Effect of paracetamol (acetaminophen) and ibuprofen on body temperature in acute ischemic stroke PISA, a phase II double-blind, randomized, placebo-controlled trial [ISRCTN98608690]

BACKGROUND: Body temperature is a strong predictor of outcome in acute stroke. In a previous randomized trial we observed that treatment with high-dose acetaminophen (paracetamol) led to a reduction of body temperature in patients with acute ischemic stroke, even when they had no fever. The purpose of the present trial was to study whether this effect of acetaminophen could be reproduced, and whether ibuprofen would have a similar, or even stronger effect. METHODS: Seventy-five patients with acute ischemic stroke confined to the anterior circulation were randomized to treatment with either 1000 mg acetaminophen, 400 mg ibuprofen, or placebo, given 6 times daily during 5 days. Treatment was started within 24 hours from the onset of symptoms. Body temperatures were measured at 2-hour intervals during the first 24 hours, and at 6-hour intervals thereafter. RESULTS: No difference in body temperature at 24 hours was observed between the three treatment groups. However, treatment with high-dose acetaminophen resulted in a 0.3°C larger reduction in body temperature from baseline than placebo treatment (95% CI: 0.0 to 0.6 °C). Acetaminophen had no significant effect on body temperature during the subsequent four days compared to placebo, and ibuprofen had no statistically significant effect on body temperature during the entire study period. CONCLUSIONS: Treatment with a daily dose of 6000 mg acetaminophen results in a small, but potentially worthwhile decrease in body temperature after acute ischemic stroke, even in normothermic and subfebrile patients. Further large randomized clinical trials are needed to study whether early reduction of body temperature leads to improved outcome

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

Assigning Defined Daily/Course Doses for Antimicrobials in Turkeys to Enable a Cross-Country Quantification and Comparison of Antimicrobial Use

Antimicrobial resistance (AMR) threatens our public health and is mainly driven by antimicrobial usage (AMU). For this reason the World Health Organization calls for detailed monitoring of AMU over all animal sectors involved. Therefore, we aimed to quantify AMU on turkey farms. First, turkey-specific Defined Daily Dose (DDDturkey) was determined. These were compared to the broiler alternative from the European Surveillance of Veterinary Antimicrobial Consumption (DDDvet), that mention DDDvet as a proxy for other poultry species. DDDturkey ranged from being 81.5% smaller to 48.5% larger compared to its DDDvet alternative for broilers. Second, antimicrobial treatments were registered on 60 turkey farms divided over France, Germany and Spain between 2014 and 2016 (20 flocks per country). Afterwards, AMU was quantified using treatment incidence (TI) per 100 days. TI expresses the percentage of the rearing period that the turkeys were treated with a standard dose of antimicrobials. Minimum, median and maximum TI at flock level and based on DDDturkey = 0.0, 10.0 and 65.7, respectively. Yet, a huge variation in amounts of antimicrobials used at flock level was observed, both within and between countries. Seven farms (12%) did not use any antimicrobials. Aminopenicillins, polymyxins, and fluoroquinolones were responsible for 72.2% of total AMU. The proportion of treating farms peaked on week five of the production cycle (41.7%), and 79.4% of the total AMU was administered in the first half of production. To conclude, not all DDDvet values for broilers can be applied to turkeys. Additionally, the results of AMU show potential for reducing and improving AMU on turkey farms, especially concerning the usage of critically important antimicrobials.</jats:p

Abstract WMP19: Pattern of Internal Carotid Artery Calcification Modifies the Effect of Intravenous Thrombolysis

Introduction: The pattern of intracranial internal carotid artery calcification (ICAC) has been identified as an effect modifier of endovascular treatment in patients with acute ischemic stroke, but it is unclear whether it modifies the effect of intravenous thrombolysis. We evaluated the association between intravenous thrombolysis and 90-day clinical outcome, follow-up infarct volume and recanalization across different patterns of ICAC. Methods: Three groups from the Dutch acute stroke study, a prospective multicentre observational cohort study, were analyzed: patients with ischemic stroke, a subgroup (1) of patients with intracranial anterior circulation occlusions and a subgroup (2) of patients with M1 occlusions. ICAC pattern was determined on admission thin-slice non-contrast CT and categorized as absent, intimal, medial or indistinguishable. The primary outcome was 90-day modified Rankin scale. Other outcomes included follow-up infarct volume, recanalization and collateral status. Associations were quantified with regression analyses and stratified by ICAC pattern. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for demographics, cardiovascular risk factors, stroke severity, occlusion site and collateral status. Results: Of the 982 patients 609 (62%) received intravenous thrombolysis and 381 (39%) had unfavorable clinical outcome. Intravenous thrombolysis was associated with a lower modified Rankin scale in the groups without ICAC (adjusted OR 0.3; 95% CI 0.1-0.9) and with a medial ICAC pattern (adjusted OR 0.5; 95% CI 0.3-0.8), but not in the groups with an intimal (adjusted OR 0.9;95%-CI:0.5-1.5) or indistinguishable pattern (adjusted OR 0.6; 95% CI 0.2-1.8). In subgroup 1 (n=220), intravenous thrombolysis was associated with recanalization only in the group with a medial ICAC pattern (adjusted OR 3.5; 95% CI 1.2-11.0). In subgroup 2 (n=148), compared to an intimal ICAC pattern a medial ICAC pattern was associated with good collateral status (adjusted OR 2.6; 95% CI 1.1-6.0). Conclusions: Intravenous thrombolysis was significantly related to favorable clinical outcome and recanalization in the group with a medial ICAC pattern, but not in the groups with other ICAC patterns. </jats:p

Biosecurity and antimicrobial use in broiler farms across nine European countries: toward identifying farm-specific options for reducing antimicrobial usage

Abstract Broiler chickens are among the main livestock sectors worldwide. With individual treatments being inapplicable, contrary to many other animal species, the need for antimicrobial use (AMU) is relatively high. AMU in animals is known to drive the emergence and spread of antimicrobial resistance (AMR). High farm biosecurity is a cornerstone for animal health and welfare, as well as food safety, as it protects animals from the introduction and spread of pathogens and therefore the need for AMU. The goal of this study was to identify the main biosecurity practices associated with AMU in broiler farms and to develop a statistical model that produces customised recommendations as to which biosecurity measures could be implemented on a farm to reduce its AMU, including a cost-effectiveness analysis of the recommended measures. AMU and biosecurity data were obtained cross-sectionally in 2014 from 181 broiler farms across nine European countries (Belgium, Bulgaria, Denmark, France, Germany, Italy, the Netherlands, Poland and Spain). Using mixed-effects random forest analysis (Mix-RF), recursive feature elimination was implemented to determine the biosecurity measures that best predicted AMU at the farm level. Subsequently, an algorithm was developed to generate AMU reduction scenarios based on the implementation of these measures. In the final Mix-RF model, 21 factors were present: 10 about internal biosecurity, 8 about external biosecurity and 3 about farm size and productivity, with the latter showing the largest (Gini) importance. Other AMU predictors, in order of importance, were the number of depopulation steps, compliance with a vaccination protocol for non-officially controlled diseases, and requiring visitors to check in before entering the farm. K-means clustering on the proximity matrix of the final Mix-RF model revealed that several measures interacted with each other, indicating that high AMU levels can arise for various reasons depending on the situation. The algorithm utilised the AMU predictive power of biosecurity measures while accounting also for their interactions, representing a first step toward aiding the decision-making process of veterinarians and farmers who are in need of implementing on-farm biosecurity measures to reduce their AMU.</jats:p