Novel Antidiabetic Therapies and Cardiovascular Risk Reduction: The Role of the Noninferiority Trial.

Diabetes is a major risk factor for cardiovascular disease, yet until now treatments for diabetes had only a modest impact on cardiovascular events. New interventions for patients with type 2 diabetes mellitus (oral empagliflozin and injectable liraglutide) are associated with unprecedented reductions in composite cardiovascular outcomes that seem disproportionate to the impact on glycated hemoglobin. This review examines in detail the recent trials that arrived at these conclusions, limitations of these studies, and how these outcomes may influence patient management in the future.

Systematic review of β blocker, aspirin, and statin in critically ill patients: importance of severity of illness and cardiac troponin.

Non-cardiac critically ill patients with type II myocardial infarction (MI) have a high risk of mortality. There are no evidence-based interventions to mitigate this risk. We systematically reviewed the literature regarding the use of medications known to reduce mortality in patients with cardiac troponin (cTn) elevation due to type I MI (β blockers, statin, and aspirin) in studies of critically ill patients without Type I MI.

Cardiac Troponin Measurement in the Critically Ill: Potential for Guiding Clinical Management.

Background: Elevated cardiac troponin (cTn) in the absence of acute coronary syndromes (ACS) is associated with increased mortality in critically ill patients. There are no evidence-based interventions that reduce mortality in this group.

Objectives: We performed a retrospective investigation of the Veterans Administration Inpatient Evaluation Center database to determine whether drugs used in ACS (β-blockers, aspirin, and statins) are associated with reduced mortality in critically ill patients.

Quantitative measurement of blood flow dynamics in embryonic vasculature using spectral Doppler velocimetry.

The biophysical effects of blood flow are known to influence the structure and function of adult cardiovascular systems. Similar effects on the maturation of the cardiovascular system have been difficult to directly and non-invasively measure due to the small size of the embryo. Optical coherence tomography (OCT) has been shown to provide high spatial and temporal structural imaging of the early embryonic chicken heart.

In vivo spectral domain optical coherence tomography volumetric imaging and spectral Doppler velocimetry of early stage embryonic chicken heart development.

Progress toward understanding embryonic heart development has been hampered by the inability to image embryonic heart structure and simultaneously measure blood flow dynamics in vivo. We have developed a spectral domain optical coherence tomography system for in vivo volumetric imaging of the chicken embryo heart. We have also developed a technique called spectral Doppler velocimetry (SDV) for quantitative measurement of blood flow dynamics.

Ultrahigh-speed optical coherence tomography imaging and visualization of the embryonic avian heart using a buffered Fourier Domain Mode Locked laser.

The embryonic avian heart is an important model for studying cardiac developmental biology. The mechanisms that govern the development of a four-chambered heart from a peristaltic heart tube are largely unknown due in part to a lack of adequate imaging technology. Due to the small size and rapid motion of the living embryonic avian heart, an imaging system with high spatial and temporal resolution is required to study these models.

4D embryonic cardiography using gated optical coherence tomography.

Simultaneous imaging of very early embryonic heart structure and function has technical limitations of spatial and temporal resolution. We have developed a gated technique using optical coherence tomography (OCT) that can rapidly image beating embryonic hearts in four-dimensions (4D), at high spatial resolution (10-15 mum), and with a depth penetration of 1.5 - 2.

Three-dimensional anatomy of the conduction system of the early embryonic rabbit heart.

The complete embryonic cardiac conduction system is difficult to view in three dimensions, primarily because there has not been a marker of all segments of the normal system throughout all stages of development. Imaging of the conduction system components within the atria has been particularly controversial because different markers reveal different pathways that may or may not represent conduction system components. The conduction system of the adult and embryonic rabbit, however, can be labeled in its entirety with the neurofilament marker, NF-160.

Emerging patterns of cardiac conduction in the chick embryo: waveform analysis with photodiode array-based optical imaging.

Major difficulties investigating the developing cardiac conduction system stem from that the embryonic heart is extremely small (< 2 mm) and cardiac activation is relatively rapid (< 8 msec). The objective of this study was to investigate the electrophysiology of the embryonic chick cardiac conduction system at periseptation stages with a photodiode array-based detection method of optical mapping capable of high spatial and temporal resolution. Previous work indicated that, in chicken embryos, a switch occurs in ventricular activation pattern from immature base-to-apex to mature apex-to-base pattern at the time of ventricular septation.

Functional imaging of the embryonic pacemaking and cardiac conduction system over the past 150 years: technologies to overcome the challenges.

Early analyses of cardiac pacemaking and conduction system (CPCS) development relied on classic histology and visual inspection of the beating heart. Current techniques that facilitate delineation of the CPCS include the use of specific antibody markers and transgenic mouse lines specifically expressing reporter genes. Assaying the function of tiny embryonic hearts required an increase in the level of spatial and temporal resolution.

Structure-function relationship in the AV junction.

In the normal heart, the atrioventricular node (AVN) is part of the sole pathway between the atria and ventricles. Under normal physiological conditions, the AVN controls appropriate frequency-dependent delay of contractions. The AVN also plays an important role in pathology: it protects ventricles during atrial tachyarrhythmia, and during sinoatrial node failure an AV junctional pacemaker can drive the heart.

Electrophysiology and anatomy of embryonic rabbit hearts before and after septation.

Mechanisms of cardiac pacemaking and conduction system (CPCS) development are difficult to study, in part because of the absence of models that are physiologically similar to humans in which we can label the entire CPCS. Investigations of the adult rabbit heart have provided insight into normal and abnormal cardiac conduction. The adult and the embryonic rabbit have an endogenous marker of the entire cardiac conduction system, neurofilament 160 (NF-160).

Developmental transitions in cardiac conduction.

The proper sequence of electrical activation of the mature four-chambered heart requires specialized conduction pathways including the His-Purkinje system and a nearly complete separation of the atrial and ventricular myocardium. We tracked the emergence of the structure of the mature His-Purkinje system in the developing chicken embryo with anti-polysialylated neural cell adhesion molecule (PSA-NCAM) and the HNK1 antibody against a sulfated carbohydrate epitope. The function of the His-Purkinje system was assayed using extracellular electrodes and high-resolution voltage-sensitive two-dimensional optical mapping.

Sculpting the cardiac outflow tract.

The cardiac outflow tract is the site of anomalies that affect a substantial proportion of individuals with congenital heart defects. The morphogenesis of this site is complex, and requires coordinated development of many cell types and tissues. It is therefore not surprising that developmental mistakes arise here, and that the steps and mechanisms of morphogenesis are still controversial and poorly understood, despite advances in molecular techniques.

The pros and cons of apoptosis assays for use in the study of cells, tissues, and organs.

Programmed cell death or apoptosis occurs in many tissues during normal development and in the normal homeostasis of adult tissues. Apoptosis also plays a significant role in abnormal development and disease. Increased interest in apoptosis and cell death in general has resulted in the development of new techniques and the revival of old ones.

Initiation of apoptosis in the developing avian outflow tract myocardium.

Apoptosis occurs within the cardiac outflow tract (OFT) myocardium during normal development of chick hearts. This peak of apoptosis occurs at stage 30-31 and coincides with dramatic remodeling of the OFT, suggesting that apoptosis occurs to allow proper alignment of the great vessels over their respective ventricles. The signals that initiate apoptosis in this setting are unknown.

Specialty services: capitation trends among physician groups.

Many health care providers, particularly those outside of California, Minnesota, and a handful of other states where managed care has become a dominant force, are hesitant to work under capitated contracts. Fear of capitation is basically fear of the unknown. If providers have the tools to track utilization patterns, gather information, and interpret it, then this fear is unjustified.

The effect of long-term high-dose naloxone infusion in experimental blunt spinal cord injury.

The effect of long-term continuous subcutaneous infusion of naloxone on blunt spinal cord injury in the rat was assessed using four tests of neurological function, seven histological categories, and two electrophysiological measures. All four neurological function tests showed a trend toward improvement in naloxone-treated animals: the degree of improvement was statistically significant in two of the four categories. A significant reduction in myelin sheath edema was found in the naloxone-treated animals.

The influence of long-term nifedipine or indomethacin therapy on neurologic recovery from experimental spinal cord injury.

Inhibition of prostaglandin pathways and calcium channel conduction has been shown to improve neurological outcome after spinal cord injury. Functional recovery from such intervention has been routinely evaluated by a simple motor examination or somatosensory evoked potentials (SSEPs) after short-term drug administration. We comprehensively evaluated the influence of continuously administered indomethacin and nifedipine on functional outcome after impact spinal cord injury.

PPOs: critical elements in their design. Part 4.

There is no certainty that PPOs will be a major factor in the marketplace. It is essential, however, that every provider closely examine the benefits and risks of participation. There is no need to rush head-long into every opportunity offered.