Measuring kindergarteners’ motivational beliefs about writing: a mixed-methods exploration of alternate assessment formats

There have been a handful of studies on kindergarteners’ motivational beliefs about writing, yet measuring these beliefs in young children continues to pose a set of challenges. The purpose of this exploratory, mixed-methods study was to examine how kindergarteners understand and respond to different assessment formats designed to capture their motivational beliefs about writing. Across two studies, we administered four assessment formats — a 4-point Likert-type scale survey, a binary choice survey, a challenge preference task, and a semi-structured interview — to a sample of 114 kindergarteners engaged in a larger writing intervention study. Our overall goals were to examine the benefits and challenges of using these assessment formats to capture kindergarteners’ motivational beliefs and to gain insight on future directions for studying these beliefs in this young age group. Many participants had a difficult time responding to the 4-point Likert-type scale survey, due to challenges with the response format and the way the items were worded. However, more simplified assessment formats, including the binary choice survey and challenge preference task, may not have fully captured the nuances and complexities of participants’ motivational beliefs. The semi-structured interview leveraged participants’ voices and highlighted details that were overlooked in the other assessment formats. Participants’ interview responses were deeply intertwined with their local, everyday experiences and pushed back on common assumptions of what constitutes negatively oriented motivational beliefs about writing. Overall, our results suggest that kindergarteners’ motivational beliefs appear to be multifaceted, contextually grounded, and hard to quantify. Additional research is needed to further understand how motivational beliefs are shaped during kindergarten. We argue that motivational beliefs must be studied in context rather than in a vacuum, in order to work toward a fair and meaningful understanding of motivational beliefs about writing that can be applied to school settings

Developing interactions with industry in rare diseases: lessons learned and continuing challenges.

The National Institutes of Health (NIH) established the Rare Diseases Clinical Research Network to address the unique challenges of performing research on rare diseases. The Urea Cycle Disorders Consortium (UCDC) was one of the original ten consortia established. The UCDC represents a unique partnership among clinicians, patients, and the NIH with a primary goal of increasing the development of therapeutics that improve patient outcomes for persons affected with a UCD. Based in part on financial incentives associated with the Orphan Drug Act biopharmaceutical and investment entities have an intense interest in engaging with research consortia like the UCDC, which have compiled potentially valuable longitudinal data characterizing outcomes in a relatively large number of affected individuals. We describe the UCDC experience and the bases for evaluating partnerships with such private entities. We review early industry interactions, the development of policies and procedures, and describe the establishment of an Industry Relations Committee, including guiding principles. Challenges encountered, particularly in the transition when products are approved, and potential solutions are discussed. By building a framework for industry partnerships that guides us in resolving inevitable challenges, we can enthusiastically pursue novel and promising collaborations that can lead to breakthroughs in therapeutic interventions for patients

Glycerol phenylbutyrate treatment in children with urea cycle disorders: Pooled analysis of short and long-term ammonia control and outcomes

OBJECTIVE: To evaluate glycerol phenylbutyrate (GPB) in the treatment of pediatric patients with urea cycle disorders (UCDs). STUDY DESIGN: UCD patients (n=26) ages 2months through 17years were treated with GPB and sodium phenylbutyrate (NaPBA) in two short-term, open-label crossover studies, which compared 24-hour ammonia exposure (AUC0-24) and glutamine levels during equivalent steady-state dosing of GPB and sodium phenylbutyrate (NaPBA). These 26 patients plus an additional 23 patients also received GPB in one of three 12-month, open label extension studies, which assessed long-term ammonia control, hyperammonemic (HA) crises, amino acid levels, and patient growth. RESULTS: Mean ammonia exposure on GPB was non-inferior to NaPBA in each of the individual crossover studies. In the pooled analyses, it was significantly lower on GPB vs. NaPBA (mean [SD] AUC0-24: 627 [302] vs. 872 [516] μmol/L; p=0.008) with significantly fewer abnormal values (15% on GPB vs. 35% on NaPBA; p=0.02). Mean ammonia levels remained within the normal range during 12months of GPB dosing and, when compared with the 12months preceding enrollment, a smaller percentage of patients (24.5% vs. 42.9%) experienced fewer (17 vs. 38) HA crises. Glutamine levels tended to be lower with GPB than with NaPBA during short-term dosing (mean [SD]: 660.8 [164.4] vs. 710.0 [158.7] μmol/L; p=0.114) and mean glutamine and branched chain amino acid levels, as well as other essential amino acids, remained within the normal range during 12months of GPB dosing. Mean height and weight Z-scores were within normal range at baseline and did not change significantly during 12months of GPB treatment. CONCLUSIONS: Dosing with GPB was associated with 24-hour ammonia exposure that was non-inferior to that during dosing with NaPBA in individual studies and significantly lower in the pooled analysis. Long-term GPB dosing was associated with normal levels of glutamine and essential amino acids, including branched chain amino acids, age-appropriate growth and fewer HA crises as compared with the 12month period preceding enrollment

Ammonia control and neurocognitive outcome among urea cycle disorder patients treated with glycerol phenylbutyrate

BACKGROUND: Glycerol phenylbutyrate is under development for treatment of urea cycle disorders (UCDs), rare inherited metabolic disorders manifested by hyperammonemia and neurological impairment. METHODS: We report the results of a pivotal phase 3, randomized, double-blind, crossover trial comparing ammonia control, assessed as 24-hour area under the curve (NH(3)-AUC(0-24hr)), and pharmacokinetics during treatment with glycerol phenylbutyrate versus sodium phenylbutyrate (NaPBA) in adult UCD patients and the combined results of 4 studies involving short- and long-term glycerol phenylbutyrate treatment of UCD patients ages 6 and above. RESULTS: Glycerol phenylbutyrate was non-inferior to NaPBA with respect to ammonia control in the pivotal study, with mean (SD) NH(3)-AUC(0-24hr) of 866 (661) versus 977 (865) μmol·h/L for glycerol phenylbutyrate and NaPBA, respectively. Among 65 adult and pediatric patients completing 3 similarly designed short term comparisons of glycerol phenylbutyrate versus NaPBA, NH(3)-AUC(0-24hr) was directionally lower on glycerol phenylbutyrate in each study, similar among all subgroups, and significantly lower (p<0.05) in the pooled analysis, as was plasma glutamine. The 24-hour ammonia profiles were consistent with slow release behavior of glycerol phenylbutyrate and better overnight ammonia control. During 12 months of open label glycerol phenylbutyrate treatment, average ammonia was normal in adult and pediatric patients and executive function among pediatric patients, including behavioral regulation, goal setting, planning and self-monitoring, was significantly improved. CONCLUSIONS: Glycerol phenylbutyrate exhibits favorable pharmacokinetics and ammonia control relative to NaPBA in UCD patients, and long-term glycerol phenylbutyrate treatment in pediatric patients was associated with improved executive function (ClinicalTrials.gov NCT00551200, NCT00947544, NCT00992459, NCT00947297)

Ammonia control and neurocognitive outcome among urea cycle disorder patients treated with glycerol phenylbutyrate

UnlabelledGlycerol phenylbutyrate is under development for treatment of urea cycle disorders (UCDs), rare inherited metabolic disorders manifested by hyperammonemia and neurological impairment. We report the results of a pivotal Phase 3, randomized, double-blind, crossover trial comparing ammonia control, assessed as 24-hour area under the curve (NH3 -AUC0-24hr ), and pharmacokinetics during treatment with glycerol phenylbutyrate versus sodium phenylbutyrate (NaPBA) in adult UCD patients and the combined results of four studies involving short- and long-term glycerol phenylbutyrate treatment of UCD patients ages 6 and above. Glycerol phenylbutyrate was noninferior to NaPBA with respect to ammonia control in the pivotal study, with mean (standard deviation, SD) NH3 -AUC0-24hr of 866 (661) versus 977 (865) μmol·h/L for glycerol phenylbutyrate and NaPBA, respectively. Among 65 adult and pediatric patients completing three similarly designed short-term comparisons of glycerol phenylbutyrate versus NaPBA, NH3 -AUC0-24hr was directionally lower on glycerol phenylbutyrate in each study, similar among all subgroups, and significantly lower (P &lt; 0.05) in the pooled analysis, as was plasma glutamine. The 24-hour ammonia profiles were consistent with the slow-release behavior of glycerol phenylbutyrate and better overnight ammonia control. During 12 months of open-label glycerol phenylbutyrate treatment, average ammonia was normal in adult and pediatric patients and executive function among pediatric patients, including behavioral regulation, goal setting, planning, and self-monitoring, was significantly improved.ConclusionGlycerol phenylbutyrate exhibits favorable pharmacokinetics and ammonia control relative to NaPBA in UCD patients, and long-term glycerol phenylbutyrate treatment in pediatric UCD patients was associated with improved executive function (ClinicalTrials.gov NCT00551200, NCT00947544, NCT00992459, NCT00947297). (HEPATOLOGY 2012)

Establishing a consortium for the study of rare diseases: The Urea Cycle Disorders Consortium

The Urea Cycle Disorders Consortium (UCDC) was created as part of a larger network established by the National Institutes of Health to study rare diseases. This paper reviews the UCDC's accomplishments over the first 6years, including how the Consortium was developed and organized, clinical research studies initiated, and the importance of creating partnerships with patient advocacy groups, philanthropic foundations and biotech and pharmaceutical companies