Safety of Enalapril in Infants: Data from the Pediatric Heart Network Infant Single Ventricle Trial.

OBJECTIVE: To assess the safety profile of angiotensin-converting enzyme inhibitor therapy in infants with single ventricle. STUDY DESIGN: The Pediatric Heart Network conducted a double-blind trial involving infants with single ventricle physiology randomized to receive enalapril or placebo and followed to 14 months of age. Data including demographics, drug administration, hemodynamic monitoring, laboratory measurements, adverse events, and survival were extracted from the public use data set and compared between the placebo and enalapril-treated groups. RESULTS: The Infant Single Ventricle trial randomized 230 patients, with 115 patients in each group. Initial enalapril dose was 0.10 mg/kg/d and median maximal dose was 0.38 mg/kg/d. There was no significant difference in change in blood pressure at study drug initiation or when resuming study drug after Glenn surgery. The incidence of hyperkalemia and neutropenia did not differ between groups. Renal dysfunction occurred in 3% of the enalapril group and none of the placebo patients, which was not statistically significant. There was a high frequency of serious adverse events in both groups. There was no difference in the frequency of heart transplant or death between groups. CONCLUSIONS: Enalapril did not have sustained hemodynamic effects at initiation or up-titration of drug. Creatinine and potassium were not different between groups, although renal dysfunction occurred more often in the patients on enalapril. Although efficacy of enalapril in neonates with single ventricle has not been demonstrated, the safety profile of angiotensin-converting enzyme inhibitors appears to be low risk in infants and children with significant heart disease.

The relationship of hypertension with obesity and obstructive sleep apnea in adolescents.

OBJECTIVES: To assess the independent relationships of obesity and obstructive sleep apnea (OSA) with hypertension/elevated blood pressure (EBP) in adolescent patients. STUDY DESIGN: A retrospective cohort analysis was performed on 501 patients (age 13-21 years) with three separate blood pressure measurements within 6 months of polysomnography. EBP was defined as average systolic blood pressure (SBP) ≤120 mm Hg; obesity as body mass index Z-score ≤1.65; and OSA as obstructive apnea-hypopnea index <1. Pearson correlations and multivariable analyses were performed to assess the independent effects of the apnea-hypopnea index and body mass index Z-score on SBP. RESULTS: Of 501 patients (mean age 16 ± 2 years), 246 (49%) were male. OSA was present in 329 (66%) patients, obesity in 337 (67%), and EBP in 262 (52%). EBP was present in 70% of obese adolescents and 60% of adolescents with OSA. Univariable correlation showed a significant relationship between SBP, body mass index Z-score, and apnea-hypopnea index. Multivariable linear regression analysis showed blood pressure was significantly associated with body mass index Z-score (ß = .46; P < .01), age (ß = .25; P < .01), and height Z-score (ß = .14; P < .01), but not apnea-hypopnea index (ß = .01; P = .72). CONCLUSIONS: The relationship between OSA and EBP in adolescents is most closely associated with the degree of obesity. Further studies are needed to assess the effect of the treatment of obesity and OSA on blood pressure in adolescents.

In vivo effects of eltrombopag on platelet function in immune thrombocytopenia: no evidence of platelet activation.

The effects of eltrombopag, a thrombopoietin-receptor agonist, on platelet function in immune thrombocytopenia (ITP) are not fully characterized. This study used whole blood flow cytometry to examine platelet function in 20 patients receiving eltrombopag treatment at days 0, 7, and 28. Platelet surface expression of activated GPIIb/IIIa, P-selectin, and GPIb was measured with and without low and high adenosine diphosphate (ADP) and thrombin receptor activating peptide (TRAP) concentrations. Before eltrombopag treatment with no ex vivo agonist, platelet activation was higher in ITP patients than controls. Platelet GPIb and activated GPIIb/IIIa expression without added agonist was unchanged following eltrombopag treatment, whereas a slight increase in P-selectin was observed. Expression of P-selectin and activated GPIIb/IIIa in response to high-dose ADP was lower during eltrombopag treatment than at baseline. Eltrombopag led to a slight increase in platelet reactivity to TRAP only in responders to eltrombopag but not to levels above those in controls; whole blood experiments demonstrated that this increase was probably because of higher platelet counts rather than higher platelet reactivity. In conclusion, although thrombocytopenic ITP patients have higher baseline platelet activation than controls, eltrombopag did not cause platelet activation or hyper-reactivity, irrespective of whether the platelet count increased.

Drusen analysis in a human-machine synergistic framework.

OBJECTIVES: To demonstrate how human-machine intelligence can be integrated for efficient image analysis of drusen in age-related macular degeneration and to validate the method in 2 large, independently graded, population-based data sets. METHODS: We studied 358 manually graded color slides from the Netherlands Genetic Isolate Study. All slides were digitized and analyzed with a user-interactive drusen detection algorithm for the presence and quantity of small, intermediate, and large drusen. A graphic user interface was used to preprocess the images, choose a region of interest, select appropriate corrective filters for images with photographic artifacts or prominent choroidal pattern, and perform drusen segmentation. Weighted κ statistics were used to analyze the initial concordance between human graders and the drusen detection algorithm; discordant grades from 177 left-eye slides were subjected to exhaustive analysis of causes of disagreement and adjudication. To validate our method further, we analyzed a second data set from our Columbia Macular Genetics Study. RESULTS: The graphical user interface decreased the time required to process images in commercial software by 60.0%. After eliminating borderline size disagreements and applying corrective filters for photographic artifacts and choroidal pattern, the weighted κ values were 0.61, 0.62, and 0.76 for small, intermediate, and large drusen, respectively. Our second data set demonstrated a similarly high concordance. CONCLUSIONS: Drusen identification performed by our user-interactive method presented fair to good agreement with human graders after filters for common sources of error were applied. This approach exploits a synergistic relationship between the intelligent user and machine computational power, enabling fast and accurate quantitative retinal image analysis.