Effects of anticholinergic and sedative medication use on fractures: A self-controlled design study

Background/Objectives: Unintentional falls are a leading cause of injury for older adults, and evidence is needed to understand modifiable risk factors. We evaluated 1-year fall-related fracture risk and whether dispensing of medications with anticholinergic/sedating properties is temporally associated with an increased odds of these fractures. Design: A retrospective cohort study with nested self-controlled analyses conducted between January 1, 2014, and December 31, 2016. Setting: Twenty percent nationwide, random sample of US Medicare beneficiaries. Participants: New users of medications with anticholinergic/sedating properties who were 66+ years old and had Medicare Parts A, B, and D coverage but no claims for medications with anticholinergic/sedating properties in the year before initiation were eligible. Measurements: We followed new users of medications with anticholinergic/sedating properties until first non-vertebral, fall-related fracture (primary outcome), Medicare disenrollment, death, or end of study data. We estimated the 1-year risk with corresponding 95% confidence intervals (CIs) of first fracture after new use. We applied the self-controlled case-crossover and case-time-control designs to estimate odds ratios (ORs) and 95% CIs by comparing anticholinergic and/or sedating medication exposure (any vs. none) during a 14-day hazard period preceding the fracture to exposure to these medications during an earlier 14-day control period. Results: A total of 1,097,989 Medicare beneficiaries initiated medications with anticholinergic/sedating properties in the study period. The 1-year cumulative incidence of fall-related fracture, accounting for death as a competing risk, was 5.0% (95% CI: 5.0%–5.0%). Using the case-crossover design (n = 41,889), the adjusted OR for the association between anticholinergic/sedating medications and fractures was 1.03 (95% CI: 0.99, 1.08). Accounting for the noted temporal trend using the case-time-control design (n = 209,395), the adjusted OR was 1.60 (95% CI: 1.52, 1.69). Conclusion: Use of anticholinergic/sedating medication was temporally associated with an increased odds of fall-related fractures. Patients and their healthcare providers should consider pharmacologic and non-pharmacologic treatments for the target condition that are safer

Quantifying cumulative anticholinergic and sedative drug load among US Medicare Beneficiaries

Purpose: Medications with anticholinergic and sedative properties are widely used among older adults despite strong evidence of harm. The drug burden index (DBI), a pharmacological screening tool, measures these properties across drug classes, and higher DBI drug exposure (DBI > 1) has been associated with certain physical function-related adverse events. Our aim was to quantify mean daily DBI drug exposure among older adults in the United States (US). Methods: We screened medications for DBI properties and operationalized the DBI for US Medicare claims. We then conducted a retrospective cohort study of a 20% random, nationwide sample of 4 137 384 fee-for-service Medicare beneficiaries aged 66+ years (134 757 039 person-months) from January 2013 to December 2016. We measured the monthly distribution based on mean daily DBI, categorized as (a) >0 vs 0 (any use) and (b) 0, 0 2, and examined temporal trends. We described patient-level factors (eg, demographics, healthcare use) associated with high (>2) vs low (0 2. Predictors of high monthly DBI drug exposure (DBI > 2) included certain indicators of increased healthcare use (eg, high number of drug claims), white race, younger age, frailty, and a psychosis diagnosis code. Conclusions: The predictors of high DBI drug exposure can inform discussions between patients and providers about medication appropriateness and potential de-prescribing. Future Medicare-based studies should assess the association between the DBI and adverse events. © 2020 John Wiley & Sons Lt

Energy loss due to defect formation from 206Pb recoils in SuperCDMS germanium detectors

The Super Cryogenic Dark Matter Search experiment at the Soudan Underground Laboratory studied energy loss associated with defect formation in germanium crystals at mK temperatures using in situ 210Pb sources. We examine the spectrum of 206Pb nuclear recoils near its expected 103 keV endpoint energy and determine an energy loss of (6:08 ± 0:18)%, which we attribute to defect formation. From this result and using TRIM simulations, we extract the first experimentally determined average displacement threshold energy of 19.7+0.6−0.5 eV for germanium. This has implications for the analysis thresholds of future germanium-based dark matter searches

On the origin and evolution of the material in 67P/Churyumov-Gerasimenko

International audiencePrimitive objects like comets hold important information on the material that formed our solar system. Several comets have been visited by spacecraft and many more have been observed through Earth- and space-based telescopes. Still our understanding remains limited. Molecular abundances in comets have been shown to be similar to interstellar ices and thus indicate that common processes and conditions were involved in their formation. The samples returned by the Stardust mission to comet Wild 2 showed that the bulk refractory material was processed by high temperatures in the vicinity of the early sun. The recent Rosetta mission acquired a wealth of new data on the composition of comet 67P/Churyumov-Gerasimenko (hereafter 67P/C-G) and complemented earlier observations of other comets. The isotopic, elemental, and molecular abundances of the volatile, semi-volatile, and refractory phases brought many new insights into the origin and processing of the incorporated material. The emerging picture after Rosetta is that at least part of the volatile material was formed before the solar system and that cometary nuclei agglomerated over a wide range of heliocentric distances, different from where they are found today. Deviations from bulk solar system abundances indicate that the material was not fully homogenized at the location of comet formation, despite the radial mixing implied by the Stardust results. Post-formation evolution of the material might play an important role, which further complicates the picture. This paper discusses these major findings of the Rosetta mission with respect to the origin of the material and puts them in the context of what we know from other comets and solar system objects

Etude de la pénétration de l'arsenic des eaux de la Bourboule en fonction de leur mode d'administration

L'absence de principe actif défini rend délicate l'étude de la biodisponibilité de la plupart des eaux minérales ; grâce à leur concentration en Arsenic, les eaux thermales de La Bourboule se prêtent à une telle étude. Les auteurs tentent d'étudier la disponibilité comparée de l'Arsenic en fonction des 3 principaux modes d'administration utilisés dans la station : aérosol, inhalation, boisson. Les concentrations sanguines et tissulaires de l'Arsenic sont appréciées par activation neutronique. Les résultats obtenus montrent une bonne disponibilité de l'Arsenic lors de l'administration orale. Les examens des différents tissus des voies respiratoires mettent en évidence la pénétration de l'arsenic jusqu'aux bronches. Malgré la sensibilité de la méthode de mesure, la diffusion de l'arsenic dans le sang à partir du tissu pulmonaire n'est pas démontrée. Les auteurs concluent sur la nécessité de pousser plus avant leurs investigations par l'étude de la distribution de l'Arsenic dans le contexte d'une cure

Monitoring of noninvasive ventilation by built-in software of home bilevel ventilators: a bench study.

BACKGROUND: Current bilevel positive-pressure ventilators for home noninvasive ventilation (NIV) provide physicians with software that records items important for patient monitoring, such as compliance, tidal volume (Vt), and leaks. However, to our knowledge, the validity of this information has not yet been independently assessed. METHODS: Testing was done for seven home ventilators on a bench model adapted to simulate NIV and generate unintentional leaks (ie, other than of the mask exhalation valve). Five levels of leaks were simulated using a computer-driven solenoid valve (0-60 L/min) at different levels of inspiratory pressure (15 and 25 cm H(2)O) and at a fixed expiratory pressure (5 cm H(2)O), for a total of 10 conditions. Bench data were compared with results retrieved from ventilator software for leaks and Vt. RESULTS: For assessing leaks, three of the devices tested were highly reliable, with a small bias (0.3-0.9 L/min), narrow limits of agreement (LA), and high correlations (R(2), 0.993-0.997) when comparing ventilator software and bench results; conversely, for four ventilators, bias ranged from -6.0 L/min to -25.9 L/min, exceeding -10 L/min for two devices, with wide LA and lower correlations (R(2), 0.70-0.98). Bias for leaks increased markedly with the importance of leaks in three devices. Vt was underestimated by all devices, and bias (range, 66-236 mL) increased with higher insufflation pressures. Only two devices had a bias < 100 mL, with all testing conditions considered. CONCLUSIONS: Physicians monitoring patients who use home ventilation must be aware of differences in the estimation of leaks and Vt by ventilator software. Also, leaks are reported in different ways according to the device used

Signal detection of drugs associated with obstructive and central sleep apnoea

International audienceWe aim to discover new safety signals of drug-induced sleep apnoea (SA), a global health problem affecting approximately 1 billion people worldwide. We first conducted a series of sequence symmetry analyses (SSA) in a cohort composed from all patients who received a first SA diagnosis or treatment between 2006 and 2018 in the Echantillon Généraliste des Bénéficaires (EGB), a random sample of the French healthcare database. We used two primary outcomes to estimate the sequence ratio (SR) for all drug classes available in France: a sensitive one (diagnosis or treatment of SA) and a specific one (Positive Airway Pressure (PAP) therapy). We then performed disproportionality analyses using the "Bayesian neural network method" on all cases of sleep apnoea (MedDRA high level term) reported up to November 2023 in the World Health Organisation (WHO) pharmacovigilance database. Among the 728,167 individuals, 46,193 had an incident diagnosis or treatment for SA and 17,080 had started an incident treatment by PAP therapy. Fifty-eight drug classes had a significant SR, with 7 considered highly plausible: opium alkaloids and derivatives, benzodiazepine derivatives, other centrally acting agents, other anxiolytics, carbamic acid esters, quinine and derivatives and antivertigo preparations; with consistent signals found for the first 3 drug classes in the disproportionality analysis. In this signal detection study, we found that opioids, benzodiazepines (but not Z-drugs) and myorelaxing agents are associated with the onset or aggravation of SA. Moreover, a new safety signal for antivertigo preparations such as betahistine emerged and needs to be further explored