Inflammatory bowel disease does not confer higher disease activity or greater radiographic progression in axial spondyloarthritis.

Objectives: To examine whether inflammatory bowel disease (IBD) influences disease activity and radiographic progression in patients with axial spondyloarthritis (axSpA).

Methods: This was a longitudinal cohort study of axSpA patients from a tertiary referral centre. Active axSpA was assessed using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI ≥4) in a dataset of 1268 patients.

Changes in unmet needs after treatment for head and neck cancers - A prospective longitudinal cohort study.

Objectives: This study aimed to assess changes in unmet needs among patients with head and neck cancer (HNC) from pre-treatment to two years post-treatment and identify factors associated with higher levels of unmet needs.

Materials & Methods: Patients treated for HNC at Princess Margaret Cancer Centre between June 2016 and February 2019 were recruited. Participants completed the Cancer Survivors' Unmet Needs Measure Questionnaire (CaSUN), the Functional Assessment of Cancer Therapy - Head and Neck (FACT-HN) questionnaire, and the EuroQol EQ-5D-5L utility and Visual Analog Scale (EQ-5D-5L and VAS) pre-treatment and at 3, 6, 12, and 24-months post-treatment.

Impact of clinical subtype and sex on first-line biologic therapy discontinuation in axial spondyloarthritis.

Objectives: To estimate the main and interaction effects of axial spondyloarthritis (axSpA) subtype and sex on first biologic disease-modifying antirheumatic drug (bDMARD) discontinuation.

Methods: This retrospective cohort study included nonradiographic axSpA (nr-axSpA) and radiographic axSpA (r-axSpA) patients initiating tumour necrosis factor or interleukin-17 inhibitors. Modified Poisson regressions were used to estimate risk ratios (RRs) for the association of subtype and sex with discontinuation, adjusting for baseline covariates.

Impact of disease manifestations on first biologic drug survival in axial spondyloarthritis: a real-life Canadian study.

Objectives: The primary objective of this study was to assess the impact of extramusculoskeletal manifestations (EMMs) and peripheral musculoskeletal features on first biologic drug survival in subjects with axial spondyloarthritis (axSpA). The secondary objective was to evaluate the impact of reasons for treatment discontinuation.

Methods: A total of 593 axSpA patients from the SpondyloArthritis Research Consortium of Canada initiating a first biologic drug were identified between 2003 and 2023.

Integrating Patient-Reported Outcomes Into Prognostication in Gastroesophageal Cancer: Results of a Population-Based Retrospective Cohort Analysis.

Background: Patient-reported outcomes measures (PROM) are self-reflections of an individual's physical functioning and emotional well-being. The Edmonton Symptom Assessment Scale (ESAS) is a simple and validated PRO tool of 10 common symptoms and a patient-reported functional status (PRFS) measure. The prognostic value of this tool is unknown in patients with gastroesophageal cancer (GEC).

Leptomeningeal carcinomatosis and brain metastases in gastroesophageal carcinoma: a real-world analysis of clinical and pathologic characteristics and outcomes.

Background: Brain metastasis (BrM) and Leptomeningeal Carcinomatosis (LMC) are uncommon complications in gastroesophageal carcinoma (GEC) patients. These patients have a poor prognosis and are challenging to treat. We described the clinicopathologic features and outcomes in the largest cohort of Central Nervous System (CNS) metastasis in GEC patients.

Clinical Validation of Human Papilloma Virus Circulating Tumor DNA for Early Detection of Residual Disease After Chemoradiation in Cervical Cancer.

Purpose: Most cervical cancers are caused by human papilloma virus (HPV), and HPV circulating tumor DNA (ctDNA) may identify patients at highest risk of relapse. Our pilot study using digital polymerase chain reaction (dPCR) showed that detectable HPV ctDNA at the end of chemoradiation (CRT) is associated with inferior progression-free survival (PFS) and that a next-generation sequencing approach (HPV-seq) may outperform dPCR. We aimed to prospectively validate HPV ctDNA as a tool for early detection of residual disease.

Proteomic and genomic profiling of plasma exosomes from patients with ankylosing spondylitis.

Introduction: Recent advances in understanding the biology of ankylosing spondylitis (AS) using innovative genomic and proteomic approaches offer the opportunity to address current challenges in AS diagnosis and management. Altered expression of genes, microRNAs (miRNAs) or proteins may contribute to immune dysregulation and may play a significant role in the onset and persistence of inflammation in AS. The ability of exosomes to transport miRNAs across cells and alter the phenotype of recipient cells has implicated exosomes in perpetuating inflammation in AS.

VikNGS: a C++ variant integration kit for next generation sequencing association analysis.

Summary: Integration of next generation sequencing data (NGS) across different research studies can improve the power of genetic association testing by increasing sample size and can obviate the need for sequencing controls. If differential genotype uncertainty across studies is not accounted for, combining datasets can produce spurious association results. We developed the Variant Integration Kit for NGS (VikNGS), a fast cross-platform software package, to enable aggregation of several datasets for rare and common variant genetic association analysis of quantitative and binary traits with covariate adjustment.

Genetic association analysis with pedigrees: Direct inference using the composite likelihood ratio.

The likelihood function represents statistical evidence given data and a model. The evidential paradigm (EP), an alternative to Bayesian and Frequentist paradigms, provides considerable theory demonstrating evidence strength for different parameter values via the ratio of likelihoods at different parameter values; thus, enabling inference directly from the likelihood function. The likelihood function, however, can be difficult to compute; for example, in genetic association studies with a binary outcome in large pedigrees.

Statistical Reasoning: Choosing and Checking the Ingredients, Inferences Based on a Measure of Statistical Evidence with Some Applications.

The features of a logically sound approach to a theory of statistical reasoning are discussed. A particular approach that satisfies these criteria is reviewed. This is seen to involve selection of a model, model checking, elicitation of a prior, checking the prior for bias, checking for prior-data conflict and estimation and hypothesis assessment inferences based on a measure of evidence.

Improving imputation in disease-relevant regions: lessons from cystic fibrosis.

Does genotype imputation with public reference panels identify variants contributing to disease? Genotype imputation using the 1000 Genomes Project (1KG; 2504 individuals) displayed poor coverage at the causal cystic fibrosis (CF) transmembrane conductance regulator () locus for the International CF Gene Modifier Consortium. Imputation with the larger Haplotype Reference Consortium (HRC; 32,470 individuals) displayed improved coverage but low sensitivity of variants clinically relevant for CF. A hybrid reference that combined whole genome sequencing (WGS) from 101 CF individuals with the 1KG imputed a greater number of single-nucleotide variants (SNVs) that would be analyzed in a genetic association study ( ≥ 0.

Goodness of fit for the logistic regression model using relative belief.

A logistic regression model is a specialized model for product-binomial data. When a proper, noninformative prior is placed on the unrestricted model for the product-binomial model, the hypothesis of a logistic regression model holding can then be assessed by comparing the concentration of the posterior distribution about with the concentration of the prior about . This comparison is effected via a relative belief ratio, a measure of the evidence that is true, together with a measure of the strength of the evidence that is either true or false.

The genetics of reading disability in an often excluded sample: novel loci suggested for reading disability in Rolandic epilepsy.

Background: Reading disability (RD) is a common neurodevelopmental disorder with genetic basis established in families segregating "pure" dyslexia. RD commonly occurs in neurodevelopmental disorders including Rolandic Epilepsy (RE), a complex genetic disorder. We performed genomewide linkage analysis of RD in RE families, testing the hypotheses that RD in RE families is genetically heterogenenous to pure dyslexia, and shares genetic influences with other sub-phenotypes of RE.

Using parametric multipoint lods and mods for linkage analysis requires a shift in statistical thinking.

Multipoint (MP) linkage analysis represents a valuable tool for whole-genome studies but suffers from the disadvantage that its probability distribution is unknown and varies as a function of marker information and density, genetic model, number and structure of pedigrees, and the affection status distribution [Xing and Elston: Genet Epidemiol 2006;30:447-458; Hodge et al.: Genet Epidemiol 2008;32:800-815]. This implies that the MP significance criterion can differ for each marker and each dataset, and this fact makes planning and evaluation of MP linkage studies difficult.

Evidence of shared genetic risk factors for migraine and rolandic epilepsy.

Purpose: Evidence for a specific association between migraine and rolandic epilepsy (RE) has been conflicting. Children with migraine frequently have electroencephalographic (EEG) abnormalities, including rolandic discharges, and approximately 50% of siblings of patients with RE exhibit rolandic discharges. We assessed migraine risk in RE probands and their siblings.

Centrotemporal sharp wave EEG trait in rolandic epilepsy maps to Elongator Protein Complex 4 (ELP4).

Rolandic epilepsy (RE) is the most common human epilepsy, affecting children between 3 and 12 years of age, boys more often than girls (3:2). Focal sharp waves in the centrotemporal area define the electroencephalographic (EEG) trait for the syndrome, are a feature of several related childhood epilepsies and are frequently observed in common developmental disorders (eg, speech dyspraxia, attention deficit hyperactivity disorder and developmental coordination disorder). Here we report the first genome-wide linkage scan in RE for the EEG trait, centrotemporal sharp waves (CTS), with genome-wide linkage of CTS to 11p13 (HLOD 4.