A Pharmacokinetic/Pharmacodynamic Study of Esomeprazole Comparing a Dual Delayed-Release Formulation (YYD601) to a Conventional Formulation Following Multiple Administrations in Healthy Adult Subjects.

Background: YYD601 is a new dual delayed-release formulation of esomeprazole, developed to enhance plasma exposure and prolong the duration of acid suppression.

Purpose: This study aimed to evaluate the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of YYD601 20 mg following single and multiple oral administrations in healthy, fasting adult Koreans, and to compare these outcomes to those of the conventional esomeprazole 20 mg capsule.

Methods: A randomized, open-label, two-period crossover study was conducted in 28 participants, who were divided into two treatment groups: one group received YYD601 20 mg, and the other received conventional esomeprazole 20 mg, once daily for five consecutive days.

Candesartan Has No Clinically Meaningful Effect on the Plasma Concentrations of Cytochrome P450 2C8 Substrate Repaglinide in Humans.

In vitro evidence shows that the acyl--D-glucuronide metabolite of candesartan inhibits cytochrome P450 (CYP) 2C8 with an inhibition constant of 7.12 M. We investigated the effect of candesartan on the plasma concentrations and glucose-lowering effect of repaglinide, a sensitive clinical CYP2C8 index substrate.

Methyltransferase Like-3-Mediated N6-Methyladenosine Modification of Long Noncoding RNA Hepatocyte Nuclear Factor 1a Antisense RNA 1/Hepatocyte Nuclear Factor 4a Antisense RNA 1 Regulates Cytochrome P450 Enzyme Expression.

Interindividual variations in the expression and activity of cytochrome P450 enzymes (CYPs) led to lower therapeutic efficacy or adverse drug events. We previously demonstrated that CYPs are regulated by the long noncoding RNAs (lncRNAs) hepatocyte nuclear factor 1a antisense RNA 1 (HNF1A-AS1) and HNF4A-AS1 via transcription factors (TFs) including hepatocyte nuclear factor 1a (HNF1A), hepatocyte nuclear factor 4a (HNF4A), and pregnane X receptor (PXR). However, the upstream mechanisms regulating HNF1A-AS1 and HNF4A-AS1 are poorly understood.

Effectiveness of a multidisciplinary and transitional nutritional intervention compared with standard care on health-related quality of life among acutely admitted medical patients aged ≥65 years with malnutrition or risk of malnutrition: A randomized controlled trial.

Background & Aim: Malnutrition, risk of malnutrition, and risk factors for malnutrition are prevalent among acutely admitted medical patients aged ≥65 years and have significant health-related consequences. Consequently, we aimed to investigate the effectiveness of a multidisciplinary and transitional nutritional intervention on health-related quality of life compared with standard care.

Methods: The study was a block randomized, observer-blinded clinical trial with two parallel arms.

Patient-Led Urate Self-Monitoring to Improve Clinical Outcomes in People With Gout: A Feasibility Study.

Objective: Self-monitored point-of-care urate-measuring devices are an underexplored strategy to improve adherence to urate-lowering therapy and clinical outcomes in gout. This study observed patient-led urate self-monitoring practice and assessed its influence on allopurinol adherence, urate control, and health-related quality of life.

Methods: People with gout (n = 31) and prescribed allopurinol self-monitored their urate concentrations (HumaSens2.

Prevalence of use of on-label and off-label psychotropics in the Greek pediatric population.

With a global increased use of psychotropics in pediatrics, their off-label use is a concern due to uncertainty and risk. Data on psychotropics use in the Greek pediatric population do not exist to date. We analyzed retrospective data from the nationwide pharmacy claim database, to estimate the prevalence of psychotropics in pediatrics focusing on off-label use (March 2016-October 2019).

Safety and efficacy of continuous subcutaneous levodopa-carbidopa infusion (ND0612) for Parkinson's disease with motor fluctuations (BouNDless): a phase 3, randomised, double-blind, double-dummy, multicentre trial.

Background: Conventional oral levodopa therapy for the treatment of Parkinson's disease can be associated with variations in plasma concentrations. Levodopa infusion strategies might provide more consistent drug delivery and fewer motor fluctuations. We aimed to assess the safety and efficacy of a continuous 24 h/day subcutaneous infusion of ND0612 (a levodopa-carbidopa solution) compared with oral immediate-release levodopa-carbidopa for the treatment of motor fluctuations in people with Parkinson's disease.

Electroencephalographic Features of Elderly Patients during Anesthesia Induction with Remimazolam: A Substudy of a Randomized Controlled Trial.

Background: Although remimazolam is used as a general anesthetic in elderly patients due to its hemodynamic stability, the electroencephalogram characteristics of remimazolam are not well known. The purpose of this study was to identify the electroencephalographic features of remimazolam-induced unconsciousness in elderly patients and compare them with propofol.

Methods: Remimazolam (n = 26) or propofol (n = 26) were randomly administered for anesthesia induction in surgical patients.

Cumulative Incidence of Thiazide-Induced Hyponatremia : A Population-Based Cohort Study.

Background: According to drug labels, the frequency of thiazide-induced hyponatremia is unknown or uncommon to very rare (that is, <1 in 10 000 to <1 in 100), but the exact burden remains unclear.

Objective: To estimate the increase in the cumulative incidence of hyponatremia using thiazide diuretics compared with nonthiazide antihypertensive drugs in routine clinical practice.

Design: Population and register-based cohort study using target trial emulation.

Benefits and challenges of electronic package leaflet (ePL) - review of ePL pilots in hospital settings in Europe.

Inclusion of package leaflets in paper format is a legal requirement in European Union (EU), therefore the electronic package leaflet (ePL) is a relatively unknown phenomenon in medicinal products in Europe. Introduction of ePL only would be a more sustainable format of providing the product information than paper package leaflet. Furthermore, ePL would support health care professionals' comprehension of product use through electronic searchability and facilitate access to up-to-date product information in respective language used.

Assessment of explicit and implicit memories during remimazolam anaesthesia using the process dissociation procedure: A prospective cohort study.

Background: Memory formation during remimazolam anaesthesia, where a bispectral index (BIS) is sometimes not maintained at less than 60 despite the maximal dose, is worthy of evaluation.

Objective: Investigate the formation of explicit and implicit memories using the process dissociation procedure during remimazolam anaesthesia at a BIS of 60 to 80.

Design: A prospective cohort study.

Association Between Age and Low-Density Lipoprotein Cholesterol Response to Statins : A Danish Nationwide Cohort Study.

Background: There is large patient-to-patient variability in the low-density lipoprotein cholesterol (LDL-C) response to statin treatment. The reduction in LDL-C may depend on the age of the patient treated-particularly in older adults, who have been substantially underrepresented in randomized controlled trials.

Objective: To investigate the association between age and the LDL-C reduction by statins.

Immunogenicity of Bacillus Calmette-Guérin in pigs: potential as a translational model of non-specific effects of BCG.

Background: Clinical and immunological studies in humans show that the live attenuated (BCG) vaccine has beneficial non-specific effects, increasing resistance against diseases other than tuberculosis. The underlying mechanisms are currently being explored. The pig exhibits considerable physiological similarity to humans in anatomy and physiology, suggesting that similar responses to BCG could be expected.

Fed and fasted bioequivalence assessment of two formulations of extended-release fixed-dose combination dapagliflozin/metformin (10/1,000 mg) tablets in healthy subjects.

Unlabelled: Two open-label, randomized, two-period crossover studies were conducted to investigate the pharmacokinetic (PK) properties, safety, and bioequivalence of the test formulation (KD4004), a new fixed-dose combination (FDC) formulation of dapagliflozin and metformin extended release (XR) tablets, relative to the reference formulation (10 mg dapagliflozin/1,000 mg metformin XR FDC tablet) in healthy subjects under fasting (Part A) and fed (Part B) conditions. After giving the dose, serial blood samples were collected for a period of 48 hours. Primary PK parameters (AUC and C) were used to assess bioequivalence between two dapagliflozin/metformin XR (10/1,000 mg) FDC formulations under fed and fasting conditions.

Frequency and characteristics of patients with bispectral index values of 60 or higher during the induction and maintenance of general anesthesia with remimazolam.

In Korea, the approved anesthetic regimen of remimazolam starts with 6 mg/kg/h or 12 mg/kg/h until loss of consciousness, followed by maintenance at 1-2 mg/kg/h. Some patients receiving remimazolam for general anesthesia experience occasional difficulty maintaining bispectral index (BIS) value ˂ 60. This retrospective study aimed to analyze the data from patients undergoing elective surgery under remimazolam based-general anesthesia to determine the frequency and physical characteristics of patients with BIS values ˂ 60.

Changes in PD-1- and CTLA-4-bearing blood lymphocytes in ICU COVID-19 patients treated with Favipiravir/Kaletra or Dexamethasone/Remdesivir: a pilot study.

COVID-19, caused by SARS-CoV-2, requires new approaches to control the disease. Programmed cell death protein (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) play important roles in T-cell exhaustion in severe COVID-19. This study evaluated the frequency of whole blood lymphocytes expressing PD-1 and CTLA-4 in COVID-19 patients upon admission to the intensive care unit (ICU) (i.

Metabolomic analysis of the inhibitory effect of phthalates and bisphenol A on the antioxidant activity of vitamin D in human samples using liquid chromatography-mass spectrometry.

Vitamin D is important because it has roles in maintaining musculoskeletal health, redox homeostasis, and the immune system; however, it is commonly dysregulated by endocrine disrupting chemicals, particularly phthalates and bisphenol A (BPA). Continuous exposure to phthalates and BPA may alter the endogenous metabolite profiles associated with vitamin D activity, although the specific metabolites are yet to be identified. In this study, we identified the endogenous metabolites altered by phthalates and BPA exposure through untargeted metabolic profiling and investigated the role of these metabolites in vitamin D activity.

Absorption, Metabolism, and Excretion of Taselisib (GDC-0032), a Potent -Sparing PI3K Inhibitor in Rats, Dogs, and Humans.

Taselisib (also known as GDC-0032) is a potent and selective phosphoinositide 3-kinase (PI3K) inhibitor that displays greater selectivity for mutant PI3K than wild-type PI3K To better understand the absorption, distribution, metabolism, and excretion properties of taselisib, mass balance studies were conducted following single oral doses of [C]taselisib in rats, dogs, and humans. Absolute bioavailability (ABA) of taselisib in humans was determined by oral administration of taselisib at the therapeutic dose followed by intravenous dosing of [C]taselisib as a microtracer. The ABA in humans was 57.

Examining the Characteristics of Colchicine-Induced Myelosuppression in Clinical Cases: A Systematic Review.

Objective: The use of colchicine has been associated with varying degrees of myelosuppression. Despite expanded use in cardiovascular and inflammatory conditions, there remains clinician concern because of potential myelosuppressive side effects. A systematic review was conducted to explore the reported myelosuppressive events of colchicine.