bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue-specific promoter utilisation of the kallikrein-related peptidase genes,KLK5andKLK7, and cellular localisation of the encoded proteins suggest roles in exocrine pancreatic function
Authors: Dong Ying , Matigian Nick , Harvey Tracey J. , Samaratunga Hemamali , Hooper John D. , Clements Judith A.
Published: December 2007

Tissue kallikrein (kallikrein 1) was first identified in pancreas and is the namesake of the kallikrein-related peptidase (KLK) family. KLK1 and the other 14 members of the human KLK family are encoded by 15 serine protease genes clustered at chromosome 19q13.4. Our Northern blot analysis of 19 normal human tissues for expression ofKLK4toKLK15identified pancreas as a common expression site for the gene cluster spanningKLK5toKLK13, as well as forKLK15which is located adjacent toKLK1. Consistent with previous reports detailing the ability ofKLKgenes to generate organ- and disease-specific transcripts, detailed molecular andin silicoanalyses indicated thatKLK5andKLK7generate transcripts in pancreas variant from those in skin or ovary. Consistently, we identified in the promoters of theseKLKgenes motifs which conform with consensus binding sites for transcription factors conferring pancreatic expression. In addition, immunohistochemical analysis revealed predominant localisation of KLK5 and KLK7 in acinar cells of the exocrine pancreas, suggesting roles for these enzymes in digestion. Our data also support expression patterns derived from gene duplication events in the humanKLKcluster. These findings suggest that, in addition to KLK1, other related KLK enzymes will function in the exocrine pancreas.
Evaluation of the ‘side door’ in carboxylesterase-mediated catalysis and inhibition
Authors: Streit Timothy M. , Borazjani Abdolsamad , Lentz Shellaine E. , Wierdl Monika , Potter Philip M. , Gwaltney Steven R. , Ross Matthew K.
Published: December 2007

Structures of mammalian carboxylesterases (CEs) reveal the presence of a ‘side door’ that is proposed to act as an alternative pore for the trafficking of substrates and products. p-Nitrobenzyl esterase (pnb CE) from Bacillus subtilis exhibits close structural homology and a similar side-door domain as mammalian CEs. We investigated the role of a specific ‘gate’ residue at the side door (i.e., Leu 362) during pnb CE-catalyzed hydrolysis of model esters, pesticides, and lipids. Recombinant pnb CE proteins containing mutations at position 362 demonstrated markedly lower k
cat and k
cat/K
m values. The mutation with the most significant impact on catalysis was the L362R mutant (k
cat/K
m was 22-fold lower). Moreover, the ability of the L362R mutant to be inhibited by organophosphates (OP) was also lower. Investigation into the altered catalytic proficiency using pH-activity studies indicated that the catalytic triad of the mutant enzyme was preserved. Furthermore, viscosity variation and carbamate inhibition experiments indicated that rates of substrate association and acylation/deacylation were lower. Finally, recombinant CEs were found to possess lipolytic activity toward cholesteryl oleate and 2-arachidonylglycerol. In summary, the L362R mutant CE markedly slowed the rate of ester hydrolysis and was less sensitive to OP inhibition. The apparent causes of the diminished catalysis are discussed.
Insulin-releasing properties of the frog skin peptide pseudin-2 and its [Lys18]-substituted analogue
Authors: Abdel-Wahab Yasser H.A. , Power Gavin J. , Ng Ming T. , Flatt Peter R. , Conlon J. Michael
Published: December 2007

Pseudin-2 is a cationic α-helical peptide that was first isolated from the skin of the paradoxical frog Pseudis paradoxa on the basis of its antimicrobial activity. We have investigated the insulin-releasing properties and cytotoxicity of the peptide, together with selected analogues with increased cationicity and hydrophobicity. At concentrations in the range 10-9–10-6 m, pseudin-2, and its [Lys18], [Phe8], and [d-Lys3,d-Lys10,d-Lys14] derivatives, stimulated insulin release from the BRIN-BD11 clonal β-cell line without increasing release of lactate dehydrogenase. The [Lys18] analogue was the most potent (46% increase in insulin release at 10-9 m) and the most effective (215% increase in insulin release at 10-6 m). The more cationic [Lys3,Lys10,Lys14] and [Lys3,Lys10,Lys14,Lys21] analogues lacked insulinotropic action and the more hydrophobic [Phe16] analogue was cytotoxic at concentrations ≥10-7 m. Pseudin-2 and [Lys18]-pseudin-2 had no effect on intracellular calcium concentrations and stimulated insulin release in the absence of external calcium. [Lys18]-pseudin-2 (10-8 m) stimulated insulin release in the presence of diazoxide and verapamil. Our results demonstrate that pseudin-2 stimulates insulin secretion from BRIN-BD11 cells by a mechanism involving Ca2+-independent pathways and identify [Lys18]-pseudin-2 as a peptide that may have potential for development as a therapeutically valuable insulinotropic agent for the treatment of type 2 diabetes.
Effects of gastric inhibitory polypeptide (GIP) and related analogues on glucagon release at normo- and hyperglycaemia in Wistar rats and isolated islets
Authors: Cassidy Roslyn S. , Irwin Nigel , Flatt Peter R.
Published: December 2007

Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone secreted by endocrine K-cells in response to nutrient absorption. This study has utilised numerous well-characterised dipeptidyl peptidase IV-resistant GIP analogues to evaluate the glucagonotropic actions of GIP in Wistar rats and isolated rat islets. Intraperitoneal administration of GIP analogues (25 nmol/kg body weight) in combination with glucose had no effect on circulating glucagon concentrations compared to controls in Wistar rats. However, plasma glucose concentrations were significantly (p<0.05 to p<0.001) lowered by the GIP-receptor agonists, N-AcGIP, GIP(Lys37)PAL and N-AcGIP(Lys37)PAL. The GIP antagonist, (Pro3)GIP, caused a significant (p<0.05) reduction in glucagon levels following concurrent administration with saline in Wistar rats. In isolated rat islets native GIP induced a significant (p<0.01) enhancement of glucagon release at basal glucose concentrations, which was completely annulled by (Pro3)GIP. Furthermore, glucagon release in the presence of GLP-1, GIP(Lys37)PAL, N-AcGIP(Lys37)PAL and (Pro3)GIP was significantly (p<0.05 to p<0.001) decreased compared to native GIP in isolated rat islets. These data indicate a modest effect of GIP on glucagon secretion from isolated rat islets, which was not observed in vivo. However, the GIP agonists N-AcGIP, GIP(Lys37)PAL and N-AcGIP(Lys37)PAL had no effect on glucagon release demonstrating an improved therapeutic potential for the treatment of type 2 diabetes.
Cathepsin V, but not cathepsins L, B and K, may release angiostatin-like fragments from plasminogen
Authors: Puzer Luciano , Barros Nilana M.T. , Paschoalin Thaysa , Hirata Izaura Y. , Tanaka Aparecida S. , Oliveira Marcelo C. , Brömme Dieter , Carmona Adriana K.
Published: December 2007

Cathepsin V is a lysosomal cysteine peptidase highly expressed in corneal epithelium; however, its function in the eye is still unknown. Here, we describe the capability of cathepsin V to hydrolyze plasminogen, which is also expressed in human cornea at levels high enough to produce physiologically relevant amounts of angiostatin-related molecules. The co-localization of these two proteins suggests an important role for the enzyme in the maintenance of corneal avascularity, essential for optimal visual performance. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of plasminogen digestion by cathepsin V revealed the generation of three major products of 60, 50 and 40 kDa, which were electrotransferred to polyvinylidene difluoride membranes and excised for characterization. NH2-terminal amino acid sequencing of these fragments revealed the sequences EKKVYL, TEQLAP and LLPNVE, respectively. These data are compatible with cleavage sites at plasminogen F94–E95, S358–T359 and V468–L469 peptide bonds generating fragments of the five-kringle domains. In contrast, we did not detect any plasminogen degradation by cathepsins B, K and L. Using a Matrigel assay, we confirmed the angiogenesis inhibition activity on endothelial cells caused by plasminogen processing by cathepsin V. Our results suggest a novel physiological role for cathepsin V related to the control of neovascularization in cornea.
Functional tyrosine residue in the active center of human dipeptidyl peptidase III
Authors: Salopek-Sondi Branka , Vukelić Bojana , Špoljarić Jasminka , Šimaga Šumski , Vujaklija Dušica , Makarević Janja , Jajčanin Nina , Abramić Marija
Published: December 2007

Human dipeptidyl peptidase III (DPP III) is a member of the metallopeptidase family M49 with an implied role in the pain-modulatory system and endogenous defense against oxidative stress. Here, we report the heterologous expression of human DPP III and the site-directed mutagenesis results which demonstrate a functional role for Tyr318 at the active site of this enzyme. The substitution of Tyr318 to Phe decreased k
cat by two orders of magnitude without altering the binding affinity of substrate, or of a competitive hydroxamate inhibitor designed to interact with S1 and S2 subsites. The results indicate that the conserved tyrosine could be involved in transition state stabilization during the catalytic action of M49 peptidases.
Neonatology and the Law
Authors: Fanaroff Jonathan M. , Martin Gilbert I.
Published: December 2007

Neonatologists are at particular risk for malpractice. Among the medical legal issues specific to clinical neonatology are newborn resuscitation, brain injury in the newborn, hyperbilirubinemia, and group B streptococcal infection. Neonatologists can minimize the risk of malpractice by maintaining competency, honing communication skills, and maintaining detailed and timely documentation.
Adverse Medical Events in the NICU
Authors: Morriss Frank H.
Published: December 2007

Adverse medical events and adverse drug events are not uncommon in NICUs, and research has been directed at determining the causes of such events as well as potential methods of reducing their occurrence. Both human fallibility and the complex adaptive system that comprises the NICU present opportunities for errors. Human factors engineering and systems can improve reliability, as can computer systems for ordering, dispensing, administering, and monitoring drugs. Barcode scanning medication dispensing and administration systems and smart pumps also have been investigated. Human factors that have contributed to errors include fatigue, communication failure, poor handoffs, problems with cross-coverage, workload, and staffing patterns. Addressing these factors can aid in reducing medical errors.
Controlling Feeding Practices: Cause or Consequence of Early Child Weight?
Authors: Farrow Claire Victoria , Blissett Jacqueline
Published: December 2007

INTRODUCTION. The exertion of control during child feeding has been associated with both underweight and overweight during childhood. What is as-yet unclear is whether controlling child feeding practices causally affect child weight or whether the use of control may be a reactive response to concerns about high or low child weight. The aims of this study were to explore the direction of causality in these relationships during infancy.

METHODS. Sixty-two women gave informed consent to take part in this longitudinal study that spanned from birth to 2 years of child age. Mothers completed the Child Feeding Questionnaire at 1 year, and their children were weighed at 1 and 2 years of age. Child weight scores were converted into standardized z scores that accounted for child age and gender.

RESULTS. Controlling for child weight at 1 year, the use of pressure to eat and restriction at 1 year significantly predicted lower child weight at 2 years.

CONCLUSIONS. Controlling feeding practices in infancy have an impact on children's weight at 2 years. The use of restrictive child feeding practices during infancy predicts lower child weight at age 2 years, which may reinforce mothers' use of this strategy in the longer term despite its potential association with disinhibition and greater child weight in later childhood.
A Comparison of Alternative Risk-Assessment Strategies for Predicting Significant Neonatal Hyperbilirubinemia in Term and Near-Term Infants
Authors: Keren Ron , Luan Xianqun , Friedman Susan , Saddlemire Stephanie , Cnaan Avital , Bhutani Vinod K.
Published: December 2007

OBJECTIVE. The purpose of this work was to compare the predictive accuracy of alternative risk-assessment strategies used to screen for the risk of significant neonatal hyperbilirubinemia.

PATIENTS AND METHODS. We conducted a prospective cohort study of 823 term and near-term newborns admitted to the well-infant nursery at the Hospital of the University of Pennsylvania. Maternal, infant, and delivery risk factors for significant hyperbilirubinemia were obtained from chart review, structured interviews with parents, and nurse assessments before discharge. Transcutaneous bilirubin measurement was performed daily until discharge and once by a visiting home nurse between 3 and 8 days of life. We used the c statistic to compare the predictive accuracy of 3 risk-assessment strategies for estimating the risk of significant neonatal hyperbilirubinemia, defined as a bilirubin level that at any time after birth exceeded or was within 1 mg/dL (17 μmol/L) of the hour-specific phototherapy treatment threshold recommended by the American Academy of Pediatrics in 2004. The compared strategies included those that use (1) a predischarge bilirubin level (obtained before 52 hours) expressed as a risk zone on an hour-specific bilirubin nomogram, (2) clinical risk factors other than the predischarge bilirubin level, and (3) a combination of the predischarge bilirubin risk zone and additional clinical risk factors.

RESULTS. Forty-eight patients (6%) developed significant neonatal hyperbilirubinemia. The predischarge (<52 hours) bilirubin level expressed as a risk zone on the bilirubin nomogram and a prediction model that combined multiple other clinical risk factors had similar accuracy for predicting significant hyperbilirubinemia. The only clinical risk factor that could be added to the predischarge risk zone to improve overall predictive accuracy was gestational age. The predischarge bilirubin risk zone and gestational age could be used to stratify patients into a large group (n = 523 [70%]) of infants with a very low (0.2%) risk of developing significant hyperbilirubinemia, a small group of infants (n = 127 [17%]) with a low (4%) risk of developing significant hyperbilirubinemia, and an even smaller group of infants (n = 100 [13%]) with a high (42%) risk of developing significant hyperbilirubinemia.

CONCLUSIONS. An infant's risk of developing significant hyperbilirubinemia can be simply and accurately assessed by using just the infant's predischarge bilirubin level and gestational age.
Timing of Solid Food Introduction in Relation to Eczema, Asthma, Allergic Rhinitis, and Food and Inhalant Sensitization at the Age of 6 Years: Results From the Prospective Birth Cohort Study LISA
Authors: Zutavern Anne , Brockow Inken , Schaaf Beate , von Berg Andrea , Diez Ulrike , Borte Michael , Kraemer Ursula , Herbarth Olf , Behrendt Heidrun , Wichmann H-Erich , Heinrich Joachim ,   LISA Study Group
Published: December 2007

OBJECTIVE. Current prophylactic feeding guidelines recommend a delayed introduction of solids for the prevention of atopic diseases. This study investigates whether a delayed introduction of solids (past 4 or 6 months) is protective against the development of eczema, asthma, allergic rhinitis, and food or inhalant sensitization at the age of 6 years.

METHODS. Data from 2073 children in the ongoing LISA birth cohort study were analyzed at 6 years of age. Multivariate logistic regression analyses were performed for all children and for children without skin or allergic symptoms within the first 6 months of life to take into account reverse causality.

RESULTS. A delayed introduction of solids (past 4 or 6 months) was not associated with decreased odds for asthma, allergic rhinitis, or sensitization against food or inhalant allergens at 6 years of age. On the contrary, food sensitization was more frequent in children who were introduced to solids later. The relationship between the timing of solid food introduction and eczema was not clear. There was no protective effect of a late introduction of solids or a less diverse diet within the first 4 months of life. However, in children without early skin or allergic symptoms were considered, eczema was significantly more frequent in children who received a more diverse diet within the first 4 months.

CONCLUSIONS. This study found no evidence supporting a delayed introduction of solids beyond 4 or 6 months for the prevention of asthma, allergic rhinitis, and food or inhalant sensitization at the age of 6 years. For eczema, the results were conflicting, and a protective effect of a delayed introduction of solids cannot be excluded. Positive associations between late introduction of solids and food sensitization have to be interpreted with caution. A true protective effect of a delayed introduction of solids on food sensitization seems unlikely.
Estimating the Effectiveness of Screening for Scoliosis: A Case-Control Study
Authors: Bunge Eveline M. , Juttmann Rikard E. , van Biezen Frans C. , Creemers Huub , Hazebroek-Kampschreur Alice A. J. M. , Luttmer Bert C. F. , Wiegersma P. Auke , de Koning Harry J. ,   for the Netherlands Evaluation Study on Screening for Scoliosis (NESCIO) Group
Published: December 2007

OBJECTIVE. The aim of this study was to test the hypothesis that screening for scoliosis is effective in reducing the need for surgical treatment.

METHODS. The study was a case-control study. A total of 125 consecutive patients who were treated surgically for idiopathic scoliosis between January 2001 and October 2004 and who were born on or after January 1, 1984, were invited; 108 agreed to participate. A total of 216 control subjects were selected randomly and anonymously, matched with respect to age and gender. For 279 adolescents, exact screening exposure and outcomes could be analyzed. Case subjects were recruited from 4 university and 6 nonuniversity Dutch hospitals; control subjects were recruited from all 37 municipal health services in the Netherlands.

RESULTS. Screen-detected patients received diagnoses at a significantly younger age than did otherwise-detected patients (10.8 ± 2.6 vs 13.4 ± 1.7 years). In total, 32.8% of the surgically treated patients had been screened between 11 and 14 years of age, compared with 43.4% of the control subjects. The odds ratio for being exposed to screening was 0.64. In total, 28% of the patients were diagnosed as having scoliosis before 11 years of age.

CONCLUSIONS. Our results showed no evidence that screening for scoliosis reduced the need for surgery. Abolishing screening seems justified, especially because the effectiveness of early treatment with bracing is still strongly debated. A randomized, controlled trial on the effectiveness of treating patients with idiopathic scoliosis with bracing is urgently needed.
A Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine Extended Release in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder
Authors: Biederman Joseph , Melmed Raun D. , Patel Anil , McBurnett Keith , Konow Jennifer , Lyne Andrew , Scherer Noreen ,   for the SPD503 Study Group
Published: December 2007

OBJECTIVE. With this study we assessed the efficacy and safety of an extended-release formulation of guanfacine compared with placebo for the treatment of children and adolescents with attention-deficit/hyperactivity disorder.

METHODS. In this multicenter, double-blind, placebo-controlled, fixed-dosage escalation study, patients aged 6 to 17 years were randomly assigned to 1 of 3 treatment groups of guanfacine extended release (2, 3, or 4 mg/day) or placebo for 8 weeks. The primary outcome measurement was the Attention-Deficit/Hyperactivity Disorder Rating Scale IV total score. Secondary measurements included Clinical Global Impression of Improvement, Parent's Global Assessment, Conners' Parent Rating Scale–Revised: Short Form, and Conners' Teacher Rating Scale–Revised: Short Form.

RESULTS. A total of 345 patients were randomly assigned to placebo (n = 86) or guanfacine extended release 2 mg (n = 87), 3 mg (n = 86), or 4 mg (n = 86) treatment groups. Least-squares mean changes from baseline to the end point in Attention-Deficit/Hyperactivity Disorder Rating Scale IV total scores were significant in all groups of children taking guanfacine extended release: −16.18 in the 2-mg group, −16.43 in the 3-mg group, and −18.87 in the 4-mg group, compared with −8.48 in the placebo group. All groups of children taking guanfacine extended release showed significant improvement on hyperactivity/impulsivity and inattentiveness subscales of the Attention-Deficit/Hyperactivity Disorder Rating Scale IV, Clinical Global Impression of Improvement, Parent's Global Assessment, Conners' Parent Rating Scale–Revised: Short Form, and Conners' Teacher Rating Scale–Revised: Short Form assessments compared with placebo. The most commonly reported treatment-emergent adverse events were headache, somnolence, fatigue, upper abdominal pain, and sedation. Small to modest changes in blood pressure, pulse rate, and electrocardiogram parameters were observed but were not clinically meaningful.

CONCLUSIONS. Guanfacine extended release met the primary and secondary efficacy end points. It was well tolerated and effective compared with placebo.
Household Food Insecurity: Associations With At-Risk Infant and Toddler Development
Authors: Rose-Jacobs Ruth , Black Maureen M. , Casey Patrick H. , Cook John T. , Cutts Diana B. , Chilton Mariana , Heeren Timothy , Levenson Suzette M. , Meyers Alan F. , Frank Deborah A.
Published: December 2007

OBJECTIVES. In this study, we evaluated the relationship between household food security status and developmental risk in young children, after controlling for potential confounding variables.

METHODS. The Children's Sentinel Nutritional Assessment Program interviewed (in English, Spanish, or Somali) 2010 caregivers from low-income households with children 4 to 36 months of age, at 5 pediatric clinic/emergency department sites (in Arkansas, Massachusetts, Maryland, Minnesota, and Pennsylvania). Interviews included demographic questions, the US Food Security Scale, and the Parents' Evaluations of Developmental Status. The target child from each household was weighed, and weight-for-age z score was calculated.

RESULTS. Overall, 21% of the children lived in food-insecure households and 14% were developmentally “at risk” in the Parents' Evaluations of Developmental Status assessment. In logistic analyses controlling for interview site, child variables (gender, age, low birth weight, weight-for-age z score, and history of previous hospitalizations), and caregiver variables (age, US birth, education, employment, and depressive symptoms), caregivers in food-insecure households were two thirds more likely than caregivers in food-secure households to report that their children were at developmental risk.

CONCLUSIONS. Controlling for established correlates of child development, 4- to 36-month-old children from low-income households with food insecurity are more likely than those from low-income households with food security to be at developmental risk. Public policies that ameliorate household food insecurity also may improve early child development and later school readiness.
Relationships of Cardiovascular Phenotypes With Healthy Weight, at Risk of Overweight, and Overweight in US Youths
Authors: Zhu Haidong , Yan Weili , Ge Dongliang , Treiber Frank A. , Harshfield Gregory A. , Kapuku Gaston , Snieder Harold , Dong Yanbin
Published: December 2007

OBJECTIVE. This study aimed to evaluate comprehensively the cardiovascular phenotypes of cardiovascular disease-free youths at risk of overweight, in comparison with healthy weight and overweight.

METHODS. Casual and ambulatory blood pressure measurements, noninvasive hemodynamic profiles, pulse wave velocity, left ventricular structure and function, and overnight sodium excretion were examined in a cohort of US black and white youths (n = 972; mean age: 17.6 ± 3.3 years).

RESULTS. The occurrence of at risk of overweight was ∼17% in either black youths or white youths. In white youths, there was a ∼2-mmHg increase in casual systolic blood pressure for each increasing step in the 3 BMI categories (healthy weight, 109.5 ± 0.5 mmHg; at risk of overweight, 111.5 ± 0.6 mmHg; overweight, 113.5 ± 1.1 mmHg). Ambulatory systolic blood pressure showed a similar increase with the increase in BMI. A blunted nocturnal decline in ambulatory diastolic blood pressure with the categorical BMI increase was observed in black youths. In both racial groups, cardiac output and stroke volume were significantly enhanced sequentially from healthy weight to at risk of overweight to overweight. In black youths, both casual and ambulatory heart rate increased significantly with the increase in BMI. Moreover, there was a linear increase of left ventricular mass index from the healthy-weight group to the at risk of overweight group, with the overweight group having the highest value. In white youths, carotid-dorsalis pedis pulse wave velocity increased significantly as the BMI increased. Regardless of race, overnight sodium excretion showed a significant increase from healthy-weight subjects to overweight subjects, with at risk of overweight subjects having intermediate values.

CONCLUSIONS. Youths at risk of overweight, compared with healthy-weight youths, seem to have increased cardiovascular risks. Our data suggest that the status of at risk of overweight already has clinical implications in youths.
Simulation of In-Hospital Pediatric Medical Emergencies and Cardiopulmonary Arrests: Highlighting the Importance of the First 5 Minutes
Authors: Hunt Elizabeth A. , Walker Allen R. , Shaffner Donald H. , Miller Marlene R. , Pronovost Peter J.
Published: December 2007

OBJECTIVES. Outcomes of in-hospital pediatric cardiopulmonary arrest are dismal. Recent data suggest that the quality of basic and advanced life support delivered to adults is low and contributes to poor outcomes, but few data regarding pediatric events have been reported. The objectives of this study were to (1) measure the median elapsed time to initiate important resuscitation maneuvers in simulated pediatric medical emergencies (ie, “mock codes”) and (2) identify the types and frequency of errors committed during pediatric mock codes.

METHODS. A prospective, observational study was conducted of 34 consecutive hospital-based mock codes. A mannequin or computerized simulator was used to enact unannounced, simulated crisis situations involving children with respiratory distress or insufficiency, respiratory arrest, hemodynamic instability, and/or cardiopulmonary arrest. Assessment included time elapsed to initiation of specific resuscitation maneuvers and deviation from American Heart Association guidelines.

RESULTS. Among the 34 mock codes, the median time to assessment of airway and breathing was 1.3 minutes, to administration of oxygen was 2.0 minutes, to assessment of circulation was 4.0 minutes, to arrival of any physician was 3.0 minutes, and to arrival of first member of code team was 6.0 minutes. Among cardiopulmonary arrest scenarios, elapsed time to initiation of compressions was 1.5 minutes and to request for defibrillator was 4.3 minutes. In 75% of mock codes, the team deviated from American Heart Association pediatric basic life support protocols, and in 100% of mock codes there was a communication error.

CONCLUSIONS. Alarming delays and deviations occur in the major components of pediatric resuscitation. Future educational and organizational interventions should focus on improving the quality of care delivered during the first 5 minutes of resuscitation. Simulation of pediatric crises can identify targets for educational intervention to improve pediatric cardiopulmonary resuscitation and, ideally, outcomes.
Longitudinal Study of Viewing Smoking in Movies and Initiation of Smoking by Children
Authors: Titus-Ernstoff Linda , Dalton Madeline A. , Adachi-Mejia Anna M. , Longacre Meghan R. , Beach Michael L.
Published: December 2007

BACKGROUND. Previous studies showed an association between viewing of smoking in movies and initiation of smoking among adolescents. However, all studies except one were cross-sectional, and none updated movie smoking exposure prospectively or assessed its influence on children.

METHODS. We enrolled elementary school students, 9 to 12 years of age, in a longitudinal study to assess the influence of movie smoking exposure on smoking initiation among children. Movie smoking content was coded for the most popular movie releases; exposure was assessed by asking children which movies they had seen, on the basis of unique lists of 50 movies sampled randomly from top box office hits and video rentals. Data collection occurred in 3 waves (the baseline survey and 2 follow-up surveys), ∼1 year apart. Movie lists were updated for each data collection wave, to reflect recent releases. Movie smoking exposure was analyzed in relation to smoking initiation by the end of the study period.

RESULTS. Approximately 80% of the children's smoking exposure occurred through movies rated G, PG, or PG-13. Children's movie smoking exposure predicted smoking initiation significantly, after adjustment for multiple covariates including child and parent characteristics. The relative risks were 1.09, 1.09, and 1.07 for a 1-decile increase of movie smoking exposure measured at the baseline, second, and third data collection waves, respectively. The adjusted attributable risk of smoking initiation attributable to movie smoking exposure was 0.35.

CONCLUSION. Our study, which is the first to enroll children in elementary school and to update movie smoking exposure longitudinally, indicates that early exposure has as much influence on smoking risk as does exposure nearer the outcome. Overall, movie smoking may be responsible for at least one third of smoking initiation for children in this age group.
Decreased Incidence of Bronchopulmonary Dysplasia After Early Management Changes, Including Surfactant and Nasal Continuous Positive Airway Pressure Treatment at Delivery, Lowered Oxygen Saturation Goals, and Early Amino Acid Administration: A Historical Cohort Study
Authors: Geary Cara , Caskey Melinda , Fonseca Rafael , Malloy Michael
Published: December 2007

OBJECTIVE. The goal was to investigate the clinical impact of 3 early management practice changes for infants of ≤1000 g.

METHODS. We performed an historical cohort study of appropriately sized, preterm infants without congenital anomalies who were born between January 2001 and June 2002 (pre–early management practice change group; n = 87) and between July 2004 and December 2005 (post–early management practice change group; n = 76).

RESULTS. Only 1 (1%) of 87 infants in the pre–early management practice change group received continuous positive airway pressure treatment in the first 24 hours of life, compared with 61 (80%) of 76 infants in the post–early management practice change group. The proportions of infants who required any synchronized intermittent mandatory ventilation during their hospital stays were 98.8% and 59.5%, respectively. The mean durations of synchronized intermittent mandatory ventilation were 35 days and 15 days, respectively. The combined incidence rates of moderate and severe bronchopulmonary dysplasia at corrected gestational age of 36 weeks were 43% and 24%, respectively. The use of vasopressor support for hypotension in the first 24 hours of life decreased from 39.1% (before early management practice changes) to 19.7% (after practice changes), the cumulative days of oxygen therapy decreased from 77 ± 52 days to 56 ± 47 days, and the proportions of infants discharged with home oxygen therapy decreased from 25.7% to 10.1%; the incidence of patent ductus arteriosus requiring surgical ligation increased from 1% to 10%.There were no differences in rates of death, intraventricular hemorrhage, periventricular leukomalacia, pneumothorax, necrotizing enterocolitis, or retinopathy of prematurity.

CONCLUSIONS. Successful early management of extremely preterm infants with surfactant treatment followed by continuous positive airway pressure treatment at delivery, lowered oxygen saturation goals, and early amino acid supplementation is possible and is associated with reductions in the incidence and severity of bronchopulmonary dysplasia.
Adolescent Varicocele: Who Is at Risk?
Authors: Kumanov Philip , Robeva Ralitsa N. , Tomova Analia
Published: December 2007

OBJECTIVES. Varicocele results from the abnormal dilation of the veins of the pampiniform plexus and is the most common identifiable cause of male infertility. It can develop during puberty and thus affect the testicular growth and function. The aim of this study was to determine the prevalence and the risk factors for the development of the varicocele among Bulgarian boys.

METHODS. In a prospective study, 6200 boys from 5 regions of the country aged 0 to 19 years were evaluated for varicocele. All were clinically healthy. Height, weight, testicular volumes, penile length, and penile circumference were also examined.

RESULTS. Varicocele was found in 4.1% of all investigated boys, whereas in the age group 10 to 19 years, it was 7.9%. After adjustment for age, the negative factors associated with the development of the disorder were height, penile length, and penile circumference, whereas the weight and BMI had a protective role. The prevalence of varicocele demonstrated clear regional differences, and it was found significantly more often among dark-eyed boys. The incidence of the disease increased rapidly during midpuberty.

CONCLUSIONS. The incidence of varicocele is related to some somatometric parameters and with the accelerated pubertal development. Longitudinal studies are needed to clarify better the relations between the adolescent varicocele and puberty.
Managing Attention-Deficit/Hyperactivity Disorder in Primary Care: A Systematic Analysis of Roles and Challenges
Authors: Power Thomas J. , Mautone Jennifer A. , Manz Patricia H. , Frye Leslee , Blum Nathan J.
Published: December 2007

OBJECTIVE. This study was designed to investigate the perceptions of primary care providers about their roles and the challenges of managing attention-deficit/hyperactivity disorder and to evaluate differences between providers who serve families primarily from urban versus suburban settings.

METHODS. The ADHD Questionnaire was developed to assess primary care provider views about the extent to which clinical activities that are involved in the management of attention-deficit/hyperactivity disorder are appropriate and feasible in primary care. Participants were asked to rate each of 24 items of the questionnaire twice: first to indicate the appropriateness of the activity given sufficient time and resources and second to indicate feasibility in their actual practice. Informants used a 4-point scale to rate each item for appropriateness and feasibility.

RESULTS. An exploratory factor analysis of primary care provider ratings of the appropriateness of clinical activities for managing attention-deficit/hyperactivity disorder identified 4 factors of clinical practice: factor 1, assessing attention-deficit/hyperactivity disorder; factor 2, providing mental health care; factor 3, recommending and monitoring approved medications; and factor 4, recommending nonapproved medications. On a 4-point scale (1 = not appropriate to 4 = very appropriate), mean ratings for items on factor 1, factor 2, and factor 3 were high, indicating that the corresponding domains of practice were viewed as highly appropriate. Feasibility challenges were identified on all factors, but particularly factors 1 and 2. A significant interaction effect, indicating differences between appropriateness and feasibility as a function of setting (urban versus suburban), was identified on factor 1. The challenges of assessing attention-deficit/hyperactivity disorder were greater for urban than for suburban primary care providers.

CONCLUSIONS. Primary care providers believe that it is highly appropriate for them to have a role in the management of attention-deficit/hyperactivity disorder. Feasibility issues were particularly salient related to assessing attention-deficit/hyperactivity disorder and providing mental health care. The findings highlight the need not only for additional training of primary care providers but also for practice-based resources to assist with school communication and collaboration with mental health agencies, especially in urban practices.
Perinatal Care at the Threshold of Viability: An International Comparison of Practical Guidelines for the Treatment of Extremely Preterm Births
Authors: Pignotti Maria Serenella , Donzelli Gianpaolo
Published: December 2007

Over the last 2 decades, the survival rate of infants born at ≤25 weeks of gestation has increased; however, significant morbidity and disability persist. The commitment for their care gives rise to a variety of complex medical, social, and ethical aspects. Decision-making is a crucial issue that involves the infant, the family, health care providers, and society. In a review of the existing guidelines, we investigated the different approaches in the care of extremely preterm births in various countries. We found that many scientific societies and professional organizations have issued guidelines that address the recommendations for the care of these fetuses/neonates although to varying degrees. In this article we compare different approaches and assess the scientific grounds of the specific recommendations. With current standards, intensive care is generally considered justifiable at ≥25 weeks, compassionate care at ≤22 weeks, and an individual approach at 23 to 24 weeks, consistent with the parents' wishes and the infant's clinical conditions at birth.
CoolSim: Using Industrial Modeling Techniques to Examine the Impact of Selective Head Cooling in a Model of Perinatal Regionalization
Authors: Gray James , Geva Alon , Zheng Zheng , Zupancic John A. F.
Published: December 2007

OBJECTIVE. A selective head-cooling device for the treatment of moderate to severe hypoxic-ischemic encephalopathy has been approved by the Food and Drug Administration for use in the United States. To reflect the complexity of health care delivery at the systems level, we used the industrial modeling technique of discrete event simulation to analyze the impact of various deployment strategies for selective head cooling and its partner technology, amplitude-integrated electroencephalography.

METHODS. We modeled the course through the perinatal system of all births in Massachusetts over a 1-year period. Cohort and care characteristics were drawn from existing databases. Results of a recently published trial were used to estimate the effects of selective head cooling. One thousand cohort replications were conducted to assess uncertainty. Several policy alternatives were examined, including no use of selective head cooling and scenarios that altered the number and placement of selective head-cooling and amplitude-integrated electroencephalography units throughout the state. Patient-level outcome and cost data were assessed.

RESULTS. For all scenarios tested, the use of amplitude-integrated electroencephalography/selective head cooling resulted in better outcomes at lower cost. However, substantial differences in transfer rates, failure-to-cool rates, and total costs were seen across scenarios. Optimal decision-making regarding the number and placement of devices led to a 16% improvement in cost savings and a 10-fold decrease in failure-to-cool rates, compared with other deployment scenarios. These results were insensitive to significant changes in model inputs.

CONCLUSIONS. On the basis of currently available data, the package of amplitude-integrated electroencephalography and selective head cooling seems to be an economically desirable intervention. Quantifiable techniques to assess system-wide technology performance provide a powerful approach to informing decisions regarding the structure and function of health care systems.
Treatment for Retinopathy of Prematurity in Denmark in a Ten-Year Period (1996–2005): Is the Incidence Increasing?
Authors: Slidsborg Carina , Olesen Henrik Bom , Jensen Peter Koch , Jensen Hanne , Nissen Kamilla Rothe , Greisen Gorm , Rasmussen Steen , Fledelius Hans Callø , la Cour Morten
Published: December 2007

OBJECTIVE. The objective of this study was to analyze the population incidence of retinopathy of prematurity treatment in Denmark in the 10-year period from 1996 to 2005.

METHODS. Patient charts of infants treated for retinopathy of prematurity and the national birth registry provide information about neonatal parameters. These parameters, along with birth in the latter half of the period (2001–2005), were analyzed as risk factors for retinopathy of prematurity. The national registry for blind and visually impaired children was accessed to obtain information about visual impairment attributable to retinopathy of prematurity in both treated and untreated infants.

RESULTS. The study population consisted of 5467 Danish preterm infants born in 1996 to 2005, with a gestational age of <32 weeks, who survived for ≥5 postnatal weeks; 2616 were born in 1996 to 2000, and 2851 were born in 2001 to 2005. The incidence of treated retinopathy of prematurity cases increased significantly from 1.3% in 1996 to 2000 to 3.5% in 2001 to 2005. Significant risk factors for retinopathy of prematurity treatment were low gestational age, small for gestational age, male gender, and multiple birth. Other, yet unknown factors contributed to the increased incidence in the latter half of the period. Of the study population, 0.6% were registered as visually impaired because of retinopathy of prematurity within 2 years after birth (early-detected visual impairment). The incidences were not significantly different between 1996 to 2000 and 2001 to 2005. Of all of the early-detected, visually impaired children, 16% had not been treated for retinopathy of prematurity and were considered screening failures.

CONCLUSIONS. The incidence of retinopathy of prematurity treatment in Denmark has more than doubled during the past half-decade. This increase could not be fully explained by increased survival rates for the infants or by changes in the investigated neonatal risk factors.
Impact of a 16-Community Trial to Promote Judicious Antibiotic Use in Massachusetts
Authors: Finkelstein Jonathan A. , Huang Susan S. , Kleinman Ken , Rifas-Shiman Sheryl L. , Stille Christopher J. , Daniel James , Schiff Nancy , Steingard Ron , Soumerai Stephen B. , Ross-Degnan Dennis , Goldmann Donald , Platt Richard
Published: December 2007

OBJECTIVES. Reducing unnecessary antibiotic use, particularly among children, continues to be a public health priority. Previous intervention studies have been limited by size or design and have shown mixed results. The objective of this study was to determine the impact of a multifaceted, community-wide intervention on overall antibiotic use for young children and on use of broad-spectrum agents. In addition, we sought to compare the intervention's impact on commercially and Medicaid-insured children.

METHODS. We conducted a controlled, community-level, cluster-randomized trial in 16 nonoverlapping Massachusetts communities, studied from 1998 to 2003. During 3 years, we implemented a physician behavior-change strategy that included guideline dissemination, small-group education, frequent updates and educational materials, and prescribing feedback. Parents received educational materials by mail and in primary care practices, pharmacies, and child care settings. Using health-plan data, we measured changes in antibiotics dispensed per person-year of observation among children who were aged 3 to <72 months, resided in study communities, and were insured by a participating commercial health plan or Medicaid.

RESULTS. The data include 223135 person-years of observation. Antibiotic-use rates at baseline were 2.8, 1.7, and 1.4 antibiotics per person-year among those aged 3 to <24, 24 to <48, and 48 to <72 months, respectively. We observed a substantial downward trend in antibiotic prescribing, even in the absence of intervention. The intervention had no additional effect among children aged 3 to <24 months but was responsible for a 4.2% decrease among those aged 24 to <48 months and a 6.7% decrease among those aged 48 to <72 months. The intervention effect was greater among Medicaid-insured children and for broad-spectrum agents.

CONCLUSIONS. A sustained, multifaceted, community-level intervention was only modestly successful at decreasing overall antibiotic use beyond substantial secular trends. The more robust impact among Medicaid-insured children and for specific medication classes provides an argument for specific targeting of resources for patient and physician behavior change.
Medication Administration Variances Before and After Implementation of Computerized Physician Order Entry in a Neonatal Intensive Care Unit
Authors: Taylor James A. , Loan Lori A. , Kamara Judy , Blackburn Susan , Whitney Donna
Published: December 2007

OBJECTIVE. The goal was to determine whether implementation of a computerized physician order entry system was associated with a decrease in medication administration variances in a NICU.

METHODS. A prospective observational study was conducted. Research nurses recorded details of medication administrations for patients in a NICU during standardized observation periods. Details of each administration were compared with the medication order; a variance was defined as a discrepancy between the order and the medication administration. Rates of variances before and after implementation of computerized physician order entry in the NICU were compared. Specific types of and reasons for variances were also compared.

RESULTS. Data on 526 medication administrations, including 254 during the pre-computerized physician order entry period and 272 after implementation of computerized physician order entry, were collected. Medication variances were detected for 19.8% of administrations during the pre-computerized physician order entry period, compared with 11.6% with computerized physician order entry (rate ratio: 0.53). Overall, administration mistakes, prescribing problems, and pharmacy problems accounted for 74% of medication variances; there were no statistically significant differences in rates for any of these specific reasons before versus after introduction of computerized physician order entry. Administration of a medication at the wrong time accounted for 53.1% of all variances. Variance rates related to giving a drug at the wrong time were significantly lower in the computerized physician order entry period than in the pre-computerized physician order entry period (rates: 6.7% and 9.9%, respectively; rate ratio: 0.53).

CONCLUSIONS. Implementation of computerized physician order entry in a NICU was associated with a significant decrease in the rate of medication administration variances. However, even with the use of computerized physician order entry, variances were noted for >11% of all medication administrations, which suggests that additional methods may be needed to improve neonatal patient safety.