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Physical assaults on mental health care workers by aggressive patients were the leading cause of occupational injuries to staff working in a community psychiatric hospital. More than dollar 1 million was estimated to be lost in 1 year because of these occupational injuries. This problem was assessed by examining the organizational factors related to safety at the hospital. The cross sectional survey design measured the perceptions of mental health care workers about the commitment of management to safety (i.e., safety climate). Overall, results indicated the subscale for safety climate was high (3.77 +/- .66 [mean +/- SD] on a 5 scale), given the magnitude of recalled incidents and injuries involving patients against staff. Safety climate was associated with three variables that included administrative controls, occupational stress, and job task demands. Results of the study were useful in determining specific changes for improving safety. The study findings demonstrated the practicality and feasibility of in-house assessments to diagnose areas that require attention, support, and improvement. [ABSTRACT FROM AUTHOR]

Current approaches in chemical hazard assessment face significant challenges because they rely on live animal testing, which is time-consuming, expensive, and ethically questionable. These concerns serve as an impetus to develop new approach methodologies (NAMs) that do not rely on live animal tests. This study explored a molecular benchmark dose (BMD) approach using a 7-day embryo-larval fathead minnow (FHM) assay to derive transcriptomic points-of-departure (tPODs) to predict apical BMDs of fluoxetine (FLX), a highly prescribed and potent selective serotonin reuptake inhibitor frequently detected in surface waters. Fertilized FHM embryos were exposed to graded concentrations of FLX (confirmed at < LOD, 0.19, 0.74, 3.38, 10.2, 47.5 μg/L) for 32 days. Subsets of fish were subjected to omics and locomotor analyses at 7 days post-fertilization (dpf) and to histological and biometric measurements at 32 dpf. Enrichment analyses of transcriptomics and proteomics data revealed significant perturbations in gene sets associated with serotonergic and axonal functions. BMD analysis resulted in tPOD values of 0.56 μg/L (median of the 20 most sensitive gene-level BMDs), 5.0 μg/L (tenth percentile of all gene-level BMDs), 7.51 μg/L (mode of the first peak of all gene-level BMDs), and 5.66 μg/L (pathway-level BMD). These tPODs were protective of locomotor and reduced body weight effects (LOEC of 10.2 μg/L) observed in this study and were reflective of chronic apical BMDs of FLX reported in the literature. Furthermore, the distribution of gene-level BMDs followed a bimodal pattern, revealing disruption of sensitive neurotoxic pathways at low concentrations and metabolic pathway perturbations at higher concentrations. This is one of the first studies to derive protective tPODs for FLX using a short-term embryo assay at a life stage not considered to be a live animal under current legislations., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: There have been no prior investigations of the cost effectiveness of transfusion strategies for trauma resuscitation. The Pragmatic, Randomized, Optimal Platelet and Plasma Ratios (PROPPR) study was a Phase III multisite, randomized trial in 680 subjects comparing the efficacy of 1:1:1 transfusion ratios of plasma and platelets to red blood cells with the 1:1:2 ratio. We hypothesized that 1:1:1 transfusion results in an acceptable incremental cost-effectiveness ratio, when estimated using patients' age-specific life expectancy and cost of care during the 30-day PROPPR trial period., Study Design and Methods: International Classification of Diseases, Ninth Revision codes were prospectively collected, and subjects were matched 1:2 to subjects in the Healthcare Utilization Program State Inpatient Data to estimate cost weights. We used a decision tree analysis, combined with standard costs and estimated years of expected survival to determine the cost effectiveness of the two treatments., Results: The 1:1:1 group had higher overall costs for the blood products but were more likely to achieve hemostasis and decreased hemorrhagic death by 24 hours (p = 0.006). For every 100 patients treated in the 1:1:1 group, eight more achieved hemostasis than in the 1:1:2 group. At 30 days, the total hospital cost per 100 patients was $5.6 million in the 1:1:1 group compared with $5.0 million in the 1:1:2 group. For each 100 patients, the 1:1:1 group had 218.5 more years of life expectancy. This was at a cost of $2994 per year gained., Conclusion: The 1:1:1 transfusion ratio in severely injured hemorrhaging trauma patients is a very cost-effective strategy for increasing hemostasis and decreasing trauma deaths., (© 2020 AABB.)

Background Men who have sex with men (MSM) are at greater risk of developing anal cancer caused by human papillomavirus (HPV) than the rest of the general population. Currently, there are no formal national guidelines in the US advising men how and when to get anal cancer screening. We sought to assess differences in demographics, familiarity and anxiety about anal cancer among men who report having had anal cancer screening (i.e. anal cytology and/or a digital anorectal examination (DARE))., Methods: MSM were recruited to participate in a study to assess the feasibility of teaching self and partner anal examinations as a means of screening for anal cancer. Data for this secondary analysis were obtained using a written pre-test and a computer-assisted self-interview. Factors associated with screening were assessed with multivariable logistic regression to allow calculation of adjusted odds ratios (aORs)., Results: Of the 197 participants with data, 145 (73.6%) reported having had anal cancer screening (either anal cytology, DARE or both) during their lifetime. Men who were younger, Black and HIV-negative were associated with decreased odds of reporting any type of anal cancer screening. For example, compared with White men, Black men were 80% less likely to report screening (aOR 0.2; 95% confidence interval (CI) 0.1-0.5). Self-perception of anal cancer knowledge was not associated with screening in multivariable analysis (aOR 1.6; 95% CI 0.6-3.9)., Conclusions: Age, race and HIV status were independently associated with a history of anal cancer screening.

Objective: Anal cancer is a common cancer among men who have sex with men (MSM); however, there is no standard screening protocol for anal cancer. We conducted a phase II clinical trial to assess the feasibility of teaching MSM to recognise palpable masses in the anal canal which is a common sign of anal cancer in men., Methods: A clinician skilled in performing digital anorectal examinations (DARE) used a pelvic manikin to train 200 MSM, aged 27-78 years, how to do a self-anal examination (SAE) for singles or a partner anal examination (PAE) for couples. The clinician then performed a DARE without immediately disclosing results, after which the man or couple performed an SAE or PAE, respectively. Percentage agreement with the clinician DARE in addition to sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for the SAE, PAE and overall., Results: Men had a median age of 52 years, 42.5% were African American and 60.5% were HIV positive. DARE detected abnormalities in 12 men while the men's SAE/PAEs detected 9 of these. A total of 93.0% of men classified the health of their anal canal correctly (95% CI 89.5 to 96.5). Overall percentage agreement, sensitivity and specificity were 93.0%, 75.0% and 94.2%, respectively, while PPV and NPV were 45.0% and 98.3%, respectively. The six men who detected the abnormality had nodules/masses ≥3 mm in size. More than half of men (60.5%) reported never checking their anus for an abnormality; however, after performing an SAE/PAE, 93.0% said they would repeat it in the future., Conclusion: These results suggest that tumours of ≥3 mm may be detectable by self or partner palpation among MSM and encourage further investigation given literature suggesting a high cure rate for anal cancer tumours ≤10 mm., Competing Interests: Competing interests: The institutions of AGN, JTH, and EYC received NIH grants or subcontracts for the submitted works and/or grants from the NIH outside of the submitted work., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: Practice management guidelines for screening and treatment of patients with blunt cerebrovascular injury (BCVI) have been associated with a decreased risk of ischemic stroke., Treatment: of patients with BCVI and multisystem injuries that delays immediate antithrombotic therapy remains controversial. The purpose of this study was to determine the timing of BCVI treatment initiation, the incidence of stroke, and bleeding complications as a result of antithrombotic therapy in patients with isolated BCVI in comparison to those with BCVI complicated by multisystem injuries., Materials and Methods: This study was a retrospective review of all adult blunt trauma patients admitted to a level 1 trauma center from 2009 to 2014 with a diagnosis of BCVI., Results: A total of 28,305 blunt trauma patients were admitted during the study period. Of these, 323 (1.1%) had 481 BCEVIs and were separated into two groups. Isolated BCVI was reported in 111 (34.4%) patients and 212 (65.6%) patients had accompanying multisystem injuries (traumatic brain injury (TBI), solid organ injury, or spinal cord injury) that contraindicated immediate antithrombotic therapy., Treatment: started in patients with isolated BCVI at a median time of 30.3 (15, 52) hours after injury in contrast to 62.4 (38, 97) hours for those with multisystem injuries (p<0.001). The incidence of stroke was identical (9.9%) between groups and no bleeding complications related to antithrombotic therapy were identified., Conclusion: The lack of bleeding complications and equivalent stroke rates between groups suggests that the presence of TBI, solid organ injury, and spinal cord injury are not contraindications to anti-thrombotic therapy for stroke prevention in patients with BCVI., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: Persistent infection with oncogenic human papillomavirus (HPV) is the primary cause of anal cancer, a disease that disproportionately affects men who have sex with men (MSM); however, there is no uniform screening protocol to detect anal cancer. This qualitative study explores whether a self-anal exam (SAE) or partner anal exam (PAE), that includes self-palpation or palpation of a partner's anal canal, is an acceptable and self-efficacious screening test, which will cue appropriate follow-up care in MSM., Methods: Twenty-four MSM living in Houston took part in four focus group sessions eliciting their responses to a study teaching them to perform an SAE or PAE (SAE/PAE). Participants were asked about the acceptability and feasibility of executing an SAE/PAE routinely. Thematic analysis of session transcripts was used to identify common patterns in participant responses., Results: Overall, participants expressed self-efficacy for performing an SAE/PAE and voiced a preference for being taught the procedure by a clinician. Participants agreed that they would consult with a clinician if they ever discovered an abnormality while performing an SAE/PAE. A lack of knowledge about anal cancer among MSM may present a barrier to adopting SAE/PAE. In discussing their experience of the exams, some participants suggested that it could become a routine practice for them., Conclusions: Our findings suggest that SAE and PAE, as a screen for anal cancer, are acceptable and feasible to MSM. Future research should explore attitudes and beliefs of MSM, with the aim of improving anal cancer education and understanding of pathologic findings.

Background: Often the clinician is faced with a diagnostic and therapeutic dilemma in patients with concomitant traumatic brain injury (TBI) and hemorrhagic shock (HS), as rapid deterioration from either can be fatal. Knowledge about outcomes after concomitant TBI and HS may help prioritize the emergent management of these patients. We hypothesized that patients with concomitant TBI and HS (TBI + HS) had worse outcomes and required more intensive care compared with patients with only one of these injuries., Methods: This is a post hoc analysis of the Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial. TBI was defined by a head Abbreviated Injury Scale score greater than 2. HS was defined as a base excess of -4 or less and/or shock index of 0.9 or greater. The primary outcome for this analysis was mortality at 30 days. Logistic regression, using generalized estimating equations, was used to model categorical outcomes., Results: Six hundred seventy patients were included. Patients with TBI + HS had significantly higher lactate (median, 6.3; interquartile range, 4.7-9.2) compared with the TBI group (median, 3.3; interquartile range, 2.3-4). TBI + HS patients had higher activated prothrombin times and lower platelet counts. Unadjusted mortality was higher in the TBI + HS (51.6%) and TBI (50%) groups compared with the HS (17.5%) and neither group (7.7%). Adjusted odds of death in the TBI and TBI + HS groups were 8.2 (95% confidence interval, 3.4-19.5) and 10.6 (95% confidence interval, 4.8-23.2) times higher, respectively. Ventilator, intensive care unit-free and hospital-free days were lower in the TBI and TBI + HS groups compared with the other groups. Patients with TBI + HS or TBI had significantly greater odds of developing a respiratory complication compared with the neither group., Conclusion: The addition of TBI to HS is associated with worse coagulopathy before resuscitation and increased mortality. When controlling for multiple known confounders, the diagnosis of TBI alone or TBI+HS was associated with significantly greater odds of developing respiratory complications., Level of Evidence: Prognostic study, level II.

Background: Medication dispensing errors are common in clinical trials, and have a significant impact on the quality and validity of a trial. Therefore, the definition, calculation and evaluation of such errors are important for supporting a trial's conclusions. A variety of medication dispensing errors can occur. In this paper, we focus on errors in trials where the intervention includes multiple therapies that must be given in a pre-specified order that varies across treatment arms and varies in duration., Methods: The Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial was a Phase III multi-site, randomized trial to compare the effectiveness and safety of 1:1:1 transfusion ratios of plasma and platelets to red blood cells with a 1:1:2 ratio. In this trial, these three types of blood products were to be transfused in a pre-defined order that differed by treatment arm. In this paper, we present approaches from the PROPPR trial that we used to define and calculate the occurrence of out of order blood transfusion errors. We applied the proposed method to calculate protocol adherence to the specified order of transfusion in each treatment arm., Results: Using our proposed method, protocol adherence was greater in the 1:1:1 group than in the 1:1:2 group (96% vs 93%) (p<0.0001), although out of order transfusion errors in both groups were low. Final transfusion ratios of plasma to platelets to red blood cells for the 1:1:1 ratio group was 0.93:1.32:1, while the transfusion ratio for the 1:1:2 ratio group was 0.48:0.48:1., Conclusions: Overall, PROPPR adherence to blood transfusion order pre-specified in the protocol was high, and the required order of transfusions for the 1:1:2 group was more difficult to achieve. The approaches proposed in this manuscript were useful in evaluating the PROPPR adherence and are potentially useful for other trials where a specific treatment orders with varying durations must be maintained., Competing Interests: Statement The authors have no declared conflicts of interest related to this manuscript., (Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial was a randomized clinical trial comparing survival after transfusion of two different blood component ratios for emergency resuscitation of traumatic massive hemorrhage. Transfusion services supporting the study were expected to provide thawed plasma, platelets, and red blood cells within 10 minutes of request., Study Design and Methods: At the 12 Level 1 trauma centers participating in PROPPR, blood components transfused and delivery times were tabulated, with a focus on universal donor (UD) plasma management. The adequacy of site plans was assessed by comparing the bedside blood availability times to study goals and the new American College of Surgeons guidelines., Results: Eleven of 12 sites were able to consistently deliver 6 units of thawed UD plasma to their trauma-receiving unit within 10 minutes and 12 units in 20 minutes. Three sites used blood group A plasma instead of AB for massive transfusion without complications. Approximately 4700 units of plasma were given to the 680 patients enrolled in the trial. No site experienced shortages of AB plasma that limited enrollment. Two of 12 sites reported wastage of thawed AB plasma approaching 25% of AB plasma prepared., Conclusion: Delivering UD plasma to massively hemorrhaging patients was accomplished consistently and rapidly and without excessive wastage in high-volume trauma centers. The American College of Surgeons Trauma Quality Improvement Program guidelines for massive transfusion protocol UD plasma availability are practicable in large academic trauma centers. Use of group A plasma in trauma resuscitation needs further study., (© 2015 AABB.)

Importance: Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials., Objective: To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio., Design, Setting, and Participants: Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013., Interventions: Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled)., Main Outcomes and Measures: Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status., Results: No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, -4.2% [95% CI, -9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, -3.7% [95% CI, -10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, -5.4% [95% CI, -10.4% to -0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6 U, P < .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications., Conclusions and Relevance: Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups., Trial Registration: clinicaltrials.gov Identifier: NCT01545232.

Importance: There are many ways a mobile stroke unit (MSU) might prove valuable for patients with ischemic and hemorrhagic stroke, such as earlier recognition, more accurate triage, improved management of blood pressure and other critical physiological variables, and eventually earlier implementation of effective therapies. The MSU may be particularly valuable for treatment of patients with acute ischemic stroke with tissue plasminogen activator (tPA) within 4.5 hours of symptom onset, the most evidence-based effective emergency treatment for the most prevalent stroke diagnosis., Objectives: To review existing data on prehospital stroke treatment, especially relevant to MSU technology, to identify gaps in our understanding of MSU feasibility, especially relevant to applying the MSU strategy in the United States, and to describe the Houston MSU program and clinical trial., Evidence Review: Published data from English-language journals in PubMed from 1995 to present reviewing early treatment with tPA and prehospital stroke evaluation and treatment., Findings: The MSU may result in an overall shift toward earlier evaluation and treatment with tPA, particularly into the first hour after symptom onset, leading to substantially better outcomes. As a result of improved clinical outcomes owing to earlier treatment, the costs of an MSU program may be offset by a reduction in the costs of long-term stroke care and an increase in quality-adjusted life-years, thereby supporting more widespread use of this technology. To make MSU deployment more practical, the vascular neurologist aboard the MSU must be replaced by a remote vascular neurologist connected to the MSU by telemedicine, reducing manpower requirements and costs., Conclusions and Relevance: The MSU strategy could dramatically transform the way acute stroke is managed in the United States. A prospective study evaluating the logistics, outcomes, and cost-effectiveness of this approach is needed and under way.

Background: Hypertension is a major risk factor for peripheral artery disease (PAD). Little is known about relative efficacy of antihypertensive treatments for preventing PAD., Objectives: To compare, by randomized treatment groups, hospitalized or revascularized PAD rates and subsequent morbidity and mortality among participants in the Antihypertensive and Lipid-Lower Treatment to Prevent Heart Attack Trial (ALLHAT)., Design: Randomized, double-blind, active-control trial in high-risk hypertensive participants., Participants: Eight hundred thirty participants with specified secondary outcome of lower extremity PAD events during the randomized phase of ALLHAT., Interventions/events: In-trial PAD events were reported during ALLHAT (1994-2002). Post-trial mortality data through 2006 were obtained from administrative databases. Mean follow-up was 8.8 years., Main Measures: Baseline characteristics and intermediate outcomes in three treatment groups, using the Kaplan-Meier method to calculate cumulative event rates and post-PAD mortality rates, Cox proportional hazards regression model for hazard ratios and 95 % confidence intervals, and multivariate Cox regression models to examine risk differences among treatment groups., Key Results: Following adjustment for baseline characteristics, neither participants assigned to the calcium-channel antagonist amlodipine nor to the ACE-inhibitor lisinopril showed a difference in risk of clinically advanced PAD compared with those in the chlorthalidone arm (HR, 0.86; 95 % CI, 0.72-1.03 and HR, 0.98; 95 % CI, 0.83-1.17, respectively). Of the 830 participants with in-trial PAD events, 63 % died compared to 34 % of those without PAD; there were no significant treatment group differences for subsequent nonfatal myocardial infarction, coronary revascularizations, strokes, heart failure, or mortality., Conclusions: Neither amlodipine nor lisinopril showed superiority over chlorthalidone in reducing clinically advanced PAD risk. These findings reinforce the compelling need for comparative outcome trials examining treatment of PAD in high-risk hypertensive patients. Once PAD develops, cardiovascular event and mortality risk is high, regardless of type of antihypertensive treatment.

Background: Forty percent of in-hospital deaths among injured patients involve massive truncal haemorrhage. These deaths may be prevented with rapid haemorrhage control and improved resuscitation techniques. The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) Trial was designed to determine if there is a difference in mortality between subjects who received different ratios of FDA approved blood products. This report describes the design and implementation of PROPPR., Study Design: PROPPR was designed as a randomized, two-group, Phase III trial conducted in subjects with the highest level of trauma activation and predicted to have a massive transfusion. Subjects at 12 North American level 1 trauma centres were randomized into one of two standard transfusion ratio interventions: 1:1:1 or 1:1:2, (plasma, platelets, and red blood cells). Clinical data and serial blood samples were collected under Exception from Informed Consent (EFIC) regulations. Co-primary mortality endpoints of 24h and 30 days were evaluated., Results: Between August 2012 and December 2013, 680 patients were randomized. The overall median time from admission to randomization was 26min. PROPPR enrolled at higher than expected rates with fewer than expected protocol deviations., Conclusion: PROPPR is the largest randomized study to enrol severely bleeding patients. This study showed that rapidly enrolling and successfully providing randomized blood products to severely injured patients in an EFIC study is feasible. PROPPR was able to achieve these goals by utilizing a collaborative structure and developing successful procedures and design elements that can be part of future trauma studies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Context: While the delivery of cell therapy after ST-segment elevation myocardial infarction (STEMI) has been evaluated in previous clinical trials, the influence of the timing of cell delivery on the effect on left ventricular function has not been analyzed., Objectives: To determine the effect of intracoronary autologous bone marrow mononuclear cell (BMC) delivery after STEMI on recovery of global and regional left ventricular function and whether timing of BMC delivery (3 days vs 7 days after reperfusion) influences this effect., Design, Setting, and Patients: A randomized, 2 × 2 factorial, double-blind, placebo-controlled trial, Timing In Myocardial infarction Evaluation (TIME) enrolled 120 patients with left ventricular dysfunction (left ventricular ejection fraction [LVEF] ≤ 45%) after successful primary percutaneous coronary intervention (PCI) of anterior STEMI between July 17, 2008, and November 15, 2011, as part of the Cardiovascular Cell Therapy Research Network sponsored by the National Heart, Lung, and Blood Institute., Interventions: Intracoronary infusion of 150 × 106 BMCs or placebo (randomized 2:1) within 12 hours of aspiration and cell processing administered at day 3 or day 7 (randomized 1:1) after treatment with PCI., Main Outcome Measures: The primary end points were change in global (LVEF) and regional (wall motion) left ventricular function in infarct and border zones at 6 months measured by cardiac magnetic resonance imaging and change in left ventricular function as affected by timing of treatment on day 3 vs day 7. The secondary end points included major adverse cardiovascular events as well as changes in left ventricular volumes and infarct size., Results: The mean (SD) patient age was 56.9 (10.9) years and 87.5% of participants were male. At 6 months, there was no significant increase in LVEF for the BMC group (45.2% [95% CI, 42.8% to 47.6%] to 48.3% [95% CI, 45.3% to 51.3%) vs the placebo group (44.5% [95% CI, 41.0% to 48.0%] to 47.8% [95% CI, 43.4% to 52.2%]) (P = .96). There was no significant treatment effect on regional left ventricular function observed in either infarct or border zones. There were no significant differences in change in global left ventricular function for patients treated at day 3 (−0.9% [95% CI, −6.6% to 4.9%], P = .76) or day 7 (1.1% [95% CI, −4.7% to 6.9%], P = .70). The timing of treatment had no significant effect on regional left ventricular function recovery. Major adverse events were rare among all treatment groups., Conclusion: Among patients with STEMI treated with primary PCI, the administration of intracoronary BMCs at either 3 days or 7 days after the event had no significant effect on recovery of global or regional left ventricular function compared with placebo., Trial Registration: clinicaltrials.gov Identifier: NCT00684021.

Background/aims: The value of the Framingham equation in predicting cardiovascular risk in African Americans and patients with chronic kidney disease (CKD) is unclear. The purpose of the study was to evaluate whether the addition of CKD and race to the Framingham equation improves risk stratification in hypertensive patients., Methods: Participants in the ALLHAT were studied. Those randomized to doxazosin, older than 74 years, and those with a history of coronary heart disease were excluded. Two risk stratification models were developed using Cox proportional hazards models in a two-thirds developmental sample. The first model included the traditional Framingham risk factors. The second model included the traditional risk factors plus CKD, defined by estimated glomerular filtration rate categories, and stratification by race (black vs non-black). The primary outcome was a composite of fatal coronary heart disease, nonfatal myocardial infarction, coronary revascularization, and hospitalized angina., Results: There were a total of 19,811 eligible subjects. In the validation cohort, there was no difference in C-statistics between the Framingham equation and the ALLHAT model including CKD and race. This was consistent across subgroups by race and sex and among those with CKD. One exception was among Non-Black women where the C-statistic was higher for the Framingham equation (0.68 vs 0.65, P = .02). In addition, net reclassification improvement was not significant for any subgroup based on race and sex, ranging from -5.5% to 4.4%., Conclusion: The addition of CKD status and stratification by race does not improve risk prediction in high-risk hypertensive patients., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Introduction: Research has demonstrated associations between sociodemographic characteristics and illness perceptions; however, the impact of cancer exposure through personal or family diagnoses is not well-studied. The purposes of this study were to examine different cancer beliefs and disparities in cancer beliefs across groups of individuals with distinct cancer histories and to identify whether cancer history predicts a set of cancer beliefs., Methods: Using Leventhal's Common Sense Model and data from the 2007 Health Information National Trends Survey (N = 7,172), we constructed multivariable logistic regression models to evaluate the effect of different stimuli, including cancer experience on cancer perceptions (e.g., prevention, causation, outcome, worry)., Results: Findings indicated significant associations between cancer history and cancer perceptions. Individuals with family and personal cancer histories were more likely than individuals without any cancer history to worry about getting cancer (OR = 3.55, 95 %CI = 2.53-4.99), agree they will develop cancer in the future (OR = 8.81, 95 %CI = 6.12-12.67) and disagree that cancer is most often caused by a person's behavior or lifestyle (OR = 1.24, 95 %CI = 1.01-1.52)., Conclusions: Cancer history affects perceptions throughout the cancer continuum. Additionally, cancer history may influence coping behaviors and outcomes. Cancer education and survivorship programs should assess important variables such as cancer history to more effectively tailor services and monitor evolving needs throughout cancer care., Implications for Cancer Survivors: Integrating cancer history information into patient education programs tailored to an individual's needs may better empower survivors and their family members to effectively promote informed decision-making about screening and preventive health behaviors, manage cancer worry, and enhance quality of life.

Context: Previous studies using autologous bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy have demonstrated safety and suggested efficacy., Objective: To determine if administration of BMCs through transendocardial injections improves myocardial perfusion, reduces left ventricular end-systolic volume (LVESV), or enhances maximal oxygen consumption in patients with coronary artery disease or LV dysfunction, and limiting heart failure or angina., Design, Setting, and Patients: A phase 2 randomized double-blind, placebo-controlled trial of symptomatic patients (New York Heart Association classification II-III or Canadian Cardiovascular Society classification II-IV) with a left ventricular ejection fraction of 45% or less, a perfusion defect by single-photon emission tomography (SPECT), and coronary artery disease not amenable to revascularization who were receiving maximal medical therapy at 5 National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network (CCTRN) sites between April 29, 2009, and April 18, 2011., Intervention: Bone marrow aspiration (isolation of BMCs using a standardized automated system performed locally) and transendocardial injection of 100 million BMCs or placebo (ratio of 2 for BMC group to 1 for placebo group)., Main Outcome Measures: Co-primary end points assessed at 6 months: changes in LVESV assessed by echocardiography, maximal oxygen consumption, and reversibility on SPECT. Phenotypic and functional analyses of the cell product were performed by the CCTRN biorepository core laboratory., Results: Of 153 patients who provided consent, a total of 92 (82 men; average age: 63 years) were randomized (n = 61 in BMC group and n = 31 in placebo group). Changes in LVESV index (-0.9 mL/m(2) [95% CI, -6.1 to 4.3]; P = .73), maximal oxygen consumption (1.0 [95% CI, -0.42 to 2.34]; P = .17), and reversible defect (-1.2 [95% CI, -12.50 to 10.12]; P = .84) were not statistically significant. There were no differences found in any of the secondary outcomes, including percent myocardial defect, total defect size, fixed defect size, regional wall motion, and clinical improvement., Conclusion: Among patients with chronic ischemic heart failure, transendocardial injection of autologous BMCs compared with placebo did not improve LVESV, maximal oxygen consumption, or reversibility on SPECT., Trial Registration: clinicaltrials.gov Identifier: NCT00824005.

Multiple outcomes (or multiple endpoints), such as mortality and recurrent myocardial infarction, are increasingly common in clinical trials and are often of interest in secondary analyses. Traditionally, a clinical trial protocol is built around a single event as its primary outcome, with several secondary outcomes specified, the analyses for which lack the same level of power. To accommodate all the relevant outcomes and to increase the power of the comparison in trials evaluating the efficacy of treatments for coronary heart disease, investigators often chose to construct a composite outcome. The more conventional composite outcome fails to account for the relative importance and the relationship (correlation) among its components. The purpose of this work is to demonstrate the usefulness of the Global Statistical Test, which considers the correlation between multiple outcomes, as an alternative strategy for these situations and to demonstrate its effect on hypothesis testing and power analysis issues in comparison with the traditional composite outcome analysis. Data from the cardiovascular clinical trial Systolic Hypertension in the Elderly Population are used as an example., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Moderate improvements in cardiac performance have been reported in some clinical settings after delivery of bone marrow mononuclear cells to patients with cardiovascular disease. However, mechanistic insights into how these cells impact outcomes are lacking. To address this, the National Heart, Lung and Blood Institute (NHLBI) Cardiovascular Cell Therapy Research Network (CCTRN) established a Biorepository Core for extensive phenotyping and cell function studies and storing bone marrow and peripheral blood for 10 years. Analyzing cell populations and cell function in the context of clinical parameters and clinical outcomes after cell or placebo treatment empower the development of novel diagnostic and prognostics. Developing such biomarkers that define the safety and efficacy of cell therapy is a major Biorepository aim., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Context: Clinical trial results suggest that intracoronary delivery of autologous bone marrow mononuclear cells (BMCs) may improve left ventricular (LV) function when administered within the first week following myocardial infarction (MI). However, because a substantial number of patients may not present for early cell delivery, the efficacy of autologous BMC delivery 2 to 3 weeks post-MI warrants investigation., Objective: To determine if intracoronary delivery of autologous BMCs improves global and regional LV function when delivered 2 to 3 weeks following first MI., Design, Setting, and Patients: A randomized, double-blind, placebo-controlled trial (LateTIME) of the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network of 87 patients with significant LV dysfunction (LV ejection fraction [LVEF] ≤45%) following successful primary percutaneous coronary intervention (PCI) between July 8, 2008, and February 28, 2011., Interventions: Intracoronary infusion of 150 × 10(6) autologous BMCs (total nucleated cells) or placebo (BMC:placebo, 2:1) was performed within 12 hours of bone marrow aspiration after local automated cell processing., Main Outcome Measures: Changes in global (LVEF) and regional (wall motion) LV function in the infarct and border zone between baseline and 6 months, measured by cardiac magnetic resonance imaging. Secondary end points included changes in LV volumes and infarct size., Results: A total of 87 patients were randomized (mean [SD] age, 57 [11] years; 83% men). Harvesting, processing, and intracoronary delivery of BMCs in this setting was feasible. Change between baseline and 6 months in the BMC group vs placebo for mean LVEF (48.7% to 49.2% vs 45.3% to 48.8%; between-group mean difference, -3.00; 95% CI, -7.05 to 0.95), wall motion in the infarct zone (6.2 to 6.5 mm vs 4.9 to 5.9 mm; between-group mean difference, -0.70; 95% CI, -2.78 to 1.34), and wall motion in the border zone (16.0 to 16.6 mm vs 16.1 to 19.3 mm; between-group mean difference, -2.60; 95% CI, -6.03 to 0.77) were not statistically significant. No significant change in LV volumes and infarct volumes was observed; both groups decreased by a similar amount at 6 months vs baseline., Conclusion: Among patients with MI and LV dysfunction following reperfusion with PCI, intracoronary infusion of autologous BMCs vs intracoronary placebo infusion, 2 to 3 weeks after PCI, did not improve global or regional function at 6 months., Trial Registration: clinicaltrials.gov Identifier: NCT00684060.

Background: In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind, practice-based, active-control, comparative effectiveness trial in high-risk hypertensive participants, risk of new-onset heart failure (HF) was higher in the amlodipine (2.5-10 mg/d) and lisinopril (10-40 mg/d) arms compared with the chlorthalidone (12.5-25 mg/d) arm. Similar to other studies, mortality rates following new-onset HF were very high (≥50% at 5 years), and were similar across randomized treatment arms. After the randomized phase of the trial ended in 2002, outcomes were determined from administrative databases., Methods and Results: With the use of national databases, posttrial follow-up mortality through 2006 was obtained on participants who developed new-onset HF during the randomized (in-trial) phase of ALLHAT. Mean follow-up for the entire period was 8.9 years. Of 1761 participants with incident HF in-trial, 1348 died. Post-HF all-cause mortality was similar across treatment groups, with adjusted hazard ratios (95% confidence intervals) of 0.95 (0.81-1.12) and 1.05 (0.89-1.25), respectively, for amlodipine and lisinopril compared with chlorthalidone, and 10-year adjusted rates of 86%, 87%, and 83%, respectively. All-cause mortality rates were also similar among those with reduced ejection fractions (84%) and preserved ejection fractions (81%), with no significant differences by randomized treatment arm., Conclusions: Once HF develops, risk of death is high and consistent across randomized treatment groups. Measures to prevent the development of HF, especially blood pressure control, must be a priority if mortality associated with the development of HF is to be addressed. Clinical Trial Registration- http://www.clinicaltrials.gov. Unique identifier: NCT00000542.

Global left ventricular (LV) ejection fraction (LVEF) has been used as a measure of improvement in LV function following cell therapy. Although the impact of cell therapy on LVEF in short- and long-term follow-up has been generally positive, there is concern that research evaluating regional therapeutics (e.g., cell or gene therapy) may require analysis of regional LV function localized to the site of intervention. Regional LV assessment is traditionally performed with qualitative or quantitative analysis of wall thickening within 16 myocardial segments, but advances in noninvasive imaging permit an increasingly more detailed and accurate evaluation of LV function. Wall-thickness measurements can now include evaluation of over 1,000 myocardial segments. In addition to higher resolution measures of wall thickening, automated assessments of myocardial segment deformation, such as strain imaging, exist. Strain imaging allows for direct evaluation of the mechanical properties that may improve following regional therapeutic intervention. Improvements in regional LV function may also be assessed by determining regional ejection fraction (EF). Regional EF offers the advantage of summarizing the end result of all of the complex deformations in the adjacent myocardial segments. Although regional EF and strain imaging, as compared with wall thickening, enhance detection of improvement in complex measures of regional myocardial function, it remains unclear whether such measures are better able to predict meaningful improvement in clinical outcomes., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The increasing worldwide prevalence of coronary artery disease (CAD) continues to challenge the medical community. Management options include medical and revascularization therapy. Despite advances in these methods, CAD is a leading cause of recurrent ischemia and heart failure, posing significant morbidity and mortality risks along with increasing health costs in a large patient population worldwide., Trial Design: The Cardiovascular Cell Therapy Research Network (CCTRN) was established by the National Institutes of Health to investigate the role of cell therapy in the treatment of chronic cardiovascular disease. FOCUS is a CCTRN-designed randomized, phase II, placebo-controlled clinical trial that will assess the effect of autologous bone marrow mononuclear cells delivered transendocardially to patients with left ventricular (LV) dysfunction and symptomatic heart failure or angina. All patients need to have limiting ischemia by reversible ischemia on single-photon emission computed tomography assessment., Results: After thoughtful consideration of both statistical and clinical principles, we will recruit 87 patients (58 cell treated and 29 placebo) to receive either bone marrow-derived stem cells or placebo. Myocardial perfusion, LV contractile performance, and maximal oxygen consumption are the primary outcome measures., Conclusions: The designed clinical trial will provide a sound assessment of the effect of autologous bone marrow mononuclear cells in improving blood flow and contractile function of the heart. The target population is patients with CAD and LV dysfunction with limiting angina or symptomatic heat failure. Patient safety is a central concern of the CCTRN, and patients will be followed for at least 5 years., (Copyright 2010 Mosby, Inc. All rights reserved.)

Aims: To determine predictors of adherence to cervical cancer screening guidelines among women working in Monterrey, Mexico. Cases (n = 94) were sexually active female store clerks working in Monterrey, Mexico, aged 18-64, who were not adherent to Official Mexican Standard cervical cancer screening guidelines; controls (n = 135) were adherent to guidelines. The outcome of interest was adherence to cervical cancer screening services according to national screening guidelines., Methods: Multivariate logistic regression analyzed knowledge factors and perceptions associated with adherence., Results: Having no or inaccurate knowledge of screening guidelines (odds ratio [OR] 11.1, 95% confidence interval [95% CI] 4.3-28.5) and no knowledge of Pap examination utility (OR 6.8, 95% CI 1.0-46.4) were associated with screening guideline nonadherence. Perceptions of fear/embarrassment (OR 16.2, 95% CI 5.1-51.5) and lower levels of spousal/partner acceptance (OR 5.8, 95% CI 1.3-25.3) of the Pap examination were associated with screening guideline nonadherence. Results were adjusted for age at initiation of sexual activity, civil status, level of education, use of family planning/birth control, and income., Conclusions: Identification of knowledge factors and perceptions that predict screening guideline adherence can inform population-specific recommendations to increase screening and reduce cervical cancer morbidity and mortality among employed Mexican women.

A realistic goal for cardiac cell therapy may be to attenuate left ventricular remodeling following acute myocardial infarction to prevent the development of congestive heart failure. Initial clinical trials of cell therapy have delivered cells 1 to 7 days after acute myocardial infarction. However, many patients at risk of developing congestive heart failure may not be ready for cell delivery at that time-point because of clinical instability or hospitalization at facilities without access to cell therapy. Experience with cell delivery 2 to 3 weeks after acute myocardial infarction has not to date been explored in a clinical trial. The objective of the LateTIME study is to evaluate by cardiac magnetic resonance the effect on global and regional left ventricular function, between baseline and 6 months, of a single intracoronary infusion of 150 × 106 autologous bone marrow mononuclear cells (compared with placebo) when that infusion is administered 2 to 3 weeks after moderate-to-large acute myocardial infarction. The 5 clinical sites of the Cardiovascular Cell Therapy Research Network (CCTRN) will enroll a total of 87 eligible patients in a 2:1 bone marrow mononuclear cells-to-placebo patient ratio; these 87 will have undergone successful percutaneous coronary intervention of a major coronary artery and have left ventricular ejection fractions ≤0.45 by echocardiography. When the results become available, this study should provide insight into the clinical feasibility and appropriate timing of autologous cell therapy in high-risk patients after acute myocardial infarction and percutaneous coronary intervention.

Objective: Because of an increase in the rate of surgical site infections (SSIs) following spinal procedures at the study hospital, we conducted a study to determine risk factors associated with the development of a SSI., Design: Case-control study., Setting: A community hospital in Houston, Texas, with more than 500 beds., Patients: Fifty-five case patients who developed SSI after spinal surgery and 179 control patients who did not develop SSI after spinal surgery., Methods: We examined patient- and hospital-associated risk factors for SSI by using existing data on patients who underwent spinal operations at the study hospital between December 2003 and August 2005. Multivariable analysis was conducted using logistic regression to determine significant risk factors associated with SSI., Results: The presence of comorbidities (odds ratio [OR], 3.15 [95% confidence interval (CI), 1.20-8.26]) and surgical duration greater than the population median of 100 minutes (OR, 2.48 [95% CI, 1.12-5.49]) were identified as independent risk factors for SSI. The use of only povidone-iodine for preoperative skin antisepsis was found to be protective (OR, 0.16 [95% CI, 0.06-0.45]). Specific operating room, hospital staff involved in the procedures, workers' compensation status, method of hair removal, smoking status, or incontinence were not statistically significant., Conclusions: The presence of comorbidities and increased surgical duration are risks for postoperative infection. The use of only povidone-iodine was found to decrease the risk of infection.

The objective of this study was to describe the clinical features of cases hospitalized with West Nile virus (WNV) infections and identify clinical parameters that could potentially predict poor outcome (death). Retrospective medical chart reviews were completed for 172 confirmed cases of WNV infection hospitalized in the Houston, Texas, metropolitan area between 2002 and 2004. Of the 172 patients, 113 had encephalitis which resulted in 17 deaths, 47 had meningitis, and 12 had uncomplicated fever. Risk factors associated with progression from encephalitis to death were absence of pleocytosis in the cerebrospinal fluid, renal insufficiency, requiring intubation and mechanical ventilation, presence of myoclonus or tremors, and loss of consciousness. These findings can aid physicians in evaluating their patients suspected of WNV infection and determining outcomes in their patients with confirmed WNV neuroinvasive disease.

While investigators designing clinical trials face the important issue of endpoint selection, an equally troublesome concern can be the a priori selection of the endpoint analysis. In this latter circumstance, there may be only one endpoint of interest in the clinical trial, but several competing endpoint analyses are available (e.g., an analysis of the endpoint that is adjusted for clinical center versus an analysis that is adjusted for geographic region versus an unadjusted analysis). An example that demonstrates the unsatisfactory conclusions that ambiguous choices can produce is offered. A procedure utilizing conditional probability is provided that permits the conservation of type I error when the investigators have one endpoint and several worthy competitor endpoint analyses that are each prospectively identified and carried out at the trial's conclusion. When the high levels of dependence among these analyses are taken into account, it is possible to carry out the hypothesis tests in a way that 1) provides practicable type I error levels for each analysis, and 2) conserves the familywise type I error. In circumstances in which the endpoint and all members of the family of analyses are selected during the design phase of the trial, this procedure provides confirmatory conclusions as opposed to exploratory findings.

Background: Limited data are available about the effectiveness of early rehabilitation after stroke., Objective: This is the 1st randomized controlled trial of constraint-induced movement therapy (CIMT) in subacute stroke to investigate neurophysiologic mechanisms and long-term outcome., Methods: Within 2 weeks after stroke, 23 patients with upper extremity (UE) weakness were randomized to 2 weeks of CIMT or traditional therapy at an equal frequency of up to 3 h/day. Motor function of the affected UE was blindly assessed before treatment, after treatment, and 3 months after stroke. Transcranial magnetic stimulation (TMS) measured the cortical area evoking movement of the affected hand., Results: Long-term improvement in motor function of the affected UE did not differ significantly between patients who received CIMT versus intensive traditional therapy. All outcome comparisons showed trends favoring CIMT over intensive traditional therapy, but none was statistically significant except for improvements in the Fugl-Meyer (FM) UE motor scale immediately following treatment and in reported quality of hand function at 3 months. Improvement in UE motor function on the FM was associated with a greater number of sites on the affected cerebral hemisphere where responses of the affected hand were evoked by TMS., Conclusions: Future trials of CIMT during early stroke rehabilitation need greater statistical power, more inclusive eligibility criteria, and improved experimental control over treatment intensity. The relationship between changes in motor function and in evoked motor responses suggests that motor recovery during the 1st 3 months after stroke is associated with increased motor excitability of the affected cerebral hemisphere.

Background: The benefit of intravenous recombinant tissue plasminogen activator (rtPA) in acute stroke is linked to clot lysis and artery recanalization. Argatroban is a direct thrombin inhibitor that safely augments the benefit of rtPA in animal stroke models. There are no human data on this combination., Design: We report the first phase of the Argatroban tPA Stroke Study, an ongoing prospective, open-label, dose-escalation, safety and activity study of argatroban and rtPA in patients with ischemic stroke. The primary outcome was incidence of intracerebral hemorrhage; secondary outcome, complete recanalization at 2 hours. After standard-dose intravenous rtPA administration, a 100-mug/kg bolus of argatroban followed by infusion of 1 mug/kg per minute for 48 hours was adjusted to a target partial thromboplastin time of 1.75 times that of the control group., Results: Fifteen patients (including 10 men) were enrolled, with a mean +/- SD age of 61 +/- 13 years. All patients had middle cerebral artery occlusions. Baseline median National Institute of Health Stroke Scale score was 14 (range, 4-25). The mean +/- SD time from symptom onset to argatroban bolus administration was 172 +/- 53 minutes. Symptomatic intracerebral hemorrhage occurred in 2 patients, including 1 with parenchymal hemorrhage type 2. Asymptomatic bleeding occurred in 1 patient and there was 1 death. Recanalization was complete in 6 patients and partial in another 4, and reocclusion occurred in 3 within 2 hours of rtPA bolus administration., Conclusion: The safety of low-dose argatroban combined with intravenous rtPA may be within acceptable limits, and its efficacy for producing fast and complete recanalization is promising, but a larger cohort of patients is required to confirm these preliminary observations.