Comparison of Prolonged Exposure vs Cognitive Processing Therapy for Treatment of Posttraumatic Stress Disorder Among US Veterans: A Randomized Clinical Trial.

Importance: Posttraumatic stress disorder (PTSD) is a prevalent and serious mental health problem. Although there are effective psychotherapies for PTSD, there is little information about their comparative effectiveness. Objective: To compare the effectiveness of prolonged exposure (PE) vs cognitive processing therapy (CPT) for treating PTSD in veterans. Design, Setting, and Participants: This randomized clinical trial assessed the comparative effectiveness of PE vs CPT among veterans with military-related PTSD recruited from outpatient mental health clinics at 17 Department of Veterans Affairs medical centers across the US from October 31, 2014, to February 1, 2018, with follow-up through February 1, 2019. The primary outcome was assessed using centralized masking. Tested hypotheses were prespecified before trial initiation. Data were analyzed from October 5, 2020, to May 5, 2021. Interventions: Participants were randomized to 1 of 2 individual cognitive-behavioral therapies, PE or CPT, delivered according to a flexible protocol of 10 to 14 sessions. Main Outcomes and Measures: The primary outcome was change in PTSD symptom severity on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) from before treatment to the mean after treatment across posttreatment and 3- and 6-month follow-ups. Secondary outcomes included other symptoms, functioning, and quality of life. Results: Analyses were based on all 916 randomized participants (730 [79.7%] men and 186 [20.3%] women; mean [range] age 45.2 [21-80] years), with 455 participants randomized to PE (mean CAPS-5 score at baseline, 39.9 [95% CI, 39.1-40.7] points) and 461 participants randomized to CPT (mean CAPS-5 score at baseline, 40.3 [95% CI, 39.5-41.1] points). PTSD severity on the CAPS-5 improved substantially in both PE (standardized mean difference [SMD], 0.99 [95% CI, 0.89-1.08]) and CPT (SMD, 0.71 [95% CI, 0.61-0.80]) groups from before to after treatment. Mean improvement was greater in PE than CPT (least square mean, 2.42 [95% CI, 0.53-4.31]; P = .01), but the difference was not clinically significant (SMD, 0.17). Results for self-reported PTSD symptoms were comparable with CAPS-5 findings. The PE group had higher odds of response (odds ratio [OR], 1.32 [95% CI, 1.00-1.65]; P < .001), loss of diagnosis (OR, 1.43 [95% CI, 1.12-1.74]; P < .001), and remission (OR, 1.62 [95% CI, 1.24-2.00]; P < .001) compared with the CPT group. Groups did not differ on other outcomes. Treatment dropout was higher in PE (254 participants [55.8%]) than in CPT (215 participants [46.6%]; P < .01). Three participants in the PE group and 1 participant in the CPT group were withdrawn from treatment, and 3 participants in each treatment dropped out owing to serious adverse events. Conclusions and Relevance: This randomized clinical trial found that although PE was statistically more effective than CPT, the difference was not clinically significant, and improvements in PTSD were meaningful in both treatment groups. These findings highlight the importance of shared decision-making to help patients understand the evidence and select their preferred treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT01928732.

Design of the National Adaptive Trial for PTSD-related Insomnia (NAP Study), VA Cooperative Study Program (CSP) #2016.

There are currently no validated pharmacotherapies for posttraumatic stress disorder (PTSD)-related insomnia. The purpose of the National Adaptive Trial for PTSD-Related Insomnia (NAP Study) is to efficiently compare to placebo the effects of three insomnia medications with different mechanisms of action that are already prescribed widely to veterans diagnosed with PTSD within U.S. Department of Veterans Affairs (VA) Medical Centers. This study plans to enroll 1224 patients from 34 VA Medical Centers into a 12- week prospective, randomized placebo-controlled clinical trial comparing trazodone, eszopiclone, and gabapentin. The primary outcome measure is insomnia, assessed with the Insomnia Severity Index. A novel aspect of this study is its adaptive design. At the recruitment midpoint, an interim analysis will be conducted to inform a decision to close recruitment to any "futile" arms (i.e. arms where further recruitment is very unlikely to yield a significant result) while maintaining the overall study recruitment target. This step could result in the enrichment of the remaining study arms, enhancing statistical power for the remaining comparisons to placebo. This study will also explore clinical, actigraphic, and biochemical predictors of treatment response that may guide future biomarker development. Lastly, due to the COVID-19 pandemic, this study will allow the consenting process and follow-up visits to be conducted via video or phone contact if in-person meetings are not possible. Overall, this study aims to identify at least one effective pharmacotherapy for PTSD-related insomnia, and, perhaps, to generate definitive negative data to reduce the use of ineffective insomnia medications. NATIONAL CLINICAL TRIAL (NCT) IDENTIFIED NUMBER: NCT03668041.

Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans.

BACKGROUND: In randomized trials, prazosin, an α1-adrenoreceptor antagonist, has been effective in alleviating nightmares associated with post-traumatic stress disorder (PTSD) in military veterans. METHODS: We recruited veterans from 13 Department of Veterans Affairs medical centers who had chronic PTSD and reported frequent nightmares. Participants were randomly assigned to receive prazosin or placebo for 26 weeks; the drug or placebo was administered in escalating divided doses over the course of 5 weeks to a daily maximum of 20 mg in men and 12 mg in women. After week 10, participants continued to receive prazosin or placebo in a double-blind fashion for an additional 16 weeks. The three primary outcome measures were the change in score from baseline to 10 weeks on the Clinician-Administered PTSD Scale (CAPS) item B2 ("recurrent distressing dreams"; scores range from 0 to 8, with higher scores indicating more frequent and more distressing dreams); the change in score from baseline to 10 weeks on the Pittsburgh Sleep Quality Index (PSQI; scores range from 0 to 21, with higher scores indicating worse sleep quality); and the Clinical Global Impression of Change (CGIC) score at 10 weeks (scores range from 1 to 7, with lower scores indicating greater improvement and a score of 4 indicating no change). RESULTS: A total of 304 participants underwent randomization; 152 were assigned to prazosin, and 152 to placebo. At 10 weeks, there were no significant differences between the prazosin group and the placebo group in the mean change from baseline in the CAPS item B2 score (between-group difference, 0.2; 95% confidence interval [CI], -0.3 to 0.8; P=0.38), in the mean change in PSQI score (between-group difference, 0.1; 95% CI, -0.9 to 1.1; P=0.80), or in the CGIC score (between-group difference, 0; 95% CI, -0.3 to 0.3; P=0.96). There were no significant differences in these measures at 26 weeks (a secondary outcome) or in other secondary outcomes. At 10 weeks, the mean difference between the prazosin group and the placebo group in the change from baseline in supine systolic blood pressure was a decrease of 6.7 mm Hg. The adverse event of new or worsening suicidal ideation occurred in 8% of the participants assigned to prazosin versus 15% of those assigned to placebo. CONCLUSIONS: In this trial involving military veterans who had chronic PTSD, prazosin did not alleviate distressing dreams or improve sleep quality. (Funded by the Department of Veterans Affairs Cooperative Studies Program; PACT ClinicalTrials.gov number, NCT00532493 .).

Iron reduction response and demographic differences between diabetics and non-diabetics with cardiovascular disease entered into a controlled clinical trial.

Iron-catalyzed oxygen-free radical-induced oxidative stress mediates the pathogenesis of diabetes and cardiovascular disease (CVD). Diabetics (n = 473) and non-diabetics (n = 804) with CVD entered into a randomized trial of iron (ferritin) reduction by calibrated phlebotomy (, Identifier NCT00032357) had comparable iron measures at entry but diabetics had a greater burden of CVD and comorbidities, lower hemoglobin and hematocrit levels, and higher glucose levels than non-diabetics. Entry iron measures were lower in diabetics on hypoglycemic therapy compared to previously untreated diabetics. Diabetics and non-diabetics had comparable iron measures during follow-up. The Loess analysis of paired ferritin and hemoglobin, and paired ferritin and glucose levels in diabetics randomized to phlebotomy showed higher ferritin levels associated with lower hemoglobin and higher glucose levels. Progressive ferritin reduction in diabetics correlated with increasing hemoglobin and decreasing glucose levels, neither of which reached levels observed in non-diabetics. We postulate that phlebotomy-triggered autophagy (ferritinophagy) released redox-active iron sequestered intracellularly, worsening anemia and glucose utilization that corrected partially with ferritin reduction. Intracellular redox-active iron levels contributory to disease, not reflected in peripheral iron measures, may persist because of glycation of iron transport proteins in diabetes. These findings suggest novel strategies for disease prevention and improving outcomes in diabetes and CVD.

Ferritin and Percent Transferrin Saturation Levels Predict Type 2 Diabetes Risk and Cardiovascular Disease Outcomes.

INTRODUCTION: Type 2 diabetes (T2D) and cardiovascular disease (CVD) risk associate with ferritin and percent transferrin saturation (%TS) levels. However, increased risk has been observed at levels considered within the "normal range" for these markers. OBJECTIVE: To define normative ferritin and %TS levels associated with T2D and CVD risk. METHODS: Six-monthly ferritin, %TS and hemoglobin levels from 1,277 iron reduction clinical trial participants with CVD (peripheral arterial disease, 37% diabetic) permitted pair-wise analysis using Loess Locally Weighted Smoothing plots. Curves showed continuous quantitative ferritin, hemoglobin (reflecting physiologic iron requirements), and %TS (reflecting iron transport and sequestration) levels over a wide range of values. Inflection points in the curves were compared to ferritin and %TS levels indicating increased T2D and CVD risk in epidemiologic and intervention studies. RESULTS: Increasing ferritin up to about 80 ng/mL and %TS up to about 25% TS corresponded to increasing hemoglobin levels, and minimal T2D and CVD risk. Displaced Loess trajectories reflected lower hemoglobin levels in diabetics compared to non-diabetics. Ferritin levels up to about 100 ng/mL paralleled proportionately increasing %TS levels up to about 55%TS corresponding to further limitation of T2D and CVD risk. Ferritin levels over 100 ng/mL did not associate with hemoglobin levels and coincided with increased T2D and CVD risk. CONCLUSIONS: Recognition of modified normal ranges for ferritin from about 15 ng/mL up to about 80- 100 ng/mL and %TS from about 15% up to about 25-55% may improve the value of iron biomarkers to assess and possibly lower T2D and CVD risk.

Racial Health Disparities, and Variant Red Cell and Iron Homeostasis.

Oxidative stress from excess iron may contribute to racial health disparities. Previously we reported improved clinical outcomes with lower ferritin and higher percent transferrin saturation (%TS) levels in White but not Black participants with peripheral arterial disease entered to a clinical trial. This report demonstrates racially variant interactions between hemoglobin, ferritin, and %TS levels. Lower hemoglobin and %TS levels, and higher ferritin levels were documented in Black compared with White participants within cardiovascular disease risk categories. Ferritin levels near 80 ng/mL related to higher hemoglobin levels in White but not Black participants. Higher %TS levels with ferritin levels above 80 ng/mL in White participants were blunted in Black participants. Ferritin/%TS ratios were significantly higher in Black than White participants. Iron incorporation into hemoglobin and scavenging by transferrin may buffer iron toxicity more effectively in White than in Black individuals. Metabolic vulnerability to iron excess may explain, in part, racial health disparities.

Cost-Effectiveness of Integrating Tobacco Cessation Into Post-Traumatic Stress Disorder Treatment.

INTRODUCTION: We examined the cost-effectiveness of smoking cessation integrated with treatment for post-traumatic stress disorder (PTSD). METHODS: Smoking veterans receiving care for PTSD (N = 943) were randomized to care integrated with smoking cessation versus referral to a smoking cessation clinic. Smoking cessation services, health care cost and utilization, quality of life, and biochemically-verified abstinence from cigarettes were assessed over 18-months of follow-up. Clinical outcomes were combined with literature on changes in smoking status and the effect of smoking on health care cost, mortality, and quality of life in a Markov model of cost-effectiveness over a lifetime horizon. We discounted cost and outcomes at 3% per year and report costs in 2010 US dollars. RESULTS: The mean of smoking cessation services cost was $1286 in those randomized to integrated care and $551 in those receiving standard care (P < .001). There were no significant differences in the cost of mental health services or other care. After 12 months, prolonged biochemically verified abstinence was observed in 8.9% of those randomized to integrated care and 4.5% of those randomized to standard care (P = .004). The model projected that Integrated Care added $836 in lifetime cost and generated 0.0259 quality adjusted life years (QALYs), an incremental cost-effectiveness ratio of $32 257 per QALY. It was 86.0% likely to be cost-effective compared to a threshold of $100 000/QALY. CONCLUSIONS: Smoking cessation integrated with treatment for PTSD was cost-effective, within a broad confidence region, but less cost-effective than most other smoking cessation programs reported in the literature.

Racial differences in iron measures and outcomes observed during an iron reduction trial in peripheral arterial disease.

Elevated body iron (ferritin) levels may contribute to adverse health outcomes. Racial differences in iron measures and clinical outcomes were observed during an iron reduction trial in peripheral arterial disease. At entry, Black compared with White participants had higher ferritin and lower red cell measures, as well as differing ferritin and percent transferrin saturation (%TS) responses, and HDL/LDL ratios associated with statin use. Lower hematocrit levels during follow-up resulted in fewer phlebotomies, less iron unloading (ferritin reduction, p=.035) and 32% less iron removed in Black compared with White participants randomized to iron reduction. Improved primary (all-cause mortality) and secondary (death plus non-fatal myocardial infarction and stroke) outcomes among White participants correlated with lower ferritin levels (p=.005 and p=.053, respectively) and higher %TS levels (p<.001 and p=.001 respectively), associations not observed in Black participants. Variant iron homeostasis contributory to racial health disparities warrants personalized intervention strategies and race-specific clinical trial design.

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.

Reduction of iron stores and clinical outcomes in peripheral arterial disease: outcome comparisons in smokers and non-smokers.

A prospective randomized trial suggested that iron (ferritin) reduction improved outcomes in smokers. The present study reanalyzed the trial results in smokers compared with non-smokers. Randomization of 1262 men with peripheral arterial disease (540 smokers and 722 non-smokers) to iron reduction (phlebotomy) or control groups permitted analysis of the effects of iron reduction and smoking on primary (all-cause mortality) and secondary (death plus non-fatal myocardial infarction or stroke) endpoints. Iron reduction resulted in significant improvement in the primary (hazard ratio [HR] 0.661, 95% confidence interval [CI] 0.45, 0.97; P = 0.036) and secondary (HR 0.64, 95% CI 0.46, 0.88; P = 0.006) endpoints compared with controls in smokers but not in non-smokers. Smokers required removal of a greater volume of blood to attain targeted ferritin reduction as compared with non-smokers (P = 0.003) and also exhibited differing characteristics from non-smokers, including significantly less statin use. Phlebotomy-related outcomes favored smokers over non-smokers. Biological linkages responsible for this unique effect offer promising lines for future iron reduction studies (ClinicalTrial.Gov Identifier: NCT00032357).

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.

Survey of providers' attitudes toward integrating smoking cessation treatment into posttraumatic stress disorder care.

A survey was administered anonymously to 45 mental health providers who delivered smoking cessation treatment integrated into posttraumatic stress disorder care (integrated care) as part of a multisite clinical trial. Survey items assessed key factors associated with successful implementation of research-based practices from the perspective of treating providers. Factors assessed included prior experiences with cessation treatment, compatibility of integrated care with current practices, feasibility of adopting integrated care into regular practice, and adequacy of training. More than half of respondents reported that integrated care delivery was feasible, and they would be considerably or extremely likely to continue delivery in routine practice. Positive prestudy beliefs and more experience delivering cessation care were associated with stronger endorsement of delivering integrated care after the study. The most frequently cited obstacle to delivering integrated care involved time limitations. Future efforts should focus on developing treatment adaptations that address provider-identified barriers and identifying clinic- and administrative-level supports that facilitate delivery of integrated care and assist providers who incorporate integrated care into clinical practice.

Longitudinal analysis of the relationship between PTSD symptom clusters, cigarette use, and physical health-related quality of life.

PURPOSE: Posttraumatic stress disorder (PTSD) symptoms, particularly numbing and hyperarousal symptoms, are related to poor physical health-related quality of life (HRQoL). Tobacco dependence is also associated with poor HRQoL, and individuals with PTSD may smoke at higher rates than the general population. Our study aimed to examine the impact of quitting smoking and changes in PTSD symptoms over time on changes in physical HRQoL. METHODS: The study used archival data from enrollees (N = 943) in a smoking cessation clinical trial for veterans with PTSD (VA Cooperative study #519). RESULTS: Two of the physical HRQoL domains were sensitive to changes in PTSD symptoms over time: General Health and Vitality. CONCLUSIONS: Our findings suggest that particular physical HRQoL domains may be subject to improvement if PTSD symptoms decrease over time.

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.

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.

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.

Effect of controlled reduction of body iron stores on clinical outcomes in peripheral arterial disease.

BACKGROUND: Published results from a controlled clinical trial in patients with peripheral arterial disease found improved outcomes with iron (ferritin) reduction among middle-aged subjects but not the entire cohort. The mechanism of the age-specific effect was explored. METHODS: Randomization to iron reduction (phlebotomy, n = 636) or control (n = 641) stratified by prognostic variables permitted analysis of effects of age and ferritin on primary (all-cause mortality) and secondary (death, nonfatal myocardial infarction, and stroke) outcomes. RESULTS: Iron reduction improved outcomes in youngest age quartile patients (primary outcome hazard ratio [HR] 0.44, 95% CI 0.21-0.92, P = .028; secondary outcome HR 0.34, 95% CI 0.19-0.61, P < .001). Mean follow-up ferritin levels (MFFL) declined with increasing entry age in controls. Older age (P = .035) and higher ferritin (P < .001) at entry predicted poorer compliance with phlebotomy and rising MFFL in iron-reduction patients. Intervention produced greater ferritin reduction in younger patients. Improved outcomes with lower MFFL were found in iron-reduction patients (primary outcome HR 1.11, 95% CI 1.01-1.23, P = .028; secondary outcome HR 1.10, 95% CI 1.0-1.20, P = .044) and the entire cohort (primary outcome HR 1.11, 95% CI 1.01-1.23, P = .037). Improved outcomes occurred with MFFL below versus above the median of the entire cohort means (primary outcome HR 1.48, 95% CI 1.14-1.92, P = .003; secondary outcome HR 1.22, 95% CI 0.99-1.50, P = .067). CONCLUSIONS: Lower iron burden predicted improved outcomes overall and was enhanced by phlebotomy. Controlling iron burden may improve survival and prevent or delay nonfatal myocardial infarction and stroke.

Médicos residentes podem realizar com segurança e eficiência técnicas de Milligan-Morgan, Ferguson e grampeadores no tratamento cirúrgico das hemorróidas? / Can residents safely and efficiently perform Milligan-Morgan, Ferguson and stapled hemorrhoidopexy?

RACIONAL: A cirurgia para hemorróidas sintomáticas é necessária em quase 10 por cento dos pacientes. Embora, a literatura sobre o tratamento cirúrgico da doença hemorroidária seja muito grande, os dados relativos à hemorroidectomia ou hemorroidopexia realizadas por residentes de treinamento é limitado. OBJETIVO: Analisar os resultados destes procedimentos em uma instituição de ensino. MÉTODOS: Foram analisados retrospectivamente os dados de todos os pacientes que se submeteram ao tratamento cirúrgico para hemorróidas entre1995 e 2007 em uma única instituição. Residentes supervisionados realizaram todos os procedimentos. As técnicas foram comparadas com base no tempo operatório, permanência hospitalar, morbidade e eficácia a longo prazo. RESULTADOS: Trezentos e trinta e três pacientes foram incluídos no estudo, 182 homens (54,6 por cento), com idade média de 45,3 anos (± 12,02). Hemorróidas de terceiro grau foram a principal indicação (81,7 por cento). Milligan-Morgan foi o procedimento mais comumente realizado (57 por cento), seguido por Ferguson e hemorroidopexia grampeada. A média de tempo operatório foi significativamente menor no grupo hemorroidopexia grampeada quando comparado com os procedimentos abertos e fechados: 49,4 ± 29,3 min vs 61,1 ± 26,5 e 67,1 ± 28,3, respectivamente (p=0,0034). Não houve diferença estatisticamente significativa entre os grupos quanto às complicações pós-operatórias ou à taxa de reoperação. O tempo de internação foi significativamente maior no grupo Milligan-Morgan quando comparado com Ferguson e grampeamento (1,41 ± 0,86 dias vs 1,19 ± 0,43 vs 1,16 ± 0,37, respectivamente). Recorrência sintomática, taxas de reoperação e o uso de ligadura elástica foram semelhantes entre os grupos. CONCLUSÃO: Os residentes sob supervisão pode executar Milligan-Morgan, Ferguson e grampeamento hemorroidário com baixa incidência de complicações e bons resultados a longo prazo. O grampeamento foi associado com menor tempo operatório, enquanto Milligan-Morgan foi correlacionada com maior tempo de hospitalização.

BACKGROUND: Surgery for symptomatic hemorrhoids is needed in almost 10 percent of the patients. Although, literature about the surgical management of hemorrhoidal disease is vast, data concerning hemorrhoidectomy or hemorrhoidopexy performed by training residents is limited. AIM: To analyze the results of these procedures in a teaching institution. METHODS: Data from all patients who underwent surgical treatment for hemorrhoids from 1995 to 2007 in a single institution were retrospectively analyzed. Residents supervised by assisting doctors performed all procedures. Techniques were compared based on operative time, hospital stay, morbidity, and long-term efficacy. RESULTS: Three hundred thirty three patients were included in the study, 182 males (54.6 percent), with a mean age of 45.3 years (± 12.02). Third degree hemorrhoids were the main indication (81.7 percent). Milligan-Morgan was the most commonly performed procedure (57 percent), followed by Ferguson and stapled hemorrhoidopexy. Mean operative time was significantly lower in the stapled hemorrhoidopexy group when compared to the open and closed procedures: 49,4 ± 29.3 min vs. 61.1 ± 26.5 and 67.1 ± 28.3, respectively (p=0.0034). There was no statistically significant difference among the groups regarding postoperative complications or reoperation rate. Length of stay was significantly higher in the Milligan-Morgan group when compared to Ferguson and stapled hemorrhoidopexy (1.41 ± 0.86 days vs. 1.19 ± 0.43 vs. 1.16 ± 0.37 respectively). Symptomatic recurrence, reoperation rates and band ligation usage were similar among groups. CONCLUSION: Residents under supervision can perform Milligan-Morgan, Ferguson and stapled hemorrhoidopexy with low incidence of complications and good long-term results. Stapled hemorrhoidopexy technique was associated with a shorter operative time, while Milligan-Morgan correlated with a longer length of stay.