British Journal of Clinical Pharmacology

Background Antibiotic pricing is a key determinant of access and stewardship in low- and middle-income countries (LMICs), yet empirical evidence on how prices are formed within pharmaceutical markets remains limited. However, there is little longitudinal evidence on how antibiotic prices behave within national pharmaceutical supply systems. This study evaluated the patterns and determinants of systemic antibiotic pricing in Tanzania using national regulatory import permit data. Methods We conduc...

BackgroundPropofol dosing guidelines recommend age-based reductions because hypnotic sensitivity increases in older adults. Most real-world evaluations of induction practice, however, have relied on total weight-normalized dose (mg/kg) rather than estimating cerebral exposure using pharmacokinetic models. Because age-related pharmacokinetic changes alter the relationship between administered dose and peak effect-site concentration (Ce,max), mg/kg surrogates may misrepresent true age-dependent ex...

Amatoxin-induced acute liver failure complicates misidentified foraged mushroom ingestion worldwide; abrupt multisystem collapse punctuates apparent improvement. Our prospective single-arm clinical trial investigated proactive toxicokinetic-based management to preserve elimination capacity: sustained enhanced hydration to maintain renal clearance; fasting plus octreotide to suppress meal-driven enterohepatic circulation; and intravenous silibinin to inhibit OATP1B3-mediated hepatic uptake, enabl...

Introduction Vonoprazan, a new oral potassium-competitive acid blocker (PCAB), has shown promise in terms of superior acid suppression when compared to Proton pump inhibitors (PPIs). We evaluated the efficacy of PCABs versus PPIs in preventing rebleeding in high-risk peptic ulcer patients after endoscopic hemostasis. Methods Following the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines, we conducted a comprehensive search for relevant studies across Medline...

ObjectivesTo estimate potential launch prices of generic semaglutide following patent expiry from 2026 and to quantify the global obesity and type 2 diabetes (T2DM) burden in countries where generic access may become possible. MethodsWe used World Bank population data and World Obesity and Diabetes Atlas prevalence estimates to calculate obesity and T2DM burden in countries where semaglutide patents expire in 2026 or were not filed. Patent status was identified using MedsPaL and cross-checked w...

BackgroundInhaled combusted cannabis and co-use of combusted cannabis and nicotine electronic cigarettes (nECIGs) are on the rise, yet their long-term cardiovascular risk is unclear due to the high prevalence of confounders in observational human studies. Using primary plasma and monocytes and a novel ex vivo mechanistic model of two early steps in atherogenesis, this study examined whether chronic combusted cannabis use is associated with atherogenic changes, as estimated by 1) monocyte transen...

Abstract Introduction Cardiovascular disease (CVD) is an important complication of type 2 diabetes (T2D). Current incident CVD-prediction models use single baseline measurements and achieve moderate performance in people with T2D, with C-indices around 0.7. Modern healthcare registries contain repeated measurements of HbA1c, LDL-cholesterol and eGFR, which could carry incremental predictive value. However, the added value of trajectory measures for CVD-risk prediction remains unclear. We aimed t...

BackgroundKetone bodies have shown potential to improve cardiac metabolism and function in patients with heart failure (HF). ObjectiveTo evaluate the effects of exogenous ketone-based interventions on cardiac function in patients with HF or related cardiometabolic risk factors. MethodsWe conducted a systematic review based on a search of MEDLINE, EMBASE, CINAHL, Cochrane Library, and Scopus from inception to January 2025. Eligible studies included randomized controlled trials evaluating exogen...

BackgroundPostoperative delirium is a common complication in surgical patients, and is associated with a multitude of negative outcomes, including mortality, dementia, and increased healthcare costs. Therefore, a better understanding of what factors contribute to postoperative delirium, especially those that can be easily obtained, is important. MethodsWe conducted a retrospective cohort study using patients from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Adult patient...

BackgroundThere is disparity between the incidence of malignant hyperthermia (MH) reactions and the prevalence of variants in the RYR1 gene associated with susceptibility to MH (where susceptibility is determined by in vitro contracture tests). Our aims were to use clinical and genetic data from the UK to explain this disparity and to examine if these data are consistent with the clinical risk of MH being inherited as an autosomal dominant trait. MethodsClinical MH and genotyping data were extr...

Background and aimsPopulation screening for liver disease in high-risk groups is recommended. Community diagnosis of liver disease is a challenge due to the asymptomatic nature of disease until very advanced stages. Moreover, regional variation in testing availability can result in people with clinically significant liver disease being missed. Machine learning (ML) has been proposed as a method to reduce diagnostic error and automate screening. We present a novel machine learning derived algorit...

BackgroundAcute myocarditis is typically self-limiting and resolves spontaneously in most cases. However, ventricular arrhythmias (VA) complications, which may be life-threatening are associated with higher rates of in-hospital complications and mortality. Catheter ablation is occasionally required for acute myocarditis associated ventricular tachycardia (VT), but data on its procedural use and outcomes, in this setting, remain limited. We aimed to determine the prevalence of VA among patients h...

Background: Acute heart failure (AHF) exhibits marked heterogeneity in diastolic hemodynamics, yet comprehensive echocardiographic assessment of diastolic function (DF) and filling pressure (FP) is often infeasible. We evaluated whether artificial intelligence-enabled electrocardiography (AI-ECG) could provide scalable DF grading and FP estimation in hospitalized AHF patients. Methods: We retrospectively studied adults hospitalized for AHF across Mayo Clinic sites (2013-2023) who received 1 dose...

BACKGROUNDPeak oxygen uptake (pVO2) is a strong, independent predictor of adverse cardiovascular outcomes, supporting cardiopulmonary exercise testing as a primary end point assessing efficacy of novel drug therapies in obstructive hypertrophic cardiomyopathy (oHCM) clinical trials. However, characterizing changes in pVO2 that patients perceive as beneficial or meaningful (ie, minimal important difference [MID]) has not been determined. METHODSData from patients with symptomatic oHCM enrolled i...

BackgroundEvolocumab promotes coronary plaque regression in patients with coronary artery disease, but little is known regarding carotid plaques (CP). This study aimed to evaluate the impact of evolocumab on top of lipid-lowering therapy (ELLT) on carotid morphological stabilization (MS) and plaque regression (PR) compared to lipid-lowering therapy (LLT) alone. MethodsAsymptomatic patients with internal carotid stenosis[≥]50% and LDL-C[≥]100 mg/dL were randomized to ELLT or LLT and monito...

BackgroundCanine impaction represents one of the most challenging clinical scenarios in orthodontic practice, with maxillary canines being the second most commonly impacted teeth after third molars. The management of impacted canines through orthodontic traction requires an advanced understanding of biomechanical principles, surgical techniques, and patient-specific factors. The decision to attempt traction must be informed by accurate differentiation between mechanical impaction and primary fai...

PurposeDespite strong evidence, real-world adoption of guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) remains suboptimal. The Get With The Guidelines-Heart Failure (GWTG-HF) program was designed to close gaps in care. We evaluated whether hospital participation in GWTG-HF is associated with greater GDMT intensity and improved outcomes. MethodsWe conducted a retrospective analysis (2013-2021) of Medicare beneficiaries with Part A and Part D hos...

BackgroundHypertension affects over 30% of adults and is the leading risk factor for cardiovascular disease. It often presents without obvious symptoms, meaning that, although effective therapies exist, hypertension remains widely undiagnosed and insufficiently treated. Genomics-based prediction methods have shown only modest benefits for these disorders, but proteomic markers have demonstrated potential for greater predictive and clinical value. MethodsWe applied a novel machine-learning based...

BackgroundThis study of Malawian children with rheumatic heart disease (RHD) sought to detect demographic, clinical, and echocardiographic risk factors for mortality. MethodsPediatric patients with RHD were recruited from March to October, 2018 from clinic rosters and inpatient consults in Lilongwe and Blantyre, Malawi. An echocardiogram was performed upon study enrollment. Cox regression analyses were performed to assess for factors associated with mortality over nearly 2 years of follow-up. ...

BACKGROUNDVisit-to-visit blood pressure variability (VVV BPV) is an important yet underutilised risk factor for cardiovascular disease (CVD) risk prediction. Incorporating VVV BPV in the model predicting CVD could improve its performance. This study aims to incorporate VVV BPV into a CVD risk prediction model and to evaluate its performance by comparing the discrimination and calibration of models using a single BP measurement versus those incorporating VVV BPV METHODSThis prospective cohort st...