Hypothermia is a bedside predictor of imminent death in patients with congestive heart failure.

BACKGROUND: Most studies on predictors of mortality for patients with congestive heart failure (CHF) have described predictors that are either difficult to measure in routine practice or are only modestly sensitive and specific. Having observed 3 patients whose body temperature decreased shortly before death, we hypothesized that hypothermia may predict inhospital mortality. METHODS: The medical records of 291 patients with a primary discharge diagnosis of CHF were selected from 423 admissions to Memorial Hermann Hospital, Houston, Tex, 1998, after excluding patients with comorbidities that confound body temperature, deaths for causes other than progressive pump failure, and readmissions except the last. Three groups were defined on the basis of admission body temperature (T adm): hypothermia groups T adm (95.5 degrees F-96.5 degrees F) and T adm < 95.5 degrees F, and reference group T adm > or = 96.6 degrees F. Several other known CHF risk factors were studied for confounding, and adjusted hazard ratios were calculated using Cox regression. RESULTS: Of the 291 patients (mean age 73 years, 47% men), 17 (6%) had hypothermia on admission. Mean hospital stay was 5 days. Of the 17 (6%) patients who died of pump failure, 5 had been hypothermic on admission. Hypothermia was significantly associated with survival, and after adjusting for New York Heart Association functional class, hazard ratio for T adm < 95.5 degrees F was 4.46 (95% confidence interval 1.38-14.3) (P trend = .0283). CONCLUSIONS: Hypothermia predicted inhospital death in these patients with CHF. If confirmed by future studies, this finding could prove useful, because temperature can be measured continuously, rapidly, and inexpensively, in or out of the hospital.

Proportional odds ratio model for comparison of diagnostic tests in meta-analysis.

BACKGROUND: Consider a meta-analysis where a 'head-to-head' comparison of diagnostic tests for a disease of interest is intended. Assume there are two or more tests available for the disease, where each test has been studied in one or more papers. Some of the papers may have studied more than one test, hence the results are not independent. Also the collection of tests studied may change from one paper to the other, hence incomplete matched groups. METHODS: We propose a model, the proportional odds ratio (POR) model, which makes no assumptions about the shape of ORp, a baseline function capturing the way OR changes across papers. The POR model does not assume homogeneity of ORs, but merely specifies a relationship between the ORs of the two tests. One may expand the domain of the POR model to cover dependent studies, multiple outcomes, multiple thresholds, multi-category or continuous tests, and individual-level data. RESULTS: In the paper we demonstrate how to formulate the model for a few real examples, and how to use widely available or popular statistical software (like SAS, R or S-Plus, and Stata) to fit the models, and estimate the discrimination accuracy of tests. Furthermore, we provide code for converting ORs into other measures of test performance like predictive values, post-test probabilities, and likelihood ratios, under mild conditions. Also we provide code to convert numerical results into graphical ones, like forest plots, heterogeneous ROC curves, and post test probability difference graphs. CONCLUSIONS: The flexibility of POR model, coupled with ease with which it can be estimated in familiar software, suits the daily practice of meta-analysis and improves clinical decision-making.

Repeated-measures modeling improved comparison of diagnostic tests in meta-analysis of dependent studies.

OBJECTIVE: Current methods for meta-analysis of diagnostic tests do not allow utilizing all the information from papers in which several tests have been studied on the same patient sample. We demonstrate how to combine several studies of diagnostic tests, where each study reports on more than one test and some tests (but not necessarily all of them) are shared with other papers selected for the meta-analysis. We adopt statistical methodology for repeated measurements for the purpose of meta-analysis of diagnostic tests. STUDY DESIGN AND SETTING: The method allows for missing values of some tests for some papers, takes into account different sample sizes of papers, adjusts for background and confounding factors including test-specific covariates and paper-specific covariates, and accounts for correlations of the repeated measurements within each paper. It does not need individual-level data, although it can be modified to use them, and uses the two-by-two table of test results vs. gold standard. RESULTS: The results are translated from diagnostic odds ratios (DOR) to more clinically useful measures such as predictive values, post-test probabilities, and likelihood ratios. Models to capture between-study variation are introduced. The fit and influence of specific studies on the regression can be evaluated. Furthermore, model-based tests for homogeneity of DORs across papers are presented. CONCLUSION: The use of this new method is illustrated using a recent meta-analysis of the D-dimer test for the diagnosis of deep venous thrombosis.

The effect of Evercare on hospital use.

OBJECTIVES: To examine the use of hospital and related medical care services of a novel managed care program using nurse practitioners (NPs) and directed specifically at long-stay nursing home residents. DESIGN: Quasi-experimental posttest design with two control groups to minimize selection bias. SETTING: Nursing homes. PARTICIPANTS: Evercare enrollees in five sites were compared with two sets of controls: nursing home residents in the same nursing homes who did not enroll in Evercare (control-in) and residents of nursing homes that did not participate in Evercare (control-out). MEASUREMENTS: Utilization data from Medicare and United Healthcare (the parent corporation for Evercare) were obtained for slightly more than 2 years. Patterns of use were assessed by calculating the monthly use rate for each group and aggregating to form annual rates. Usages addressed included hospital admissions and days, emergency room visits, therapy services, mental health services, and podiatry. Adjustments were made to correct for age, race, and sex. Because the groups differed in terms of the rate of cognitive impairment, the analysis was stratified on this variable. RESULTS: The incidence of hospitalizations was twice as high in control residents as in Evercare residents (4.63 and 4.67 per 100 enrollees per month vs 2.43 in the 15 months after census, P<.001). This difference corresponded to Evercare's use of intensive service days. The same pattern held for preventable hospitalizations (0.80 and 0.86 vs 0.28, P<.001). The pattern held when residents were stratified by cognitive status. On average, using a NP is estimated to save about $103,000 a year in hospital costs per NP. CONCLUSION: The use of active primary care provided by NPs may have prevented the occurrence of some hospitalizable events, but its major effect was allowing cases to be managed more cost-effectively.

Plaque blush, branch location, and calcification are angiographic predictors of progression of mild to moderate coronary stenoses.

BACKGROUND: Angiographic predictors of plaque progression are weak and few: length, irregular surface, turbulence, low shear, and (in some studies) eccentricity and calcification. Having noted plaques that briefly retained dye after angiography, we interpreted these as plaques with a fissured surface or neovascularization and hypothesized that progression would be predicted by "plaque blush." METHODS: Plaques (<50% diameter stenosis) in 68 pairs of angiograms, 5.6 +/- 4.8 months apart, were reviewed by 2 blinded observers. The presence of plaque blush, calcification, clot (mobile defect), eccentricity, and a branch point location were compared between progressing (> or =20% stenosis increase) and nonprogressing plaques. RESULTS: Sixteen lesions in 15 patients progressed from 29% +/- 13% to 68% +/- 14% over a period of 8.1 +/- 7.9 months. Patients with and without progression were similar in sex, age, congestive heart disease risk factors, medications, interval between angiograms, clinical presentation, and initial stenosis severity. By logistic regression, plaque blush (BL) (P =.002), calcification (CA) (P =.024), and a branch (BR) point location (P =.001) predicted plaque progression. The odds ratio for plaque progression (ORp) was calculated as ORp = e(2.5 x BL + 1.8 x CA + 2.6 x BR). Using an ORp of 1/3, the model has 81% sensitivity and 77% specificity. A second analysis in which each progressive lesion was compared with proximal and distal lesions and with one in a different coronary artery yielded similar results. CONCLUSIONS: In mild to moderate coronary stenoses, studied retrospectively, plaque blush (a new sign) and a branch point location were strong predictors of plaque progression, whereas calcification was a weak predictor of progression.

Outcomes of managed care of dually eligible older persons.

PURPOSE: To assess changes in various functional and satisfaction measures between older persons enrolled in Minnesota Senior Health Options (MSHO), a managed care program for older persons eligible for both Medicare and Medicaid. DESIGN AND METHODS: We used two sets of matched controls for MSHO enrollees and their families and matched controls living in the community and in nursing homes: Persons in the same county who were eligible to enroll but did not enroll in MSHO and persons in other metropolitan areas where MSHO is not available. For the community sample, we used questionnaires to measure functional status (activities of daily living), pain, unmet care needs, satisfaction, and caregiver burden. Approximately 2 years after the first survey, we resurveyed respondents who lived in the community at the time of the first survey. For the nursing home residents, we used annual assessments to calculate case mix to compare changes in functional levels over time. RESULTS: There were few significant differences in change over time between the MSHO sample and the two control groups. Out-of-area controls showed greater increases in pain but in-area controls showed less interference from pain. Compared with out-of-area controls, MSHO clients showed greater increase in homemaker use, meals on wheels, and outpatient rehabilitation. Compared with in-area controls, they showed more use of meals on wheels and less help from family with household tasks. There were few differences in satisfaction, but the MSHO families showed significantly lower burden than controls on five items. IMPLICATIONS: The analyses show only modest evidence of benefit from MSHO compared with the two control groups. The model represented by MSHO does not appear to generate substantial differences in outcomes across function, satisfaction, and caregiver burden.

Thermography basket catheter: in vivo measurement of the temperature of atherosclerotic plaques for detection of vulnerable plaques.

We have developed an intravascular thermography basket catheter to measure the temperature of the vessel wall to locate foci of inflammation. Our 3 Fr thermography basket catheter is a thermocouple-based catheter made of a nitinol expandable and externally controllable basket system loaded with nine small and flexible built-in thermosensors. It is equipped with real-time data acquisition software with a thermal resolution of 0.0001 degrees C and a sampling rate of 20 readings per second. In 10 inbred cholesterol-fed dogs with femoral (but not carotid) atherosclerosis, we found foci of warmth on the surface of atherosclerotic but not disease-free regions (P < 0.05). Marked temperature heterogeneity was also observed in the aortas of atherosclerotic Watanabe rabbits but not in normal rabbits. The catheters showed satisfactory accuracy, reproducibility, and safety. If confirmed in further studies, it has the potential to be utilized in detection of vulnerable plaques.

Influenza infection exerts prominent inflammatory and thrombotic effects on the atherosclerotic plaques of apolipoprotein E-deficient mice.

BACKGROUND: The role of infection in the development and complications of atherosclerosis has been the focus of much attention. We reported previously that influenza vaccination was associated with reduced risk of recurrent myocardial infarction. Here, we report the effect of influenza A virus on the apolipoprotein E-deficient (apoE(-/-)) mouse, an animal model of atherosclerosis. METHODS AND RESULTS: Twenty-four apoE(-/-) mice >24 months old were injected with 1 LD(50) (lethal dose 50) of influenza A virus. Ten wild-type C57BL/6 infected mice and 11 noninfected age-matched apoE(-/-) mice served as controls. Multiple aortic sections were studied histologically 3, 5, and 10 days later. The infected mice showed markedly increased intimal cellularity compared with the noninfected apoE(-/-) mice. No aortic abnormalities were seen in infected wild-type mice. Ten infected apoE(-/-) mice had a significant subendothelial infiltrate composed of a heterogeneous group of cells that stained positively for smooth muscle cell actin, F4/80 (macrophages), and CD3 (T lymphocytes). One case of subocclusive platelet and fibrin-rich thrombus was seen. CONCLUSIONS: This study shows that influenza infection promotes inflammation, smooth muscle cell proliferation, and fibrin deposition in atherosclerotic plaques.

pH Heterogeneity of human and rabbit atherosclerotic plaques; a new insight into detection of vulnerable plaque.

BACKGROUND: Atherosclerotic plaques are heterogeneous with respect to inflammation, calcification, vascularity, oxygen, and temperature. We hypothesized that they also vary in pH and measured pH in living human carotid endarterectomized atherosclerotic plaques (CEA), Watanabe heritable hyperlipidemic (WHHL) rabbit aortas and human umbilical arteries (HUA). METHODS AND RESULTS: We measured pH of CEA of 48 patients, nine WHHL rabbit aortas and 11 HUA specimens (as controls) using a glass type microelectrode mounted on a micromanipulator in a 37 degrees C incubator. We also used single emission and also dual emission fluorescence ratio imaging microscopy employing pH-sensitive probes to confirm pH heterogeneity. Mean pH measured at 415 points of CEA was 7.55+/-0.32; at 275 points of WHHL rabbit aortas it was 7.40+/-0.43; and in 233 points of HUA it was 7.24+/-0.1. In CEA, pH of yellow (lipid-rich) areas was significantly lower than pH in calcified areas (7.15+/-0.01 vs. 7.73+/-0.01, P<0.0001). The coefficients of variation (heterogeneity) of pH in CEA, WHHL rabbit aortas, and HUA were 0.038+/-0.010, 0.039+/-0.007, and 0.009+/-0.003, respectively (P=0.0001). Fluorescence microscopic imaging confirmed pH heterogeneity in both humans and rabbits but not in HUA. In a variance components analysis 82% of the heterogeneity was due to the within-plaque variation and 2% was attributable to between-plaque variation. CONCLUSIONS: Our findings support the hypothesis of pH heterogeneity in plaques, and suggest a possible role for detecting low pH in the detection of plaque vulnerability. The source of pH heterogeneity particularly acidic pH, its impact on the stability of plaques and its potential clinical utility in locating vulnerable plaques remain to be evaluated.