Congenital Hypothyroidism and the Importance of Universal Newborn Screening

Congenital hypothyroidism (CH) is one of the most common preventable causes of mental retardation in children. Early diagnosis and treatment prevent the devastating outcome of mental retardation. Clinical features of CH are subtle and are not evident early in the neonatal period. Therefore, universal newborn screening (NS) is effective in detecting CH and implementing early treatment. This article reviews the current literature regarding the epidemiology, etiology, classification, clinical features, diagnosis of primary CH, and the management of abnormal newborn screen as well as treatment and prognosis of primary CH and outlines the importance of universal newborn screening in preventing mental retardation.     

Pharmacokinetics of voriconazole administered concomitantly with fluconazole and population-based simulation for sequential use

In clinical practice, antifungal therapy may be switched from fluconazole to voriconazole; such sequential use poses the potential for drug interaction due to cytochrome P450 2C19 (CYP2C19)-mediated inhibition of voriconazole metabolism. This open-label, randomized, two-way crossover study investigated the effect of concomitant fluconazole on voriconazole pharmacokinetics in 10 subjects: 8 extensive metabolizers and 2 poor metabolizers of CYP2C19. The study consisted of 4-day voriconazole-only and 5-day voriconazole-plus-fluconazole treatments, separated by a 14-day washout. Voriconazole pharmacokinetics were determined by noncompartmental analyses. A physiologically based pharmacokinetic model was developed in Simcyp (Simcyp Ltd., Sheffield, United Kingdom) to predict the magnitude of drug interaction should antifungal therapy be switched from fluconazole to voriconazole, following various simulated lag times for the switch. In CYP2C19 extensive metabolizers, fluconazole increased the maximum plasma concentration and the area under the plasma concentration-time curve (AUC) of voriconazole by 57% and 178%, respectively. In poor metabolizers, however, voriconazole pharmacokinetics were unaffected by fluconazole. The simulations based on pharmacokinetic modeling predicted that if voriconazole was started 6, 12, 24, or 36 h after the last dose of fluconazole, the voriconazole AUC ratios (sequential therapy versus voriconazole only) after the first dose would be 1.51, 1.41, 1.28, and 1.14, respectively. This suggests that the remaining systemic fluconazole would result in a marked drug interaction with voriconazole for ≥ 24 h. Although no safety issues were observed during coadministration, concomitant use of fluconazole and voriconazole is not recommended. Frequent monitoring for voriconazole-related adverse events is advisable if voriconazole is used sequentially after fluconazole.     

Accuracy of the Emotion Thermometers (ET) Screening Tool in Patients Undergoing Surgery for Upper Gastrointestinal Malignancies

Distress is common in patients with gastrointestinal cancers. Most conventional scales are too long for routine clinic use. We tested the Emotion Thermometers (ET) tool, a brief visual-analogue scale. There are four emotional upset thermometers: distress, anxiety, depression, and anger. Sixty-nine surgical patients were recruited from an academic hospital clinic in 2012; 64 had complete data for Beck depression inventory and ET. The sample size was modest due to the specialist nature of the sample. We examined sensitivity, specificity, and area under the receiver-operator-curve. A dimensional multi-domain approach to screening for emotional disorders is preferable to using the distress thermometer alone and can be achieved with little extra time burden to clinicians. The ET is a diagnostic tool that is primarily designed for screening to identify cancer patients who would benefit by enhanced psychosocial care.     

Monitoring the performance of mycobacteriology laboratories: a proposal for standardized indicators

SETTING: Thailand Tuberculosis (TB) Active Surveillance Network: Bangkok, Chiang Rai, Phuket, Tak and Ubon-Ratchathani, Thailand. BACKGROUND: Mycobacteriology laboratories in resource-limited, high TB burden settings are expanding to perform conventional solid media culture and broth-based mycobacteriology culture. Indicators that measure how well a laboratory performs sputum microscopy have been developed and broadly implemented. Routine monitoring of sputum culture performance, however, is not as common. DESIGN: We implemented indicators for monitoring the quality of laboratory services in five province-level mycobacteriology culture facilities in Thailand. These indicators were derived from literature review, consultation with subject matter experts and our program experience. CONCLUSIONS: We believe that an international consensus document providing monitoring guidelines for mycobacteriology laboratories is urgently needed.