RESUMO
OBJECTIVE: To investigate the clinical use patterns, clinical effect and safety of cyclosporine A (CSA) in juvenile idiopathic arthritis (JIA) in the setting of routine clinical care. METHODS: An open-ended, phase IV post marketing surveillance study was conducted among members of the Pediatric Rheumatology Collaborative Study Group (PRCSG) and of the Paediatric Rheumatology International Trials Organisation (PRINTO) to identify patients with polyarticular course JIA who had received CSA during the course of their disease. RESULTS: A total of 329 patients, half of whom had systemic JIA, were collected in 21 countries. Data were collected during 1240 routine clinic visits. CSA was started at a mean of 5.8 years after disease onset and was given at a mean dose of 3.4 mg/kg/day. The drug was administered in combination with MTX in 61% and along with prednisone in 65% of the patients who were still receiving CSA. Among patients who were still receiving CSA therapy at the last reported visit, remission was documented in 9% of the patients, whereas in 61% of the patients the disease activity was rated as moderate or severe. The most frequent reason for discontinuation of CSA was insufficient therapeutic effect (61% of the patients); only 10% of the patients stopped CSA because of remission. In 17% of the patients, side effects of therapy was given as the primary reason for discontinuation. CONCLUSION: This survey suggests that CSA may have a less favourable efficacy profile than MTX and etanercept, whereas the frequency of side effects may be similar. The exact place of CSA in the treatment of JIA can only be established via controlled clinical trial.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Ciclosporina/uso terapêutico , Vigilância de Produtos Comercializados , Artrite Juvenil/fisiopatologia , Criança , Quimioterapia Combinada , Nível de Saúde , Humanos , Metotrexato/uso terapêutico , Prednisona/uso terapêutico , Indução de Remissão , Índice de Gravidade de DoençaRESUMO
To evaluate the relationship between tumor burden and circulating immune complexes (IC) in malignant melanoma, we tested sera collected serially from 15 normal donors and 53 patients. Forty-eight of these had Stage III or IV disease at the outset of the study. The median survival time (MST) of ten patients with Stage IV disease whose sera contained C1q-binding IC at the outset of the study was 4.7 months; the MST of the 25 Stage IV patients whose sera were initially free of IC by this test was 8.65 months (p less than 0.02). C1q-binding IC were not found in the initial serum samples from 13 patients with Stage III or 5 patients with Stage I disease. Abnormal C1q binding tests were measured in 4 of 67 sera (6%) from 13 patients who remained free of evident tumor for up to 41 months. IC were detected in 13 of 39 sera (33%) from 19 patients with progressively growing tumors and in 21 of 68 sera (31%) from 21 patients who were initially free of disease but developed recurrences later, or who had significant remissions of variable duration during follow-up. The MST of 31 patients whose serial serum samples remained free of C1q-binding IC was 15.8 months. Twelve patients whose sera were initially free of circulating IC later developed abnormal serum C1q-binding levels. Their MST was 10.3 months. The MST of ten patients with persistently abnormal serum IC levels was 4.7 months. C1q-binding IC were reciprocally related to the presence of complement-dependent antibodies, cytotoxic for cultured allogeneic malignant melanoma cells in sera from 29 of these patients (r = -0.491;p = 0.003). These results suggest that the appearance of circulating C1q-binding IC is pathophysiologically important in malignant melanoma. Measurement of C1q-binding IC may be useful in assigning prognosis in this disease.
Assuntos
Complexo Antígeno-Anticorpo/análise , Citotoxinas/análise , Melanoma/análise , Enzimas Ativadoras do Complemento/análise , Complemento C1q , Humanos , Melanoma/diagnóstico , Prognóstico , Estudos ProspectivosRESUMO
Pharmacologic management of juvenile rheumatoid arthritis is only one of several modalities necessary for effective control. The stepping stones to proper management include a planned long-range program, physical therapy with swimming, good health habits, and consultation with other health professionals who are part of the management team. Pharmacologic therapy includes nonsteroidal anti-inflammatory drugs initially, occasionally corticosteroids, and slow-acting antirheumatic drugs, including injectable gold when therapeutic response is inadequate. Early experiences with oral gold are reported here. Auranofin (triethylphosphine gold) was administered to 21 patients with juvenile rheumatoid arthritis during a segment I, open ended, open-label, noncontrolled trial designed to establish safety and preliminary efficacy. Initial dosage was 0.1 mg/kg per day; incremental increases to 0.2 mg/kg per day were allowed (with usual increase to 0.15 mg/kg per day). Aspirin (80 mg/kg per day) or tolmetin (20 to 40 mg/kg per day), or naproxen (400 to 600 mg/m2 per day) were allowed as rapidly acting antiinflammatory agents. Stable measurable plasma concentrations of gold were attained in all patients during the study. More than half the patients sustained clinically significant improvement (greater than 25 percent) with regard to the number and severity of joints with swelling, pain on motion, and tenderness. In nine of the 19 patients, the total number of joints with active arthritis decreased by at least 25 percent. All articular disease indices measured indicated improvement of group mean changes between the initial and final visit. Eleven of 16 patients with an elevated erythrocyte sedimentation rate showed decreases of at least 25 percent. The group given higher dosages had a greater proportion of responders in regard to decreases in erythrocyte sedimentation rate (nine of 11 patients). Four of six patients whose serums contained rheumatoid factor showed decreases in the titers. Discontinuation of auranofin was necessary in two patients: one because of headache and one because of hematuria and anemia associated with a severe flare-up of polyarticular disease. The results from this trial reveal sufficient patient improvement to plan a double-blind trial of auranofin in children with juvenile rheumatoid arthritis.
Assuntos
Anti-Inflamatórios/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Aurotioglucose/análogos & derivados , Ouro/análogos & derivados , Administração Oral , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/sangue , Auranofina , Aurotioglucose/efeitos adversos , Aurotioglucose/sangue , Aurotioglucose/uso terapêutico , Criança , Pré-Escolar , Humanos , Cooperação do PacienteRESUMO
Results from three randomized placebo-controlled trials were combined in a meta-analysis to compare the clinical utility of four advanced drug therapy agents used to treat juvenile rheumatoid arthritis (JRA): D-penicillamine (10 mg/kg/d), hydroxychloroquine (6 mg/kg/d), auranofin (oral gold, 0.15 to 0.20 mg/kg/d), and two low dose levels of methotrexate [5MTX, 5 mg/M2/wk; 10MTX, 10 mg/M2/wk]. A total of 520 children with JRA were enrolled into these trials. Only 10MTX resulted in significantly greater improvement than placebo in variables that assess effectiveness: physician's global assessment, a composite index, and erythrocyte sedimentation rate. Treatment effect sizes were the largest in the 10MTX group for all articular disease indices. The short-term safety profiles were similar across all treatment groups. It is concluded that the current trend among pediatric rheumatologists to use oral methotrexate as the first advanced drug therapy in JRA is appropriate and that the minimum effective dose is 10 mg/M2/wk.
Assuntos
Artrite Juvenil/tratamento farmacológico , Hidroxicloroquina/administração & dosagem , Metotrexato/administração & dosagem , Penicilamina/administração & dosagem , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Masculino , Metotrexato/efeitos adversos , Penicilamina/efeitos adversos , Estudos Prospectivos , Resultado do TratamentoRESUMO
Patients with Group A beta-hemolytic streptococcal infection and articular disease who do not fulfill the modified Jones criteria for a diagnosis of acute rheumatic fever (ARF) have been classified as poststreptococcal reactive arthritis/arthralgia. We reviewed the initial clinical characteristics and outcome of 12 poststreptococcal reactive arthritis/arthralgia patients. During the initial episode all had arthritis or arthralgia and a documented streptococcal infection. None had carditis and none received prophylactic antibiotic therapy during an average follow-up of 17 months (range, 6 to 42 months). One patient developed classic ARF with valvulitis 18 months after the initial episode. Two children had later episodes of arthritis and two had at least one additional episode of arthralgia. Poststreptococcal reactive arthritis/arthralgias seems to be part of the disease spectrum of ARF and therefore the use of prophylactic antibiotic therapy to prevent subsequent development of ARF and carditis in these patients should, perhaps, be reconsidered.
Assuntos
Artrite/etiologia , Infecções Estreptocócicas/complicações , Adolescente , Antibacterianos/uso terapêutico , Artrite/diagnóstico , Artrite/prevenção & controle , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Miocardite/prevenção & controle , Prognóstico , Febre Reumática/diagnóstico , Febre Reumática/prevenção & controle , Streptococcus pyogenesRESUMO
Juvenile rheumatoid arthritis (JRA) is a heterogeneous group of autoimmune diseases resulting in chronic idiopathic peripheral arthritis. The aetiology of JRA is unclear, and current pharmacotherapy is ameliorative rather than curative. Nonsteroidal anti-inflammatory drugs are given initially, but only one-third to one-fourth of patients are managed adequately with these agents. Advanced therapeutic drugs, frequently referred to as disease-modifying antirheumatic drugs or second-line agents, are given to the child with aggressive or resistant disease. Among these, the antimetabolite methotrexate has proven to be the most effective in alleviating articular disease manifestations and reducing laboratory parameters of inflammation. When given orally in low dosages (10 to 15 mg/m2/week), methotrexate is well tolerated, without evidence of substantial bone marrow suppression or severe hepatotoxicity. Extensive long term tolerability data are not yet available for children, but longitudinal studies in adult patients with rheumatoid arthritis suggest that the drug may be given safely for extended periods in many patients. Paediatric rheumatologists are beginning to give higher dosages of methotrexate (up to 1 mg/kg/week) parenterally with some success. The long term consequences of higher dose methotrexate in children are unknown. Methotrexate has now become, and will probably remain for some time, the drug of first choice for children with recalcitrant JRA.
Assuntos
Artrite Juvenil/tratamento farmacológico , Metotrexato/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Humanos , Infecções/etiologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Metotrexato/uso terapêutico , Reprodução/efeitos dos fármacos , RiscoRESUMO
OBJECTIVES: To translate into Argentine Spanish and cross-culturally adapt the Childhood Health Assessment Questionnaire (CHAQ) and validate the adapted instrument in Argentine patients with juvenile rheumatoid arthritis (JRA). METHODS: Five bilingual Argentine pediatric rheumatologists translated into Argentine Spanish and cross-culturally adapted the United States English CHAQ. Pretesting was done in a sample of 23 parents using a probe question technique. Parents of 70 patients with JRA and 21 healthy children (controls) participated in the validation phase. All were from Argentina. RESULTS: The mean disability index (DI) scores for patients with systemic, polyarticular, or pauciarticular onset JRA were 0.64, 0.32, and 0.1, respectively. Healthy controls averaged 0.2. Intercomponent correlations were between 0.4 and 0.9, suggesting internal consistency, but also some redundancy. Test-retest reliability, studied at a 1-week interval, was moderate (mean DI 0.44 [in clinic] and 0.29 [one week later], Pearson's correlation = 0.82). We compared CHAQ scores from 15 parents with those of their children > 10 years of age. Significantly higher DI scores were given by patients than their respective parents (P > 0.019), but the pairwise scores (parent-patient) were highly correlated (r = 0.986). CONCLUSIONS: Cross-cultural adaptation of the US CHAQ to Argentina required few changes. Although DI scores for all patient subgroups were higher than for controls subjects, the scores were low, particularly for those with pauciarticular disease. Prospective studies designed to examine the sensitivity to change and predictive validity will help to assess further the usefulness of the adapted CHAQ in the Argentine population.
Assuntos
Atividades Cotidianas , Artrite Juvenil/etnologia , Artrite Juvenil/fisiopatologia , Pessoas com Deficiência/classificação , Nível de Saúde , Inquéritos e Questionários/normas , Tradução , Adolescente , Argentina , Estudos de Casos e Controles , Criança , Pré-Escolar , Comparação Transcultural , Humanos , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Estados UnidosRESUMO
Evidence-based medicine (EBM) has increasingly gained importance over the past two decades. This review defines and discusses EBM in the light of specific issues relating to pediatrics and pediatric rheumatology. The efforts of pediatric rheumatologists to practice and promote EBM are summarized.
Assuntos
Medicina Baseada em Evidências , Pediatria/normas , Reumatologia/normas , Criança , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto/normasRESUMO
Rheumatology made its debut as a legitimate subspecialty of pediatrics sometime in the 1940s in Europe, and in the 1970s in North America. Therapy of juvenile rheumatoid arthritis has evolved from salicylates and gold injections to newer, less toxic nonsteroidal anti-inflammatory drugs and methotrexate. Corticosteroids remain as important drugs when life-threatening complications or blinding iridocyclitis develop. Immune response modifiers and gene therapies offer considerable potential for eventually halting or curing the disease but have yet to make a substantial impact on therapy. Methods for the correct conduct and interpretation of data from clinical trials are discussed.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Anti-Inflamatórios não Esteroides/história , Antirreumáticos/história , Artrite Juvenil/história , Artrite Juvenil/terapia , Criança , Terapia Genética , História do Século XX , Humanos , Reumatologia/históriaRESUMO
Despite questions regarding its validity as an estimator of inflammatory disease activity, monitoring of the erythrocyte sedimentation rate (ESR) continues to be routine practice among pediatric rheumatologists caring for children with juvenile rheumatoid arthritis (JRA). We studied a large group of patients with JRA in order to determine the degree of correlation between clinically apparent inflammation and the ESR. regression and correlation analyses and descriptive statistical techniques were used to establish the relationship between 1) the ESR and the amount of clinically apparent inflammation at a point in time, and 2) changes in the ESR and the corresponding changes in apparent inflammation. One hundred fifty-nine children with JRA who were participants in a double-blind, controlled trial of two antirheumatic drugs were assessed for clinical and laboratory evidence of inflammatory disease activity at an initial visit, and then periodically for the duration of the one year study. Results showed that, at the initial assessment, neither the total number of joints with active arthritis nor the severity score correlated well with the ESR (r = .196 and .245 respectively). These findings were independent of the course type of JRA and age of the child. Changes from baseline in inflammation showed little correlation (r less than .25) with changes in the ESR. These findings suggest that the ESR is a relatively poor indicator of the amount of articular inflammation present, and that changes of disease activity are not reflected closely by changes in the ESR among children with JRA.
Assuntos
Artrite Juvenil/diagnóstico , Sedimentação Sanguínea , Adolescente , Artrite Juvenil/tratamento farmacológico , Criança , Ensaios Clínicos como Assunto , Método Duplo-Cego , Seguimentos , Humanos , Hidroxicloroquina/uso terapêutico , Penicilamina/uso terapêutico , Distribuição AleatóriaRESUMO
The assessment of overall health status of a child with juvenile rheumatoid arthritis (JRA) is complex and multi-dimensional. The general physical examination is complemented by a rheumatological evaluation that includes determination of articular indices of inflammation and duration of inactivity stiffness. Laboratory assessment plays a critical role in monitoring side effects of pharmacologic management, but is limited in its ability to portray accurately the degree of active inflammation. Newly measureable indicators of inflammatory activity, such as serum cytokine and soluble cytokine receptors will likely become part of routine laboratory assessment in the future. Radiographs remain a useful tool for assessing disease progression, but may be replaced in the future by magnetic resonance imaging. In recent years, rheumatologists have realized that measurement of overall physical and psycho-social functional ability, quality of life, and pain are major descriptors to consider during routine follow-up. They are also critical in the assessment of long-term clinical effectiveness. The importance of nutritional assessment has also been realized. This section seeks to describe some of the methodologic approaches currently used to assess the variables mentioned above, and includes a brief discussion of the evolving instrumentation which attempts to measure variables of a more cognitive or subjective aspect.
Assuntos
Artrite Juvenil/diagnóstico , Artrite Juvenil/fisiopatologia , Adolescente , Artrite Juvenil/terapia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estado Nutricional , Medição da Dor , Exame Físico , Prognóstico , Amplitude de Movimento ArticularRESUMO
Certain major histocompatibility complex (MHC) class I and class II genes are uniquely associated with early onset pauciarticular juvenile rheumatoid arthritis (JRA). As in other autoimmune diseases, these associations are likely to reflect contributions of the MHC to a trimolecular complex formed by HLA, lymphocyte T cell receptor and the putative antigen. The HLA genes associated with JRA are currently the best understood component of this complex. Recent findings demonstrated that combinations of genes, even within class II, play an important role. Data generated by DNA sequencing techniques have clarified the splits of given genes involved in disease, e.g., the HLA-DRw8 allele, HLA-DRB1*0801 rather than HLA-DRB1*0802, which does not carry an increased risk for disease. Recent findings suggest that aberrant sequences in particular genes are unimportant. Substantial challenges remain; including establishing the particular HLA DNA nucleotides critical to antigen presentation. It is probable that new and specific therapeutic approaches will be developed which will utilize the immunogenetic data now being accumulated.
Assuntos
Artrite Juvenil/imunologia , Adolescente , Artrite Juvenil/genética , Criança , Pré-Escolar , Humanos , Complexo Principal de Histocompatibilidade/genética , Complexo Principal de Histocompatibilidade/imunologiaRESUMO
OBJECTIVE: This study was undertaken to evaluate the long-term safety and effectiveness of etanercept alone or in combination with methotrexate (MTX) in children with selected categories of juvenile idiopathic arthritis (JIA). METHODS: Patients ages 2-18 years with rheumatoid factor (RF)-positive or RF-negative polyarthritis, systemic JIA, or extended oligoarthritis were eligible for the study. Patients received MTX alone (> or =10 mg/m(2)/week [ approximately 0.3 mg/kg/week], maximum dosage 1 mg/kg/week), etanercept alone (0.8 mg/kg/week, maximum dose 50 mg), or etanercept plus MTX for 3 years in an open-label, nonrandomized study. Safety was assessed by measuring rates of adverse events, and effectiveness was assessed using the physician's global assessment of disease activity and the pediatric total joint assessment. RESULTS: A total of 197, 103, and 294 patients were enrolled in the MTX, etanercept, and etanercept plus MTX groups, respectively. Exposure-adjusted rates of adverse events were similar among the 3 treatment groups (18.3, 18.7, and 21.6 per 100 patient-years in the MTX, etanercept, and etanercept plus MTX groups, respectively). Respective rates per 100 patient-years of serious adverse events (4.6, 7.1, and 6.0) and medically important infections (1.3, 1.8, and 2.1) were also similar among the 3 treatment groups. Scores for physician's global assessment and total active joints improved from baseline, and improvement was maintained for the duration of the study. CONCLUSION: These data confirm the findings of other long-term studies and suggest that etanercept or etanercept plus MTX has an acceptable safety and effectiveness profile in children with selected categories of JIA. Improvement was maintained for 3 years in those continuing to receive medication.
Assuntos
Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Artrite Juvenil/classificação , Artrite Juvenil/tratamento farmacológico , Imunoglobulina G/efeitos adversos , Imunoglobulina G/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Adolescente , Antirreumáticos/administração & dosagem , Artrite Juvenil/metabolismo , Criança , Pré-Escolar , Avaliação da Deficiência , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Etanercepte , Feminino , Humanos , Imunoglobulina G/administração & dosagem , Injeções Subcutâneas , Estudos Longitudinais , Masculino , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Receptores do Fator de Necrose Tumoral/administração & dosagem , Sistema de Registros , Fator Reumatoide/metabolismo , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the ability of various definitions of improvement to distinguish between patients with juvenile rheumatoid arthritis (JRA) treated with active drug from those given placebo in randomized trials. METHODS: A core set of 6 response (outcome) variables for use in JRA has been reported. These core variables were combined into a number of "definitions of improvement" for the purpose of classifying individual patients as either "clinically significantly improved" or "not improved." We used a large dataset from randomized controlled trials to test the discriminant ability (sensitivity to change) of the definitions. We calculated the proportion of patients classified as "improved" by each definition in each of the treatment and control groups. RESULTS: Effect sizes were weak in 4 of the treatment regimens used (D-penicillamine, hydroxychloroquine, auranofin, and very low dose methotrexate) and no definition discriminated well between drug and placebo treated groups. Definitions that required 20 to 30% improvement in 3 to 4 of the 6 core set variables showed statistically significant differences in the proportions of patients who were classified as improved in the group treated with low dose methotrexate (10 mg/m2 body surface area/wk) compared to placebo. A definition resembling the Paulus criteria used in adult RA trials (4 of 6 core set variables improved by > or = 20%) performed well, as did the definition selected previously as the best for JRA (3 of 6 core set variables improved by > or = 30%, not more than one worsening by > 30%). CONCLUSION: Definitions that require 20 to 30% improvement in 3 to 4 core outcome variables are sensitive to change and are able to clearly distinguish between treated and control groups when an effective drug is being tested. Further testing of their validity is under way.
Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Auranofina/uso terapêutico , Análise Discriminante , Humanos , Hidroxicloroquina/uso terapêutico , Metotrexato/uso terapêutico , Penicilamina/uso terapêutico , Placebos , Resultado do TratamentoRESUMO
OBJECTIVE: To estimate the degree of redundancy among articular response variables used routinely in juvenile chronic arthritis (JCA) clinical trials. METHODS: We obtained data from a large, computerised databank holding information from multiple clinical trials in children with JCA to determine Pearson correlation coefficients for changes from baseline values in articular response variables. All 508 JCA patients who entered the analysis of efficacy of the original trials were included in the present study. An r value of 0.7 or greater was considered evidence of colinearity. RESULTS: When changes in joint counts of articular manifestations were compared with changes in the respective severity scores (for example swollen joint count versus swelling severity score), the r values were always > or = 0.7. Three articular response variables related to the assessment of pain are all highly correlated with each other. The number of joints with active arthritis was correlated with the number of joints with swelling and the swelling score. Change in the overall severity score was highly correlated (r > or = 0.7) with change in nearly all articular response variables. CONCLUSIONS: Many endpoints reported in JCA trials are redundant, especially counts and scores of the same articular measure. Eliminating redundant variables would provide the same information with less complexity, and decrease the probability of statistical error and ambiguous results.
Assuntos
Artrite Juvenil/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Índice de Gravidade de Doença , Resultado do Tratamento , Artrite Juvenil/fisiopatologia , Criança , Humanos , Articulações/fisiopatologia , Projetos de PesquisaRESUMO
OBJECTIVE: To estimate the frequency of documented clinically significant gastrointestinal (GI) side effects secondary to nonsteroidal antiinflammatory drugs (NSAID) therapy and to describe the adverse events. METHODS: Computerized medical records of 702 patients with juvenile rheumatoid arthritis (JRA) administered NSAID were searched for the occurrence of clinically significant gastropathy (esophagitis, gastritis, peptic ulcer disease). RESULTS: Five children were identified who had a total of 10 events of gastropathy documented by either barium swallow or endoscopy, and thought to be attributable to NSAID therapy. Each child had at least 2 separate events of clinically significant gastropathy. CONCLUSION: Although mild GI disturbances are frequent side effects associated with NSAID therapy, the number of children with JRA who experience clinically significant gastropathy appears to be low.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Artrite Juvenil/tratamento farmacológico , Gastropatias/induzido quimicamente , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Sistemas de Informação , Masculino , Prontuários MédicosRESUMO
Studies of pediatric clinic populations have shown that a high proportion of children with rheumatic complaints demonstrate hypermobility of the joints. In order to compare the frequency and nature of articular complaints in children with hypermobility to that seen in nonhypermobile controls, we examined 192 normal students aged 5-19 years. Overall, 34% (41/109 girls and 25/83 boys) were found to be hypermobile. Consenting parents of hypermobile children were given a questionnaire and interview designed to detect a history of arthritis/arthralgia, as were parents of age and sex matched nonhypermobile controls. Fifty percent of the hypermobile group had a history of arthralgia, compared to 20% of controls. Ten percent in each group had had arthritis. Data from our comparative study supports the possible association between joint hypermobility and the development of articular complaints in children.
Assuntos
Artrite/complicações , Instabilidade Articular/complicações , Articulações , Dor/complicações , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
We calculated the time required for therapeutic benefit to become apparent following initiation of treatment with D-penicillamine (DP), hydroxychloroquine (HCQ), or placebo (each administered concomitantly with a nonsteroidal antiinflammatory drug) using data from a double-blind, randomized 12-month trial in 162 patients with juvenile rheumatoid arthritis. Using previously published criteria to classify the outcome, we found that 60% of the HCQ group, 46% of the DP group, and 39% of the placebo group responded favorably after 12 months of therapy. Data from examinations between the initial and final assessments were used to determine when the response first occurred. Approximately 50% of all patients who showed improvement at 12 months had already done so by 2 months. After 6 months, 96% of the DP group, 88% of the HCQ group, and 85% of the placebo group responders had met the criteria for response. The average time until response was attained was 105 days for the DP group, 129 days for the HCQ group, and 140 days for the placebo group. Our results indicate that a favorable response to these slow-acting antirheumatic drugs is unlikely if improvement has not occurred within the first 6 months of therapy.
Assuntos
Artrite Juvenil/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Penicilamina/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Juvenil/fisiopatologia , Criança , Feminino , Previsões , Humanos , Masculino , Placebos , Fatores de TempoRESUMO
During an uncontrolled, open-labelled, open-ended clinical trial of auranofin in children with juvenile rheumatoid arthritis (JRA) we obtained serial blood samples for the purpose of assessing gold content. Our objectives were (1) to observe the pattern of blood gold concentrations over a period of time in children undergoing long-term oral gold therapy, and (2) to observe the effect of changing dosage levels on blood gold concentrations. The initial dosage of auranofin was 0.1 mg/kg/day with allowable increases to 0.2 mg/kg/day. A concurrent nonsteroidal anti-inflammatory drug was allowed. Twenty-one patients were enrolled in the study, and we obtained 2 or more serial samples on 13 of the children. At a constant dosage of 0.1 mg/kg/day, steady state blood gold concentrations were attained in 11 to 13 weeks of therapy and, in the absence of a dosage change, remained remarkably constant through extended periods. The blood gold concentration was related to total daily dosage rather than to the cumulative amount of gold received. Increasing or decreasing the dose resulted in a direct effect on concentration. The clinical value of blood gold levels resulting from auranofin therapy in JRA will have to be established through double-blind controlled trials.