Association of low body temperature and poor outcomes in patients admitted with worsening heart failure: a substudy of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial.

AIMS: Risk stratification in patients admitted with worsening heart failure (HF) is essential for tailoring therapy and counselling. Risk models are available but rarely used, in part because many require laboratory and imaging results that are not routinely available. Body temperature is associated with prognosis in other illnesses, and we hypothesized that low body temperature would be associated with worse outcomes in patients admitted with worsening HF. METHODS AND RESULTS: The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial was an event-driven, randomized, double-blind, placebo-controlled study of tolvaptan in 4133 patients hospitalized for worsening HF with an EF <40%. Co-primary endpoints were all-cause mortality and cardiovascular (CV) death or HF rehospitalization. Body temperature was measured orally at randomization and entered in analyses both as a continuous variable and categorized into three groups (<36 °C, 36-36.5 °C, and >36.5 °C) using Cox regression models. The composite of CV death or HF rehospitalization occurred in 1544 patients within 1 year. For every 1 °C decrease in body temperature, the risk of adverse outcomes increased by 16% [hazard raio (HR) 1.16, 95% confidence interval (CI) 1.04-1.28], after adjustment for age, gender, race, systolic blood pressure, EF, blood urea nitrogen, and serum sodium. In fully adjusted analysis, the risk of adverse outcomes in the lowest body temperature group (<36 °C) was 51% higher than that of the index group (>36.5 °C) (HR 1.35, 95% CI 1.15-1.58). CONCLUSIONS: Low body temperature is an independent marker of poor cardiovascular outcomes in patients admitted with worsening HF and reduced EF.

Americans on health care reform: results from polls conducted with Zogby International, Inc.

During a time of uncertainty regarding the future of the American health care system, an assessment, over time, of Americans' opinion on different legislative or health policy directions is a valuable asset to decision makers. After polling over 10,000 Americans via three polls on these topics over four months, a few distinct trends have emerged. When it comes to health care reform, Americans want a "tune-up," not a "trade-in" of their health care system by implementing reforms that allow the system to work more efficiently for the largest number of people possible, paying for it through savings found by reducing extraneous and wasteful spending and by increasing the quality of care. A clear sense of equity is also evident, as a majority do not agree with insurance companies using pre-existing health conditions as a metric in determining eligibility and believe in mandating that those who are employed, except for the smallest companies, should be covered.

Utilizing a trauma systems approach to benchmark and improve combat casualty care.

BACKGROUND: Derived from the necessity to improve the outcomes of soldiers injured on the battlefield, the U.S. military forces developed and implemented the Joint Theater Trauma System (JTTS) and the Joint Theater Trauma Registry based on U.S. civilian trauma system models. The purpose of this analysis was to develop battlefield injury outcome benchmark metrics and to evaluate the impact of JTTS-driven performance improvement interventions. METHODS: To quantify these achievements, the Joint Theater Trauma Registry captured mechanistic, physiologic, diagnostic, therapeutic, and outcome data on 18,377 injured patients from January 2004 to May 2008 for analysis. Benchmarks were developed and statistically validated by using control chart methodology. RESULTS: The majority (66.4%) of battlefield wounds were penetrating mechanism, 23.3% of all patients had an Injury Severity Score of > or = 16, 21.8% had a base deficit of > or = 5, 30.5% of patients required blood, and 6.8% required massive transfusion (> or = 10 units red blood cell per 24 hours). In this severely injured population from the battlefield, the JTTS developed several pertinent benchmark metrics to assess quality of care associated with postinjury complications and mortality. The implementation of 27 JTTS-developed evidenced-based clinical practice guidelines and an improved information dissemination process was associated with a decrease in aggregate postinjury complications by 54%. CONCLUSIONS: Despite the numerous challenges of a global trauma system, the JTTS has set the standard for trauma care on the modern battlefield utilizing evidence-based medicine. The development of injury care benchmarks enhanced the evolution of the combat casualty care performance improvement process within the trauma system.

Circadian body temperature variability is an indicator of poor prognosis in cardiomyopathic hamsters.

BACKGROUND: Low body temperature is an independent predictor of poor prognosis in patients with congestive heart failure. The cardiomyopathic hamster develops progressive biventricular dysfunction, resulting in heart failure death at 9 months to 1 year of life. Our goal was to use cardiomyopathic hamsters to examine the relationship between body temperature and heart failure decompensation and death. METHODS AND RESULTS: To this end, we implanted temperature and activity transducers with telemetry into the peritoneal space of 46 male Bio-TO-2 Syrian cardiomyopathic hamsters. Multiple techniques, including computing mean temperature, frequency domain analysis, and nonlinear analysis, were used to determine the most useful method for predicting poor prognosis. Data from 44 hamsters were included in our final analysis. We detected a decline in core body temperature in 98% of the hamsters 8+/-4 days before death (P < .001). We examined the dominant frequency of temperature variation (ie, the circadian rhythm) by using cosinor analysis, which revealed a significant decrease in the amplitude of the body temperature circadian rhythm 8 weeks before death (0.28 degrees C; 95% CI, 0.26-0.31) compared to baseline (0.36 degrees C; 95% CI, 0.34-0.39; P=.005). The decline in the circadian temperature variation preceded all other evidence of decompensation. CONCLUSIONS: We conclude that a decrease in the amplitude of the body temperature circadian rhythm precedes fatal decompensation in cardiomyopathic hamsters. Continuous temperature monitoring may be useful in predicting preclinical decompensation in patients with heart failure and in identifying opportunities for therapeutic intervention.

Influenza virus directly infects, inflames, and resides in the arteries of atherosclerotic and normal mice.

OBJECTIVE: Influenza can trigger heart attacks, and vaccination against influenza reduces the risk of cardiovascular events. Currently, it is believed that influenza virus in general does not disseminate to extra-pulmonary tissues. We assessed the vascular effects of influenza infection and whether the virus can directly infect atherosclerotic arteries in mice. METHODS/RESULTS: We intranasally infected 4 different types of mice--atherosclerotic apo E-deficient (our primary model), LDL receptor knockout, C57BL/6, and outbred Swiss--with influenza A/HK (H3/N2) virus. On day 7 after infection, we cultured viable virus from lung, aorta, and heart tissue, but not from the blood of apo E-deficient mice. Immunofluorescence studies showed influenza A virus NP1 protein and real time polymerase chain reaction (PCR) assay showed RNA in the aorta of infected apo E-deficient mice. Infected mice had significantly higher blood levels of chemokines and cytokines than control mice. At the local level, gene expression for several chemokines and cytokines was increased and eNOS expression was decreased. Infected mice had a higher density of macrophages in plaque than did control mice. CONCLUSIONS: We have shown for the first time that influenza virus can directly infect and reside in atherosclerotic arteries and that infection was associated with systemic and arterial-level pro-inflammatory changes.

Use of oseltamivir after influenza infection is associated with reduced incidence of recurrent adverse cardiovascular outcomes among military health system beneficiaries with prior cardiovascular diseases.

BACKGROUND: Influenza infection has been associated with increased risk of adverse cardiac and cerebral vascular outcomes. Oseltamivir, a treatment for influenza, has been shown to decrease the severity of an influenza episode, but few data exist regarding its potentially protective effect against recurrent vascular outcomes among influenza patients with a history of vascular disease. METHODS AND RESULTS: Electronic healthcare service and pharmacy records for 37,482 TRICARE beneficiaries, aged 18 and older, with a coded history of cardiovascular (CV) disease and a subsequent diagnosis of influenza from October 1, 2003, through September 30, 2007, were examined. Subjects were grouped according to whether they had filled a prescription for oseltamivir within 2 days of their influenza diagnosis. The incidence of recurrent CV events within 30 days after the influenza diagnosis among oseltavmivir-treated and untreated subjects was 8.5% and 21.2%, respectively (P<0.005). Subject age was a persistent and significant contributor to the likelihood of recurrent CV outcomes. After controlling for the differences in demographics among treated and untreated cohorts using a propensity-scored logistic regression model, a statistically significant protective effect was associated with oseltamivir treatment (odds ratio, 0.417; 95% CI, 0.349 to 0.498). CONCLUSIONS: Our findings suggests that oseltamivir treatment for influenza is associated with significant decrease in the risk of recurrent CV events in subjects with a history of CV disease. These findings merit confirmation in further prospective and controlled studies. Meanwhile, in patients with CV disease, strict adherence with current practice guidelines for prevention and treatment of influenza is recommended.

Antibody-labeled liposomes for CT imaging of atherosclerotic plaques: in vitro investigation of an anti-ICAM antibody-labeled liposome containing iohexol for molecular imaging of atherosclerotic plaques via computed tomography.

We evaluated the specific binding of anti-intercellular adhesion molecule 1 (ICAM-1) conjugated liposomes (immunoliposomes, or ILs) to activated human coronary artery endothelial cells (HCAEC) with the purpose of designing a computed tomographic imaging agent for early detection of atherosclerotic plaques. Covalent attachment of anti-ICAM-1 monoclonal antibodies to pre-formed liposomes stabilized with polyethylene glycol yielded ILs, with a coupling efficiency of the ICAM-1 to the liposomes of 10% to 24%. The anti-ICAM-1-labeled ILs had an average diameter of 136 nm as determined by dynamic light-scattering and cryogenic electron microscopy. The ILs' encapsulation of 5-[N-acetyl-(2,3-dihydroxypropyl)-amino)-N, N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-benzene-1,3-dicarboxamide (iohexol) was determined to be 18% to 19% by a dialysis technique coupled with ultraviolet detection of free iohexol. This encapsulation corresponded to 30 to 38 mg iodine per mL IL solution, and the ILs exhibited 91% to 98.5% iohexol retention at room temperature and under physiologic conditions. The specific binding of the ILs to cultured, activated HCAEC was measured using flow cytometry, enzyme-linked immunosorbent assays, and fluorescence microscopy. The immunosorbent assays demonstrated the specificity of binding of anti-ICAM-1 to ICAM-1 compared with control studies using nonspecific immunoglobulin G-labeled ILs. Flow cytometry and fluorescence microscopy experiments demonstrated the expression of ICAM-1 on the surface of activated HCAEC. Therefore, our iohexol-filled ILs demonstrated potential for implementation in computed tomographic angiography to noninvasively detect atherosclerotic plaques that are prone to rupture.

Temporal trends in anti-diabetes drug use in TRICARE following safety warnings in 2007 about rosiglitazone.

PURPOSE: To describe utilization patterns for anti-diabetes medications among a cohort of diabetes patients in the Military Health System (MHS) before and after warnings about rosiglitazone issued in May 2007. METHODS: We used segmented regression analysis to compare changes in the level and trend of rosiglitazone utilization and use of other anti-diabetes therapies in the period prior to the drug warnings (between April 2006 and May 2007) and the period after the warnings were issued (between October 2007 and May 2008). RESULTS: The level and trend of rosiglitazone use changed after the highly publicized warnings. The number of prescriptions filled fell by almost 7000 after the warning (p < 0.001). The number of prescriptions filled for pioglitazone, sulfonylureas, and other diabetes drugs increased significantly after the warnings (p < 0.05 in all models). Overall, the level and trend of filled prescriptions per month for all anti-diabetic drugs did not significantly change after the warnings. CONCLUSIONS: Utilization patterns changed in response to warnings about rosiglitazone. While overall utilization of anti-diabetic drugs did not change, further study is needed to determine the associated health outcomes.

Racial and ethnic health disparities in TRICARE.

BACKGROUND: As a major provider of health care for racial and ethnic minority groups, the federal government has affirmed its commitment to the elimination of health disparities. Although numerous studies have examined health care disparities in various federal systems of care, few have examined these issues within TRICARE, the Department of Defense (DoDJ's program for providing health care coverage to members of the uniformed services and their dependents. METHODS: This study provides an exploratory analysis examining apparent disparities in health status, access to and satisfaction with care, and use of preventive care using the 2007 Health Care Survey of DoD Beneficiaries. Analyses compare outcomes by race/ethnicity and between TRICARE beneficiaries and national norms derived from the National Consumer Assessment of Health Plans Study Benchmarking Database and the National Healthcare Disparities Report, and are stratified by duty status. RESULTS: Compared to black non-Hispanics, a higher proportion of white non-Hispanic active-duty and retiree TRICARE beneficiaries reported good to excellent health status. However, on most measures, we found no differences between white non-Hispanic beneficiaries and members of racial/ethnic groups. When differences did exist, minority populations were likely to report better access to and use of services than whites. CONCLUSIONS: Although health disparities exist in health status and some measures of preventive care, black non-Hispanics and Hispanics often receive more equitable care under TRICARE than in the nation as a whole. These findings suggest the need to explore the characteristics of TRICARE that may be associated with more-favorable outcomes for racial and ethnic minority groups.

The association between oseltamivir use and adverse neuropsychiatric outcomes among TRICARE beneficiaries, ages 1 through 21 years diagnosed with influenza.

UNLABELLED: Recent reports out of Japan have linked therapeutic use of the oral neuraminidase inhibitor oseltamivir with adverse neuropsychiatric outcomes in adolescents. OBJECTIVE: To assess if protective measures should be taken to mitigate potential adverse outcomes among United States Department of Defense (DoD) pediatric beneficiaries who are prescribed oseltamivir therapeutically. STUDY GROUP: DoD healthcare beneficiaries, ages 1 through 21 years, who received a diagnosis of influenza from 1 October 2006 through 30 September 2007. METHODS: A retrospective cohort study using electronic healthcare service and pharmacy fill. Cross tabulations and propensity-adjusted logistic regression analyses were performed to compare the frequency of adverse neuropsychiatric outcomes among those treated therapeutically with oseltamivir with those that were not. RESULTS: The prevalences of neuropsychiatric diagnoses following the influenza diagnosis overall and among the treated and untreated groups were 3.5%, 3.0%, and 3.8%, respectively (p < .05). A statistically significant protective effect was associated with oseltamivir treatment (prevalence odds ratio (POR) = 0.82 (95% CI, 0.69, 0.96)) in a propensity-adjusted regression model. The model significantly associated increasing patient age with the likelihood of an adverse neuropsychiatric outcome, but the associations with patient gender and parental rank, a proxy used for socioeconomic status, were not statistically Significant. CONCLUSIONS: Our retrospective study found no evidence that oseltamivir treatment for influenza increased the risk of adverse neuropsychiatric outcomes among the study population. An additional study focusing on prospective medical surveillance of influenza patients is warranted.

Humanitarian assistance and disaster relief: changing the face of defense.

The US Department of Defense (DOD) is evolving to meet new security challenges in the twenty-first century. Today's challenges result from growing political, environmental, and economic instability in important areas of the globe that threaten national and global security. Immediate outreach to foreign nations in times of violent instability or natural disaster fosters security and stability both for the affected country and for the United States. Foreign humanitarian assistance (FHA) is a rapidly evolving military mission that addresses conflict prevention, conflict, postconflict, and natural disasters. With DOD's extensive global medical resources, it is often uniquely qualified to execute a critical role in relief and/or public health efforts. When and how the American military will act in FHA and disaster relief is a still evolving doctrine with three issues deserving particular attention: aligning operations with host government leadership, preserving humanitarian space, and tailoring the US military's unique resources to the specific political and medical situation at hand. The DOD's response to a large-scale earthquake in Peru suggests useful approaches to these three issues, provides a template for future FHA mission, and points to strategic decisions and operational capabilities that need further development to establish the FHA mission firmly within DOD's repertoire of security engagement activities.

TRICARE Management Activity Healthcare Facility Evidence-Based Design Survey.

UNLABELLED: This report summarizes findings from the TRICARE Management Activity (TMA) Healthcare Facility Evidence-Based Design Survey. TMA conducted 382 telephone interviews with active duty (AD) personnel and 36 interviews with AD spouses to solicit their opinions regarding 10 proposed healthcare facility design features that could improve the comfort and convenience of a hospital stay. The survey was composed of 10 multiple-choice questions that were based on recent findings in evidence-based healthcare facility design features. RESULTS: The 4 most important features for all respondents include having space in the patient room for overnight visitors, privacy features, and individual control of lighting and temperature. CONCLUSION: Developing specific hospital design plans will likely require continuing to work with patients and their loved ones to develop well-defined requirements. Potential study techniques include interviewing in facilities, holding focus groups, and observing patient and family behavior in the facility.

Factors contributing to suboptimal vaccination against influenza: results of a nationwide telephone survey of persons with cardiovascular disease.

Vaccination against influenza averts cardiovascular events and is recommended for all patients with coronary heart disease. Because data were unavailable regarding vaccination rates among such patients' household contacts, we sought to estimate the rate of influenza vaccination in persons with cardiovascular disease and their contacts. In 2004, we conducted a random, nationwide telephone survey of 1,202 adults (age, > or = 18 yr) to ascertain knowledge, attitudes, and behaviors regarding influenza vaccination. Of the interviewees, 134 (11.1%) had histories of heart disease or stroke. Of these 134, 57% were men, and 45% were > or = 65 years of age. Overall, 57% were inoculated against influenza in 2003-2004, and 68% intended the same during 2004-2005. Vaccination rates increased with age: 48% (ages, 18-49 yr), 68% (ages, 50-64 yr), and 75% (age, > or = 65 yr). Forty of 69 respondents (58%) reported that their spouses were vaccinated, and 7 of 21 (33%) reported the inoculation of children < or = 17 years old in their household. Only 65% of the 134 patients considered themselves to be of high-risk status. Chief reasons for remaining unvaccinated were disbelief in being at risk and fear of contracting influenza from the vaccine. Although seasonal influenza vaccination is recommended for all coronary heart disease patients and their household contacts, the practice is less prevalent than is optimal. Intensified approaches are needed to increase vaccination rates. These findings suggest a need to increase vaccination efforts in high-risk subjects, particularly amidst the emerging H1N1 pandemic.

An iodinated liposomal computed tomographic contrast agent prepared from a diiodophosphatidylcholine lipid.

Herein we report a novel vesicle-forming iodinated contrast agent for applications in computed tomographic (CT) imaging and drug delivery. Specifically, we have chemically modified a phosphatidylcholine lipid that is commonly used in liposome formation to create an iodinated lipid that self-assembles into approximately 50-150 nm iodoliposomes possessing as-prepared imaging contrast functionality. These iodoliposomes are structurally organized such that the iodinated moieties are contained within the vesicle's bilayer, leaving the liposomal interior unoccupied and thus available for encapsulating drugs. The iodoliposomes were characterized using electron microscopy and dynamic light scattering. We also calculated the iodoliposomes' iodine encapsulation efficiency, which was sufficient for use in current CT imaging protocols. These iodinated liposomes could also serve as multifunctional carriers upon the encapsulation of pharmaceutical agents, permitting simultaneous CT imaging and therapeutic treatment. Alternatively, the commercially available iodinated contrast agent iohexol could be encapsulated inside the iodoliposomes' aqueous core to further enchance their imaging contrast.

Creating healing environments in support of the U.S. Military: a commitment to quality through the built environment.

The U.S. Military Health System (MHS) provides care to 9.2 million beneficiaries with approximately 130 thousand military and civilian staff in 70 military hospitals, 411 primary care clinics, and 417 dental clinics around the world. In anticipation of nearly $11 billion of new medical construction planned for the next 5 years, this paper describes the commitment of the MHS leadership and its approach to creating healing physical environments across the system, employing a set of principles, projected outcomes, and design features to achieve world-class facilities for service members and the military "family." The results of a survey of active duty personnel and spouses indicated a desire for MHS facilities to provide space for family members to be able to spend the night, to control environmental features such as lighting and temperature, and to communicate more effectively with family and friends outside the facility via e-mail and telephone.

Decreasing body temperature predicts early rehospitalization in congestive heart failure.

BACKGROUND: In congestive heart failure (CHF), a low body temperature at hospital admission predicts in-hospital mortality. We hypothesized that a postdischarge reduction in body temperature predicts early CHF rehospitalization and death. METHODS: We reviewed the records of 198 patients discharged after CHF hospitalization. We categorized the patients as hypothermic or normothermic (cutoff point, 36.3 degrees C/97.4 degrees F) according to body temperature at discharge. We classified the 2 groups according to the direction of temperature change between discharge and the first follow-up visit: normothermic/non-decreasing temperature (N+), normothermic/decreasing temperature (N-), hypothermic/non-decreasing temperature (H+), and hypothermic/decreasing temperature (H-). RESULTS: Ninety-three patients (47%) had decreasing temperatures, and 105 patients (53%) had non-decreasing temperatures. Kaplan-Meier analysis revealed a significant intergroup difference in survival (P = .01) and rehospitalization time (P = .005). On logistic regression, a decreasing temperature was significantly associated with rehospitalization within 180 days (odds ratio, 4.01; 95% confidence interval, 1.63-10.02; P = .003). On Cox regression, the hazard ratios for death were 3.19 (P = .07), 6.49 (P = .004), and 5.17 (P = .07), for the N-, H+, and H- groups, respectively, versus the N+ group. For rehospitalization time, the hazard ratios were 7.02 (P = .01), 4.24 (P = .08), and 13.43 (P = .005) for the N-, H+, and H- groups, respectively, versus the N+ group. CONCLUSION: Decreasing body temperatures can predict readmission, decreased time to rehospitalization, and (in combination with hypothermia) decreased survival.

Devices in heart failure: potential methods for device-based monitoring of congestive heart failure.

Congestive heart failure has long been one of the most serious medical conditions in the United States; in fact, in the United States alone, heart failure accounts for 6.5 million days of hospitalization each year. One important goal of heart-failure therapy is to inhibit the progression of congestive heart failure through pharmacologic and device-based therapies. Therefore, there have been efforts to develop device-based therapies aimed at improving cardiac reserve and optimizing pump function to meet metabolic requirements. The course of congestive heart failure is often worsened by other conditions, including new-onset arrhythmias, ischemia and infarction, valvulopathy, decompensation, end-organ damage, and therapeutic refractoriness, that have an impact on outcomes. The onset of such conditions is sometimes heralded by subtle pathophysiologic changes, and the timely identification of these changes may promote the use of preventive measures. Consequently, device-based methods could in the future have an important role in the timely identification of the subtle pathophysiologic changes associated with congestive heart failure.