How group structure impacts the numbers at risk for coronary artery disease: polygenic risk scores and nongenetic risk factors in the UK Biobank cohort.

The UK Biobank (UKB) is a large cohort study that recruited over 500,000 British participants aged 40-69 in 2006-2010 at 22 assessment centers from across the United Kingdom. Self-reported health outcomes and hospital admission data are 2 types of records that include participants' disease status. Coronary artery disease (CAD) is the most common cause of death in the UKB cohort.

Impact of elexacaftor/tezacaftor/ivacaftor on respiratory colonization in an adult cystic fibrosis clinic.

Background: Little research has been completed on the correlation between cystic fibrosis (CF) modulator therapy and its effect on respiratory cultures in CF patients. This study evaluated the effect of elexacaftor/tezacaftor/ivacaftor (ETI) on respiratory colonization with Pseudomonas aeruginosa.

Methods: This single center, IRB approved, retrospective chart review compared patient data two years immediately prior to ETI initiation with patient data two years post-initiation from January 2017-December 2022.

Striatal response to negative feedback in a stop signal task operates as a multi-value learning signal.

Background And Aim: We examined error-driven learning in fMRI activity of 217 subjects in a stop signal task to obtain a more robust characterization of the relation between behavioral measures of learning and corresponding neural learning signals than previously possible.

Methods: The stop signal task is a two-alternative forced choice in which participants respond to an arrow by pressing a left or right button but must inhibit that response on 1 in 7 trials when cued by an auditory "stop signal." We examined post-error learning by comparing brain activity (BOLD signal) and behavioral responses on trials preceded by successful (correct stop) vs.

Plain language summary of erdafitinib in locally advanced or metastatic urothelial carcinoma: a phase 2 study with long-term follow-up.

What Is This Summary About?: This is a plain language summary of two articles describing the results from a study called BLC2001. The study examined the effect of a medication called erdafitinib on participants with a type of cancer known as urothelial carcinoma that had either spread beyond the bladder or urinary tract into surrounding organs and/or nearby muscles (locally advanced) and was not removable by surgery (unresectable) or had spread to other parts of the body (metastatic). In this study, researchers wanted to learn if erdafitinib was safe and effective at stopping or reducing tumor growth in participants with locally advanced and unresectable or metastatic urothelial carcinoma with certain genetic alterations (changes in DNA sequence) in two related genes called fibroblast growth factor receptor 2 () and 3 ().

The Design and Implementation of a Novel Mental Health Literacy Educational Intervention Program in Gaelic Footballers.

Context: Lack of education, stigma, and negative self-attitudes are key barriers to help-seeking in Gaelic footballers. With the prevalence of mental health issues in Gaelic footballers and the increased risk of experiencing mental health challenges after injury, mental health literacy (MHL) interventions are necessary.

Objectives: To design and implement a novel MHL educational intervention program in Gaelic footballers.

A 13-Year-Old Male Patient With Severe Multifocal Pneumonia and Bronchiectasis That Required Extracorporeal Membrane Oxygenation.

A 13-year-old male patient with intermittent asthma and joint hypermobility presented to the ED in acute hypoxemic respiratory distress. He reported experiencing cough, increased work of breathing, and worsening chest pain for 3 days before presentation. He also reported fatigue and decreased appetite for 2 weeks.

Do our movement skills impact our cognitive skills? Exploring the relationship between cognitive function and fundamental movement skills in primary school children.

Objectives: The literature suggests that there is a relationship between motor function and cognitive development however, few studies have explored the specific role of Functional Movement Skills on cognitive function. This research aimed to determine if Functional Movement Skills predict cognitive function, when accounting for confounding factors, in a sample of primary school children in Ireland.

Design: Cross-sectional.

Eliciting judgements about dependent quantities of interest: The SHeffield ELicitation Framework extension and copula methods illustrated using an asthma case study.

Pharmaceutical companies regularly need to make decisions about drug development programs based on the limited knowledge from early stage clinical trials. In this situation, eliciting the judgements of experts is an attractive approach for synthesising evidence on the unknown quantities of interest. When calculating the probability of success for a drug development program, multiple quantities of interest-such as the effect of a drug on different endpoints-should not be treated as unrelated.

Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study.

Background: Erdafitinib, a pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, was shown to be clinically active and tolerable in patients with advanced urothelial carcinoma and prespecified FGFR alterations in the primary analysis of the BLC2001 study at median 11 months of follow-up. We aimed to assess the long-term efficacy and safety of the selected regimen of erdafitinib determined in the initial part of the study.

Methods: The open-label, non-comparator, phase 2, BLC2001 study was done at 126 medical centres in 14 countries across Asia, Europe, and North America.

Exposure-response analyses of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma.

Background: Exposure-response analyses were conducted to explore the relationship between selected efficacy and safety endpoints and serum phosphate (PO4) concentrations, a potential biomarker of efficacy and safety, in locally advanced or metastatic urothelial carcinoma patients with FGFR alterations treated with erdafitinib.

Methods: Data from two dosing regimens of erdafitinib in a phase 2 study (NCT02365597), 6 and 8-mg/day with provision for pharmacodynamically guided titration per serum PO4 levels, were analyzed using Cox proportional hazard or logistic regression models. Efficacy endpoints were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).

Erdafitinib's effect on serum phosphate justifies its pharmacodynamically guided dosing in patients with cancer.

A population pharmacokinetic (PK)-pharmacodynamic (PD) model was developed using data from 345 patients with cancer. The population PK-PD model evaluated the effect of erdafitinib total and free plasma concentrations on serum phosphate concentrations after once-daily oral continuous (0.5-12 mg) and intermittent (10-12 mg for 7 days on/7 days off) dosing, and investigated the potential covariates affecting erdafitinib-related changes in serum phosphate levels.

Response (minimum clinically relevant change) in ASD symptoms after an intervention according to CARS-2: consensus from an expert elicitation procedure.

The lack of consensual measures to monitor core change in Autism Spectrum Disorder (ASD) or response to interventions leads to difficulty to prove intervention efficacy on ASD core symptoms. There are no universally accepted outcome measures developed for measuring changes in core symptoms. However, the CARS (Childhood Autism Rating Scale) is one of the outcomes recommended in the EMA Guideline on the clinical development of medicinal products for the treatment of ASD.

Impact of Payor-Initiated Switching of Inhaled Corticosteroids on Lung Function.

Objectives: To evaluate the impact of a payor-initiated formulary change in inhaled corticosteroid coverage on lung function in patients with asthma and on provider prescribing practices. This formulary change, undertaken in August 2016 by a Medicaid payor in Kentucky, eliminated coverage of beclomethasone dipropionate, a metered dose inhaler (MDI), in favor of mometasone furoate, available as MDI and dry powder inhaler (DPI).

Study Design: A retrospective chart review was conducted on children with asthma ages 6-18 years covered by the relevant payor from a university-based pediatric practice who were seen before the formulary change (February to July 2016) and after (February to July 2017).

Fear Avoidance After Injury and Readiness to Return to Sport in Collegiate Male and Female Gaelic Games Players.

Background: Injuries are common in collegiate Gaelic games, and negative psychological responses to injury, such as fear avoidance and a lack of psychological readiness to return to sport, can affect players during their rehabilitation and their subsequent return to sport. Thus, identifying these responses in players can allow clinicians to address these issues during rehabilitation. This study aimed to examine fear avoidance and psychological readiness to return to sport in collegiate Gaelic games players.

Predictively consistent prior effective sample sizes.

Determining the sample size of an experiment can be challenging, even more so when incorporating external information via a prior distribution. Such information is increasingly used to reduce the size of the control group in randomized clinical trials. Knowing the amount of prior information, expressed as an equivalent prior effective sample size (ESS), clearly facilitates trial designs.

Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma.

Background: Alterations in the gene encoding fibroblast growth factor receptor () are common in urothelial carcinoma and may be associated with lower sensitivity to immune interventions. Erdafitinib, a tyrosine kinase inhibitor of FGFR1-4, has shown antitumor activity in preclinical models and in a phase 1 study involving patients with alterations.

Methods: In this open-label, phase 2 study, we enrolled patients who had locally advanced and unresectable or metastatic urothelial carcinoma with prespecified alterations.

The Role of Expert Judgment in Statistical Inference and Evidence-Based Decision-Making.

This article resulted from our participation in the session on the "role of expert opinion and judgment in statistical inference" at the October 2017 ASA Symposium on Statistical Inference. We present a strong, unified statement on roles of expert judgment in statistics with processes for obtaining input, whether from a Bayesian or frequentist perspective. Topics include the role of subjectivity in the cycle of scientific inference and decisions, followed by a clinical trial and a greenhouse gas emissions case study that illustrate the role of judgments and the importance of basing them on objective information and a comprehensive uncertainty assessment.

Sterility and Stability Testing of Preservative-free Albuterol.

Background: Continuous albuterol administration (CAA) is commonly used in hospitalized patients for treatment of asthma exacerbations. Due to higher dose requirements, CAA requires large volumes of albuterol obtained from multidose vials containing benzalkonium chloride (BAC). BAC is a common pharmaceutical preservative and potent bronchoconstrictor, which may antagonize the bronchodilation effects of albuterol.