervention produced modest short-term improvements in body composition, but the economic incentive of a free 1-year gym membership provided to all participants was a more potent intervention than the education and social support intervention tested. However, longer-term fitness enhancement remains elusive and demands research and policy attention. These findings have policy implications in that employer-/insurer-subsidized gym memberships may require interventions targeting other levels of change (e.g., physical or social/environmental) to foster sustainable fitness improvements.

Adult↗

PubMed2004

Optimal design of experiments with anticipated pattern of missing observations.

We propose a general method of designing an experiment when there are potentially failing trials. We use polynomial models and the Michaelis-Menten model as examples and construct different types of optimal designs under a broad class of response probability functions. We show that the usual optimal designs, that assume all observations are available at the end of the experiment, can be quite inefficient if the anticipated missingness pattern is not accounted for at the design stage. We also investigate robustness properties of the proposed designs to specification of their nominal values and the response probability functions.

Data Collection↗

PubMed2004

Classifying structural joint damage in rheumatoid arthritis as progressive or nonprogressive using a composite definition of joint radiographic change: a preliminary proposal.

OBJECTIVE: To categorize radiographic joint damage as progressive or nonprogressive in individuals with rheumatoid arthritis (RA) participating in clinical studies. METHODS: Using the total Sharp radiographic damage score, erosion score, and joint space narrowing (JSN) score for 751 serial films of the hand/wrist and forefoot obtained from 190 patients with early RA during 6-60 months of followup (mean 31 months), various threshold values for progression of joint damage were evaluated singly and in various combinations. For each patient, the progression rate was estimated from the linear regression line for all available radiographic time points. After preliminary screening, 23 candidate definitions were tested to select a definition that discriminated well between radiographic progression and radiographic nonprogression. RESULTS: The definition selected describes radiographic nonprogression in individual patients as an increase of < or =0.1 in the standardized response mean of the trimmed population (the central 95% of patients) for > or =5 of 6 change measures (erosion scores and JSN scores for the fingers, wrists, and feet). Using this definition, 59% of the 190 patients with early RA were defined as having nonprogressive radiographic damage. Moreover, 95% of 95 patients with progression of the total Sharp score at or below the median and 24% of 95 patients with progression of the total Sharp score above the median were defined as having nonprogressive joint damage (chi(2) = 98, P < 0.0001), as were 97% of patients in the lowest quintile of total Sharp score progression rates and none of the patients in the highest progression quintile. Patients defined as nonprogressors had significantly lower baseline levels of C-reactive protein and lower erythrocyte sedimentation rates compared with patients defined as progressors, and those patients in the nonprogressive joint damage group more frequently had American College of Rheumatology 20% and 50% improvement criteria responses, "good" improvements (decrease of > or =1.2) in the Disease Activity Score, and > or =50% decreases in the swollen joint counts during the first 2 years of followup. CONCLUSION: RA joint damage in an observational cohort can be classified as progressive or nonprogressive with the use of a composite definition. Validation and/or refinement of this definition is needed by utilizing the data from controlled clinical trials that compare placebo with active treatment.

Antirheumatic Agents↗

PubMed2004

Interaction between RANKL and HLA-DRB1 genotypes may contribute to younger age at onset of seropositive rheumatoid arthritis in an inception cohort.

OBJECTIVE: To determine whether the RANKL and HLA-DRB1 "shared epitope" (SE) genotypes contribute to the development of rheumatoid arthritis (RA). METHODS: We studied 237 patients with early RA (within 15 months of symptom onset) who were seropositive for rheumatoid factor. HLA-DRB1 genotyping was performed using the polymerase chain reaction (PCR)-based oligonucleotide probe assay. RANKL polymorphisms were analyzed using PCR pyrosequencing for SNP1 and fluorescence-based PCR for the presence or absence of the TAAA insertion. RESULTS: The presence of SE-containing DRB1*04 alleles was associated with an earlier age at RA onset (mean +/- SD 47 +/- 12.7 years versus 53 +/- 12.5 years in SE- patients; P = 0.0004). The 2 novel RANKL polymorphisms were in strong linkage disequilibrium (P < 0.0001) and were associated with earlier ages at disease onset (e.g., for the CC versus CT/TT genotypes, 44 +/- 13.5 years versus 51 +/- 12.7 years; P = 0.0080). The mean age at disease onset in SE+ patients with the RANKL-CC genotype (35 +/- 7.2 years) was a mean of 18 years younger than in SE- patients with RANKL-CT/TT (53 +/- 12.5 years; P < 0.0001) and was 17 years younger than in SE- patients with RANKL-CC (52 +/- 13.2 years; P = 0.0005). The proportion of patients with both the SE and RANKL risk alleles was highest (23%) in those who developed RA during their third decade of life (ages 20-30 years), with a declining trend among those who developed RA during their fourth (16%), fifth (5%), and sixth or later (0%) decades. Interestingly, 92% of the patients diagnosed as having RA between ages 20 and 30 years carried at least 1 of the RA-associated DRB1*04 alleles, suggesting a strong influence of the SE in the early onset of RA. The majority of patients who developed RA symptoms in their third to fifth decades (74 of 119 [62%]) carried at least 1 copy of the DRB1*04 alleles; in contrast, fewer than half of the patients who developed RA in their sixth decade or later (50 of 118 [42%]) had DRB1*04 alleles. RANKL genotypes were not associated with erosive disease at baseline or with the yearly progression rate of radiographic joint damage. CONCLUSION: This study provides the first evidence that novel RANKL polymorphisms were associated with an earlier age at RA onset in SE+, but not SE-, patients and that an interaction between SE-containing HLA-DRB1 and RANKL polymorphisms increased the disease penetrance, resulting in a mean age at RA onset that was 18-20 years younger. Our results also suggested genetic differences between patients with early-onset and those with late-onset RA.

Adult↗

PubMed2004

High-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis trial: lessons learned.

OBJECTIVES: To review important findings, or lessons, that were learned about measures of response, design, conduct, and analysis of a randomized, controlled trial (RCT), even though the trial failed to demonstrate efficacy of d-penicillamine. METHODS: One hundred thirty-four patients with early (< or =18 months), diffuse systemic sclerosis (SSc) were entered into an RCT (high-dose [822 mg daily] vs low-dose [120 mg every other day] D-penicillamine) and were followed up regularly for up to 4 years. Because analysis failed to show efficacy for D-penicillamine in early diffuse SSc, all data were pooled for additional secondary analyses. RESULTS: This RCT showed that trials of potential disease-modifying interventions can be completed in SSc using the American College of Rheumatology guidelines. This RCT used an active control. After analysis, we were not able to tell whether either dose was effective or ineffective. That experience argues in favor of using placebo controls until such time as an active control can be found that truly modifies the disease. Skin score and the disability index of the Health Assessment Questionnaire (HAQ-DI) were valid predictors of outcome. Along with the physician global assessment, they also were valid measures of response. CONCLUSIONS: Even in studies that are therapeutically "negative," careful evaluation of the data can examine other hypotheses and thereby provide important insights into other aspects of trial design, outcome measures, patient function, and trial conduct.

Adult↗

PubMed2004

Dating the "window of therapeutic opportunity" in early rheumatoid arthritis: accuracy of patient recall of arthritis symptom onset.

OBJECTIVE: A "window of therapeutic opportunity" has been hypothesized to be present in early rheumatoid arthritis (RA). To determine the date of this window, we must know the symptom-onset date of the RA. Patients participating in an observational study of early aggressive rheumatoid factor (RF) positive RA were evaluated to assess the accuracy of their recall of symptom-onset date by comparing the onset date they reported at the first visit with that reported on subsequent 6-monthly questionnaires. METHODS: One hundred eighty-six patients with early RA (at entry: median disease duration 5.8 mo, mean RF 413.8 +/- 630.7 IU/ml, 20.6 +/- 10.9 swollen and 23.7 +/- 13.4 tender joints) completed a self-reported mailed questionnaire every 6 months for up to 5 years. As a part of each questionnaire, patients were asked to recall their RA symptom-onset date. These dates were then compared to the dates reported on the initial questionnaire. RESULTS: Thirteen months after symptom onset (i.e., about 6 mo after study entry) 61% of patients recalled the symptom-onset date (within 1 mo) that they had reported at baseline; the proportion decreased to 39% at 31 months and 25% after 70 months. During this period, the proportion overestimating RA duration remained about 20%, but the proportion underestimating it increased from 23% at 13 months to 39% at 31 months, and to 50% after 56 months. Patients with longer disease duration, less disease activity, and higher pain levels tended to be less accurate. CONCLUSION: Accuracy of recall of RA symptom-onset date by patients tends to decline over a period of 5 years. This should be taken into consideration when enrolling patients, when interpreting the findings of early RA clinical trials, and when attempting to ascertain the presence of a window of therapeutic opportunity.

Arthritis, Rheumatoid↗

PubMed2003

Correlation of single time-point damage scores with observed progression of radiographic damage during the first 6 years of rheumatoid arthritis.

OBJECTIVE: Aggressive treatment of early rheumatoid arthritis (RA) is recommended to prevent irreversible joint damage. We evaluated the usefulness of single time-point joint radiographs for deciding whether early RA is erosive or nonerosive. METHODS: In an observational study, 179 patients with recent onset of RA symptoms (median 5.1 mo), positive rheumatoid factor, and active polyarthritis had 2 to 8 radiographic observations of hands, wrists, and forefeet during 6 to 60 months of followup. Linear regression lines for all available radiographs were used to determine progression rates of total Sharp score (TSS), erosion score (ES), and joint space narrowing score (JSNS) of each patient. RESULTS: Using the average of 2 readers' scores, intraclass correlation coefficient was 0.97 and smallest detectable difference was 3.07 for ES, 0.93 and 7.52 for JSNS, and 0.90 and 12.71 for TSS. Mean progression rates per year were 1.20 (ES), 0.67 (JSNS), and 1.85 (TSS). Single time-point radiographs taken within 6 months of symptom onset did not correlate with progression rates (r = 0.01 to 0.07); between 7 and 18 months correlations were weak (r = 0.23 to 0.35), but were better for ES between 19 and 72 months (r = 0.60 to 0.81). Among 53 patients (31%) with no progression of TSS, only 10 of them had zero scores at baseline. Among all 630 radiographs with TSS > or = 1, 25% were associated with progression rates < or = 0. CONCLUSION: Erosion scores of single radiographic examinations done > 18 months after onset of RA symptoms correlated with progression rates, but earlier radiographs did not sufficiently predict erosive or nonerosive status to guide disease modifying antirheumatic drug treatment decisions.

Adult↗

PubMed2002

Design issues for the Michaelis-Menten model.

We discuss design issues for the Michaelis-Menten model and use geometrical arguments to find optimal designs for estimating a subset of the model parameters, or a linear combination of the parameters. We propose multiple-objective optimal designs when the parameters have different levels of interest to the researcher. In addition, we compare six commonly used sequence designs in the biological sciences for estimating parameters and, propose optimal choices for the parameters for geometric designs using closed-form efficiency formulas.

Algorithms↗

PubMed2002

Predictors and outcomes of scleroderma renal crisis: the high-dose versus low-dose D-penicillamine in early diffuse systemic sclerosis trial.

OBJECTIVE: The reported frequency of scleroderma M01-R renal crisis (SRC) in diffuse systemic sclerosis (SSc; scleroderma) is 15-20%. Early use of angiotensin-converting enzyme (ACE) inhibitors has markedly improved outcome. The present analysis reexamines the prognostic factors for and outcome of SRC in a prospective cohort of patients with early diffuse SSc. METHODS: We retrospectively evaluated the cohort of SSc patients who participated in the High-Dose Versus Low-Dose D-Penicillamine in Early Diffuse SSc trial. Patients with diffuse cutaneous scleroderma were enrolled if their disease duration was <18 months. Because the trial failed to show a difference between treatment groups, the data were pooled. RESULTS: One hundred thirty-four SSc patients entered the observation period a mean +/- SD of 0.8 +/- 0.3 years after onset of SSc. SRC occurred in 18 patients a mean +/- SD of 0.9 +/- 1.1 years after entry. During a mean +/- SD 4.0 +/- 1.1 years of followup after entry, 9 of the 18 patients died (mean +/- SD 0.6 +/- 0.9 years after SRC onset). Baseline characteristics that predicted SRC included a modified Rodnan skin thickness score of >or=20 (P < 0.01), enlarged cardiac silhouette on radiograph (P = 0.04), large joint contractures (wrist, elbow, knee) (P = 0.008), and prednisone use at entry (P = 0.01). Baseline characteristics that did not predict SRC included age, sex, race, Health Assessment Questionnaire score, fist closure, handspread, lung involvement, muscle weakness, erythrocyte sedimentation rate, and platelet count. In 5 of 10 subjects for whom at least 2 sequential skin scores were available, skin scores increased significantly (P = 0.012) in the 6 months before onset of SRC. CONCLUSION: SRC occurred in 13% of patients soon (mean 11 months) after entry into the cohort. Predictors of SRC identified in this study included higher than average skin score, prednisone use at study entry, large joint contractures, and heart enlargement. Our data suggest, however, that low-dose prednisone alone was not associated with the onset of SRC, except in the appropriate clinical setting. Although ACE inhibitors and dialysis are now readily available, SRC continues to be associated with poor survival (in this study, 50% of patients with SRC died).

Adult↗

PubMed2002

Autoantibodies in early seropositive rheumatoid arthritis, before and during disease modifying antirheumatic drug treatment.

OBJECTIVE: Autoantibodies observed in patients with rheumatoid arthritis (RA) during clinical trials of immunomodulating agents may cause concern about possible induction of autoimmunity by the therapeutic intervention. We determined the frequency and variability of selected autoantibodies in patients with early rheumatoid factor (RF) positive RA during a prospective observational study. METHOD: The study cohort consisted of 276 patients with active RA and with RF > or = 40 IU, who were enrolled between January 1, 1993, and April 1, 2000, before starting disease modifying antirheumatic drug (DMARD) therapy (average duration of symptoms, 7 mo). During an average of 3.5 years followup, a panel of autoantibodies was determined at entry, 6 months, 12 months, and yearly thereafter, in addition to routine clinical, radiographic, and laboratory assessments. After enrollment, patients were treated with DMARD at the discretion of their rheumatologists. RESULTS: At entry before any DMARD therapy, antinuclear antibody (ANA; by HEp-2) values were negative in 31%, borderline (8 IU/ml) in 26%, and > 8 (mean 65.5 IU/ml) in 41%. Tender and swollen joint counts, Disease Activity Score, and RF values were significantly higher in those with ANA > 8. During followup 726 paired serial specimens were available; 12.5% changed from negative to positive ANA and 12.3% from positive to negative. Additional autoantibodies were present in specimens of 20% of the subjects; 8% had 2 and 1.4% had 3 other autoantibodies. Anti-dsDNA was detected in 13 (5.5%) patients; 4 changed from negative to positive and one from positive to negative. SSA IgG and SSB IgG autoantibodies were both present in one of these patients. Ribosomal P protein autoantibodies were noted in 2 other patients, but Sm (Smith) and uRNP/snRNP IgG autoantibodies were not present in any patient. No patient had a diagnosis of systemic lupus erythematosus. Antithyroid peroxidase (20 patients), parietal cell (15), smooth muscle (14), reticulin (9), mitochondrial (5), striational (2), SSB (2) and SCL-70 (1) autoantibodies were detected in some specimens. Seven patients were diagnosed with hypothyroidism, one with chronic thyroiditis, one with hepatitis C, and 9 with malignancies. CONCLUSION: In patients with early RF positive RA the frequent occurrence of autoantibodies before and during treatment with standard DMARD may make it difficult to attribute their presence to new therapies.

Adult↗