Choosing a pediatric recipient for orthotopic liver transplantation

Between March 3, 1981, and June 1, 1984, 216 children were evaluated for orthotopic liver transplantation. Of the 216 patients, 117 (55%) had recelved at least one liver transplant by June 1, 1985. Fifty-five (25%) died before transplantation. The 117 patients who received transplants were grouped according to severity of disease and degree of general decompensation at the time of transplantation. The severity of a patient's medical condition with the possible exception of deep hepatic coma, did not predict outcome following orthotopic liver transplantation. Seventy variables were assessed at the time of the evaluation. Twenty-three of the 70 variables were found to have prognostic significance with regard to death from progressive liver disease before transplantation. These 23 variables were Incorporated into a multivariate model to provide a means of determining the relative risk of death among pediatric patients with end-stage liver disease. This information may allow more informed selection of candidates awaiting liver transplantation. © 1987 The C. V. Mosby Company

Age of Child, More than HPV Type, Is Associated with Clinical Course in Recurrent Respiratory Papillomatosis

Background: RRP is a devastating disease in which papillomas in the airway cause hoarseness and breathing difficulty. The disease is caused by human papillomavirus (HPV), 6 or 11 and is very variable. Patients undergo multiple surgeries to maintain a patent airway and in order to communicate vocally. Several small studies have been published in which most have noted that HPV 11 is associated with a more aggressive course. Methodology/Principal Findings: Papilloma biopsies were taken from patients undergoing surgical treatment of RRP and were subjected to HPV typing. 118 patients with juvenile-onset RRP with a least 1 year of clinical data and infected with a single HPV type were analyzed. HPV 11 was encountered in 40% of the patients. By our definition, most of the patients in the sample (81%) had run an aggressive course. The odds of a patient with HPV 11 running an aggressive course were 3.9 times higher that that of patients with HPV 6 (Fisher's exact p=0.017). However, clinical course was more closely associated with age of the patient (at diagnosis and at the time of the current surgery) than with HPV type. Patients with HPV 11 were diagnosed at a younger age (2.4y) than were those with HPV 6 (3.4y) (p=0.014). Both by multiple linear regression and by multiple logistics regression HPV type was only weakly associated with metrics of disease course when simultaneously accounting for age. Conclusions/Significance Abstract: The course of RRP is variable and a quarter of the variability can be accounted for by the age of the patient. HPV 11 is more closely associated with a younger age at diagnosis than it is associated with an aggressive clinical course. These data suggest that there are factors other than HPV type and age of the patient that determine disease course. © 2008 Buchinsky et al

2016 ACR-EULAR adult dermatomyositis and polymyositis and juvenile dermatomyositis response criteria-methodological aspects

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

2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Juvenile Dermatomyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative

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

2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Juvenile Dermatomyositis An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative

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

Interventions outside the workplace for reducing sedentary behaviour in adults under 60 years of age

Background Adults spend a majority of their time outside the workplace being sedentary. Large amounts of sedentary behaviour increase the risk of type 2 diabetes, cardiovascular disease, and both all‐cause and cardiovascular disease mortality. Objectives Primary • To assess effects on sedentary time of non‐occupational interventions for reducing sedentary behaviour in adults under 60 years of age Secondary • To describe other health effects and adverse events or unintended consequences of these interventions • To determine whether specific components of interventions are associated with changes in sedentary behaviour • To identify if there are any differential effects of interventions based on health inequalities (e.g. age, sex, income, employment) Search methods We searched CENTRAL, MEDLINE, Embase, Cochrane Database of Systematic Reviews, CINAHL, PsycINFO, SportDiscus, and ClinicalTrials.gov on 14 April 2020. We checked references of included studies, conducted forward citation searching, and contacted authors in the field to identify additional studies. Selection criteria We included randomised controlled trials (RCTs) and cluster RCTs of interventions outside the workplace for community‐dwelling adults aged 18 to 59 years. We included studies only when the intervention had a specific aim or component to change sedentary behaviour. Data collection and analysis Two review authors independently screened titles/abstracts and full‐text articles for study eligibility. Two review authors independently extracted data and assessed risk of bias. We contacted trial authors for additional information or data when required. We examined the following primary outcomes: device‐measured sedentary time, self‐report sitting time, self‐report TV viewing time, and breaks in sedentary time. Main results We included 13 trials involving 1770 participants, all undertaken in high‐income countries. Ten were RCTs and three were cluster RCTs. The mean age of study participants ranged from 20 to 41 years. A majority of participants were female. All interventions were delivered at the individual level. Intervention components included personal monitoring devices, information or education, counselling, and prompts to reduce sedentary behaviour. We judged no study to be at low risk of bias across all domains. Seven studies were at high risk of bias for blinding of outcome assessment due to use of self‐report outcomes measures. Primary outcomes Interventions outside the workplace probably show little or no difference in device‐measured sedentary time in the short term (mean difference (MD) ‐8.36 min/d, 95% confidence interval (CI) ‐27.12 to 10.40; 4 studies; I² = 0%; moderate‐certainty evidence). We are uncertain whether interventions reduce device‐measured sedentary time in the medium term (MD ‐51.37 min/d, 95% CI ‐126.34 to 23.59; 3 studies; I² = 84%; very low‐certainty evidence) We are uncertain whether interventions outside the workplace reduce self‐report sitting time in the short term (MD ‐64.12 min/d, 95% CI ‐260.91 to 132.67; I² = 86%; very low‐certainty evidence). Interventions outside the workplace may show little or no difference in self‐report TV viewing time in the medium term (MD ‐12.45 min/d, 95% CI ‐50.40 to 25.49; 2 studies; I² = 86%; low‐certainty evidence) or in the long term (MD 0.30 min/d, 95% CI ‐0.63 to 1.23; 2 studies; I² = 0%; low‐certainty evidence). It was not possible to pool the five studies that reported breaks in sedentary time given the variation in definitions used. Secondary outcomes Interventions outside the workplace probably have little or no difference on body mass index in the medium term (MD ‐0.25 kg/m², 95% CI ‐0.48 to ‐0.01; 3 studies; I² = 0%; moderate‐certainty evidence). Interventions may have little or no difference in waist circumference in the medium term (MD ‐2.04 cm, 95% CI ‐9.06 to 4.98; 2 studies; I² = 65%; low‐certainty evidence). Interventions probably have little or no difference on glucose in the short term (MD ‐0.18 mmol/L, 95% CI ‐0.30 to ‐0.06; 2 studies; I² = 0%; moderate‐certainty evidence) and medium term (MD ‐0.08 mmol/L, 95% CI ‐0.21 to 0.05; 2 studies, I² = 0%; moderate‐certainty evidence) Interventions outside the workplace may have little or no difference in device‐measured MVPA in the short term (MD 1.99 min/d, 95% CI ‐4.27 to 8.25; 4 studies; I² = 23%; low‐certainty evidence). We are uncertain whether interventions improve device‐measured MVPA in the medium term (MD 6.59 min/d, 95% CI ‐7.35 to 20.53; 3 studies; I² = 70%; very low‐certainty evidence). We are uncertain whether interventions outside the workplace improve self‐reported light‐intensity PA in the short‐term (MD 156.32 min/d, 95% CI 34.34 to 278.31; 2 studies; I² = 79%; very low‐certainty evidence). Interventions may have little or no difference on step count in the short‐term (MD 226.90 steps/day, 95% CI ‐519.78 to 973.59; 3 studies; I² = 0%; low‐certainty evidence) No data on adverse events or symptoms were reported in the included studies. Authors' conclusions Interventions outside the workplace to reduce sedentary behaviour probably lead to little or no difference in device‐measured sedentary time in the short term, and we are uncertain if they reduce device‐measured sedentary time in the medium term. We are uncertain whether interventions outside the workplace reduce self‐reported sitting time in the short term. Interventions outside the workplace may result in little or no difference in self‐report TV viewing time in the medium or long term. The certainty of evidence is moderate to very low, mainly due to concerns about risk of bias, inconsistent findings, and imprecise results. Future studies should be of longer duration; should recruit participants from varying age, socioeconomic, or ethnic groups; and should gather quality of life, cost‐effectiveness, and adverse event data. We strongly recommend that standard methods of data preparation and analysis are adopted to allow comparison of the effects of interventions to reduce sedentary behaviour

Statistical evaluation of diagnostic performance: topics in ROC analysis

Statistical evaluation of diagnostic performance in general and Receiver Operating Characteristic (ROC) analysis in particular are important for assessing the performance of medical tests and statistical classifiers, as well as for evaluating predictive models or algorithms. This book presents innovative approaches in ROC analysis, which are relevant to a wide variety of applications, including medical imaging, cancer research, epidemiology, and bioinformatics. Statistical Evaluation of Diagnostic Performance: Topics in ROC Analysis covers areas including monotone-transformation techniques in parametric ROC analysis, ROC methods for combined and pooled biomarkers, Bayesian hierarchical transformation models, sequential designs and inferences in the ROC setting, predictive modeling, multireader ROC analysis, and free-response ROC (FROC) methodology. The book is suitable for graduate-level students and researchers in statistics, biostatistics, epidemiology, public health, biomedical engineering, radiology, medical imaging, biomedical informatics, and other closely related fields. Additionally, clinical researchers and practicing statisticians in academia, industry, and government could benefit from the presentation of such important and yet frequently overlooked topics