Polyradiculitis as a Neurological Complication Associated with Adagrasib: A Case Report.

Introduction: Adagrasib is an upcoming anticancer treatment for KRAS G12C-mutated non-small-cell lung carcinoma, colorectal cancer and potentially other solid tumors harboring this mutation. It is generally well-tolerated and reports of neurological adverse events so far have been limited.

Case Presentation: We present to our best knowledge the first case of a 70-year-old woman who was admitted with polyradiculitis as a treatment-related complication of adagrasib.

Azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a phase II randomised controlled trial.

Background: African children with severe malaria are at increased risk of non-typhoidal salmonellae co-infection. Broad-spectrum antibiotics are recommended by guidelines but the optimal class and dose have not been established. We investigated the optimal dose of oral dispersible azithromycin and whether simple clinical criteria and point-of-care biomarkers could target antibiotics to those at greatest risk of bacterial co-infection.

Impact of two human milk oligosaccharides and lactose on the faecal microbiome of infants with probable cow's milk allergy.

Cow's milk protein allergy (CMPA) in infancy is associated with intestinal microbial dysbiosis, characterised by low Bifidobacteriaceae levels. The present study aimed to investigate the impact of two human milk oligosaccharides (HMO), lactose (L), and their combination on the faecal microbiome and metabolome of infants with CMPA. Stool samples of 12 term infants with probable CMPA (mean age 4.

A comparison of the renal function biomarkers serum creatinine, pro-enkephalin and cystatin C to predict clearance of pemetrexed.

Introduction: For drugs with a narrow therapeutic window, there is a delicate balance between efficacy and toxicity, thus it is pivotal to administer the right dose from the first administration onwards. Exposure of pemetrexed, a cytotoxic drug used in lung cancer treatment, is dictated by kidney function. To facilitate optimized dosing of pemetrexed, accurate prediction of drug clearance is pivotal.

Model-informed dose optimization of mycophenolic acid in pediatric kidney transplant patients.

Purpose: We aimed to develop and evaluate a population PK model of mycophenolic acid (MPA) in pediatric kidney transplant patients to aid MPA dose optimization.

Methods: Data were collected from pediatric kidney transplant recipients from a Dutch academic hospital (Radboudumc, the Netherlands). Pharmacokinetic model-building and model-validation analyses were performed using NONMEM.

Development and validation of an ultra-performance liquid chromatography-tandem mass spectrometry method to quantify the small molecule inhibitors adagrasib, alectinib, brigatinib, capmatinib, crizotinib, lorlatinib, selpercatinib, and sotorasib in human plasma.

Small molecule inhibitors (SMIs) are increasingly being used in the treatment of non-small cell lung cancer. To support pharmacokinetic research and clinical treatment monitoring, our aim was to develop and validate an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) assay for quantification of eight SMIs: adagrasib, alectinib, brigatinib, capmatinib, crizotinib, lorlatinib, selpercatinib, and sotorasib. Development of the UPLC-MS/MS assay was done by trying different columns and eluents to optimize peak shape.

An Evidence-Based Rationale for Dose De-escalation of Subcutaneous Atezolizumab.

Background: Atezolizumab is a programmed death-ligand 1 (PD-L1) checkpoint inhibitor for the treatment of different forms of cancer. The subcutaneous formulation of atezolizumab has recently received approval. However, treatment with atezolizumab continues to be expensive, and the number of patients needing treatment with this drug continues to increase.

Maternal Sepsis.

Sepsis is the second leading cause of pregnancy-related mortality in the United States. Early recognition, treatment, and escalation of care for the obstetric patient affected by sepsis mitigate the risk of mortality and improve patient outcomes. In this article, we provide an overview of maternal sepsis and address topics of maternal pathophysiology, early warning signs, diagnostic criteria, early goal-directed therapy, and contemporary critical care practices.

A sub-pharmacological test dose does not predict individual docetaxel exposure in prostate cancer patients.

Purpose: Docetaxel is a cytotoxic drug used for first-line treatment of various malignancies. It has a narrow therapeutic index and shows wide interpatient variability in clearance and toxicity. Tools for individual dose optimization are needed to maximize efficacy and avoid toxicity.

Market Entry Agreements for Innovative Pharmaceuticals Subject to Indication Broadening: A Case Study for Pembrolizumab in The Netherlands.

Objectives: Managed entry agreements and especially financial-based agreements are commonly used in European countries for innovative cancer pharmaceuticals. These agreements facilitate access to innovative treatments while mitigating financial risks for payers. This study focuses on the confidential price agreement made by the Dutch government for the reimbursement of pembrolizumab, the implications of broadening indications on cost-effectiveness, and the viability or desirability of said agreement.

Model-Informed Development of a Cost-Saving Dosing Regimen for Sacituzumab Govitecan.

Background: The antibody-drug conjugate sacituzumab govitecan is approved for metastatic triple-negative breast cancer and has shown promising results in various other types of cancer. Its costs may limit patient access to this novel effective treatment modality.

Objective: The purpose of this study was to develop an evidence-based rational dosing regimen that results in targeted drug exposure within the therapeutic range while minimizing financial toxicity, to improve treatment access.

Proactive monitoring of drug-drug interactions between direct oral anticoagulants and small-molecule inhibitors in patients with non-small cell lung cancer.

Background: Small-molecule inhibitors (SMIs) have revolutionised the treatment of non-small cell lung cancer (NSCLC). However, SMI-induced drug-drug interactions (DDIs) with frequently co-administered direct oral anticoagulants (DOACs), increase thromboembolic and bleeding risks. This study investigated and proactively managed the consequences of DOAC-SMI DDIs.

Effects of Tirzepatide vs Semaglutide on β-Cell Function, Insulin Sensitivity, and Glucose Control During a Meal Test.

Context: In a clinical study, tirzepatide, a glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist (GIP/GLP-1RA), provided superior glycemic control vs the GLP-1RA semaglutide. The physiologic mechanisms are incompletely understood.

Objective: This work aimed to evaluate treatment effects by model-based analyses of mixed-meal tolerance test (MMTT) data.

Artemether-lumefantrine with or without single-dose primaquine and sulfadoxine-pyrimethamine plus amodiaquine with or without single-dose tafenoquine to reduce Plasmodium falciparum transmission: a phase 2, single-blind, randomised clinical trial in Ouelessebougou, Mali.

Background: Artemether-lumefantrine is widely used for uncomplicated Plasmodium falciparum malaria; sulfadoxine-pyrimethamine plus amodiaquine is used for seasonal malaria chemoprevention. We aimed to determine the efficacy of artemether-lumefantrine with and without primaquine and sulfadoxine-pyrimethamine plus amodiaquine with and without tafenoquine for reducing gametocyte carriage and transmission to mosquitoes.

Methods: In this phase 2, single-blind, randomised clinical trial conducted in Ouelessebougou, Mali, asymptomatic individuals aged 10-50 years with P falciparum gametocytaemia were recruited from the community and randomly assigned (1:1:1:1) to receive either artemether-lumefantrine, artemether-lumefantrine with a single dose of 0·25 mg/kg primaquine, sulfadoxine-pyrimethamine plus amodiaquine, or sulfadoxine-pyrimethamine plus amodiaquine with a single dose of 1·66 mg/kg tafenoquine.

The pharmacokinetics and pharmacodynamics of ibogaine in opioid use disorder patients.

Objective: Ibogaine is a hallucinogenic drug that may be used to treat opioid use disorder (OUD). The relationships between pharmacokinetics (PKs) of ibogaine and its metabolites and their clinical effects on side effects and opioid withdrawal severity are unknown. We aimed to study these relationships in patients with OUD undergoing detoxification supported by ibogaine.

Understanding and maximising the community impact of seasonal malaria chemoprevention in Burkina Faso (INDIE-SMC): study protocol for a cluster randomised evaluation trial.

Introduction: Seasonal malaria chemoprevention (SMC) involves repeated administrations of sulfadoxine-pyrimethamine plus amodiaquine to children below the age of 5 years during the peak transmission season in areas of seasonal malaria transmission. While highly impactful in reducing malaria burden in controlled research settings, the impact of SMC on infection prevalence is moderate in real-life settings. It remains unclear what drives this efficacy decay.

Development of a target concentration intervention to individualize paroxysmal nocturnal hemoglobinuria treatment with pegcetacoplan.

Pegcetacoplan (Aspaveli®/Empaveli™) is a factor C3 inhibitor that is approved for the treatment of paroxysmal nocturnal hemoglobinuria. An individualized dosing strategy might be useful to improve patient-friendliness and cost-effectiveness of this very expensive drug. Therefore, the aim of this study was to develop an individualized treatment regimen for pegcetacoplan based on the pharmacokinetic-pharmacodynamic data of the manufacturer.

Urinary Tract Infection and Progression to Pyelonephritis: Group B versus .

 Group B (GBS) colonization of the lower urinary tract in pregnancy is associated with severe infections such as chorioamnionitis, endometritis, and pyelonephritis. The objective of this study was to compare rates of progression to pyelonephritis between GBS and lower urinary tract infections (LUTIs), as well as compare infectious and obstetric morbidity secondary to these pathogens.  Retrospective cohort of pregnant women with LUTIs (asymptomatic bacteria or acute cystitis [AC]) from a single health system between July 2013 and May 2019.