Evaluation of tuberculosis diagnostics in children: 1. Proposed clinical case definitions for classification of intrathoracic tuberculosis disease. Consensus from an expert panel

There is a critical need for improved diagnosis of tuberculosis in children, particularly in young children with intrathoracic disease as this represents the most common type of tuberculosis in children and the greatest diagnostic challenge. There is also a need for standardized clinical case definitions for the evaluation of diagnostics in prospective clinical research studies that include children in whom tuberculosis is suspected but not confirmed by culture of Mycobacterium tuberculosis. A panel representing a wide range of expertise and child tuberculosis research experience aimed to develop standardized clinical research case definitions for intrathoracic tuberculosis in children to enable harmonized evaluation of new tuberculosis diagnostic technologies in pediatric populations. Draft definitions and statements were proposed and circulated widely for feedback. An expert panel then considered each of the proposed definitions and statements relating to clinical definitions. Formal group consensus rules were established and consensus was reached for each statement. The definitions presented in this article are intended for use in clinical research to evaluate diagnostic assays and not for individual patient diagnosis or treatment decisions. A complementary article addresses methodological issues to consider for research of diagnostics in children with suspected tuberculosis.     

Usefulness of Doppler Echocardiographic Left Ventricular Diastolic Function and Peak Exercise Oxygen Consumption to Predict Cardiovascular Outcomes in Patients With Systolic Heart Failure (from HF-ACTION)

Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) was a multicenter, randomized controlled trial designed to examine the safety and efficacy of aerobic exercise training versus usual care in 2,331 patients with systolic heart failure (HF). In HF-ACTION patients with rest transthoracic echocardiographic measurements, the predictive value of 8 Doppler echocardiographic measurements-left ventricular (LV) diastolic dimension, mass, systolic (ejection fraction) and diastolic (mitral valve peak early diastolic/peak late diastolic [E/A] ratio, peak mitral valve early diastolic velocity/tissue Doppler peak early diastolic myocardial velocity [E/E'] ratio, and deceleration time) function, left atrial dimension, and mitral regurgitation severity-was examined for a primary end point of all-cause death or hospitalization and a secondary end point of cardiovascular disease death or HF hospitalization. Also compared was the prognostic value of echocardiographic variables versus peak oxygen consumption (Vo(2)). Mitral valve E/A and E/E' ratios were more powerful independent predictors of clinical end points than the LV ejection fraction but less powerful than peak Vo(2). In multivariate analyses for predicting the primary end point, adding E/A ratio to a basic demographic and clinical model increased the C-index from 0.61 to 0.62, compared with 0.64 after adding peak Vo(2). For the secondary end point, 6 echocardiographic variables, but not the LV ejection fraction or left atrial dimension, provided independent predictive power over the basic model. The addition of E/E' or E/A to the basic model increased the C-index from 0.70 to 0.72 and 0.73, respectively (all p values <0.0001). Simultaneously adding E/A ratio and peak Vo(2) to the basic model increased the C-index to 0.75 (p <0.0005). No echocardiographic variable was significantly related to the change from baseline to 3 months in exercise peak Vo(2). In conclusion, the addition of echocardiographic LV diastolic function variables improves the prognostic value of a basic demographic and clinical model for cardiovascular disease outcomes.     

Clinical, histopathologic, and genetic features of pediatric primary myelofibrosis--an entity different from adults

Primary myelofibrosis is a chronic myeloproliferative neoplasm characterized by cytopenias, leukoerythroblastosis, extramedullary hematopoiesis, hepatosplenomegaly and bone marrow fibrosis. Primary myelofibrosis is a rare disorder in adults; children are even less commonly affected by this entity, with the largest pediatric case series reporting on three patients. Most literature suggests spontaneous resolution of myelofibrosis without long term complications in the majority of affected children. We describe the clinical, pathologic, and molecular characteristics and outcomes of nineteen children with primary myelofibrosis treated in our center from 1984 to 2011. Most patients had cytopenia significant enough to require supportive therapy. No child developed malignant transformation and only five of the 19 children (26%) had spontaneous resolution of disease. Sequence analyses for JAK2V617F and MPLW515L mutations were performed on bone marrow samples from 17 and six patients, respectively, and the results were negative. In conclusion, analysis of this large series of pediatric patients with primary myelofibrosis demonstrates distinct clinical, hematologic, bone marrow, and molecular features from adult patients.     

Mental Disorders and Cigarette Use among Adults in the United States

Background: The goal of this study was to determine the association between mental disorders and cigarette consumption and nicotine dependence. Methods: Data were drawn from the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC), a nationally representative survey of adults (N = 43,093) aged 18 and older. Relationships between specific anxiety disorders, mood disorders, nondependent cigarette use, nicotine dependence among the whole sample, and nicotine dependence among cigarette users were examined. Results: After adjusting for demographics and comorbid mental disorders, generalized anxiety disorder (OR = 1.16 (1.29-1.51)), specific phobia (OR = 1.35 (1.21-1.51)), panic disorder (PD) (OR = 1.90 (1.62-2.23)), major depression (MDD) (OR = 1.31 (1.16-1.48)), and bipolar disorder (OR = 1.30 (1.09-1.54)) were associated with increased likelihood of nondependent cigarette use. Specific phobia (OR = 1.69 (1.49-1.91)), PD (OR = 1.82 (1.50-2.21)), MDD (OR = 1.59 (1.38-1.84)), and bipolar disorder (OR = 1.71 (1.39-2.09)) were associated with increased odds of nicotine dependence among the whole sample; social phobia (OR = 1.69 (1.19-2.40)), specific phobia (OR = 1.69 (1.43-2.01)), MDD (OR = 1.65 (1.34-2.02)), and bipolar disorder (OR = 2.38 (1.74-3.24)) were associated with increased risk of nicotine dependence among cigarette users. Conclusions: Specific anxiety disorders and mood disorders were uniquely associated with nondependent cigarette use, nicotine dependence among the whole sample, and the risk of nicotine dependence among cigarette users in the United States. Findings suggest that demographic differences, comorbid mood, anxiety, substance, and personality disorders all contributed to previously observed associations between mental disorders and nicotine dependence, explaining these links in some but not all cases. (Am J Addict 2012;21:416-423).