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1.  Pediatric Severe Sepsis in US Children’s Hospitals 
Objective
To compare the prevalence, resource utilization, and mortality for pediatric severe sepsis identified using two established identification strategies.
Design
Observational cohort study from 2004–2012.
Setting
Forty-four pediatric hospitals contributing data to the Pediatric Health Information Systems database.
Patients
Children ≤18 years of age.
Measurements and Main Results
We identified patients with severe sepsis or septic shock by using two International Classification of Diseases, 9th edition-Clinical Modification (ICD9-CM) based coding strategies: 1) combinations of ICD9-CM codes for infection plus organ dysfunction (combination code cohort); 2) ICD9-CM codes for severe sepsis and septic shock (sepsis code cohort). Outcomes included prevalence of severe sepsis, as well as hospital and intensive care unit (ICU) length of stay (LOS), and mortality. Outcomes were compared between the two cohorts examining aggregate differences over the study period and trends over time. The combination code cohort identified, 176,124 hospitalizations (3.1% of all hospitalizations), while the sepsis code cohort identified 25,236 hospitalizations (0.45%), a 7-fold difference. Between 2004 and 2012, the prevalence of sepsis increased from 3.7% to 4.4% using the combination code cohort and from 0.4% to 0.7% using the sepsis code cohort (p<0.001 for trend in each cohort). LOS (hospital and ICU) and costs decreased in both cohorts over the study period (p<0.001). Overall hospital mortality was higher in the sepsis code cohort than the combination code cohort (21.2%, (95% CI: 20.7–21.8 vs. 8.2%,(95% CI: 8.0–8.3). Over the 9 year study period, there was an absolute reduction in mortality of 10.9% (p<0.001) in the sepsis code cohort and 3.8% (p<0.001) in the combination code cohort.
Conclusions
Prevalence of pediatric severe sepsis increased in the studied US children’s hospitals over the past 9 years, though resource utilization and mortality decreased. Epidemiologic estimates of pediatric severe sepsis varied up to 7-fold depending on the strategy used for case ascertainment.
doi:10.1097/PCC.0000000000000225
PMCID: PMC4221502  PMID: 25162514
Pediatrics; Sepsis; Critical Care; Epidemiology
2.  Antithrombin concentrate use in children: a multicenter cohort study 
The Journal of pediatrics  2013;163(5):10.1016/j.jpeds.2013.06.036.
Objective
To describe the off-label use of antithrombin concentrate in tertiary care pediatric hospitals across the United States.
Study design
This is a retrospective, multicenter, cohort study of 4,210 admissions of children less than 18 years of age who received antithrombin concentrate between 2002 and 2011 within the Pediatric Health Information System administrative database. An on-label admission was defined as an admission with an International Classification of Diseases diagnostic code for a primary hypercoagulable state; admissions without this code were classified as off-label.
Results
Over the 10 year study period, off-label use of antithrombin concentrate increased 5-fold. Overall, 97% of study subjects received antithrombin off-label. Neonates < 30 days old was the largest age group (45.7%) of use; 87% of patients had at least one complex chronic condition with congenital heart/lung defects being the most prevalent primary diagnosis (36.3%). Extracorporeal membrane oxygenation (ECMO) was the most common procedure associated with antithrombin use (43.7%).
Conclusions
The off-label use of antithrombin concentrate is increasing rapidly, particularly in critically-ill children receiving ECMO, with few parallel studies to substantiate its safety or efficacy. Further pre-clinical and controlled clinical studies are critical to expanding our knowledge of this drug. In the meantime, antithrombin concentrate should be used judiciously by clinicians and following guidelines instated by hospitals.
doi:10.1016/j.jpeds.2013.06.036
PMCID: PMC3812320  PMID: 23932317
Pediatric Health Information System; extracorporeal membrane oxygenation; extracorporeal life support; anticoagulation therapy; critical care
3.  HCC surveillance results in earlier HCC detection: results from an Indian cohort 
SpringerPlus  2014;3:610.
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide, with an increased incidence in South Asia. In order to describe the effect of surveillance for HCC with biannual ultrasound and alpha-fetoprotein (AFP) on diagnosis and survival in an Indian population a retrospective cohort-control study was performed at two liver clinics in India. The medical records of 3,258 patients with cirrhosis who received surveillance for HCC were reviewed, and 100 patients who developed HCC identified. Sixty-four cirrhotic patients diagnosed with HCC during the same time period without a history of surveillance were included and survival, BCLC stage at diagnosis, and treatment were compared.
Patients who underwent surveillance were more likely to be diagnosed with potentially curable or treatable BCLC Stage 0/A disease and Stage B/C disease respectively, than late Stage D disease (χ2 = 0.0007). Patients diagnosed at an earlier stage of HCC lived significantly longer after diagnosis than patients diagnosed at a later stage (Stage 0/A: 15.6 ± 14.2 months vs. Stage B/C: 9.43 ± 19.7 months vs. Stage D: 5.59 ± 11.9 months; p = 0.0006). While treatment for HCC improved overall survival, only 28% of eligible patients received treatment, explaining the lack of survival benefit noted in the surveillance group. Surveillance for HCC led to detection of HCC at earlier stages. The impact of surveillance on improved mortality could not be evaluated given the limited number of patients who received treatment. HCC surveillance has the potential to improve survival in South Asian patients with cirrhosis only if improvements in access to appropriate treatment are made.
doi:10.1186/2193-1801-3-610
PMCID: PMC4209002  PMID: 25392781
Hepatocellular carcinoma; Surveillance; Ultrasounds; Survival; Treatment; India
4.  National Trends in Psychotropic Medication Use in Young Children: 1994–2009 
Pediatrics  2013;132(4):615-623.
OBJECTIVE:
To examine recent national trends in psychotropic use for very young children at US outpatient medical visits.
METHODS:
Data for 2- to 5-year-old children (N = 43 598) from the 1994–2009 National Ambulatory and National Hospital Ambulatory Medical Care Surveys were used to estimate the weighted percentage of visits with psychotropic prescriptions. Multivariable logistic regression was used to identify factors associated with psychotropic use. Time effects were examined in 4-year blocks (1994–1997, 1998–2001, 2002–2005, and 2006–2009).
RESULTS:
Psychotropic prescription rates were 0.98% from 1994–1997, 0.83% from 1998–2001, 1.45% from 2002–2005, and 1.00% from 2006–2009. The likelihood of preschool psychotropic use was highest in 2002–2005 (1994–1997 adjusted odds ratio [AOR] versus 2002–2005: 0.67; 1998–2001 AOR versus 2002–2005: 0.63; 2006–2009 AOR versus 2002–2005: 0.64), then diminished such that the 2006–2009 probability of use did not differ from 1994–1997 or from 1998–2001. Boys (AOR versus girls: 1.64), white children (AOR versus other race: 1.42), older children (AOR for 4 to 5 vs 2 to 3 year olds: 3.87), and those lacking private insurance (AOR versus privately insured: 2.38) were more likely than children from other groups to receive psychotropic prescriptions.
CONCLUSIONS:
Psychotropic prescription was notable for peak usage in 2002–2005 and sociodemographic disparities in use. Further study is needed to discern why psychotropic use in very young children stabilized in 2006–2009, as well as reasons for increased use in boys, white children, and those lacking private health insurance.
doi:10.1542/peds.2013-1546
PMCID: PMC4074650  PMID: 24082002
psychotropic medications; stimulant medications; psychostimulants; very young children; preschoolers; behavioral disorders; mental health disorders; psychiatric disorders
5.  Identifying Pediatric Community-acquired Pneumonia Hospitalizations: Accuracy of Administrative Billing Codes 
JAMA pediatrics  2013;167(9):851-858.
Importance
Community-acquired pneumonia (CAP) remains one of the most common indications for pediatric hospitalization in the United States, and it is frequently the focus of research and quality studies. Use of administrative data is increasingly common for these purposes, although proper validation is required to ensure valid study conclusions.
Objective
To validate administrative billing data for childhood community-acquired pneumonia (CAP) hospitalizations.
Design
Case-control.
Setting
Four freestanding children’s hospitals in the United States.
Participants
Medical records of a 25% random sample of 3,646 children (n=998) discharged in 2010 with at least one ICD-9-CM code representing possible pneumonia were reviewed. Discharges (matched on date of admission) without a pneumonia-related discharge code were also reviewed to identify potential missed pneumonia cases. Two reference standards, based on provider diagnosis alone (provider-confirmed) or in combination with clinical and radiographic evidence of pneumonia (definite), were used to identify CAP.
Main Exposure
Twelve ICD-9-CM based coding strategies, each using a combination of primary or secondary codes representing pneumonia or pneumonia-related complications. Six algorithms excluded children with complex chronic conditions.
Main Outcome Measures
Sensitivity, specificity, negative and positive predictive values (NPV, PPV) of the twelve identification strategies.
Results
For provider-confirmed CAP (n=680), sensitivity ranged from 60.7–99.7%; specificity 75.7–96.4%; PPV 67.9–89.6%; and NPV 82.6–99.8%. For definite CAP (n=547), sensitivity ranged from 65.6–99.6%; specificity 68.7–93.0%; PPV 54.6–77.9%; and NPV 87.8–99.8%. Unrestricted use of the pneumonia-related codes was inaccurate, although several strategies improved specificity to >90% with variable impact on sensitivity. Excluding children with complex chronic conditions demonstrated the most favorable performance characteristics. Performance of the algorithms was similar across institutions.
Conclusions and Relevance
Administrative data are valuable for studying pediatric CAP hospitalizations. The strategies presented here will aid in the accurate identification of relevant and comparable patient populations for both research and performance improvement studies.
doi:10.1001/jamapediatrics.2013.186
PMCID: PMC3907952  PMID: 23896966
Pneumonia; Validation Studies; Epidemiology; Benchmarking; Healthcare
6.  Hospital Variation in Postoperative Infection and Outcome After Congenital Heart Surgery 
The Annals of thoracic surgery  2013;96(2):10.1016/j.athoracsur.2013.04.024.
Background
Several initiatives aim to reduce postoperative infection across a variety of surgical patients as a means to improve overall quality of care and reduce variation across centers. However, the association of infection rates with hospital-level outcomes and resource utilization has not been well described. We evaluated this association across a multicenter cohort undergoing congenital heart surgery.
Methods
The Society of Thoracic Surgeons Congenital Heart Surgery Database was linked to resource utilization data from the Pediatric Health Information Systems Database for hospitals participating in both (2006 to 2010). Hospital-level infection rates (sepsis, wound infection, mediastinitis, endocarditis, pneumonia) adjusted for patient risk factors and case mix were calculated using Bayesian methodology, and association with hospital mortality rates, postoperative length of stay (LOS), and total costs evaluated.
Results
The cohort included 32,856 patients (28 centers); 3.7% had a postoperative infection. Across hospitals, the adjusted infection rate varied from 0.9% to 9.8%. Hospitals with the highest infection rates had longer (LOS) (13.2 vs 11.7 days, p < 0.001) and increased hospital costs ($71,100 vs $65,100, p < 0.001), but similar mortality rates (odds ratio 0.99, 95% confidence interval 0.80 to 1.21, p = 0.9). The proportion of variation in costs and LOS explained by infection was 15% and 6%, respectively.
Conclusions
Infection after congenital heart surgery contributes to prolonged LOS and increased costs on a hospital level. However, given that infection rates alone explained relatively little of the variation in these outcomes across hospitals, further study is needed to identify additional factors that may be targeted in initiatives to reduce variation and improve outcomes across centers.
doi:10.1016/j.athoracsur.2013.04.024
PMCID: PMC3828204  PMID: 23816416
7.  Prevalence of Bacteremia in Hospitalized Pediatric Patients With Community-acquired Pneumonia 
Background
National guidelines recommend obtaining blood cultures in children hospitalized with moderate or severe community-acquired pneumonia (CAP). The objectives of this study were to determine the prevalence of bacteremia in children, identify factors associated with bacteremia and quantify the influence of positive blood cultures on clinical management in children hospitalized with CAP.
Methods
This multicenter retrospective study included children from 60 days to 18 years of age requiring hospitalization for CAP. Categories analyzed were bacteremia, culture negative and no culture.
Results
Blood cultures were performed in 369 (56%) of 658 children with CAP. The prevalence of bacteremia was 7% (4.7–10.1%) in patients with a blood culture obtained. Bacteremia occurred in 21% of patients with a pleural drainage procedure and 75% of patients with distant site of infection (eg, osteomyelitis). Patients with bacteremia had longer duration of fever before admission and higher C-reactive protein values compared with those with negative or no blood culture. However, differences in white blood cell count and erythrocyte sedimentation rate between those with bacteremia and those without were not significant. Contamination rates were low and similar across institutions, ranging from 1% to 3.8% (P = 0.63). Blood culture–directed changes in antibiotic management occurred in 33% of patients with a contaminated culture and 65% of bacteremic patients. Antibiotic therapy was narrowed in 26% of bacteremic patients at hospital discharge.
Conclusion
The prevalence of bacteremia was higher than previously reported in children hospitalized with CAP and consistent across children’s hospitals. Positive blood cultures should prompt change to narrow-spectrum antibiotic therapy.
doi:10.1097/INF.0b013e318290bf63
PMCID: PMC3907948  PMID: 23518826
bacteremia; children; community-acquired pneumonia; hospitalized
8.  Designing a Pediatric Severe Sepsis Screening Tool 
We sought to create a screening tool with improved predictive value for pediatric severe sepsis (SS) and septic shock that can be incorporated into the electronic medical record and actively screen all patients arriving at a pediatric emergency department (ED). “Gold standard” SS cases were identified using a combination of coded discharge diagnosis and physician chart review from 7,402 children who visited a pediatric ED over 2 months. The tool’s identification of SS was initially based on International Consensus Conference on Pediatric Sepsis (ICCPS) parameters that were refined by an iterative, virtual process that allowed us to propose successive changes in sepsis detection parameters in order to optimize the tool’s predictive value based on receiver operating characteristics (ROC). Age-specific normal and abnormal values for heart rate (HR) and respiratory rate (RR) were empirically derived from 143,603 children seen in a second pediatric ED over 3 years. Univariate analyses were performed for each measure in the tool to assess its association with SS and to characterize it as an “early” or “late” indicator of SS. A split-sample was used to validate the final, optimized tool. The final tool incorporated age-specific thresholds for abnormal HR and RR and employed a linear temperature correction for each category. The final tool’s positive predictive value was 48.7%, a significant, nearly threefold improvement over the original ICCPS tool. False positive systemic inflammatory response syndrome identifications were nearly sixfold lower.
doi:10.3389/fped.2014.00056
PMCID: PMC4058838  PMID: 24982852
severe sepsis; screening tool; algorithm; emergency department; SIRS
9.  Quality Improvement Methods Increase Appropriate Antibiotic Prescribing for Childhood Pneumonia 
Pediatrics  2013;131(5):e1623-e1631.
OBJECTIVE:
In August 2011, the Pediatric Infectious Disease Society and Infectious Disease Society of America published an evidence-based guideline for the management of community-acquired pneumonia (CAP) in children ≥3 months. Our objective was to evaluate if quality improvement (QI) methods could improve appropriate antibiotic prescribing in a setting without a formal antimicrobial stewardship program.
METHODS:
At a tertiary children’s hospital, QI methods were used to rapidly implement the Pediatric Infectious Disease Society/Infectious Disease Society of America guideline recommendations for appropriate first-line antibiotic therapy in children with CAP. QI interventions focused on 4 key drivers and were tested separately in the emergency department and on the hospital medicine resident teams, using multiple plan-do-study-act cycles. Medical records of eligible patients were reviewed weekly to determine the success of prescribing recommended antibiotic therapy. The impact of these interventions on our outcome was tracked over time on run charts.
RESULTS:
Appropriate first-line antibiotic prescribing for children admitted with the diagnosis of CAP increased in the emergency department from a median baseline of 0% to 100% and on the hospital medicine resident teams from 30% to 100% within 6 months of introducing the guidelines locally at Cincinnati Children’s Hospital Medical Center and has been sustained for 3 months.
CONCLUSIONS:
Our study demonstrates that QI methods can rapidly improve adherence to national guidelines even in settings without a formal antimicrobial stewardship program to encourage judicious antibiotic prescribing for CAP.
doi:10.1542/peds.2012-2635
PMCID: PMC3639461  PMID: 23589819
pneumonia; antibiotic use; pediatric
10.  The antimicrobial activity of Azadirachta indica, Mimusops elengi, Tinospora cardifolia, Ocimum sanctum and 2% chlorhexidine gluconate on common endodontic pathogens: An in vitro study 
European Journal of Dentistry  2014;8(2):172-177.
Objective:
To check the antimicrobial activity of Azadirachta indica (Neem), Ocimum sanctum (Tulsi), Mimusops elelngi (Bakul), Tinospora cardifolia (Giloy) and Chlorhexidine Gluconate (CHX) on common endodontic pathogens like Streptococcus mutans, Enterococcus faecalis and staphylococcus aureus.
Materials and Methods:
The agar diffusion test was used to check the antimicrobial activity of the Methanolic extracts of the medicinal plants along with CHX. Six different concentrations of the tested agents were used for the study. The values of Zone of Inhibition were tabulated according to the concentration of the tested agent and data was statistically analyzed using ANOVA and Bonferroni post- hoc tests. The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentrations (MBC) values were also recorded.
Results:
All the plants extracts showed considerable antimicrobial activity against selected endodontic pathogens. At 3mg. concentration, O.sanctum was the most effective against S. mutans, M. elengi showed highest zone of inhibition against E.faecalis, whereas CHX was the most effective agent against S.aureus. CHX was also the most consistent of all the medicaments testes, showing inhibitory effect against all the tree pathogens at all the selected concentrations.
Conclusions:
The Methanolic extract of A.Indica, O.sanctum, M. Elengi, T.cardifolia and Chlorhexidine Gluconate has considerable antimicrobial activity against S. mutans, E. faecalis and S. aureus.
doi:10.4103/1305-7456.130591
PMCID: PMC4054046  PMID: 24966766
Antimicrobial activity; chlorhexidine gluconate; endodontic pathogens; medicinal plant extracts
11.  Species-Specific PCR Improves Detection of Bacterial Pathogens in Parapneumonic Empyema Compared with 16S PCR and Culture 
doi:10.1097/INF.0b013e3182784ec1
PMCID: PMC3618625  PMID: 23558326
Pneumonia; Bacterial/*complications/*epidemiology; Pneumonia; Pneumococcal; Empyema; Pleural Streptococcus pneumoniae; Polymerase chain reaction; Molecular Diagnostics
12.  Pretreatment SUVmax predicts progression-free survival in early-stage non-small cell lung cancer treated with stereotactic body radiation therapy 
Background
This retrospective study aims to assess the usefulness of SUVmax from FDG-PET imaging as a prognosticator for primary biopsy-proven stage I NSCLC treated with SBRT.
Methods
This study includes 95 patients of median age 77 years, with primary, biopsy-confirmed peripheral stage IA/IB NSCLC. All patients were treated with 60Gy in 3 fractions with a median treatment time of six days. Local, regional, and distant failures were evaluated independently according to the terms of RTOG1021. Local, regional, and distant control, overall- and progression-free survival were estimated by the Kaplan-Meier method. Cox proportional hazards regression was performed to determine whether SUVmax, age, KPS, gender, tumor size/T stage, or smoking history influenced outcomes. SUVmax was evaluated as both a continuous and as a dichotomous variable using a cutoff of <5 and ≥5.
Results
Median follow-up for the cohort was 16 months. Median OS and PFS were 25.3 and 40.3 months, respectively. SUV with a cutoff value of 5 predicted for OS and PFS (p = .024 for each) but did not achieve significance for LC (p = .256). On Cox univariate regression analysis, SUV as a dichotomous variable predicted for both OS and PFS (p = .027 and p = .030, respectively). Defined as a continuous variable, SUVmax continued to predict for OS and PFS (p = .032 and p = .003), but also predicted LC (p = .045) and trended toward significance for DC (p = .059).
SUVmax did not predict for OS as a dichotomous or continuous variable. It did, however, predict for PFS as a continuous variable (p = .008), neared significance for local control (p = .057) and trended towards, significance for distant control (p = .092).
Conclusions
SUVmax appears to be a statistically and clinically significant independent prognostic marker for progression-free survival in patients with stage I NSCLC treated with SBRT. Prospective studies to more accurately define the role of tumor FDG uptake in the prognosis of NSCLC are warranted.
doi:10.1186/1748-717X-9-41
PMCID: PMC3922961  PMID: 24479954
13.  Health Insurance and Length of Stay for Children Hospitalized With Community-Acquired Pneumonia 
BACKGROUND
Disparities in patterns of care and outcomes for ambulatory-care sensitive childhood conditions such as community-acquired pneumonia (CAP) persist. However, the influence of insurance status on length of stay (LOS) for children hospitalized with CAP remains unexplored.
METHODS
Secondary analysis of children (<18 years) hospitalized with CAP sampled in the Kids’ Inpatient Database (KID) for years 1997, 2000, 2003, and 2006. Insurance status (private, public, uninsured) was based on claims data. Hospital LOS was calculated in days. Taking into account the complex sampling design, negative binomial regression models produced adjusted estimates of incidence rate ratios (IRR) for hospital LOS for children by insurance status.
RESULTS
There was little variation in the categories of insurance status of children hospitalized with CAP between 1997 and 2006, with at least 40% privately insured, at least 40% publicly insured, and at least 5% uninsured in each sampled year. In all years, publicly insured children had a significantly longer hospital stay than privately insured children, and uninsured children had a significantly shorter hospital stay than privately insured children. These observed differences persisted after multivariate adjustment.
CONCLUSIONS
Differences in LOS between uninsured, publicly insured, and privately insured children with CAP raise concerns about potential differences in hospital discharge practices related to insurance status and type. As healthcare reform is implemented, policy makers should strengthen efforts to reduce these disparities in order to achieve health for the population.
doi:10.1002/jhm.959
PMCID: PMC3877930  PMID: 21972214
14.  Differential Case Ascertainment in Clinical Registry vs. Administrative Data and Impact on Outcomes Assessment in Pediatric Heart Surgery 
The Annals of thoracic surgery  2012;95(1):197-203.
Background
Administrative datasets are often used to assess outcomes and quality in pediatric heart surgery; however their accuracy regarding case ascertainment is unclear. We linked patient data (2004–2010) from the STS Congenital Heart Surgery Database (clinical registry), and Pediatric Health Information Systems Database (administrative database) from hospitals participating in both to evaluate differential coding/classification of operations between datasets, and subsequent impact on outcomes assessment.
Methods
Eight individual benchmark operations and the RACHS-1 categories were evaluated. The primary outcome was in-hospital mortality.
Results
The cohort included 59,820 patients (33 centers). There was a >10% difference in the number of patients identified between datasources for half of the benchmark operations. Negative predictive value of the administrative (vs. clinical) data was high (98.8–99.9%); positive predictive value was lower (56.7–88.0%). Overall agreement between datasources in RACHS-1 category assignment was 68.4%. These differences translated into significant differences in outcomes assessment, ranging from an underestimation of mortality associated with truncus arteriosus repair by 25.7% in the administrative vs. clinical data (7.01% vs. 9.43%, p=0.001), to an overestimation of mortality associated with VSD repair by 31.0% (0.78% vs. 0.60%, p=0.1). For the RACHS-1 categories, these ranged from an underestimation of Category 5 mortality by 40.5%, to an overestimation of Category 2 mortality by 12.1%; these differences were not statistically significant.
Conclusions
This study demonstrates differences in case ascertainment between administrative and clinical registry data for children undergoing heart surgery, which translated into important differences in outcomes assessment.
doi:10.1016/j.athoracsur.2012.08.074
PMCID: PMC3777807  PMID: 23141907
congenital heart disease; health policy; outcomes
15.  Variability in Processes of Care and Outcomes among Children Hospitalized with Community-Acquired Pneumonia 
Background
Substantial care variation occurs in a number of pediatric diseases.
Methods
We evaluated the variability in health care resource utilization and its association with clinical outcomes among children, aged 1–18 years, hospitalized with community acquired pneumonia (CAP). Each of 29 children’s hospitals contributing data to the Pediatric Hospital Information System was ranked based on the proportion of CAP patients receiving each of 8 diagnostic tests. Primary outcome variable was length of stay (LOS), re-visit to the ED or readmission within 14 days of discharge.
Results
Of 21,213 children hospitalized with non-severe CAP, median age was 3 years (interquartile range [IQR], 1–6 years). Laboratory testing and antibiotic usage varied widely across hospitals; cephalosporins were the most commonly prescribed antibiotic. There were large differences in the processes of care by age categories. The median LOS was 2 days (IQR, 1–3 days) and differed across hospitals; 25% of hospitals had median LOS >= 3 days. Hospital-level variation occurred in 14-day ED visits and 14-day readmission, ranging from 0.9 to 4.9% and 1.5% to 4.4%, respectively. Increased utilization of diagnostic testing was associated with longer hospital LOS (p=0.036) but not with probability of 14-day readmission (Spearman’s ρ = 0.234; p=0.225). There was an inverse correlation between LOS and 14-day revisit to the ED (ρ=−0.48, p=0.013).
Conclusions
Wide variability occurred in diagnostic testing for children hospitalized with CAP. Increased diagnostic testing was associated with a longer LOS. Earlier hospital discharge did not correlate with increased 14-day readmission. The precise interaction of increased utilization with longer LOS remains unclear.
doi:10.1097/INF.0b013e31825f2b10
PMCID: PMC3504613  PMID: 22653486
pneumonia; bacterial pneumonia; disease management; epidemiology; evidence-based medicine
17.  The effect of periodontal treatment on C-reactive protein: A clinical study 
Background:
Chronic periodontitis in amultifactorial inflammatory disease which is caused by various microorganisms. Many studies have found close association between chronic periodontitis and C-reactive protein (CRP). CRPis an inflammatory marker which increases in all inflammatory condition.
Aims and Objective:
The present clinical study was designed to show the effect of periodontal treatment on the CRP levels of gingival crevicular fluid and to determine the effect of nonsurgical therapy in minimizing the CRP levels in chronic generalized periodontitis.
Material and Method:
Gingival crevicular fluid was collected using a micro capillary pipette that was hand calibrated at every 1 mm till 10 mm, from selected sites in the subjects on the 1st, 14th and 45th days.
Results and Conclusion:
Decreased CRP levels of gingival crevicular fluid were observed at the end of the study. There was a 37% reduction in probing pocket depth and 45% gain in clinical attachment level and a reduction of about 57% after 14 days and 90% reduction of CRP levels in gingival crevicular fluid after 45 days. Thus, the results show that the presence of CRP level is more significant in gingival crevicular fluid and confirms the underlying inflammatory component of the disease activity in chronic periodontitis.
doi:10.4103/0976-9668.116991
PMCID: PMC3783784  PMID: 24082736
C-reactive protein; GCF; periodontitis
18.  Early Prediction of Postmeningitic Hearing Loss in Children Using Magnetic Resonance Imaging 
Objective
To determine whether early gadolinium-enhanced magnetic resonance imaging (GdMRI) can reliably detect meningitic labyrinthitis and thereby predict which children are at high risk for hearing loss. Permanent sensorineural hearing loss (SNHL) remains a common sequela of bacterial meningitis, and early diagnosis of the associated suppurative labyrinthitis can be difficult, especially in critically ill, sedated patients and young children.
Design
Retrospective cohort study.
Setting
Tertiary pediatric hospital.
Participants
Twenty-three survivors of bacterial meningitis (median age, 15 months [range, 3 months–14 years]) who had undergone brain GdMRI during the acute disease and had subsequent ear-specific audiometric data.
Main Outcome Measure
Blinded to disease and outcome, a neuroradiologist rated the relative enhancement of each cochlea on T1-weighted images using a 4-point scale. Scores were then correlated with the degree of hearing loss on subsequent testing.
Results
Sensorineural hearing loss occurred in 15 of 46 ears (8 of 23 patients). Enhancement on GdMRI was detected in 13 of the 15 ears that later developed SNHL but was absent in all 31 unaffected ears. Thus, GdMRI was 87% sensitive and 100% specific for predicting which ears would develop permanent SNHL. In the subgroup with pneumococcal meningitis (n=15), GdMRI was 100% sensitive and 100% specific. Labyrinthine enhancement was detectable as early as 1 day after diagnosis.
Conclusion
Gadolinium-enhanced MRI detected meningitic labyrinthitis at early stages and accurately predicted which patients would later develop hearing loss.
doi:10.1001/archoto.2011.13
PMCID: PMC3670148  PMID: 21339394
19.  Opportunities and challenges in linking information across databases in pediatric cardiovascular medicine 
Multicenter databases are increasingly utilized in pediatric cardiovascular research. In this review, we discuss the rational for using these types of data sources, provide several examples of how large datasets have been utilized in clinical research, and describe different mechanisms for linking databases to enable studies not possible with individual datasets alone.
doi:10.1016/j.ppedcard.2011.12.004
PMCID: PMC3651671  PMID: 23671377
congenital heart disease; outcomes research
20.  Trends in Endocarditis Hospitalizations at US Childrens Hospitals: Impact of the 2007 American Heart Association Antibiotic Prophylaxis Guidelines 
American heart journal  2012;163(5):894-899.
Background
In 2007, the American Heart Association recommended cessation of antibiotic prophylaxis for infective endocarditis (IE) prior to dental procedures for all but those at highest risk of adverse outcomes from IE. The impact of these guidelines is unclear. We evaluated IE hospitalizations at US children’s hospitals during this time period.
Methods
Children <18yrs hospitalized from 2003–2010 with IE at 37 centers in the Pediatric Health Information Systems Database were included. Using Poisson regression, we evaluated the number IE hospitalizations over time (raw and indexed to total hospital admissions).
Results
A total of 1157 IE cases were identified; 68% had congenital heart disease (CHD). The raw number of IE cases did not change significantly over time (+1.6% difference post vs. pre guidelines, 95%CI −6.4 to +10.3%, p=0.7). When the number of IE cases was indexed per 1000 hospital admissions, there was a significant decline during the time prior to the guidelines (annual change = −5.9%, 95% CI −9.9 to −1.8, p=0.005), and a similar decline in the post-guidelines period, such that the difference between the two time periods was not significant (p=0.15). In subgroup analysis, no significant change over time in IE cases (raw or indexed) was found in the CHD subset, those 5–18yrs (subgroup most likely receiving dental care), or in cases coded as oral streptococci.
Conclusions
We found no evidence that release of new antibiotic prophylaxis guidelines was associated with a significant change in IE admissions across 37 US children’s hospitals.
doi:10.1016/j.ahj.2012.03.002
PMCID: PMC3408007  PMID: 22607869
22.  Comparative Analysis of Antifibrinolytic Medications in Pediatric Heart Surgery 
Objectives
Recent studies suggest adverse events associated with aprotinin in adults may not occur in children, and there is interest in further pediatric study of aprotinin. However, there are limited contemporary data comparing aprotinin to other available antifibrinolytics [aminocaproic acid (ACA) and tranexamic acid (TXA)] to guide current practice and aid in potential trial design. We performed a comparative analysis in a large multicenter cohort.
Methods
The Society of Thoracic Surgeons Congenital Heart Surgery Database (2004–2008) was linked to medication data from the Pediatric Health Information Systems Database. Efficacy and safety outcomes were evaluated in multivariable analysis adjusting for patient and center factors overall, and in neonates and those undergoing redo sternotomy.
Results
There were 22,258 patients (25 centers) included: median age 7.6m (interquartile range 2.6–43.4). Aprotinin (vs. no drug) was associated with a significant reduction in combined hospital mortality/bleeding requiring surgical intervention overall (OR 0.81 95%CI 0.68–0.91), and in the redo sternotomy subgroup (OR 0.57 95%CI 0.40–0.80). There was no benefit in neonates, and no difference in renal failure requiring dialysis in any group. In comparative analysis, there was no difference in outcome in aprotinin vs. ACA recipients. TXA (vs. aprotinin) was associated with significantly reduced mortality/bleeding requiring surgical intervention overall (OR 0.47 95%CI 0.30–0.74) and in neonates (OR 0.30 95%CI 0.15–0.58).
Conclusions
These observational data suggest aprotinin is associated with reduced bleeding and mortality in children undergoing heart surgery with no increase in dialysis. Comparative analyses suggest similar efficacy of ACA and improved outcomes associated with TXA.
doi:10.1016/j.jtcvs.2011.06.048
PMCID: PMC3288966  PMID: 22264414
23.  Incidence of and Risk Factors for Community Acquired Pneumonia in US HIV-Infected Children, 2000–2005 
AIDS (London, England)  2011;25(5):717-720.
Summary
The incidence of and risk factors for community-acquired pneumonia (CAP) are described from 2000–2005 in a multicenter US cohort of HIV-infected children. In 736 patients, 87 episodes of CAP (33.2 events/1,000 PY) had a mean CD4% of 23% (controls: 30%) and mean CD4 count of 668 cells/mm3 (controls: 870 cells/mm3). CAP incidence decreased 44% from 2000–2001 to 2002–2005. On multivariate analysis, viral load ≥100,000 copies/mL (OR 3.98; CI: 1.05–15.13) was associated with CAP. Herd immunity through pneumococcal immunization may have diluted the effect of individual immunization in this cohort.
doi:10.1097/QAD.0b013e3283440583
PMCID: PMC3576877  PMID: 21252630
HIV; Pneumonia; Pediatric
24.  Perioperative Methylprednisolone and Outcome in Neonates Undergoing Heart Surgery 
Pediatrics  2012;129(2):e385-e391.
BACKGROUND:
Recent studies have called into question the benefit of perioperative corticosteroids in children undergoing heart surgery, but have been limited by the lack of placebo control, limited power, and grouping of various steroid regimens together in analysis. We evaluated outcomes across methylprednisolone regimens versus no steroids in a large cohort of neonates.
METHODS:
Clinical data from the Society of Thoracic Surgeons Database were linked to medication data from the Pediatric Health Information Systems Database for neonates (≤30 days) undergoing heart surgery (2004–2008) at 25 participating centers. Multivariable analysis adjusting for patient and center characteristics, surgical risk category, and within-center clustering was used to evaluate the association of methylprednisolone regimen with outcome.
RESULTS:
A total of 3180 neonates were included: 22% received methylprednisolone on both the day before and day of surgery, 12% on the day before surgery only, and 28% on the day of surgery only; 38% did not receive any perioperative steroids. In multivariable analysis, there was no significant mortality or length-of-stay benefit associated with any methylprednisolone regimen versus no steroids, and no difference in postoperative infection. In subgroup analysis by surgical-risk group, there was a significant association of methylprednisolone with infection consistent across all regimens (overall odds ratio 2.6, 95% confidence interval 1.3–5.2) in the lower-surgical-risk group.
CONCLUSIONS:
This multicenter observational analysis did not find any benefit associated with methylprednisolone in neonates undergoing heart surgery and suggested increased infection in certain subgroups. These data reinforce the need for a large randomized trial in this population.
doi:10.1542/peds.2011-2034
PMCID: PMC3269116  PMID: 22271697
congenital heart disease; heart surgery; outcomes
25.  Delayed Acyclovir Therapy and Death Among Neonates With Herpes Simplex Virus Infection 
Pediatrics  2011;128(6):1153-1160.
OBJECTIVE:
To determine the association of delayed acyclovir therapy with death among neonates with herpes simplex virus (HSV) infection.
METHODS:
A multicenter, retrospective, cohort study was conducted between January 1, 2003, and December 31, 2009, with 1086 neonates (age: ≤28 days) with HSV infection from 41 tertiary care children's hospitals. Early acyclovir therapy was defined as initiation of intravenous acyclovir treatment within 1 day after hospital admission, and delayed acyclovir therapy was defined as initiation of treatment >1 and ≤7 days after hospital admission. Multivariate logistic regression models determined the association between delayed acyclovir therapy and death, with the use of propensity scores for each neonate's likelihood of receiving delayed acyclovir treatment to control for differences in illness severity between groups.
RESULTS:
The median age was 10 days. Delayed acyclovir therapy was administered to 262 neonates (24.1%). In most cases (86.2%) of delayed receipt, acyclovir administration occurred on the second or third day of hospitalization. The overall mortality rate was 7.3% (95% confidence interval: 5.8%–9.0%); 9.5% of those who received delayed acyclovir treatment and 6.6% of those who received early acyclovir treatment died. In a multivariate analysis, delayed acyclovir therapy was associated with significantly greater odds of death (adjusted odds ratio: 2.63 [95% confidence interval: 1.36–5.08]) compared with early acyclovir therapy.
CONCLUSIONS:
In this multicenter observational study of neonates with HSV infection, delayed initiation of acyclovir therapy was associated with in-hospital death. Our data support the use of empiric acyclovir therapy for neonates undergoing testing for HSV infection.
doi:10.1542/peds.2011-0177
PMCID: PMC3387895  PMID: 22123868
herpes simplex virus; neonate; acyclovir; therapy

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