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Biomedical subjects

D J Lovell

Publications and source records attributed to D J Lovell.

At least 19 recordsLinked to original sources
PubMed2003

Lupus headaches in childhood-onset systemic lupus erythematosus: relationship to disease activity as measured by the systemic lupus erythematosus disease activity index (SLEDAI) and disease damage.

The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) is the most commonly used measure of disease activity for children with systemic lupus erythematosus (SLE). For headaches to be scored in the SLEDAI as a symptom of active disease, they have to be nonresponsive to narcotic analgesia. This may affect the overall estimation of disease activity, especially because headaches are common among children with SLE and narcotic analgesia is rarely used for headache therapy in paediatrics. Moreover, the importance of headaches for the development of damage and their relation to other clinical parameters and outcomes has not been well described for children with SLE. We reviewed the medical charts of an inception cohort of children (n = 63) who were newly diagnosed with SLE. Information on headaches and other disease parameters was obtained. Disease activity and damage were measured using the SLEDAI and the Systemic Lupus International Collaboration Clinics/American College of Rheumatology Damage Index (SDI), respectively. It has been shown that the accumulated burden of active disease as measured by serial SLEDAI scores over time is one of the best predictors of eventual damage to children with SLE. New-onset or significant increase of severe and/or persistent headaches (LHA) were reported in 43% of the patients during a mean follow-up of 3.6 years. LHA occurred preferentially among patients with elevated levels of antiphospholipid antibodies (aPL) (P < 0.02) and only 6% of all LHA episodes were treated with narcotics and thus considered for the measurement of disease activity in the SLEDAI. LHA were unrelated to proxy-measures of disease activity, such as the need to intensify therapies. When used in children, the insensitivity of the SLEDAI to capture LHA did not seem to decrease the responsiveness of the SLEDAI to detect clinically important worsening of disease, or negatively impact on its ability to predict damage.

Adolescent↗
PubMed2001

Current medication choices in juvenile rheumatoid arthritis II--update of a survey performed in 1993.

The documentation of treatments used for Juvenile Rheumatoid Arthritis (JRA) is important to allow for the evaluation of practice patterns for future outcome studies. A survey of nine pediatric rheumatologists was performed between September 1999 and February 2000. Each of the physicians prospectively recorded demographic and treatment information on consecutively sampled JRA patients (n=395). Pauciarticular onset JRA was present in 46%, polyarticular onset JRA in 35%, and systemic onset JRA in 19% of the children. Naproxen was the most frequently prescribed medication (55% of the patients), followed by methotrexate (MTX), which was used in 39% of the patients. Folic acid supplementation (1 mg/day) was provided to 69% of the patients treated with MTX. Etanercept was used in 11% of the children. Eleven percent of the patients received corticosteroids, and 13% of children on corticosteroids took calcium supplements. Uveitis was present in 8% and had a chronic course in 79% of those cases. Although systemic medications were used in 50% of the children with uveitis to control eye inflammation, severe damage to the eyes developed in 30% of them. Fourteen percent of the patients required gastroprotective medications. Compared with findings of a similar survey performed in 1993, there was no significant change in the frequency of use of naproxen, but nabumetone is now more often prescribed, and COX-2 inhibitors have been introduced in the therapy of JRA. Changes among second-line agents used for JRA have also occurred, although there was no change in the frequency of use of MTX or corticosteroids. JRA continues to be a treatment challenge for the practicing pediatric rheumatologist. Patients often show incomplete response to the currently available medications. Therefore, new therapeutic agents need to be evaluated for their use in JRA, and the treatment of JRA associated uveitis especially needs to be improved.

Journal Article↗
PubMed2001

Etanercept in the treatment of macrophage activation syndrome.

Macrophage activation syndrome (MAS), a recognized complication of systemic juvenile rheumatoid arthritis (sJRA), has been associated with significant morbidity and mortality. Dysregulation of macrophage-lymphocyte interactions leading to uncontrolled proliferation of highly activated macrophages and massive release of proinflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) appears to be central to the pathogenesis of this syndrome. Until now the mainstay of therapy has been corticosteroids and cyclosporin A. We describe a patient with MAS and sJRA successfully treated with the anti-TNF agent etanercept. The outcome in this patient suggests etanercept might be an effective therapeutic agent in MAS.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group.

BACKGROUND: We evaluated the safety and efficacy of etanercept, a soluble tumor necrosis factor receptor (p75):Fc fusion protein, in children with polyarticular juvenile rheumatoid arthritis who did not tolerate or had an inadequate response to methotrexate. METHODS: Patients 4 to 17 years old received 0.4 mg of etanercept per kilogram of body weight subcutaneously twice weekly for up to three months in the initial, open-label part of a multicenter trial. Those who responded to treatment then entered a double-blind study and were randomly assigned to receive either placebo or etanercept for four months or until a flare of the disease occurred. A response was defined as an improvement of 30 percent or more in at least three of six indicators of disease activity, with no more than one indicator worsening by more than 30 percent. RESULTS: At the end of the open-label study, 51 of the 69 patients (74 percent) had had responses to etanercept treatment. In the double-blind study, 21 of the 26 patients who received placebo (81 percent) withdrew because of disease flare, as compared with 7 of the 25 patients who received etanercept (28 percent) (P=0.003). The median time to disease flare with placebo was 28 days, as compared with more than 116 days with etanercept (P<0.001). In the double-blind study, there were no significant differences between the two treatment groups in the frequency of adverse events. CONCLUSIONS: Treatment with etanercept leads to significant improvement in patients with active polyarticular juvenile rheumatoid arthritis. Etanercept is well tolerated by pediatric patients.

Activities of Daily Living↗
PubMed2000

Total-body bone mineral content in non-corticosteroid-treated postpubertal females with juvenile rheumatoid arthritis: frequency of osteopenia and contributing factors.

OBJECTIVE: To determine the extent of low total-body bone mineral content (BMC) in non-corticosteroid-treated white postpubertal females with juvenile rheumatoid arthritis (JRA) compared with healthy age- and race-matched female controls, and to identify variables that significantly contribute to total-body BMC. METHODS: Thirty-six females with definite JRA who had never received corticosteroids and 51 healthy female controls were evaluated. All subjects had had their first menstrual period at least 2 years prior to enrollment. Total-body BMC, lumbar spine bone mineral density, and body composition were determined by dual x-ray absorptiometry. Total-body BMC Z-scores were calculated for JRA patients using data from controls. JRA patients were dichotomized into those with "normal" bone mass (total-body BMC at or above the mean or no more than 1 SD below the mean) and those with "low" bone mass (total-body BMC more than 1 SD below the mean). Comparisons of anthropometric measurements, laboratory measurements of bone metabolism, disease activity, dietary intake, and physical activity were performed. Stepwise logistic regression was utilized to determine the presence or absence of low total-body BMC and to identify associated contributing factors. RESULTS: Total-body BMC was 4.5% lower in JRA patients than in controls (mean +/- SD 2,050 +/- 379 gm versus 2,143 +/- 308 gm; P = 0.21). Twenty-five of 36 patients (69.4%) had "normal" and 11 of 36 (30.6%) had "low" total-body BMC. Comparison of JRA patients with "normal" versus those with "low" total-body BMC revealed significant differences in disease characteristics, anthropometric and physical development characteristics, laboratory measures of bone mineralization, and dietary intake. The final regression model contained only lean mass (P = 0.01), which accounted for 76.3% of the variance in total-body BMC. The odds ratio for lean mass was 0.4451 (95% confidence interval 0.2374-0.8348). CONCLUSION: In this study, approximately 30% of the subjects in a sample of postpubertal female patients with mild-to-moderate, non-corticosteroid-treated JRA had low bone mass. The predictor variable that significantly contributed to total-body BMC was lean mass, which demonstrated a protective effect of 0.56 risk reduction for low total-body BMC.

Adolescent↗
PubMed1999

Assessment of bone mineral density in adults with a history of juvenile chronic arthritis: a cross-sectional long-term followup study.

OBJECTIVE: To assess bone mineral density (BMD) and bone turnover in adults with a history of juvenile chronic arthritis (JCA) or persistent JCA, and to identify predictors of reduced BMD. METHODS: Sixty-five white patients (mean age 32.2 years) with a history of JCA and 65 age-, sex-, height-, and weight-matched healthy control subjects participated in the study. Densitometry of the left hip and the lumbar spine was performed, and osteocalcin (bone formation marker) and crosslinks (bone resorption marker) were measured. In addition, bone-related clinical parameters were assessed in the JCA group. RESULTS: BMD in the hip and lumbar spine was significantly lower in the JCA group than in the controls. Levels of osteocalcin and crosslinks were significantly increased in the JCA group. According to WHO definitions, significantly more subjects in the JCA group had "osteopenia" and "osteoporosis" than would be expected in a normal population sample. Active disease at the time of the study (1996-1997), baseline erosions evaluated in 1979, Steinbrocker functional class in 1996-1997, polyarticular course of JCA, and history of systemic steroid treatment for more than 1 year were significantly associated with reduced BMD. In linear regression analysis including both the JCA and control groups, presence of JCA proved to be the factor most strongly associated with reduced BMD, explaining approximately 20% of its variation. CONCLUSION: Reduced BMD and evidence of increased bone turnover suggest that JCA patients may be at risk of developing premature osteoporosis and associated fractures later in life. The data are consistent with the concept that BMD in JCA is determined by many factors.

Adult↗
PubMed1999

Development of validated disease activity and damage indices for the juvenile idiopathic inflammatory myopathies. II. The Childhood Myositis Assessment Scale (CMAS): a quantitative tool for the evaluation of muscle function. The Juvenile Dermatomyositis Disease Activity Collaborative Study Group.

OBJECTIVE: To develop, validate, and determine the measurement characteristics of a quantitative tool for assessing the severity of muscle involvement in children with idiopathic inflammatory myopathies. METHODS: The Childhood Myositis Assessment Scale (CMAS) was developed from 2 existing observational functional assessment tools to assess muscle function in the areas of strength and endurance across a wide range of ability and ages. The 14 ordinal items included were chosen to assess primarily axial and proximal muscle groups and are ranked with standard performance and scoring methods. Following the development of the CMAS, a training video and written instructions were developed and reviewed by the physicians participating in this study. Subsequently, utilizing a randomized block design, 12 physicians independently scored 10 children (9 with dermatomyositis, 1 with polymyositis; ages 4-15 years) twice in one day (morning and afternoon) on the CMAS. A pediatric physical therapist performed quantitative manual muscle strength testing (MMT) twice on each child (morning and afternoon), including the neck, trunk, and proximal and distal extremity muscle groups. RESULTS: The CMAS has a potential range of 0-51, with higher scores indicating greater muscle strength and endurance. The observed mean for the 10 patients was 36.4 (median 44, SD 14.1, observed range 5-51). The total score for the CMAS correlated with the physician's global assessment (by visual analog scale) of disease activity, the MMT score, serum creatine kinase level, and the Juvenile Arthritis Functional Assessment Report score. The score on the CMAS was not correlated with patient age. Interrater reliability (Kendall's coefficient of concordance) ranged from 0.77 to 1.0 for individual items (all P < 0.001), and overall, it was 0.95 (P < 0.001). Intrarater reliability for the individual physicians was measured by correlation of the CMAS scores for each patient on 2 separate evaluations and ranged from 0.97 to 0.99, with an overall correlation for all physicians of 0.98 (all P < 0.001). CONCLUSION: The CMAS demonstrated an acceptable range of observed scores, excellent convergent validity, and excellent inter- and intrarater reliability. The CMAS is validated to quantitatively assess muscle function in the areas of strength and endurance in children with idiopathic inflammatory myopathies. It can be used in routine clinical care as well as therapeutic trials.

Adolescent↗
PubMed1998

Substance use among adolescents with juvenile rheumatoid arthritis.

OBJECTIVE: To determine the prevalence of substance use among adolescents with juvenile rheumatoid arthritis and to assess available opportunities for rheumatologists to identify high risk teens. METHODS: Fifty-two teens (mean age 13.9 years, 86% female) completed questionnaires regarding substance use (alcohol, tobacco, marijuana, and other illicit substances), functional disability, and frequency of health care contacts. RESULTS: Alcohol use was reported by 30.7% of teens, including 23.5% of those for whom methotrexate was prescribed; 15.4% reported tobacco use in the last year, and 13.4% reported other illicit substance use in their lifetime, although most use was experimental. No teen reported marijuana use. The majority reported regular contact with their rheumatologist but only 26.9% were ever interviewed alone. CONCLUSION: Many teens with juvenile rheumatoid arthritis, including those prescribed methotrexate, used substances, especially alcohol. When rheumatologists see adolescents, particularly in situations where methotrexate may be prescribed, a clinical setting conductive to confidentially, physician comfort in asking about sensitive topics such as substance abuse, and referral relationships with skilled adolescent health and substance abuse counseling providers are essential.

Activities of Daily Living↗
PubMed1997

Preliminary definition of improvement in juvenile arthritis.

OBJECTIVE: To identify a core set of outcome variables for the assessment of children with juvenile arthritis (JA), to use the core set to develop a definition of improvement to determine whether individual patients demonstrate clinically important improvement, and to promote this definition as a single efficacy measure in JA clinical trials. METHODS: A core set of outcome variables was established using a combination of statistical and consensus formation techniques. Variables in the core set consisted of 1) physician global assessment of disease activity; 2) parent/patient assessment of overall well-being; 3) functional ability; 4) number of joints with active arthritis; 5) number of joints with limited range of motion; and 6) erythrocyte sedimentation rate. To establish a definition of improvement using this core set, 21 pediatric rheumatologists from 14 countries met, and, using consensus formation techniques, scored each of 72 patient profiles as improved or not improved. Using the physicians' consensus as the gold standard, the chi-square, sensitivity, and specificity were calculated for each of 240 possible definitions of improvement. Definitions with sensitivity or specificity of <80% were eliminated. The ability of the remaining definitions to discriminate between the effects of active agent and those of placebo, using actual trial data, was then observed. Each definition was also ranked for face validity, and the sum of the ranks was then multiplied by the kappa statistic. RESULTS: The definition of improvement with the highest final score was as follows: at least 30% improvement from baseline in 3 of any 6 variables in the core set, with no more than 1 of the remaining variables worsening by >30%. The second highest scoring definition was closely related to the first; the third highest was similar to the Paulus criteria used in adult rheumatoid arthritis trials, except with different variables. This indicates convergent validity of the process used. CONCLUSION: We propose a definition of improvement for JA. Use of a uniform definition will help standardize the conduct and reporting of clinical trials, and should help practitioners decide if a child with JA has responded adequately to therapy. We are in the process of prospectively validating this definition and several others that scored highly.

Arthritis, Rheumatoid↗
PubMed1997

Predictors of total body bone mineral density in non-corticosteroid-treated prepubertal children with juvenile rheumatoid arthritis.

OBJECTIVE: To determine the extent of significant osteopenia in prepubertal patients with juvenile rheumatoid arthritis (JRA) not treated with corticosteroids and to identify variables that are highly related to bone mineralization in this population. METHODS: In a cross-sectional study, 48 JRA patients and 25 healthy control subjects ages 4.6-11.0 years were evaluated. Total body bone mineral density (TB BMD) was determined by Hologic dual energy x-ray absorptiometry. All patients were prepubertal (Tanner stage I or II) and had never taken corticosteroids. For comparison, JRA patients were divided into "low" TB BMD (Z score < or =-1) or "normal" TB BMD (Z score >-1). RESULTS: The overall mean +/- SD TB BMD scores did not differ between the JRA subjects (0.75 +/- 0.06 gm/cm2) and controls (0.73 +/- 0.07 gm/cm2; P > 0.30). However, 29.2% of the JRA patients had low TB BMD, whereas only 16% would be expected to have low TB BMD based on the standard normal distribution (goodness of fit chi(2) = 4.84, P = 0.01). The mean Z score for the JRA patients with low TB BMD was -1.43, and for those with normal TB BMD, it was 0.32. The JRA subjects with low TB BMD were significantly younger, had more active articular disease, greater physical function limitation, higher erythrocyte sedimentation rate, higher joint count severity score, lower body mass index, lower lean body mass, less participation in organized sports, and more protein and vitamin D in their diet compared with JRA patients with normal TB BMD (all P < 0.05). Using logistic regression, a model including age at JRA onset, Juvenile Arthritis Functional Assessment Report (JAFAR) score, triceps skin-fold percentiles, percentage US recommended daily allowance for dietary magnesium intake, and serum 1,25-dihydroxyvitamin D levels was able to accurately segregate 79.6% of the JRA subjects into either the low or normal TB BMD groups (chi(2) = 20.5, P = 0.001). CONCLUSION: This study demonstrated that in a mildly to moderately ill prepubertal JRA population that had never been exposed to corticosteroids, almost 30% had significantly low TB BMD. The patients with low TB BMD had more active and severe articular disease and greater physical function limitation. Disease-related parameters in JRA appear to exert a negative effect on bone mineralization even in prepubertal children, which can be demonstrated despite the exclusion of corticosteroid-treated patients.

Adrenal Cortex Hormones↗
PubMed1997

Outcome in pediatric rheumatic disease.

Outcome assessment has been a focus of recent research in rheumatic diseases and in pediatric rheumatology. The establishment of a preliminary core set of outcome variables for juvenile rheumatoid arthritis patients and a preliminary definition of improvement using these variables have been important steps toward standardization of outcome assessment. A population-based epidemiologic study has added to our knowledge of long-term outcome in juvenile arthritis and confirms the chronicity of disease that was found in previous studies. Standardization of outcome assessment in pediatric systemic lupus erythematosus has not been achieved to the same extent as in juvenile rheumatoid arthritis, but renal survival and overall mortality are important outcomes in this disease that are easily quantified. Recent studies of pediatric systemic lupus erythematosus demonstrate similarities with respect to organ involvement and overall survival between adult and pediatric lupus patients.

Arthritis, Juvenile↗
PubMed1997

International trials in paediatric rheumatology: current status.

Current treatment of children with juvenile chronic arthritis (JCA) has been changed significantly by the results of randomized controlled trials (RCTs). However, due to low market appeal of JCA, few RCTs are being funded by drug companies and none in the more rare childhood rheumatic diseases. In addition, RCTs have several limitations when used for a chronic illness such as JCA. To deal with this situation, the Pediatric Rheumatology International Trials Organization (PRINTO) is being organized to perform effectiveness trials in addition to efficacy trials in a variety of paediatric rheumatic illnesses.

Arthritis, Juvenile↗
PubMed1996

Intravenous immunoglobulin in the treatment of polyarticular juvenile rheumatoid arthritis: a phase I/II study. Pediatric Rheumatology Collaborative Study Group.

OBJECTIVE: To obtain preliminary information about the safety and efficacy of intravenous immune globulin (IVIG: Iveegam, Immuno AG, Vienna) in the treatment of polyarticular juvenile rheumatoid arthritis (poly-JRA) resistant to other forms therapy. METHODS: We used a multicentered, phase I/II blinded-withdrawal design with stratified entry. All patients began by receiving open infusions of IVIG at a dose between 1.5 and 2.0 g/kg/infusion (100 g maximum) bimonthly for the first 2 months, then monthly for up to 6 months. Beginning at Month 3, those who met the criteria for "clinically important improvement" were randomized to receive monthly infusions for 4 months of either placebo or IVIG in a double blind (DB) phase. Patients were permitted nonsteroidal antiinflammatory drugs, slow acting antirheumatic drugs, and low dose (< 10 mg/day) prednisone at constant doses. An "early escape" provision in the DB allowed those who showed "clinically important worsening" to again receive IVIG (if taking placebo) or a higher dose of IVIG (if taking the lower dose of IVIG). RESULTS: Efficacy. Twenty-five children entered the trial and 19 (76%) met the criteria for "clinically important improvement" during the open phase (OP) and entered the DB. Three patients completed the OP but failed to meet the criteria for response, and 3 patients dropped out of the OP, none of whom showed benefit from IVIG. Treatment effect sizes produced by IVIG were moderate to large for all variables in the OP. Patients who continued IVIG in the DB continued to show improvement over that achieved in the OP. Those given placebo showed a rapid loss of efficacy, suggesting IVIG has a limited duration of effect after discontinuation. Safety. No patient developed serious or unexpected adverse side effects in the open or DB phases, and none dropped out of the study due to toxicity or side effects. CONCLUSION: Substantial clinical improvement from IVIG is produced in about three-fourths of patients with poly-JRA during open administration, but the duration of the beneficial effect is short after discontinuation. Those with disease < 3 years' duration may be more likely to respond than those who have had their disease for > 5 years. Short term safety is excellent.

Adolescent↗