Medicine and Health Sciences Commons^™

Increase In The Proportion Of Patients Hospitalized With Acute Myocardial Infarction With Do-Not-Resuscitate Orders Already In Place Between 2001 And 2007: A Nonconcurrent Prospective Study, Jane Saczynski, Ezra Gabbay, David Mcmanus, Richard Mcmanus, Joel Gore, Jerry Gurwitz, Darleen Lessard, Robert Goldberg

Richard H. McManus

BACKGROUND AND OBJECTIVE: Shared decision making and advance planning in end-of-life decisions have become increasingly important aspects of the management of seriously ill patients. Here, we describe the use and timing of do-not-resuscitate (DNR) orders in patients hospitalized with acute myocardial infarction (AMI). STUDY DESIGN AND SETTING: The nonconcurrent prospective study population consisted of 4182 patients hospitalized with AMI in central Massachusetts in four annual periods between 2001 and 2007. RESULTS: One-quarter (25%) of patients had a DNR order written either prior to or during hospitalization. The frequency of DNR orders remained constant (24% in 2001; 26% in 2007). Among …

Transitions, Risks, And Actions In Coronary Events--Center For Outcomes Research And Education (Trace-Core): Design And Rationale, Molly Waring, Richard Mcmanus, Jane Saczynski, Milena Anatchkova, David Mcmanus, Randolph Devereaux, Robert Goldberg, Jeroan Allison, Catarina Kiefe

Richard H. McManus

Background: Cardiovascular disease continues to cause significant morbidity, mortality, and impaired quality of life, with unrealized health gains from the underuse of available evidence. The Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education (TRACE-CORE) aims to advance the science of acute coronary syndromes by examining the determinants and outcomes of the quality of transition from hospital to community and by quantifying the impact of potentially modifiable characteristics associated with decreased quality of life, rehospitalization, and mortality. Methods and Results: TRACE-CORE comprises a longitudinal multiracial cohort of patients hospitalized with acute coronary syndromes, 2 research projects, …

Increase In The Proportion Of Patients Hospitalized With Acute Myocardial Infarction With Do-Not-Resuscitate Orders Already In Place Between 2001 And 2007: A Nonconcurrent Prospective Study, Jane Saczynski, Ezra Gabbay, David Mcmanus, Richard Mcmanus, Joel Gore, Jerry Gurwitz, Darleen Lessard, Robert Goldberg

Richard H. McManus

BACKGROUND AND OBJECTIVE: Shared decision making and advance planning in end-of-life decisions have become increasingly important aspects of the management of seriously ill patients. Here, we describe the use and timing of do-not-resuscitate (DNR) orders in patients hospitalized with acute myocardial infarction (AMI). STUDY DESIGN AND SETTING: The nonconcurrent prospective study population consisted of 4182 patients hospitalized with AMI in central Massachusetts in four annual periods between 2001 and 2007. RESULTS: One-quarter (25%) of patients had a DNR order written either prior to or during hospitalization. The frequency of DNR orders remained constant (24% in 2001; 26% in 2007). Among …

Transitions, Risks, And Actions In Coronary Events--Center For Outcomes Research And Education (Trace-Core): Design And Rationale, Molly Waring, Richard Mcmanus, Jane Saczynski, Milena Anatchkova, David Mcmanus, Randolph Devereaux, Robert Goldberg, Jeroan Allison, Catarina Kiefe

Richard H. McManus

Background: Cardiovascular disease continues to cause significant morbidity, mortality, and impaired quality of life, with unrealized health gains from the underuse of available evidence. The Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education (TRACE-CORE) aims to advance the science of acute coronary syndromes by examining the determinants and outcomes of the quality of transition from hospital to community and by quantifying the impact of potentially modifiable characteristics associated with decreased quality of life, rehospitalization, and mortality. Methods and Results: TRACE-CORE comprises a longitudinal multiracial cohort of patients hospitalized with acute coronary syndromes, 2 research projects, …

Fabry's Disease With Lvot Obstruction: Diagnosis And Management, Jacob Blount, James Wu, Matthew Martinez

James K Wu MD

A 46-year-old male was diagnosed with hypertrophic cardiomyopathy (HCM) and severe left ventricular outflow tract (LVOT) obstruction. Genetic testing revealed that this was a "mimic of HCM" and the true diagnosis was Fabry's disease, although there were no other clinical features of Fabry's. Despite maximal medical therapy he remained symptomatic from the outflow tract gradient and required surgical myectomy for symptom relief. This case illustrates the diagnosis of an HCM mimic by genetic testing.

Hiv/Aids And Development In The Pacific, Trevor Cullen

Trevor A Cullen

No abstract provided.

Treating Methicillin-Resistant Staphylococcus Aureus With The Drug Vancomycin In A Home Infusion Therapy Setting, Joshua Webb, Alberto Coustasse, Dennis Emmett

Dennis Emmett

The basic purpose of this paper is to examine the effects the home infusion therapy has on the cost, duration of, and effectiveness of treatment between those individuals under 60 and those 60 and over. The results show that those 60 and over had a slightly higher cost/day. The older age group had slightly smaller treatment duration, then the younger group. The number of adverse effects was small. The results suggest that home infusion therapy appears to be a viable alternative to hospitalization.

The Uncertainty Of The Egfr, Tony Badrick, Peter Turner

Tony Badrick

The estimated glomerular filtration rate (eGFR) is a parameter derived from the serum creatinine, patient age and gender and is used to ascertain renal function. It is subject to variation because of the analytical error of the creatinine measurement and biological variation. The widespread use of the eGFR to classify renal disease has led to the identification of more patients with marginal chronic kidney disease but because of the uncertainty of the eGFR it has also led to over-diagnosis of some kidney disease. There is a well described age relation with eGFR.The uncertainty of the eGFR at the critical decision …

Unique Transcriptional Profile Of Sustained Ligand-Activated Preconditioning In Pre- And Post-Ischemic Myocardium, Kevin Ashton, Amanda Tupicoff, Grant Williams-Pritchard, Can Kiessling, Louise See Hoe, John Headrick, Jason Peart

Kevin Ashton

Background: Opioidergic SLP (sustained ligand-activated preconditioning) induced by 3–5 days of opioid receptor (OR) agonism induces persistent protection against ischemia-reperfusion (I-R) injury in young and aged hearts, and is mechanistically distinct from conventional preconditioning responses. We thus applied unbiased gene-array interrogation to identify molecular effects of SLP in pre- and post-ischemic myocardium. Methodology/Principal Findings: Male C57Bl/6 mice were implanted with 75 mg morphine or placebo pellets for 5 days. Resultant SLP did not modify cardiac function, and markedly reduced dysfunction and injury in perfused hearts subjected to 25 min ischemia/45 min reperfusion. Microarray analysis identified 14 up- and 86 down-regulated …

Managing A Cardiac Emergency, C Midei, Terry Capuano

Terry A Capuano MBA, MSN, RN, FACHE, NE-BC

No abstract provided.

Diabetes Care Trends In The Ma Patient Centered Medical Home Initiative (Ma Pcmhi) At Mid-Point, Sai Cherala, Judith Steinberg, Stephen Baker

Sai Cherala

Background: The MA PCMHI is a multi-payer demonstration involving 45 primary care practices. Thirty-one (31) practices receive additional financial support; all receive technical assistance.

Objectives: To assess data trends in diabetes quality measures from participating adult practices.

Study Design: Quality improvement study utilizing practices’ self-reported data on clinical quality measures. Diabetes measures included blood pressure, LDL cholesterol and hemoglobin A1C control and depression screening.

Methods: Monthly quality data from 38 practices reported June 2011 (baseline) through November 2012 were evaluated. Using a general linear mixed model Analysis of Variance (ANOVA), an overall comparison across time and pair-wise comparisons between times …

Prioritising Cvd Prevention Therapy - Absolute Risk Versus Individual Risk Factors, Jenny Doust, Sharon Sanders, Jonathon Shaw, Paul Glasziou

Jenny Doust

Background: Previous studies suggest that a high proportion of persons at high risk of cardiovascular disease in Australia are not receiving adequate disease prevention with blood pressure and lipid lowering therapy. However, it is not clear how a move to an absolute risk factor approach will affect the proportion of the population that is treated with blood pressure and lipid lowering therapy versus treatment based on individual risk factors. Methods: We classified participants in the AusDiab follow up cohort study who had no previous history of cardiovascular disease and who were not taking blood pressure or lipid lowering medication currently …

Systematic Review Did Not Consider Problem Of Treatment Effects, Su May Liew, Jenny Doust, Paul Glasziou

Jenny Doust

Extract: Siontis and colleagues’ systematic review comparing established risk prediction models for cardiovascular disease is a useful validation of previous studies, but they seem to have ignored the problem of treatment effects.

Coronary Artery Disease, Coronary Revascularization, And Outcomes In Chronic Advanced Systolic Heart Failure, Mihai Gheorghiade, James Flaherty, Gregg Fonarow, Ravi Desai, Richard Lee, David Mcgiffin, Thomas Love, Inmaculada Aban, Eric Eichhorn, Robert Bonow, Ali Ahmed

Ravi V Desai MD

No abstract provided.

Cooperative Effects Of Drug-Resistance Mutations In The Flap Region Of Hiv-1 Protease, Jennifer Foulkes-Murzycki, Christina Rosi, Nese Yilmaz, Robert Shafer, Celia Schiffer

Celia A. Schiffer

Understanding the interdependence of multiple mutations in conferring drug resistance is crucial to the development of novel and robust inhibitors. As HIV-1 protease continues to adapt and evade inhibitors while still maintaining the ability to specifically recognize and efficiently cleave its substrates, the problem of drug resistance has become more complicated. Under the selective pressure of therapy, correlated mutations accumulate throughout the enzyme to compromise inhibitor binding, but characterizing their energetic interdependency is not straightforward. A particular drug resistant variant (L10I/G48V/I54V/V82A) displays extreme entropy-enthalpy compensation relative to wild-type enzyme but a similar variant (L10I/G48V/I54A/V82A) does not. Individual mutations of sites …

Gene-Based Therapy For Alpha-1 Antitrypsin Deficiency, Christian Mueller, Terence Flotte

Christian Mueller

Alpha-1 antitrypsin Deficiency (AATD) has been an attractive target for the development of gene therapy because it is a common single gene disorder, for which there would appear to be significant benefit to be gained for lung disease patients by augmentation of plasma levels of wild-type (M) alpha-1 antitrypsin (AAT). While a significant proportion of patients also have liver disease, which is unlikely to be benefitted by augmentation, the potential to treat or prevent lung disease by replacement of plasma levels to at least 11 microMolar (571 mcg/ml) is the basis upon which several protein replacement therapies have been licensed …

Structural And Thermodynamic Basis Of Amprenavir/Darunavir And Atazanavir Resistance In Hiv-1 Protease With Mutations At Residue 50, Seema Mittal, Rajintha Bandaranayake, Nancy King, Moses Prabu-Jeyabalan, Madhavi Nalam, Ellen Nalivaika, Nese Yilmaz, Celia Schiffer

Celia A. Schiffer

Drug resistance occurs through a series of subtle changes that maintain substrate recognition but no longer permit inhibitor binding. In HIV-1 protease, mutations at I50 are associated with such subtle changes that confer differential resistance to specific inhibitors. Residue I50 is located at the protease flap tips, closing the active site upon ligand binding. Under selective drug pressure, I50V/L substitutions emerge in patients, compromising drug susceptibility and leading to treatment failure. The I50V substitution is often associated with amprenavir (APV) and darunavir (DRV) resistance, while the I50L substitution is observed in patients failing atazanavir (ATV) therapy. To explain how APV, …

Micrornas In Liver Disease, Gyongyi Szabo, Shashi Bala

Gyongyi Szabo

Small, noncoding microRNAs (miRNAs) regulate diverse biological functions in the liver and increasing evidence suggests that they have a role in liver pathology. This Review summarizes advances in the field of miRNAs in liver diseases, inflammation and cirrhosis. MicroRNA-122, the most abundant miRNA in hepatocytes, has well-defined roles in HCV replication, and data indicate that it also serves as a viable therapeutic target. The role of miR-122 is also emerging in other liver diseases. Ample evidence exists for the important regulatory potential of other miRNAs in conditions associated with liver inflammation related to alcohol use, the metabolic syndrome or autoimmune …

Factors Associated With The Risk Of Adenoma Recurrence In Distal And Proximal Colon, Adeyinka Laiyemo, Chyke Doubeni, Paul Pinsky, V. Paul Doria-Rose, Pamela Marcus, Robert Schoen, Elaine Lanza, Amanda Cross

Chyke A. Doubeni

Background/Aims: Colonoscopy may be less effective in preventing cancer in the proximal colon. We evaluated whether risk factors for adenoma recurrence exhibit differential effect on adenoma recurrence by colon subsite.

Methods: We examined the association of age, sex, body mass index, smoking status and use of nonsteroidal anti-inflammatory drugs (NSAIDs) on proximal and distal adenoma recurrence among 1,864 participants in the Polyp Prevention Trial. We used multinomial logistic regression models to calculate the relative risk ratios (RRR) and 95% CI.

Results: 733 (39.3%) participants had adenoma recurrence (228 distal only, 369 proximal only and 136 synchronous proximal and distal adenoma). …

Short- And Long-Term Risk Of Colorectal Adenoma Recurrence Among Whites And Blacks, Adeyinka Laiyemo, Chyke Doubeni, Hassan Brim, Hassan Ashktorab, Robert Schoen, Samir Gupta, Aline Charabaty, Elaine Lanza, Duane Smoot, Elizabeth Platz, Amanda Cross

Chyke A. Doubeni

BACKGROUND: It is unclear whether the higher burden from colorectal cancer among blacks is due to an increased biological susceptibility. OBJECTIVE: To determine whether non-Hispanic blacks (blacks) have a higher risk of adenoma recurrence than non-Hispanic whites (whites) after removal of colorectal adenoma. DESIGN: Secondary analysis of the Polyp Prevention Trial (PPT) data. SETTING: United States. PATIENTS: Patients were 1668 self-identified whites and 153 blacks who completed the 4-year trial. Of these, 688 whites and 55 blacks enrolled in a posttrial, passive Polyp Prevention Trial Continued Follow-up Study (PPT-CFS) and underwent another colonoscopy. MAIN OUTCOME MEASUREMENTS: Recurrence and location of …

Screening Colonoscopy And Risk For Incident Late-Stage Colorectal Cancer Diagnosis In Average-Risk Adults: A Nested Case-Control Study, Chyke Doubeni, Sheila Weinmann, Kenneth Adams, Aruna Kamineni, Diana Buist, Arlene Ash, Carolyn Rutter, V. Paul Doria-Rose, Douglas Corley, Robert Greenlee, Jessica Chubak, Andrew Williams, Aimee Kroll-Desrosiers, Eric Johnson, Joseph Webster, Kathryn Richert-Boe, Theodore Levin, Robert Fletcher, Noel Weiss

Chyke A. Doubeni

BACKGROUND: The effectiveness of screening colonoscopy in average-risk adults is uncertain, particularly for right colon cancer. OBJECTIVE: To examine the association between screening colonoscopy and risk for incident late-stage colorectal cancer (CRC). DESIGN: Nested case-control study. SETTING: Four U.S. health plans. PATIENTS: 1039 average-risk adults enrolled for at least 5 years in one of the health plans. Case patients were aged 55 to 85 years on their diagnosis date (reference date) of stage IIB or higher (late-stage) CRC during 2006 to 2008. One or 2 control patients were selected for each case patient, matched on birth year, sex, health plan, …

Human Monoclonal Antibody Mbl-Hcv1 Delays Hcv Viral Rebound Following Liver Transplantation: A Randomized Controlled Study, R. Chung, F. Gordon, M. Curry, T. Schiano, S. Emre, K. Corey, J. Markmann, M. Hertl, J. Pomposelli, E. Pomfret, S. Florman, M. Schilsky, Teresa Broering, Robert Finberg, Gyongyi Szabo, Phillip Zamore, U. Khettry, Gregory Babcock, Donna Ambrosino, Brett Leav, Mark Leney, H. Smith, Deborah Molrine

Gyongyi Szabo

Rapid allograft infection complicates liver transplantation (LT) in patients with hepatitis C virus (HCV). Pegylated interferon-alpha and ribavirin therapy after LT has significant toxicity and limited efficacy. The effect of a human monoclonal antibody targeting the HCV E2 glycoprotein (MBL-HCV1) on viral clearance was examined in a randomized, double-blind, placebo-controlled pilot study in patients infected with HCV genotype 1a undergoing LT. Subjects received 11 infusions of 50 mg/kg MBL-HCV1 (n=6) or placebo (n=5) intravenously with three infusions on day of transplant, a single infusion on days 1 through 7 and one infusion on day 14 after LT. MBL-HCV1 was well-tolerated …

Iron-Induced Cardiac Damage: Role Of Apoptosis And Deferasirox Intervention, Yeling Wang, Miaozong Wu, Rabaa Al-Rousan, Hua Liu, Jacqueline Fannin, Satyanarayana Paturi, Ravi Arvapalli, Anjaiah Katta, Sunil Kakarla, Kevin Rice, William Triest, Eric Blough

Kevin M Rice

Excess cardiac iron levels are associated with cardiac damage and can result in increased morbidity and mortality. Here, we hypothesize that elevations in tissue iron can activate caspase-dependent signaling, which leads to increased cardiac apoptosis and fibrosis, and that these alterations can be attenuated by iron chelation. Using an iron-overloaded gerbil model, we show that increased cardiac iron is associated with reduced activation of Akt (Ser473 and Thr308), diminished phosphorylation of the proapoptotic regulator Bad (Ser136), and an increased Bax/Bcl-2 ratio. These iron-overload-induced alterations in Akt/Bad phosphorylation and Bax/Bcl-2 ratio were coupled with increased activation of the downstream caspase-9 (40/38- …

Gender Differences And Predictors Of Mortality In Spontaneous Coronary Artery Dissection: A Review Of Reported Cases, Ellen Thompson, Sueellen Ferraris, Todd Gress, Victor Ferraris

Ellen A. Thompson

Spontaneous coronary artery dissection (SCAD) is a rare but potentially lethal event.1,2 It is a separation between the intimal and medial wall of the coronary vessel. The potential result of the dissection is obstruction of the vessel lumen and subsequent myocardial ischemia. Prior to the widespread use of coronary angiography, diagnosis was made at autopsy.2 From reported cases, some trends have been identified. There are reported associations with female sex,2,3 exercise,4–7pregnancy and postpartum state,8–12 coronary artery disease,2, 13, 14 and connective tissue disorders.9,15,16 The left anterior descending artery is more affected in women; the right coronary artery is more often …

Gender Differences And Predictors Of Mortality In Spontaneous Coronary Artery Dissection: A Review Of Reported Cases, Ellen Thompson, Sueellen Ferraris, Todd Gress, Victor Ferraris

Todd W. Gress

Spontaneous coronary artery dissection (SCAD) is a rare but potentially lethal event.1,2 It is a separation between the intimal and medial wall of the coronary vessel. The potential result of the dissection is obstruction of the vessel lumen and subsequent myocardial ischemia. Prior to the widespread use of coronary angiography, diagnosis was made at autopsy.2 From reported cases, some trends have been identified. There are reported associations with female sex,2,3 exercise,4–7pregnancy and postpartum state,8–12 coronary artery disease,2, 13, 14 and connective tissue disorders.9,15,16 The left anterior descending artery is more affected in women; the right coronary artery is more often …

Compliance With The Centers For Disease Control And Prevention Recommendations For The Diagnosis And Treatment Of Sexually Transmitted Diseases, Bryan Kane, Linda Degutis, Helen Sayward, Gail D'Onofrio

Bryan G Kane MD

No abstract provided.

Tca Cycle Inactivation In Staphylococcus Aureus Alters Nitric Oxide Production In Raw 264.7 Cells, Chandirasegaran Massilamany, Arunakumar Gangaplara, Donald Gardner, James Musser, David Steffen, Greg Somerville, Jay Reddy

Greg A. Somerville

Inactivation of the Staphylococcus aureus tricarboxylic acid (TCA) cycle delays the resolution of cutaneous ulcers in a mouse soft tissue infection model. In this study, it was observed that cutaneous lesions in mice infected with wild-type or isogenic aconitase mutant S. aureus strains contained comparable inflammatory infiltrates, suggesting the delayed resolution was independent of the recruitment of immune cells. These observations led us to hypothesize that staphylococcal metabolism can modulate the host immune response. Using an in vitro model system involving RAW 264.7 cells, the authors observed that cells cultured with S. aureus aconitase mutant strains produced significantly lower amounts …

Impaired Overload-Induced Hypertrophy Is Associated With Diminished Mtor Signaling In Insulin-Resistant Skeletal Muscle Of The Obese Zucker Rat, Anjaiah Katta, Sudarsanam Kundla, Sunil Kakarla, Miaozong Wu, Jacqueline Fannin, Satyanarayana Paturi, Hua Liu, Hari Addagarla, Eric Blough

Eric Blough

Recent data have suggested that insulin resistance may be associated with a diminished ability of skeletal muscle to undergo hypertrophy (Paturi S, Gutta AK, Kakarla SK, Katta A, Arnold EC, Wu M, Rice KM, Blough ER. J Appl Physiol 108: 7–13, 2010). Here we examine the effects of insulin resistance using the obese Zucker (OZ) rat with increased muscle loading on the regulation of the mammalian target of rapamycin (mTOR) and its downstream signaling intermediates 70-kDa ribosomal protein S6 kinase (p70S6k), ribosomal protein S6 (rpS6), eukaryotic elongation factor 2 (eEF2), and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). Compared with …

Iron-Induced Cardiac Damage: Role Of Apoptosis And Deferasirox Intervention, Yeling Wang, Miaozong Wu, Rabaa Al-Rousan, Hua Liu, Jacqueline Fannin, Satyanarayana Paturi, Ravi Arvapalli, Anjaiah Katta, Sunil Kakarla, Kevin Rice, William Triest, Eric Blough

Ravi K. Arvapalli

Excess cardiac iron levels are associated with cardiac damage and can result in increased morbidity and mortality. Here, we hypothesize that elevations in tissue iron can activate caspase-dependent signaling, which leads to increased cardiac apoptosis and fibrosis, and that these alterations can be attenuated by iron chelation. Using an iron-overloaded gerbil model, we show that increased cardiac iron is associated with reduced activation of Akt (Ser473 and Thr308), diminished phosphorylation of the proapoptotic regulator Bad (Ser136), and an increased Bax/Bcl-2 ratio. These iron-overload-induced alterations in Akt/Bad phosphorylation and Bax/Bcl-2 ratio were coupled with increased activation of the downstream caspase-9 (40/38- …

Not Just Full Of Hot Air: Hyperbaric Oxygen Therapy Increases Survival In Cases Of Necrotizing Soft Tissue Infections, Joshua Shaw, Charles Psoinos, Timothy Emhoff, Heena Santry

Joshua J Shaw

INTRODUCTION: The utility of hyperbaric oxygen therapy (HBOT) in the treatment for necrotizing soft tissue infections (NSTI) has not been proven. Previous studies have been subject to significant selection bias since HBOT is not universally available at all medical centers and there is often considerable delay associated with its initiation. We examined the utility of HBOT for the treatment of NSTI in the modern era by isolating centers that have their own HBOT facilities. METHODS: We queried all centers in the University Health Consortium (UHC) database from 2008 to 2010 that have their own HBOT facilities (N=14). Cases of NSTI …