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Biomedical subjects

B M Feldman

Publications and source records attributed to B M Feldman.

At least 37 records · Page 2Linked to original sources
PubMed2003

Construct validation of the Health Utilities Index and the Child Health Questionnaire in children undergoing cancer chemotherapy.

The objective of this study was to evaluate the construct validity of two questionnaire-based measures of health-related quality of life (HRQL) in children undergoing cancer chemotherapy: the Health Utilities Index (HUI) and the Child Health Questionnaire (CHQ). Subjects were children hospitalised for chemotherapy. To examine construct validity: (1). a priori expected relations between CHQ concepts and HUI attributes were examined; (2). HUI and CHQ summary scores were compared to visual analogue scale (VAS) scores. Ease of completion was rated using a 5-point categorical scale and completion time was recorded. A total of 36 subjects were included. The maximum score was seen in 15 (47%) of HUI3 assessments. As predicted, CHQ body pain was moderately correlated with HUI3 pain (r=0.51), CHQ physical functioning was moderately correlated with HUI2 mobility (r=0.58) and CHQ mental health was moderately correlated with HUI2 emotion (r=0.53). Only the CHQ psychosocial subscale (and not HUI) was correlated with VAS (r=0.44). The CHQ and the HUI were both easy to use. The HUI questionnaires required less time to complete (mean=3.1, s.d.=1 min) compared with CHQ (mean=13.1, s.d.=3.4 min, P<0.0001). In conclusion, HUI and CHQ demonstrated construct validity in children undergoing cancer chemotherapy. The Health Utilities Index is subject to a ceiling effect whereas CHQ requires more time to complete.

Adolescent↗
PubMed2003

Validity of a modified standard gamble elicited from parents of a hospital-based cohort of children.

OBJECTIVES: To examine the validity of a modified standard gamble (Mod SG) (nondeath baseline) by comparing these scores to SG (death baseline), time trade off (TTO), visual analog scale (VAS), Health Utilities Index (HUI), and Child Health Questionnaire (CHQ). METHODS: Respondents were parents of in-patients with cancer receiving chemotherapy and parents of children without cancer attending outpatient clinics. Construct validity was determined by comparing a priori hypotheses to actual correlations between measures. Discriminant validity was examined by anticipating that in-patients with cancer would have lower HRQL than outpatients. RESULTS: 85 families were included. Both Mod SG and SG were moderately correlated with TTO (r=0.50 and r=0.49; P<.01 for both). Both Mod SG and SG were moderately correlated with TTO (r=0.47 and r=0.05, P<0.002 for both). CONCLUSION: The Mod SG did not perform better than SG. Two nonoverlapping groups of HRQL measures were demonstrated.

Adolescent↗
PubMed2002

Clinical relevance of the risk factors for coronary artery inflammation in Kawasaki disease.

The objective of this study was to determine predictive factors in children with Kawasaki disease (KD) with which we could distinguish the patients with KD who are either at very low risk or at very high risk for coronary artery inflammation (i.e., either patients who do not need intravenous immunoglobulin treatment or patients in whom more aggressive or even experimental therapies should be considered). Prospectively collected demographic, clinical, and laboratory data on 344 patients treated for KD were correlated with the patients' echocardiographic findings. The parameters studied were age, sex, duration of the fever, erythrocyte sedimentation rate, hemoglobin, white blood cell count, platelet count, and serum albumin. These were examined both in bivariable comparisons and in multiple logistic regression models. Low serum albumin, age <1 year, and the duration of the fever prior to treatment were risk factors for coronary arteritis. In the multivariable models, their combined predictive value for coronary lesions was poor, especially when identifying the patients at a low risk for coronary artery lesions (CALs). In fact, 44 of 98 patients with CALs were falsely classified to the low-risk group. Ten of 14 patients younger than 1 year of age, who also had low serum albumin (<30 g/L), had echocardiographically verified CALs, and 7 (50%) had a definite coronary artery aneurysm. We could not distinguish a group at such a low risk that these patients could be left untreated. Young patients with low albumin run a very high risk for CALs.

Adolescent↗
PubMed2002

Health-related quality-of-life treatments for severe haemophilia: utility measurements using the Standard Gamble technique.

Prophylaxis for haemophilia improves outcomes, but at a substantial cost. Cost-utility analysis balances improvements seen in health-related quality of life (HRQoL) against costs, with the purpose of aiding healthcare decision-making. This analysis uses a measure of HRQoL known as utility. The objective of this study was to measure HRQoL (utility) values for states of health that result from on-demand therapy or prophylaxis. The HRQoL for different health states (including target joint bleeding, different intensities of prophylaxis, and indwelling intravenous catheters [ports]) was measured for healthy adults (n=30), parents of haemophilic children (n=30), and adults with haemophilia (n=28). Parents and patients rated health states similarly. Healthy adults gave the lowest ratings. The following rank, in order of HRQoL, was obtained: prophylaxis (low > medium > high) > on-demand therapy > prophylaxis with port> prophylaxis with infected port > on-demand therapy with development of a target joint. We conclude that: (1) haemophilia and its treatment reduce HRQoL; (2) prophylaxis is preferred to on-demand therapy; (3) intravenous ports substantially reduce HRQoL; (4) and an intravenous port to provide prophylaxis is preferable to on-demand therapy if a target joint develops.

Adult↗
PubMed2002

Clinical outcomes in juvenile dermatomyositis.

Juvenile dermatomyositis is a chronic inflammatory illness of unknown etiology that affects primarily muscle and skin. It has an incidence of 2-3 per 1,000,000, per year. The disease can affect other organ systems, including the gastrointestinal tract, lungs, and heart. In addition, calcinosis is seen in one-third of patients. The mainstay of therapy is corticosteroids; some children require additional immunosuppressive agents because of corticosteroid resistance or intolerance. Functional outcomes have become good with modern treatments, but the disease remains chronic in a large number of children and sequelae are often seen.

Calcinosis↗
PubMed2001

A three-stage clinical trial design for rare disorders.

Many clinical trials of uncommon diseases are underpowered because of the difficulty of recruiting adequate numbers of subjects. We propose a clinical trial design with improved statistical power compared to the traditional randomized trial for use in clinical trials of rare diseases. The three-stage clinical trial design consists of an initial randomized placebo-controlled stage, a randomized withdrawal stage for subjects who responded, and a third randomized stage for placebo non-responders who subsequently respond to treatment. Test level and power were assessed by computer-intensive exact calculations. The three-stage clinical trial design was found to be consistently superior to the traditional randomized trial design in all cases examined, with sample sizes typically reduced by 20 per cent to 30 per cent while maintaining comparable power. When a treatment clearly superior to placebo was considered, our design reached a power of 75 per cent with a sample of 21 patients compared with the 52 needed to attain this power when only a randomized controlled trial was used. In situations where patient numbers are limited, a three-stage clinical trial design may be a more powerful design than the traditional randomized trial for detecting clinical benefits.

Clinical Trials as Topic↗
PubMed2001

The clinical meaning of functional outcome scores in children with juvenile arthritis.

OBJECTIVE: The Childhood Health Assessment Questionnaire (CHAQ) is the most widely used measure of function in childhood arthritis and yields a score of 0 (no disability) to 3 (very severe disability). This study ascertained the cutoff levels for CHAQ scores that represent no, mild, moderate, and severe disability, to determine the minimal clinically important change in scores and to determine whether the minimal important change in scores is similar for parent-reported assessments and the self-assessments provided by their older children. METHODS: One hundred thirty-six parents of children with arthritis were interviewed. They were asked to complete the CHAQ by assessing their child's functional status under 3 categories: current health, a hypothetical small improvement, and a hypothetical small worsening. They also completed a categorical scale of subjective disability. Those children who were > or = 10 years old also completed the CHAQ interview separately. RESULTS: The pediatric patients had mostly no, mild, or moderate disability. For those children rated as having no disability, the median CHAQ score was 0. The median CHAQ scores corresponding to mild, mild-to-moderate, and moderate disability were 0.13, 0.63, and 1.75, respectively. The minimal clinically important improvement was a reduction in score of 0.13. The minimal clinically important deterioration was a median change in score of 0.75. This discrepancy may be due to the ceiling effect seen with the CHAQ. There were no significant differences when the children assessed themselves. CONCLUSION: Clinicians, as well as researchers setting protocols, should aim for a mimimum improvement of 0.13 in the CHAQ score when treating pediatric patients with arthritis.

Arthritis, Juvenile↗
PubMed2001

Oxidation of zinc-binding cysteine residues in transcription factor proteins.

Recent results on the oxidation of cysteine residues that bind zinc in transcription factors and their analogous peptides and in related proteins and model systems are reviewed. Two classes of oxidants, the transition metals and dioxygen, hydrogen peroxide, and related species, are considered, and the role of metal ions in suppressing or enhancing Cys oxidation is a major focus. Cysteines in the zinc-bound structures of transcription factors are less susceptible to oxidation than in the metal-free form, and this appears to correlate with reduced accessibility of the thiolates to oxidants. Substitution of other metal ions for Zn(II) increases the rate of Cys oxidation, apparently through increased oxidant accessibility. Reactions that result in reversible or irreversible oxidation of these zinc-binding cysteines under biological conditions are identified in the context of deleterious implications for gene expression.

Amino Acid Sequence↗
PubMed2001

The arthritis of inflammatory childhood myositis syndromes.

OBJECTIVE: Arthritis has been an associated finding in juvenile dermatomyositis (JDM), but its prevalence, course, and response to therapy has not been well described. We investigated the frequency, course, and clinical and radiographic features in a large cohort of patients with JDM. METHODS: The charts of 94 patients with idiopathic myositis (1984-99) were reviewed: 80 JDM, 3 juvenile polymyositis (JPM), 5 amyopathic JDM, and 6 overlap myositis syndromes. Compiled data included demographics, clinical features, a detailed description of the arthritis, investigations (radiographs, autoantibodies), course, and response to therapy. All radiographs were independently reviewed by a single radiologist. RESULTS: Sixty-one percent (95% CI 50-72%) of patients with JDM had arthritis. The arthritis was reported a median 4.5 mo (range -73.6 to 76.6 mo) after the JDM onset. When compared to patients with no arthritis, the occurrence of arthritis was not significantly related to sex, race, positive antinuclear antibody or rheumatoid factor, calcinosis, nodules, vasculitis, or Raynaud's phenomenon. The initial involvement was pauciarticular in 67% and polyarticular in 33%. In the pauci group, asymptomatic knee effusions were the predominant finding (n = 19, 58%), and in 18 patients may have been the result of steroid therapy. Two patients evolved from a pauci onset to a polyarticular course. All responded to therapy (corticosteroids; 47 were taking other medications) with remission of the arthritis within a median of 2.0 mo (range 0.1-64.5 mo). However, the arthritis recurred in 39% as the corticosteroids were tapered. Four patients with JDM eventually required corticosteroid wrist injections, with resolution of the arthritis. The arthritis was nonerosive in all cases. No patient with JPM had arthritis. Three of 5 patients with amyopathic JDM and 4 of 6 with overlap myositis syndrome had a nonerosive polyarthritis. CONCLUSION: Nonerosive arthritis involving the knees, wrists, elbows, and fingers is a frequent manifestation of JDM and other idiopathic childhood myositis. The arthritis is seen early in the course of JDM and often responds to treatment. However, the arthritis may recur with tapering of corticosteroids despite remission of the JDM. In a significant proportion of JDM cases, arthritis is the major sequela and may warrant further medical therapy or intraarticular corticosteroid injections.

Adolescent↗
PubMed2001

Validation of the Childhood Health Assessment Questionnaire in the juvenile idiopathic myopathies. Juvenile Dermatomyositis Disease Activity Collaborative Study Group.

OBJECTIVE: To examine the validity of the Childhood Health Assessment Questionnaire (CHAQ) in patients with juvenile idiopathic inflammatory myopathy (IIM). METHODS: One hundred fifteen patients were enrolled in a multicenter collaborative study, during which subjects were assessed twice, 7-9 months apart. Physical function was measured using the CHAQ. Internal reliability was assessed using adjusted item-total correlations and item endorsement rates. Construct validity was assessed by comparing predicted and actual correlations of the CHAQ with other measures of physical function and disease activity. Responsiveness was assessed by calculating effect size (ES) and standardized response mean (SRM) in a group of a priori defined "improvers." RESULTS: Item-total correlations were high (rs range = 0.35-0.81), suggesting all items were related to overall physical function. Manual muscle testing and the Childhood Myositis Assessment Scale correlated moderate to strongly with the CHAQ (r = -0.64 and -0.75, both p < 0.001). Moderate correlations were also seen with the physician global assessment of disease activity (rs = 0.58, p < 0.001), parent global assessment of overall health (rs = -0.65, p < 0.001), Steinbrocker function class (rs = 0.69, p < 0.001), and global skin activity (rs = 0.40, p < 0.001), while global disease damage and skin damage had low correlations (rs = 0.13 and 0.07, p > or =0.17). Responsiveness of the CHAQ was high, with ES = 1.05 and SRM = 1.20. CONCLUSION: In this large cohort of patients with juvenile IIM, the CHAQ exhibited internal reliability, construct validity, and strong responsiveness. We conclude that the CHAQ is a valid measure of physical function in juvenile IIM, appropriate for use in therapeutic trials, and potentially in the clinical care of these patients.

Adolescent↗
PubMed2000

Medium- and long-term functional outcomes in a multicenter cohort of children with juvenile dermatomyositis.

OBJECTIVE: To evaluate functional outcomes in a cohort of patients with juvenile dermatomyositis (DM). METHODS: A retrospective inception cohort of patients diagnosed as having juvenile DM between January 1, 1984 and January 1, 1995 was established at 4 Canadian tertiary care pediatric centers. Informed consent was obtained. Each subject was interviewed by telephone or in person. The primary outcome was physical function, as measured by the Childhood Health Assessment Questionnaire (CHAQ). Additional outcomes were educational and vocational achievement, growth, development of calcinosis, patient satisfaction with outcome, and development of other illnesses. Data regarding illness presentation, treatment, and disease course were obtained through chart review. RESULTS: Sixty-five of 80 patients (81%; 46 females and 19 males) could be contacted. The median followup time was 7.2 years (range 3.2-13.9 years), with a median age at followup of 13 years (range 7-26 years). Twenty-four patients (37%) had a monocyclic course, while the remaining 41 (63%) had a chronic continuous or polycyclic course. Sixty-two patients (95%) were treated with corticosteroids, while 41 (63%) received a second-line agent. Physical function was excellent, with a median CHAQ score of 0 (range 0-2.50). Eighteen patients had scores >0, and only 5 had moderate-to-severe disability, as defined by a CHAQ score >1.0. Females had higher CHAQ scores, and all but 1 of the patients with scores >0 were female (range 0-2.50; P = 0.015). Patients with a chronic continuous course also had higher CHAQ scores. Sixteen patients in the chronic continuous group had CHAQ scores >0 (range 0-2.50; P = 0.0009). Calcinosis developed in 22 patients (34%) and persisted to followup in 14. Development of calcinosis was not related to initial therapy, sex, or disease course, but was significantly associated with higher CHAQ scores (range 0-1.0 versus 0-2.5; P = 0.01). At the time of followup, 26 patients (40%) still had rash, 15 (23%) still reported weakness, and 23 (35%) continued taking medications, despite the fact that all were at least 3 years postdiagnosis. There was 1 death. CONCLUSION: In general, patients in this cohort had favorable outcomes. Most had CHAQ scores of 0, and only 8% met our definition of moderate-to-severe disability. However, many patients continued to have chronic disease, persistent rash, and continued taking medications >3 years after diagnosis. Further research is needed to improve outcomes for patients with juvenile DM.

Adolescent↗
PubMed2000

Early predictors of poor functional outcome in systemic-onset juvenile rheumatoid arthritis: a multicenter cohort study.

OBJECTIVE: To examine the ability of a previously described set of criteria to predict poor functional outcome in a large, multicenter cohort of children with systemic-onset juvenile rheumatoid arthritis (JRA). METHODS: All children who were diagnosed with systemic-onset JRA since 1980 at the Hospital for Sick Children (Toronto), since 1983 at the Isaac Walton Killam Hospital for Children (Halifax), and since 1981 at the Children's Hospital of Eastern Ontario (Ottawa) were evaluated. Patients were included in the study if they had been evaluated clinically within 6 months of diagnosis and had been followed up for at least 2 years. Patients were divided into 4 cohorts according to their length of followup: 2-4 years, 4-7 years, 7-10 years, and >10 years. Using previously described criteria for destructive arthritis in children with systemic-onset JRA, the patients were classified as either high risk or low risk for poor functional outcome based on the data from their 6-month visit. High-risk patients had active systemic disease (persistent fever or corticosteroid requirement for control of systemic disease) and a platelet count > or =600 x 10(9)/liter. Poor outcome was defined as moderate or severe disability (defined as a score of > or =0.75 on the Childhood Health Assessment Questionnaire) or disease-associated death. RESULTS: Among 122 eligible patients with systemic-onset JRA, we were able to contact 111 (91%) for outcome data. The mean followup period was 7.7 years (SD 3.7). The mean age at outcome assessment was 13.5 years (SD 5.3). There were 51 boys and 60 girls. Twenty-four patients (22%) had moderate-to-severe disability and 2 patients died; these 26 patients were considered to have had a poor outcome. We could determine risk classification for 104 patients. Twenty-four patients (23%) met the criteria for high risk at the 6-month visit. Overall, the risk of a poor functional outcome was significantly higher in the high-risk group (relative risk 3.3, 95% confidence interval [95% CI] 1.73-6.43, P = 0.0004). This risk was most marked in the cohort with > 10 years of followup (relative risk 4.3, 95% CI 1.82-10.29, P = 0.006). CONCLUSION: The presence of active systemic disease at 6 months, as characterized by fever or the need for corticosteroids, and thrombocytosis strongly predicted the development of a poor functional outcome in these patients. This was especially apparent with longterm followup. Our study validates the previously developed prognostic criteria for systemic-onset JRA.

Activities of Daily Living↗
PubMed2000

Methotrexate and corticosteroid therapy for pediatric localized scleroderma.

INTRODUCTION: Localized scleroderma (LS) can cause permanent disability, and there is no universally accepted effective treatment. Methotrexate (MTX) has been shown to be effective in the treatment of systemic sclerosis. OBJECTIVES: To determine the efficacy and tolerability of MTX and corticosteroid therapy in patients with LS. METHODS: MTX, 0.3 to 0.6 mg/kg per week, was given to 10 patients (6 girls, 4 boys; mean age, 6.8 years; mean disease duration before starting treatment, 4 years) with active LS. In addition, pulse intravenous methylprednisolone, 30 mg/kg for 3 days monthly for 3 months, was given to 9 patients at the initiation of therapy. RESULTS: One patient discontinued taking MTX after a month; the remaining 9 patients responded. The median time to response was 3 months (95% CI, 1.15-4.85). One responder discontinued taking MTX after a year because of leukopenia; the LS worsened within 2 months. In another patient LS flared up after 10 months and responded to an increased dose of MTX and intravenous methylprednisolone. At the last follow-up visit, all patients who continued to receive MTX therapy had inactive skin lesions. CONCLUSION: Treatment with MTX and corticosteroids appears to be effective in the treatment of LS and is generally well tolerated. A placebo-controlled study is necessary to confirm the efficacy of MTX therapy in LS.

Administration, Oral↗
PubMed2000

Children with morphea have normal self-perception.

We evaluated the self-esteem and quality of life of 47 children with morphea with the use of the Harter self-perception profile for children and Visual Analog Scale. Most children with morphea have normal self-worth and a high quality of life. Morphea, like some other childhood chronic illnesses, does not impair self-esteem.

Adolescent↗
PubMed2000

Distinction of quality of life, health related quality of life, and health status in children referred for rheumatologic care.

OBJECTIVE: Current health status measures [sometimes called quality of life (QOL) measures] are based on the values of their designers. QOL, though, reflects the idiosyncratic values of each individual. We investigated whether children referred for rheumatologic care differentiate between the concepts of health related quality of life (HRQOL), overall QOL, and health status. METHODS: One hundred twenty-two consecutive children seen at a pediatric rheumatology referral clinic completed a new global self-report quality of life scale (Quality of My Life), a functional impairment scale (Childhood Health Assessment Questionnaire), and a disease severity visual analog scale. Sixty children were seen for a followup assessment. RESULTS: HRQOL was somewhat lower than overall QOL (median 6.6 vs 8.6 out of 10; respectively) in this sample of patients. Our subjects did differentiate between overall QOL and HRQOL and health status. Health status, as measured by disease severity, accounted for only a moderate amount of variability in HRQOL (R2 = 0.25, p< or =0.0001). Health status measured by functional disability accounted for even less of the variability in HRQOL (R2 = 0.047, p = 0.013). Similarly, HRQOL accounted for only a moderate amount of the variability seen in overall QOL (R2 = 0.31, p< or =0.0001). CONCLUSION: The goal of most health professionals is to improve their patients' overall QOL. QOL, though, appears to be a broad and idiosyncratic construct affected only moderately by health. Health status, global HRQOL, and overall QOL all provide independent information. All 3 measures should be considered for use in research studies. HRQOL and overall QOL reflect patients' own values, and therefore may offer important information for clinicians in addition to health status.

Adolescent↗
PubMed2000

Innovative strategies for trial design.

Most clinical trial designs used in evaluating therapies require large numbers of subjects. Childhood rheumatic diseases are rare and large numbers of subjects are not available. We have largely been unsuccessful in developing evidence based therapeutics for pediatric rheumatology. Because these diseases are rare, it is important for each clinical trial to enroll all possible subjects, and it is important to extract as much information as possible from each subject. Placebo controlled randomized studies are sometimes seen as unacceptable to physicians and patients. We need study designs that are more acceptable and that will increase accrual. Some clinical trial designs, especially those that involve crossover treatment assignments, can increase the amount of information that each subject contributes. These types of studies can only be used for treatments that are reversible. For treatments that may permanently affect the disease course, I propose the randomized placebo phase design as one way of increasing study acceptability and accrual.

Arthritis, Juvenile↗
PubMed2000

Intravenous immunoglobulin therapy for juvenile dermatomyositis: efficacy and safety.

OBJECTIVE: To assess the efficacy of intravenous immunoglobulin (IVIG) for the treatment of juvenile dermatomyositis (JDM) in patients who were unresponsive to corticosteroids (steroid resistant or steroid dependent) or showed unacceptable toxicity. METHODS: A retrospective chart review of the course of all patients with JDM treated with IVIG who attended the Dermatomyositis Clinic at The Hospital for Sick Children, Toronto, Canada, from August 1986 to December 1996. RESULTS: Eighteen patients with JDM were treated with IVIG. Ten patients were taking additional 2nd line treatments, methotrexate, azathioprine, cyclosporine, and cyclophosphamide. The main indication for starting IVIG was the failure of steroid therapy to induce remission of JDM. Twelve patients showed clinical improvement with IVIG. In these patients, the corticosteroid dose was reduced by > 50% for > 3 months without clinical or biochemical flare. Nine of these 12 patients had IVIG alone as a 2nd line agent, whereas 3 patients were treated with additional agents. Six patients remained steroid dependent; they subsequently required multiple agents to induce remission of JDM. CONCLUSION: Most steroid dependent or steroid resistant patients in our clinic were able to markedly reduce their dose of corticosteroid with the addition of IVIG. Given the retrospective nature of our data and the fact that multiple agents were sometimes used together, it will be important to confirm these findings in a controlled trial.

Antirheumatic Agents↗