Assessing Photostability of mAb Formulations In Situ Using Light-Coupled NMR Spectroscopy.

Biopharmaceuticals, such as monoclonal antibodies (mAbs), need to maintain their chemical and physical stability in formulations throughout their lifecycle. It is known that exposure of mAbs to light, particularly UV, triggers chemical and physical degradation, which can be exacerbated by trace amounts of photosensitizers in the formulation. Although routine assessments of degradation following defined UV dosages are performed, there is a fundamental lack of understanding regarding the intermediates, transient reactive species, and radicals formed during illumination, as well as their lifetimes and immediate impact post-illumination. In this study, we used light-coupled NMR spectroscopy to monitor in situ live spectral changes in sealed samples during and after UV-A illumination of different formulations of four mAbs without added photosensitizers. We observed a complex evolution of spectra, reflecting the appearance within minutes of transient radicals during illumination and persisting for minutes to tens of minutes after the light was switched off. Both mAb and excipient signals were strongly affected by illumination, with some exhibiting fast irreversible photodegradation and others exhibiting partial recovery in the dark. These effects varied depending on the mAb and the presence of excipients, such as polysorbate 80 (PS80) and methionine. Complementary ex situ high-performance size-exclusion chromatography analysis of the same formulations post-UV exposure in the chamber revealed significant loss of purity, confirming formulation-dependent degradation. Both approaches suggested the presence of degradation processes initiated by light but continuing in the dark. Further studies on photoreaction intermediates and transient reactive species may help mitigate the impact of light on biopharmaceutical degradation.

Core Components and Implementation Determinants of Multilevel Service Delivery Frameworks Across Child Mental Health Service Settings.

Multilevel service delivery frameworks are approaches to structuring and organizing a spectrum of evidence-based services and supports, focused on assessment, prevention, and intervention designed for the local context. Exemplar frameworks in child mental health include positive behavioral interventions and supports in education, collaborative care in primary care, and systems of care in community mental health settings. Yet, their high-quality implementation has lagged. This work proposes a conceptual foundation for multilevel service delivery frameworks spanning diverse mental health service settings that can inform development of strategic implementation supports. We draw upon the existing literature for three exemplar multilevel service delivery frameworks in different child mental health service settings to (1) identify core components common to each framework, and (2) to highlight prominent implementation determinants that interface with each core component. Six interrelated components of multilevel service delivery frameworks were identified, including, (1) a systems-level approach, (2) data-driven problem solving and decision-making, (3) multiple levels of service intensity using evidence-based practices, (4) cross-linking service sectors, (5) multiple providers working together, including in teams, and (6) built-in implementation strategies that facilitate delivery of the overall model. Implementation determinants that interface with core components were identified at each contextual level. The conceptual foundation provided in this paper has the potential to facilitate cross-sector knowledge sharing, promote generalization across service settings, and provide direction for researchers, system leaders, and implementation intermediaries/practitioners working to strategically support the high-quality implementation of these frameworks.

Comparing Informants for Mental Health Screening at the Preschool Level.

Universal screening for mental health in preschools provides the opportunity for early identification and early intervention, but guidance regarding which informants to use is needed. Preschoolers' (N = 535) parent and teacher reports across two screening forms were analyzed to determine similarities and discrepancies for classification results and screener scores. The analyses also examined if an additional rater provided incrementally valid information to the prediction of longitudinal kindergarten outcomes. Parents' and teachers' screening scores were significantly correlated across forms by rater and across raters. However, categorical classification results indicated that teachers were more likely than parents to rate preschoolers in at-risk ranges across forms. Finally, hierarchical regression analyses revealed teacher ratings were predictive of kindergarten social-emotional, cognitive, and academic outcomes, and that the addition of parent ratings did not significantly improve prediction of outcomes. Implications are discussed in the context of multiple raters within multiple-gating screening procedures.

Moving towards Implementation of Universal Mental Health Screening by Examining Attitudes toward School-based Practices.

Universal mental health screening is a proactive approach to identify students who may benefit from prevention or early intervention services. Despite known benefits, few schools are engaging in screening efforts and it is critical to examine factors that may impede or enhance implementation. Following implementation of a universal screening program across five preschools and elementary schools, this study investigated the attitudes of teachers (N = 40) and parents (N = 330) and found strong agreement among stakeholders about the acceptability and appropriateness of universal mental health screening. Teachers and parents expressed less willingness to regularly complete screening forms, yet teachers reported that the Behavior Assessment System for Children - Third Edition: Behavioral Emotional Screening System was a usable screening tool. Implications and future directions to enhance implementation efforts are discussed.

Metabolic Architecture of Acute Exercise Response in Middle-Aged Adults in the Community.

BACKGROUND: Whereas regular exercise is associated with lower risk of cardiovascular disease and mortality, mechanisms of exercise-mediated health benefits remain less clear. We used metabolite profiling before and after acute exercise to delineate the metabolic architecture of exercise response patterns in humans. METHODS: Cardiopulmonary exercise testing and metabolite profiling was performed on Framingham Heart Study participants (age 53±8 years, 63% women) with blood drawn at rest (n=471) and at peak exercise (n=411). RESULTS: We observed changes in circulating levels for 502 of 588 measured metabolites from rest to peak exercise (exercise duration 11.9±2.1 minutes) at a 5% false discovery rate. Changes included reductions in metabolites implicated in insulin resistance (glutamate, -29%; P=1.5×10-55; dimethylguanidino valeric acid [DMGV], -18%; P=5.8×10-18) and increases in metabolites associated with lipolysis (1-methylnicotinamide, +33%; P=6.1×10-67), nitric oxide bioavailability (arginine/ornithine + citrulline, +29%; P=2.8×10-169), and adipose browning (12,13-dihydroxy-9Z-octadecenoic acid +26%; P=7.4×10-38), among other pathways relevant to cardiometabolic risk. We assayed 177 metabolites in a separate Framingham Heart Study replication sample (n=783, age 54±8 years, 51% women) and observed concordant changes in 164 metabolites (92.6%) at 5% false discovery rate. Exercise-induced metabolite changes were variably related to the amount of exercise performed (peak workload), sex, and body mass index. There was attenuation of favorable excursions in some metabolites in individuals with higher body mass index and greater excursions in select cardioprotective metabolites in women despite less exercise performed. Distinct preexercise metabolite levels were associated with different physiologic dimensions of fitness (eg, ventilatory efficiency, exercise blood pressure, peak Vo2). We identified 4 metabolite signatures of exercise response patterns that were then analyzed in a separate cohort (Framingham Offspring Study; n=2045, age 55±10 years, 51% women), 2 of which were associated with overall mortality over median follow-up of 23.1 years (P≤0.003 for both). CONCLUSIONS: In a large sample of community-dwelling individuals, acute exercise elicits widespread changes in the circulating metabolome. Metabolic changes identify pathways central to cardiometabolic health, cardiovascular disease, and long-term outcome. These findings provide a detailed map of the metabolic response to acute exercise in humans and identify potential mechanisms responsible for the beneficial cardiometabolic effects of exercise for future study.

The perspective of school leaders on the implementation of evidence-based practices: A mixed methods study.

Background: School leaders play an integral role in the use of implementation strategies, which in turn support special education teachers in the implementation of evidence-based practices (EBPs). In this convergent mixed methods study, we explored school leaders' perceptions of the facilitators and barriers to EBP implementation, particularly for students receiving special education, as well as the importance and feasibility of 15 implementation strategies. Method: School leaders (N = 22, principals, assistant principals, school psychologists, etc.) participated in a semistructured interview that included three parts-qualitative questions, quantitative ratings of strategies' importance and feasibility, and discussion of the top three implementation strategies. Data strands were analyzed independently and then integrated to generate meta-inferences. Results: The qualitative data identified facilitators such as access to resources about the intervention (e.g., professional development) and collaboration and teamwork, while barriers centered on lack of school supports, culture/climate, and organizational factors (e.g., lack of communication). The quantitative data indicated that the implementation strategy provide ongoing consultation/coaching was rated as important and feasible. Monitor the progress of the implementation effort was rated as important but less feasible, while conduct educational meetings and change the environment were rated as feasible, but less important. Build partnerships to support implementation was rated as less important and feasible. There was convergence and divergence in mixed methods findings. Conclusion: This study underscores the critical need to increase school leaders' knowledge and skills related to implementation science to better leverage implementation strategies that address the confluence of relevant implementation determinants.

School leaders, such as principals, assistant principals, and school psychologists, are responsible for supporting special education teachers in doing interventions (e.g., through teacher training). In this study, we interviewed 22 school leaders to understand what factors support or hinder teachers in doing interventions, especially for students receiving special education. We also provided school leaders with a list of 15 strategies that may be used to support teachers, to determine which strategies school leaders think are the most important and feasible in schools. Our results indicated that it is important to train school leaders on how to move research into practice settings, such as schools. It is equally important for researchers and policymakers to understand the priorities of school leaders.

Interleukin receptor family member ST2 concentrations in patients following heart transplantation.

OBJECTIVE: To evaluate soluble (s) ST2 as a biomarker of rejection, allograft vasculopathy and mortality after orthotopic heart transplantation (OHT). METHODS: sST2 concentrations were measured in 241 patients following OHT. RESULTS: Elevated sST2 was associated with cellular rejection (CR) ≥ 1R, with highest rates of CR in the 4th sST2 quartile (p = 0.003). No significant association between sST2 and antibody-mediated rejection or allograft vasculopathy was found. sST2 ≥ 30 ng/mL independently predicted death over 7-year follow-up (HR = 2.01; 95% CI 1.15-3.51; p = 0.01). CONCLUSION: Concentrations of sST2 are associated with the presence of CR and predict long-term mortality following OHT.

Multidisciplinary care of patients receiving cardiac resynchronization therapy is associated with improved clinical outcomes.

AIMS: Although cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with heart failure, a significant minority of patients do not respond adequately to this therapy. The objective of this study was to examine the impact of a 'multidisciplinary care' (MC) approach on the clinical outcome in CRT patients. METHODS AND RESULTS: The clinical outcome in patients prospectively receiving MC (n = 254) was compared with a control group of patients who received conventional care (CC, n = 173). The MC group was followed prospectively in an integrated clinic setting by a team of subspecialists from the heart failure, electrophysiology, and echocardiography service at 1-, 3-, and 6-months post-implant. All patients had echocardiographic-guided optimization at their 1-month visit. The proportional hazards model (adjusting for all covariates) and Kaplan-Meier time to first event curves were compared between the two groups, over a 2-year follow-up. The long-term outcome was measured as a combined endpoint of heart failure hospitalization, cardiac transplantation, or all-cause mortality. The clinical characteristics between the MC and CC groups at baseline were comparable (age, 68 ± 13 vs. 69 ± 12; NYHA III, 90 vs. 82%; ischaemic cardiomyopathy 55 vs. 64%, P = NS, respectively). The event-free survival was significantly higher in the multidisciplinary vs. the CC group (P = 0.0015). A significant reduction in clinical events was noted in the MC group vs. the CC group (hazard ratio: 0.62, 95% CI: 0.46-0.83, P = 0.001). CONCLUSION: Integrated MC may improve 2-year event-free survival in patients receiving cardiac resynchronization therapy. Prospective randomized studies are needed to validate our findings.

Quality of life and chronic heart failure therapy guided by natriuretic peptides: results from the ProBNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) study.

BACKGROUND: Heart failure (HF) treatment guided by amino-terminal pro-B type natriuretic peptide (NT-proBNP) may reduce cardiovascular event rates compared to standard-of-care (SOC) management. Comprehensive understanding regarding effect of NT-proBNP guided care on patient-reported quality of life (QOL) remains unknown. METHODS: One hundred fifty-one subjects with HF due to left ventricular systolic dysfunction were randomized to either SOC HF management or care with a goal to reduce NT-proBNP values ≤1000 pg/mL. Effects of HF on QOL were assessed using the Minnesota Living with HF Questionnaire (MLHFQ) quarterly, with change (Δ) in score assessed across study procedures and as a function of outcome. RESULTS: Overall, baseline MLHFQ score was 30. Across study visits, QOL improved in both arms, but was more improved and sustained in the NT-proBNP arm (repeated measures P = .01); NT-proBNP patients showing greater reduction in MLHFQ score (-10.0 vs -5.0; P = .05), particularly in the physical scale of the questionnaire. Baseline MLHFQ scores did not correlate with NT-proBNP; in contrast, ∆MLHFQ scores modestly correlated with ∆NT-proBNP values (ρ = .234; P = .006) as did relative ∆ in MLHFQ score and NT-proBNP (ρ = .253; P = .003). Considered in tertiles, less improvement in MLHFQ scores was associated with a higher rate of HF hospitalization, worsening HF, and cardiovascular death (P = .001). CONCLUSIONS: We describe novel associations between NT-proBNP concentrations and QOL scores among patients treated with biomarker guided care. Compared to SOC HF management, NT-proBNP guided care was associated with greater and more sustained improvement in QOL (Clinical Trial Registration: www.clinicaltrials.govNCT00351390).

Young patients with nonischemic cardiomyopathy have higher likelihood of left ventricular recovery during left ventricular assist device support.

BACKGROUND: Recovery of ventricular function during left ventricular assist device (LVAD) support allowing device explantation occurs infrequently. We explored the hypothesis that certain patient profiles are more likely to exhibit LV recovery during LVAD support. METHODS AND RESULTS: A retrospective analysis of data from the HeartMate II bridge to transplant (BTT) and destination therapy (DT) trials was conducted, including 490 BTT, 600 DT, and 18 compassionate-use patients. Of the 1,108 patients, 20 (1.8%; 10 BTT, 10 DT) were explanted owing to LV recovery. The median age was 33 years, and 12 patients (60%) were <40 years of age. History of heart failure was <1 year for 11 patients (61%), and the primary etiology was nonischemic (90%). Of the patients with nonischemic etiologies and <1-year history of heart failure, 13% were explanted. Three patients required LVAD reimplantation; of the remaining 17, 16 remain alive. At follow-up (median 510 days), the mean ejection fraction was 42% (20%-67%) and the mean left ventricular end-diastolic diameter was 55 ± 8 mm. At the 2-year follow-up (n = 13), patients were New York Heart Association functional class I or II and overall survival rate was 85 ± 11%. CONCLUSIONS: The results of this study suggest that LV recovery is most likely to occur in young patients (<40 years) with nonischemic cardiomyopathy of <1 year duration. Two-year postexplant survival was excellent.

Heart failure outcomes and benefits of NT-proBNP-guided management in the elderly: results from the prospective, randomized ProBNP outpatient tailored chronic heart failure therapy (PROTECT) study.

BACKGROUND: Elderly patients with heart failure (HF) have a worse prognosis than younger patients. We wished to study whether elders benefit from natriuretic peptide-guided HF care in this single-center study. METHODS AND RESULTS: A total of 151 patients with HF resulting from left ventricular systolic dysfunction (LVSD) were treated with HF treatment by standard-of-care (SOC) management or guided by N-terminal pro-B type natriuretic peptide (NT-proBNP) values (with a goal to lower NT-proBNP ≤1000 pg/mL) over 10 months. The primary end point for this post-hoc analysis was total cardiovascular events in 2 age categories (<75 and ≥75 years). In those ≥75 years of age (n = 38), NT-proBNP values increased in the SOC arm (2570 to 3523 pg/mL, P = .01), but decreased in the NT-proBNP-guided arm (2664 to 1418 pg/mL, P = .001). Elderly patients treated with SOC management had the highest rate of cardiovascular events, whereas the elderly with NT-proBNP management had the lowest rate of cardiovascular events (1.76 events per patient versus 0.71 events per patient, P = .03); the adjusted logistic odds for cardiovascular events related to NT-proBNP-guided care for elders was 0.24 (P = .008), whereas in those <75 years (n = 113), the adjusted logistic odds for events following NT-proBNP-guided care was 0.61 (P = .10). CONCLUSIONS: Natriuretic peptide-guided HF care was well tolerated and resulted in substantial improvement in cardiovascular event rates in elders (ClinicalTrials.Gov #00351390).

Structural School Characteristics and Neighborhood Risk Factors: Associations with Student-Reported School Climate in a Large, Urban Public School District in the United States.

School climate consistently predicts youth academic success, social-emotional well-being, and substance use, and positive school climate can buffer the negative effects of community violence exposure on youth development. Various structural school and neighborhood factors have been associated with school climate, but prior research has not examined these relations comprehensively. We examined the relation between 18 school building and school neighborhood factors with student-reported school climate among 15,833 students in 124 public schools in a large, urban district in the United States. In this sample, attendance rate was most consistently associated with school climate (ß = 0.015; p < .001). Teacher years of experience, mobility rate, number of students in special education, adult arrests in the school neighborhood, and service calls for shootings and dirty streets and alleys in the school neighborhood were also significantly associated with various domains of school climate. These findings highlight the need for future longitudinal research on the influence of both school building and school neighborhood factors on school climate for public schools. Schools in our sample had a wide range of school climate scores despite consistently high crime rates and other structural risk factors such as low socioeconomic status throughout the city, so there are implications for researchers and education leaders to work together to identify opportunities for schools to foster positive school climate despite systemic school and/or neighborhood risk factors.

Interactional quality in middle schools: Latent profiles and their associations with teacher, classroom, and school compositional factors.

High quality teacher-student interactions are critical for the healthy social-emotional, behavioral, and academic development of middle school students. However, few studies have explored patterns of teacher-student interactions in middle school classrooms or the relation between teacher-, classroom-, and school-level factors and patterns of interaction. The current study employed latent profile analyses (LPA) to identify patterns of teacher-student interactional quality in a sample of 334 teachers from 41 schools serving middle school students within the Mid-Atlantic region of the U.S. Three distinct profiles of teacher-student interactional quality were identified that were characteristic of higher, lower, and intermediate quality and were differentially related to teacher, classroom, and school characteristics. Compared to classrooms with lower interactional quality, classrooms with "higher" or "intermediate" profiles were more likely to be taught by early career teachers, to have higher rates of observed student cooperation, and to be in schools in rural fringe areas. Classrooms with lower interactional quality were more likely to have larger student-to-teacher ratios and higher rates of student disruptive behaviors than classrooms with intermediate interactional quality and to be in schools with a higher percentage of out-of-school suspensions than classrooms with higher interactional quality. These findings suggest that interventions at the teacher, classroom, and school levels may promote positive teacher-student interactions, such as consultation to support teachers' effective classroom management, alternatives to out-of-school suspensions, and smaller student-to-teacher ratios.

Coordination mode dependent excited state behavior in group 8 phosphino(terthiophene) complexes.

The ground and excited state behavior of four Ru(II) and Os(II) bipyridyl complexes containing the 3'-(diphenylphosphino)-2,2':5',2''-terthiophene (PT(3)) ligand in two different coordination modes (P,S and P,C) is reported. The complexes are generally stable under extended photoirradiation, except for [Ru(bpy)(2)PT(3)-P,S](PF(6))(2) which decomposes. Emission lifetimes and transient absorption spectra and lifetimes have been obtained for all the complexes. These data support a PT(3) ligand based lowest excited state in the case of both P,S bound complexes, and a charge separated lowest excited state in both P,C bound complexes, conclusions supported by Density Functional Theory (DFT) calculations.

Organizational Context in General and Special Education: An Exploratory Investigation to Describe the Perspective of School Leaders.

Organizational context (e.g., climate, culture, resources) can impede or enhance implementation of evidence-based practices in general education settings or special education settings serving students with autism spectrum disorder. We examined the relations between organizational context and individual (i.e., implementation leadership, administrator- or service provider-role) or school (i.e., enrollment size, public/nonpublic school type) characteristics. Participants were administrative or service providing leaders (n = 34) from 11 schools in one state on the East Coast of the United States. School leaders' average ratings of the organizational context were generally more positive for special education than general education; however, greater culture stress was reported for special education. Correlation analyses indicated being an administrator and implementation leadership were positively associated with implementation climate in both education settings. Being an administrator was also positively associated with cultural effort (i.e., how hard people work towards achieving goals) in special education, but negatively associated with culture stress in general education. In special education, nonpublic schools had better climates (both learning and implementation), but more culture stress. Additionally, school enrollment size was negatively related to available resources and implementation climate in special education. Investigating the similarities and differences in organizational context across educational settings is needed in future research.

Specifying and Reporting Implementation Strategies Used in a School-Based Prevention Efficacy Trial.

BACKGROUND: Implementation strategies used to enhance the implementation of interventions during efficacy and effectiveness studies are rarely reported. Tracking and reporting implementation strategies during these phases has potential to improve future research studies and real-world implementation. We present an exemplar of how this might be executed by specifying and reporting the implementation strategies that were used during a school-based efficacy trial, Project POWER, which tested a trauma-informed prevention program delivered by a university research team, community members, and school staff facilitators in 29 schools. METHODS: Following the conclusion of the 4-year trial, core Project POWER research team members identified the implementation strategies that supported intervention delivery during the trial using an established taxonomy of school-based implementation strategies. The actors, actions, action targets, temporality, dose, and implementation outcomes were specified using established implementation strategies reporting guidelines. RESULTS: The research team identified 37 implementation strategies that were used during the Project POWER trial. Most strategies fell within the categories of Train and Educate Stakeholders, Use Evaluative and Iterative Strategies, and Develop Stakeholder Interrelationships. Actors included members of the research team and partner schools. Strategies were used multiple times during the preparation and implementation phases. Action targets were most often characteristics of individuals, implementation process, and characteristics of the inner setting. Strategies predominantly targeted the implementation outcomes of fidelity, acceptability, feasibility, and adoption. CONCLUSIONS: This study provided evidence that implementation strategies are used and can be identified in efficacy research using a retrospective approach. Identifying and specifying implementation strategies used during the initial phases of the translational research pipeline can inform the implementation strategies that are carried forward, adapted, or discontinued in future trials and routine practice to improve implementation and effectiveness outcomes.

Social and Contextual Influences on Mental Health Following an Episode of Mass Violence.

Few studies explore how the recovery context following an episode of mass violence affects posttragedy mental health (MH), despite clear implications for developing posttrauma supports. Following a mass murder, this prospective, longitudinal study examined how reactions to media coverage, family reactions, and disappointment in social support influenced posttragedy MH (posttraumatic stress, depression, anxiety), above and beyond the influence of pretragedy MH, pretragedy victimization, and objective exposure. University students who participated in a study of college adjustment prior to the mass murder (n = 593) were recontacted and provided information on their posttragedy life (n = 142). Students (n = 84) also responded to open-ended questions about what was the most stressful part of the tragedy and psychological effects of the mass murder. After accounting for pretragedy victimization and MH, and objective exposure to events, hierarchical regression analyses indicated that distress related to media coverage and stronger family reactions contributed to higher levels of posttraumatic stress symptoms and anxiety, but not depression. Disappointment with social support was not significantly related to posttragedy MH. Common themes in student comments include grief, feeling vulnerable/unsafe, concern for the impact on others, stress related to media coverage, proximity to the events, changes in psychosocial adjustment, and returning to daily life. Results suggest that negative reactions to media coverage and family reactions that are overprotective or distressing negatively affect survivors' MH, beyond their objective exposure to the violence, pretragedy MH, and pretragedy victimization.

Serum albumin and mortality in acutely decompensated heart failure.

BACKGROUND: Although hypoalbuminemia has been associated with decreased survival in chronic systolic heart failure (HF), its role for prognosticating outcomes in those with acutely decompensated heart failure (ADHF) has not been established. METHODS AND RESULTS: 438 consecutive patients with ADHF (mean age 75±13 years, mean left ventricular ejection fraction 41%±20%) admitted to a large community hospital were studied. The mean serum albumin level for the group was 3.4 g/dL; quintile analysis demonstrated an inflection of risk for death below this value. Patients with hypoalbuminemia (defined as a serum albumin<3.4 g/dL; N=236, 54% overall) were more likely to have prior HF, more severe HF symptoms, more likely to be edematous, and had more prevalent prognostically meaningful laboratory abnormalities, such as a higher frequency of renal dysfunction and elevated B-type natriuretic peptide. Independent associations between anemia, hyponatremia, lack of therapy with vasodilators at presentation, prior history of obstructive airways disease, severe tricuspid regurgitation, low serum cholesterol, and the presence of a pleural effusion on chest radiography were found with reduced serum albumin; interestingly, body mass index was not predictive of albumin levels. In Cox proportional hazards analysis, hypoalbuminemia predicted 1-year mortality (hazard ratio [HR]adjusted=2.05, 95% CI 1.10-3.81, P=.001). Reduced serum albumin concentrations were prognostic across a wide range of body mass index but had highest HR in obese patients (HRadjusted=4.39 [95% CI=1.66 to 11.60], P=.003). As well, hypoalbuminemia was mainly predictive of outcomes among those with systolic HF (HRadjusted=5.00, 95% CI=2.17-11.5, P<.001). CONCLUSION: Hypoalbuminemia is common among patients with ADHF and is independently associated with increased one year mortality in patients admitted with ADHF.

Design and methods of the Pro-B Type Natriuretic Peptide Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) Study.

BACKGROUND: Serial measurements of N-terminal pro-B type natriuretic peptide (NT-proBNP) provide prognostic information in patients with chronic heart failure (HF). Changes in NT-proBNP concentrations parallel prognosis; however, it remains unclear whether HF care with a goal to maximize medical therapy and also lower NT-proBNP concentrations is superior to standard HF care alone. AIMS: The aim of the study was to evaluate the hypothesis that an HF strategy guided by NT-proBNP reduces cardiovascular events compared to standard of care HF management. METHODS: In a prospective randomized single-center trial, subjects with New York Heart Association class II to IV systolic HF (left ventricular ejection fraction < or =40%) will be enrolled. Both groups will receive standard HF management (with a goal for minimizing HF symptoms and achieving maximal dosages of therapies with proven mortality benefit in HF), whereas one group ("NT-proBNP") will also have treatment adjustments to reduce NT-proBNP concentrations < or =1,000 pg/mL. The primary end point of the trial is total cardiovascular events for a 1-year period; secondary end points will include effects of NT-proBNP-guided care on cardiac structure and function, quality of life, and total costs of care. RESULTS: Enrollment began in 2006; of the original 300 planned, thus far, 151 subjects have been randomized. Interim analysis in November 2009 indicated significant reduction of events in the NT-proBNP arm. Full results are expected in 2010. CONCLUSIONS: The Pro-B Type Natriuretic Peptide Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) Study will test the hypothesis that therapy guided by NT-proBNP concentrations will be superior to standard of care HF management (www.clinicaltrials.gov identifier NCT00351390).