R Lawrence Moss

Nationwide Children's Hospital, Columbus, Ohio, United States

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Publications (75)238.35 Total impact

  • 2014 American Academy of Pediatrics National Conference and Exhibition; 10/2014
  • 2014 American Academy of Pediatrics National Conference and Exhibition; 10/2014
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    ABSTRACT: To test the hypothesis that an exploratory proteomics analysis of urine proteins with subsequent development of validated urine biomarker panels would produce molecular classifiers for both the diagnosis and prognosis of infants with necrotizing enterocolitis (NEC). Urine samples were collected from 119 premature infants (85 NEC, 17 sepsis, 17 control) at the time of initial clinical concern for disease. The urine from 59 infants was used for candidate biomarker discovery by liquid chromatography/mass spectrometry. The remaining 60 samples were subject to enzyme-linked immunosorbent assay for quantitative biomarker validation. A panel of 7 biomarkers (alpha-2-macroglobulin-like protein 1, cluster of differentiation protein 14, cystatin 3, fibrinogen alpha chain, pigment epithelium-derived factor, retinol binding protein 4, and vasolin) was identified by liquid chromatography/mass spectrometry and subsequently validated by enzyme-linked immunosorbent assay. These proteins were consistently found to be either up- or down-regulated depending on the presence, absence, or severity of disease. Biomarker panel validation resulted in a receiver-operator characteristic area under the curve of 98.2% for NEC vs sepsis and an area under the curve of 98.4% for medical NEC vs surgical NEC. We identified 7 urine proteins capable of providing highly accurate diagnostic and prognostic information for infants with suspected NEC. This work represents a novel approach to improving the efficiency with which we diagnose early NEC and identify those at risk for developing severe, or surgical, disease.
    The Journal of pediatrics 01/2014; · 4.02 Impact Factor
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    ABSTRACT: We implemented and validated a linkage algorithm for cases in both the National Surgical Quality Improvement Program-Pediatric (NSQIP-Peds) and the Pediatric Health Information System (PHIS) to investigate healthcare utilization during the first post-operative year. NSQIP-Peds and PHIS cases from our institution who were operated on between January 2010 and September 2011 were matched on gender and dates of birth, admission, and discharge. Rates of true matches were validated using medical records. We examined rates of emergency department (ED) visits, hospital readmissions, potentially preventable readmissions (PPR), and hospital charges within one year of the NSQIP-Peds encounter. Of the 2,409 NSQIP-Peds and 61,147 PHIS records, 93.6% met match criteria with 92.5% being true matches. Post-operative ED visit rates were 7.8% within 30days, 17.2% between 31-180days, and 18.1% between 181-365days. Readmission rates were 5.5% within 30days, 9.3% between 31-180days, and 8.4% between 181-365days. In patients undergoing inpatient procedures, 10.6% had readmissions within 30days, and 23.7% had readmissions within 365days that were potentially preventable. Using indirect identifiers, a linked NSQIP-Peds-PHIS dataset demonstrated high rates of ED visits, readmissions, and PPR in the first post-operative year. This dataset may provide a more comprehensive way to study health care utilization and clinical outcomes.
    Journal of Pediatric Surgery 01/2014; 49(1):207-12. · 1.38 Impact Factor
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    ABSTRACT: Background Anthropomorphic data is an important indicator of child health. This study sought to determine whether anthropomorphic data of extreme weight was a significant predictor of peri-operative morbidity in pediatric surgery. Study Design This was a cohort study of children 29 days up to 18 years of age undergoing surgical procedures at participating American College of Surgeons’ National Surgical Quality Improvement Program Pediatric (ACS-NSQIP Pediatric) hospitals in 2011 and 2012. The primary outcomes were composite morbidity and surgical site infection. The primary predictor of interest was weight percentile divided into three categories (less than or equal to 5th percentile, 6th to 94th, or greater than or equal to 95th percentile). A hierarchical multivariate logistic model, adjusting for procedure case-mix, demographic and clinical patient characteristic variables, was used to quantify the relationship between weight percentile category and outcomes. Results Children at or below the 5th weight percentile had 1.19-fold higher odds of developing overall postoperative morbidity than children in the non-extreme range (95% CI: 1.10-1.30) when controlling for clinical variables. Yet, these children did not have higher odds of developing surgical site infection. Children at or above the 95th weight percentile did not have a significant increase in overall postoperative morbidity. However, they were at 1.35-fold increased odds of surgical site infection compared to those in the middle range while controlling for clinical variables (95% CI: 1.16-1.57). Conclusions Both extremely high and extremely low weight percentile scores may be associated with increased postoperative complications after controlling for clinical variables.
    Journal of the American College of Surgeons 01/2014; · 4.50 Impact Factor
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    ABSTRACT: Background Urgent operation has been considered the only appropriate management of acute appendicitis in children for decades. The purpose of this study was to investigate the feasibility of non-operative management of uncomplicated acute appendicitis in children. Study Design A prospective non-randomized clinical trial of children with uncomplicated acute appendicitis comparing non-operative management to urgent appendectomy was performed. The primary outcome is the 30-day success rate of non-operative management. Secondary outcomes include comparisons of disability days, missed school days, hospital length of stay (LOS), and measures of quality of life and healthcare satisfaction. Results Seventy-seven patients were enrolled during October 2012-October 2013; 30 chose non-operative management and 47 chose surgery. There were no significant differences in demographic or clinical characteristics. The immediate and 30-day success rates of non-operative management were 93% (n=28/30) and 90% (n=27/30). There was no evidence of progression of appendicitis to rupture at the time of surgery in the three patients that failed non-operative management. Compared to the surgery group, the non-operative group had fewer disability days (3 vs. 17 days, p<0.0001), returned to school more quickly (3 vs. 5 days, p=0.008), and exhibited higher quality of life scores in both the child (93 vs. 88, p=0.01) and the parent (96 vs. 90, p=0.03), but incurred a longer LOS (38 vs. 20 hours, p<0.0001). Conclusions Non-operative management of uncomplicated acute appendicitis in children is feasible with a high 30-day success rate and short-term benefits including a quicker recovery and improved quality of life scores. Additional follow-up will allow for determination of a longer-term success rate, safety, and cost-effectiveness.
    Journal of the American College of Surgeons 01/2014; · 4.50 Impact Factor
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    ABSTRACT: Necrotizing enterocolitis (NEC) is a major source of neonatal morbidity and mortality. Since there is no specific diagnostic test or risk of progression model available for NEC, the diagnosis and outcome prediction of NEC is made on clinical grounds. The objective in this study was to develop and validate new NEC scoring systems for automated staging and prognostic forecasting. A six-center consortium of university based pediatric teaching hospitals prospectively collected data on infants under suspicion of having NEC over a 7-year period. A database comprised of 520 infants was utilized to develop the NEC diagnostic and prognostic models by dividing the entire dataset into training and testing cohorts of demographically matched subjects. Developed on the training cohort and validated on the blind testing cohort, our multivariate analyses led to NEC scoring metrics integrating clinical data. MACHINE LEARNING USING CLINICAL AND LABORATORY RESULTS AT THE TIME OF CLINICAL PRESENTATION LED TO TWO NEC MODELS: (1) an automated diagnostic classification scheme; (2) a dynamic prognostic method for risk-stratifying patients into low, intermediate and high NEC scores to determine the risk for disease progression. We submit that dynamic risk stratification of infants with NEC will assist clinicians in determining the need for additional diagnostic testing and guide potential therapies in a dynamic manner. http://translationalmedicine.stanford.edu/cgi-bin/NEC/index.pl and smartphone application upon request.
    PLoS ONE 01/2014; 9(2):e89860. · 3.53 Impact Factor
  • Mehul V Raval, R Lawrence Moss
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    ABSTRACT: Necrotizing enterocolitis (NEC) is the most common surgical emergency occurring in neonatal intensive care unit (NICU) patients. Among patients with NEC, those that require surgery experience the poorest outcomes and highest mortality. Surgical intervention, while attempting to address the intestinal injury and ongoing mulitfactorial physiologic insults in NEC is associated with its own stresses that may compound the ongoing physiologic derangement. Surgery is thus reserved for those patients with clear indication for intervention such as pneumoperitoneum, confirmed stool or pus in the peritoneal cavity, or worsening clinical status. The purpose of this review is to briefly describe the physiologic stress induced by surgical intervention in the preterm, low birth weight patient with NEC and to provide a contemporary overview of available surgical management options for NEC. The optimal surgical plan employed is strongly influenced by clinical judgment and theoretical benefits in terms of minimizing physiologic stressors while providing temporary and/or definitive treatment in a timely fashion. While the choice of operation has not been shown to have a significant effect on any clinically important outcomes, ongoing investigations continue to study both short and long-term outcomes in patients with NEC.
    Pathophysiology 12/2013;
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    ABSTRACT: A multicenter study of pectus excavatum was described previously. This report presents our final results. Patients treated surgically at 11 centers were followed prospectively. Each underwent a preoperative evaluation with CT scan, pulmonary function tests, and body image survey. Data were collected about associated conditions, complications, and perioperative pain. One year after treatment, patients underwent repeat chest CT scan, pulmonary function tests, and body image survey. A subset of 50 underwent exercise pulmonary function testing. Of 327 patients, 284 underwent Nuss procedure and 43 underwent open procedure without mortality. Of 182 patients with complete follow-up (56%), 18% had late complications, similarly distributed, including substernal bar displacement in 7% and wound infection in 2%. Mean initial CT scan index of 4.4 improved to 3.0 post operation (severe >3.2, normal = 2.5). Computed tomography index improved at the deepest point (xiphoid) and also upper and middle sternum. Pulmonary function tests improved (forced vital capacity from 88% to 93%, forced expiratory volume in 1 second from 87% to 90%, and total lung capacity from 94% to 100% of predicted (p < 0.001 for each). VO2 max during peak exercise increased by 10.1% (p = 0.015) and O2 pulse by 19% (p = 0.007) in 20 subjects who completed both pre- and postoperative exercise tests. There is significant improvement in lung function at rest and in VO2 max and O2 pulse after surgical correction of pectus excavatum, with CT index >3.2. Operative correction significantly reduces CT index and markedly improves the shape of the entire chest, and can be performed safely in a variety of centers.
    Journal of the American College of Surgeons 12/2013; 217(6):1080-9. · 4.50 Impact Factor
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    ABSTRACT: Appendectomy is one of the highest volume procedures in children performed across a variety of hospital types in the U.S. potentially making it the ideal procedure to target when assessing hospital and surgeon quality. Though appendiceal perforation rate has been identified as a potential quality target reflecting primary care access, perforation rates have little association with hospital or surgeon quality. The utility and reliability of appendectomy as a target procedure to judge hospital quality based on outcomes beyond perforation rates are unknown. Using the 2008 Nationwide Inpatient Sample, hospital pediatric appendectomy volumes were determined. Based on literature review, a variety of complication rate thresholds to identify hospital outlier status were determined using sample size calculations. The percent of U.S. hospitals that could exceed volume thresholds in order to be reliably compared was determined. Several complication rates of interest were identified ranging from mortality at 0.19% to a composite overall morbidity at 6.44%. Minimum hospital caseloads required to detect a doubling of complication rates included 127 cases for a composite overall morbidity, 276 cases for wound infection, 285 cases for negative appendectomy, 335 cases for intra-abdominal abscess, 438 cases for postoperative ileus, and 4,729 cases for mortality. Based on annual volumes, only 22% of hospitals met the minimum volume thresholds for a composite overall morbidity. In order to use other outcomes to assess quality, multiple year aggregate data are needed in order to generate volumes sufficient for comparison. Even with 5year aggregate data less than 2% of hospitals could be compared based on mortality. For the vast majority of complications very few hospitals accrue enough procedure specific volume with appendectomy to judge quality even with multiple years of data collection. In order to best assess hospital quality in children's surgery alternate targets beyond procedure specific traditional outcomes warrant exploration.
    Journal of Pediatric Surgery 11/2013; 48(11):2313-9. · 1.38 Impact Factor
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    ABSTRACT: Necrotising enterocolitis (NEC) is a major source of neonatal morbidity and mortality. The management of infants with NEC is currently complicated by our inability to accurately identify those at risk for progression of disease prior to the development of irreversible intestinal necrosis. We hypothesised that integrated analysis of clinical parameters in combination with urine peptide biomarkers would lead to improved prognostic accuracy in the NEC population. Infants under suspicion of having NEC (n=550) were prospectively enrolled from a consortium consisting of eight university-based paediatric teaching hospitals. Twenty-seven clinical parameters were used to construct a multivariate predictor of NEC progression. Liquid chromatography/mass spectrometry was used to profile the urine peptidomes from a subset of this population (n=65) to discover novel biomarkers of NEC progression. An ensemble model for the prediction of disease progression was then created using clinical and biomarker data. The use of clinical parameters alone resulted in a receiver-operator characteristic curve with an area under the curve of 0.817 and left 40.1% of all patients in an 'indeterminate' risk group. Three validated urine peptide biomarkers (fibrinogen peptides: FGA1826, FGA1883 and FGA2659) produced a receiver-operator characteristic area under the curve of 0.856. The integration of clinical parameters with urine biomarkers in an ensemble model resulted in the correct prediction of NEC outcomes in all cases tested. Ensemble modelling combining clinical parameters with biomarker analysis dramatically improves our ability to identify the population at risk for developing progressive NEC.
    Gut 09/2013; · 10.73 Impact Factor
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    ABSTRACT: BACKGROUND The American College of Surgeons National Surgical Quality Improvement Program-Pediatric was initiated in 2008 to drive quality improvement in children's surgery. Low mortality and morbidity in previous analyses limited differentiation of hospital performance.METHODS:Participating institutions included children's units within general hospitals and free-standing children's hospitals. Cases selected by Current Procedural Terminology codes encompassed procedures within pediatric general, otolaryngologic, orthopedic, urologic, plastic, neurologic, thoracic, and gynecologic surgery. Trained personnel abstracted demographic, surgical profile, preoperative, intraoperative, and postoperative variables. Incorporating procedure-specific risk, hierarchical models for 30-day mortality and morbidities were developed with significant predictors identified by stepwise logistic regression. Reliability was estimated to assess the balance of information versus error within models.RESULTS:In 2011, 46 281 patients from 43 hospitals were accrued; 1467 codes were aggregated into 226 groupings. Overall mortality was 0.3%, composite morbidity 5.8%, and surgical site infection (SSI) 1.8%. Hierarchical models revealed outlier hospitals with above or below expected performance for composite morbidity in the entire cohort, pediatric abdominal subgroup, and spine subgroup; SSI in the entire cohort and pediatric abdominal subgroup; and urinary tract infection in the entire cohort. Based on reliability estimates, mortality discriminates performance poorly due to very low event rate; however, reliable model construction for composite morbidity and SSI that differentiate institutions is feasible.CONCLUSIONS:The National Surgical Quality Improvement Program-Pediatric expansion has yielded risk-adjusted models to differentiate hospital performance in composite and specific morbidities. However, mortality has low utility as a children's surgery performance indicator. Programmatic improvements have resulted in actionable data.
    PEDIATRICS 08/2013; · 4.47 Impact Factor
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    ABSTRACT: Necrotizing enterocolitis remains a common cause of morbidity and mortality in the neonatal period. Despite many advances in the management of the critically ill neonate, the exact etiology, attempts at prevention and determining best treatment for NEC have been elusive. Unfortunately, the overall survival for this poorly understood and complex condition has not improved. NEC is a condition that can and should be studied with randomized prospective trials (RCTs). This chapter reviews the current evidence-based trials for this condition thus far performed.
    Seminars in Pediatric Surgery 05/2013; 22(2):117-21. · 2.40 Impact Factor
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    ABSTRACT: Purpose To characterize variation among Children's Hospitals with Emergency Department (ED) discharge following successful enema reduction of intussusception, and to explore the impact of this practice on readmission risk, cumulative resource utilization and patient outcomes. Methods We conducted a 5-year audit (2007-2011) of the Pediatric Health Information System database to identify patients with intussusception who were successfully managed by enema reduction. Hospitals with a rate of ED discharge higher than the average rate from all 33 hospitals were analyzed as the "ED-Discharge" group (n=7), and those with a lower rate were analyzed as the "ED-Admit" group (n=26) (Figure). Groups were compared with readmission rate and total cumulative case-related hospital costs, charges, and length of stay (LOS) from index and readmission encounters. Rates of recurrent intussusception and operative management were also compared for the readmitted cohort. Results 3,880 patients managed with enema reduction were identified from 33 hospitals. There was significant variability in the practice of ED discharge across hospitals (overall rate: 13%[506/3880]; range: 0-90.9%; p<0.0001; Figure). The ED discharge rate was 49.9% (428/857) for the ED-Discharge group (range: 20-90.9%) and 2.6% (78/3023) for the ED-Admit group (range: 0-7.7%). Compared with the ED-Admit group, ED-Discharge hospitals had a higher readmission rate (10.9%[93/855] vs. 8.0%[242/3033], OR: 1.4 [95%CI:1.1-1.8]; p=0.0076), but a shorter index and cumulative LOS (mean index LOS: 1.6 vs. 2.0days; p<0.0001; mean cumulative LOS: 1.8 vs. 2.2days; p<0.0001). Furthermore, patients treated at ED-Discharge hospitals had 44% lower median case-related hospital costs ($1438 [IQR:$813-$2322] vs. $2545 [IQR:$1972-$3517]; p<0.0001) and 38% lower median charges ($3857 [IQR:$2462-$5952] vs. $6232 [IQR:$4809-$8200]; p<0.0001) during the index admission, and 41% lower median cumulative hospital costs ($1540 [IQR:$881-$2524] vs. $2612 [IQR:$2013-$3735]; p<0.0001) and 36% lower cumulative charges ($4133 [IQR:$2606-$6393] vs. $6405 [IQR:$4919-$8668]; p<0.0001) after factoring in readmission encounters. Moreover, the median cumulative cost and charges at each of the 7 hospitals in the ED-Discharge group were lower than those from the collective ED-Admit group, suggesting that the relative cost-benefit was not due to any single outlier(s) within the ED Discharge group. For the readmitted cohort, patients treated at ED-Discharge hospitals were more likely to require repeat enema reduction at readmission (58.1%[54/93] vs. 34.3%[83/242]; p<0.0001) though there was no difference between groups with mean readmission LOS (2.0 vs. 2.1days; p=0.90) or the need for operative management (ED-Discharge 1.1%[1/93] vs. ED-Admit 4.1%[10/242]; p=0.16). Conclusion Discharge from the ED following enema reduction is associated with markedly lower treatment-related costs, charges and length of stay compared with inpatient admission. Although there is an increased risk of readmission following ED discharge, this practice remains cost-effective and does not increase the need for operative management. Collaborative efforts should focus on further defining selection criteria to increase the generalizability of this treatment strategy.
    2012 American Academy of Pediatrics National Conference and Exhibition; 10/2012
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    ABSTRACT: Purpose The objectives of this study were 2-fold: 1) To identify patient characteristics associated with utilization of computed tomography (CT) and ultrasound (US) in the diagnosis of pediatric appendicitis, and 2) To calculate and compare standardized imaging rates between Children's Hospitals following adjustment for characteristics associated with increased utilization. Methods We performed a retrospective audit of the Pediatric Health Information System database (1/2009-9/2011) to identify all patients diagnosed with acute appendicitis who underwent appendectomy during the same admission at 40 Children's Hospitals. Hierarchical multivariable regression using General Estimating Equations to adjust for clustering was used to examine the influence of age, gender, race, insurance status, median household income and the presence of chronic medical conditions on CT and US utilization. Standardized imaging rates were calculated and compared between hospitals with utilization outliers defined as those whose rate and 95% Confidence Intervals (CI) did not include the overall mean rate. Results 28,038 patients were identified (hospital median:631, range:179-2,107). Characteristics associated with (or a strong trend toward) increased imaging utilization (CT or US) included Hispanic race (Hispanic vs. White:OR 1.51[95%CI:1.29-1.78]), female gender (OR 1.25[95%CI:1.16-1.34]), chronic medical conditions (OR 1.19[95%CI:1.03-1.37]), and very young and adolescent age groups (3-7y vs. 8-12y:OR 1.08[95%CI:0.99-1.18]; 13-18y vs. 8-12y:OR 1.11[95%CI:1.02-1.20]). Following standardization, a 3.2-fold variation in the rate of any imaging was observed across hospitals (overall rate:50.8%; range:23.2%-75.2%;p<0.0001) with sub-group analysis revealing a 33.5-fold variation in the rate of CT scanning (overall rate:23.7%; range:1.7%-57.9%;p<0.0001;figure), a 67-fold variation in US utilization (overall rate:31.8%; range:0%-67.5%;p<0.0001;figure), and a 15-fold variation in the rate of patients receiving both imaging modalities (overall rate:5.8%; range:0%-14.8%;p<0.0001). When compared to the overall standardized rate from the entire cohort, 30%(12/40) of hospitals were found to have significantly higher imaging rates (either CT or US) and 25%(10/40) had significantly lower rates. Further sub-group analysis demonstrated that 35%(14/40) of hospitals had significantly higher rates of CT utilization relative to the group while 35%(14/40) of hospitals had lower rates. Similarly, 35%(14/40) of hospitals had significantly higher rates of US utilization while 50%(20/40) of hospitals had lower rates (figure). Twenty-five percent (10/40) of hospitals had significantly higher rates of redundant imaging (both CT and US), while 43%(17/40) of hospitals had lower rates. There was a strong inverse correlation between the use of CT and US across hospitals (Spearman's r=-0.711;p<0.0001;figure), and no correlation was found between hospital volume and imaging rates for CT (r=-0.114;p=0.80), US (r=0.035;p=0.83), or the use of any imaging modality (r=-0.114;p=0.49). Conclusion Significant variation exists among Children's Hospitals in the use of diagnostic imaging for appendicitis. Establishment of a collaborative quality improvement platform through which imaging protocols can be shared and prospectively audited against relevant outcomes may provide an effective strategy for reducing resource utilization and radiation exposure associated with pediatric appendicitis.
    2012 American Academy of Pediatrics National Conference and Exhibition; 10/2012
  • Kathleen M Dominguez, R Lawrence Moss
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    ABSTRACT: Necrotizing enterocolitis (NEC) is the most common acquired gastrointestinal disease of premature neonates and is a serious cause of morbidity and mortality. NEC is one of the leading causes of death in neonatal intensive care units. Surgical treatment is necessary in patients whose disease progresses despite medical therapy. Surgical options include peritoneal drainage and laparotomy, with studies showing no difference in outcome related to approach. Survivors, particularly those requiring surgery, face serious sequelae.
    Clinics in perinatology 06/2012; 39(2):387-401. · 1.54 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate a cohort of children undergoing imaging prior to appendectomy in order to identify factors that were associated with undergoing computed tomography (CT) alone as compared to ultrasound (US) alone or US and CT. The Kids' Inpatient Database was queried for children 1-18 y of age with imaging reported. Logistic regression models identified factors associated with CT-alone imaging modality. There were 6519 patients (69.5%) who underwent CT alone, 2076 (22.1%) who underwent US alone, and 782 (8.4%) who underwent US and CT. The negative appendectomy rates were higher for US alone (6.5%) and US and CT (6.6%) compared to the CT alone group (3.6%, P < 0.001). The perforated appendicitis rates were highest for the US and CT group (36.3%) compared to the CT alone group (31.8%) and the US alone group (29.8%, P = 0.004). Older patients were more likely to undergo CT alone compared to younger patients (odds ratio [OR] 1.44, 95% confidence interval [CI] 1.26-1.64). Girls were less likely to undergo CT alone compared to boys (OR 0.51, 95% CI 0.46-0.56). Hospital factors associated with lower CT-alone imaging included children's centers (OR 0.46, 95% CI 0.41-0.52), teaching hospitals (OR 0.53, 95% CI 0.48-0.60), and urban location (OR 0.40, 95% CI 0.32-0.49). Though patient factors such as age and sex influence imaging use, children's centers are associated with lower CT-alone imaging compared to non-children's centers. As focus increases on limiting CT use in children, opportunities for improvement based on hospital factors exist.
    Journal of Surgical Research 04/2012; 177(1):131-6. · 2.02 Impact Factor
  • Loren Berman, R Lawrence Moss
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    ABSTRACT: Necrotizing enterocolitis (NEC) is a leading cause of death among patients in the neonatal intensive care unit, carrying a mortality rate of 15-30%. Its pathogenesis is multifactorial and involves an overreactive response of the immune system to an insult. This leads to increased intestinal permeability, bacterial translocation, and sepsis. There are many inflammatory mediators involved in this process, but thus far none has been shown to be a suitable target for preventive or therapeutic measures. NEC usually occurs in the second week of life after the initiation of enteral feeds, and the diagnosis is made based on physical examination findings, laboratory studies, and abdominal radiographs. Neonates with NEC are followed with serial abdominal examinations and radiographs, and may require surgery or primary peritoneal drainage for perforation or necrosis. Many survivors are plagued with long term complications including short bowel syndrome, abnormal growth, and neurodevelopmental delay. Several evidence-based strategies exist that may decrease the incidence of NEC including promotion of human breast milk feeding, careful feeding advancement, and prophylactic probiotic administration in at-risk patients. Prevention is likely to have the greatest impact on decreasing mortality and morbidity related to NEC, as little progress has been made with regard to improving outcomes for neonates once the disease process is underway.
    Seminars in Fetal and Neonatal Medicine 06/2011; 16(3):145-50. · 3.51 Impact Factor
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    ABSTRACT: The aim of the study was to prospectively determine risk factors for the development of parenteral nutrition-associated liver disease (PNALD) in infants who underwent surgery for necrotizing enterocolitis (NEC), the most common cause of intestinal failure in children. : From February 2004 to February 2007, we diagnosed 464 infants with NEC, of whom 180 had surgery. One hundred twenty-seven patients were available for full analysis. PNALD was defined as serum direct bilirubin ≥ 2 mg/dL or ALT ≥ 2 × the upper limit of normal in the absence of sepsis after ≥ 14 days of exposure to PN. Median gestational age was 26 weeks and 68% were boys. Seventy percent of the cohort developed PNALD and the incidence of PNALD varied significantly across the 6 study sites, ranging from 56% to 85% (P = 0.05). Multivariable logistic regression analysis identified small-bowel resection or creation of jejunostomy (odds ratio [OR] 4.96, 95% confidence interval [CI] 1.97-12.51, P = 0.0007) and duration of PN in weeks (OR 2.37, 95% CI 1.56-3.60, P < 0.0001) as independent risk factors for PNALD. Preoperative exposure to PN was also associated with the development of PNALD; the risk of PNALD was 2.6 (95% CI 1.5-4.7; P = 0.001) times greater in patients with ≥ 4 weeks of preoperative PN compared with those with less preoperative PN use. Breast milk feedings, episodes of infection, and gestational age were not related to the development of PNALD. The incidence of PNALD is high in infants with NEC undergoing surgical treatment. Risk factors for PNALD are related to signs of NEC severity, including the need for small-bowel resection or proximal jejunostomy, as well as longer exposure to PN. Identification of these and other risk factors can help in the design of clinical trials for the prevention and treatment of PNALD and for clinical assessment of patients with NEC and prolonged PN dependence.
    Journal of pediatric gastroenterology and nutrition 04/2011; 52(5):595-600. · 2.18 Impact Factor
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    ABSTRACT: The objective of this study was to compare demographic and clinical events in three groups of preterm neonates: those with necrotizing enterocolitis totalis (NEC-T), those with NEC non-totalis (NEC non-T) and in preterm patients without NEC. This retrospective case-control study was conducted at Yale New Haven Children's Hospital using patient data from January 1991 to December 2007. Study patients were less than 36 weeks of gestational age (GA) at birth, without gastrointestinal (GI) malformations. Cases (NEC-T) were diagnosed at operation or at autopsy with observation of >80% necrosis of the GI tract. Two control groups were assigned: Group 1 or NEC non-T and Group II or Non-NEC. Two to four controls per case were matched to cases by GA at birth±2 weeks. Demographic and clinical data for the day of diagnosis and retrospectively up to 7 days preceding diagnosis were recorded for those with NEC-T and NEC. Group II controls were matched for date of birth and day of life, in addition to GA at birth. A total of 14 075 patients were admitted to the Newborn Special Care Unit during the study interval. Overall 328 patients (2.3%) developed NEC≥Bell's Stage II; 39 patients met inclusion criteria for NEC-T case status; 148 NEC non-T and 110 non-NEC controls were assigned. In the comparison of NEC T and NEC non-T neonates, use of breast milk was associated with decreased risk of NEC-T, adjusted odds ratio (OR)=0.26, 95% confidence interval (CI) of OR=0.08-0.085, P=0.03. When NEC T and non-NEC patients were compared, having reached full-enteral feeds before the date of diagnosis of the matched case (adjusted OR=28.5, 95% CI of OR=2.7-299, P=0.005) and use of breast milk (adjusted OR=0.09, 95% CI of OR=0.02-0.56, P=0.01) were significantly different between the two groups. Breast milk usage was significantly associated with decreased occurrence of NEC-T in our comparison of NEC-T, NEC non-T and non-NEC patients. Although there were some differences, the majority of demographic and clinical variables assessed were not shown to be significantly different between cases and controls. This highlights the need for more biological data in assessing risk of developing NEC-T.
    Journal of perinatology: official journal of the California Perinatal Association 03/2011; 31(11):730-8. · 1.59 Impact Factor

Publication Stats

1k Citations
238.35 Total Impact Points

Institutions

  • 2012–2014
    • Nationwide Children's Hospital
      • Department of Surgery
      Columbus, Ohio, United States
    • American College of Surgeons
      Chicago, Illinois, United States
  • 2013
    • The Ohio State University
      • Division of Pediatric Surgery
      Columbus, Ohio, United States
  • 2000–2013
    • Lucile Packard Children’s Hospital at Stanford
      Palo Alto, California, United States
  • 2004–2012
    • Yale-New Haven Hospital
      • Pediatric Surgery Program
      New Haven, Connecticut, United States
  • 2011
    • Montefiore Medical Center
      • Department of Pediatrics
      New York City, NY, United States
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 2010
    • Boston Children's Hospital
      Boston, Massachusetts, United States
  • 2003–2010
    • Yale University
      • Department of Surgery
      New Haven, Connecticut, United States
    • University of Alabama at Birmingham
      • Department of Pediatrics
      Birmingham, AL, United States
  • 2003–2004
    • Stanford Medicine
      • • Division of Pediatric Cardiac Surgery
      • • Division of Epidemiology
      Stanford, California, United States
  • 1999–2003
    • Stanford University
      • • Division of Neonatal and Developmental Medicine
      • • Division of Pediatric General Surgery
      • • Department of Surgery
      Stanford, CA, United States