ABSTRACT
Sleeping enough is associated with a reduced risk of mortality and dementia. New evidence support regular physical exercise, including at home, as a corner stone intervention to prevent falls and fractures. In contrast, supplementation with high doses of vitamin D is ineffective and even deleterious in this indication and a routine screening in asymptomatic adults is not recommended. Several studies illustrate our difficulties in prescribing and deprescribing in frail older patients and a study suggests that statins in cardiovascular primary prevention should considered only when a patient's life expectancy exceeds 2.5 years. Finally, several studies have fueled the debate about screening for hearing impairment.
Dormir ni trop ni trop peu est associé à une réduction du risque de mortalité et de déclin cognitif. De nouvelles études confirment que l'exercice physique régulier, y compris à domicile, constitue la clé de voûte de la prévention des chutes et des fractures. Par contre, la supplémentation par de hautes doses de vitamine D n'est pas efficace, voire délétère, dans cette indication et le dépistage systématique d'un déficit n'est pas recommandé chez les patients adultes asymptomatiques. Plusieurs études illustrent nos difficultés à prescrire et déprescrire, chez les patients âgés fragiles, et une étude suggère qu'un traitement de statines en prévention cardiovasculaire primaire ne se justifie que si l'espérance de vie du patient dépasse 2,5 ans. Finalement, plusieurs études sont venues nourrir le débat sur le dépistage de la presbyacousie.
Subject(s)
Fractures, Bone , Vitamin D , Accidental Falls/prevention & control , Adult , Aged , Exercise , Humans , VitaminsABSTRACT
Pediatric drug development is hampered by biological, clinical, and formulation challenges associated with age-based populations. A primary cause for this lack of development is the inability to accurately predict ontogenic changes that affect pharmacokinetics (PK) in children using traditional preclinical animal models. In response to this issue, our laboratory has conducted a proof-of-concept study to investigate the potential utility of juvenile pigs to serve as surrogates for children during preclinical PK testing of selected rifampin dosage forms. Pigs were surgically modified with jugular vein catheters that were externalized in the dorsal scapular region and connected to an automated blood sampling system (PigTurn-Culex-L). Commercially available rifampin capsules were administered to both 20 and 40 kg pigs to determine relevant PK parameters. Orally disintegrating tablet formulations of rifampin were also developed and administered to 20 kg pigs. Plasma samples were prepared from whole blood by centrifugation and analyzed for rifampin content by liquid chromatography-tandem mass spectrometry. Porcine PK parameters were determined from the resultant plasma-concentration time profiles and contrasted with published rifampin PK data in human adults and children. Results indicated significant similarities in dose-normalized absorption and elimination parameters between pigs and humans. Moreover, ontogenic changes observed in porcine PK parameters were consistent with ontogenic changes reported for human PK. These results demonstrate the potential utility of the juvenile porcine model for predicting human pediatric PK for rifampin. Furthermore, utilization of juvenile pigs during formulation testing may provide an alternative approach to expedite reformulation efforts during pediatric drug development.