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.

Prognostic impact of neurocognitive disorders in older patients with cancer: the ELCAPA prospective cohort study.

OBJECTIVE: To assess the prognostic value of neurocognitive disorder (NCD) for 12 month-overall mortality in patients aged 70 or more with a solid cancer. DESIGN: prospective, observational, multicenter cohort. SETTING AND PARTICIPANTS: We analyzed data from the ELCAPA longitudinal multicenter observational cohort of patients aged 70 or over, referred for a geriatric assessment (GA) before a new cancer treatment modality between January 31st, 2007, and December 29th, 2017. We defined the baseline NCD in four classes: no NCD, mild NCD, moderate NCD, and major NCD, based on the Mini-Mental State Examination (MMSE) score, memory complaint, and the Instrumental Activities of Daily Living (IADL) score. STATISTICAL METHODS: We compared the baseline characteristics of patients according to NCD classes, globally and by pairs (with Bonferroni' correction). Prognosis value of NCD classes were analysed by using univariable and then multivariable 12 month survival analysis with age as time-variable and with and without adjustement for the treatment strategy (curative, palliative or exclusive supportive care). RESULTS: 2784 patients with solid-cancer were included, with a median [interquartile range] age of 82 [78;86]. 36% of the patients were free of NCD, 34% had a mild NCD, 17% had a moderate NCD, and 13% had a major NCD. We identified the following independent prognostic factors for 12 month-overall mortality: NCD (adjusted hazard ratio (aHR) [95% confidence interval (CI)] for a major NCD = 1.54 [1.19-1.98] (p < 0.001), type of cancer, metastatic status, inpatient consultation, poor general health (assessed as the level of fatigue and Eastern Cooperative Oncology Group performance status [ECOG-PS]), greater weight loss, palliative treatment, and exclusive supportive care. Additional adjustment for the treatment strategy did not greatly change the strength of the association of a major NCD with 12 month-overall mortality (HR [95%CI] = 1.78 [1.39-2.29] (p < 0.001). CONCLUSION: Our results suggest that the presence of a major NCD has direct prognostic value (independently of other geriatric factors, the type of cancer and the treatment strategy) in older patients with a solid cancer.

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.

[Pyoderma gangrenosum and hemopathies in older patients]. / Pyoderma gangrenosum et hémopathies chez la personne âgée.

Pyoderma gangrenosum (PG) belongs to neutrophilic dermatoses. PG can have different clinical presentations (ulcerated, bullous, pustular), is often painful, and preferentially affects the lower limbs. The diagnosis can be challenging, and a cutaneous biopsy is often necessary, which shows an aseptic cutaneous infiltrate of neutrophils. The association with inflammatory or hematologic conditions is frequent, especially in older patients. The hematologic diseases the most frequently associated with PG are myelodysplastic syndrome, followed by monoclonal gammopathy of undetermined significance. Because of the strong impact of its treatment, recognition of PG is crucial. The treatment is based on first-line corticosteroids and topical or systemic immunosuppressive drugs and most often leads to a favourable outcome. The management of an acute hematologic disease would further improve the prognosis of PG. The singularity of geriatric patients encourages to thoroughly balance the risks and benefits of the recommended drugs and to consider associated non-drug measures. Here, we propose a review of the scientific literature about the association between PG and hematologic diseases, with a special focus on older patients, accompanied by the report of two cases in geriatric ward.

Modifiable factors associated with postoperative atrial fibrillation in older patients with hip fracture in an orthogeriatric care pathway: a nested case-control study.

BACKGROUND: Few data are available regarding post-operative atrial fibrillation (POAF) in non-cardiothoracic surgery, particularly orthopedic surgery. Hence, given the frequent incidence of POAF after surgery and its marked impact, we need to identify modifiable factors associated with POAF after hip fracture surgery in older patients. METHODS: We conducted a nested case-control study in the unit for perioperative geriatric care of an academic hospital in Paris from July 1, 2009 to December 31, 2019, enrolling all consecutive patients aged ≥ 70 years with hip fracture surgery and no history of permanent AF before admission (retrospective analysis of prospectively collected data). Patients with and without POAF were matched 1:5 on 5 baseline characteristics (age, hypertension, diabetes, coronary artery disease, cardiac failure). RESULTS: Of the 757 patients included, 384 were matched, and 64 had POAF. The incidence of POAF was 8.5%. The mean age was 86 ± 6 years, 298 (78%) patients were female, and the median Charlson Comorbidity Index was 6 (interquartile range 4-8). The median time from surgery to the occurrence of POAF was 2 days (1-4). On multivariable conditional logistic regression analysis (matched cohort), the modifiable factors present at admission associated with POAF were time to surgery > 48 h (odds ratio [OR] = 1.66, 95% confidence interval [1.01-2.81]) and > 2 units of packed red blood cells (OR = 3.94, [1.50-10.03]). CONCLUSIONS: This study provides new information about POAF in older patients with hip fracture surgery, a surgical emergency whose complexity requires multidisciplinary care.

Importance of human capital, field knowledge and experience to improve pest locust management.

BACKGROUND: A poorly organised risk management system may dysfunction when used. The consequences can be dramatic for those supposed to be protected. Since the 1960s, preventive control strategies, with field officers as living memory, have been developed to monitor locusts. Preserving their experience of past plagues is consequently essential. Wrong use of their knowledge can disrupt the whole management chain. We explored these conditions using a multi-agent model representing a preventive system. We simulated how the field teams' tendency to repeatedly visit past outbreak areas (hotspots) by allocating them an attraction weight can help in preventing plagues. RESULTS: When field teams' attention remained constant over time, there was dramatic decrease in the number of plagues, with increasing interest in hotspots, as long as interest was less than 2.5 times more than elsewhere. When the field teams were only attentive during recession times, plagues were better controlled using a low weight for hotspots. The spatial structure of hotspot distribution had an effect: the more frequent and the bigger the hotspots, the lower the optimal hotspot weighting needed to reduce plagues. CONCLUSION: Orienting surveys towards hotspots particularly during recession times reduces plagues. The spatial structure of locust habitats may influence the way they are managed. Habitats located outside the multiple hotspots of species such as the desert locust should be visited more frequently than those with only one hotspot, such as the South American locust. The decline/loss of the field officers' experience highlights the need to save, capitalise and disseminate this knowledge. © 2021 Society of Chemical Industry.

The limitations of locust preventive management faced with spatial uncertainty: exploration with a multi-agent model.

BACKGROUND: The spatial structure of locust outbreaks is a major aspect of preventive management that relies on where survey teams have to be sent if they are to react in time to any upsurge. The concentration of areas propitious to outbreaks has been documented for many species. Areas where preventive management fails to collect information because of insecurity or remoteness constitute other limits. We explored these conditions using a spatially explicit multi-agent model representing a preventive management system. We simulated areas where field teams had limited or no access and areas where the probability of initial outbreaks was concentrated in hotspots. RESULTS: A strong effort by the budget holder to maintain funding over time might be cancelled out with 5% of a territory having limited access. The larger the area of no access, the worse the proportion of plague years. Multiple no access areas generated more plagues than only one no access area of an equivalent size because more fronts must be controlled. Concentrating outbreaks in hotspots increased the probability of plagues. One hotspot alone was easier to control than several same-sized hotspots. The period of the budget holder's cyclical behaviour between awareness and reduction in funding was longer with one hotspot than with several. CONCLUSION: These results highlight the need to consider the spatial conditions and accessibility of locust species when planning the sustainability of management systems. Despite significant budgets to set in place a preventive management system, cyclical locust outbreaks may be related to these spatial conditions. © 2019 Society of Chemical Industry.

Novel insights into the systemic treatment of lung cancer malignant pleural effusion.

Lung cancer is the most common fatal malignancy worldwide. Approximately 75% of non-small-cell lung cancer (NSCLC) patients are diagnosed at an advanced or a metastatic stage. Since 2007, NSCLC patients with malignant pleural effusion (MPE) are staged as M1 disease. During the last decades, chemotherapeutic agents failed to offer a significant improvement of survival in patients with metastatic disease. The current review aims to summarize the actual situation of the recently developed therapies in patients with lung cancer and MPE.

Comparison of cytology, chest computed and positron emission tomography findings in malignant pleural effusion from lung cancer.

BACKGROUND: Malignant pleural effusion (MPE) is a common medical problem in lung cancer (LC). Pleural fluid cytology (PFC), chest computed tomography (CCT) and positron emission tomography (PET) findings are helpful as first line approach. The objectives of this study were to evaluate whether there is a correlation between PFC, CCT and PET in patients with MPE due to LC. METHODS: We selected patients from our electronic files. Data of PFC, pleural biopsy (PB), CCT and PET have been recorded and analyzed. RESULTS: A total of 101 consecutive patients (66 males, 65.3%) with a mean age of 66.2±31 years were selected. Types of LC were adenocarcinoma in 71 patients (70.2%), squamous in 13 (12.8%), small-cell in 12 (11.8%) and large cell in 5 (4.9%). CCT showed nodules in 6 (5.9%), pleural thickening in 8 (7.9%) and both in 17 (16.8%) patients. PFC was positive in 55/91 thoracentesis (60.4%) and 32/52 thoracoscopy (61.5%), while PB in 38/40 performed (95%). PET fixation was found in 32/47 (68%) patients who had MPE at diagnosis. When we associate PFC to CCT and PET findings, the yield in our study becomes 90%. No correlation was observed between CCT findings and PFC (P=0.62) between PFC and PET fixation (P=0.63) or between CCT and PET (P=0.06). CONCLUSIONS: In our cohort of LC patients with MPE, we observed a high sensitivity for PFC, while in most of the cases no findings were observed in CCT. PET had a relative low sensitivity. However, when all 3 methods were combined the yield was 90%.

Improving preventive locust management: insights from a multi-agent model.

BACKGROUND: Preventive management of locust plagues works in some cases but still fails frequently. The role of funding institution awareness was suggested as a potential facilitating factor for cyclic locust plagues. We designed a multi-agent system to represent the events of locust plague development and a management system with three levels: funding institution, national control unit and field teams. A sensitivity analysis identified the limits and improvements of the management system. RESULTS: The model generated cyclic locust plagues through a decrease in funding institution awareness. The funding institution could improve its impact by increasing its support by just a few percent. The control unit should avoid hiring too many field teams when plagues bring in money, in order to ensure that surveys can be maintained in times of recession. The more information the teams can acquire about the natural system, the more efficient they will be. CONCLUSION: We argue that anti-locust management should be considered as a complex adaptive system. This not only would allow managers to prove to funders the random aspect of their needs, but would also enable funders and decision-makers to understand and integrate their own decisions into the locust dynamics that still regularly affect human populations. © 2017 Society of Chemical Industry.

Climate-driven geographic distribution of the desert locust during recession periods: Subspecies' niche differentiation and relative risks under scenarios of climate change.

The desert locust is an agricultural pest that is able to switch from a harmless solitarious stage, during recession periods, to swarms of gregarious individuals that disperse long distances and affect areas from western Africa to India during outbreak periods. Large outbreaks have been recorded through centuries, and the Food and Agriculture Organization keeps a long-term, large-scale monitoring survey database in the area. However, there is also a much less known subspecies that occupies a limited area in Southern Africa. We used large-scale climatic and occurrence data of the solitarious phase of each subspecies during recession periods to understand whether both subspecies climatic niches differ from each other, what is the current potential geographical distribution of each subspecies, and how climate change is likely to shift their potential distribution with respect to current conditions. We evaluated whether subspecies are significantly specialized along available climate gradients by using null models of background climatic differences within and between southern and northern ranges and applying niche similarity and niche equivalency tests. The results point to climatic niche conservatism between the two clades. We complemented this analysis with species distribution modeling to characterize current solitarious distributions and forecast potential recession range shifts under two extreme climate change scenarios at the 2050 and 2090 time horizon. Projections suggest that, at a global scale, the northern clade could contract its solitarious recession range, while the southern clade is likely to expand its recession range. However, local expansions were also predicted in the northern clade, in particular in southern and northern margins of the current geographical distribution. In conclusion, monitoring and management practices should remain in place in northern Africa, while in Southern Africa the potential for the subspecies to pose a threat in the future should be investigated more closely.

Frozen Sections in Pleural Pathology: A Valuable Tool.

BACKGROUND: Knowledge of pleural malignancy can lead to immediate pleurodesis during thoracoscopy. However, the accuracy of pleural frozen sections is largely unknown. OBJECTIVES: To investigate the accuracy of frozen sections in pleural tumor pathology. METHODS: A total of 156 frozen pleural sections performed with the question of malignancy were retrospectively reviewed. The original frozen sections were compared to the permanent section slides which were considered as the gold standard. The influence of the following parameters on the frozen section response was evaluated: specimen size, clinical information, as well as the processing by a specialized pulmonary pathologist or not. The reasons of discrepancies were categorized as sampling errors or interpretation errors. RESULTS: Frozen sections made up 16.4% of 951 pleural biopsies performed in the same time period. Accurate diagnosis was feasible in 92.3% of the cases. There were 7 (4.5%) deferred (inconclusive) cases and 5 (3.2%) discrepant cases. Sensitivity of the method was 96.26%, specificity 97.87%, the positive predictive value was 99.04%, and the negative predictive value was 92%. There was no association between the responses given during frozen section and specimen size, clinical information, or the evaluation by a specialized pulmonary pathologist. Four of the 12 cases were sampling errors, while 8 cases were interpretation errors mostly made in the absence of fat tissue invasion. Thus, paucicellular lesions without prominent invasion - fat invasion or haphazardly invading cellular proliferation - were those posing most of the difficulties during frozen section. CONCLUSIONS: Frozen sections are a highly accurate tool in pleural pathology. Thus, they can be used when an immediate pleurodesis is requested.

Efficacy of Whole-Lung Lavage in Pulmonary Alveolar Proteinosis: A Multicenter International Study of GELF.

BACKGROUND: New therapies have emerged in the treatment of pulmonary alveolar proteinosis (PAP) and, therefore, there is a real need to evaluate the efficacy of whole-lung lavage (WLL) in this rare disease. OBJECTIVES: The aim of this study was to assess the efficacy of WLL in patients with PAP. METHODS: We included 33 patients from 12 centers, which are members of the French-Speaking Thoracic Endoscopy Group, for analysis. Data collection concerned patients and disease characteristics, pulmonary function tests (PFTs) and technical information on the procedure. RESULTS: The median age of the patients was 44 years (range 13-77). There were 23 (71.9%) patients with respiratory insufficiency at presentation. All patients underwent WLL by general anesthesia and selective lung ventilation, except 1 who underwent awake flexible bronchoscopy. We noted differences in the technique, as 12 (36.36%) patients had percussion during the procedure and only 4 (12.1%) patients underwent 2-lung lavage during 1 anesthesia. A median of 12 L was used to perform WLL (1.0-40 L). Complications occurred in 11 (33.3%) patients, and 18 (56.25%) of them relapsed in a median period of 16.9 months. No significant changes were found in any PFT parameters studied, except for PaO2, which was significantly improved by 6.375 mm Hg (p = 0.0213) after the procedure compared to before. CONCLUSIONS: Although the application of the WLL technique was variable, overall, it significantly improved patients' short-term respiratory condition by improving PaO2. However, a long-term effect needs to be confirmed, as many of our patients relapsed.