White Coat Hypertension Persistence in Children and Adolescents: The Pediatric Nephrology Research Consortium Study.

OBJECTIVES: To determine whether youth with white coat hypertension on initial ambulatory blood pressure monitoring (ABPM) continue to demonstrate the same pattern on repeat ABPM. STUDY DESIGN: Retrospective longitudinal cohort study of patients referred for high blood pressure (BP) and diagnosed with white coat hypertension by ABPM who had follow-up ABPM 0.5-4.6 years later at 11 centers in the Pediatric Nephrology Research Consortium. We classified ABPM phenotype using the American Heart Association guidelines. At baseline, we classified those with hypertensive BP in the clinic as "stable white coat hypertension," and those with normal BP as "intermittent white coat hypertension." We used multivariable generalized linear mixed effect models to estimate the association of baseline characteristics with abnormal ABPM phenotype progression. RESULTS: Eighty-nine patients met the inclusion criteria (median age, 13.9 years; 78% male). Median interval time between ABPM measurements was 14 months. On follow-up ABPM, 61% progressed to an abnormal ABPM phenotype (23% ambulatory hypertension, 38% ambulatory prehypertension). Individuals age 12-17 years and those with stable white coat hypertension had greater proportions progressing to either prehypertension or ambulatory hypertension. In the multivariable models, baseline wake systolic BP index ≥0.9 was significantly associated with higher odds of progressing to ambulatory hypertension (OR 3.07, 95% CI 1.02-9.23). CONCLUSIONS: The majority of the patients with white coat hypertension progressed to an abnormal ABPM phenotype. This study supports the 2017 American Academy of Pediatrics Clinical Practice Guideline's recommendation for follow-up of ABPM in patients with white coat hypertension.

Are Complex Skull Fractures Indicative of Either Child Abuse or Major Trauma in the Era of 3-Dimensional Computed Tomography Imaging?

OBJECTIVE: The aim of the study was to determine whether complex skull fractures are more indicative of child abuse or major trauma than simple skull fractures. DESIGN: This is a retrospective chart and imaging review of children diagnosed with a skull fracture. Subjects were from 2 pediatric tertiary care centers. Children younger than 4 years who underwent a head computed tomography with 3-dimensional rendering were included. We reviewed the medical records and imaging for type of skull fracture, abuse findings, and reported mechanism of injury. A complex skull fracture was defined as multiple fractures of a single skull bone, fractures of more than 1 skull bone, a nonlinear fracture, or diastasis of greater than 3 mm. Abuse versus accident was determined at the time of the initial evaluation with child abuse physician team confirmation. RESULTS: From 2011 to 2012, 287 subjects were identified by International Classification of Diseases, Ninth Revision, code. The 147 subjects with a cranial vault fracture and available 3-dimensional computed tomography composed this study's subjects. The average age was 12.3 months. Seventy four (50.3%) had complex and 73 (49.7%) had simple fractures. Abuse was determined in 6 subjects (4.1%), and a determination could not be made for 5 subjects. Adding abused children from 2013 to 2014 yielded 15 abused subjects. Twelve of the abused children (80%) had complex fractures; more than the 66 (48.5%) of 136 accidentally injured children (P = 0.001; relative risk = 1.65 [1.21-2.24]). However, among children with a complex fracture, the positive predictive value for abuse was only 7%. CONCLUSIONS: Complex skull fractures frequently occur from accidental injuries. This study suggests that the presence of complex skull fractures should not be used alone when making a determination of abuse.

Using a Multi-Institutional Pediatric Learning Health System to Identify Systemic Lupus Erythematosus and Lupus Nephritis: Development and Validation of Computable Phenotypes.

BACKGROUND AND OBJECTIVES: Performing adequately powered clinical trials in pediatric diseases, such as SLE, is challenging. Improved recruitment strategies are needed for identifying patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Electronic health record algorithms were developed and tested to identify children with SLE both with and without lupus nephritis. We used single-center electronic health record data to develop computable phenotypes composed of diagnosis, medication, procedure, and utilization codes. These were evaluated iteratively against a manually assembled database of patients with SLE. The highest-performing phenotypes were then evaluated across institutions in PEDSnet, a national health care systems network of >6.7 million children. Reviewers blinded to case status used standardized forms to review random samples of cases (n=350) and noncases (n=350). RESULTS: Final algorithms consisted of both utilization and diagnostic criteria. For both, utilization criteria included two or more in-person visits with nephrology or rheumatology and ≥60 days follow-up. SLE diagnostic criteria included absence of neonatal lupus, one or more hydroxychloroquine exposures, and either three or more qualifying diagnosis codes separated by ≥30 days or one or more diagnosis codes and one or more kidney biopsy procedure codes. Sensitivity was 100% (95% confidence interval [95% CI], 99 to 100), specificity was 92% (95% CI, 88 to 94), positive predictive value was 91% (95% CI, 87 to 94), and negative predictive value was 100% (95% CI, 99 to 100). Lupus nephritis diagnostic criteria included either three or more qualifying lupus nephritis diagnosis codes (or SLE codes on the same day as glomerular/kidney codes) separated by ≥30 days or one or more SLE diagnosis codes and one or more kidney biopsy procedure codes. Sensitivity was 90% (95% CI, 85 to 94), specificity was 93% (95% CI, 89 to 97), positive predictive value was 94% (95% CI, 89 to 97), and negative predictive value was 90% (95% CI, 84 to 94). Algorithms identified 1508 children with SLE at PEDSnet institutions (537 with lupus nephritis), 809 of whom were seen in the past 12 months. CONCLUSIONS: Electronic health record-based algorithms for SLE and lupus nephritis demonstrated excellent classification accuracy across PEDSnet institutions.

Hormonal status and test condition, but not sexual experience, modulate partner preference in female rats.

A series of experiments was conducted to determine the contributions of hormonal status, test condition, and sexual experience to the display of partner preference by female rats. Preference for a sexually active male rat over a sexually receptive female rat was assessed in independent groups of female rats tested in a condition limiting physical contact (No Contact) and a condition allowing for sexual interaction (Contact). Although hormonal status and test condition influenced the preference for a sexually active male, repeated testing and sexual experience had no effect. Experiment 1 demonstrated that independent of test condition, preference for the male is stronger in estrogen- and progesterone-primed rats than in rats receiving the vehicle. Moreover, independent of hormone condition, rats tested in the No Contact condition exhibit a stronger preference for the male than rats tested in the Contact condition, reflecting in part the active pacing of mating stimulation by sexually receptive rats tested in the Contact condition. Experiment 2 showed that the overall pattern of partner preference in proestrous and diestrous rats was similar to that observed in ovariectomized, estrogen- and progesterone-primed, and oil-treated rats, respectively. In Experiment 3, rats primed with estrogen alone did not exhibit a preference for the male even though fully receptive. Experiments 4 and 5 demonstrated that sexual experience does not affect the expression of preference for the male in estrogen- and progesterone-primed rats. The present findings demonstrate that the female rat's preference for the male is stable across repeated tests and is not affected by sexual experience. Our results also confirm that gonadal hormones influence the expression of a preference for a sexually active male versus a sexually receptive female and demonstrate that the magnitude of preference is modulated by test conditions.

Chronic administration of anabolic steroids disrupts pubertal onset and estrous cyclicity in rats.

Use of anabolic-androgenic steroids (AASs) is becoming increasingly popular among adolescent girls, yet the effects of AASs on female physiology and development are not well understood. The present study compared the effects of chronic exposure to three individual AASs, stanozolol (0.05-5 mg/kg), 17alpha-methyltestosterone (0.5-5 mg/kg), and methandrostenolone (0.5-5 mg/kg) on the onset of puberty and estrous cyclicity in the rat. Female rats received daily injections of AASs for 30 days (Postnatal Day [PN] 21-51). Rats receiving the highest dose of each of the AASs (5 mg/kg) displayed vaginal opening at a younger age than rats receiving the oil vehicle. The day of first vaginal estrus was delayed in rats receiving stanozolol (5 mg/kg) or 17alpha-methyltestosterone (0.5-5 mg/kg) but not in rats receiving methandrostenolone. At the highest dose (5 mg/kg), each of the AASs reduced the incidence of regular estrous cyclicity during the treatment period. Concurrent administration (on PN21-51) of the androgen receptor antagonist, flutamide (10 mg/kg, twice daily), reversed the effects of 17alpha-methyltestosterone (5 mg/kg) on vaginal opening. Flutamide administration also eliminated the effects of stanozolol (5 mg/kg) and 17alpha-methyltestosterone (5 mg/kg) on the day of first vaginal estrus. In contrast, rats receiving flutamide and methandrostenolone (5 mg/kg) exhibited first vaginal estrus earlier than controls. The present results indicate that chronic exposure to AASs during development has deleterious effects on the female neuroendocrine axis and that these effects appear be mediated via multiple mechanisms.