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Background: As technology evolves, so does the integration of technology into health care delivery. Telemedicine, the use of information technology to provide remote health care, aims to i...

OBJECTIVES To measure the burden of delirium in older adults with or without Alzheimer disease or related disorders (ADRDs). DESIGN Prospective, observational cohort. SETTING Inpatient hospital and study participants' homes. PARTICIPANTS A subset (n = 267) of older medical and surgical patients and their caregivers enrolled in the Better Assessment of Illness study. MEASUREMENTS Delirium burden was measured using the DEL-B instrument (range = 0-40, with higher scores indicating greater burden) in caregivers (DEL-B-C) and patients 1 month after hospitalization. Severity of cognitive impairment (Montreal Cognitive Assessment [MoCA]), delirium presence (Confusion Assessment Method [CAM]), and delirium severity (CAM-Severity [CAM-S]) were measured during hospitalization and at 1-month follow-up. ADRD diagnosis was determined by a clinical consensus process. RESULTS For patients with (n = 56) and without (n = 211) ADRD, both DEL-B instruments had good internal consistency. DEL-B-C scores had a median (interquartile range) among caregivers of patients with and without ADRD of 9 (5-15) and 5 (1-11), respectively (P

Editor’s PerspectiveWhat We Already Know about This TopicWhat This Article Tells Us That Is NewBackgroundPostoperative delirium and postoperative cognitive dysfunction share risk factors and may co-occur, but their relationship is not well established. The primary goals of this study were to describe the prevalence of postoperative cognitive dysfunction and to investigate its association with in-hospital delirium. The authors hypothesized that delirium would be a significant risk factor for postoperative cognitive dysfunction during follow-up.MethodsThis study used data from an observational study of cognitive outcomes after major noncardiac surgery, the Successful Aging after Elective Surgery study. Postoperative delirium was evaluated each hospital day with confusion assessment method–based interviews supplemented by chart reviews. Postoperative cognitive dysfunction was determined using methods adapted from the International Study of Postoperative Cognitive Dysfunction. Associations between delirium and postoperative cognitive dysfunction were examined at 1, 2, and 6 months.ResultsOne hundred thirty-four of 560 participants (24%) developed delirium during hospitalization. Slightly fewer than half (47%, 256 of 548) met the International Study of Postoperative Cognitive Dysfunction-defined threshold for postoperative cognitive dysfunction at 1 month, but this proportion decreased at 2 months (23%, 123 of 536) and 6 months (16%, 85 of 528). At each follow-up, the level of agreement between delirium and postoperative cognitive dysfunction was poor (kappa less than .08) and correlations were small (r less than .16). The relative risk of postoperative cognitive dysfunction was significantly elevated for patients with a history of postoperative delirium at 1 month (relative risk = 1.34; 95% CI, 1.07–1.67), but not 2 months (relative risk = 1.08; 95% CI, 0.72–1.64), or 6 months (relative risk = 1.21; 95% CI, 0.71–2.09).ConclusionsDelirium significantly increased the risk of postoperative cognitive dysfunction in the first postoperative month; this relationship did not hold in longer-term follow-up. At each evaluation, postoperative cognitive dysfunction was more common among patients without delirium. Postoperative delirium and postoperative cognitive dysfunction may be distinct manifestations of perioperative neurocognitive deficits.

Osteosarcoma (OS) patients exhibit poor overall survival, partly due to copy number variations (CNVs) resulting in dysregulated gene expression and therapeutic resistance. To identify actionable prognostic signatures of poor overall survival, we employed a systems biology approach using public databases to integrate CNVs, gene expression, and survival outcomes in pediatric, adolescent, and young adult OS patients. Chromosome 8 was a hotspot for poor prognostic signatures. The MYC-RAD21 copy number gain (8q24) correlated with increased gene expression and poor overall survival in 90% of the patients (n = 85). MYC and RAD21 play a role in replication-stress, which is a therapeutically actionable network. We prioritized replication-stress regulators, bromodomain and extra-terminal proteins (BETs), and CHK1, in order to test the hypothesis that the inhibition of BET + CHK1 in MYC-RAD21+ pediatric OS models would be efficacious and safe. We demonstrate that MYC-RAD21+ pediatric OS cell lines were sensitive to the inhibition of BET (BETi) and CHK1 (CHK1i) at clinically achievable concentrations. While the potentiation of CHK1i-mediated effects by BETi was BET-BRD4-dependent, MYC expression was BET-BRD4-independent. In MYC-RAD21+ pediatric OS xenografts, BETi + CHK1i significantly decreased tumor growth, increased survival, and was well tolerated. Therefore, targeting replication stress is a promising strategy to pursue as a therapeutic option for this devastating disease.

Background Extraskeletal osteosarcoma is an extremely rare disease, comprising less than 0.1% of all cancers diagnosed in the United States, of which less than 5% occur in the upper extremities. The management of two cases of pediatric upper extremity extraskeletal osteosarcoma is discussed. Case description Two children initially noticed painless left upper extremity masses at the ages of 16 and 13, respectively. Following a period of several months, both lesions became symptomatic, necessitating operative intervention, which revealed giant cell-rich extraskeletal osteosarcoma; PET staging following gross total resection revealed no residual or metastatic disease in either patient. After extensive discussion with the patients and family, adjuvant chemotherapy was initiated for one patient, and adjuvant radiation therapy was initiated in both patients. Conclusions Despite the rarity of these tumors, the importance of radiation therapy has been established by current and ongoing studies such as the Children's Oncology Group study ARST0332. Radiation therapy remains an important component of the multimodality therapy comprising optimal treatment of this disease, despite the relative paucity of long-term outcome data derived from level I evidence.

The MAJORANA Collaboration is constructing the MAJORANA DEMONSTRATOR, an ultralow background, 40-kg modular high purity Ge (HPGe) detector array to search for neutrinoless double-beta decay (0νββ-decay) in 76Ge. The goal of the experiment is to demonstrate a background rate at or below 3 counts/(t-y) in the 4 keV region of interest (ROI) around the 2039 keV Q-value for 76Ge 0νββ-decay. In this paper, the status of the MAJORANA DEMONSTRATOR, including its design and measurements of properties of the HPGe crystals is presented.

Introduction: In everyday practice, angiotensin converting enzyme inhibitors and beta-blockers are cornerstone treatments in patients with (cardio-)vascular disease. Clear data that evaluate the effects of the combination of these agents on morbidity and mortality are lacking. Methods: In this retrospective pooled analysis of three large perindopril outcome trials (ADVANCE, EUROPA, PROGRESS), clinical outcomes were evaluated in 29,463 patients with vascular disease. Multivariate Cox regression analyses were performed in patients randomized to a perindopril-based regimen or placebo (treatment effect), and data were stratified according to background beta-blocker treatment. The primary endpoint was a composite of cardiovascular mortality, non-fatal myocardial infarction, and stroke. Results: The cumulative incidence of the primary endpoint over mean follow-up of 4.0 years (Sd 1.0) was significantly lower in the beta-blocker/perindopril group (9.6%; 545/5700 patients) as compared to beta-blocker/placebo (11.8%; 676/5718 patients) (p < 0.01). Adding perindopril to existing beta-blocker treatment reduced the relative risk of the primary endpoint by 20% (hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.71–0.90), non-fatal myocardial infarction by 23% (HR 0.77; 95% CI 0.65–0.91), and all-cause mortality by 22% (HR 0.78; 95% CI 0.68–0.88) as compared to placebo. Significant treatment benefit was not observed for stroke (HR 0.93; 95% CI 0.75–1.15). Significance was maintained for the primary endpoint and cardiovascular endpoints when data were further stratified by baseline hypertension. However, the mortality benefit was only observed in patients with hypertension with background beta-blocker use. Conclusions: These data suggest that the beneficial cardioprotective effects of perindopril treatment are additive to the background beta-blockers use.

The MAJORANA Collaboration is constructing the MAJORANA Demonstrator, an ultra-low background, 44-kg modular high-purity Ge (HPGe) detector array to search for neutrinoless double-beta decay in Ge-76. The phenomenon of surface micro-discharge induced by high-voltage has been studied in the context of the MAJORANA Demonstrator. This effect can damage the front-end electronics or mimic detector signals. To ensure the correct performance, every high-voltage cable and feedthrough must be capable of supplying HPGe detector operating voltages as high as 5 kV without exhibiting discharge. R&D measurements were carried out to understand the testing system and determine the optimum design configuration of the high-voltage path, including different improvements of the cable layout and feedthrough flange model selection. Every cable and feedthrough to be used at the MAJORANA Demonstrator was characterized and the micro-discharge effects during the MAJORANA Demonstrator commissioning phase were studied. A stable configuration has been achieved, and the cables and connectors can supply HPGe detector operating voltages without exhibiting discharge., 9 pages, 12 figures, 8 tables, submitted to NIM A

Statins, angiotensin-converting enzyme (ACE) inhibitors, and calcium channel blockers (CCBs) have markedly changed the clinical progression of patients with coronary artery disease (CAD). The goal of this paper is to review the rationale and evidence for combining these three drug classes in hypertensive patients with hypercholesterolemia or CAD. Data sources include a literature search for publications on the use of a statin combined with various antihypertensive drugs in patients with hypertension and hypercholesterolemia or stable CAD. Hypercholesterolemia and hypertension constitute major physiological risk factors of ischemic heart disease. Current guidelines recommend a global approach to risk management, using agents that address as many risk factors as possible. Dual combination therapies are an important component of guideline-recommended therapy in hypertension. Our review of the literature indicates that triple therapy with a statin, ACE inhibitor, and CCB is associated with a significant reduction in major cardiovascular events. For example, a post hoc analysis in 1056 patients with stable CAD participating in the EUROPA trial indicated that the addition of perindopril to a CCB and a lipid-lowering agent was associated with a 46 % reduction in the composite of cardiovascular death, myocardial infarction, and resuscitated cardiac arrest (p = 0.023). In addition, single pill formulations are known to result in better adherence to the treatment. Single-pill formulations that combine a statin, an ACE inhibitor, and a CCB appear to offer an effective approach to the management of global cardiovascular risk.

Background Long-term survival for all patients with osteosarcoma using current aggressive adjuvant chemotherapy and surgical resection is between 60% and 70%. In patients who present with nonmetastatic, high-grade extremity osteosarcoma of bone, limb salvage surgery is favored, when appropriate, over amputation to preserve the limb, because limb salvage may lead to a superior quality of life compared with amputation. However, concern remains that in the attempt to preserve the limb, close or microscopically positive surgical margins may have an adverse effect on event-free survival.

Resume Introduction Le recours a une transfusion de culots de globules rouges chez un patient drepanocytaire majeur est parfois indispensable. L’hemolyse post-transfusionnelle retardee est une complication rare mais potentiellement grave. Cette manifestation peut survenir a tout âge. Elle est probablement sous-diagnostiquee du fait du peu de signes specifiques. Observations Nous decrivons dans cet article, les signes cliniques, biologiques et les aleas de la prise en charge therapeutique de trois cas d’hemolyse post-transfusionnelle retardee. La chromatographie haute performance evaluant le pourcentage d’HbA1 est l’examen permettant d’etablir le diagnostic. La physiopathologie de cet evenement est encore mal connue. Plusieurs traitements ont ete utilises, cependant, la prise en charge therapeutique reste discutee a l’heure actuelle. Conclusion La transfusion de tout patient susceptible d’avoir une hemolyse post-transfusionnelle retardee est fortement deconseillee car elle risque d’aggraver l’hemolyse. La prevention d’une recidive est primordiale.

The MAJORANA DEMONSTRATOR is an experiment constructed to search for neutrinoless double-beta decay in $^{76}$Ge and to demonstrate the feasibility to deploy a large-scale experiment in a phased and modular fashion. It consists of two modules of natural and $^{76}$Ge-enriched germanium detectors totalling 44.1 kg, operating at the 4850' level of the Sanford Underground Research Facility in Lead, South Dakota, USA. Commissioning of the experiment began in June 2015, followed by data production with the full detector array in August 2016. The ultra-low background and record energy resolution achieved by the MAJORANA DEMONSTRATOR enable a sensitive neutrinoless double-beta decay search, as well as additional searches for physics beyond the Standard Model. I will discuss the design elements that enable these searches, along with the latest results, focusing on the neutrinoless double-beta decay search. I will also discuss the current status and the future plans of the MAJORANA DEMONSTRATOR, as well as the plans for a future tonne-scale $^{76}$Ge experiment., 4 pages. Proceedings of The 39th International Conference on High Energy Physics (ICHEP2018), 4-11 July, 2018, Seoul, Korea. Submitted to Proceedings of Science

Background/Objectives: To describe the design, procedures, and cohort for the Better ASsessment of ILlness ­(BASIL) study, which is conducted to develop and test new delirium severity measures, compare them with existing measures, and examine related clinical outcomes. Methods: Prospective cohort study with 1 year follow-up of study participants at a large teaching hospital in Boston, Massachusetts. After brief cognitive testing and the Delirium Symptom Interview, delirium and delirium severity were rated daily in the hospital using the Confusion Assessment Method (CAM) and CAM-Severity score, the Delirium Rating Scale-Revised-98 (DRS-R-98), and the Memorial Delirium Assessment Scale (MDAS). Other key study variables included comorbidity, physical function (basic and instrumental activities of daily living [ADL]), ratings of subjective health and well-being, and clinical outcomes (length of stay, 30 day rehospitalization, nursing home admission, healthcare utilization). Follow-up interviews occurred at 1- and 12-month with patients and families. In 42 patient interviews, inter-rater reliability for key variables was assessed. Results: Of 768 eligible patients approached, 469 were screened and 352 enrolled, yielding an overall study response rate of 67% for potentially eligible participants. The mean participant was 80.3 years old (SD 6.8) and 203 (58%) were female. The majority of patients were medically complex with Charlson Comorbidity Scores ≥2 (192 patients, 55%), and 102 (29%) met criteria for dementia. Inter-rater reliability assessments (n = 42 pairs) were high for overall ratings of presence or absence of delirium by CAM (κ = 1.0), delirium severity by DRS-R-98 and MDAS (weighted kappa, κ = 1.0 for each) and for ADL impairment (κ = 1.0). For eligible participants at each time point, 278 out of 308 (90%) completed the 1-month follow-up and 132 out of 256 (53%) have completed the 12-month follow-up to date, which is still in progress. Among those who completed interviews, there was only 1–3% missing data on most major outcomes (delirium, basic ADL, and readmission). Conclusion: The BASIL study presents an innovative effort to advance the conceptualization and measurement of delirium severity. Unique strengths include the diverse cohort with complete high quality data and longitudinal follow-up, along with detailed collection of multiple delirium measures daily during hospitalization.

Aim To evaluate the impact of antithrombotic regimens during the medical phase of treatment among 13,819 patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) treated with an early invasive strategy in the acute catheterization and urgent intervention triage strategy (ACUITY) trial. Methods and results Endpoints included composite major adverse cardiac events (MACE), major bleeding, and net adverse clinical events (NACE; MACE or major bleeding). The median (interquartile range) duration of antithrombin use in the medical only treatment phase was 6.5 (1.8–22.5) hours. MACE, major bleeding, and NACE during the medical only phase occurred in 63 (0.5%), 117 (0.9%), and 178 (1.3%) patients, respectively. MACE rates in the medical-treatment-only phase were not significantly different between the four randomized medical regimens used (heparin alone, bivalirudin alone, heparin plus a glycoprotein IIb/IIIa inhibitor [GPI], and bivalirudin plus GPI) (Ptrend = 0.65). The lowest rates of major bleeding and NACE during the medical treatment phase occurred in patients treated with bivalirudin alone (Ptrend = 0.0006 and Ptrend = 0.0004, respectively). Conclusions In patients with NSTE-ACS undergoing an early invasive strategy, treatment with bivalirudin alone significantly reduced major bleeding and improved net clinical outcomes during the upstream medical management phase with comparable rates of MACE. © 2015 Wiley Periodicals, Inc.

Colorectal cancer (CRC) is the third leading cause of cancer death worldwide. It is also the third most common cancer diagnosis among men, and the second most common cancer diagnosis among women. Globally, CRC can account for nearly 694,000 annual deaths. It is widely appreciated that CRC is the result of dysregulated cellular pathways that promote an inappropriate stem-cell-like phenotype, apoptotic resistance, unchecked proliferation and metastatic spread. While no single pathway is responsible for all of these attributes, an array of recent studies suggests a pivotal role for abnormal Notch-1 signaling in CRC, in part due to interconnectivity of Notch with other pathways. This review will summarize recent evidence for a role of Notch signaling in CRC, will consider interconnectivity between Notch and other pathways involved in CRC and will discuss the possible utility of targeting Notch as a CRC therapeutic.

The accuracy of the 12-lead electrocardiogram in detecting coronary artery occlusion is limited. We sought to determine the incidence, distribution, and outcomes of patients who have total occlusion of the culprit artery but present with non-ST-segment elevation myocardial infarction (NSTEMI). The randomized Acute Catheterization and Urgent Intervention Triage Strategy trial enrolled 13,819 patients presenting with non-ST-segment elevation acute coronary syndromes who underwent an early invasive strategy. The present study includes 1,319 patients with baseline biomarker elevation (NSTEMI) and no history of coronary artery bypass graft who underwent percutaneous coronary intervention of a single culprit vessel. We compared the baseline characteristics and outcomes according to whether the culprit vessel was occluded (baseline Thrombolysis In Myocardial Infarction [TIMI] 0 to 1) or patent (TIMI 2 to 3 flow) by angiographic core laboratory assessment. TIMI 0 to 1 flow in the culprit artery was present in 262 of 1,319 (19.9%) patients. The incidence of coronary occlusion was 28.4%, 19.3%, and 12.6% in patients with NSTEMI because of right coronary, left circumflex, and left anterior descending artery disease, respectively. Patients with an occluded culprit artery were more commonly men and had ST-segment deviation ≥1 mm. One-year outcomes, including death (3.5% vs 3.0%, p = 0.68) and myocardial infarction (8.4% vs 9.6%, p = 0.47), did not differ significantly between patients with versus without occluded culprit arteries, respectively. In conclusion, the present study demonstrates that the culprit artery is totally occluded in approximately 1 in 5 patients presenting with NSTEMI and single-vessel disease; however, the presence of total occlusion in NSTEMI was not associated with an incremental hazard of death or reinfarction at 1 year.

Objective: To assess the effectiveness of renin-angiotensin aldosterone system (RAAS) inhibitors to prevent all-cause and cardiovascular death, myocardial infarction and stroke in hypertensive patients considering the number needed to treat (NNT). Methods: Data from a meta-analysis of 18 prospective, randomized, controlled morbidity-mortality trials (68 343 RAAS inhibitor; 84 543 control) were used to calculate NNTs for the prevention of all-cause and cardiovascular mortality, myocardial infarction, and stroke. Results: Angiotensin-converting enzyme (ACE) inhibitors were used in 7 trials and angiotensin receptor blockers (ARBs) in 11 trials. Mean follow-up was 4.3 years. The annual incidence rate of all-cause mortality was 0.0233 in patients randomized to RAAS inhibitors versus 0.0252 in controls (hazard ratio 0.95, 95% confidence interval 0.91 to 0.99). The corresponding median NNT to prevent one death was 113 (2.5-97.5th percentile, 85 to 168) in favor of RAAS inhibitors, which was driven by ACE inhibitors (NNT 67, 2.5-97.5th percentile, 53 to 92) rather than ARBs (NNT 335, 2.5-97.5th percentile, -4341 to 5076). Results for cardiovascular mortality (NNT 116 for ACE inhibitors and 409 for ARBs, respectively) and myocardial infarction (NNT 80 and 338, respectively) also appeared to be driven by ACE inhibitors. We found a lower NNT for stroke in favor of ARB (NNT 337 and 131, respectively) although this difference was statistically non-significant. Conclusion: Among hypertensive patients, ACE inhibitors but not ARBs, substantially reduce all-cause and cardiovascular mortality and myocardial infarction. (C) 2014 Published by Elsevier Ireland Ltd.

Background beta-Blockers relieve angina/ischemia in stable coronary artery disease (CAD), and angiotensin-converting enzyme inhibitors prevent CAD outcomes. In EUROPA, the angiotensin-converting enzyme inhibitor perindopril reduced cardiovascular outcomes in low-risk stable CAD patients over 4.2 years. This post hoc analysis examined whether the addition of perindopril to beta-blocker in EUROPA had additional benefits on outcomes compared with standard therapy including beta-blocker. Methods EUROPA was a multicenter, double-blind, placebo-controlled, randomized trial in patients with documented stable CAD. Randomized EUROPA patients who received beta-blocker at baseline were identified, and the effect on cardiovascular outcomes of adding perindopril or placebo was analyzed. Endpoints were the same as those in EUROPA. Results At baseline, 62% (n = 7534 [3789 on perindopril and 3745 on placebo]) received beta-blocker. Treatment with perindopril/beta-blocker reduced the relative risk of the primary end point (cardiovascular death, nonfatal myocardial infarction, and resuscitated cardiac arrest) by 24% compared with placebo/beta-blocker (HR, 0.76; 95% CI, 0.64-0.91; P = .002). Addition of perindopril also reduced fatal or nonfatal myocardial infarction by 28% (HR, 0.72; 95% CI, 0.59-0.88; P = .001) and hospitalization for heart failure by 45% (HR, 0.55; 95% CI, 0.33-0.93; P = .025). Serious adverse drug reactions were rare in both groups, and cardiovascular death and hospitalizations occurred less often with perindopril/beta-blocker. Conclusions The addition of perindopril to beta-blocker in stable CAD patients was safe and resulted in reductions in cardiovascular outcomes and mortality compared with standard therapy including beta-blocker.

The Majorana Collaboration is constructing a system containing 40kg of HPGe detectors to demonstrate the feasibility and potential of a future tonne-scale experiment capable of probing the neutrino mass scale in the inverted-hierarchy region. To realize this, a major goal of the Majorana Demonstrator is to demonstrate a path forward to achieving a background rate at or below 1 cnt/(ROI-t-y) in the 4 keV region of interest around the Q-value at 2039 keV. This goal is pursued through a combination of a significant reduction of radioactive impurities in construction materials with analytical methods for background rejection, for example using powerful pulse shape analysis techniques profiting from the p-type point contact HPGe detectors technology. The effectiveness of these methods is assessed using simulations of the different background components whose purity levels are constrained from radioassay measurements.

The MAJORANA DEMONSTRATOR will search for the neutrinoless double beta decay (ββ(0ν)) of the isotope 76Ge with a mixed array of enriched and natural germanium detectors. In view of the next generation of tonne-scale germanium-based ββ(0ν)-decay searches, a major goal of the MAJORANA DEMONSTRATOR is to demonstrate a path forward to achieving a background rate at or below 1 cnt/(ROI-t-y) in the 4 keV region of interest (ROI) around the 2039-keV Q-value of the 76Ge ββ(0ν)-decay. Such a requirement on the background level significantly constrains the design of the readout electronics, which is further driven by noise and energy resolution performances. We present here the low-noise low- background front-end electronics developed for the low-capacitance p-type point contact (P-PC) germanium detectors of the MAJORANA DEMONSTRATOR. This resistive-feedback front-end, specifically designed to have low mass, is fabricated on a radioassayed fused-silica substrate where the feedback resistor consists of a sputtered thin film of high purity amorphous germanium and the feedback capacitor is based on the capacitance between gold conductive traces.

Background: Angiotensin-converting-enzyme inhibition reduces the risk of cardiovascular events at a group level. Presumably, the absolute effect of treatment varies between individuals. We sought to develop multivariable prediction scores to estimate individual treatment effect of perindopril in patients with stable coronary artery disease (sCAD). Methods: In EUROPA trial participants, we estimated the individual patient 5-year absolute risk reduction (ARR) of major adverse cardiovascular events(MACE) by perindopril. Predictions were based on a new Coxproportional-hazards model with clinical characteristics and an external risk score in combination with the observed relative risk reduction. Second, a genetic profile modifying the relative efficacy of perindopril was added. The individual patient ARR was defined as the difference in MACE risk with and without treatment. The group level impact of selectively treating patients with the largest predicted treatment effect was evaluated using net benefit analysis. Results: The risk score combining clinical and genetic characteristics estimated the 5-year absolute treatment effect to be absent or adverse in 27% of patients. On the other hand, the risk score estimated a small 5-year ARR of = 50) in 20% of patients, a modest ARR of 2-4% (NNT5 25-50) in 26%, and a large ARR of >= 4% (NNT5

High purity germanium (HPGe) crystals will be used for the MAJORANA DEMONSTRATOR, where they serve as both the source and the detector for neutrinoless double beta decay. It is crucial for the experiment to understand the performance of the HPGe crystals. A variety of crystal properties are being investigated, including basic properties such as energy resolution, efficiency, uniformity, capacitance, leakage current and crystal axis orientation, as well as more sophisticated properties, e.g. pulse shapes and dead layer and transition layer distributions. In this paper, we will present our measurements that characterize the HPGe crystals. We will also discuss our simulation package for the detector characterization setup, and show that additional information can be extracted from data-simulation comparisons., Comment: To appear in the Proceedings of the 13th International Conference on Topics in Astroparticle and Underground Physics, TAUP 2013 (F. Avignone & W. Haxton, editors, Physics Procedia, Elsevier)

Although lesion complexity is predictive of outcomes after balloon angioplasty, it is unclear whether complex lesions continue to portend a worse prognosis in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) with contemporary interventional therapies. We sought to assess the impact of angiographic lesion complexity, defined by the modified American College of Cardiology/American Heart Association classification, on clinical outcomes after PCI in patients with ACS and to determine whether an interaction exists between lesion complexity and antithrombin regimen outcomes after PCI. Among the 3,661 patients who underwent PCI in the Acute Catheterization and Urgent Intervention Triage strategy study, patients with type C lesions (n = 1,654 [45%]) had higher 30-day rates of mortality (1.2% vs 0.6%, p = 0.049), myocardial infarction (9.2% vs 6.3%, p = 0.0006), and unplanned revascularization (4.3% vs 3.1%, p = 0.04) compared with those without type C lesions. In multivariate analysis, type C lesions were independently associated with myocardial infarction (odds ratio [95% confidence interval] = 1.37 [1.04 to 1.80], p = 0.02) and composite ischemia (odds ratio [95% confidence interval] = 1.49 [1.17 to 1.88], p = 0.001) at 30 days. Bivalirudin monotherapy compared with heparin plus a glycoprotein IIb/IIIa inhibitor reduced major bleeding complications with similar rates of composite ischemic events, regardless of the presence of type C lesions. There were no interactions between antithrombotic regimens and lesion complexity in terms of composite ischemia and major bleeding (p [interaction] = 0.91 and 0.80, respectively). In conclusion, patients with ACS with type C lesion characteristics undergoing PCI have an adverse short-term prognosis. Treatment with bivalirudin monotherapy reduces major hemorrhagic complications irrespective of lesion complexity with comparable suppression of adverse ischemic events as heparin plus glycoprotein IIb/IIIa inhibitor.

International audience; The seismic performance of timber-framed structures filled with stones and earth mortar has been analyzed by introducing the structural subscales (cell, wall, house) at which monotonic and cyclic loadings were considered. This article aims to present the dynamic behavior of a house as determined through shaking table tests. Based on this experimental multiscale analysis, this paper confirms that timbered masonry structures offer effective seismic resistance; moreover, such a comprehensive analysis helps enhance understanding of the seismic-resistant behavior of timber-framed structures with infill. This paper also aids ongoing development of a numerical tool intended to predict the seismic-resistant behavior of this type of structure.

Objective The session will discuss strategies for outbreak prevention, detection, and response for global health security and explore how these activities inform both domestic and international initiatives. Innovations in epidemiology, laboratory, informatics, investment, and coordination for disease surveillance will be discussed. Introduction Multiple agencies are involved in global disease surveillance and coordination of activities is essential to achieve broad public health impact. Multiple examples of effective and collaborative initiatives exist. The WHO/AFRO developed Integrated Disease Surveillance and Response (IDSR) framework, adopted by 43 of the 46 AFRO member states and applied in other WHO regions, was the first framework designed to strengthen national disease surveillance and response systems. The WHO International Health Regulations (IHR) 2005 are an agreement between 196 countries to prevent, detect and respond to the international spread of disease. In 2013 CDC worked with Uganda and Vietnam to demonstrate the development of surveillance, laboratory, and emergency response center capacity and link data systems for six outbreak prone diseases. More recently, the Global Health Security Agenda (GHSA) was launched with the support of 28 countries, WHO, OIE and FAO just as Ebola was beginning to emerge in West Africa. This panel brings together CDC, local implementing partners, academic technical partners, and international non-government donor to discuss current and evolving strategies for prevention, detection, and response activities needed for global health security.

Hypertension has now become very prevalent in sub-Saharan Africa, in part due to the region's epidemiologic transition. Its long asymptomatic onset explains its late recognition and thus the high frequency of complications. Sociocultural conditions play an important role in the genesis of the disease in this region and in the difficulties encountered in its management. The breakdown of traditional ways of life, growing urbanization, and the switch to a western lifestyle and diet all have well-known deleterious effects on the cardiovascular system. High salt consumption, sedentarity, overweight and alcohol intake all promote these developments. The insufficient availability of medical care, poverty, and poor understanding of chronic diseases complicate the medical management of hypertension. In these regions, it is now a public health challenge that requires the training of healthcare workers and the involvement of the society as a whole, including political decisions, health education for school-children, and actions by social organizations and local officials and leaders. This communication must always respect traditional customs. Both curative measures and preventive actions are essential. Priority must be given to combatting excessive salt consumption, for the results of its reduction are known to be rapid and positive. Preventing or reducing overweight and obesity, sedentarity, and alcohol and tobacco consumption are effective steps against hypertension, but also atheromatous cardiovascular diseases and diabetes. Drug therapy must meet the three essential criteria: it must be effective, available, and inexpensive. Hypertension is not inevitable, but reflects changes in society. It appears to be transmitted in part by modern lifestyles, which can be modified.

Objectives: This study evaluated the impact of nonculprit vessel myocardial perfusion on outcomes of non–ST-segment elevation acute coronary syndromes (NSTE-ACS) patients.Background: ST-segment ele...

Objectives: Our objective was to investigate the actual incidence and clinical determinants of cough leading to discontinuation of ACE-inhibitors. Cough is the most frequent reason to stop ACE-inhibitor treatment. Methods: We studied 27,492 ACE-inhibitor naive patients randomized to the ACE-inhibitor perindopril or placebo using individual data of 3 clinical trials. Multivariate logistic regression analysis was used to study the incidence of cough in relation to baseline clinical characteristics including racial background. Results: In 27,492 patients with cardiovascular disease, 1076 patients discontinued ACE-inhibitor perindopril due to cough (3.9%), 703 patients during run-in period of 4 weeks and 373 patients during a mean four years of follow-up. Significant determinants of cough were female gentler (OR 1.92 95% CI 1.68-2.18), age above 65 years (OR 1.53 95% CI 1.35-1.73), and concomitant use of lipid-lowering agents (OR 1.37; 95% CI 1.181.59). A simple clinical risk score composed of these 3 predictors of cough mounted to an odds ratio of 44 (95% CI 3.1-5.4) in the subjects with highest score (i.e all determinants present). Racial background was not related to a differential incidence of cough in patients of Caucasian or Asian descendent (OR 1.1195% CI 0.92-1.39). Conclusion: This large combined analysis of randomized clinical trials in 27,492 patients showed an overall lower incidence of cough leading to discontinuation of ACE-inhibitors (3.9%) as compared to literature. CIinical determinants of such cough are older age, female gender and concomitant use of lipid-lowering agents. In contrast, racial differences were not related to the incidence of cough. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Background Total knee arthroplasty (TKA) is one of the most clinically successful and cost-effective interventions in medicine. Implant malalignment can be a cause of early failure following total knee arthroplasty. Computer-assisted surgery has been employed to improve the precision of component alignment. Questions/purpose: We asked (1) What is the average coronal plane alignment of the first 100 patients undergoing computer-assisted total knee arthroplasty at our institution? (2) How do our clinical and radiographic results compare to those values reported in the literature? (3) Was a ‘learning curve’ present as evidenced by improvements in coronal plane alignment over time? Methods We retrospectively reviewed our first 100 patients undergoing computer navigated total knee arthroplasty. We calculated postoperative knee range of motion (ROM), coronal alignment as well as preoperative and postoperative Knee Society Scores. Minimum follow-up was 4.3 years (0.2-8.25 years). Results Of the 100 patients, average postoperative limb alignment was 0.9° varus compared to the mechanical axis. Seventy-nine percent of patients had coronal plane alignment of ±3°. Knee Society Scores improved on average from 60 preoperatively (52-67) to 85 postoperatively (56-97). Conclusion Computer-assisted total knee arthroplasty is potentially a way to improve component alignment and overall patient satisfaction. In our cohort, average coronal alignment was similar to literature reported values for navigated and conventional total knee arthroplasty. The benefit of this technology remains unproven. Level of evidence Level IV Bertrand TE, Bolognesi MP. Clinical Outcomes of First 100 Navigated Total Knee Arthroplasties at Duke University Medical Center. The Duke Orthop J 2014;4(1):13-18.

The Majorana Collaboration is constructing the Majorana Demonstrator , an ultra-low background, 40-kg modular high purity Ge detector array to search for neutrinoless double-beta decay in 76Ge. In view of the next generation of tonne-scale Ge-based neutrinoless double-beta decay searches that will probe the neutrino mass scale in the inverted-hierarchy region, a major goal of the Demonstrator is to demonstrate a path forward to achieving a background rate at or below 1 count/tonne/year in the 4 keV region of interest around the Q-value at 2039 keV. The current status of the Demonstrator is discussed, as are plans for its completion.

Aims: We aimed to determine whether preprocedural analysis of multislice computed tomography (MDCT) scan could accurately predict the “line of perpendicularity” (LP) of the aortic annulus and corresponding C-arm angulations required for prosthesis delivery. Methods and Results: A 3D analysis of preprocedural MDCT dedicated to define the LP of the aortic annulus was performed in 60 consecutive patients referred for transcatheter aortic valve replacement (TAVR). In 24 patients, the analysis was performed retrospectively to evaluate reproducibility. In 11 patients of this cohort, additional fluoroscopy and MDCT were performed postprocedure to compare the LP of the aortic annulus and the LP of the implanted bioprosthesis. In 36 patients, the analysis was performed prospectively and the results were available at the time of the procedure. In those 36 patients, the postprocedure fluoroscopy-defined LP of the implanted bioprosthesis was used to validate the LP of the aortic annulus as predicted by MDCT. Intraobserver and interobserver reproducibility of the 3D analysis of MDCT to define the LP of the aortic annulus (j 5 1 and 0.94, respectively) and of the bioprosthesis (j5 1 and 1, respectively) were excellent. Comparison between the LP of the aortic annulus and the LP of the bioprosthesis showed that the two LPs were virtually identical, demonstrating both self-centering of the device during implantation and the possibility to use the LP of the implanted bioprosthesis as a surrogate of the LP of the aortic annulus. In the prospective cohort, the ability of MDCT analysis to predict the LP of the aortic annulus was very good (accuracy 5 94% and j 5 0.89). Conclusion: Automated 3D analysis of preimplantation MDCT accurately predicts the LP of the aortic annulus and the corresponding C-arm position required for TAVR. V C

A study of signals originating near the lithium-diffused n+ contact of p-type point contact (PPC) high purity germanium detectors (HPGe) is presented. The transition region between the active germanium and the fully dead layer of the n+ contact is examined. Energy depositions in this transition region are shown to result in partial charge collection. This provides a mechanism for events with a well defined energy to contribute to the continuum of the energy spectrum at lower energies. A novel technique to quantify the contribution from this source of background is introduced. Experiments that operate germanium detectors with a very low energy threshold may benefit from the methods presented herein.

Objectives The aim of this study was to determine whether pre-procedural analysis of multidetector row computed tomography (MDCT) scans could accurately predict the “line of perpendicularity” (LP) of the aortic annulus and corresponding C-arm angulations required for prosthesis delivery and impact the outcome of the procedure. Background Optimal positioning of the transcatheter aortic prosthesis is paramount to transcatheter aortic valve replacement (TAVR) procedural success. Methods All patients referred for TAVR at our center underwent a routine pre-procedural MDCT scan. A 3-dimensional (3D) analysis using software dedicated to define the LP of the aortic annulus and the corresponding C-arm positioning was performed in 71 consecutive patients. In 35 patients, the results of the MDCT analysis were not available at the time of the procedure (angiography cohort). In that cohort the position of the C-arm was determined during the procedure using ad-hoc angiography. In 36 patients, the MDCT analysis was performed pre-procedure and results were available at the time of the procedure (MDCT cohort). In that cohort the position of the C-arm was derived from the MDCT analysis rather than by ad-hoc angiography. Results Intraobserver and interobserver reproducibility of MDCT analysis to predict the LP of the aortic annulus were excellent (kappa = 1 and 0.94, respectively). Patient variations of the LP ranged >70°. Compared with the angiography cohort, the MDCT cohort was associated with a significant decrease in implantation time (p = 0.0001), radiation exposure (p = 0.02), amount of contrast (p = 0.001), and risk of acute kidney injury (p = 0.03). Additionally, the combined rate of valve malposition and aortic regurgitation was also reduced (6% vs. 23%, p = 0.03). Conclusions Automated 3D analysis of pre-implantation MDCT accurately predicts the LP of the aortic annulus and the corresponding C-arm position required for TAVR. With this approach, the implantation of the balloon-expandable prosthetic valve can be performed without an aortogram in the majority of cases and still be safe, with a low rate of valve malpositioning and regurgitation.

Objective Moderate to severe aortic regurgitation is occurring in 20% to 30% of cases after transcatheter aortic valve implantation. Methods The purpose of the study was to investigate the impact of a prospective policy of “oversizing” the Edwards SAPIEN bioprosthesis (Edwards Lifesciences LLC, Irvine, Calif) relative to the diameter of the aortic annulus on the rate and severity of aortic regurgitation in 28 consecutive patients initially considered eligible for transcatheter aortic valve implantation on the basis of angiography, multislice computed tomography, and transthoracic echocardiography. This policy included the systematic use of transesophageal echocardiography to exclude borderline patients and the modification of the procedure to use the larger device possible. The results were studied on an individual patient basis. Results Because 6 of 28 patients (21%) had an annulus diameter greater than 24 mm by transesophageal echocardiography, 22 patients underwent implantation of the Edwards SAPIEN prosthesis. In 6 of 22 patients, the procedure was adapted to follow our “oversizing” policy. As a result, the “prosthesis/annulus cover index” was 12.4% ± 4.3%. The procedure was successful in 21 of 22 patients (95%), and 18 patients were available for echocardiography at 1 month. Although a moderate to severe aortic regurgitation was observed pretreatment in 4 of 18 patients (22%), it was no longer the case at 1 month (0/18, 0%; P = .03). The improvement was secondary to a disappearance of the aortic regurgitation in all 7 patients with a significant aortic regurgitation at pretreatment, whereas the new aortic regurgitations appearing in 5 of the 11 patients with no aortic regurgitation at pretreatment were only mild aortic regurgitations. Conclusions In patients with a successful implantation of an Edwards SAPIEN valve, a simple “oversizing” policy based on a systematic use of transesophageal echocardiography and modification of the procedure may prevent the occurrence of moderate and severe aortic regurgitations.

The optimal revascularization strategy for diabetic patients with multivessel coronary artery disease (MVD) remains uncertain for lack of an adequately powered, randomized trial. The FREEDOM trial was designed to compare contemporary coronary artery bypass grafting (CABG) to percutaneous coronary intervention (PCI) with drug-eluting stents in diabetic patients with MVD against a background of optimal medical therapy.A total of 1,900 diabetic participants with MVD were randomized to PCI or CABG worldwide from April 2005 to March 2010. FREEDOM is a superiority trial with a mean follow-up of 4.37 years (minimum 2 years) and 80% power to detect a 27.0% relative reduction. We present the baseline characteristics of patients screened and randomized, and provide a comparison with other MVD trials involving diabetic patients.The randomized cohort was 63.1 ± 9.1 years old and 29% female, with a median diabetes duration of 10.2 ± 8.9 years. Most (83%) had 3-vessel disease and on average took 5.5 ± 1.7 vascular medications, with 32% on insulin therapy. Nearly all had hypertension and/or dyslipidemia, and 26% had a prior myocardial infarction. Mean hemoglobin A1c was 7.8 ± 1.7 mg/dL, 29% had low-density lipoprotein70 mg/dL, and mean systolic blood pressure was 134 ± 20 mm Hg. The mean SYNTAX score was 26.2 with a symmetric distribution. FREEDOM trial participants have baseline characteristics similar to those of contemporary multivessel and diabetes trial cohorts.The FREEDOM trial has successfully recruited a high-risk diabetic MVD cohort. Follow-up efforts include aggressive monitoring to optimize background risk factor control. FREEDOM will contribute significantly to the PCI versus CABG debate in diabetic patients with MVD.

Our understanding of the development and progression of atherosclerosis has increased substantially over the past decades. A significant role for the renin-angiotensin-aldosterone system (RAAS) in this process has gained appreciation in recent years. Preclinical and clinical studies have associated components of the RAAS with various cardiovascular disease conditions. Classically known for its contribution to hypertension, dysregulation of the system is now also believed to promote vascular inflammation, fibrosis, remodeling, and endothelial dysfunction, all intimately related to atherosclerosis. The reduction in cardiovascular mortality and morbidity, as seen with the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, supports the concept that RAAS is involved in the pathogenesis of atherosclerotic disease. However, the underlying molecular mechanisms of the pathophysiology remain to be completely understood. Evidence points toward additional benefit from therapeutic approaches aiming at more complete inhibition of the system and the possible utility of renin or aldosterone in the prediction of cardiovascular outcome. This review will summarize the current knowledge from clinical studies regarding the presumptive role of renin and aldosterone in the prediction and management of patients with atherosclerosis. For this purpose, a literature search was performed, focusing on available clinical data regarding renin or aldosterone and cardiovascular outcome. (Am Heart J 2011;162:585-96.)

Objectives The objective of this study is to investigate the incidence and clinical implications of thrombus on baseline angiography among patients presenting with non–ST-segment elevation acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). Background Given current advances in the pharmacological and mechanical treatment of ACS patients managed with an early invasive strategy, the incidence and prognostic importance of pre-procedural lesion thrombus is warranted. Methods In the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial, a total of 3,627 patients with moderate- and high-risk ACS undergoing PCI had their baseline and final post-PCI angiograms analyzed by an independent angiographic core laboratory. Results Patients with thrombus (n = 530 [15%]) compared with those without thrombus had higher rates of impaired final epicardial coronary flow (final Thrombolysis In Myocardial Infarction [TIMI] flow grade 3: 89.6% vs. 97.1%, p Conclusions Pre-procedural thrombus was present in 15% of moderate- and high-risk ACS patients undergoing PCI in the ACUITY trial. Baseline thrombus predicts increased ischemic complications at 30 days including a 3-fold increased risk of death as well as MI up to 1 year. Further evaluation of adjunctive pharmacotherapy is needed in this high-risk population.

Objectives This study sought to develop a risk score predictive of bleeding in patients undergoing percutaneous coronary intervention (PCI) and to investigate the impact of bleeding on subsequent mortality. Background Bleeding complications after PCI have been independently associated with early and late mortality. Methods This study represents a patient-level pooled analysis including 17,034 patients undergoing PCI from 3 large, randomized trials of bivalirudin versus heparin plus glycoprotein IIb/IIIa inhibitors, including the REPLACE-2 (Randomized Evaluation of PCI Linking Angiomax to Reduced Clinical Events), ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy), and HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trials. We developed a risk score to predict noncoronary artery bypass graft (CABG)–related TIMI (Thrombolysis In Myocardial Infarction) major bleeding and evaluated the impact of various types of bleeding on 1-year mortality. Results A non-CABG–related TIMI major bleed occurred within 30 days in 267 patients (1.6%), and death occurred in 497 patients (2.9%) within 1 year. A risk score was developed to predict the bleeding risk of patients undergoing PCI, consisting of 7 variables (serum creatinine, age, sex, presentation, white blood cell count, cigarette smoking, and randomized treatment). The TIMI major bleeding rates increased by bleeding risk score groups: from 0.4% for those in the lowest to 5.8% for those in the highest risk group. Non-CABG–related TIMI major bleeding and the occurrence of myocardial infarction within 30 days were independent predictors of subsequent mortality, with respective hazard ratios of 4.2 and 2.9, each p Conclusions Non-CABG–related bleeding within 30 days is strongly associated with an increased risk of subsequent mortality at 1 year in patients undergoing PCI for all indications. A risk score was established to calculate the bleeding risk for patients undergoing PCI, allowing therapeutic decision making to minimize the incidence of bleeding.

Automated classification of biological cells according to their 3D morphology is highly desired in a flow cytometer setting. We have investigated this possibility experimentally and numerically using a diffraction imaging approach. A fast image analysis software based on the gray level co-occurrence matrix (GLCM) algorithm has been developed to extract feature parameters from measured diffraction images. The results of GLCM analysis and subsequent classification demonstrate the potential for rapid classification among six types of cultured cells. Combined with numerical results we show that the method of diffraction imaging flow cytometry has the capacity as a platform for high-throughput and label-free classification of biological cells.

Introduction Since the first heart catheterization performed by Werner Forssmann on himself in 1929, this technique has undergone an extraordinary expansion and widespread application. Today, several million heart catheterizations are performed throughout the world each year. Heart catheterization is not only a fantastic investigative tool that provides precise information regarding anatomy and physiology, but it also offers a number of important and very effective interventions. Forssmann imagined heart catheterization as a delivery mechanism for drugs to enhance their efficacy, and heart catheterization has indeed become, in a large number of cases, a therapeutic tool. Cardiac catheterizations are performed in a large number of centers worldwide, and the complication rate is low. Nevertheless, zero risk does not exist in medicine. This analysis focuses on the procedural risks of cardiac catheterization and coronary angiography but does not discuss the risks related to specific interventions (e.g., the risks of stent implantation, atherectomy, or systemic anaphylactoid reactions to iodinated contrast media). Actually, vital risks of heart catheterization are very rare, and most complications are related to the access site.

Clinical outcomes in patients with acute coronary syndromes randomized in the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial who underwent percutaneous coronary intervention (PCI) of saphenous vein grafts (SVGs) were examined. The ACUITY trial assessed the safety and efficacy of bivalirudin alone versus bivalirudin plus a glycoprotein (GP) IIb/IIIa inhibitor versus heparin plus a GP IIb/IIIa inhibitor in 13,819 patients with moderate- and high-risk acute coronary syndromes, 7,789 of whom underwent PCI. A total of 329 patients (4.2%) underwent PCI of SVGs in ACUITY. The primary end points at 30 days were composite ischemia or major adverse cardiac events (death, myocardial infarction, or unplanned target vessel revascularization), major bleeding (unrelated to coronary artery bypass grafting), and net adverse clinical events (composite ischemia or major bleeding). The rates of ischemic, bleeding, and net clinical end points were similar with bivalirudin monotherapy, bivalirudin plus a GP IIb/IIIa inhibitor, and heparin plus a GP IIb/IIIa inhibitor. Net adverse clinical outcome rates at 30 days were 22%, 26%, and 22% (p = 0.67), respectively, for the 3 groups. Major adverse cardiac event rates at 1 year were 37%, 37%, and 43% (p = 0.95), respectively. Minor bleeding unrelated to coronary artery bypass grafting at 30 days was significantly lower with bivalirudin alone compared with heparin plus a GP IIb/IIIa inhibitor (26% vs 38%, p = 0.05). In conclusion, bivalirudin is an effective anticoagulant in PCI of SVGs in acute coronary syndromes, with similar rates of major adverse cardiac events and net adverse cardiac events and lower minor bleeding complications in comparison with heparin plus a GP IIb/IIIa inhibitor or bivalirudin plus a GP IIb/IIIa inhibitor.

Background— Contemporary adjunctive pharmacology and revascularization strategies have improved the prognosis of patients with acute coronary syndromes (ACSs). We sought to identify the clinical and angiographic predictors of cardiac ischemic events in patients with ACSs treated with an early invasive strategy. Methods and Results— Multivariable logistic regression was used to analyze the relation between baseline characteristics and 30-day and 1-year composite ischemia (death, myocardial infarction, or unplanned revascularization) among the 6921 ACS patients included in the prespecified angiographic substudy of the Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial. Of the 6921 patients, 3826 (55.3%) were treated with percutaneous coronary intervention, 755 (10.9%) with coronary artery bypass grafting, and 2340 (33.8%) with medical therapy. Composite ischemia occurred in 595 (8.6%) patients at 30 days and in 1153 (17.4%) at 1 year. Renal insufficiency, biomarker elevation, ST-segment deviation, nonuse of aspirin or thienopyridine, insulin-treated diabetes, older age, baseline lower hemoglobin value, history of percutaneous coronary intervention, and current smoking were independently associated with 30-day or 1-year ischemic events. Angiographic characteristics predicting ischemic events included number of diseased vessels, moderate/severe calcification, worst percent diameter stenosis, jeopardy score, lower left ventricular ejection fraction, lesion eccentricity, and thrombus. With use of receiver operating characteristic methodology, the c statistic improved for the predictive model by adding angiographic to clinical parameters for the 30-day composite ischemia (from 0.62 to 0.68) and myocardial infarction (from 0.64 to 0.71) and 1-year composite ischemia (from 0.61 to 0.65) and myocardial infarction (from 0.63 to 0.69) end points. Conclusions— Among ACS patients managed with an early invasive strategy, baseline angiographic markers of disease burden, calcification, lesion severity, lower left ventricular ejection fraction, and morphological characteristics provided important added independent predictive value for 30-day and 1-year ischemic outcomes, beyond the well-recognized clinical risk factors. These findings emphasize the prognostic importance of the diagnostic angiogram in the risk stratification of patients presenting with ACSs. Clinical Trial Registration— URL: http://clinicaltrials.gov . Unique identifier: NCT00093158.

Abciximab and eptifibatide have been shown to reduce ischemic complications compared with heparin alone in patients with acute coronary syndromes who undergo percutaneous coronary intervention. Whether 1 agent is safer and/or more effective has not been prospectively examined. The aim of this study was to assess the outcomes related to downstream glycoprotein IIb/IIIa inhibitor treatment selection during percutaneous coronary intervention in 2,211 patients with moderate and high-risk acute coronary syndromes in the prospective multicenter Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial. The protocol permitted operator selection of abciximab (n = 835) or eptifibatide (n = 1,376) for routine use in the trial. Multivariate and propensity-based adjustments were used to assess the independent association of glycoprotein IIb/IIIa inhibitor treatment selection with prespecified study end points. Compared to patients receiving eptifibatide, those administered abciximab were older, more likely to be enrolled outside of North America, more frequently had biomarker elevations and ST-segment deviation, but had fewer baseline cardiac risk factors and previous revascularization procedures. After multivariate propensity-based adjustment, abciximab was independently associated with significantly fewer net clinical adverse events (odds ratio 0.61, 95% confidence interval 0.42 to 0.90, p = 0.01), mediated by composite ischemia (odds ratio 0.61, 95% confidence interval 0.38 to 0.98, p = 0.04) and major bleeding (odds ratio 0.58, 95% confidence interval 0.34 to 1.00, p = 0.051). In conclusion, in this prespecified but nonrandomized comparison in patients with acute coronary syndromes who underwent percutaneous coronary intervention with catheterization laboratory initiation of glycoprotein IIb/IIIa inhibitors, the use of abciximab rather than eptifibatide was associated with improved clinical outcomes at 30 days. These findings should be viewed as exploratory in light of the nonrandomized and heterogeneous nature of the comparator groups and significant potential for residual confounding.

Aims The efficacy of angiotensin-converting enzyme (ACE)-inhibitors in stable coronary artery disease (CAD) may be increased by targeting the therapy to those patients most likely to benefit. However, these patients cannot be identified by clinical characteristics. We developed a genetic profile to predict the treatment benefit of ACE-inhibitors exist and to optimize therapy with ACE-inhibitors. Methods and resultsIn 8907 stable CAD patients participating in the randomized placebo-controlled EUROPA-trial, we analysed 12 candidate genes within the pharmacodynamic pathway of ACE-inhibitors, using 52 haplotype-tagging-single nucleotide polymorphisms (SNPs). The primary outcome was the reduction in cardiovascular mortality, non-fatal myocardial infarction, and resuscitated cardiac arrest during 4.2 years of follow-up. Multivariate Cox regression was performed with multiple testing corrections using permutation analysis. Three polymorphisms, located in the angiotensin-II type I receptor and bradykinin type I receptor genes, were significantly associated with the treatment benefit of perindopril after multivariate adjustment for confounders and correction for multiple testing. A pharmacogenetic score, combining these three SNPs, demonstrated a stepwise reduction of risk in the placebo group and a stepwise decrease in treatment benefit of perindopril with an increasing scores (interaction P < 0.0001). A pronounced treatment benefit was observed in a subgroup of 73.5 of the patients [hazard ratio (HR) 0.67; 95 confidence interval (CI) 0.56-0.79], whereas no benefit was apparent in the remaining 26.5 (HR 1.26; 95 CI 0.97-1.67) with a trend towards a harmful effect. In 1051 patients with cerebrovascular disease from the PROGRESS-trial, treated with perindopril or placebo, an interaction effect of similar direction and magnitude, although not statistically significant, was observed. Conclusion The current study is the first to identify genetic determinants of treatment benefit of ACE-inhibitor therapy. We developed a genetic profile which predicts the treatment benefit of ACE-inhibitors and which could be used to optimize therapy.

AIMS: Presentation with an acute coronary syndrome (ACS) on chronic aspirin therapy is an independent predictor of adverse short-term outcomes. Whether this finding applies to chronic thienopyridine use, and with the contemporary invasive management of ACS, is unknown. METHODS AND RESULTS: In ACUITY, 13819 patients with moderate and high-risk ACS were studied; patients transferred from an outside hospital were excluded from the present analysis, given uncertain preadmission antiplatelet status. Endpoints included major adverse cardiovascular events (MACE: death, myocardial infarction, or unplanned revascularization), major bleeding, and net adverse clinical events (NACE). Among 11313 study patients, 31 % were naive for antiplatelet agent, 49% were receiving aspirin alone, and 20% were on dual antiplatelet therapy. Chronic antiplatelet users were older and had a higher risk profile. After adjusting for baseline differences, chronic antiplatelet therapy (single or dual) was not associated with an increased incidence of 30-day MACE, bleeding, or NACE. However, patients on chronic aspirin or dual antiplatelet therapy at presentation had significantly higher 1-year rates of MACE [odds ratio (95% confidence interval) = 1.17 (1.01–1.36), P = 0.03 and 1.29 (1.02–1.64), P = 0.03, respectively]. Patients presenting on dual antiplatelet therapy had significantly greater adjusted MACE at 1-year than those on aspirin alone [odds ratio (95% confidence interval) = 1.34 (1.15–1.56), P