Effects of enhanced pacing modalities on health care resource utilization and costs in bradycardia patients: An analysis of the randomized MINERVA trial.

BACKGROUND: Many patients who suffer from bradycardia and need cardiac pacing also have atrial fibrillation (AF). New pacemaker algorithms, such as atrial preventive pacing and atrial antitachycardia pacing (DDDRP) and managed ventricular pacing (MVP), have been specifically designed to reduce AF occurrence and duration and to minimize the detrimental effects of right ventricular pacing. The randomized MINimizE Right Ventricular pacing to prevent Atrial fibrillation and heart failure trial established that DDDRP + MVP pacing modality reduced permanent AF in bradycardia patients as compared with standard dual-chamber pacing (DDDR). OBJECTIVE: The aim of this study was to estimate the cost savings due to lower AF-related health care utilization events based on health care costs from the United States and the European Union. METHODS: Dual-chamber pacemaker patients with a history of paroxysmal or persistent AF were randomly assigned to receive DDDR (n = 385) or the advanced features (DDDRP + MVP; n = 383). We used published health care costs from the United States and the European Union (Italy, Spain, and the United Kingdom) to estimate the costs associated with AF-related hospitalizations and emergency visits. RESULTS: The rate of AF-related hospitalizations was significantly lower in the DDDRP + MVP group than in the conventional pacemaker group (DDDR group; 42% reduction; incidence rate ratio 0.58). Similarly, a significant reduction of 68% was observed for AF-related emergency department visits (incidence rate ratio 0.32; P < .001). As a consequence, DDDRP + MVP could potentially reduce health care costs by 40%-44%. Over a ten-year period, the cost savings per 100 patients ranged from $35,702 in the United Kingdom to $121,831 in the United States. CONCLUSION: New pacing algorithms such as DDDRP + MVP used in the MINimizE Right Ventricular pacing to prevent Atrial fibrillation and heart failure trial successfully reduced AF-related health care utilization, resulting in significant cost savings to payers.

Palladium-catalyzed reaction of aryl iodides with acetic anhydride. A carbon monoxide-free synthesis of acetophenones.

[reaction: see text] The palladium-catalyzed reaction of aryl iodides with acetic anhydride provides a straightforward and experimentally simple carbon monoxide-free route to acetophenones. The reaction tolerates a wide range of functionalized aryl iodides. Acetophenones are isolated in excellent yield with a variety of neutral, slightly electron-rich, and slightly electron-poor aryl iodides, whereas moderate yields are obtained with aryl iodides containing strongly electron-withdrawing substituents.

Activation of p16 gene silenced by DNA methylation in cancer cells by phosphoramidate derivatives of 2'-deoxyzebularine.

We report herein the application of the phosphoramidate ProTide technology to improve the metabolism of the DNA methytransferase inhibitor, zebularine (Z). Zebularine is a riboside that must undergo a complex metabolic transformation before reaching the critical 2'-deoxyzebularine 5'-triphosphate (dZTP). Because 2'-deoxyzebularine (dZ) is not phosphorylated and therefore inactive, the ProTide strategy was employed to bypass the lack of phosphorylation of dZ and the inefficient reduction of zebularine 5'-diphosphate by ribonucleotide-diphosphate reductase required for zebularine. Several compounds were identified as more potent inhibitors of DNA methylation and stronger inducers of p16 tumor suppressor gene than zebularine. However, their activity was dependent on the administration of thymidine to overcome the potent inhibition of thymidylate synthase (TS) and deoxycytidine monophosphate (dCMP) deaminase by dZMP, which deprives cells of essential levels of thymidine. Intriguingly, the activity of the ProTides was cell line-dependent, and activation of p16 was manifest only in Cf-Pac-1 pancreatic ductal adenocarcinoma cells.