Impact analysis of infant antibiotic exposure on the burden of asthma: a simulation modeling study.

Background: Infant antibiotic use is associated with increased risk of asthma. We examined the population impact of antibiotic exposure in the first year of life on the burden of pediatric asthma in British Columbia, Canada, using simulation modeling.

Methods: We performed a Bayesian meta-analysis of empirical studies to construct dose-response equations between antibiotic exposure in the first year of life and pediatric (<19 years of age) asthma.

Non-parametric inference on calibration of predicted risks.

Moderate calibration, the expected event probability among observations with predicted probability z being equal to z, is a desired property of risk prediction models. Current graphical and numerical techniques for evaluating moderate calibration of risk prediction models are mostly based on smoothing or grouping the data. As well, there is no widely accepted inferential method for the null hypothesis that a model is moderately calibrated.

A parametric model to jointly characterize rate, duration, and severity of exacerbations in episodic diseases.

Background: The natural history of many chronic diseases is characterized by periods of increased disease activity, commonly referred to as flare-ups or exacerbations. Accurate characterization of the burden of these exacerbations is an important research objective.

Methods: The purpose of this work was to develop a statistical framework for nuanced characterization of the three main features of exacerbations: their rate, duration, and severity, with interrelationships among these features being a particular focus.

16-year trends in asthma hospital admissions in Canada.

Background: Asthma hospitalizations declined rapidly in many parts of the world, including Canada, in the 1990s and early 2000s.

Objective: To examine whether the declining trend of asthma hospitalizations persisted in recent years in Canada.

Methods: Using the Canadian comprehensive nationwide hospitalization data (2002-2017), we identified hospital admissions with the main International Classification of Diseases codes for asthma.

Patterns of alpha-linolenic acid incorporation into phospholipids in H4IIE cells.

Alpha linolenic acid (ALA) is an 18-carbon essential fatty acid found in plant-based foods and oils. While much attention has been placed on conversion of ALA to long chain polyunsaturated fatty acids, alternative routes of ALA metabolism exist and may lead to formation of other bioactive metabolites of ALA. The current study employed a non-targeted metabolomics approach to profile ALA metabolites that are significantly upregulated by ALA treatment.

Recommendations for the use of propensity score methods in multiple sclerosis research.

Background: With many disease-modifying therapies currently approved for the management of multiple sclerosis, there is a growing need to evaluate the comparative effectiveness and safety of those therapies from real-world data sources. Propensity score methods have recently gained popularity in multiple sclerosis research to generate real-world evidence. Recent evidence suggests, however, that the conduct and reporting of propensity score analyses are often suboptimal in multiple sclerosis studies.

Serum neurofilament light chain correlates with myelin and axonal magnetic resonance imaging markers in multiple sclerosis.

Background: Neurofilaments are cytoskeletal proteins that are detectable in the blood after neuroaxonal injury. Multiple sclerosis (MS) disease progression, greater lesion volume, and brain atrophy are associated with higher levels of serum neurofilament light chain (NfL), but few studies have examined the relationship between NfL and advanced magnetic resonance imaging (MRI) measures related to myelin and axons. We assessed the relationship between serum NfL and brain MRI measures in a diverse group of MS participants.

Alteration of the dietary methionine: Cysteine ratio modulates the inflammatory response to an inter-peritoneal injection of lipopolysaccharide in wistar rats.

Sulphur amino acids (SAA) are essential for multiple physiological/metabolic processes, with the ratio of dietary methionine: cysteine (Met:Cys) being an important contributor to pro-inflammatory responses, including TNF-α activity. The current study was designed to determine the effect an altered dietary SAA ratio, and the resulting reliance on the transsulfuration pathway to supply Cys, will have on the inflammatory response. In the present study, 100 µg/kg of an intraperitoneal (IP) injection of lipopolysaccharide (LPS) was used as a model for systemic inflammation.

Long-Term Natural History of Severe Asthma Exacerbations and Their Impact on the Disease Course.

The long-term natural history of asthma in terms of successive severe exacerbations and the influence of each exacerbation on the course of the disease is not well studied. To investigate the long-term natural history of asthma among patients who are hospitalized for asthma for the first time in terms of the risk of future severe exacerbations and heterogeneity in this risk across patients. Using the administrative health databases of British Columbia, Canada (January 1, 1997 to March 31, 2016), we created an incident cohort of patients with at least one asthma exacerbation that required inpatient care.

Model-Based ROC Curve: Examining the Effect of Case Mix and Model Calibration on the ROC Plot.

Background: The performance of risk prediction models is often characterized in terms of discrimination and calibration. The receiver-operating characteristic (ROC) curve is widely used for evaluating model discrimination. However, when comparing ROC curves across different samples, the effect of case mix makes the interpretation of discrepancies difficult.

Dealing With Treatment-Confounder Feedback and Sparse Follow-up in Longitudinal Studies: Application of a Marginal Structural Model in a Multiple Sclerosis Cohort.

The beta-interferons are widely prescribed platform therapies for patients with multiple sclerosis (MS). We accessed a cohort of patients with relapsing-onset MS from British Columbia, Canada (1995-2013), to examine the potential survival advantage associated with beta-interferon exposure using a marginal structural model. Accounting for potential treatment-confounder feedback between comorbidity, MS disease progression, and beta-interferon exposure, we found an association between beta-interferon exposure of at least 6 contiguous months and improved survival (hazard ratio (HR) = 0.

Effects of cyanidin 3--glucoside and hydrochlorothiazide on T-cell phenotypes and function in spontaneously hypertensive rats.

Immune system dysfunction may contribute to the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). We examined the effects of the anthocyanin, cyanidin 3-O-glucoside (C3G), and the diuretic, hydrochlorothiazide (HCT), on T-cell function in SHR. Five-week-old male SHR and Wistar-Kyoto (WKY) rats received water (n = 8/SHR; n = 8/WKY), 10 mg kg-1 day-1 C3G (n = 8/SHR; n = 8/WKY), 10 mg kg-1 day-1 HCT (n = 8/SHR; n = 8/WKY), or 10 mg kg-1 day-1 C3G + 10 mg kg-1 day-1 HCT (n = 8/SHR; n = 8/WKY) by oral gavage for 15 weeks.

Should the number of acute exacerbations in the previous year be used to guide treatments in COPD?

Background: In contemporary management of chronic obstructive pulmonary disease (COPD), the frequent exacerbator phenotype, based on a 12-month history of acute exacerbation of COPD (AECOPD), is a major determinant of therapeutic recommendations. However, there is considerable debate as to the stability of this phenotype over time.

Methods: We used fundamental principles in time-to-event analysis to demonstrate that variation in the frequent exacerbator phenotype has two major sources: variability in the underlying AECOPD rate and randomness in the occurrence of individual AECOPDs.

Adjusting for differential misclassification in matched case-control studies utilizing health administrative data.

In epidemiological studies of secondary data sources, lack of accurate disease classifications often requires investigators to rely on diagnostic codes generated by physicians or hospital systems to identify case and control groups, resulting in a less-than-perfect assessment of the disease under investigation. Moreover, because of differences in coding practices by physicians, it is hard to determine the factors that affect the chance of an incorrectly assigned disease status. What results is a dilemma where assumptions of non-differential misclassification are questionable but, at the same time, necessary to proceed with statistical analyses.

Multiple sclerosis: effect of beta interferon treatment on survival.

Worldwide, the beta interferons remain the most commonly prescribed disease-modifying drugs for multiple sclerosis. However, it is unclear if they alter survival. We investigated the association between beta interferon and mortality in the 'real-world' setting.

Ginseng Berry Extract Rich in Phenolic Compounds Attenuates Oxidative Stress but not Cardiac Remodeling post Myocardial Infarction.

The cardioprotective effects of ginseng root extracts have been reported. However, nothing is known about the myocardial actions of the phenolic compounds enriched in ginseng berry. Therefore, this study was undertaken to investigate the effects of American ginseng berry extract (GBE) in an experimental model of myocardial infarction (MI).

Healthcare Providers Underestimate Patients' Glucocorticoid Use in Crohn's Disease.

Background: One of the therapy goals for Crohn's disease (CD) is glucocorticoid-free remission. Studies have shown care setting-specific variations in inflammatory bowel disease (IBD) management.

Aims: The principal objective of this study was to assess concordance between patient-reported and physician-reported outcomes in two different care settings (IBD centers and community practices).

A randomized, controlled, crossover study of appetite-related sensations after consuming snacks made from buckwheat.

With the rising incidence of overweight and obesity in developed countries, there is an interest in developing food products that may aid in satiety and reduce energy intake. Buckwheat (Fagopyrum esculentum) is a gluten-free edible seed that has been previously shown to induce changes in postprandial concentrations of satiety hormones; however, subjective measures of appetite-related sensations and objective measures of energy intake at subsequent meals following buckwheat consumption have not been measured. Thirty-eight healthy adults were recruited to participate in a randomized, controlled, crossover trial with the main objective to determine if consuming snacks made from buckwheat would increase satiety and reduce energy intake compared with snacks comparable in serving size, physical characteristics, and nutrient composition.

Effect of adherence to the first-generation injectable immunomodulatory drugs on disability accumulation in multiple sclerosis: a longitudinal cohort study.

Objective: To examine the association between optimal adherence to the first-generation injectable immunomodulatory drugs (IMDs) for multiple sclerosis (MS) and subsequent disability accumulation.

Methods: We accessed prospectively collected linked clinical and administrative health data from British Columbia, Canada. Subjects with MS treated with a first-generation injectable IMD at an MS clinic (1996-2004) were followed until their last clinic visit before 2009.

Bayesian analysis of pair-matched case-control studies subject to outcome misclassification.

We examine the impact of nondifferential outcome misclassification on odds ratios estimated from pair-matched case-control studies and propose a Bayesian model to adjust these estimates for misclassification bias. The model relies on access to a validation subgroup with confirmed outcome status for all case-control pairs as well as prior knowledge about the positive and negative predictive value of the classification mechanism. We illustrate the model's performance on simulated data and apply it to a database study examining the presence of ten morbidities in the prodromal phase of multiple sclerosis.

Evaluating the safety of β-interferons in MS: A series of nested case-control studies.

Objective: To examine the association between interferon-β (IFN-β) and potential adverse events using population-based health administrative data in British Columbia, Canada.

Methods: Patients with relapsing-remitting multiple sclerosis (RRMS) who were registered at a British Columbia Multiple Sclerosis Clinic (1995-2004) were eligible for inclusion and were followed up until death, absence from British Columbia, exposure to a non-IFN-β disease-modifying drug, or December 31, 2008. Incidence rates were estimated for each potential adverse event (selected a priori and defined with ICD-9/10 diagnosis codes from physician and hospital claims).

Lingonberry anthocyanins protect cardiac cells from oxidative-stress-induced apoptosis.

Lingonberry grown in northern Manitoba, Canada, contains exceptionally high levels of anthocyanins and other polyphenols. Previous studies from our lab have shown that lingonberry anthocyanins can protect H9c2 cells from ischemia-reperfusion injury and anthocyanin-rich diets have been shown to be associated with decreased cardiovascular disease and mortality. Oxidative stress can impair function and trigger apoptosis in cardiomyocytes.

Identification of treatment responders based on multiple longitudinal outcomes with applications to multiple sclerosis patients.

Identification of treatment responders is a challenge in comparative studies where treatment efficacy is measured by multiple longitudinally collected continuous and count outcomes. Existing procedures often identify responders on the basis of only a single outcome. We propose a novel multiple longitudinal outcome mixture model that assumes that, conditionally on a cluster label, each longitudinal outcome is from a generalized linear mixed effect model.