Place of bidirectional endoscopy in the assessment of iron deficiency in the elderly

International audienceIron 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) be 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 upper lesion and 40% of 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 anesthesia. 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.La carence martiale est une pathologie fréquente chez les patients âgés. Elle est le plus souvent due à des lésions digestives et se pose donc la question de la balance bénéfice-risque et de la rentabilité des explorations digestives chez les patients âgés.Les recommandations anglaises préconisent de réaliser des explorations digestives couplées (fibroscopie oeso-gastro-duodénale (FOGD) et coloscopie) dans le même temps, sans qu’il n’existe de limite d’âge supérieur. Dans les études réalisées chez les plus de 75 ans, la rentabilité diagnostique varie entre 63 et 68 %, ce qui est semblable à celle chez les plus jeunes, avec environ 40 % de lésions hautes et de lésions basses. La découverte simultanée de lésions digestives hautes et basses représente environ 10 % des patients âgés. Les complications de la FOGD sont rares et essentiellement liées à l’anesthésie, tandis qu’il existe un petit sur-risque de perforation chez les plus âgés, moins important en cas de coloscanner. Les contre-indications aux endoscopies digestives sont exceptionnelles. En cas d’endoscopies négatives se posera la question de la poursuite ou non des explorations

Assessment of DOAC in GEriatrics (ADAGE study): rivaroxaban/apixaban concentrations and thrombin generation profiles in NVAF very elderly patients

International audienceBackground: Although a growing number of very elderly patients with atrial fibrillation (AF), multiple conditions and polypharmacy, receive direct oral anticoagulants (DOAC), few studies specifically investigated both apixaban/rivaroxaban pharmacokinetics and pharmacodynamics in such patients. Aims: To investigate: i/DOAC concentration-time profiles; ii/thrombin generation (TG); and iii/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 1-5 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, 79.5% receiving reduced-dose regimen. We observed important inter-individual variabilities (CV) whatever the regimen, at Cmax [49-46%] and Cmin [75-61%] in 15mg-rivaroxaban and 2.5mg-apixaban patients, respectively. Dose regimen was associated with Cmax and Cmin 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/thrombo-embolic 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 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

International audienceBackground: 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

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

International audienceBackground: There is limited information describing the characteristics and outcomes of hospitalized older patients with confirmed coronavirus disease 2019 (COVID-19).Methods: 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, 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 to 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 to 2.63), ADL score < 4 (OR, 1.84; 95% CI, 1.25 to 2.70), asthenia (OR, 1.59; 95% CI, 1.08 to 2.32), quick Sequential Organ Failure Assessment score ≥ 2 (OR, 2.63; 95% CI, 1.64 to 4.22) and specific COVID-19 anomalies on chest computerized tomography (OR, 2.60; 95% CI, 1.07 to 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

Empirical antibiotic therapy modalities for Enterobacteriaceae bloodstream infections in older patients and their impact on mortality: a multicentre retrospective study

International audiencePurpose: Enterobacteriaceae (EB) bloodstream infections (BSI) are frequent and serious in older patients. Physicians are faced with the dilemma of prescribing early appropriate empirical antibiotics to limit the risk of death, and sparing broad-spectrum antibiotic prescription. The aim of the study was to assess the rate of appropriate empirical antibiotics prescription to treat EB BSI in older patients and its impact on survival.Methods: This study conducted in 49 centres enrolled retrospectively up to the 10 last consecutive patients aged 75 years and over and treated for EB BSI. Factors related to in-hospital death were investigated using logistic regression.Results: Among the 487 enrolled patients (mean age 86 ± 5.9 years), 70% had at least one risk factor of being infected by third-generation cephalosporins (3GC)-resistant strain; however, only 13.8% of EB strains were resistant to 3GC. An empirical antimicrobial treatment was initiated for 418 patients (85.8%), and for 86% (n = 360/418) of them, it was considered appropriate. In-hospital mortality was 12.7% (n = 62) and was related to the severity of infection (OR 3.17, CI 95% 1.75-5.75), while a urinary portal of entry was protective (OR 0.34, CI 95% 0.19-0.60). Neither the absence of nor inappropriate empirical antibiotics prescription was associated with increased mortality.Conclusion: While patients enrolled in this study were at risk of being infected by multidrug-resistant bacteria, yet mainly treated with 3GC, empirical antibiotics prescription was appropriate in most cases and did not influence mortality

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

International audienceA 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

The cerebral network of COVID-19-related encephalopathy: a longitudinal voxel-based 18F-FDG-PET study

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Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Correction: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

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