Importance of cytochrome 3A4 and 2D6-mediated drug-drug interactions in oxycodone consumption among older adults hospitalized for hip fracture: a cross-sectional study.

Hip fracture is a common injury and represents a major health problem with an increasing incidence. In older adults, opioids such as oxycodone are often preferred to other analgesics such as tramadol because of a lower risk of delirium. Different parameters, such as inhibition of cytochrome P450 (CYP450) 2D6 and/or 3A4, can potentially lead to pharmacokinetic variations of oxycodone representing a risk of adverse drugs effects or lack of drug response. There is a risk of drug-drug interactions involving CYP450 in older adults due to the high prevalence of polypharmacy. This study sought to identify patient characteristics that influence oxycodone administration. A single-center observational study included 355 patients with a hip fracture hospitalized in a geriatric postoperative unit. Composite endpoint based on form, duration, and timing to intake separated patients into three groups: "no oxycodone", "low oxycodone ", and "high oxycodone ". CYP450 interactions were studied based on a composite variable defining the most involved CYP450 pathways between CYP2D6 and CYP3A4. CYP450 interactions with CYP2D6 pathway involved were associated with the risk of "high oxycodone" [odds ratio adjusted on age and the type of hip fracture (OR*) 4.52, 95% confidence interval (CI) 1.39-16.83, p = 0.02)], as well as serum albumin levels (OR* 1.09, 95% CI 1.02-1.17, p = 0.01). Cognitive impairment was negatively associated with the risk of "high oxycodone" (OR* 0.38, 95% CI 0.18-0.77, p = 0.02). This study showed an association between CYP2D6 interactions and higher oxycodone consumption indirectly reflecting the existence of uncontrolled postoperative pain.

[COVID-19, state of medical knowledge]. / Covid-19, état des connaissances médicales.

Coronavirus disease 2019 caused one of the largest health crises ever known. It is primarily defined as a viral respiratory infection, and the symptomatology can take various forms, particularly among the elderly population, who are most at risk of severe disease. Despite rapid scientific advances, therapeutics unfortunately are still very limited, especially for this category of patients. The priority is therefore to adopt and comply with preventive measures as far as possible, while awaiting possible progress.

[Normal sensory aging]. / Le vieillissement sensoriel normal.

Normal aging can be defined as the result of the effects of genetic and environmental factors to which subjects are exposed throughout their lives. This process is slow and progressive and must be distinguished from disease. All organs are subject to aging in a physiological way.

[Malnutrition in the elderly, screening and treatment]. / Malnutrition chez la personne âgée, dépister et prendre en charge.

Undernutrition is defined as an imbalance between the body's energy intake and requirements. It is present in 30 to 70% of hospitalised elderly people and its consequences are severe. Systematic screening and early treatment are an integral part of global geriatric care. The aetiological approach must be exhaustive (medico-psychosocial problems) and integrate difficulties related to the physiological ageing of the organism.

[Assessment to carry out with a patient who has suffered a fall]. / Bilan à réaliser devant un patient chuteur.

A fall in an elderly person can lead to severe complications. It is a serious event which must not be minimised in any way and which must serve as a warning signal for the caregiver. The exploration of the factors involved requires a detailed and comprehensive evaluation of the patient. A complete assessment coordinated by a geriatric doctor is recommended.

Acrylamide induces accelerated endothelial aging in a human cell model.

Acrylamide (AAM) has been recently discovered in food as a Maillard reaction product. AAM and glycidamide (GA), its metabolite, have been described as probably carcinogenic to humans. It is widely established that senescence and carcinogenicity are closely related. In vitro, endothelial aging is characterized by replicative senescence in which primary cells in culture lose their ability to divide. Our objective was to assess the effects of AAM and GA on human endothelial cell senescence. Human umbilical vein endothelial cells (HUVECs) cultured in vitro were used as model. HUVECs were cultured over 3 months with AAM or GA (1, 10 or 100 µM) until growth arrest. To analyze senescence, ß-galactosidase activity and telomere length of HUVECs were measured by cytometry and semi-quantitative PCR, respectively. At all tested concentrations, AAM or GA reduced cell population doubling compared to the control condition (p < 0.001). ß-galactosidase activity in endothelial cells was increased when exposed to AAM (≥10 µM) or GA (≥1 µM) (p < 0.05). AAM (≥10 µM) or GA (100 µM) accelerated telomere shortening in HUVECs (p < 0.05). In conclusion, in vitro chronic exposure to AAM or GA at low concentrations induces accelerated senescence. This result suggests that an exposure to AAM might contribute to endothelial aging.