Pharmacokinetics and pharmacodynamics of drug‒drug interactions in hospitalized older adults treated with direct oral anticoagulants.

PURPOSE: Polypharmacy is a frequent situation in older adults that increases the risk of drug-drug interactions (DDIs), both pharmacokinetic (PK) and pharmacodynamic (PD). Direct oral anticoagulants (DOACs) are frequently prescribed in older adults, mainly because of the high prevalence of atrial fibrillation (AF). DOACs are subject to cytochrome P450 3A4 (CYP3A4)- and/or P-glycoprotein (P-gp)-mediated PK DDIs and PD DDIs when co-administered with drugs that interfere with platelet function. The aim of our study was to assess the prevalence of DDIs involving DOACs in older adults and the associated risk factors at admission and discharge. METHODS: This was a cross-sectional study conducted in an acute geriatric unit between January 1, 2018 and December 31, 2022, including patients over 75 years of age treated with DOACs at admission and/or discharge, for whom a comprehensive collection of co-medications was performed. RESULTS: From 909 hospitalizations collected, the prevalence of PK DDIs involving DOACs was 16.9% at admission and 20.7% at discharge, and the prevalence of PD DDIs was 20.7% at admission and 20.2% at discharge. Factors associated with DDIs were bleeding history [adjusted odds ratio (ORa) 1.74, 95% confidence interval (CI) 1.13-2.68], number of drugs > 6 (ORa 2.54, 95% CI 1.88-3.46) and reduced dose of DOACs (ORa 0.39, 95% CI 0.28-0.54) at admission and age > 87 years (ORa 0.74, 95% CI 0.55-0.99), number of drugs > 6 (ORa 2.01, 95% CI 1.48-2.72) and reduced dose of DOACs (ORa 0.41, 95% CI 0.30-0.57) at discharge. CONCLUSION: This study provides an indication of the prevalence of DDIs as well as the profile of DDIs and patients treated with DOACs.

[Proper use of oral anticoagulants in the elderly patient]. / Le bon usage des anticoagulants oraux chez le patient âgé.

Direct oral anticoagulants (DOACs) are tending to supplant antivitamin K inhibitors (VKAs) in their common indications, dominated in elderly patients by atrial fibrillation and venous thromboembolism. Nevertheless, it remains necessary to know how best to use VKAs for which there are still indications. It is also important not to assume that AODs can be prescribed without risk, while ignoring certain particularities in their handling, particularly in the most fragile patients with co-morbidities and multiple medications.

[A geriatric perspective on the sixth IPCC synthesis report]. / Un point de vue gériatrique sur le sixième rapport de synthèse du Giec.

Climate change brings with it many foreseeable consequences for ecosystems and populations, including health consequences that could have a particular impact on older populations. Extreme climatic events, including heat waves, are associated with higher morbidity and mortality among the elderly. Air pollution has a deleterious effect on illnesses associated with aging, or which become more frequent with age. The health consequences of climate change must be anticipated, as they will require the adaptation of healthcare systems, which could be of particular interest to geriatric medicine.

[Intravenous iron supplementation in the elderly patient]. / Supplémentation ferrique par voie intraveineuse chez le patient âgé.

Iron deficiency, absolute or functional, is a common pathology in elderly patients and the way of iron replacement therapy is a recurrent issue. It seems to be necessary to treat by intravenous iron instead of oral therapy because of defective iron absorption or side effects. Depending on the molecule chosen, the modes of administration, whether dilution, dose or rhythm, vary. The major risk of intravenous iron replacement is anaphylaxis, which is very rare, this is why it has to be an hospital administration.

[Strokes and Giant cell arteritis: imaging characteristics]. / AVC et Horton : caractéristiques de l'imagerie.

Giant cell arteritis (GCA) is associated with an increased risk of cardio- or cerebro-vascular death. The stroke rate in patients with GCA varies between 2.7 and 7.4%. The etiological diagnosis may be challenging between atherosclerotic stroke and stroke related to GCA. Case of an old woman who had ischemic stroke and concomitant diagnosis of GCA and brain imaging characteristics.

[Tardive dyskinesia following discontinuation of neuroleptic therapy in 87-year-old patient]. / Dyskinésies tardives et neuroleptiques chez une patiente de 87 ans.

In the absence of a therapeutic alternative, the use of neuroleptics in geriatrics should be limited to the bare minimum, given their potentially serious deleterious effects in frail elderly patients. Dyskinesia is one of their most common side effects. Case of an elderly patient in whom the dyskinesia was revealed following abrupt cessation of a neuroleptic taken in the long term with discussions of the etiological hypotheses of this rare situation, which nevertheless deserve to be known.

[Von Willebrand disease in the elderly]. / Maladie de Willebrand du sujet âgé.

Von Willebrand disease in the elderly. Von Willebrand disease (VWD) is a rare inherited haemorrhagic disorder, the prevalence of symptomatic individuals is around 1/10 000. Von Willebrand factor level increases with advanced age, explaining a lower frequency and a lower severity of cutaneous haemorrhagic symptoms with aging. The management of comorbidities in VWD patients is multidisciplinary, on a case by case basis, taking into account scientific society guidelines and haemostasis expert recommendations. The haemorrhagic risk should be systematically evaluated before an invasive procedure or the start of treatment with anticoagulant or antiplatelet drugs, or before the use of some cancer chemotherapy.

Maladie de Willebrand du sujet âgé. La maladie de Willebrand est une maladie hémorragique rare héréditaire (prévalence des formes symptomatiques : 1/10 000). Le facteur Willebrand augmente physiologiquement avec l'âge, d'où une diminution de la fréquence et de la sévérité de la symptomatologie hémorragique. La prise en charge des comorbidités des patients âgés doit rester multidisciplinaire et se faire au cas par cas, en adaptant les recommandations des sociétés savantes et des spécialistes de l'hémostase. Le risque hémorragique est à évaluer avant toute procédure invasive ou tout traitement pouvant majorer ce risque (anticoagulants, antiagrégants plaquettaires, certaines chimiothérapies anticancéreuses).

[Adaptation of the home, the occupational therapist's assessment]. / Adaptation du domicile, une expertise ergothérapique.

When the functional independence of elderly people starts to diminish, the choice of adapted assistive devices and some simple modifications to the home can allow them to continue to perform their daily tasks safely and easily. Likewise, when physical dependency is established, the choice of relevant assistive devices enables these people to continue living in their home in the right conditions, both for the person concerned as well as for their direct carers. In these different situations, the assessment by the occupational therapist enables the solutions to be adjusted to the capacities, the morphology and the lifestyles of the elderly person.

[Oral administration of medicines in elderly patients and adaptation of galenic forms]. / Prise orale de médicaments chez les patients âgés et adaptations galéniques.

Physiological ageing and pathologies can have an influence on the pharmacology of numerous medicines, leading to serious iatrogenic accidents, polypharmacy and incorrect use of a medicine in elderly people. An observational study carried out in a short-stay geriatric unit focused on the issues surrounding the difficulties the elderly may encounter when taking medicines and the prevalence of the manipulation of galenic forms.

[What happened after meprobamate's withdrawal? Survey in two nursing homes]. / Enquête dans deux Ehpad sur le retrait du méprobamate.

We have conducted in two nursing homes a survey to study the impact of meprobamate's withdrawal, at the beginning of 2012, in terms of extent of prescribing to others psychotropic drugs and occurrence of adverse events. After meprobamate's withdrawal, 65 % of residents did not receive alternative medication and within three months after meprobamate stopping, adverse events (drowsiness, falls and hospitalization) decreased while agitation did not increase.

[Prescription for proton pump inhibitors in geriatrics]. / Prescription des inhibiteurs de la pompe à protons en gériatrie.

Proton pump inhibitors are widely prescribed, notably for the over 65s, despite there being significant side effects in the geriatric population. It is therefore important that doctors, caregivers and patients are fully aware of the recognised indications of PPIs and on the less well-known problems inherent to their prescription.

Prevalence and factors associated with inappropriate dosing of apixaban and rivaroxaban in hospitalized older adults with atrial fibrillation: a cross-sectional study.

INTRODUCTION: Atrial fibrillation (AF) is a common condition among older adults, requiring anticoagulation therapy to prevent thromboembolic events. Direct oral anticoagulants (DOACs) are now recommended as first-line therapy for this purpose. Apixaban and rivaroxaban are two direct-factor Xa inhibitors whose dosing is based on various factors (age, weight, creatinine, and creatinine clearance) that can affect the pharmacokinetics of the medication. This study aimed to evaluate factors associated with inappropriate dosing of apixaban or rivaroxaban based on the summary of product characteristics. METHODS: A retrospective, single-center study included 777 hospitalizations of patients treated with apixaban or rivaroxaban for AF between 1 January 2018 and 31 December 2022. Primary endpoint assessed whether the dose of apixaban or rivaroxaban was within the summary of product characteristics used by European Medicine Agency (EMA). RESULTS: Inappropriate dosing of apixaban or rivaroxaban is noted for approximately 30% of hospitalizations mostly underdosing. Factors associated with the risk of inappropriate dosing were the presence of cognitive impairment [adjusted odds ratio (OR*) 1.65, 95% confidence interval (CI) 1.19-2.29, p value (p) = 0.002], weight per kilogram increase (OR* 1.03, 95% CI 1.01-1.04, p < 0.0001), and history of bleeding under apixaban or rivaroxaban (OR* 1.94, 95% CI 1.24-3.03, p = 0.003). CONCLUSION: This study highlighted the high prevalence of inappropriate apixaban or rivaroxaban doses in older adults, particularly underdosing, which increases the risk of thromboembolism.

[Management of oral anticoagulants by elderly patients at home]. / Gestion des anticoagulants oraux au domicile par les patients âgés.

Improving the management of a vitamin K antagonist (VKA) treatment helps to reduce the risk of haemorrhage. To assess the treatment methods and the quality of education of elderly patients, a telephone survey was carried out in 2011 of 100 patients treated with a VKA. The patients, or main carers managing the treatment at home, have adequate knowledge of their treatment. The education of elderly patients therefore seems to be a reasonable and viable objective.

Lumbar puncture training with healthcare simulation improves self-confidence and practical skills of French medical residents in geriatrics.

PURPOSE: To assess the skill level and self-confidence of medical residents in geriatrics with regard to conducting the lumbar puncture (LP) procedure and to study the potential benefits of training with simulation and virtual reality. METHODS: First, a questionnaire survey was conducted among all French residents in geriatrics in the Paris area to assess their knowledge and self-confidence regarding the practice of LP in older adults. Second, we set up a simulation LP training session combined with virtual reality (3D video) training for selected respondents of the first survey. Third, we performed post-simulation survey for the attendees of the simulation training. Finally, a follow-up survey was conducted to examine the change in self-confidence and the success rate in clinical practice. RESULTS: Fifty-five residents responded to the survey (response rate = 36.4%). The importance of mastering LP was fully recognized by the residents in geriatrics (95.3%), so most of them (94.5%) advocated for the need for additional practical training. Fourteen residents took part in the training (average rating = 4.7 on a 5-point scale). Simulation was regarded by 83% of the respondents as the most useful tool for their practice. We observed a significant pre/post-training mean improvement in self-estimated success of 20.6% (Wilcoxon matched-pairs signed-rank W = - 36, p = 0.008). The post-training success rate of the residents in real-life clinical practice was good (85.8%). CONCLUSION: Residents were aware of the importance of mastering LP and requested additional training. Simulation may represent a major driver to improve their self-confidence and practical skills.

Assessment of DOAC in GEriatrics (Adage Study): Rivaroxaban/Apixaban Concentrations and Thrombin Generation Profiles in NVAF Very Elderly Patients.

BACKGROUND: Although a growing number of very elderly patients with atrial fibrillation (AF), multiple conditions, and polypharmacy receive direct oral anticoagulants (DOACs), few studies specifically investigated both apixaban/rivaroxaban pharmacokinetics and pharmacodynamics in such patients. AIMS: To investigate: (1) DOAC concentration-time profiles; (2) thrombin generation (TG); and (3) clinical outcomes 6 months after inclusion in very elderly AF in-patients receiving rivaroxaban or apixaban. METHODS: Adage-NCT02464488 was an academic prospective exploratory multicenter study, enrolling AF in-patients aged ≥80 years, receiving DOAC for at least 4 days. Each patient had one to five blood samples at different time points over 20 days. DOAC concentrations were determined using chromogenic assays. TG was investigated using ST-Genesia (STG-ThromboScreen, STG-DrugScreen). RESULTS: We included 215 patients (women 71.1%, mean age: 87 ± 4 years), 104 rivaroxaban and 111 apixaban, and 79.5% receiving reduced-dose regimen. We observed important inter-individual variabilities (coefficient of variation) whatever the regimen, at C max [49-46%] and C min [75-61%] in 15 mg rivaroxaban and 2.5 mg apixaban patients, respectively. The dose regimen was associated with C max and C min plasma concentrations in apixaban (p = 0.0058 and p = 0.0222, respectively), but not in rivaroxaban samples (multivariate analysis). Moreover, substantial variability of thrombin peak height (STG-ThromboScreen) was noticed at a given plasma concentration for both xabans, suggesting an impact of the underlying coagulation status on TG in elderly in-patients. After 6-month follow-up, major bleeding/thromboembolic event/death rates were 6.7%/1.0%/17.3% in rivaroxaban and 5.4%/3.6%/18.9% in apixaban patients, respectively. CONCLUSION: Our study provides original data in very elderly patients receiving DOAC in a real-life setting, showing great inter-individual variability in plasma concentrations and TG parameters. Further research is needed to understand the potential clinical impact of these findings.

[Sleep apnea syndrome and cognitive impairment]. / Syndrome d'apnées du sommeil et troubles cognitifs.

The sleep apnoea syndrome is a common disorder, unrecognised in the elderly. Several studies have shown that it can cause or exacerbate cognitive impairment, mainly related to attention, memory and learning and adaptation abilities. However, continuous positive airway pressure treatment appears to be effective on these cognitive disorders, including in elderly patients.Accordingly, the sleep apnoea syndrome can be a conceivable diagnostic as part of the cognitive deterioration check-up in elderly patients.

[Hodgkin lymphoma in the elderly]. / Le lymphome de Hodgkin chez le sujet âgé

We report a case of Hodgkin's lymphoma in a patient aged 75, presenting with acute cardiopulmonary insufficiency, hospitalized in a geriatrics ward. The deterioration of his general condition and the discovery of several lymph nodes led us to perform an aspiration of a lymph node and a bone marrow biopsy. Reed-Sternberg cells, pathognomonic of Hodgkin's disease were identified on the smears and biopsy sections. Due to the poor condition of the patient, it was decided not to treat with chemotherapy. The diagnostic approach and treatment strategy of Hodgkin's disease are summarized in this paper, especially the particular features of the disease in the elderly.

[Management of complications with antivitamin K in elderly people]. / Gestion des accidents des antivitamines K chez la personne âgée.

latrogenic complications with antivitamin K (AVK) largely entail haemorrhages, apparently more frequent in the elderly. Recent French and North American recommendations are available and must be widely circulated, in community practices as well as hospitals, in order to improve the treatment of overdoses and/or haemorrhagic accidents under AVK.

Bidirectional endoscopy in the assessment of iron deficiency in the elderly.

Iron deficiency is a common pathology in elderly patients. It is most often due to lesions in the digestive tract, which raises the issue of benefit/risk balance and yield from investigation. Current UK guidelines recommend that bidirectional endoscopy (oesophago-gastro-duodenoscopy and colonoscopy) is performed synchronously, with no upper age limit. In studies conducted in people over 75 years of age, the diagnostic yield varies between 63 and 68%, which is similar to that in younger people, with approximately 40% revealing upper lesions and 40% lower lesions. Approximately 10% of elderly patients show upper and lower digestive lesions at the same time. Complications as a result of oesophago-gastro-duodenoscopy are rare and mainly related to anaesthesia. The main complication of colonoscopy is perforation and there is a slightly higher risk of perforation in older patients. This risk is less significant for computed tomographic colonography. Contraindications of endoscopies are very rare. When endoscopy is negative, this raises the question of whether further investigations should be pursued.