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Wiviott S.D.,Harvard University | White H.D.,Green City | Ohman E.M.,Duke University | Fox K.A.A.,University of Edinburgh | And 17 more authors.
The Lancet | Year: 2013

Background Treatment with prasugrel and aspirin improves outcomes compared with clopidogrel and aspirin for patients with acute coronary syndrome who have had angiography and percutaneous coronary intervention; however, no clear benefit has been shown for patients managed first with drugs only. We assessed outcomes from the TRILOGY ACS trial based on whether or not patients had coronary angiography before treatment was chosen. Methods TRILOGY ACS (ClinicalTrials.gov number NCT00699998) was a randomised controlled trial, done at more than 800 sites worldwide. Patients with non-ST-elevation acute coronary syndrome who were selected for management with revascularisation were randomly assigned to clopidogrel or prasugrel. The primary endpoint was cardiovascular death, myocardial infarction, or stroke at 30 months. In the present analysis we assessed differences in the primary endpoint by angiography status and whether the effects of treatment on the primary endpoint differed between patients who had angiography before enrolment and those who had not. Findings 7243 patients younger than 75 years were included in the TRILOGY ACS primary analysis. 3085 (43%) had angiography at baseline, 4158 (57%) had not. Fewer patients who had angiography reached the primary endpoint at 30 months compared with those who did not have angiography, according to Kaplan-Meier analysis (281/3085 [12·8%] vs 480/4158 [16·5%], adjusted hazard ratio [HR] 0·63, 95% CI 0·53-0·75; p<0·0001). The proportion of patients who reached the primary endpoint was lower in the prasugrel group than in the clopidogrel group for those who had angiography (122/1524 [10·7%] vs 159/1561 [14·9%], HR 0·77, 95% CI 0·61-0·98; p=0·032) but did not differ between groups in patients who did not have angiography (242/2096 [16·3%] vs 238/2062 [16·7%], HR 1·01, 0·84-1·20; p=0·94; p interaction=0·08). Overall, TIMI major bleeding and GUSTO severe bleeding were rare. Bleeding outcomes tended to be higher with prasugrel but did not differ significantly between treatment groups in either angiography cohort. Interpretation Among patients who had angiography who took prasugrel there were fewer cardiovascular deaths, myocardial infarctions, or strokes than in those who took clopidogrel. This result needs to be corroborated, but it is consistent with previous trials of more versus less intensive antiplatelet treatment. When angiography is done for acute coronary syndrome and anatomic coronary disease confirmed, the benefits and risks of intensive antiplatelet treatment exist whether the patient is treated with drugs or percutaneous coronary intervention.


Der Mesropian P.J.,State University of New York at Buffalo | Kalamaras J.S.,University at Albany | Eisele G.,Albany Medical Center | Phelps K.R.,Albany Stratton Medical Center | And 3 more authors.
Clinical Nephrology | Year: 2014

Aim: To compare long-term outcomes in CA-AKI to HA-AKI. The hypothesis was that renal and patient survival would be better in CA-AKI than in HA-AKI. Methods: Retrospective cohort analysis of patients hospitalized from 2004 to 2005, in Upstate New York Veterans Affairs hospitals. The groups: CA-AKI (n = 560), HA-AKI (n = 158), or No AKI (NA) (n = 2,320). Risk, injury, failure, loss, and end-stage kidney (RIFLE) criterion was used to define AKI. Primary outcomes: doubling of serum creatinine, endstage renal disease (ESRD), death, and a composite of the three. Secondary outcomes: de novo chronic kidney disease (CKD), recovery of renal function, and re-admission rate. The cumulative incidence of outcomes was determined over a period of 3 years after discharge. Results: CA-AKI was 3.5 times as prevalent as HA-AKI. In comparison to patients with HA-AKI, those with CA-AKI had better estimated glomerular filtration rate (71.3 vs. 61.1 mL/min/1.73 m2, p < 0.001) and lower prevalence of CKD (42.3 vs. 51.9%, p = 0.03) at baseline. More patients with CA-AKI than HA-AKI met RIFLE failure criterion (43.8 vs. 29.1%, p < 0.001). By 3 years, no differences were found for the individual primary and secondary outcomes tested (all p > 0.05). Conclusions: CA-AKI was found to be considerably more common than HA-AKI and had similar long-term consequences. © 2014 Dustri-Verlag Dr. K. Feistle.


O'Donoghue M.L.,Brigham and Women's Hospital | Vaidya A.,University of California at San Francisco | Afsal R.,Hamilton Health Sciences | Alfredsson J.,Linköping University | And 11 more authors.
Journal of the American College of Cardiology | Year: 2012

Objectives: The purpose of this study was to conduct a meta-analysis to examine an invasive or conservative strategy in diabetic versus nondiabetic patients. Background: Diabetic patients are at increased risk of cardiovascular events after an acute coronary syndrome, yet it remains unknown whether they derive enhanced benefit from an invasive strategy. Methods: Randomized trials comparing an invasive versus conservative treatment strategy were identified. The prevalence of cardiovascular events through 12 months was reported for each trial, stratified by diabetes mellitus status and randomized treatment strategy. Relative risk (RR) ratios and absolute risk reductions were combined using random-effects models. Results: Data were combined across 9 trials comprising 9,904 subjects of whom 1,789 (18.1%) had diabetes mellitus. The RRs for death, nonfatal myocardial infarction (MI), or rehospitalization with an acute coronary syndrome for an invasive versus conservative strategy were similar between diabetic patients (RR: 0.87; 95% confidence interval [CI]: 0.73 to 1.03) and nondiabetic patients (RR: 0.86; 95% CI: 0.70 to 1.06; p interaction = 0.83). An invasive strategy reduced nonfatal MI in diabetic patients (RR: 0.71; 95% CI: 0.55 to 0.92), but not in nondiabetic patients (RR: 0.98; 95% CI: 0.74 to 1.29; p interaction = 0.09). The absolute risk reduction in MI with an invasive strategy was greater in diabetic than nondiabetic patients (absolute risk reduction: 3.7% vs. 0.1%; p interaction = 0.02). There were no differences in death or stroke between groups (p interactions 0.68 and 0.20, respectively). Conclusions: An early invasive strategy yielded similar RR reductions in overall cardiovascular events in diabetic and nondiabetic patients. However, an invasive strategy appeared to reduce recurrent nonfatal MI to a greater extent in diabetic patients. These data support the updated guidelines that recommend an invasive strategy for patients with diabetes mellitus and non-ST-segment elevation acute coronary syndromes. © 2012 American College of Cardiology Foundation.


Desai K.P.,Albany Medical College | Sidhu M.S.,Albany Medical College | Sidhu M.S.,Albany Medical Center | Sidhu M.S.,Albany Stratton Medical Center | And 3 more authors.
Trends in Cardiovascular Medicine | Year: 2014

The past decade has been associated with profound progress in both the assessment and treatment of stable ischemic heart disease (SIHD) patients. The many randomized clinical trials, observational studies, and post hoc analyses continue to elucidate the role of coronary anatomy and ischemic burden in treating our patients in routine clinical practice, with the preponderance of the current scientific evidence base suggesting that coronary anatomy does indeed trump physiology in predicting future coronary events in SIHD patients. However, the many clinical studies and post hoc analyses, while provocative, are relatively underpowered; therefore, an important question remains as to whether anatomic burden or ischemic burden can most reliably identify patients who would derive clinical benefits from an initial invasive strategy, regardless of prognostic value. © 2014.


PubMed | Albany Stratton Medical Center, SUNY Downstate Medical Center, University of Connecticut, Indiana University and 3 more.
Type: | Journal: International journal of psychophysiology : official journal of the International Organization of Psychophysiology | Year: 2017

Differences in fast beta (20-28 Hz) electroencephalogram (EEG) oscillatory activity distinguish some individuals with psychiatric and substance use disorders, suggesting that it may be a useful endophenotype for studying the genetics of disorders characterized by neural hyper-excitability. Despite the high heritability estimates provided by twin and family studies, there have been relatively few genetic studies of beta EEG, and to date only one genetic association finding has replicated (i.e., GABRA2).In a sample of 1,564 individuals from 117 families of European Ancestry (EA) drawn from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a Genome-Wide Association Study (GWAS) on resting-state fronto-central fast beta EEG power, adjusting regression models for family relatedness, age, sex, and ancestry. To further characterize genetic findings, we examined the functional and behavioral significance of GWAS findings.Three intronic variants located within DSE (dermatan sulfate epimerase) on 6q22 were associated with fast beta EEG at a genome wide significant level (p<5x10In this sample of EA families enriched for AUDs, fast beta EEG is associated with variants within DSE on 6q22; the most significant SNP influences the mRNA expression of DSE and ROS1 in hippocampus and temporal cortex, brain regions important for beta EEG activity. Gene-based tests suggest evidence of association with related genes, ZEB2, RND3, MCTP1, CTBP2, and beta EEG. Converging data from GWAS, gene expression, and gene-networks presented in this study provide support for the role of genetic variants within DSE and related genes in neural hyperexcitability, and has highlighted two potential candidate genes for AUD and/or related neurological conditions: ZEB2 and CTBP2. However, results must be replicated in large, independent samples.


Marzilli M.,Universitaria Pisana | Merz C.N.B.,Cedars Sinai Heart Institute | Boden W.E.,Albany Stratton Medical Center | Bonow R.O.,Northwestern University | And 8 more authors.
Journal of the American College of Cardiology | Year: 2012

In the current pathophysiological model of chronic ischemic heart disease (IHD), myocardial ischemia and exertional angina are caused by obstructive atherosclerotic plaque, and the clinical management of IHD is centered on the identification and removal of the stenosis. Although this approach has been in place for years, several lines of evidence, including poor prognostic impact, suggest that this direct relationship may present an oversimplified view of IHD. Indeed, a large number of studies have found that IHD can occur in the presence or absence of obstructive coronary artery disease and that atherosclerosis is just 1 element in a complex multifactorial pathophysiological process that includes inflammation, microvascular coronary dysfunction, endothelial dysfunction, thrombosis, and angiogenesis. Furthermore, the high recurrence rates underscore the fact that removing stenosis in patients with stable IHD does not address the underlying pathological mechanisms that lead to the progression of nonculprit lesions. The model proposed herein shifts the focus away from obstructive epicardial coronary atherosclerosis and centers it on the microvasculature and myocardial cell where the ischemia is taking place. If the myocardial cell is placed at the center of the model, all the potential pathological inputs can be considered, and strategies that protect the cardiomyocytes from ischemic damage, regardless of the causative mechanism, can be developed. © 2012 American College of Cardiology Foundation.


PubMed | Albany Stratton Medical Center and University of Iowa
Type: Journal Article | Journal: Journal of oncology translational research | Year: 2016

To investigate outcomes and prognostic factors in patients treated with once daily high-dose (60 Gy) radiation therapy (HDRT) and concurrent platinum-based chemotherapy in limited stage small cell lung cancer (LS-SCLC). While we await current phase III trials to determine optimal radiation dose fractionation schemes in LS-SCLC, we report our experience in LS-SCLC with once daily HDRT. We hypothesized that HDRT would achieve similar efficacy and tolerability as twice daily therapy.We conducted a single institution retrospective review of all patients with LS-SCLC who underwent curative intent treatment from 2005-2013. Patients treated with HDRT (60 Gy) and concurrent chemotherapy (cisplatin or carboplatin and etoposide) were included in our analysis. Clinicopathologic variables assessed include gender, performance status, time to treatment, response to treatment, toxicity, volumetric tumor response at 3 months, and use of prophylactic cranial irradiation (PCI).42 patients with LS-SCLC who initiated concurrent chemoradiation from 2005 to 2013 were included in the analysis. 38 patients (90%) completed definitive treatment to the lung; 16 (38%) also completed PCI. Median failure free survival (FFS) and overall survival (OS) were 11.9 and 23.1 months, respectively. Two-year and 5-year OS rates were 47% (CI=30-62%) and 21% (CI=7-38%), respectively. On univariate analysis, PCI was associated with improved FFS but this was not significant (p=0.18). Gender was the only co-variate significantly associated with statistical differences in FFS (p=0.03) and OS (p=0.02). Grade 3 and 4 esophagitis were 10.5% and 2.6%, respectively. Pre-HDRT tumor volume and 3-month post-treatment tumor volume were both associated with FFS (p<0.01) but not OS.In this single institution series, daily HDRT demonstrated a 2-year OS of 47% in LS-SCLC. This compares well to the historical survival of daily fractionation (47%) from INT 0096 reported by Turrisi


Mathew R.O.,Albany Stratton Medical Center | Hsu W.-H.,Albany State University | Young Y.,Albany State University
American Journal of Physical Medicine and Rehabilitation | Year: 2013

Objective: The aim of this study was to assess the relationship between selfreported disease burden (stroke, congestive heart failure, diabetes, chronic obstructive pulmonary disease, arthritis, or cancer) and functional improvement during and after inpatient rehabilitation among older adults with hip fractures. Design: This is a longitudinal study examining 238 community-dwelling adults 65 yrs or older with unilateral hip fractures who underwent surgical repair and inpatient rehabilitation and were followed for 1 yr after discharge from the inpatient rehabilitation facility. The Functional Independence Measure (FIM) instrument was the outcome variable, collected at inpatient rehabilitation facility admission and discharge and at 2, 6, and 12 mos after discharge from the inpatient rehabilitation facility. A mixed-effect model was applied to quantify FIM functional improvement patterns between groups with and without selected preexisting chronic conditions while adjusting for potential confounders. Results: Maximum functional improvement occurred during rehabilitation and the first 6 mos after rehabilitation for all six chronic conditions under study. In regard to the effect of disease on selected FIMoutcomes, comparedwith patientswithout the selected preexisting chronic conditions, those who have had a stroke had significantly worse self care (β = j0.33; P = 0.02), transfer (β = j0.36; P = 0.03), and locomotion (β = j0.84; P = 0.0005) ratings, whereas the patients with congestive heart failure had significantly worse transfer (β =j0.59; P=0.001) and locomotion (β =j0.71; P = 0.01) ratings. Significant interactions in stroke with time were seen in self-care (β = j0. 03; P = 0.04), suggesting that those who have had a stroke before hip fracture had poorer functional improvement over time than those who did not have the conditions. The patients with congestive heart failure demonstrated a faster rate of recovery over time in locomotion than those without (β = 0.06; P = 0.03). Conclusions: Intervention strategies shouldmonitor the first 6 mos after discharge from inpatient rehabilitation, during which the maximum level of functional improvement is expected. However, the individuals who have had a stroke had poor functional improvement at 1 yr (adjusted mean FIM score, 5.74) than those who have not had a stroke (adjusted mean FIM score, 6.56). The patients who have had a stroke required human supervision at 12 mos after rehabilitation. Therefore, long-term care needs should be monitored in the discharge plan. Copyright © 2013 by Lippincott Williams & Wilkins.

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