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We assessed the performance of the new Life Technologies Proton sequencer by comparing whole-exome sequence data in a Centre d’Etude du Polymorphisme Humain trio (family 1463) to the Illumina HiSeq instrument. To simulate a typical user’s results, we utilized the standard capture, alignment and variant calling methods specific to each platform. We restricted data analysis to include the capture region common to both methods. The Proton produced high quality data at a comparable average depth and read length, and the Ion Reporter variant caller identified 96 % of single nucleotide polymorphisms (SNPs) detected by the HiSeq and GATK pipeline. However, only 40 % of small insertion and deletion variants (indels) were identified by both methods. Usage of the trio structure and segregation of platform-specific alleles supported this result. Further comparison of the trio data with Complete Genomics sequence data and Illumina SNP microarray genotypes documented high concordance and accurate SNP genotyping of both Proton and Illumina platforms. However, our study underscored the problem of accurate detection of indels for both the Proton and HiSeq platforms.

Abstract Background Germline mutations in the BRCA1 and BRCA2 genes account for 20–25 % of inherited breast cancers and about 10 % of all breast cancer cases. Detection of BRCA mutation carriers can lead to therapeutic interventions such as mastectomy, oophorectomy, hormonal prevention therapy, improved screening, and targeted therapies such as PARP-inhibition. We estimate that African Americans and Hispanics are 4–5 times less likely to receive BRCA screening, despite having similar mutation frequencies as non-Jewish Caucasians, who have higher breast cancer mortality. To begin addressing this health disparity, we initiated a nationwide trial of BRCA testing of Latin American women with breast cancer. Patients were recruited through community organizations, clinics, public events, and by mail and Internet. Subjects completed the consent process and questionnaire, and provided a saliva sample by mail or in person. DNA from 120 subjects was used to sequence the entirety of BRCA1 and BRCA2 coding regions and splice sites, and validate pathogenic mutations, with a total material cost of $85/subject. Subjects ranged in age from 23 to 81 years (mean age, 51 years), 6 % had bilateral disease, 57 % were ER/PR+, 23 % HER2+, and 17 % had triple-negative disease. Results A total of seven different predicted deleterious mutations were identified, one newly described and the rest rare. In addition, four variants of unknown effect were found. Conclusions Application of this strategy on a larger scale could lead to improved cancer care of minority and underserved populations.

Abstract Inflammatory bowel disease (IBD), consisting of Crohn’s disease and ulcerative colitis, is recognized across the world, though Canada has among the highest burdens of IBD in the world. The Canadian Gastro-Intestinal Epidemiology Consortium (CanGIEC) led a six-province study that demonstrated the compounding prevalence of IBD in Canada from 400 per 100,000 in 2002 to 636 per 100,000 in 2014. The prevalence in 2023 is estimated at 825 per 100,000, meaning that over 320,000 people in Canada are living with IBD. Prevalence is forecasted to rise by 2.44% per year such that 1.1% of the population, 470,000 Canadians, will live with IBD by 2035. The overall incidence of IBD in 2023 is 30 per 100,000 person-years, indicating that over 11,000 Canadians will be newly diagnosed with IBD in 2023. Incidence is forecasted to rise by 0.58% per year up to 32.1 per 100,000 by 2035. The rising incidence of IBD is propelled by pediatric-onset IBD, which is rising by 1.23% per year from 15.6 per 100,000 in 2023 to 18.0 per 100,000 in 2035. In contrast, incidence rates among adults and seniors are relatively stable. Understanding the determinates of IBD has expanded through prospective cohort studies such as the Crohn’s and Colitis Canada Genetic, Environmental, Microbial (CCC-GEM) project. Consensus recommendations towards diet, lifestyle, behavioural and environmental modifications have been proposed by international organizations with the goal of optimizing disease control and ultimately preventing the development of IBD. Despite these efforts, Canadian healthcare systems will need to prepare for the rising number of people living with IBD. Lay Summary Inflammatory bowel disease (IBD) is a disease that causes the intestines to inflame. IBD is something that is found in every country around the world. We have the highest number of people with IBD in the world compared to the total population. In 2002, one in every 250 (119,000) Canadians had IBD. In 2023, one in every 121 (320,000) Canadians has IBD. By 2035, one in every 91 (470,000) Canadians will have IBD. Roughly 11,000 Canadians will develop IBD in 2023. Rates of children developing IBD are rising. The rates of adults developing IBD are not changing. The rates of seniors developing IBD are also not changing. New research looks for better ways to care for IBD. New research also looks for ways to prevent IBD. One such project is Crohn’s and Colitis Canada Genetic, Environmental, Microbial project. This research suggests diet and lifestyle changes to improve the lives of people with IBD. The same changes may help reduce the number of people who develop IBD.

Abstract People living with inflammatory bowel disease (IBD) and their caregivers are faced with indirect and out-of-pocket costs that they would not otherwise experience. These costs impact one’s ability to contribute to the economy to their fullest potential. The indirect costs of IBD in Canada are estimated to be at least $1.51 billion in 2023 and include costs associated with lost productivity resulting from a combination of missed work (absenteeism), decreased workplace productivity (presenteeism), unemployment, premature mortality, and caregiving costs. Unemployment is the largest contributor to indirect costs ($1.14 billion), followed by costs of absenteeism and presenteeism ($285 million). Caregiving costs for children with IBD are estimated to be nearly $58 million. Canadians with IBD also pay $536 million every year for care that is not covered by universal or supplemental private health insurance; this includes allied healthcare (e.g., care provided by psychologists), medication, and other supportive therapy. Combined, the indirect and out-of-pocket costs of IBD in Canada are estimated at more than $2 billion CAD in 2023. This is substantially higher than the estimate of $1.29 billion in Crohn’s and Colitis Canada’s 2018 Impact of IBD report with differences attributable to a combination of rising prevalence, inflation, and the addition of presenteeism and caregiving costs to the total indirect costs. Lay Summary Inflammatory bowel disease (IBD) is very costly to people with IBD and society. The cost of IBD includes drugs, hospital stays, and surgery. It also includes lost productivity and out-of-pocket costs. Lost productivity can be starting a career later in life, retiring early, or lost work for sick time. Out-of-pocket costs include costs for travel to clinics, dietary needs, or medical supplies not covered by insurance. There are many other costs for care for people with IBD. In this article, we review lost productivity and out-of-pocket costs for IBD. In Canada, in 2023, these costs were at least $1.51 billion. Unemployment among people with IBD totaled roughly $1.14 billion. Costs of lost work time totaled roughly $285 million. Costs for childcare for children with IBD totaled nearly $58 million. Canadians with IBD also pay $536 million yearly for care not covered insurance. Combined, these costs for IBD in Canada will be more than $2 billion this year. up from roughly $1.29 billion in 2018. This increase is because people have IBD, inflation, and additional costs of IBD.

ObjectiveWe examined the relationship between trimester of SARS-CoV-2 infection, illness severity, and risk for preterm birth.Study designWe analyzed data for 6336 pregnant persons with SARS-CoV-2 infection in 2020 in the United States. Risk ratios for preterm birth were calculated for illness severity, trimester of infection, and illness severity stratified by trimester of infection adjusted for age, selected underlying medical conditions, and pregnancy complications.ResultPregnant persons with critical COVID-19 or asymptomatic infection, compared to mild COVID-19, in the second or third trimester were at increased risk of preterm birth. Pregnant persons with moderate-to-severe COVID-19 did not show increased risk of preterm birth in any trimester.ConclusionCritical COVID-19 in the second or third trimester was associated with increased risk of preterm birth. This finding can be used to guide prevention strategies, including vaccination, and inform clinical practices for pregnant persons.

Abstract Healthcare utilization among people living with inflammatory bowel disease (IBD) in Canada has shifted from inpatient management to outpatient management; fewer people with IBD are admitted to hospitals or undergo surgery, but outpatient visits have become more frequent. Although the frequency of emergency department (ED) visits among adults and seniors with IBD decreased, the frequency of ED visits among children with IBD increased. Additionally, there is variation in the utilization of IBD health services within and between provinces and across ethnocultural and sociodemographic groups. For example, First Nations individuals with IBD are more likely to be hospitalized than the general IBD population. South Asian children with Crohn’s disease are hospitalized more often than their Caucasian peers at diagnosis, but not during follow-up. Immigrants to Canada who develop IBD have higher health services utilization, but a lower risk of surgery compared to individuals born in Canada. The total direct healthcare costs of IBD, including the cost of hospitalizations, ED visits, outpatient visits, endoscopy, cross-sectional imaging, and medications are rising rapidly. The direct health system and medication costs of IBD in Canada are estimated to be $3.33 billion in 2023, potentially ranging from $2.19 billion to $4.47 billion. This is an increase from an estimated $1.28 billion in 2018, likely due to sharp increases in the use of biologic therapy over the past two decades. In 2017, 50% of total direct healthcare costs can be attributed to biologic therapies; the proportion of total direct healthcare costs attributed to biologic therapies today is likely even greater. Lay Summary It is expensive to care for people with inflammatory bowel disease (IBD). IBD may make a person need to go to the hospital, take medicine, or have surgery. The cost of caring for people with IBD has been growing over the past 20 years. This is partly because of more expensive medicines called biologics. Biologics started being used in Canada in 2001 and are now very common. Now, biologics make up more than half the total cost of treating IBD. In 2018, we believe that the total cost of hospitals, surgeries and medicines to treat IBD was $1.28 billion. Today, in 2023, we estimate that the total cost to treat IBD is roughly $3.33 billion. In this article, we have gathered data from published studies that let us evaluate the current cost of caring for IBD in Canada. We show how different people, such as indigenous people with IBD, people with IBD living inside or outside of cities, or children with IBD use Canadian healthcare systems in different ways, and how that affects the cost to care for people with IBD. We need to understand these costs to make sure we can continue providing the best care for people with IBD.

Abstract The burden of inflammatory bowel disease (IBD) (i.e., associated direct and indirect costs, prevalence of disease, personal impact to the individual and to caregivers) continues to increase in Canada. The prevalence of IBD has increased since Crohn’s and Colitis Canada’s 2018 Impact of IBD report from an estimated 270,000 Canadians living with IBD in 2018 to an estimated 322,600 Canadians living with IBD today in 2023. Consequently, associated costs of IBD have also dramatically increased from an estimated $2.57 billion in 2018 to an estimated $5.38 billion in 2023; this increase is due to multiple factors including increased prevalence of disease, inflation, and additional identified factors (e.g., presenteeism, costs of childcare). Beyond the economic impact of IBD, these diseases have a significant impact on people living with the disease and their caregivers, including different presentations of disease, different commonly associated extra-intestinal manifestations or comorbid conditions, and different barriers to accessing care. In this supplementary issue, we review: Evolving trends in the epidemiology of IBD; updated estimates of indirect and direct costs (including out-of-pocket costs) associated with IBD; information specific to IBD in children, adolescents, and seniors; issues related to IBD pertaining to sex and gender; information specific to risks associated with COVID-19 and cancer related to IBD; an overview of current treatments for IBD; and evolving care models, including access to care. Lay Summary Inflammatory bowel disease (IBD) affects many people. IBD is a disease that causes the intestines to become inflamed. This impact of IBD includes the number of people living with IBD, the cost to treat IBD, and personal impact on people living with IBD and their families. The burden of IBD is rising in Canada. In 2018, roughly 270,000 Canadians were living with IBD. In 2023, roughly 322,600 Canadians are living with IBD. The costs to treat people with IBD are also rising. Treating IBD cost roughly $2.57 billion in 2018. In 2023, treating IBD costs roughly $5.38 billion. This increase is because more people are living with IBD. Costs have also increased. Further, we include extra factors in the cost—like the cost of childcare. IBD also has a major impact on people living with the disease. The effects of the disease can be different for children versus seniors or others with IBD. Other medical conditions may be more common for people with IBD, such as cancer or infections. Also, different groups like Indigenous people or people living outside of cities may have problems accessing care. These and other issues about the care of IBD are reviewed in this summary.

Background The purpose of this report is to evaluate the quality of data sources used to study cough and cold medication (CCM) safety in children via the Pediatric Cough and Cold Safety Surveillance System. Methods The System utilized the National Poison Data System (NPDS), FDA Adverse Event Reporting System (FAERS), English-language medical literature, manufacturer postmarket safety databases, and news/media reports to identify cases from January 2008 through September 2016. Each data source was evaluated by the proportion of detected cases determined to be eligible (met case criteria) and the proportion determined to be evaluable (able to determine causal relationship between adverse event and exposure). Results A total of 7184 unique cases were identified from 27,597 detected reports. Of these, 6447 (89.7%) were evaluable. The data source with the highest volume of detected cases was news/media; however, only 0.3% of those cases were eligible for panel review and only 0.2% (24 out of 13,450 cases) were evaluable. The data source with the highest proportion of eligible and evaluable cases was NPDS with 7691 detected cases, 6113 (79.5%) eligible cases, and 5587 (72.6%) evaluable cases. Conclusions The data sources utilized to evaluate the safety profile of pediatric CCMs yielded variable detection and evaluation rates, but overall provided a comprehensive look at exposures that otherwise cannot be studied in clinical trials. While this study suggests that each source made a valuable contribution and that evaluable cases are generalizable, improvements are needed in case completeness and accuracy to enhance the quality of postmarket safety evaluations.

Abstract Rates of inflammatory bowel disease (IBD) in Canadian children and adolescents are among the highest in the world, and the incidence is rising most rapidly in children under five years of age. These young children may have either a typical form of IBD with multi-factorial aetiology, or they may have a monogenic form. Despite the growing number of children in Canada living with this important chronic disease, there are few available medical therapies approved by Health Canada due to the omission of children from most clinical trials of newly developed biologics. As a result, off-label use of medications is common, and physicians have learned to use existing therapies more effectively. In addition, most Canadian children are treated in multidisciplinary, specialty clinics by physicians with extra training or experience in IBD, as well as specialist nurses, dietitians, mental health care providers and other allied health professionals. This specialized clinic approach has facilitated cutting edge research, led by Canadian clinicians and scientists, to understand the causes of IBD, the optimal use of therapies, and the best ways to treat children from a biopsychosocial perspective. Canadians are engaged in work to understand the monogenic causes of IBD; the interaction between genes, the environment, and the microbiome; and how to address the mental health concerns and medical needs of adolescents and young adults transitioning from paediatric to adult care. Lay Summary This article reviews studies about inflammatory bowel disease (IBD) in children. IBD is an disease that causes inflamed intestines. Children are the fastest growing group that develop IBD. Not all drugs for IBD can be used by children. This is partly because children are not usually part of initial dug trials. Drug trials usually need to show safety in adults before they can be tested in children. Canadian researchers are leading the way in studies to improve care for children with IBD. They are doing this by creating care teams with specialists in different areas. These teams provide IBD care, mental healthcare, diet and nutrition plans and other important care. These care teams also help guide IBD specialists to find the right treatment for each person. The right treatment for each person means finding the right dose and the right course of therapies.

To the Editor: Turley et al. (July 1 issue) 1 state that MyOme “appears” to currently provide embryo selection using polygenic scores (ESPS) for nondisease traits. Although it may have appeared to be so, it is in fact not the case. Their statement was based on archived draft materials. We are conducting free-to-participant studies to assess the utility and tractability of ESPS. Although some participants have sought information on traits such as educational attainment, we determined that these issues distract from our health-focused conversation and mission. We generally agree with the recommendations of Turley et al. regarding messaging, augmented by an . . .