Multimetric feature selection for analyzing multicategory outcomes of colorectal cancer: random forest and multinomial logistic regression models.

Colorectal cancer (CRC) is one of the most common cancers worldwide, and a leading cause of cancer deaths. Better classifying multicategory outcomes of CRC with clinical and omic data may help adjust treatment regimens based on individual's risk. Here, we selected the features that were useful for classifying four-category survival outcome of CRC using the clinical and transcriptomic data, or clinical, transcriptomic, microsatellite instability and selected oncogenic-driver data (all data) of TCGA. We also optimized multimetric feature selection to develop the best multinomial logistic regression (MLR) and random forest (RF) models that had the highest accuracy, precision, recall and F1 score, respectively. We identified 2073 differentially expressed genes of the TCGA RNASeq dataset. MLR overall outperformed RF in the multimetric feature selection. In both RF and MLR models, precision, recall and F1 score increased as the feature number increased and peaked at the feature number of 600-1000, while the models' accuracy remained stable. The best model was the MLR one with 825 features based on sum of squared coefficients using all data, and attained the best accuracy of 0.855, F1 of 0.738 and precision of 0.832, which were higher than those using clinical and transcriptomic data. The top-ranked features in the MLR model of the best performance using clinical and transcriptomic data were different from those using all data. However, pathologic staging, HBS1L, TSPYL4, and TP53TG3B were the overlapping top-20 ranked features in the best models using clinical and transcriptomic, or all data. Thus, we developed a multimetric feature-selection based MLR model that outperformed RF models in classifying four-category outcome of CRC patients. Interestingly, adding microsatellite instability and oncogenic-driver data to clinical and transcriptomic data improved models' performances. Precision and recall of tuned algorithms may change significantly as the feature number changes, but accuracy appears not sensitive to these changes.

Is the Proportion of Patients with "Successful" Outcomes After Two-stage Revision for Prosthetic Joint Infection Different When Applying the Musculoskeletal Infection Society Outcome Reporting Tool Compared with the Delphi-based Consensus Criteria?

BACKGROUND: There are a variety of criteria for defining successful treatment after two-stage exchange arthroplasty for prosthetic joint infection (PJI). To accurately assess current practices and improve techniques, it is important to first establish reliable, clinically relevant, reproducible criteria for defining persistent infection and "successful" outcomes. QUESTION/PURPOSE: Is the proportion of patients considered to have successful management of PJI after two-stage resection arthroplasty smaller using 2019 Musculoskeletal Infection Society Outcome Reporting Tool (MSIS ORT) criteria than when using a Delphi-based criterion? METHODS: Patients were retrospectively identified by Current Procedural Technology codes for resection arthroplasty with placement of an antibiotic spacer for infected THA or TKA between April 1, 2011 and January 1, 2018 at a tertiary academic institution. The initial review identified 180 procedures during this time period. Nine patients had documented transition of care outside the system, 16 did not meet the MSIS criteria for chronic PJI, and 34 patients were excluded for lack of documented 2-year follow-up. The mean follow-up duration of the final cohort of 121 procedures in 120 patients was approximately 3.7 ± 1.7 years. Forty percent (49 of 121) of the procedures were performed on the hip and 60% (72 of 121) were performed on the knee. The mean time from primary THA or TKA to explantation was 4.6 years. The mean age of the patients at the time of explantation was 66 years. The mean time from spacer placement to replantation was 119 days. The final 121 patient records were reviewed by a single reviewer and outcomes were subsequently assigned to "successful" and "unsuccessful" outcomes based on the MSIS ORT and Delphi-based consensus criterion, two previously published and validated multidimensional definition schemes. Chi-squared and t-test analyses were performed to identify differences between "successful" and "unsuccessful" outcomes with respect to patient baseline characteristics using each outcome-reporting criterion. RESULTS: Overall, the MSIS ORT classified a smaller proportion of patients as having a "successful" treatment outcome after two-stage exchange arthroplasty for PJI than the Delphi-based consensus method did (MSIS: 55% [63 of 114], Delphi: 70% [71 of 102]; relative risk 0.79 [0.65-0.98]; p = 0.03). However, there were no differences when stratified by hips (MSIS: 55% [26 of 47], Delphi: 74% [29 of 39]; relative risk 0.74 [0.54-1.02]; p = 0.07) and knees (MSIS: 55% [37 of 67], Delphi: 67% [42 of 63]; relative risk 0.83 [0.63-1.09]; p = 0.19). Notably, the disease of 16% of the patients (19 of 121) was not classifiable per the Delphi method because these patients never underwent reimplantation. CONCLUSION: The present study demonstrated that the MSIS criteria detect fewer instances of "successful" infection management after two-stage resection arthroplasty for PJI than the Delphi method in this cohort. Based on these findings, researchers and surgeons should aim for standardized reporting after intervention for PJI to allow for a better comparison of outcomes across different studies and ultimately allow for improved techniques and approaches to the treatment of PJI. LEVEL OF EVIDENCE: Level III, diagnostic study.

Nursing diagnoses and outcomes for children with nutritional anomalies: a descriptive study.

OBJECTIVES: to develop nursing diagnoses and outcomes for children with nutritional anomalies based on terms found in a children's clinical protocol and on the 2017 International Classification for Nursing Practice. METHODS: exploratory-descriptive study, conducted with the validation of diagnoses/outcomes by six nurses of the children's clinic of the Federal District's teaching hospital. It was based on the cross-mapping between the terms of International Classification for Nursing Practice 2017 and the terms of a children's health care protocol. The list of nursing diagnosis/outcomes was developed, then submitted to the validation process using a Likert-type scale and considering statements with content validity index > 0.79 to be validated. RESULTS: a total of 51 diagnoses/outcomes were generated, and of those, 11 were contained in International Classification for Nursing Practice. Those that were not in it were evaluated for similarity and comprehensiveness in relation to International Classification for Nursing Practice. Thirty nursing diagnoses/outcomes were validated with CVI > 0.79 among the nurses in the validation process. CONCLUSIONS: this study will allow the formation of a terminological International Classification for Nursing Practice subset aimed at children's nutrition.

Using Autoantibodies and Cutaneous Subset to Develop Outcome-Based Disease Classification in Systemic Sclerosis.

OBJECTIVE: To describe the associations between autoantibodies, clinical presentation, and outcomes among patients with systemic sclerosis (SSc) in order to develop a novel SSc classification scheme that would incorporate both antibodies and the cutaneous disease subset as criteria. METHODS: Demographic and clinical characteristics, including cutaneous subset, time of disease and organ complication onset, and autoantibody specificities, were determined in a cohort of SSc subjects. Survival analysis was used to assess the effect of the autoantibodies on organ disease and death. RESULTS: The study included 1,325 subjects. Among the antibody/skin disease subsets, anticentromere antibody-positive patients with limited cutaneous SSc (lcSSc) (n = 374) had the highest 20-year survival (65.3%), lowest incidence of clinically significant pulmonary fibrosis (PF) (8.5%) and scleroderma renal crisis (SRC) (0.3%), and lowest incidence of cardiac SSc (4.9%), whereas the frequency of pulmonary hypertension (PH) was similar to the mean value in the SSc cohort overall. The anti-Scl-70+ groups of patients with lcSSc (n = 138) and patients with diffuse cutaneous SSc (dcSSc) (n = 149) had the highest incidence of clinically significant PF (86.1% and 84%, respectively, at 15 years). Anti-Scl-70+ patients with dcSSc had the lowest survival (32.4%) and the second highest incidence of cardiac SSc (12.9%) at 20 years. In contrast, in anti-Scl-70+ patients with lcSSc, other complications were rare, and these patients demonstrated the lowest incidence of PH (6.9%) and second highest survival (61.8%) at 20 years. Anti-RNA polymerase antibody-positive SSc patients (n = 147) had the highest incidence of SRC (28.1%) at 20 years. The anti-U3 RNP+ SSc group (n = 56) had the highest incidence of PH (33.8%) and cardiac SSc (13.2%) at 20 years. Among lcSSc patients with other autoantibodies (n = 295), the risk of SRC and cardiac SSc was low at 20 years (2.7% and 2.4%, respectively), while the frequencies of other outcomes were similar to the mean values in the full SSc cohort. Patients with dcSSc who were positive for other autoantibodies (n = 166) had a poor prognosis, demonstrating the second lowest survival (33.6%) and frequent organ complications. CONCLUSION: These findings highlight the importance of autoantibodies, cutaneous subset, and disease duration when assessing morbidity and mortality in patients with SSc. Our novel classification scheme may improve disease monitoring and benefit future clinical trial designs in SSc.

Nursing diagnoses and outcomes for children with nutritional anomalies: a descriptive study / Los diagnósticos y resultados de enfermería sobre niños con alteración nutricional: un estudio descriptivo / Diagnósticos e resultados de enfermagem à criança com alteração nutricional: estudo descritivo

ABSTRACT Objectives: to develop nursing diagnoses and outcomes for children with nutritional anomalies based on terms found in a children's clinical protocol and on the 2017 International Classification for Nursing Practice. Methods: exploratory-descriptive study, conducted with the validation of diagnoses/outcomes by six nurses of the children's clinic of the Federal District's teaching hospital. It was based on the cross-mapping between the terms of International Classification for Nursing Practice 2017 and the terms of a children's health care protocol. The list of nursing diagnosis/outcomes was developed, then submitted to the validation process using a Likert-type scale and considering statements with content validity index > 0.79 to be validated. Results: a total of 51 diagnoses/outcomes were generated, and of those, 11 were contained in International Classification for Nursing Practice. Those that were not in it were evaluated for similarity and comprehensiveness in relation to International Classification for Nursing Practice. Thirty nursing diagnoses/outcomes were validated with CVI > 0.79 among the nurses in the validation process. Conclusions: this study will allow the formation of a terminological International Classification for Nursing Practice subset aimed at children's nutrition.

RESUMEN Objetivos: elaborar enunciados diagnósticos y resultados de enfermería sobre el niño con alteración nutricional a partir de términos encontrados en el protocolo clínico pediátrico y en la Clasificación Internacional para la Práctica de Enfermería 2017. Métodos: estudio exploratorio-descriptivo, con la validación de diagnósticos/resultados realizada por seis enfermeras de una Clínica pediátrica del Hospital-Escuela del Distrito Federal (Brasil). Se realizó un mapeo cruzado entre los términos de la Clasificación Internacional para la Práctica de Enfermería 2017 y los términos del Protocolo de Atención Sanitaria del Niño. Se elaboró una lista de diagnósticos/resultados de enfermería, a la cual se sometió al proceso de validación, que utilizó la escala tipo Likert por medio del índice de validez de contenido, que considera válido el enunciado que posee IVC > 0,79. Resultados: de los 51 enunciados diagnósticos/resultados obtenidos, 11 estaban presentes en la Clasificación Internacional para la Práctica de Enfermería. Los diagnósticos no presentes se evaluaron mediante la similitud y el alcance de la Clasificación Internacional para la Práctica de Enfermería. Treinta enunciados diagnósticos/resultados de enfermería con ICV > 0,79 fueron validados por los enfermeros en el proceso. Conclusiones: este estudio puede permitir la formación de un subconjunto terminológico Clasificación Internacional para la Práctica de Enfermería en torno a la nutrición del niño.

RESUMO Objetivos: elaborar enunciados diagnósticos e resultados de enfermagem à criança com alteração nutricional a partir de termos encontrados em protocolo clínico pediátrico e a Classificação Internacional para a Prática de Enfermagem 2017. Métodos: estudo exploratório-descritivo, realizado com validação de diagnósticos/resultados por seis enfermeiras da clínica pediátrica do hospital-escola do Distrito Federal. Realizou-se mapeamento cruzado entre os termos da Classificação Internacional para a Prática de Enfermagem 2017 com termos do protocolo de atenção à saúde da criança. Foram elaborados a lista de diagnósticos/resultados de enfermagem, essa lista foi submetida ao processo de validação com utilização da escala tipo Likert por meio do índice de validade de conteúdo, que considera validado o enunciado que possuir IVC > 0,79. Resultados: gerados 51 enunciados diagnósticos/resultados, dessas, 11 constantes na Classificação Internacional para a Prática de Enfermagem. Os diagnósticos não constantes foram avaliados conforme similaridade e abrangência à Classificação Internacional para a Prática de Enfermagem. 30 enunciados diagnósticos/resultados de enfermagem foram validados, possuindo ICV > 0,79 entre os enfermeiros, no processo de validação. Conclusão: este estudo possibilitará a formação de um subconjunto terminológico Classificação Internacional para a Prática de Enfermagem voltado à nutrição da criança.

Nonparametric estimation of the cumulative incidence function under outcome misclassification using external validation data.

Misclassification of outcomes or event types is common in health sciences research and can lead to serious bias when estimating the cumulative incidence functions in settings with competing risks. Recent work has shown how to estimate nonparametric cumulative incidence functions in the presence of nondifferential outcome misclassification when the misclassification probabilities are known. Here, we extend this approach to account for misclassification that is differential with respect to important predictors of the outcome using misclassification probabilities estimated from external validation data. Moreover, we propose a bootstrap approach in which the observations from both the main study data and the external validation study are resampled to allow the uncertainty in the misclassification probabilities to propagate through the analysis into the final confidence intervals, ensuring appropriate confidence interval coverage probabilities. The proposed estimator is shown to be uniformly consistent and simulation studies indicate that both the estimator and the standard error estimation approach perform well in finite samples. The methodology is applied to estimate the cumulative incidence of death and disengagement from HIV care in a large cohort of HIV infected individuals in sub-Saharan Africa, where a significant death underreporting issue leads to outcome misclassification. This analysis uses external validation data from a separate study conducted in the same country.

Definitions, adjudication, and reporting of pulmonary embolism-related death in clinical studies: A systematic review.

BACKGROUND: Pulmonary embolism (PE)-related death is a component of the primary outcome in many venous thromboembolism (VTE) studies. The absence of a standardized definition for PE-related death hampers study outcome evaluation and between-study comparisons. OBJECTIVES: To summarize definitions for PE-related death used in recent VTE studies and to assess the PE-related death rate. PATIENTS/METHODS: A systematic literature search was conducted on 26 April 2018 from 1 January 2014 up to the search date in MEDLINE, Embase, and CENTRAL. Cohort studies and randomized trials in which PE-related death was included in the primary outcome were eligible. Screening of titles, abstracts, and full-text articles, and data extraction were independently performed in duplicate by two authors. Study outcomes included the definition for PE-related death, VTE case-fatality rate, and death due to PE rate. Descriptive statistics were used to analyze the data. RESULTS: Of the 6807 identified citations, 83 studies were included of which 27% were randomized trials, 31% were prospective, and 42% retrospective cohort studies. Thirty-five studies (42%) had a central adjudication committee. Thirty-eight (46%) reported a definition for PE-related death of which the most frequently used components were "autopsy-confirmed PE" (50%), "objectively confirmed PE before death" (55%), and "unexplained death" (58%). Median VTE case-fatality rate was 1.8% (interquartile range, 0.0-13). CONCLUSIONS: Only half of the included studies reported definitions for PE-related death, which were very heterogeneous. Case-fatality rate of VTE events varied widely across studies. Standardization of the definition and guidance on adjudication and reporting of PE-related death is needed.

New SMS classification of cochleovestibular malformation and its impact on decision-making.

OBJECTIVE: To propose a new classification of inner-ear anomalies that is more clinically oriented and surgically relevant: the SMS (Sawai Man Singh) classification of cochleovestibular malformations. METHODS: A retrospective multicentric study was conducted of 436 cochlear implantations carried out in 3 Indian tertiary care institutes. Patients with anomalous anatomy were included and classified, as per the new SMS classification, into cochleovestibular malformation types I, II, III and IV, based on cochlear morphology, modiolus and lamina cribrosa. RESULTS: There were 19, 23, 8 and 4 patients with cochleovestibular malformation types I, II, III and IV, respectively. Two-year post-operative Meaningful Auditory Integration Scale scores were statistically analysed. CONCLUSION: This new classification for inner-ear anomalies is a simpler, more practical, outcome-oriented classification that can be used to better plan the surgery. These merits make it a more uniform classification for recording results.

A systematic review of validated suicide outcome classification in observational studies.

BACKGROUND: Suicidal outcomes, including ideation, attempt, and completed suicide, are an important drug safety issue, though few epidemiological studies address the accuracy of suicidal outcome ascertainment. Our primary objective was to evaluate validated methods for suicidal outcome classification in electronic health care database studies. METHODS: We performed a systematic review of PubMed and EMBASE to identify studies that validated methods for suicidal outcome classification published 1 January 1990 to 15 March 2016. Abstracts and full texts were screened by two reviewers using prespecified criteria. Sensitivity, specificity, and predictive value for suicidal outcomes were extracted by two reviewers. Methods followed PRISMA-P guidelines, PROSPERO Protocol: 2016: CRD42016042794. RESULTS: We identified 2202 citations, of which 34 validated the accuracy of measuring suicidal outcomes using International Classification of Diseases (ICD) codes or algorithms, chart review or vital records. ICD E-codes (E950-9) for suicide attempt had 2-19% sensitivity, and 83-100% positive predictive value (PPV). ICD algorithms that included events with 'uncertain' intent had 4-70% PPV. The three best-performing algorithms had 74-92% PPV, with improved sensitivity compared with E-codes. Read code algorithms had 14-68% sensitivity and 0-56% PPV. Studies estimated 19-80% sensitivity for chart review, and 41-97% sensitivity and 100% PPV for vital records. CONCLUSIONS: Pharmacoepidemiological studies measuring suicidal outcomes often use methodologies with poor sensitivity or predictive value or both, which may result in underestimation of associations between drugs and suicidal behaviour. Studies should validate outcomes or use a previously validated algorithm with high PPV and acceptable sensitivity in an appropriate population and data source.

A machine learning based model for Out of Hospital cardiac arrest outcome classification and sensitivity analysis.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) affects nearly 400,000 people each year in the United States of which only 10% survive. Using data from the Cardiac Arrest Registry to Enhance Survival (CARES), and machine learning (ML) techniques, we developed a model of neurological outcome prediction for OHCA in Chicago, Illinois. METHODS: Rescue workflow data of 2639 patients with witnessed OHCA were retrieved from Chicago's CARES. An Embedded Fully Convolutional Network (EFCN) classification model was selected to predict the patient outcome (survival with good neurological outcomes or not) based on 27 input features with the objective of maximizing the average class sensitivity. Using this model, sensitivity analysis of intervention variables such as bystander cardiopulmonary resuscitation (CPR), targeted temperature management, and coronary angiography was conducted. RESULTS: The EFCN classification model has an average class sensitivity of 0.825. Sensitivity analysis of patient outcome shows that an additional 33 patients would have survived with good neurological outcome if they had received lay person CPR in addition to CPR by emergency medical services and 88 additional patients would have survived if they had received the coronary angiography intervention. CONCLUSIONS: ML modeling of the complex Chicago OHCA rescue system can predict neurologic outcomes with a reasonable level of accuracy and can be used to support intervention decisions such as CPR or coronary angiography. The discriminative ability of this ML model requires validation in external cohorts to establish generalizability.

Impact of Disagreement Between Two Risk Group Models on Prognosis in Patients With Metastatic Renal-Cell Carcinoma.

PURPOSE: To investigate the impact of the risk group disagreement between the Memorial Sloan Kettering Cancer Center (MSKCC) and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) models on prognosis. PATIENTS AND METHODS: We retrospectively evaluated 176 patients with metastatic renal-cell carcinoma who were treated with tyrosine kinase inhibitors as first-line therapy in 5 hospitals between October 2008 and August 2018. The risk group classification differences between the MSKCC and the IMDC models were evaluated using criteria of agreement (identical risk group in both the MSKCC and IMDC models) and disagreement (not identical risk group in both the MSKCC and IMDC models). The agreement of risk stratification between the models was evaluated using the Cohen κ coefficient. Oncologic outcomes were compared between the agreement and disagreement groups. RESULTS: The number of patients with agreement, upgrade, and downgrade was 135 (77%), 39 (22%), and 2 (1.1%), respectively. Of 41 patients with disagreement, reclassification from the MSKCC-intermediate to the IMDC-poor risk group was most frequent (n = 34, 19%). The Cohen κ coefficient for agreement was substantial, with κ = 0.613 (P < .001). Significantly poorer prognosis was observed in patients with disagreement than in those with agreement. Neutrophil count, hemoglobin, serum calcium concentration, and C-reactive protein were significantly different between the groups. CONCLUSION: Disagreement between the MSKCC and IMDC models may have a negative impact on prognosis in patients with metastatic renal-cell carcinoma. The inclusion of systematic inflammation markers in a risk model may be essential for prognosis prediction.

Validation of the Knowledge and Self-management Nursing Outcomes Classification for Adults With Diabetes.

People with diabetes have to self-manage their health conditions to promote, maintain, and restore their health. The Nursing Outcomes Classification provides two outcomes for people with diabetes to evaluate their knowledge and self-management behaviors. The purpose of this study was to validate these two Nursing Outcomes Classification outcomes for adults with diabetes. A descriptive exploratory design using the Delphi technique was used. Two groups of experts were invited for validation of the outcomes. Descriptive statistics were used to determine definition adequacy, clinical usefulness, and content similarity. The Outcome Content Validity method was used to evaluate each outcome and the indicators. A total of 16 nurse experts participated in this study. The definition adequacy of the two Nursing Outcomes Classification outcomes was rated higher than 4.0 out of 5. Clinical usefulness was rated higher than 4.0 out of 5. The range of content validity of the two Nursing Outcomes Classification outcomes was from 0.89 to 0.92 (perfect score is 1.0). The invited experts reported that the content of this outcome pair was very similar. By using validated Nursing Outcomes Classification outcomes, nurses who take care of patients with diabetes can evaluate patient outcomes effectively and determine the effect of nursing interventions accurately.

An Assessment of Clinically Important Differences on the Worst Pain Severity Item of the Modified Brief Pain Inventory in Patients with Diabetic Peripheral Neuropathic Pain.

Objectives: Using patient global impression of change (PGIC) as an anchor, an approximately 30% reduction on an 11-point numeric pain intensity rating scale (PI-NRS) is considered a clinically important difference (CID) in pain. Our objective was to define the CID for another pain measure, the worst pain severity (WPS) item of the modified Brief Pain Inventory (m-BPI). Methods: In this post hoc analysis of a double-blind, placebo-controlled, phase 2 study, 452 randomized patients with diabetic peripheral neuropathic pain (DPNP) were followed over 5 weeks, with m-BPI data collected weekly and PGIC at treatment conclusion. Receiver operating characteristic (ROC) curves (via logistic regression) were used to determine the changes in the m-BPI-WPS score that best predicted ordinal clinical improvement thresholds (i.e., "minimally improved" or better) on the PGIC. Results: Similar to the PI-NRS, a change of -3 (raw) or -33.3% from the baseline on the m-BPI-WPS optimized prediction for the "much improved" or better PGIC threshold and represents a CID. There was a high correspondence between observed and predicted PGIC categories at each PGIC threshold (ROC AUCs were 0.78-0.82). Conclusions: Worst pain on the m-BPI may be used to assess clinically important improvements in DPNP studies. Findings require validation in larger studies.

Deep learning applied to whole-brain connectome to determine seizure control after epilepsy surgery.

OBJECTIVE: We evaluated whether deep learning applied to whole-brain presurgical structural connectomes could be used to predict postoperative seizure outcome more accurately than inference from clinical variables in patients with mesial temporal lobe epilepsy (TLE). METHODS: Fifty patients with unilateral TLE were classified either as having persistent disabling seizures (SZ) or becoming seizure-free (SZF) at least 1 year after epilepsy surgery. Their presurgical structural connectomes were reconstructed from whole-brain diffusion tensor imaging. A deep network was trained based on connectome data to classify seizure outcome using 5-fold cross-validation. RESULTS: Classification accuracy of our trained neural network showed positive predictive value (PPV; seizure freedom) of 88 ± 7% and mean negative predictive value (NPV; seizure refractoriness) of 79 ± 8%. Conversely, a classification model based on clinical variables alone yielded <50% accuracy. The specific features that contributed to high accuracy classification of the neural network were located not only in the ipsilateral temporal and extratemporal regions, but also in the contralateral hemisphere. SIGNIFICANCE: Deep learning demonstrated to be a powerful statistical approach capable of isolating abnormal individualized patterns from complex datasets to provide a highly accurate prediction of seizure outcomes after surgery. Features involved in this predictive model were both ipsilateral and contralateral to the clinical foci and spanned across limbic and extralimbic networks.

Quality of reporting of outcomes in phase III studies of pulmonary tuberculosis: a systematic review.

BACKGROUND: Despite more than 60 years of clinical trials, tuberculosis (TB) still causes a high global burden of mortality and morbidity. Treatment currently requires multiple drugs in combination, taken over a prolonged period. New drugs are needed to shorten treatment duration, prevent resistance and reduce adverse events. However, to improve on current methodology in drug development, a more complete understanding of the existing clinical evidence base is required. METHODS: A systematic review was undertaken to summarise outcomes reported in phase III trials of patients with newly diagnosed pulmonary TB. A systematic search of databases (PubMed, MEDLINE, EMBASE, CENTRAL and LILACs) was conducted on 30 November 2017 to retrieve relevant peer-reviewed articles. Reference lists of included studies were also searched. This systematic review considered all reported outcomes. RESULTS: Of 248 included studies, 229 considered "on-treatment" outcomes whilst 148 reported "off-treatment" outcomes. There was wide variation and ambiguity in the definition of reported outcomes, including their relationship to treatment and in the time points evaluated. Additional challenges were observed regarding the analysis approach taken (per protocol versus intention to treat) and the varying durations of "intensive" and "continuation" phases of treatment. Bacteriological outcomes were most frequently reported but radiological and clinical data were often included as an implicit or explicit component of the overall definition of outcome. CONCLUSIONS: Terminology used to define long-term outcomes in phase III trials is inconsistent, reflecting evolving differences in protocols and practices. For successful future cumulative meta-analysis, the findings of this review suggest that greater availability of individual patient data and the development of a core outcome set would be desirable. In the meantime, we propose a simple and logical approach which should facilitate combination of key evidence and inform improvements in the methodology of TB drug development and clinical trials.

A classification system for verifying the long-term efficacy of resective surgery for drug-resistant seizures.

OBJECTIVE: To verify the long-term efficacy of resective surgery, we created a classification system in which strictly defined patterns of postoperative seizure emergence are incorporated as basic components and the seizure states throughout the entire follow-up period are assessed comprehensively. METHODS: In our system, Class I has three subclasses (A-C); subclasses A and B are identical to Engel I-A and I-B, respectively. Subclass C comprises patients whose disabling seizures remit within the first 2 years postoperatively. Patients in Class II have only 1-3 days with disabling seizures throughout follow-up after the first 2 years. Patients in Class III have a maximum of 3 seizure days annually, and those in Class IV have ≥4 seizure days annually after the first 2 years. Classes II-IV each have 2 subclasses (A and B): subclass A, late recurrence (i.e., the first seizure occurs after 2 years postoperatively); and subclass B, early recurrence (i.e., first seizure within 2 years). In 646 patients who underwent resective surgery (temporal lobe resection, 74.6%) and were followed for at least 8 years (mean, 14.6 years), we analyzed three patterns of postoperative seizures: early remission, late recurrence, and occasional seizures. In addition, we investigated the differences between the long-term seizure outcomes of the cohort as determined according to our system and the Engel scale. RESULTS: Overall, 52.9% of the cohort experienced at least one disabling seizure postoperatively throughout the follow-up period; in 1/3 of these patients, the first seizure occurred after 2 years. In 73.8% of the 80 patients who manifested the running-down phenomenon, seizure remission occurred within the first 2 years. In addition, 36.7% of the 283 patients who had disabling seizures after 2 years experienced only 1-3 seizure days. Engel Class I-C included about 30% of the patients who had ≥4 seizure days after 2 years. The long-term seizure outcomes, determined according to our system, were: Class I, 56.2% (C, 9.1%) of the overall cohort; Class II, 16.1% (A, 11.0%); and Class III/IV, 27.7% (A, 6.6%). CONCLUSION: Our system clarifies the actual effect of resective surgery more precisely than the Engel scale and thus may be useful for comparing outcomes between different surgical procedures or for identifying potential risk factors predicting unfavorable outcome.

Validation of the Clavien-Dindo Grading System in Urology by the European Association of Urology Guidelines Ad Hoc Panel.

CONTEXT: Since 2012 uniformed reporting of complications after urological procedures has been advocated by the European Association of Urology (EAU) guidelines. The Clavien-Dindo grading system was recommended to report the outcomes of urologic procedures. OBJECTIVE: To validate the Clavien-Dindo grading system in urology. DESIGN, SETTING, AND PARTICIPANTS: Members of the EAU working group compiled a list of case scenarios including those with minor and major complications. A survey was administered online via Survey Monkey to the members of EAU committees for the appropriate grading according to the Clavien-Dindo classification of surgical complications. Scenarios with intraoperative complications were intentionally included to assess respondents' awareness of the Clavien-Dindo applicability. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Survey data collected were used to calculate agreement rates and to estimate the overall inter-rater agreement on all cases using Fleiss' kappa (κ). Differences in agreement rates for each scenario among groups with different criteria about the system were estimated using the chi-square test. RESULTS AND LIMITATIONS: Evaluable responses were received from 81 out of 174 invited raters (46.5%). Of them 56.9% believed that the Clavien-Dindo system was adequate for grading postoperative complications. The agreement rate was over a score of ≥80% in nine cases, 60-79% in 10 cases, 40-59% in 14 cases, and <40% in two cases. Interestingly, the agreement rate on the nonapplicability of the Clavien-Dindo system was quite low, ranging from 27.5% to 67.2% (κ=0.147). Being a resident rather than a specialist affected only the distribution of agreement rates in case 1 (ie, score IIIb: 83.3% vs 94.1%). Being an academic or having affiliation did not have any impact on the distribution of agreement rates in all cases but one. CONCLUSIONS: The Clavien-Dindo classification is a standardised approach to grade and report postoperative complications in urology and should be used systematically. However, it does not apply for intraoperative complications, and there is a need for an additional tool. PATIENT SUMMARY: A rigorous methodology is mandatory when surgeons report about complications after surgery. In this study, the European Association of Urology Guidelines Panel has validated the use of the Clavien-Dindo grading system in urology.

A taxonomy has been developed for outcomes in medical research to help improve knowledge discovery.

OBJECTIVES: There is increasing recognition that insufficient attention has been paid to the choice of outcomes measured in clinical trials. The lack of a standardized outcome classification system results in inconsistencies due to ambiguity and variation in how outcomes are described across different studies. Being able to classify by outcome would increase efficiency in searching sources such as clinical trial registries, patient registries, the Cochrane Database of Systematic Reviews, and the Core Outcome Measures in Effectiveness Trials (COMET) database of core outcome sets (COS), thus aiding knowledge discovery. STUDY DESIGN AND SETTING: A literature review was carried out to determine existing outcome classification systems, none of which were sufficiently comprehensive or granular for classification of all potential outcomes from clinical trials. A new taxonomy for outcome classification was developed, and as proof of principle, outcomes extracted from all published COS in the COMET database, selected Cochrane reviews, and clinical trial registry entries were classified using this new system. RESULTS: Application of this new taxonomy to COS in the COMET database revealed that 274/299 (92%) COS include at least one physiological outcome, whereas only 177 (59%) include at least one measure of impact (global quality of life or some measure of functioning) and only 105 (35%) made reference to adverse events. CONCLUSIONS: This outcome taxonomy will be used to annotate outcomes included in COS within the COMET database and is currently being piloted for use in Cochrane Reviews within the Cochrane Linked Data Project. Wider implementation of this standard taxonomy in trial and systematic review databases and registries will further promote efficient searching, reporting, and classification of trial outcomes.

The Whitaker Classification of Craniosynostosis Outcomes: An Assessment of Interrater Reliability.

BACKGROUND: The Whitaker classification is a simple and widely used system for describing aesthetic outcomes after craniosynostosis surgery. The purpose of this study is to evaluate its interrater reliability for patients who have undergone fronto-orbital surgery. METHODS: A retrospective review of patients with craniosynostosis who underwent surgical intervention at a tertiary referral center was conducted. Inclusion criteria were as follows: single-suture craniosynostosis, surgical intervention before age 2 years, and photographs taken before revisions between 5 and 20 years of age. Thirteen craniofacial surgeons independently reviewed the subjects' photographs and assigned Whitaker classifications. Interrater reliability was assessed with the Cohen kappa statistic. RESULTS: Twenty-nine subjects were included. Average ages at surgery and at the time of postoperative photography were 0.8 year and 12.8 years, respectively. The κ value for all 13 raters was 0.1567 (p < 0.0001), indicating "slight agreement." Pairwise comparisons demonstrated κ values ranging from 0.0384 to 0.5492. The average rating for the set of 29 photographs differed significantly across the 13 raters (p = 0.0020) and ranged from 1.79 ± 0.68 to 2.79 ± 0.77. Finally, we found that average Whitaker classification did not differ significantly between subjects who subsequently underwent cranioplasty and/or fronto-orbital advancement and those who did not (subsequent procedures, 2.45 ± 0.55; no subsequent procedures, 1.88 ± 0.78; p = 0.1087). CONCLUSIONS: The Whitaker classification exhibits low interrater reliability and does not predict future treatment. It may benefit craniofacial surgeons to create new evaluation tools with greater precision, to improve the quality of patient care and craniofacial outcomes research.

The H.O.U.S.E. classification: a novel endoscopic retrograde cholangiopancreatography (ERCP) complexity grading scale.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a technically challenging endoscopic procedure, harboring a wide range of complexities within every single investigation. Classifications of the complexity of ERCP have been presented, but do not include modern endoscopic treatment modalities. In order to be able to target resources and compare the results of different endoscopic centers, a new complexity grading system for ERCP is warranted. This study launches a new complexity grading scale for ERCP-the H.O.U.S.E.-classification. METHODS: The medical record of every patient undergoing ERCP 2009-2011 at the Karolinska University Hospital was reviewed, regarding the complexity of the procedure, and categorized into one out of three-grades in the HOUSE classification system, and concomitantly graded according to the Cotton grading system. All ERCP-procedures were also registered in the Swedish registry for gallstone surgery and ERCP (GallRiks) and correlations between the grading systems and procedure related variables as well as outcomes were made. RESULTS: Between 2009 and 2011, 2185 ERCPs were performed at the Karolinska University Hospital, Huddinge. One thousand nine hundred fifty-four of those were index-ERCPs. Another 23 patients were excluded due to lack of postoperative complication registrations, leaving 1931 ERCP procedures to be analyzed. The procedure times were 40 ± 0.7, 65 ± 1.5 and 106 ± 3.2 min, respectively (HOUSE 1-3). The corresponding pancreatitis rates were 3.4, 7.0 and 6.8% and the postoperative complication rates 11.1, 15.7 and 12.8%, respectively. CONCLUSIONS: The HOUSE-classification is a novel grading scale for ERCP-complexity. The system can be implemented in clinical practice to allocate resources and allow the comparisons of results between different endoscopic centers. Further studies are warranted to further sharpen this instruments validitity and general clinical relevance.