BACKGROUND: There are limited data on the outcomes of rechallenge with anti-tuberculosis therapy (ATT) following anti-tuberculosis drug-induced liver injury (AT-DILI) in a high HIV prevalence setting OBJECTIVES: To describe the outcomes of rechallenge with first-line ATT METHOD: Hospitalised participants with AT-DILI who were enrolled into a randomised controlled trial of N-acetylcysteine in Cape Town, South Africa, were followed up until completion of ATT rechallenge. We described rechallenge outcomes, and identified associations with recurrence of liver injury on rechallenge (positive rechallenge RESULTS: Seventy-nine participants were rechallenged of whom 41 (52%) were female. Mean age was 37 years (standard deviation [s.d.] ±10). Sixty-eight (86%) were HIV-positive, of whom 34 (50%) were on antiretroviral therapy (ART) at time of AT-DILI presentation. Five participants had serious adverse reactions to an aminoglycoside included in the alternate ATT regimen given after first-line ATT interruption: acute kidney injury in three and hearing loss in two. The median time from first-line ATT interruption to start of first-line ATT rechallenge was 13 days (interquartile range [IQR]: 8-18 days). Antiretroviral therapy was interrupted for a median of 32 days (IQR: 17-58) among HIV-positive participants on ART before AT-DILI. Fourteen participants had positive rechallenge (18%). Positive rechallenge was associated with pyrazinamide rechallenge (P = 0.005), female sex (P = 0.039) and first episode of tuberculosis (TB) (P = 0.032 CONCLUSION: Rechallenge was successful in most of our cohort. Pyrazinamide rechallenge should be carefully considered

Rilpivirine, a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), is included as an option in first-line antiretroviral therapy (ART) for antiretroviral-naïve individuals in treatment guidelines in high-income countries, including the United States and many European countries. Rilpivirine is available in a single-tablet fixed-dose combination, has a favourable tolerability profile and is of relatively low cost. However, rilpivirine has reduced efficacy in patients commencing ART at high viral loads. Therefore, baseline viral load testing is required before commencing rilpivirine, and it is not recommended for patients commencing therapy with a viral load greater than 100 000 copies/mL. Rilpivirine is not included in the treatment regimens recommended by the World Health Organization (WHO), which form the basis of treatment guidelines in many lower- and middle-income countries. Some patients commencing standard first-line regimens experience treatment-limiting toxicity. A low-cost rilpivirine-containing fixed-dose combination would potentially be a useful addition to treatment options available in South Africa and other countries in the region, for patients who do not tolerate standard first-line ART. In this article, we explore the utility of rilpivirine as an option in ART in South Africa and the region in the context of current public-sector regimens. We consider what role rilpivirine might play if first-line therapy moves to a dolutegravir-based regimen, as has already happened in some lower- and middle-income countries, including Botswana, Kenya and Brazil. Finally, we describe emerging evidence for rilpivirine in the prevention of HIV transmission.

Introduction: Cerebellar mutism syndrome refers to the muteness (lack of speech) that follows lesions of the cerebellum. It’s characterized by a late onset, limited duration, and in some cases long-term language sequelae. Its pathogenesis it s not clear yet, but it has been attributed a role to a damage of the dentate nucleus and of the dento-rubro-thalamic tract. Objectives: Identify potential risk factors (clinical or anatomical) to predict the onset of cerebellar mutism after posterior fossa surgery Compare, using MRI analysis and DTI tractography, the integrity of the dento-rubro-thalamic tract in patients with and without cerebellar mutism. Methods: Prospective follow up study of patients operated of posterior fossa tumors between November 2012 and 2013. We performed a study with DTI of the dento rubro thalamic tract in pacients with and without postoperative mutism. Results: 53 patients under the diagnosis of posterior fossa tumor underwent surgical resection. 5 pacients presented postoperative mutism (9,4%). There was a significant association between postoperative medulloblastoma diagnosis and postoperative mutism. Tumor volume was not significant. The volume of left and right dento rubro thalamic tract were significantly lower in patients with cerebellar mutism. The fractional anisotropy of the right superior cerebellar peduncle was also lower in patients with postoperative mutism. Conclusions: The postoperative cerebellar mutism is a relevant complication after a posterior fossa surgery. Our study supports the role of dento rubro thalamic tract damage in the pathogenesis of this syndrome. Special care must be taken during surgery to prevent damage to this tract.

Introducción: El síndrome mutismo cerebeloso consiste en falta del habla posterior a lesiones del cerebelo. Se caracteriza por inicio tardío, duración limitada, y ocasionalmente secuelas lingüísticas. Su patogenia no está clara, pero se ha atribuido un rol a daños en el núcleo dentado y en la vía dento-rubro-talámica. Objetivos: Identificar posibles factores de riesgo (clínicos o anatómicos) asociados a la aparición de mutismo cerebeloso después de una cirugía de fosa posterior. Comparar, mediante un análisis de resonancia magnética (IRM) y tractografía por tensor de difusión (DTI), la integridad de la vía dento-rubro-talámica en pacientes con y sin mutismo cerebeloso. Métodos: Estudio prospectivo de pacientes operados por tumores de fosa posterior entre noviembre de 2012 y 2013. Se analizó con DTI la vía dento-rubro-talámica en pacientes con y sin mutismo postoperatorio. Se comparó la volumetría del tracto en ambas cohortes. Resultados: Cincuenta y tres pacientes con diagnóstico de tumor de fosa posterior fueron sometidos a cirugía de exéresis. Cinco pacientes presentaron mutismo postoperatorio (9,4%). Hubo una asociación significativa entre el diagnóstico de meduloblastoma y mutismo postoperatorio. El volumen tumoral no fue significativo. El volumen de la vía dento-rubro-talámica fue significativamente menor en pacientes con mutismo, en forma bilateral, así como la anisotropía fraccional del pedúnculo cerebeloso derecho. Conclusiones: El mutismo cerebeloso es una complicación relevante después de una cirugía de fosa posterior. Nuestro estudio apoya el papel del daño de la vía dento-rubro-talámica en la patogénesis de este síndrome. Se debe tener especial cuidado durante la cirugía para prevenir daños al núcleo dentado.

Background: In recent years, otic thermometers to measure body temperature in children have become increasingly popular as they reflect changes in body temperature sooner than other thermometers. The have become valuable assets in hospital emergency rooms; however, their accuracy and reliability need further studies. Objective: To compare corporal temperature readings between an otic thermometer and mercury axillary and rectal thermometers. Patients and Method: 50 patients under the age of 5, who were treated at the emergency room of our hospital, were randomly chosen to participate in this study. Temperature was measured on their right and left ears using an otic thermometer, and their rectal and right axillary temperature was taken using mercury thermometers. Patients were separated into 2 subgroups for comparison, children under and over 6 months old. Results: The results between the 2 subgroups were very similar. The average temperature obtained by rectal thermometers was 0.414°C higher than the average right-ear temperature (p < 0.001) and 0.438°c higher than the average left-ear temperature (p < 0.001). Conclusion: The otic thermometer's reading is significantly lower than the one obtained using mercury rectal and axillary thermometers.

Introducción: En los últimos años han aparecido nuevos métodos para medir la temperatura en niños, como el termómetro digital ótico. Siendo este un método más rápido para medir la temperatura y por lo tanto ideal para el servicio de urgencias, es necesario conocer su confiabilidad. Objetivo: Comparar los valores de temperatura corporal que entrega el termómetro ótico digital con los termómetros de mercurio axilar y rectal. Pacientes y Método: Se efectuó la medición de la temperatura en 50 pacientes menores de 5 años elegidos al azar, que consultaron en el Servicio de Urgencia del Hospital de Niños y Cunas de Viña del Mar. Se les midió la temperatura con un termómetro digital ótico al lado izquierdo y derecho, y las temperaturas axilar derecha y rectal con termómetros de mercurio. EL análisis de los resultados se efectuó en el grupo estudiado, separado en dos grupos, menores y mayores de 6 meses. Resultados: Los resultados entre ambos subgrupos fueron los mismos. La temperatura media rectal obtenida fue 0,414°C más alta que la media ótica derecha (p < 0,001) y 0,438°C más alta que la temperatura media ótica izquierda (p < 0,001). Conclusión: El termómetro ótico digital entrega una temperatura significativamente más baja que la que entregan los termómetros de mercurio axilar y rectal.

The prevalence of hepatitis B virus (HBV) infection in 1 765 HIVpositive patients in rural Eastern Cape was 7.1%. This is lower than the previously reported rural prevalence and is similar to urban prevalence. Male sex and baseline alanine aminotransferase (ALT) were significant predictors of HBV status. Most HBV-positive patients had normal baseline ALT, making ALT an insensitive screening test for HBV status.

In this paper, the genetic transformation of somatic embryos of mango cv. 'Ataulfo' with the Bell pepper J1 defensin gene was performed. In vitro tests showed that protein extracts from processed embryos inhibited the growth of Colletotrichum gloeosporioides, Aspergillus niger and Fusarium sp. In contrast, protein extracts from embryos without change did not affect the growth of fungi. These results, together with the amplification of J1 and nptII genes of the genomic DNA, show the incorporation and expression of the transgene in the embryos.

En el presente trabajo se realizó la transformación genética de embriones somáticos de mango cv. 'Ataulfo con el gen de la defensina J1 de chile pimiento. En ensayos in vitro se demostró que extractos proteicos de embriones transformados inhibieron el crecimiento de Colletotrichum gloeosporioides, Aspergillus niger y Fusarium sp. En contraste, extractos proteicos de embriones sin transformar no afectaron el crecimiento de los hongos. Estos resultados, junto con la amplificación de los genes J1 y nptII del ADN genómico, nos indican la incorporación y la expresión del transgen en los embriones.

BACKGROUND: Many drugs are eliminated by the kidneys and therefore may require dose adjustment in patients with renal impairment. The need for dose adjustment is frequently neglected by prescribers. METHODS: We reviewed folders of patients admitted to the Groote Schuur Hospital general medical wards between January and March 2008. Patients with renal impairment, defined as an estimated glomerular filtration rate (eGFR) <50 ml per minute per 1.73 m², were identified. In-patient prescriptions were captured if they were written after clinical notes indicated impaired renal function, or >1 day after renal function tests were performed. We determined what proportion of these prescriptions required dose adjustment and whether drug doses were appropriately adjusted. RESULTS: We found renal impairment in 32% (97/301) of medical admissions. There were 615 prescription entries for the 97 patients with renal impairment. Dose adjustment was required in 19% (117/615) of prescription entries, and only 32% (37/117) of these prescription entries were correctly dose adjusted. Of 97 patients, 69 received one or more drugs that required dose adjustment (median 1, range 1 - 5). All drug doses were correctly adjusted in 12% (8/69) of patients. Importantly, in the majority of patients (59% (41/69)) no doses had been correctly adjusted. CONCLUSION: Consistent with international studies, drug dose adjustment in patients with renal impairment in a South African hospital was frequently neglected. Strategies to alert clinicians of the need for dose adjustment in renal impairment should be considered, including automated eGFR reporting and computerised aids to guide drug dosing, that account for renal impairment.

OBJECTIVE: To describe province-wide outcomes and temporal trends of the Western Cape Province antiretroviral treatment (ART) programme 5 years since inception, and to demonstrate the utility of the WHO monitoring system for ART. METHODS: The treatment programme started in 2001 through innovator sites. Rapid scaling-up of ART provision began early in 2004, located predominantly in primary-care facilities. Data on patients starting ART were prospectively captured into facility-based registers, from which monthly cross-sectional activity and quarterly cohort reports were aggregated. Retention in care, mortality, loss to follow-up and laboratory outcomes were calculated at 6-monthly durations on ART. FINDINGS: By the end of March 2006, 16 234 patients were in care. The cohort analysis included 12 587 adults and 1709 children. Women accounted for 70% of adults enrolled. After 4 and 3 years on ART respectively, 72.0% of adults (95% confidence interval, CI: 68.0-75.6) and 81.5% (95% CI: 75.7-86.1) of children remained in care. The percentage of adults starting ART with CD4 counts less than50 cells/µl fell from 51.3% in 2001 to 21.5% in 2005, while mortality at 6 months fell from 12.7% to 6.6%, offset in part by an increase in loss to follow-up (reaching 4.7% at 6 months in 2005). Over 85% of adults tested had viral loads below 400 copies/ml at 6-monthly durations until 4 years on ART. CONCLUSION: The location of care in primary-care sites in this programme was associated with good retention in care, while the scaling-up of ART provision was associated with reduced early mortality.

OBJETIVO: Describir los resultados y las tendencias temporales a escala provincial del programa de tratamiento antirretroviral (TAR) de la Provincia de El Cabo Occidental a los 5 años de su puesta en marcha y demostrar la utilidad del sistema de vigilancia de la OMS para el TAR. MÉTODOS: El programa de tratamiento dio comienzo en 2001 a partir de establecimientos innovadores. La rápida expansión del suministro de TAR comenzó a principios de 2004 y se centró predominantemente en los servicios de atención primaria. Los datos sobre los pacientes que comenzaron el TAR se reunieron de forma prospectiva en los registros de los centros, a partir de los cuales se elaboraron informes mensuales transversales de actividad e informes trimestrales de cohortes. La retención en el sistema de atención, la mortalidad, las pérdidas para el seguimiento y las variables de laboratorio se calcularon considerando los periodos de 6 meses de TAR. RESULTADOS: Al final de marzo de 2006 se estaba tratando a 16 234 pacientes. El análisis de cohortes abarcó a 12 587 adultos y 1709 niños. Las mujeres representaban el 70% de todos los adultos estudiados. Al cabo de 4 y 3 años de TAR, respectivamente, el 72,0% de los adultos (intervalo de confianza del 95%, IC95%: 68,0-75,6) y el 81,5% (IC95%: 75,7-86,1) de los niños seguían atendidos. El porcentaje de adultos que comenzaron el TAR con recuentos de CD4 inferiores a 50 células/µl cayó del 51,3% en 2001 al 21,5% en 2005, mientras que la mortalidad a 6 meses cayó del 12,7% al 6,6%, compensada en parte por un aumento de las pérdidas para el seguimiento (que alcanzó el 4,7% a los 6 meses en 2005). Más del 85% de los adultos analizados presentaron cargas virales inferiores a 400 copias/ml a intervalos de 6 meses durante los 4 años de TAR. CONCLUSIÓN: La ubicación de la asistencia en los centros de atención primaria en este programa se asoció a una buena retención de los pacientes, mientras que la expansión del TAR se asoció a una disminución de la mortalidad temprana.

OBJECTIF: Décrire les résultats à l'échelle provinciale et les tendances dans le temps du programme de traitement antirétroviral (ART) de la province du Cap-Occidental, 5 ans après son lancement et démontrer l'utilité du système de surveillance de l'OMS pour ce traitement. MÉTHODS: Le programme de traitement a débuté en 2001 au niveau de sites « novateurs ». Un rapide passage à l'échelle supérieure de la délivrance du traitement a commencé début 2004, à partir essentiellement d'établissement de soins de santé primaire. Des données relatives aux patients entamant un traitement ART ont été recueillies de manière prospective dans les registres des établissements de soins, ce qui a permis de constituer des rapports mensuels d'activité et des rapports trimestriels de cohorte. Les taux de rétention sous traitement et de mortalité, ainsi que les nombres de perdus pour le suivi et les résultats de laboratoire ont été calculés tous les 6 mois sous ART. RÉSULTATS: Fin mars 2006, 16 234 patients étaient sous traitement. L'analyse de cohorte a porté sur 12 587 adultes et 1709 enfants. Les femmes représentaient 70 % des adultes inclus dans l'étude. Après 4 et 3 ans sous traitement ART, respectivement 72,0 % des adultes (intervalle de confiance à 95 % : 68,0-75,6) et 81,5 % des enfants (IC à 95 % : 75,7-86,1) étaient encore sous traitement. Le pourcentage des adultes débutant le traitement ART avec une numération des CD4 inférieure à 50 cellules/µl est tombé de 51,3 % en 2001 à 21,5 % en 2005, tandis que la mortalité à 6 mois passait de 12,7 % à 6,6 %, baisse en partie compensée par l'augmentation du nombre de perdus pour le suivi (atteignant 4,7 % à 6 mois en 2005). Plus de 85 % des adultes dépistés présentaient une charge virale inférieure à 400 copies/ml tous les 6 mois jusqu'à 4 ans sous ART. CONCLUSION: La dispensation par ce programme des soins dans des sites de soins de santé primaire était associée à un taux de rétention satisfaisant, tandis que l'élargissement du programme était associé à une réduction de la mortalité précoce.