Contribution of Cytochrome P450 and ABCB1 Genetic Variability on Methadone Pharmacokinetics, Dose Requirements, and Response

Although the efficacy of methadone maintenance treatment (MMT) in opioid dependence disorder has been well established, the influence of methadone pharmacokinetics in dose requirement and clinical outcome remains controversial. The aim of this study is to analyze methadone dosage in responder and nonresponder patients considering pharmacogenetic and pharmacokinetic factors that may contribute to dosage adequacy. Opioid dependence patients (meeting Diagnostic and Statistical Manual of Mental Disorders, [4th Edition] criteria) from a MMT community program were recruited. Patients were clinically assessed and blood samples were obtained to determine plasma concentrations of (R,S)-, (R) and (S)- methadone and to study allelic variants of genes encoding CYP3A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19, and P-glycoprotein. Responders and nonresponders were defined by illicit opioid consumption detected in random urinalysis. The final sample consisted in 105 opioid dependent patients of Caucasian origin. Responder patients received higher doses of methadone and have been included into treatment for a longer period. No differences were found in terms of genotype frequencies between groups. Only CYP2D6 metabolizing phenotype differences were found in outcome status, methadone dose requirements, and plasma concentrations, being higher in the ultrarapid metabolizers. No other differences were found between phenotype and responder status, methadone dose requirements, neither in methadone plasma concentrations. Pharmacokinetic factors could explain some but not all differences in MMT outcome and methadone dose requirements

Cómo diseñar talleres para promover la salud en grupos comunitarios

Una de las estrategias de promoción de la salud es el desarrollo de habilidades para la vida considerando a las propias personas como principal recurso para la salud. Un taller ha de conseguir que sus participantes se conviertan en «activos» para tomar decisiones y generar salud, centrándose en el desarrollo y adquisición de habilidades en grupo de una manera motivadora y con la finalidad de alcanzar unos objetivos. Los conceptos que fundamentan el diseño de un taller y que han de plantearse como etapa 0 son: planificación participativa, capacitar, aprendizaje significativo, aprender en grupo y técnicas participativas. Las etapas que se deben seguir para diseñar un taller y facilitar su aplicación son: etapa 0 de fundamentación, etapa inicial, de acogida y de evaluación inicial; etapa central o de construcción del aprendizaje basado en la adquisición de conocimientos, actitudes y habilidades, y etapa final o de evaluación

Quiste adventicial de arteria poplítea y su relación con la articulación de la rodilla. Histología y resonancia magnética

El quiste adventicial de arteria poplítea es una causa poco frecuente de síntomas isquémicos de extremidades inferiores. No obstante, es importante considerarlo en el diagnóstico diferencial de individuos jóvenes afectos de claudicación intermitente gemelar. Pese a que la etiología y patogenia de esta entidad permanece todavía incierta, un correcto diagnóstico permite al especialista restaurar el flujo sanguíneo normal de la extremidad. Caso clínico. Paciente de 57 años con claudicación intermitente y portador de un quiste adventicial de arteria poplítea, en el que su comunicación con la articulación de la rodilla puede demostrarse por resonancia magnética y confirmarse por cirugía. Conclusión. La resonancia magnética es una prueba diagnóstica que pudo mostrar claramente esta patología y reforzar la hipótesis sinovial

Aneurismas poplíteos. Evolución y factores pronósticos en la trombosis del saco

Objetivos. Conocer la evolución de aneurismas poplíteos tratados quirúrgicamente y evaluar factores pronósticos en la trombosis del saco. Pacientes y métodos. Desde mayo de 1993 hasta junio del año 2005, 43 pacientes presentaron 64 aneurismas poplíteos (diámetro medio: 2,8 cm; intervalo: 1,2-8 cm); de ellos, 19 (29%) han recibido tratamiento médico (compensación tras trombosis), dos (3%) aneurismectomía más injerto terminoterminal vía posterior, 22 (34%) exclusión por ligadura más bypass poplíteo-poplíteo y, por último, 21 (32%) exclusión y bypass femoropoplíteo. Hemos realizado un estudio descriptivo transversal en los 43 aneurismas tratados mediante exclusión y bypass (67%). Mediante eco-Doppler de control se evaluó: diámetro, presencia de flujo o trombosis del aneurisma y permeabilidad del bypass. Se analizó, mediante regresión de Cox, si existía asociación estadísticamente significativa entre la trombosis postoperatoria del saco aneurismático y los siguientes factores: diámetro preoperatorio del aneurisma, edad, factores de riesgo cardiovascular, comorbilidad, tipo de tratamiento, run-off, permeabilidad del bypass y presencia de aneurisma contralateral o de aorta. Resultados. De 43 aneurismas intervenidos, se pudieron evaluar 25 (56%). Se detectó flujo Doppler intraaneurismático en cuatro casos (16%); de éstos, hubo crecimiento del saco en tres (12%), y en uno (4%) disminuyó. De los 21 casos (84%) con trombosis completa del saco, se detectó su crecimiento en dos (8%), y en los 19 restantes (76%) disminuyó. El control clínico medio fue de 65 meses (intervalo: 1-128 meses). No se detectaron roturas ni síntomas compresivos. El tipo de cirugía resultó ser el único factor estadísticamente significativo (p = 0,04). Conclusiones. La reparación quirúrgica no garantiza la trombosis del aneurisma. El bypass poplíteo-poplíteo muestra mayores garantías en la trombosis del saco aneurismático

Assessment of radiolucent lines in cemented shoulder hemi-arthroplasties: study of concordance and reproducibility

We report on the concordance and reproducibility of the evaluation of radiolucent lines in the humeral component of shoulder arthroplasty. Thirty-two shoulder prostheses were assessed independently, on two occasions, by five observers. The level of inter- and intra-observer agreement was calculated using the kappa statistic. Intra-observer agreement: the overall kappa values ranged from 0 to 0.6, meaning poor, fair and moderate agreement levels. Inter-observer agreement: when the anteroposterior (AP) views were analysed, the values obtained for the bone–cement interface ranged from 0.290 to 0.539, meaning a poor-to-moderate agreement. For the cement–implant interface, the values ranged from 0.064 to 0.684, meaning a poor-to-good agreement. When radiolucent lines of the humeral component were analysed, inter-observer agreement proved to be as low as that obtained when total hip or knee components were analysed. Intra-observer agreement showed better results

Enhanced infection prophylaxis reduces mortality in severely immunosuppressed HIV-infected adults and older children initiating antiretroviral therapy in Kenya, Malawi, Uganda and Zimbabwe: the REALITY trial

Meeting abstract FRAB0101LB from 21st International AIDS Conference 18–22 July 2016, Durban, South Africa. Introduction: Mortality from infections is high in the first 6 months of antiretroviral therapy (ART) among HIV‐infected adults and children with advanced disease in sub‐Saharan Africa. Whether an enhanced package of infection prophylaxis at ART initiation would reduce mortality is unknown. Methods: The REALITY 2×2×2 factorial open‐label trial (ISRCTN43622374) randomized ART‐naïve HIV‐infected adults and children >5 years with CD4 <100 cells/mm3. This randomization compared initiating ART with enhanced prophylaxis (continuous cotrimoxazole plus 12 weeks isoniazid/pyridoxine (anti‐tuberculosis) and fluconazole (anti‐cryptococcal/candida), 5 days azithromycin (anti‐bacterial/protozoal) and single‐dose albendazole (anti‐helminth)), versus standard‐of‐care cotrimoxazole. Isoniazid/pyridoxine/cotrimoxazole was formulated as a scored fixed‐dose combination. Two other randomizations investigated 12‐week adjunctive raltegravir or supplementary food. The primary endpoint was 24‐week mortality. Results: 1805 eligible adults (n = 1733; 96.0%) and children/adolescents (n = 72; 4.0%) (median 36 years; 53.2% male) were randomized to enhanced (n = 906) or standard prophylaxis (n = 899) and followed for 48 weeks (3.8% loss‐to‐follow‐up). Median baseline CD4 was 36 cells/mm3 (IQR: 16–62) but 47.3% were WHO Stage 1/2. 80 (8.9%) enhanced versus 108(12.2%) standard prophylaxis died before 24 weeks (adjusted hazard ratio (aHR) = 0.73 (95% CI: 0.54–0.97) p = 0.03; Figure 1) and 98(11.0%) versus 127(14.4%) respectively died before 48 weeks (aHR = 0.75 (0.58–0.98) p = 0.04), with no evidence of interaction with the two other randomizations (p > 0.8). Enhanced prophylaxis significantly reduced incidence of tuberculosis (p = 0.02), cryptococcal disease (p = 0.01), oral/oesophageal candidiasis (p = 0.02), deaths of unknown cause (p = 0.02) and (marginally) hospitalisations (p = 0.06) but not presumed severe bacterial infections (p = 0.38). Serious and grade 4 adverse events were marginally less common with enhanced prophylaxis (p = 0.06). CD4 increases and VL suppression were similar between groups (p > 0.2). Conclusions: Enhanced infection prophylaxis at ART initiation reduces early mortality by 25% among HIV‐infected adults and children with advanced disease. The pill burden did not adversely affect VL suppression. Policy makers should consider adopting and implementing this low‐cost broad infection prevention package which could save 3.3 lives for every 100 individuals treated