Many prospective biomedical studies collect longitudinal clinical and lifestyle data that are both continuous and discrete. In some studies, there is interest in the association between a binary outcome and the values of these longitudinal measurements at a specific time point. A common problem in these studies is inconsistency in timing of measurements and missing follow‐ups which can lead to few measurements at the time of interest. Some methods have been developed to address this problem, but are only applicable to continuous measurements. To address this limitation, we propose a new class of joint models for a binary outcome and longitudinal explanatory variables of mixed types. The longitudinal model uses a latent normal random variable construction with regression splines to model time‐dependent trends in mean with a Dirichlet Process prior assigned to random effects to relax distribution assumptions. We also standardize timing of the explanatory variables by relating the binary outcome to imputed longitudinal values at a set time point. The proposed model is evaluated through simulation studies and applied to data from a cancer survivor study of participants in the Women's Health Initiative.

Preliminary evidence suggests that commonly used genetic tests may be less likely to identify a genetic etiology for ALS-FTD in patients of underrepresented race, ethnicity, and ancestry (REA), as compared to European REA. Patients of underrepresented REA may therefore be less likely to receive accurate and specific genetic counseling information and less likely to have access to gene-targeted therapies currently in clinical trials. We compiled outcome data from 1911 ALS-FTD patients tested at a commercial laboratory over a seven-year period for C9orf72 hexanucleotide repeat expansion (HRE) alone or C9orf72 and multigene sequencing panel testing. We compared the incidence of pathogenic (P), likely pathogenic (LP), and uncertain variants in C9orf72 and other ALS-FTD genes, as well as age at testing, in patients of different REA. The diagnostic rate in patients of European REA (377/1595, 23.64%) was significantly higher than in patients of underrepresented REA (44/316, 13.92%) (p < 0.001). Patients of European REA were more likely to have the C9orf72 HRE (21.3%) than patients of underrepresented REA (10.4%) (p < 0.001). The overall distribution of positive test outcomes in all tested genes was significantly different between the two groups, with relatively more P and LP variants in genes other than C9orf72 identified in patients of underrepresented REA. The incidence of uncertain test outcomes was not significantly different between patients of European and underrepresented REA. Patients with positive test outcomes were more likely to be younger than those with negative or uncertain outcomes. Although C9orf72 HRE assay has been advocated as the first, and in some cases, only genetic test offered to patients with ALS-FTD in the clinical setting, this practice may result in the reduced ascertainment of genetic ALS-FTD in patients of diverse REA.

Introduction The use of echocardiography to evaluate the probability for pulmonary hypertension (PH) in pregnant women has not been reported or correlated with outcomes. We hypothesized that in women with elevated right ventricular systolic pressure (RVSP) on echocardiography first identified during pregnancy, those with low probability for PH would have fewer major adverse cardiac events (MACE). Methods We performed a retrospective cohort study of pregnant women with RVSP >35 mm Hg on echocardiogram first identified during pregnancy. Women were classified as intermediate‐high probability for PH (HP) or low probability for PH (LP) based on simplified European Society of Cardiology echocardiographic criteria. Maternal cardiac, obstetric, and fetal outcomes were assessed. Results A total of 77 women met inclusion criteria (mean age 30 ± 5 years), with 45 (58%) classified as HP and 32 (42%) as LP. There were 21 (27%) women who experienced MACE, more commonly in the HP cohort (HP 18 (40%) women vs. LP 3 (9%) women, P = .01). The echocardiographic criteria for intermediate‐high probability of PH identified women at risk for MACE with 85% sensitivity and 52% specificity. The negative predictive value for MACE in women meeting low echocardiographic probability for PH criteria was 91%. Conclusions In women with elevated RVSP on echocardiography first identified during pregnancy, those with low echocardiographic PH probability are at significantly lower risk for MACE during pregnancy, though the risk is not eliminated. This may be useful to risk stratify pregnant women with suspected PH, guiding tertiary care referral and invasive catheterization.

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Introduction: Pregnancy is contraindicated in women with pulmonary hypertension (PH), yet many still decide to pursue pregnancy. Hypothesis: We hypothesized improved maternal mortality with PH at our center’s cardio-obstetrics program and sought to identify factors to estimate the risk of major adverse cardiac events (MACE). Methods: Pregnant women with right ventricular systolic pressure (RVSP) ≥35 mmHg or tricuspid regurgitant velocity > 2.8 m/s on transthoracic echocardiogram (TTE) were identified. Women with intermediate to high probability PH by ESC criteria (TTE or catheterization, n = 70) were classified using the 6 th World Society of PH definitions. Results: In 70 women with PH (30 ± 6 years-old, RVSP 52 ± 16 mmHg) there were 12 (17%) with WHO Group 1 PH, 45 (64%) with Group 2 PH, 4 (6%) with Group 3 PH and 9 (13%) with Group 5 PH (Figure A). Baseline characteristics were similar except: Group 1 PH had 83% on prostacyclin (PC) therapy, higher RVSP (78 ± 20 mmHg vs. Groups 2 (46 ± 9), 3 (44 ± 2 mmHg) and 5 PH (48 ± 10mmHg), p<0.01), and compared to Group 2 PH, more Group 1 PH women were diagnosed pre-pregnancy (9 (75%) vs. 12 (27%), p = 0.01) and had cardio-obstetrics care (10 (83%) vs. 16 (36%), p < 0.01) (Figure B - E). There were no peripartum deaths, however 3 (4.3%) women with Group 2 PH had late mortality (7 ± 4 months post-partum). MACE occurred in 24 (34%) women and was more likely in those with: NYHA FC ≥ 2 (95% CI 4.7-57, p < 0.01), pre-eclampsia (95% CI 1.2-13, p = 0.03), RVSP >50 mmHg (95% CI 1.3-10, p = 0.02) and LVEF <50% (95% CI 1.1-8.8, p = 0.04) (Figure F). Preterm birth occurred in 32 (49%) pregnancies, with no neonatal mortality. Conclusion: To conclude, in a large single center cohort we report 100% 1-year survival in Groups 1, 3, and 5 PH, with most Group 1 PH patients on PC therapy and under cardio-obstetrics care. We identify Group 2 PH as an under-recognized group for adverse outcomes in pregnancy, with NYHA FC, pre-eclampsia, RVSP >50 mmHg and LVEF <50% associated with increased MACE.