Reducing inequities in colorectal cancer screening in North America

Colorectal cancer (CRC) is an important cause of mortality and morbidity in North America. Screening using a fecal occult blood test, flexible sigmoidoscopy, or colonoscopy reduces CRC mortality through the detection and treatment of precancerous polyps and early stage CRC. Although CRC screening participation has increased in recent years, large inequities still exist. Minorities, new immigrants, and those with lower levels of education or income are much less likely to be screened. This review provides an overview of the commonly used tests for CRC screening, disparities in CRC screening, and promising methods at the individual, provider, and system levels to reduce these disparities. Overall, to achieve high CRC participation rates and reduce the burden of CRC in the population, a multi-faceted approach that uses strategies at all levels to reduce CRC screening disparities is urgently required

Lessons Learned: It Takes a Village to Understand Inter-Sectoral Care Using Administrative Data across Jurisdictions

Cancer care is complex and exists within the broader healthcare system. The CanIMPACT team sought to enhance primary cancer care capacity and improve integration between primary and cancer specialist care, focusing on breast cancer. In Canada, all medically-necessary healthcare is publicly funded but overseen at the provincial/territorial level. The CanIMPACT Administrative Health Data Group’s (AHDG) role was to describe inter-sectoral care across five Canadian provinces: British Columbia, Alberta, Manitoba, Ontario and Nova Scotia. This paper describes the process used and challenges faced in creating four parallel administrative health datasets. We present the content of those datasets and population characteristics. We provide guidance for future research based on ‘lessons learned’. The AHDG conducted population-based comparisons of care for breast cancer patients diagnosed from 2007-2011. We created parallel provincial datasets using knowledge from data inventories, our previous work, and ongoing bi-weekly conference calls. Common dataset creation plans (DCPs) ensured data comparability and documentation of data differences. In general, the process had to be flexible and iterative as our understanding of the data and needs of the broader team evolved. Inter-sectoral data inconsistencies that we had to address occurred due to differences in: 1) healthcare systems, 2) data sources, 3) data elements and 4) variable definitions. Our parallel provincial datasets describe the breast cancer diagnostic, treatment and survivorship phases and address ten research objectives. Breast cancer patient demographics reflect inter-provincial general population differences. Across provinces, disease characteristics are similar but underlying health status and use of healthcare services differ. Describing healthcare across Canadian jurisdictions assesses whether our provincial healthcare systems are delivering similar high quality, timely, accessible care to all of our citizens. We have provided a description of our experience in trying to achieve this goal and include a list of ‘lessons learned’ and a study process checklist for future use

Direct Observation of Single Amyloid-β(1-40) Oligomers on Live Cells: Binding and Growth at Physiological Concentrations

Understanding how amyloid-β peptide interacts with living cells on a molecular level is critical to development of targeted treatments for Alzheimer's disease. Evidence that oligomeric Aβ interacts with neuronal cell membranes has been provided, but the mechanism by which membrane binding occurs and the exact stoichiometry of the neurotoxic aggregates remain elusive. Physiologically relevant experimentation is hindered by the high Aβ concentrations required for most biochemical analyses, the metastable nature of Aβ aggregates, and the complex variety of Aβ species present under physiological conditions. Here we use single molecule microscopy to overcome these challenges, presenting direct optical evidence that small Aβ(1-40) oligomers bind to living neuroblastoma cells at physiological Aβ concentrations. Single particle fluorescence intensity measurements indicate that cell-bound Aβ species range in size from monomers to hexamers and greater, with the majority of bound oligomers falling in the dimer-to-tetramer range. Furthermore, while low-molecular weight oligomeric species do form in solution, the membrane-bound oligomer size distribution is shifted towards larger aggregates, indicating either that bound Aβ oligomers can rapidly increase in size or that these oligomers cluster at specific sites on the membrane. Calcium indicator studies demonstrate that small oligomer binding at physiological concentrations induces only mild, sporadic calcium leakage. These findings support the hypothesis that small oligomers are the primary Aβ species that interact with neurons at physiological concentrations

Contribution of Intrinsic Reactivity of the HIV-1 Envelope Glycoproteins to CD4-Independent Infection and Global Inhibitor Sensitivity

Human immunodeficiency virus (HIV-1) enters cells following sequential activation of the high-potential-energy viral envelope glycoprotein trimer by target cell CD4 and coreceptor. HIV-1 variants differ in their requirements for CD4; viruses that can infect coreceptor-expressing cells that lack CD4 have been generated in the laboratory. These CD4-independent HIV-1 variants are sensitive to neutralization by multiple antibodies that recognize different envelope glycoprotein epitopes. The mechanisms underlying CD4 independence, global sensitivity to neutralization and the association between them are still unclear. By studying HIV-1 variants that differ in requirements for CD4, we investigated the contribution of CD4 binding to virus entry. CD4 engagement exposes the coreceptor-binding site and increases the “intrinsic reactivity” of the envelope glycoproteins; intrinsic reactivity describes the propensity of the envelope glycoproteins to negotiate transitions to lower-energy states upon stimulation. Coreceptor-binding site exposure and increased intrinsic reactivity promote formation/exposure of the HR1 coiled coil on the gp41 transmembrane glycoprotein and allow virus entry upon coreceptor binding. Intrinsic reactivity also dictates the global sensitivity of HIV-1 to perturbations such as exposure to cold and the binding of antibodies and small molecules. Accordingly, CD4 independence of HIV-1 was accompanied by increased susceptibility to inactivation by these factors. We investigated the role of intrinsic reactivity in determining the sensitivity of primary HIV-1 isolates to inhibition. Relative to the more common neutralization-resistant (“Tier 2-like”) viruses, globally sensitive (“Tier 1”) viruses exhibited increased intrinsic reactivity, i.e., were inactivated more efficiently by cold exposure or by a given level of antibody binding to the envelope glycoprotein trimer. Virus sensitivity to neutralization was dictated both by the efficiency of inhibitor/antibody binding to the envelope glycoprotein trimer and by envelope glycoprotein reactivity to the inhibitor/antibody binding event. Quantitative differences in intrinsic reactivity contribute to HIV-1 strain variability in global susceptibility to neutralization and explain the long-observed relationship between increased inhibitor sensitivity and decreased entry requirements for target cell CD4

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Evaluating the Impact of the COVID-19 Pandemic on New Cancer Diagnoses and Oncology Care in Manitoba

Individuals with cancer are vulnerable to infection with SARS-CoV-2, the virus causing COVID-19. Physical distancing, the reallocation of health care resources, and the implementation of procedures to reduce the spread of COVID-19 may also have serious consequences for people with cancer. We evaluated the impact of COVID-19 on new cancer diagnoses and oncology care in Manitoba, Canada using an interrupted time series design and data from the Manitoba Cancer Registry and CancerCare Manitoba’s (CCMB) electronic medical record. In April 2020, there was a 23% decrease in new cancer diagnoses, a 21% decrease in pathology reports, and a 43% reduction in surgical resections. There was no difference in new cancer diagnoses by August 2020, surgery by July 2020, and pathology reports by September 2020. From April 2020 to June 2021, there was a 13% decrease in radiotherapy (RT) fractions, an 18% decrease in UCC visits, and a 52% decrease in in-person visits. There was no change in intravenous chemotherapy visits per month, first RT visits, or overall patient visits. The impact of COVID-19 on shifts in the stage at diagnosis and survival will be assessed in future analyses

Interval colorectal cancer rates after Hemoccult Sensa and survival by detection mode for individuals diagnosed with colorectal cancer in Winnipeg, Manitoba.

OBJECTIVE:To assess the performance of the Sensa fecal occult blood test (FOBT) in a population-based screening program. SETTING:Manitoba, Canada. METHODS:This historical cohort study included individuals 52 to 74 years of age diagnosed with colorectal cancer (CRC) from 2008 to 2013. CRCs were categorized by detection following a screening program FOBT (Sensa), non-program FOBT (non-Sensa), or no FOBT. Screening program CRCs were classified as program-detected, interval program, or non-compliant. Logistic regression was used to compare characteristics by detection mode. Cox regression adjusted for lead-time was used to examine the effect of detection mode on survival. RESULTS:1,498 individuals were diagnosed with CRC; 132 (8.8%) had a screening program FOBT, 626 (41.8%) had a non-program FOBT, and 740 (49.4%) had no FOBT. Of the screening program FOBT CRCs, 72 were program-detected (54.5%), 42 were interval program (31.8%), and 18 were non-compliant (13.6%). Sensa interval cancer rate was 37.4% and sensitivity was 63.1% (95% Confidence Interval (CI): 54.3%-72.0%). The risk of death for individuals that had a non-program (Hazard ratio (HR) = 0.57, 95% CI:0.44-0.75) or a screening program FOBT (HR = 0.55, 95% CI:0.31-0.97) was lower than no FOBT. There was no significant difference in the risk of death for interval, non-compliant, and non-program CRCs compared to program-detected CRCs. Adjusting for lead time bias, sex, income quintile, tumour location, and age at diagnosis did not appreciably change the risk estimates. CONCLUSION:More than one-third of CRCs may not be detected by Sensa. There may be no difference in survival between CRC detected by Sensa and non-Sensa FOBTs