Total MI Research Articles

Minimum Mutual Information and Non-Gaussianity through the Maximum Entropy Method: Estimation from Finite Samples

The Minimum Mutual Information (MinMI) Principle provides the least committed, maximum-joint-entropy (ME) inferential law that is compatible with prescribed marginal distributions and empirical cross constraints. Here, we estimate MI bounds (the MinMI values) generated by constraining sets Tcr comprehended by mcr linear and/or nonlinear joint expectations, computed from samples of N iid outcomes. Marginals (and their entropy) are imposed by single morphisms of the original random variables. N-asymptotic formulas are given both for the distribution of cross expectation’s estimation errors, the MinMI estimation bias, its variance and distribution. A growing Tcr leads to an increasing MinMI, converging eventually to the total MI. Under N-sized samples, the MinMI increment relative to two encapsulated sets Tcr1 ⊂ Tcr2 (with numbers of constraints mcr1<mcr2 ) is the test-difference δH = Hmax 1, N - Hmax 2, N ≥ 0 between the two respective estimated MEs. Asymptotically, δH follows a Chi-Squared distribution 1/2NΧ2 (mcr2-mcr1) whose upper quantiles determine if constraints in Tcr2/Tcr1 explain significant extra MI. As an example, we have set marginals to being normally distributed (Gaussian) and have built a sequence of MI bounds, associated to successive non-linear correlations due to joint non-Gaussianity. Noting that in real-world situations available sample sizes can be rather low, the relationship between MinMI bias, probability density over-fitting and outliers is put in evidence for under-sampled data.

Abstract 9897: Frequency of Non-Systems Delays in STEMI Patients Undergoing Primary PCI and Implications for Door-to-Balloon Time Reporting. A Report from The ACTION Registry®-GWTG™ and AHA

Introduction: Door to balloon (D2B) time ≤90 minutes (min), and percentage of primary PCI patients (pts) with a D2B ≤90 min are used as performance metrics by many organizations. Pts can be excluded from this measure if they have a non-systems related delay. However, how frequently exclusions occur, and how it affects the reporting of D2B times at the hospital level is unknown. Methods: The percentage of pts having non-systems delays (cardiac arrest, intubation, difficult vascular access, etc) for primary PCI at the hospital level was calculated using data from the ACTION Registry®-GWTG™. Pts were excluded if the first ECG was not diagnostic, or were transferred to or from another hospital. Hospitals having < 36 primary PCIs during the study period were also excluded. Hospitals were categorized into three groups based on tertiles of percentage of excluded pts. The percentage of hospitals with a D2B ≤90 min in ≥90% of pts were calculated by first including and then excluding pts that had non-systems delays. Results: From 1/1/07-3/31/11, 43,909 pts from 294 hospitals were included. The percentage of exclusions recorded differed substantially among hospitals, ranging from 0-68% of pts (median 9.2% [IQR 5.6%, 13.5%] with low tertile ≤7.1%, intermediate tertile 7.1% to 11.2% and high tertile ≥11.2%. Reasons for exclusion included vascular access difficulty (7.8%) cardiac arrest/intubation (38%) and PCI procedural difficulties (20%). There were no significant differences in hospital annual total MI, STEMI, or primary PCI volumes, or hospital bed size among the three groups. Including pts with non-systems delays significantly increased D2B times and decreased the proportion of pts achieving D2B ≤90 min as well as percentage of hospitals having ≥90% of STEMI pts with D2B ≤90 min (TABLE). Discussion: The proportion of pts excluded from D2B reporting varies substantially among hospitals. This has an important impact on reported performance measures.

Impact of Tumor Infiltrating T Cells in Patients with Follicular Lymphoma At Diagnosis

Abstract 769Previous global gene expression profiling (GEP) studies have demonstrated non-malignant tumor-infiltrating immune cells present in the tumor at diagnosis were among the molecular features of the most important prognostic markers (Sandeep et al. NEJM 2004). We investigated the molecular mechanisms whereby tumor infiltrating T cells (TILs) are altered in the FL microenvironment and examined GEP of highly purified, sorted infiltrating CD4 and CD8 T cells from previously cryopreserved single cell suspensions of lymph node (LN) biopsies at the time of diagnosis in treatment naive patients with FL (n=12) and compared them to those isolated from reactive tonsils (n=7) as well as peripheral blood (PB) (n=10) of age matched healthy donors. In both CD4 and CD8, among the most downregulated genes in FL TILs were ACTN1 and IL17A, and the most upregulated genes were PMCH, ETV1, TNFRSF9 and NAMPT.PMCH is not expressed in PB T cells, but its expression is highly induced when healthy PB T cells are cultured, either in cell contact or in transwell culture, with FL cells. Using well characterized tissue microarrays of diagnostic FL samples (n=172) we now show that the T-cell expressed genes of PMCH, ETV1 and NAMPT have prognostic significance for survival and time to transformation in FL. Patients with higher percentage (p=0.039, median survival 10.59yr vs 19.20yr) and number (p=0.016, median survival 8.67yr vs 19.01yr) of PMCH expressing cells in intrafollicular and higher percentage (p=0.021, median survival 8.18yr vs 16.5yr) in interfollicular area had significantly longer disease specific survival (DSS) compared with patient with low number of PMCH expressing cells. Patients with higher percentage (p=0.014, median survival 19.01yr vs 11.75) and number (p=0.032, median survival 19.01yr vs 12.41yr) of ETV1 expressing cells in intrafollicular area showed significantly shorter DSS comparing to those with lower percentage and number of ETV1 expressing cells. Furthermore, the higher total MI of NAMPT expression showed significantly longer DSS (p=0.003, median survival 7.62yr vs 18.28yr) as well.Pathway analysis indicated disruption in multiple cellular pathways including actin-based motility/cytoskeleton formation which is in keeping with our previous studies where we have shown altered T cell expression of genes regulating actin in CLL (Gorgun et al, JCI 2005) and AML (De Lieu et al, Blood 2009). Using Time-Lapse Imaging we demonstrated both CD4 and CD8 TILs from patients with FL (n=7) have significantly impaired motility compared to those of healthy TILs from reactive tonsil (n=4) (p<0.025). We have further demonstrated that short term culture of allogeneic healthy T cells with FL cells from treatment naive patients (n=8) directly induce significantly impaired T cell motility compared to culture of these T cells with healthy allogeneic non malignant B cells (n=6)(p<0.05).Taken together, these data indicate that TILs in patients with FL are abnormal in terms of their gene expression and function. Furthermore, we provide evidence supporting the role that FL cells play in inducing changes in immune cells in the tumor microenvironment. In addition, we have shown that changes in the protein level in tumor infiltrating T-cells have an impact on the survival and time to transformation in patients with FL. We are further characterizing the mechanisms of gene expression alteration in TILs of patients with FL and its functional consequences in the biology and of the disease. Since non-malignant infiltrating immune cells have a crucial role in the outcome of patients with FL, understanding the nature and impact of the abnormalities induced in TILs in these patients is vital before any immunotherapeutic strategies can be implemented to attempt to alter the immune microenvironment in FL. Disclosures:Gribben:Roche: Honoraria; Celgene: Honoraria; GSK: Honoraria; Mundipharma: Honoraria; Gilead: Honoraria; Pharmacyclics: Honoraria.

An Analysis of Medical Costs of Diabetic Patients in a University Hospital (1996~2005)

Background: The aim of this research was to find out the costs of diabetes , as research in a prospective cohort study looking into the development of diabetic complicat ions followed by treatment intervention by a medical institution. The research compared the changes in med ical costs by following-up on the treatment details of diagnosed diabetes for the last 10 years in a university hospital. Methods: The research used data of outpatient, inpatient, pharmaceutical and total medical costs, from 1996 to 2005, of individual patients who were diagnosed with diabeti c patients, to analyze the outpatient and inpatient total medical cost changes over the years. Results: After antidiabetic drug, in the case of outpatient treatment, pharmaceutical costs increased on average by about 25,000 won a month for diabetic patients witho ut complications and by 35,000 won for diabetic patients with microvascular complications. Outpatient medical costs were affected after drug treatment by as much of an increase as created by the pharmaceu tical costs. The total medical costs, that is the sum of inpatient and outpatient costs, decreased by 30~40% compared to that before drug treatment. In the case of total medical cost, MI or ESRD cost 2~3 times more in pharmaceutical costs than before the development of complications. The total medical costs of diabet ic patients with CVA, MI and ESRD complications increased in the first year after development of the complication, and th is was followed by a decrease in the next year, showing a tendency to remain constant with no increase or decrease over subsequent years. This means that the total medical costs of patients with complications remain continuously large throughout the life of the diagnosed patient. Conclusion: For diabetic patients, pharmaceutical costs are the most important factor in determining outpatient medical costs. (KOREAN DIABETES J 32:366-376, 2008)

Abstract 3095: Prognostic Significance Of Post-revascularisation Irreversible Myocardial Injury Detected By Cardiovascular Magnetic Resonance Imaging

Background The prognostic significance of revascularization procedure related myocardial injury is uncertain. Delayed enhancement CMR (DE-CMR) has been shown to reliably identify areas of irreversible myocardial injury. We evaluated the prognostic significance of procedure related myocardial injury in a consecutive series of patients undergoing high risk PCI or CABG. Methods/Results 152 patients underwent DE-CMR pre and 1– 6 days post elective PCI or CABG. Primary endpoint was defined as total mortality, non-fatal MI, ventricular arrhythmia terminated by ICD (VA), and unstable angina or heart failure requiring hospitalization. Secondary endpoint was the composite of total mortality, non-fatal MI and VA. During a median follow-up of 2.9 years, 27 patients (18%) reached the primary endpoint and 12 patients (8%) the secondary endpoint. 49 patients (32%) had evidence of new myocardial hyperenhancement (HE) with a median mass of 5.0g (IQR 4.8 –7.1). In a univariate analysis, age, LV EF post intervention, and presence of new HE were predictive of the primary outcome. Elevated troponin (at 24 h) showed a trend towards poorer outcome. In a multivariate Cox regression analysis only age and presence of new HE (HR 2.7, 95% CI 1.1, 5.8) remained independently correlated with occurrence of the primary endpoint. New myocardial HE was the single independent predictor of the composite secondary endpoint (HR 4.2 95% CI 1.2, 16.1). Conclusion Even small amounts of procedure-related myocardial injury are associated with poorer medium term clinical outcomes. CMR identified myocardial injury may be a stronger prognostic marker than cardiac troponin in the setting of coronary revascularisation.

Transfer with GP IIb/IIIa inhibitor tirofiban for primary percutaneous coronary intervention vs. on-site thrombolysis in patients with ST-elevation myocardial infarction (STEMI): a randomized open-label study for patients admitted to community hospitals

Our study aimed to compare two reperfusion strategies in patients with ST-elevation myocardial infarction (STEMI) admitted initially to a community hospital without catheterization facilities. Four hundred and one patients with STEMI admitted to community hospital (13 hospitals, radius 20-150 km from cath-lab) were randomized to on-site thrombolysis or to transport with tirofiban (10 microg/kg bolus i.v. + i.v. infusion 0.1 microg/kg/min) for primary PCI in single invasive centre. Primary endpoints were total mortality, recurrent MI (re-AMI), and stroke during 1 year follow-up. Delay to reperfusion defined as interval between admission and start of fibrinolysis or primary PCI was 35 and 145 min (P < 0.0001). Mean time of tirofiban administration to PCI in transfer group was: 122.3 +/- 35.7 min. Mortality was not different during hospitalization and at 30th-day, with trend towards lower mortality at 1 year in transport group (12.5 vs. 7.0%, P = 0.061). There were no differences in the rate of re-AMI and stroke, with trend towards lower incidence of re-AMI in transfer group at 1 year (7.5 vs. 3.5%, P = 0.073). Composite of death/re-AMI/stroke was higher in on-site group during follow-up (15.5 vs. 8.0%, P = 0.019; 21.5 vs. 11.4%, P = 0.006, respectively, at 30th-day and 1 year). Outcomes at 1 year follow-up suggest that transportation with adjunctive therapy with GP IIb/IIIa inhibitor tirofiban for primary PCI is superior to on-site thrombolysis for patient with STEMI presenting to hospital without catheterization facilities.

Dogma Disputed: Can Aggressively Lowering Blood Pressure in Hypertensive Patients with Coronary Artery Disease Be Dangerous?

Because coronary perfusion occurs mainly during diastole, patients with coronary artery disease (CAD) could be at increased risk for coronary events if diastolic pressure falls below critical levels. To determine whether low blood pressure could be associated with excess mortality and morbidity in this population. A secondary analysis of data from the International Verapamil-Trandolapril Study (INVEST), which was conducted from September 1997 to February 2003. 862 sites in 14 countries. 22 576 patients with hypertension and CAD. Patients from INVEST were randomly assigned to a verapamil sustained-release- or atenolol-based strategy; blood pressure control and outcomes were equivalent. An unadjusted quadratic proportional hazards model was used to evaluate the relationship between average on-treatment blood pressure and risk for the primary outcome (all-cause death, nonfatal stroke, and nonfatal myocardial infarction [MI]), all-cause death, total MI, and total stroke. A second model adjusted for differences in baseline covariates. The relationship between blood pressure and the primary outcome, all-cause death, and total MI was J-shaped, particularly for diastolic pressure, with a nadir at 119/84 mm Hg. After adjustment, the J-shaped relationship persisted between diastolic pressure and primary outcome. The MI-stroke ratio remained constant over a wide blood pressure range, but at a lower diastolic blood pressure, there were substantially more MIs than strokes. An interaction between decreased diastolic pressure and history of revascularization was observed; low diastolic pressure was associated with a relatively lower risk for the primary outcome in patients with revascularization than in those without revascularization. This is a post hoc analysis of hypertensive patients with CAD. The risk for the primary outcome, all-cause death, and MI, but not stroke, progressively increased with low diastolic blood pressure. Excessive reduction in diastolic pressure should be avoided in patients with CAD who are being treated for hypertension.

Hospital Variation in Mortality After First Acute Myocardial Infarction in Denmark From 1995 to 2002

This study used linked data from the National Hospital Registry to determine the factors that contribute to differences between hospitals in all-cause mortality after first acute myocardial infarction (AMI) between 1995 and 2002. The study included 64,321 patients with their first admission for AMI between 1995 and 2002 and surviving the day of admission. Multilevel logistic regression was used to determine the relationships between regional and hospital characteristics and 28-day and 365-day mortality after adjusting for individual characteristics, period, and medical history. Tertiary cardiac care centers (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.67-0.96) and main regional hospitals (OR, 0.90; 95% CI, 0.80-0.99) had improved 28-day mortality compared with local hospitals. A 2-fold increase in annual total MI volume decreased 28-day mortality (OR, 0.91; 95% CI, 0.87-0.94) and 365-day mortality (OR, 0.95; 95% CI, 0.91-0.98). Differences between hospitals were more substantial for short-term mortality, such that patients were about twice as likely to die within 28 days in hospitals with the worst performance versus those with the best performance. Higher regional AMI incidence was associated with lower mortality before 2000; this disappeared after 2000. Other regional contextual characteristics had very modest effects on mortality. Type of hospital, and especially total MI volume at the hospital level, were significantly associated with mortality after AMI. Individual hospitals varied substantially in both short- and long-term mortality.

Incidence of MI is equivalent with verapamil SR-based and atenolol-based strategies in patients with hypertension and CAD: the international verapamil SR-trandolapril study

P-423 Key Words: Myocardial Infarction, Verapamil, Invest

Model indicators for maternal and child health: an overview of process, product, and applications.

Further improvements in the health of mothers and children depend, in part, on collecting, analyzing, and interpreting relevant data correctly. Despite consistent efforts to improve data capacity and use during the past two decades, the need persists for a model set of maternal and child health (MCH) indicators to guide decisions about health conditions to be monitored, elements to be included in data sets, and definitions of measures. This article describes development, key characteristics, and major applications of a set of MCH Model Indicators (MCH MI) created to address these needs. A conceptual model with five domains was created to organize and guide development of the indicators. The development process included systematic specification of concepts, formulas, age/gender groups, and data sources, as well as recommendations for frequency of surveillance. Information sources included published reports and expert opinion. There are 217 indicators distributed across domains as follows: 75 health status, 9 contextual characteristics, 16 health systems capacity and adequacy, 49 risk/protective status, and 68 health and related services. Twenty of the indicators, all of them in the health status domain, are recommended for routine surveillance. The indicators can be used to identify and address MCH problems, to complement and expand other sets of MCH indicators, to serve as standards for consistent definitions, to provide guidance for creation and revision of MCH and related data bases, and to provide a foundation for the development of related sets of indicators. Some of the indicators require further development, but the total MCH MI package constitutes a solid foundation for subsequent work, as well as for ongoing modifications that are essential if the Model Indicators are to remain responsive to MCH needs.

Organization of the forelimb area in squirrel monkey motor cortex: representation of digit, wrist, and elbow muscles.

The EMG in 8 to 14 hand, forearm, and arm muscles evoked by intracortical electrical stimulation was recorded at 433 sites in layer V in the region of the forelimb area of the primary motor cortex (MI) of three squirrel monkeys during ketamine anesthesia. At each site, the EMG was recorded at movement threshold (T) and at 1.5T and 2T at each site (but less than or equal to 60 microA), and the threshold movement was noted. In the animals examined, the total MI forelimb area identified by movements or EMG occupied about 25 to 35 mm2. At most sites from which a forelimb movement was evoked, EMG activity was evoked in one or more of the recorded muscles. One group of sites located rostrolaterally to the main forelimb area was separated by an intervening zone largely related to the face. The average area from which digit, wrist, elbow, or shoulder movement was evoked at threshold was nearly the same, and their movement thresholds were not significantly different. Average movement thresholds across the anterior-posterior extent of MI were also similar. All muscles recorded could be activated by cortical stimulation. Most commonly more than one muscle was activated from a single site. The highest individual EMG levels were produced at sites from which more than one muscle was activated. These results suggest that small regions of MI influence multiple muscles. Individual muscles were typically activated at multiple, spatially separated locations. For many muscles, increasing the stimulation intensity revealed additional separate areas of activation. Spatial locations of different muscles showed considerable interanimal variation. The size of most muscle representations was relatively large. The smallest representations always included the intrinsic hand muscles and the largest included the proximal muscles. Orderly topographic relationships among forelimb joints or muscles within the MI forelimb area were not apparent. Although distal muscle activation tended to be found posteriorly in the forelimb area and proximal muscles tended to be activated from anterior sites, both could be activated from broadly distributed and overlapping areas. The broad, overlapping nature of the muscle representation supports the concept that a small region of cortex is involved in controlling functional groups of muscles. The intermingling of muscle representations may provide a substrate for local cortical interactions among territories representing various muscle synergies or for changing associations of muscle groups. The representation plan derived from these mappings contains elements of all previously described summaries of MI organization.(ABSTRACT TRUNCATED AT 400 WORDS)