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.

[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.

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.

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.

Older patients with COVID-19 and neuropsychiatric conditions: A study of risk factors for mortality.

BACKGROUND: Little is known about risk factors for mortality in older patients with COVID-19 and neuropsychiatric conditions. METHODS: We conducted a multicentric retrospective observational study at Assistance Publique-Hôpitaux de Paris. We selected inpatients aged 70 years or older, with COVID-19 and preexisting neuropsychiatric comorbidities and/or new neuropsychiatric manifestations. We examined demographics, comorbidities, functional status, and presentation including neuropsychiatric symptoms and disorders, as well as paraclinical data. Cox survival analysis was conducted to determine risk factors for mortality at 40 days after the first symptoms of COVID-19. RESULTS: Out of 191 patients included (median age 80 [interquartile range 74-87]), 135 (71%) had neuropsychiatric comorbidities including cognitive impairment (39%), cerebrovascular disease (22%), Parkinsonism (6%), and brain tumors (6%). A total of 152 (79%) patients presented new-onset neuropsychiatric manifestations including sensory symptoms (6%), motor deficit (11%), behavioral (18%) and cognitive (23%) disturbances, gait impairment (11%), and impaired consciousness (18%). The mortality rate at 40 days was 19.4%. A history of brain tumor or Parkinsonism or the occurrence of impaired consciousness were neurological factors associated with a higher risk of mortality. A lower Activities of Daily Living score (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.58-0.82), a neutrophil-to-lymphocyte ratio ≥ 9.9 (HR 5.69, 95% CI 2.69-12.0), and thrombocytopenia (HR 5.70, 95% CI 2.75-11.8) independently increased the risk of mortality (all p < .001). CONCLUSION: Understanding mortality risk factors in older inpatients with COVID-19 and neuropsychiatric conditions may be helpful to neurologists and geriatricians who manage these patients in clinical practice.

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 and Outcomes of 821 Older Patients With SARS-Cov-2 Infection Admitted to Acute Care Geriatric Wards.

BACKGROUND: There is limited information describing the characteristics and outcomes of hospitalized older patients with confirmed coronavirus disease 2019 (COVID-19). METHOD: We conducted a multicentric retrospective cohort study in 13 acute COVID-19 geriatric wards, from March 13 to April 15, 2020, in Paris area. All consecutive patients aged 70 years and older, with confirmed COVID-19, were enrolled. RESULTS: Of the 821 patients included in the study, the mean (SD) age was 86 (7) years; 58% were female; 85% had ≥2 comorbidities; 29% lived in an institution; and the median [interquartile range] Activities of Daily Living scale (ADL) score was 4 [2-6]. The most common symptoms at COVID-19 onset were asthenia (63%), fever (55%), dyspnea (45%), dry cough (45%), and delirium (25%). The in-hospital mortality was 31% (95% confidence interval [CI] 27-33). On multivariate analysis, at COVID-19 onset, the probability of in-hospital mortality was increased with male gender (odds ratio [OR] 1.85; 95% CI 1.30-2.63), ADL score <4 (OR 1.84; 95% CI 1.25-2.70), asthenia (OR 1.59; 95% CI 1.08-2.32), quick Sequential Organ Failure Assessment score ≥2 (OR 2.63; 95% CI 1.64-4.22), and specific COVID-19 anomalies on chest computerized tomography (OR 2.60; 95% CI 1.07-6.46). CONCLUSIONS: This study provides new information about older patients with COVID-19 who are hospitalized. A quick bedside evaluation at admission of sex, functional status, systolic arterial pressure, consciousness, respiratory rate, and asthenia can identify older patients at risk of unfavorable outcomes.

The wide spectrum of COVID-19 neuropsychiatric complications within a multidisciplinary centre.

A variety of neuropsychiatric complications has been described in association with COVID-19 infection. Large scale studies presenting a wider picture of these complications and their relative frequency are lacking. The objective of our study was to describe the spectrum of neurological and psychiatric complications in patients with COVID-19 seen in a multidisciplinary hospital centre over 6 months. We conducted a retrospective, observational study of all patients showing neurological or psychiatric symptoms in the context of COVID-19 seen in the medical and university neuroscience department of Assistance Publique Hopitaux de Paris-Sorbonne University. We collected demographic data, comorbidities, symptoms and severity of COVID-19 infection, neurological and psychiatric symptoms, neurological and psychiatric examination data and, when available, results from CSF analysis, MRI, EEG and EMG. A total of 249 COVID-19 patients with a de novo neurological or psychiatric manifestation were included in the database and 245 were included in the final analyses. One-hundred fourteen patients (47%) were admitted to the intensive care unit and 10 (4%) died. The most frequent neuropsychiatric complications diagnosed were encephalopathy (43%), critical illness polyneuropathy and myopathy (26%), isolated psychiatric disturbance (18%) and cerebrovascular disorders (16%). No patients showed CSF evidence of SARS-CoV-2. Encephalopathy was associated with older age and higher risk of death. Critical illness neuromyopathy was associated with an extended stay in the intensive care unit. The majority of these neuropsychiatric complications could be imputed to critical illness, intensive care and systemic inflammation, which contrasts with the paucity of more direct SARS-CoV-2-related complications or post-infection disorders.

[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.