Dihydroartemisinin-Piperaquine and Artemether-Lumefantrine for Treating Uncomplicated Malaria in African Children: A Randomised, Non-Inferiority Trial

BACKGROUND: Artemisinin combination therapies (ACTs) are currently the preferred option for treating uncomplicated malaria. Dihydroartemisinin-piperaquine (DHA-PQP) is a promising fixed-dose ACT with limited information on its safety and efficacy in African children. METHODOLOGY/PRINCIPAL FINDINGS: The non-inferiority of DHA-PQP versus artemether-lumefantrine (AL) in children 6-59 months old with uncomplicated P. falciparum malaria was tested in five African countries (Burkina Faso, Kenya, Mozambique, Uganda and Zambia). Patients were randomised (2:1) to receive either DHA-PQP or AL. Non-inferiority was assessed using a margin of -5% for the lower limit of the one-sided 97.5% confidence interval on the treatment difference (DHA-PQP vs. AL) of the day 28 polymerase chain reaction (PCR) corrected cure rate. Efficacy analysis was performed in several populations, and two of them are presented here: intention-to-treat (ITT) and enlarged per-protocol (ePP). 1553 children were randomised, 1039 receiving DHA-PQP and 514 AL. The PCR-corrected day 28 cure rate was 90.4% (ITT) and 94.7% (ePP) in the DHA-PQP group, and 90.0% (ITT) and 95.3% (ePP) in the AL group. The lower limits of the one-sided 97.5% CI of the difference between the two treatments were -2.80% and -2.96%, in the ITT and ePP populations, respectively. In the ITT population, the Kaplan-Meier estimate of the proportion of new infections up to Day 42 was 13.55% (95% CI: 11.35%-15.76%) for DHA-PQP vs 24.00% (95% CI: 20.11%-27.88%) for AL (p<0.0001). CONCLUSIONS/SIGNIFICANCE: DHA-PQP is as efficacious as AL in treating uncomplicated malaria in African children from different endemicity settings, and shows a comparable safety profile. The occurrence of new infections within the 42-day follow up was significantly lower in the DHA-PQP group, indicating a longer post-treatment prophylactic effect. TRIAL REGISTRATION: Controlled-trials.com ISRCTN16263443

Main results of the Ouabain and Adducin for Specific Intervention on Sodium in Hypertension Trial (OASIS-HT): a randomized placebo-controlled phase-2 dose-finding study of rostafuroxin

Background. The Ouabain and Adducin for Specific Intervention on Sodium in Hypertension (OASIS-HT) Trial was a phase 2 dose-finding study of rostafuroxin, a digitoxygenin deivative, which selectively antagonizes the effects of endogenous ouabain (EO) on Na+,K+-ATPase and mutated adducin. Rostafuroxin lowered blood pressure (BP) in some animal models and in humans. Methods. OASIS-HT consisted of 5 concurrently running double-blind cross-over studies. After 4 weeks without treatment, 435 patients with uncomplicated systolic hypertension (140-169 mm Hg) were randomized to rostafuroxin (0.05, 0.15, 0.5, 1.5 or 5.0 mg/d) or matching placebo, each treatment period lasting 5 weeks. The primary endpoint was the reduction in systolic office BP. Among the secondary endpoints were diastolic office BP, 24 h ambulatory BP, plasma EO concentration and renin activity, 24-h urinary sodium and aldosterone excretion, and safety. ANOVA considered treatment sequence (fixed effect), subjects nested within sequence (random), period (fixed), and treatment (fixed). Results. Among 410 analyzable patients (40.5% women; mean age, 48.4 years), the differences in the primary endpoint (rostafuroxin minus placebo) ranged from -0.18 mm Hg (P=0.90) on 0.15 mg/d rostafuroxin to 2.72 mm Hg (P=0.04) on 0.05 mg/d. In the 5 dosage arms combined, the treatment effects averaged 1.30 mm Hg (P=0.03) for systolic office BP; 0.70 mm Hg (P=0.08) for diastolic office BP; 0.36 mm Hg (P=0.49) for 24-h systolic BP; and 0.05 mm Hg (P=0.88) for 24-h diastolic BP. In the 2 treatment groups combined, systolic (-1.36 mm Hg) and diastolic (-0.97 mm Hg) office BPs decreased from week 5 to 10 (P for period effect ≤=0.028), but carry-over effects were not significant (P≥=0.11). All other endpoints were not different on rostafuroxin and placebo. Minor side-effects occurred with similarly low frequency on rostafuroxin and placebo. Conclusions. In 5 concurrently running double-blind cross-over studies rostafuroxin did not reduce BP at any dose. Trial Registration: NCT00415038 http://www.clinicaltrials.gov)

Acidentes de trânsito no Brasil de 1998 a 2010: muitas mudanças e poucos resultados

The paper describes the situation of road traffic accidents in Brazil since 1998, when a new Brazilian traffic law was approved, up to the year 2010. A review of both academic and non-academic literature was carried out, including journals (both indexed and non-indexed), technical reports, author searches, searches in paper reference lists and direct contact with researchers. The main problems related to road traffic accidents in Brazil identified were the increase in the absolute number of deaths and in the mortality rates, a rapid increase in the number of motorcycles, and drink & driving. Influent authors in the field and centers of expertise were identified. Some potential solutions are presented by the authors, who suggest that the public offices related to traffic regulation and control are not taking suitable measures for control and reduction of road traffic accidents.O artigo descreve a situação dos acidentes de trânsito no Brasil, desde a implementação do Código de Trânsito Brasileiro de 1998 até o ano de 2010. Foi realizada análise dos principais trabalhos científicos e publicações não acadêmicas nacionais. A revisão de literatura incluiu periódicos indexados, não indexados, relatórios técnicos, busca específica por autores, referências bibliográficas de artigos e contato com pesquisadores. Os principais problemas do trânsito brasileiro identificados foram aumento do número absoluto de mortos e das taxas de mortalidade, ampliação da frota de motocicletas e o uso de álcool. Foram identificados autores influentes e ilhas de produção de conhecimento nas áreas pesquisadas. Os autores apresentam algumas possíveis soluções e sugerem que o poder público não tem assumido a responsabilidade que lhe cabe no controle e redução dos acidentes de trânsito.El articulo describe la situación de los accidentes de tránsito en Brasil, desde la implementación del Código de Transito Brasileño de 1998 hasta el año de 2010. Se realizó análisis de los principales trabajos científicos y publicaciones no académicas nacionales. La revisión de literatura incluyó periódicos indexados, no indexados, informes técnicos, búsqueda especifica por autores, referencias bibliográficas de artículos y contacto con investigadores. Los principales problemas de tránsito brasileño identificados fueron aumento del número absoluto de muertos y de las tasas de mortalidad, ampliación de la flota de motocicletas y el uso de alcohol. Se identificaron autores influyentes e islas de producción de conocimiento en las áreas investigadas. Los autores presentaban algunas posibles soluciones y sugieren que el poder público no ha asumido la responsabilidad que le cabe en el control y reducción de los accidentes de tránsito