Impact of hypertensive disorders of pregnancy and gestational diabetes mellitus on offspring cardiovascular health in early adolescence.

BACKGROUND: Adverse pregnancy outcomes, including hypertensive disorders of pregnancy and gestational diabetes mellitus, influence maternal cardiovascular health long after pregnancy, but their relationship to offspring cardiovascular health following in-utero exposure remains uncertain. OBJECTIVE: To examine associations of hypertensive disorders of pregnancy or gestational diabetes mellitus with offspring cardiovascular health in early adolescence. STUDY DESIGN: This analysis used data from the prospective Hyperglycemia and Adverse Pregnancy Outcome Study from 2000 to 2006 and the Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study from 2013 to 2016. This analysis included 3317 mother-child dyads from 10 field centers, comprising 70.8% of Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study participants. Those with pregestational diabetes and chronic hypertension were excluded. The exposures included having any hypertensive disorders of pregnancy or gestational diabetes mellitus vs not having hypertensive disorders of pregnancy or gestational diabetes mellitus, respectively (reference). The outcome was offspring cardiovascular health when aged 10-14 years, on the basis of 4 metrics: body mass index, blood pressure, total cholesterol level, and glucose level. Each metric was categorized as ideal, intermediate, or poor using a framework provided by the American Heart Association. The primary outcome was defined as having at least 1 cardiovascular health metric that was nonideal vs all ideal (reference), and the second outcome was the number of nonideal cardiovascular health metrics (ie, at least 1 intermediate metric, 1 poor metric, or at least 2 poor metrics vs all ideal [reference]). Modified poisson regression with robust error variance was used and adjusted for covariates at pregnancy enrollment, including field center, parity, age, gestational age, alcohol or tobacco use, child's assigned sex at birth, and child's age at follow-up. RESULTS: Among 3317 maternal-child dyads, the median (interquartile) ages were 30.4 (25.6-33.9) years for pregnant individuals and 11.6 (10.9-12.3) years for children. During pregnancy, 10.4% of individuals developed hypertensive disorders of pregnancy, and 14.6% developed gestational diabetes mellitus. At follow-up, 55.5% of offspring had at least 1 nonideal cardiovascular health metric. In adjusted models, having hypertensive disorders of pregnancy (adjusted risk ratio, 1.14 [95% confidence interval, 1.04-1.25]) or having gestational diabetes mellitus (adjusted risk ratio, 1.10 [95% confidence interval, 1.02-1.19]) was associated with a greater risk that offspring developed less-than-ideal cardiovascular health when aged 10-14 years. The above associations strengthened in magnitude as the severity of adverse cardiovascular health metrics increased (ie, with the outcome measured as ≥1 intermediate, 1 poor, and ≥2 poor adverse metrics), albeit the only statistically significant association was with the "1-poor-metric" exposure. CONCLUSION: In this multinational prospective cohort, pregnant individuals who experienced either hypertensive disorders of pregnancy or gestational diabetes mellitus were at significantly increased risk of having offspring with worse cardiovascular health in early adolescence. Reducing adverse pregnancy outcomes and increasing surveillance with targeted interventions after an adverse pregnancy outcome should be studied as potential avenues to enhance long-term cardiovascular health in the offspring exposed in utero.

Disparities in electronic health record portal access and use among patients with cancer.

BACKGROUND: Electronic health record-linked portals may improve health-care quality for patients with cancer. Barriers to portal access and use undermine interventions that rely on portals to reduce cancer care disparities. This study examined portal access and persistence of portal use and associations with patient and structural factors before the implementation of 3 portal-based interventions within the Improving the Management of symPtoms during And following Cancer Treatment (IMPACT) Consortium. METHODS: Portal use data were extracted from electronic health records for the 12 months preceding intervention implementation. Sociodemographic factors, mode of accessing portals (web vs mobile), and number of clinical encounters before intervention implementation were also extracted. Rurality was derived using rural-urban commuting area codes. Broadband access was estimated using the 2015-2019 American Community Survey. Multiple logistic regression models tested the associations of these factors with portal access (ever accessed or never accessed) and persistence of portal use (accessed the portal ≤20 weeks vs ≥21 weeks in the 35-week study period). RESULTS: Of 28 942 eligible patients, 10 061 (35%) never accessed the portal. Male sex, membership in a racial and ethnic minority group, rural dwelling, not working, and limited broadband access were associated with lower odds of portal access. Younger age and more clinical encounters were associated with higher odds of portal access. Of those with portal access, 25% were persistent users. Using multiple modalities for portal access, being middle-aged, and having more clinical encounters were associated with persistent portal use. CONCLUSION: Patient and structural factors affect portal access and use and may exacerbate disparities in electronic health record-based cancer symptom surveillance and management.

Association of American Identity with Cardiovascular Health in South Asian Americans: The MASALA Study.

Background: Ethnic and national identity may influence cardiovascular health (CVH)-related behaviors, such as dietary preference. To better understand how acculturation is related to CVH among South Asian American adults, we evaluated the association of self-rated American identity with CVH factors among participants of the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study. Methods: Multivariable linear regression quantified the associations of self-rated American identity [1 (low American identity) to 10 (high American identity)] with CVH factors, including measures of cholesterol, blood pressure, and blood glucose. The role of diet quality, physical activity, and social support in mediating these associations was evaluated. Results: Participants (n = 771) lived in the United States for an average of 27 (SD 11) years. The mean self-rated American identity score was 5.5 (2.4). After adjustment, a 5-point higher American identity score was associated with 6.5 mg/dL higher low-density lipoprotein cholesterol, 6.6 mg/dL higher total cholesterol, 2.9 mmHg higher systolic blood pressure, and 1.4 mmHg higher diastolic blood pressure. Accounting for diet quality, physical activity, or social support does not alter these associations. Conclusions: Higher self-rated American identity is associated with worse CVH factors among South Asian American adults.

Implementation and evaluation of an expanded electronic health record-integrated bilingual electronic symptom management program across a multi-site Comprehensive Cancer Center: The NU IMPACT protocol.

BACKGROUND: People with cancer experience symptoms that adversely affect quality of life. Despite existing interventions and clinical guidelines, timely symptom management remains uneven in oncology care. We describe a study to implement and evaluate an electronic health record (EHR)-integrated symptom monitoring and management program in adult outpatient cancer care. METHODS: Our cancer patient-reported outcomes (cPRO) symptom monitoring and management program is a customized EHR-integrated installation. We will implement cPRO across all Northwestern Memorial HealthCare (NMHC) hematology/oncology clinics. We will conduct a cluster randomized modified stepped-wedge trial to evaluate patient and clinician engagement with cPRO. Further, we will embed a patient-level randomized clinical trial to evaluate the impact of an additional enhanced care (EC; cPRO plus web-based symptom self-management intervention) relative to usual care (UC; cPRO alone). The project uses a Type 2 hybrid effectiveness-implementation approach. The intervention will be implemented across seven regional clusters within the healthcare system comprising 32 clinic sites. A 6-month prospective pre-implementation enrollment period will be followed by a post-implementation enrollment period, during which newly enrolled, consenting patients will be randomly assigned (1:1) to EC or UC. We will follow patients for 12 months post-enrollment. Patients randomized to EC will receive evidence-based symptom-management content on cancer-related concerns and approaches to enhance quality of life, using a web-based tool ("MyNM Care Corner"). This design allows for within- and between-site evaluation of implementation plus a group-based comparison to demonstrate effectiveness on patient-level outcomes. DISCUSSION: The project has potential to guide implementation of future healthcare system-level cancer symptom management programs. http://ClinicalTrials.gov # NCT03988543.

Inflammatory Activity After Diverse Fertility Treatments: A Multicenter Analysis in the Modern Multiple Sclerosis Treatment Era.

BACKGROUND AND OBJECTIVES: Patients with multiple sclerosis (MS) may seek fertility treatment (FT)-including in vitro fertilization (IVF). Variable relapse risk after IVF has been reported in small historical cohorts, with more recent studies suggesting no change in annualized relapse rate (ARR). The objective of this study was to evaluate ARR 12 months pre-FT and 3 months post-FT in a multicenter cohort and identify factors associated with an increased risk of relapse. METHODS: Patients with clinically isolated syndrome (CIS) or MS aged 18-45 years with at least 1 FT from January 1, 2010, to October 14, 2021, were retrospectively identified at 4 large academic MS centers. The exposed period of 3 months after FT was compared with the unexposed period of 12 months before FT. FTs included controlled ovarian stimulation followed by fresh embryo transfer (COS-ET), COS alone, embryo transfer (ET) alone, and oral ovulation induction (OI). The Wilcoxon signed rank test and mixed Poisson regression models with random effects were used to compare ARR pre-FT vs post-FT, with the incidence rate ratio (IRR) and 95% CI reported. RESULTS: One hundred twenty-four FT cycles among 65 patients with MS (n = 56) or CIS (n = 9) were included: 61 COS-ET, 19 COS alone, 30 ET alone, and 14 OI. The mean age at FT was 36.5 ± 3.8 years, and the mean disease duration was 8.2 ± 5.0 years. Across 80 cycles with COS, only 5 relapses occurred among 4 unique patients within 3 months of treatment. The mean ARR after COS and before was not different (0.26 vs 0.25, p = 0.37), and the IRR was 0.95 (95% CI: 0.52-1.76, p = 0.88). No cycles with therapeutic disease-modifying therapies (DMTs) during COS had 3 months relapse (ARR 0 post-COS vs 0.18 pre-COS, p = 0.02, n = 34). Relapse rates did not vary by COS protocol. Among COS-ET cycles that achieved pregnancy (n = 43), ARR decreased from 0.26 to 0.09 (p = 0.04) within the first trimester of pregnancy. There were no relapses 3 months after ET alone and 1 relapse after OI. DISCUSSION: In this modern multicenter cohort of patients with MS undergoing diverse FTs, which included 43% on DMTs, we did not observe an elevated relapse risk after FT.

Comparative cardiovascular effects of GLP-1 agonists using real-world data.

AIMS: There is limited research using real-world data to evaluate protective cardiovascular effects of glucagon-like peptide-1 (GLP-1) agonists among adults with type 2 diabetes (T2D) early in treatment. MATERIALS AND METHODS: We conducted a retrospective, active comparator cohort study using 2011-2015 administrative claims data to compare cardiovascular disease (CVD) event rates following initiation of exenatide extended-release (E-ER), exenatide immediate-release (E-IR) or liraglutide in T2D adults who previously received no other antidiabetic medication (ADM) except metformin. The primary outcome was time to first major adverse CVD event (ischaemic heart disease, stroke, congestive heart failure or peripheral arterial disease) after starting GLP-1. Cox proportional hazards regression was used to model the association between index GLP-1 and CVD events, adjusting for baseline patient, prescriber and plan characteristics. Primary analyses included all patients with ≥2 prescription fills for the index GLP-1, regardless of subsequent refill adherence or initiation of other ADM after index date. RESULTS: Compared with liraglutide, neither E-ER nor E-IR was associated with risk of composite major CVD events (hazard ratios [HRs] for E-ER and E-IR: 1.33 [95% C.I. 0.73-2.39] and 1.30 [0.81-2.09]). No associations were observed between event rates for individual CVD components. The HR for an ischaemic event with E-IR relative to liraglutide was 1.85 (95% C.I. 0.97-3.53). Adjusting for time-varying exposure to other ADM and CVD medications after index date produced similar results. CONCLUSIONS: Initiating either immediate or extended-release exenatide rather than liraglutide was not associated with significant differences in CVD risk in this observational real-world study.

DOAC compared with warfarin for VTE in patients with obesity: a retrospective cohort study conducted through the VENUS network.

The effectiveness and safety of direct oral anticoagulants (DOAC) compared with warfarin remains uncertain in obese patients. We assessed the comparative effectiveness and safety of DOACs with warfarin for the treatment of VTE among obese patients. This multi-center retrospective cohort study included adults with a BMI ≥ 35 kg/m2 or weight ≥ 120 kg prescribed either DOAC (apixaban, dabigatran, edoxaban, rivaroxaban) or warfarin for a VTE diagnosis. The primary outcome was the 12-month rate of recurrent VTE. The secondary outcome was the 12-month rate of major bleeding. Among 5626 patients, 67% were prescribed warfarin and 33% were prescribed a DOAC. The 12-month VTE recurrence rate was 3.6% (67/1823) for patients treated with DOAC compared with 3.8% (143/3664) for patients treated with warfarin [odds ratio for recurrent VTE on warfarin versus DOAC (OR) (95% CI).07 (0.80, 1.45)]. The 12-month major bleeding rate was 0.5% (10/1868) for patients on DOAC versus 2.4% (89/3758) on warfarin [OR 4.25 (2.19, 8.22)]. Similar proportions of recurrent VTE occurred across BMI thresholds on DOAC and warfarin: for BMI ≥ 35 kg/m2 (N = 5412), 3.6% versus 3.8%, respectively [OR 1.08 (0.80, 1.46)]; for BMI ≥ 40 kg/m2 (N = 2321), 4.4% versus 3.5%, respectively [OR 0.80 (0.51, 1.26)]; and for BMI ≥ 50 kg/m2 (N = 560), 3.1% versus 3.7%, respectively [OR 1.18 (0.39, 3.56)]. Similar proportions of recurrent VTE occurred in patients with obesity treated for VTE with DOACs and warfarin. DOACs were associated with lower major bleeding compared to warfarin in patients with obesity and VTE.

Telehealth utilization and patient satisfaction in an ambulatory movement disorders center during the COVID-19 pandemic.

INTRODUCTION: Studies suggest that patients are satisfied with telehealth in ambulatory settings. However, tele-neurology satisfaction data are limited by a small sample size and COVID-19-era data is not specific to movement disorders clinics. In this prospective observational study, telehealth utilization during the COVID-19 pandemic was assessed, and patient satisfaction was compared between telehealth and in-person visits in an outpatient movement disorders center. METHODS: Patients ≥18 years who completed an appointment at Northwestern's Movement Disorders Clinic were invited to complete a post-visit Medallia survey. The primary outcomes of the survey were likelihood to recommend (LTR) provider, LTR location, and 'spent enough time,' on a 0-10 scale. Responses were categorized into in-person vs. telehealth groups. RESULTS: Telehealth utilization significantly increased from a pre-COVID timeframe rate of 0.3% (Nov 2019 to Feb 2020) to 39.5% during the COVID-19 pandemic (March 2020 through April 2021) (p-value < 0.001). During the COVID-19 pandemic, 621 patients responded to the post-visit Medallia survey (response rate = 30%), including 365 in-person and 256 telehealth visits. No significant differences were observed between in-person and telehealth encounters in LTR provider (p = 0.892), LTR location (p = 0.659), and time spent (p = 0.395). Additional subgroup multivariable analysis did not support differences in satisfaction between different age groups. DISCUSSION: With its large sample size, our study demonstrates that in the setting of increased TH utilization in movement disorders clinic during the COVID-19 pandemic, patients reported similar satisfaction with telehealth compared to in-person visits. This study supports the utility of telehealth to provide specialized neurologic clinic care.

Examining changes in clinical management and postpartum readmissions for hypertensive disorders of pregnancy over time.

OBJECTIVE: In response to 2013 guidelines for hypertensive disorders of pregnancy (HDP), our study examined changes in antenatal management and postpartum readmission (PPR) over time. STUDY DESIGN: This is a retrospective cohort study of individuals diagnosed antenatally with HDP who delivered at a tertiary care center from 2012 to 2017. MAIN OUTCOME MEASURES: The primary outcome was postpartum readmission for HDP in 2012-2013 vs 2014-2017. Secondary outcomes included intravenous magnesium administration and prescription for oral (PO) antihypertensive medication during delivery admission. Multivariable logistic regression models assessed differences in outcomes over time, adjusted for age, race, and payer status, for HDP with and without severe features, defined by ACOG criteria. RESULTS: Of 5,300 eligible individuals, 73.5 % had HDP without severe features and 26.5 % had severe features. The PPR frequency in this cohort was 1.1 % (N = 59). There was no difference in PPR for individuals with HDP without severe features (aOR 0.73; 95 % CI 0.28-1.88) or with severe features (aOR 1.30; 95 % CI 0.50-3.39) by epoch. Magnesium administration for HDP with severe features remained below 80 % over time. Magnesium administration for HDP without severe features and discharge prescriptions for PO medications for HDP with severe features were lower after 2013. Neither magnesium administration nor discharge prescriptions were associated with decreased odds of PPR. CONCLUSION: Although there was no difference in PPR for HDP after 2013, there were changes in antenatal management of HDP, including decreased magnesium administration for individuals with HDP without severe features and PO medication for individuals with severe features.

South Asians Active Together (SAATH): Protocol for a multilevel physical activity intervention trial for South Asian American mother and daughter dyads.

South Asian (SA), including Asian Indian and Pakistani Americans, have a high burden of cardiometabolic risk factors and low levels of physical activity (PA). Increasing PA in the U.S. population is a national priority; however, SA American women and girls experience unique barriers to PA that are not addressed by current promotion efforts. To address this gap, our community-based participatory research partnership developed the South Asians Active Together (SAATH) intervention. This study is a two-arm randomized clinical trial to evaluate the effects, mediators, and implementation of the 18-week SAATH intervention. A total of 160 mother-daughter dyads will be randomized in a 1:1 ratio to the SAATH intervention and control groups. The intervention was designed for mother-daughter dyads and targets individual, interpersonal, and family levels through (1) group exercise classes, (2) mother-daughter discussions, and (3) peer group discussions. The intervention targets the environment level through community partner meetings aimed at creating environment changes to enhance PA opportunities for SA women and girls. The control group will receive PA education materials. We hypothesize that dyads who receive the intervention will have significantly greater increases in moderate- and vigorous-intensity PA (MVPA) from baseline to 4 months, compared to the control group. MVPA will be measured at 12 months in intervention participants to examine if changes are sustained. A process evaluation will use the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework. This study will fill knowledge gaps about the effectiveness and implementation of culturally adapted, community-based PA interventions for SA women and girls.

Genetic Factors Associated with Prostate Cancer Conversion from Active Surveillance to Treatment.

Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for prostate cancer, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9×10-7 and GAB2, p = 2.0×10-6). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% Confidence Interval [CI]= 0.94-1.36); whereas, decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04-1.50). These results suggest that germline genetics may help inform and individualize the decision of AS-or the intensity of monitoring on AS-versus treatment for the initial management of patients with low-risk PC.

Social influence of adult children on parental health behavior among South Asian immigrants: findings from the MASALA (Mediators of Atherosclerosis in South Asians Living in America) study.

Objectives: Examine the social influence of adult children on the cardiovascular-related health behaviors of older South Asian (SA) immigrants to inform lifestyle interventions.Design: This mixed-methods study used data from an ancillary study of social networks (2014-2018) in the Mediators of Atherosclerosis in South Asians Living in America cohort. Phase 1 was a quantitative analysis of self-reported diet and physical activity among SA adults (n = 448, mean age = 58 years, SD 8.4) who named at least one adult child to their social network. The Alternative Healthy Eating Index (AHEI) was used to measure parents' diet; higher numbers indicate a healthier diet (range 0-110). Phase 2 was a thematic content analysis of in-depth qualitative interviews from a subsample of these parents (n = 23, mean age = 55, SD 7.6).Results: Parents with an adult child in their network who consumed uncooked vegetables daily had mean parental AHEI score 1.5 points higher (adjusted p-value = 0.03) than those who had a child in the network who ate uncooked vegetables less often. When at least one adult child in their network ate fresh fruit daily compared to less frequently or when at least one child ate non-SA food daily compared to less frequently, mean parental AHEI scores were higher by 2.0 (adjusted p-value = 0.01) and 1.6 (adjusted p-value = 0.03) points respectively. Parents with an adult child in their network who exercised at least weekly were more likely to meet guideline-recommended physical activity levels than parents with children who exercised less often (76% v. 56%, adjusted p-value = 0.02). Adult children provided social support and were seen as 'role models' for healthy behavior, especially when adopting Western health behaviors.Conclusion: Positive role modeling and support from adult children were important facilitators of healthy behavior change in older SA immigrants and can inform health behavior interventions for SA adults.

Re-Analysis of the STEADY-PD II Trial-Evidence for Slowing the Progression of Parkinson's Disease.

BACKGROUND: Recent examination of the STEADY-PD III isradipine clinical trial data concluded that early-stage Parkinson's disease (PD) participants who had longer exposure to isradipine had a significant delay in their need for symptomatic medication, as well as a lower medication burden at the end of the trial. These findings suggest that greater exposure to isradipine might slow disease progression. OBJECTIVES: To test this hypothesis, the data from the STEADY-PD II isradipine clinical trial, in which an extended-release (ER) formulation of the drug was used, was re-examined. METHODS: The re-analysis of the STEADY-PD II data was restricted to participants assigned placebo or tolerable isradipine treatment (10 mg isradipine/day or less). The effect of isradipine treatment was assessed by Unified Parkinson's Disease Rating Scale (UPDRS) at the end of the 52-week trial, rather than by last observation carried forward at the beginning of symptomatic therapy. RESULTS: Participant cohorts were well-matched for baseline disability, initial disease progression, and time to initiation of symptomatic therapy. Participants given 10 mg/day ER isradipine had significantly smaller total and part 3 UPDRS scores at the end of the trial than did the placebo cohort. Post hoc adjustment for symptomatic therapy diminished the statistical significance of these differences. In those participants not taking a monoamine oxidase B inhibitor, the progression in UPDRS scores also was significantly reduced. CONCLUSIONS: These results are consistent with the recent secondary analysis of the STEADY-PD III clinical trial-suggesting that clinically attainable brain exposure to isradipine may slow early-stage PD progression. © 2021 International Parkinson and Movement Disorder Society.

Benign tumors in TSC are amenable to treatment by GD3 CAR T cells in mice.

Mutations underlying disease in tuberous sclerosis complex (TSC) give rise to tumors with biallelic mutations in TSC1 or TSC2 and hyperactive mammalian target of rapamycin complex 1 (mTORC1). Benign tumors might exhibit de novo expression of immunogens, targetable by immunotherapy. As tumors may rely on ganglioside D3 (GD3) expression for mTORC1 activation and growth, we compared GD3 expression in tissues from patients with TSC and controls. GD3 was overexpressed in affected tissues from patients with TSC and also in aging Tsc2+/- mice. As GD3 overexpression was not accompanied by marked natural immune responses to the target molecule, we performed preclinical studies with GD3 chimeric antigen receptor (CAR) T cells. Polyfunctional CAR T cells were cytotoxic toward GD3-overexpressing targets. In mice challenged with Tsc2-/- tumor cells, CAR T cells substantially and durably reduced the tumor burden, correlating with increased T cell infiltration. We also treated aged Tsc2+/- heterozygous (>60 weeks) mice that carry spontaneous Tsc2-/- tumors with GD3 CAR or untransduced T cells and evaluated them at endpoint. Following CAR T cell treatment, the majority of mice were tumor free while all control animals carried tumors. The outcomes demonstrate a strong treatment effect and suggest that targeting GD3 can be successful in TSC.

Costs for commercially insured adults prescribed second-line diabetes medications.

OBJECTIVES: To examine differences in health care costs associated with choice of second-line antidiabetes medication (ADM) for commercially insured adults with type 2 diabetes. STUDY DESIGN: Retrospective cohort study with multiple pretests and posttests. METHODS: Included patients initiated second-line ADM therapy between 2011 and 2015, with variable follow-up through 2017. The 6 index medication classes were sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), basal insulin, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and thiazolidinediones (TZDs). Multivariable regression models compared between-class changes in adjusted quarterly costs after second-line ADM initiation. RESULTS: The study cohort included 34,963 adults. Most were prescribed a sulfonylurea (46.0%) or DPP-4 inhibitor (30.4%). Adjusted quarterly index medication costs were significantly higher for all patients receiving nonsulfonylurea medications, ranging from $108 (95% CI, $99-$118) for TZDs to $742 (95% CI, $720-$765) for GLP-1 RAs. Changes in quarterly total health care costs were significantly higher for all nonsulfonylurea classes. Conversely, changes in quarterly nonpharmacy medical costs were significantly lower for patients receiving DPP-4 inhibitors (-$67; 95% CI, -$92 to -$43), GLP-1 RAs (-$43; 95% CI, -$85 to -$1), and SGLT-2 inhibitors (-$46; 95% CI, -$87 to -$6); changes in all other quarterly costs besides the index medication were significantly lower for patients receiving DPP-4 inhibitors (-$60; 95% CI, -$94 to -$26) and SGLT-2 inhibitors (-$113; 95% CI, -$169 to -$57). CONCLUSIONS: The higher cost of nonsulfonylurea medications was the main driver of relative increases in total costs. Relative decreases in nonpharmacy medical costs among patients receiving newer ADM classes reflect these medications' potential value.

Associations of Maternal Cardiovascular Health in Pregnancy With Offspring Cardiovascular Health in Early Adolescence.

Importance: Pregnancy may be a key window to optimize cardiovascular health (CVH) for the mother and influence lifelong CVH for her child. Objective: To examine associations between maternal gestational CVH and offspring CVH. Design, Setting, and Participants: This cohort study used data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study (examinations: July 2000-April 2006) and HAPO Follow-Up Study (examinations: February 2013-December 2016). The analyses included 2302 mother-child dyads, comprising 48% of HAPO Follow-Up Study participants, in an ancillary CVH study. Participants were from 9 field centers across the United States, Barbados, United Kingdom, China, Thailand, and Canada. Exposures: Maternal gestational CVH at a target of 28 weeks' gestation, based on 5 metrics: body mass index, blood pressure, total cholesterol level, glucose level, and smoking. Each metric was categorized as ideal, intermediate, or poor using pregnancy guidelines. Total CVH was categorized as follows: all ideal metrics, 1 or more intermediate (but 0 poor) metrics, 1 poor metric, or 2 or more poor metrics. Main Outcomes and Measures: Offspring CVH at ages 10 to 14 years, based on 4 metrics: body mass index, blood pressure, total cholesterol level, and glucose level. Total CVH was categorized as for mothers. Results: Among 2302 dyads, the mean (SD) ages were 29.6 (2.7) years for pregnant mothers and 11.3 (1.1) years for children. During pregnancy, the mean (SD) maternal CVH score was 8.6 (1.4) out of 10. Among pregnant mothers, the prevalence of all ideal metrics was 32.8% (95% CI, 30.6%-35.1%), 31.7% (95% CI, 29.4%-34.0%) for 1 or more intermediate metrics, 29.5% (95% CI, 27.2%-31.7%) for 1 poor metric, and 6.0% (95% CI, 3.8%-8.3%) for 2 or more poor metrics. Among children of mothers with all ideal metrics, the prevalence of all ideal metrics was 42.2% (95% CI, 38.4%-46.2%), 36.7% (95% CI, 32.9%-40.7%) for 1 or more intermediate metrics, 18.4% (95% CI, 14.6%-22.4%) for 1 poor metric, and 2.6% (95% CI, 0%-6.6%) for 2 or more poor metrics. Among children of mothers with 2 or more poor metrics, the prevalence of all ideal metrics was 30.7% (95% CI, 22.0%-40.4%), 28.3% (95% CI, 19.7%-38.1%) for 1 or more intermediate metrics, 30.7% (95% CI, 22.0%-40.4%) for 1 poor metric, and 10.2% (95% CI, 1.6%-20.0%) for 2 or more poor metrics. The adjusted relative risks associated with 1 or more intermediate, 1 poor, and 2 or more poor (vs all ideal) metrics, respectively, in mothers during pregnancy were 1.17 (95% CI, 0.96-1.42), 1.66 (95% CI, 1.39-1.99), and 2.02 (95% CI, 1.55-2.64) for offspring to have 1 poor (vs all ideal) metrics, and the relative risks were 2.15 (95% CI, 1.23-3.75), 3.32 (95% CI,1.96-5.62), and 7.82 (95% CI, 4.12-14.85) for offspring to have 2 or more poor (vs all ideal) metrics. Additional adjustment for categorical birth factors (eg, preeclampsia) did not fully explain these significant associations (eg, relative risk for association between 2 or more poor metrics among mothers during pregnancy and 2 or more poor metrics among offspring after adjustment for an extended set of birth factors, 6.23 [95% CI, 3.03-12.82]). Conclusions and Relevance: In this multinational cohort, better maternal CVH at 28 weeks' gestation was significantly associated with better offspring CVH at ages 10 to 14 years.

Evaluating the maternal and perinatal sequelae of severe gestational hypertension.

BACKGROUND: Hypertensive disorders of pregnancy are widespread and have long-standing implications for women's health. Historically, the management of "severe gestational hypertension," or the presence of severely elevated blood pressures without any other signs or symptoms of end-organ damage meeting the criteria for preeclampsia, has been unclear. The new American College of Obstetricians and Gynecologists guidelines based on expert opinion recommend that severe gestational hypertension be treated similarly to preeclampsia with severe features, but data regarding outcomes for women with this diagnosis have been limited. OBJECTIVE: This study aimed to compare the maternal and perinatal sequelae of severe gestational hypertension with that of other types of hypertensive disorders of pregnancy. STUDY DESIGN: This is a retrospective cohort study of women with hypertensive disease of pregnancy who delivered at a single tertiary care center between February and December 2018. Women with chronic hypertension; hemolysis, elevated liver enzymes, and low platelet count syndrome; preexisting kidney, liver, rheumatologic, or hematologic disorders; or multifetal pregnancies were excluded. Women were categorized as having severe gestational hypertension if they had a sustained systolic blood pressure of >160 mm Hg or a diastolic blood pressure of >110 mm Hg without other criteria for preeclampsia. The primary comparison was between women with severe gestational hypertension and women with preeclampsia without severe features. Secondary comparisons included women with severe gestational hypertension vs women with other types of hypertensive disease of pregnancy. The primary outcome for this analysis was small-for-gestational-age birth. We also evaluated other maternal and neonatal morbidities including but not limited to pulmonary embolism, stroke, eclampsia, blood transfusion, mechanical ventilation, intensive care unit admission, death, 5-minute Apgar score of ≤4, umbilical cord pH, neonatal intensive care unit admission of >2 days, respiratory distress syndrome, and neonatal death. Bivariate analyses using chi-square tests and logistic regressions adjusting for race, ethnicity, age, body mass index, parity, and insurance status were performed to compare frequencies of outcomes for each type of hypertensive disease of pregnancy with those of severe gestational hypertension. RESULTS: Of 2076 women eligible for inclusion, 12.2% (n=254) had severe gestational hypertension and 379 (18.2%) had preeclampsia without severe features. Although there was no difference in the odds of small-for-gestational-age birth between women with severe gestational hypertension and women with preeclampsia without severe features (14.7% vs 9.8%; adjusted odds ratio, 0.72; 95% confidence interval, 0.44-1.21), the latter were significantly less likely to receive a prescription for antihypertensive medication at discharge (OR 0.11, 95% CI 0.06-0.22) or to be readmitted postpartum (OR 0.14, 95% CI 0.04-0.50). CONCLUSION: There was no difference in the primary outcome, that is, rate of small-for-gestational-age birth, between women with severe gestational hypertension and women with preeclampsia without severe features. However, women with severe gestational hypertension had greater odds of other maternal and neonatal morbidities than women with preeclampsia without severe features or mild gestational hypertension. These findings support recent recommendations regarding the management of women with severe gestational hypertension.

Associations of gestational cardiovascular health with pregnancy outcomes: the Hyperglycemia and Adverse Pregnancy Outcome study.

BACKGROUND: The American Heart Association's formal characterization of cardiovascular health combines several metrics in a health-oriented, rather than disease-oriented, framework. Although cardiovascular health assessment during pregnancy has been recommended, its significance for pregnancy outcomes is unknown. OBJECTIVE: The purpose of this study was to examine the association of gestational cardiovascular health-formally characterized by a combination of 5 metrics-with adverse maternal and newborn outcomes. STUDY DESIGN: We analyzed data from the Hyperglycemia and Adverse Pregnancy Outcome study, including 2304 mother-newborn dyads from 6 countries. Maternal cardiovascular health was defined by the combination of the following 5 metrics measured at a mean of 28 (24-32) weeks' gestation: body mass index, blood pressure, lipids, glucose, and smoking. Levels of each metric were categorized using pregnancy guidelines, and the total cardiovascular health was scored (0-10 points, where 10 was the most favorable). Cord blood was collected at delivery, newborn anthropometrics were measured within 72 hours, and medical records were abstracted for obstetrical outcomes. Modified Poisson and multinomial logistic regression were used to test the associations of gestational cardiovascular health with pregnancy outcomes, adjusted for center and maternal and newborn characteristics. RESULTS: The average age of women at study exam was 29.6 years old, and they delivered at a mean gestational age of 39.8 weeks. The mean total gestational cardiovascular health score was 8.6 (of 10); 36.3% had all ideal metrics and 7.5% had 2+ poor metrics. In fully adjusted models, each 1 point higher (more favorable) cardiovascular health score was associated with lower risks for preeclampsia (relative risk, 0.67 [95% confidence interval, 0.61-0.73]), unplanned primary cesarean delivery (0.88 [0.82-0.95]), newborn birthweight >90th percentile (0.81 [0.75-0.87]), sum of skinfolds >90th percentile (0.84 [0.77-0.92]), and insulin sensitivity <10th percentile (0.83 [0.77-0.90]). Cardiovascular health categories demonstrated graded associations with outcomes; for example, relative risks (95% confidence intervals) for preeclampsia were 3.13 (1.39-7.06), 5.34 (2.44-11.70), and 9.30 (3.95-21.86) for women with ≥1 intermediate, 1 poor, or ≥2 poor (vs all ideal) metrics, respectively. CONCLUSION: More favorable cardiovascular health at 24 to 32 weeks' gestation was associated with lower risks for several adverse pregnancy outcomes in a multinational cohort.