Objective: To describe characteristics of sleep (quality, duration, efficiency, and insomnia) in a cohort of highgrade epithelial ovarian cancer (EOC) survivors who have completed and responded to first-line chemotherapy, and to explore their relationships with disease recurrence. Methods: In this cohort of 97 women, sleep and other factors were assessed at baseline and 4 months later. The distribution of participants by categories of sleep characteristics were calculated. Hazard ratios (HRs) and 95 % confidence intervals (95 % CI) for the association between each sleep characteristic and recurrence were estimated using the Cox proportional hazards model, and adjusted for confounding using propensity scores. Associations were estimated for all women and among those defined as fully platinum-sensitive. Results: At baseline, just over half of participants (52.6 % to 56.7 %) had poor sleep quality, efficiency and duration, while most (62.9 %) did not experience insomnia. Distributions remained similar 4 months later. During follow-up, 47 recurrences occurred. Among all participants, HRs (95 % CIs) of recurrence were close to the value of 1, indicating no association, for sleep quality and efficiency, 1.22 (0.66-2.23) for not meeting vs. meeting sleep duration guidelines and 0.68 (0.34-1.39) for the presence vs. absence of insomnia. In fully platinum-sensitive women, the HRs (95 % CIs) were 1.50 (0.64-3.53) for not meeting duration guidelines, 1.25 (0.56-2.79) for poor sleep efficiency, 1.44 (0.55-3.72) for the presence of insomnia, and remained null for sleep quality. Conclusion: Most EOC survivors have poor sleep quality, duration, and efficiency. Research with larger sample sizes is required to better understand the relationship between these sleep characteristics and the risk of recurrence.

PDF file - 118K, Supplementary Table I. Description of potential predictors. Supplementary Table II: Number of missing values for each of the variables by survey.

Colorectal cancer remains the top leading cancer worldwide. Accumulating evidence suggests periodontal pathogens are involved in colorectal carcinogenesis, indicating the need for high-quality epidemiological evidence linking periodontal disease (PD) and colorectal cancer (CRC). Thus, we conducted the first population-based case-control study that was specifically designed to investigate the association between compromised oral health and sporadic CRC. A total of 348 incident cases of colon or rectal cancer, and 310 age and sex frequency-matched controls, from the Montreal island and Laval population participated in the study. Data were collected on PD and on several CRC risk factors using validated questionnaires. A life-course approach was used to document long-term history regarding lifestyle factors. Multivariable unconditional logistic regression analysis was used to estimate the rate ratio (RR) quantifying the association between CRC and PD. Results showed that the rate of new diagnosis of CRC in persons with a positive history of PD was 1.45 times higher than in those with a negative history of PD adjusting for age, sex, BMI, education, income, diabetes, family history of CRC, regular use of nonsteroidal anti-inflammatory drugs, lifetime cumulative smoking, lifetime consumption of red meats, processed meats, and alcoholic drinks, and lifetime total physical activity score (adjusted RR= 1.45; 95% CI 1.04-2.01; p=0.026). Our results support the hypothesis of an association between PD and sporadic CRC risk.

As evidence has been linking the oral bacterium Fusobacterium nucleatum (F. nucleatum) to colorectal tumorigenesis , we aimed to produce preliminary data on the expression of F. nucleatum in both oral and colorectal body sites in cases diagnosed with colorectal neoplasms (CRN) and CRN-free controls. We conducted a pilot hospital-based case–control study among patients who underwent colonoscopy examination. Saliva samples and biopsies from healthy colon mucosa from CRN cases and CRN-free controls, and from tumors in cases, were collected, as well as data on periodontal condition and potential CRN risk factors. A total of 22 CRN cases and 21 CRN-free controls participated in this study, with a total of 135 biospecimens collected and analyzed by qPCR for detection and quantification of F. nucleatum . The detection rate of F. nucleatum was 95% in saliva samples and 18% in colorectal mucosa specimens. The median (95% CI) salivary F. nucleatum level was 0.35 (0.15–0.82) and 0.12 (0.05–0.65) in case and control groups, respectively, with a Spearman correlation of 0.64 (95% CI 0.2–0.94) between F. nucleatum level in saliva and healthy colorectal mucosa in controls. Our study results support the need for and the feasibility of further studies that aim to investigate the association between oral and colorectal levels of F. nucleatum in CRN cases and controls. Clinical Relevance: Considering the current evidence linking F. nucleatum to colorectal carcinogenesis, investigating the role of oral F. nucleatum expression in its colorectal enrichment is crucial for colorectal cancer screening and prevention avenues.

PURPOSE:To examine the effect of maternal gestational diabetes mellitus on the risk of asthma in the offspring. METHODS:This cohort study used data from 19,933 children in the National Longitudinal Survey of Children and Youth (NLSCY), 1994/1995-2008/2009, Canada. Children were followed until the first-time report of having health professional-diagnosed asthma (hereafter incident asthma), loss to follow-up, or end of the NLSCY follow-up, whichever occurred first. As a surrogate for Cox proportional hazards regression, pooled logistic regression models, crude and adjusted for potential confounders, were fitted to estimate the effect of gestational diabetes mellitus on the risk of asthma in the offspring. RESULTS:Among the 19,933 children, 1,178 (5.9%) had mothers with gestational diabetes mellitus. The median duration of follow-up was 4 (interquartile range: 4) years. A total of 1639 children in the cohort had reported incident asthma during the follow-up, and 119 of them had mothers with gestational diabetes mellitus. The adjusted hazard ratio for the association between gestational diabetes mellitus and incident asthma in offspring was 1.25 (95% confidence interval [CI] 1.03, 1.51). CONCLUSIONS:Our findings suggest that gestational diabetes mellitus increases the risk of asthma in the offspring.

Abstract Study Objectives This study aims to assess whether the nocturnal wear of dentures has an effect on the quality of sleep and oral-health-related quality of life of the edentulous elderly with untreated sleep apnea. Methods A single-blind randomized cross-over design with two sequences and two periods was used. Participants (n = 77) were randomly assigned either to sequence 1 (nocturnal wear followed by nocturnal nonwear of the denture for 30–30 days) or sequence 2 (nocturnal nonwear followed by nocturnal wear of denture for 30–30 days). The primary sleep outcome was the quality of sleep, assessed through sleep fragmentation measured as Apnea–Hypopnea Index (AHI) and respiratory arousal from portable polysomnography. Secondary outcomes were daytime sleepiness, sleep quality (Pittsburgh Sleep Quality Index, PSQI) and oral-health-related quality of life measured by validated questionnaires. Results The mean paired difference in AHI scores for the period of wearing versus not wearing dentures at night was small 1.0 event per hour (p = 0.50; 95% confidence interval (CI) = −2.0 to 4.1). The mean respiratory arousal index was higher when wearing dentures at night than when not wearing dentures at night, with a mean paired difference of 2.3 events per hour (p = 0.05; 95% CI = 0.0 to 4.6). No difference in sleepiness and PSQI were noted. Wearing dentures at night resulted in a statistically significantly higher mean score of psychological discomfort when compared to not wearing dentures at night. Conclusions The results provide some support to usual practice guidelines to remove dentures at night in edentulous elders suffering from sleep apnea. Clinical trial registration NCT01868295.

Aim & methods: We compared propensity score matching (PSM) and coarsened exact matching (CEM) in balancing baseline characteristics between treatment groups using observational data obtained from a pan-Canadian prostate cancer radiotherapy database. Changes in effect estimates were evaluated as a function of improvements in balance, using results from randomized clinical trials to guide interpretation. Results: CEM and PSM improved balance between groups in both comparisons, while retaining the majority of original data. Improvements in balance were associated with effect estimates closer to those obtained in randomized clinical trials. Conclusion: CEM and PSM led to substantial improvements in balance between comparison groups, while retaining a considerable proportion of original data. This could lead to improved accuracy in effect estimates obtained using observational data in a variety of clinical situations.

BACKGROUND:Coronavirus Disease 2019 (COVID-19) has variable clinical presentation, from asymptomatic to severe disease leading to death. Biochemical markers may help with management and prognostication of COVID-19 patients; however, their utility is still under investigation. METHODS:A retrospective study was conducted to evaluate alanine aminotransferase, C-reactive protein (CRP), ferritin, lactate, and high sensitivity troponin T (TnT) levels in 67 patients who were admitted to a Canadian tertiary care centre for management of COVID-19. Logistic, cause-specific Cox proportional-hazards, and accelerated failure time regression modelling were performed to assess the associations of initial analyte concentrations with in-hospital death and length of stay in hospital; joint modelling was performed to assess the associations of the concentrations over the course of the hospital stay with in-hospital death. RESULTS:Initial TnT and CRP concentrations were associated with length of stay in hospital. Eighteen patients died (27%), and the median initial TnT concentration was higher in patients who died (55 ng/L) than those who lived (16 ng/L; P < 0.0001). There were no survivors with an initial TnT concentration > 64 ng/L. While the initial TnT concentration was predictive of death, later measurements were not. Only CRP had prognostic value with both the initial and subsequent measurements: a 20% increase in the initial CRP concentration was associated with a 14% (95% confidence interval (CI): 1-29%) increase in the odds of death, and the hazard of death increased 14% (95% CI: 5-25%) for each 20% increase in the current CRP value. While the initial lactate concentration was not predictive of death, subsequent measurements were. CONCLUSION:CRP, lactate and TnT were associated with poorer outcomes and appear to be useful biochemical markers for monitoring COVID-19 patients.

e12532 Background: Early Breast Cancer Trialist Collaborative Group meta-analysis suggested significant reduction in bone metastasis and breast cancer mortality among post-menopausal women diagnosed with early breast cancer when treated with an adjuvant bisphosphonate. Cancer Care Ontario and American Society of Clinical Oncology clinical practice guideline published in 2017, recommends the use of an adjuvant bisphosphonate in postmenopausal women who are candidates for adjuvant systemic therapy. Our goal was to evaluate trends and factors associated with adjuvant bisphosphonate usage since the guideline’s publication. Methods: This study is a retrospective review of postmenopausal women treated for early breast at the London Regional Cancer Program from 2017-2018. Univariate and a multivariable logistic regression models were used to investigate factors potentially associated with adjuvant bisphosphonate use including age, stage, grade, estrogen receptor, progesterone receptor, HER2 receptor status and previous use of adjuvant chemotherapy. The percentage of patients offered, receiving and declining therapy was also recorded and the time interval from surgery to start of bisphosphonate therapy (< 6 months, 6-12 months or >12 months). Results: We identified 286 postmenopausal breast cancer patients, of whom 75 (28%) received adjuvant bisphosphonate therapy. In our multivariable model, cancer stage [odds ratio (OR) stage II vs. I=2.26, 95% confidence interval (CI) 1.08-4.74) and OR Stage III vs. I=4.94, 95% CI 1.84-13.17] and previous use of adjuvant chemotherapy (OR=2.76, 95%CI 1.37-5.55) were significantly associated with adjuvant bisphosphonate use. Among 133 patients who received adjuvant systemic chemotherapy, 51% were offered adjuvant bisphosphonate and of these 81% patients accepted therapy. Among a total of 75 patients receiving adjuvant bisphosphonate therapy 19% initiated therapy within 6 months of surgery, 48% within 6-12 months of surgery, and 33% after 12 months following surgery. Conclusions: Stage and previous use of chemotherapy were significantly associated with adjuvant bisphosphonate therapy. Our study observes the potential underutilization of adjuvant bisphosphonate therapy and possible need to start treatment earlier in some patients. Further education and awareness of the clinical practice guidelines regarding adjuvant bisphosphonate therapy may be warranted and additional population-based study investigating treatment patterns and real-world effectiveness.

Abstract Background Despite a considerable amount of epidemiological research for identification of risk factors involved in the development of colorectal cancer, the current understanding of the etiology of this disease remains rather poor. Accumulating evidence suggests a potentially important role of infection with Fusobacterium nucleatum in the colon in colorectal carcinogenesis. The objective of this systematic review is to synthesize the epidemiological evidence on the association between infection with Fusobacterium nucleatum in the colon and colorectal cancer. Methods This systematic review will include observational studies (cohort, case-control, cross-sectional) in humans in which the role of Fusobacterium nucleatum in the etiology of colorectal cancer was investigated. MEDLINE, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews will be searched using a comprehensive search strategy and manual screening of references. Two reviewers will independently identify eligible studies and extract the data from the included studies. The quality of studies will be assessed by using the Newcastle-Ottawa scale. Random-effects models will be used to estimate pooled measures of association (where feasible). Meta-regression and subgroup analyses will be conducted to explore the potential sources of heterogeneity. The Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement will be followed for reporting. Discussion Deepening knowledge regarding the etiology of colorectal cancer and the potential implications of Fusobacterium nucleatum in this disease is instrumental for prevention, diagnosis, and treatment of this often-fatal disease. This review will produce summarized current evidence on this topic. Systematic review registration This systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 10 July 2018 (registration number CRD42018095866).

Background Despite a considerable amount of epidemiological research for identification of risk factors involved in the development of colorectal cancer, the current understanding of the etiology of this disease remains rather poor. Accumulating evidence suggests a potentially important role of infection with Fusobacterium nucleatum in the colon in colorectal carcinogenesis. The objective of this systematic review is to synthesize the epidemiological evidence on the association between infection with Fusobacterium nucleatum in the colon and colorectal cancer. Methods This systematic review will include observational studies (cohort, case - control, cross-sectional) in humans in which the role of Fusobacterium nucleatum in the etiology of colorectal cancer was investigated. MEDLINE, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews will be searched using a comprehensive search strategy and manual screening of references. Two reviewers will independently identify eligible studies and extract the data from the included studies. The quality of studies will be assessed by using the Newcastle-Ottawa scale. Random-effects models will be used to estimate pooled measures of association (where feasible). Meta-regression and subgroup analyses will be conducted to explore the potential sources of heterogeneity. The Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement will be followed for reporting. Discussion Deepening knowledge regarding the etiology of colorectal cancer and the potential implications of Fusobacterium nucleatum in this disease is instrumental for prevention, diagnosis, and treatment of this often-fatal disease. This review will produce summarized current evidence on this topic. Systematic review registration This systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 10 July 2018 (registration number CRD42018095866).

Background: Asthma exacerbation trajectories in children after incident asthma diagnosis are understudied. Objective: To identify trajectories of asthma exacerbation and predictors of these trajectories in children with incident asthma. Methods: Children from the National Longitudinal Survey of Children and Youth, Canada, with incident asthma were followed-up for up to 12 years during childhood. Latent class growth modeling was used to identify distinct asthma exacerbation trajectory groups. Multinomial logistic regression was performed to identify predictors of trajectory group membership. Results: The mean age at asthma diagnosis among 403 children was 5.9 years. Three distinct trajectories were identified: low increasing (21.3% of children), medium decreasing (45.8% of children), and high decreasing (32.8% of children). Asthma attack probability increased gradually after diagnosis in low increasing group, decreased from moderate level after diagnosis to almost zero probability at the end of follow-up in the medium decreasing group, and decreased after diagnosis but remained higher in the high decreasing group than the other 2 groups at 12 years after diagnosis. Children having more siblings at home were more likely to belong to the medium decreasing and high decreasing trajectory groups, whereas children older at asthma diagnosis were less likely to belong to the medium decreasing and high decreasing trajectory groups than the low increasing trajectory group. Conclusion: Our results suggest that children with incident asthma follow 3 distinct trajectories of asthma exacerbations after asthma diagnosis. The trajectory group with initial moderate exacerbation probability has better long-term prognosis. (C) 2019 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Despite a considerable amount of epidemiological research for identification of risk factors involved in the development of colorectal cancer, the current understanding of the etiology of this disease remains rather poor. Accumulating evidence suggests a potentially important role of infection with Fusobacterium nucleatum in the colon in colorectal carcinogenesis. The objective of this systematic review is to synthesize the epidemiological evidence on the association between infection with Fusobacterium nucleatum in the colon and colorectal cancer. This systematic review will include observational studies (cohort, case-control, cross-sectional) in humans in which the role of Fusobacterium nucleatum in the etiology of colorectal cancer was investigated. MEDLINE, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews will be searched using a comprehensive search strategy and manual screening of references. Two reviewers will independently identify eligible studies and extract the data from the included studies. The quality of studies will be assessed by using the Newcastle-Ottawa scale. Random-effects models will be used to estimate pooled measures of association (where feasible). Meta-regression and subgroup analyses will be conducted to explore the potential sources of heterogeneity. The Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement will be followed for reporting. Deepening knowledge regarding the etiology of colorectal cancer and the potential implications of Fusobacterium nucleatum in this disease is instrumental for prevention, diagnosis, and treatment of this often-fatal disease. This review will produce summarized current evidence on this topic. This systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 10 July 2018 (registration number CRD42018095866).

Purpose: Incretin-based medications are a novel class of agents for the treatment of type-2 diabetes mellitus (DM2). The safety profile of these medications is not firmly established, and concerns have been raised about their potential carcinogenicity. The objective of our study was to produce new evidence on the effect of incretin-based medications on cancer risk in patients with DM2. Methods: We conducted a retrospective cohort study with data from the Clinical Practice Research Datalink and the Hospital Episodes Statistics in the UK. New users of either an incretin-based medication (n=18885) or a sulfonylurea medication (n=36929) between 2007 and 2013 were identified and followed for up to 8years. Cox proportional-hazards models were used to estimate the quasi-intention-to-treat and quasi-per-protocol hazard-ratios for the association between incretin-based medications with cancer while adjusting for potential confounders. Results: The adjusted hazard ratio (95% confidence interval) for use of incretin-based medications versus use of sulfonylurea medications for the overall-cancer outcome was 0.97 (0.90, 1.05) in the quasi-intention-to-treat analysis and 0.90 (0.81, 1.00) in the quasi-per-protocol analysis. In both analyses, the hazard-ratio functions over the 8-year follow-up seemed fairly constant, and the 8-year cumulative-risk functions in the two subcohorts were similar. Conclusions: Our study suggests that the use of incretin-based medications in patients with DM2 does not increase the risk of cancer relative to the use of sulfonyl-urea medications, at least in the first several years of the use. Further research is needed to assess long-term effects of the use of incretin-based medications on cancer risk.

individuals diagnosed at an older age must live to that age to be diagnosed and included in the cystic fibrosis registry, which leads to an "immortal" survival time bias.The relationship between age at diagnosis and survival is complex and must be interpreted with caution, as noted by Fieuws and colleagues.Although older age at diagnosis inherently increases the risk for death because of age effects, older age at diagnosis may also reflect milder disease and reduced risk for death.However, being diagnosed later in life also means there were additional years of untreated cystic fibrosis, which could result in a negative effect on health and, hence, result in an increased risk for death.We again thank Fieuws and colleagues for bringing attention to this important issue and for highlighting that older age at diagnosis may not necessarily be a risk factor for worse outcomes in adult-diagnosed cystic fibrosis, a message we would not want miscommunicated to patients.

BACKGROUND:Despite a considerable amount of epidemiological research for identification of risk factors involved in the development of colorectal cancer, the current understanding of the etiology of this disease remains rather poor. Accumulating evidence suggests a potentially important role of infection with Fusobacterium nucleatum in the colon in colorectal carcinogenesis. The objective of this systematic review is to synthesize the epidemiological evidence on the association between infection with Fusobacterium nucleatum in the colon and colorectal cancer.METHODS:This systematic review will include observational studies (cohort, case-control, cross-sectional) in humans in which the role of Fusobacterium nucleatum in the etiology of colorectal cancer was investigated. MEDLINE, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews will be searched using a comprehensive search strategy and manual screening of references. Two reviewers will independently identify eligible studies and extract the data from the included studies. The quality of studies will be assessed by using the Newcastle-Ottawa scale. Random-effects models will be used to estimate pooled measures of association (where feasible). Meta-regression and subgroup analyses will be conducted to explore the potential sources of heterogeneity. The Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement will be followed for reporting.DISCUSSION:Deepening knowledge regarding the etiology of colorectal cancer and the potential implications of Fusobacterium nucleatum in this disease is instrumental for prevention, diagnosis, and treatment of this often-fatal disease. This review will produce summarized current evidence on this topic.SYSTEMATIC REVIEW REGISTRATION:This systematic review protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 10 July 2018 (registration number CRD42018095866).

Purpose: To examine the age, period, and cohort effects on asthma prevalence among Canadian adults from 1994/1995 to 2010/2011. Methods: Using data from the National Population Health Survey, 13,616 Canadian adults were followed for 16 years. Age was limited to 18-80 years during follow-up. Modified Poisson regression models with generalized estimating equations were used to estimate age, period, and cohort effects on asthma and active asthma prevalence after accounting for sociodemographic factors. Model-based standardization was performed to estimate standardized rates. Results: Overall asthma prevalence increased from 5% in 1994/1995 to 11% in 2010/2011; decreasing from 12% for 20-year-olds to 6% for 50-60-year-olds and then increased to 8% for 80-year-olds. Individuals aged 20 years had the steepest increase in prevalence between 1994/1995 and 2010/2011. Active asthma prevalence increased from 5% in 1994/1995 to 8% in 2010/2011; decreasing from 8% for 20-year-olds to 5% for 50-60-year-olds and then increased to 6% for 80-year-olds. Conclusions: Our findings suggest the presence of age, period, and cohort effects on prevalence of asthma overall and presence of age and period effects on active asthma prevalence in Canadian adults. (C) 2019 Elsevier Inc. All rights reserved.

Using a genetic risk score (GRS) to predict a phenotype in a target sample can be complicated by missing data on the single nucleotide polymorphisms (SNPs) that comprise the GRS. This is usually addressed by imputation, omission of the SNPs or by replacing the missing SNPs with proxy SNPs. To assess the impact of the omission and proxy approaches on effect size estimation and predictive ability of weighted and unweighted GRS with small numbers of SNPs, we simulated a dichotomous phenotype conditional on real genotype data. We considered scenarios in which the proportion of missing SNPs ranged from 20-70%. We assessed the impact of omitting or replacing missing SNPs on the association between the GRS and phenotype, the corresponding statistical power and the area under the receiver operating curve. Omission resulted in a larger bias towards the null value of the effect size, a smaller predictive ability and greater loss of statistical power than proxy approaches. The predictive ability of a weighted GRS that includes SNPs with large weights depends of the availability of these large-weight SNPs.

This chapter is devoted to Cartan's structural theory of infinite continuous groups. We thoroughly analyze its genesis and subsequent development. Cartan's approach to infinite continuous groups was characterized by a sharp break with the past tradition dating back to Lie, Engel, Medolaghi, and Vessiot. Such a discontinuity involved at least two aspects of the theory, the technical tools employed and the priorities of the theory itself. On the technical side, Cartan made a great profit of his theory of exterior differential systems, namely of his existence and uniqueness results for not integrable Pfaffian systems. As far as priorities were concerned, the Cartan theory was marked by a radical change of perspective: the emphasis was not put anymore on the problem of determining all infinite continuous groups of transformations in a given number of variables; rather, Cartan considered to be essential developing a structural theory of such groups in which the notion of isomorphism played a central role. Cartan's reinterpretation of Lie's equivalence theory is singled out as the main driving force in the genetical process leading to Cartan's structural theory of infinite groups.