Employment Status and HIV Viral Load in Chilean Adult Population: A Propensity Score Analysis.

We set out to investigate the potential impact of unemployment on HIV viral load in individuals living with HIV at the biggest HIV-related healthcare centre in Chile. We analysed a cross-sectional dataset of 803 adults living with HIV on antiretroviral therapy. The main exposure was employment status.

Prevention of Stroke in Intracerebral Haemorrhage Survivors with Atrial Fibrillation: Rationale and Design for PRESTIGE-AF Trial.

Adequate secondary prevention in survivors of intracerebral hemorrhage (ICH) who also have atrial fibrillation (AF) is a long-standing clinical dilemma because these patients are at increased risk of recurrent ICH as well as of ischemic stroke. The efficacy and safety of oral anticoagulation, the standard preventive medication for ischemic stroke patients with AF, in ICH patients with AF are uncertain. PRESTIGE-AF is an international, phase 3b, multi-center, randomized, open, blinded end-point assessment (PROBE) clinical trial that compared the efficacy and safety of direct oral anticoagulants (DOACs) with no DOAC (either no antithrombotic treatment or any antiplatelet drug).

Dietary changes following a lifestyle-based intervention for dementia risk reduction - results from the AgeWell.de study.

Purpose: We investigated the effects of a multidomain lifestyle intervention conducted in older adults at increased risk for dementia on participants' diet.

Methods: Secondary analyses of the cluster-randomized AgeWell.de-trial, testing a multidomain intervention (optimization of nutrition and medication, enhancement of physical, social and cognitive activity) in older adults at increased dementia risk.

The "specific" P-glycoprotein inhibitor zosuquidar (LY335979) also weakly inhibits human organic cation transporters.

Zosuquidar (LY335979) is a widely used experimental P-glycoprotein (P-gp) inhibitor, which is commended as very potent but also as very specific for P-gp. In this in vitro and in silico study, we demonstrated for the first time that zosuquidar also inhibits organic cation transporters (OCT) 1-3, albeit less potently than P-gp. This still has to be kept in mind when zosuquidar is used to inhibit cellular efflux of P-gp substrates that are concurrently transported into the cells by OCTs.

Expectations and opinions regarding the implementation of a computerized physician order entry (CPOE) system - a before-and-after survey.

Despite the documented beneficial effects of computerized physician order entry (CPOE) systems and despite numerous incentives for their adoption in various countries around the globe implementation teams encounter unexpected difficulties when launching CPOE systems. This survey aimed at gathering users' opinions on CPOE implementation. Additional factors that can be influenced by CPOE implementation were equally considered, namely workplace satisfaction, interprofessional collaboration, patient safety climate, system usability, and organisational readiness to implement change.

Phenotypes of Patients with Direct Oral Anticoagulant (DOAC) Underdosing in Atrial Fibrillation: Results from the ARENA Registry.

Background And Objectives: Oral anticoagulation in patients with atrial fibrillation is crucial to prevent thrombus formation in the heart, a major cause of ischemic stroke. The appropriate dose of direct oral anticoagulants (DOAC) - either standard or reduced dose - must be chosen individually in accordance with defined patient characteristics. However, a significant proportion of patients receive inappropriately low DOAC doses (underdosing).

S100A1ct: A Synthetic Peptide Derived From S100A1 Protein Improves Cardiac Performance and Survival in Preclinical Heart Failure Models.

Background: The EF-hand Ca sensor protein S100A1 has been identified as a molecular regulator and enhancer of cardiac performance. The ability of S100A1 to recognize and modulate the activity of targets such as SERCA2a (sarcoplasmic reticulum Ca ATPase) and RyR2 (ryanodine receptor 2) in cardiomyocytes has mostly been ascribed to its hydrophobic C-terminal α-helix (residues 75-94). We hypothesized that a synthetic peptide consisting of residues 75 through 94 of S100A1 and an N-terminal solubilization tag (S100A1ct) could mimic the performance-enhancing effects of S100A1 and may be suitable as a peptide therapeutic to improve the function of diseased hearts.

A Highly Sensitive UPLC-MS/MS Method for the Quantification of the Organic Cation Transporters' Mediated Metformin Uptake and Its Inhibition in Cells.

Metformin is the gold standard substrate for evaluating potential inhibitors of the organic cation transporters (OCTs). Here, we established a UPLC-MS/MS assay to quantify metformin in cell pellets with a range of 0.05-50 ng/mL using 6-deuterated metformin as an internal standard.

Understanding Voriconazole Metabolism: A Middle-Out Physiologically-Based Pharmacokinetic Modelling Framework Integrating In Vitro and Clinical Insights.

Background And Objective: Voriconazole (VRC), a broad-spectrum antifungal drug, exhibits nonlinear pharmacokinetics (PK) due to saturable metabolic processes, autoinhibition and metabolite-mediated inhibition on their own formation. VRC PK is also characterised by high inter- and intraindividual variability, primarily associated with cytochrome P450 (CYP) 2C19 genetic polymorphism. Additionally, recent in vitro findings indicate that VRC main metabolites, voriconazole N-oxide (NO) and hydroxyvoriconazole (OHVRC), inhibit CYP enzymes responsible for VRC metabolism, adding to its PK variability.

Polypharmacy in Older Patients with Multimorbidity: The Agreement Between Patient and General Practitioner-Reported Drugs Observed in a Pilot cRCT.

Polypharmacy (≥5 drugs) increases the risk of discrepancies between patient- and general practitioner (GP)-reported drugs, leading to adverse outcomes. This explorative analysis assesses the agreement between patient- and GP-reported drugs under the influence of a paper-based patient portfolio in a pilot cluster randomized controlled trial (cRCT). Complete data were available for 68 patients aged 65 or older (26 were female), with multimorbidity, polypharmacy, and at least one hospitalization in the past year.

Role of the RNA binding protein IGF2BP1 in cancer multidrug resistance.

The insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1), a member of a conserved family of single-stranded RNA-binding proteins (IGF2BP1-3), is expressed in a broad range of fetal tissues, placenta and more than sixteen cancer types but only in a limited number of normal adult tissues. IGF2BP1is required for the transport from nucleus to cytoplasm of certain mRNAs that play essential roles in embryogenesis, carcinogenesis, and multidrug resistance (MDR), by affecting their stability, translation, or localization. The purpose of this review is to gather and present information on MDR mechanisms in cancer and the significance of IGF2BP1 in this context.

Proposal for a new study design and endpoint in research on medication history taking.

Introduction: Medication history errors at hospital admission are common and effective strategies to improve the quality of medication histories are still being researched. However, studies on new approaches regarding medication history taking are often time-consuming and resource-intensive. The gold standard when evaluating the quality of medication histories is the comparison of a to the original.

Real-World Application of a Quantitative Systems Pharmacology (QSP) Model to Predict Potassium Concentrations from Electronic Health Records: A Pilot Case towards Prescribing Monitoring of Spironolactone.

Quantitative systems pharmacology (QSP) models are rarely applied prospectively for decision-making in clinical practice. We therefore aimed to operationalize a QSP model for potas-sium homeostasis to predict potassium trajectories based on spironolactone administrations. For this purpose, we proposed a general workflow that was applied to electronic health records (EHR) from patients treated in a German tertiary care hospital.

Continuity of medication information transfer and continuous medication supply during hospital-to-home transitions - nationwide surveys in hospital and community pharmacies after implementing new legal requirements in Germany.

Background: While successful information transfer and seamless medication supply are fundamental to medication safety during hospital-to-home transitions, disruptions are frequently reported. In Germany, new legal requirements came into force in 2017, strengthening medication lists and discharge summaries as preferred means of information transfer. In addition to previous regulations - such as dispensing medication at discharge by hospital pharmacies - hospital physicians were now allowed to issue discharge prescriptions to be supplied by community pharmacies.

Dose-dependent induction of CYP3A activity by St. John's wort alone and in combination with rifampin.

The dose dependence of the effect of enzyme inducers and the effect of the combined administration of two inducers that exert their effect via the same induction pathway (pregnane X receptor) have not been well studied. Using oral midazolam microdoses (30 μg), we have investigated CYP3A4 induction by St. John's wort (SJW) in 11 healthy volunteers using low (300 mg/day containing 7.

General practitioners' perspectives on lifestyle interventions for cognitive preservation in dementia prevention.

Background: General practitioners (GPs) play a crucial role in identifying cognitive impairment and dementia and providing post-diagnostic care. This study investigates (1) how promising GP consider lifestyle changes to maintain cognitive performance in general, (2) GP beliefs about the power of modifiable health and lifestyle factors to maintain cognitive performance, and (3) whether those beliefs vary by GP age.

Methods: As part of the AgeWell.

Identifying Predictors of Heart Failure Readmission in Patients From a Statutory Health Insurance Database: Retrospective Machine Learning Study.

Background: Patients with heart failure (HF) are the most commonly readmitted group of adult patients in Germany. Most patients with HF are readmitted for noncardiovascular reasons. Understanding the relevance of HF management outside the hospital setting is critical to understanding HF and factors that lead to readmission.

Effects of a multidomain intervention against cognitive decline on dementia risk profiles - Results from the AgeWell.de trial.

Introduction: Dementia risk scores constitute promising surrogate outcomes for lifestyle interventions targeting cognitive function. We investigated whether dementia risk, assessed using the LIfestyle for BRAin health (LIBRA) index, was reduced by the AgeWell.de intervention.

Event Analysis for Automated Estimation of Absent and Persistent Medication Alerts: Novel Methodology.

Background: Event analysis is a promising approach to estimate the acceptance of medication alerts issued by computerized physician order entry (CPOE) systems with an integrated clinical decision support system (CDSS), particularly when alerts cannot be interactively confirmed in the CPOE-CDSS due to its system architecture. Medication documentation is then reviewed for documented evidence of alert acceptance, which can be a time-consuming process, especially when performed manually.

Objective: We present a new automated event analysis approach, which was applied to a large data set generated in a CPOE-CDSS with passive, noninterruptive alerts.

Exploring the heterogeneity in community pharmacist-led medication review studies - A systematic review.

Background: Findings on the effectiveness of medication reviews led by community pharmacists (CPs) are often inconclusive. It has been hypothesized that studies are not sufficiently standardized, and thus, it is difficult to draw conclusions.

Objective(s): To examine differences in the way CP-led medication review studies are set up.

Quality of life in a high-risk group of elderly primary care patients: characteristics and potential for improvement.

Purpose: Quality of Life (QoL) is associated with a bandwidth of lifestyle factors that can be subdivided into fixed and potentially modifiable ones. We know too little about the role of potentially modifiable factors in comparison to fixed ones. This study examines four aspects of QoL and its associations with 15 factors in a sample of elderly primary care patients with a high risk of dementia.