Network meta-regression for ordinal outcomes: Applications in comparing Crohn's disease treatments.

Crohn's disease (CD) is a life-long condition associated with recurrent relapses characterized by abdominal pain, weight loss, anemia, and persistent diarrhea. In the US, there are approximately 780 000 CD patients and 33 000 new cases added each year. In this article, we propose a new network meta-regression approach for modeling ordinal outcomes in order to assess the efficacy of treatments for CD.

Geo-mapping of young people in residential aged care.

Objective: Reducing the need for permanent accommodation in nursing homes (residential aged care services) for young people is a major challenge in Australia and internationally. This study investigated the use of innovative geo-mapping strategies to describe the geographical distribution of young people living in residential aged care services (RACS).

Methods: Geographic Information System software was used to generate 13 choropleth maps using data from the Australian Institute of Health and Welfare.

Injury characteristics of the Pulse Nightclub shooting: Lessons for mass casualty incident preparation.

Background: On the morning of June 12, 2016, an armed assailant entered the Pulse Nightclub in Orlando, Florida, and initiated an assault that killed 49 people and injured 53. The regional Level I trauma center and two community hospitals responded to this mass casualty incident. A detailed analysis was performed to guide hospitals who strive to prepare for future similar events.

Comparative effect of sodium butyrate and sodium propionate on proliferation, cell cycle and apoptosis in human breast cancer cells MCF-7.

Introduction: Short-chain fatty acids (SCFAs) are ubiquitous lipids produced as a result of bacterial fermentation of dietary fiber. While their role in colorectal cancer is well known, the effect of SCFAs in breast cancer is poorly defined.

Objective: To understand the various effects of SCFAs on breast carcinogenesis, we investigated the effect of sodium butyrate (NaB) and sodium propionate (NaP) in MCF-7 cell line.

Child Electronic Growth Monitoring System: An innovative and sustainable approach for establishing the Kaduna Infant Development (KID) Study in Nigeria.

Background: Developing countries bear the burden of childhood stunting but lack resources for cohort studies to develop preventive strategies. To enable future prospective studies, we designed and tested the Child Electronic Growth Monitoring System (CEGROMS) using a readily available electronic data capture platform, the Research Electronic Data Capture (REDCap).

Objectives: To demonstrate the feasibility of using CEGROMS for data collection for a pilot study for the Kaduna Infant Development (KID) Birth Cohort Study in Nigeria.

A hierarchical testing approach for detecting safety signals in clinical trials.

Detecting safety signals in clinical trial safety data is known to be challenging due to high dimensionality, rare occurrence, weak signal, and complex dependence. We propose a new hierarchical testing approach for analyzing safety data from a typical randomized clinical trial. This approach accounts for the hierarchical structure of adverse events (AEs), that is, AEs are categorized by system organ class (SOC).

Prevalence, antimicrobial resistance and risk factors for campylobacteriosis in Lebanon.

Introduction: The rapid increase in Campylobacter strains resistant to antibiotics represents a major problem for public health. In Lebanon, campylobacteriosis is underdiagnosed since bacteria detection in stool samples is not performed routinely. This study aims to evaluate the prevalence, sources and routes of transmission, risk factors and antimicrobial susceptibility patterns of Campylobacter spp.

Effect of eliglustat on the pharmacokinetics of digoxin, metoprolol, and oral contraceptives and absorption of eliglustat when coadministered with acid-reducing agents.

Eliglustat is an oral substrate reduction therapy indicated for patients with Gaucher disease type 1. Based on in vitro data, clinical trials were conducted to assess the potential for drug-drug interactions between eliglustat and digoxin (P-glycoprotein substrate), metoprolol (sensitive CYP2D6 substrate), a combined oral contraceptive (CYP3A substrate), and acid-reducing agents. Healthy subjects were enrolled in four Phase 1 clinical studies to evaluate the effect of eliglustat on the pharmacokinetics, safety, and tolerability of digoxin (N = 28), metoprolol (N = 14), and a combined oral contraceptive (N = 30) and the effect of acid-reducing agents on eliglustat pharmacokinetics, safety, and tolerability (N = 24).

Partial least squares for functional joint models with applications to the Alzheimer's disease neuroimaging initiative study.

Many biomedical studies have identified important imaging biomarkers that are associated with both repeated clinical measures and a survival outcome. The functional joint model (FJM) framework, proposed by Li and Luo in 2017, investigates the association between repeated clinical measures and survival data, while adjusting for both high-dimensional images and low-dimensional covariates based on the functional principal component analysis (FPCA). In this paper, we propose a novel algorithm for the estimation of FJM based on the functional partial least squares (FPLS).

Effects of paroxetine, ketoconazole, and rifampin on the metabolism of eliglustat, an oral substrate reduction therapy for Gaucher disease type 1.

Eliglustat is an oral glucosylceramide synthase inhibitor indicated for the long-term treatment of adults with Gaucher disease type 1 and CYP2D6 extensive, intermediate, or poor metabolizer phenotypes. Eliglustat is metabolized primarily by CYP2D6 and to a lesser extent by CYP3A4 and is a substrate of P-glycoprotein (P-gp). Three studies evaluated the effects of paroxetine (strong CYP2D6 inhibitor), ketoconazole (strong CYP3A4 and P-gp inhibitor), and rifampin (strong CYP3A4/P-gp inducer; OATP inhibitor) on the pharmacokinetics of orally administered eliglustat in healthy adults.

Aerosol Pirfenidone Pharmacokinetics after Inhaled Delivery in Sheep: a Viable Approach to Treating Idiopathic Pulmonary Fibrosis.

Purpose: Inhaled delivery of pirfenidone to the lungs of patients with idiopathic pulmonary fibrosis holds promise to eliminate oral-observed side effects while enhancing efficacy. This study aimed to comprehensively describe the pulmonary pharmacokinetics of inhaled aerosol pirfenidone in healthy adult sheep.

Methods: Pirfenidone concentrations were evaluated in plasma, lung-derived lymph and epithelial lining fluid (ELF) with data subjected to non-compartmental pharmacokinetic analysis.

Joint analysis of single-cell and bulk tissue sequencing data to infer intratumor heterogeneity.

Many computational methods have been developed to discern intratumor heterogeneity (ITH) using DNA sequence data from bulk tumor samples. These methods share an assumption that two mutations arise from the same subclone if they have similar mutant allele-frequencies (MAFs), and thus it is difficult or impossible to distinguish two subclones with similar MAFs. Single-cell DNA sequencing (scDNA-seq) data can be very informative for ITH inference.

Deaths of young people living in residential aged care: a national population-based descriptive epidemiological analysis of cases notified to Australian coroners.

Aim: This study provides a descriptive epidemiological analysis stratified by age of deaths reported to Australian Coroners of residential aged care facility residents aged under 65 years.

Method: A national population-based retrospective analysis was conducted of deaths of Australian residential aged care facility residents reported to Australian Coroners between 2000 and 2013. Descriptive statistics compared adult residents categorised using age by factors relating to the individual, incident and death investigation.

The Gene Has Potential as a Pan-Cancer Biomarker, While Discriminating between Different Tumor Types.

Due to the elevated rates of incidence and mortality of cancer, early and accurate detection is crucial for achieving optimal treatment. Molecular biomarkers remain important screening and detection tools, especially in light of novel blood-based assays. DNA methylation in cancer has been linked to tumorigenesis, but its value as a biomarker has not been fully explored.

A new Bayesian joint model for longitudinal count data with many zeros, intermittent missingness, and dropout with applications to HIV prevention trials.

In longitudinal clinical trials, it is common that subjects may permanently withdraw from the study (dropout), or return to the study after missing one or more visits (intermittent missingness). It is also routinely encountered in HIV prevention clinical trials that there is a large proportion of zeros in count response data. In this paper, a sequential multinomial model is adopted for dropout and subsequently a conditional model is constructed for intermittent missingness.

Akt1 and Akt2 Isoforms Play Distinct Roles in Regulating the Development of Inflammation and Fibrosis Associated with Alcoholic Liver Disease.

Akt kinase isoforms (Akt1, Akt2, and Akt3) have generally been thought to play overlapping roles in phosphoinositide 3-kinase (PI3K)-mediated-signaling. However, recent studies have suggested that they display isoform-specific roles in muscle and fat. To determine whether such isoform-specificity is observed with respect to alcoholic liver disease (ALD) progression, we examined the role of Akt1, Akt2, and Akt3 in hepatic inflammation, and pro-fibrogenic proliferation and migration using Kupffer cells, hepatic stellate cells (HSC), and hepatocytes in an ethanol and lipopolysaccharide (LPS)-induced two-hit model in vitro and in vivo.

Applying dignity of risk principles to improve quality of life for vulnerable persons.

Objectives: Freedom of choice impacts quality of life. Expressed through dignity of risk (DoR), nursing home (NH) residents should be afforded the dignity to take risks to enhance well-being. How DoR is understood and implemented in the context of aged care remains largely unknown.

Neonatal Toxic Shock Syndrome-Like Exanthematous Disease in North America.

Neonatal toxic shock syndrome (TSS)-like exanthematous disease (NTED) is a syndrome first reported in Japan. Neonates develop systemic exanthema, thrombocytopenia, and fever usually during the first week of life. The disease is distinguished from frank TSS because affected infants are not severely ill and do not meet TSS criteria.

International Transferability of Research Evidence in Residential Long-term Care: A Comparative Analysis of Aged Care Systems in 7 Nations.

Objective: To compare publicly available information on aged care systems in 7 countries to determine the degree of transferability for research on aged care between these countries.

Design: A cross-country comparative analysis.

Setting: Aged care systems in 7 countries classified as liberal welfare states (Australia, Canada, Japan, New Zealand, Switzerland, United Kingdom, and United States).

A Powerful Global Test Statistic for Functional Statistical Inference.

We consider the problem of performing an association test between functional data and scalar variables in a varying coefficient model setting. We propose a functional projection regression model and an associated global test statistic to aggregate relatively weak signals across the domain of functional data, while reducing the dimension. An optimal functional projection direction is selected to maximize signal-to-noise ratio with ridge penalty.