Veterans Affairs Health Care System

Palo Alto, CA, United States

Veterans Affairs Health Care System

Palo Alto, CA, United States
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Adabag S.,Veterans Affairs Health Care System | Adabag S.,University of Minnesota | Rector T.S.,Veterans Affairs Health Care System | Rector T.S.,University of Minnesota | And 8 more authors.
European Journal of Heart Failure | Year: 2014

Aims Sudden cardiac death (SCD) accounts for ∼ 25% of all deaths in heart failure with preserved ejection fraction (HFpEF). However, strategies to identify HFpEF patients at a higher risk of SCD have not been developed.Methods and results We studied 4128 patients with HFpEF enrolled in the Irbesartan in Patients with Heart Failure and Preserved Ejection Fraction (I-PRESERVE) trial. All SCDs were adjudicated by a clinical endpoint committee. Cumulative incidences of SCD were estimated counting other deaths as competing risks. Cox regression analysis was used to generate a risk model for SCD. During a mean follow-up of 4.1 years, 231 (5.6%) patients died suddenly and 650 (15.7%) died non-suddenly. A multivariable model in 3480 patients including age, gender, history of diabetes and myocardial infarction, LBBB on ECG, and the natural logarithm of NT-proBNP identified a subgroup of 837 (24%) patients with ≥10% cumulative incidence of SCD over 5 years, accounting for other deaths as competing risk (Harrell's C index 0.75). The 5-year cumulative incidences of SCD in the higher and lower risk groups were 11% and 4%, respectively. In the higher risk group, 32% of deaths were SCD compared with 26% in the entire I-PRESERVE cohort.Conclusions A multivariable prediction model identified patients with HFpEF who have a ≥10% risk of SCD over 5 years, similar to the risk of SCD in the Sudden Cardiac Death in Heart Failure (SCD-Heft) trial. This model may be useful for selecting patients with HFpEF for SCD prevention trials. © 2014 The Authors European Journal of Heart Failure.


Fink H.A.,11 Health | Hemmy L.S.,11 Health | MacDonald R.,Center for Chronic Disease Outcomes Research 111 0 | Carlyle M.H.,Optum Health | And 8 more authors.
Annals of Internal Medicine | Year: 2015

Background: Risks for intermediate- and long-term cognitive impairment after cardiovascular procedures in older adults are poorly understood. Purpose: To summarize evidence about cognitive outcomes in adults aged 65 years or older at least 3 months after coronary or carotid revascularization, cardiac valve procedures, or ablation for atrial fibrillation. Data Sources: MEDLINE, Cochrane, and Scopus databases from 1990 to January 2015; ClinicalTrials.gov; and bibliographies of reviews and eligible studies. Study Selection: English-language trials and prospective cohort studies. Data Extraction: One reviewer extracted data, a second checked accuracy, and 2 independently rated quality and strength of evidence (SOE). Data Synthesis: 17 trials and 4 cohort studies were included; 80% of patients were men, and mean age was 68 years. Cognitive function did not differ after the procedure between on- and off-pump coronary artery bypass grafting (CABG) (n = 6; low SOE), hypothermic and normothermic CABG (n = 3; moderate to low SOE), or CABG and medical management (n = 1; insufficient SOE). One trial reported lower risk for incident cognitive impairment with minimal versus conventional extracorporeal CABG (risk ratio, 0.34 [95% CI, 0.16 to 0.73]; low SOE). Two trials found no difference between surgical carotid revascularization and carotid stenting or angioplasty (low and insufficient SOE, respectively). One cohort study reported increased cognitive decline after transcatheter versus surgical aortic valve replacement but had large selection and outcome measurement biases (insufficient SOE). Limitations: Mostly low to insufficient SOE; no pertinent data for ablation; limited generalizability to the most elderly patients, women, and persons with substantial baseline cognitive impairment; and possible selective reporting and publication bias. Conclusion: Intermediate- and long-term cognitive impairment in older adults attributable to the studied cardiovascular procedures may be uncommon. Nevertheless, clinicians counseling patients before these procedures should discuss the uncertainty in their risk for adverse cognitive outcomes. Primary Funding Source: Agency for Healthcare Research and Quality. © 2015 American College of Physicians.


News Article | November 11, 2016
Site: www.sciencedaily.com

A large national study has confirmed the value of high-intensity statin treatments for people with cardiovascular disease, according to researchers at the Stanford University School of Medicine. Over the duration of a year, the researchers found that patients taking high-intensity statins had an increased chance of survival over those on moderate-intensity statins. The study will be published online Nov. 9 in JAMA Cardiology. Statins, a class of drugs that lowers cholesterol levels in the blood, are commonly prescribed for preventing the acceleration of cardiovascular disease caused by the buildup of plaque in the arteries, which can lead to heart attacks and stroke. Health-care providers have long debated the benefits of prescribing high-intensity statins to their patients with cardiovascular disease. Patients, in turn, have been hesitant to take them because of equivocal messages from their doctors and internet searches of patient and doctor perspectives. "Previously, there was definitely a certain amount of fear on the patient's part because most people don't like taking medication," said Paul Heidenreich, MD, professor of cardiovascular medicine and the study's senior author. Some studies have shown an increased risk of side effects, such as diabetes or muscle damage, associated with higher-intensity statins. In 2013, the American College of Cardiology and American Heart Association jointly recommended high-intensity statin therapy for patients with atherosclerotic cardiovascular disease who were no older than 75. The ACC/AHA guidelines differed, however, from guidelines established in 2014 by the Veterans Affairs Health Care System, which recommended only moderate-intensity statins, noting the lack of conclusive evidence that higher-intensity statins are more beneficial than those of moderate intensity. In their study, Heidenreich and his team found evidence to support the ACC/AHA guidelines. They determined that high-intensity statins do in fact increase rates of survival, not only in younger and middle-aged patients with cardiovascular disease, but also in a patient population not well-studied: adults over 75. "The greatest strength of this study is that we used a very large, well-defined clinical cohort," said Fatima Rodriguez, MD, a cardiology fellow at Stanford and the study's lead author. "The results show that high-intensity statins confer a survival advantage for patients with cardiovascular disease, including older adults." The researchers studied the medical records of 509,766 patients across the country receiving care from the Veterans Affairs Health Care System. "This is a very large patient population rich in cardiovascular disease," said Rodriguez. "In addition to defining this large, national patient population, we also had access to their detailed clinical data, including comorbidities and cholesterol values." The primary purpose was to look at overall patient death rates from 2013 to 2014, the researchers said. They included patients with coronary artery disease, cerebrovascular disease and peripheral artery disease. "These are basically the three main areas affected by plaque buildup -- the heart, the brain and the large arteries of the rest of the body," Heidenreich said. Patients were taking high-intensity, moderate-intensity or low-intensity statins in many different but commonly prescribed forms, such as rosuvastatin and atorvastatin. The researchers also followed one group that wasn't taking any statins. Patients had different severities of cardiovascular disease, making some more likely to be prescribed higher-intensity statins than others. So the researchers assigned each patient a score for the propensity to receive high-intensity statins and adjusted the results of the study accordingly. The results showed a 9 percent increased chance of survival for patients taking high-intensity statins compared to those receiving moderate-intensity treatments. "We found basically the same risk reductions reviewed by the Veterans Affairs guidelines, but they didn't think the benefit was significant because the sample size was small," Heidenreich said. "We have so many more patients, we can be confident that it wasn't due to chance." The study considered data from patients over 75 -- a group little studied in clinical trials. It found that patients between the ages of 75 and 85 taking high-intensity statins had a survival-rate benefit comparable to that of younger patients: a 9 percent higher chance of survival compared to those on moderate-intensity statins. "Our results suggest that clinical trial data from heart studies for those younger than 75 could also be applied to this older population," Heidenreich said. Finally, they studied the effect of different doses within the high-intensity statin group. Patients treated with the maximum dose of statins were 10 percent more likely to survive than patients on submaximal doses. "This suggests to practitioners that instead of starting a patient on a low dose, just to go ahead and put them on the maximum dose they can tolerate," Rodriguez said. A limitation of the study was that the researchers were unable to determine whether patients died of cardiovascular disease or another cause. The next step, researchers said, is to find out why some patients who should be on high-intensity statins are not. They hope doctors will take their study's results into consideration when prescribing statins. "There are a lot of guidelines and recommendations out there, so I think we also have to make the system better," Rodriguez said. "Maybe hospitals can employ a clinical reminder to doctors, a message that pops up on the doctor's screen that asks why a cardiovascular patient isn't on a high-intensity statin." The researchers also hope to follow up on longer-term data from these patient populations. "Not only do we hope to continue studying this population, but we also hope to study patients without prior cardiovascular disease but who are at high risk for it," said Rodriguez. Finally, they hope these results will help to settle the debate on which guidelines doctors should use when prescribing statins to patients. Heidenreich said, "We think this should give clinicians, physicians and nurse practitioners more comfort in following the American College of Cardiology and American Heart Association guidelines and putting people with prior cardiovascular disease on a high-intensity statin."


News Article | November 10, 2016
Site: www.eurekalert.org

A large national study has confirmed the value of high-intensity statin treatments for people with cardiovascular disease, according to researchers at the Stanford University School of Medicine. Over the duration of a year, the researchers found that patients taking high-intensity statins had an increased chance of survival over those on moderate-intensity statins. The study will be published online Nov. 9 in JAMA Cardiology. Statins, a class of drugs that lowers cholesterol levels in the blood, are commonly prescribed for preventing the acceleration of cardiovascular disease caused by the buildup of plaque in the arteries, which can lead to heart attacks and stroke. Health-care providers have long debated the benefits of prescribing high-intensity statins to their patients with cardiovascular disease. Patients, in turn, have been hesitant to take them because of equivocal messages from their doctors and internet searches of patient and doctor perspectives. "Previously, there was definitely a certain amount of fear on the patient's part because most people don't like taking medication," said Paul Heidenreich, MD, professor of cardiovascular medicine and the study's senior author. Some studies have shown an increased risk of side effects, such as diabetes or muscle damage, associated with higher-intensity statins. In 2013, the American College of Cardiology and American Heart Association jointly recommended high-intensity statin therapy for patients with atherosclerotic cardiovascular disease who were no older than 75. The ACC/AHA guidelines differed, however, from guidelines established in 2014 by the Veterans Affairs Health Care System, which recommended only moderate-intensity statins, noting the lack of conclusive evidence that higher-intensity statins are more beneficial than those of moderate intensity. In their study, Heidenreich and his team found evidence to support the ACC/AHA guidelines. They determined that high-intensity statins do in fact increase rates of survival, not only in younger and middle-aged patients with cardiovascular disease, but also in a patient population not well-studied: adults over 75. "The greatest strength of this study is that we used a very large, well-defined clinical cohort," said Fatima Rodriguez, MD, a cardiology fellow at Stanford and the study's lead author. "The results show that high-intensity statins confer a survival advantage for patients with cardiovascular disease, including older adults." The researchers studied the medical records of 509,766 patients across the country receiving care from the Veterans Affairs Health Care System. "This is a very large patient population rich in cardiovascular disease," said Rodriguez. "In addition to defining this large, national patient population, we also had access to their detailed clinical data, including comorbidities and cholesterol values." The primary purpose was to look at overall patient death rates from 2013 to 2014, the researchers said. They included patients with coronary artery disease, cerebrovascular disease and peripheral artery disease. "These are basically the three main areas affected by plaque buildup -- the heart, the brain and the large arteries of the rest of the body," Heidenreich said. Patients were taking high-intensity, moderate-intensity or low-intensity statins in many different but commonly prescribed forms, such as rosuvastatin and atorvastatin. The researchers also followed one group that wasn't taking any statins. Patients had different severities of cardiovascular disease, making some more likely to be prescribed higher-intensity statins than others. So the researchers assigned each patient a score for the propensity to receive high-intensity statins and adjusted the results of the study accordingly. The results showed a 9 percent increased chance of survival for patients taking high-intensity statins compared to those receiving moderate-intensity treatments. "We found basically the same risk reductions reviewed by the Veterans Affairs guidelines, but they didn't think the benefit was significant because the sample size was small," Heidenreich said. "We have so many more patients, we can be confident that it wasn't due to chance." The study considered data from patients over 75 -- a group little studied in clinical trials. It found that patients between the ages of 75 and 85 taking high-intensity statins had a survival-rate benefit comparable to that of younger patients: a 9 percent higher chance of survival compared to those on moderate-intensity statins. "Our results suggest that clinical trial data from heart studies for those younger than 75 could also be applied to this older population," Heidenreich said. Finally, they studied the effect of different doses within the high-intensity statin group. Patients treated with the maximum dose of statins were 10 percent more likely to survive than patients on submaximal doses. "This suggests to practitioners that instead of starting a patient on a low dose, just to go ahead and put them on the maximum dose they can tolerate," Rodriguez said. A limitation of the study was that the researchers were unable to determine whether patients died of cardiovascular disease or another cause. The next step, researchers said, is to find out why some patients who should be on high-intensity statins are not. They hope doctors will take their study's results into consideration when prescribing statins. "There are a lot of guidelines and recommendations out there, so I think we also have to make the system better," Rodriguez said. "Maybe hospitals can employ a clinical reminder to doctors, a message that pops up on the doctor's screen that asks why a cardiovascular patient isn't on a high-intensity statin." The researchers also hope to follow up on longer-term data from these patient populations. "Not only do we hope to continue studying this population, but we also hope to study patients without prior cardiovascular disease but who are at high risk for it," said Rodriguez. Finally, they hope these results will help to settle the debate on which guidelines doctors should use when prescribing statins to patients. Heidenreich said, "We think this should give clinicians, physicians and nurse practitioners more comfort in following the American College of Cardiology and American Heart Association guidelines and putting people with prior cardiovascular disease on a high-intensity statin." The work is an example of Stanford Medicine's focus on precision health, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill. Other Stanford affiliated co-authors are David Maron, MD, clinical professor of medicine and Joshua Knowles, MD, PhD, assistant professor of medicine. The Stanford University School of Medicine consistently ranks among the nation's top medical schools, integrating research, medical education, patient care and community service. For more news about the school, please visit http://med. . The medical school is part of Stanford Medicine, which includes Stanford Health Care and Lucile Packard Children's Hospital Stanford. For information about all three, please visit http://med. .


Keuken M.C.,University of Amsterdam | Hardie A.,University of San Diego | Dorn B.T.,University of San Diego | Dev S.,University of San Diego | And 5 more authors.
Brain Research | Year: 2011

Perceiving and interpreting social information richness is something that humans do automatically whenever they engage in social interactions. Numerous studies have identified neural substrates, including mirror neurons that may enable such social perception. In this study, we temporarily disrupted activity in the left inferior frontal gyrus (LIFG) using repetitive transcranial magnetic stimulation (rTMS). We investigated whether this cortical region, that is hypothesized to include mirror neurons, plays a central role in social perception. The LIFG was stimulated in the experimental condition (n = 18), the vertex was targeted in the control condition (n = 19). Disrupting LIFG, but not vertex, increased reaction times during an emotion recognition task, and eliminated the suppression of the 8-12 Hz EEG μ rhythm, postulated as an index of mirroring activity. The results of this study provide further evidence for the role of the human mirror neuron system (MNS) in social perception, and indicate that the MNS can be measured with EEG. © 2011 Elsevier B.V. All rights reserved.


Kossowsky J.,University of Basel | Wilhelm F.H.,University of Salzburg | Roth W.T.,Stanford University | Roth W.T.,Veterans Affairs Health Care System | Schneider S.,Ruhr University Bochum
Journal of Child Psychology and Psychiatry and Allied Disciplines | Year: 2012

Background: Separation anxiety disorder (SAD) is one of the most common anxiety disorders in childhood and is predictive of adult anxiety disorders, especially panic disorder. However, the disorder has seldom been studied and the attempt to distinguish SAD from other anxiety disorders with regard to psychophysiology has not been made. We expected exaggerated anxiety as well as sympathetic and respiratory reactivity in SAD during separation from the mother. Method: Participants were 49 children with a principal diagnosis of SAD, 21 clinical controls (CC) with a principal diagnosis of anxiety disorder other than SAD, and 39 healthy controls (HC) not meeting criteria for any current diagnosis. Analyses of covariance controlling for age were used to assess sympathetic and parasympathetic activation (preejection period and respiratory sinus arrhythmia) as well as cardiovascular (heart rate, mean arterial pressure, total peripheral resistance), respiratory (total breath time, minute ventilation, tidal volume, end-tidal CO 2, respiratory variability), electrodermal, and self-report (anxiety, cognitions, symptoms) variables during baseline, 4-min separation from, and reunion with the mother. Results: Children with a diagnosis of SAD were characterized by elevated self-reported anxiety responses to separation and increased sympathetic reactivity compared with CC and HC groups. The SAD group also displayed greater vagal withdrawal and higher reactivity in multiple cardiovascular, respiratory, and electrodermal measures compared with the HC group, while corresponding responses were less in the CC group and not significantly different from the other groups. Conclusions: Separation from the mother elicits greater autonomic, respiratory, and experiential responses in children with SAD. Our findings based on brief experimental separation demonstrate differential subjective and physiological manifestations of specific anxiety diagnoses, thus supporting the validity of the diagnostic category of SAD. © 2011 Association for Child and Adolescent Mental Health.


Xiong Z.,Veterans Affairs Health Care System | Thangavel R.,Veterans Affairs Health Care System | Thangavel R.,University of Iowa | Kempuraj D.,Veterans Affairs Health Care System | And 5 more authors.
Journal of Alzheimer's Disease | Year: 2014

Inflammatory responses are increasingly implicated in the pathogenesis of neurodegenerative diseases such as in Alzheimer's disease (AD). Interleukin-33 (IL-33), a member of IL-1 family, is constitutively expressed in the central nervous system and thought to be an important mediator of glial cell response to neuropathological lesions. Proinflammatory molecules are highly expressed at the vicinity of amyloid plaques (APs) and neurofibrillary tangles (NFTs), the hallmarks of AD pathology. We have investigated the expression of IL-33 and ST2 in relation to APs and NFTs in human AD and non-AD control brains by immunohistochemistry. Sections from the entorhinal cortex, where APs and NFTs appear in early stages of AD, were used for immunohistochemistry. Mouse primary astrocytes were cultured and incubated with amyloid-β1-42 (Aβ1-42), component of plaque for 72 h and analyzed for the expression of IL-33 by flow cytometry. We found strong expression of IL-33 and ST2 in the vicinity of Aβ and AT8 labelled APs and NFTs respectively, and in the glial cells in AD brains when compared to non-AD control brains. IL-33 and ST2 positive cells were also significantly increased in AD brains when compared to non-AD brains. Flow cytometric analysis revealed incubation of mouse astrocytes with Aβ1-42 increased astrocytic IL-33 expression in vitro. These results suggest that IL-33, an alamin cytokine, may induce inflammatory molecule release from the glial cells and may play an important role in the pathogenesis of AD.


Raddant A.C.,University of Iowa | Russo A.F.,University of Iowa | Russo A.F.,Veterans Affairs Health Care System
Headache | Year: 2014

Objective To examine calcitonin gene-related peptide (CGRP) gene expression under inflammatory conditions using trigeminal ganglia organ cultures as an experimental system. These cultures have increased proinflammatory signaling that may mimic neurogenic inflammation in the migraine state. Background The trigeminal nerve sends peripheral pain signals to the central nervous system during migraine. Understanding the dynamic processes that occur within the trigeminal nerve and ganglion may provide insights into events that contribute to migraine pain. A neuropeptide of particular interest is CGRP, which can be elevated and play a causal role in migraine. However, most studies have overlooked a second splice product of the Calca gene that encodes calcitonin (CT), a peptide hormone involved in calcium homeostasis. Importantly, a precursor form of CT called procalcitonin (proCT) can act as a partial agonist at the CGRP receptor and elevated proCT has recently been reported during migraine. Methods We used a trigeminal ganglion whole organ explant model, which has previously been demonstrated to induce pro-inflammatory agents in vitro. Quantitative polymerase chain reaction and immunohistochemistry were used to evaluate changes in messenger ribonucleic acid (mRNA) and protein levels of CGRP and proCT. Results Whole mouse trigeminal ganglia cultured for 24 hours showed a 10-fold increase in CT mRNA, with no change in CGRP mRNA. A similar effect was observed in ganglia from adult rats. ProCT immunoreactivity was localized in glial cells. Cutting the tissue blunted the increase in CT, suggesting that induction required the close environment of the intact ganglia. Consistent with this prediction, there were increased reactive oxygen species in the ganglia, and the elevated CT mRNA was reduced by antioxidant treatment. Surprisingly, reactive oxygen species were increased in neurons, not glia. Conclusions These results demonstrate that reactive oxygen species can activate proCT expression from the CGRP gene in trigeminal glia by a paracrine regulatory mechanism. We propose that this glial recruitment pathway may occur following cortical spreading depression and neurogenic inflammation to increase CGRP nociceptive actions in migraine. © 2014 American Headache Society.


Lembke A.,Stanford University | Humphreys K.,Stanford University | Humphreys K.,Veterans Affairs Health Care System
Journal of Groups in Addiction and Recovery | Year: 2012

Moderation Management (MM) is a mutual-help organization for problem drinkers who are not alcohol-dependent. MM members pursue a goal of moderate drinking as defined by specific guidelines for frequency and quantity of alcohol consumption. MM's program for change is based primarily on cognitive restructuring and behavioral self-control enhancement and has no inherent spiritual component. MM's definition of the "nondependent" problem drinker is based on the individual's ability to adhere to MM guidelines, which include an initial 30-day abstinence period followed by limits on daily consumption. MM's members, on average, are less alcohol-dependent and have higher social capital than individuals who participate in Alcoholics Anonymous or seek inpatient alcohol treatment. Although no longitudinal studies to date have examined the efficacy of MM, there are positive outcome data for similar cognitive and brief behavioral interventions delivered by health care professionals. Critics of MM claim the organization feeds denial among dependent drinkers and thereby delays abstinence-oriented treatment, but its defenders point out that MM may prevent some problem drinkers from progressing to a more deteriorated state such that abstinence would be necessary. Randomized trials examining whether MM is more effective than no treatment, or if it is comparable to existing evidence-based ambulatory treatments, are needed to resolve this debate. That many MM members have never sought help before suggests the organization has some public health value by widening the range of attractive options available to people with alcohol use disorders. © 2012 Copyright Taylor and Francis Group, LLC.


Patel B.N.,Duke University | Giacomini C.,Stanford University | Jeffrey R.B.,Stanford University | Willmann J.K.,Stanford University | And 2 more authors.
Cancer Imaging | Year: 2013

Extrapancreatic perineural spread in pancreatic adenocarcinoma contributes to poor outcomes, as it is known to be a major contributor to positive surgical margins and disease recurrence. However, current staging classifications have not yet taken extrapancreatic perineural spread into account. Four pathways of extrapancreatic perineural spread have been described that conveniently follow small defined arterial pathways. Small field of view three-dimensional (3D) volume-rendered multidetector computed tomography (MDCT) images allow visualization of small peripancreatic vessels and thus perineural invasion that may be associated with them. One such vessel, the posterior inferior pancreaticoduodenal artery (PIPDA), serves as a surrogate for extrapancreatic perineural spread by pancreatic adenocarcinoma arising in the uncinate process. This pictorial review presents the normal and variant anatomy of the PIPDA with 3D volume-rendered MDCT imaging, and emphasizes its role as a vascular landmark for the diagnosis of extrapancreatic perineural invasion from uncinate adenocarcinomas. Familiarity with the anatomy of PIPDA will allow accurate detection of extrapancreatic perineural spread by pancreatic adenocarcinoma involving the uncinate process, and may potentially have important staging implications as neoadjuvant therapy improves. © 2013 International Cancer Imaging Society.

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