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Geraldine Poenou,1 Teona Dimitru Dimitru,1– 3 Ludovic Lafaie,4,5 Valentine Mismetti,5,6 Marco Heestermans,5,7 Laurent Bertoletti1,5,8 1Therapeutic and Vascular Medicine Department, University Hospital of Saint Etienne, Saint Etienne, France; 2Internal Medicine Department, University Hospital Santa Lucía, Cartagena, Murcia, Spain; 3Catholic University San Antonio, Murcia, Spain; 4Geriatric Department, University Hospital of Saint Etienne, Saint Etienne, France; 5INSERM, UMR1059, Haemostasis and Vascular Dysfunction Team, Jean Monnet University, Saint-Etienne, F-42055, France; 6Pneumology Department, University Hospital of Saint Etienne, Saint Etienne, France; 7Auvergne-Rhône-Alpes French Blood Donation Agency, Saint-Etienne, F-42100, France; 8INSERM, CIC-1408, University Hospital of Saint Etienne, Saint Etienne, FranceCorrespondence: Laurent Bertoletti, Therapeutic and Vascular Medicine Department, University Hospital of Saint Etienne, Saint Etienne, France, Tel +33477827771, Fax +33477820482, Email Laurent.bertoletti@gmail.comAbstract: During the past decade, emergence of direct oral anticoagulants (DOACs) has drastically improved the prevention of thrombosis. However, several unmet needs prevail in the field of thrombosis prevention, even in the DOACs’ era. The use of DOACs is still constrained and the drugs cannot be administered in every clinical scenario, such as an increased anticoagulant-associated bleeding risk, particularly in some specific populations (cancer – notably those with gastrointestinal or genitourinary cancer – and frail patients), the impossibility to be used in certain patients (eg, end-stage kidney failure during hemodialysis, pregnancy and breastfeeding), and their lack of efficacy in certain clinical scenarios (eg, mechanical heart valves, triple-positive antiphospholipid syndrome). Efforts to find a factor that upon antagonization prevents thrombosis but spares haemostasis have resulted in the identification of coagulation factor XI (FXI) as a therapeutic target. After briefly recapitulating the role of factor XI in the balance of haemostasis, we propose a narrative review of the key data published to date with compounds targeting factor XI to prevent thrombosis as well as the main ongoing clinical studies, opening up prospects for improving the care of patients requiring thrombosis prevention.Keywords: FXI inhibitor, venous thromboembolic events, thromboprophylaxis, anticoagulant, clinical trials

Background: Data on patients aged 90 or older are rare. This study aims to describe clinical characteristics, treatment strategies, and clinical outcomes (rates of VTE recurrence, major bleeding, and mortality), during the first 3 months of anticoagulant treatment for VTE, depending on the treatment period., Methods: We analyzed data from RIETE, an ongoing global observational registry of patients with objectively confirmed acute VTE, grouped in 5-year intervals (2004-2008, 2009-2013, 2014-2018, and 2019-2023)., Results: Among 3477 patients aged 90 or older, clinical characteristics have changed over time (less heart failure, more dementia), with an increase in PE diagnoses from 57% in 2004-2008 to 69% in 2019-2023 (p-trends <0.001), but of lower severity. For long-term therapy, there was an increase in patients receiving DOACs (p-trends <0.001), with a decrease in patients on VKAs (p-trends <0.001). Mortality and fatal PE respectively showed a temporal trend: 19% and 4% in 2004-2008 to 15% (p-trends 0.026) and 2% (p-trends 0.002) in 2019-2023. In multivariable analyses, fatal PE declined from 2004 to 2023 (HR: 0.91; 95% CI: 0.87-0.96). Compared with VKAs, receiving LMWH during the first 3 months of anticoagulation was associated with a higher risk of major bleeding (HR: 1.91; 95% CI: 1.16-3.14) and death (HR: 2.20; 95% CI: 1.71-2.82). The effect seems to be the opposite for DOACs (HR: 0.50; 95% CI: 0.20-1.30 for major bleeding; HR: 0.86; 95% CI: 0.57-1.28 for all-cause death)., Conclusions: Fatal PE declined from 2004 to 2023, despite an increase in the diagnosis of PE. Since the arrival of DOACs, there seems to be better management of the therapeutic and diagnostic aspects of VTE in this population, underlining the need for further research on patients aged 90 or older., (© 2024 The American Geriatrics Society.)

Acquired deforming hypertonia (ADH) affects the daily care of numerous nursing home residents. The aim of this study was to analyze the practice, aims, and effectiveness of botulinum toxin injections (BTxis) in the treatment of older patients with contractures, an indication for which BTxis are still underused. Data were extracted retrospectively from medical records regarding population, contractures, and injections. A prospective analysis was conducted to evaluate treatment goals set by goal attainment scaling (GAS) at T0 and at T1, to evaluate the therapeutic effects. We also recorded the occurrence of side effects, using a telephone questionnaire. This study included 41 patients older than 70 years who had received one or more BTxis for the first time between January 2018 and December 2021. Most of the older people we included lived in an institution (66%), manifested severe dependence, and presented significant morbi-mortality (37% of the patients died in the year after the last injection). The main objectives of these injections were purely comfort, without any functional goals. The GAS scores suggested effectiveness for comfort GAS scores. No complications were recorded. This study highlights the BTxis potential to address the needs of a larger number of older patients with ADH.

Primary dose reduction (PDR) in the first course of chemotherapy is an empirical practice, commonly used in older population. Patients over 70 years old receiving a first course of chemotherapy for a solid tumor were enrolled. A total of 179 patients were included. Standard dose was used in 69.8% of patients, while 30.2% received PDR of chemotherapy. Only 29.6% received a standardized geriatric assessment. Patients receiving standard doses presented 83.2% of toxicities, while 68% of toxicities were reported in patients receiving PDR. The toxicity rate was significantly decreased in patients treated with reduced first-cycle dose of chemotherapy.

Background: Age is a major risk factor for venous thromboembolism (VTE), yet patients aged ≥90 years are under-represented in clinical trials of anticoagulant therapy. The objectives were to describe and compare patient clinical characteristics, treatments, and outcomes (VTE recurrence, bleeding, and mortality) during the first 3 months of anticoagulation between VTE patients aged ≥90 years and those aged <90 years., Methods: We analyzed data from the Registro Informatizado Enfermedad TromboEmbὀlica (RIETE), an ongoing global observational registry of patients with objectively confirmed acute VTE., Results: From January 2001 to October 2022, 96,701 patients were registered in RIETE, of whom 3262 (3.4%) were aged ≥90 years. Patients aged ≥90 years were less likely to be men, and to have experienced cancer or recent surgery, but more likely to manifest immobility, chronic heart failure, anemia, renal insufficiency, or dementia than those aged <90 years. Most (99.6%) patients aged ≥90 years were receiving anticoagulant therapy. During the first 3 months, 26 patients aged ≥90 years developed VTE recurrences, 116 experienced major bleeding, and 564 died. Among patients initially presenting with pulmonary embolism (PE), deaths due to PE exceeded those due to fatal bleeding (76 vs. 19). Among those initially presenting with isolated deep-vein thrombosis (DVT), it was the reverse (2 vs. 11 deaths)., Conclusions: In patients aged ≥90 years, the difference in the outcome of anticoagulant treatment depending on the initial presentation of VTE could suggest a need for different management approaches. Clinical trials evaluating the optimal duration of anticoagulation according to initial VTE presentation are warranted to limit excess deaths in this particular population., (© 2023 The American Geriatrics Society.)

Direct oral anticoagulants against activated factor X and thrombin were the last milestone in thrombosis treatment. Step by step, they replaced antivitamin K and heparins in most of their therapeutic indications. As effective as the previous anticoagulant, the decreased but persistent risk of bleeding while using direct oral anticoagulants has created space for new therapeutics aiming to provide the same efficacy with better safety. On this basis, drug targeting factor XI emerged as an option. In particular, cancer patients might be one of the populations that will most benefit from this technical advance. In this review, after a brief presentation of the different factor IX inhibitors, we explore the potential benefit of this new treatment for cancer patients.

Vaccination coverage is insufficient for influenza, pneumococcus, and herpes zoster in people over the age of 65 in France, even though these are common infectious diseases. Using a computerised questionnaire, the aim of our study was to assess the knowledge of general practitioners, geriatricians, infectious diseases specialists and interns in the Loire region about the vaccination against these three diseases in elderly subjects, to identify the obstacles to vaccination, and to evaluate whether the provision of knowledge modifies the prescriptions and vaccination recommendations made to patients. Of the 125 responses from doctors and interns, 90.2 % are correct for influenza, 69.2 % for pneumococcus, and 32.8 % for herpes zoster, with no significant difference between specialities. By providing information, practitioners are more willing to vaccinate their patients against influenza (99 %), pneumococcus (93 %), and herpes zoster (39 %). The main obstacles to vaccination are the patient's refusal (85 %), the doctor's lack of knowledge and time (70 % and 41 % respectively), doubts about the vaccine's effectiveness (28 %), and fear of side effects (21 %).

The management (diagnostic and therapeutic) of cancer in the geriatric population involves a number of complex difficulties. The aim of this study was to assess the impact of a medical specialty on the diagnostic and therapeutic management of elderly cancer patients. Four clinical scenarios of cancer in the geriatric population, with a dedicated survey to gather information regarding each clinical case's diagnostic and therapeutic approaches, as well as the different criteria influencing physicians' therapeutic decisions, were exposed to geriatricians, oncologists, and radiotherapists in Saint-Etienne. The surveys were filled out by 13 geriatricians, 11 oncologists, and 7 radiotherapists. There was a homogeneity of responses regarding the confirmation of cancer diagnostics in the elderly. There were strong disparities (inter- and intra-specialties) for several clinical situations regarding the therapeutic management of cancer. There were significant disparities in terms of surgical management, the implementation of a chemotherapy protocol, and the adaptation of the chemotherapy dosage. Contrary to oncologists, who primarily consider the G8 and the Karnofsky score, geriatric autonomy scores and frailty with cognitive assessment were the key factors determining diagnostic/therapeutic therapy for geriatricians. These results raise important ethical questions, requiring specific studies in geriatric populations to provide the homogenous management of elderly patients with cancer.

Rationale: The ARS finance geriatric hotlines in order to improve the articulation between town medicine and the hospital. The objective of our study is to describe the health status and the care pathway of subjects aged over 75 years hospitalised in a geriatric short stay hospital via a geriatric hotline., Materials and Methods: This prospective multicentre study included 1,451 subjects over 24 months. The primary endpoint was the average length of stay. The secondary endpoints were medico-socio-demographic data., Results: The population hospitalised via a hotline is comparable to that usually found in geriatric short stay services. The length of stay is correlated with the lifestyle and the mode of discharge (p < 0.001). There was a significant excess risk of non-return to the previous place of residence according to age, average length of stay, comorbidities and degree of dependence., Conclusion: The care pathway for elderly people over 75 years old hospitalised through the hotline is optimised, with an average length of stay of 14 days, demonstrating a good link between town medicine and hospital. This approach allows for the early management of elderly subjects in the geriatric care system.

Direct oral anticoagulants (DOACs) are now an option in the prevention and treatment of venous thromboembolic events (VTE) in patients with active cancer. Pharmacokinetics of DOACs are largely influenced by efflux transporters derived from ABC transporters, notably by P-glycoprotein (P-gp). The aim of this study was to assess the potential P-gp-mediated drug-drug interactions between 11 tyrosine kinase inhibitors (TKIs) with apixaban and rivaroxaban. Bidirectional permeabilities of apixaban and rivaroxaban were investigated across MDCK-MDR1 models, to determine half maximal inhibitory concentration (IC 50 ). Several categories of interaction risks based on IC 50 values can be distinguished depending on the TKI and DOAC used. IC 50 values of less than 10 μM were observed with the combination of erlotinib, nilotinib with both DOACs, and with dabrafenib and apixaban. IC 50 values between 10 and 100 μM were seen for axitinib, crizotinib, dasatinib, imatinib, and lapatinib with apixaban, and for axitinib, crizotinib, dabrafenib, idelalisib, imatinib, and vemurafenib with rivaroxaban. A risk of drug-drug interaction was found in vitro between TKIs and DOACs. In vivo pharmacokinetic studies are needed to ensure the safety of prescribing DOACs in cancer patients on TKI therapy, in order to avoid major, potentially preventable bleeding events., (© 2022 Société Française de Pharmacologie et de Thérapeutique.)

In cancer patients, pulmonary embolism (PE) is the second leading cause of death after the cancer itself, most likely because of difficulties in diagnosing the disease due to its nonclassical presentation. The risk of PE recurrence and possibly the case-fatality rate depends on whether the patient presents a symptomatic PE, an unsuspected PE, a subsegmental PE, or a catheter-related PE. Choosing the best therapeutic option is challenging and should consider the risk of both the recurrence of thrombosis and the occurrence of bleeding. The purpose of this review is to provide an overview of the clinical characteristics and the treatment of cancer-associated PE, which could benefit clinicians to better manage the deadliest form of thrombosis associated with cancer. After a brief presentation of the epidemiological data, we will present the current attitude towards the diagnosis and the management of cancer patients with PE. Finally, we will discuss the perspectives of how the medical community can improve the management of this severe medical condition.

Background: The time-course response after a single injection of botulinum toxin (BoNT) for post-stroke spasticity is debated. We addressed this issue by conducting a systematic review and a pharmacodynamic model-based meta-analysis., Methods: We searched Medline, PeDro and Google Scholar databases up to March 2020, selecting randomized controlled trials of post-stroke and traumatic brain injury patients with arm or leg muscle hypertonia, comparing BoNT to placebo, or different BoNT preparations. The main outcome was change in Modified Ashworth Scale (MAS) score. A non-linear mixed effect model was used to estimate maximal toxin and placebo effects (Emax and EPlacebo), the effect disappearance half-life (T1/2off) of BoNT and the doses achieving 50 and 80% of Emax (D50 and D80). The equivalence ratios between different BoNT preparations were calculated from D50 values. Adverse events were recorded., Results: Altogether, 2,236 unique records were screened by 2 independent reviewers: 35 eligible trials including 3011 patients (95% post-stroke) were identified. For all BoNT preparations, the BoNT Emax of -1.11 (95% credible interval -1.31; -0.29) was reached at 5 weeks; the maximal placebo effect was -0.30 (-0.37; -0.22). Both D50 and D80 differed significantly by muscle volume. At D50, the equivalence ratio was significantly higher for abobotulinumtoxinA (3.35) than onabotulinumtoxinA and lower for letibotulinumtoxinA (0.41). T1/2off was longer for abobotulinumtoxinA than for onabotulinumtoxinA and the other preparations (13.1 weeks [95% credible interval 7.7; 19.3] vs 8.6 weeks [7.1; 10.1]). Adverse events were minor, with a weak, but significant, dose-response relation for muscle weakness., Conclusions: This first pharmacodynamic model-based meta-analysis of individuals with stroke revealed that for all BoNT-A preparations, BoNT-A injections to treat spasticity have maximal effect at 5 weeks. The T1/2off was longer for abobotulinumtoxinA than other preparations. Differences between certain BoNT unit scales were also confirmed., Competing Interests: Declaration of Competing Interest Pascal Giraux and Etienne Ojardias received meeting sponsorship from Allergan, Ipsen, and Merz and compensation for consulting from Merz. Etienne Ojardias received through his institution a research support grant from Merz. Pascal Giraux is a co-founder of the Dessintey company. The other authors declare no conflict of interest., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Introduction: Management of venous thromboembolic events (VTE) has been completely changed after the introduction of direct oral anticoagulants (DOAC). VTE is common in the geriatric population, but the management of DOACs remains complex because of the lack of specific data in this polymedicated fragile population.An exhaustive search of anticoagulants in the indication of VTE was performed on PubMed, including data from clinical trials, observational studies, real-world data, drug-drug interaction studies, as well as various guidelines from scientific societies., Areas Covered: The present review aims to summarize our current knowledge on the era of DOACs in the management of VTE in the elderly. This involves learning the pharmacokinetics/pharmacodynamics of drugs specific to geriatrics, the problem of drug-drug interactions, and the main randomized clinical trials validating the use of DOACs., Expert Opinion: DOACs have become an essential part of the management of VTE in the elderly, both for their efficacy and safety. However, we are faced with a list of unmet needs, such as the relevance of DOACs in the very elderly, cancer patients, and those with renal impairment. Clinicians and pharmacists must remain cautious about comedications, as well as about the patient's comorbidities.

Faced with an aging French population, the demand for unscheduled care is growing. In order to avoid referring elderly patients to emergency departments, which are unsuitable for them, the Regional Health Agencies have created telephone hot lines dedicated to geriatrics. They are exclusively accessible to general practitioners in order to obtain advice or a place in a geriatric hospital. General practitioners are rarely asked about the value of this tool in their practice., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Vitamin D may be a central biological determinant of COVID-19 outcomes. The objective of this quasi-experimental study was to determine whether bolus vitamin D3 supplementation taken during or just before COVID-19 was effective in improving survival among frail elderly nursing-home residents with COVID-19. Sixty-six residents with COVID-19 from a French nursing-home were included in this quasi-experimental study. The "Intervention group" was defined as those having received bolus vitamin D3 supplementation during COVID-19 or in the preceding month, and the "Comparator group" corresponded to all other participants. The primary and secondary outcomes were COVID-19 mortality and Ordinal Scale for Clinical Improvement (OSCI) score in acute phase, respectively. Age, gender, number of drugs daily taken, functional abilities, albuminemia, use of corticosteroids and/or hydroxychloroquine and/or antibiotics (i.e., azithromycin or rovamycin), and hospitalization for COVID-19 were used as potential confounders. The Intervention (n = 57; mean ± SD, 87.7 ± 9.3years; 79 %women) and Comparator (n = 9; mean, 87.4 ± 7.2years; 67 %women) groups were comparable at baseline, as were the COVID-19 severity and the use of dedicated COVID-19 drugs. The mean follow-up time was 36 ± 17 days. 82.5 % of participants in the Intervention group survived COVID-19, compared to only 44.4 % in the Comparator group (P = 0.023). The full-adjusted hazard ratio for mortality according to vitamin D3 supplementation was HR = 0.11 [95 %CI:0.03;0.48], P = 0.003. Kaplan-Meier distributions showed that Intervention group had longer survival time than Comparator group (log-rank P = 0.002). Finally, vitamin D3 supplementation was inversely associated with OSCI score for COVID-19 (β=-3.84 [95 %CI:-6.07;-1.62], P = 0.001). In conclusion, bolus vitamin D3 supplementation during or just before COVID-19 was associated in frail elderly with less severe COVID-19 and better survival rate., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: COVID-19 has infected millions of people worldwide, particularly in older adults. The first cases of possible reinfection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were reported in April 2020 among older adults., Design/setting: In this brief report, we present three geriatric cases with two episodes of SARS-CoV-2 infection separated by a symptom-free interval., Participants: The participants of this brief report are three cases of hospitalized geriatric women., Measurements/results: We note clinical and biological worsening during the second episode of COVID-19 for all three patients. Also, there is a radiological aggravation. The second episode of COVID-19 was fatal in all three cases., Conclusion: This series of three geriatric cases with COVID-19 diagnosed two times apart for several weeks questions the possibility of reinfection with SARS-CoV-2. It raises questions in clinical practice about the value of testing for SARS-CoV-2 infection again in the event of symptomatic reoccurrence. J Am Geriatr Soc 68:2179-2183, 2020., (© 2020 The American Geriatrics Society.)

Introduction: Alzheimer's disease or other Dementias (ADD) and postmenopausal osteoporosis are two major public health problems with a huge impact on mortality. Here, we examined the prevalence of ADD in postmenopausal women with osteoporosis, monitored within a dedicated fracture liaison service., Methods: We conducted a cross-sectional observational study in a population of 2041 women, visiting the university hospital of Saint-Etienne for a peripheral fragility fracture. We assessed the prevalence of ADD among these patients and compared to French population. We also compared the characteristics of women with ADD and without ADD., Results: ADD prevalence was on average 13.5% in the population of interest with a mean age of 85years. As women with ADD were older than women without ADD, the prevalence of the disease significantly increased with age as 0%, 1.8%, 13% and 29.7% in<55, 55-74, 75-79 and 85-89years old groups, respectively. Proximal femoral fracture was the most frequent fracture (77%) followed by wrist fracture (13%), and then proximal humerus fracture (10%). ADD prevalence observed in our study was 3 to 4 times the ADD prevalence in France. Despite the overall increase of the ADD prevalence with age, it was still 2.2 and 1.9 times that of the French female population in the 80-84 and 85-89 age groups respectively., Conclusion: ADD prevalence was higher in postmenopausal women with severe osteoporosis, especially those with femoral fractures. Thus, our results incite to a more efficient care of this population with a high risk of fracture and mortality., (Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Objective: to report a case of familial hypocalciuric hypercalcemia (FHH) in an older patient and highlight the diagnostic challenges in geriatric populations., Case Presentation: We report the diagnosis of FHH in an 88-year-old polypathological patient with hypercalcemia discovered during a check-up for cardiac decompensation. Despite a confusing clinical presentation with gout symptoms, including repeated episodes of knee arthritis, persistent hypercalcemia conducted further investigations. Biological tests excluded primary or hyperparathyroidism and malignancy-related hyperparathyroidism, confirming the diagnosis of FHH through the detection of an inhibitory mutation in the calcium-sensing receptor gene., Conclusion: This case suggests to clinicians the possibility of FHH in older patients with unexplained hypercalcemia. In geriatric patients, the diagnosis is complicated because of the poly-pathology: here hypercalcemia was associated with a confusing gout crisis, which was triggered by diuretic treatment for heart failure.