Risk-prediction tool for identifying hospitalized children with a predisposition for development of venous thromboembolism: Peds-Clot clinical Decision Rule.

BACKGROUND: The prevalence of VTE is increasing in tertiary pediatric hospitals. Identification of high-risk populations using uniform criteria is required to develop evidence-based VTE prevention guidelines. OBJECTIVE: To develop a VTE risk prediction rule, the Peds-Clot clinical Decision Rule (PCDR), to identify high-risk children who were at increased risk of developing VTE. METHODS: This retrospective case-control study developed the PCDR using a derivation cohort (173 cases, 346 controls) and validated it on a separate validation cohort (100 cases, 100 controls). A uniform data collection strategy was applied to derive both the samples. Conditional logistic regression analyses were used to develop a risk-prediction model. Each significant predictor was assigned a score based on its beta coefficient and the PCDR was developed. ROC curves were derived to test the performance of the PCDR. RESULTS: Characteristics of derivation and validation cohorts were comparable. Six risk factors (positive blood stream infection, central venous catheter, direct admission to ICU/NICU, hospitalization for ≥ 7 days, immobilization for > 72 h, and use of birth control pills) formed the final risk prediction model (risk score range, 0.5-9.5). A risk score of 3 or more identified high-risk children at a sensitivity of 70% and specificity of 80% and AUC of 0.852 (95% confidence interval, 0.814-0.890). The application of a risk score to the validation sample showed sensitivity 57% and specificity 88% and an AUC of 0.875 (95% confidence interval, 0.82-0.924). CONCLUSION: Incorporation of the PCDR in routine clinical care can be an attractive strategy to identify high-risk hospitalized children with a predisposition for VTE. The clinical utility of the PCDR needs validation in prospective studies.

Differential effects of kinins on cardiomyocyte hypertrophy and interstitial collagen matrix in the surviving myocardium after myocardial infarction in the rat.

BACKGROUND: Left ventricular remodeling after myocardial infarction (MI) involves the hypertrophic growth of cardiomyocytes and the accumulation of fibrillar collagen in the interstitial space. We evaluated the role of kinins in postinfarction ventricular remodeling and their potential contribution to the antiremodeling effects of ACE inhibition and angiotensin II type 1 (AT1) receptor blockade. METHODS AND RESULTS: Rats underwent coronary artery ligation followed by chronic B2 kinin receptor blockade with icatibant. Additional groups of infarcted rats were treated with the ACE inhibitor lisinopril or the AT1 receptor antagonist ZD7155, each separately and in combination with icatibant. B2 kinin receptor blockade enhanced the interstitial deposition of collagen after MI, whereas morphological and molecular markers of cardiomyocyte hypertrophy (cardiac weight, myocyte cross-sectional area, prepro-atrial natriuretic factor mRNA expression) were not affected. Chronic ACE inhibition and AT1 receptor blockade reduced collagen deposition and cardiomyocyte hypertrophy after MI. The inhibitory action of ACE inhibition and AT1 receptor blockade on interstitial collagen was partially reversed by B2 kinin receptor blockade. However, B2 kinin receptor blockade did not attenuate the effects of ACE inhibition and AT1 receptor blockade on cardiomyocyte hypertrophy. CONCLUSIONS: (1) Kinins inhibit the interstitial accumulation of collagen but do not modulate cardiomyocyte hypertrophy after MI. (2) Kinins contribute to the reduction of myocardial collagen accumulation by ACE inhibition and AT1 receptor blockade. (3) The effects of ACE inhibition and AT1 receptor blockade on cardiomyocyte hypertrophy are related to a reduced generation/receptor blockade of angiotensin II.