Use of biomarkers to assess tissue specific androgen adequacy: defining male hypogonadism.

PURPOSE: The criteria for normal testosterone have been established by expert consensus rather than by evidence. We determined whether a cutoff point for normal could be established using biomarkers. MATERIALS AND METHODS: We performed an exploratory investigation of 1,492 hypogonadal men pooled from 7 registration trials. Serum testosterone, prostate specific antigen and hematocrit were measured at baseline and after 90 days of continuous testosterone replacement therapy. RESULTS: Baseline prostate specific antigen, percent change in prostate specific antigen and hematocrit appeared to be most strongly related to baseline serum testosterone. Subgroup analysis and visual inspection of linear spline fit of these data suggested an approximate serum testosterone cutoff for normal of 300 ng/dl for percent change in hematocrit, and 200 ng/dl for baseline prostate specific antigen and percent change in prostate specific antigen. CONCLUSIONS: This exploratory study revealed considerable variation among individuals and target tissues in individuals. Further study should be performed using standardized assays in a broader population.

Proton pump inhibitor use in infants: FDA reviewer experience.

The Food and Drug Administration has completed its review of 4 clinical trials evaluating the use of proton pump inhibitors (PPIs) in infants (ages 1 month to <12 months) for the treatment of gastroesophageal reflux disease (GERD). An Advisory Committee meeting was held in November 2010 to discuss the potential reasons why PPI use in these trials failed to show a benefit in infants with GERD, and directions for future study. The present review summarizes the findings from the clinical trials. Potential mechanisms for the failed clinical trials are discussed. The safety of long-term use is also discussed. As a result of our analysis and review, the authors agree with the Advisory Committee members that PPIs should not be administered to treat the symptoms of GERD in the otherwise healthy infant without the evidence of acid-induced disease.

Incomplete event documentation in medical records of lung transplant recipients.

CONTEXT: The medical record is frequently used in clinical studies as a source of information on illness events experienced by patients; however, it may be incomplete. OBJECTIVE: To estimate the extent of incompletely documented acute bronchopulmonary events in a transplant clinic medical record at a single university medical center, using home monitoring data. DESIGN, SETTING, AND SUBJECTS: Trends in daily home monitoring data were compared to contemporaneous medical record documentation at 150 different times in 30 lung transplant recipients over 45 subject-years. OUTCOME MEASURE: Proportion of acute bronchopulmonary illness events documented in clinic medical record. RESULTS: By using home monitoring data in a new way, we found that 40% of events actually suffered by lung recipients could not be ascertained to have occurred from the clinic medical record alone. All missed encounters occurred away from the transplant clinic, and involved hospitalizations and telephone prescriptions. CONCLUSIONS: Using the clinic medical record alone to identify acute bronchopulmonary events in lung transplant recipients may result in missing 40% of events. This has important ramifications for studies relying on the medical record for acute event ascertainment in lung transplantation and possibly other chronic diseases.

Comparison of Bayesian, classical, and heuristic approaches in identifying acute disease events in lung transplant recipients.

This study compares a typical heuristic algorithm with classical and Bayesian regression models in ascertaining the presence of acute bronchopulmonary disease events in lung transplant recipients. These models attempt to predict whether an epoch will end in an event, based on the preceding two weeks of data. The data consist of 150 two-week epochs of daily to biweekly spirometry and symptom covariates for 30 subjects over 60 subject-years. Seventy-five 'event' epochs end on a day when an acute bronchopulmonary disease event is documented in the medical record; 75 randomly selected 'non-event' epochs end on a day when no event is documented. The data are partitioned by randomly assigning 15 subjects for training and the remaining 15 subjects for testing. For cross-validation, a second random partition is generated from the same data set. The statistical models are trained and tested on both partitions. For the heuristic algorithm, its historical event classifications on the same test cases are used. Classification performance on both partitions of all models is compared using receiver operating characteristic curves, sensitivity and specificity, and a Shannon information score. Data partition did not appreciably affect statistical model performance. All statistical models, unlike the heuristic algorithm, performed significantly different than chance (family significance < 0.05, Pearson independence chi-square, Bonferroni multiple correction), and better than the heuristic algorithm. The best models were Bayesian changepoint models. Through a clinically oriented discussion, a case classified by all of these algorithms is presented, suggesting the clinical usefulness of the Bayesian approach compared with the classical and heuristic approaches.