Evidence-Based Decision Support for a Structured Care Program on Polypharmacy in Multimorbidity: A Guideline Upgrade Based on a Realist Synthesis

Evidence-based clinical guidelines generally consider single conditions, and rarely multimorbidity. We developed an evidence-based guideline for a structured care program to manage polypharmacy in multimorbidity by using a realist synthesis to update the German polypharmacy guideline including the following five methods: formal prioritization in focus groups; systematic guideline review of evidence-based multimorbidity/polypharmacy guidelines; evidence search/synthesis and recommendation development; multidisciplinary consent of recommendations; feasibility test of updated guideline. We identified the need for a better description of the target group, decision support, prioritization of medication, consideration of patient preferences and anticholinergic properties, and of healthcare interfaces. We conducted a systematic guideline review of eight guidelines and extracted and synthesized recommendations using the Ariadne principles. We also included 48 systematic reviews. We formulated and agreed upon 34 recommendations for the revised guideline. During the feasibility test, guideline use enabled 57% of GPs to identify problems, leading to medication changes in 49% and self-assessed improvement in 56% of patients. Although 58% of GPs felt that it was too long, 92% recommended it. Polypharmacy should be systematically reviewed at least annually. Patients, family members, and healthcare professionals should monitor and adjust it using prospective process validation, taking into account patient preferences and agreed treatment goals.

The Effect of Addition of Bagasse Ash and Eggshell Powder on CBR Value of Clay Soil

In the construction of road construction, soil bearing capacity, such as the CBR value, needs to be considered. In clay soil, the CBR value of the soil is low, so that stabilization material can be added to its repair. In this study, the stabilization materials used were waste materials in the form of bagasse ash and eggshell powder. Variations in the mixture of bagasse ash mixture used in this study were 7%, 10%, and 13% plus 3% eggshell powder. Testing in this study includes testing moisture content, sieve analysis, specific gravity, consistency limits, compaction testing, and CBR. The soil classification system used is the Unified classification (USCS), a test guideline based on SNI. From the CBR soaked test, it was found that the CBR value of clay soil increased along with the increase in the percentage of bagasse ash plus 3% eggshell powder and the increase in collisions on the soil. The percentage increase in the CBR value of clay soil with a mixture of stabilization to clay soil is 92.303%. at 65 blow. So that bagasse ash and eggshell powder greatly affect the increase in the CBR value of clay soil.

Inter-laboratory comparison of water solubility methods applied to difficult-to-test substances

Water solubility is perhaps the single most important physical–chemical property determining the environmental fate and effects of organic compounds. Its determination is particularly challenging for compounds with extremely low solubility, frequently referred to as “difficult-to-test” substances and having solubility’s generally less than 0.1 mg/L. The existing regulatory water solubility test for these compounds is the column elution method. Its applicability, however, is limited, to non-volatile solid or crystalline hydrophobic organic compounds. There currently exists no test guideline for measuring the water solubility of very hydrophobic liquid, and potentially volatile, difficult-to-test compounds. This paper describes a “slow-stir” water solubility methodology along with results of a ring trial across five laboratories evaluating the method’s performance. The slow-stir method was applied to n-hexylcyclohexane, a volatile, liquid hydrophobic hydrocarbon. In order to benchmark the inter-laboratory variability associated with the proposed slow-stir method, the five laboratories separately determined the solubility of dodecahydrotriphenylene, a hydrophobic solid compound using the existing column elution guideline. Results across the participating laboratories indicated comparable reproducibility with relative standard deviations (RSD) of 20% or less reported for each test compound – solubility method pair. The inter-laboratory RSD was 16% for n-hexylcyclohexane (mean 14 µg/L, n = 5) using the slow-stir method. For dodecahydrotriphenylene, the inter-laboratory RSD was 20% (mean 2.6 µg/L, n = 4) using the existing column elution method. This study outlines approaches that should be followed and the experimental parameters that have been deemed important for an expanded ring trial of the slow-stir water solubility method.

Inert agricultural spray adjuvants may increase the adverse effects of selected insecticides on honey bees (Apis mellifera L.) under laboratory conditions

Currently, more than 350 spray adjuvants are registered in Germany (January 2021). Unlike plant protection products (PPPs), adjuvants are not subjected to regulatory risk assessment. In practice, numerous combinations of PPPs and adjuvants are therefore possible. Thus, tank mixtures containing insecticides that are classified as nonhazardous to bees and approved for use in bee attractive crops may raise pollinator safety concerns when mixed with efficacy increasing adjuvants. This study analyzes whether selected “PPP-adjuvant” combinations result in increased mortality and pose an elevated risk to honey bees. To answer this question, we chose six common spray adjuvants of different classes for laboratory screening. These were then tested in a total of 30 tank mixtures, each with a neonicotinoid (acetamiprid), pyrethroid (lambda-cyhalothrin), diamide (chlorantraniliprole), carbamate (pirimicarb), and butenolide (flupyradifurone) formulation. We followed OECD test guideline 214 (acute contact test) but adopted the use of a professional spray chamber for more realistic exposures. Our results showed that, in total, 50% of all combinations significantly reduced the lifespan of caged honey bees in comparison to individual application of insecticides. In contrast, none of the adjuvants alone affected bee mortality (Cox proportional hazard model, p > 0.05). With four of the five insecticide formulations, the organosilicone surfactant Break-Thru® S 301 significantly increased bee mortality within 72 h (for all insecticides except chlorantraniliprole). Furthermore, acetamiprid yielded the highest and second-highest mortality increases from a tank mixture with the crop oil surfactants LI-700 (hazard ratio = 28.84, p < 0.05) and Break-Thru® S 301 (hazard ratio = 14.66, p < 0.05), respectively. In the next step, field trials should be performed to provide a more realistic exposure scenario under colony conditions to verify these findings.

Brief communication: new perspectives on the calculation of bioaccumulation factors for active substances in living organisms

Today, there are no ready-to-use convenient tools in ecotoxicology to diagnose and predict the accumulation and effects of chemical substances on living organisms, accounting for exposure situations that are known to be complex (routes of exposure, metabolization processes, cocktail effects, etc.). Regarding plant protection products in marketing authorization applications, regulation No 283/2013 (EU) defines the data requirements for active substances with a bioaccumulation test on fish according to OECD Test guideline 305. This paper presents new perspectives on the estimation of the bioaccumulation factors via an innovative ready-to-use web tool providing these factors, associated with their uncertainty to facilitate the daily work of regulators, but also of any user, by benefiting of a freely available and user-friendly on-line interface avoiding to invest into underlying mathematical and statistical technicalities. This tool, MOSAICbioacc, is available at https://mosaic.univ-lyon1.fr/bioacc, and can be used by any environmental scientists, ecotoxicologists or managers when accumulation-depuration data are collected and need to be easily and quickly analysed.

Attachment Efficiency of Nanomaterials to Algae as an Important Criterion for Ecotoxicity and Grouping

Engineered nanomaterials (ENMs) based on CeO2 and TiO2 differ in their effects on the unicellular green alga Raphidocelis subcapitata but these effects do not reflect the physicochemical parameters that characterize such materials in water and other test media. To determine whether interactions with algae can predict the ecotoxicity of ENMs, we studied the attachment of model compounds (three subtypes of CeO2 and five subtypes of TiO2) to algal cells by light microscopy and electron microscopy. We correlated our observations with EC50 values determined in growth inhibition assays carried out according to the Organisation for Economic Co-operation and Development (OECD) test guideline 201. Light microscopy revealed distinct patterns of ENM attachment to algal cells according to the type of compound, with stronger interactions leading to greater toxicity. This was confirmed by electron microscopy, which allowed the quantitative assessment of particle attachment. Our results indicate that algal extracellular polymeric substances play an important role in the attachment of ENMs, influencing the formation of agglomerates. The attachment parameters in short-term tests predicted the toxicity of CeO2 and TiO2 ENMs and can be considered as a valuable tool for the identification of sets of similar nanoforms as requested by the European Chemicals Agency in the context of grouping and read-across.