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2.  Serum Tocopherol Levels in Very Preterm Infants After a Single Dose of Vitamin E at Birth 
Pediatrics  2013;132(6):e1626-e1633.
Our aim was to examine the impact of a single enteral dose of vitamin E on serum tocopherol levels. The study was undertaken to see whether a single dose of vitamin E soon after birth can rapidly increase the low α-tocopherol levels seen in very preterm infants. If so, this intervention could be tested as a means of reducing the risk of intracranial hemorrhage.
Ninety-three infants <27 weeks’ gestation and <1000 g were randomly assigned to receive a single dose of vitamin E or placebo by gastric tube within 4 hours of birth. The vitamin E group received 50 IU/kg of vitamin E as dl-α-tocopheryl acetate (Aquasol E). The placebo group received sterile water. Blood samples were taken for measurement of serum tocopherol levels by high-performance liquid chromatography before dosing and 24 hours and 7 days after dosing.
Eighty-eight infants received the study drug and were included in the analyses. The α-tocopherol levels were similar between the groups at baseline but higher in the vitamin E group at 24 hours (median 0.63 mg/dL vs 0.42 mg/dL, P = .003) and 7 days (2.21 mg/dL vs 1.86 mg/dL, P = .04). There were no differences between groups in γ-tocopherol levels. At 24 hours, 30% of vitamin E infants and 62% of placebo infants had α-tocopherol levels <0.5 mg/dL.
A 50-IU/kg dose of vitamin E raised serum α-tocopherol levels, but to consistently achieve α-tocopherol levels >0.5 mg/dL, a higher dose or several doses of vitamin E may be needed.
PMCID: PMC3838534  PMID: 24218460
vitamin E; preterm infants
3.  Multiscale Representation of Genomic Signals 
Nature methods  2014;11(6):689-694.
Genomic information is encoded on a wide range of distance scales, ranging from tens of base pairs to megabases. We developed a multiscale framework to analyze and visualize the information content of genomic signals. Different types of signals, such as GC content or DNA methylation, are characterized by distinct patterns of signal enrichment or depletion across scales spanning several orders of magnitude. These patterns are associated with a variety of genomic annotations, including genes, nuclear lamina associated domains, and repeat elements. By integrating the information across all scales, as compared to using any single scale, we demonstrate improved prediction of gene expression from Polymerase II chromatin immunoprecipitation sequencing (ChIP-seq) measurements and we observed that gene expression differences in colorectal cancer are not most strongly related to gene body methylation, but rather to methylation patterns that extend beyond the single-gene scale.
PMCID: PMC4040162  PMID: 24727652
4.  Incidence, management and outcomes of cardiovascular insufficiency in critically ill term and late preterm newborn infants 
American journal of perinatology  2014;31(11):947-956.
To characterize the incidence, management and short term outcomes of cardiovascular insufficiency (CVI) in mechanically ventilated newborns, evaluating 4 separate pre-specified definitions.
Study Design
Multicenter, prospective cohort study of infants ≥34 weeks gestational age (GA) and on mechanical ventilation during the first 72 hours. CVI was prospectively defined as either (1) mean arterial pressure (MAP)
Of 647 who met inclusion criteria, 419 (65%) met ≥1 definition of CVI. Of these, 98% received fluid boluses, 36% inotropes and 17% corticosteroids. Of treated infants, 46% did not have CVI as defined by a MAP < GA ± signs of inadequate perfusion. Inotrope therapy was associated with increased mortality (11.1% vs. 1.3%; P < 0.05).
More than half of the infants met at least one definition of CVI. However, almost half of the treated infants met none of the definitions. Inotropic therapy was associated with increased mortality. These findings can help guide the design of future studies of CVI in newborns.
PMCID: PMC4127379  PMID: 24515617
blood pressure; cardiovascular insufficiency; mechanical ventilation; inotrope; fluid bolus; glucocorticoid; outcomes; newborn
To determine if current retinopathy of prematurity screening guidelines1 adequately identify treatable ROP in a contemporary cohort of extremely low gestation infants.
Study Design
Data from the Surfactant, Positive Pressure, and Pulse Oximetry Randomized Trial were used. Inborn infants 24 0/7 to 27 6/7 weeks gestational age with consent prior to delivery were enrolled in 2005-2009. Severe retinopathy of prematurity (Type 1 retinopathy of prematurity or treatment with laser, cryotherapy, or bevacizumab) or death was the primary outcome for the randomized trial. Examinations followed then current American Academy of Pediatrics (AAP) screening recommendations, beginning by 31-33 weeks postmenstrual age.2,3
1316 infants were enrolled in the trial. 997 of the 1121 who survived to first eye exam had final retinopathy of prematurity outcome determined. 137 (14% of 997) met criteria for severe retinopathy of prematurity and 128 (93%) of those had sufficient data (without missing or delayed exams) to determine age of onset of severe retinopathy of prematurity. Postmenstrual age at onset was 32.1 to 53.1 wks. In this referral center cohort, 1.4% (14/997) developed severe retinopathy of prematurity after discharge.
Our contemporary data support the 2013 AAP screening guidelines for ROP for infants 24 0/7 to 27 6/7 weeks gestational age.1 Some infants do not meet treatment criteria until after discharge home. Post-discharge follow-up of infants who are still at risk for severe ROP is crucial for timely detection and treatment.
PMCID: PMC3969774  PMID: 24503911
extremely premature infant
Pharmacists play an increasingly important role in medication therapy management, which requires communicating effectively with patients. Pharmacy students completed the Self-Assessment of Perceived Level of Cultural Competence (SAPLCC) questionnaire, and their results were used to identify patterns in self-assessment of cultural competence. In general, students rated their knowledge as less than their skills and attitudes. Important differences were found by race, comparing each group with its counterparts: African American students rated their perceived competencies regarding patient discrimination and barriers to health care at a significantly higher level; Asian American students rated their attitudes to engaging in self-reflection and their knowledge in multicultural issues at significantly lower level; and White students rated their awareness regarding racial dynamics at a significantly lower level. It is recommended to consider the students’ cultural, racial, and ethnic backgrounds before developing curriculum in cultural competence and, perhaps, to develop targeted educational interventions for specific groups.
PMCID: PMC4175523  PMID: 23395945
Cultural competence; pharmacy students; minority health care providers; training; assessment; racial dynamics; curriculum
Physical fitness testing is a common tool for motivating employees with strenuous occupations to reach and maintain a minimum level of fitness. Nevertheless, the use of such tests can be hampered by several factors, including required compliance with US antidiscrimination laws. The Highland Park (Texas) Department of Public Safety implemented testing in 1991, but no single test adequately evaluated its sworn employees, who are cross-trained and serve as police officers and firefighters. In 2010, the department's fitness experts worked with exercise physiologists from Baylor Heart and Vascular Hospital to develop and evaluate a single test that would be equitable regardless of race/ethnicity, disability, sex, or age >50 years. The new test comprised a series of exercises to assess overall fitness, followed by two sequences of job-specific tasks related to firefighting and police work, respectively. The study group of 50 public safety officers took the test; raw data (e.g., the number of repetitions performed or the time required to complete a task) were collected during three quarterly testing sessions. The statistical bootstrap method was then used to determine the levels of performance that would correlate with 0, 1, 2, or 3 points for each task. A sensitivity analysis was done to determine the overall minimum passing score of 17 points. The new physical fitness test and scoring system have been incorporated into the department's policies and procedures as part of the town's overall employee fitness program.
PMCID: PMC4059562  PMID: 24982558
Firefighters who have received an implantable cardioverter-defibrillator (ICD) are asked to retire or are permanently placed on restricted duty because of concerns about their being incapacitated by an ICD shock during a fire emergency. We present the case of a 40-year-old firefighter who, after surviving sudden cardiac arrest and undergoing ICD implantation, sought to demonstrate his fitness for active duty by completing a high-intensity, occupation-specific cardiac rehabilitation training program. The report details the exercise training, ICD monitoring, and stress testing that he underwent. During the post-training treadmill stress test in firefighter turnout gear, the patient reached a functional capacity of 17 metabolic equivalents (METs), exceeding the 12-MET level required for his occupation. He had no ICD shock therapy or recurrent sustained arrhythmias during stress testing or at any time during his cardiac rehabilitation stay. By presenting this case, we hope to stimulate further discussion about firefighters who have an ICD, can meet the functional capacity requirements of their occupation, and want to return to work.
PMCID: PMC4059573  PMID: 24982569
Nature immunology  2008;10(1):116-125.
A major challenge in vaccinology is to prospectively determine vaccine efficacy. Here we have used a systems biology approach to identify early gene ‘signatures’ that predicted immune responses in humans vaccinated with yellow fever vaccine YF-17D. Vaccination induced genes that regulate virus innate sensing and type I interferon production. Computational analyses identified a gene signature, including complement protein C1qB and eukaryotic translation initiation factor 2 alpha kinase 4—an orchestrator of the integrated stress response—that correlated with and predicted YF-17D CD8+ T cell responses with up to 90% accuracy in an independent, blinded trial. A distinct signature, including B cell growth factor TNFRS17, predicted the neutralizing antibody response with up to 100% accuracy. These data highlight the utility of systems biology approaches in predicting vaccine efficacy.
PMCID: PMC4049462  PMID: 19029902
Pediatrics  2013;131(6):e1865-e1873.
To investigate the relationships among blood pressure (BP) values, antihypotensive therapies, and in-hospital outcomes to identify a BP threshold below which antihypotensive therapies may be beneficial.
Prospective observational study of infants 230/7 to 266/7 weeks’ gestational age. Hourly BP values and antihypotensive therapy use in the first 24 hours were recorded. Low BP was investigated by using 15 definitions. Outcomes were examined by using regression analysis controlling for gestational age, the number of low BP values, and illness severity.
Of 367 infants enrolled, 203 (55%) received at least 1 antihypotensive therapy. Treated infants were more likely to have low BP by any definition (P < .001), but for the 15 definitions of low BP investigated, therapy was not prescribed to 3% to 49% of infants with low BP and, paradoxically, was administered to 28% to 41% of infants without low BP. Treated infants were more likely than untreated infants to develop severe retinopathy of prematurity (15% vs 8%, P = .03) or severe intraventricular hemorrhage (22% vs 11%, P < .01) and less likely to survive (67% vs 78%, P = .02). However, with regression analysis, there were no significant differences between groups in survival or in-hospital morbidity rates.
Factors other than BP contributed to the decision to use antihypotensive therapies. Infant outcomes were not improved with antihypotensive therapy for any of the 15 definitions of low BP investigated.
PMCID: PMC3666108  PMID: 23650301
extremely preterm infant; antihypotensive therapy; blood pressure; hypotension
As resident attrition disrupts educational and workload balance and reduces the number of graduating physicians to care for patients, an ongoing goal of graduate medical education programs is to retain residents.
We compared annual rates of resident attrition in obstetrics and gynecology (Ob-Gyn) with other clinical specialties of similar or larger size during a recent 10-year period, and explored the reasons for resident attrition.
In this observational study, we analyzed annual data from the American Medical Association Graduate Medical Education Census between academic years 2000 and 2009 for residents who entered Ob-Gyn and other core clinical specialties. Our primary outcome was the trend in averaged annual attrition rates.
The average annual attrition was 196 ± 12 (SD) residents, representing 4.2% ± 0.5% of all Ob-Gyn residents. Rates of attrition were consistently higher among men (5.3%) and international medical school graduates (7.6%). The annual rate of attrition was similar to that for other clinical specialties (mean: 4.0%; range: from 1.5% in emergency medicine to 7.9% in psychiatry). The attrition rates for Ob-Gyn residents were relatively stable for the 10-year period (range: 3.6% in 2008 to 5.1% in 2006). Common reasons for attrition were transition to another specialty (30.0%), withdrawal/dismissal (28.2%), transfer to another Ob-Gyn program (25.4%), and leave of absence (2.2%). These proportions remained fairly constant during this 10-year period.
The average annual attrition rate of residents in Ob-Gyn was 4.2%, comparable to most other core clinical specialties.
PMCID: PMC3693692  PMID: 24404271
Objective. To evaluate the efficacy of faculty-led problem-based learning (PBL) vs online simulated-patient case in fourth-year (P4) pharmacy students.
Design. Fourth-year pharmacy students were randomly assigned to participate in either online branched-case learning using a virtual simulation platform or a small-group discussion. Preexperience and postexperience student assessments and a survey instrument were completed.
Evaluation. While there were no significant differences in the preexperience test scores between the groups, there was a significant increase in scores in both the virtual-patient group and the PBL group between the preexperience and postexperience tests. The PBL group had higher postexperience test scores (74.8±11.7) than did the virtual-patient group (66.5±13.6) (p=0.001).
Conclusion. The PBL method demonstrated significantly greater improvement in postexperience test scores than did the virtual-patient method. Both were successful learning methods, suggesting that a diverse approach to simulated patient cases may reach more student learning styles.
PMCID: PMC4028585  PMID: 24850938
virtual patient; simulation; problem-based learning; pharmacy education
The Journal of pediatrics  2012;162(4):685-690.e1.
To test the hypothesis that high-risk ventilator-dependent extremely low birth weight (ELBW; BW ≤1000g) infants treated with seven days of hydrocortisone will have larger total brain tissue volumes than placebo treated infants.
Study design
A predetermined sample size of 64 ELBW infants, between 10 to 21 days old and ventilator-dependent with a respiratory index score ≥2, were randomized to systemic hydrocortisone (17 mg/kg cumulative dose) or saline placebo. Primary outcome was total brain tissue volume. Volumetric MRI was performed at 38 weeks postmenstrual age; brain tissue regions were segmented and quantified automatically with a high degree of accuracy and nine structures were segmented manually. All analyses of regional brain volumes were adjusted by postmenstrual age at MRI scan.
The study groups were similar at baseline and eight infants died in each arm. Unadjusted total brain tissue volume (mean±SD) in the hydrocortisone (N=23) and placebo treated infants (N=21) was 272±40.3 cm3 and 277.8±59.1 cm3, respectively (adjusted mean difference: 6.35 cm3 (95% CI: (−20.8, 32.5); P=0.64). Three of the 31 hydrocortisone treated infants and five of the 33 placebo treated infants survived without severe BPD (RR 0.62, 95% CI: 0.13, 2.66; P=0.49). No significant differences were noted in pre-specified secondary outcomes of regional structural volumes or days on respiratory support. No adverse effects of hydrocortisone were observed.
Low dose hydrocortisone in high-risk ventilator-dependent infants after a week of age had no discernible effect on regional brain volumes or pulmonary outcomes prior to NICU discharge.
PMCID: PMC3609889  PMID: 23140612
Bronchopulmonary dysplasia; corticosteroids; extremely low birth weight; magnetic resonance imaging; brain injury; mechanical ventilation
Engaging community residents to obtain their feedback in conducting clinical research, and including them as leaders in implementing applicable health advances is crucial for success and sustaining large center awards.
Forty-four adult men and women participated in one of four focus groups. Two groups each (one African American and one Caucasian) were conducted in Baton Rouge and in New Orleans.
In an effort to determine the knowledge, attitudes, and beliefs Louisiana residents have about the Louisiana Clinical and Translational Science (LA CaTS) Center concept, four main themes emerged from focus group participants concerning the state’s research institutions, and what it means to have these institutions operating under one umbrella to improve the quality of health of its people: 1) academic/research institutions of the State are uniformly widely recognized and held in high regard; 2) increasing awareness of clinical research is a necessity; 3) establishing the LA CaTS Center is an excellent idea; and 4) effective communication including delivery style is crucial to partnerships and especially to the community.
Focus group discussions can provide insight into community residents’ perceptions, beliefs, motivations and patterns of behavior for strategically planning for large center awards.
PMCID: PMC3971466  PMID: 24138681
Research; Partnerships
The Journal of Pediatrics  2012;161(2):264-269.e2.
To assess the impact of emperic antifungal therapy of invasive candidiasis on subsequent outcomes in premature infants.
Study design
This was a cohort study of infants ≤1000 g birth weight cared for at Neonatal Research Network sites. All infants had at least 1 positive culture for Candida. Emperic antifungal therapy was defined as receipt of a systemic antifungal on the day of or the day before the first positive culture for Candida was drawn. We created Cox proportional hazards and logistic regression models stratified on propensity score quartiles to determine the effect of emperic antifungal therapy on survival, time to clearance of infection, retinopathy of prematurity, bronchopulmonary dysplasia, end-organ damage, and neurodevelopmental impairment (NDI).
136 infants developed invasive candidiasis. The incidence of death or NDI was lower for infants who received emperic antifungal therapy (19/38, 50%) compared with those who had not (55/86, 64%; odds ratio=0.27 [95% confidence interval 0.08–0.86]). There was no significant difference between the groups for any single outcome or other combined outcomes.
Emperic antifungal therapy was associated with increased survival without NDI. A prospective randomized trial of this strategy is warranted.
PMCID: PMC3380169  PMID: 22424952
Candida; neonate; mortality; neurodevelopmental impairment
PLoS ONE  2013;8(5):e62804.
Our objective was to investigate diverse clinical antecedents of total and regional brain volume abnormalities and white matter hyperintensity volume on term MRI in extremely low birth weight (birth weight ≤1000 g) survivors. A consecutive cohort of extremely low birth weight infants who survived to 38 weeks postmenstrual age (n = 122) and a control group of 16 healthy term newborns underwent brain MRI at term-equivalent age. Brain volumes were measured using semi-automated and manual segmentation methods. Using multivariable linear regression, clinical antecedents were correlated with volumes of total brain tissue, white matter hyperintensities, and regional tissues/structures, adjusted for age at MRI, total cranial volume, and total tissue volume. Regional brain volumes were markedly reduced in extremely low birth weight infants as compared to term newborns (relative difference range: −11.0%, −35.9%). Significant adverse clinical associations for total brain tissue volume included: small for gestational age, seizures, caffeine therapy/apnea of prematurity, duration of parenteral nutrition, pulmonary hemorrhage, and white matter injury (p<0.01 for each; relative difference range: −1.4% to −15.0%). Surgery for retinopathy of prematurity and surgery for necrotizing enterocolitis or spontaneous intestinal perforation were significantly associated with increasing volume of white matter hyperintensities. Regional brain volumes are sensitive to multiple perinatal factors and neonatal morbidities or interventions. Brain growth measurements in extremely low birth weight infants can advance our understanding of perinatal brain injury and development.
PMCID: PMC3650008  PMID: 23671636
Current guidelines, initially published in 1995, recommend antenatal corticosteroids for mothers with preterm labor from 24–34 weeks gestational age, but not before 24 weeks because of lack of data. However, many infants born before 24 weeks are provided intensive care now.
To determine if antenatal corticosteroids are associated with improvement in major outcomes in infants born at 22 and 23 weeks.
Design, Setting, Participants
Data for this cohort study were collected prospectively on 401–1000 gram inborn infants (N=10,541) of 22–25 weeks gestation born between 1993–2009 at 23 academic perinatal centers in the United States. Certified examiners unaware of exposure to antenatal corticosteroids performed follow-up examinations on 4,924 (86.5%) of the infants born in 1993–2008 who survived to 18–22 months. Logistic regression models generated adjusted odds ratios, controlling for maternal and neonatal variables.
Main Outcome Measures
Mortality and neurodevelopmental impairment at 18–22 months corrected age
Death or neurodevelopmental impairment at 18–22 months was lower for infants whose mothers received antenatal corticosteroids born at 23 weeks (antenatal corticosteroids, 83.4% vs no antenatal corticosteroids, 90.5%; adjusted odds ratio 0.58; 95% CI, 0.42–0.80), at 24 weeks (antenatal corticosteroids, 68.4% vs no antenatal corticosteroids, 80.3%; adjusted odds ratio 0.62; 95% CI, 0.49–0.78), and at 25 weeks (antenatal corticosteroids, 52.7% vs no antenatal corticosteroids, 67.9%; adjusted odds ratio 0.61; 95% CI, 0.50–0.74) but not at 22 weeks (antenatal corticosteroids, 90.2% vs no antenatal corticosteroids, 93.1%; adjusted odds ratio 0.80; 95% CI, 0.29–12.21). Death by 18–22 months, hospital death, death/intraventricular hemorrhage/periventricular leukomalacia, and death/necrotizing enterocolitis were significantly lower for infants born at 23, 24, and 25 weeks gestational age if the mothers had received antenatal corticosteroids but the only outcome significantly lower at 22 weeks was death/necrotizing enterocolitis (antenatal corticosteroids, 73.5% vs no antenatal corticosteroids, 84.5%; adjusted odds ratio 0.54; 95% CI, 0.30–0.97).
Among infants born at 23–25 weeks gestation, use of antenatal corticosteroids compared to non-use was associated with a lower rate of death or neurodevelopmental impairment at 18–22 months.
PMCID: PMC3565238  PMID: 22147379
prematurity; infant mortality; neonatal intensive care; neurodevelopmental impairment; lung maturation; limits of viability
Cell host & microbe  2011;9(6):463-471.
Leishmania parasites infect macrophages, cells normally involved in innate defense against pathogens. L. amazonensis and L. major cause severe or mild disease, respectively, consistent with each parasite’s ability to survive within activated macrophages. The mechanisms underlying increased virulence of L. amazonensis are mostly unknown. We show that L. amazonensis promotes its own survival by inducing expression of CD200, an immunoregulatory molecule that inhibits macrophage activation. L. amazonensis does not form typical non-healing lesions in CD200−/− mice and cannot replicate in CD200−/− macrophages, an effect reversed by exogenous administration of soluble CD200-Fc. The less virulent L. major does not induce CD200 expression and forms small, self-healing lesions in both wild type and CD200−/− mice. Notably, CD200-Fc injection transforms the course of L. major infection to one resembling L. amazonensis, with large, non-healing lesions. CD200-dependent iNOS inhibition allows parasite growth in macrophages, identifying a mechanism for the increased virulence of L. amazonensis.
PMCID: PMC3118640  PMID: 21669395
Rationale: Benefits of identifying risk factors for bronchopulmonary dysplasia in extremely premature infants include providing prognostic information, identifying infants likely to benefit from preventive strategies, and stratifying infants for clinical trial enrollment.
Objectives: To identify risk factors for bronchopulmonary dysplasia, and the competing outcome of death, by postnatal day; to identify which risk factors improve prediction; and to develop a Web-based estimator using readily available clinical information to predict risk of bronchopulmonary dysplasia or death.
Methods: We assessed infants of 23–30 weeks' gestation born in 17 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and enrolled in the Neonatal Research Network Benchmarking Trial from 2000–2004.
Measurements and Main Results: Bronchopulmonary dysplasia was defined as a categorical variable (none, mild, moderate, or severe). We developed and validated models for bronchopulmonary dysplasia risk at six postnatal ages using gestational age, birth weight, race and ethnicity, sex, respiratory support, and FiO2, and examined the models using a C statistic (area under the curve). A total of 3,636 infants were eligible for this study. Prediction improved with advancing postnatal age, increasing from a C statistic of 0.793 on Day 1 to a maximum of 0.854 on Day 28. On Postnatal Days 1 and 3, gestational age best improved outcome prediction; on Postnatal Days 7, 14, 21, and 28, type of respiratory support did so. A Web-based model providing predicted estimates for bronchopulmonary dysplasia by postnatal day is available at
Conclusions: The probability of bronchopulmonary dysplasia in extremely premature infants can be determined accurately using a limited amount of readily available clinical information.
PMCID: PMC3136997  PMID: 21471086
bronchopulmonary dysplasia; prematurity; low-birth-weight infant
Pediatrics  2011;127(5):817-826.
Guidelines for prevention of group B streptococcal (GBS) infection have successfully reduced early onset (EO) GBS disease. Study results suggest that Escherichia coli is an important EO pathogen.
To determine EO infection rates, pathogens, morbidity, and mortality in a national network of neonatal centers.
Infants with EO infection were identified by prospective surveillance at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Network centers. Infection was defined by positive culture results for blood and cerebrospinal fluid obtained from infants aged ≤72 hours plus treatment with antibiotic therapy for ≥5 days. Mother and infant characteristics, treatments, and outcomes were studied. Numbers of cases and total live births (LBs) were used to calculate incidence.
Among 396 586 LBs (2006–2009), 389 infants developed EO infection (0.98 cases per 1000 LBs). Infection rates increased with decreasing birth weight. GBS (43%, 0.41 per 1000 LBs) and E coli (29%, 0.28 per 1000 LBs) were most frequently isolated. Most infants with GBS were term (73%); 81% with E coli were preterm. Mothers of 67% of infected term and 58% of infected preterm infants were screened for GBS, and results were positive for 25% of those mothers. Only 76% of mothers with GBS colonization received intrapartum chemoprophylaxis. Although 77% of infected infants required intensive care, 20% of term infants were treated in the normal newborn nursery. Sixteen percent of infected infants died, most commonly with E coli infection (33%).
In the era of intrapartum chemoprophylaxis to reduce GBS, rates of EO infection have declined but reflect a continued burden of disease. GBS remains the most frequent pathogen in term infants, and E coli the most significant pathogen in preterm infants. Missed opportunities for GBS prevention continue. Prevention of E coli sepsis, especially among preterm infants, remains a challenge.
PMCID: PMC3081183  PMID: 21518717
neonatal sepsis; group B streptococcal disease; Escherichia coli infection
The purpose of this study was to evaluate the clinical feasibility of a new method to orient three-dimensional (3D) computed tomography (CT) models to the natural head position (NHP). This method utilizes a small and inexpensive digital orientation device to record NHP in 3D. This device consists of a digital orientation sensor attached to the patient via a facebow and an individualized bite jig. The study was designed to answer two questions: 1) whether the weight of the new device can negatively influence the NHP; and 2) wether the new method is as accurate as the gold standard.
Materials and Methods
Fifteen patients with craniomaxillofacial deformities were included in the study. Each patient’s NHP is recorded 3 times. The 1st NHP was recorded using a laser scanning method without the presence of the digital orientation device. The 2nd NHP was recorded using the digital orientation device. Simultaneously, the 3rd NHP wa also recorded using the laser scanning method. Each recorded NHP measurement was then transferred to the patient’s 3D CT facial model, resulting in 3 different orientations for each patient. They include: the orientation generated using the laser scanning method without the presence of the digital orientation sensor and facebow (Orientation 1); the orientation generated using the laser scanning method with the presence of the digital orientation sensor and facebow (Orientation 2); and the orientation generated using the digital orientation device (Orientation 3). The comparisons are then made between Orientations 1 and 2, and Orientations 2 and 3, respectively. Statistical analyses are performed.
The results show that in each pair, the delta between the 2 measurements is not statistically significantly different from 0 degrees. In addition, in the 1st pair, Bland and Altman’s lower and upper limits of the delta between the 2 measurements are within 1.5° in pitch and sub-degree in roll and yaw. In the 2nd pair, the limits of the delta in all three dimensions are within 0.5°.
Our technique can accurately record NHP in three dimensions and precisely transfer it to a 3D model. In addition, the extra weight of the digital orientation sensor and facebow has minimal influence on the self-balanced NHP establishment.
PMCID: PMC3053123  PMID: 21353923
Natural head position; self-balanced; three-dimensional; recording; transferring; computed tomography; computer modeling
A 65-year-old male athlete with coronary artery disease enrolled in our cardiac rehabilitation (CR) program after successful coronary artery bypass graft surgery following an acute myocardial infarction. Unlike the typical sedentary cardiac patient in his age group, he loved to participate in hurdle events at masters division track meets (competitions for athletes aged 30 years and older). He expressed a strong desire to return to his sport, so we designed a sport-specific, symptom-limited exercise program that enabled him to train safely but at a higher intensity than is typically allowed in conventional CR programs. Although his measured peak heart rates during the sport-specific sessions were significantly higher than the calculated maximum heart rate limits usually imposed on patients during conventional CR exercise training, the patient had no adverse events and safely reached his fitness goal. When developing a CR plan, health care professionals should consider the patient's goals, not just his or her age.
PMCID: PMC3246852  PMID: 22275782
Pediatrics  2010;126(4):e865-e873.
Invasive candidiasis is a leading cause of infection-related morbidity and mortality in extremely low-birth-weight (<1000 g) infants. We quantify risk factors predicting infection in high-risk premature infants and compare clinical judgment with a prediction model of invasive candidiasis.
The study involved a prospective observational cohort of infants <1000 g birth weight at 19 centers of the NICHD Neonatal Research Network. At each sepsis evaluation, clinical information was recorded, cultures obtained, and clinicians prospectively recorded their estimate of the probability of invasive candidiasis. Two models were generated with invasive candidiasis as their outcome: 1) potentially modifiable risk factors and 2) a clinical model at time of blood culture to predict candidiasis.
Invasive candidiasis occurred in 137/1515 (9.0%) infants and was documented by positive culture from ≥ 1 of these sources: blood (n=96), cerebrospinal fluid (n=9), urine obtained by catheterization (n=52), or other sterile body fluid (n=10). Mortality was not different from infants who had positive blood culture compared to those with isolated positive urine culture. Incidence varied from 2–28% at the 13 centers enrolling ≥ 50 infants. Potentially modifiable risk factors (model 1) included central catheter, broad-spectrum antibiotics (e.g., third-generation cephalosporins), intravenous lipid emulsion, endotracheal tube, and antenatal antibiotics. The clinical prediction model (model 2) had an area under the receiver operating characteristic curve of 0.79, and was superior to clinician judgment (0.70) in predicting subsequent invasive candidiasis. Performance of clinical judgment did not vary significantly with level of training.
Prior antibiotics, presence of a central catheter, endotracheal tube, and center were strongly associated with invasive candidiasis. Modeling was more accurate in predicting invasive candidiasis than clinical judgment.
PMCID: PMC3045840  PMID: 20876174
Candidiasis; premature infant; risk factors
The New England journal of medicine  2011;364(7):603-615.
Retinopathy of prematurity is a leading cause of childhood blindness worldwide. Peripheral retinal ablation with conventional (confluent) laser therapy is destructive, causes complications, and does not prevent all vision loss, especially in cases of retinopathy of prematurity affecting zone I of the eye. Case series in which patients were treated with vascular endothelial growth factor inhibitors suggest that these agents may be useful in treating retinopathy of prematurity.
We conducted a prospective, controlled, randomized, stratified, multicenter trial to assess intravitreal bevacizumab monotherapy for zone I or zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity. Infants were randomly assigned to receive intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally. The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks’ postmenstrual age.
We enrolled 150 infants (total sample of 300 eyes); 143 infants survived to 54 weeks’ postmenstrual age, and the 7 infants who died were not included in the primary-outcome analyses. Retinopathy of prematurity recurred in 4 infants in the bevacizumab group (6 of 140 eyes [4%]) and 19 infants in the laser-therapy group (32 of 146 eyes [22%], P = 0.002). A significant treatment effect was found for zone I retinopathy of prematurity (P = 0.003) but not for zone II disease (P = 0.27).
Intravitreal bevacizumab monotherapy, as compared with conventional laser therapy, in infants with stage 3+ retinopathy of prematurity showed a significant benefit for zone I but not zone II disease. Development of peripheral retinal vessels continued after treatment with intravitreal bevacizumab, but conventional laser therapy led to permanent destruction of the peripheral retina. This trial was too small to assess safety.
PMCID: PMC3119530  PMID: 21323540
Folate-associated one carbon metabolism (FOCM) may play an important role in colorectal carcinogenesis. Variation in FOCM genes may explain some of the underlying risk of colorectal cancer.
This study utilized data from 1,805 population-based colorectal cancer cases and 2,878 matched sibling controls from the Colon Cancer Family Registry (C-CFR). We used a comprehensive tagSNP approach to select 395 tagSNPs in 15 genes involved in folate and vitamin B12 metabolism. Genotyping was performed using the Illumina GoldenGate or Sequenom platforms. Risk factor and dietary data were collected using self-completed questionnaires. MSI status was determined using standard techniques and tumor subsite was obtained from pathology reports. The association between SNPs and colorectal cancer was assessed using conditional logistic regression with sibships as the matching factor and assuming a log additive or co-dominant model.
In the log additive model, two linked (r2=0.99) tagSNPs in the DHFR gene (rs1677693 and rs1643659) were associated with a significant decrease in CRC risk after correction for multiple testing (OR=0.87; 95% CI=0.71 – 0.94; P=0.029 and OR=0.87 95% CI=0.71 – 0.95, P=0.034 for rs1677693 and rs1643659 respectively. These two linked (r2=0.99) tagSNPs and one tagSNP in the MTR gene (rs4659744) were significantly associated with reduced CRC risk only among individuals not using multivitamin supplements.
Overall, we found only moderate evidence that genetic variation in 15 folate pathway genes may affect CRC risk except in non multivitamin users.
This study suggests that multivitamin supplement use may modify the association between folate pathway genes and CRC risk in a post folic acid supplemented population.
PMCID: PMC2950115  PMID: 20615890
Colorectal Cancer; TagSNP; Folate Supplementation; Multivitamins; Microsatellite Instability; Colon subsite; ADA; ADH1C; AHCY; AMD1; CBS; DHFR; GIF; CUBN; MAT2A; MTHFD1; MTR; MTRR; SHMT1; TCN2; TYMS

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