Faculty Bibliography

BACKGROUND:The assessment of clinical guideline adherence for the evaluation of pulmonary embolism (PE) via computed tomography pulmonary angiography (CTPA) currently requires either labor-intensive, retrospective chart review or prospective collection of PE risk scores at the time of CTPA order. The recording of clinical data in a structured manner in the electronic health record (EHR) may make it possible to automate the calculation of a patient's PE risk classification and determine whether the CTPA order was guideline concordant. OBJECTIVES/OBJECTIVE:The objective of this study was to measure the performance of automated, structured-data-only versions of the Wells and revised Geneva risk scores in emergency department encounters during which a CTPA was ordered. The hypothesis was that such an automated method would classify a patient's PE risk with high accuracy compared to manual chart review. METHODS:We developed automated, structured-data-only versions of the Wells and revised Geneva risk scores to classify 212 emergency department (ED) encounters during which a CTPA was performed as "PE Likely" or "PE Unlikely." We then combined these classifications with D-dimer ordering data to assess each encounter as guideline concordant or discordant. The accuracy of these automated classifications and assessments of guideline concordance were determined by comparing them to classifications and concordance based on the complete Wells and revised Geneva scores derived via abstractor manual chart review. RESULTS:The automatically derived Wells and revised Geneva risk classifications were 91.5% and 92% accurate compared to the manually determined classifications, respectively. There was no statistically significant difference between guideline adherence calculated by the automated scores as compared to manual chart review (Wells: 70.8 vs. 75%, p = 0.33 | Revised Geneva: 65.6 vs. 66%, p = 0.92). CONCLUSION/CONCLUSIONS:The Wells and revised Geneva score risk classifications can be approximated with high accuracy using automated extraction of structured EHR data elements in patients who received a CTPA. Combining these automated scores with D-dimer ordering data allows for the automated assessment of clinical guideline adherence for CTPA ordering in the emergency department, without the burden of manual chart review.

INTRODUCTION/BACKGROUND:We sought to characterize the effects of PSA registry errors on clinical research by comparing cohorts based on cancer registry PSA values with those based directly on results in the electronic health record. METHODS:We defined example cohorts of men with prostate cancer using data from the Veterans Health Administration: those with a PSA values less than 4.0 ng/mL, 4.0 to 10.0 ng/mL, 10.0 to 20.0 ng/mL, and 20.0 to 98.0 ng/mL. We compared the composition of each cohort and overall patient survival when using PSA values from either the VA Central Cancer Registry versus the gold standard electronic health record laboratory file results. RESULTS:There was limited agreement between cohorts defined using either the cancer registry PSA values versus the laboratory file of the electronic health record. The least agreement was seen in patients with PSA values < 4.0 ng/mL (58%) and greatest among patients with PSA values between 4.0 and 10.0 ng/mL (89%). In each cohort, patients assigned to a cohort based only on the cancer registry PSA value had significantly different overall survival when compared with patients assigned based on both the registry and laboratory file PSA values. CONCLUSIONS:Cohorts based exclusively on cancer registry PSA values may have high rates of misclassification that can introduce concerning differences in key characteristics and result in measurable differences in clinical outcomes.

In this article, we discuss a case in which a 16-year-old birth-assigned male came out to her parents as transgender. She is referred to the gender management program at a large pediatric academic center to discuss hormone therapy. She was initially evaluated by a psychiatrist, diagnosed with gender dysphoria and anxiety, and treated with medication and psychotherapy. When her anxiety was well controlled and she met eligibility and readiness criteria, she was referred to 1 of 2 pediatric endocrinologists in the gender management program to discuss hormone therapy. As part of the discussion about the risks/benefits of estrogen therapy, the pediatric endocrinologist discussed options for fertility preservation (FP) before potentially gonadotoxic therapy. The patient stated that she was not interested in FP. Her mother requested procedures to preserve the possibility that the daughter could have biological children someday. We asked experts in the care of transgender youth to discuss ways in which the doctor could respond to this disagreement between parents and a teenager about FP.

Considering the vast ongoing challenge of preventing obesity, the time has come to reconceptualize and change the way we study the development of obesity in childhood. The developmental cascade model, which refers to the cumulative consequences and spreading downstream effects of risk and protective factors, offers a longitudinal framework for understanding obesity. This perspective elucidates the way an accumulation of risk factors, across and within biopsychosocial spheres and phases of development, can propel individuals toward obesity. In this article, we use a theory-driven model-building approach and a review of published literature to propose a developmental cascade model of pediatric obesity focused on proximal biopsychosocial influences (e.g., genetic, intrapersonal, familial). A two-stage scoping review conducted in January 2015 and May 2016 identified 1315 unique studies; 310 were included in the final review. The proposed developmental cascade model provides a basis for testing hypothesized cascades with multiple intervening variables and complex longitudinal processes. Moreover, the model informs future research by resolving seemingly contradictory findings on pathways to obesity previously thought to be distinct (low self-esteem, consuming sugary foods, and poor sleep cause obesity) that are actually processes working together over time (low self-esteem causes consumption of sugary foods which disrupts sleep quality and contributes to obesity). The resultant empirical findings of such inquiries are highly informative for identifying the timing and specific targets of preventive interventions across and within developmental phases. The implications of such a cascade model of pediatric obesity for health psychology and developmental and prevention sciences are discussed.

PURPOSE/OBJECTIVE:To conduct a meta-analysis of studies investigating discrepancy rates and clinical impact of imaging secondary interpretations and to identify factors influencing these rates. METHODS:EMBASE and PubMed databases were searched for original research investigations reporting discrepancy rates for secondary interpretations performed by radiologists for imaging examinations initially interpreted at other institutions. Two reviewers extracted study information and assessed study quality. Meta-analysis was performed. RESULTS:Twenty-nine studies representing a total of 12,676 imaging secondary interpretations met inclusion criteria; 19 of these studies provided data specifically for oncologic imaging examinations. Primary risks of bias included availability of initial interpretations, other clinical information, and reference standard before the secondary interpretation. The overall discrepancy rate of secondary interpretations compared with primary interpretations was 32.2%, including a 20.4% discrepancy rate for major findings. Secondary interpretations were management changing in 18.6% of cases. Among discrepant interpretations with an available reference standard, the secondary interpretation accuracy rate was 90.5%. The overall discrepancy rates by examination types were 28.3% for CT, 31.2% for MRI, 32.7% for oncologic imaging, 43.8% for body imaging, 39.9% for breast imaging, 34.0% for musculoskeletal imaging, 23.8% for neuroradiologic imaging, 35.5% for pediatric imaging, and 19.7% for trauma imaging. CONCLUSION/CONCLUSIONS:Most widely studied in the context of oncology, imaging secondary interpretations commonly result in discrepant interpretations that are management changing and more accurate than initial interpretations. Policymakers should consider these findings as they consider the value of, and payment for, secondary imaging interpretations.

DPP (dipeptidyl peptidase)-4 inhibitors are antidiabetic drugs that may increase heart failure in high-risk patients. NPY (neuropeptide Y) is coreleased with norepinephrine, causes vasoconstriction via the Y1 receptor, and is degraded by DPP4 to NPY (3-36) in vitro. NPY (3-36) decreases release of norepinephrine via the Y2 receptor. We tested the hypothesis that DPP4 inhibition would potentiate the vasoconstrictor effect of NPY. Eighteen nonsmokers (12 healthy controls and 6 with type 2 diabetes mellitus) participated in 1 of 2 randomized, double-blind, placebo-controlled crossover studies. First, subjects were randomized to order of treatment with sitagliptin 100 mg/d versus placebo for 7 days separated by 4-week washout. On the last day of treatment, NPY was infused by brachial artery and forearm blood flow was measured using plethysmography. Blood samples were collected after each dose. NPY infusions were repeated after 90-minute washout and intra-arterial enalaprilat. Second, 5 healthy subjects were randomized to crossover treatment with sitagliptin 100 mg/d plus valsartan 160 mg/d versus placebo plus valsartan. NPY infusions were performed on the seventh day of treatment. NPY caused dose-dependent vasoconstriction. During enalaprilat, sitagliptin significantly potentiated NPY-induced vasoconstriction in controls and diabetics ( P≤0.02 for forearm blood flow in either group). Baseline norepinephrine release was increased during sitagliptin and enalaprilat, but not further by NPY. Sitagliptin increased the ratio of NPY to NPY (3-36). During valsartan, sitagliptin also significantly potentiated NPY-induced vasoconstriction ( P=0.009 for forearm blood flow). Potentiation of endogenous NPY could contribute to cardiovascular effects of DPP4 inhibitors in patients taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.

African Americans carrying two apolipoprotein L1 gene (APOL1) renal risk variants have a high risk for nephropathy. However, only a minority develops end-stage renal disease (ESRD). Hence, modifying factors likely contribute to initiation of kidney disease such as endogenous (HIV infection) or exogenous (interferon treatment) environmental modifiers. In this report, genome-wide association studies and a meta-analysis were performed to identify novel loci for nondiabetic ESRD in African Americans and to detect genetic modifiers in APOL1-associated nephropathy. Two African American cohorts were analyzed, 1749 nondiabetic ESRD cases and 1136 controls from Wake Forest and 901 lupus nephritis (LN)-ESRD cases and 520 controls with systemic lupus erythematosus but lacking nephropathy from the LN-ESRD Consortium. Association analyses adjusting for APOL1 G1/G2 renal-risk variants were completed and stratified by APOL1 risk genotype status. Individual genome-wide association studies and meta-analysis results of all 2650 ESRD cases and 1656 controls did not detect significant genome-wide associations with ESRD beyond APOL1. Similarly, no single nucleotide polymorphism showed significant genome-wide evidence of an interaction with APOL1 risk variants. Thus, although variants with small individual effects cannot be ruled out and are likely to exist, our results suggest that APOL1-environment interactions may be of greater clinical importance in triggering nephropathy in African Americans than APOL1 interactions with other single nucleotide polymorphisms.

American society tends to medicalize or criminalize social problems. Criminal justice reformers have made arguments for a positive role in the relief of poverty that are similar to those aired in healthcare today. The consequences of criminalizing poverty caution against its continued medicalization.