Central versus local adjudication of myocardial infarction in a cardiac biomarker trial.

OBJECTIVES: The impact of regulatory requirements, which require central adjudication for the diagnosis of acute myocardial infarction (AMI) in cardiac biomarker studies, is unclear. We determined the impact of local (at the site of subject enrollment) versus central adjudication of AMI on final diagnosis. METHODS: This is a retrospective analysis of data from the Myeloperoxidase in the Diagnosis of Acute Coronary Syndromes Study, an 18-center prospective study of patients with suspected acute coronary syndromes, with enrollment from December 19, 2006, to September 20, 2007. Local adjudication of AMI was performed by a single site investigator at each center following the protocol-specified definition and according to the year 2000 definition of AMI, which based cardiac troponin (cTn) elevation on local cut points for each of the 13 different assays. After completion of the Myeloperoxidase in the Diagnosis of Acute Coronary Syndromes Study primary analysis and to evaluate a new troponin assay, a Food and Drug Administration-mandated central adjudication was performed by 3 investigators at different institutions. This adjudication used the 2007 Universal Definition of AMI, which differs by use of the manufacturer's 99th percentile cTn cut point. We describe the outcome of this process and compare it with the local adjudication. Central adjudicators were not blinded to local adjudications. For central adjudication, discrepant diagnoses were resolved by consensus. Local versus central cTn cut points differed for 6 assays. Both definitions required a rise and/or fall of cTn. Discrepant cases were reviewed by the lead author. Difficult cases were defined as having a difference between local and central adjudication, an elevated cTn with a temporal rise and fall, and a negative or absent risk stratification test. Statistics were by χ(2), κ, and logistic regression. RESULTS: Of 1,107 patients enrolled, 11 had indeterminate central adjudication, leaving 1,096 for analysis. In spite of high agreement across central versus local adjudicators, κ = 0.79 (95% CI [0.73, 0.85]), AMI was diagnosed more often by central adjudication, 134 (12.2%) versus 104 (9.5%), with 44 local diagnoses (4%) changed from non-AMI to AMI (n = 37) or AMI to non-AMI (n = 7) (P < .001). These 44 represented 34% (95% CI 26%-42%) of 141 cases in which either central or local adjudication was AMI. Of diagnoses changed to AMI, 3 reasons contributed approximately one-third each: the local use of a non-99th percentile cTn cutoff (32%), the possibility of human error (34%), and difficult cases (34%). CONCLUSION: Despite an acceptable κ, over a third of patients with a diagnosis of AMI were not assigned that diagnosis by both sets of adjudicators. This supports the importance of 1 standard method for diagnosis of AMI.

Childhood peer reputation as a predictor of competence and symptoms 10 years later.

This study examined the differential developmental significance of multiple domains of peer reputation in childhood for current and future competence and symptoms. Participants were 205 children from a normative school cohort who completed assessments in grades 3-6 and then again 10 years later. Through re-analysis of original data from the Revised Class Play (RCP; N=612), new narrow-band subscales were examined as distinct correlates and predictors of competence in age-relevant developmental tasks and psychological well being as indexed by internalizing symptoms. Findings support the differentiation of peer exclusion, withdrawal, and sadness within the broad sensitive-isolated domain of reputation, as well as the distinctive meaning of reputations for Popularity-Leadership and Prosocial Behavior within the broad Sociable-Leader domain. When the Sensitive-Isolated predictors were considered, academic and job competence at the 10-year follow-up were predicted uniquely and negatively by peer exclusion, problems in the social and romantic domains were predicted distinctively by withdrawal from peers, and internalizing symptoms were uniquely predicted by childhood reputation as Sad-Sensitive. When the Sociable-Leader predictors were considered, academic and (for ethnic minority youth) job success was predicted by a Prosocial reputation, social success was forecasted by Popularity-Leadership, and romantic competence was predicted positively by Popularity-Leadership and negatively by Prosocial reputation. Negative academic and job outcomes were also predicted by a childhood reputation as Aggressive-Disruptive. Results are discussed in relation to conceptualizing and measuring peer social competence and its relation to later adaptation.

The role of developmental assets in predicting academic achievement: a longitudinal study.

A sample of 370 students in the 7th-9th grades in 1998 was followed for 3 years through the 10th-12th grades in order to investigate the relation of "developmental assets"--positive relationships, opportunities, skills, values, and self-perceptions--to academic achievement over time, using actual GPA as the key outcome variable. The greater the number of developmental assets students reported in the 7th-9th grades, the higher their GPA in the 10th-12th grades. Students who stayed stable or increased in their asset levels had significantly higher GPAs in 2001 than students whose asset levels decreased. Increases in assets were significantly associated with increases in GPA. Experiencing in 1998 clusters of specific assets increased by 2-3 times the odds of students having a B+ or higher GPA in 2001. The results offer promising evidence that a broad focus on building the developmental nutrients in young people's lives may contribute to academic success.