Implementation of Pharmacogenetics in First-Line Care: Evaluation of Its Use by General Practitioners.

Pharmacogenetics (PGx) can explain/predict drug therapy outcomes. There is, however, unclarity about the use and usefulness of PGx in primary care. In this study, we investigated PGx tests ordered by general practitioners (GPs) in 2021 at Dept.

Modification of the association between paroxetine serum concentration and SERT-occupancy by ABCB1 (P-glycoprotein) polymorphisms in major depressive disorder.

Background: Selective serotonin reuptake inhibitors (SSRIs) exert substantial variability in effectiveness in patients with major depressive disorder (MDD), with up to 50-60% not achieving adequate response. Elucidating pharmacokinetic factors that explain this variability is important to increase treatment effectiveness.

Objectives: To examine potential modification of the relationship between paroxetine serum concentration (PSC) and serotonin transporter (SERT)-occupancy by single nucleotide polymorphisms (SNPs) of the ABCB1 gene, coding for the P-glycoprotein (P-gp) pump, in MDD patients.

Design and methods of the 'monitoring outcomes of psychiatric pharmacotherapy' (MOPHAR) monitoring program - a study protocol.

Background: At many outpatient departments for psychiatry worldwide, standardized monitoring of the safety of prescribed psychotropic drugs is not routinely performed in daily clinical practice. Therefore it is unclear to which extent the drugs used by psychiatric outpatients are prescribed effectively and safely. These issues warrant structured monitoring of medication use, (pre-existing) co-morbidities, effectiveness and side effects during psychiatric outpatient treatment.

Metabolic Syndrome at an Outpatient Clinic for Bipolar Disorders: A Case for Systematic Somatic Monitoring.

Objectives: The primary objective of the study was to determine whether the Monitoring Outcomes of Psychiatric Pharmacotherapy (MOPHAR) program improved somatic monitoring practices at an outpatient clinic for bipolar disorders in the Netherlands. The secondary objective was to determine in MOPHAR the frequency of metabolic syndrome (compared with its measurability before MOPHAR) and treatment thereof.

Methods: Frequencies of physical examinations and laboratory tests before (retrospectively) and after (prospectively) the active introduction of MOPHAR were compared among adult patients (N=155).

Monitoring of somatic parameters at outpatient departments for mood and anxiety disorders.

Introduction: Somatic complications account for the majority of the 13-30 years shortened life expectancy in psychiatric patients compared to the general population. The study aim was to assess to which extent patients visiting outpatient departments for mood and anxiety disorders were monitored for relevant somatic comorbidities and (adverse) effects of psychotropic drugs-more specifically a) metabolic parameters, b) lithium safety and c) ECGs-during their treatment.

Methods: We performed a retrospective clinical records review and cross-sectional analysis to assess the extent of somatic monitoring at four outpatient departments for mood and anxiety disorders in The Netherlands.

Limited Evidence for Risk Factors for Proarrhythmia and Sudden Cardiac Death in Patients Using Antidepressants: Dutch Consensus on ECG Monitoring.

Currently, there is a lack of international and national guidelines or consensus documents with specific recommendations for electrocardiogram (ECG) screening and monitoring during antidepressant treatment. To make a proper estimation of the risk of cardiac arrhythmias and sudden (cardiac) death during antidepressant use, both the drug and patient-specific factors should be taken into account; however, solid evidence on how this should be done in clinical practice is lacking. Available recommendations on the management of QT(c) prolongation (with antidepressant treatment) emphasize that special attention should be given to high-risk patients; however, clinicians are in need of more concrete suggestions about how to select patients for ECG screening and monitoring.

Availability of CYP2D6 genotyping results in general practitioner and community pharmacy medical records.

Aim: To investigate the availability of CYP450-2D6 (CYP2D6) genotyping results in general practitioner (GP) and/or community pharmacy records, and the influence thereof on psychotropic CYP2D6 substrate dosing.

Materials & Methods: Primary outcome was the percentage of patients genotyped for CYP2D6 with their genotype/phenotype registered in GP and/or pharmacy records. Secondary outcome was the number of defined daily doses of psychotropic CYP2D6 substrates prescribed after genotyping.

Medication Discrepancies at Outpatient Departments for Mood and Anxiety Disorders in the Netherlands: Risks and Clinical Relevance.

Objective: To identify discrepancies between actual drug use by outpatients with mood and anxiety disorders and medication overviews from health care providers as well as to investigate the clinical relevance of those discrepancies.

Methods: A cross-sectional study in adults visiting 1 of 4 participating outpatient departments for mood and anxiety disorders was conducted between March and November 2014. DSM-5 criteria were used to assign the psychiatric diagnosis.

Rosiglitazone is a superior bronchodilator compared to chloroquine and β-adrenoceptor agonists in mouse lung slices.

Background: Current therapy for relieving bronchoconstriction may be ineffective in severe asthma, particularly in the small airways. The aim of this study was to further characterise responses to the recently identified novel bronchodilators rosiglitazone (RGZ) and chloroquine (CQ) under conditions where β-adrenoceptor agonist efficacy was limited or impaired in mouse small airways within lung slices.

Methods: Relaxation to RGZ and CQ was assessed following submaximal methacholine (MCh) pre-contraction, in slices treated overnight with either RGZ, CQ or albuterol (ALB) (to induce β-adrenoceptor desensitization), and in slices treated with caffeine/ryanodine in which contraction is associated with increases in Ca2+ sensitivity in the absence of contractile agonist-induced Ca2+ oscillations.

Noncanonical WNT-5A signaling regulates TGF-β-induced extracellular matrix production by airway smooth muscle cells.

Transforming growth factor β (TGF-β), a key mediator of fibrotic responses, is increased in asthma and drives airway remodeling by inducing expression of extracellular matrix (ECM) proteins. We investigated the molecular mechanisms underlying TGF-β-induced ECM expression by airway smooth muscle cells and demonstrate a novel link between TGF-β and Wingless/integrase 1 (WNT) signaling in ECM deposition. Airway smooth muscle expresses abundant WNT ligands, with the noncanonical WNT-5A being the most profoundly expressed.