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.

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.

[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.

[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.

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.

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.

Clinical characteristics of sleep apnea in middle-old and oldest-old inpatients: symptoms and comorbidities.

BACKGROUND: Obstructive sleep apnea (OSA) is prevalent in older adults but still underdiagnosed for many reasons, such as underreported symptoms, non-specific ones because of the comorbidities and polypharmacy, or the social belief of sleep problems as normal with aging. OBJECTIVES: To identify salient symptoms and comorbidities associated with OSA, diagnosed by nocturnal respiratory polygraphy in geriatric inpatients. METHOD: We conducted a retrospective, cross-sectional study in a sample of 102 geriatric inpatients from a French Geriatric University Hospital. We reviewed medical records to collect demographic, medical information including comorbidities, the geriatric cumulative illness rating scale (CIRS-G), subjective sleep-related symptoms and data of overnight level three portable sleep polygraphy recording. RESULTS: Among classic OSA symptoms, only excessive daytime sleepiness (p = 0.02) and nocturnal choking (p = 0.03) were more prevalent in older inpatients with OSA (n = 64) than in those without (n = 38). The prevalence of comorbidities and mean CIRS-G scores were not different between groups except for the lower prevalence of chronic obstructive pulmonary disease and the higher level of creatinine clearance in OSA patients. Multivariate analysis showed OSA was associated with excessive daytime sleepiness (OR = 2.83, p = 0.02) in symptoms-related model and with composite CIRS-G score (OR 1.26, p = 0.04) in comorbidities-related model. CONCLUSIONS: Only excessive daytime sleepiness and comorbidity severity (composite CIRS-G score) were associated with the objective diagnosis of OSA, while other usual clinical OSA symptoms and comorbidities in geriatric inpatients were not. These findings emphasize the importance of excessive daytime sleepiness symptom, when reported in comorbid older patients, strongly suggesting OSA and requiring adequate nocturnal exploration.

Exercise Interventions With Trained Home Helpers for Preventing Loss of Autonomy and Falls in Community-Dwelling Older Adults Receiving Home Heath Physical Therapy T4H: A Randomized Controlled Pilot Study.

BACKGROUND AND PURPOSE: Older adults at risk for falls live independently in the community in their own home and have rehabilitation needs. However, little is known about whether home coaching of older adults can decrease falls at home. We sought to determine whether a novel program for preventing falls and a loss of exercise capacity, the T4H program, in which home helpers act as exercise coaches by using an information technology (IT) device, was acceptable and feasible. METHODS: Between February 2015 and October 2015, we performed a cluster randomized controlled trial in which home helpers either assisted older adults 75 years and over, to participate in the T4H program, or provided standard home help over 3 months. We assessed levels of acceptability and satisfaction among the older adults and home helpers with regard to the exercise program and the technologies used. To measure efficacy, the main outcome measures for the older adults were the absence of falls requiring medical or paramedical care, unplanned hospitalizations, walking ability in a Timed Up and Go test (TUG), and self-care ability by the Barthel Index at the 3-month follow-up visit. RESULTS AND DISCUSSION: Overall, 35 older adults were included, aged 89 years and with 68.6% women. Eighty-five percent of the respondents were pleased or very pleased to have participated in the T4H exercise program, 70% were satisfied with the IT devices, and 92% were satisfied with their home helper's level of involvement. Two of the 4 home helper respondents were satisfied or very satisfied with the exercise program, and 2 were moderately satisfied. The proportions of older adult participants with no falls or no unplanned hospitalizations were higher in the T4H group (92.3% and 85.7%, respectively) than in the control group (81.8% and 71.4%, respectively), although these intergroup differences were not statistically significant. The T4H and control groups did not differ significantly with regard to the TUG time (median [IQR]: 27.6 seconds [17.9-58.6] vs 30.7 seconds [19.7-57.2], respectively) or the Barthel Index (median [IQR]: 90 [75-95] and 90 [75-95], respectively). CONCLUSIONS: The novel T4H home help model was feasible and was associated with a high level of participant satisfaction. We observed a trend toward fewer falls and hospitalizations and better quality of life in the older adults.

[Place of bidirectional endoscopy in the assessment of iron deficiency in the elderly]. / Place des explorations digestives couplées dans le bilan d'une carence martiale chez le sujet âgé.

Iron deficiency is a common pathology in elderly patients. It is most often due to digestive lesions, so we wonder the benefit-risk balance and yield of digestive explorations. The English recommendations recommend that bidirectional endoscopy (esophagogastroduodenoscopy (EGD) and colonoscopy) is performed at the same time, without any upper age limit. In studies conducted in people over 75 years of age, the yield of diagnostic varies between 63 and 68%, which is similar to that of younger people. There is about 40% of the upper lesion and 40% of the lower lesion. The simultaneous discovery of upper and lower digestive lesions represents about 10% of elderly patients. Complications of EGD are rare and mainly related to anaesthesia. The main complication of colonoscopy is perforation and there is a small over-risk of perforation in older patients. This risk is less important when we use computed tomographic colonography. Contraindications of endoscopies are very rare. In case of negative endoscopies, we will wonder if we need further explorations or not.

[Geriatric units at the beginning of the 2020 COVID-19 epidemic in France]. / Les unités de gériatrie au début de l'épidémie du Covid-19 de 2020 en France.

The COVID-19 epidemic that started in November in China became a national epidemic from March 16, 2020 with the declaration of population containment in order to reduce the spread of the virus in France. From March 17 to March 27, 2020, the monitoring unit of the French society of geriatrics and gerontology decided to conduct a survey to analyze the implementation of the mobilization of geriatric units, given that this epidemic had shown that it resulted in excess mortality mainly among the elderly. The survey was able to bring together the response of 34 services, nine of which were located in a high epidemic cluster zone. Dedicated acute geriatric units for patients infected with COVID-19 were present in eight facilities, only outside the cluster zones. Nine geriatric follow-up and rehabilitation services were dedicated, an additional telemedicine activity concerned 35% of the facilities, and family listening and tablet communication facilities concerned 36% of the facilities. This survey is a snapshot of an initial moment in the epidemic. It provides an opportunity to describe the context in which this epidemic occurred in terms of geriatric policy, and to assess the responsiveness and inventiveness of these services in meeting the needs of the elderly.

[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.

[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.

[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.

Evaluation of a prescription support-tool for chronic management of oral antithrombotic combinations in adults using clinical vignettes: protocol of a randomised controlled trial.

INTRODUCTION: Improving the appropriateness of prescriptions of oral antithrombotic (AT) drugs, especially AT combinations, is crucial because these drugs are implicated in bleeding events. We developed a prescription support-tool synthesising guidelines on chronic management of oral AT combinations. Our main objective is to assess the impact of this tool on improving the prescription of oral ATs to comply with guidelines. METHODS AND ANALYSIS: A randomised controlled trial will be conducted among French general practitioners and cardiologists involved in outpatient settings. Physicians will be invited to participate to an online survey by email via physician associations, social networks or word of mouth. They will be randomised to two arms: the experimental arm (access to the prescription support-tool) or the control arm (no prescription support-tool). Then, all participants will be presented three different clinical vignettes illustrating outpatient clinical situations and will be asked to propose prescriptions for each vignette (number of ATs, type, dosage and duration). A computer-generated randomisation scheme implemented in the online survey will be used to allocate physicians to the experimental or control arm and then stratified by medical specialty. The primary outcome will be fully appropriate prescription of oral ATs ie, that comply with the guidelines in terms of number of drugs, drug class, dosage and duration. To demonstrate a 5% increase in this proportion, we will need to include a minimum of 230 physicians per arm. A logistic mixed model with a clinical vignette-effect and a physician-effect nested in the arm of the study will be used. ETHICS AND DISSEMINATION: The Institutional Review Board of Inserm (IRB00003888) approved our research project (no. 18-492). If the prescription support-tool improves the prescription of oral ATs, we will create an interactive web tool and will assess its impact in terms of clinical outcomes in real-life. TRIAL REGISTRATION NUMBER: NCT03630874; Pre-results.

Predisposing and precipitating factors for delirium in community-dwelling older adults admitted to hospital with this condition: A prospective case series.

BACKGROUND: Factors associated with delirium among community-dwelling older adults have been poorly studied. Our aim was to describe the prevalence of predisposing and precipitating factors for delirium among patients admitted for delirium and to assess whether these factors were appropriately recognized at the first patient assessment at hospital. METHODS: Consecutive community-dwelling individuals admitted to three geriatric acute care units with a confirmed initial diagnosis of delirium were prospectively included. An independent investigator recorded, using a predefined form, any acute medical condition considered by the attending geriatrician to be a precipitating factor, at the first patient assessment and at the end of his stay in acute care. RESULTS: A total of 208 patients were included, 80.0% had a pre-existing cognitive or neurological disorder, or both. The most frequent precipitating factor found were infections (49.0% of all patients, mainly lung and urinary tract infections), followed by drugs (30.8%), dehydration (26.4%) and electrolytic disturbances (18.7%, mostly hyponatremia). 91% of patients had a cerebral imagery, but acute neurological conditions were found in only 18.3%. Fewer precipitating factors were found at first than at final assessment (1.4 (95%CI 1.3-1.6) versus 1.9 (95%CI 1.8-2.0) respectively, p<0.001). This difference was significant for all main categories of precipitating factors. CONCLUSIONS: Infections, followed by drugs and hydro-electrolytic disorders seem to be the most frequent precipitating factors for delirium in community-dwelling elderly individuals. Early diagnostic and management of precipitating factors in these patients should be improved, as a significant number of them are missed at the initial assessment.

[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).