Absorbed Dose-Response Relationship in Patients with Gastroenteropancreatic Neuroendocrine Tumors Treated with [177Lu]Lu-DOTATATE: One Step Closer to Personalized Medicine.

[177Lu]Lu-DOTATATE has been approved for progressive and inoperable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that overexpress somatostatin receptors. The absorbed doses by limiting organs and tumors can be quantified by serial postinfusion scintigraphy measurements of the γ-emissions from 177Lu. The objective of this work was to explore how postinfusion [177Lu]Lu-DOTATATE dosimetry could influence clinical management by predicting treatment efficacy (tumor shrinkage and survival) and toxicity. Methods: Patients with GEP-NETs treated with [177Lu]Lu-DOTATATE between 2016 and 2022 and who underwent dosimetry were included. Absorbed doses were calculated for healthy organs (liver, kidneys, bone marrow, and spleen) and tumors using PLANET Dose and the local energy deposition method based on serial posttreatment SPECT/CT. Up to 5 lesions per site were selected and measured on images collected at baseline and 3 mo after treatment end (measurement masked to the somatostatin receptor imaging uptake). For toxicity assessment, laboratory parameters were regularly monitored. Clinical data, including time to death or progression, were collected from the patients' health records. Correlations between absorbed doses by organs and toxicity and between absorbed doses by lesions and tumor volume variation were studied using regression models. Results: In total, 35 dosimetric studies were performed in patients with mostly grade 2 (77%) tumors and metastases in liver (89%), lymph nodes (77%), and bone (34%), and 146 lesions were analyzed: 1-9 lesions per patient, mostly liver metastases (65%) and lymph nodes (25%). The median total absorbed dose by tumors was 94.4 Gy. The absorbed doses by tumors significantly decreased between cycles. The absorbed dose by tumors was significantly associated with tumor volume variation (P < 0.001) 3 mo after treatment end, and it was a significant prognostic factor for survival. Toxicity analysis showed a correlation between the decrease of hematologic parameters such as lymphocytes or platelet concentrations and the absorbed doses by the spleen or bone marrow. The mean absorbed dose by the kidneys was not correlated with nephrotoxicity during the studied period. Conclusion: In patients treated with [177Lu]Lu-DOTATATE for GEP-NETs, tumor and healthy organ dosimetry can predict survival and toxicities, thus influencing clinical management.

Parents' depression and anxiety associated with hyperactivity-inattention and emotional symptoms in children during school closure due to COVID-19 in France.

Several risk factors of children's mental health issues have been identified during the pandemic of COronaVIrus Disease first appeared in 2019 (COVID-19). This study aims to fill the knowledge gap regarding the association between parents' and children's mental health issues during the COVID-19 school closure in France. We conducted a cross-sectional analysis of data collected in the SAPRIS-ELFE study during the COVID-19 pandemic in France. Using multinomial logistic regressions, we estimated associations between parents' and children's mental health issues. Symptoms of anxiety were assessed by the General Anxiety Disorder-7 (GAD-7) and depression by the Patient Health Questionnaire-9 (PHQ-9) for the parents. Hyperactivity/inattention and emotional symptoms in children were assessed by the Strengths and Difficulties Questionnaire (SDQ). The sample included 3496 children aged 8 to 9 years, of whom 50.0% were girls. During the school closure, 7.1% of responding parents had moderate to severe levels of anxiety and 6.7% had moderate to severe levels of depression. A total of 11.8% of the children had an abnormal hyperactivity/inattention score and 6.6% had an abnormal emotional symptoms score. In multivariate regression models, parental moderate to severe level of anxiety and moderate to severe level of depression were associated with abnormal hyperactivity-inattention score (adjusted Odds Ratio (aOR) 3.31; 95% Confidence Interval (CI) 2.33-4.70 and aOR 4.65; 95% CI 3.27-6.59, respectively) and abnormal emotional symptoms score in children (aOR 3.58; 95% CI 2.33-5.49 and aOR 3.78; 95 CI 2.47-5.78 respectively). Children whose parents have symptoms of anxiety and/or depression have an increased likelihood of symptoms of hyperactivity/inattention and emotional symptoms during school closures in France due to COVID-19. Our findings suggest that public health initiatives should target parents and children to limit the impact of such crises on their mental health issues.

Longitudinal impact of psychosocial status on children's mental health in the context of COVID-19 pandemic restrictions.

Emerging research suggests that the prevalence of child and adolescent mental health problems has increased considerably during the COVID-19 crisis. However, there have been few longitudinal studies on children's mental health issues according to their social determinants in this context, especially in Europe. Our aim was to investigate the association between family socioeconomic status (SES) and children' mental health during the period of school closure due to COVID-19. Longitudinal data came from 4575 children aged 8-9 years old in 2020 and participating in the ELFE population-based birth cohort that focuses on children's health, development and socialization. Parents completed the Strengths and Difficulties Questionnaire (SDQ) when children were (a) 5 years of age and (b) 9 years of age, which corresponded to the period of school closure due to the COVID-19 pandemic in France. We retrieved data from the ELFE cohort collected on children from birth to age 5 years (birth, 1 year, 2 years, 3,5 years and 5 years). Socioeconomic status (SES) was measured based on information obtained when the child was 5 years old. Data were analyzed using multinomial logistic regression models. Children's elevated levels of symptoms of Attention-deficit/Hyperactivity disorder (ADHD) during the period of school closure were significantly associated with prior low family SES (aOR 1.26, 95% CI 1.08-1.48). Children's elevated symptoms of hyperactivity/inattention and of emotional symptoms were associated with decline in income during the COVID crisis (respectively, aOR 1.38, 95% CI 1.16-1.63 and aOR 1.23, 95% CI 1.01-1.51). Moreover, when testing interactions, a low prior SES was significantly associated with a higher risk of emotional symptoms aOR 1.54 (1.07-2.21), only for children whose families experienced a decline in income, while gender, parental separation and prior mental health difficulties were not associated. This study underlines the impact of the financial crisis related to the COVID-19 epidemic on children's mental health. Both pre-existing family SES before lockdown and more proximal financial difficulties during the COVID crisis were negatively associated with children's psychological difficulties during the period of school closure. The pandemic appears to exacerbate mental health problems in deprived children whose families suffer from financial difficulties.

Emotional and attention-deficit/hyperactivity disorder symptoms of preterm vs. full-term children during COVID-19 pandemic restrictions.

BACKGROUND: Preterm children are at higher risk of developing mental health problems than full-term children. Deterioration of children's mental health was observed during COVID-19 pandemic restrictive measures. Our study compared emotional and attention-deficit/hyperactivity disorder (ADHD) symptoms during school closure between preterm and full-term children. METHODS: Data from two French birth cohorts-ELFE and EPIPAGE-2-were used. In 2011, infants born ≥22 weeks' gestation were recruited. Parents completed the Strengths and Difficulties Questionnaire when the children were 9 years old and experiencing school closure. Multivariate multinomial logistic regression models were used. RESULTS: Subjects included 4164 full-term and 1119 preterm children. In univariate analyses, compared to full-term children: extremely and very preterm children more frequently had abnormal and borderline ADHD scores (odds ratio [OR] 1.86, 95% confidence interval [CI] 1.50-2.30, OR 1.42, 95% CI 1.08-1.85, respectively) and abnormal emotional scores (OR 1.86, 95% CI 1.43-2.40); moderate to late preterm children more often had abnormal ADHD scores (OR 1.33, 95% CI 1.01-1.78). The associations did not remain when previous symptoms at 5 years old were considered. CONCLUSIONS: School closure during lockdown did not appear to increase the risk of mental health problems in preterm compared to full-term children. IMPACT STATEMENT: Preterm children are at higher risk of developing mental health problems than full-term children. Deterioration in children's mental health was observed during COVID-19 pandemic restrictions. However, whether preterm children were a particularly vulnerable subgroup during school closure is unclear. In univariate analyses, extremely and very preterm children more often had abnormal and borderline ADHD symptoms and abnormal emotional symptom scores than full-term children. The associations did not remain significantly associated when previous symptoms were considered. Preterm compared to full-term children more often suffer from ADHD and emotional symptoms, but school closure during lockdown did not appear to increase this risk.

Children's mental and behavioral health, schooling, and socioeconomic characteristics during school closure in France due to COVID-19: the SAPRIS project.

COVID-19 limitation strategies have led to widespread school closures around the world. The present study reports children's mental health and associated factors during the COVID-19 school closure in France in the spring of 2020. We conducted a cross-sectional analysis using data from the SAPRIS project set up during the COVID-19 pandemic in France. Using multinomial logistic regression models, we estimated associations between children's mental health, children's health behaviors, schooling, and socioeconomic characteristics of the children's families. The sample consisted of 5702 children aged 8-9 years, including 50.2% girls. In multivariate logistic regression models, children's sleeping difficulties were associated with children's abnormal symptoms of both hyperactivity-inattention (adjusted Odds Ratio (aOR) 2.05; 95% Confidence Interval 1.70-2.47) and emotional symptoms (aOR 5.34; 95% CI 4.16-6.86). Factors specifically associated with abnormal hyperactivity/inattention were: male sex (aOR 2.29; 95% CI 1.90-2.76), access to specialized care prior to the pandemic and its suspension during school closure (aOR 1.51; 95% CI 1.21-1.88), abnormal emotional symptoms (aOR 4.06; 95% CI 3.11-5.29), being unschooled or schooled with assistance before lockdown (aOR 2.13; 95% CI 1.43-3.17), and tutoring with difficulties or absence of a tutor (aOR 3.25; 95% CI 2.64-3.99; aOR 2.47; 95% CI 1.48-4.11, respectively). Factors associated with children's emotional symptoms were the following: being born pre-term (aOR 1.34; 95% CI 1.03-1.73), COVID-19 cases among household members (aOR 1.72; 95% CI 1.08-2.73), abnormal symptoms of hyperactivity/inattention (aOR 4.18; 95% CI 3.27-5.34) and modest income (aOR 1.45; 95% CI 1.07-1.96; aOR 1.36; 95% CI 1.01-1.84). Multiple characteristics were associated with elevated levels of symptoms of hyperactivity-inattention and emotional symptoms in children during the period of school closure due to COVID-19. Further studies are needed to help policymakers to balance the pros and cons of closing schools, taking into consideration the educational and psychological consequences for children.

Risk of Severe Maternal Morbidity After Bariatric Surgery: Retrospective Cohort Study.

OBJECTIVE: We assessed whether bariatric surgery before pregnancy lowers the risk of severe maternal morbidity to a level comparable to no obesity. SUMMARY OF BACKGROUND DATA: Obesity is a risk factor for severe maternal morbidity, but the potential for bariatric surgery to reduce the risk has not been studied. METHODS: We analyzed a retrospective cohort of 2,412,075 deliveries between 1989 and 2019 in Quebec, Canada. The main exposure measures were bariatric surgery before pregnancy and obesity without bariatric surgery, compared with no obesity. The outcome was severe maternal morbidity, a composite of life-threatening pregnancy complications. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association between bariatric surgery and severe maternal morbidity, adjusted for maternal characteristics. RESULTS: A total of 2654 deliveries (0.1%) were in women who had bariatric surgery, and 70,041 (29.0 per 1000) were in women who had severe maternal morbidity. Risk of severe maternal morbidity was not significantly elevated for bariatric surgery (RR 1.20; 95% CI 0.98-1.46), but was greater for obesity compared with no obesity (RR 1.60; 95% CI 1.55-1.64). Bariatric surgery was not associated with morbidities such as severe preeclampsia, sepsis, and cardiac complications compared with no obesity, but obesity was associated with elevated risks of these and other severe morbidities. Bariatric surgery was associated, however, with intensive care unit admission, compared with no obesity. CONCLUSIONS: Pregnant women with prior bariatric surgery have similar risks as nonobese women for most types of severe maternal morbidity, except for intensive care unit admission.

Maternal Mental Disorders and Pediatric Infectious Diseases: A Retrospective Cohort Study.

BACKGROUND: Maternal stress and depression are associated with infections in offspring, but there is a paucity of data for other mental disorders. METHODS: We conducted a retrospective cohort study of 832,290 children born between 2006 and 2016 in hospitals of Quebec, Canada. We identified maternal mental disorders before and during pregnancy, and admissions for otitis media, pneumonia, infectious enteritis and other infections in children before 13 years of age. We used Cox proportional hazards regression to estimate hazard ratios (HRs) with 95% confidence intervals (CI) for the association between maternal mental disorders and the risk of pediatric infectious diseases, adjusted for maternal age, comorbidity, socioeconomic disadvantage, and other confounders. RESULTS: The incidence of pediatric infection hospitalization was higher for maternal mental disorders compared with no disorder (66.1 vs. 41.1 cases per 1000 person-years). Maternal mental disorders were associated with 1.38 times the risk of otitis media (95% CI: 1.35-1.42), 1.89 times the risk of bronchitis (95% CI: 1.68-2.12), and 1.65 times the risk of infectious enteritis in offspring (95% CI: 1.57-1.74). Stress and anxiety disorders (HR 1.49, 95% CI: 1.46-1.53) and personality disorders (HR 1.55, 95% CI: 1.49-1.61) were more strongly associated with the risk of pediatric infection hospitalization than other maternal mental disorders. Associations were prominent in the first year of life and weakened with age. CONCLUSIONS: Maternal mental disorders are risk factors for infectious disease hospitalization in offspring. Women with mental disorders may benefit from psychosocial support to reduce the risk of serious infections in their children.