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

Background: While long-term cessation is an outcome of interest in adult smokers, little is known about discontinuing smoking in adolescent smokers. The objective was to identify the predictors of the occurrence of smoking discontinuation in novice smokers.Methods: Data were available for 620 adolescent smokers participating in a longitudinal study on the natural course of nicotine dependence. Data on smoking discontinuation (i.e., stopping smoking for ≥12 consecutive months) were collected in 20 cycles over five years from grade 7 to 11 (1999–2005). Data on 37 potential predictors representing a wide range of demographic, psychosocial, health, lifestyle, smoking-related, and context-related characteristics were collected once, 2 to 3 times, or 20 times. Pooled logistic regression was used to test the association between each potential predictor and smoking discontinuation, adjusting for potential confounders.Results: Forty percent of 620 participants discontinued smoking during follow up. Male sex [OR (95% confidence interval), 1.8 (1.3–2.4)], age [1.3 (1.1–1.5)], cigarette package warnings [0.6 (0.5–0.9)], team sports participation [1.4 (1.1–1.9)], family stress [0.7 (0.6–1.0)], worrying about weight [0.6 (0.5–0.9)], overweight [0.7 (0.5–1.0)], illicit drugs use [0.5 (0.4–0.7)], tolerance [0.6 (0.4–1.0)], and other nicotine dependence symptoms [1.0 (0.9–1.0)] were statistically significantly associated with smoking discontinuation.Conclusions: Both individual and context-level factors were associated with smoking discontinuation.Impact: Programs and policy targeting novice adolescent smokers may be more effective if factors associated with long-term smoking discontinuation are taken into consideration. In particular, young smokers may need help with dependence symptoms, body weight issues, family functioning, and polysubstance use. Cigarette package warnings may be effective in helping adolescents discontinue smoking. Cancer Epidemiol Biomarkers Prev; 23(6); 1090–101. ©2014 AACR.

Traditional cancer treatments based on chemo- and/or radiotherapy effectively kill only differentiated cancer cells, while metastasis and recurrences are caused by surviving cancer resistant cells (CRC) or a special subpopulation of cancer cells known as cancer stem cells (CSC). Both of these cell types compromise anticancer treatment through various mechanisms, including withdrawal of the anticancer drug through ATP-binding cassette transporters, increased expression of DNA repair genes, or transition to a quiescent phenotype. In contrast to many cancers, where energy consumption is due to glycolysis (Warburg effect), the bioenergetics of CSC and CRC is most often related to oxidative phosphorylation, that is, dependent on mitochondrial function. Therefore, compounds that induce mitochondrial dysfunction (MDF), such as some antibiotics, may represent an alternative approach to anticancer therapy. This review summarizes the major recent works on the use of antibiotics to target tumors via CSC and suggests next steps for developing this approach.

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 non-steroidal 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.

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 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.

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.

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 = 18 885) or a sulfonylurea medication (n = 36 929) between 2007 and 2013 were identified and followed for up to 8 years. 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 sulfonylurea 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.

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.

The objective of this study was to analyze the effect of acetylcholinesterase inhibitors (AChEIs) on the risk of osteoporotic fractures in Alzheimer patients. A nested case-control study was conducted on 1190 cases and 4760 controls. The use of AChEIs was found to decrease the risk of osteoporotic fractures in these patients. The objective of this study is to estimate the extent to which the use of AChEIs is associated with a reduction in the risk of osteoporotic fractures. A nested case-control study was conducted using data from the UK Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) database (1998–2013). The study cohort consisted of Alzheimer’s Disease (AD) patients aged ≥ 65 years with no previous history of osteoporotic fractures at cohort baseline. Cases were individuals who suffered an osteoporotic fracture during the study period, whereas controls were subject who did not experience any osteoporotic fractures during the same period. Controls were drawn from the population time at risk while being matched to the cases in respect to age, sex, up-to-standard follow-up in the CPRD, calendar time, and duration of AD (control-to-case ratio: 4-to-1). Information on the use of AChEIs and the relevant potential confounders was ascertained from the CPRD database for all the cases and controls. We identified 1190 cases and 4760 controls. Compared to non-users, any use of AChEIs prior to the fracture was associated with a reduction in the fracture risk [adjusted odds ratio (OR) 0.80 (confidence interval (CI) 95%, 0.70–0.91)]. The use of AChEIs corresponding to a proportion of days covered of 0.8–1.0 was associated with a lower osteoporotic fracture risk compared to non-use [adjusted OR 0.76 (CI 95%, 0.66–0.87)]. In this study using large primary care databases, the use and treatment adherence to AChEIs were associated with a decreased risk of osteoporotic fractures in elderly AD patients.

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.

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.

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.

Please find below the correction for the paragraph under the Heading "Materials and methods - Regulatory approval".

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.

Studies on dietary changes and their associated factors are limited, particularly with respect to younger cardiovascular patients. Our objective was to evaluate the factors associated with fruit and vegetable intake among adults with premature acute coronary syndrome (ACS) 1 year after the event. We used data from GENESIS-PRAXY, a multicentre prospective study of adults aged 18-55 years, hospitalised for ACS. Participants were 704 adults from 24 centres in Canada, 1 in USA and 1 in Switzerland. Data were collected through questionnaires and chart reviews at baseline and 1 year post-ACS. Fruit and vegetable intake was low among adults with premature ACS, and remained suboptimal at 1 year post-ACS, with only 21% meeting the minimum recommendations of at least 5 daily servings. The findings suggest that patient lifestyle characteristics, such as the number of hours spent at work and baseline intake are factors that may be associated with the intake of fruits and vegetables. More research is needed to assess effective strategies to increase fruit and vegetable intake among patients with premature ACS so that they meet dietary recommendations.

Background. In Sub-Saharan Africa, maternal and neonatal morbidity and mortality rates are asso- ciated with underutilization of skilled birth attendance (SBA). In 2007, Burkina Faso introduced a subsidy scheme for SBA fees. The objective of this study was to evaluate the effect of Burkina Faso's subsidy policy on SBA rate across socioeconomic status (SES) strata. Methods. We used a quasi-experimental design. The data sources were two representative surveys (n ¼ 1408 and n ¼ 1403) of women from Houndeand Ziniarehealth districts of Burkina Faso, and a survey of health centres assessing structural quality of care. Multilevel Poisson regression models were used with robust variance estimators. We estimated adjusted rate ratios (RR) and rate differ- ences (RD) as a function of time and SES. Results. For lowest-SES women, immediately upon the introduction of the subsidy policy, the rate of SBA was 45% higher (RR ¼ 1.45, 95% confidence interval (CI): 1.19-1.77) than expected in the ab- sence of subsidy introduction. The results indicated a sustained effect after introduction of the sub- sidy policy, based on RR estimate (95% CI) of 1.48 (1.21-1.81) at 2 years. For middle-SES women, the RR estimates were 1.28 (1.09-1.49) immediately after introduction of the subsidy policy and 1.30 (1.11-1.51) at 2 years, respectively. For highest-SES women, the RR estimates were 1.19 (1.02- 1.38) immediately after subsidy introduction and 1.21 (1.06-1.38) at 2 years, respectively. The RD (95% CI) was 14% (3-24%) for lowest-SES women immediately after introduction of the policy, and the effect was sustained at 14% (4-25%) at 2 years. Conclusion. Our study suggests that the introduction of a user-fee subsidy in Burkina Faso resulted in increased rates of SBA across all SES strata. The increase was sustained over time and strongest among the poorest women. These findings have important implications for evidence-informed pol- icymaking in Burkina Faso and other countries in Sub-Saharan Africa.

Introduction The few population-based studies that investigate the association between cannabis use and adiposity are inconclusive possibly because nicotine moderates the effect of cannabis on adiposity. The objective was to test the hypotheses that the association between cannabis use and adiposity in young men and women is modified by cigarette smoking. Methods Data were drawn from the Nicotine Dependence in Teens (NDIT) study, a 13-year prospective cohort investigation of the natural course of nicotine dependence. A total of 271 males and 319 females aged 12–13 years at cohort inception provided data on past-year cannabis use and number of cigarettes smoked per day in the past three months, at age 20 years. Outcomes included change in body mass index (BMI) and in waist circumference (WC) from ages 17 to 24 years. The hypothesis was tested in multiple linear regression models that included interaction terms for cannabis use and cigarette smoking and controlled for physical activity, sedentary behavior, alcohol use, and level of the outcome at baseline. Results The association between cannabis use and change in adiposity was U-shaped in male non-smokers and in females, and an inverted U-shape in male smokers. In males, the interaction between cannabis use and cigarette smoking was significant in both the models for change in BMI (p = 0.004; n = 271) and change in WC (p = 0.04; n = 250). In females, the interaction between cannabis use and cigarette smoking was not significant. Conclusion Smoking cigarettes appears to modify the association between cannabis use and adiposity in young men.

Access to care may be implicated in disparities between men and women in death after acute coronary syndrome, especially among younger adults. We aimed to assess sex-related differences in access to care among patients with premature acute coronary syndrome and to identify clinical and gender-related determinants of access to care.We studied 1123 patients (18-55 yr) admitted to hospital for acute coronary syndrome and enrolled in the GENESIS-PRAXY cohort study. Outcome measures were door-to-electrocardiography, door-to-needle and door-to-balloon times, as well as proportions of patients undergoing cardiac catheterization, reperfusion or nonprimary percutaneous coronary intervention. We performed univariable and multivariable logistic regression analyses to identify clinical and gender-related determinants of timely procedures and use of invasive procedures.Women were less likely than men to receive care within benchmark times for electrocardiography (≤ 10 min: 29% v. 38%, p = 0.02) or fibrinolysis (≤ 30 min: 32% v. 57%, p = 0.01). Women with ST-segment elevation myocardial infarction (MI) were less likely than men to undergo reperfusion therapy (primary percutaneous coronary intervention or fibrinolysis) (83% v. 91%, p = 0.01), and women with non-ST-segment elevation MI or unstable angina were less likely to undergo nonprimary percutaneous coronary intervention (48% v. 66%, p0.001). Clinical determinants of poorer access to care included anxiety, increased number of risk factors and absence of chest pain. Gender-related determinants included feminine traits of personality and responsibility for housework.Among younger adults with acute coronary syndrome, women and men had different access to care. Moreover, fewer than half of men and women with ST-segment elevation MI received timely primary coronary intervention. Our results also highlight that men and women with no chest pain and those with anxiety, several traditional risk factors and feminine personality traits were at particularly increased risk of poorer access to care.

Background Recent cross-sectional studies suggest some adolescents who have never smoked cigarettes experience nicotine dependence (ND) symptoms and that exposure to second-hand smoke, social exposure to smoking, and alcohol use are plausible correlates. The aim of this study was to replicate and extend these findings by investigating possible predictors of ND symptoms longitudinally. Method Participants included 847 secondary school students who had never smoked cigarettes enrolled in the Nicotine Dependence in Teens Study. Adolescents completed self-report questionnaires measuring smoking status, ND symptoms, and risk factors for ND in smokers (i.e., socio-demographic indicators, social exposure to smoking, psychosocial indicators, and substance use) in 20 survey cycles from 7 to 11th grade. Generalized estimating equations, which account for repeated measures within individuals, were used to test the predictors of ND symptoms. Results Consistent with previous research, 7.8% of never-smokers across all cycles endorsed at least one ND symptom. Younger age ( p ≤ .001), country of birth ( p ≤ .05), peer smoking ( p ≤ .001), teacher smoking ( p ≤ .05), depression ( p ≤ .05), stress ( p ≤ .001), lower self-esteem ( p ≤ .05), impulsivity ( p ≤ .05), and alcohol use ( p ≤ .001) predicted greater ND symptoms in multivariable modeling. Conclusions Replicating previous cross-sectional findings, peer smoking and alcohol use predicted ND symptoms among never-smoking adolescents. Extending these findings, previous predictors only observed among ever-smokers, including socio-demographic and psychosocial indicators, also predicted ND symptoms. This longitudinal investigation demonstrated the temporal relation of the predictors preceding ND symptoms. Future research should consider longer prospective studies with younger children to capture early onset of ND symptoms and with longer follow-up to detect eventual smoking uptake.

Background: \ud \ud Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear.\ud \ud Methods: \ud \ud We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts.\ud \ud Findings: \ud \ud The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14–1·83) and the presence of either LPA SNP (1·88, 1·40–2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81–1·11 and either LPA SNP 1·10, 0·92–1·31) or cardiovascular mortality (0·99, 0·81–1·2 and 1·13, 0·90–1·40, respectively) or in the validation studies.\ud \ud Interpretation: \ud \ud In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established.\ud \ud Funding: \ud \ud Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny.

Aims: Access to anti-depressants, and prognosis in younger depressed men and women with acute coronary syndrome (ACS) requires further investigation. We assessed the prevalence of depression, antidepressant prescription, and the association of depression with major adverse cardiovascular events (MACE) in men and women with premature ACS. Methods and results: 1071 ACS men and women (≤ 55 years) were recruited between January 2009 and April 2013 into GENESIS PRAXY, a multicentre prospective observational cohort study, from 24 hospitals in Canada, one in the US and one in Switzerland. Depression was measured by self-report using the Diagnostic and Statistical Manual of Mental Disorders criteria. Prescription of antidepressants at baseline and 12 months, and MACE over 12 months, were assessed using medical chart review and self-report. Depression was present in 20% of men and 32% of women. Only 1% of men and women with no antidepressants at hospital admission were prescribed antidepressants at hospital discharge. Depressed men were 3 times less likely than depressed women to be prescribed antidepressants. The determinants of antidepressants at 12 months included the presence of cardiovascular risk factors in men, and the presence of depression in women. In sex-specific Cox regressions, depressed men had a 2.57 times greater risk of MACE compared with non-depressed men (95% CI: 1.53-4.32), which difference was not seen in women (HR=0.71, 95% CI=0.28-1.81). Conclusion: Despite a decade of sensitization, depression still needs to be better treated after ACS, especially in young men, given that depression is a potent risk factor for adverse outcomes.

Studies suggest that young women are at highest risk for failing to recognise early symptoms of acute coronary syndrome (ACS).To examine sex differences in prodromal symptoms occurring days and weeks prior to the acute presentation of ACS. We also examined health-seeking behaviours and prehospital management in young patients.Prospective cross-sectional analysis of 1145 patients (368 women) hospitalised for ACS, aged ≤55 years, from the GENdEr and Sex DetermInantS of Cardiovascular Disease: From Bench to Beyond Premature Acute Coronary SYndrome cohort study (January 2009-April 2013). Prodromal symptoms were determined using the McSweeney Acute and Prodromal Myocardial Infarction Symptom questionnaire. Health-seeking behaviour and prehospital care were determined by questionnaires.The median age was 49 years. The prevalence of prodromal symptoms was high and more women reported symptoms than men (85% vs 72%, p0.0001). Symptoms were similar between sexes and included unusual fatigue, sleep disturbances, anxiety and arm weakness/discomfort. Chest pain was less common in both sexes (24%). Women were more likely to seek care (49% vs 42%, p=0.04). Among those who sought care, women were more likely to use an ambulance for their ACS compared with men (52% vs 39%). Cardiovascular risk-reduction therapy use was low (≤40%) in all patients and less than half perceived their care provider suspected a cardiac source.Prior to ACS, women were more likely to experience prodromal symptoms and seek medical attention than men. Prehospital care was generally similar between sexes but demonstrated underutilisation of risk-reduction therapies in at-risk young adults.

Position du problème: La parodontite chronique et l’édentement sont des affections buccodentaires chroniques qui, depuis quelques décennies, sont incriminées dans la survenue de différents types de cancers. Cette revue de littérature avait pour but d’examiner l’association entre le cancer colorectal et ces affections buccodentaires. Résultats: Les études épidémiologiques évaluant une association potentielle entre la parodontite, l’édentement et le cancer colorectal sont peu nombreuses. Cependant, plusieurs mécanismes plaident en faveur de cette association, notamment l’inflammation, la nutrition et possiblement l’infection par certains pathogènes, comme le suggère cette revue de la littérature., Background: Chronic periodontitis and tooth loss are chronic oral conditions that, in recent decades, have been implicated in the occurence of certain types of cancer. In this review, we address the question of whether colorectal cancer is associated with these oral conditions. Results: Epidemiological studies evaluating a potential association between periodontitis, tooth loss and colorectal cancer are scarce. However, several mechanisms argue in favor of this association, notably inflammation, nutrition and possibly infection by specific bacteria, as suggested by this literature review.

Background Over past decades, the incidence of acute coronary syndrome (ACS) has increased in young women, and greater mortality rates after discharge were observed among young women vs men. We revisited this issue with contemporary data from the Gen d e r and S ex Determ i nant s of Cardiovascular Disease: From Bench to Beyond Pr emature A cute Coronary S y ndrome (GENESIS-PRAXY), a multicentre prospective cohort study. Methods One thousand two hundred thirteen patients were enrolled in GENESIS-PRAXY from 26 centres across Canada, the United States, and Switzerland between January 2009 and April 2013. We assessed major adverse cardiac events (MACE) and mortality over 12 months after ACS. The role of sex as a predictor of outcomes was determined with Cox proportional hazard regression analysis. Results We included 1163 patients with complete data. The occurrence of MACE was 9% and 8% in women and men, respectively ( P = 0.75), and 1% of women and men died during follow-up. In adjusted models, there was no sex difference in the risk of MACE or mortality. The proportion of patients with all-cause rehospitalization was higher in women (13%) compared with men (9%; P = 0.006), but cardiac rehospitalization rates were similar in both sexes regardless of ACS type. Among first rehospitalizations, the majority was classified as cardiac related (69%), with chest pain or angina (28%) and myocardial infarction (19%) reported as the most common reasons for first rehospitalization. Conclusions Women were more likely than men to be rehospitalized for all causes but not for a cardiac cause. In contrast to earlier studies, men and women had similar mortality and MACE outcomes at 1 year.

Purpose Coffee and black tea are among the most consumed beverages worldwide. Although their potential role in lung cancer occurrence has been investigated in several studies, results have been inconclusive. We investigated the associations between intake of coffee and black tea with lung cancer in a population-based case–control study in Montreal, Canada. Methods These analyses included 1130 cases and 1483 controls. Adjusted odds ratios (ORs) were estimated between four metrics of coffee and black tea consumption (frequency, average daily amount, duration, and cumulative amount) and lung cancer, using unconditional logistic regression. Results The adjusted ORs (95% confidence intervals) for lung cancer comparing daily to never consumers were 0.73 (0.49–1.10) for coffee and 1.05 (0.85–1.31) for black tea. Analyses of other metrics did not reveal any clear patterns of increasing or decreasing risk with increasing amounts or duration of consumption. There was no strong evidence of OR modification by sex or smoking level. The OR estimates did not materially differ by histological subtype for either of the beverages. Conclusion Our results do not provide strong support for associations between consumption of coffee and black tea and lung cancer.

Summary Background Around 90% of deaths from ovarian cancer are due to high-grade serous cancer (HGSC), which is frequently diagnosed at an advanced stage. Several cancer organisations made a joint recommendation that all women with specified symptoms of ovarian cancer should be tested with the aim of making an early diagnosis. In the Diagnosing Ovarian Cancer Early (DOvE) study we investigated whether open-access assessment would increase the rate of early-stage diagnosis. Methods Between May 1, 2008, and April 30, 2011, we enrolled women who were aged 50 years or older and who had symptoms of ovarian cancer. They were offered diagnostic testing with cancer antigen (CA-125) blood test and transvaginal ultrasonography (TVUS) at a central and a satellite open-access centre in Montreal, QC, Canada. We compared demographic characteristics of DOvE patients with those of women in the same age-group in the general population of the area, and compared indicators of disease burden with those in patients with ovarian cancer referred through the usual route to our gynaecological oncology clinic (clinic patients). Findings Among 1455 women assessed, 402 (27·6%) were in the highest-risk age group (≥65 years). 239 (16·4%) of 1455 required additional investigations. 22 gynaecological cancers were diagnosed, 11 (50%) of which were invasive ovarian cancers, including nine HGSC. The prevalence of invasive ovarian cancer, therefore, was one per 132 women (0·76%), which is ten times higher than that reported in screening studies. DOvE patients were significantly younger, more educated, and more frequently English speakers than were women in the general population. They also presented with less tumour burden than did the 75 clinic patients (median CA-125 concentration 72 U/mL, 95% CI 12–1190 vs 888 U/mL, 440–1936; p=0·010); Eight (73%) tumours were completely resectable in DOvE patients, compared with 33 (44%) in clinic patients (p=0·075). Seven (78%) of the HGSC in the DOvE group originated outside the ovaries and five were associated with only slightly raised CA-125 concentrations and minimal or no ovarian abnormalities on TVUS. Interpretation The proportion of HGSC that originated outside the ovaries in this study suggests that early diagnosis programmes should aim to identify low-volume disease rather than early-stage disease, and that diagnostic approaches should be modified accordingly. Although testing symptomatic women may result in earlier diagnosis of invasive ovarian cancer, large-scale implementation of this approach is premature. Funding Canadian Institutes of Health Research, Montreal General Hospital Foundation, Royal Victoria Hospital Foundation, Cedar's Cancer Institute, and La Fondation du Cancer Monique Malenfant-Pinizzotto.

Summary Objective The objective of the study was to test the hypothesis that greater fluctuations in physical activity lead to greater increases in body fat during adolescence. Methods Seven hundred fifty-six adolescents in Montreal, Canada, aged 12–13 years at baseline, completed a 7-d physical activity recall questionnaire every 3 months over 5 years. Body mass index (BMI), waist circumference, and triceps and subscapular skinfold thickness were measured at baseline and at the end of follow-up. Subject-specific linear regressions, expressing physical activity as a function of time, were fitted and physical activity fluctuation scores were obtained by averaging the absolute values of regression residuals. The association between body fat after 5 years and the physical activity fluctuation score was assessed in linear regressions adjusting for baseline body fat, average number of physical activity sessions per week, diet and sociodemographic variables. Results Among boys, there were statistically significant positive associations between physical activity fluctuation and BMI (β, 95% confidence interval: 0.12, 0.02–0.21) and triceps skinfold (0.40, 0.17–0.63). The associations with waist circumference or subscapular skinfold were not statistically significant (0.22, −0.04–0.49; 0.13, −0.05–0.32, respectively). In girls, there were statistically significant negative associations between physical activity fluctuation and BMI (−0.12, −0.20 to −0.03), waist circumference (−0.54, −0.91 to −0.17), subscapular skinfold (−0.41, −0.56 to −0.26) and triceps skinfold (−0.22, −0.38 to −0.05). Conclusion Physical activity fluctuations appear to affect body fat during adolescence. Sex-specific interventions may be needed given that greater physical activity fluctuations seem unfavourable for boys and beneficial for girls.

The effect of screen time during secondary school on percent body fat was examined in a cohort of 744 Canadian adolescents aged 12-13 years at baseline. Participants completed self-reported questionnaires on television viewing and computer use in 19 survey cycles over 57 months from 1999 to 2005. Triceps skinfold thickness and subscapular skinfold thickness were measured in survey cycles 1 and 19. Four screen-time trajectory groups identified in growth mixture modeling included steady-low screen time (73% of the sample), steady-high (10%), increasers (9%), and decreasers (8%). The effect of screen-time trajectory on percent body fat at survey cycle 19 was modeled in boys and girls separately by using linear regression, adjusting for baseline percent body fat and physical activity. Relative to that of steady-low screen-time trajectory group boys, percent body fat was 2.9 (95% confidence interval: 0.7, 5.0) and 2.4 (95% confidence interval: 0.5, 4.2) percentage units higher on average among "increasers" and "steady-high" trajectory group boys, respectively. There was no evidence that screen time has an effect on percent body fat in girls overall, although physical activity modified the association between screen time and percent body fat in both sexes. Efforts to prevent obesity in youth should emphasize reducing screen time.

Background— Prescription plans frequently use restrictive strategies to control drug expenditures. Increased restrictions may reduce access to evidence-based therapy among patients with chronic disease. We sought to evaluate the impact of increased restrictions on medication use among heart failure (HF) patients. Methods and Results— We conducted a population-based cohort study of administrative data from 3 Canadian provinces. During 1998 to 2001, Quebec (QC) had a minimally restrictive plan, whereas Ontario (ON) and British Columbia (BC) had more restrictive prescription plans. We evaluated drug use at 30 days of discharge stratified by prescription plan. Provincial rates of filled prescriptions for HF drugs in QC, ON, and BC were 62%, 58%, and 47% for angiotensin-converting enzyme inhibitors; 34%, 22%, and 16% for β-blockers; 9%, 5%, and 3% for angiotensin receptor blockers; and 79%, 76%, and 62% for loop diuretics, respectively. In multivariate analyses, patients residing in provinces with restrictive plans were less likely to be prescribed drugs that were restricted, such as β-blockers (odds ratio, 0.53; 95% CI, 0.46 to 0.60; 0.36, 0.29 to 0.44, for ON and BC, respectively) and angiotensin receptor blockers (0.50, 0.45 to 0.56; 0.38, 0.32 to 0.46, for ON and BC, respectively), than drugs with no restrictions, such as loop diuretics (0.81, 0.74 to 0.88; 0.40, 0.36 to 0.45, for ON and BC, respectively) and angiotensin-converting enzyme inhibitors (0.80, 0.75 to 0.86; 0.47, 0.43 to 0.52, for ON and BC, respectively). Conclusion— Among HF patients, residing in a province with a more restrictive prescription plan may be associated with lower use of restricted HF medications over and above the expected regional differences in HF drug use across provinces.

Few prospective studies of smoking initiation have investigated a wide range of time-varying and invariant predictor variables at the individual and contextual levels concurrently. In this study (1999-2005), 877 Canadian students (mean age = 12.7 years) who had never smoked at baseline completed self-report questionnaires on cigarette smoking and 32 predictor variables in 20 survey cycles during secondary school. Height and weight were measured in survey cycles 1, 12, and 19. School administrators completed questionnaires on school tobacco control policies/activities, and trained observers collected data on access to tobacco products in commercial establishments near schools. Younger age, single-parent family status, smoking by parents, siblings, friends, and school staff, stress, impulsivity, lower self-esteem, feeling a need to smoke, not doing well at school, susceptibility to tobacco advertising, alcohol use, use of other tobacco products, and attending a smoking-tolerant school were independent determinants of smoking initiation. Independent determinants of daily smoking onset among initiators of nondaily smoking included smoking by siblings and friends, feeling a need to smoke, susceptibility to tobacco advertising, use of other tobacco products, and self-perceived mental and physical addiction. Adolescent tobacco control programs should address multiple individual and contextual-level risk factors. Strategies that address nicotine dependence symptoms are also needed for adolescents who have already initiated smoking.

Purpose To study the effect of cigarette use on height and adiposity in adolescents. Methods Data on cigarette use were collected every 3 months for 5 years from adolescents initially 12–13 years of age. Height, weight, and triceps skinfold thickness were measured in survey cycles 1, 12, and 19. Multivariate linear regression models were fitted to estimate the association between cigarette use and the anthropometric measures in a dataset that pooled data over two time periods, from survey cycles 1–12 and from survey cycles 12–19. Results Data were available for 451 boys and 478 girls. Seven percent of boys and 14% of girls smoked ≥30 cigarettes per month on average during the first time period; 9% of boys and 18% of girls smoked ≥30 cigarettes per month on average during the second time period. In boys, a 100-cigarette per month increment in cigarette use over the preceding 2.5 years was independently associated with lower body mass index (−0.4 kg/m 2 ) and shorter height (−0.7 cm). In girls, cigarette use was not associated with height or adiposity. Conclusions While there was no relation in girls, cigarette use appears to decrease body mass index and height in boys. Young girls may be less likely to take up cigarette smoking if tobacco control messages emphasize that cigarette use may not be associated with reduced weight in adolescent females.

Although related to inflammatory markers in adults, little is known about the association between cigarette smoking and C-reactive protein (CRP) in adolescent smokers. We examined the association between high-sensitivity CRP (hs-CRP) concentrations and smoking in youth. We used data from a cross-sectional, province-wide survey of a representative sample of youth conducted in Quebec, Canada, in 1999. Data were collected in self-report questionnaires completed by participants and their parents. Participants provided a fasting blood sample, and anthropometric measures were undertaken by trained technicians. The present analysis pertains to 1,501 adolescents aged 13 and 16 years who completed questionnaires and for whom blood samples were available. The independent association between a six-category indicator of smoking status and elevated hs-CRP, defined as a value at least in the 90th percentile of the age- and sex-specific CRP distribution, was assessed in multiple logistic regression analyses controlling for potential confounders. Relative to never-smokers, the odds ratios (95% confidence intervals) for puffers (i.e., never smoked a whole cigarette), those who smoked but not in the past month, light past-month smokers, moderate past-month smokers, and heavy past-month smokers were 1.04 (0.55-1.98), 1.76 (1.06-2.94), 1.39 (0.70-2.76), 2.07 (0.96-4.42), and 2.40 (1.18-4.88), respectively. Our data suggest a positive association between smoking status and elevated CRP in adolescents, and in particular among heavier past-month smokers. Damage related to cigarette smoking may begin soon after tobacco use initiation, reinforcing the preventive message that no level of smoking is safe in youth.

Background— High systolic blood pressure (SBP) occurs more frequently both among men and boys than among women and girls. No longitudinal study has investigated whether the impact of SBP determinants differ according to sex in youth. Methods and Results— Between 1999 and 2005, an adolescent cohort (n=1267) completed a questionnaire survey and underwent biannual blood pressure and anthropometric assessment (grades 7, 9, and 11). Boys accounted for ≈50% of those with high SBP at grade 7 and 9 assessments but 67% of those with high SBP at the grade 11 assessment. As computed through a generalized estimating equations logistic regression model (sex, age, sex and age interaction term, overweight, physical activity, sedentary behavior, heart rate, household income, tobacco use, and 4 language categories), the likelihood of high SBP values among boys compared with girls was 1.29 (95% CI, 0.77 to 2.16) in grade 7, 1.98 (95% CI, 1.35 to 2.93) in grade 9, and 2.74 (95% CI, 1.52 to 4.94) in grade 11. Although there was a significant interaction between sex and age, interaction terms of sex with overweight, sedentary behavior, and physical activity were not statistically significant. Overweight (odds ratio [OR], 2.63; 95% CI, 1.76 to 3.92) and sedentary behavior (OR, 1.17 for increment of 5 hours weekly; 95% CI 1.04 to 1.33) demonstrated positive associations with high SBP values. Physical activity was inversely associated with the presence of high SBP (OR, 0.92 for increment of 5 activities in 7 days; 95% CI, 0.84 to 1.00). Conclusions— Boys are more likely than girls to develop high SBP as they approach adulthood. Even among overweight adolescents, reducing sedentary behavior and increasing physical activity may lower the risk of high SBP.

Therapeutic approaches in systemic lupus erythematosus (SLE) have evolved over the last few decades, but their impact on prevention of organ damage is unknown. The objective of this study was to compare new cumulative damage in SLE patients across different calendar periods. Patients from a large SLE cohort were divided into two subcohorts; the first diagnosed and followed between 1978 and 1988 (cohort #1, n = 100) and the second between 1989 and 1999 (cohort #2, n = 51). Initial Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) scores, and changes in scores over the observation intervals, were compared for the two groups. Logistic regression estimated adjusted odds ratios (OR) comparing damage accrual between the two cohorts. Medication exposures were noted. Baseline characteristics were similar between the two groups. At first assessment, the adjusted OR for a SLICC/ACR DI score ≥1 was 1.79 (95% CI 0.82, 3.88) for cohort #1 versus cohort #2. At the end of the observation interval, the adjusted OR for a SLICC/ACR DI score ≥1 was 1.22 (0.58, 2.55) for cohort #1 versus cohort #2. The adjusted OR for accruing damage over the observation interval in cohort #1 versus cohort #2 was 0.94 (0.39, 2.44). Increased medication exposure was evident for cohort #2 compared to cohort #1. Despite increased therapeutic measures used for patients in more recent periods, our data do not establish a clear difference in damage accrual. This emphasizes the need for strategies to effectively treat lupus-specific manifestations, while minimizing side effects and comorbidities.