Effect of dietary supplementation with ultramicronized palmitoylethanolamide in maintaining remission in cats with nonflea hypersensitivity dermatitis: a double-blind, multicentre, randomized, placebo-controlled study

Background Feline nonflea hypersensitivity dermatitis (NFHD) is a frequent cause of over-grooming, scratching and skin lesions. Multimodal therapy often is necessary. Hypothesis/Objectives To investigate the efficacy of ultramicronized palmitoylethanolamide (PEA-um) in maintaining methylprednisolone-induced remission in NFHD cats. Animals Fifty-seven NFHD cats with nonseasonal pruritus were enrolled originally, of which 25 completed all study requirements to be eligible for analysis. Methods and materials Cats were randomly assigned to PEA-um (15 mg/kg per os, once daily; n = 29) or placebo (n = 28) while receiving a 28 day tapering methylprednisolone course. Cats responding favourably to methylprednisolone were then administered only PEA-um (n = 21) or placebo (n = 23) for another eight weeks, followed by a four week long treatment-free period. Cats were maintained in the study until relapse or study end, whichever came first. Primary outcome was time to relapse. Secondary outcomes were pruritus Visual Analog Scale (pVAS), SCORing Feline Allergic Dermatitis scale (SCORFAD) and owner Global Assessment Score (GAS). Results Mean relapse time was 40.5 days (+/- 7.8 SE) in PEA-um treated cats (n = 13) and 22.2 days (+/- 3.7 SE) for placebo (n = 12; P = 0.04). On Day 28, the severity of pruritus was lower in the PEA-um treated cats compared to placebo (P = 0.03). Mean worsening of pruritus at the final study day was lower in the PEA-um group compared to placebo (P = 0.04), whereas SCORFAD was not different between groups. Mean owner GAS at the final study day was better in the PEA-um than the placebo-treated group (P = 0.05). Conclusion and clinical importance Ultramicronized palmitoylethanolamide could represent an effective and safe option to delay relapse in NFHD cats

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Using Case-Based Reasoning to Focus Model-Based Diagnostic Problem Solving

The aim of this paper is to present an approach to the integration of Case-Based Reasoning with Model-Based Reasoning in diagnostic problem solving. Such an integration is exploited by defining adaptation criteria on solutions retrieved by a case-based reasoner, in order to focus the model-based reasoner in the search for the solution of the current case and avoiding, as much as possible, the computation of the solution from scratch. Such adaptation criteria strictly rely on a formad theory of diagnosis that allows us to define different adaptation levels, relative to the trade-off between \u201caccuracy of the solution\u201d and \u201ccomputational effort\u201d. A simple example in the domain of car engine faults is presented and some important aspects are finally pointed out on the basis of our preliminary experiments