Risk-based lung cancer screening performance in a universal healthcare setting.

Globally, lung cancer is the leading cause of cancer death. Previous trials demonstrated that low-dose computed tomography lung cancer screening of high-risk individuals can reduce lung cancer mortality by 20% or more. Lung cancer screening has been approved by major guidelines in the United States, and over 4,000 sites offer screening. Adoption of lung screening outside the United States has, until recently, been slow. Between June 2017 and May 2019, the Ontario Lung Cancer Screening Pilot successfully recruited 7,768 individuals at high risk identified by using the PLCOm2012noRace lung cancer risk prediction model. In total, 4,451 participants were successfully screened, retained and provided with high-quality follow-up, including appropriate treatment. In the Ontario Lung Cancer Screening Pilot, the lung cancer detection rate and the proportion of early-stage cancers were 2.4% and 79.2%, respectively; serious harms were infrequent; and sensitivity to detect lung cancers was 95.3% or more. With abnormal scans defined as ones leading to diagnostic investigation, specificity was 95.5% (positive predictive value, 35.1%), and adherence to annual recall and early surveillance scans and clinical investigations were high (>85%). The Ontario Lung Cancer Screening Pilot provides insights into how a risk-based organized lung screening program can be implemented in a large, diverse, populous geographic area within a universal healthcare system.

Decision making under uncertainty in the diagnosis and management of Alzheimer's Disease in primary care: A study protocol applying concepts from neuroeconomics.

Background: The current management of patients with Dementia, primarily with Alzheimer's Disease (AD) is rapidly evolving. However, limited information is available about the current gaps and decision-making in primary care. Objectives: To evaluate factors associated with gaps, risk preferences regarding diagnostic and therapeutic choices in the management of patients with AD by primary care physicians (PCP) from across Canada. Methods: We propose a non-interventional, cross-sectional pilot study involving 120 primary care physicians referred from the College of Family Physicians of Canada to assess diagnostic and therapeutic decisions in the management of ten simulated AD-related case-scenarios commonly encountered in clinical practice. We initially describe the current landscape and gaps regarding diagnostic and therapeutic challenges in the management of patients with AD in primary care. Then, we provide concepts from behavioral economics and neuroeconomics applied to medical decision-making. Specifically, we include standardized tests to measure risk aversion, physicians' reactions to uncertainty, and questions related to risk preferences in different domains. Finally, we summarize the protocol to be implemented to address our goals. The primary study outcome is the proportion of participants that elect to defer initial investigations to the specialist and the associated factors. Secondary outcomes include the proportion of PCP willing to order cerebral spinal fluid studies, PET scans, or initiate treatment according to the simulated case-scenarios. The study will be conducted in English and French. Conclusions: The study findings will contribute a better understanding of relevant factors associated with diagnostic and therapeutic decisions of PCP in the management of AD, identifying participant's preferences and evaluating the role of behavioral aspects such tolerance to uncertainty, aversion to ambiguity, and therapeutic inertia.

An update to the recommended core content for sun safety messages for public education in Canada: A consensus report.

Reducing ultraviolet radiation exposure decreases the risk of skin cancer and eye damage. Between 1996 and 2006, Canadians increased their time in the sun without improving protection. National consensus on sun protection information for the public was last achieved in 1994. Public messages have since been modified inconsistently. The Ontario Sun Safety Working Group initiated a review of messages and engaged a scientific panel to draft message content. Working Group members then delivered a national consensus process, engaging a National Steering Committee, a health communications expert and representatives from 28 organizations through a workshop with pre- and post-workshop surveys. The result of the consensus process is the updated Recommended Core Content for Sun Safety Messages in Canada. Four groups of statements comprise the new content: Key Facts, Primary Recommended Protective Action Statements, Additional Recommended Protective Action Statements, and Tips for Implementing the Primary Protective Actions. Organizations are encouraged to adopt, at minimum, the Primary Recommended Protective Action Statements as the basis for public messaging. The recommended core content establishes a common understanding of what is needed for effective sun protection. The underlying expectation is that, as a key next step, content will be tailored for different subpopulations and health promotion campaigns.

Assessment of reliability and validity of IBD phenotyping within the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) IBD Genetics Consortium (IBDGC).

BACKGROUND: The NIDDK IBD Genetics Consortium (IBDGC) collects DNA and phenotypic data from inflammatory bowel disease (IBD) subjects to provide a resource for genetic studies. No previous studies have been performed on the reliability and validity of phenotypic determinations in either Crohn's disease (CD) or ulcerative colitis (UC) using primary records. Our aim was to determine the reliability and validity of these phenotypic assessments. METHODS: The de-identified records of 30 IBD patients were reviewed by 2 phenotypers per center using a standard protocol for phenotypic assessment. Each phenotyper evaluated 10 charts on 2 occasions 5 months apart. Reliability was expressed as the kappa (kappa) statistic. Performance characteristics were determined by comparison to a consensus-derived "gold standard" and by generation of receiver operating characteristic (ROC) curves. RESULTS: Agreement for diagnosis was excellent (kappa = 0.82; 95% confidence interval [CI]: 0.71-0.92). Agreement for CD location was good for jejunal, ileal, colorectal, and perianal disease with kappa between 0.60 and 0.74 but was fair for esophagogastroduodenal (kappa = 0.36). Agreement for UC extent (kappa = 0.67; 95% CI: 0.48-0.85), and CD behavior (kappa = 0.67; 95% CI: 0.49-0.83) were very good. Area under the ROC curves was greater than 0.84 for diagnosis, CD behavior, UC extent, and ileal and colonic CD location. CONCLUSIONS: IBD phenotype classification using a standard protocol exhibited very good to excellent inter- and intrarater agreement and validity. This study highlights the importance of standard protocols in generating reliable and valid phenotypic assessments. The data will facilitate estimates of phenotyping misclassification rates that should be considered when making inferences from IBD genotype-phenotype studies.

Refined genomic localization and ethnic differences observed for the IBD5 association with Crohn's disease.

Although the general association of the inflammatory bowel disease (IBD) 5 region on chromosome 5q31 to Crohn's disease (CD) has been replicated repeatedly, the identity of the precise causal variant within the region remains unknown. A recent report proposed polymorphisms in solute carrier family 22, member 4 (SLC22A4) organic cation transporter 1(OCTN1) and solute carrier family 22, member 5 (SLC22A5) (OCTN2) as responsible for the IBD5 association, but definitive, large-sample comparison of those polymorphisms with others known to be in strong linkage disequilibrium was not performed. We evaluated 1879 affected offspring and parents ascertained by a North American IBD Genetics Consortium for six IBD5 tag single nucleotide polymorphisms (SNPs) to evaluate association localization and ethnic and subphenotypic specificity. We confirm association to the IBD5 region (best SNP IGR2096a_1/rs12521868, P<0.0005) and show this association to be exclusive to the non-Jewish (NJ) population (P=0.00005) (risk allele undertransmitted in Ashkenazi Jews). Using Phase II HapMap data, we demonstrate that there are a set of polymorphisms, spanning genes from prolyl 4-hydroxylase (P4HA2) through interferon regulatory factor 1 (IRF1) with equivalent statistical evidence of association to the reported SLC22A4 variant and that each, by itself, could entirely explain the IBD5 association to CD. Additionally, the previously reported SLC22A5 SNP is rejected as the potential causal variant. No specificity of association was seen with respect to disease type and location, and a modest association to ulcerative colitis is also observed. We confirm the importance of IBD5 to CD susceptibility, demonstrate that the locus may play a role in NJ individuals only, and establish that IRF1, PDLIM, and P4HA2 may be equally as likely to contain the IBD5 causal variant as the OCTN genes.

Inflammatory bowel disease characteristics among African Americans, Hispanics, and non-Hispanic Whites: characterization of a large North American cohort.

OBJECTIVES: Inflammatory bowel disease (IBD), comprising primarily of Crohn's disease (CD) and ulcerative colitis (UC), is increasingly prevalent in racial and ethnic minorities. This study was undertaken to characterize racial differences in disease phenotype in a predominantly adult population. METHODS: Phenotype data on 830 non-Hispanic white, 127 non-Hispanic African American, and 169 Hispanic IBD patients, recruited from six academic centers, were abstracted from medical records and compiled in the NIDDK-IBD Genetics Consortium repository. We characterized racial differences in family history, disease location and behavior, surgical history, and extraintestinal manifestations (EIMs) using standardized definitions. RESULTS: African American CD patients were more likely than whites to develop esophagogastroduodenal CD (OR = 2.8; 95% CI: 1.4-5.5), colorectal disease (OR = 1.9; 95% CI: 1.1-3.4), perianal disease (OR = 1.7; 95% CI: 1.03-2.8), but less likely to have ileal involvement (OR = 0.55; 95% CI: 0.32-0.96). They were also at higher risk for uveitis (OR = 5.5; 95% CI: 2.3-13.0) and sacroiliitis (OR = 4.0; 95% CI: 1.55-10.1). Hispanics had higher prevalence of perianal CD (OR = 2.9; 95% CI: 1.8-4.6) and erythema nodosum (3.3; 95% CI: 1.7-6.4). Among UC patients, Hispanics had more proximal disease extent. Both African American and Hispanic CD patients, but not UC patients, had lower prevalences of family history of IBD than their white counterparts. CONCLUSIONS: There are racial differences in IBD family history, disease location, and EIMs that may reflect underlying genetic variations and have important implications for diagnosis and management of disease. These findings underscore the need for further studies in minority populations.

Phenotype-stratified genetic linkage study demonstrates that IBD2 is an extensive ulcerative colitis locus.

OBJECTIVES: The complete elucidation of genetic variants that contribute to inflammatory bowel disease (IBD) will likely include variants that increase risk to both Crohn's disease and ulcerative colitis as well as variants that increase risk for particular phenotypic subsets. The purpose of this study was to assess phenotypic subsets that contribute to the major IBD susceptibility loci. METHODS: This linkage study encompassed 904 affected relative pairs, representing the largest combined phenotyped cohort to date, and allowing for meaningful subset analyses. Genetic linkage data were stratified by disease location and age at diagnosis. RESULTS: We establish that some loci, notably the IBD3 and chromosome 3q linkage regions demonstrate contributions from both small intestine and colon cohorts, whereas others, notably the IBD1 (NOD2/CARD15) and IBD2 regions increase risk for small intestine or colon inflammation, respectively. The strongest linkage evidence in this study was for the subset of extensive ulcerative colitis in the region of IBD2 (lod 3.27; p < 0.001). Evidence for linkage in the region of NOD2/CARD15 (IBD1) was stronger for the subset of Crohn's patients with ileal disease (lod 2.56; p= 0.035) compared to the overall Crohn's group, consistent with previous findings that NOD2/CARD15 variants are associated with ileal disease. CONCLUSIONS: Analyses incorporating disease location in IBD increase the power and enhance the accuracy of genomic localization. Our data provide strong evidence that extensive ulcerative colitis represents a pathophysiologic subset of IBD.