<p><strong>OBJECTIVES: </strong>To determine the natural history of pediatric hypertension.</p>

<p><strong>METHODS: </strong>We conducted a 72-month retrospective cohort study among 165 primary care sites. Blood pressure measurements from two consecutive 36 month periods were compared.</p>

<p><strong>RESULTS: </strong>Among 398 079 primary care pediatric patients ages 3 to 18, 89 347 had ≥3 blood pressure levels recorded during a 36-month period, and 43 825 children had ≥3 blood pressure levels for 2 consecutive 36-month periods. Among these 43 825 children, 4.3% (1881) met criteria for hypertension (3.5% [1515] stage 1, 0.8% [366] stage 2) and 4.9% (2144) met criteria for elevated blood pressure in the first 36 months. During the second 36 months, 50% (933) of hypertensive patients had no abnormal blood pressure levels, 22% (406) had elevated blood pressure levels or &lt;3 hypertensive blood pressure levels, and 29% (542) had ≥3 hypertensive blood pressure levels. Of 2144 patients with elevated blood pressure in the first 36 months, 70% (1492) had no abnormal blood pressure levels, 18% (378) had persistent elevated blood pressure levels, and 13% (274) developed hypertension in the second 36-months. Among the 7775 patients with abnormal blood pressure levels in the first 36-months, only 52% (4025) had ≥3 blood pressure levels recorded during the second 36-months.</p>

<p><strong>CONCLUSIONS: </strong>In a primary care cohort, most children initially meeting criteria for hypertension or elevated blood pressure had subsequent normal blood pressure levels or did not receive recommended follow-up measurements. These results highlight the need for more nuanced initial blood pressure assessment and systems to promote follow-up of abnormal results.</p>

<p>Randomized controlled trials are the "gold standard" for estimating the causal effects of treatments. However, it is often not feasible to conduct such a trial because of ethical concerns or budgetary constraints. We expand upon an approach to the analysis of observational data sets that mimics a sequence of randomized studies by implementing propensity score models within each trial to achieve covariate balance, using weighting and matching. The methods are illustrated using data from a safety study of the relationship between second-generation antipsychotics and type 2 diabetes (outcome) in Medicaid-insured children aged 10-18 years across the United States from 2003 to 2007. Challenges in this data set include a rare outcome, a rare exposure, substantial and important differences between exposure groups, and a very large sample size. </p>

<p><strong>OBJECTIVE: </strong>To determine how hypotension in the first 48 h of sepsis management impacts acute kidney injury (AKI) development and persistence.</p>

<p><strong>STUDY DESIGN: </strong>Retrospective study of patients &gt; 1 month to &lt; 20 years old with sepsis in a pediatric ICU between November 2012 and January 2015 (n = 217). All systolic blood pressure (SBP) data documented within 48 h after sepsis recognition were collected and converted to percentiles for age, sex, and height. Time below SBP percentiles and below pediatric advanced life support (PALS) targets was calculated by summing elapsed time under SBP thresholds during the first 48 h. The primary outcome was new or persistent AKI, defined as stage 2 or 3 AKI present between sepsis day 3-7 using Kidney Disease: Improving Global Outcomes creatinine definitions. Secondary outcomes included AKI-free days (days alive and free of AKI) and time to kidney recovery.</p>

<p><strong>RESULTS: </strong>Fifty of 217 sepsis patients (23%) had new or persistent AKI. Patients with AKI spent a median of 35 min under the first SBP percentile, versus 4 min in those without AKI. After adjustment for potential confounders, the odds of AKI increased by 9% with each doubling of minutes spent under this threshold (p = 0.03). Time under the first SBP percentile was also associated with fewer AKI-free days (p = 0.02). Time spent under PALS targets was not associated with AKI.</p>

<p><strong>CONCLUSIONS: </strong>The duration of severe systolic hypotension in the first 48 h of pediatric sepsis management is associated with AKI incidence and duration when defined by age, sex, and height norms, but not by PALS definitions. Graphical abstract.</p>

<p><strong>OBJECTIVE: </strong>The majority of the children with a central line who present to the emergency department with fever or other signs of bacteremia do not have a central line-associated bloodstream infection (CLABSI). Our objective was to develop a clinical prediction model for CLABSI among this group of children in order to ultimately limit unnecessary hospital admissions and antibiotic use.</p>

<p><strong>METHODS: </strong>We performed a nested case-control study of children with a central line who presented to the emergency department of an urban, tertiary care children's hospital between January 2010 and March 2015 and were evaluated for CLABSI with a blood culture.</p>

<p><strong>RESULTS: </strong>The final multivariable model developed to predict CLABSI consisted of 12 factors: age younger than 5 years, black race, use of total parenteral nutrition, tunneled central venous catheter, double-lumen catheter, absence of other bacterial infection, absence of viral upper respiratory tract infection symptoms, diarrhea, emergency department temperature greater than 39.5°C, fever prior to presentation, neutropenia, and spring/summer season. The clinical prediction score had good discrimination for CLABSI with a c-statistic of 0.81 (confidence interval, 0.77-0.85). A cut point less than 6 was associated with a sensitivity of 98.5% and a negative predictive value of 99.2% for CLABSI.</p>

<p><strong>CONCLUSIONS: </strong>We were able to identify risk factors and develop a clinical prediction model for CLABSI in children presenting to the emergency department. Once validated in future study, this clinical prediction model could be used to assess the need for hospitalization and/or antibiotics among this group of patients.</p>

<p><strong>INTRODUCTION: </strong>Children with chronic kidney disease (CKD) risk progressing to end-stage kidney disease (ESKD). The majority of CKD causes in children are related to congenital anomalies of the kidney and urinary tract, which may be treated by urologic care.</p>

<p><strong>OBJECTIVE: </strong>To examine the association of ESKD with urologic care in children with CKD.</p>

<p><strong>STUDY DESIGN: </strong>This was a nested case-control study within the Chronic Kidney Disease in Children (CKiD) prospective cohort study that included children aged 1-16 years with non-glomerular causes of CKD. The primary exposure was prior urologic referral with or without surgical intervention. Incidence density sampling matched each case of ESKD to up to three controls on duration of time from CKD onset, sex, race, age at baseline visit, and history of low birth weight. Conditional logistic regression analysis was performed to estimate rate ratios (RRs) for the incidence of ESKD.</p>

<p><strong>RESULTS: </strong>Sixty-six cases of ESKD were matched to 153 controls. Median age at baseline study visit was 12 years; 67% were male, and 7% were black. Median follow-up time from CKD onset was 14.9 years. Seventy percent received urologic care, including 100% of obstructive uropathy and 96% of reflux nephropathy diagnoses. Cases had worse renal function at their baseline visit and were less likely to have received prior urologic care. After adjusting for income, education, and insurance status, urology referral with surgery was associated with 50% lower risk of ESKD (RR 0.50 [95% confidence interval [CI] 0.26-0.997), compared to no prior urologic care (Figure). After excluding obstructive uropathy and reflux nephropathy diagnoses, which were highly correlated with urologic surgery, the association was attenuated (RR 0.72, 95% CI 0.24-2.18).</p>

<p><strong>DISCUSSION: </strong>In this study, urologic care was commonly but not uniformly provided to children with non-glomerular causes of CKD. Underlying specific diagnoses play an important role in both the risk of ESKD and potential benefits of urologic surgery.</p>

<p><strong>CONCLUSION: </strong>Within the CKiD cohort, children with non-glomerular causes of CKD often received urologic care. Urology referral with surgery was associated with lower risk of ESKD compared to no prior urologic care but depended on specific underlying diagnoses.</p>

<p><strong>BACKGROUND: </strong>Maintaining high water intake reduces kidney stone recurrence, but is difficult to do. Strategies to reduce stone recurrence among adolescents are lacking.</p>

<p><strong>METHODS: </strong>We conducted an ecological momentary assessment study to identify factors associated with water intake among 25 adolescents with nephrolithiasis. Over 7-days, participants used smart bottles to self-monitor water intake and received questionnaires randomly four times daily that were completed in real-time on mobile devices. The questionnaires ascertained awareness of water intake volume, awareness of water intake goals, perceived need to drink, access to water, alternative beverage consumption, and attitudes towards bathrooms. Linear mixed-effects models were fit to estimate the association between momentary responses and daily water intake.</p>

<p><strong>RESULTS: </strong>Over 175 person-days, 595 (85%) assessments were completed. Median daily water intake was 1304mL (IQR 848-1832); 20% of participants met their intake goal for ≥4 days. Unawareness of water intake volume was associated with drinking 690mL less water a day (p=0.04). A strong self-perceived need to drink more was associated with drinking 1954 mL less water each day compared to no need to drink more (p&lt;0.01). Unawareness of intake goals was weakly associated with drinking 1129 mL less water each day(p=0.1). Access to water, alternative beverage consumption, and bathroom aversion were not associated with water intake.</p>

<p><strong>CONCLUSIONS: </strong>Unawareness of water volume consumed and low responsiveness to the perceived need to drink more were associated with low water intake. Interventions that help adolescents recognize when and identify how to increase water intake may be effective in reducing stone recurrence.</p>

<p><strong>BACKGROUND: </strong>Little data exist on acute kidney injury (AKI) risk factors in pediatric sepsis. We identified risk factors and inpatient outcomes associated with AKI at sepsis recognition in children with severe sepsis.</p>

<p><strong>METHODS: </strong>Retrospective, cross-sectional study with inpatient outcome description of 315 patients &gt; 1&nbsp;month to &lt; 20&nbsp;years old with severe sepsis in a pediatric intensive care unit over 3&nbsp;years. Exposures included demographics, vitals, and laboratory data. The primary outcome was kidney disease: Improving Global Outcomes creatinine-defined AKI within 24&nbsp;h of sepsis recognition. Factors associated with AKI and AKI severity were identified using multivariable Poisson and multinomial logistic regression, respectively.</p>

<p><strong>RESULTS: </strong>AKI was present in 42% (133/315) of severe sepsis patients, and 26% (83/315) had severe (stage 2/3) AKI. In multivariable-adjusted analysis, hematologic/immunologic comorbidities, malignancies, chronic kidney disease (CKD), abdominal infection, admission illness severity, and minimum systolic blood pressure (SBP) ≤ 5th percentile for age and sex within 24&nbsp;h of sepsis recognition were associated with AKI. Factors associated with mild AKI were CKD and abdominal infection, while factors associated with severe AKI were younger age, hematologic/immunologic comorbidities, malignancy, abdominal infection, and minimum SBP ≤ 5th percentile. Patients with AKI had increased hospital mortality (17 vs. 8%, P = 0.02) and length of stay [median 20 (IQR 10-47) vs. 16&nbsp;days (IQR 7-37), P = 0.03].</p>

<p><strong>CONCLUSIONS: </strong>In pediatric severe sepsis, AKI is associated with age, comorbidities, infection characteristics, and hypotension. Future evaluation of risk factors for AKI progression during sepsis is warranted to minimize AKI progression in this high-risk population.</p>

<p><strong>PURPOSE: </strong>Use electronic health record (EHR) data to (1) estimate the risk of arrhythmia associated with inhaled short-acting beta-2 agonists (SABA) in pediatric patients and (2) determine whether risk varied by on-label versus off-label prescribing.</p>

<p><strong>METHODS: </strong>Retrospective cohort study of 335&nbsp;041 children ≤18&nbsp;years using EHR primary care data from 2 pediatric health systems (2011-2013). A series of monthly pseudotrials were created, using propensity score methodology to balance baseline characteristics between SABA-exposed (identified by prescription) and SABA-unexposed children. Association between SABA and subsequent arrhythmia for each health system was estimated through pooled logistic regression with separate estimates for children initiating under and over 4&nbsp;years old (off-label and on-label, respectively).</p>

<p><strong>RESULTS: </strong>Eleven percent of the cohort received a SABA prescription, 57% occurred under the age of 4&nbsp;years (off-label). During the follow-up period, there were 283 first arrhythmia events, most commonly atrial tachyarrhythmias and premature ventricular/atrial contractions. In 1 health system, adjusted risk for arrhythmia was increased among exposed children (OR 1.89, 95% CI 1.31-2.73) without evidence of interaction between label status and risk. The absolute adjusted rate difference was 3.6/10&nbsp;000 person-years of SABA exposure. The association between SABA exposure and arrhythmias was less strong in the second system (OR 1.26, 95% CI 0.30-5.33).</p>

<p><strong>CONCLUSION: </strong>Using EHR data, we could estimate the risk of a rare event associated with medication use and determine difference in risk related to on-label versus off-label status. These findings support the value of EHR-based data for postmarketing drug studies in the pediatric population.</p>

<p><strong>PURPOSE: </strong>To determine the association between urology consultation and emergency department (ED) revisits for children with urinary stones.</p>

<p><strong>MATERIALS AND METHODS: </strong>This retrospective cohort study included patients ≤18 years-old who presented to an ED in South Carolina with a urinary stone from 1997-2015. The primary exposure was urology consultation during the index ED visit. The primary outcome was a stone-related ED revisit occurring within 180 days of discharge from an index ED visit. Secondary outcomes included CT utilization, inpatient admission, and emergent surgery.</p>

<p><strong>RESULTS: </strong>Among 5,642 index ED visits for acute urinary stones, 11% resulted in at least one stone-related ED revisit within 180 days. Fifty-nine percent of revisits occurred within 30-days of discharge and 39% were due to pain. The odds of ED revisit were highest within the first 48-hours of discharge (odds ratio [OR] 22.6, 95% confidence interval [CI] 18.0-28.5) and rapidly decreased thereafter. Urology consultation was associated with a 37% lower adjusted odds of ED revisit (OR 0.63, 95% CI 0.44-0.90) and 68% lower odds of CT utilization across all ED visits (OR 0.32, 95% CI 0.15-0.69). Among those who revisited, the frequency of pain complaints was 27% among those with urologic consultation at the index visit and 39% among those without.</p>

<p><strong>CONCLUSIONS: </strong>Urology consultation was associated with decreased ED revisits and CT imaging among pediatric patients with urinary stones. Future studies should identify the patients that benefit most from urology consultation and ascertain processes of care that decrease ED revisits among high-risk patients.</p>

<p>Temperature and relative humidity have opposing effects on evaporative water loss, the likely mediator of the temperature-dependence of nephrolithiasis. However, prior studies considered only dry-bulb temperatures when estimating the temperature-dependence of nephrolithiasis. We used distributed lag non-linear models and repeated 10-fold cross-validation to determine the daily temperature metric and corresponding adjustment for relative humidity that most accurately predicted kidney stone presentations during hot and cold periods in South Carolina from 1997 to 2015. We examined three metrics for wet-bulb temperatures and heat index, both of which measure the combination of temperature and humidity, and for dry-bulb temperatures: (1) daytime mean temperature; (2) 24-h mean temperature; and (3) most extreme 24-h temperature. For models using dry-bulb temperatures, we considered four treatments of relative humidity. Among 188,531 patients who presented with kidney stones, 24-h wet bulb temperature best predicted kidney stone presentation during summer. Mean cross-validated residuals were generally lower in summer for wet-bulb temperatures and heat index than the corresponding dry-bulb temperature metric, regardless of type of adjustment for relative humidity. Those dry-bulb models that additionally adjusted for relative humidity had higher mean residuals than other temperature metrics. The relative risk of kidney stone presentations at the 99th percentile of each temperature metric compared to the respective median temperature in summer months differed by temperature metric and relative humidity adjustment, and ranged from an excess risk of 8-14%. All metrics performed similarly in winter. The combination of temperature and relative humidity determine the risk of kidney stone presentations, particularly during periods of high heat and humidity. These results suggest that metrics that measure moist heat stress should be used to estimate the temperature-dependence of kidney stone presentations, but that the particular metric is relatively unimportant.</p>