To Prescribe or Not to Prescribe? Consumer Access to Life-Enhancing Products.

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.

Rehospitalization during the first year of life by insurance status.

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.

Practice-tailored facilitation to improve pediatric preventive care delivery: a randomized trial.

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.

Proposed regulations for research with biospecimens: responses from stakeholders at CTSA consortium institutions.

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.

Trajectory and correlates of growth of extremely-low-birth-weight adolescents.

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: a multi-level family and school intervention targeting obesity in urban youth.

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.

A clinical trial to maintain glycemic control in youth with type 2 diabetes.

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.).

Determinants of glycemic control in youth with type 2 diabetes at randomization in the TODAY study.

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)], ß-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 ß-cell function and not insulin sensitivity.

Idiopathic short stature: decision making in growth hormone use.

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.

Change in prevalence of chronic conditions between childhood and adolescence among extremely low-birth-weight children.

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.

Overcoming burdens in the regulation of clinical research in children. Proceedings of a consensus conference, in historical context.

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.

A national study of physician recommendations to initiate and discontinue growth hormone for short stature.

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.

The presence of GAD and IA-2 antibodies in youth with a type 2 diabetes phenotype: results from the TODAY study.

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.

Growth hormone and health policy.

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.

Development and validation of a questionnaire to assess carbohydrate and insulin-dosing knowledge in youth with type 1 diabetes.

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.