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Chronic estrogen treatment increases levels of eNOS protein in cerebral microvessels of male and female rats. This increase in eNOS protein correlates with our previous functional findings indicating that estrogen exposure increases NO modulation of cerebrovascular reactivity in both male and female animals. Upregulation of eNOS expression may contribute to the neuroprotective effect of estrogen.

Objective To characterize the absolute risks for older patients of readmission to hospital and death in the year after hospitalization for heart failure, acute myocardial infarction, or pneumonia. Design Retrospective cohort study. Setting 4767 hospitals caring for Medicare fee for service beneficiaries in the United States, 2008-10. Participants More than 3 million Medicare fee for service beneficiaries, aged 65 years or more, surviving hospitalization for heart failure, acute myocardial infarction, or pneumonia. Main outcome measures Daily absolute risks of first readmission to hospital and death for one year after discharge. To illustrate risk trajectories, we identified the time required for risks of readmission to hospital and death to decline 50% from maximum values after discharge; the time required for risks to approach plateau periods of minimal day to day change, defined as 95% reductions in daily changes in risk from maximum daily declines after discharge; and the extent to which risks are higher among patients recently discharged from hospital compared with the general elderly population. Results Within one year of hospital discharge, readmission to hospital and death, respectively, occurred following 67.4% and 35.8% of hospitalizations for heart failure, 49.9% and 25.1% for acute myocardial infarction, and 55.6% and 31.1% for pneumonia. Risk of first readmission had declined 50% by day 38 after hospitalization for heart failure, day 13 after hospitalization for acute myocardial infarction, and day 25 after hospitalization for pneumonia; risk of death declined 50% by day 11, 6, and 10, respectively. Daily change in risk of first readmission to hospital declined 95% by day 45, 38, and 45; daily change in risk of death declined 95% by day 21, 19, and 21. After hospitalization for heart failure, acute myocardial infarction, or pneumonia, the magnitude of the relative risk for hospital admission over the first 90 days was 8, 6, and 6 times greater than that of the general older population; the relative risk of death was 11, 8, and 10 times greater. Conclusions Risk declines slowly for older patients after hospitalization for heart failure, acute myocardial infarction, or pneumonia and is increased for months. Specific risk trajectories vary by discharge diagnosis and outcome. Patients should remain vigilant for deterioration in health for an extended time after discharge. Health providers can use knowledge of absolute risks and their changes over time to better align interventions designed to reduce adverse outcomes after discharge with the highest risk periods for patients.

The cytoplasmic domain of the integrin beta4 subunit mediates both association with the hemidesmosomal cytoskeleton and recruitment of the signaling adaptor protein Shc. To examine the significance of these interactions during development, we have generated mice carrying a targeted deletion of the beta4 cytoplasmic domain. Analysis of homozygous mutant mice indicates that the tail-less alpha6beta4 binds efficiently to laminin 5, but is unable to integrate with the cytoskeleton. Accordingly, these mice display extensive epidermal detachment at birth and die immmediately thereafter from a syndrome resembling the human disease junctional epidermolysis bullosa with pyloric atresia (PA-JEB). In addition, we find a significant proliferative defect. Specifically, the number of precursor cells in the intestinal epithelium, which remains adherent to the basement membrane, and in intact areas of the skin is reduced, and post-mitotic enterocytes display increased levels of the cyclin-dependent kinase inhibitor p27(Kip). These findings indicate that the interactions mediated by the beta4 tail are crucial for stable adhesion of stratified epithelia to the basement membrane and for proper cell-cycle control in the proliferative compartments of both stratified and simple epithelia.

Background Despite increasing attention on reducing relatively costly hospital practices while maintaining the quality of care, few studies have examined how hospitals use the intensive care unit (ICU), a high-cost setting, for patients admitted with heart failure (HF). We characterized hospital patterns of ICU admission for patients with HF and determined their association with the use of ICU-level therapies and patient outcomes. Methods and Results We identified 166,224 HF discharges from 341 hospitals in the 2009–10 Premier Perspective® database. We excluded hospitals with <25 HF admissions, patients <18 years old, and transfers. We defined ICU as including medical ICU, coronary ICU, and surgical ICU. We calculated the percent of patients admitted directly to an ICU. We compared hospitals in the top-quartile (high ICU admission) with the remaining quartiles. The median percentage of ICU admission was 10% (Interquartile Range 6% to 16%; range 0% to 88%). In top-quartile hospitals, treatments requiring an ICU were used less often: percentage of ICU days receiving mechanical ventilation (6% top quartile versus 15% others), non-invasive positive pressure ventilation (8% versus 19%), vasopressors and/or inotropes (9% versus 16%), vasodilators (6% versus 12%), and any of these interventions (26% versus 51%). Overall HF in-hospital risk standardized mortality was similar (3.4% versus 3.5%; P = 0.2). Conclusions ICU admission rates for HF varied markedly across hospitals and lacked association with in-hospital risk-standardized mortality. Greater ICU use correlated with fewer patients receiving ICU interventions. Judicious ICU use could reduce resource consumption without diminishing patient outcomes.

Objectives To determine the hospitalization rates and outcomes of endocarditis among older adults. Background Endocarditis is the most serious cardiovascular infection and is especially common among older adults. Little is known about recent trends for endocarditis hospitalizations and outcomes. Methods Using Medicare inpatient Standard Analytic Files, we identified all Fee-For-Service beneficiaries aged ≥65 years with a principal or secondary diagnosis of endocarditis from 1999-2010. We used Medicare Denominator Files to report hospitalizations per 100,000 person-years. Rates of 30-day and 1-year mortality were calculated using Vital Status Files. We used mixed-effects models to calculate adjusted rates of hospitalization and mortality and to compare the results before and after 2007, when the American Heart Association revised recommendations for endocarditis prophylaxis. Results Overall, 262,658 beneficiaries were hospitalized with endocarditis. The adjusted hospitalization rate increased from 1999-2005, reaching 83.5 per 100,000 person-years in 2005, and declined during 2006-2007. After 2007, the decline continued, reaching 70.6 per 100,000 person-years in 2010. Adjusted 30-day and 1-year mortality rates ranged from 14.2% to 16.5% and from 32.6% to 36.2%, respectively. There were no consistent changes in adjusted rates of 30-day and 1-year mortality after 2007. Trends in rates of hospitalization and outcomes were consistent across demographic subgroups. Adjusted rates of hospitalization and mortality declined consistently in the subgroup with principal diagnosis of endocarditis. Conclusions Our study highlights the high burden of endocarditis among older adults. We did not observe an increase in adjusted rates of hospitalization or mortality associated with endocarditis after publication of the 2007 guidelines.

ObjectiveTo characterise the trends in the left ventricular assist device (LVAD) implantation rates and outcomes between 2004 and 2011 in the Medicare population. Since the approval of the HeartMate II in 2008, the use of LVADs has steadily climbed. Given the increase in LVAD use, issues around discharge disposition, post-implant hospitalisations and costs require further understanding.MethodsWe examined LVAD implantation rates and short-term and long-term outcomes among Medicare fee-for-service beneficiaries hospitalised for LVAD implantation. We also conducted analyses among survivors 1-year post-discharge to examine rehospitalisation rates. Lastly, we reported Centers for Medicare & Medicaid Services (CMS) payments for both index hospitalisation and rehospitalisations 1 year post-discharge.ResultsA total of 2152 LVAD implantations were performed with numbers increasing from 107 in 2004 to 612 in 2011. The 30-day mortality rate decreased from 52% to 9%, and 1-year mortality rate decreased from 69% to 31%. We observed no change in overall length of stay, but post-procedure length of stay increased. We also found an increase in home discharge dispositions from 26% to 53%. Between 2004 and 2010, the rehospitalisation rate increased and the number of hospital days decreased. The adjusted CMS payment for the index hospitalisation increased from $188 789 to $225 697 over time but decreased for rehospitalisation from $60 647 to $53 630.ConclusionsLVAD implantations increased over time. We found decreasing 30-day and 1-year mortality rates and increasing home discharge disposition. The proportion of patients rehospitalised among 1-year survivors remained high with increasing index hospitalisation cost, but decreasing post-implantation costs over time.

Protocol deviations occur commonly when thrombolytic therapy is given to stroke patients in routine clinical practice. Patients who receive thrombolysis with major protocol deviations have higher rates of in-hospital mortality and serious extracranial hemorrhage than patients in the NINDS cohort.