This study aims to assess the potential effects of zanubrutinib on the activity of cytochrome P450 (CYP) enzymes and drug transporter proteins using a cocktail probe approach.

To characterize relationships between apolipoprotein A-I (apoA-I) exposure and cholesterol efflux capacity (CEC) and covariate effects following CSL112 (apoA-I [human]) administration in an integrated population including acute myocardial infarction (AMI) patients.

Given the increasing emergence of drug resistance in Plasmodium, new antimalarials are urgently required. P218 is an aminopyridine that inhibits dihydrofolate reductase being developed as a malaria chemoprotective drug. Assessing the effect of new compounds on cardiac intervals is key during early drug development to determine their cardiac safety.

In response to the COVID-19 pandemic, Health Education England (HEE) and the University of Birmingham provided National Health Service (NHS) staff free access to SCRIPT, a national eLearning programme for safer prescribing and therapeutics. The eLearning was particularly for those returning to work or being redeployed. In the year March 2020-21, 3412 users registered to access portfolios and opened an aggregate of 17 198 modules. Each user completed a median of 2 (range 1-50, interquartile range [IQR] 1-7) assessed learning modules. Marks improved from pre-test to post-test by a median of 2 (IQR 0-3) marks out of 10. The most frequently selected modules were Adherence and Concordance (1109 users), Fluids (981 users) and Diabetic Emergencies (818 users). A total of 878 users accessed the unassessed COVID-19 module. The SCRIPT modules provided standardised education in core principles relating to prescribing and therapeutics, and were used by professionals from many healthcare disciplines.

Abrocitinib is a selective Janus kinase 1 inhibitor for the treatment of moderate-to-severe atopic dermatitis. Herein we describe the time-course of drug-induced platelet reduction following abrocitinib administration, identify covariates affecting platelet counts, and determine the probability of patients experiencing thrombocytopaenia while receiving abrocitinib.

Develop a population pharmacokinetic (PopPK) model to characterise the pharmacokinetics (PK) of anti-programmed cell death protein-1 (PD-1) antibody dostarlimab, identify covariates of clinical relevance, and investigate efficacy/safety exposure-response (ER) relationships.

To perform network meta-analysis for a head-to-head comparison of various interventions used in coronavirus disease 2019 (COVID-19) on mortality, clinical recovery, time to clinical improvement and the occurrence of serious adverse events.

The aim of this study was to explore the level of agreement on drug-drug interaction (DDI) information listed in three major online drug information resources (DIRs) in terms of: (1) interacting drug pairs; (2) severity rating; (3) evidence rating; and (4) clinical management recommendations.

There is significant interest in the potential for nebulised unfractionated heparin (UFH), as a novel therapy for patients with COVID-19 induced acute hypoxaemic respiratory failure requiring invasive ventilation. The scientific and biological rationale for nebulised heparin stems from the evidence for extensive activation of coagulation resulting in pulmonary microvascular thrombosis in COVID-19 pneumonia. Nebulised delivery of heparin to the lung may limit alveolar fibrin deposition and thereby limit progression of lung injury. Importantly, laboratory studies show that heparin can directly inactivate the SARS-CoV-2 virus, thereby prevent its entry into and infection of mammalian cells. UFH has additional anti-inflammatory and mucolytic properties that may be useful in this context. METHODS AND INTERVENTION: The Can nebulised HepArin Reduce morTality and time to Extubation in Patients with COVID-19 Requiring invasive ventilation Meta-Trial (CHARTER-MT) is a collaborative prospective individual patient data analysis of on-going randomised controlled clinical trials across several countries in five continents, examining the effects of inhaled heparin in patients with COVID-19 requiring invasive ventilation on various endpoints. Each constituent study will randomise patients with COVID-19 induced respiratory failure requiring invasive ventilation. Patients are randomised to receive nebulised heparin or standard care (open label studies) or placebo (blinded placebo-controlled studies) while under invasive ventilation. Each participating study collect a pre-defined minimum dataset. The primary outcome for the meta-trial is the number of ventilator-free days up to day 28 day, defined as days alive and free from invasive ventilation.

Chronic inflammation is a risk factor for cardiovascular disease (CVD). IL-6 signalling perturbation through IL-6 or IL-6R blockade may have potential benefit on cardiovascular risk. It is unknown whether targeting either IL-6 or IL-6 receptor may result in similar effects on CVD and adverse events. We compared the anticipated effects of targeting IL-6 and IL-6 receptor on cardiometabolic risk and potential side effects.

To identify linzagolix doses, an oral GnRH receptor antagonist, that effectively lower oestradiol (E2) to relieve endometriosis-related pelvic pain without compromising bone health.

Prophylactic treatment of haemophilia A patients with factor VIII (FVIII) concentrate focuses on maintaining a minimal trough FVIII activity level to prevent bleeding. However, due to differences in bleeding tendency, the pharmacokinetic (PK)-guided dosing approach may be suboptimal. An alternative approach could be the addition of haemostatic pharmacodynamic (PD) parameters, reflecting a patient's unique haemostatic balance. Our aim was to develop a population PK/PD model, based on FVIII activity levels and Nijmegen Haemostasis Assay (NHA) patterns, a global haemostatic assay that measures thrombin/plasmin generation simultaneously.

The aim of this systematic review was to identify generic instruments for drug discontinuation in patients with polypharmacy in the primary care setting.

In X-linked hypohidrotic ectodermal dysplasia, the most frequent ectodermal dysplasia, an inherited deficiency of the signalling protein ectodysplasin A1 (EDA1) impairs the development of the skin and its appendages, various eccrine glands, and dentition. The severe hypohidrosis common to X-linked hypohidrotic ectodermal dysplasia patients may lead to life-threatening hyperthermia, especially during hot weather or febrile illness. Fc-EDA, an EDA1 replacement protein known to prevent the disease in newborn animals, was tested in 2 clinical trials (human adults and neonates) and additionally administered under compassionate use to 3 infants in utero. The data support the safety of Fc-EDA and efficacy if applied prenatally. Anti-drug antibodies were detected after intravenous administration in adult males and nonpregnant females, but not in pregnant women when Fc-EDA was delivered intra-amniotically. Most importantly, there was no detectable immune response to the investigational drug in neonates treated by intravenous infusions and in infants who had received Fc-EDA in utero. In conclusion, the safety profile of this drug encourages further development of prenatal EDA1 replacement therapy.

To investigate the effects of the strong cytochrome P450 (CYP) 3A inhibitor itraconazole and the strong CYP3A inducer rifampicin on the pharmacokinetics of single-dose esaxerenone, a nonsteroidal mineralocorticoid receptor blocker, in healthy Japanese subjects.

Pupillography is a noninvasive and cost-effective method to determine autonomic nerve activity. Genetic variants in cytochrome P450 (CYP), dopamine receptor (DRD2, DRD3), serotonin receptor (HTR2A, HTR2C) and ATP-binding cassette subfamily B (ABCB1) genes, among others, were previously associated with the pharmacokinetics and pharmacodynamics of antipsychotic drugs. Our aim was to evaluate the effects of aripiprazole and olanzapine on pupillary light reflex related to pharmacogenetics.

Antihistamines make up the first line of treatments against motion-sickness. Still, their efficacy and specific mechanism have come into question. The aim of this study was to investigate the effect of meclizine on motion-sensitivity.

To develop a semi-mechanistic model, based on glutathione depletion and predict a previously identified intra-individual reduction in busulfan clearance to aid in more precise dosing.

Hydrochlorothiazide-induced photosensitivity may increase squamous cell carcinoma (SCC), basal cell carcinoma (BCC) and lip cancer risk. The aim was to quantify these risks.

Explore the efficacy, safety and tolerability of the dual sodium-glucose cotransporter (SGLT) 1 and 2 inhibitor, licogliflozin in patients with type-2 diabetes mellitus (T2DM) and heart failure.