Peer Support for Post Intensive Care Syndrome Self-Management (PS-PICS): Study protocol for peer mentor training.

AIMS: The primary aim of the Peer Support for Post Intensive Care Syndrome Self-Management (PS-PICS) peer mentor training trial is to determine the feasibility for peer mentor training to connect new ICU survivors with survivors who have made successful recoveries. Secondary aims are to also examine peer mentor eligibility, recruitment and retention rates and assess changes in participant knowledge of Post Intensive Care Syndrome (PICS), reported symptoms and health-related quality of life. DESIGN: Prospective clinical feasibility trial. METHODS: This study received funding from the National Institutes of Health funded P30 Center for Excellence (2014-2020). Up to 20 adult patients who have had an ICU stay of 3 days or longer more than 3 months ago will be enrolled into the study. Participants will undergo a 6-week peer mentor training program to learn how to promote healthy self-management behaviours, social connections, and well-being using motivational interviewing (MI). Participants will complete surveys about their recovery at 3 points during the study: prior to training, 6 weeks post-training and 3 months post-training. Survey questions will be used to assess trends in participant social isolation, depression, functional status, and self-management behaviours. DISCUSSION: Enrollment closes by December 2020. As a feasibility trial, power sufficient for hypothesis testing will not be available. However, study operations and intervention fidelity contribute to future research knowledge and participant characteristics and longitudinal outcomes will yield data on intervention feasibility. This study is the first use of embedding peer-led motivational interviewing training into a peer support intervention for ICU survivors. IMPACT: Current self-management interventions are limited for ICU survivors and do not sufficiently address barriers to promoting self-management behaviours or improving their health status, well-being and cost of health. This study will provide data to develop and implement interventions for the self-management of PICS-related symptoms and sequelae.

Emerging frontiers in healthcare research and delivery.: the 16th Annual HMO Research Network Conference, March 21-24, 2010, Austin, Texas.

The Health Maintenance Organization Research Network (HMORN), a consortium of 16 healthcare delivery systems with integrated research centers, held their 16(th) annual conference in Austin, Texas from March 21-24, 2010. The conference was hosted by Scott & White Healthcare. Its theme "Emerging Frontiers in Healthcare Research and Delivery" reflected the objective of the conference which was to build synergy among scientists and clinicians to influence the health of the nation; to demonstrate the network's commitment to reach beyond traditional collaborators; discuss tools and technologies; and to expand opportunities for public-private partnerships in cutting-edge healthcare research and delivery. More than 320 researchers and healthcare professionals, representing each of the member HMOs, participated in this conference. Representatives from the AHRQ, CDC, NCI and NIH met with researchers to advance the quality and breadth of public domain research in HMOs. The objective of this article is to provide information about the HMORN and its 16(th) annual conference.

Activation of protein kinase A by atrial natriuretic peptide in neonatal rat cardiac fibroblasts: role in regulation of the local renin-angiotensin system.

There is an inverse relationship between renin and atrial natriuretic peptide (ANP) levels in the plasma. Since both the ANP and renin-angiotensin system (RAS) are upregulated in development and cardiac hypertrophy, we tested whether ANP differentially regulates RAS in cardiac cells. Cardiac fibroblasts isolated from neonatal rats were treated with ANP(1-28), a biologically active fragment of ANP. Renin and angiotensinogen (Ao) mRNA levels were measured by quantitative multiplex RT-PCR and protein levels determined by Western blot analysis. ANP(1-28) increased renin and Ao mRNA levels (737+/-131% and 178+/-51.3%) with EC50 values of 4.12+/-0.3 and 8.67+/-0.22 nmol/L, respectively. At the protein level, secretion of renin and Ao was significantly enhanced resulting in approximately 4-fold increase in ANG II level in the medium. The effect of ANP(1-28) on renin and Ao mRNA expression were reproduced by 8-bromo-cyclic GMP. Inhibition of protein kinase G (PKG) with KT5823 blunted ANP(1-28)-induced upregulation of renin, but not Ao mRNA, while inhibition of protein kinase A (PKA) with KT5720 attenuated the upregulation of both renin and Ao mRNA. These findings suggest that unlike in plasma, ANP positively regulates the RAS in cardiac fibroblasts, which may have a significant role in development of the fetal heart.

Evidence of a novel intracrine mechanism in angiotensin II-induced cardiac hypertrophy.

Angiotensin II (Ang II) has a significant role in regulating cardiac homeostasis through humoral, autocrine and paracrine pathways, via binding to the plasma membrane AT1 receptor. Recent literature has provided evidence for intracrine growth effects of Ang II in some cell lines, which does not involve interaction with the plasma membrane receptor. We hypothesized that such intracrine mechanisms are operative in the heart and likely participate in the cardiac hypertrophy induced by Ang II. Adenoviral and plasmid vectors were constructed to express Ang II peptide intracellularly. Neonatal rat ventricular myocytes (NRVMs) infected with the adenoviral vector showed significant hypertrophic growth as determined by cell size, protein synthesis and enhanced cytoskeletal arrangement. Adult mice injected with the plasmid vector developed significant cardiac hypertrophy after 48 h, without an increase in blood pressure or plasma Ang II levels. This was accompanied by increased transcription of transforming growth factor-beta (TGF-beta) and insulin-like growth factor-1 (IGF-1) genes. Losartan did not block the growth effects, excluding the involvement of extracellular Ang II and the plasma membrane AT1 receptor. These data demonstrate a previously unknown growth mechanism of Ang II in the heart, which should be considered when designing therapeutic strategies to block Ang II actions.

Integrins: novel therapeutic targets for cardiovascular diseases.

Integrins are the principle mediators of molecular dialog between a cell and its extracellular matrix environment. The unique combinations of integrin subunits determine which extracellular matrix molecules are recognized by a cell. Recent studies have demonstrated that remodeling in heart and vasculature is linked to alterations in extracellular matrix and integrin expression. The roles of integrins in controlling cellular behavior have made these molecules highly attractive drug targets. New insights into mechanisms whereby the extracellular matrix takes part in the control of smooth muscle cell proliferation and cardiac growth suggest a number of putative targets for future therapies that can be applied to increase plaque stability, prevent the clinical consequences of atherosclerosis and improve outcomes after interventional procedures such as cardiac transplantation. Therapeutic candidates include antibodies, cyclic peptides, peptidomimetics and small molecules. The integrin inhibitors Integrilin and ReoPro have been approved as blood thinners in cardiovascular disease, and newer agents are undergoing testing. Although integrin function is important in the cardiovascular system, there are wide gaps in knowledge. In this review, we discuss the primary mechanisms of action and signaling of integrins in the cardiac and vascular system in normal and pathological states, as well as therapeutic strategies for targeting these molecules in the cardiovascular system.

Cyclooxygenase-2 inhibitors: a painful lesson.

Non-steroidal anti-inflammatory drugs (NSAIDs) represent a clinically important class of agents. NSAIDs are commonly used in treatment of conditions such as headache, fever, inflammation and joint pain. Complications often arise from chronic use of NSAIDs. Gastrointestinal (GI) toxicity in the form of gastritis, peptic erosions and ulcerations and GI bleeds limit usage of NSAIDs. These toxicities are thought to be due to cyclooxygenase (COX)-1 blockade. COX-1 generates cytoprotective prostanoids such as prostaglandin (PG) E2 and prostacyclin (PGI2). COX-2 inhibitors, commonly referred to as coxibs, were developed to inhibit inflammatory prostanoids without interfering with production of COX-1 prostanoids. Concerns over cardiovascular safety, however, have evolved based on the concept of inhibition of COX-2-derived endothelial prostanoids without inhibition of platelet thromboxane A2, leading to increased cardiovascular risk. The Celecoxib Long-Term Arthritis Safety Study (CLASS) trial did not show a significant increase in cardiovascular risk for celecoxib (Celebrex), but results of the Vioxx Gastrointestinal Outcomes Research (VIGOR) study showed an increased cardiovascular risk with long-term daily usage of rofecoxib in patients with rheumatoid arthritis. The Adenomatous Poly Prevention on Vioxx (APPROVe) trial further evaluated cardiovascular effects of rofecoxib and recently led to removal of this drug from the marketplace. Coxibs affect renal function via blockade of normal COX-2 functions. COX-2 expression increases in high renin states and in response to a high-sodium diet or water deprivation. PGI2 and PGE2 are the most important renal prostanoids. PGI2 inhibition results in hyperkalemia. PGE2 inhibition results in sodium retention, which leads to hypertension, peripheral edema and potentially exacerbation of heart failure. This review article discusses beneficial and deleterious effects associated with prostanoids produced by COX-1 and COX-2 in various organs and how blockade of these products translates into clinical medicine.