ABSTRACT
OBJECTIVE: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. METHODS: Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology, and pediatric clinics worldwide. Several statistical methods were utilized to derive the classification criteria. RESULTS: Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cutoff of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) "probable IIM," had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to "definite IIM." A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50-<55% as "possible IIM." CONCLUSION: The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology, and pediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of "definite," "probable," and "possible" IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.
Subject(s)
Myositis/classification , Myositis/diagnosis , Practice Guidelines as Topic , Rheumatology/standards , Symptom Assessment/standards , Adolescent , Adult , Biopsy/standards , Child , Consensus , Europe , Female , Humans , Male , Middle Aged , Muscle, Skeletal/pathology , Sensitivity and Specificity , Societies, Medical , Symptom Assessment/methods , United States , Young AdultABSTRACT
OBJECTIVE: To describe the methodology used to develop new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIMs) and their major subgroups. METHODS: An international, multidisciplinary group of myositis experts produced a set of 93 potentially relevant variables to be tested for inclusion in the criteria. Rheumatology, dermatology, neurology and paediatric clinics worldwide collected data on 976 IIM cases (74% adults, 26% children) and 624 non-IIM comparator cases with mimicking conditions (82% adults, 18% children). The participating clinicians classified each case as IIM or non-IIM. Generally, the classification of any given patient was based on few variables, leaving remaining variables unmeasured. We investigated the strength of the association between all variables and between these and the disease status as determined by the physician. We considered three approaches: (1) a probability-score approach, (2) a sum-of-items approach criteria and (3) a classification-tree approach. RESULTS: The approaches yielded several candidate models that were scrutinised with respect to statistical performance and clinical relevance. The probability-score approach showed superior statistical performance and clinical practicability and was therefore preferred over the others. We developed a classification tree for subclassification of patients with IIM. A calculator for electronic devices, such as computers and smartphones, facilitates the use of the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria. CONCLUSIONS: The new EULAR/ACR classification criteria provide a patient's probability of having IIM for use in clinical and research settings. The probability is based on a score obtained by summing the weights associated with a set of criteria items.
ABSTRACT
OBJECTIVE: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. METHODS: Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and paediatric clinics worldwide. Several statistical methods were used to derive the classification criteria. RESULTS: Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cut-off of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) 'probable IIM', had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to 'definite IIM'. A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50 to <55% as 'possible IIM'. CONCLUSIONS: The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of 'definite', 'probable' and 'possible' IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.
Subject(s)
Myositis/classification , Myositis/diagnosis , Rheumatology/standards , Adult , Biopsy/standards , Child , Consensus , Diagnosis, Differential , Europe , Humans , Muscle, Skeletal/pathology , Probability , Reference Values , Rheumatology/organization & administration , Sensitivity and Specificity , Societies, Medical/organization & administration , United StatesABSTRACT
Objective: The objective was to describe the methodology used to develop new response criteria for adult DM/PM and JDM. Methods: Patient profiles from prospective natural history data and clinical trials were rated by myositis specialists to develop consensus gold-standard ratings of minimal, moderate and major improvement. Experts completed a survey regarding clinically meaningful improvement in the core set measures (CSM) and a conjoint-analysis survey (using 1000Minds software) to derive relative weights of CSM and candidate definitions. Six types of candidate definitions for response criteria were derived using survey results, logistic regression, conjoint analysis, application of conjoint-analysis weights to CSM and published definitions. Sensitivity, specificity and area under the curve were defined for candidate criteria using consensus patient profile data, and selected definitions were validated using clinical trial data. Results: Myositis specialists defined the degree of clinically meaningful improvement in CSM for minimal, moderate and major improvement. The conjoint-analysis survey established the relative weights of CSM, with muscle strength and Physician Global Activity as most important. Many candidate definitions showed excellent sensitivity, specificity and area under the curve in the consensus profiles. Trial validation showed that a number of candidate criteria differentiated between treatment groups. Top candidate criteria definitions were presented at the consensus conference. Conclusion: Consensus methodology, with definitions tested on patient profiles and validated using clinical trials, led to 18 definitions for adult PM/DM and 14 for JDM as excellent candidates for consideration in the final consensus on new response criteria for myositis.
Subject(s)
Dermatomyositis/therapy , Area Under Curve , Humans , Logistic Models , Minimal Clinically Important Difference , Polymyositis/therapy , Treatment OutcomeABSTRACT
To develop response criteria for juvenile dermatomyositis (DM). We analysed the performance of 312 definitions that used core set measures from either the International Myositis Assessment and Clinical Studies Group (IMACS) or the Paediatric Rheumatology International Trials Organisation (PRINTO) and were derived from natural history data and a conjoint analysis survey. They were further validated using data from the PRINTO trial of prednisone alone compared to prednisone with methotrexate or cyclosporine and the Rituximab in Myositis (RIM) trial. At a consensus conference, experts considered 14 top candidate criteria based on their performance characteristics and clinical face validity, using nominal group technique. Consensus was reached for a conjoint analysis-based continuous model with a total improvement score of 0-100, using absolute per cent change in core set measures of minimal (≥30), moderate (≥45), and major (≥70) improvement. The same criteria were chosen for adult DM/polymyositis, with differing thresholds for improvement. The sensitivity and specificity were 89% and 91-98% for minimal improvement, 92-94% and 94-99% for moderate improvement, and 91-98% and 85-86% for major improvement, respectively, in juvenile DM patient cohorts using the IMACS and PRINTO core set measures. These criteria were validated in the PRINTO trial for differentiating between treatment arms for minimal and moderate improvement (p=0.009-0.057) and in the RIM trial for significantly differentiating the physician's rating for improvement (p<0.006). The response criteria for juvenile DM consisted of a conjoint analysis-based model using a continuous improvement score based on absolute per cent change in core set measures, with thresholds for minimal, moderate, and major improvement.
Subject(s)
Dermatomyositis/therapy , Outcome Assessment, Health Care/standards , Severity of Illness Index , Adolescent , Adult , Child , Child, Preschool , Consensus , Humans , Randomized Controlled Trials as Topic , Sensitivity and SpecificityABSTRACT
To develop response criteria for adult dermatomyositis (DM) and polymyositis (PM). Expert surveys, logistic regression, and conjoint analysis were used to develop 287 definitions using core set measures. Myositis experts rated greater improvement among multiple pairwise scenarios in conjoint analysis surveys, where different levels of improvement in 2 core set measures were presented. The PAPRIKA (Potentially All Pairwise Rankings of All Possible Alternatives) method determined the relative weights of core set measures and conjoint analysis definitions. The performance characteristics of the definitions were evaluated on patient profiles using expert consensus (gold standard) and were validated using data from a clinical trial. The nominal group technique was used to reach consensus. Consensus was reached for a conjoint analysis-based continuous model using absolute per cent change in core set measures (physician, patient, and extramuscular global activity, muscle strength, Health Assessment Questionnaire, and muscle enzyme levels). A total improvement score (range 0-100), determined by summing scores for each core set measure, was based on improvement in and relative weight of each core set measure. Thresholds for minimal, moderate, and major improvement were ≥20, ≥40, and ≥60 points in the total improvement score. The same criteria were chosen for juvenile DM, with different improvement thresholds. Sensitivity and specificity in DM/PM patient cohorts were 85% and 92%, 90% and 96%, and 92% and 98% for minimal, moderate, and major improvement, respectively. Definitions were validated in the clinical trial analysis for differentiating the physician rating of improvement (p<0.001). The response criteria for adult DM/PM consisted of the conjoint analysis model based on absolute per cent change in 6 core set measures, with thresholds for minimal, moderate, and major improvement.
Subject(s)
Dermatomyositis/therapy , Outcome Assessment, Health Care/standards , Severity of Illness Index , Adolescent , Adult , Child , Child, Preschool , Consensus , Humans , Polymyositis/therapy , Randomized Controlled Trials as Topic , Sensitivity and SpecificityABSTRACT
OBJECTIVE: To develop response criteria for juvenile dermatomyositis (DM). METHODS: We analyzed the performance of 312 definitions that used core set measures from either the International Myositis Assessment and Clinical Studies Group (IMACS) or the Paediatric Rheumatology International Trials Organisation (PRINTO) and were derived from natural history data and a conjoint analysis survey. They were further validated using data from the PRINTO trial of prednisone alone compared to prednisone with methotrexate or cyclosporine and the Rituximab in Myositis (RIM) trial. At a consensus conference, experts considered 14 top candidate criteria based on their performance characteristics and clinical face validity, using nominal group technique. RESULTS: Consensus was reached for a conjoint analysis-based continuous model with a total improvement score of 0-100, using absolute percent change in core set measures of minimal (≥30), moderate (≥45), and major (≥70) improvement. The same criteria were chosen for adult DM/polymyositis, with differing thresholds for improvement. The sensitivity and specificity were 89% and 91-98% for minimal improvement, 92-94% and 94-99% for moderate improvement, and 91-98% and 85-86% for major improvement, respectively, in juvenile DM patient cohorts using the IMACS and PRINTO core set measures. These criteria were validated in the PRINTO trial for differentiating between treatment arms for minimal and moderate improvement (P = 0.009-0.057) and in the RIM trial for significantly differentiating the physician's rating for improvement (P < 0.006). CONCLUSION: The response criteria for juvenile DM consisted of a conjoint analysis-based model using a continuous improvement score based on absolute percent change in core set measures, with thresholds for minimal, moderate, and major improvement.
Subject(s)
Antirheumatic Agents/therapeutic use , Dermatomyositis/drug therapy , Glucocorticoids/therapeutic use , Adolescent , Alanine Transaminase/metabolism , Aspartate Aminotransferases/metabolism , Child , Creatine Kinase/metabolism , Cyclosporine/therapeutic use , Dermatomyositis/metabolism , Dermatomyositis/physiopathology , Europe , Fructose-Bisphosphate Aldolase/metabolism , Humans , L-Lactate Dehydrogenase/metabolism , Logistic Models , Methotrexate/therapeutic use , Muscle Strength , Outcome Assessment, Health Care , Patient Reported Outcome Measures , Prednisone/therapeutic use , Reproducibility of Results , Rheumatology , Rituximab/therapeutic use , Societies, Medical , Surveys and Questionnaires , Treatment Outcome , United StatesABSTRACT
OBJECTIVE: To develop response criteria for adult dermatomyositis (DM) and polymyositis (PM). METHODS: Expert surveys, logistic regression, and conjoint analysis were used to develop 287 definitions using core set measures. Myositis experts rated greater improvement among multiple pairwise scenarios in conjoint analysis surveys, where different levels of improvement in 2 core set measures were presented. The PAPRIKA (Potentially All Pairwise Rankings of All Possible Alternatives) method determined the relative weights of core set measures and conjoint analysis definitions. The performance characteristics of the definitions were evaluated on patient profiles using expert consensus (gold standard) and were validated using data from a clinical trial. The nominal group technique was used to reach consensus. RESULTS: Consensus was reached for a conjoint analysis-based continuous model using absolute percent change in core set measures (physician, patient, and extramuscular global activity, muscle strength, Health Assessment Questionnaire, and muscle enzyme levels). A total improvement score (range 0-100), determined by summing scores for each core set measure, was based on improvement in and relative weight of each core set measure. Thresholds for minimal, moderate, and major improvement were ≥20, ≥40, and ≥60 points in the total improvement score. The same criteria were chosen for juvenile DM, with different improvement thresholds. Sensitivity and specificity in DM/PM patient cohorts were 85% and 92%, 90% and 96%, and 92% and 98% for minimal, moderate, and major improvement, respectively. Definitions were validated in the clinical trial analysis for differentiating the physician rating of improvement (P < 0.001). CONCLUSION: The response criteria for adult DM/PM consisted of the conjoint analysis model based on absolute percent change in 6 core set measures, with thresholds for minimal, moderate, and major improvement.
Subject(s)
Antirheumatic Agents/therapeutic use , Dermatomyositis/drug therapy , Alanine Transaminase/metabolism , Aspartate Aminotransferases/metabolism , Creatine Kinase/metabolism , Dermatomyositis/metabolism , Dermatomyositis/physiopathology , Europe , Fructose-Bisphosphate Aldolase/metabolism , Humans , L-Lactate Dehydrogenase/metabolism , Logistic Models , Muscle Strength , Outcome Assessment, Health Care , Patient Reported Outcome Measures , Polymyositis/drug therapy , Polymyositis/metabolism , Polymyositis/physiopathology , Rheumatology , Societies, Medical , Surveys and Questionnaires , Treatment Outcome , United StatesABSTRACT
Although the primary risk factors for pressure ulcer development - pressure, shear, skin temperature, moisture, and friction - have been identified for decades, the relative contribution of each to this risk remains unclear. To confirm the results of and expand upon earlier research into the relative contributions of interface pressures, shear stress, and skin temperature among 4 healthy volunteers, a study involving 6 additional healthy 40- to 75-year-old volunteers was conducted and results of the 2 studies were pooled. All 3 variables (interface pressures, shear stress, and skin temperature) were systematically and randomly varied. In the prone position, volunteers each underwent 18 test conditions representing different combinations of temperature (28Ë C, 32Ë C, 36Ë C), pressure (8.0 and 13.3 kPa), and shear (0, 6.7, and 14.0 kPa) using a computer-controlled indenter applied to the sacrum for 20 minutes exerting weights of 100 g and 200 g to induce 0.98 N and 1.96 N of shear force, respectively. Each condition was tested twice, resulting in a total of 360 trials. Magnitude of postload reactive hyperemia as an index of ischemia was measured by laser Doppler flowmetry. Fixed effects regression models were used to predict 3 different indices of reactive hyperemic magnitude. Friedman tests were performed to compare the reactive hyperemia among 3 different skin temperatures or shear stresses under the same amount of localized pressure. In all regression models, pressure and temperature were highly significant predictors of the extent of reactive hyperemia (P <0.0001 and P <0.0001, respectively); the contributions of shear stress were not statistically significant (P = 0.149). With higher temperature, reactive hyperemia increased significantly, especially at greater localized pressure and shear stress, and the difference was more profound between 32Ë C and 36Ë C than between 28Ë C and 32Ë C. These results confirm that, in laboratory settings, temperature is an important factor in tissue ischemia. Additional studies examining the relative importance of pressure, shear, and temperature and potential effects of lowering temperature on tissue ischemia in healthy volunteers and patients at risk for pressure ulcer development are warranted. Because deformation at weight-bearing areas often results in blood flow occlusion, actively lowering the temperature may reduce the severity of ischemia and lower pressure ulcer risk. In this study, shear did not appear to contribute to ischemia in the dermal tissues when assessed using laser Doppler; further work is needed to examine its effect on deeper layers, particularly with regard to nonischemic mechanisms.
Subject(s)
Hyperemia/complications , Pressure Ulcer/nursing , Pressure/adverse effects , Shear Strength/physiology , Skin Temperature , Stress, Mechanical , Aged , Female , Healthy Volunteers , Humans , Hyperemia/nursing , Hyperemia/prevention & control , Ischemia/physiopathology , Male , Middle AgedABSTRACT
Biological drugs are much more complicated than chemically synthesized, small-molecule drugs; for instance, their size is much larger, their structure is more complicated, they can be sensitive to environmental conditions such as temperature or pressure, and they may expose patients to immunogen reactions. Consequently, the assessment of biosimilarity calls for greater circumspection than the evaluation of bioequivalence. The present communication discusses scientific factors and some current issues related to biosimilarity and the interchangeability of drug products. The scientific factors include questions involving endpoint selection, the one-size-fits-all criterion, and the need for a more flexible approach, e.g., evaluation of the degree of similarity (i.e., responding to the question of "how similar is similar?"; a review of study designs that are useful for the assessment of biosimilarity and drug interchangeability; and tests for the comparability of critical quality attributes at various stages of the manufacturing process). Current issues include the choice of reference standards and the relevant study designs; criteria for biosimilarity, as well as for interchangeability and for comparability; the determination of the noninferiority margin; and the concepts of the stepwise approach to biosimilarity studies and of their assessment by the totality of the evidence. The calculation of sample sizes is discussed for crossover (including some higher-order schemes) and parallel designs.
Subject(s)
Biosimilar Pharmaceuticals , Clinical Trials as Topic/methods , Drug Discovery/methods , Endpoint Determination , Research Design , Biosimilar Pharmaceuticals/pharmacokinetics , Biosimilar Pharmaceuticals/pharmacology , Biosimilar Pharmaceuticals/therapeutic use , Drug Approval , Humans , Reference Standards , Sample SizeABSTRACT
OBJECTIVE: Because juvenile idiopathic inflammatory myopathies (IIMs) are potentially life-threatening systemic autoimmune diseases, we examined risk factors for juvenile IIM mortality. METHODS: Mortality status was available for 405 patients (329 with juvenile dermatomyositis [DM], 30 with juvenile polymyositis [PM], and 46 with juvenile connective tissue disease-associated myositis [CTM]) enrolled in nationwide protocols. Standardized mortality ratios (SMRs) were calculated using US population statistics. Cox regression analysis was used to assess univariable associations with mortality, and random survival forest (RSF) classification and Cox regression analysis were used for multivariable associations. RESULTS: Of 17 deaths (4.2% overall mortality), 8 (2.4%) were in juvenile DM patients. Death was related to the pulmonary system (primarily interstitial lung disease [ILD]) in 7 patients, gastrointestinal system in 3, and multisystem in 3, and of unknown etiology in 4 patients. The SMR for juvenile IIMs overall was 14.4 (95% confidence interval [95% CI] 12.2-16.5) and was 8.3 (95% CI 6.4-10.3) for juvenile DM. The top mortality risk factors in the univariable analysis included clinical subgroup (juvenile CTM, juvenile PM), antisynthetase autoantibodies, older age at diagnosis, ILD, and Raynaud's phenomenon at diagnosis. In multivariable analyses, clinical subgroup, illness severity at onset, age at diagnosis, weight loss, and delay to diagnosis were the most important predictors from RSF; clinical subgroup and illness severity at onset were confirmed by multivariable Cox regression analysis. CONCLUSION: Overall mortality was higher in juvenile IIM patients, and several early illness features were identified as risk factors. Clinical subgroup, antisynthetase autoantibodies, older age at diagnosis, and ILD are also recognized as mortality risk factors in adult myositis.
Subject(s)
Myositis/diagnosis , Myositis/mortality , Adolescent , Adult , Child , Early Diagnosis , Female , Follow-Up Studies , Humans , Male , Risk Factors , Young AdultABSTRACT
OBJECTIVE: To differentiate juvenile polymyositis (PM) and muscular dystrophy, both of which may present with chronic muscle weakness and inflammation. METHODS: We studied 39 patients with probable or definite juvenile PM and 9 patients with muscular dystrophies who were initially misdiagnosed as having juvenile PM. Differences in demographic, clinical, and laboratory results; outcomes; and treatment responses were evaluated by Fisher's exact and rank sum tests. Random forests classification analysis and logistic regression were performed to examine significant differences in multivariable models. RESULTS: Clinical features and serum muscle enzyme levels were similar between juvenile PM and dystrophy patients, except 89% of dystrophy patients had muscle atrophy compared with 46% of juvenile PM patients. Dystrophy patients had a longer delay to diagnosis (median 12 versus 4 months) and were less frequently hospitalized than juvenile PM patients (22% versus 74%). No dystrophy patients, but 54% of juvenile PM patients, had a myositis autoantibody. Dystrophy patients more frequently had myopathic features on muscle biopsy, including diffuse variation of myofiber size, fiber hypertrophy, and myofiber fibrosis (44-100% versus 8-53%). Juvenile PM patients more frequently had complex repetitive discharges on electromyography and a complete response to treatment with prednisone or other immunosuppressive agents than dystrophy patients (44% versus 0%). Random forests analysis revealed that the most important features in distinguishing juvenile PM from dystrophies were myositis autoantibodies, clinical muscle atrophy, and myofiber size variation on biopsy. Logistic regression confirmed muscle atrophy, myofiber fibrosis, and hospitalization as significant predictors. CONCLUSION: Muscular dystrophy can present similarly to juvenile PM. Selected clinical and laboratory features are helpful in combination in distinguishing these conditions.
Subject(s)
Diagnosis, Differential , Muscular Dystrophies/diagnosis , Polymyositis/diagnosis , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Muscular Dystrophies/blood , Muscular Dystrophies/physiopathology , Polymyositis/blood , Polymyositis/physiopathologyABSTRACT
The problem for assessing biosimilarity and drug interchangeability of follow-on biologics (biosimilar products) is studied. Unlike the generic products, the development of biosimilar products is much more complicated because of fundamental differences in functional structures and manufacturing processes. As a result, the criteria and standard methods for the design and analysis of bioequivalence assessment of generic drug products may not be directly applicable to assessing biosimilarity of biosimilar products. In this article, we provide some scientific considerations for criteria, design, and analysis regarding the assessment of biosimilarity and drug interchangeability of biosimilar products. In addition, we discuss scientific and practical issues raised at the 2010 FDA public hearing and the 2011 FDA public meeting on biosimilar products.
Subject(s)
Biosimilar Pharmaceuticals/analysis , Drug Evaluation/methods , Algorithms , Drug Approval , Government Regulation , United States , United States Food and Drug AdministrationABSTRACT
The Food and Drug Administration issued on February 9, 2012, drafts of three new guidance documents about the demonstration of biosimilarity. One of these deals with scientific considerations. It suggests, among others, that demonstration of biosimilarity be developed by a stepwise (step-by-step) approach and that it be assessed by considering the totality of the evidence. This communication provides comments on some scientific factors and issues that still remain unanswered or unsolved. They include the question 'how similar is considered to be highly similar?' considerations of criteria for and the degree of biosimilarity; alternatives of study design and sample size requirements; statistical methods for achieving the totality of the evidence needed for biosimilarity; and methods needed for the assessment of drug interchangeability. It is anticipated that the comments will assist the revision of the guidance documents.
Subject(s)
Biosimilar Pharmaceuticals/analysis , Drug Approval , Drug Evaluation/methods , United States Food and Drug Administration , Drug Evaluation/statistics & numerical data , Guidelines as Topic , Pharmacokinetics , Research Design , United StatesABSTRACT
We consider variable selection when missing values are present in the predictor variables. We compare using complete cases with multiple imputation using backward selection (backwards stepping) and least angle regression. These are studied using a data set from a rheumatological disease (myositis). We find that the coefficients are slightly different and the estimated standard errors are smaller in the complete cases (not a surprise). This seems to be due to the fact that because the estimated residual variance is small the complete cases are more homogeneous than the full data cases.
Subject(s)
Data Interpretation, Statistical , Child , Dermatomyositis/epidemiology , Female , Humans , Incidence , Male , Regression AnalysisABSTRACT
OBJECTIVE: We undertook this study to validate the Myositis Damage Index (MDI) in juvenile and adult myositis, to describe the degree and types of damage and to develop predictors of damage. METHODS: Retrospective MDI evaluations and prospective assessment of disease activity and illness features were conducted. Patients with juvenile-onset disease (n = 143) were evaluated a median of 18 months after diagnosis; 135 patients were assessed 7-9 months later, and 121 were last assessed a median of 82 months after diagnosis. Ninety-six patients with adult-onset dermatomyositis or polymyositis had a baseline assessment a median of 30 months after diagnosis; 77 patients had a 6-month followup evaluation, and 55 had a final assessment a median of 60 months after diagnosis. RESULTS: Damage was present in 79% of juvenile patients and in 97% of adult patients. In juveniles, scarring, contractures, persistent weakness, muscle dysfunction, and calcinosis were most frequent (23-30%) at the last evaluation. In adults, muscle atrophy, muscle dysfunction, and muscle weakness were most frequent (74-84%). MDI severity correlated with physician-assessed global damage, serum creatinine, and muscle atrophy on magnetic resonance imaging, and in juveniles also with functional disability and weakness. MDI damage scores and frequency were highest in patients with a chronic illness course and in adult patients who died. Predictors of damage included functional disability, duration of active disease, disease severity at diagnosis, physician-assessed global disease activity, and illness features, including ulcerations in children and pericarditis in adults. CONCLUSION: Damage is common in myositis after a median duration of 5 years in patients with adult-onset disease and 6.8 years in patients with juvenile-onset disease. The MDI has good content, construct, and predictive validity in juvenile and adult myositis.
Subject(s)
Dermatomyositis/physiopathology , Myositis/physiopathology , Polymyositis/physiopathology , Severity of Illness Index , Adolescent , Adult , Calcinosis/epidemiology , Calcinosis/etiology , Calcinosis/physiopathology , Child , Cicatrix/epidemiology , Cicatrix/etiology , Cicatrix/physiopathology , Dermatomyositis/complications , Disease Progression , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Muscle Weakness/epidemiology , Muscle Weakness/etiology , Muscle Weakness/physiopathology , Muscular Atrophy/epidemiology , Muscular Atrophy/etiology , Muscular Atrophy/physiopathology , Polymyositis/complications , Predictive Value of Tests , Reproducibility of Results , Retrospective StudiesABSTRACT
This article discusses predicting damage in patients with juvenile myositis after treatment with various medications. These data were taken from medical records and not randomized. Investigators advocate using propensity scores for analysis of such non-randomized studies in order to reduce the effect of selection of treatment. Thus far, the studies have typically been comparing drug administration versus no drug after including a propensity score to compensate for potential bias in selecting patients for use of the agent. In this study, we use propensity scoring for multiple treatments given singly or in combination. We study two methods. We use a multiple logistic regression model with continuous propensity scores and a model that develops strata based on the dichotomous treatment assignment (received drug or not). We find the multiple logistic regression models predict damage better than the dichotomous model. In many cases, the propensity score also accounts for the effect of the treatment.
ABSTRACT
OBJECTIVE: The Cutaneous Assessment Tool (CAT) is a comprehensive, semiquantitative tool for the assessment of skin disease in juvenile dermatomyositis (DM). The goal of this study was to determine whether alternative scoring methods would shorten the CAT without compromising its measurement characteristics. METHODS: A total of 113 children with juvenile DM were assessed at baseline; 94 were assessed again 7-9 months later. Interrater reliability, internal consistency, construct validity, and responsiveness were obtained using the original scoring method and 2 alternative methods: the maximum and binary scoring methods. RESULTS: Spearman's correlations of the maximum and binary methods with the original were both 0.98 (P < 0.0001) for the CAT activity score, and 0.96 and 0.98, respectively (P < 0.0001), for the CAT damage score. Values obtained for interrater reliability, internal consistency, construct validity, and responsiveness were similar for all 3 scoring methods. Although there was a trend toward the maximum method having higher interrater reliability and the binary method having higher responsiveness, the confidence intervals were overlapping and no statistically significant differences were observed. Correlation coefficients for the 3 scoring methods with other measures of myositis disease activity and damage were very similar. CONCLUSION: The maximum and binary methods of scoring the CAT have measurement characteristics similar to the original method. Adoption of one of these abbreviated scoring methods should increase its acceptability to clinicians and researchers.
Subject(s)
Dermatomyositis/diagnosis , Severity of Illness Index , Child , Cohort Studies , Humans , Observer Variation , Reproducibility of ResultsABSTRACT
OBJECTIVE: To provide preliminary validation of the Cutaneous Assessment Tool (CAT), a new tool to assess cutaneous manifestations of juvenile dermatomyositis (DM), and to explore the clinical meaning of CAT scores. METHODS: Children with juvenile DM (n = 113) were assessed at baseline and 7-9 months later (n = 94). Internal consistency, redundancy, construct validity, and responsiveness of the CAT were examined. CAT scores corresponding to ordinal global assessments were determined. RESULTS: Item-total correlations ranged from 0.27-0.67 for activity lesions present in > or =10% of patients; item-domain and domain-total correlations ranged from 0.25-0.99. Cronbach's alpha was 0.79 for the CAT activity score and 0.74 for the CAT damage score. As predicted, the CAT activity score correlated strongly with both global disease activity and skin disease activity and moderately with the Childhood Myositis Assessment Scale, whereas the CAT damage score correlated moderately with the physician global disease and skin disease damage scores. Median CAT activity scores of 1, 7, 13, 18, and 31 corresponded to absent, mild, moderate, severe, and extremely severe skin disease activity, respectively. Median CAT damage scores of 0, 1, 2, and 5 correlated with the same descriptions of damage (severe and extremely severe combined). CONCLUSION: Preliminary validation of the CAT demonstrated good internal consistency, nonredundancy, good construct validity, and appropriate responsiveness. The CAT is a comprehensive, semiquantitative assessment tool for skin disease in juvenile DM.