Predictors of low and very low bone mineral density in long-term childhood acute lymphoblastic leukemia survivors: Toward personalized risk prediction.

BACKGROUND: Cohorts of childhood acute lymphoblastic leukemia (cALL) survivors reaching adulthood are increasing. Approximately 30% of survivors meet criteria for low bone mineral density (BMD) 10 years after diagnosis. We investigated risk factors for low BMD in long-term cALL survivors. METHODS: We recruited 245 cALL survivors from the PETALE (Prévenir les effets tardifs des traitements de la leucémie aiguë lymphoblastique chez l'enfant) cohort, who were treated with the Dana Farber Cancer Institute protocols, did not experience disease relapse or hematopoietic stem cell transplants, and presented with more than 5 years of event-free survival. Median time since diagnosis was 15.1 years. RESULTS: Prevalence of low DXA-derived BMD (Z-score ≤-1) ranged between 21.9% and 25.3%, depending on site (lumbar spine (LS-BMD), femoral neck (FN-BMD), and total body (TB-BMD), and between 3.7% and 5.8% for very low BMD (Z-score ≤-2). Males had a higher prevalence of low BMD than females for all three outcomes (26%-32% vs. 18%-21%), and male sex acted as a significant risk factor for low BMD in all models. Treatment-related factors such as cumulative glucocorticoid (GC) doses and cranial radiation therapy (CRT) were associated with lower BMDs in the full cohort and in females at the FN-BMD site. CONCLUSION: Low and very low BMD is more prevalent in male cALL survivors. Male sex, high cumulative GC doses, CRT, risk group, and low body mass index (BMI) were identified as risk factors for low BMD. A longer follow-up of BMD through time in these survivors is needed to establish if low BMD will translate into a higher risk for fragility fractures through adulthood.

Disclosing One's Non-Heterosexual Sexual Orientation at Work in 2020: A Survey of Quebec LGBQ Workers.

Concealing one's non-heterosexual orientation (NHO) remains a protection strategy against workplace discrimination used by many lesbian, gay, bisexual, and queer (LGBQ+) individuals. This article explores four sets of correlates (identity and individual trajectory, social support, professional position, and structural and cultural work context) relative to three levels of outness (total, partial, and null). Online cross-sectional data of 2,106 LGBQ+ participants from Quebec (Canada) showed that 27% reported total outness, while 64% reported partial outness, and 9%, null outness. Multinomial hierarchical regression analyses revealed that each set of correlates significantly contributed to levels of workplace NHO outness. The two sets of variables making the largest contributions to levels of outness were those pertaining to identity and individual trajectory (14% of the variance) and structural and cultural work context (9%). Compared to partial outness, null outness was associated with an unaccepting work climate, while total outness was more likely in contexts with organizational support (e.g., with the presence of an inclusivity policy). Without trivializing the influence of non-workplace factors on outness levels, the present findings support the need to develop an inclusive and accepting work climate for LGBQ+ individuals.

An exact regression-based approach for the estimation of natural direct and indirect effects with a binary outcome and a continuous mediator.

In the causal mediation framework, a number of parametric regression-based approaches have been introduced in recent years for estimating natural direct and indirect effects for a binary outcome in an exact manner, without invoking simplifying assumptions based on the rareness or commonness of the outcome. However, most of these works have focused on a binary mediator. In this article, we aim at a continuous mediator and introduce an exact approach for the estimation of natural effects on the odds ratio, risk ratio, and risk difference scales. Our approach relies on logistic and linear models for the outcome and mediator, respectively, and uses numerical integration to calculate the nested counterfactual probabilities underlying the definition of natural effects. Formulas for the delta method standard errors for all effects estimators are provided. The performance of our proposed exact estimators was evaluated in simulation studies that featured scenarios with different levels of outcome rareness/commonness, including a marginally but not conditionally rare outcome scenario. Furthermore, we evaluated the merit of Firth's penalization to mitigate the bias in the logistic regression coefficients estimators for the smallest outcome prevalences and sample sizes investigated. Using a SAS macro provided, we implemented our approach to assess the effect of placental abruption on low birth weight mediated by gestational age. We found that our exact natural effects estimators worked properly in both simulated and real data applications.

Social resource patterns and health outcomes among Canadian LGBTQ2+ adults: A latent class analysis.

BACKGROUND: Decades of research have shown a strong association between wellbeing, health, and social resources. LGBTQ2+ communities are among those who historically have been excluded from accessing quality social resources. However, little is known about how access to different types of resources influences mental health and wellbeing. METHOD: Data were drawn from an online sample of 3890 LGBTQ2+ people aged 18 years and older in Quebec, Canada. We identified key social resource patterns (from family of origin, friends, partner, neighbourhood, and LGBTQ2+ community) and investigated differences in socio-demographic and health outcomes across classes. RESULTS: A five-class solution best fitted the data, highlighting distinctive patterns in access to five key social resources: moderate friend support access (42.14%), overall high support access (23.51%), high friend support access (18.06%), only close ties support access (10.90%) and overall low support access (5.39%). Marginalized groups (trans and non-binary people, racialized or disabled people, immigrants) were less likely to access diverse, high-quality social resources. Accessing diverse social resources, particularly close ties (e.g., family of origin), was associated with better health outcomes. In the absence of close ties, having at least one other social resource was associated with better health outcomes compared to having limited access to all resources. CONCLUSIONS: We found a major imbalance in social resource access among LGBTQ2+ people. Creating safe spaces for LGBTQ2+ people and ensuring access to high-quality social resources is important in sustaining their health and wellbeing.

Sexual orientation and gender identity and expression conversion exposure and their correlates among LGBTQI2+ persons in Québec, Canada.

BACKGROUND: Despite greater acceptance of sexual and gender diversity and the scientific consensus that same-gender attraction, creative gender expression, and transness are not mental illnesses, LGBTQI2+ persons are still commonly told that they can or should change their sexual orientation, gender identity, or gender expression (SOGIE). The aim of this study was to describe the prevalence of SOGIE conversion efforts, including their sociodemographic correlates, among LGBTQI2+ persons. METHODS: Using community-based sampling, we assessed SOGIE conversion attempts and involvement in conversion services of 3,261 LGBTQI2+ persons aged 18 years and older in Quebec, Canada. RESULTS: A quarter of respondents experienced SOGIE conversion attempts, and fewer than 5% were involved in conversion services. Over half of those who were involved in SOGIE conversion services consented to them, but the services' goals were made clear and explicit to only 55% and 30% of those who engaged in SO and GIE conversion, respectively. The results also suggest that family plays a key role in SOGIE conversion attempts and services utilization, and that indigenous, intersex, transgender, non-binary, and asexual persons, people of colour, as well as individuals whose sexual orientation is not monosexual (i.e., bisexual, pansexual) were more likely to have been exposed to conversion attempts and involved in conversion services. CONCLUSIONS: This study found that the prevalence of conversion efforts is substantial. Interventions to protect LGBTQI2+ people from such attempts should focus not only on legal bans, but also on supporting families who need to be counseled in accepting sexual and gender diversity. Health professionals need to be adequately trained in LGBTQI2+ affirmative approaches. Religious therapists should consult with colleagues and undergo supervision to ensure that their religious beliefs do not interfere with their practice.

Parametric-Regression-Based Causal Mediation Analysis of Binary Outcomes and Binary Mediators: Moving Beyond the Rareness or Commonness of the Outcome.

In the causal mediation framework, several parametric-regression-based approaches have been introduced in the last decade for estimating natural direct and indirect effects. For a binary outcome, a number of proposed estimators use a logistic model and rely on specific assumptions or approximations that may be delicate or not easy to verify in practice. To circumvent the challenges prompted by the rare outcome assumption in this context, an exact closed-form natural-effects estimator on the odds ratio scale was recently introduced for a binary mediator. In this work, we further push this exact approach and extend it for the estimation of natural effects on the risk ratio and risk difference scales. Explicit formulas for the delta method standard errors are provided. The performance of our proposed exact estimators is demonstrated in simulation scenarios featuring various levels of outcome rareness/commonness. The total effect decomposition property on the multiplicative scales is also examined. Using a SAS macro (SAS Institute, Inc., Cary, North Carolina) we developed, our approach is illustrated to assess the separate effects of exposure to inhaled corticosteroids and placental abruption on low birth weight mediated by prematurity. Our exact natural-effects estimators are found to work properly in both simulations and the real data example.

Predictors of Vertebral Deformity in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia: The PETALE Study.

BACKGROUND: The prevalence of vertebral deformities in long-term survivors of childhood acute lymphoblastic leukemia (ALL) is unknown. Our objectives were to identify the prevalence of vertebral deformities and their risk factors among long-term childhood ALL survivors. METHODS/RESULTS: We recruited 245 (49% male) long-term childhood ALL survivors from the Preventing Late Adverse Effects of Leukemia Cohort (French-Canadian ALL survivors treated between the years 1987 and 2010 with the Dana Farber Cancer Institute clinical trials protocols, who did not experience disease relapse and/or receive hematopoietic stem cell transplant). Median age at recruitment was 21.7 years (range, 8.5-41) and median time since diagnosis was 15.1 years (range, 5.4-28.2). All participants underwent spine radiograph and dual-energy X-ray absorptiometry scans. The prevalence of vertebral deformity was 23% with 88% classified as grade 1 according to the Genant method. The majority of vertebral deformities were clinically silent. Regression analysis confirmed male sex (risk ratio [RR] = 1.94; 95% confidence interval [CI], 1.16-3.24; P = 0.011), higher glucocorticoid cumulative dose (RR = 1.05; 95% CI, 1.00-1.10; P = 0.032), and back pain (RR = 2.44; 95% CI, 1.56-3.84; P < 0.001) as predictors of prevalent vertebral deformity. Sex differences in vertebral deformity predictors emerged. CONCLUSIONS: We report a significant prevalence of vertebral deformities in this young cohort. Male sex, cumulative glucocorticoid dose, and back pain were identified as predictors of prevalent vertebral deformity. Back pain emerging as a strong predictor of vertebral deformity underscores the importance of ongoing bone health surveillance in survivors with persistent vertebral deformities treated with these earlier protocols.

Biomarkers of cardiometabolic complications in survivors of childhood acute lymphoblastic leukemia.

Survivors of childhood acute lymphoblastic leukemia (cALL) are at higher risk of developing cardiometabolic complications. We aimed at exploring the associations between biomarkers of inflammation, oxidative stress, endothelial function, endotoxemia and cardiometabolic risk factors. We conducted a cross-sectional analysis in 246 cALL survivors (mean age, 22.1 ± 6.3 years; mean time since diagnosis, 15.5 ± 5.2 years) and evaluated the associations using a series of logistic regressions. Using structural equation models, we also tested if the relationship between endotoxemia and cardiometabolic complications was mediated by the latent (unobserved) variable inflammation inferred from the observed biomarkers CRP, TNF-α and IL-6. High leptin-adiponectin ratio was associated with obesity [adjusted OR = 15.7; 95% CI (6.2-39.7)], insulin resistance [20.6 (5.2-82.1)] and the metabolic syndrome [11.2 (2.6-48.7)]. Higher levels of plasminogen activator inhibitor-1 and tumor necrosis factor-α were associated with obesity [3.37 (1.6-7.1) and 2.34 (1.3-4.2), respectively] whereas high C-reactive protein levels were associated with insulin resistance [3.3 (1.6-6.8)], dyslipidemia [2.6 (1.4-4.9)] and MetS [6.5 (2.4-17.9)]. Our analyses provided evidence for a directional relationship between lipopolysaccharide binding protein, related to metabolic endotoxemia, inflammation and cardiometabolic outcomes. Identification of biomarkers and biological mechanisms could open new avenues for prevention strategies to minimize the long-term sequelae, improve follow-up and optimize the quality of life of this high-risk population.

Comparing two counterfactual-outcome approaches in causal mediation analysis of a multicategorical exposure: An application for the estimation of the effect of maternal intake of inhaled corticosteroids doses on birthweight.

Although medical research frequently involves an exposure variable with three or more discrete levels, detailed presentations of mediation techniques for dealing with multicategorical (multilevel) exposures are sparse. In this paper, we study two causal mediation approaches applicable to such a type of exposure for continuous mediator and outcome: the closed-form regression-based approach of Valeri and VanderWeele, and the marginal structural model-based approach of Lange, Vansteelandt, and Bekaert. While the consideration of multicategorical exposures is found explicitly addressed in the literature for the latter approach, this is, to our knowledge, not yet the case for the former. We first illustrate the application of the two aforementioned approaches to assess the dose-response relationship between maternal intake of inhaled corticosteroids and birthweight, where this relationship is potentially mediated by gestational age. More specifically, we provide a precise roadmap for the application of the regression-based approach and of the marginal structural model-based approach on our cohort of pregnancies. Expressions for the natural direct and indirect effects associated with our categorical exposure are provided and, for the regression-based approach, analytic formulas for standard error calculation using the delta method are presented for these effects. Second, a simulation study which mimics our data is presented to add to current knowledge on these causal mediation techniques. Results from this study highlight the relevance to assess robustness of mediation results obtained from multicategorical exposures, most notably for the least prevalent of exposure categories.

Physical Activity and Sedentary Behaviors in Childhood Acute Lymphoblastic Leukemia Survivors.

INTRODUCTION: More than two thirds of survivors have long-term adverse effects, and no study proposes a portrait of physical activity level in childhood acute lymphoblastic leukemia survivors. The aims of this study were to present the cardiorespiratory fitness (CRF) levels of survivors detailed overview sedentary activities portrait. METHODS: A total of 247 childhood acute lymphoblastic leukemia survivors were included in our study. Survivors underwent a cardiopulmonary exercise test on ergocycle and completed physical activity and sedentary questionnaires to assess their leisure physical and sedentary activities and total daily energy expenditure. RESULTS: Up to 67% of survivors (84% below 18 y and 60% 18 y of age or above) did not fulfill the physical activity guidelines. Their CRF was reduced by almost 16% in regard to their predicted maximum oxygen consumption (VO2peak). Almost three quarters of the survivors (70% below 18 y and 76% 18 y of age or above) spent >2 hours/day in leisure sedentary activities. Adult survivors who received high doses of anthracyclines and those who received radiation therapy had decreased odds to spend ≥2 hours/day in sedentary activities. CONCLUSIONS: Our results showed that survivors, especially children, were not active enough and had a reduced CRF. This study highlights the importance of promoting physical activity in survivors, especially because they are exposed to an increased risk of chronic health problems, which could be mitigated by physical activity.

Childhood Acute Lymphoblastic Leukemia Survivors Have a Substantially Lower Cardiorespiratory Fitness Level Than Healthy Canadians Despite a Clinically Equivalent Level of Physical Activity.

Introduction: As the survival rate of childhood acute lymphoblastic leukemia (ALL) continues to improve, the physical deconditioning is becoming an increasingly common problem in survivors. The aim of this study was to compare the cardiorespiratory fitness and physical activity levels of survivors and control participants. Methods: A total of 221 childhood ALL survivors (114 males and 107 females), diagnosed between 1987 and 2010 and treated according to Dana Farber Cancer Institute-ALL 87-01 to 05-01 protocols at Sainte-Justine University Health Center (SJUHC), Montreal (Canada), and 825 control participants (364 males and 461 females), recruited in the Canadian Health Measures Survey (cycle 2) during 2009 to 2011 by Statistics Canada, were included in our analyses. In both survivors and controls, cardiorespiratory fitness and moderate to vigorous physical activity (MVPA) were assessed. Results: Survivors' V̇O2 peak was found to be 22% lower than that of controls. Cardiorespiratory fitness was different between the survivors (32.4 ± 8.3 mL/(kg·min); ß = 0.11; 95% confidence interval [CI] 0.07-0.14) and the controls (41.6 ± 9.4 mL/(kg·min); ß = 0.16; 95% CI 0.13-0.18), despite a clinically equivalent level of MVPA [survivors (27.5 ± 27.4 min/day) and controls (33.4 ± 24.2 min/day)]. Status (being survivor) and the age of the participants were negatively associated with cardiorespiratory fitness, whereas MVPA and male gender were positively associated with cardiorespiratory fitness. Conclusion: We observed that for a clinically equivalent level of MVPA, cardiorespiratory fitness was significantly lower in survivors compared with controls. Our findings showed that female survivors were most affected, compared with male survivors. These findings allow further understanding of the physiological differences between childhood ALL survivors and control participants and have important implications for this high-risk population of survivors.

A Bayesian multivariate latent t-regression model for assessing the association between corticosteroid and cranial radiation exposures and cardiometabolic complications in survivors of childhood acute lymphoblastic leukemia: a PETALE study.

BACKGROUND: Childhood acute lymphoblastic leukemia (cALL) is the most frequent pediatric cancer. Over the past decades, treatment of cALL has significantly improved, with cure rates close to 90%. However intensive chemotherapy and cranial radiotherapy (CRT) during a critical period of a child's development have been shown to lead to significant long-term side effects including cardiometabolic complications. Using the PETALE (Prévenir les effets tardifs des traitements de la leucémie aiguë lymphoblastique chez l'enfant) cALL survivor cohort, we investigated the association between combined cumulative corticosteroids (CS) doses and CRT exposures and obesity, insulin resistance, (pre-)hypertension, and dyslipidemia jointly. METHODS: A Bayesian multivariate latent-t model which accounted for our correlated binary outcomes was used for the analyses (n = 241 survivors). CS doses were categorized as low (LD) or high (HD). Combined exposure levels investigated were: 1) LD/no CRT; 2) LD/CRT, and; 3) HD/CRT. We also performed complementary sensitivity analyses for covariate adjustment. RESULTS: Prevalence of cardiometabolic complications ranged from 12.0% for (pre-)hypertension to 40.2% for dyslipidemia. The fully adjusted odds ratio (OR) for dyslipidemia associated with LD/CRT (vs. LD/No CRT) was OR = 1.98 (95% credible interval (CrI): 1.02 to 3.88). LD/CRT level also led to a 0.15 (95% CrI: 0.00 to 0.29) excess risk to develop at least one cardiometabolic complication. Except for obesity, adjusted results for the highest exposure category HD/CRT were generally similar to those for LD/CRT albeit not statistically significant. White blood cell count at diagnosis, a proxy for cALL burden at diagnosis, was found associated with insulin resistance (OR = 1.08 for a 10-unit increase (× 109/L), 95% CrI: 1.02 to 1.14). CONCLUSIONS: Our results indicated that combined LD/CRT exposure is a likely determinant of dyslipidemia among cALL survivors. No evidence was found to suggest that high doses of CS lead to additional risk for obesity, insulin resistance, (pre-)hypertension, and dyslipidemia beyond that induced by CRT. The multivariate model selected for analyses was judged globally useful to assess potential exposure-related concomitance of binary outcomes.

Prevention of Long-term Adverse Health Outcomes With Cardiorespiratory Fitness and Physical Activity in Childhood Acute Lymphoblastic Leukemia Survivors.

BACKGROUND: Most childhood acute lymphoblastic leukemia (ALL) survivors develop chronic treatment-related adverse effects several years after the end of therapy. A regular practice of physical activity and a good cardiorespiratory fitness have the potential to reduce the risk of chronic disease and improve quality of life. The aim of this study was to evaluate in a cohort of ALL survivors, the association between a good cardiorespiratory fitness or the respect of physical activity guidelines and major long-term health outcomes. METHODS: In total, 247 ALL survivors underwent a cardiopulmonary exercise test, completed a physical activity questionnaire and a battery of clinical examinations. We calculated the odds ratio to obtain the preventive fraction (PF) to evaluate the effects of the cardiorespiratory fitness and physical activity levels on health outcomes (ie, obesity, metabolic health, cardiac health, cognitive health and mood, bone health). RESULTS: Despite their young age, 88% of the participants presented at least one adverse health outcome, and 46% presented ≥3. Their cardiorespiratory fitness was also lower than expected with a median VO2 peak reaching 84% of the predicted value. In the analyses using cardiorespiratory fitness, statistically significant PFs were observed for obesity (0.30), low-high-density lipoprotein-cholesterol (0.21) and depression (0.26). In the physical activity level analyses, statistically significant PFs were observed for obesity, depression, and low bone mineral density, with a PF of 0.55, 0.81, and 0.60, respectively. CONCLUSIONS: Our results indicate that a good cardiorespiratory fitness and physical activity level induced a preventive action for most health outcomes studied and was associated with a lower late adverse effects prevalence in ALL survivors.

Point: Risk Ratio Equations for Natural Direct and Indirect Effects in Causal Mediation Analysis of a Binary Mediator and a Binary Outcome-A Fresh Look at the Formulas.

In this article, we review the formulas for the natural direct and indirect effects' risk ratios introduced by Ananth and VanderWeele (Am J Epidemiol. 2011;174(1):99-108) for causal mediation analysis of a binary mediator and a binary outcome. In particular, we show that the closed-form equations Ananth and VanderWeele provided do not correspond to the log-binomial model specified by these authors for the mediator variable, but rather to a logistic model. We then provide risk ratio equations for natural direct and indirect effects that truly pertain to a log-binomial model. We conclude with a discussion on the practical implications of the binary mediator model's specification by analysts. The related impact can be negligible or not, depending on the rareness of the mediator.

Psychological risk in long-term survivors of childhood acute lymphoblastic leukemia and its association with functional health status: A PETALE cohort study.

BACKGROUND: Recent research has suggested that long-term pediatric cancer survivors were at risk of important physical and psychological morbidities. To date, we do not know to what extent functional health status contributes to psychological risk and which domains are most important. The aim of this study was to systematically explore which functional domain could explain anxiety, depression, and distress symptoms. PROCEDURE: We used data available for 105 adolescents and 182 adults successfully treated for childhood acute lymphoblastic leukemia at two Canadian sites part of the PETALE cohort. Participants were ≥5 years postdiagnosis, aged 22 ± 6 years, 52% female, and 49% acute lymphoblastic leukemia high-risk status. The contribution of health functional status (15D/16D questionnaires) to self-reported anxiety, depression, and distress (Beck scales and distress thermometer) was evaluated using adjusted logistic regression models. RESULTS: Prevalence rates found for mild-severe anxiety, depression, and distress were 14%, 21%, and 30% among adolescents and 27%, 20%, and 19% among adults. Frequent health domains associated with psychological risk were sleeping and breathing in adolescents, and vitality/fatigue, discomfort/symptoms, mental function, and sleeping in adults. Mental function was systematically associated with psychological risk across age groups (median OR = 10.00, 95% CI 3.01-33.71). Exploratory mediation bootstrapping analyses suggested that the effect on psychological risk of overall health status and mental function problems was partly explained by social/work/school functioning. CONCLUSION: The results identified important functional health domains that could be targeted for interventions preventing psychological risk: vitality/fatigue, discomfort/symptoms, sleeping, and mental function issues. Health domains probably affect mood partly by limiting social/work/school functioning.

A Bayesian finite mixture of bivariate regression model for causal mediation analyses.

Building on the work of Schwartz et al, Joint Bayesian analysis of birthweight and censored gestational age using finite mixture models in Statistics in Medicine, we propose a Bayesian finite mixture of bivariate regression model for causal mediation analyses. Using an identifiability condition within each component of the mixture, we express the natural direct and indirect effects of the exposure on the outcome as functions of the component-specific regression coefficients. On the basis of simulated data, we examine the behavior of the model for estimating these effects in situations where the associations between exposure, mediator, and outcome are confounded or not. Additionally, we demonstrate that this mixture model can be used to account for heterogeneity arising through unmeasured binary or categorical mediator-outcome confounders. Considering gestational age as a potential mediator, we then illustrate our mediation mixture model to estimate the natural direct and indirect effects of exposure to inhaled corticosteroids during pregnancy on birthweight using a cohort of asthmatic women from the province of Quebec (Canada).

Using a Mixture-of-Bivariate-Regressions Model to Explore Heterogeneity of Effects of the Use of Inhaled Corticosteroids on Gestational Age and Birth Weight Among Pregnant Women With Asthma.

Asthma is a heterogeneous disease, and responses to asthma medications vary noticeably among patients. A substantively oriented objective of this study was to explore the potentially heterogeneous effects of exposure to maternal inhaled corticosteroids (ICS) on gestational age (GA) at delivery and birth weight (BW) using a cohort of 6,197 pregnancies among women with asthma (Quebec, Canada, 1998-2008). A methodologically oriented objective was to comprehensively describe the application of a Bayesian 2-component mixture-of-bivariate-regressions model to address this issue and estimate the effects of ICS on GA and BW jointly. Based on the proposed model, no association between ICS and GA/BW was found for a large proportion of asthmatic pregnancies. However, a positive association between ICS exposure and GA/BW was revealed in a small subset of pregnancies comprising mainly preterm and low-birth-weight infants. A novel application of this model was also subsequently performed using BW z score instead of BW as the outcome variable. In conclusion, the studied mixture-of-bivariate-regressions model was useful for detecting heterogeneity in the effect of ICS on GA and BW in our population of women with asthma. These analyses pave the way for analogous uses of this model for general assessment of exposure effect heterogeneity for these perinatal outcomes.

Correction to: On the use of the outcome variable "small for gestational age" when gestational age is a potential mediator: a maternal asthma perspective.

CORRECTION: Following publication of the original article [1], the authors reported that the following four references in Table 2 are incorrect.

Cardiometabolic Risk Factors in Childhood, Adolescent and Young Adult Survivors of Acute Lymphoblastic Leukemia - A Petale Cohort.

Our objectives were to assess the prevalence of cardiometabolic complications in children, adolescents, and young adult survivors of childhood acute lymphoblastic leukemia (cALL), to identify their predictors and the risk compared to the Canadian population. We performed a cardiometabolic assessment of cALL survivors from the PETALE cohort (n = 247, median age at visit of 21.7 years). In our group, overweight and obesity affected over 70% of women. Pre-hypertension and hypertension were mostly common in men, both adults (20%) and children (19%). Prediabetes was mainly present in women (6.1% of female adult survivors) and 41.3% had dyslipidemia. Cranial radiation therapy was a predictor of dyslipidemia (RR: 1.60, 95% CI: 1.07-2.41) and high LDL-cholesterol (RR: 4.78, 95% CI: 1.72-13.28). Male gender was a predictor for pre-hypertension and hypertension (RR: 5.12, 95% CI: 1.81-14.46). Obesity at the end of treatment was a predictor of obesity at interview (RR: 2.07, 95% CI: 1.37-3.14) and of metabolic syndrome (RR: 3.04, 95% CI: 1.14-8.09). Compared to the general population, cALL survivors were at higher risk of having the metabolic syndrome, dyslipidemia, pre-hypertension/hypertension and high LDL-cholesterol, while the risk for obesity was not different. Our results support the need for early screening and lifestyle intervention in this population.