Outcome and Prognostic Factors of COVID-19 Infection in Swiss Cancer Patients: Final Results of SAKK 80/20 (CaSA).

Purpose: These are the final results of a national registry on cancer patients with COVID-19 in Switzerland. Methods: We collected data on symptomatic COVID-19-infected cancer patients from 23 Swiss sites over a one-year period starting on 1 March 2020. The main objective was to assess the outcome (i.

Pharmacokinetic modelling and simulation to optimize albendazole dosing in hookworm- or Trichuris trichiura-infected infants to adults.

Background: Albendazole is the most commonly used drug in preventive chemotherapy programmes against soil-transmitted helminth (STH) infections, with the standard dose of 400 mg resulting in suboptimal clinical outcomes. Population pharmacokinetic (PK) models that could inform dosing strategies are not yet available.

Methods: A population pharmacokinetic model was developed based on micro-blood samples collected from 252 patients aged 2 to 65 years, infected with either hookworm or Trichuris trichiura and treated with albendazole doses ranging from of 200 to 800 mg.

Pharmacometric Analysis of Tribendimidine Monotherapy and Combination Therapies To Achieve High Cure Rates in Patients with Hookworm Infections.

In the treatment of hookworm infections, pharmacotherapy has been only moderately successful and drug resistance is a threat. Therefore, novel treatment options including combination therapies should be considered, in which tribendimidine could play a role. Our aims were to (i) characterize the pharmacokinetics of tribendimidine's metabolites in adolescents receiving tribendimidine monotherapy or in combination with ivermectin or oxantel pamoate, (ii) evaluate possible drug-drug interactions (DDI), (iii) link exposure to response, and (iv) identify a treatment strategy associated with high efficacy, i.

Efficacy and safety of ascending dosages of albendazole against in preschool-aged children, school-aged children and adults: A multi-cohort randomized controlled trial.

Background: The efficacy of the widely used albendazole against the soil-transmitted helminth is limited; yet optimal doses, which may provide increased efficacy, have not been thoroughly investigated to date.

Methods: A randomized-controlled trial was conducted in Côte d'Ivoire with preschool-aged children (PSAC), school-aged children (SAC), and adults infected with . Participants were randomly assigned (1:1:1:1) using computer-generated randomization.

Ivermectin Dosing Strategy to Achieve Equivalent Exposure Coverage in Children and Adults.

Ivermectin is a commonly used broad-spectrum antiparasitic drug, yet doses that produce consistent exposure coverage across age have not been characterized, and no data are available in children weighing < 15 kg. First, a population pharmacokinetic model is developed based on data from 200 children and 11 adults, treated with 100-600 μg/kg ivermectin. Second, model-based simulations are performed to identify a dosing strategy that achieves equivalent exposure coverage in children and adults.

Pharmacokinetics of ascending doses of ivermectin in Trichuris trichiura-infected children aged 2-12 years.

Background: Yearly, millions of children are treated globally with ivermectin mainly for neglected tropical diseases. Anatomical, physiological and biochemical differences between children and adults may result in changes in pharmacokinetics. However, paediatric pharmacokinetic data of ivermectin are lacking.

Pharmacokinetics of Albendazole, Albendazole Sulfoxide, and Albendazole Sulfone Determined from Plasma, Blood, Dried-Blood Spots, and Mitra Samples of Hookworm-Infected Adolescents.

Albendazole is an effective anthelmintic intensively used for decades. However, profound pharmacokinetic (PK) characterization is missing in children, the population mostly affected by helminth infections. Blood microsampling would facilitate PK studies in pediatric populations but has not been applied to quantify albendazole's disposition.

and Drug-Drug Interaction Study of the Effects of Ivermectin and Oxantel Pamoate on Tribendimidine.

Soil-transmitted helminth (STH) infections still remain a major health problem in poor rural settings. The lack of efficacious drugs against all STH species raises interest in drug combinations. Drug-drug interactions (DDIs) are, however, of major concern, so careful and characterization is needed.

Preventive Chemotherapy in the Fight against Soil-Transmitted Helminthiasis: Achievements and Limitations.

Soil-transmitted helminths (STHs) are endemic in more than half of the world's countries. The World Health Organization has advocated targeted preventive chemotherapy (PC) to control STH infections by distributing albendazole or mebendazole to at-risk populations. While the overall impact and sustainability of this strategy is disputed, a decrease in moderate and heavy STH infections can be largely attributed to a scale-up of drug distribution.

Efficacy and Safety of Ivermectin Against Trichuris trichiura in Preschool-aged and School-aged Children: A Randomized Controlled Dose-finding Trial.

Background: Although trichuriasis affects millions of children worldwide, recommended drugs lack efficacy and new treatment options are urgently needed. Ivermectin has promising potential to complement the anthelminthic armamentarium.

Methods: A randomized placebo-controlled trial was conducted in rural Côte d'Ivoire to provide evidence on the efficacy and safety of ascending oral ivermectin dosages in preschool-aged children (PSAC) and school-aged children (SAC) infected with Trichuris trichiura.

Evaluation of a novel micro-sampling device, Mitra™, in comparison to dried blood spots, for analysis of praziquantel in Schistosoma haematobium-infected children in rural Côte d'Ivoire.

Pharmacokinetic (PK) studies with paediatric populations are increasing in importance for drug development. However, conventional PK sampling methods are characterised by invasiveness and low patient adherence, unsuitable for use with sensitive population, such as children. Mitra™ is a novel volumetric absorptive micro-sampling device, which offers an alternative to the dried blood spotting (DBS) technique, a current popular sampling technique within PK studies.

Site-Specific Polymer Conjugation Stabilizes Therapeutic Enzymes in the Gastrointestinal Tract.

The site-specific conjugation of polymers to multiple engineered cysteine residues of a prolyl endopeptidase leads to its stabilization in the gastrointestinal tract of rats, without compromising the activity relative to the native enzyme. The importance of polymer attachment sites is investigated, as well as the significance of polymer structure.

Improving oral drug bioavailability with polycations?

The administration of drugs via the oral route is challenging due to the (bio)chemical aggressivity of the digestive system and to the presence of barriers that hinder cell uptake and access to the bloodstream. Indeed, the gastrointestinal tract is characterized by large variations of pH, the presence of enzymes and surfactants, and by absorption barriers such as mucus and the epithelium. Thus, many compounds such as proteins and nucleic acids do not reach the systemic circulation due to their premature degradation and/or large size.

Impact of scaffold rigidity on the design and evolution of an artificial Diels-Alderase.

By combining targeted mutagenesis, computational refinement, and directed evolution, a modestly active, computationally designed Diels-Alderase was converted into the most proficient biocatalyst for [4+2] cycloadditions known. The high stereoselectivity and minimal product inhibition of the evolved enzyme enabled preparative scale synthesis of a single product diastereomer. X-ray crystallography of the enzyme-product complex shows that the molecular changes introduced over the course of optimization, including addition of a lid structure, gradually reshaped the pocket for more effective substrate preorganization and transition state stabilization.

Novel role of the serine protease inhibitor elafin in gluten-related disorders.

Objectives: Elafin, an endogenous serine protease inhibitor, modulates colonic inflammation. We investigated the role of elafin in celiac disease (CD) using human small intestinal tissues and in vitro assays of gliadin deamidation. We also investigated the potential beneficial effects of elafin in a mouse model of gluten sensitivity.

PEG nanocages as non-sheddable stabilizers for drug nanocrystals.

Many potent drugs are difficult to administer intravenously due to poor aqueous solubility. One validated approach for addressing this issue is to process them into colloidal dispersions known as "nanocrystals" (NCs). However, NCs possess high-energy surfaces that must be stabilized with surfactants to prevent aggregation.