Bruce K. Chow

Outcomes in Patients with Acute Non–Q-Wave Myocardial Infarction Randomly Assigned to an Invasive as Compared with a Conservative Management Strategy

Background Non–Q-wave myocardial infarction is usually managed according to an “invasive” strategy (i.e., one of routine coronary angiography followed by myocardial revascularization). Methods We randomly assigned 920 patients to either “invasive” management (462 patients) or “conservative” management, defined as medical therapy and noninvasive testing, with subsequent invasive management if indicated by the development of spontaneous or inducible ischemia (458 patients), within 72 hours of the onset of a non–Q-wave infarction. Death or nonfatal infarction made up the combined primary end point. Results During an average follow-up of 23 months, 152 events (80 deaths and 72 nonfatal infarctions) occurred in 138 patients who had been randomly assigned to the invasive strategy, and 139 events (59 deaths and 80 nonfatal infarctions) in 123 patients assigned to the conservative strategy (P=0.35). Patients assigned to the invasive strategy had worse clinical outcomes during the first year of follow-up. The numb...

Decreased Cancer Risk After Iron Reduction in Patients With Peripheral Arterial Disease: Results From a Randomized Trial

BACKGROUND Excess iron has been implicated in cancer risk through increased iron-catalyzed free radical-mediated oxidative stress. METHODS A multicenter randomized, controlled, single-blinded clinical trial (VA Cooperative Study #410) tested the hypothesis that reducing iron stores by phlebotomy would influence vascular outcomes in patients with peripheral arterial disease. Patients without a visceral malignancy in the last 5 years (n = 1277) were randomly assigned to control (n = 641) or iron reduction (n = 636). Occurrence of new visceral malignancy and cause-specific mortality data were collected prospectively. Cancer and mortality outcomes in the two arms were compared using intent-to-treat analysis with a Cox proportional hazards regression model. Statistical tests were two-sided. RESULTS Patients were followed up for an average of 4.5 years. Ferritin levels were similar in both groups at baseline but were lower in iron reduction patients than control patients across all 6-month visits (mean = 79.7 ng/mL, 95% confidence interval [CI] = 73.8 to 85.5 ng/mL vs 122.5 ng/mL, 95% CI = 115.5 to 129.5 ng/mL; P < .001). Risk of new visceral malignancy was lower in the iron reduction group than in the control group (38 vs 60, hazard ratio [HR] = 0.65, 95% CI = 0.43 to 0.97; P = .036), and, among patients with new cancers, those in the iron reduction group had lower cancer-specific and all-cause mortality (HR = 0.39, 95% CI = 0.21 to 0.72; P = .003; and HR = 0.49, 95% CI = 0.29 to 0.83; P = .009, respectively) than those in the control group. Mean ferritin levels across all 6-monthly visits were similar in patients in the iron reduction and control groups who developed cancer but were lower among all patients who did not develop cancer than among those who did (76.4 ng/mL, 95% CI = 71.4 to 81.4 ng/mL, vs 127.1 ng/mL, 95% CI = 71.2 to 183.0 ng/mL; P = .017). CONCLUSIONS Iron reduction was associated with lower cancer risk and mortality. Further studies are needed to define the role of body iron in cancer risk.

Integrating Tobacco Cessation Into Mental Health Care for Posttraumatic Stress Disorder: A Randomized Controlled Trial

CONTEXT Most smokers with mental illness do not receive tobacco cessation treatment. OBJECTIVE To determine whether integrating smoking cessation treatment into mental health care for veterans with posttraumatic stress disorder (PTSD) improves long-term smoking abstinence rates. DESIGN, SETTING, AND PATIENTS A randomized controlled trial of 943 smokers with military-related PTSD who were recruited from outpatient PTSD clinics at 10 Veterans Affairs medical centers and followed up for 18 to 48 months between November 2004 and July 2009. INTERVENTION Smoking cessation treatment integrated within mental health care for PTSD delivered by mental health clinicians (integrated care [IC]) vs referral to Veterans Affairs smoking cessation clinics (SCC). Patients received smoking cessation treatment within 3 months of study enrollment. MAIN OUTCOME MEASURES Smoking outcomes included 12-month bioverified prolonged abstinence (primary outcome) and 7- and 30-day point prevalence abstinence assessed at 3-month intervals. Amount of smoking cessation medications and counseling sessions delivered were tested as mediators of outcome. Posttraumatic stress disorder and depression were repeatedly assessed using the PTSD Checklist and Patient Health Questionnaire 9, respectively, to determine if IC participation or quitting smoking worsened psychiatric status. RESULTS Integrated care was better than SCC on prolonged abstinence (8.9% vs 4.5%; adjusted odds ratio, 2.26; 95% confidence interval [CI], 1.30-3.91; P = .004). Differences between IC vs SCC were largest at 6 months for 7-day point prevalence abstinence (78/472 [16.5%] vs 34/471 [7.2%], P < .001) and remained significant at 18 months (86/472 [18.2%] vs 51/471 [10.8%], P < .001). Number of counseling sessions received and days of cessation medication used explained 39.1% of the treatment effect. Between baseline and 18 months, psychiatric status did not differ between treatment conditions. Posttraumatic stress disorder symptoms for quitters and nonquitters improved. Nonquitters worsened slightly on the Patient Health Questionnaire 9 relative to quitters (differences ranged between 0.4 and 2.1, P = .03), whose scores did not change over time. CONCLUSION Among smokers with military-related PTSD, integrating smoking cessation treatment into mental health care compared with referral to specialized cessation treatment resulted in greater prolonged abstinence. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00118534.

Sexual Function Outcomes in Women Treated for Posttraumatic Stress Disorder

BACKGROUND This study examined dysfunctional sexual behavior and sexual concerns in women treated for posttraumatic stress disorder (PTSD). There were three objectives: to characterize the relationship between symptoms of PTSD and sexual outcomes, to examine the effect of treatment on sexual outcomes, and to examine the relationship between change in PTSD and change in sexual outcomes. METHODS Female veterans and active duty personnel with PTSD (n = 242), 93% of whom had experienced sexual trauma, were randomly assigned to receive 10 weekly sessions of either Prolonged Exposure or Present-Centered Therapy. PTSD and sexual outcomes were assessed before and after treatment and then 3 and 6 months later. RESULTS At baseline, the reexperiencing, numbing, and hyperarousal symptom clusters were related to one or both sexual outcomes. Although prior analyses had shown that Prolonged Exposure resulted in better PTSD outcomes, there were no differences between treatments for either dysfunctional sexual behavior or sexual concerns. However, loss of PTSD diagnosis was associated with improvements in sexual concerns. CONCLUSIONS The findings suggest that clinically meaningful improvements in PTSD are necessary in order to reduce sexual problems in traumatized women.

PTSD and depression as predictors of physical health-related quality of life in tobacco-dependent veterans.

OBJECTIVE Smoking, depression and PTSD are related to poor physical health outcomes and health-related quality of life (HRQoL). Previous studies examining the effects of quitting smoking on HRQoL have been mixed. This study aimed to examine the effects of PTSD, depressive symptoms and smoking cessation on HRQoL in a sample receiving treatment for PTSD. METHOD This study utilized archival interview and self-report data from a clinical trial (VA Cooperative Study 519) that recruited tobacco dependent veterans with chronic PTSD (N=943). RESULTS Analyses were conducted using hierarchical linear modeling and indicated that PTSD and depressive symptoms differentially affected the various physical health status domains. Additionally, quitting smoking was associated with better self-perceived health status and social functioning. CONCLUSION Our findings further explain the interrelationships of PTSD, depression, and smoking in the prediction of physical HRQoL and advocate the importance of integrated care.

The Statin–Iron Nexus: Anti-Inflammatory Intervention for Arterial Disease Prevention

OBJECTIVES We postulated the existence of a statin-iron nexus by which statins improve cardiovascular disease outcomes at least partially by countering proinflammatory effects of excess iron stores. METHODS Using data from a clinical trial of iron (ferritin) reduction in advanced peripheral arterial disease, the Iron and Atherosclerosis Study, we compared effects of ferritin levels versus high-density lipoprotein to low-density lipoprotein ratios (both were randomization variables) on clinical outcomes in participants receiving and not receiving statins. RESULTS Statins increased high-density lipoprotein to low-density lipoprotein ratios and reduced ferritin levels by noninteracting mechanisms. Improved clinical outcomes were associated with lower ferritin levels but not with improved lipid status. CONCLUSIONS There are commonalities between the clinical benefits of statins and the maintenance of physiologic iron levels. Iron reduction may be a safe and low-cost alternative to statins.

Smoking intensity and severity of specific symptom clusters in posttraumatic stress disorder

Smoking prevalence among patients with posttraumatic stress disorder (PTSD) is over 40%. Baseline data from the VA Cooperative Studies Program trial of integrated versus usual care for smoking cessation in veterans with PTSD (N = 863) were used in multivariate analyses of PTSD and depression severity, and 4 measures of smoking intensity: cigarettes per day (CPD), Fagerström Test for Nicotine Dependence (FTND), time to first cigarette, and expired carbon monoxide. Multivariate regression analysis showed the following significant associations: CPD with race (B = -7.16), age (B = 0.11), and emotional numbing (B =0 .16); FTND with race (B = -0.94), education (B = -0.34), emotional numbing (B = 0.04), significant distress (B = -0.12), and PHQ-9 (B = 0.04); time to first cigarette with education (B = 0.41), emotional numbing (B = -0.03), significant distress (B = 0.09), and PHQ-9 (B = -0.03); and expired carbon monoxide with race (B = -9.40). Findings suggest that among veterans with PTSD, White race and emotional numbing were most consistently related to increased smoking intensity and had more explanatory power than total PTSD symptom score. Results suggest specific PTSD symptom clusters are important to understanding smoking behavior in patients with PTSD.

Smoking Outcome Expectancies in Military Veteran Smokers With Posttraumatic Stress Disorder

INTRODUCTION Smoking outcome expectancies were investigated in treatment-seeking military Veteran smokers with posttraumatic stress disorder (PTSD). The investigation of smoking outcome expectancies may enhance our understanding of the relationship between PTSD and cigarette smoking. METHODS Participants were 943 military Veterans with a diagnosis of PTSD who were current smokers enrolled in a randomized multisite effectiveness trial to test whether the integration of smoking cessation treatment into mental health care (integrated care) improves prolonged abstinence rates compared with referral to specialized smoking cessation clinics (usual care). Using confirmatory factor analysis (CFA), we evaluated the conceptual model of smoking outcome expectancies measured on the Smoking Consequences Questionnaire-Adult (SCQ-A) version. The Kraemer method of mediation analysis was used to investigate the role of smoking outcome expectancies in mediating relationships between PTSD symptoms and smoking behavior, tobacco dependence, and abstinence self-efficacy. RESULTS The CFA supported the 10-factor structure of the SCQ-A in smokers with PTSD. Relationships between measures of PTSD symptoms and tobacco dependence were mediated by the smoking outcome expectancy regarding negative affect reduction. This same smoking outcome expectancy mediated relationships between PTSD symptoms and smoking abstinence self-efficacy. CONCLUSIONS The findings support the use of the SCQ-A as a valid measure of smoking outcome expectancies in military Veteran smokers with PTSD. Moreover, they suggest that smoking outcome expectancies may play an important role in explaining the relationship between PTSD and cigarette smoking.

The influence of posttraumatic stress disorder numbing and hyperarousal symptom clusters in the prediction of physical health status in veterans with chronic tobacco dependence and posttraumatic stress disorder.

Abstract Smoking and PTSD are predictors of poor physical health status. This study examined the unique contribution of PTSD symptoms in the prediction of the SF-36 physical health status subscales accounting for cigarette smoking, chronic medical conditions, alcohol and drug use disorders, and depression. This study examined baseline interview and self-report data from a national tobacco cessation randomized, controlled trial (Veterans Affairs Cooperative Study 519) that enrolled tobacco-dependent veterans with chronic PTSD (N = 943). A series of blockwise multiple regression analyses indicated that PTSD numbing and hyperarousal symptom clusters explained a significant proportion of the variance across all physical health domains except for the Physical Functioning subscale, which measures impairments in specific physical activities. Our findings further explain the impact of PTSD on health status by exploring the way PTSD symptom clusters predict self-perceptions of health, role limitations, pain, and vitality.

Design of VA Cooperative Study #591: CERV-PTSD, Comparative Effectiveness Research in Veterans with PTSD

CERV-PTSD is a randomized controlled trial of two of the most effective treatments for PTSD, Prolonged Exposure (PE) and Cognitive Processing Therapy (CPT). Despite solid evidence that both treatments are effective, there is limited evidence about their effectiveness relative to one another. The primary objective is to compare the effectiveness of PE and CPT for reducing PTSD symptom severity in a healthcare system that offers both treatments. The secondary objective is to compare the effectiveness of PE and CPT for reducing the severity of comorbid mental health problems and service utilization as well as improving functioning and quality of life. The tertiary objective is to examine whether discrepancy between patient preferences and treatment assignment reduces the effectiveness of each treatment. Exploratory analyses will examine whether demographic and clinical characteristics predict differential response to PE and CPT. The study is designed to randomize 900 male and female veterans with PTSD due to any traumatic military event to receive PE or CPT. The standard dose of treatment is 12 weekly sessions but veterans who improve more rapidly may finish in fewer sessions and veterans who improve more slowly may have additional sessions. The primary outcome is improvement in PTSD symptoms, measured during and after treatment and then 3 and 6 months later. As a large multi-site trial with men and women, CERV-PTSD is designed to advance the delivery of care for PTSD by providing conclusive information about whether one treatment is better than the other, overall, and for different types of patients.