Predicting trace metal solubility and fractionation in urban soils from isotopic exchangeability

Metal-salt amended soils (MA, n = 23), and historically-contaminated urban soils from two English cities (Urban, n = 50), were investigated to assess the effects of soil properties and contaminant source on metal lability and solubility. A stable isotope dilution method, with and without a resin purification step, was used to measure the lability of Cd, Cu, Ni, Pb and Zn. For all five metals in MA soils, lability (%E-values) could be reasonably well predicted from soil pH value with a simple logistic equation. However, there was evidence of continuing time-dependent fixation of Cd and Zn in the MA soils, following more than a decade of storage under air-dried conditions, mainly in high pH soils. All five metals in MA soils remained much more labile than in Urban soils, strongly indicating an effect of contaminant source on metal lability in the latter. Metal solubility was predicted for both sets of soil by the geochemical speciation model WHAM-VII, using E-values as an input variable. For soils with low metal solution concentrations, over-estimation of Cd, Ni and Zn solubility was associated with binding to the Fe oxide fraction while accurate prediction of Cu solubility was dependent on humic acid content. Lead solubility was most poorly described, especially in the Urban soils. Generally, slightly poorer estimation of metal solubility was observed in Urban soils, possibly due to a greater incidence of high pH values. The use of isotopically exchangeable metal to predict solubility is appropriate both for historically contaminated soils and where amendment with soluble forms of metal is used, as in toxicological trials. However, the major limitation to predicting solubility may lie with the accuracy of model input variables such as humic acid and Fe oxide contents where there is often a reliance on relatively crude analytical estimations of these variables

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

Development of a versatile laboratory experiment to teach the metabolic transformation of hydrolysis

In this paper we describe an easy, reliable, versatile and inexpensive laboratory experiment to teach the metabolic transformation of hydrolysis to Pharmacy students. The experiment does not require the sacrifice of any experimental animal, or any work with organs or tissues, and so can be implemented in a typical university chemistry laboratory. We used acetylsalicylic acid (ASA), hexyl salicylate (HS) and two enzymes, a lipase and an esterase. Since both ASS and HS liberate salicylic acid (SA) upon hydrolysis, students can evaluate the different enzymatic transformations by monitoring the amount of SA liberated. The learning outcomes are an enhanced student understanding of: (1) the process of hydrolysis; (2) the application of enzymatic transformations of molecules from food to xenobiotics; (3) the differences between the general specificity of substrate of both enzymes; (4) the concepts of the lipophilic pocket; (5) the catalytic triad and its regioselectivity in relation to the ester bond. A questionnaire was administered to participating students at three points in time: at the beginning of the module, after enzymatic hydrolysis was taught in class, and after the laboratory experiment. From an analysis of the questionnaire data we conclude that this practical helped Pharmacy students to understand these concepts

Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci

Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25610-8), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genomewide significant association