Oumaima Kaabi

Background: Gestational diabetes mellitus (GDM) is linked with adverse health outcomes for both mother and infant and increases the risk of type 2 diabetes mellitus (T2DM) and long-term metabolic dysfunction postpartum. American Samoa experiences among the highest prevalence of GDM globally, with estimates suggesting 26–42% of women develop the condition. To date, no studies have attempted to understand the underlying etiology of GDM in Pacific Islanders or examine population-specific progression from GDM to T2DM. The GROW study will characterize glucose homeostasis, diabetes progression, and the impact of a Pacific-specific variant (rs373863828) in the CREBRF gene, which is known to protect against T2DM, on glucose metabolism during and after pregnancy. Methods: We will establish a prospective cohort study of 350 pregnant women in American Samoa, enrolled in their first trimester and followed through 18 months postpartum. Participants will be genotyped for CREBRF rs373863828 and undergo frequently-sampled oral glucose tolerance test (fs-OGTTs), glycated hemoglobin (HbA1c), and continuous glucose monitoring (CGM) measurements to identify glycemic patterns across the perinatal period. Participants will complete questionnaires assessing reproductive health history, diet, physical activity, sleep, and psychosocial health. We will examine associations between CREBRF genotype and glucose homeostasis across pregnancy and postpartum and evaluate risk of GDM and subsequent T2DM. We will also explore associations between CREBRF genotype, changes in insulin secretion in pregnancy, and risk of adverse birth outcomes. Discussion: Findings from this study are expected to inform precision medicine approaches to diabetes prevention, refine public health policies and clinical guidelines, and support community-based interventions aimed at reducing GDM and T2DM among Pacific Islander women and more broadly.

Sex chromosome aneuploidy (SCA) is a group of conditions characterized by an atypical number of X and/or Y chromosomes, which are associated with various mental health diagnoses (MHD). Individuals with Klinefelter syndrome (KS), Turner syndrome (TS), or Turner mosaicism (TM) were identified using an electronic health record screening algorithm, followed by a review of karyotype data and clinical notes. Each patient with KS was matched with 10 non‐SCA males, and each TS or TM participant was matched with 10 non‐SCA females. Poisson regression models accounting for matched design and controlling for enrollment duration were used to calculate prevalence ratios (PR) and 95% confidence intervals (CI) for various MHD categories. When 282 KS patients were compared with male referents, the top three differences in prevalence were observed for feeding and eating disorders (PR = 4.2; 95% CI: 1.6, 11.1), disruptive, impulsive‐control, and conduct disorders (PR = 3.4; 95% CI: 2.3, 5.0), and suicidal ideation (PR = 3.5; 95% CI 2.0, 5.9). Among 263 TS/TM patients, the corresponding PR estimates relative to female referents were the highest for neurodevelopmental disorders (3.6; 95% CI: 2.7, 4.8) and disruptive, impulsive‐control, and conduct disorders (2.0; 95% CI: 1.2, 3.6). When the data were stratified according to age at the time of MHD linkages, the PR estimates varied across the groups, but the 95% CIs largely overlapped. People with SCA carry a greater burden of MHD than comparable persons without SCA. Management of mental health comorbidities is a relatively neglected healthcare priority in this group of patients.

Background: There is an ongoing syndemic of HIV and sexually transmitted infections (STIs) in the United States, particularly among men who have sex with men (MSM). We have increasingly effective and diverse measures of prevention, including various types of pre-exposure prophylaxis (PrEP) for HIV prevention and doxycycline postexposure prophylaxis (doxyPEP) for STI prevention. As options expand, we need to understand how to use a combination of these strategies and other supports for MSM to best curb the syndemic. Objective: We designed a patient-preference trial to understand patient preferences for PrEP and doxyPEP, how preferences may change over time, and methods for preventing premature discontinuation of PrEP. Methods: We enrolled HIV-negative MSM in metropolitan Atlanta, Georgia. Participants could elect to take PrEP (daily or on-demand), doxyPEP, both, or neither, along with app-based support to evaluate for risk factors of discontinuation or behavioral changes that might affect their choice of prevention methods. Participants were able to switch prevention methods at any time. Oral PrEP and doxyPEP users are currently being offered quarterly in-person or at-home HIV, syphilis, gonorrhea, and chlamydia testing along with opportunities for motivational interviewing. Results: We enrolled individuals from November 2021 to September 2023. Among 240 participants, the median age was 30 (IQR 25-35), 63% (n=150) self-identified as non-Hispanic Black, and 69% (n=166) were insured. Most participants (n=144, 60%) elected to take daily PrEP plus doxyPEP, with a smaller proportion taking on-demand PrEP plus doxyPEP (n=34, 14%) or daily PrEP without doxyPEP (n=33, 14%). Conclusions: We designed an ongoing study to evaluate the preferences for PrEP and doxyPEP among MSM in metropolitan Atlanta. Enrollment was completed in 22 months and included a diverse cohort of MSM that will be followed longitudinally to evaluate prevention preferences over time. At baseline, most participants preferred to take a combination of daily PrEP and doxyPEP for HIV and STI prevention. Trial Registration: Clinicaltrials.gov NCT05072093; https://clinicaltrials.gov/study/NCT05072093 International Registered Report Identifier (IRRID): DERR1-10.2196/56096

Context: Although the increased burden of mental health problems among patients with classic 46,XX congenital adrenal hyperplasia (CAH) is well-documented, it remains unclear if this comorbidity is attributable to the burden of living with a chronic medical condition or the potential psychosocial/sexual consequences of being born with a difference of sex development (DSD) and its associated clinical management. Objective: To compare the prevalence of psychiatric diagnoses among patients with CAH and 3 reference groups: matched males and females from the general population, and females with type 1 diabetes mellitus (T1DM). Methods: This was a retrospective cross-sectional study using 3 large integrated health systems. Participants included patients with CAH (n = 115), general population male and female referents (n = 1150 per group), and 66 002 female T1DM referents. Results: The prevalence of depression, anxiety, personality disorders, and suicidal ideation was higher among CAH participants than in males and females from the general population, but similar to or lower than in T1DM referents. Patients with CAH were more likely to be diagnosed with neurodevelopmental disorders than both female reference groups, whereas the prevalence of elimination disorders (predominantly enuresis) and gender dysphoria was higher in the CAH cohort than in all reference groups. Conclusion: Females with classic CAH experience a higher burden of psychiatric illness, including anxiety and depression, than demographically similar men and women in the general population. The similar psychiatric burden between females with CAH and T1DM suggests that morbidity may be influenced by the challenges associated with managing a chronic condition. Investigating long-term mental health trajectories in this population will require longitudinal studies.

BACKGROUND There is an ongoing syndemic of HIV and sexually transmitted infections (STIs) in the United States, particularly among men who have sex with men (MSM). We have increasingly effective and diverse measures of prevention, including various types of pre-exposure prophylaxis (PrEP) for HIV prevention and doxycycline postexposure prophylaxis (doxyPEP) for STI prevention. As options expand, we need to understand how to use a combination of these strategies and other supports for MSM to best curb the syndemic. OBJECTIVE We designed a patient-preference trial to understand patient preferences for PrEP and doxyPEP, how preferences may change over time, and methods for preventing premature discontinuation of PrEP. METHODS We enrolled HIV-negative MSM in metropolitan Atlanta, Georgia. Participants could elect to take PrEP (daily or on-demand), doxyPEP, both, or neither, along with app-based support to evaluate for risk factors of discontinuation or behavioral changes that might affect their choice of prevention methods. Participants were able to switch prevention methods at any time. Oral PrEP and doxyPEP users are currently being offered quarterly in-person or at-home HIV, syphilis, gonorrhea, and chlamydia testing along with opportunities for motivational interviewing. RESULTS We enrolled individuals from November 2021 to September 2023. Among 240 participants, the median age was 30 (IQR 25-35), 63% (n=150) self-identified as non-Hispanic Black, and 69% (n=166) were insured. Most participants (n=144, 60%) elected to take daily PrEP plus doxyPEP, with a smaller proportion taking on-demand PrEP plus doxyPEP (n=34, 14%) or daily PrEP without doxyPEP (n=33, 14%). CONCLUSIONS We designed an ongoing study to evaluate the preferences for PrEP and doxyPEP among MSM in metropolitan Atlanta. Enrollment was completed in 22 months and included a diverse cohort of MSM that will be followed longitudinally to evaluate prevention preferences over time. At baseline, most participants preferred to take a combination of daily PrEP and doxyPEP for HIV and STI prevention. CLINICALTRIAL Clinicaltrials.gov NCT05072093; https://clinicaltrials.gov/study/NCT05072093 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/56096