Population pharmacokinetics and exposure-response analysis of durvalumab in combination with gemcitabine and cisplatin in patients with advanced biliary tract cancer.

Purpose: Durvalumab in combination with gemcitabine/cisplatin has shown a favorable benefit-risk profile in the TOPAZ-1 study for advanced biliary tract cancers (BTC). This analysis evaluated the population pharmacokinetics (PopPK) of durvalumab, and exposure-response for efficacy and safety (ERES) of TOPAZ-1.

Methods: The PopPK model for durvalumab was updated using data from 5 previously analysed studies and TOPAZ-1.

[Mechanisms of action of antidepressive pharmacotherapy: brain and mind-body and environment].

Background: Novel antidepressive substances are challenging the explanations for the mechanisms of action of traditional psychopharmacology.

Objective: What could be the shared effects of various antidepressants and in this context what role do extrapharmacological factors, such as the body and environment, play?

Material And Method: The available literature on clinical and preclinical data for assumed combined active factors of serotonergic psychedelic drugs, (es)ketamine, monoaminergic antidepressants and zuranolone are presented and the influence of context factors on the individual mechanisms of action is discussed.

Results: There are many indications that classical and novel pharmacological approaches could share similar mechanisms of action in the treatment of depression.

Risk Factors for Residual Unablated Tumour Following CT-Guided Percutaneous Renal Cryoablation: Lessons from the EuRECA Registry.

Objective: To assess tumour factors that reduce primary technical efficacy (PTE) from CT-guided renal cryoablation.

Methods: Patients were taken from the EuRECA registry between December 2014 and November 2020. To focus on tumour factors rather than individual technique, this study was limited to cases using CT and excluded procedures using cone beam, US, MRI, or laparoscopy.

Individualization of piperacillin dosage based on therapeutic drug monitoring with or without model-informed precision dosing: a scenario analysis.

Background: Model-informed precision dosing (MIPD) combines population pharmacokinetic knowledge with therapeutic drug monitoring (TDM) to optimize dosage adjustment. It could improve target concentration attainment over empirical TDM, still widely practised for broad-spectrum antibiotics.

Objectives: To evaluate the respective performance of TDM and MIPD in achieving target piperacillin exposure.

The Potential of Poetry in Mental Health Nurse Pre-registration Education.

This paper examines the potential of poetry as a resource within mental health nurse pre-registration education. There has long been a debate as to whether the art or the science of nursing should be foregrounded within pre-registration education, especially in the UK within recent years as the latest Nursing and Midwifery Council's standards of pre-registration education appear to have shifted the focus towards the acquisition of skills, giving less consideration to the holistic transformatory process of education. The paper uses the conceptualisation of education by Beista, who proposes that education can be considered in relation to the three domains of qualification, socialisation and subjectification.

Synergistic effect of sarcopenia and ASA status in predicting mortality after emergency laparotomy: a systematic review and meta-analysis with meta-regression.

The aim of this study was to investigate the relationship between sarcopenia and American Society of Anesthesiologists (ASA) status in predicting post-operative mortality after emergency laparotomy. A PRISMA-compliant systematic review and meta-analysis (using random effects modelling) was performed searching for studies reporting 30-day mortality risk in patients with sarcopenia undergoing emergency laparotomy. The ASA status of sarcopenic and non-sarcopenic patients was determined, and the effect of difference in ASA status on 30-day mortality in sarcopenic and non-sarcopenic patients was determined via a meta-regression model.

CAR T access and outcomes in large B-cell lymphoma according to ethnicity and socioeconomic deprivation in the UK.

Data on the impact of ethnic and socioeconomic factors on Chimeric antigen receptor (CAR) T-cell therapy (access and outcomes are limited, but key to understand whether results from the registration trials are generalizable to real-world patient populations. Here, we analysed ethnicity, socioeconomic deprivation and referral patterns in a cohort of 314 large B-cell lymphoma patients approved for third-line CD19 CAR-T across three large UK CAR-T centres. Patients from deprived areas had a lower infusion rate compared to low deprivation areas (73% vs.

Organic Spacers Modulated Low Dose X-Ray Detection in Hybrid Halide 2D Perovskites: Unveiling Exciton Dynamics.

In this study, we investigate how modulating organic spacers in perovskites influences their X-ray detection performance and reveal the mechanism of low-dose detection with high sensitivity using femtosecond-transient absorption spectroscopy (fs-TAS). Particularly, we employ N,N,N',N'-tetramethyl-1,4-phenylenediammonium (TMPDA) and N,N-dimethylphenylene-p-diammonium (DPDA) as organic spacers to synthesize 2D perovskite single crystals (SCs). We find that DPDA-based SCs exhibit reduced interplanar spacing between inorganic layers, leading to increased lattice packing.

Prevalence and Risk Factors of Acute Kidney Injury After Colorectal Cancer Surgery.

Purpose: Acute kidney injury is a sentinel event affecting colorectal cancer patients either as a consequence of surgery or systemic chemotherapy. It is highly correlated with both short and long-term adverse outcomes. This work aimed to study the prevalence, risk factors, and impact on survival of postoperative (PO-AKI) and post-chemotherapy (PC-AKI) after colorectal cancer (CRC) surgery in Egyptian patients.

Piloting of a Decision Aid for Recurrent Tonsillitis.

Objective: Currently, there is no adult-specific decision aid (DA) to support decision-making regarding recurrent tonsillitis. This study intends to address this gap by piloting a prototype DA.

Design: Randomised clinical trial.

Approach to Endocrine Hypertension: A Case-Based Discussion.

Purpose Of Review: Hypertension remains a major chronic disease morbidity across the world, even in the twenty-first century, affecting ≈40% of the global population, adversely impacting the healthcare budgets in managing the high incidence of cardiovascular disease (CVD) complications and mortality because of elevated blood pressure (BP). However, evaluation and management of endocrine hypertension are not optimal in clinical practice. With three unique clinical case scenarios, we update the evidence base for diagnostic evaluation and management of endocrine hypertension in this review to inform appropriate day-to-day clinical practice decisions.

Rethinking speech sound disorder (SSD) in non-syndromic cleft lip and palate: The importance of recognizing phonological and language difficulties.

Background: Children born with cleft palate ± lip (CP ± L) are at risk of speech sound disorder (SSD). Up to 40% continue to have SSD at age 5-6 years. These difficulties are typically described as articulatory in nature and often include cleft speech characteristics (CSC) hypothesized to result from structural differences.

Comprehensive Review and Meta-Analysis of Psychological and Pharmacological Treatment for Intermittent Explosive Disorder: Insights From Both Case Studies and Randomized Controlled Trials.

Intermittent explosive disorder (IED) is characterized by sudden, disproportionate outbursts of anger that can severely impact individuals' quality of life, causing difficulties in maintaining relationships, issues at work or school and potential legal troubles. This study aimed to systematically review and meta-analyse the effectiveness of psychological and pharmacological treatments for IED, drawing insights from both case studies and randomized controlled trials (RCTs). A total of 12 RCTs and 14 case studies were included in this comprehensive analysis.

Feasibility of robotic surgery in elderly patients with rectal cancer: a meta-analysis.

Rectal cancer's prevalence increases with an aging population, disproportionately affecting the elderly. The suitability of surgical interventions for this demographic is contentious due to underrepresentation during surgery. This study examines the practicality of utilizing Da Vinci surgery for rectal cancer patients who are 70 years and older.

[Histomorphologically defined renal cell carcinomas 2025 : Current WHO classification and emerging future subtypes].

Background: The latest edition of the WHO classification of urinary and male genital tumours was published in 2022. The revision was based on the newest scientific literature. This article summarizes the updated recommendations regarding the classification of histomorphologically defined tumours.

Self-management behaviors do not affect remission but mediate between mental health and disease outcomes in a longitudinal study of rheumatoid arthritis.

Mental health has been shown to impact rheumatoid arthritis (RA) outcomes and is associated with self-management behaviors. The extent to which mental health impacts outcomes via different self-management behaviours has not been thoroughly investigated. Adult RA patients who were starting a new medication or dosage were recruited to a prospective cohort with follow-ups at 3 and 12-months covering clinical and patient-reported outcomes.

Impact of Pharmacovigilance Interventions Targeting Fluoroquinolones on Antibiotic Use in the Netherlands and the United Kingdom.

Purpose: Fluoroquinolones are antibiotics associated with adverse events that prompted the European Medicines Agency to implement risk minimization measures (RMMs) in 2018/19 and 2020. Our aim is to assess the RMMs' impact on antibiotic prescriptions in primary care during 2014-2023.

Methods: We assessed antibiotic prescriptions using CPRD GOLD (the United Kingdom, UK) and PHARMO (the Netherlands, NL).

Reproducibility of fetal ultrasound doppler parameters used for growth assessment.

Objectives: To produce standards of references for quality control and assess the reproducibility of fetal ultrasound Doppler measurements commonly used for blood flow assessment in fetal growth.

Methods: Women with singleton normal pregnancies were prospectively recruited at University College London Hospital, UK, between 24 and 41 weeks. Umbilical artery (UA), middle cerebral artery (MCA), and their pulsatility indices (PI), resistance indices (RI) and ratios such as cerebro-placental (CPR) and umbilical cerebral ratio (UCR) were obtained twice by two sonographers in training or after completion of training, blind to each other's measurements.

The global prevalence of Chlamydia trachomatis genital infection in pregnant women: a meta-analysis.

Background: Chlamydia trachomatis genital infection is one of the most common sexually transmitted bacterial infections with severe detrimental effects on pregnant women and fetuses. CTGI increases the risk of ectopic pregnancy, exogenous fetal infection, and respiratory complications such as bronchitis and pneumonia. According to the different published reports, this systematic review and meta-analysis study aimed to evaluate the global prevalence of CTGI in pregnant women.

Robust metabolomic age prediction based on a wide selection of metabolites.

Chronological age is a major risk factor for numerous diseases. However, chronological age does not capture the complex biological aging process. the difference between the chronological age and biologically driven aging could be more informative in reflecting health status.

Prevalence of Popular Smoking Cessation Aids in England and Associations With Quit Success.

Importance: A wide range of medications, noncombustible nicotine products, behavioral support, and alternative treatments are available in England to help people stop smoking. Understanding their effectiveness outside of clinical trial settings can support informed decision-making.

Objectives: To provide up-to-date estimates of the prevalence of different smoking cessation aids and associations with quit success and to explore moderation by socioeconomic position.