A New Stochastic Approach for Modeling Glycemic Disturbances in Type 2 Diabetes.

OBJECTIVE: To improve insulin treatment in type 2 diabetes (T2D) using model-based control techniques, the underlying model needs to be individualized to each patient. Due to the impact of unknown meals, exercise and other factors on the blood glucose, it is difficult to utilize available data from continuous glucose monitors (CGMs) for model fitting and parameter estimation purposes. METHODS: To overcome this problem, we propose a novel method for modeling the glycemic disturbances as a stochastic process. To differentiate meals from other glycemic disturbances, we model the meal intake as a separate stochastic process while encompassing all other disturbances in another stochastic process. Using particle filtering, we validate the model on simulations as well as on clinical data. RESULTS: Based on simulated CGM data, the residuals generated by the particle filter are white, indicating a good model fit. For the clinical data, we use parameter values estimated based on fasting glucose data. The residuals obtained from clinical CGM data contain correlations up to lag 5. CONCLUSION: The proposed model is shown to adequately describe the meal-induced glucose fluctuations in simulated CGM data while validations on clinical CGM data show promising results as well. SIGNIFICANCE: The proposed model may lay the grounds for new ways of utilizing available CGM data, including CGM-based parameter estimation and stochastic optimal control.

Impact of a computer assisted navigation system on radiation exposure during pediatric ablation procedures.

BACKGROUND: During catheter ablation procedures, non-radiologic navigation systems may reduce fluoroscopic exposure and energy applications, as well as improve procedural success rates. OBJECTIVE: To examine the impact of a non-radiologic navigation system on ablation procedures in pediatric patients, the procedural characteristics and success rates prior to and following incorporation of the LocaLisa (LL) navigation system into a pediatric electrophysiology laboratory were compared. METHODS: Between January 2000 and April 2005, 246 consecutive patients underwent catheter ablation for either Atrioventricular Reentry Tachycardia AVRT (168) or Atrioventricular Nodal Reentry Tachycardia AVNRT (78). Ablation procedures performed prior to LL (108) were compared to ablation procedures performed using LL (113). The first 25 patients using LL were censored to remove the bias of a learning curve. RESULTS: There was no difference in demographic features between the two groups. Statistically significant decreases were found in the diagnostic (11.4 +/- 6.1 min v 18.8 +/- 9.8 min w/o LL), ablation (5.7 +/- 10.3 vs 18.5 +/- 20.1 min w/o LL) and total (17.2 +/- 12.6 vs 37.3 +/- 21.3 min w/o LL) fluoroscopy times for the LL group, as well as in the total number of energy applications (9.0 +/- 8.5 vs 12.3 +/- 12.2 w/o LL). Success rates were 99.1% w/ LL v 97.2% w/o LL (p = NS). No major complications were observed in either group. CONCLUSIONS: The use of a computer assisted navigation system significantly decreased the diagnostic, ablation, and total fluoroscopy times, as well as the number of energy applications, without affecting procedural success or complication rates. Non-radiologic navigation systems reduce radiation exposure during transcatheter electrophysiologic procedures and thus lower the lifetime radiation cumulative risk, a goal particularly important in children.

Transcatheter cryotherapy for the treatment of supraventricular tachyarrhythmias in children: a single center experience.

INTRODUCTION: Transcatheter cryotherapy is an emerging technology for the treatment of children with supraventricular tachyarrhythmias. Limited data exist regarding the use of cryoablation therapy in children. We report a single center's experience with transcatheter cryoablation in the pediatric population. METHODS AND RESULTS: A retrospective review of demographic, procedural and outcome data was performed for patients undergoing cryoablation for treatment of supraventricular tachycardia (SVT). A historical control group was taken from the 3 years preceding the introduction of cryoablation. Between August 2003 and November 2005, 83 cryoablation procedures were performed in 81 patients (age: 4 to 21 years, mean: 13.4 years) for AV nodal reentrant tachycardia (AVNRT--53), AV reentrant tachycardia (AVRT--20), ectopic atrial tachycardia (EAT--9), and junctional ectopic tachycardia (JET--1). The acute success rate for all procedures was 88% (AVNRT: 96%, AVRT: 85%, EAT: 55%, and JET: 100%). Of 72 patients that underwent successful cryoablation, nine experienced recurrence of SVT (12.5%). The control group consisted of 73 patients (AVNRT--60, AVRT--13). There were no differences in demographic data between the two groups. The overall success rate for the RFA group (96%) was identical to that for patients with AVNRT and AVRT undergoing cryoablation. The recurrence rate for RFA (10%) was less but not significantly different than that for cryoablation (12%). There were no complications in either group. CONCLUSIONS: Cryoablation is a safe and effective alternative for the treatment of SVT in children.

Transcription repression and blocks in cell cycle progression in hypoplastic left heart syndrome.

Hypoplastic left heart syndrome (HLHS) is characterized by abnormally developed atrial septum and a severe underdevelopment of the left side of the heart. Despite significant advances in its surgical management, little is known about the molecular abnormalities in this syndrome. To gain molecular insights into HLHS, expression profiling by gene-chip microarray (Affymetrix U133 2.0) and by real-time RT-PCR was performed in the atrial septum of patients diagnosed with HLHS and compared with age-matched non-HLHS patients. Hierarchical clustering of all expressed genes with a P < 0.01 of all tissue samples showed two main clusters, one of HLHS and the other of non-HLHS, suggesting different expression patterns by the two groups. Net affix followed by real-time RT-PCR analysis identified the differentially expressed genes to be those involved in chromatin remodeling, cell cycle regulation, and transcriptional regulation. These included remodeling factors, histone deactylase 2 and SET and MYND domain containing 1; transcription factors, FoxP1, and components of the calcineurin-nuclear factor of activated T cells signaling pathway; and cell cycle regulators, cyclin-dependent kinase (CDK)-4, phosphatase and tensin homolog, and p18. Since these factors play essential roles in heart growth and development, the abnormal expression pattern suggests that these molecules may contribute to the pathogenesis of HLHS.