Vancomycin toxicity in neonates: a review of the evidence.

PURPOSE OF REVIEW: Vancomycin is a first-line agent in the treatment of serious Gram-positive infections in the neonatal population. The published evidence on vancomycin toxicity in neonates is limited. This review summarizes preclinical studies and clinical trials describing vancomycin toxicity. We discuss proposed pathophysiology and summarize evidence supporting dose-response relationships, genetic and environmental determinants, and consider future research required to further define vancomycin toxicity. RECENT FINDINGS: Current dosing regimens for vancomycin result in subtherapeutic levels in a large proportion of patients. Higher daily doses have been proposed, which have led to concerns regarding increased toxicity. Nephrotoxicity occurs in 1-9% of neonates receiving currently recommended doses. The incidence is highest in those receiving concomitant nephrotoxic drugs. Vancomycin-associated ototoxicity is rare in patients of all ages. Exposure-toxicity relationships in relation to nephrotoxicity and ototoxicity have not been clearly defined in neonates receiving vancomycin. SUMMARY: Current evidence supports the favourable safety profile of vancomycin in neonates. Further studies that address safety concerns relating to high-dose intermittent dosing regimens are needed. Such studies must include robust and standardized definitions of renal and hearing impairment, and include follow-up of sufficient length to establish the long-term implications of experimental findings

International Laboratory Comparison of Influenza Microneutralization Assays for A(H1N1) pdm09, A(H3N2), and A(H5N1) Influenza Viruses by CONSISE

The microneutralization assay is commonly used to detect antibodies to influenza virus, and multiple protocols are used worldwide. These protocols differ in the incubation time of the assay as well as in the order of specific steps, and even within protocols there are often further adjustments in individual laboratories. The impact these protocol variations have on influenza serology data is unclear. Thus, a laboratory comparison of the 2-day enzyme-linked immunosorbent assay (ELISA) and 3-day hemagglutination (HA) microneutralization (MN) protocols, using A(H1N1)pdm09, A(H3N2), and A(H5N1) viruses, was performed by the CONSISE Laboratory Working Group. Individual laboratories performed both assay protocols, on multiple occasions, using different serum panels. Thirteen laboratories from around the world participated. Within each laboratory, serum sample titers for the different assay protocols were compared between assays to determine the sensitivity of each assay and were compared between replicates to assess the reproducibility of each protocol for each laboratory. There was good correlation of the results obtained using the two assay protocols in most laboratories, indicating that these assays may be interchangeable for detecting antibodies to the influenza A viruses included in this study. Importantly, participating laboratories have aligned their methodologies to the CONSISE consensus 2-day ELISA and 3-day HA MN assay protocols to enable better correlation of these assays in the future

Comparing Diet and Exercise Monitoring Using Smartphone App and Paper Diary: A Two-Phase Intervention Study

Background: There is increasing recognition that personalized approaches may be more effective in helping people establish healthier eating patterns and exercise more, and that this approach may be particularly effective in adolescents. Objective: The objective of this study was to investigate the use of a smartphone app (FoodWiz2) in supporting healthy lifestyle choices in adolescence. Methods: Participants (N=34: 11 male, 23 female) aged 16-19 years in full- or part-time education were recruited from sixth form colleges, schools, and other further education establishments in Norfolk and Suffolk, United Kingdom, between February and May 2015. Participants recorded food intake and exercise using a paper diary for 4-5 weeks and then used the app for the same duration. Initial nutrition education and general support were provided during the paper diary use, but the app included personalized messages sent in response to app activity. At the end of each study phase, participants completed an online questionnaire to describe their experience of using the paper diary and app. Results: Record completion declined throughout the study, possibly affected by examination pressure. Food intake data showed increased fruit consumption and significantly reduced consumption of chocolate snacks (P=.01) and fizzy drinks (P=.002) among participants using the app. Questionnaire responses indicated that the app was generally preferred to the paper diary, in particular, the app was seen as less boring to use (P=.03) and more acceptable in social settings (P<.001). Conclusions: This app-based approach has shown the potential for a more effective approach to improving adolescent diet and exercise levels

Comparative uptake of fluoride ion into enamel from various topical fluorides in vitro

The document attached has been archived with permission from the Australian Dental Association (8 March 2008). An external link to the publisher’s copy is included.Background: There are many forms of topical fluoride available today, making the decision as to which is most effective to manage the immediate caries risk problem at hand, very difficult. The objective of this project was to determine the concentration and pattern of fluoride ion uptake into enamel from a variety of categories of topical fluoride recently available in Australia. Methods: Extracted, intact molar teeth were sectioned to provide six plates of smooth surface enamel. Windows of enamel 2 x 6mm were exposed to a variety of topical fluorides for periods simulating those used in vivo. Following drying, the slates of enamel were exposed to 2ml of 0.1M HCl as a chemical biopsy agent for incremental periods of time. The concentrations of fluoride ion in the biopsy solutions for both test and background (control) slates of enamel were determined directly using a fluoride combination selective electrode in conjunction with a high impedance pH meter. Cumulative amounts of fluoride were determined for each topical fluoride agent. Results: The concentrations of fluoride ion taken up into enamel were generally proportional to those present in each agent. However, those from APF gel greatly exceeded the amounts taken up from NaF gel. Also, the concentrations taken up from some of the highly concentrated metal fluorides were surprisingly low. Prior etching of enamel increased uptake and prolonged application of APF gel provided no extra benefit. Conclusions: Some topical fluorides, e.g., APF gel, provided a greatly increased uptake and to a greater depth than other self-application products. However, the frequency of its use should be considered with caution where patients have glassbased restorations.N Pai, J McIntyre, N Tadic and C Laparidi

International Laboratory Comparison of Influenza Microneutralization Assays for A(H1N1)pdm09, A(H3N2), and A(H5N1) Influenza Viruses by CONSISE

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Gender gaps in the path to adulthood for young females and males in six African countries from the 1990s to the 2010s

In this paper, we study on a comparative basis the school-to-work transition of young women and young men in six countries in sub-Saharan Africa, and we examine how this has evolved over recent years, based on the data collected by Demographic and Health Surveys. We examine educational attainments and the nature of early jobs young people are able to obtain, as well as considering their relationship to marriage and fertility outcomes, factors which are likely to be particularly relevant for young women. A pooled regression analysis shows that educational levels have increased substantially and gender gaps have narrowed in most countries. Access to better jobs has improved much more slowly with unchanging gender gaps in most countries, so that agriculture is still the dominant sector of employment for most young men and women. We model correlates of key educational outcomes and access to different types of jobs those controlling for individual- and household-level characteristics, including marital status, presence of children and wealth. Attaining a high level of education is unsurprisingly critical for access to the best jobs and is also associated with young women delaying marriage and childbearing

A frequentist framework of inductive reasoning

Reacting against the limitation of statistics to decision procedures, R. A. Fisher proposed for inductive reasoning the use of the fiducial distribution, a parameter-space distribution of epistemological probability transferred directly from limiting relative frequencies rather than computed according to the Bayes update rule. The proposal is developed as follows using the confidence measure of a scalar parameter of interest. (With the restriction to one-dimensional parameter space, a confidence measure is essentially a fiducial probability distribution free of complications involving ancillary statistics.) A betting game establishes a sense in which confidence measures are the only reliable inferential probability distributions. The equality between the probabilities encoded in a confidence measure and the coverage rates of the corresponding confidence intervals ensures that the measure's rule for assigning confidence levels to hypotheses is uniquely minimax in the game. Although a confidence measure can be computed without any prior distribution, previous knowledge can be incorporated into confidence-based reasoning. To adjust a p-value or confidence interval for prior information, the confidence measure from the observed data can be combined with one or more independent confidence measures representing previous agent opinion. (The former confidence measure may correspond to a posterior distribution with frequentist matching of coverage probabilities.) The representation of subjective knowledge in terms of confidence measures rather than prior probability distributions preserves approximate frequentist validity.Comment: major revisio

Agency, qualia and life: connecting mind and body biologically

Many believe that a suitably programmed computer could act for its own goals and experience feelings. I challenge this view and argue that agency, mental causation and qualia are all founded in the unique, homeostatic nature of living matter. The theory was formulated for coherence with the concept of an agent, neuroscientific data and laws of physics. By this method, I infer that a successful action is homeostatic for its agent and can be caused by a feeling - which does not motivate as a force, but as a control signal. From brain research and the locality principle of physics, I surmise that qualia are a fundamental, biological form of energy generated in specialized neurons. Subjectivity is explained as thermodynamically necessary on the supposition that, by converting action potentials to feelings, the neural cells avert damage from the electrochemical pulses. In exchange for this entropic benefit, phenomenal energy is spent as and where it is produced - which precludes the objective observation of qualia