The utility of efavirenz-based prophylaxis against HIV infection. A systems pharmacological analysis

Pre-exposure prophylaxis (PrEP) is considered one of the five “pillars” by UNAIDS to reduce HIV transmission. Moreover, it is a tool for female self-protection against HIV, making it highly relevant to sub-Saharan regions, where women have the highest infection burden. To date, Truvada is the only medication for PrEP. However, the cost of Truvada limits its uptake in resource-constrained countries. Similarly, several currently investigated, patent-protected compounds may be unaffordable in these regions. We set out to explore the potential of the patent-expired antiviral efavirenz (EFV) as a cost-efficient PrEP alternative. A population pharmacokinetic model utilizing data from the ENCORE1 study was developed. The model was refined for metabolic autoinduction. We then explored EFV cellular uptake mechanisms, finding that it is largely determined by plasma protein binding. Next, we predicted the prophylactic efficacy of various EFV dosing schemes after exposure to HIV using a stochastic simulation framework. We predicted that plasma concentrations of 11, 36, 1287 and 1486ng/mL prevent 90% sexual transmissions with wild type and Y181C, K103N and G190S mutants, respectively. Trough concentrations achieved after 600 mg once daily dosing (median: 2017 ng/mL, 95% CI:445–9830) and after reduced dose (400 mg) efavirenz (median: 1349ng/mL, 95% CI: 297–6553) provided complete protection against wild-type virus and the Y181C mutant, and median trough concentrations provided about 90% protection against the K103N and G190S mutants. As reduced dose EFV has a lower toxicity profile, we predicted the reduction in HIV infection when 400 mg EFV-PrEP was poorly adhered to, when it was taken “on demand” and as post-exposure prophylaxis (PEP). Once daily EFV-PrEP provided 99% protection against wild-type virus, if ≥50% of doses were taken. PrEP “on demand” provided complete protection against wild-type virus and prevented ≥81% infections in the mutants. PEP could prevent >98% infection with susceptible virus when initiated within 24 h after virus exposure and continued for at least 9 days. We predict that 400 mg oral EFV may provide superior protection against wild-type HIV. However, further studies are warranted to evaluate EFV as a cost-efficient alternative to Truvada. Predicted prophylactic concentrations may guide release kinetics of EFV long-acting formulations for clinical trial design

Earlier egg laying in the barn owl "Tyto alba"

In vier Probeflächen im nördlichen Deutschland wurde übereinstimmend festgestellt, dass sich der Legebeginn in den vergangenen Jahren um 0,43 bis 0,87 Tage je Jahr vorverlegt hat. Dies wird als Reaktion auf die allgemeine Erderwärmung gedeutet.For all four study areas in northern Germany the authors found that egg laying has been advanced for 0,43 to 0,87 d per year. This is interpreted as reaction to the global warming. An English translation of the paper is available at www.kniprath-barn-owl.de

Erste Ergebnisse der Evaluation des Förderprogramms „Mathe macht stark“ für den Anfangsunterricht

Am Ende der vierten Klasse verfügen 20% der Schülerinnen und Schüler in Schleswig-Holstein nur über basale mathematische Kompetenzen (Haag/ Roppelt 2012). Gleichzeitig ist bekannt, dass mathematische Fähigkeiten im Kindergarten oder bei der Einschulung die Mathematikleistung am Ende der Grundschulzeit relativ gut vorhersagen können (Krajewski/ Schneider 2006). Es erscheint deswegen sinnvoll, mit einer Förderung der mathematischen Kompetenzen möglichst früh zu beginnen. Dabei stellt sich die Frage, wie sich ein solches Förderprogramm möglichst wirksam implementieren lässt – auch vor dem Hintergrund, dass bis zu 40% der Grundschullehrkräfte in Schleswig-Holstein Mathematik unterrichten, ohne im Studium Grundlagen zur Mathematik und ihrer Didaktik gelernt zu haben (Stanat et al. 2012). Aus diesem Grund hat das Institut für Qualitätsentwicklung an Schulen in Schleswig-Holstein (IQSH) das Förderprogramm „Mathe macht stark – Grundschule“ entwickelt, implementiert und im Schuljahr 2013/2014 gemeinsam mit dem IPN Kiel eine Evaluationsstudie gestartet. Das Design der Evaluation und erste Ergebnisse werden in diesem Beitrag berichtet

Safety and efficacy of blood exchange transfusion for priapism complicating sickle cell disease.

BACKGROUND: Priapism is unwanted painful penile erection that affects about 36% of boys and men with sickle cell disease (SCD) most of whom have sickle cell anemia. Clinically, priapism could be stuttering, minor, or major. The first two types are mild, last \u3c 4 h, are usually treated at home, have good prognosis with normal sexual function. The major type of priapism lasts \u3e4 h, associated with severe pain, requires hospitalization; often does not respond to medical treatment and may require shunt surgery. Untreated major priapism and surgical intervention often cause impotence. In this study, we report our 15-year experience in treating adult patients with SCD and major priapism with blood exchange transfusion after being refractory to other medical therapies. METHODS: Adult male African Americans patients with SCD and major priapism were enrolled in this study and followed for 15 years. A Haemonitics V-50 machine was initially used for whole blood exchange and was later replaced with Cobe Spectra machine for RBC exchange. RESULTS: We used 239 blood exchanges requiring 1,136 RBC units. We maintained a post-exchange hemoglobin level of about 10 g/dL and hemoglobin S level \u3c 30%. None of the patients had any neurological complications such as headache, seizures, neurological deficits, or obtundation post-exchange. CONCLUSION: Together, the data indicate that blood exchange transfusion for the treatment of patients with SCD and major priapism is efficacious and safe

Critical terms in future studies

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