Coronary Disease and Modifying Cardiovascular Risk in Adult Congenital Heart Disease Patients: Should General Guidelines Apply?

There are >1.4 million adult congenital heart disease (CHD; ACHD) patients living in the United States. Coronary artery disease (CAD) is at least as prevalent in ACHD patients as in the general population and has become a leading cause of their mortality. In the majority of cases, CAD in the ACHD population is driven by the presence of traditional cardiovascular disease (CVD) risk factors. 80% of ACHD patients have at least one CVD risk factor. Hypertension (HTN), obesity and physical inactivity are frequently seen in both pediatric and adult patients with CHD. Many ACHD patients demonstrate abnormal glucose metabolism and are at an increased risk for developing diabetes. Current guidelines for CVD risk assessment and prevention do not specifically mention patients with CHD but are likely applicable to most of these patients. Specific CHD populations have "high-risk" lesions that are associated with an increased risk of CVD complications and may warrant intensified screening and treatment. These include patients with a history of coarctation of the aorta or with prior coronary artery ostial manipulation (patients with a history of d-transposition of the great arteries or anomalous aortic origin of a coronary artery). The physiology of single ventricle patients is also poorly suited for the effects of superimposed CVD; these patients may benefit from intensified treatment of CVD risk factors, particularly HTN and obesity

Optimal Maintenance of a Spanning Tree

In this paper, we show that keeping track of history enables significant improvements in the communication complexity of dynamic network protocols. We present a communication optimal maintenance of a spanning tree in a dynamic network. The amortized (on the number of topological changes) message complexity is O(V), where V is the number of nodes in the network. The message size used by the algorithm is O(log |ID|) where |ID | is the size of the name space of the nodes. Typically, log |ID | = O(log V). Previous algorithms that adapt to dynamic networks involved Ω(E) messages per topological change—inherently paying for re-computation of the tree from scratch. Spanning trees are essential components in many distributed algorithms. Some examples include broadcast (dissemination of messages to all network nodes), multicast, reset (general adaptation of static algorithms to dynamic networks), routing, termination detection, and more. Thus, our efficient maintenance of a spanning tree implies the improvement of algorithms for these tasks. Our results are obtained using a novel technique to save communication. A node uses information received in the past in order to deduce present information from the fact that certain messages were NOT sent by the node’s neighbor. This technique is one of our main contributions

Characteristics of pediatric pulmonary hypertension trials registered on ClinicalTrials.gov

The investigation of pediatric pulmonary hypertension (PH) drugs has been identified as a high priority by the United States National Institutes of Health (NIH). Studying pediatric PH is challenging due to the rare and heterogeneous nature of the disease. We sought to define the pediatric PH clinical trials landscape, to evaluate areas of trial success or failure, and to identify potential obstacles to the study of pediatric PH drugs. Interventional pediatric (ages 0-17 years) PH trials registered on ClinicalTrials.gov from June 2005 through December 2014 were analyzed. There were 45 pediatric PH trials registered during the study period. Median (IQR) projected trial enrollment was 40 (24-63), with seven trials (16%) targeting > 100 participants. Industry was the most common trial sponsor (n = 23, 50%), with only two (4.4%) NIH-sponsored trials. Phosphodiesterase inhibitors were the most frequently studied drug (n = 18, 39%). Single group study designs were used in 44% (n = 20) with an active comparator (parallel, factorial, or cross-over designs) in 25 trials, including 22 with randomization and ten that were double-blinded. Study outcomes varied markedly with inconsistent use of known surrogate and composite endpoints. One-third of trials (n = 15, 33%) were terminated, predominantly due to poor participant enrollment. Of the 17 completed trials, 11 had published results and only three efficacy trials met their primary endpoint. There are unique challenges to drug development in pediatric PH, including enrolling patients, identifying appropriate study endpoints, and conducting randomized, controlled, double-blind trials where the likelihood of meeting the study endpoint is optimized