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The Methodology of Curation for Scientific Research Findings
OPINION LEADERSHIP on Cardiovascular Diseases
Volume Two
Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation
Epilogue to Volume Two
Aviva Lev-Ari, PhD, RN, Editor-in-Chief, BioMed e-Series of e-Books
Part 1: Curation is another Methodology for Creation of Scientific Knowledge.
OPINION LEADERSHIP: We are developers of new methodologies for Research Finding exposition and dissemination
The Curation process involves development of numerous avenues for exposition of the scientific product and its dissemination, among them:
- scientific articles on Scientific Journals,
- Books, e-Books
- Addresses by Leader Scientists,
- multimedia presentations (Audio and Video),
- Expert Panel Discussions,
- Correspondence among Scientists,
- archive of experiment results, thematic Literature surveys,
- Libraries of Open Source Code,
- Comprehensive Thematic Bibliographies,
- Shareable Libraries of Annotated Genomics Research
In our curations we have used several from the above list. We take great pride in our presentations of critiques and synthesis of research results. We represent one alternative to Academic Publishing. Instead of divergence into millions of publications per year, we focus on the Frontier, we select several seminal articles and aggregate the outcomes, their significance in context and creatively we identify interrelationsnot included in each of the components of the assembly.
Part 2: Cardiovascular Diseases – Predicted Cost of Care and the Affordable Care Act
- Cost of Care for Cardiovascular Medical Diagnoses
- Impact of 2013 HealthCare Reform in the US
- Patient Protection and Affordable Care Act Featured at RAND
OPINION LEADERSHIP: We identify the potential of Cardiac Regeneration to be the frontier for Cardiovascular Disease near-cure
In the United States, heart failure afflicts about 6 million people (1), costs $34.4 billion each year (2), and is now the single most common discharge diagnosis in those over 65 (3). Although enormous progress has been made in managing acute cardiovascular illnesses such as heart attacks, many patients go on to develop late sequelae of their disease, including heart failure and arrhythmia. Thus, the growing number of these patients in some ways represents a burden of our success. It also reflects the incomplete success of most current therapies, which mitigate and manage but do not cure the disease.
https://www.sciencemag.org/content/338/6114/1549.summary
OPINION LEADERSHIP: We identify ACCESS to HealthCare Services to be the cardinal factor of success for the Affordable Care Act (ACA).
On January 10, 2014 Jonathan Cohn wrote in the New Republic: The Kids Are Alright: Another Obamacare Lesson from Massachusetts
Youth is not be the same thing as health. A 33-year-old with diabetes will run up bigger physician and drug bills than a 61-year-old with no serious medical problems. But, as a general rule, younger means healthier. And the early numbers haven’t seemed that encouraging.
Overall, according to a study by the Kaiser Family Foundation, about 40 percent of the people who could eventually buy coverage through Obamacare marketplaces are between the ages of 18 and 34. But, as of December, just 22 percent of the people signing up for coverage in California were in that demographic. Other states reported similar data. The federal government hasn’t yet provided an age breakdown for people getting insurance through healthcare.gov, the website it operates on behalf of 36 other states. But it will probably provide that information soon. When it does, the numbers may not look any better.
Is this a big deal? One way to answer that question is by looking at the best test case available: Massachusetts, which introduced a similar reform scheme in 2007. Thanks to analysis from Jonathan Gruber, the MIT economist who was an architect of both the Massachusetts and federal reforms, we know that enrollment was slow to get rolling in Massachusetts—and that, relatively speaking, healthy people came into the system late. Now Gruber has done a new analysis, breaking down enrollment specifically by age, and provided it to the New Republic.
The graph above tells the story. Over the course of the first year, the proportion of young people (in this case, ages 19 to 34) who had obtained health coverage through the Massachusetts insurance exchange grew. In other words, they were more likely to sign up late.
The precise figures don’t mean a lot, in part because the Massachusetts analogy is hardly perfect. John Sexton of Breitbart (yes, that Breitbart) has written about some of the key distinctions. But the trend is pretty clear—and, according to Gruber, it provides some important lessons. “These data aren’t 100 percent predictive for every state, most importantly because of differences across states in the share of the potential market that is young,” Gruber says. “But these facts highlight two things. First, you don’t need a huge/majority share of enrollees to be young for markets to function well. Second, the young tend to wait to sign up until closer to the deadline.
Obamacare could obviously unfold differently, with plenty of variation from state to state. In some places, participation among the young might not rise the way it did in Massachusetts—or, at least, it might not reach the same levels. But that doesn’t mean those states are destined for an insurance “death spiral,” in which carriers jack up rates so high that only the very sick stay in the system.
Part 3: Causes of Cardiovascular Diseases
- Human Genome: Congenital Etiological Sources of Cardiovascular Disease
- The Role of Calcium in Health and Disease
- Vasculature and Myocardium: Diagnosing the Conditions of Disease
OPINION LEADERSHIP: We identify two pivotal research directions in the effort to understand the Etiology of Cardiovascular Diseases
1. The Research Frontier on Cardiac Regeneration by Anthony Rosenzweig, M.D.
Professor of Medicine, Beth Israel Deaconess Medical Center on Cardiac Regeneration and How does Excercise help the Heart
This article represents the FRONTIER on Cardiac Regeneration as developed by Anthony Rosenzweig in Science 338, 1549 (2012).
Point #1: Current Pharmacotherapy for Cardiovascular Diseases and Heart Failure
Point #2: Dynamic model for the Adult heart capacity for cardiomyogenesis to compensate for losses occurring in heart failure: recognition of even limited regenerative capacity in the heart
Point #3: Results of Multiple Cell Therapy Clinical Trials
Point #4: The Endogenous Regeneration Potential
Point #5: On pathways regulating cardiomyocyte regeneration in animal models
Point #6: Prof. A. Rosenzweig’s Summary and His Future Outlook of Cardiac Regeneration
- We are still relatively early in the development of new approaches to cardiovascular disease. It will be some time before we know the conclusion of what will likely be a long and challenging road ahead.
- Almost as challenging is conveying to patients and policymakers an appropriate perspective that balances unmitigated enthusiasm for the scientific discoveries, cautious optimism for the broader implications, and humble acknowledgment that though even the most appealing ideas may fail, there is only one way to find out.
Anthony Rosenzweig, M.D. Professor of Medicine, Beth Israel Deaconess Medical Center
We are interested in why the heart fails. Heart failure is an enormous and growing cause of death and disability throughout the world. In addition, the heart provides a model system for studying fundamental cellular processes from cell growth and programmed death, to cell-lineage determination and regeneration. Recently we’ve been interested in understanding how exercise protects the heart against heart failure. A variety of high throughput profiling techniques are being used to identify pathways differentially regulated in heart growth associated with exercise in comparison to the heart growth that precedes heart failure. A recently identified transcriptional pathway involved C/EBPβ and CITED4 not only reproduces many of the effects of exercise and protects the heart from heart failure, but appears to enhance the heart’s regenerative capacity(Bostrom et al Cell, 2010). In vivo gain- and loss-of-function models are being used to explore the functional effects and molecular mechanisms of this pathway in more detail. Other ongoing studies are investigating cardiac micro-RNAs regulated by exercise and their potential protective effects in the heart.
http://connects.catalyst.harvard.edu/Profiles/display/Person/10161
2. Biology of the Nucleus and Gene Expression @ Spiegelman Lab, Harvard Medical School
- Transcriptional Basis of Energy Metabolism
- Regulation of Fat Cell Differentiation
- Metabolic Control through the PGC-1 Coactivators
- Chemical Biology of the PGC-1 Coactivators
β-Aminoisobutyric Acid Induces Browning of White Fat and Hepatic β-Oxidation and Is Inversely Correlated with Cardiometabolic Risk Factors. Cell Metab. 2014 Jan 7;19(1):96-108. doi: 10.1016/j.cmet.2013.12.003.
Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab. 2013 Nov 5;18(5):649-59. doi: 10.1016/j.cmet.2013.09.008. Epub 2013 Oct 10.
http://research4.dfci.harvard.edu/spiegelmanlab/research.htm
Part 4: Risks and Biomarkers for Cardiovascular Diseases
OPINION LEADERSHIP: We identify as fruitful area of further study –
1. Genetic Determinants of Potassium Sensitivity and Hypertension. Integrated Computational and Experimental Analysis of the Neuroendocrine Transcriptome in Genetic Hypertension Identifies Novel Control Points for the Cardiometabolic Syndrome
2. Essential hypertension, a common complex disease, displays substantial genetic influence. Contemporary methods to dissect the genetic basis of complex diseases such as the genomewide association study are powerful, yet a large gap exists betweens the fraction of population trait variance explained by such associations and total disease heritability.
3. There are many roles for biomarkers to be subject for further research:
- risk assessment
- disease status
- mechanism of injury
- severity of disease
- response to interventions
The following topics address a small set of examples from an exhausting list of biomarkers:
- The Role of Calcium in Health and Disease
- Vasculature and Myocardium: Diagnosing the Conditions of Disease
- Conduction Dysfunction and ElectroPhysiology of the Heart
- Cardiovascular Imaging: Diagnosing the Condition of the Disease and Determining Course of Treatment
Part 5: Advances in Treatment of Cardiovascular Diseases
- Vasculature and Myocardium: Diagnosing the Conditions of Disease
- The Role of Calcium in Health and Disease
- Conduction Dysfunction and ElectroPhysiology of the Heart
- Cardiovascular Imaging: Diagnosing the Condition of the Disease and Determining Course of Treatment
OPINION LEADERSHIP: We identify the frontier of Treatment for Cardiovascular diseases to embrace potentially the following trends:
Sources of Evidence in Identifying Risk Factors for Cardiovascular Disease will continue to be derived from a combination of research methodologies:
- Basic research
- Epidemiological research
- Descriptive
- Analytical
- Observational
- Case-control studies
- Cohort studies
- Randomized trials
Physical Activity:
- Cumulative long-term PA has a protective effect on incidence of all-cause and CVD-attributable mortality compared with long-term physical inactivity.
- In men, but not women, long-term PA also appears to have a protective effect on incidence of CVD.
Is it Hypertension or Physical Inactivity: Cardiovascular Risk and Mortality – New results in 3/2013
Heart doi:10.1136/heartjnl-2012-303461
Cardiovascular Imaging:
Comparison of the longitudinal, radial, circumferential, rotational and torsional mechanics of the left ventricle (LV) in patients with constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM), and detect the new quantitative parameters to differentiate CP and RCM using two-dimensional speckle tracking imaging (2-D STI) method. Torsion, longitudinal and radial strain measured by 2-D STI method can provide useful information to differentiate CP and RCM.
http://heart.bmj.com/content/97/Suppl_3/A210.2.abstract
Pharmacotherapy:
Increase in use of Biological Based Therapy (BBT) among cardiovascular patients to avoid side effects of prescription drugs.
In recent years, the interest of using Biological Based Therapy (BBT) in disease management has increased dramatically in the medical and layman communities. The amount of valid scientific research in this area of therapy continues to increase. Yet, there are still many unknowns concerning BBT, especially in the area of adverse effects and drug interactions. The finding of a high prevalence of BBT (47.5%) use among cardiovascular patients and the lack of communication between patients and their physicians/pharmacists should be addressed by the health care community. Higher education level, as shown in the present study and other previous investigations [1,3,6,22], is associated with an increased use of BBT, but it does not necessarily mean that these patients are aware of the potential detrimental effects of BBT, as demonstrated in the current study. In cardiovascular patients, the perceived effectiveness and safety of BBT, and assumed lack of side effects of these products as opposed to traditional medications, highlights an area for further education. A high incidence of potential drug-BBT interactions was also identified in this study (42 interactions in 94 users). Given that the use of BBT can have a direct effect on patient care, and users of these therapies do not always voluntarily report their use of these products to their providers, health care professionals need to inquire about BBT use routinely. Collecting complete patient histories and educating patients about potential dangers and possibilities of adverse effects and interactions between prescription medications and BBT (or other CAM) will lead to better overall patient care.
http://www.biomedcentral.com/1472-6882/5/4
Genomics is been harnessed for Familial and non-familial Cardomyopathies Diagnosis and Treatment
Genetic and phenotypic heterogeneity that characterises all cardiomyopathies pose major clinical challenges. In this article, we focus on the task of diagnosis, exploring how a systematic clinical approach can be used to identify specific disorders and guide the selection of further diagnostic tests, including molecular genetic analysis.
Cardiomyopathies are defined as disorders of heart muscle unexplained by coronary artery disease, hypertension, valvular disease or congenital heart disease.1 They are classified by morphological and functional phenotype into
- hypertrophic cardiomyopathy (HCM),
- dilated cardiomyopathy (DCM),
- restrictive cardiomyopathy (RCM), and
- arrhythmogenic right ventricular cardiomyopathy (ARVC) subtypes
http://heart.highwire.org/content/99/19/1451.extract
Iron Metabolism and Mitochondrial Mechanisms
Mitochondrial iron trafficking and the integration of iron metabolism between the mitochondrion and cytosol
The field of mitochondrial iron metabolism and trafficking that has recently been stimulated by the discovery of proteins involved in mitochondrial iron storage (mitochondrial ferritin) and transport (mitoferrin-1 and -2). In addition, recent work examining mitochondrial diseases (e.g., Friedreich’s ataxia) has established that communication exists between iron metabolism in the mitochondrion and the cytosol. This finding has revealed the ability of the mitochondrion to modulate whole-cell iron-processing to satisfy its own requirements for the crucial processes of heme and ISC synthesis. Knowledge of mitochondrial iron-processing pathways and the interaction between organelles and the cytosol could revolutionize the investigation of iron metabolism.
http://www.pnas.org/content/early/2010/05/20/0912925107
Role of Calcium and Gene therapy in treatment of Pulmonary Arterial Hypertension and Heart Failure
Inhalable Gene Therapy for Pulmonary Arterial Hypertension and Percutaneous Intra-coronary Artery Infusion for Heart Failure
Sinus Node Dysfunction (SND): Patient Education
Educate patients to recognize symptoms of SND. Family members should learn cardiopulmonary resuscitation (CPR).
Because most pediatric patients with SND have already received surgery for CHD (eg, Mustard procedure, Fontan procedure), their education is focused on recognizing symptoms of CHF and tachyarrhythmias, such as atrial flutter/fibrillation, which are usually poorly tolerated.
Patients who are on antiarrhythmic medication for atrial flutter or fibrillation should be instructed to take their medication regularly and to visit the cardiologist as scheduled. They should also be cognizant of the adverse effects and toxicity of the medication.
In patents who have already received a Mustard or Fontan procedure, undergoing yearly echocardiography to monitor cardiac function is advisable. If cardiac function is decreased, anti-CHF management should be started and close follow-ups with the cardiologist are advisable.
Patients who have a pacemaker should be instructed on the means of obtaining regular checks. Such checks are usually achieved from home with a transtelephonic monitor that transmits to a central monitoring station, which, in turn, contacts the cardiologist in case a problem is detected (eg, device malfunction, arrhythmia).
Patients who have an intracardiac defibrillator (ICD) device should receive the same instructions that patients who have pacemakers receive. Because patients with ICDs often are placed on antiarrhythmic medication, they also should receive instruction regarding medication schedules and information about adverse effects and toxicity.
In addition, in patients with frequent atrial flutter or fibrillation episodes, which are followed by a shock from the ICD, patients are instructed to avoid activities that may pose a risk to themselves and/or other people (eg, driving). They also receive instruction on when to go to the cardiologist or the emergency department.
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