Core Outcome Sets for Medium-Chain Acyl-CoA Dehydrogenase Deficiency and Phenylketonuria.

BACKGROUND: Evidence to guide treatment of pediatric medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency and phenylketonuria (PKU) is fragmented because of large variability in outcome selection and measurement. Our goal was to develop core outcome sets (COSs) for these diseases to facilitate meaningful future evidence generation and enhance the capacity to compare and synthesize findings across studies. METHODS: Parents and/or caregivers, health professionals, and health policy advisors completed a Delphi survey and participated in a consensus workshop to select core outcomes from candidate lists of outcomes for MCAD deficiency and PKU. Delphi participants rated the importance of outcomes on a nine-point scale (1-3: not important, 4-6: important but not critical, 7-9: critical). Candidate outcomes were progressively narrowed down over 3 survey rounds. At the workshop, participants evaluated the remaining candidate outcomes using an adapted nominal technique, open discussion, and voting. After the workshop, we finalized the COSs and recommended measurement instruments for each outcome. RESULTS: There were 85, 61, and 53 participants across 3 Delphi rounds, respectively. The candidate core outcome lists were narrowed down to 20 outcomes per disease to be discussed at the consensus workshop. Voting by 18 workshop participants led to COSs composed of 8 and 9 outcomes for MCAD deficiency and PKU, respectively, with measurement recommendations. CONCLUSIONS: These are the first known pediatric COSs for MCAD deficiency and PKU. Adoption in future studies will help to ensure best use of limited research resources to ultimately improve care for children with these rare diseases.

Outcomes in pediatric studies of medium-chain acyl-coA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU): a review.

BACKGROUND: Inherited metabolic diseases (IMDs) are a group of individually rare single-gene diseases. For many IMDs, there is a paucity of high-quality evidence that evaluates the effectiveness of clinical interventions. Clinical effectiveness trials of IMD interventions could be supported through the development of core outcome sets (COSs), a recommended minimum set of standardized, high-quality outcomes and associated outcome measurement instruments to be incorporated by all trials in an area of study. We began the process of establishing pediatric COSs for two IMDs, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU), by reviewing published literature to describe outcomes reported by authors, identify heterogeneity in outcomes across studies, and assemble a candidate list of outcomes. METHODS: We used a comprehensive search strategy to identify primary studies and guidelines relevant to children with MCAD deficiency and PKU, extracting study characteristics and outcome information from eligible studies including outcome measurement instruments for select outcomes. Informed by an established framework and a previously published pediatric COS, outcomes were grouped into five, mutually-exclusive, a priori core areas: growth and development, life impact, pathophysiological manifestations, resource use, and death. RESULTS: For MCAD deficiency, we identified 83 outcomes from 52 articles. The most frequently represented core area was pathophysiological manifestations, with 33 outcomes reported in 29/52 articles (56%). Death was the most frequently reported outcome. One-third of outcomes were reported by a single study. The most diversely measured outcome was cognition and intelligence/IQ for which eight unique measurement instruments were reported among 14 articles. For PKU, we identified 97 outcomes from 343 articles. The most frequently represented core area was pathophysiological manifestations with 31 outcomes reported in 281/343 articles (82%). Phenylalanine concentration was the most frequently reported outcome. Sixteen percent of outcomes were reported by a single study. Similar to MCAD deficiency, the most diversely measured PKU outcome was cognition and intelligence/IQ with 39 different instruments reported among 82 articles. CONCLUSIONS: Heterogeneity of reported outcomes and outcome measurement instruments across published studies for both MCAD deficiency and PKU highlights the need for COSs for these diseases, to promote the use of meaningful outcomes and facilitate comparisons across studies.

Ambulation of patients who are mechanically ventilated: nurses' views.

Aims Equipment and skills in intensive care have advanced dramatically, and early rehabilitation and ambulation for patients in intensive care units (ICUs) are part of their journey to recovery. The aim of this study is to understand better nurses' perspectives on ambulating mechanically ventilated patients, and to determine why this is not a routine part of ICU patient care. Method Interpretative phenomenological analysis was used to extract data from semi-structured interviews. The questions were piloted twice before being used in the main study. Results Two overarching themes, staff anxiety and organisational culture, were identified, within which there are several subthemes. The study also found that education and training programmes could increase staff confidence and consequently result in routine ambulation of mechanically ventilated patients. Conclusion The study identified that nursing staff are aware of the benefits of ambulation for patients in ICUs, but the personal satisfaction gained from undertaking this activity does not outweigh the anxiety it causes. This is compounded by the organisational culture of ICUs; for example, the hierarchical pyramid of leadership, which dictates that consultants decide when patients are ready to ambulate.

Multicollinearity is a red herring in the search for moderator variables: A guide to interpreting moderated multiple regression models and a critique of Iacobucci, Schneider, Popovich, and Bakamitsos (2016).

Multicollinearity is irrelevant to the search for moderator variables, contrary to the implications of Iacobucci, Schneider, Popovich, and Bakamitsos (Behavior Research Methods, 2016, this issue). Multicollinearity is like the red herring in a mystery novel that distracts the statistical detective from the pursuit of a true moderator relationship. We show multicollinearity is completely irrelevant for tests of moderator variables. Furthermore, readers of Iacobucci et al. might be confused by a number of their errors. We note those errors, but more positively, we describe a variety of methods researchers might use to test and interpret their moderated multiple regression models, including two-stage testing, mean-centering, spotlighting, orthogonalizing, and floodlighting without regard to putative issues of multicollinearity. We cite a number of recent studies in the psychological literature in which the researchers used these methods appropriately to test, to interpret, and to report their moderated multiple regression models. We conclude with a set of recommendations for the analysis and reporting of moderated multiple regression that should help researchers better understand their models and facilitate generalizations across studies.

Confirmatory factor analysis of the Reynolds Intellectual Assessment Scales (RIAS) in Canadian children.

The purpose of the current study was to assess the validity of the Reynolds Intellectual Assessment Scale's (RIAS) index and subtest scores by examining whether the RIAS conforms to Carroll's ( 1993 ) three-stratum theory of cognitive ability and the Cattell-Horn Gf-Gc (Horn & Cattell, 1966 ) theory of intelligence upon which it was based. Factor structures of RIAS scores from typically developing (n = 187) and mixed clinical groups (n = 164), 4-18 years old, were compared using confirmatory factor analysis. The results were mixed, with some findings supporting the validity of the Composite Intelligence Index (CIX), Nonverbal Intelligence Index (NIX), and Verbal Intelligence Index (VIX) while others suggested that the CIX and NIX in particular should be interpreted with caution, depending on the population in which the RIAS is being used. The functioning of the two nonverbal subtests in all analyses suggested that the RIAS's nonverbal subtests are most problematic, with the greatest impact on the RIAS's validity as a measure of overall, verbal, and nonverbal intelligence. The RIAS's use as a general cognitive screener is supported but caution is recommended if the RIAS is being used to make important diagnostic, qualification for services, forensic, or placement decisions.

Implementing peer-assisted case management to help homeless veterans with mental illness transition to independent housing.

Formerly homeless mentally ill veterans are at an important crossroads when they move from living in an institutional setting such as a shelter or supportive residential facility to independent living. We hypothesized that peer advisors, veterans with severe mental illness who had been homeless previously, graduated from a Healthcare for Homeless Veterans program, and subsequently maintained independent, stable housing could assist other veterans make a successful transition to independent living. Pilot data suggests that participants who received peer advisors were more likely to follow up with assessments than were controls. In this report, we describe a pilot peer advisor program, its implementation, and pilot data on program administration.

Response Mode Effects and Moral Values.

In five studies, we measured the extent to which subjects weight moral product attributes in different response modes. We found that nonprice judgments such as likelihood of purchase ratings were more reflective of expressed moral attitudes than were pricing responses, and that holistic price evaluations were especially unlikely to reflect moral considerations. Post-task ratings confirmed the preference results, as did an experiment controlling for the influence of task goals. Our results have implications for compatibility theories of preference elicitation, the predictability of respondent ratings of attribute unacceptability, and the measurement of utilities for morally charged attributes. Copyright 2001 Academic Press.