bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of Early Childhood Overweight
Authors: Salsberry Pamela J. , Reagan Patricia B.
Published: December 2005

Objective. To study the dynamic processes that drive development of childhood overweight by examining the effects of prenatal characteristics and early-life feeding (breastfeeding versus bottle feeding) on weight states through age 7 years. We test a model to determine whether prenatal characteristics and early-life feeding influence the development of a persistent early tendency toward overweight and/or whether prenatal characteristics and early-life feeding factors influence the likelihood that children will change weight states as they get older.

Methods. Data from the National Longitudinal Survey of Youth’s Child-Mother file were used to implement these analyses. A total of 3022 children were included in this sample. For inclusion in this sample, valid information on height and weight during 3 consecutive interviews when the child was aged 24 to 95 months as well as valid data on prenatal and birth characteristics were needed. The primary outcome measure was childhood overweight (BMI >95th percentile). Multivariate logistic models and first-order Markov models were estimated.

Results. Early development of childhood overweight was associated with race, ethnicity, maternal prepregnancy obesity, maternal smoking during pregnancy, and later birth years. In later years, the factor that contributed the most to being overweight was having been overweight in the previous observation period. However, with conditioning on the child’s having been overweight in the previous observation period, the prenatal factors that contributed to early childhood overweight, except for birth cohort, were also associated with development of overweight among children who had previously been normal weight and perpetuated the persistence of overweight over time.

Conclusions. This research suggests that prenatal characteristics, particularly race, ethnicity, maternal smoking during pregnancy, and maternal prepregnancy obesity, exert influence on the child’s weight states through an early tendency toward overweight, which then is perpetuated as the child ages. These findings are intriguing as they provide additional clues to the genesis of childhood overweight and suggest that overweight prevention may need to begin before pregnancy and in early childhood.
Project 27/28: Inquiry Into Quality of Neonatal Care and Its Effect on the Survival of Infants Who Were Born at 27 and 28 Weeks in England, Wales, and Northern Ireland
Authors: Acolet Dominique , Elbourne Diana , McIntosh Neil , Weindling Michael , Korkodilos Marilena , Haviland Jo , Modder Jo , Macintosh Mary ,   on behalf of the Confidential Enquiry Into Maternal and Child Health
Published: December 2005

Objective. To identify variations in standards of neonatal care in the first week of life that might have contributed to deaths in infants who were born at 27 and 28 weeks' gestation.

Methods. A case-control study was conducted of infants who were born at 27 and 28 weeks' gestation in England, Wales, and Northern Ireland during a 2-year period. Cases were neonatal deaths; control subjects were randomly selected survivors at day 28. Main outcome measures were failures of prespecified standards of care or deficiencies in care reported by regional panels assessing anonymized medical records.

Results. Failures of standards of care relating to ventilatory support (adjusted odds ratio [OR]: 3.29; 95% confidence interval [CI]: 1.97–5.49), cardiovascular support (OR: 2.37; 95% CI :1.36–4.13), and thermal care (OR: 1.71; 95% CI: 1.21–2.43) were associated with neonatal death. Frequencies of unmet resuscitation standards (range: 3%–46%) and of delays in surfactant administration (range: 38%–40%) were similar in cases and control subjects. Panels identified significantly more deficiencies in all aspects of neonatal care in cases with the exception of the management of infection. Stratification by clinical condition of infants at birth showed a stronger association between overall standard of care and death when infants were in a good condition at birth.

Conclusions. Our findings suggest an association between quality of neonatal care and neonatal deaths, most marked for early thermal care and ventilatory and cardiovascular support. Poor overall quality of care was more strongly associated with deaths when the infant was in a good condition at birth.
Impact of Cardiac Rehabilitation on the Exercise Function of Children With Serious Congenital Heart Disease
Authors: Rhodes Jonathan , Curran Tracy J. , Camil Laurel , Rabideau Nicole , Fulton David R. , Gauthier Naomi S. , Gauvreau Kimberlee , Jenkins Kathy J.
Published: December 2005

Objectives. The exercise capacity of children with congenital heart disease (CHD) is often depressed. This depression is thought to be attributable to (1) residual hemodynamic defects and (2) deconditioning secondary to physical inactivity. We hypothesized that this latter component would be ameliorated by a formal cardiac rehabilitation program designed specifically for children. The objective of this study was to characterize the effect of a cardiac rehabilitation program on the exercise performance of children with CHD and to define the physiologic mechanisms that might account for any improvements that are observed.

Methods. Nineteen patients with CHD who were referred for exercise testing and found to have a peak oxygen consumption (VO2) and/or peak work rate <80% of predicted were enrolled in the study. Sixteen patients (11 Fontan patients, 5 with other CHD) completed the program and had postrehabilitation exercise tests, results of which were compared with the prerehabilitation studies.

Results. Improvements were found in 15 of 16 patients. Peak VO2 rose from 26.4 ± 9.1 to 30.7 ± 9.2 mL/kg per min; peak work rate from 93 ± 32 to 106 ± 34 W, and the ventilatory anaerobic threshold from 14.2 ± 4.8 to 17.4 ± 4.5 mL/kg per min. The peak heart rate and peak respiratory exchange ratio did not change, suggesting that the improvements were not attributable merely to an increased effort. In contrast, the peak oxygen pulse rose significantly, from 7.6 ± 2.8 to 9.7 ± 4.1 mL/beat, an improvement that can be attributed only to an increase in stroke volume and/or oxygen extraction at peak exercise. No patient experienced rehabilitation-related complications.

Conclusion. Cardiac rehabilitation can improve the exercise performance of children with CHD. This improvement is mediated by an increase in stroke volume and/or oxygen extraction during exercise. Routine use of formal cardiac rehabilitation may greatly reduce the morbidity of complex CHD.
Randomized Clinical Trial of Behavioral and Nutrition Treatment to Improve Energy Intake and Growth in Toddlers and Preschoolers With Cystic Fibrosis
Authors: Powers Scott W. , Jones Julie S. , Ferguson Kathleen S. , Piazza-Waggoner Carrie , Daines Cori , Acton James D.
Published: December 2005

Objective. To conduct a randomized clinical trial comparing a behavioral and nutrition intervention (BEH) with a usual care control condition (CTL) for children (ages 18 months to 4 years) with cystic fibrosis (CF) and pancreatic insufficiency. This trial was designed to (1) evaluate a randomized comparison of BEH with CTL over 8 weeks, (2) provide a replication of the impact of BEH by inviting the CTL group to receive BEH after 8 weeks, and (3) examine the maintenance of BEH at 3- and 12-month follow-up.

Methods. Of 14 eligible children, 10 were randomly assigned and initiated treatment (71% recruitment rate). Four participants were randomly assigned to BEH, and 6 were assigned to CTL (5 of whom chose to crossover to BEH). BEH included nutrition counseling to increase energy intake (via types of foods and addables/spreadables) and child behavioral management training to teach parents differential attention and contingency management skills. CTL was consistent with the 2002 CF Foundation Consensus Conference Guidelines for nutritional care.

Results. BEH led to greater increases in energy intake pre- to posttreatment than CTL as measured by calories per day (842 kcal/day vs −131 kcal/day change). On receiving BEH, the change in energy intake was replicated with the CTL group (892 kcal/day change). At 3- and 12-month follow-up, energy intake was maintained (672 kcal/day increase from baseline and 750 kcal/day increase from baseline, respectively). Children in this study met or exceeded normal weight and height velocities from pretreatment to the 3-month follow-up (mean weight: 1.4 kg/6 months; mean height: 5.1 cm/6 months) and from posttreatment to the 12-month follow-up (mean weight: 2.5 kg/12 months; mean height: 8.3 cm/12 months).

Conclusions. Toddlers and preschoolers who have CF and received BEH were able to meet the energy intake recommendations for this disease and maintain these gains up to 12 months after treatment. In addition, these children demonstrated weight and height velocities from pretreatment to 12-month follow-up, consistent with the goal of normal growth. BEH is a promising, evidence-based, early nutritional intervention for children with CF. An upcoming multisite clinical trial will test BEH versus an attention control condition using a larger sample (N = 100), providing additional evidence about the efficacy of this treatment for energy intake and growth in young children with CF.
Why Do Women Stop Breastfeeding? Findings From the Pregnancy Risk Assessment and Monitoring System
Authors: Ahluwalia Indu B. , Morrow Brian , Hsia Jason
Published: December 2005

Objective. We examined breastfeeding behaviors, periods of vulnerability for breastfeeding cessation, reasons for breastfeeding cessation, and the association between predelivery intentions and breastfeeding behaviors.

Study Design. Using 2 years (2000 and 2001) of data from the Pregnancy Risk Assessment and Monitoring System we assessed the percentage of women who began breastfeeding, continued for <1 week, continued for 1 to 4 weeks, and continued for >4 weeks and their reasons for not initiating or stopping. Predelivery breastfeeding intentions of women and their relationship with subsequent breastfeeding behaviors were examined also.

Results. We found that 32% of women did not initiate breastfeeding, 4% started but stopped within the first week, 13% stopped within the first month, and 51% continued for >4 weeks. Younger women and those with limited socioeconomic resources were more likely to stop breastfeeding within the first month. Reasons for cessation included sore nipples, inadequate milk supply, infant having difficulties, and the perception that the infant was not satiated. Women who intended to breastfeed, thought they might breastfeed, or had ambivalent feelings about breastfeeding were more likely to initiate breastfeeding and to continue through the vulnerable periods of early infancy than were those who did not plan to breastfeed.

Conclusions. Our findings indicate a need to provide extensive breastfeeding support after delivery, particularly to women who may experience difficulties in breastfeeding.
Effectiveness and Side Effects of an Escalating, Stepwise Approach to Indomethacin Treatment for Symptomatic Patent Ductus Arteriosus in Premature Infants Below 33 Weeks of Gestation
Authors: Sperandio Markus , Beedgen Bernd , Feneberg Reinhard , Huppertz Christina , Brüssau Jürgen , Pöschl Johannes , Linderkamp Otwin
Published: December 2005

Objective. Symptomatic patent ductus arteriosus (sPDA) is a common problem in premature infants and can be treated effectively with intravenous indomethacin, leading to permanent ductal closure in 70% to 80% of infants. Infants who do not respond to pharmacologic closure of the duct ultimately have to undergo surgical or interventional closure of the PDA. Optimizing the pharmacologic treatment could offer an interesting approach to reduce the number of infants who need surgical closure of the duct.

Methods. We conducted a retrospective analysis in infants who were <33 weeks’ gestation, had sPDA, and were treated with high-dose intravenous indomethacin. From 1993 to 2002, 129 infants with sPDA received indomethacin after diagnosis of sPDA was confirmed by echocardiography. Treatment was started in all infants with intravenous indomethacin (0.2 mg/kg given 5 times at 0 hours, 12 hours, 24 hours, 48 hours, and 72 hours). When the ductus was still open at 36 hours, indomethacin every 12 hours was continued and single doses increased up to 1 mg/kg until ductal closure was achieved.

Results. In 68 (53%) of 129 infants who were treated with indomethacin, ductal closure occurred during intermediate-dose indomethacin therapy (up to 1.5 mg/kg total dose). In the 61 initial nonresponders, the continuation of indomethacin led to ductal closure in 59 infants. When infants who were treated with an intermediate dose were compared with the initial nonresponders, no differences in the incidences of renal or electrolyte abnormalities, gastrointestinal bleeding, intraventricular hemorrhage, or periventricular leukomalacia were found.

Conclusions. High-dose indomethacin after intermediate-dose therapy resulted in an overall closure rate of 98.5% (127 of 129). Although single indomethacin doses of up to 1 mg/kg were given, high-dose indomethacin was safe.
Office Spirometry in Primary Care Pediatrics: A Pilot Study
Authors: Zanconato Stefania , Meneghelli Giorgio , Braga Raffaele , Zacchello Franco , Baraldi Eugenio ,   on behalf of the Working Group
Published: December 2005

Objective. The aim of this study was to investigate the validity of office spirometry in primary care pediatric practices.

Methods. Ten primary care pediatricians undertook a spirometry training program that was led by 2 pediatric pulmonologists from the Pediatric Department of the University of Padova. After the pediatricians' training, children with asthma or persistent cough underwent a spirometric test in the pediatrician's office and at a pulmonary function (PF) laboratory, in the same day in random order. Both spirometric tests were performed with a portable turbine flow sensor spirometer. We assessed the quality of the spirometric tests and compared a range of PF parameters obtained in the pediatricians' offices and in the PF laboratory according to the Bland and Altman method.

Results. A total of 109 children (mean age: 10.4 years; range: 6–15) were included in the study. Eighty-five (78%) of the spirometric tests that were performed in the pediatricians' offices met all of the acceptability and reproducibility criteria. The 24 unacceptable test results were attributable largely to a slow start and failure to satisfy end-of-test criteria. Only the 85 acceptable spirometric tests were considered for analysis. The agreement between the spirometric tests that were performed in the pediatrician's office and in the PF laboratory was good for the key parameters (forced vital capacity, forced expiratory volume in 1 second, and forced expiratory flow between 25% and 75%). The repeatability coefficient was 0.26 L for forced expiratory volume in 1 second (83 of 85 values fall within this range), 0.30 L for forced vital capacity (81 values fall within this range), and 0.58 L/s for forced expiratory flow between 25% and 75% (82 values fall within this range). In 79% of cases, the primary care pediatricians interpreted the spirometric tests correctly.

Conclusions. It seems justifiable to perform spirometry in pediatric primary care, but an integrated approach involving both the primary care pediatrician and certified pediatric respiratory medicine centers is recommended because effective training and quality assurance are vital prerequisites for successful spirometry.
Masturbation in Infancy and Early Childhood Presenting as a Movement Disorder: 12 Cases and a Review of the Literature
Authors: Yang Michele L. , Fullwood Erika , Goldstein Joshua , Mink Jonathan W.
Published: December 2005

Purpose. Infantile masturbation (gratification behavior) is not commonly identified as a cause of recurrent paroxysmal movements. Extensive and fruitless investigations may be pursued before establishing this diagnosis. Sparse literature is available regarding masturbatory behavior as a whole, but literature available as case reports describes common features. The purpose of this case series is to describe consistent features in young children with posturing accompanying masturbation.

Methods. Twelve patients presenting to a pediatric movement disorders clinic with a suspected movement disorder were determined to have postures and movements associated with masturbation. We reviewed the clinical history, examination, and home videotapes of these patients.

Results. Our patients had several features in common: (1) onset after the age of 3 months and before 3 years; (2) stereotyped episodes of variable duration; (3) vocalizations with quiet grunting; (4) facial flushing with diaphoresis; (5) pressure on the perineum with characteristic posturing of the lower extremities; (6) no alteration of consciousness; (7) cessation with distraction; (8) normal examination; and (9) normal laboratory studies.

Conclusions. The identification of these common features by primary care providers should assist in making this diagnosis and eliminate the need for extensive, unnecessary testing. Direct observation of the events is crucial, and the video camera is a useful tool that may help in the identification of masturbatory behavior.
Infections and Kawasaki Disease: Implications for Coronary Artery Outcome
Authors: Benseler Susanne M. , McCrindle Brian W. , Silverman Earl D. , Tyrrell Pascal N. , Wong Joseph , Yeung Rae S.M.
Published: December 2005

Objective. We sought to determine the effect of coincident infection, at time of diagnosis of Kawasaki disease (KD), on treatment response and coronary artery outcome.

Methods. A single-center, retrospective study of 129 consecutive patients diagnosed with typical KD between January 1997 and December 1998 was performed. Standardized clinical assessments, laboratory, microbiology, and imaging test results plus treatment regimens were reviewed. Coronary arteries were visualized by using echocardiography, and coronary artery lesions (CALs) were reported as body surface area–adjusted z scores. Infection-positive and -negative groups were identified, and clinical, laboratory, and treatment data were analyzed. The effect of infections and other outcome variables on CAL development was determined by multivariate regression analysis.

Results. (1) Concurrent infections: 33% of children with typical KD had ≥1 confirmed infection at KD diagnosis. (2) Treatment response: the presence of infection did not alter the response to treatment with intravenous immunoglobulin, with resolution of fever in 83% of children after 1 dose of intravenous immunoglobulin together with aspirin administration regardless of presence or absence of infection. (3) Coronary outcome: in total, 31% of the patients developed CALs. Both the proven-infection and no-proven-infection groups had a similar CAL frequency. (4) Multivariate regression analysis: proven infection did not increase the risk of coronary artery involvement even after adjusting for other factors impacting on coronary artery outcomes.

Conclusions. Infections are common at diagnosis of KD. A broad spectrum of infectious agents was found. Infections at diagnosis of KD did not affect the patients' response to treatment and coronary artery outcome when compared with those patients without infections.
The Use of Tamoxifen to Improve Height Potential in Short Pubertal Boys
Authors: Kreher Nerissa C. , Eugster Erica A. , Shankar R. Ravi
Published: December 2005

A retrospective chart review of 7 pubertal boys who were treated with tamoxifen was conducted to determine the effects of this therapy on skeletal maturation and predicted adult height. Tamoxifen significantly decreased the rate of skeletal maturation and increased the predicted adult height without negative effects on sexual maturation. Additional evaluation of this therapy is now required to determine if the increase in predicted adult height results in a clinically significant increase in final adult height.
Cross-national Study of Fighting and Weapon Carrying as Determinants of Adolescent Injury
Authors: Pickett William , Craig Wendy , Harel Yossi , Cunningham John , Simpson Kelly , Molcho Michal , Mazur Joanna , Dostaler Suzanne , Overpeck Mary D. , Currie Candace E. ,   on behalf of the HBSC Violence and Injuries Writing Group
Published: December 2005

Objectives. We sought to (1) compare estimates of the prevalence of fighting and weapon carrying among adolescent boys and girls in North American and European countries and (2) assess in adolescents from a subgroup of these countries comparative rates of weapon carrying and characteristics of fighting and injury outcomes, with a determination of the association between these indicators of violence and the occurrence of medically treated injury.

Design and Setting. Cross-sectional self-report surveys using 120 questions were obtained from nationally representative samples of 161082 students in 35 countries. In addition, optional factors were assessed within individual countries: characteristics of fighting (9 countries); characteristics of weapon carrying (7 countries); and medically treated injury (8 countries).

Participants. Participants included all consenting students in sampled classrooms (average age: 11–15 years).

Measures. The primary measures assessed included involvement in physical fights and the types of people involved; frequency and types of weapon carrying; and frequency and types of medically treated injury.

Results. Involvement in fighting varied across countries, ranging from 37% to 69% of the boys and 13% to 32% of the girls. Adolescents most often reported fighting with friends or relatives. Among adolescents reporting fights, fighting with total strangers varied from 16% to 53% of the boys and 5% to 16% of the girls. Involvement in weapon carrying ranged from 10% to 21% of the boys and 2% to 5% of the girls. Among youth reporting weapon carrying, those carrying handguns or other firearms ranged from 7% to 22% of the boys and 3% to 11% of the girls. In nearly all reporting countries, both physical fighting and weapon carrying were significantly associated with elevated risks for medically treated, multiple, and hospitalized injury events.

Conclusions. Fighting and weapon carrying are 2 common indicators of physical violence that are experienced by young people. Associations of fighting and weapon carrying with injury-related health outcomes are remarkably similar across countries. Violence is an important issue affecting the health of adolescents internationally.
The Effects of Multisystemic Therapy on Diabetes Stress Among Adolescents With Chronically Poorly Controlled Type 1 Diabetes: Findings From a Randomized, Controlled Trial
Authors: Ellis Deborah A. , Frey Maureen A. , Naar-King Sylvie , Templin Thomas , Cunningham Phillippe B. , Cakan Nedim
Published: December 2005

Objective. The goal of this study was to determine whether multisystemic therapy (MST), an intensive, home-based psychotherapy, could decrease diabetes-related stress among adolescents with chronically poorly controlled type 1 diabetes. Stress was also evaluated as a mediator of the effect of MST on adherence and metabolic control.

Methods. A randomized, controlled trial was conducted with 127 adolescents with type 1 diabetes mellitus and chronically poor metabolic control (hemoglobin A1c levels of ≥8% at study enrollment and for the past 1 year) who received their diabetes care in a children's hospital located in a major Midwestern city. Participants assigned randomly to MST received treatment for ∼6 months. Data were collected at baseline and at a 7-month posttest (ie, treatment termination). Changes in diabetes-related stress, as measured with a self-report questionnaire, were assessed. Structural equation models were used to test the degree to which changes in stress levels mediated the ability of the MST intervention to improve adherence and metabolic control.

Results. In intent-to-treat analyses, participation in MST was associated with significant reductions in diabetes-related stress. Tests for moderation found no significant effects of age, gender, or ethnicity, which suggests that the intervention was equally effective in reducing diabetes stress for all participants. However, structural equation modeling did not provide support for diabetes stress as the mechanism through which MST improved health outcomes. Rather, the final model suggested that MST improved metabolic control through increased regimen adherence.

Conclusions. Intensive, home-based psychotherapy reduces diabetes-related stress among adolescents with chronically poorly controlled type 1 diabetes. Such stress reductions are important for the psychological wellbeing of a subset of youths with diabetes who are at high risk for future health complications.
Tolerance of Laparoscopy and Thoracoscopy in Neonates
Authors: Kalfa Nicolas , Allal Hossein , Raux Olivier , Lopez Manuel , Forgues Dominique , Guibal Marie-Pierre , Picaud Jean-Charles , Galifer René-Benoit
Published: December 2005

Objectives. Video-surgery in neonates is recent. Data on the respiratory, hemodynamic, and thermic effects during the first month of life are still sparse. This study aimed to evaluate the tolerance of video-surgery in neonates and to determine the risk factors of per-operative complications.

Methods. From 1994 to 2004, 49 neonates (mean age: 11 days; weight: 3285 g) underwent 50 video-surgical procedures. Indications for laparoscopy were duodenal atresias, volvulus with malrotation, pyloric stenosis, gastroesophageal reflux, cystic lymphangiomas, ovarian cysts, biliary atresia, and congenital diaphragmatic hernias; indications for thoracoscopy were esophageal atresias and tracheoesophageal fistula.

Results. Median operative time was 79 minutes. Mean insufflation pressure was 6.7 mm Hg (range: 3–13). Oxygen saturation decreased, especially with thoracic insufflation or high-pressure pneumoperitoneum. Systolic arterial pressure, which decreased in 20% of the patients, was controlled easily with vascular expansion. Thermic loss (mean postoperative temperature: 35.6°C) was proportional to the duration of insufflation. No surgical incident was noted. Ten anesthetic incidents occurred (20%), 3 of which required temporary or definitive interruption of insufflation (O2 saturation <70%). Risk factors for an incident were low preoperative temperature, high variation of end-tidal pressure of CO2, surgical time >100 minutes, thoracic insufflation, and a high oxygen or vascular expansion requirement at the beginning of insufflation.

Conclusion. The neonate's high sensitivity to insufflation is an important limiting factor of video-surgery. The described profile of the neonate at risk may help to reduce the frequency of adverse effects of this technique and improve its tolerance.
First Reported Case of Neisseria meningitidis Periorbital Cellulitis Associated With Meningitis
Authors: Chand David V. , Hoyen Claudia K. , Leonard Ethan G. , McComsey Grace A.
Published: December 2005

Cellulitis is a rare manifestation of meningococcal disease. We describe the case of a previously healthy 4-month-old female infant who developed periorbital cellulitis associated with meningococcal meningitis.
A Randomized, Controlled Trial of the Effectiveness of Community-Based Case Management in Insuring Uninsured Latino Children
Authors: Flores Glenn , Abreu Milagros , Chaisson Christine E. , Meyers Alan , Sachdeva Ramesh C. , Fernandez Harriet , Francisco Patricia , Diaz Beatriz , Diaz Ana Milena , Santos-Guerrero Iris
Published: December 2005

Background. Lack of health insurance adversely affects children’s health. Eight million US children are uninsured, with Latinos being the racial/ethnic group at greatest risk for being uninsured. A randomized, controlled trial comparing the effectiveness of various public insurance strategies for insuring uninsured children has never been conducted.

Objective. To evaluate whether case managers are more effective than traditional methods in insuring uninsured Latino children.

Design. Randomized, controlled trial conducted from May 2002 to August 2004.

Setting and Participants. A total of 275 uninsured Latino children and their parents were recruited from urban community sites in Boston.

Intervention. Uninsured children were assigned randomly to an intervention group with trained case managers or a control group that received traditional Medicaid and State Children’s Health Insurance Program (SCHIP) outreach and enrollment. Case managers provided information on program eligibility, helped families complete insurance applications, acted as a family liaison with Medicaid/SCHIP, and assisted in maintaining coverage.

Main Outcome Measures. Obtaining health insurance, coverage continuity, the time to obtain coverage, and parental satisfaction with the process of obtaining insurance for children were assessed. Subjects were contacted monthly for 1 year to monitor outcomes by a researcher blinded with respect to group assignment.

Results. One hundred thirty-nine subjects were assigned randomly to the intervention group and 136 to the control group. Intervention group children were significantly more likely to obtain health insurance (96% vs 57%) and had ∼8 times the adjusted odds (odds ratio: 7.78; 95% confidence interval: 5.20–11.64) of obtaining insurance. Seventy-eight percent of intervention group children were insured continuously, compared with 30% of control group children. Intervention group children obtained insurance significantly faster (mean: 87.5 vs 134.8 days), and their parents were significantly more satisfied with the process of obtaining insurance.

Conclusions. Community-based case managers are more effective than traditional Medicaid/SCHIP outreach and enrollment in insuring uninsured Latino children. Case management may be a useful mechanism to reduce the number of uninsured children, especially among high-risk populations.
Unexpected Increased Mortality After Implementation of a Commercially Sold Computerized Physician Order Entry System
Authors: Han Yong Y. , Carcillo Joseph A. , Venkataraman Shekhar T. , Clark Robert S.B. , Watson R. Scott , Nguyen Trung C. , Bayir Hülya , Orr Richard A.
Published: December 2005

Objective. In response to the landmark 1999 report by the Institute of Medicine and safety initiatives promoted by the Leapfrog Group, our institution implemented a commercially sold computerized physician order entry (CPOE) system in an effort to reduce medical errors and mortality. We sought to test the hypothesis that CPOE implementation results in reduced mortality among children who are transported for specialized care.

Methods. Demographic, clinical, and mortality data were collected of all children who were admitted via interfacility transport to our regional, academic, tertiary-care level children’s hospital during an 18-month period. A commercially sold CPOE program that operated within the framework of a general, medical-surgical clinical application platform was rapidly implemented hospital-wide over 6 days during this period. Retrospective analyses of pre-CPOE and post-CPOE implementation time periods (13 months before and 5 months after CPOE implementation) were subsequently performed.

Results. Among 1942 children who were referred and admitted for specialized care during the study period, 75 died, accounting for an overall mortality rate of 3.86%. Univariate analysis revealed that mortality rate significantly increased from 2.80% (39 of 1394) before CPOE implementation to 6.57% (36 of 548) after CPOE implementation. Multivariate analysis revealed that CPOE remained independently associated with increased odds of mortality (odds ratio: 3.28; 95% confidence interval: 1.94–5.55) after adjustment for other mortality covariables.

Conclusions. We have observed an unexpected increase in mortality coincident with CPOE implementation. Although CPOE technology holds great promise as a tool to reduce human error during health care delivery, our unanticipated finding suggests that when implementing CPOE systems, institutions should continue to evaluate mortality effects, in addition to medication error rates, for children who are dependent on time-sensitive therapies.
The Role of the Pediatrician in Rural Emergency Medical Services for Children
Authors:   Committee on Pediatric Emergency Medicine
Published: December 2005

This Policy Statement was revised. See https://doi.org/10.1542/peds.2012-2547.

In rural America, pediatricians can play a key role in the development, implementation, and ongoing supervision of emergency medical services for children. Pediatricians may represent the only source of pediatric expertise for a large region and are a vital resource for rural physicians (eg, general and family medicine, emergency medicine), other rural health care professionals (physician assistants, nurse practitioners, emergency medical technicians), and local emergency medical services medical directors. They can provide education about management and prevention of pediatric illness and injury; appropriate equipment for the acutely ill or injured child; and acute, chronic, and rehabilitative care. In addition to providing clinical expertise, the pediatrician may be involved in quality assurance, clinical protocol development, and advocacy and may serve as a liaison between emergency medical services and other entities working with children (eg, school nurses, child care centers, athletic programs, and programs for children with special health care needs).
Sex steroid-producing enzymes in human breast cancer
Authors: Suzuki Takashi , Miki Yasuhiro , Nakamura Yasuhiro , Moriya Takuya , Ito Kiyoshi , Ohuchi Noriaki , Sasano Hironobu
Published: December 2005

It is well known that sex steroids are involved in the growth of breast cancers, and the great majority of breast carcinomas express estrogen (ER), progesterone (PR), and androgen (AR) receptors. In particular, recent studies have demonstrated that estrogens and androgens are locally produced in breast carcinoma tissues, and total blockade of in situ estrogen production potentially leads to an improvement in prognosis of breast cancer patients. Therefore, it is important to obtain a better understanding of sex steroid-producing enzymes in breast carcinoma tissues. In this review, we summarize recent studies on the expression and regulation of enzymes related to intratumoral production of estrogens (aromatase, 17β-hydroxysteroid dehydrogenase type 1 (17βHSD1), and steroid sulfatase (STS) etc) and androgens (17βHSD5 and 5α-reductase) in human breast carcinoma tissues, and discuss the biological and/or clinical significance of these enzymes. The cellular localization of aromatase in breast carcinoma tissues still remains controversial. Therefore, we examined localization of aromatase mRNA in breast carcinoma tissues by laser capture microdissection/real time-polymerase chain reaction. Aromatase mRNA expression was detected in both carcinoma and intratumoral stromal cells, and the expression level of aromatase mRNA was higher in intratumoral stromal cells than in carcinoma cells in the cases examined. We also examined an association among the immunoreactivity of enzymes related to intratumoral estrogen production and ERs in breast carcinoma tissues, but no significant association was detected. Therefore, the enzymes responsible for the intratumoral production of estrogen may not always be the same among breast cancer patients, and not only aromatase but also other enzymes such as STS and 17βHSD1 may have important therapeutic potential as targets for endocrine therapy in breast cancer patients.
The anti-oestrogen ICI 182,780, but not tamoxifen, inhibits the growth of MCF-7 breast cancer cells refractory to long-term oestrogen deprivation through down-regulation of oestrogen receptor and IGF signalling
Authors: Martin L-A , Pancholi S , Chan C M W , Farmer I , Kimberley C , Dowsett M , Johnston S R D
Published: December 2005

Long-term culture of MCF-7 wild-type (wt) cells in steroid-depleted medium (LTED) results in hypersensitivity to oestradiol (E2) coinciding with elevated levels of ERα and enhanced growth factor signalling. In this study, we aimed to compare the effects of the pure anti-oestrogen ICI 182,780 (ICI) with the competitive anti-oestrogen tamoxifen (TAM) on oestrogen and IGF signalling in these cells. Wt MCF-7 and LTED cells were treated with a log 7 concentration range of E2, TAM or ICI. Effects on cell growth, ERα transactivation, expression of ERα, ERβ and components of the IGF pathway were measured with and without insulin. In the presence of insulin, growth of LTED cells was refractory to TAM but inhibited by ICI and E2. In the absence of insulin, LTED cells showed persistent hypersensitivity to E2, and remained inhibited by ICI but were largely unaffected by TAM. ICI but not TAM inhibited ER-mediated gene transcription and treatment with ICI resulted in a dose-dependent reduction in ERα levels whilst having no effect on ERβ expression. IGF-I receptor and insulin receptor substrate 2 levels were increased in LTED versus the Wt MCF-7 cells, and ICI but not TAM reduced their expression in a dose-dependent fashion. Thus IGF signalling as well as ERα expression and function are enhanced during LTED. While the resultant cells are resistant to TAM, ICI down-regulates ERα, reducing IGF signalling and cell growth. These results support the use of ICI in women with ER-positive breast cancer who have relapsed on an aromatase inhibitor.
The p53-homologue p63 may promote thyroid cancer progression
Authors: Malaguarnera Roberta , Mandarino Angelo , Mazzon Emanuela , Vella Veronica , Gangemi Piero , Vancheri Carlo , Vigneri Paolo , Aloisi Alessandra , Vigneri Riccardo , Frasca Francesco
Published: December 2005

Inactivation of p53 and p73 is known to promote thyroid cancer progression. We now describe p63 expression and function in human thyroid cancer. TAp63α is expressed in most thyroid cancer specimens and cell lines, but not in normal thyrocytes. However, in thyroid cancer cells TAp63α fails to induce the target genes (p21Cip1, Bax, MDM2) and, as a consequence, cell cycle arrest and apoptosis occur. Moreover, TAp63α antagonizes the effect of p53 on target genes, cell viability and foci formation, and p63 gene silencing by small interfering (si) RNA results in improved p53 activity. This unusual effect of TAp63α depends on the protein C-terminus, since TAp63β and TAp63γ isoforms, which have a different arrangement of their C-terminus, are still able to induce the target genes and to exert tumour-restraining effects in thyroid cancer cells. Our data outline the existence of a complex network among p53 family members, where TAp63α may promote thyroid tumour progression by inactivating the tumour suppressor activity of p53.
Molecular aspects of gefitinib antiproliferative and pro-apoptotic effects in PTEN-positive and PTEN-negative prostate cancer cell lines
Authors: Festuccia C , Muzi P , Millimaggi D , Biordi L , Gravina G L , Speca S , Angelucci A , Dolo V , Vicentini C , Bologna M
Published: December 2005

To date, no effective therapeutic treatment allows abrogation of the progression of prostate cancer (PCa) to more invasive forms. One of the major targets for the therapy in PCa can be epidermal growth factor receptor (EGFR), which signals via the phosphoinositide 3′-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) pathways, among others. Despite multiple reports of overexpression in PCa, the reliance on activated EGFR and its downstream signalling to the PI3K and/or MAPK/extracellular signal-regulated kinase (ERK) pathways has not been fully elucidated. We reported that the EGFR-selective tyrosine kinase inhibitor gefitinib (ZD1839; Iressa) is able to induce growth inhibition, G1 arrest and apoptosis in PCa cells and that its effectiveness is associated primarily with phosphatase and tensin homologue deleted from chromosome 10 (PTEN) expression (and thus Akt activity). In fact PTEN-negative PCa cells are slowly sensitive to gefitinib treatment, because this molecule is unable to downregulate PI3K/Akt activity. PI3K inhibition, by LY294002 or after PTEN transfection, restores EGFR-stimulated Akt signalling and sensitizes the cells to pro-apoptotic action of gefitinib. The MAPK pathway seems to be involved primarily on cell-growth modulation because dual blockade of EGFR and ERK1/2 phosphorylation potentiates growth inhibition (both not cell apoptosis) in PTEN-positive PCa cells and reduced EGF-mediated growth in PTEN-negative cells. Thus the effectiveness of gefitinib requires growth factor receptor-stimulated PI3K/Akt and MAPK signalling to be intact and functional. The loss of the PTEN activity leads to uncoupling of this signalling pathway, determining a partial gefitinib resistance. Moreover, gefitinib sensitivity may be maintained in these cells through its inhibitory potential in MAPK/ERK pathway activity, modulating proliferative EGFR-triggered events. Therefore, our data suggest that the inhibition of EGFR signalling can result in a significant growth reduction and in increased apoptosis in EGFR-overexpressing PCa cells with different modalities, which are regulated by PTEN status, and this may have relevance in the clinical setting of PCa.
Prognostic factors and survival in endocrine tumor patients: comparison between gastrointestinal and pancreatic localization
Authors: Panzuto Francesco , Nasoni Silvia , Falconi Massimo , Corleto Vito Domenico , Capurso Gabriele , Cassetta Sara , Di Fonzo Michela , Tornatore Valentina , Milione Massimo , Angeletti Stefano , Cattaruzza Maria Sofia , Ziparo Vincenzo , Bordi Cesare , Pederzoli Paolo , Fave Gianfranco Delle
Published: December 2005

Since gastro-entero-pancreatic endocrine tumors are rare and heterogeneous diseases, their prognosis and long-term survival are not well known. This study aimed at identifying prognostic factors and assessing long-term survival in gastro-entero-pancreatic endocrine tumors. A total of 156 patients enrolled. Prognostic factors were determined by univariate/multivariate analysis; survival rates were assessed by the Kaplan–Meier method. The tumors were non-functioning in 59.6% of patients, and originated from the pancreas in 42.9%. At diagnosis, 64.3% of patients had metastases. The tumors were well differentiated in 89.6% of patients. Ki67 was >2% in 39.6% of patients. Primary tumor size was >3 cm in 49.6% of cases studied. For the univariate analysis, the negative prognostic factors were: pancreatic origin (rate ratio 4.64, P = 0.0002), poorly differentiated tumor (rate ratio 7.70, P = 0.0001), primary tumor size >3 cm (rate ratio 4.26, P = 0.0009), presence of distant metastases (liver: rate ratio 5.88, P = 0.01; distant extra-hepatic: rate ratio 13.41, P = 0.0008). The pancreatic site, the poor degree of differentiation and the distant metastases were confirmed as negative prognostic factors at multivariate analysis. Overall 5-year survival rate was 77.5%. Survival rates differed according to: primary tumor site (62% for pancreatic vs 89.9% for gastrointestinal tract, P = 0.0001) and size (65.7% for >3 cm vs 88.8% for ≤ 3 cm, P = 0.0003), degree of differentiation (22% for poor vs 86.8% for good, P<0.0001), Ki67 (53.5% for > 2% vs 90.1% for ≤ 2%, P = 0.003), metastases (96.1, 77, 73.3 and 50.1% for absent, local, liver and distant extra-hepatic metastases respectively), age at diagnosis (85.3% for ≤ 50 years vs 70.3% for > 50 years, P = 0.03). Although 64.3% of gastro-entero-pancreatic endocrine tumors present metastases at diagnosis, the 5-year survival rate is 77.5%. Pancreatic site, a poor degree of tumor cell differentiation and distant extra-hepatic metastases are the major negative prognostic factors.
Estrogen receptor-α mediates gene expression changes and growth response in ovarian cancer cells exposed to estrogen
Authors: O’Donnell Amanda J M , Macleod Kenneth G , Burns David J , Smyth John F , Langdon Simon P
Published: December 2005

Estrogens play a significant role in the development, growth, invasion and metastasis of ovarian tumors. The transcriptional program regulated by 17β-estradiol (E2) in human ovarian cancer cell lines was analyzed using cDNA microarrays containing 1200 cancer-related genes. Twenty-eight transcripts had at least a threefold change in expression in E2-treated PEO1 ovarian carcinoma cells compared with controls. These differences were confirmed by real-time quantitative PCR and shown to be dependent upon the expression of functional estrogen receptor-α (ERα). Consistent with this, these gene expression changes were blocked by the anti-estrogen tamoxifen. The use of ERα- and ERβ-specific ligands allowed molecular dissection of the E2 response and showed that ERα activation was responsible for the observed changes in gene expression, whereas ERβ played no significant role. Inhibition of de novo protein synthesis by cycloheximide was used to distinguish between primary and secondary target genes regulated by E2. Actinomycin D was used to show that changes in gene expression levels induced by E2 were a result of changes in transcription and not due to changes in mRNA stability. The results presented here demonstrate that estrogen-driven growth of epithelial ovarian carcinoma is mediated by activation of ERα-mediated, and not ERβ-mediated, transcription.
Tamoxifen treatment for breast cancer enforces a distinct gene-expression profile on the human endometrium: an exploratory study
Authors: Gielen S C J P , Kühne L C M , Ewing P C , Blok L J , Burger C W
Published: December 2005

Tamoxifen treatment for breast cancer increases proliferation of the endometrium, resulting in an enhanced prevalence of endometrial pathologies, including endometrial cancer. An exploratory study was performed to begin to understand the molecular mechanism of tamoxifen action in the endometrium. Gene-expression profiles were generated of endometrial samples of tamoxifen users and compared with matched controls. The pathological classification of samples from both groups included atrophic/inactive endometrium and endometrial polyps. Unsupervised clustering revealed that samples of tamoxifen users were, irrespective of pathological classification, fairly similar and consequently form a subgroup distinct from the matched controls. Using SAM analysis (a statistical method to select genes differentially expressed between groups), 256 differentially expressed genes were selected between the tamoxifen and control groups. Upon comparing these genes with oestrogen-regulated genes, identified under similar circumstances, 95% of the differentially expressed genes turned out to be tamoxifen-specific. Finally, construction of a gene-expression network of the differentially expressed genes revealed that 69 genes centred around five well-known genes: TP53, RELA, MYC, epidermal growth factor receptor and β-catenin. This could indicate that these well-known genes, and the pathways in which they function, are important for tamoxifen-controlled proliferation of the endometrium.