Medicine and Health Sciences Commons^™

Adjusting Medicare Capitation Payments Using Prior Hospitalization Data, Arlene Ash, Frank Porell, Leonard Gruenberg, Eric Sawitz, Alexa Beiser

Frank Porell

The diagnostic cost group approach to a reimbursement model for health maintenance organizations is presented. Diagnostic information about previous hospitalizations is used to create empirically determined risk groups, using only diagnoses involving little or no discretion in the decision to hospitalize. Diagnostic cost group and other models (including Medicare's current formula and other prior-use models) are tested for their ability to predict future costs, using R2 values and new measures of predictive performance. The diagnostic cost group models perform relatively well with respect to a range of criteria, including administrative feasibility, resistance to provider manipulation, and statistical accuracy.

Competition Between Ski And Creb-Binding Protein For Binding To Smad Proteins In Transforming Growth Factor-Beta Signaling, Weijun Chen, Suvana Lam, Hema Srinath, Celia Schiffer, William Royer, Kai Lin

Celia A. Schiffer

The family of Smad proteins mediates transforming growth factor-beta (TGF-beta) signaling in cell growth and differentiation. Smads repress or activate TGF-beta signaling by interacting with corepressors (e.g. Ski) or coactivators (e.g. CREB-binding protein (CBP)), respectively. Specifically, Ski has been shown to interfere with the interaction between Smad3 and CBP. However, it is unclear whether Ski competes with CBP for binding to Smads and whether they can interact with Smad3 at the same binding surface on Smad3. We investigated the interactions among purified constructs of Smad, Ski, and CBP in vitro by size-exclusion chromatography, isothermal titration calorimetry, and mutational studies. Here, …

Mass Spectrometry Analysis Of Hiv-1 Vif Reveals An Increase In Ordered Structure Upon Oligomerization In Regions Necessary For Viral Infectivity, Jared Auclair, Karin Green, Shivender Shandilya, James Evans, Mohan Somasundaran, Celia Schiffer

Celia A. Schiffer

HIV-1 Vif, an accessory protein in the viral genome, performs an important role in viral pathogenesis by facilitating the degradation of APOBEC3G, an endogenous cellular inhibitor of HIV-1 replication. In this study, intrinsically disordered regions are predicted in HIV-1 Vif using sequence-based algorithms. Intrinsic disorder may explain why traditional structure determination of HIV-1 Vif has been elusive, making structure-based drug design impossible. To characterize HIV-1 Vif's structural topology and to map the domains involved in oligomerization we used chemical cross-linking, proteolysis, and mass spectrometry. Cross-linking showed evidence of monomer, dimer, and trimer species via denaturing gel analysis and an additional …

Exploring The Role Of The Solvent In The Denaturation Of A Protein: A Molecular Dynamics Study Of The Dna Binding Domain Of The 434 Repressor, Celia Schiffer, Volker Dötsch, Kurt Wuthrich, Wilfred Van Gunsteren

Celia A. Schiffer

Molecular dynamics simulations of the DNA binding domain of 434 repressor are presented which aim at unraveling the role of solvent in protein denaturation. Four altered solvent models, each mimicking various possible aspects of the addition of a denaturant to the aqueous solvent, were used in the simulations to analyze their effects on the stability of the protein. The solvent was altered by selectively changing the Coulombic interaction between water and protein atoms and between different water molecules. The use of a modified solvent model has the advantage of mimicking the presence of denaturant without having denaturant molecules present in …

Structural Analysis Of Human Immunodeficiency Virus Type 1 Crf01_Ae Protease In Complex With The Substrate P1-P6., Rajintha Bandaranayake, Moses Prabu-Jeyabalan, Junko Kakizawa, Wataru Sugiura, Celia Schiffer

Celia A. Schiffer

The effect of amino acid variability between human immunodeficiency virus type 1 (HIV-1) clades on structure and the emergence of resistance mutations in HIV-1 protease has become an area of significant interest in recent years. We determined the first crystal structure of the HIV-1 CRF01_AE protease in complex with the p1-p6 substrate to a resolution of 2.8 A. Hydrogen bonding between the flap hinge and the protease core regions shows significant structural rearrangements in CRF01_AE protease compared to the clade B protease structure.

When Is Informed Consent Required In Cluster Randomized Trials In Health Research?, Andrew Mcrae, Charles Weijer, Ariella Binik, Jeremy Grimshaw, Robert Boruch, Jamie Brehaut, Allan Donner, Martin P Eccles, Raphael Saginur, Angela White, Monica Taljaard

Charles Weijer

This article is part of a series of papers examining ethical issues in cluster randomized trials (CRTs) in health research. In the introductory paper in this series, we set out six areas of inquiry that must be addressed if the cluster trial is to be set on a firm ethical foundation. This paper addresses the second of the questions posed, namely, from whom, when, and how must informed consent be obtained in CRTs in health research? The ethical principle of respect for persons implies that researchers are generally obligated to obtain the informed consent of research subjects. Aspects of CRT …

Characterization Of The Lignin Signature In Lake Mead, Nv, Sediment: Comparison Of On-Line Flash Chemopyrolysis (600°C) And Off-Line Chemolysis (250°C), Spencer Steinberg, Elkas Nemr, Mark Rudin

Mark J. Rudin

The distribution of lignin in sediment is a useful tool for tracing the transport of land-derived organic matter in an aquatic environment. Tetramethylammonium hydroxide (TMAH) flash chemopyrolysis, or chemolysis followed by GC-MS analysis can be used for evaluating the origin of organic carbon in sediments. TMAH chemopyrolysis or chemolysis of organic matter produces a myriad of semi-volatile products. Among these products are methylated phenols which are an indirect measure of lignin in sediment. In this study, total organic carbon, elemental carbon, and lignin were measured in Lake Mead sediments. This study indicates that terrestrial runoff makes a contribution to Lake …

Who Is The Research Subject In Cluster Randomized Trials In Health Research?, Andrew Mcrae, Charles Weijer, Ariella Binik, Angela White, Jeremy Grimshaw, Robert Boruch, Jamie Brehaut, Allan Donner, Martin Eccles, Raphael Saginur, Merrick Zwarenstein, Monica Taljaard

Charles Weijer

This article is part of a series of papers examining ethical issues in cluster randomized trials (CRTs) in health research. In the introductory paper in this series, we set out six areas of inquiry that must be addressed if the CRT is to be set on a firm ethical foundation. This paper addresses the first of the questions posed, namely, who is the research subject in a CRT in health research? The identification of human research subjects is logically prior to the application of protections as set out in research ethics and regulation. Aspects of CRT design, including the fact …

30-Year Trends In Heart Failure In Patients Hospitalized With Acute Myocardial Infarction, David Mcmanus, Marcello Chinali, Jane Saczynski, Joel Gore, Jorge Yarzebski, Frederick Spencer, Darleen Lessard, Robert Goldberg

Jorge L. Yarzebski

Despite significant advances in its treatment, acute myocardial infarction (AMI) remains an important cause of heart failure (HF). Contemporary data remain lacking, however, describing long-term trends in incidence rates, demographic and clinical profiles, and outcomes of patients who develop HF as a complication of AMI. Our study sample consisted of 11,061 residents of the Worcester (Massachusetts) metropolitan area hospitalized with AMI at all greater Worcester hospitals in 15 annual study periods from 1975 to 2005. Overall, 32.4% of patients (n = 3,582) with AMI developed new-onset HF during their acute hospitalization. Patients who developed HF were generally older, more likely …

Recent Trends In The Incidence, Treatment, And Outcomes Of Patients With Stemi And Nstemi, David Mcmanus, Joel Gore, Jorge Yarzebski, Frederick Spencer, Darleen Lessard, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: despite the widespread use of electrocardiographic changes to characterize patients presenting with acute myocardial infarction, little is known about recent trends in the incidence rates, treatment, and outcomes of patients admitted for acute myocardial infarction further classified according to the presence of ST-segment elevation. The objectives of this population-based study were to examine recent trends in the incidence and death rates associated with the 2 major types of acute myocardial infarction in residents of a large central Massachusetts metropolitan area. METHODS: We reviewed the medical records of 5383 residents of the Worcester (MA) metropolitan area hospitalized for either ST-segment …

Declining Length Of Stay For Patients Hospitalized With Ami: Impact On Mortality And Readmissions, Jane Saczynski, Darleen Lessard, Frederick Spencer, Jerry Gurwitz, Joel Gore, Jorge Yarzebski, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: Length of hospital stay after acute myocardial infarction decreased significantly in the 1980s and 1990s. Whether length of stay has continued to decrease during the 2000s, and the impact of decreasing length of stay on rehospitalization and mortality, is unclear. We describe decade-long (1995-2005) trends in length of stay after acute myocardial infarction, and examine whether declining length of stay has impacted early rehospitalization and postdischarge mortality in a population-based sample of hospitalized patients.

METHODS: The study sample consisted of 4184 patients hospitalized with acute myocardial infarction in a central New England metropolitan area during 6 annual periods (1995, …

Management And Outcomes Of Renal Disease And Acute Myocardial Infarction, Paul Santolucito, Dennis Tighe, David Mcmanus, Jorge Yarzebski, Darleen Lessard, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: Contemporary trends in the management and outcomes of chronic kidney disease patients who develop an acute myocardial infarction have not been adequately described, particularly from the more generalizable perspective of a population-based investigation. METHODS: The study population consisted of 6219 residents of the Worcester, Massachusetts, metropolitan area who were hospitalized with acute myocardial infarction in 6 annual periods between 1995 and 2005. Patients were categorized as having preserved kidney function (n=3154), mild to moderate chronic kidney disease (n=2313), or severe chronic kidney disease (n=752) at the time of hospital admission. RESULTS: Patients with chronic kidney disease were more likely …