Faculty Bibliography

Primary aldosteronism is a frequent cause of resistant hypertension and is associated with an increased risk of developing diabetes mellitus. Aldosterone impairs insulin secretion in isolated islets, and insulin secretion is increased in aldosterone synthase-deficient mice. We hypothesized that treatment for primary aldosteronism increases insulin secretion and insulin sensitivity in humans. We conducted a prospective cohort study in patients with primary aldosteronism, with assessment of glucose metabolism before and 3 to 12 months after treatment. Participants underwent treatment for primary aldosteronism with adrenalectomy or a mineralocorticoid receptor antagonist at the discretion of their treating physician. We assessed insulin secretion and insulin sensitivity by hyperglycemic and hyperinsulinemic-euglycemic clamps, respectively, on 2 study days after a 5-day standardized diet. After treatment, the C-peptide and insulin response during the hyperglycemic clamp increased compared with pretreatment (ΔC-peptide at 90-120 minutes +530.5±384.1 pmol/L, P=0.004; Δinsulin 90-120 minutes +183.0±122.6, P=0.004). During hyperinsulinemic-euglycemic clamps, insulin sensitivity decreased after treatment (insulin sensitivity index 30.7±6.2 versus 18.5±4.7 nmol·kg^-1·min^-1·pmol^-1·L; P=0.02). Insulin clearance decreased after treatment (872.8±207.6 versus 632.3±178.6 mL/min; P=0.03), and disposition index was unchanged. We conclude that the insulin response to glucose increases and insulin clearance decreases after treatment for primary aldosteronism, and these effects were not due to alterations in creatinine clearance or plasma cortisol. These studies may provide further insight into the mechanism of increased diabetes mellitus risk in primary aldosteronism.

OBJECTIVES/OBJECTIVE:Fetal exposure to phthalates and bisphenols may lead to vascular developmental adaptations, which program later cardiovascular disease. We examined the associations of fetal exposure to phthalates and bisphenols with childhood blood pressure. METHODS:In a population-based, prospective cohort study among 1,064 mother-child pairs, we measured maternal urine phthalate and bisphenol concentrations in first, second and third trimester of pregnancy. We measured childhood blood pressure at the mean age of 9.7 years (standard deviation 0.2 years) old. Analyses were performed for the total group, and for boys and girls separately. RESULTS:Maternal urine phthalate concentrations were not associated with childhood blood pressure among boys. Higher third trimester maternal urine concentrations of high molecular weight phthalates (HMWP), di-2-ehtylhexylphthalate (DEHP) and di-n-octylphthalate (DNOP) were associated with lower systolic and diastolic blood pressure among girls (p-values < 0.01). Also, higher second trimester maternal urine total bisphenol and bisphenol A concentrations were associated with higher systolic blood pressure among boys (p values < 0.01), but tended to be associated with a lower diastolic blood pressure among girls. CONCLUSIONS:Our results suggest sex-dependent associations of maternal urine phthalate and bisphenol concentrations during pregnancy with childhood blood pressure. Further studies are needed to explore the underlying mechanisms and long term consequences.

PURPOSE/OBJECTIVE:Despite known benefits of cardiac rehabilitation (CR), early termination (failure to complete >1 mo of CR) attenuates these benefits. We analyzed whether early termination varied by referral indication in the context of recent growth in patients referred for heart failure with reduced ejection fraction (HFrEF). METHODS:We reviewed records from 1111 consecutive patients enrolled in the NYU Langone Health Rusk CR program (2013-2017). Sessions attended, demographics, and comorbidities were abstracted, as well as primary referral indication: HFrEF or ischemic heart disease (IHD; including post-coronary revascularization, post-acute myocardial infarction, or chronic stable angina). We compared rates of early termination between HFrEF and IHD, and used multivariable logistic regression to determine whether differences persisted after adjusting for relevant characteristics (age, race, ethnicity, body mass index, smoking, hypertension, chronic obstructive pulmonary disease, and depression). RESULTS:Mean patient age was 64 yr, 31% were female, and 28% were nonwhite. Most referrals (85%) were for IHD; 15% were for HFrEF. Early termination occurred in 206 patients (18%) and was more common in HFrEF (26%) than in IHD (17%) (P < .01). After multivariable adjustment, patients with HFrEF remained at higher risk of early termination than patients with IHD (unadjusted OR = 1.73, 95% CI, 1.17-2.54; adjusted OR = 1.53, 95% CI, 1.01-2.31). CONCLUSIONS:Nearly 1 in 5 patients in our program terminated CR within 1 mo, with HFrEF patients at higher risk than IHD patients. While broad efforts at preventing early termination are warranted, particular attention may be required in patients with HFrEF.

Beta amyloid (Aβ) accumulation is the earliest pathological marker of Alzheimer's disease (AD), but early AD pathology also affects white matter (WM) integrity. We performed a cross-sectional study including 44 subjects (23 healthy controls and 21 mild cognitive impairment or early AD patients) who underwent simultaneous PET-MR using 18F-Florbetapir, and were categorized into 3 groups based on Aβ burden: Aβ- [mean mSUVr ≤1.00], Aβi [1.00 < mSUVr <1.17], Aβ+ [mSUVr ≥1.17]. Intergroup comparisons of diffusion MRI metrics revealed significant differences across multiple WM tracts. Aβi group displayed more restricted diffusion (higher fractional anisotropy, radial kurtosis, axonal water fraction, and lower radial diffusivity) than both Aβ- and Aβ+ groups. This nonmonotonic trend was confirmed by significant continuous correlations between mSUVr and diffusion metrics going in opposite direction for 2 cohorts: pooled Aβ-/Aβi and pooled Aβi/Aβ+. The transient period of increased diffusion restriction may be due to inflammation that accompanies rising Aβ burden. In the later stages of Aβ accumulation, neurodegeneration is the predominant factor affecting diffusion.

Directed acyclic graphs (DAGs), a prominent tool for expressing assumptions in epidemiologic research, are most useful when the hypothetical data generating structure is correctly encoded. Understanding a study's data generating structure and translating that data structure into a DAG can be challenging, but these skills are often glossed over in training. Campbell and Stanley's framework for causal inference has been extraordinarily influential in social science training programs but has received less attention in epidemiology. Their work, along with subsequent revisions and enhancements based on practical experience conducting empirical studies, presents a catalog of 37 threats to validity describing reasons empirical studies may fail to deliver causal effects. We interpret most of these threats to study validity as suggestions for common causal structures. Threats are organized into issues of statistical conclusion validity, internal validity, construct validity, or external validity. To assist epidemiologists in drawing the correct DAG for their application, we map the correspondence between threats to validity and epidemiologic concepts that can be represented with DAGs. Representing these threats as DAGs makes them amenable to formal analysis with d-separation rules and breaks down cross-disciplinary language barriers in communicating methodologic issues.

Rationale & Objectives/UNASSIGNED:Recent data demonstrate that center volume is not a factor in the outcomes of adult kidney transplant recipients. This study assessed whether center volume affects graft survival in pediatric patients who received a kidney transplant. Study Design/UNASSIGNED:Case-cohort study. Setting & Participants/UNASSIGNED:Kidney transplantation centers, recipients younger than 18 years. Results/UNASSIGNED: = 0.02. Although outcomes for deceased donor kidney recipients were similar in the 3 volume categories, outcomes in patients who received a living kidney donation were better in the high-volume centers. Low household income was associated with poorer outcomes. However, 3-year graft survival was similar in the 3 center volume categories in high and low mean household income states. Limitations/UNASSIGNED:Lack of information for complications and individual family household income of recipients. Conclusions/UNASSIGNED:Transplantation outcomes are worse in pediatric patients treated at lower-volume centers. The difference was more pronounced for patients receiving living versus deceased donor kidneys. The distribution of household income in pediatric transplant recipients may also be a factor that contributes to lower 3-year graft survival in low-volume centers.

Background and Objectives: To rapidly develop, implement, and evaluate emergency department (ED) clinical protocols for initiation of buprenorphine (E

OBJECTIVE:To explore the impact of an adapted goals-of-care communications skills workshop created for ED physicians from the physicians' perspective. METHODS:Semi-structured, one-on-one audio-recorded interviews lasting 30-60 min were conducted with twelve physicians who had completed the training workshop. Interviews explored the experience of undertaking the workshop, its impact on their clinical practice and their ability to teach new skills to other clinicians using learnt techniques. Descriptive content analysis was performed on interview transcripts. RESULTS:Participants reported positive experiences of the workshop. The analysis identified four main themes and ten subthemes dealing with workshop content and its impact on subsequent ED-based clinical practice. There were: 1) value and future improvements for the course; 2) value of the course to practice; 3) value of the course for teaching residents and 4) barriers to application of learning. Specifically recommended components include the use of mnemonics, mechanisms to introduce difficult conversations and a positive feedback environment. Participant-recommended refinements to the workshop included emphasising urgency, replicating the chaotic ED environment and expanding content to include more ED-focused goals-of-care discussions. CONCLUSION/CONCLUSIONS:A short, focused training workshop directed at improving palliative care communication skills among ED clinicians appears to be welcomed and useful.

OBJECTIVES/OBJECTIVE:To assess relations of prepregnancy maternal and paternal obesity with offspring behavioral problems and psychiatric symptoms at 7-8 years in the Upstate KIDS study, a prospective cohort study. STUDY DESIGN/METHODS:Maternal body mass index (BMI) was calculated from prepregnancy height and weight provided in vital records or self-report at 4 months postpartum. Mothers reported paternal height and weight. At 7-8 years, mothers indicated if their children had been diagnosed with ADHD or anxiety (n = 1915). Additionally, children's behavior was measured with the Strengths and Difficulties Questionnaire at 7 years of age (n = 1386) and the Vanderbilt ADHD Diagnostic Parent Rating Scale at 8 years of age (n = 1484). Based on Strengths and Difficulties Questionnaire scores, we identified children with borderline behavioral problems. Adjusted risk ratios (aRR) and 95% CIs were estimated with robust multivariable Poisson regression. RESULTS:had higher risks of reported ADHD (aRR, 1.14, 95% CI, 0.78-1.69; aRR, 1.96, 95% CI, 1.29-2.98; and aRR, 1.82, 95% CI,1.21-2.74, respectively). Risks of hyperactivity problems identified by the Strengths and Difficulties Questionnaire and a positive screen for inattentive or hyperactive/impulsive behavior with the Vanderbilt ADHD Diagnostic Parent Rating Scale were also higher with increasing maternal prepregnancy BMI. Paternal BMI was not associated with child outcomes. CONCLUSIONS:Our findings suggest that maternal, rather than paternal, obesity is associated with maternal report of child ADHD diagnosis and inattentive or hyperactivity problems. Further research is needed to understand how maternal obesity might influence these behavioral changes during or after pregnancy.