Cohort Profile: Quebec Longitudinal Study of Child Development (QLSCD).

PURPOSE: The Quebec Longitudinal Study of Child Development (QLSCD) was designed to examine the long-term associations of preschool physical, cognitive, social, and emotional development with biopsychosocial development across childhood, adolescence, and young adulthood. METHODS: QLSCD is an ongoing prospective cohort including 2120 singletons born in 1997/1998 in the Canadian province of Quebec. So far, data have been collected annually or every 2 years from child ages 5 months to 21 years. The cohort currently includes 1245 participants. Data available include a range of environmental (e.g., family characteristics, child behaviour, educational attainment, mental health), biological (e.g., hair cortisol, genetic, epigenetic), and administrative data. RESULTS: QLSCD has contributed to the understanding of children's psychosocial development, including the development of physical aggression and anxiety. QLSCD articles have advanced scientific knowledge on the influence of early childhood factors on childhood, adolescent, and young adult mental health, including the effect of participation in early childcare on cognitive and behavioural development, the developmental origins of adolescent and young adult mental health problems and suicide risk, and the development of interpersonal difficulties (e.g., peer victimisation) from preschool years to adolescence. CONCLUSION: QLSCD has given major contributions to our understanding of the link between different aspects of child development and biopsychosocial development during the first two decades of life. Unique features include the presence of environmental, biological, and administrative data, long-term follow-up with frequent data collections, and use of data from multiple informants, including teachers, mothers, fathers, and the children themselves.

Drivers of variation in telemedicine use during the COVID-19 pandemic: The experience of a large academic cardiovascular practice.

BACKGROUND: COVID-19 spurred rapid adoption and expansion of telemedicine. We investigated the factors driving visit modality (telemedicine vs. in-person) for outpatient visits at a large cardiovascular center. METHODS: We used electronic health record data from March 2020 to February 2021 from four cardiology subspecialties (general cardiology, electrophysiology, heart failure, and interventional cardiology) at a large academic health system in Northern California. There were 21,912 new and return visits with 69% delivered by telemedicine. We used hierarchical logistic regression and cross-validation methods to estimate the variation in visit modality explained by patient, clinician, and visit factors as measured by the mean area under the curve. RESULTS: Across all subspecialties, the clinician seen was the strongest predictor of telemedicine usage, while primary visit diagnosis was the next most predictive. In general cardiology, the model based on clinician seen had a mean area under the curve of 0.83, the model based on the primary diagnosis had a mean area under the curve of 0.69, and the model based on all patient characteristics combined had a mean area under the curve of 0.56. There was significant variation in telemedicine use across clinicians within each subspecialty, even for visits with the same primary visit diagnosis. CONCLUSION: Individual clinician practice patterns had the largest influence on visit modality across subspecialties in a large cardiovascular medicine practice, while primary diagnosis was less predictive, and patient characteristics even less so. Cardiovascular clinics should reduce variability in visit modality selection through standardized processes that integrate clinical factors and patient preference.

Clinical and Radiologic Disease Activity in Pregnancy and Postpartum in MS.

OBJECTIVE: To evaluate radiologic and clinical inflammatory activity in women with MS during pregnancy and postpartum. METHODS: We performed a retrospective analysis of prospectively collected clinical and MRI reports for women who became pregnant while followed at the University of California, San Francisco MS Center between 2005 and 2018. Proportion of brain MRIs with new T2-hyperintense or gadolinium enhancing (Gd+) lesions (primary outcome) and annualized relapse rate (ARR; secondary) were compared before and after pregnancy. RESULTS: We identified 155 pregnancies in 119 women (median Expanded Disability Status Scale [EDSS] 2.0). For the 146 live birth pregnancies, prepregnancy ARR was 0.33; ARR decreased during pregnancy, particularly the third trimester (ARR 0.10, p = 0.017) and increased in the 3 months postpartum (ARR 0.61, p = 0.012); and 16% of women experienced a clinically meaningful increase in EDSS. Among 70 pregnancies with paired brain MRIs available, 53% had new T2 and/or Gd+ lesions postpartum compared with 32% prepregnancy (p < 0.001). Postpartum clinical relapses were associated with Gd+ lesions (p < 0.001). However, even for patients without postpartum relapses, surveillance brain MRIs revealed new T2 and/or Gd+ lesions in 31%. Protective effects of exclusive breastfeeding for ≥3 months (odds ratio = 0.3, 95% confidence interval 0.1-0.9) were observed for relapses. CONCLUSIONS: Building on previous reports of increased relapse rate in the first 3 months postpartum, we report a significant association between inflammation on MRI and this clinical activity. We also detected postpartum radiologic activity in the absence of relapses. Both clinical and radiologic reassessment may inform optimal treatment decision-making during the high-risk early postpartum period.

Comparison of MS inflammatory activity in women using continuous versus cyclic combined oral contraceptives.

BACKGROUND: Many women with multiple sclerosis (MS) report fluctuating symptoms across their menstrual cycle. Oral contraceptives (OCs) alter hormonal levels across the menstrual cycle. While cyclic OCs administer hormones for 21 days, followed by a week of placebo, continuous OCs can administer continuous doses of hormones for up to 3 months. Previous studies have suggested that OC use is associated with lower MS-related inflammation. We hypothesized that due to reduced hormonal fluctuations, women with MS might experience less inflammatory activity (clinical relapses+MRI) on continuous OCs than on cyclic OCs. METHODS: We performed a retrospective analysis of prospectively collected data. For women with MS aged 18-50 seen at the UCSF Center for MS and Neuroinflammation, we extracted data on OC use from the Electronic Medical Records (EMR). All variables were confirmed using manual clinical chart review. We identified 19 women with relapsing forms of MS on continuous OCs and matched them (2:1 when possible) to women on cyclic OCs for OC formulation, age, MS duration and DMT type. Inflammatory activity in the two groups was then compared using log-rank tests (time to new relapse, new T2-weighted lesion formation, and gadolinium-enhancing lesion formation) and t-tests (annualized relapse rate). We also performed subgroup analyses in women with at least 1 year (N = 28) and 2 years (N = 21) of clinical observation. A power calculation was performed. RESULTS: There was no difference in time to relapse (p = 0.50) between continuous and cycling OC users. However, continuous OC users showed a statistical trend to longer time to T2 lesion formation (p = 0.09) and longer time to contrast-enhancing lesion formation (p = 0.05). In patients with at least 1 year of observation, there was a significant difference in time to T2 lesion formation (p = 0.03) and time to contrast-enhancing lesion formation (p = 0.02). CONCLUSION: In this exploratory study, women on continuous OCs showed a trend towards less inflammatory activity on MRI relative to women on cyclic OCs. This difference was not reflected in relapse rates. We estimate that 342 patients would be required for an adequately powered cohort study to evaluate such an effect. Our findings provide reassurance that for women using continuous OCs to alleviate menstrual fluctuations in symptoms, there is not an increase in MS-related inflammatory activity.

Discovery of a Potent and Selective Steroidal Glucocorticoid Receptor Antagonist (ORIC-101).

The glucocorticoid receptor (GR) has been linked to therapy resistance across a wide range of cancer types. Preclinical data suggest that antagonists of this nuclear receptor may enhance the activity of anticancer therapy. The first-generation GR antagonist mifepristone is currently undergoing clinical evaluation in various oncology settings. Structure-based modification of mifepristone led to the discovery of ORIC-101 (28), a highly potent steroidal GR antagonist with reduced androgen receptor (AR) agonistic activity amenable for dosing in androgen receptor positive tumors and with improved CYP2C8 and CYP2C9 inhibition profile to minimize drug-drug interaction potential. Unlike mifepristone, 28 could be codosed with chemotherapeutic agents readily metabolized by CYP2C8 such as paclitaxel. Furthermore, 28 demonstrated in vivo antitumor activity by enhancing response to chemotherapy in the GR+ OVCAR5 ovarian cancer xenograft model. Clinical evaluation of safety and therapeutic potential of 28 is underway.