Social Media and Selfie-Related Mortality Amid COVID-19: Interrupted Time Series Analysis.

BACKGROUND: COVID-19 had a considerable impact on mortality, but its effect on behaviors associated with social media remains unclear. As travel decreased due to lockdowns during the pandemic, selfie-related mortality may have decreased, as fewer individuals were taking smartphone photographs in risky locations. OBJECTIVE: In this study, we examined the effect of the COVID-19 pandemic on trends in selfie-related mortality. METHODS: We identified fatal selfie-related injuries reported in web-based news reports worldwide between March 2014 and April 2021, including the deaths of individuals attempting a selfie photograph or anyone else present during the incident. The main outcome measure was the total number of selfie-related deaths per month. We used interrupted time series regression to estimate the monthly change in the number of selfie-related deaths over time, comparing the period before the pandemic (March 2014 to February 2020) with the period during the pandemic (March 2020 to April 2021). RESULTS: The study included a total of 332 selfie-related deaths occurring between March 2014 and April 2021, with 18 (5.4%) deaths during the pandemic. Most selfie-related deaths occurred in India (n=153, 46.1%) and involved men (n=221, 66.6%) and young individuals (n=296, 89.2%). During the pandemic, two-thirds of selfie-related deaths were due to falls, whereas a greater proportion of selfie-related deaths before the pandemic were due to drowning. Based on interrupted time series regression, there was an average of 1.3 selfie-related deaths per month during the pandemic, compared with 4.3 deaths per month before the pandemic. The number of selfie-related deaths decreased by 2.6 in the first month of the pandemic alone and continued to decrease thereafter. CONCLUSIONS: Our findings indicate that the COVID-19 pandemic led to a marked decrease in selfie-related mortality, suggesting that lockdowns and travel restrictions likely prevented hazardous selfie-taking. The decrease in selfie-related mortality occurred despite a potential increase in social media use during the pandemic.

Association between caesarean birth and childhood cancer: An age-lagged approach.

AIM: We assessed the association between caesarean birth and age-specific risks of childhood cancer. METHODS: We followed a cohort of 1 034 049 children between 2006 and 2020 in Quebec, Canada, from birth until age 14 years. The exposure was caesarean, operative vaginal, or spontaneous vaginal birth. The outcome included haematopoietic or solid tumours. We calculated hazard ratios (HR) and 95% confidence intervals (CI) for the association between mode of delivery and childhood cancer in age-lagged analyses, adjusted for potential confounders. RESULTS: A total of 249 415 (24.1%) children were born by caesarean and 97 411 (9.4%) by operative vaginal delivery. Compared with spontaneous vaginal birth, caesarean was associated with 1.16 times the risk of any cancer (95% CI 1.04-1.30), 1.12 times the risk of haematopoietic cancer (95% CI 0.92-1.36) and 1.21 times the risk of solid tumours (95% 1.06-1.39). Associations strengthened at 2 years of age and were greatest for lymphoma and sarcoma. Operative vaginal birth was not significantly associated with the risk of cancer. CONCLUSION: Caesarean birth may be associated with selected childhood cancers, including lymphoma and sarcoma early in childhood. The underlying reasons for the associations require further investigation, including whether mucosal dysbiosis or labour hormone exposure explain the excess risk.

Hyperemesis Gravidarum and the Potential for Cancer: A Longitudinal Cohort Study over Three Decades.

BACKGROUND: Our objective was to assess whether hyperemesis gravidarum is associated with the risk of endodermal, mesodermal, and ectodermal human chorionic gonadotropin (hCG) receptor+ cancer in women. METHODS: We performed a longitudinal cohort study of 1,343,040 women who were pregnant between 1989 and 2019 in Quebec, Canada. We identified women with and without hyperemesis gravidarum and followed them over time to capture incident cancers, grouped by embryonic germ cell layer of origin and organ hCG receptor positivity. We used time-varying Cox regression to model hazard ratios (HR) and 95% confidence intervals (CI) for the association between hyperemesis gravidarum and cancer onset, adjusted for maternal age, comorbidity, multiple gestation, fetal congenital anomaly, socioeconomic deprivation, and time period. RESULTS: Women with hyperemesis gravidarum had a greater risk of endodermal cancer compared with no hyperemesis gravidarum (5.8 vs. 4.8 per 10,000 person-years; HR, 1.36; 95% CI, 1.17-1.57), but not mesodermal or ectodermal cancer. Severe hyperemesis with metabolic disturbance was more strongly associated with cancer from the endodermal germ layer (HR, 1.97; 95% CI, 1.51-2.58). The association between hyperemesis gravidarum and endodermal cancer was driven by bladder (HR, 2.49; 95% CI, 1.37-4.53), colorectal (HR, 1.41; 95% CI, 1.08-1.84), and thyroid (HR, 1.43; 95% CI, 1.09-1.64) cancer. CONCLUSIONS: Women with hyperemesis gravidarum have an increased risk of cancers arising from the endodermal germ cell layer, particularly bladder, colorectal, and thyroid cancers. IMPACT: Future studies identifying the pathways linking hyperemesis gravidarum with endodermal tumors may help improve the detection and management of cancer in women.

Varying Impact of Gestational Diabetes Mellitus on Incidence of Childhood Cancers: An Age-Stratified Retrospective Cohort Study.

OBJECTIVE: We studied the association between gestational diabetes mellitus and early versus late childhood cancer. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study of 1 million children born between 2006 and 2019 in Quebec, Canada. We identified children who were exposed to gestational diabetes mellitus in utero and followed them from birth up to 14 years of age to identify new-onset cancers. We estimated hazard ratios (HRs) for the association between gestational diabetes mellitus and childhood cancer using Cox proportional regression models with adjustment for covariates through inverse propensity score weights. RESULTS: A total of 83,626 children (8.2%) were exposed to gestational diabetes mellitus, and 1,702 developed cancer during 7.6 million person-years of follow-up. Children exposed to gestational diabetes mellitus had a higher risk of any cancer (HR 1.19, 95% CI 1.01-1.40), with signals present for blood cancer (HR 1.27, 95% CI 0.92-1.76) and solid tumors (HR 1.14, 95% CI 0.94-1.40). The association between gestational diabetes mellitus and cancer was strongest early in life and decreased with age. Gestational diabetes mellitus was associated with 1.47 times the risk of any cancer (95% CI 1.21-1.79), 1.44 times the risk of solid cancer (95% CI 1.12-1.87), and 1.61 times the risk of blood cancer (95% CI 1.09-2.36) in children age <2 years. Gestational diabetes mellitus was not significantly associated with blood or solid cancers after 2 years of age, and all associations disappeared after 6 years. CONCLUSIONS: Hyperglycemia may be carcinogenic in utero and may be a novel risk factor for early childhood cancer.

Matched cohort study of hospitalization in children who have siblings with cancer.

BACKGROUND: Health outcomes of children in families affected by cancer are poorly understood. The authors assessed the risk of hospitalization in children who have a sibling with cancer. METHODS: This was a longitudinal cohort study in which 1600 children who had a sibling with cancer were matched to 32,000 children who had unaffected siblings in Quebec, Canada, from 2006 to 2020. The exposure of interest was having a sibling with cancer. Outcomes included hospitalization for pneumonia, asthma, fracture, and other morbidities any time after the sibling was diagnosed with cancer. The children were followed over time, and Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the impact of having a sibling with cancer on the risk of hospitalization before age 14 years, adjusted for patient characteristics. RESULTS: Children who had a sibling with cancer had an increased risk of hospitalization compared with unaffected children (HR, 1.15; 95% CI, 1.02-1.29). Conditions associated with a greater risk of hospitalization included pneumonia, hemangioma, other skin conditions, sleep apnea, and inflammatory bowel disease. The risk of hospitalization was greatest for children whose older sibling had cancer (HR, 1.16; 95% CI, 1.01-1.32) and for children whose sibling had hematopoietic cancer (HR, 1.22; 95% CI, 1.01-1.48). CONCLUSIONS: Children who have a sibling with cancer are at risk of hospitalization for conditions such as pneumonia, inflammatory bowel disease, and other morbidities. Families affected by childhood cancer may benefit from additional support to facilitate care for all children in the family. LAY SUMMARY: Little is known about the health of children who have a brother or sister with cancer. The authors studied the types of hospitalization experienced by children who have siblings with cancer. The results indicated that having a sibling with cancer increased the chance of being hospitalized for pneumonia and other conditions that could have been preventable. The results also indicated that children who had an older sibling with cancer or a sibling with blood cancer had a greater chance of being hospitalized. The findings highlight the importance of providing timely care for children in families affected by childhood cancer.

Cardiovascular disease and cancer in women with accreta and retained placenta: a longitudinal cohort study.

PURPOSE: The association between placental detachment disorders and risk of chronic disease is unclear. We determined the association of placenta accreta and retained placenta with risk of future maternal cardiovascular disease and cancer. METHODS: We tracked a longitudinal cohort of 541,051 pregnant women over a period of 13 years (2006-2019) in Quebec, Canada. The main exposure measures were placenta accreta and retained placenta in any pregnancy. Outcomes included future hospitalizations for cardiovascular disease and cancer. Using Cox regression models adjusted for maternal characteristics, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association of accreta and retained placenta with cardiovascular disease and cancer at 13 years. RESULTS: The incidence of cardiovascular hospitalization was 21.2 per 10,000 person-years for accreta and 23.4 per 10,000 for retained placenta with postpartum hemorrhage, compared with 20.3 per 10,000 for neither placental disorder. Cancer incidence followed a similar pattern, with rates highest for retained placenta with hemorrhage. Retained placenta with hemorrhage was associated with 1.19 times the risk of cardiovascular disease (95% CI 1.03-1.38) and 1.27 times the risk of cancer (95% CI 1.06-1.53). Retained placenta with hemorrhage was associated with heart failure (HR 1.84, 95% CI 1.04-3.27), cardiomyopathy (HR 1.88, 95% CI 1.03-3.43), and cervical cancer (HR 2.03, 95% CI 1.17-3.52). Accreta and retained placenta without hemorrhage were not associated with these outcomes. CONCLUSION: Retained placenta with hemorrhage may be a risk marker for cardiovascular disease and certain cancers later in life.

The Role of Oxidative Stress and Inflammation in Cardiometabolic Health of Children During Cancer Treatment and Potential Impact of Key Nutrients.

Significance: The 5-year survival rate of childhood cancers is now reaching 84%. However, treatments cause numerous acute and long-term side effects. These include cardiometabolic complications, namely hypertension, dyslipidemia, hyperglycemia, insulin resistance, and increased fat mass. Recent Advances: Many antineoplastic treatments can induce oxidative stress (OxS) and trigger an inflammatory response, which may cause acute and chronic side effects. Critical Issues: Clinical studies have reported a state of heightened OxS and inflammation during cancer treatment in children as the result of treatment cytotoxic action on both cancerous and noncancerous cells. Higher levels of OxS and inflammation are associated with treatment side effects and with the development of cardiometabolic complications. Key nutrients (omega-3 polyunsaturated fatty acids, dietary antioxidants, probiotics, and prebiotics) have the potential to modulate inflammatory and oxidative responses and, therefore, could be considered in the search for adverse complication prevention means as long as antineoplastic treatment efficiency is maintained. Future Directions: There is a need to better understand the relationship between cardiometabolic complications, OxS, inflammation and diet during pediatric cancer treatment, which represents the ultimate goal of this review. Antioxid. Redox Signal. 35, 293-318.

Optimizing childhood oncology care transition from pediatric to adult settings: A survey of primary care physicians' and residents' perspectives.

PURPOSE: The majority of childhood cancer survivors suffer from late adverse effects after the completion of treatment. The prospect of most survivors reaching middle-age is a relatively new phenomenon, and the ways by which current and future primary care physicians (PCPs) will address this novel public health challenge are uncertain. METHODS: A survey assessing knowledge level and information delivery preferences regarding long-term follow-up guidelines for adult patients having survived a childhood cancer was distributed by e-mail through the Quebec (Canada) national associations of PCPs and residents (n=238). RESULTS: Participants reported an estimated average of 2.9 ± 1.9 cancer survivors in their yearly caseload, and only 35.3% recalled having provided services to at least one survivor in the last year. Most participants indicated ignoring validated follow-up guidelines for these patients (average score 1.66 on a Likert scale from "1-totally disagreeing" to "5-totally agreeing"). Scarce access to personalized follow-up guidelines and lack of clinical exposure to cancer survivors were identified as main obstacles in providing optimal care to these patients (respective averages of 1.66 and 1.84 on a Likert scale from "1- is a major obstacle" to "5-is not an obstacle at all"). CONCLUSION: The PCPs and residents rarely provide care for childhood cancer adult survivors. On an individual basis, there is a clear need for increased awareness, education and collaboration regarding long-term care of childhood cancer adult survivors during medical training. On a more global basis, structural, organizational and cultural changes are also needed to ensure adequate care transition.

Residential exposure to electromagnetic fields during pregnancy and risk of child cancer: A longitudinal cohort study.

OBJECTIVE: We assessed whether exposure to electromagnetic fields during pregnancy increases the risk of childhood cancer. METHODS: We studied a retrospective cohort of 784,944 newborns in Quebec, Canada between 2006 and 2016 who were followed for cancer one decade after birth. The exposures were residential distance to the nearest high voltage power transformer station and transmission line. We determined the incidence of childhood cancer, and estimated hazard ratios and 95% confidence intervals (CI) in Cox proportional hazards regression models adjusted for maternal and birth characteristics. RESULTS: There were 1114 incident cases of cancer during 4,647,472 person-years of follow-up. Residential proximity to transformer stations was associated with a somewhat greater risk of cancer, but there was no association with transmission lines. Compared with 200 m, a distance of 80 m from a transformer station was associated with a hazard ratio of 1.08 (95% CI 0.98, 1.20) for any cancer, 1.04 (95% CI 0.88, 1.23) for hematopoietic cancer, and 1.11 (95% CI 0.99, 1.25) for solid tumours. CONCLUSIONS: Residential proximity to transformer stations is associated with a borderline risk of childhood cancer, but the absence of an association with transmission lines suggests no causal link.

The PETALE study: Late adverse effects and biomarkers in childhood acute lymphoblastic leukemia survivors.

BACKGROUND: Childhood cancer survivorship issues represent an established public health challenge. Most late adverse effects (LAEs) have been demonstrated to be time and treatment dependent. The PETALE study is a multidisciplinary research project aiming to comprehensively characterize LAEs and identify associated predictive biomarkers in childhood acute lymphoblastic leukemia (cALL) survivors. METHODS: cALL survivors treated at Sainte-Justine University Health Center with Dana-Farber Cancer Institution-ALL protocols 87-01 through 2005-01 were eligible. During Phase I of the study, the participants underwent comprehensive clinical, biologic, and psychosocial investigation targeting metabolic syndrome, cardiotoxicity, bone morbidity, neurocognitive problems, and quality of life issues. Whole-exome sequencing was performed for all participants. Subjects identified with an extreme phenotype during Phase I were recalled for additional testing (Phase II). RESULTS: Phase I included 246 survivors (recall rate 71.9%). Of those, 85 participants completed Phase II (recall rate 88.5%). Survivors agreeing to participate in Phase I (n = 251) were similar to those who refused (n = 31) in terms of relapse risk profile, radiotherapy exposure, and age at the time of study. Participants, however, tended to be slightly older at diagnosis (6.1 vs. 4.7 years old, P = 0.08), with a higher proportion of female agreeing to participate compared with males (93.2 vs. 86.5%, P = 0.07). CONCLUSION: The PETALE study will contribute to comprehensively characterize clinical, psychosocial, biologic, and genomic features of cALL survivors using an integrated approach. Expected outcomes include LAE early detection biomarkers, long-term follow-up guidelines, and recommendations for physicians and health professionals.

Expression of the senescence marker p16INK4a in skin biopsies of acute lymphoblastic leukemia survivors: a pilot study.

BACKGROUND: Most childhood cancer survivors will develop ionizing radiation treatment-related health conditions that, in many instances, resemble age-associated pathologies. Treatment-induced premature senescence could be an underlying mechanism. FINDINGS: Here we wanted to know whether the expression of p16INK4a, a senescence/aging biomarker, is increased in skin biopsies of acute lymphoblastic leukemia survivors (ALL), previously exposed to chemotherapy and radiation therapy. Several years post-treatments, we found p16INK4a mRNA levels are 5.8 times higher in scalp skin biopsies (targeted by cranial irradiation therapy) compared to buttocks skin biopsies (n = 10, p = 0.01). CONCLUSIONS: These results demonstrate for the first time that premature senescence is induced in pediatric cancer survivors and that p16INK4a expression could be used as a potential biomarker in this population.

Role of NOS3 DNA variants in externalizing behavioral problems observed in childhood leukemia survivors.

OBJECTIVE: Neuropsychological problems occurrence varies among childhood cancer survivors, and associated risk factors have not been fully deciphered. We wanted to study the role of genetic variants in behavioral problems in this population. STUDY DESIGN: Behavioral problems in pediatric acute lymphoblastic leukemia patients (n=138) were investigated longitudinally, using the Child Behavior Checklist questionnaire and multilevel statistical modeling. Thirty-four candidate polymorphisms, related to anticancer drug effects, were investigated. RESULTS: NOS3 gene functional polymorphisms showed significant association: patients homozygous for the minor allele at investigated loci showed decreased externalizing behavioral problems scores over time (t tests: T-786C n=69, P=0.003; G894T n=71, P=0.065). The effect was even more pronounced for individuals that are homozygous for the -786C844T haplotype (t test, n=69, P<0.001) and results were supported by multilevel modeling analyses (P<0.001). No such association was observed for internalizing behavioral problems. CONCLUSION: NOS3 variants modulate externalizing problems individual trajectories, likely in relationship with glucocorticoid exposure.

Predictive factors of internalized and externalized behavioral problems in children treated for acute lymphoblastic leukemia.

BACKGROUND: Pediatric cancer survivors are at increased risk of various neurological and psychological problems. The prevalence of behavioral problems was assessed in a longitudinal study in pediatric patients with an acute lymphoblastic leukemia (ALL). Multilevel modeling was used to identify associated predictive factors. PROCEDURE: ALL patients and their parents (n = 138) took part to this study. Patients were treated according to the Dana-Farber Cancer Institute (DFCI) consortium protocols 91-01 or 95-01. Mothers filled out questionnaires providing a measure of behavioral problems for their child at diagnosis and during the subsequent 4 years, and of their perceived familial stress at diagnosis and post-induction. RESULTS: Prevalence of internalized behavioral problems at diagnosis was increased [42% above 1 standard deviation (SD); P < 0.001], but it normalized over time. Internalized problems resolved more slowly in the presence of medical variables associated with increased stress related to the disease (hospitalization duration, P < 0.001; relapse risk at diagnosis, P < 0.001). Externalized behavioral problems were within the expected normal range, but more sustained over time with the 95-01 than with the 91-01 treatment protocols (P < 0.05), likely due to the type of corticosteroid (CS) used (dexamethasone vs. prednisone). CONCLUSIONS: Assessment of both internalized and externalized problems is required in this population. The impact of pharmacological variables on externalized behavioral problems is likely related to CS use.

Pharmacogenetics of the neurodevelopmental impact of anticancer chemotherapy.

Pharmacogenetics holds the promise of minimizing adverse neurodevelopmental outcomes of cancer patients by identifying patients at risk, enabling the individualization of treatment and the planning of close follow-up and early remediation. This review focuses first on methotrexate, a drug often implicated in neurotoxicity, especially when used in combination with brain irradiation. The second focus is on glucocorticoids that have been found to be linked to adverse developmental effects in relation with the psychosocial environment. For both examples, we review how polymorphisms of genes encoding enzymes involved in specific mechanisms of action could moderate adverse neurodevelopmental consequences, eventually through common final pathways such as oxidative stress. We discuss a multiple hit model and possible strategies required to rise to the challenge of this integrative research.