Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-label, blinded-endpoint clinical trial.

Background: Studies have suggested that evening dosing with antihypertensive therapy might have better outcomes than morning dosing. The Treatment in Morning versus Evening (TIME) study aimed to investigate whether evening dosing of usual antihypertensive medication improves major cardiovascular outcomes compared with morning dosing in patients with hypertension.

Methods: The TIME study is a prospective, pragmatic, decentralised, parallel-group study in the UK, that recruited adults (aged ≥18 years) with hypertension and taking at least one antihypertensive medication.

Adverse events and overall health and well-being after COVID-19 vaccination: interim results from the VAC4COVID cohort safety study.

Objectives: To describe the incidence of adverse events (AEs), reactogenicity symptoms, menstrual changes and overall self-rated improvement in health and well-being after COVID-19 vaccination.

Design: VAC4COVID is an ongoing prospective, active observational, post-authorisation cohort safety study (PASS) of UK-approved vaccines for COVID-19 disease.

Setting: The study is conducted through a secure website (www.

Systematic review and meta-analysis of prophylaxis use with intravenous contrast exposure to prevent contrast-induced nephropathy.

Purpose: Iodinated radiographic contrast media has been associated with an acute deterioration in renal function, termed contrast induced nephropathy (CIN). This review aims to establish the efficacy of prophylaxis interventions used in adult patients prior to intravenous exposure to iodinated contrast to reduce the risk of CIN.

Methods: An electronic search for published peer-reviewed articles was performed, supplemented with manual review of references from previous systematic reviews and the National Institute for Health and Care Excellence guidelines.

Fibroblast growth factor 15/19 expression, regulation, and function: An overview.

Since the discovery of fibroblast growth factor (FGF)-19 over 20 years ago, our understanding of the peptide and its role in human biology has moved forward significantly. A member of a superfamily of paracrine growth factors regulating embryonic development, FGF19 is unique in that it is a dietary-responsive endocrine hormone linked with bile acid homeostasis, glucose and lipid metabolism, energy expenditure, and protein synthesis during the fed to fasted state. FGF19 achieves this through targeting multiple tissues and signaling pathways within those tissues.

Tissue-specific mechanisms of bile acid homeostasis and activation of FXR-FGF19 signaling in preterm and term neonatal pigs.

The tissue-specific molecular mechanisms involved in perinatal liver and intestinal farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling are poorly defined. Our aim was to establish how gestational age and feeding status affect bile acid synthesis pathway, bile acid pool size, ileal response to bile acid stimulation, genes involved in bile acid-FXR-FGF19 signaling and plasma FGF19 in neonatal pigs. Term ( = 23) and preterm ( = 33) pigs were born via cesarean section at 100% and 90% gestation, respectively.

Analgesic use and associated adverse events in patients with chronic kidney disease: a systematic review and meta-analysis.

Background: Treating pain in the context of chronic kidney disease (CKD) is challenging because of altered pharmacokinetics and pharmacodynamics, with an increased risk of toxicity and drug adverse events in this population. The aims of this systematic review and meta-analysis were to assess the prevalence of analgesic use and establish the risk of analgesics-related adverse events, in patients with CKD.

Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed.

Developing an AKI Consensus Definition for Database Research: Findings From a Scoping Review and Expert Opinion Using a Delphi Process.

Rationale & Objective: The KDIGO (Kidney Disease: Improving Global Outcomes) definition of acute kidney injury (AKI) is frequently used in studies to examine the epidemiology of AKI. This definition is variably interpreted and applied to routinely collected health care data. The aim of this study was to examine this variation and to achieve consensus in how AKI should be defined for research using routinely collected health care data.

Depletion and enrichment of phytosterols in soybean oil lipid emulsions directly associate with serum markers of cholestasis in preterm parenteral nutrition-fed pigs.

Background: Clinical reports show a positive correlation between phytosterol concentrations and severity of cholestatic liver disease markers in infants during long-term administration of parenteral lipid emulsions. Establishing a causal link between phytosterols and cholestasis has been complicated by confounding factors of lipid emulsion load, fatty acid composition, and vitamin E in many of these studies. The goal of this study is to determine whether altering the phytosterol concentration within a common soybean oil-based emulsion will alter the onset and severity of cholestasis in parenterally fed preterm piglets.

Parenteral lipids shape gut bile acid pools and microbiota profiles in the prevention of cholestasis in preterm pigs.

Multi-component lipid emulsions, rather than soy-oil emulsions, prevent cholestasis by an unknown mechanism. Here, we quantified liver function, bile acid pools, and gut microbial and metabolite profiles in premature parenterally fed pigs given a soy-oil lipid emulsion, Intralipid (IL), a multi component lipid emulsion, SMOFlipid (SMOF), a novel emulsion with a modified fatty-acid composition [experimental emulsion (EXP)], or a control enteral diet (ENT) for 22 days. We assayed serum cholestasis markers, measured total bile acid levels in plasma, liver, and gut contents, and analyzed colonic bacterial 16S rRNA gene sequences and metabolomic profiles.

Deprivation and kidney disease-a predictor of poor outcomes.

There is a growing body of evidence for the role of deprivation in a broad spectrum of diseases including renal disease. Deprivation has been demonstrated to be associated with poorer outcomes across a range of renal diseases including acute kidney injury (AKI), chronic kidney disease and transplantation. In this issue of , Hounkpatin .

The value of mentorship in medical education.

Background: The transition from senior medical student to working safely and effectively as a new junior doctor is one of the biggest challenges that a new graduate will face. In 2014 the General Medical Council published The state of medical education and practice in the UK, reporting that some new doctors continue to struggle with increased responsibilities. We classify these instances as a 'performance gap', describing occasions in clinical practice where an individual exceeds their performance capacity.

Impact of particular antiepileptic drugs on the survival of patients with glioblastoma multiforme.

Object: Glioblastoma multiforme (GBM) is the most common astrocytic brain tumor and carries a dire prognosis. Despite current therapeutic options--surgery, radiotherapy, and chemotherapy--survival varies from 11.3 to 14.