Safety, tolerability, pharmacokinetics, and antimalarial activity of MMV533: a phase 1a first-in-human, randomised, ascending dose and food effect study, and a phase 1b Plasmodium falciparum volunteer infection study.

Background: Novel antimalarials are needed to address emerging resistance to artemisinin and partner drugs. We did two trials to evaluate safety, tolerability, pharmacokinetics, and activity against blood stage Plasmodium falciparum for the drug candidate MMV533.

Methods: A phase 1a first-in-human (FIH) trial was conducted at Nucleus Network (Melbourne, VIC, Australia).

COVID-19 Vaccination Recommendations for Immunocompromised Patient Populations: Delphi Panel and Consensus Statement Generation in the United States.

Introduction: The United States Advisory Committee on Immunization Practices (ACIP) and the Centers for Disease Control (CDC) recommend COVID-19 vaccines for all immunocompromised individuals. Certain disease groups are at increased risk of comorbidity and death for which disease-specific recommendations should be considered. The objective of the Delphi panel of experts was to summarize expert consensus on COVID-19 vaccinations for patients with rheumatologic disease, renal disease, hematologic malignancy and solid organ transplant (SOT) in the US.

Delphi Panel Consensus Statement Generation: COVID-19 Vaccination Recommendations for Immunocompromised Populations in the European Union.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare systems globally. The lack of quality guidelines on the management of COVID-19 in rheumatologic disease, renal disease, hematological malignancy, and solid organ transplant recipients has resulted in a wide variation in clinical practice.

Methods: Using a Delphi process, a panel of 16 key opinion leaders developed clinical practice statements regarding vaccine recommendations in areas where standards are absent or limited.

Computing optimal drug dosing regarding efficacy and safety: the enhanced OptiDose method in NONMEM.

Recently, an optimal dosing algorithm (OptiDose) was developed to compute the optimal drug doses for any pharmacometrics model for a given dosing scenario. In the present work, we enhance the OptiDose concept to compute optimal drug dosing with respect to both efficacy and safety targets. Usually, these are not of equal importance, but one is a top priority, that needs to be satisfied, whereas the other is a secondary target and should be achieved as good as possible without failing the top priority target.

Low-Density Lipoprotein Cholesterol Testing Following Myocardial Infarction Hospitalization Among Medicare Beneficiaries.

Background: Low-density lipoprotein cholesterol (LDL-C) is used to guide lipid-lowering therapy after a myocardial infarction (MI). Lack of LDL-C testing represents a missed opportunity for optimizing therapy and reducing cardiovascular risk.

Objectives: The purpose of this study was to estimate the proportion of Medicare beneficiaries who had their LDL-C measured within 90 days following MI hospital discharge.

A randomized, open-label two-period crossover pilot study to evaluate the relative bioavailability in the fed state of atovaquone-proguanil (Atoguanil™) versus atovaquone-proguanil hydrochloride (Malarone®) in healthy adult participants.

Atoguanil™ is a novel complex of atovaquone (ATV) and proguanil (PG) with enhanced ATV bioavailability compared to Malarone®. This pilot study assessed whether the relative bioavailability (F) of ATV, PG, and the primary PG metabolite cycloguanil (CG) following a single oral dose in the fed state of Atoguanil was similar to Malarone despite a 50% lower ATV dose. This open-label, single-dose, randomized 2-period, 2-treatment, balanced crossover study was conducted between 17th November 2021 and 18th March 2022.

Comparison of Synthetic Data Generation Techniques for Control Group Survival Data in Oncology Clinical Trials: Simulation Study.

Background: Synthetic patient data (SPD) generation for survival analysis in oncology trials holds significant potential for accelerating clinical development. Various machine learning methods, including classification and regression trees (CART), random forest (RF), Bayesian network (BN), and conditional tabular generative adversarial network (CTGAN), have been used for this purpose, but their performance in reflecting actual patient survival data remains under investigation.

Objective: The aim of this study was to determine the most suitable SPD generation method for oncology trials, specifically focusing on both progression-free survival (PFS) and overall survival (OS), which are the primary evaluation end points in oncology trials.

Understanding Treatment Preferences for Patients with Tricuspid Regurgitation.

Unlabelled: Tricuspid regurgitation (TR) is a high-prevalence disease associated with poor quality of life and mortality. This quantitative patient preference study aims to identify TR patients' perspectives on risk-benefit tradeoffs. A discrete-choice experiment was developed to explore TR treatment risk-benefit tradeoffs.

The Role of Low Mineral Water Consumption in Reducing the Mineral Density of Bones and Teeth: A Narrative Review.

Low mineral water has gained increasing attention due to its potential health implications concerning bone mineral density (BMD) and dental health. Reverse osmosis (RO) systems to purify water are in use extensively, and these systems, in addition to removing impurities from water, also remove 92-99% of beneficial minerals like calcium, lead, fluoride, magnesium, and iron. These minerals are essential for maintaining optimal mineral density of teeth and bones, thereby preserving bone and teeth health.

Pharmacodynamic Age Structured Population Model For Cell Trafficking.

Objectives: Cell trafficking encompasses movement of the immune system cells (e.g., granulocytes, lymphocytes) between the blood and the extravascular tissues (e.

Reduced heart failure-related healthcare costs with Furoscix versus in-hospital intravenous diuresis in heart failure patients: the FREEDOM-HF study.

Compare heart failure (HF) costs of Furoscix use at home compared with inpatient intravenous (IV) diuresis. Prospective, case control study of chronic HF patients presenting to emergency department (ED) with worsening congestion discharged to receive Furoscix 80 mg/10 ml 5-h subcutaneous infusion for ≤7 days. 30-day HF-related costs in Furoscix group derived from commercial claims database compared with matched historical patients hospitalized for <72 h.

Population pharmacokinetics of atacicept in systemic lupus erythematosus: An analysis of three clinical trials.

B cell stimulating factor (BLyS) and a proliferation-inducing ligand (APRIL) are targets for novel treatments in patients with systemic lupus erythematosus (SLE). Atacicept is a recombinant, soluble fusion protein that blocks BLyS and APRIL activity. This study characterized the pharmacokinetic (PK) profile of atacicept using a population PK model and identified covariates explaining the PK variability.

Antibody seropositivity and endemicity of chikungunya and Zika viruses in Nigeria.

Unlabelled: Mosquito-borne infections are of global health concern because of their rapid spread and upsurge, which creates a risk for coinfections. chikungunya virus (CHIKV), an arbovirus disease transmitted by or , and malaria, a parasitic disease transmitted by , are prevalent in Nigeria and neighbouring countries, but their burden and possible coinfections are poorly understood. In this study, we investigated the antibody seropositivity and endemicity of chikungunya and Zika viruses (ZIKV) in three regions of Nigeria.

Lung Function Decline in Cystic Fibrosis: Impact of Data Availability and Modeling Strategies on Clinical Interpretations.

Studies estimating the rate of lung function decline in cystic fibrosis have been inconsistent regarding the methods used. How the methodology used impacts the validity of the results and comparability between studies is unknown. The Cystic Fibrosis Foundation established a work group whose tasks were to examine the impact of differing approaches to estimating the rate of decline in lung function and to provide analysis guidelines.

Psychometric properties of the Alzheimer's Disease Cooperative Study - Activities of Daily Living for Mild Cognitive Impairment (ADCS-MCI-ADL) scale: a post hoc analysis of the ADCS ADC-008 trial.

Background: The Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale for use in Mild Cognitive Impairment (MCI), the ADCS-ADL-MCI, is an evaluation scale with information provided by an informant/caregiver to describe the functional impairment of patients with MCI. As the ADCS-ADL-MCI has yet to undergo a full psychometric evaluation, this study aimed to evaluate the measurement properties of the ADCS-ADL-MCI in subjects with amnestic MCI.

Methods: Measurement properties, including item-level analysis, internal consistency reliability, test-retest reliability, construct validity (convergent/discriminant, known-groups validity), and responsiveness were evaluated using data from the ADCS ADC-008 trial, a 36-month, multicenter, placebo-controlled study in 769 subjects with amnestic MCI (defined by clinical criteria and a global clinical dementia rating, CDR, score of 0.

A Survey of Patient Experience in CML: American and Canadian Perspectives.

Purpose: With treatment, chronic myeloid leukemia (CML) has a favorable prognosis, however, individuals with CML experience impairment to their quality of life (QoL). The aim of this study was to examine the perspectives and experiences of individuals with CML and to understand their challenges communicating with their CML physician.

Patients And Methods: An online survey in adults with CML (n=100) in the US and Canada assessed QoL, patient-provider relationships, treatment satisfaction, and understanding of CML and treatment goals via the MD Anderson Symptom Inventory, the Cancer Therapy Satisfaction Questionnaire and de novo survey questions.

Declining Enrolment and Other Challenges in IBD Clinical Trials: Causes and Potential Solutions.

Background: Rates of enrolment in clinical trials in inflammatory bowel disease [IBD] have decreased dramatically in recent years. This has led to delays, increased costs and failures to develop novel treatments.

Aims: The aim of this work is to describe the current bottlenecks of IBD clinical trial enrolment and propose solutions.

Computing optimal drug dosing with OptiDose: implementation in NONMEM.

Determining a drug dosing recommendation with a PKPD model can be a laborious and complex task. Recently, an optimal dosing algorithm (OptiDose) was developed to compute the optimal doses for any pharmacometrics/PKPD model for a given dosing scenario. In the present work, we reformulate the underlying optimal control problem and elaborate how to solve it with standard commands in the software NONMEM.

Pediatric Population Pharmacokinetic Modeling and Exposure-Response Analysis of Ambrisentan in Pulmonary Arterial Hypertension and Comparison With Adult Data.

This study aimed to develop a population pharmacokinetic (PK) model of ambrisentan in pediatric patients (8 to <18 years) with pulmonary arterial hypertension (PAH) and compare pediatric ambrisentan systemic exposure with previously reported adult data. Association of ambrisentan exposure with efficacy (6-minute walking distance) and safety (adverse events) were exploratory analyses. A population PK model was developed using pediatric PK data.

Web based resource for Statistical Consultants in the Pharmaceutical Industry.

The intention of this article is to highlight sources of web-based reference material and software that will aid consulting statisticians when designing clinical trials. The article includes websites that provide links to explanation of statistical concepts for non-statisticians, regulatory guidelines, and free statistical study design software.

A Phase 1 pharmacokinetic study of a single-dose bioadhesive clindamycin 2% gel for bacterial vaginosis.

Objectives: To evaluate pharmacokinetics (PK) of a single dose of an investigational 2% clindamycin phosphate vaginal gel in healthy women by assessment of plasma and vaginal clindamycin concentrations over 7 days, and assess safety.

Methods: Single-centre, Phase 1, single-dose PK study. Blood and vaginal samples were collected daily and safety was evaluated through to Day 7.

KRAS mutation predict response and outcome in advanced non-small cell lung carcinoma without driver alterations receiving PD-1 blockade immunotherapy combined with platinum-based chemotherapy: a retrospective cohort study from China.

Background: The selection of patients for immunotherapy remains challenging given the lack of highly specific and highly sensitive biomarkers. Kirsten rat sarcoma () mutation is the most frequent molecular alteration found in advanced non-small cell lung carcinoma (NSCLC). We explored whether mutation status predicted the effects of first-line immune checkpoint inhibitor (ICI) treatment and platinum-based chemotherapy in Chinese patients with advanced NSCLC.