Jobayer Hossain

Benefits of a Pediatric Antimicrobial Stewardship Program at a Children's Hospital

OBJECTIVE: To prospectively evaluate the effect of a comprehensive antimicrobial stewardship program on antimicrobial use, physician interventions, patient outcomes, and rates of antimicrobial resistance. METHODS: Active surveillance of antimicrobial use with intervention and real-time feedback to providers and reinforcement of prior authorization for selected antimicrobials were introduced at a pediatric teaching hospital. Antimicrobial-use indications were incorporated as a mandatory field in the computerized information system. An automated report of antimicrobials prescribed, doses, patient demographics, and microbiology data was generated and reviewed by an infectious-disease pharmacist and a pediatric infectious-disease physician. Antimicrobial use, expressed as the number of doses administered per 1000 patient-days, was measured 3 years before and after the implementation of the program. RESULTS: Total antimicrobial use peaked at 3089 doses administered per 1000 patient-days per year in 2003–2004 before implementation of the program and steadily decreased to 1904 doses administered per 1000 patient-days per year during the postintervention period. Targeted-antimicrobial use declined from 1250 to 988 doses administered per 1000 patient-days per year. Nontargeted-antimicrobial use declined from 1839 to 916 doses administered per 1000 patient-days per year. Rates of antimicrobial resistance to broad-spectrum antimicrobials among the most common Gram-negative bacilli remained low and stable over time. CONCLUSIONS: The successful implementation of antimicrobial stewardship strategies had a significant impact on reducing targeted- and nontargeted-antimicrobial use, improving quality of care of hospitalized children and preventing emergence of resistance.

Metformin use in children with obesity and normal glucose tolerance – effects on cardiovascular markers and intrahepatic fat

Abstract Objective: To determine if metformin improves markers of inflammation, thrombosis, and intrahepatic fat contents in children with uncomplicated obesity. Methods: Obese children with normal glucose tolerance but elevated highly sensitive C-reactive protein (hsCRP) and/or fibrinogen concentrations (>2 standard deviations) were randomized to structured diet/exercise or diet/exercise and metformin for 6 months. Blood samples, dual energy X-ray absorptiometry data, and liver magnetic resonance images were obtained. Results: Forty-two of 66 recruited children (7–18 years) completed 6 months. Weight loss was modest but more pronounced in the metformin group (–4.9±1.0 kg) than in the diet/exercise group (–1.7±1.1 kg, p<0.03), whereas hsCRP and fibrinogen decreased more in the diet/exercise pubertal group. Baseline intrahepatic fat was high but decreased only in the diet/exercise (not metformin) pubertal group. Conclusions: Six months of metformin therapy improved weight loss and reduced abdominal adiposity, but did not enhance the beneficial effect of diet and exercise on markers related to inflammation, thrombosis, or hepatic fat in obese children with normal glucose tolerance.

Pharmacokinetics and Pharmacodynamics of Oral and Transdermal 17β Estradiol in Girls with Turner Syndrome

CONTEXT The type, dose, and route of 17β-estradiol (E(2)) used to feminize girls with Turner syndrome (TS) is not well established. OBJECTIVE The objective of the study was to characterize pharmacokinetics and pharmacodynamics of oral vs. transdermal E(2). SETTING The study was conducted at a clinical research center. SUBJECTS Ten girls with TS, mean age 17.7 ± 0.4 (se) yr and 20 normally menstruating controls (aged 16.8 ± 0.4 yr) participated in the study. INTERVENTIONS TS subjects were randomized 2 wk each to: low-dose daily oral (0.5 mg) and biweekly transdermal E(2) (0.0375 mg) with 2 wk washout in between or high-dose oral (2.0 mg) and transdermal (0.075 mg), studied for 24 h each. Tandem mass spectrometry E(2) and estrone (E(1)) assays and a recombinant cell bioassay were used. RESULTS Controls consisted of the following: E(2), 96 ± 11 pg/ml (se), E(1), 70 ± 7 (mean follicular/luteal). TS consisted of the following: E(2), average concentration on low-dose oral, 18 ± 2.1 pg/ml, low-dose transdermal, 38 ± 13, high-dose oral, 46 ± 15, high-dose transdermal, 114 ± 31 pg/ml. E(1) concentrations were much higher on oral E(2) (low or high dose) than transdermal in TS and higher than controls. Bioestrogen was closest to normal in the high-dose transdermal group. LH and FSH decreased more in transdermal than oral low-dose routes and similarly in the high-dose oral and transdermal groups. IGF-I concentrations were variable (P = NS) among groups, and low-density lipoprotein/high-density lipoprotein cholesterol responses were variable. CONCLUSIONS Transdermal E(2) results in E(2), E(1), and bioestrogen concentrations closer to normal and achieves greater suppression of LH/FSH in lower doses compared with normal. Whether the long-term metabolic effects of estrogen differ using the same form of E(2), depending on route, awaits further study in TS.

Insulin Resistance and Adiposity in Relation to Serum β-Carotene Levels

OBJECTIVE To determine the effects of placebo vs an encapsulated supplement of fruit and vegetable juice concentrate (FVJC) on serum β-carotene levels, insulin resistance, adiposity, and subclinical inflammation in boys. STUDY DESIGN Thirty age-matched prepubertal boys (9 lean and 21 overweight (OW); age range, 6-10 years) were studied. All participants received nutrition counseling and were randomized to receive FVJC or placebo capsules for 6 months. Total cholesterol, triglycerides, lipid corrected β-carotene, serum retinol, glucose, insulin, retinol binding protein-4, leptin, adiponectin, leptin-to-adiponectin ratio, high-sensitivity C-reactive protein, and interleukin-6 were measured before and after the 6-month intervention. Homeostasis model assessment-insulin resistance (HOMA-IR), acute insulin response to intravenous glucose, along with abdominal fat mass (dual-energy x-ray absorptiometry) were also determined. RESULTS Baseline β-carotene concentrations correlated inversely with HOMA-IR, leptin-to-adiponectin ratio, and abdominal fat mass (P ≤ .01). FVJC intake increased β-carotene concentrations (P ≤ .001) but did not influence retinol or retinol binding protein-4. Retinol insufficiency <1.047 μM was present in 18% of the entire cohort at baseline and in 37% at 6 months. HOMA-IR decreased after supplementation in the OW cohort, when adjusted for percent weight change (P = .014). The percent change in abdominal fat mass increased in the placebo group and decreased in the FVJC group (P = .029). CONCLUSIONS A 6-month supplementation with FVJC in the presence of nutritional counseling was associated with an increase in serum β-carotene concentrations and a reduction in adiposity in conjunction with an improvement in insulin resistance in OW boys.

Decreased fracture incidence after 1 year of pamidronate treatment in children with spastic quadriplegic cerebral palsy

Aim  The aim of this study was to assess the rate of fracture before and after a 1‐year course of intravenous pamidronate in children with spastic quadriplegic cerebral palsy (CP) who had previously experienced fractures.

Correlates of Patient Portal Enrollment and Activation in Primary Care Pediatrics

OBJECTIVE To identify the demographic, practice site, and clinical predictors of patient portal enrollment and activation among a pediatric primary care population. METHODS We conducted a cross-sectional analysis of the primary care database of an academic childrens hospital that introduced a patient portal in December 2007. RESULTS We analyzed data for 84,015 children. Over a 4-year period, 38% enrolled in the portal; of these, 26% activated the account. The adjusted odds of portal enrollment was lower for adolescents, Medicaid recipients, low-income families, Asian or other race, and Hispanic ethnicity, and higher for patients with more office encounters, and presence of autism on the problem list. Once enrolled, the odds of portal activation [adjusted odds ratio (95% confidence interval)] was decreased for: Medicaid [0.55 (0.50-0.61)] and uninsured [0.79 (0.64-0.97)] (vs private insurance), black [0.53 (0.49-0.57)] and other [0.80 (0.71-0.91)] (vs white race), Hispanic ethnicity [0.77 (0.62-0.97)], and increased for: infant age [1.26 (1.15-1.37)] (vs school age), attendance at a resident continuity practice site [1.91 (1.23-2.97)], living further away from the practice (vs under 2 miles)[4.5-8.8 miles: 1.14 (1.02-1.29); more than 8.8 miles: 1.19 (1.07-1.33)], having more office encounters (vs 1-3) [4-7 encounters: 1.40 (1.24-1.59); 8-12 encounters: 1.58 (1.38-1.81); 13+ encounters: 2.09 (1.72-2.55)], and having 3 or more items on the problem list (vs 0) [1.19 (1.07-1.33)]. CONCLUSIONS Sociodemographic disparities exist in patient portal enrollment/activation in primary care pediatrics. Attendance at a resident continuity practice site, living farther away from the practice, having more office encounters, and having more problem list items increased the odds of portal activation.

Can the Newest Vital Sign Be Used to Assess Health Literacy in Children and Adolescents

Context. We evaluated the validity of the Newest Vital Sign (NVS) as a brief screen for health literacy in children. Objectives. To (a) test the hypothesis that child performance on the NVS correlates with performance on a test of child reading comprehension and (b) establish age-based cutoffs for expected performance on the NVS. Design. Children aged 7 to 17 years were administered the NVS followed by the Gray Silent Reading Test (GSRT). Results. The NVS score correlated strongly with GSRT score (ρ = 0.71, P < .0001) and increased with age. Children aged 7 to 9 years had a median NVS score of 1 (interquartile range = 1-2); children aged 10 to 17 years had a median score of 3 (interquartile range = 2-4), P < .0001. Conclusion. The NVS performs well in this population. Children aged 10 to 17 years with an NVS score lower than 2 may have low health literacy.

Association Between Peanut Allergy and Asthma Morbidity

OBJECTIVE To evaluate the relationship between peanut allergy and asthma morbidity in school-age children. STUDY DESIGN The study involved a medical chart review to assess the association of peanut allergy with asthma morbidity in children beyond age 3 years. Peanut allergy was assessed by specific and validated criteria. A Poisson regression model was used to compare the frequency of systemic steroid use and of hospitalization for asthma beyond age 3 years in children with asthma with and without peanut allergy. RESULTS Children with peanut allergy had a 2.32-times greater rate of hospitalization (P = .03) and a 1.59-times greater rate of systemic steroid use (P <.001) after controlling for covariates. CONCLUSIONS Peanut allergy serves as an early marker for asthma morbidity. Early prevention and intervention can improve quality of care.

A randomized, double blind, placebo-controlled pilot trial of the safety and efficacy of atorvastatin in children with elevated low-density lipoprotein cholesterol (LDL-C) and type 1 diabetes.

Children with type 1 diabetes (T1D) and elevated LDL‐C have an increased risk for cardiovascular disease, a process that can begin in childhood.

Assessing genotype-phenotype correlation in Costello syndrome using a severity score

Purpose:Costello syndrome, a rare genetic disorder with multisystemic involvement, is caused by germline HRAS mutations. Because several different missense mutations have been reported, a severity scoring system was developed to assess a possible genotype–phenotype correlation.Methods:Records of 78 individuals with Costello syndrome were scored in early childhood, childhood, and young adulthood by a reviewer blinded to the individuals’ specific mutations. These scores were based on certain medically relevant feeding, neurologic, orthopedic, endocrine, cardiac, malignancy, and mortality manifestations. Individuals’ severity scores were then grouped by the particular HRAS mutation. The mixed-model approach for repeated-measures analysis of variance with unstructured within-subject correlation, pairwise comparisons, and contrast were used to determine whether the severity scores differed by mutation.Results:Although the sample size was small, individuals with the p.G12A or p.G12C HRAS change were more severely affected than those with other HRAS mutations. Regardless of the mutation, severity did not increase significantly over time.Conclusion:Despite its limitations, including the small number of individuals with rare mutations and possibly incomplete medical records, this work providing the first quantitative assessment of phenotypic severity in a Costello syndrome cohort supports a medically relevant genotype–phenotype correlation.Genet Med 2013:15(7):554–557