Carvedilol reduces the costs of medical care in severe heart failure: An economic analysis of the COPERNICUS study applied to the United Kingdom

Background: The aim of this study was to determine the effects of carvedilol on the costs related to the treatment of severe chronic heart failure (CHF). Methods: Costs for the treatment for heart failure within the National Health Service (NHS) in the United Kingdom (UK) were applied to resource utilisation data prospectively collected in all patients randomized into the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study. Unit-specific, per them (hospital bed day) costs were used to calculate expenditures due to hospitalizations. We also included costs of carvedilol treatment, general practitioner surgery/office visits, hospital out-patient clinic visits and nursing home care based on estimates derived from validated patterns of clinical practice in the UK. Results: The estimated cost of carvedilol therapy and related ambulatory care for the 1156 patients assigned to active treatment was 530,771 pound (44.89 pound per patient/month of follow-up). However, patients assigned to carvedilol were hospitalised less often and accumulated fewer and less expensive days of admission. Consequently, the total estimated cost of hospital care was 3.49 pound million in the carvedilol group compared with 4.24 pound million for the 1133 patients in the placebo arm. The cost of post-discharge care was also less in the carvedilol than in the placebo group (479,200 pound vs. 548,300) pound. Overall, the cost per patient treated in the carvedilol group was 3948 pound compared to 4279 pound in the placebo group. This equated to a cost of 385.98 pound vs. 434.18 pound, respectively, per patient/month of follow-up: an 11.1% reduction in health care costs in favour of carvedilol. Conclusions: These findings suggest that not only can carvedilol treatment increase survival and reduce hospital admissions in patients with severe CHF but that it can also cut costs in the process.

Is mortality from heart failure increasing in Australia? An analysis of official data on mortality for 1997-2003

Objective To assess whether trends in mortality from heart failure(HF) in Australia are due to a change in awareness of the condition or real changes in its epidemiology. Methods We carried out a retrospective analysis of official data on national mortality data between 1997 and 2003. A death was attributed to HF if the death certificate mentioned HF as either the underlying cause of death (UCD) or among the contributory factors. Findings From a total of 907 242 deaths, heart failure was coded as the UCD for 29 341 (3.2%) and was mentioned anywhere on the death certificate in 135 268 (14.9%). Between 1997 and 2003, there were decreases in the absolute numbers of deaths and in the age-specific and age-standardized mortality rates for HF either as UCD or mentioned anywhere for both sexes. HF was mentioned for 24.6% and 17.8% of deaths attributed to ischaemic heart disease and circulatory disease, respectively, and these proportions remained unchanged over the period of study. In addition, HF as UCD accounted for 8.3% of deaths attributed to circulatory disease and this did not change materially from 1997 to 2003. Conclusion The decline in mortality from HF measured as either number of deaths or rate probably reflects a real change in the epidemiology of HF. Population-based studies are required to determine accurately the contributions of changes in incidence, survival and demographic factors to the evolving epidemiology of HF.

An automated failure mode and effect analysis based on high-level design specificication with behavior trees

Formal methods have significant benefits for developing safety critical systems, in that they allow for correctness proofs, model checking safety and liveness properties, deadlock checking, etc. However, formal methods do not scale very well and demand specialist skills, when developing real-world systems. For these reasons, development and analysis of large-scale safety critical systems will require effective integration of formal and informal methods. In this paper, we use such an integrative approach to automate Failure Modes and Effects Analysis (FMEA), a widely used system safety analysis technique, using a high-level graphical modelling notation (Behavior Trees) and model checking. We inject component failure modes into the Behavior Trees and translate the resulting Behavior Trees to SAL code. This enables us to model check if the system in the presence of these faults satisfies its safety properties, specified by temporal logic formulas. The benefit of this process is tool support that automates the tedious and error-prone aspects of FMEA.

Medical students' personal experience of high-stakes failure:case studies using interpretative phenomenological analysis

Abstract (provisional): Background Failing a high-stakes assessment at medical school is a major event for those who go through the experience. Students who fail at medical school may be more likely to struggle in professional practice, therefore helping individuals overcome problems and respond appropriately is important. There is little understanding about what factors influence how individuals experience failure or make sense of the failing experience in remediation. The aim of this study was to investigate the complexity surrounding the failure experience from the student’s perspective using interpretative phenomenological analysis (IPA). Methods The accounts of 3 medical students who had failed final re-sit exams, were subjected to in-depth analysis using IPA methodology. IPA was used to analyse each transcript case-by-case allowing the researcher to make sense of the participant’s subjective world. The analysis process allowed the complexity surrounding the failure to be highlighted, alongside a narrative describing how students made sense of the experience. Results The circumstances surrounding students as they approached assessment and experienced failure at finals were a complex interaction between academic problems, personal problems (specifically finance and relationships), strained relationships with friends, family or faculty, and various mental health problems. Each student experienced multi-dimensional issues, each with their own individual combination of problems, but experienced remediation as a one-dimensional intervention with focus only on improving performance in written exams. What these students needed to be included was help with clinical skills, plus social and emotional support. Fear of termination of the their course was a barrier to open communication with staff. Conclusions These students’ experience of failure was complex. The experience of remediation is influenced by the way in which students make sense of failing. Generic remediation programmes may fail to meet the needs of students for whom personal, social and mental health issues are a part of the picture.

A meta -analysis of empirical research studies on resilience among students at -risk for school failure

Being at-risk is a growing problem in the U.S. because of disturbing societal trends such as unemployment, divorce, substance abuse, child abuse and neglect, and the new threat of terrorist violence. Resilience characterizes individuals who rebound from or adapt to adversities such as these, and academic resilience distinguishes at-risk students who succeed in school despite hardships. ^ The purpose of this research was to perform a meta-analysis to examine the power of resilience and to suggest ways educators might improve academic resilience, which was operationalized by satisfactory test scores and grades. In order to find all studies that were relevant to academic resilience in at-risk kindergarten through 12th-grade students, extensive electronic and hardcopy searches were conducted, and these resulted in a database of 421 articles. Two hundred eighty seven of these were rejected quickly, because they were not empirical research. Upon further examination, another 106 were rejected for not meeting study protocol criteria. Ultimately, 28 studies were coded for study level descriptors and effect size variables. ^ Protective factors for resilience were found to originate in physical, psychological, and behavioral domains on proximal/intraindividual, transitional/intrafamilial, or distal/extrafamilial levels. Effect sizes (ESs) for these were weighted and the means for each level or category were interpreted by commonly accepted benchmarks. Mean effect sizes for proximal (M = .27) and for transitional (M = .15) were small but significant. The mean effect size for the distal level was insignificant. This supported the hypotheses that the proximal level was the source of most protective factors for academic resilience in at-risk students followed by the transitional level. The distal effect size warranted further research particularly in light of the small number of studies (n = 11) contributing effect sizes to that category. A homogeneity test indicated a search for moderators, i.e., study variables affecting outcomes, was justified. “Category” was the largest moderator. Graphs of weighted mean effect sizes in the physical, psychological, and behavioral domains were plotted for each level to better illustrate the findings of the meta-analysis. Suggestions were made for combining resilience development with aspects of positive psychology to promote resilience in the schools. ^

Predicting success or failure of tax -base revenue sharing attempts: A comparative analysis

To promote regional or mutual improvement, numerous interjurisdictional efforts to share tax bases have been attempted. Most of these efforts fail to be consummated. Motivations to share revenues include: narrowing fiscal disparities, enhancing regional cooperation and economic development, rationalizing land-use, and minimizing revenue losses caused by competition to attract and keep businesses. Various researchers have developed theories to aid understanding of why interjurisdictional cooperation efforts succeed or fail. Walter Rosenbaum and Gladys Kammerer studied two contemporaneous Florida local-government consolidation attempts. Boyd Messinger subsequently tested their Theory of Successful Consolidation on nine consolidation attempts. Paul Peterson's dual theories on Modern Federalism posit that all governmental levels attempt to further economic development and that politicians act in ways that either further their futures or cement job security. Actions related to the latter theory often interfere with the former. Samuel Nunn and Mark Rosentraub sought to learn how interjurisdictional cooperation evolves. Through multiple case studies they developed a model framing interjurisdictional cooperation in four dimensions. ^ This dissertation investigates the ability of the above theories to help predict success or failure of regional tax-base revenue sharing attempts. A research plan was formed that used five sequenced steps to gather data, analyze it, and conclude if hypotheses concerning the application of these theories were valid. The primary analytical tools were: multiple case studies, cross-case analysis, and pattern matching. Data was gathered from historical records, questionnaires, and interviews. ^ The results of this research indicate that Rosenbaum-Kammerer theory can be a predictor of success or failure in implementing tax-base revenue sharing if it is amended as suggested by Messinger and further modified by a recommendation in this dissertation. Peterson's Functional and Legislative theories considered together were able to predict revenue sharing proposal outcomes. Many of the indicators of interjurisdictional cooperation forwarded in the Nunn-Rosentraub model appeared in the cases studied, but the model was not a reliable forecasting instrument. ^

Individual Differences in the Neural Response to Personal Goal Pursuit Success and Failure: A Developmental Analysis

Regulatory focus theory (RFT) proposes two different social-cognitive motivational systems for goal pursuit: a promotion system, which is organized around strategic approach behaviors and "making good things happen," and a prevention system, which is organized around strategic avoidance and "keeping bad things from happening." The promotion and prevention systems have been extensively studied in behavioral paradigms, and RFT posits that prolonged perceived failure to make progress in pursuing promotion or prevention goals can lead to ineffective goal pursuit and chronic distress (Higgins, 1997).

Research has begun to focus on uncovering the neural correlates of the promotion and prevention systems in an attempt to differentiate them at the neurobiological level. Preliminary research suggests that the promotion and prevention systems have both distinct and overlapping neural correlates (Eddington, Dolcos, Cabeza, Krishnan, & Strauman, 2007; Strauman et al., 2013). However, little research has examined how individual differences in regulatory focus develop and manifest. The development of individual differences in regulatory focus is particularly salient during adolescence, a crucial topic to explore given the dramatic neurodevelopmental and psychosocial changes that take place during this time, especially with regard to self-regulatory abilities. A number of questions remain unexplored, including the potential for goal-related neural activation to be modulated by (a) perceived proximity to goal attainment, (b) individual differences in regulatory orientation, specifically general beliefs about one's success or failure in attaining the two kinds of goals, (c) age, with a particular focus on adolescence, and (d) homozygosity for the Met allele of the catechol-O-methyltransferase (COMT) Val158Met polymorphism, a naturally occurring genotype which has been shown to impact prefrontal cortex activation patterns associated with goal pursuit behaviors.

This study explored the neural correlates of the promotion and prevention systems through the use of a priming paradigm involving rapid, brief, masked presentation of individually selected promotion and prevention goals to each participant while being scanned. The goals used as priming stimuli varied with regard to whether participants reported that they were close to or far away from achieving them (i.e. a "match" versus a "mismatch" representing perceived success or failure in personal goal pursuit). The study also assessed participants' overall beliefs regarding their relative success or failure in attaining promotion and prevention goals, and all participants were genotyped for the COMT Val158Met polymorphism.

A number of significant findings emerged. Both promotion and prevention priming were associated with activation in regions associated with self-referential cognition, including the left medial prefrontal cortex, cuneus, and lingual gyrus. Promotion and prevention priming were also associated with distinct patterns of neural activation; specifically, left middle temporal gyrus activation was found to be significantly greater during prevention priming. Activation in response to promotion and prevention goals was found to be modulated by self-reports of both perceived proximity to goal achievement and goal orientation. Age also had a significant effect on activation, such that activation in response to goal priming became more robust in the prefrontal cortex and in default mode network regions as a function of increasing age. Finally, COMT genotype also modulated the neural response to goal priming both alone and through interactions with regulatory focus and age. Overall, these findings provide further clarification of the neural underpinnings of the promotion and prevention systems as well as provide information about the role of development and individual differences at the personality and genetic level on activity in these neural systems.

Proteomic analysis of coronary sinus serum reveals leucine-rich α2-glycoprotein as a novel biomarker of ventricular dysfunction and heart failure

BACKGROUND: Heart failure (HF) prevention strategies require biomarkers that identify disease manifestation. Increases in B-type natriuretic peptide (BNP) correlate with increased risk of cardiovascular events and HF development. We hypothesize that coronary sinus serum from a high BNP hypertensive population reflects an active pathological process and can be used for biomarker exploration. Our aim was to discover differentially expressed disease-associated proteins that identify patients with ventricular dysfunction and HF.

METHODS AND RESULTS: Coronary sinus serum from 11 asymptomatic, hypertensive patients underwent quantitative differential protein expression analysis by 2-dimensional difference gel electrophoresis. Proteins were identified using mass spectrometry and then studied by enzyme-linked immunosorbent assay in sera from 40 asymptomatic, hypertensive patients and 105 patients across the spectrum of ventricular dysfunction (32 asymptomatic left ventricular diastolic dysfunction, 26 diastolic HF, and 47 systolic HF patients). Leucine-rich α2-glycoprotein (LRG) was consistently overexpressed in high BNP serum. LRG levels correlate significantly with BNP in hypertensive, asymptomatic left ventricular diastolic dysfunction, diastolic HF, and systolic HF patient groups (P≤0.05). LRG levels were able to identify HF independent of BNP. LRG correlates with coronary sinus serum levels of tumor necrosis factor-α (P=0.009) and interleukin-6 (P=0.021). LRG is expressed in myocardial tissue and correlates with transforming growth factor-βR1 (P<0.001) and α-smooth muscle actin (P=0.025) expression.

CONCLUSIONS: LRG was identified as a serum biomarker that accurately identifies patients with HF. Multivariable modeling confirmed that LRG is a stronger identifier of HF than BNP and this is independent of age, sex, creatinine, ischemia, β-blocker therapy, and BNP.

Analysis of the failure of cracked biscuits

Cracks or checks in biscuits weaken the material and cause the product to break at low load levels that are perceived as injurious to product quality. In this work, the structural response of circular digestive biscuits, with diameter 72 mm and thickness 7.2 mm, simply supported around the circumference and loaded by a central concentrated force was investigated by experiment and theory. Tests were conducted to quantify the distribution in breakage strength for structurally sound biscuits, biscuits with natural checks and biscuits with a single known part-through crack. For sound biscuits the breakage force is Normally distributed with a mean of 12.5 N and standard deviation of 1.2 N. For biscuits with checks, the corresponding statistics are 9.6 N ± 2.62 N respectively. The presence of a crack weakens the biscuit and strength, as measured by breakage force falls almost linearly with crack length and crack depth. The orientation of the crack, whether radial or tangential, and its location (i.e. position of the crack mid-point on the biscuit surface) are also important. Deep, radial, cracks located close to the biscuit centre can reduce the strength by up to 50%. Two separate failure criteria were examined for sound and cracked biscuits respectively. The results from these tests were in good accord with theory. For a biscuit without defects, breakage occurred when maximum biscuit stress reached or exceeded the failure stress of 420 kPa. For a biscuit with cracks, breakage occurred as above or alternatively when its critical stress intensity factor of 18 kPam0.5 was reached.

What Are Effective Program Characteristics of Self-Management Interventions in Patients With Heart Failure? : An Individual Patient Data Meta-analysis

Background To identify those characteristics of self-management interventions in patients with heart failure (HF) that are effective in influencing health-related quality of life, mortality, and hospitalizations. Methods and Results Randomized trials on self-management interventions conducted between January 1985 and June 2013 were identified and individual patient data were requested for meta-analysis. Generalized mixed effects models and Cox proportional hazard models including frailty terms were used to assess the relation between characteristics of interventions and health-related outcomes. Twenty randomized trials (5624 patients) were included. Longer intervention duration reduced mortality risk (hazard ratio 0.99, 95% confidence interval [CI] 0.97–0.999 per month increase in duration), risk of HF-related hospitalization (hazard ratio 0.98, 95% CI 0.96–0.99), and HF-related hospitalization at 6 months (risk ratio 0.96, 95% CI 0.92–0.995). Although results were not consistent across outcomes, interventions comprising standardized training of interventionists, peer contact, log keeping, or goal-setting skills appeared less effective than interventions without these characteristics. Conclusion No specific program characteristics were consistently associated with better effects of self-management interventions, but longer duration seemed to improve the effect of self-management interventions on several outcomes. Future research using factorial trial designs and process evaluations is needed to understand the working mechanism of specific program characteristics of self-management interventions in HF patients.