Assessing the prevalence of anticholinergic and sedative medications to avoid in older adults from the French Health Data System.

Background: In older people, medications with anticholinergic or sedative properties are associated with falls, frailty, and functional and cognitive impairment. These medications are often described as a subset of potentially inappropriate medications (PIMs). We examined the prevalence of anticholinergic or sedative medications to avoid in older people in France in 2023.

A Pathologist's Guide to Non-clinical Safety Assessment of Adoptive Cell Therapy Products.

Through two decades of research and development, adoptive cell therapies (ACTs) have revolutionized treatment for hematologic malignancies. Many of the seven US Food and Drug Administration (FDA)-approved products are proven to be a curative last line of defense against said malignancies. The ACTs, known more commonly as chimeric antigen receptor (CAR) T-cells, utilize engineered lymphocytes to target and destroy cancer cells in a patient-specific, major histocompatibility complex (MHC)-independent manner, acting as "living drugs" that adapt to and surveil the body post-treatment.

Opinion on the Importance of Sharing Toxicologic Pathology Data for Educational and/or Scientific Purposes.

Sharing pathology data is critical for educational and scientific purposes. Since most pharmaceutical or (agro)chemical companies outsource nonclinical safety assessment studies to contract research organizations (CROs), the pathology data of those studies are not owned by the investigator but is the legal property of the respective company sponsoring the work. Although some companies have installed policies that govern sharing of pathology data, many companies generally do not allow the external use of data by either the CRO-based study pathologist or the sponsor pathologist.

Impact of cumulative exposure to anticholinergic and sedative drugs on cognition in older adults: a memory clinic cohort study.

Background: Long-term exposure to anticholinergic and sedative drugs could be a modifiable risk factor for cognitive decline. The objective of this study was to measure the association between previous cumulative anticholinergic and sedative drug exposure (Drug Burden Index) and cognitive decline.

Methods: A cohort study (MEMORA cohort) was conducted in a French memory clinic for patients attending a consultation between November 2014 and December 2020, with at least 2 Mini-Mental State Examination (MMSE) measurements (≥ 6 months apart) and available medication data from the local Primary Health Insurance Fund database (n = 1,970).

Potentially inappropriate medications and anticholinergic and sedative burden in older community-dwelling patients with advanced chronic kidney disease.

Objective: Regarding older patients, multiple chronic conditions lead to the intake of multiple medications, involving a higher risk of adverse drug events. In older patients with advanced chronic kidney disease, the medication exposure was poorly explored. The aim of this study was to describe the use of potentially inappropriate medications and medications with anticholinergic and sedative properties in older community-dwelling patients with advanced chronic kidney disease.

Amino Acid Solutions for Lu-Oxodotreotide Premedication: A Tolerance Study.

Background: The co-infusion of amino acid solutions during peptide receptor radionuclide therapy reduces the tubular reabsorption of 177Lu-oxodotreotide, thus minimizing nephrotoxicity. In our nuclear medicine department, the patients received two different types of amino acid perfusion over time: a commercial solution (CS) containing 10% amino acids, and a 2.5% lysine−arginine (LysArg) hospital preparation, produced by a referral laboratory.

Polypharmacy and medication regimen complexity in older patients with hemophilia or von willebrand disease: the M'HEMORRH-AGE study.

Background: In older patients, multiple chronic conditions lead topolypharmacy which is associated with a higher risk of adverse drug events. Nowadays, the medication exposure of older patients with bleeding disorders has been poorly explored.

Aim: The aim of this study was to assess the prevalence of polypharmacy and the medication regimen complexity in older community-dwelling patients with hemophilia or von Willebrand Disease (VWD).

Potentially inappropriate medications and anticholinergic and sedative burden in older patients with haemophilia or von Willebrand disease: The M'HEMORRH-AGE study.

What Is Known And Objective: In older patients, multiple chronic conditions lead to the intake of multiple medications and a higher risk of adverse drug events. The exposure to inappropriate medications in older patients with bleeding disorders is poorly explored. The aim of this study was to describe the exposure to potentially inappropriate medications (PIMs) and medications with anticholinergic and sedative properties in older community-dwelling patients with haemophilia or von Willebrand Disease (VWD).

Drug-related problems in older patients with advanced chronic kidney disease identified during pretransplant comprehensive geriatric assessment.

Background: Older patients with advanced chronic kidney disease may be exposed to a higher risk of adverse drug events due to chronic kidney disease and aging. The integration of clinical pharmacist into pretransplant comprehensive geriatric assessment is an opportunity to perform medication optimization.

Objective: The aim was to describe drug-related problems in older patients with advanced chronic kidney disease.

Pretransplant Comprehensive Geriatric Assessment in Older Patients with Advanced Chronic Kidney Disease.

Background: In older patients with advanced chronic kidney disease (CKD), the decision of kidney transplantation (KT) is a challenge for nephrologists. The use of comprehensive geriatric assessment (CGA) is increasingly gaining interest into the process of decision-making about treatment modality choice for CKD. The aim of this study was to assess the prevalence of geriatric impairment and frailty in older dialysis and nondialysis patients with advanced CKD using a pretransplant CGA model and to identify geriatric impairments influencing the geriatricians' recommendations for KT.

Exposure to Anticholinergic and Sedative Drugs and Healthcare Costs in Older Patients with Neurocognitive Disorders.

Background: Literature supports an increasing number of older patients living with neurocognitive disorders alongside with their annual worldwide costs. Therapeutic management of behavioral and psychological symptoms includes the use of anticholinergic and sedative drugs for which significant exposure is negatively associated with clinical outcomes.

Objective: The aim of this study was to assess the healthcare costs differences related to an increase in the exposure to anticholinergic and sedative drugs in older patients with neurocognitive disorder.

Genomics Integrated Systems Transgenesis (GENISYST) for gain-of-function disease modelling in Göttingen Minipigs.

Göttingen Minipigs show several anatomical, physiological, and pathogenetical similarities to humans and serve an important role in translational studies for example as large animal models of disease. In recent years, the number of transgenic Göttingen Minipigs models has increased, as advanced genetic techniques simplify the generation of animals with precisely tailored modifications. These modifications are designed to replicate genetic alterations responsible for human disease.

Medication exposure and frailty in older community-dwelling patients: a cross-sectional study.

Objective To investigate the association between the medication exposure, measured by the polypharmacy/excessive polypharmacy and the anticholinergic and/or sedative drug exposure, on frailty status among French older community-dwelling patients. Setting day-care unit in France (Lyon), with retrospective data from July, 2017 to March, 2018. Method This monocentric cross-sectional study included community-dwelling patients aged 65 years and over and admitted at the day-care unit for a geriatric evaluation.

Intra-Articular Hyaluronic Acid and Chondroitin Sulfate: Pharmacokinetic Investigation in Osteoarthritic Rat Models.

Background: Viscosupplementation of synovial fluid with intra-articular (IA) injections of hyaluronic acid (HA) is widely used for symptomatic treatment of osteoarthritis (OA). Herein we present HCS, a new combination of chemicals, associating HA and chondroitin sulfate (CS), both members of the glycosaminoglycan (GAGs) family, which are major components of the joint. HA provides viscosity to the synovial fluid and CS provides elasticity to the cartilage.

Toxicologic Pathology Forum*: Opinion on Integrating Innovative Digital Pathology Tools in the Regulatory Framework.

Digital pathology is defined as the ability to examine digitized microscopic slides and to generate qualitative and quantitative data. The field of digital pathology is rapidly evolving and has the potential to revolutionize toxicologic pathology. Techniques such as automated 2-D image analysis, whole slide imaging, and telepathology are already considered "mature" technologies and have been used for decades in exploratory studies; however, many organizations are reluctant to use digital pathology in regulatory toxicology studies.

Intranodal Angiomyomatous Hamartoma in a Cynomolgus Monkey.

We describe here an angiomyomatous hamartoma in the right axillary lymph node of a three-year-old male cynomolgus monkey ( Macaca fascicularis), used as a control subject in a short-term toxicity study. This is a very rare lesion that has been reported almost exclusively in inguinal lymph nodes, and to date only in human beings. In the present case, light microscopy revealed partial replacement of the lymph node parenchyma by a disorganized, irregular vascular network, sparsely distributed smooth muscle cells, and a fibro-adipocytic stroma.

OBE022, an Oral and Selective Prostaglandin F Receptor Antagonist as an Effective and Safe Modality for the Treatment of Preterm Labor.

Preterm birth is the major challenge in obstetrics, affecting ∼10% of pregnancies. Pan-prostaglandin synthesis inhibitors [nonsteroidal anti-inflammatory drugs (NSAIDs)] prevent preterm labor and prolong pregnancy but raise concerns about fetal renal and cardiovascular safety. We conducted preclinical studies examining the tocolytic effect and fetal safety of the oral prodrug candidate OBE022 [()-2-amino-3-methyl-butyric acid ()-3-{[(S)-3-(biphenyl-4-sulfonyl)-thiazolidine-2-carbonyl]-amino}-3-(4-fluoro-phenyl)-propyl ester] and its parent OBE002 [()-3-(biphenyl-4-sulfonyl)-thiazolidine-2-carboxylic acid [(S)-1-(4-fluoro-phenyl)-3-hydroxy-propyl]-amide], both potent and highly selective antagonist of the contractile prostaglandin F (PGF ) receptor (FP).

A human relevance investigation of PPARα-mediated key events in the hepatocarcinogenic mode of action of propaquizafop in rats.

Propaquizafop is an herbicide with demonstrated hepatocarcinogenic activity in rodents. A rodent-specific mode of action (MOA) in the liver via activation of peroxisome proliferator-activated receptor α (PPARα) has been postulated based on existing data. Experience with PPARα-inducing pharmaceuticals indicates a lack of human relevance of this MOA.

Comparative analysis of the oral mucosae from rodents and non-rodents: Application to the nonclinical evaluation of sublingual immunotherapy products.

Background: A comparative characterization of the oral mucosa in various animals is needed to identify the best animal model(s) for nonclinical evaluation of sublingual immunotherapy products. With this aim, we studied the histological characteristics and immune cell infiltrates of oral mucosae from common animal species.

Methods: Three oral regions (i.

Systematic review of cost-effectiveness analyses for combinations of prevention strategies against human papillomavirus (HPV) infection: a general trend.

Background: Due to the arrival of multi-valent HPV vaccines, it is more and more important to have a better understanding of the relationship between vaccination and screening programmes. This review aimed to: (1) collect published evidence on the cost-effectiveness profile of different HPV prevention strategies and, in particular, those combining vaccination with changes in screening practices; (2) explore the cost-effectiveness of alternative preventive strategies based on screening and vaccination.

Methods: A systematic literature review was conducted in order to identify the relevant studies regarding the cost-effectiveness of prevention strategies against HPV infection.

A comparative public health and budget impact analysis of pneumococcal vaccines: The French case.

In 2002, a pneumococcal conjugate vaccine (PCV) was introduced to French infants and toddlers. A change has been witnessed in the incidence of pneumococcal diseases in adults: the incidence of invasive pneumococcal disease (IPD) of serotypes covered by PCV decreased, and serotypes not covered by PCV increased. This study aimed to quantify the public health and budget impact of pneumococcal vaccination strategies in at-risk adults in France over 5 years.

Carcinogenicity testing of eliglustat in mice and rats.

Eliglustat is a novel glucosylceramide synthase inhibitor for long-term oral treatment of type 1 Gaucher disease (GD1), an inherited metabolic disorder. The carcinogenic potential of this drug has been evaluated in lifetime carcinogenicity bioassays in mice and rats. Administration of eliglustat to Swiss CD-1 mice at 0, 10, 25 or 75 mg/kg/day for 104 weeks by dietary admixture did not influence survival or bodyweight evolution, or produce any clinical indication of poor condition.

Development of a Delayed-Type Hypersensitivity (DTH) Model in the Cynomolgus Monkey.

Although a T-dependent antibody response (TDAR) assay is generally recommended as the first-line immune function assay in nonclinical immunotoxicity evaluation, second-line assays such as delayed-type hypersensitivity (DTH) to measure cell-mediated responses can provide helpful additional information. In this study, male Cynomolgus monkeys were injected intramuscularly either once or twice with 1 mg Keyhole Limpet Hemocyanin (KLH) or twice with a commercially available tetanus vaccine (40 IU tetanus toxoid + 0.06 mg aluminum hydroxide).

The utility of the minipig as an animal model in regulatory toxicology.

In this article we review the value and utility of the minipig as an animal model in regulatory toxicity testing. Our review is based on detailed consideration of the comparative biology of the minipig, and of the practical features of toxicity testing in the minipig. The minipig presents a favourable profile as a non-rodent toxicology model, in terms of the similarity to man and also in terms of applicability to different study types.