Preoperative Staphylococcus Aureus Screening and Targeted Decolonization in Cardiac Surgery.

BACKGROUND: We assessed the impact of preoperative Staphylococcus aureus screening and targeted decolonization on the incidence of postoperative methicillin-resistant S aureus (MRSA) colonization, intensive care unit MRSA transmission, and surgical site infections in cardiac surgery patients. METHODS: We reviewed medical records for all adult patients during two periods: preintervention (January 2007 to April 2010) and intervention (January 2011 to December 2014). In the intervention period, we performed nasal screening for methicillin-sensitive S aureus and MRSA using polymerase chain reaction within 30 days of the operation. Colonized patients received intranasal mupirocin twice daily and chlorhexidine baths daily for 5 days; patients colonized with MRSA also received prophylactic vancomycin plus cefazolin with contact isolation precautions. Nasal surveillance for MRSA was performed on intensive care unit admission and weekly thereafter. Multivariable logistic regression models were constructed to determine risk factors for postoperative MRSA colonization, and surgical site infections and the impact of our screening program was assessed in these models. Poisson regression was used to assess MRSA transmission. RESULTS: Comparing 2,826 preintervention and 4,038 intervention patients, cases differed in age, diabetes mellitus, preoperative infection, preoperative length of stay, and bypass time (all p ≤ 0.03). Intervention patients had risk-adjusted reductions in MRSA colonization (odds ratio 0.53, 95% confidence interval [CI]: 0.37 to 0.76, p < 0.001), transmission (incidence rate ratio 0.29, 95% CI: 0.13 to 0.65, p = 0.002), and surgical site infections (odds ratio 0.58, 95% CI: 0.40 to 0.86, p = 0.007). Increased duration of preoperative decolonization therapy was associated with decreased postoperative MRSA colonization (odds ratio 0.73, 95% CI: 0.53 to 1.00, p = 0.05). CONCLUSIONS: Preoperative S aureus screening with targeted decolonization was associated with reduced MRSA colonization, transmission, and surgical site infections. Duration of preoperative therapy correlated with decreased frequency of postoperative MRSA colonization.

Hospital Bed Type, the Electronic Medical Record, and Safe Bed Elevation in the Intensive Care Setting.

In mechanically ventilated patients, head of bed (HOB) elevation above 30° decreases the risk of ventilator-associated pneumonia. The research team studied (a) compliance with proper HOB elevation in their cardiac surgical intensive care unit, (b) the accuracy of HOB angles recorded in the electronic medical record (EMR), and (c) the effect of bed type on (a) and (b). Nurses were polled to discover how HOB angles were measured in practice. HOB angles were compliant in 80% of observations. Compliance was more frequent in beds with side-of-bed angle indicators (SBI) than beds with under-bed angle indicators (UBI; 88% vs 77%, P = .04). Charting in the EMR was accurate in 50% of SBI bed observations but only 20% of UBI bed observations (P < .0001). Sixty-seven percent of nurses used the SBI; 27% used the UBI; 6% used estimation alone. Though compliance was suboptimal, compliance and EMR accuracy were significantly associated with bed type. Bedside indicators are underutilized.

A Predictive Model and Risk Score for Unplanned Cardiac Surgery Intensive Care Unit Readmissions.

BACKGROUND: Readmissions or "bounce back" to the intensive care unit (ICU) following cardiac surgery is associated with an increased risk of morbidity and mortality. We sought to identify clinical and system-based factors associated with ICU bounce backs in order to generate a Bounce Back After Transfer (BATS) prediction score. METHODS: We prospectively collected the clinical and financial records of all patients undergoing coronary artery bypass grafting (CABG) or surgical aortic valve replacement (AVR) between May 2013 and March 2014. Multivariable logistic regression was used to identify independent predictors of bounce backs to the ICU which served as the basis for our BATS score. RESULTS: Of the 532 patients that underwent CABG or AVR during the study period, 35 (6.6%) were readmitted to the ICU. After risk adjustment, female sex, NYHA class III/IV, urgent or emergent operative status, and postoperative renal failure were the predictors of ICU bounce backs utilized to create the BATS score. Patients in the low (<5), moderate (5-10), and high-risk (>10) score cohorts experienced bounce back rates of 3.0%, 10.4%, and 42%, respectively. After adjusting for preoperative patient risk, ICU bounce back resulted in an increase in $68,030 to a patient's total hospital charges. CONCLUSIONS: A predictive model (BATS) can determine the risk of a bounce back to the ICU after transfer to the floor. We speculate that determination of a patient's BATS upon ICU transfer would allow targeted floor care and decrease bounce back rates, along with postoperative morbidity, mortality, and cost of care.

Designing a quality improvement program with electronic health records: New York City's Health eQuits.

Despite clear recommendations for identifying and intervening with smokers, clinical preventive practice is inconsistent in primary care. Use of electronic health records could facilitate improvement. Community health centers treating low-income and Medicaid recipients with greater smoking prevalence than the general population were recruited for a pilot program. Key design elements used to engage centers' participation include designating a project champion at each organization, confirming ability to transmit data for reporting and participation, and offering money to facilitate initial engagement; however, financial incentives did not motivate all organizations. Other methods to elicit participation and to motivate practice change included building on centers' previous experiences with similar programs, utilizing existing relationships with state cessation centers, and harnessing the "competitive" spirit-sharing both good news and areas for improvement to stimulate action. These experiences and observations may assist others in designing programs to improve clinical interventions with smokers.

Increases in smoking cessation interventions after a feedback and improvement initiative using electronic health records -- 19 community health centers, New York City, October 2010-March 2012.

Quitting smoking substantially reduces smokers' risk for smoking-related morbidity and mortality and can increase life expectancy by up to a decade. Most smokers want to quit and make at least one medical provider visit annually. Health care providers can play an important role in helping smokers quit by documenting patients' tobacco use, advising smokers to quit, and providing evidence-based cessation treatments or referrals for treatment, but many providers and practices do not regularly take these actions. Systems to increase provider screening and delivery of cessation interventions are available; in particular, electronic health records (EHRs) can be powerful tools to facilitate increased cessation interventions. This analysis reports on an EHR-based pay-for-improvement initiative in 19 community health centers (CHCs) in New York City (NYC) that sought to increase smoking status documentation and cessation interventions. At the end of the initiative, the mean proportion of patients who were documented as smokers in CHCs had increased from 24% to 27%, whereas the mean proportion of documented smokers who received a cessation intervention had increased from 23% to 54%. Public health programs and health systems should consider implementing strategies to equip and train clinical providers to use information technology to increase delivery of cessation interventions.

Effect of an electronic alert on treatment of skin and soft tissue infections.

This is a prospective intervention study conducted between 2007 and 2011 to evaluate whether an electronic alert can influence provider practice in treatment of skin and soft tissue infections (SSTIs). A best-practice alert (BPA) was programmed to appear for intervention ICD-9 SSTI diagnoses. Controls were patients who had other SSTI ICD-9 codes where the BPA was not programmed to fire. Rate of culture taken in patients was compared between patients in the intervention and control groups. We found that cultures were taken among 13.5% of the intervention group and 5.4% of the control group (p <.0001). A logistic regression analysis controlling for covariates showed the odds of the intervention group having a culture taken was 2.6 times that of the control group. The results of this study support the use of BPAs for improving the management of SSTIs.

A protocol-driven approach to early extubation after heart surgery.

OBJECTIVE: We assessed the effectiveness of standardized protocols in decreasing postoperative mechanical ventilation time to <6 hours. METHODS: In 2061 patients undergoing coronary bypass, the proportion extubated in <6 hours was calculated for 3 sequential time periods. During period 1 patients were weaned per baseline practices; during period 2, per a protocol developed by a multidisciplinary committee; and during period 3, as in period 2 but with paralytic reversal and extubation performed at lower body temperatures and an extubation reminder sheet prominently displayed. We used a χ(2) test to examine differences in ventilation times among the 3 time periods and logistic regression modeling to control for independent risk factors for prolonged ventilation. As measures of patient safety, we examined rates of reintubation and rates of patient shivering following paralytic reversal. RESULTS: Twelve percent of patients were extubated in <6 hours during period 1, 24% during period 2 (P < .01), and 38% during period 3 (P < .01 compared with both periods 1 and 2). After controlling for 12 risk factors, patients were more likely to be extubated in <6 hours during period 2 (odds ratio, 2.39; 95% confidence interval, 1.84-3.10) and period 3 (odds ratio, 5.05; 95% confidence interval, 3.65-6.99) than during period 1. There was no difference in reintubation rates across periods, and the rate of patient shivering did not increase with paralytic reversal at lower body temperature. CONCLUSIONS: The standardized protocols outlined in this article dramatically improved early extubation performance.

A survey of knowledge, attitudes, and beliefs of medical students concerning antimicrobial use and resistance.

Physicians who are insufficiently prepared to make choices on antibiotic selection may use antibiotics inappropriately. We surveyed medical students' perceptions and attitudes about their training on antimicrobial use to identify gaps in medical education. Medical students at an urban medical school in the northeast were e-mailed a link to an online survey. The survey was online for 1 week, after which time the survey responses were downloaded and analyzed. Thirty percent of medical students responded to the survey (n = 304). The majority of third- and fourth-year medical students believe that antibiotics are overused in the hospital and in outpatient areas. Over three quarters of the students would like more education on antibiotic selection, and 83% wanted this education to be during the third year of medical school. The resources they used the most for antibiotic selection included other physicians and handheld programs such as Epocrates, but no clear resource emerged as the dominant preference. Medical students recognized the importance of judicious antibiotic use and would like greater instruction on how to choose antibiotics appropriately. Medical school curricula should be expanded in the third year of medical school to provide students with additional training timed with their clinical rotations.

Preserved expression of GLUT4 prevents enhanced agonist-induced vascular reactivity and MYPT1 phosphorylation in hypertensive mouse aorta.

We previously showed that GLUT4 expression is decreased in arterial smooth muscle of deoxycorticosterone acetate (DOCA)-salt hypertensive rats and that GLUT4-knockout mice have enhanced arterial reactivity. Therefore, we hypothesized that increased GLUT4 expression in vascular smooth muscle in vivo would prevent enhanced arterial reactivity and possibly reduce blood pressure in DOCA-salt hypertensive mice. Adult wild-type (WT) and GLUT4 transgenic (TG) mice were subjected to DOCA-salt hypertension with uninephrectomy or underwent uninephrectomy and remained normotensive. GLUT4 expression was increased more than twofold in the aortas of GLUT4 TG mice compared with WT aortas. Eight weeks after implantation of the DOCA pellets, GLUT4 expression decreased by 75% in aortas of WT hypertensive mice, but not in GLUT4 TG hypertensive aortas. Systolic blood pressure was significantly and similarly increased in WT and GLUT4 TG DOCA-salt mice compared with their respective sham-treated controls (159 vs. 111 mmHg). Responsiveness to the contractile agonist 5-HT was significantly increased in aortic rings from WT DOCA-salt mice but remained normal in GLUT4 TG DOCA mice. Phosphorylation of the myosin phosphatase targeting subunit MYPT1 was significantly enhanced in aortas of WT DOCA-salt mice, and this increase was prevented in GLUT4 TG mice. MYPT1 phosphorylation was also increased in nonhypertensive GLUT4-knockout mice. Myosin phosphatase, a major negative regulator of calcium sensitivity, is itself negatively regulated by phosphorylation of MYPT1. Therefore, our results show that preservation of GLUT4 expression prevents enhanced arterial reactivity in hypertension, possibly via effects on myosin phosphatase activity.

Hypotension, lipodystrophy, and insulin resistance in generalized PPARgamma-deficient mice rescued from embryonic lethality.

We rescued the embryonic lethality of global PPARgamma knockout by breeding Mox2-Cre (MORE) mice with floxed PPARgamma mice to inactivate PPARgamma in the embryo but not in trophoblasts and created a generalized PPARgamma knockout mouse model, MORE-PPARgamma knockout (MORE-PGKO) mice. PPARgamma inactivation caused severe lipodystrophy and insulin resistance; surprisingly, it also caused hypotension. Paradoxically, PPARgamma agonists had the same effect. We showed that another mouse model of lipodystrophy was hypertensive, ruling out the lipodystrophy as a cause. Further, high salt loading did not correct the hypotension in MORE-PGKO mice. In vitro studies showed that the vasculature from MORE-PGKO mice was more sensitive to endothelial-dependent relaxation caused by muscarinic stimulation, but was not associated with changes in eNOS expression or phosphorylation. In addition, vascular smooth muscle had impaired contraction in response to alpha-adrenergic agents. The renin-angiotensin-aldosterone system was mildly activated, consistent with increased vascular capacitance or decreased volume. These effects are likely mechanisms contributing to the hypotension. Our results demonstrated that PPARgamma is required to maintain normal adiposity and insulin sensitivity in adult mice. Surprisingly, genetic loss of PPARgamma function, like activation by agonists, lowered blood pressure, likely through a mechanism involving increased vascular relaxation.

GLUT4 facilitative glucose transporter specifically and differentially contributes to agonist-induced vascular reactivity in mouse aorta.

OBJECTIVE: We hypothesized that GLUT4 is a predominant facilitative glucose transporter in vascular smooth muscle cells (VSMCs), and GLUT4 is necessary for agonist-induced VSMC contraction. METHODS AND RESULTS: Glucose deprivation and indinavir, a GLUT4 antagonist, were used to assess the role of GLUT4 and non-GLUT4 transporters in vascular reactivity. In isolated endothelium-denuded mouse aorta, approximately 50% of basal glucose uptake was GLUT4-dependent. Norepinephrine-mediated contractions were dependent on both GLUT4 and non-GLUT4 transporters, serotonin (5-HT)-mediated contractions were mainly GLUT4-dependent, and prostaglandin (PG) F(2alpha)-mediated contractions were dependent on non-GLUT4 transporters, whereas indinavir had no effect in GLUT4 knockout vessels. We also observed a 46% decrease in GLUT4 expression in aortas from angiotensin II hypertensive mice. Indinavir caused a less profound attenuation of maximal 5-HT-mediated contraction in these vessels, corresponding to the lower GLUT4 levels in the hypertensive aortas. Finally, and somewhat surprisingly, chronic GLUT4 knockout was associated with increased vascular reactivity compared with that in wild-type animals, suggesting that chronic absence or reduction of GLUT4 expression in VSMCs leads to opposite effects observed with acute inhibition of GLUT4. CONCLUSIONS: Thus, we conclude that GLUT4 is constitutively expressed in large arteries and likely participates in basal glucose uptake. In addition, GLUT4, as well as other non-GLUT4 facilitative glucose transporters, are necessary for agonist-induced contraction, but each transporter participates in VSMC contraction selectively, depending on the agonist, and changes in GLUT4 expression may account for some of the functional changes associated with vascular diseases like hypertension.

Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model.

CONTEXT: Recent studies have suggested a link between inhaled particulate matter exposure in urban areas and susceptibility to cardiovascular events; however, the precise mechanisms remain to be determined. OBJECTIVE: To test the hypothesis that subchronic exposure to environmentally relevant particulate matter, even at low concentrations, potentiates atherosclerosis and alters vasomotor tone in a susceptible disease model. DESIGN, SETTING, AND PARTICIPANTS: Between July 21, 2004, and January 12, 2005, 28 apolipoprotein E-/- (apoE-/-) mice were, based on randomized assignments, fed with normal chow or high-fat chow and exposed to concentrated ambient particles of less than 2.5 microm (PM2.5) or filtered air (FA) in Tuxedo, NY, for 6 hours per day, 5 days per week for a total of 6 months. MAIN OUTCOME MEASURES: Composite atherosclerotic plaque in the thoracic and abdominal aorta and vasomotor tone changes. RESULTS: In the high-fat chow group, the mean (SD) composite plaque area of PM2.5 vs FA was 41.5% (9.8%) vs 26.2% (8.6%), respectively (P<.001); and in the normal chow group, the composite plaque area was 19.2% (13.1%) vs 13.2% (8.1%), respectively (P = .15). Lipid content in the aortic arch measured by oil red-O staining revealed a 1.5-fold increase in mice fed the high-fat chow and exposed to PM2.5 vs FA (30.0 [8.2] vs 20.0 [7.0]; 95% confidence interval [CI], 1.21-1.83; P = .02). Vasoconstrictor responses to phenylephrine and serotonin challenge in the thoracic aorta of mice fed high-fat chow and exposed to PM2.5 were exaggerated compared with exposure to FA (mean [SE], 134.2% [5.2%] vs 100.9% [2.9%], for phenylephrine, and 156.0% [5.6%] vs 125.1% [7.5%], for serotonin; both P = .03); relaxation to the endothelium-dependent agonist acetylcholine was attenuated (mean [SE] of half-maximal dose for dilation, 8.9 [0.2] x 10(-8) vs 4.3 [0.1] x 10(-8), respectively; P = .04). Mice fed high-fat chow and exposed to PM2.5 demonstrated marked increases in macrophage infiltration, expression of the inducible isoform of nitric oxide synthase, increased generation of reactive oxygen species, and greater immunostaining for the protein nitration product 3-nitrotyrosine (all P<.001). CONCLUSION: In an apoE-/- mouse model, long-term exposure to low concentration of PM2.5 altered vasomotor tone, induced vascular inflammation, and potentiated atherosclerosis.

Rapid-onset endothelial dysfunction with adriamycin: evidence for a dysfunctional nitric oxide synthase.

Adriamycin (ADR) is a commonly used chemotherapeutic agent that is believed to exert its effects through the generation of oxygen free radicals. We hypothesized that administration of a single dose of ADR results in endothelial nitric oxide synthase (eNOS)-dependent generation of superoxide (O2*-) and acute endothelial dysfunction. A single dose of ADR (10 mg/kg i.v.) administered to rabbits resulted in rapid attenuation of agonist-dependent responses to acetylcholine and calcium ionophore (A23187). In vitro exposure of ring segments to ADR for < 30 min resulted in O2*- generation measured by electron spin resonance (ESR) with the spin trap segments 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide (BMPO) that was abolished by endothelial denudation and incubation with diphenyliodonium (DPI) (10 microM) but not L-NMMA (10 microM). Brachial artery flow-mediated dilation (FMD) in patients undergoing chemotherapy with ADR was markedly attenuated after a single dose of ADR (6.5 +/- 1.0 to 2.5 +/- 1.1% (p = 0.0004, time to end of infusion 27 +/- 8 min) while endothelial-independent dilatation with nitroglycerin was unchanged (16.3 +/- 3.1 and 14.33 +/- 2.1% respectively, p = 0.36). Serum nitrite and nitrate concentrations fell from 50 +/- 6 micromol/l pre-ADR to 33 +/- 6 micromol/l post-ADR infusion (p = 0.0005) while serum concentrations of CD141 thrombomodulin and von Willebrand factor (vWF) activity remained unchanged after ADR infusion (36 +/- 13 to 52 +/- 22% ng/ml versus 3.25 +/- 0.98 to 3.01 +/- 0.91%, respectively, p = NS for pre versus post for both). Doppler indices of diastolic function (IVRT, DT and E/A ratios) were not altered in response to ADR. In conclusion, ADR administration results in rapid depletion of systemic NO* levels and attenuation of agonist-dependent responses in rabbits and flow-mediated dilation in the brachial artery of humans. ESR measurements in rabbit ring suggest an endothelial origin for radical production via flavin-containing oxido-reductases such as eNOS or NADPH cytochrome P450 reductase. These findings may have implications for cardiovascular complications noted with ADR.

Chronic iron administration increases vascular oxidative stress and accelerates arterial thrombosis.

BACKGROUND: Iron overload has been implicated in the pathogenesis of ischemic cardiovascular events. However, the effects of iron excess on vascular function and the thrombotic response to vascular injury are not well understood. METHODS AND RESULTS: We examined the effects of chronic iron dextran administration (15 mg over 6 weeks) on thrombosis, systemic and vascular oxidative stress, and endothelium-dependent vascular reactivity in mice. Thrombus generation after photochemical carotid artery injury was accelerated in iron-loaded mice (mean time to occlusive thrombosis, 20.4+/-8.5 minutes; n=10) compared with control mice (54.5+/-35.5 minutes, n=10, P=0.009). Iron loading had no effect on plasma clotting, vessel wall tissue factor activity, or ADP-induced platelet aggregation. Acute administration of dl-cysteine, a reactive oxygen species scavenger, completely abrogated the effects of iron loading on thrombus formation, suggesting that iron accelerated thrombosis through a pro-oxidant mechanism. Iron loading enhanced both systemic and vascular reactive oxygen species production. Endothelium-dependent vasorelaxation was impaired in iron-loaded mice, indicating reduced NO bioavailability. CONCLUSIONS: Moderate iron loading markedly accelerates thrombus formation after arterial injury, increases vascular oxidative stress, and impairs vasoreactivity. Iron-induced vascular dysfunction may contribute to the increased incidence of ischemic cardiovascular events that have been associated with chronic iron overload.

Altered tetrahydrobiopterin metabolism in atherosclerosis: implications for use of oxidized tetrahydrobiopterin analogues and thiol antioxidants.

OBJECTIVE: Tetrahydrobiopterin (BH4) is of fundamental importance for the normal function of endothelial NO synthase. The purpose of this study was to investigate the effects of hyperlipidemia on vascular BH4 levels and the effect of supplementation with sepiapterin in the presence and absence of N-acetylcysteine (NAC). METHODS AND RESULTS: New Zealand White rabbits were fed normal chow (normocholesterolemic [NC] group) or hyperlipidemic chow (hyperlipidemic [HL] group) for 8 to 10 weeks. Mean cholesterol levels were 1465+/-333 and 53+/-17 mg/dL in the HL and NC group, respectively. Markedly diminished BH4 levels were found in the HL group compared with the NC group, but these levels could be restored after 6 hours of incubation with sepiapterin. Peak relaxations to acetylcholine and A23187 were impaired in the HL group. Supplementation with sepiapterin resulted in a further diminution of relaxation in the HL but not NC group. Incubation with NAC for 6 hours failed to raise BH4 levels, whereas NAC in conjunction with sepiapterin raised BH4 levels approximately 221-fold. However, this increase did not improve relaxations to A23187 and acetylcholine. CONCLUSIONS: Prolonged exposure to sepiapterin impairs vasorelaxation in hyperlipidemia despite repletion of endogenous BH4. Antioxidant thiols do not correct this impairment. These studies have implications for the use of sepiapterin in the correction of vasomotor tone in atherosclerosis.

Mineralocorticoid receptor antagonism in experimental atherosclerosis.

BACKGROUND: Aldosterone has been implicated in the effects of angiotensin II in the vasculature. We hypothesized that there is local expression of the mineralocorticoid receptor (MR) in the vasculature and that the use of a selective aldosterone receptor antagonist (SARA) improves endothelial function in early atherosclerosis. METHODS AND RESULTS: New Zealand rabbits were placed on normal chow or 1% cholesterol diets, randomized to placebo or SARA (eplerenone, 50 mg/kg twice daily), and killed at the end of 6 weeks for various studies. In the hyperlipidemic (HL) chow group, there was a 2.3-fold increase in superoxide (O2*-)) generation. SARA normalized O2*- generation in intact aortas and reduced NADH and NADPH oxidase activity to basal levels (0.31+/-0.04 and 0.27+/-0.02 in HL versus 0.16+/-0.05 and 0.07+/-0.02 in HL-SARA, respectively; P<0.01 by ANOVA). This was associated with improvements in peak relaxations to the endothelial-dependent agonist acetylcholine (82+/-6% in HL-SARA versus 61+/-4 in HL; P<0.01 by ANOVA; ED(50) 6.8x10(-8) mol/L in HL-SARA and 1.2x10(-7) mol/L in HL; P=NS) to near-normal levels. Vessels from the HL group demonstrated hyperreactivity to angiotensin II that could not be corrected with SARA. Plasma aldosterone levels by radioimmunoassay demonstrated a 4- to 5-fold increase in response to SARA but no differences with lipid feeding. Real-time reverse transcriptase-polymerase chain reaction studies revealed expression of MR in the aorta of HL rabbits and those of controls. CONCLUSIONS: MR antagonism improves endothelial function and reduces O2*- generation in diet-induced atherosclerosis. Targeting aldosterone by blocking its receptor has potential antiatherosclerotic effects.