Understanding the Role of Pharmacometrics-Based Clinical Decision Support Systems in Pediatric Patient Management: A Case Study Using Lyv Software.

Pharmacometrics could play a key role in shifting pediatric pharmacotherapy from dosing for an average patient to individualizing dosing. Clinicians can have these quantitative tools at their disposal without requiring significant training through the development of clinical decision support systems with easy-to-use interfaces that have a back-end analysis engine or pharmacometric model that uses extensive electronic health record data to predict an individualized dose for each patient. There has been increased development of these clinical decision support systems recently, and for these tools to make the proper breakthrough into clinical practice, it is of utmost importance to perform rigorous testing to ensure adequate predictive performance. In this article, we walk through the components of a decision support tool and the testing required to determine its robustness using an example of a decision support tool we developed for vancomycin dosing in pediatrics.

Nationality and sociocultural factors influence athlete development and sport outcomes: Perspectives from United States and Austrian youth alpine ski racing.

Geographical regions possess distinct sporting cultures that can influence athletic development from a young age. The United States (US) and Austria both produce elite alpine ski racers, yet have distinct sport structures (i.e., funding, skiing prominence). In this exploratory study, we investigated sport outcomes and psychological profiles in adolescent alpine ski racers attending skill development academies in the US (N= 169) and Austria (N= 209). Sport participation and psychological questionnaires (mental toughness, perfectionism, grit, coping, burnout) were administered to athletes. In Austria, athletes participated in fewer extracurricular sports, began competing and training younger, and accumulated less practice hours than athletes in the US. Athletes in the US reported greater burnout than athletes in Austria. Finally, in the US, women accumulated more practice hours and experienced more parental pressure than men, while men accumulated more practice hours in Austria. Austria's skiing-centric sport culture may encourage athletes to fully immerse into the sport, contributing to positive psychological outcomes. Reduced sport opportunities in the US beyond educational institutions may pressure athletes to practice more to ensure continued competitive skiing. Stressors for sport participation will be unique to gender in each country though, given their implicit gender stigmas for sport participation.

Characteristics and Outcomes of Pediatric Patients Supported With Ventricular Assist Device-A Multi-Institutional Analysis.

OBJECTIVES: The use of ventricular assist devices for pediatric patients with heart failure is increasing, but is associated with significant morbidity and mortality. Our objectives were to describe the admission outcomes and resource utilization of pediatric patients supported with ventricular assist devices, utilizing a multicenter database. DATA SOURCES: Pediatric Health Information System database (comprising 49 nonprofit children's hospitals). STUDY SELECTION: Retrospective cohort analysis of the database from January 2006 to September 2015 for all admissions less than or equal to 21 years old with ventricular assist device implantation. DATA EXTRACTION: The primary outcome was hospital mortality. The secondary outcomes were hospital length of stay and adjusted cost. DATA SYNTHESIS: We analyzed 744 ventricular assist device implantations (740 patients), 422 (57%) males, and 363 (49%) non-Hispanic white. Median age at admission was 5.9 years (interquartile range, 0.9-13.5 yr), and median length of stay was 69 days (interquartile range, 36-122 d). The overall hospital mortality was 188 (25%), whereas 395 (53%) were transplanted and 141 (19%) were discharged on ventricular assist device. Extracorporeal membrane oxygenation was used, in addition to ventricular assist device, in 340 (46%). The majority of ventricular assist device implantations (453, 61%) were from 2011 to 2015 (compared to 2006-2010). More patients discharged on ventricular assist device from 2011 to 2015 (23% vs 13% in 2006-2010; p = 0.001). There was no difference in median age, mortality, length of stay, or adjusted costs between these time periods. On multivariable analysis, underlying congenital heart disease, renal failure, liver congestion, sepsis, cerebrovascular accident, and extracorporeal membrane oxygenation were associated with hospital mortality. Sepsis and ventricular assist device replacement/repair were associated with higher adjusted cost and longer length of stay. CONCLUSIONS: The pediatric ventricular assist device experience continues to grow, with a significant increase in the number of patients undergoing ventricular assist device implantation and a higher proportion being discharged from hospital on ventricular assist device support in recent years. Underlying congenital heart disease, renal failure, sepsis, cerebrovascular accident, and extracorporeal membrane oxygenation are significantly associated with hospital mortality.

Population Pharmacokinetic Assessment of Vancomycin Dosing in the Large Pediatric Patient.

The most appropriate vancomycin dosing strategy in pediatric patients weighing ≥70 kg (weight based versus non-weight based) to achieve an area under the concentration-time curve (AUC) of ≥400 mg·liter/h and a trough concentration of <20 mg/liter is not known. Population pharmacokinetic analysis determined that dosing of vancomycin should be weight based using fat-free mass, with appropriate adjustment for kidney dysfunction.

Utility of state-level influenza disease burden and severity estimates to investigate an apparent increase in reported severe cases of influenza A(H1N1) pdm09 - Arizona, 2015-2016.

The Arizona Department of Health Services identified unusually high levels of influenza activity and severe complications during the 2015-2016 influenza season leading to concerns about potential increased disease severity compared with prior seasons. We estimated state-level burden and severity to compare across three seasons using multiple data sources for community-level illness, hospitalisation and death. Severity ratios were calculated as the number of hospitalisations or deaths per community case. Community influenza-like illness rates, hospitalisation rates and mortality rates in 2015-2016 were higher than the previous two seasons. However, ratios of severe disease to community illness were similar. Arizona experienced overall increased disease burden in 2015-2016, but not increased severity compared with prior seasons. Timely estimates of state-specific burden and severity are potentially feasible and may provide important information during seemingly unusual influenza seasons or pandemic situations.

Evaluating the contribution of differences in lean mass compartments for resting energy expenditure in African American and Caucasian American children.

BACKGROUND: Resting energy expenditure (REE), adjusted for total lean mass (LM), is lower in African American (AA) than Caucasian American (CA) children. Some adult studies suggest that AA-CA differences in lean mass compartments explain this REE difference. Similar data are limited in children. OBJECTIVE: To evaluate differences in compartment-specific lean mass between AA and CA children and examine the individual contributions of high-metabolic rate-at-rest trunk lean mass (TrLM) and low-metabolic-rate-at-rest appendicular lean mass (AppLM) for AA-CA differences in REE. METHODS: We studied a convenience sample of 594 AA (n = 281) and CA (n = 313) children. REE was measured by using indirect calorimetry; dual-energy X-ray absorptiometry was used to assess body composition. ANCOVAs were performed to examine AA-CA differences in TrLM, AppLM and REE. After accounting for age, sex, height, pubertal development, bone mass and adiposity, REE was evaluated adjusting for total LM (model A) and separately adjusting for TrLM and AppLM (model B). RESULTS: African American children had greater adjusted AppLM (17.8 ± 0.2 [SE] vs. 16.0 ± 0.2 kg, p < 0.001) and lower TrLM (17.2 ± 0.2 vs. 17.7 ± 0.2 kg, p = 0.022) than CA children. REE adjusted for total LM was 77 ± 16 kcal/d lower in AA than CA (p < 0.001). However, after accounting separately for AppLM and TrLM, the discrepancy in REE between the groups declined to 28 ± 19 kcal/d (p = 0.14). In the adjusted model, both TrLM (p < 0.001) and AppLM (p < 0.027) were independently associated with REE. CONCLUSION: In children, AA-CA differences in REE appear mostly attributable to differences in body composition. Lower REE in AA children is likely due to lower TrLM and greater AppLM.

Accounting for urban biogenic fluxes in regional carbon budgets.

Many ecosystem models incorrectly treat urban areas as devoid of vegetation and biogenic carbon (C) fluxes. We sought to improve estimates of urban biomass and biogenic C fluxes using existing, nationally available data products. We characterized biogenic influence on urban C cycling throughout Massachusetts, USA using an ecosystem model that integrates improved representation of urban vegetation, growing conditions associated with urban heat island (UHI), and altered urban phenology. Boston's biomass density is 1/4 that of rural forests, however 87% of Massachusetts' urban landscape is vegetated. Model results suggest that, kilogram-for-kilogram, urban vegetation cycles C twice as fast as rural forests. Urban vegetation releases (RE) and absorbs (GEE) the equivalent of 11 and 14%, respectively, of anthropogenic emissions in the most urban portions of the state. While urban vegetation in Massachusetts fully sequesters anthropogenic emissions from smaller cities in the region, Boston's UHI reduces annual C storage by >20% such that vegetation offsets only 2% of anthropogenic emissions. Asynchrony between temporal patterns of biogenic and anthropogenic C fluxes further constrains the emissions mitigation potential of urban vegetation. However, neglecting to account for biogenic C fluxes in cities can impair efforts to accurately monitor, report, verify, and reduce anthropogenic emissions.

Assessment of inpatient admissions and top 25 medications for obese pediatric patients at two academic hospitals.

PURPOSE: Inpatient admissions and the top 25 medications for obese pediatric patients at two academic hospitals were assessed. METHODS: Children age 2-17 years were included if they were obese and admitted to either hospital on or after January 1, 2011, and discharged before December 31, 2011. Obesity was defined as a body mass index of ≥95th percentile for age and sex. The objectives of this study were to determine the percentage of hospital admissions involving obese children and compile a list of medications prescribed to these patients. The top 25 medications prescribed were further evaluated to determine their pharmacokinetic disposition in obese patients. RESULTS: Obese children accounted for 18.8% of the 15,119 admissions for children age 2-17 years at the two study hospitals. No significant difference was noted in the number of obese pediatric children admitted between institutions. A total of 28,234 medications were ordered for this population, with a median number of 8 medications prescribed per admission. Sixteen of the same medications (64.0%) ranked in the top 25 at each facility. The most commonly prescribed medications for these patients included analgesics, antimicrobials, corticosteroids, bronchodilators, and gastrointestinal agents. CONCLUSION: Obese children accounted for 18.8% of admissions for patients age 2-17 years at two academic hospitals over a 1-year period. The most commonly prescribed medications for these children included analgesics, antimicrobials, corticosteroids, bronchodilators, and gastrointestinal agents. The literature guiding the dosing of these medications in this population was limited to seven studies, representing just three medications.

Variability in Treatment of Post-coarctectomy Hypertension: A Multicenter Study.

Many pharmacologic therapies are available for treatment of post-coarctectomy hypertension in pediatric patients, which may lead to variability in care. Evaluation of trends in pharmacotherapy is necessary to evaluate quality of care. The Pediatric Health Information System database was queried from 2004 to 2013 for patients >30 days of age who had an ICD-9 code for coarctation of the aorta repair of coarctation by end-to-end anastomosis and had a RACHS-1 score of 2. Patients were excluded if they were admitted for >30 days, underwent mechanical circulatory support, or expired during the admission. Patient demographic and hospital data were collected along with antihypertensive pharmacotherapy. Trends in antihypertensive, analgesic, and sedative pharmacotherapy were evaluated, and multivariable statistical analysis was used to determine variables that significantly influenced cost. A total of 1636 patients [66.6 % male, median age 1.5 years (IQR 0.31-5.3)] met study criteria. Patients received a median of 3 (IQR 2-4) antihypertensive medications for a median of 8 days (IQR 5-11). Intravenous antihypertensive therapy was prescribed for a median 3 days (IQR 2-5) and oral therapy for a median of 1 day (IQR 1-2). Antihypertensive therapy was continued at discharge in 79.8 % of patients. Hospital cost increased by 36 % over the study period (p < 0.01), and nicardipine, dexmedetomidine, and intravenous acetaminophen were most strongly associated with increased cost (p < 0.001). Variability in the pharmacotherapy of post-coarctectomy hypertension in pediatric patients exists, and the use of newer agents may be influencing the cost of care.

Adherence to Anticoagulant Therapy in Pediatric Patients Hospitalized With Pulmonary Embolism or Deep Vein Thrombosis: A Retrospective Cohort Study.

OBJECTIVES: The American College of Chest Physicians recommends anticoagulant therapy for at least 3 months in children hospitalized for venous thromboembolism. The objectives of the study were to evaluate the medication utilization patterns and predictors of adherence to anticoagulant therapy in pediatric population. METHODS: Texas Medicaid medical and prescription claims from September 1, 2007 to December 12, 2012 were extracted for children (<18 years) hospitalized for pulmonary embolism (PE) or deep vein thrombosis (DVT). The index date was defined as the date of the first prescription of an anticoagulant given within 14 days of discharge. Proportion of days covered (≥80% vs <80%) was used to assess adherence to anticoagulants while controlling for demographics, cause of hospitalization, history of nonsteroidal anti-inflammatory drug use, anticoagulant use, malignancy, drug type, and Charlson comorbidity index (CCI). KEY FINDINGS: The patients (n = 60) had a mean (± standard deviation [SD]) age of 14.2 (±4.8) years, were primarily female (56.7%), African American (55.0%), enoxaparin users (58.3%), and had a mean (±SD) CCI of 18.3 (±37.7). The mean (±SD) adherence rates for warfarin and enoxaparin were 85.5% (±22.7%) and 78.7% (±27.8%), respectively. Overall, 66.7% were adherent (≥80%) to anticoagulant therapy. Logistic regression showed that increasing age was significantly associated with adherence to anticoagulant therapy, after controlling for other covariates (odds ratio = 1.5, 95% confidence interval = 1.13-1.85). CONCLUSION: Nearly one-third of the pediatric patients on anticoagulant therapy after discharge from PE or DVT were still nonadherent. Further research is needed to highlight the factors responsible for nonadherence in pediatric patients.

Canine parvovirus in Australia: the role of socio-economic factors in disease clusters.

To identify clusters of canine parvoviral related disease occurring in Australia during 2010 and investigate the role of socio-economic factors contributing to these clusters, reported cases of canine parvovirus were extracted from an on-line disease surveillance system. Reported residential postcode was used to locate cases, and clusters were identified using a scan statistic. Cases included in clusters were compared to those not included in such clusters with respect to human socioeconomic factors (postcode area relative socioeconomic disadvantage, economic resources, education and occupation) and dog factors (neuter status, breed, age, gender, vaccination status). During 2010, there were 1187 cases of canine parvovirus reported. Nineteen significant (P<0.05) disease clusters were identified, most commonly located in New South Wales. Eleven (58%) clusters occurred between April and July, and the average cluster length was 5.7 days. All clusters occurred in postcodes with a significantly (P<0.05) greater level of relative socioeconomic disadvantage and a lower rank in education and occupation, and it was noted that clustered cases were less likely to have been neutered (P=0.004). No significant difference (P>0.05) was found between cases reported from cluster postcodes and those not within clusters for dog age, gender, breed or vaccination status (although the latter needs to be interpreted with caution, since vaccination was absent in most of the cases). Further research is required to investigate the apparent association between indicators of poor socioeconomic status and clusters of reported canine parvovirus diseases; however these initial findings may be useful for developing geographically- and temporally-targeted prevention and disease control programs.

Comparison of contraceptive choices of rural and urban US adults aged 18-55 years: an analysis of 2004 behavioral risk factor surveillance survey data.

INTRODUCTION: Although sexually active US adults wanting to prevent pregnancy have a wide variety of birth control methods readily available, there is little research that documents the contraceptive choices of rural adults in comparison to urban adults. This study compared the contraceptive choices of rural with urban adults. The comparative analysis joins the recent dialog in population health focused on assessing health related differences to detect if these are indicative of rural health disparities. DESIGN: This was a cross-sectional study analyzing 2004 Behavioral Risk Factor Surveillance Survey (BRFSS) data. Place of residence was ascertained by re-coding the state/county FIPS code as either urban or rural, based on 2003 Rural-Urban Continuum Codes from the US Office of Management and Budget (setting: US households; participants: US adults 18-55 years). MAIN OUTCOME MEASURES: characteristics and contraceptive method choice of rural adults using birth control. RESULTS: A multivariate regression model performed with 'use of birth control' as the dependent variable yielded that rural in comparison with urban adults 18-55 years were more likely to use female or male sterilization, non-injectable and injectable hormones for birth control. They were less likely to use: condoms, a diaphragm or NuvaRing, emergency contraception, withdrawal or rhythm methods. Additionally, in comparison with urban adults, rural persons younger than 35 years, those who had children younger than 18 years living with them, those who were partnered, males and those living in households with an income of less than US$35,000 were more likely to report using some form of contraception. CONCLUSION: There were differences in the contraception choices of urban and rural adults. How much primary care provider preferences explains the differences is not known and bears further exploration. These results should prove useful to healthcare providers as well as public health family planning programs.

Medication dosing and renal insufficiency in a pediatric cardiac intensive care unit: impact of pharmacist consultation.

Pediatric patients who have undergone cardiac surgery are at risk for renal insufficiency. The impact of pharmacist consultation in the pediatric cardiac intensive care unit (ICU) has yet to be defined. Patients admitted to the pediatric cardiac ICU at our institution from January through March of 2006 were included. Patient information, collected retrospectively, included: demographics, cardiac lesion/surgery, height, weight, need for peritoneal or hemodialysis, need for mechanical support, highest and lowest serum creatinine, ICU length of stay (LOS), renally eliminated medications, pharmacist recommendations (accepted or not), and appropriateness of dosing changes.There were 140 total admissions (131 patients; age: 3.0 +/- 6.3 years) during the study period. In total, 14 classes of renally eliminated medications were administered, with 32.6 +/- 56.4 doses administered per patient admission. Thirty-seven patient admissions had one or more medications adjusted for renal insufficiency; the most commonly adjusted medication was ranitidine. Patients who required medication adjustment for renal dysfunction were significantly younger compared to those patients not requiring medication adjustment. Pharmacist recommendations were responsible for 96% of medication adjustments for renal dysfunction, and the recommendations were accepted and appropriate all of the time. The monetary impact of pharmacist interventions, in doses saved, was approximately $12,000. Pharmacist consultation can result in improved dosing of medications and cost savings. The youngest patients are most at risk for inappropriate dosing.

Therapeutic levels of intravenous procainamide in neonates: a retrospective assessment.

STUDY OBJECTIVES: To evaluate dosing and pharmacokinetic parameters of intravenous continuous-infusion procainamide in neonates, and to identify dosage regimens and factors leading to therapeutic procainamide levels and minimal adverse events. DESIGN: Retrospective, observational study. SETTING: Pediatric hospital. PATIENTS: . Twenty-one patients (seven preterm, 14 full term) younger than 30 days who received continuous-infusion procainamide therapy for more than 15 hours or had two consecutive therapeutic procainamide levels obtained while receiving therapy between June 1, 2002, and December 31, 2005. MEASUREMENTS AND MAIN RESULTS: Data on demographics, dosing, drug levels, and adverse effects were collected. Doses that achieved therapeutic levels were documented, and procainamide clearance was calculated and evaluated with regard to renal function and gestational age in patients who were at steady state. Mean clearance and mean N-acetylprocainamide (NAPA):procainamide ratios were compared between preterm and term neonates. No patients experienced hemodynamic instability or other adverse effects due to procainamide. Procainamide was given as a mean +/- SD 9.6 +/- 1.5-mg/kg bolus in 20 of 21 patients before continuous infusion. The mean +/- SD dose at which two therapeutic levels were achieved was 37.56 +/- 13.52 microg/kg/minute. Procainamide clearance was 6.36 +/- 8.85 ml/kg/minute and correlated with creatinine clearance (r=0.78, p<0.00001) and age at day of sampling (r=0.49, p<0.00001). The NAPA:procainamide ratio at steady state was 0.84 +/- 0.53; two patients were determined to be fast acetylators (ratio > 1). Preterm infants had lower mean clearance rates (p<0.001) but higher NAPA:procainamide ratios (p<0.01) than those of term infants. Five patients experienced seven supratherapeutic levels while receiving therapy; four of these patients were preterm, and all had creatinine clearances less than 30 ml/minute/1.73 m(2). Three patients had four pairs of levels obtained after discontinuation of procainamide, and elimination rate constant and half-life were calculated. CONCLUSION: Procainamide can be safely used in neonates, with no short-term adverse effects. The dosage regimen for intravenous procainamide required to achieve therapeutic levels in neonates is similar to that of older infants and children. Doses may need to be reduced in premature infants and in those with renal dysfunction.

Intravascular ultrasonographic assessment of the results of coronary artery stenting.

We studied 12 patients undergoing elective coronary stent implantation for either recurrent restenosis or adverse lesion appearance. By use of a 4.8F 20 MHz intravascular ultrasound catheter, the conventional angioplasty site was examined before and after coronary stent implantation. Quantitative angiographic analysis revealed the expected excellent final result with a group mean poststent diameter reduction of 14 +/- 9% and a cross-sectional area reduction of 22 +/- 13%. Angiographic analysis also indicated an increase in minimum stenosis diameter from 1.8 +/- 0.6 mm after conventional balloon angioplasty to 2.8 +/- 0.3 mm after coronary stent implantation. Quantitative analysis of the corresponding intravascular ultrasound images, however, revealed significant residual endoluminal obstruction. Fractional plaque area remained unchanged from 30 +/- 12% after conventional balloon angioplasty to 32 +/- 11% after stent implantation. The circumferential distribution of plaque increased significantly from 0.44 +/- 0.17 to 0.55 +/- 0.15 (p = 0.03) after stent implantation. Despite the lack of significant change in the ultrasound-determined minimum stenosis diameter after stent placement, there was a borderline significant increase in the plaque-free lumen area (before stent, 6.35 +/- 1.55 mm2; after stent, 7.25 +/- 1.6 mm2; p = 0.06). Thus, in contrast to the substantial improvement in the angiographically assessed residual luminal obstruction after stent implantation compared with the prestent condition, considerably less improvement was found by intravascular ultrasound-assessed examination. Morphometric analysis indicated a tendency toward circumferential remodeling of plaque. The inherently different approaches to vascular imaging represented by contrast angiography and intravascular ultrasound techniques appear to provide complementary information.(ABSTRACT TRUNCATED AT 250 WORDS)