During embryonic development the myocardium enlarges by the proliferation of cardiac myocytes. Shortly after birth, cardiac myocytes lose their capacity for mitogenesis, and further growth of the myocardium to meet the increasing hemodynamic demand of an elevated blood pressure and blood volume occurs by enlargement of existing muscle cells (hypertrophy). Similarly, the restoration of myocardial contractile performance lost to ischemia or viral infection is dependent on the recovery of injured myocytes and on the compensatory enlargement of agonist myocytes. Thus, an understanding of the controlling factors of myocardial protein synthesis and growth has implications for cardiac ontogeny, adaptation to chronic physiologic and pathophysiologic stimuli, and recovery from injury.Cardiac hypertrophy is produced by a variety of stimuli in culture and in vivo (1), including, but not limited to, mechanical stretch (2, 3), neurotransmitters (4, 5), and hormones (6, 7). As the biochemistry of myocardial growth is experimentally revealed, some common intracellular signaling pathways appear among primary stimuli. For example, stretch-induced cardiomyocyte hypertrophy is mediated, in part, by the local production of angiotensin II (8), and several hypertrophic stimuli, angiotensin II, norepinephrine, and endothelin-1, act through G q protein-coupled receptors (9 -11) and activate mitogen-activated protein kinases (12, 13). Direct evidence of G q involvement in cardiac growth was provided by microinjection of G q neutralizing antibodies to block the hypertrophic response of neonatal rat ventricular myocytes to the ␣ 1 -adrenergic agonist phenylephrine (9). Thus cardiac hypertrophy appears to be mediated, at least for several stimuli, by agonists of G q proteincoupled receptors.In addition to promoting myocardial growth, angiotensin II, norepinephrine, and endothelin-1 are vasoactive substances. Interestingly, Katz (14) speculated that angiotensin II evolved from a primitive growth factor and assumed additional regulatory roles in the cardiovascular system, such as stimulation of aldosterone production and smooth muscle contraction. It is conceivable that other vasoactive substances went through a similar evolutionary process, especially in consideration of the finding that Ca 2ϩ signaling is important for angiotensin II activation of mitogen-activated protein kinase in cardiac myocytes (13).Prostaglandin F 2␣ (PGF 2␣ ) 1 is a vasoactive substance that stimulates protein synthesis in skeletal and smooth muscle cells in culture (15,16). Moreover, PGF 2␣ regulates, in part, stretch-induced skeletal myoblast growth (16), and the effects of exogenous PGF 2␣ on vascular smooth muscle hypertrophy are most likely mediated by a PGF-specific receptor (15). As to the heart, PGF 2␣ was increased in the left ventricles of rabbits by acute pressure overload (17), and PG synthase inhibitors blocked cardiac growth induced by hypertension (18) and clenbuterol (19). These observations and others suggested that PGF 2␣ may play a role in the con...

An evidence-based standard care pathway for neonatal jaundice can significantly improve multiple dimensions of value, including reductions in cost and length of stay.

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To help stem ever increasing health care costs, clinicians, administrators, payors, and families must better communicate about the value of care options. Our institution sought to create a value analysis framework, based on local implementation of over 50 clinical pathways.From January to March 2015, a multidisciplinary team of clinicians, nursing, pharmacy, informatics, and analytics developed a cost dashboard, and a value analysis and decision-making framework. We reviewed all clinical pathway recommendations and measures, and examined issues related to implementing pathways. We examined specific line item costs for each pathway patient population.Our value analysis and decision-making framework is based upon 3 population-level comparisons: operational factors/ implementability, benefits, and costs/complications. We used the framework to scope new projects, to better target clinical recommendations, and to evaluate pathways postimplementation. From April through December 2015, we used this framework to prospectively analyze 19 pathway improvement proposals. The tool helped us to identify 16 improvements to implement (15 predicted to save costs), as well as identifying challenges facing 3 additional improvements.The value analysis and decision-making framework helps to ensure clinical recommendations are evaluated more broadly than just from a cost perspective. Systematic evaluation using this framework can improve populationbased decision-making. More research is needed in how to ensure that value analysis is performed to guide sustainable implementation of recommendations locally, and how to identify other institutions that may benefit from replicating successful implementations, so that the highest value care can be provided to patients everywhere.

We conclude that properly constructed computerized order sets can be effective in altering physician ordering practices through standardization.