Assessing the Risk of QT Prolongation in a Psychiatric Inpatient Cohort: A Retrospective Cross-Sectional Study.

Background: QT prolongation is a potential serious adverse drug reaction, and assessing the risk of QT-prolonging drugs is routinely included in psychotropic medication reviews. However, the actual clinical benefits of such assessments are unknown. We investigate whether QT prolongation (QTc value > 480 ms) manifests in psychiatric inpatients at risk of QT prolongation as identified by assessing drug regimens.

Steps to construct educational interventions on sexual dysfunction for healthcare professionals and patients. Experiences from the SECRET research study-group.

Objectives: To design an educational intervention on sexual dysfunction for patients suffering from schizophrenia and diabetes based on patients' and other relevant stakeholders' preferences, and to offer transparency into the basic decision-making process behind a final design.

Methods: We conducted a three-part investigation to explore theory, preferences, and feasibility based on literature searches and interviews with patients, healthcare professionals, heads of Assertive Community Treatment Centres and experts. Based on a content analysis of this material, a draft of the intervention was developed.

A systematic review of pharmacogenetic testing to guide antipsychotic treatment.

Pharmacogenomics could optimize antipsychotic treatment by preventing adverse drug reactions, improving treatment efficacy or relieving the cost burden on the healthcare system. Here we conducted a systematic review to investigate whether pharmacogenetic testing in individuals undergoing antipsychotic treatment influences clinical or economic outcomes. On 12 January 2024, we searched MEDLINE, EMBASE, PsycINFO and Cochrane Centrale Register of Controlled Trials.

A low dietary sodium dose is associated with a more pronounced aldosterone response in normotensive than in hypertensive individuals.

In this comprehensive meta-regression analysis encompassing 79 randomized controlled trials, we observed that in populations assigned to a high sodium intake level exceeding 94 mmol, there was no discernible link between plasma aldosterone levels and sodium intake. However, among populations with normal blood pressure subjected to a lower sodium intake, falling below 111 mmol (N = 1544), the association between sodium intake and plasma aldosterone levels manifested as a decrease of 192 pg/ml per 100 mmol of sodium (95% CI - 303 to - 81). In hypertensive populations (N = 1145), this association was less pronounced, with a reduction of 46 pg/ml per 100 mmol sodium, (95% CI - 112 to 20).

Monotreatment With Conventional Antirheumatic Drugs or Glucocorticoids in Rheumatoid Arthritis: A Network Meta-Analysis.

Importance: This is the first network meta-analysis to assess outcomes associated with multiple conventional synthetic disease-modifying antirheumatic drugs and glucocorticoid.

Objective: To analyze clinical outcomes after treatment with conventional synthetic disease-modifying antirheumatic drugs and glucocorticoid among patients with rheumatoid arthritis.

Data Sources: With no time restraint, English language articles were searched in MEDLINE, Embase, Cochrane Central, ClinicalTrials.

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This review summarises the effect of common medication on sleep patterns. Evaluation of current medication status is an important part of the assessment in case of complaints of disturbed sleep. Medication may affect sleep continuity and sleep architecture directly via effects on wake or sleep promoting neurotransmitter systems and indirectly via beneficial therapeutic effects or unwanted side effects.

Onset of Action of Selected Second-Generation Antipsychotics (Pines)-A Systematic Review and Meta-Analyses.

Recommendations for duration of treatment with antipsychotics before considering a switch vary from 2 to 8 weeks, although several studies suggest a rapid onset of action. The objective of this review was to estimate time to onset of action and time to maximum antipsychotic effect of asenapine, olanzapine, quetiapine, and zotepine (pines). We searched bibliographic databases for randomized, placebo-controlled trials in adults with schizophrenia estimating the antipsychotic effect of pines over time.

Is the CYP2D6 Genotype Associated with Antipsychotic-Induced Weight Gain?

Antipsychotic-induced weight gain (AIWG) is a serious adverse effect. Studies have linked genetically-predicted CYP2D6 metabolic capacity to AIWG. The evidence, however, is ambiguous.

Language-agnostic pharmacovigilant text mining to elicit side effects from clinical notes and hospital medication records.

We sought to craft a drug safety signalling pipeline associating latent information in clinical free text with exposures to single drugs and drug pairs. Data arose from 12 secondary and tertiary public hospitals in two Danish regions, comprising approximately half the Danish population. Notes were operationalised with a fastText embedding, based on which we trained 10 270 neural-network models (one for each distinct single-drug/drug-pair exposure) predicting the risk of exposure given an embedding vector.

The Utility of Pharmacogenetics Testing in Psychiatric Populations.

The implementation of pharmacogenetic tests including multiple gene variants has shown promising potential as a decision-making tool for optimizing psychopharmacological treatment regimens and reducing treatment costs. However, the varying clinical validity of gene variants included in pharmacogenetic test batteries, and inconsistencies in their translation into medical recommendations between commercially available pharmacogenetic tests, complicates their rational implementation. Thus, there is a need for well-designed, reproducible studies documenting the clinical significance of the various genetic variants.

CYP2D6 Genotyping and Antipsychotic-Associated Extrapyramidal Adverse Effects in a Randomized Trial of Aripiprazole Versus Quetiapine Extended Release in Children and Adolescents, Aged 12-17 Years, With First Episode Psychosis.

Purpose/background: The aim of this study was to examine the association between genetically predicted CYP2D6 phenotypes and extrapyramidal symptoms (EPSs).

Methods/procedures: Data from the Tolerability and Efficacy of Antipsychotics trial of adolescents with first-episode psychosis randomized to aripiprazole versus quetiapine extended release were studied. Extrapyramidal symptom assessments included the Simpson-Angus Scale and the Barnes Akathisia Rating Scale.

Cellular Uptake and Intracellular Phosphorylation of GS-441524: Implications for Its Effectiveness against COVID-19.

GS-441524 is an adenosine analog and the parent nucleoside of the prodrug remdesivir, which has received emergency approval for treatment of COVID-19. Recently, GS-441524 has been proposed to be effective in the treatment of COVID-19, perhaps even being superior to remdesivir for treatment of this disease. Evaluation of the clinical effectiveness of GS-441524 requires understanding of its uptake and intracellular conversion to GS-441524 triphosphate, the active antiviral substance.

Influence of sodium intake and change in sodium intake on plasma-renin in man.

Background: Low sodium intake stimulates the production and activity of renin. The aim is to analyse the association between a large range of sodium intake and the plasma renin activity (PRA).

Methods: We performed electronic searches for articles published between January 1st 1946 and March 18th 2020 and updated on January 21st 2021.

Variation of drugs involved in acute drug toxicity presentations based on age and sex: an epidemiological approach based on European emergency departments.

Objective: To analyse the relative percentage of acute recreational drug toxicity emergency department (ED) presentations involving the main drug groups according to age and sex and investigate different patterns based on sex and age strata.

Methods: We analysed all patients with acute recreational drug toxicity included by the Euro-DEN Plus dataset (22 EDs in 14 European countries) between October 2013 and December 2016 (39 months). Drugs were grouped as: opioids, cocaine, cannabis, amphetamines, gamma-hydroxybutyrate (GHB), hallucinogens, new psychoactive substances (NPS), benzodiazepines and ketamine.

The effect of activated charcoal on drug exposure following intravenous administration: A meta-analysis.

Activated charcoal both reduces primary drug absorption and enhances drug elimination. However, the two mechanisms of action overlap and are indistinguishable from each other. In order to estimate the extend of enhanced elimination, we summarized the effect of activated charcoal on intravenously administered drugs, where reduced drug exposure can be attributed to enhanced elimination.

Effects of low sodium diet versus high sodium diet on blood pressure, renin, aldosterone, catecholamines, cholesterol, and triglyceride.

Background: Recent cohort studies show that salt intake below 6 g is associated with increased mortality. These findings have not changed public recommendations to lower salt intake below 6 g, which are based on assumed blood pressure (BP) effects and no side-effects.

Objectives: To assess the effects of sodium reduction on BP, and on potential side-effects (hormones and lipids) SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to April 2018 and a top-up search in March 2020: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.

Effect of Routine Cytochrome P450 2D6 and 2C19 Genotyping on Antipsychotic Drug Persistence in Patients With Schizophrenia: A Randomized Clinical Trial.

Importance: Genetic polymorphism of genes encoding the drug metabolizing enzymes, cytochrome P450 2D6 and 2C19 (CYP2D6 and CYP2C19), is associated with treatment failure of and adverse reactions to psychotropic drugs. The clinical utility of routine CYP2D6 and CYP2C19 genotyping (CYP testing) is unclear.

Objective: To estimate whether routine CYP testing effects the persistence of antipsychotic drug treatment.

Different Original and Biosimilar TNF Inhibitors Similarly Reduce Joint Destruction in Rheumatoid Arthritis-A Network Meta-Analysis of 36 Randomized Controlled Trials.

The effect of five approved tumour necrosis factor inhibitors (TNFi: infliximab, etanercept, adalimumab, certolizumab, and golimumab) on joint destruction in rheumatoid arthritis (RA) have been compared versus methotrexate (MTX) in randomized controlled trials (RCTs) but have not been compared directly to each other or to an otherwise untreated placebo control. The present analysis compares effects of standard doses, high doses, and low doses of TNFis on radiographic joint destruction in RA and relate these effects to MTX and placebo by means of a Bayesian network meta-analysis. We identified 31 RCTs of the effect of TNFis on joint destruction and 5 RCTs with controls, which indirectly could link otherwise untreated placebo controls to the TNFi treatments in the network.

Dose-response relation between dietary sodium and blood pressure: a meta-regression analysis of 133 randomized controlled trials.

Background: The projected reduced mortality effect of reduced sodium intake in model-based studies conflicts with the observed increased mortality associated with low sodium intake in population studies. This may reflect an overestimation of the dose-response relation between sodium reduction (SR) and blood pressure (BP) used in mortality modeling studies.

Objectives: The present meta-regression analysis sought to estimate the dose-response relations between SR and BP in study groups with mean BP above or below the 75th percentile of the general population.

The impact of human CES1 genetic variation on enzyme activity assessed by ritalinic acid/methylphenidate ratios.

The present clinical trial investigated the impact of selected SNPs in CES1 on the metabolic activity of the enzyme. For this purpose, we used methylphenidate (MPH) as a pharmacological probe and the d-RA/d-MPH (metabolite/parent drug) ratios as a measure of enzymatic activity. This metabolic ratio (MR) was validated against the AUC ratios (AUC /AUC ).