Search

Objective: To determine current expert opinion and recommendations regarding the controversial issue of the use of growth hormone (GH) to treat short children who do not have classical GH deficiency (non-GHD children).Study Design: Analysis of a national survey mailed to 534 US physician experts on the management of short stature (pediatric endocrinologists) with a response rate of 81.3%.Main Outcome Measure: The experts' GH treatment recommendations.Results: The physicians reported that approximately 58% of their current patients undergoing GH therapy have classical GH deficiency, while 42% have other conditions. The proportion of physicians who recommended GH treatment of short non-GHD children ranged from 1% to 74% over all case scenarios presented. The likelihood of GH being recommended depended on the physiological growth characteristics of the child (ie, the child's height, growth rate, and predicted adult height), contingency factors (ie, strong family wishes or a reduction in GH cost), and physician beliefs (ie, the impact of short stature on well-being, the effectiveness of GH therapy). Each of these factors exerted highly significant, independent, and additive effects on decisions to recommend GH.Conclusion: Our results indicate that many pediatric endocrinologists consider GH treatment appropriate for selected short non-GHD children, going beyond current Food and Drug Administration-approved indications for GH. Decisions to recommend GH for a non-GHD child rest on a combination of medical, social, and perceptual factors; variations in treatment patterns stem from variations in these influences. Future GH use will likely be determined not only by the results of controlled trials, but also by family preferences, producer pricing, and physician perceptions of the value of height and GH therapy. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency of islet cell autoimmunity in youth clinically diagnosed with type 2 diabetes and describe associated clinical and laboratory findings.Research Design and Methods: Children (10-17 years) diagnosed with type 2 diabetes were screened for participation in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. Measurements included GAD-65 and insulinoma-associated protein 2 autoantibodies using the new National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health (NIDDK/NIH) standardized assays, a physical examination, and fasting lipid, C-peptide, and A1C determinations.Results: Of the 1,206 subjects screened and considered clinically to have type 2 diabetes, 118 (9.8%) were antibody positive; of these, 71 (5.9%) were positive for a single antibody, and 47 were positive (3.9%) for both antibodies. Diabetes autoantibody (DAA) positivity was significantly associated with race (P < 0.0001), with positive subjects more likely to be white (40.7 vs. 19%) (P < 0.0001) and male (51.7 vs. 35.7%) (P = 0.0007). BMI, BMI z score, C-peptide, A1C, triglycerides, HDL cholesterol, and blood pressure were significantly different by antibody status. The antibody-positive subjects were less likely to display characteristics clinically associated with type 2 diabetes and a metabolic syndrome phenotype, although the range for BMI z score, blood pressure, fasting C-peptide, and serum lipids overlapped between antibody-positive and antibody-negative subjects.Conclusions: Obese youth with a clinical diagnosis of type 2 diabetes may have evidence of islet autoimmunity contributing to insulin deficiency. As a group, patients with DAA have clinical characteristics significantly different from those without DAA. However, without islet autoantibody analysis, these characteristics cannot reliably distinguish between obese young individuals with type 2 diabetes and those with autoimmune diabetes. [ABSTRACT FROM AUTHOR]

Context: There is concern in both the medical community and the general public about mechanisms of medical decision making and the interplay of physician and insurer decisions in determining access to care.Objective: To examine the medical process influencing access to growth hormone (GH) therapy for childhood short stature by comparing coverage policies of US insurers with the treatment recommendations of US physicians.Design and Participants: Independent national representative surveys were mailed to insurers (private, Blue Cross/Blue Shield, health maintenance organizations, programs for Children with Special Health Care Needs, and Medicaid programs, n=113), primary care physicians (n=1504), and pediatric endocrinologists (n=534) with response rates of 75%, 60%, and 81%, respectively. Each survey included identical case scenarios. Primary care physicians were asked decisions about referrals to pediatric endocrinologists. Endocrinologists were asked GH treatment recommendations. Insurers were asked coverage decisions for GH therapy.Main Outcome Measures: Insurer coverage decisions for GH in specific case scenarios were compared with the recommendations of primary care physicians and pediatric endocrinologists.Results: Physician recommendations and insurance coverage decisions differed strikingly. For example, while 96% of pediatric endocrinologists recommended GH therapy for children with Turner syndrome, insurer policies covered GH therapy for only 52% of these children. Overall, referral and treatment decisions by physicians resulted in recommendations for GH therapy in 78% of children with GH deficiency, Turner syndrome, or renal failure; of those recommended for treatment, 28% were denied coverage by insurers. Similarly, GH therapy would be recommended by physicians for only 9% of children with idiopathic short stature, but insurers would not cover GH for the vast majority of these children. Furthermore, the data indicated considerable variation among insurers regarding coverage policies for GH (P<.01).Conclusions: Access to GH therapy differs depending on the type of insurance coverage. The deep discord between physician recommendations and insurance coverage decisions, exemplified by these findings, represents a major challenge to mechanisms of health care decision making, access, and costs. [ABSTRACT FROM AUTHOR]

Background: Inpatient falls and subsequent injuries are among the most common hospital-acquired conditions with few effective prevention methods., Objective: To evaluate the effectiveness of patient education videos and fall prevention visual signalling icons when added to bed exit alarms in improving acutely hospitalised medical-surgical inpatient fall and injury rates., Design: Performance improvement study with historic control., Setting: Four medical-surgical units in one US public acute care hospital., Study Participants: Adult medical-surgical inpatients units., Interventions: A 4 min video was shown to patients by trained volunteers. Icons of individual patient risk factors and interventions were placed at patients' bedsides. Beds with integrated three-mode sensitivity exit alarms were activated for confused patients at risk of falling., Main Outcome Measures: The main outcome measure is the incident rate per 1000 patient days (PDs) for patient falls, falls with any injury and falls with serious injury. The incident rate ratio (IRR) for each measure compared January 2009-September 2010 (baseline) with the follow-up period of January 2015-December 2015 (intervention)., Results: Falls decreased 20% from 4.78 to 3.80 per 1000 PDs (IRR 0.80, 95% CI 0.66 to 0.96); falls with any injury decreased 40% from 1.01 to 0.61 per 1000 PDs (IRR 0.60, 95% CI 0.38 to 0.94); and falls with serious injury 85% from 0.159 to 0.023 per 1000 PDs (IRR 0.15, 95% CI 0.01 to 0.85). Icons were not fully implemented., Conclusion: The first known significant reduction of falls, falls with injury and falls with serious injury among medical-surgical inpatients was achieved. Patient education and continued use of bed exit alarms were associated with large decreases in injury. Icons require further testing. Multicentre randomised controlled trials are needed to confirm the effectiveness of icons and video interventions and exit alarms., Competing Interests: Competing interests: None declared.

With rapid biotechnological advances in specialty drugs and direct-to-consumer advertising, consumers are under tremendous pressure to look, perform, feel, and live better. This is often accomplished through the use of life-enhancing products, sometimes referred to as performance-enhancing products, which can be accessed only through a gatekeeper, such as a physician. Integrating consumer and medical research, this article investigates how physicians make trade-offs between objective medical and nonmedical factors to determine consumers' access to life-enhancing products by examining US pediatric endocrinologists' prescription decisions for growth hormone (GH) for healthy but short children. The results of a conjoint study indicate that consumer medical criteria have less impact on a physician's decision to prescribe GH if the consumer requests a prescription or the physician believes in the intangible product benefits, and more impact when the product is more expensive. A physician's length of experience increases the impact of consumer medical criteria and decreases the influence of a consumer's preference for a prescription on the decision to prescribe. Overall, this research shows that not all consumers have equal access to life-enhancing products; their access depends on a complex combination of medical and nonmedical factors related to the consumer, product, and the physician.

Objective: To assess the association of insurance status on infant rehospitalization in a population-based setting., Methods: In this longitudinal retrospective study, hospitalizations were tracked for 1 year after birth discharge for 203 031 infants born in hospitals during 2008 using data from the New York State Inpatient Database. Relative risk was estimated using multivariable negative binomial regression models., Results: Rehospitalization occurred in 9010 infants (4.4%). Medicaid coverage and being uninsured were strong predictors of rehospitalizations after adjustment for birth weight and other factors. Medicaid also bears a disproportionate share of the economic burden. Normal birth weight infants have the lowest risk, but comprise the majority of costs. Jaundice and acute bronchiolitis were the leading causes of rehospitalization within 30 days and 1 year, respectively., Discussion: Future research can explore the preventability of rehospitalizations, and evaluate novel strategies for discharge and postnatal care coordination especially for uninsured and Medicaid-enrolled infants., (© The Author(s) 2014.)

Objective: Evolving primary care models require methods to help practices achieve quality standards. This study assessed the effectiveness of a Practice-Tailored Facilitation Intervention for improving delivery of 3 pediatric preventive services., Methods: In this cluster-randomized trial, a practice facilitator implemented practice-tailored rapid-cycle feedback/change strategies for improving obesity screening/counseling, lead screening, and dental fluoride varnish application. Thirty practices were randomized to Early or Late Intervention, and outcomes assessed for 16 419 well-child visits. A multidisciplinary team characterized facilitation processes by using comparative case study methods., Results: Baseline performance was as follows: for Obesity: 3.5% successful performance in Early and 6.3% in Late practices, P = .74; Lead: 62.2% and 77.8% success, respectively, P = .11; and Fluoride: <0.1% success for all practices. Four months after randomization, performance rose in Early practices, to 82.8% for Obesity, 86.3% for Lead, and 89.1% for Fluoride, all P < .001 for improvement compared with Late practices' control time. During the full 6-month intervention, care improved versus baseline in all practices, for Obesity for Early practices to 86.5%, and for Late practices 88.9%; for Lead for Early practices to 87.5% and Late practices 94.5%; and for Fluoride, for Early practices to 78.9% and Late practices 81.9%, all P < .001 compared with baseline. Improvements were sustained 2 months after intervention. Successful facilitation involved multidisciplinary support, rapid-cycle problem solving feedback, and ongoing relationship-building, allowing individualizing facilitation approach and intensity based on 3 levels of practice need., Conclusions: Practice-tailored Facilitation Intervention can lead to substantial, simultaneous, and sustained improvements in 3 domains, and holds promise as a broad-based method to advance pediatric preventive care., (Copyright © 2014 by the American Academy of Pediatrics.)

Secondary research with biospecimens acquired through clinical care and through research is often conducted without the informed consent of individuals from whom the specimens were acquired. While such uses are consistent with the current federal regulations, surveys of the general public suggest that many individuals would prefer more information and choice regarding research use of biospecimens. The federal government issued an Advance Notice of Proposed Rulemaking (ANPRM) in 2011 that proposed a number of potential changes in the regulations governing human subjects. These proposed regulations are particularly pertinent to institutions committed to research involving human subjects-including institutions in the NIH-funded Clinical and Translational Science Awards (CTSA) consortium. In this study, we reviewed public responses by CTSA-funded institutions and CTSA-affiliated organizations and groups regarding the proposed changes in the ANPRM with respect to research with biospecimens. Our results indicate that the majority of responses to the ANPRM from CTSA institutions were not supportive of the proposed changes. While many responses acknowledge a need to change current research practices regarding biospecimens, the proposed changes in the ANPRM received only limited support from this subgroup of academic research institutions., (© 2014 Wiley Periodicals, Inc.)

Background: Catch-up growth may predispose to obesity and metabolic sequelae. We sought to examine the trajectory and correlates of growth and catch up among extremely-low-birth-weight (ELBW) (<1 kg) adolescents., Methods: A cohort study of 148 neurologically normal ELBW children and 115 normal-birth-weight (NBW) controls born during the period 1992-1995 was conducted. Longitudinal measures of gender-specific growth of ELBW children from birth, in addition to growth and measures of obesity of ELBW and NBW children at 14 y, were evaluated., Results: Following neonatal growth failure, ELBW children had accelerated growth, but at 8 y, they still had lower weight and height z scores than NBW children. By 14 y, ELBW boys had caught up in growth to their NBW controls, but ELBW girls remained significantly smaller. ELBW children, however, did not differ from their controls in measures of obesity. In hierarchical multiple regression analyses, only maternal BMI and weight gain during infancy and childhood predicted the ELBW children's 14-y weight z scores, BMI z scores, and abdominal circumference. Perinatal risk factors, including intrauterine growth, only predicted growth up to 20 mo., Conclusion: Maternal BMI and rate of growth, rather than perinatal factors, predict 14-y obesity among neurologically normal ELBW adolescents.

IMPACT (Ideas Moving Parents and Adolescents to Change Together) is a 3-group randomized, multi-level trial comparing the efficacy of two distinct behavioral interventions and a control condition on body mass index (BMI) in middle school urban youth who are overweight/obese. Interventions include: (1) SystemCHANGE (SC), a promising new behavior change approach that focuses on system redesign of the family environment and daily routines; (2) HealthyCHANGE (HC), a cognitive-behavioral and Motivational Interviewing (MI)-consistent approach to behavior change that focuses on increasing intrinsic motivation, self-monitoring, goal setting, and problem solving; and (3) diet and physical education counseling (attention control). In addition, about half of the participants are enrolled in a K-8 public school that offers an innovative community-sponsored fitness program, augmented by study-supported navigators. In addition to the primary interventions effects, the study assesses the moderating effect of the school environment on BMI, blood pressure, cardiovascular risk factors, and quality of life. The sample consists of 360 children entering 6th grade from a large urban school district in the Midwest, identified through an existing BMI screening program. The intervention period is 36 months, and measures are obtained at baseline, 12, 24, and 36 months. Using intent-to-treat analyses across the 36-month intervention window, we hypothesize that both SC and HC will have a greater impact on BMI and other health outcomes compared to health education alone, and that the enriched school environment will enhance these effects. This manuscript describes IMPACT's study design and methods., (© 2013.)

Objective: To investigate insulin sensitivity and secretion indices and determinants of glycemic control in youth with recent-onset type 2 diabetes (T2DM) at randomization in the TODAY study, the largest study of youth with T2DM to date., Methods: We examined estimates of insulin sensitivity [1/fasting insulin (1/I(F)), fasting glucose/insulin (G(F) /I(F)), 1/fasting C-peptide (1/C(F)), G(F) /C(F)], β-cell function [insulinogenic index (ΔI30/ΔG30), and ΔC30/ΔG30], and disposition index (DI) in the TODAY cohort of 704 youth (14.0 ± 2.0 yr; diabetes duration 7.8 ± 5.8 months; 64.9% female; 41.1% Hispanic, 31.5% Black, 19.6% White, 6.1% American Indian, and 1.7% Asian) according to hemoglobin A1c (HbA1c) quartiles at study randomization. The randomization visit followed a run-in period (median 71 d) during which glycemic control (HbA1c ≤ 8% for at least 2 months) was achieved with metformin alone. These measures were also examined in relation to screening HbA1c levels before run-in., Results: Insulin secretion indices declined with increasing HbA1c quartiles, at randomization (ΔC30/ΔG30: 0.11 ± 0.09, 0.10 ± 0.19, 0.07 ± 0.06, and 0.03 ± 0.03 ng/mL per mg/dL, p < 0.0001; DI: 0.03 ± 0.03, 0.03 ± 0.05, 0.02 ± 0.02, and 0.01 ± 0.01 mg/dL(-1) , p < 0.0001) and at screening, with no significant difference in insulin sensitivity. There were no significant differences in estimates of insulin sensitivity or secretion between genders or across the different racial groups. At randomization and screening, HbA1c correlated with DI (r = -0.3, p < 0.001), with ΔC30/ΔG30, but not with insulin sensitivity estimates., Conclusions: In youth with recent-onset T2DM treated with metformin, glycemic control, as measured by HbA1c, appears to be associated with residual β-cell function and not insulin sensitivity., (© 2012 John Wiley & Sons A/S.)

Background: Despite the increasing prevalence of type 2 diabetes in youth, there are few data to guide treatment. We compared the efficacy of three treatment regimens to achieve durable glycemic control in children and adolescents with recent-onset type 2 diabetes., Methods: Eligible patients 10 to 17 years of age were treated with metformin (at a dose of 1000 mg twice daily) to attain a glycated hemoglobin level of less than 8% and were randomly assigned to continued treatment with metformin alone or to metformin combined with rosiglitazone (4 mg twice a day) or a lifestyle-intervention program focusing on weight loss through eating and activity behaviors. The primary outcome was loss of glycemic control, defined as a glycated hemoglobin level of at least 8% for 6 months or sustained metabolic decompensation requiring insulin., Results: Of the 699 randomly assigned participants (mean duration of diagnosed type 2 diabetes, 7.8 months), 319 (45.6%) reached the primary outcome over an average follow-up of 3.86 years. Rates of failure were 51.7% (120 of 232 participants), 38.6% (90 of 233), and 46.6% (109 of 234) for metformin alone, metformin plus rosiglitazone, and metformin plus lifestyle intervention, respectively. Metformin plus rosiglitazone was superior to metformin alone (P=0.006); metformin plus lifestyle intervention was intermediate but not significantly different from metformin alone or metformin plus rosiglitazone. Prespecified analyses according to sex and race or ethnic group showed differences in sustained effectiveness, with metformin alone least effective in non-Hispanic black participants and metformin plus rosiglitazone most effective in girls. Serious adverse events were reported in 19.2% of participants., Conclusions: Monotherapy with metformin was associated with durable glycemic control in approximately half of children and adolescents with type 2 diabetes. The addition of rosiglitazone, but not an intensive lifestyle intervention, was superior to metformin alone. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; TODAY ClinicalTrials.gov number, NCT00081328.).

Short stature is a common concern in pediatrics. Several ambiguities and controversies persist, especially with regard to criteria, cost, medical necessity and outcomes of growth hormone (GH) therapy for idiopathic short stature (ISS). Due to these ambiguities and controversies, a series of decisions by primary care physicians (whether to refer the short child to a pediatric endocrinologist), pediatric endocrinologist (whether to recommend GH treatment), families (whether to raise concern about short stature and whether to agree to undertake treatment), and third party payers (whether to cover the costs of GH therapy) influence which individual short children will receive GH in the US. Together, these decisions determine overall GH use. Apart from child's growth characteristics, several non-physiological factors drive the critical decisions of these stakeholders. This article focuses on current ambiguities and controversies regarding GH therapy in ISS, discusses the decision-makers involved in GH therapy, and explores the factors influencing their decisions.

Background: Many investigators are concerned that the modes of implementation and enforcement of the federal regulations designed to protect children are unduly impeding pediatric clinical research., Objective: To assess regulatory impediments to clinical research involving children and to develop recommendations to ameliorate them., Participants: The Pediatric Endocrine Society and The Endocrine Society convened a consensus conference involving experts and stakeholders in patient-oriented research involving children and adolescents in 2008., Consensus Process: Following presentations that reviewed problematic issues around key regulations, participants divided into working groups to develop potential solutions that could be adopted at local and federal levels. Presentations to the full assembly were then debated. A writing committee then drafted a summary of the discussions and main conclusions, placing them in historical context, and submitted it to all participants for comment with the aim of developing consensus., Conclusions: Recommendations designed to facilitate the ethical conduct of research involving children addressed the interpretation of ambiguous regulatory terms such as "minimal risk" and "condition" and called for the development by professional societies of best practice primers for common research procedures that would be informative to both investigators and institutional review boards. A call was issued for improved guidance from the Office for Human Research Protections and Food and Drug Administration as well as for the development by professional societies of a process to monitor progress in improving human subject research regulation. Finally, a need for systematic research to define the nature and extent of institutional obstacles to pediatric research was recognized.

Context: Extremely low-birth-weight (ELBW) children have high rates of chronic conditions during childhood. Information on their trajectory of health during adolescence is needed for health care planning., Objective: To examine changes in the rates of chronic conditions between the ages of 8 and 14 years among ELBW children compared with normal-birth-weight (NBW) controls., Design, Setting, and Participants: Cohort study conducted from 2004 through 2009 of 181 ELBW children (weight < 1 kg) and 115 NBW controls of similar sociodemographic status born from 1992 through 1995 in Cleveland, Ohio., Main Outcome Measures: Rates of chronic conditions overall (measured with the revised Questionnaire for Identifying Children With Chronic Conditions) and rates of asthma and obesity., Results: The overall rates of chronic conditions did not change significantly between the ages of 8 and 14 years among ELBW children (75% at age 8 years vs 74% at age 14 years) or NBW controls (37% at age 8 years vs 47% at age 14 years). In generalized estimating equations logistic regression adjusting for sociodemographic status, sex, and race, ELBW children continued to have a higher rate of chronic conditions than NBW controls at age 14 years (74% vs 47%, respectively, adjusted odds ratio [AOR], 2.8 [95% confidence interval {CI}, 1.7 to 4.6]). Rates of asthma requiring medication did not change between the ages of 8 and 14 years among ELBW children (23% at both ages) but increased among NBW controls from 8% at age 8 years to 17% at age 14 years (P = .002). Differences in rates of asthma between ELBW and NBW children were no longer significant at the age of 14 years (23% vs 17%, respectively; AOR, 1.5 [95% CI, 0.8 to 2.8]). Mean z scores for body mass index increased in ELBW children from 0.06 at age 8 years to 0.38 at age 14 years (P <.001) and rates of obesity increased from 12% at age 8 years to 19% at age 14 years (P = .02). However, the scores and rates did not change among NBW controls such that at the age of 14 years the differences between ELBW and NBW children in mean z scores for body mass index (0.38 vs 0.56, respectively; adjusted mean difference -0.2 [95% CI, -0.5 to 0.1]) or rates of obesity (19% vs 20%, respectively; AOR, 1.1 [95% CI, 0.6 to 2.0]) were not significant., Conclusions: Among ELBW children, rates of overall chronic conditions and asthma did not change between the ages of 8 and 14 years but the rate of obesity increased. Compared with NBW controls, the rates of chronic conditions were higher but there were no significant differences in the rates of asthma or obesity.

Objectives: Overall growth hormone (GH) use depends on decisions to both initiate treatment and continue treatment. The determinants of both are unclear. We studied how physicians decided to begin GH in idiopathic short stature and how, after an initial course of treatment, they decided to continue, intensify (increase the dose), or terminate treatment., Methods: We used a national census study of 727 pediatric endocrinologists involving a structured questionnaires with a factorial experimental design. Main outcome measures were GH recommendations for previously untreated children and those children who were treated with GH for 1 year., Results: The response rate was 90%. In previously untreated children, recommendations to initiate GH were consistent with guidelines and also influenced by family preferences and physician attitudes (P<.001). In children treated with GH, recommendations on whether to continue GH were influenced by the growth response to therapy (P<.01) but were divided regarding course of action. With identical growth responses to treatment, physician decisions diverged (intensify versus discontinue GH) and were driven by independent, nonphysiologic, and contextual factors (eg, physician attitudes, family preferences, and GH-initiation recommendation; each P<.001). Together, attitudinal and contextual factors exerted more influence on continuation decisions than did the growth response to therapy., Conclusions: Physician decisions to initiate GH are largely consistent with evidence-based medicine. However, decisions about continuing GH vary and are strongly influenced by factors other than response to treatment. With a potential market of 500 000 US children and costs exceeding $10 billion per year, changes in GH use may depend on potentially modifiable physician attitudes and family preferences as much as physiologic evidence.

GH treatment for short children is representative of many frontline issues in health care policy. In this paper, we highlight key policy issues exemplified by GH, focusing on pharmaceutical innovation, insurance coverage and pricing, and physician decisions, and we discuss their implications for endocrinology and GH use.

Objective: The study examined the influence of parent involvement and family factors on body mass index (BMI) change in a pediatric obesity treatment program., Methods: A total of 104 children and their caregivers were examined during a 12-week obesity intervention. Participants (mean age = 11.42 years; SD = 2.83) and their caregivers completed measures of family environment and depression prior to enrollment. Children's BMI and parental involvement were rated weekly during the intervention. Logistic regressions were conducted to examine the role of sociodemographic factors, family characteristics, and parent involvement on weight., Results: Children with the lowest parent involvement were less likely to lose any weight or have clinically significant (>or=2 kg) weight loss. Demographics and family factors did not predict BMI change. Parent involvement related to ethnicity, absences and physical activity., Conclusions: Parental involvement may be helpful in identifying who is likely to do well in a weight loss program.

OBJECTIVE The American Diabetes Association advocates insulin regimens for youth with type 1 diabetes that involve adjusting insulin dose based on carbohydrate intake and blood glucose level. Implementing these regimens requires knowledge about carbohydrate content of foods and subsequent calculations of insulin dose, skills that may be difficult to gauge in practice. Therefore, we sought to develop and validate a questionnaire, the PedCarbQuiz (PCQ), to assess carbohydrate and insulin-dosing knowledge in youth with type 1 diabetes. RESEARCH DESIGN AND METHODS After development by an expert panel, the PCQ was administered to 75 youth with type 1 diabetes or their parents. Reliability was assessed by Cronbach alpha and split-half testing. To assess validity, scores were correlated with A1C, expert assessments, parent educational level, and complexity of insulin regimen. RESULTS PCQ mean score was 87 +/- 9.7% (range 42-98%). Cronbach alpha was 0.88, and correlation of split halves was 0.59 (P < 0.0001). Higher PCQ scores correlated significantly with lower A1C (r = -0.29, P = 0.01) and expert assessments (r = 0.56, P < 0.001). Scores were significantly higher in parents with college degrees than in those without (P = 0.01) and in participants with more complex insulin regimens (P = 0.003). CONCLUSIONS The PCQ is a novel, easily administered instrument to assess knowledge about carbohydrates and insulin dosing calculations. Initial analyses support the reliability and validity of the PCQ.

Background: Candidates for specialty drugs, the fastest growing and costliest pharmaceuticals, typically originate with primary care referrals. However, little is known about what drives such referrals-especially for large populations such as short, otherwise normal children (idiopathic short stature). Recent expanded approval of growth hormone (GH) makes more than 585,000 US children eligible for such treatment, potentially costing over $11 billion/y., Methods: To quantify the relative impact of patient physiological indicators, physician characteristics, and consumer preferences on referrals to endocrinologists (and potential access to GH) for short children, a national study of 1268 randomly selected US pediatricians was conducted, based on a full factorial experimental design in a structured survey., Results: While patient indicators (height, growth pattern) influenced referrals (P < 0.001), consumer drivers (family concern) and physician attitudes had almost as great an impact-especially for children with less severe growth impairment (P < 0.001). Physician belief that short stature impairs emotional well-being and physician characteristics (female, older, shorter, beliefs about drug company information) increased referrals (P < 0.03-0.001)-independent of growth parameters., Conclusions: Referral recommendations that create the pool of candidates for the specialty drug GH are heavily swayed by physician characteristics and consumer preferences, particularly in the absence of compelling physiological evidence. This makes most of children with short stature strikingly susceptible to nonphysiological influences on referrals that render them candidates for this specialty drug. Only 1 additional referral per US pediatrician would likely increase GH costs by over $100 million/y.

Background: Delivery of GH via inhalation is a potential alternative to injection. Previous studies of inhaled GH in adults have demonstrated safety and tolerability., Objective: We sought to assess safety and tolerability of inhaled GH in children and to estimate relative bioavailability and biopotency between inhaled GH and sc GH., Design/methods: This pediatric multicenter, randomized, double-blind, placebo-controlled, crossover trial had two 7-d treatment phases. Patients received inhaled GH and sc GH in the alternate phase. Placebo was administered by the route opposite from active drug. GH and IGF-I levels were measured at multiple time points. Pharmacokinetics were assessed using noncompartmental methods., Results: Twenty-two GH-deficient children aged 6-16 yr were treated. Absorption of GH appeared to be faster after inhalation with maximum serum concentrations measured at 1-4 h compared with 2-8 h for sc GH. Mean relative bioavailability for inhaled GH was 3.5% (90% confidence interval 2.7-4.4%). Mean relative biopotency, based on IGF-I response, was 5.5% (confidence interval 5.2-5.8%). Similar dose-dependent increases in mean serum GH area under the curve and IGF-I changes from baseline were seen after inhaled and sc GH doses. Inhaled GH was well tolerated and preferred to injection. No significant changes in pulmonary function tests were seen., Conclusions: In this first pediatric trial of GH delivered by inhalation, it was well tolerated and resulted in dose-dependent increases in serum GH and IGF-I levels. This study establishes that delivery of GH via the deep lung is feasible in children.

Purpose of Review: To provide an overview of treatments for childhood obesity, highlighting recent advances and recommendations., Recent Findings: The three main treatment modalities are lifestyle interventions, medications, and bariatric surgery. Recent data support the short-term effectiveness of lifestyle interventions, and show that continued behavioral intervention increases the likelihood of a sustained effect for up to 2 years. New studies and regulatory decisions on medications for obesity (including orlistat, sibutramine, and metformin) are discussed. Emerging data suggest substantial weight loss after bariatric surgery in morbidly obese adolescents but also indicate adverse effects. An expert panel recently provided guidelines that alter definitions of obesity and offer a framework for obesity management. These guidelines are compared with others, and integrated recommendations presented., Summary: While primary prevention of childhood obesity is important, broadly effective methods to do so are not yet available. Given the large population of obese children and the risks they face, an emphasis on treatment is also critical. We suggest a staged approach, emphasizing early intervention and lifestyle changes. We also suggest limiting bariatric surgery to selected adolescents in Institutional Review Board-approved research studies. Health-policy interventions can facilitate both prevention and treatment of childhood obesity.

The GHRH receptor is expressed in the somatotroph cell of the anterior pituitary, where it functions to mediate GHRH-stimulated GH release. To study pituitary and somatotroph cell-specific expression of this gene, a transgenic mouse model and complementary cell culture experiments were developed. The activity of the 1.6-kb proximal rat GHRH receptor promoter was examined in vivo by generating transgenic mice with the promoter directing expression of a luciferase reporter. The promoter directs tissue-specific expression; luciferase is highly expressed in the pituitary but absent from 14 other tissues. Immunocytochemistry experiments show that transgene expression is targeted to GH-expressing somatotroph cells. The transgene is 5-fold more highly expressed in males than females, and there is an increase in transgene expression leading up to the onset of puberty. The 1.6-kb promoter was further examined in cell culture experiments, which revealed that the promoter is selectively activated in pituitary cells and that promoter-reporter expression in nonpituitary cells can be enhanced by the pituitary-specific transcription factor Pit-1. EMSAs identified 10 short regions that specifically bind Pit-1 with highly variable relative affinities. The highest affinity site was previously identified and is required for Pit-1 activation of the promoter. Four additional sites contribute to Pit-1 regulation of the promoter and are important to achieving full activation of the gene. The results show that the 1.6-kb promoter is sufficient to direct tissue- and cell-specific expression in vivo and is regulated by Pit-1.

The best treatment option for children with Type 2 diabetes has not yet been established. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study is currently testing the efficacy of three therapies: metformin, metformin plus rosiglitazone and metformin plus an intensive lifestyle intervention. The relative cost-effectiveness of these therapies is also being examined. This review discusses the rationale for the design and methods applied in the economic analysis. The design of the economic analysis in the TODAY study was influenced by the existing literature and two primary study parameters: the nature of the interventions and the participants' age. The lifestyle intervention is an intensive behavioral intervention comprising diet and physical activity. Since economic factors influence both diet and physical activity, the analytical plan includes measurement of food and exercise-related purchases. Due to the young age of the participants, the impact of the intervention on adult caregivers is also included in the analysis. This analysis focuses on the time spent by the caregivers in both medical treatment and nutrition- and activity-related activities, and the value of this time relative to usual activities. Important methodological questions include how and when to collect information, not only on medical costs, but also on the impact of caregiver time, travel, food and equipment purchases. In the TODAY study, these latter resources are being measured by regularly administered surveys completed by the caregivers. The approach to the cost-effectiveness assessment undertaken by the TODAY study is one of the first in diabetes research to focus on youth and to include a societal perspective, regular and prospective assessment of clinician and caregiver time, and a comprehensive assessment of the costs associated with lifestyle behaviors. It can serve as a model for future studies of diabetes treatments.

Background: Physician decisions to discontinue prescription medications for chronic conditions are fundamental determinants of drug use but have been inadequately studied. The decision to stop growth hormone (GH) therapy is an important example because of high cost (approximately $26,000/y for a 48-kg child), complexity of treatment options, and expansion of patient populations., Aim: The aim of this study was to identify the factors that influence physician recommendations in the process of discontinuing therapy., Design: A random sample of half of U.S. pediatric endocrinologists (n = 265) was mailed a survey that included case scenarios of GH-deficient adolescents. Decision options involved a 2-stage framework to 1) initiate change in ongoing GH therapy (by discussing discontinuing GH with the family but not yet stopping treatment), and 2) take action to discontinue ongoing GH therapy (by terminating GH or reducing the dose to adult maintenance level)., Main Outcome Measure: Physician recommendations., Results: The response rate was 83.8%. Physiological indices of growth potential (growth velocity, bone age) significantly influenced discontinuation decisions (both P < 0.001). However, family preference, child's height, and physician attitudes exerted independent effects (each P < 0.05). Treatment price had little influence. Together, these variables accounted for 60% to 70% of the variation in recommendations. Their relative influence differed by stage in the discontinuation process., Conclusion: The variables in our framework substantially explain discontinuation decisions. The data demonstrate the importance of both physiological and nonphysiological factors. The results suggest that physicians value even small gains as final height approaches, although an additional 20% expenditure may be needed to gain the last 1% to 3% of adult height.

The diagnostic term, idiopathic short stature, has emerged over the past 30 years and refers to children with short stature of unknown etiology. Controversy exists regarding the scope of the diagnosis and options for its treatment. This article reviews origins of the diagnosis idiopathic short stature and current diagnostic criteria, scientific advances in delineating etiologies of idiopathic short stature, management options, and implications of management decisions for child health.