Quantifying breast milk intake by term and preterm infants for input into paediatric physiologically based pharmacokinetic models

Despite the many benefits of breast milk, mothers taking medication are often uncertain about the risks of drug exposure to their infants and decide not to breastfeed. Physiologically based pharmacokinetic models can contribute to drug‐in‐milk safety assessments by predicting the infant exposure and subsequently, risk for toxic effects that would result from continuous breastfeeding. This review aimed to quantify breast milk intake feeding parameters in term and preterm infants using literature data for input into paediatric physiologically based pharmacokinetic models designed for drug‐in‐milk risk assessment. Ovid MEDLINE and Embase were searched up to July 2, 2019. Key study reference lists and grey literature were reviewed. Title, abstract and full text were screened in nonduplicate. Daily weight‐normalized human milk intake (WHMI) and feeding frequency by age were extracted. The review process retrieved 52 studies. A nonlinear regression equation was constructed to describe the WHMI of exclusively breastfed term infants from birth to 1 year of age. In all cases, preterm infants fed with similar feeding parameters to term infants on a weight‐normalized basis. Maximum WHMI was 152.6 ml/kg/day at 19.7 days, and weighted mean feeding frequency was 7.7 feeds/day. Existing methods for approximating breast milk intake were refined by using a comprehensive set of literature data to describe WHMI and feeding frequency. Milk feeding parameters were quantified for preterm infants, a vulnerable population at risk for high drug exposure and toxic effects. A high‐risk period of exposure at 2–4 weeks of age was identified and can inform future drug‐in‐milk risk assessments.     

18F-AV1451 PET imaging and multimodal MRI changes in progressive supranuclear palsy

Journal of Neurology - Progressive supranuclear palsy (PSP) is characterized by deposition of straight filament tau aggregates in the grey matter (GM) of deep nuclei and cerebellum. We examined the...     

Debugging Adaptive Deep Brain Stimulation for Parkinson's Disease

Deep brain stimulation (DBS) is a successful treatment for patients with Parkinson's disease. In adaptive DBS, stimulation is titrated according to feedback about clinical state and underlying pathophysiology. This contrasts with conventional stimulation, which is fixed and continuous. In acute trials, adaptive stimulation matches the efficacy of conventional stimulation while delivering about half the electrical energy. The latter means potentially fewer side-effects. The next step is to determine the long-term efficacy, efficiency, and side-effect profile of adaptive stimulation, and chronic trials are currently being considered by the medical devices industry. However, there are several different approaches to adaptive DBS, and several possible limitations have been highlighted. Here we review the findings to date to ascertain how and who to stimulate in chronic trials designed to establish the long-term utility of adaptive DBS. © 2020 International Parkinson and Movement Disorder Society     

Pydiflumetofen Co-Formulated with Prothioconazole: A Novel Fungicide for Fusarium Head Blight and Deoxynivalenol Control

Fusarium head blight (FHB) is an important disease of small grain cereals worldwide, resulting in reduced yield and quality as well as the contamination of harvested grains with mycotoxins. The key mycotoxin of concern is deoxynivalenol (DON), which has legislative and advisory limits in numerous countries. Cereal growers have a number of control options for FHB including rotation, cultivation, and varietal resistance; however, growers are still reliant on fungicides applied at flowering as part of an IPM program. Fungicides currently available to control FHB are largely restricted to triazole chemistry. This study conducted three field experiments to compare a new co-formulation of pydiflumetofen (a succinate dehydrogenase inhibitor (SDHI) with the tradename ADEPIDYN^™) and prothioconazole (a triazole) against current standard fungicides at various timings (flag leaf fully emerged, mid-head emergence, early flowering, and late flowering) for the control of FHB and DON. Overall, the co-formulation showed greater efficacy compared to either pydiflumetofen alone or current fungicide chemistry. This greater activity was demonstrated over a wide range of spray timings (flag leaf fully emerged to late flowering). The availability of an SDHI with good activity against FHB and the resulting DON contamination of harvested grain will give growers an additional tool within an IPM program that will provide a greater flexibility of spray application windows and reduce fungicide resistance selection pressure.