Combination of probenecid-sulphadoxine-pyrimethamine for intermittent preventive treatment in pregnancy

The antifolate sulphadoxine-pyrimethamine (SP) has been used in the intermittent prevention of malaria in pregnancy (IPTp). SP is an ideal choice for IPTp, however, as resistance of Plasmodium falciparum to SP increases, data are accumulating that SP may no longer provide benefit in areas of high-level resistance. Probenecid was initially used as an adjunctive therapy to increase the blood concentration of penicillin; it has since been used to augment concentrations of other drugs, including antifolates. The addition of probenecid has been shown to increase the treatment efficacy of SP against malaria, suggesting that the combination of probenecid plus SP may prolong the useful lifespan of SP as an effective agent for IPTp. Here, the literature on the pharmacokinetics, adverse reactions, interactions and available data on the use of these drugs in pregnancy is reviewed, and the possible utility of an SP-probenecid combination is discussed. This article concludes by calling for further research into this potentially useful combination

A saturated map of common genetic variants associated with human height

Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes(1). Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel(2)) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants

Current evidence on intradermal influenza vaccines administered by Soluvia\u2122 licensed micro injection system

Among the several strategies explored for (1) the enhancement of the immune response to influenza immunization, (2) the improvement of the vaccine acceptability and (3) the overcoming of the egg-dependency for vaccine production, intradermal administration of influenza vaccine emerges as a promising alternative to conventional intramuscular route, thanks to the recent availability of new delivery devices and the perception of advantages in terms of immunogenicity, safety, reduction of antigen content and acceptability. Data from clinical trials performed in children, adults < 60 y and elderly people and post-marketing surveillance demonstrate that actually, licensed intradermal influenza vaccines, Intanza\u2122 9 and 15 \ub5g and Fluzone\u2122 Intradermal, administered by the microinjection system Soluvia\u2122, show an excellent acceptability, tolerability and safety profile. Formulations containing 9 and 15 \u3bcg per strain demonstrate, respectively, comparable and superior immunogenicity than conventional intramuscular vaccines. Licensed intradermal influenza vaccines can be considered a valid alternative to standard intramuscular vaccination offering significant advantages in low-responder populations and helping to increase influenza vaccination coverage rates especially in people with fear of needles or high apprehension associated with annual vaccination

Long-term follow-up of children with benign abducens nerve palsy

PurposeBenign abducens nerve palsy is rare in childhood. Diagnosis is made by exclusion, and the severe underlying pathologies have to be ruled out. The aim of our study was to present the largest single-center series of patients with the longest period of follow-up to confirm the benign nature of this entity.Patients and methodsWe carried out a retrospective study of 12 consecutive children with benign abducens nerve palsy. All children underwent a careful orthoptic and ophthalmic examination during acute presentation and follow-up.ResultsPainless palsies were associated with a preceding infection or immunization in five patients. The left eye was affected in nine children and no bilateral case was found. No sex differences were seen. Recovery was observed within 6 months in all cases, and ipsilateral recurrences occurred in three children. Three children required strabismus surgery. None of the patients developed long-term recurrences or neurological abnormalities during a mean follow-up of more than 9 years.ConclusionsOur data support earlier findings, such as painless and predominately left-sided occurrence, spontaneous recovery within 6 months, and ipsilateral recurrence. In contrast to much of the literature, we did not find a female preponderance. Exclusion of severe causes and close follow-up is mandatory for these patients. As none of the patients developed long-term recurrences or neurological sequelae, this entity can be regarded as a benign condition without malignant associations or complications