Leaders in Pharmaceutical Business Intelligence Group, LLC, Doing Business As LPBI Group, Newton, MA

Archive for the ‘Bio Instrumentation in Experimental Life Sciences Research’ Category

Why should Quality Assurance be difficult and awkward? Take a strategic view on achieving compliance (focus on ISO 13485)

Posted in Academic Publishing, Advanced Drug Manufacturing Technology, Bio Instrumentation in Experimental Life Sciences Research, Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Prevention: Research & Programs, Cardiac and Cardiovascular Surgical Procedures, Drug Delivery Platform Technology, Ecosystems & Industrial Concentration in the Medical Device Sector, FDA Regulatory Affairs, FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, GLP, ISO 14155, Health Economics and Outcomes Research, HealthCare IT, Imaging-based Cancer Patient Management, International Global Work in Pharmaceutical, ISO 10993 for Product Registration: FDA & CE Mark for Development of Medical Devices and Diagnostics, Medical Devices R&D Investment, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Melatonin & Circadian Regulation, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Population Health Management, Genetics & Pharmaceutical, Quality Assurance, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Technology Transfer: Biotech and Pharmaceutical, Translational Research, Translational Science, tagged CE, Confluence, Design control, Document management, European medical device directive, FDA, ISO, ISO 13485, JIRA, product traceability, QA Procedures, Quality Assurance, Records, regulations, Reimbursement on January 17, 2014| 1 Comment »

Why should Quality Assurance be difficult and awkward? Take a strategic view on achieving compliance (focus on ISO 13485)

 Reporter: Dror Nir, PhD

Converting life-science innovations into useful products involves allocation of significant resources to handling of regulatory processes. A typical approach that makes the management of these processes difficult and awkward is starting your project and later patching it with a QA system. It then becomes a source of sever headaches to many people who need to live and operate according to such patch.

I hope that the following post by Rina will inspire you all.

It is all too easy to dive into the list of requirements contained within the ISO 13485 and achieve compliance by just ticking the boxes: looking at one requirement or one area at a time and making sure you have put in place something to address that requirement. This may easily result in a quality system that feels like a patchwork. Compliant, perhaps, but most certainly awkward and difficult to sustain.

The second most common mistake is to not ask yourself how software tools can help in setting up the quality system. “We already have MS Word, MS Excel, email, and we can always print a document and have it signed.” This is only a solution if you think that the quality system is a one-off activity. In the longer run, the system turns out to be a constant struggle with non-integrated elements that have no cohesion.

A better way to address compliance is to:

1. Accept the fact that the quality system is a long term commitment and that it is very demanding.
2. Assume that the right software tools do help.
3. Think strategically, reviewing the whole standard, and try to identify the different areas, in respect to what type of software would help address those.

---

Real life example: A company maintains an Excel list of all corrective actions. The date of effectiveness check is filled in manually. A QA engineer needs to review the Excel spreadsheet once a week to identify which effectiveness checks are due. Last audit revealed that in most cases, effectiveness checks were not followed up.

Real life question: Meetings and other events are registered in a calendar and you are reminded when they are due. Wouldn’t it be easier if effectiveness checks due dates were also linked to a calendar? Putting those dates in Excel does not make more sense than putting your meetings in Excel…..

---

What follows is how we can divide the ISO-13485:2003 in regard to the type of software features which can help us. You do not need to be an IT expert to follow the logic or the explanation – if you know the standard and see my examples hopefully you will get the idea.

In any case, I put here the complete mapping of the ISO into the different categories I describe. I also mention the main Atlassian tools we use to address each area. In future posts we will dive deeper into each of those categories and provide more details on exactly how we achieve easy and sustainable, compliance.

So, as promised, these are the various categories that appear in the ISO 13485:2003:

1. Document management: These are the various requirements relating to the procedures, manuals, and device related documents you need to have, and how they should be handled within the organization. The ISO elaborates in quite a detailed manner about how the controlled documents needs to be approved, who should access them, etc. Confluence is the key tool we use to handle all these requirements.
2. Procedures and records are the evidence that the organization lives up to its quality system: The various procedures and work instructions should be followed consistently on a daily basis, forms or other records should be collected as evidence. Some examples (with reference to the standard section):
   • Training( 6.2.2).
   • Customer complaints: (8.5.1).
   • Corrective and preventive actions: (8.5.2, 8.5.3)
   • Subcontractor approvals( 7.4.1)
   • Purchasing forms( 7.4.1).

Those records may be created as electronic or physical paper forms which need to be completed by the authorized person. However, a much better way is to implement an automatic workflow that makes it easier for the team to create, follow, and document all the various tasks they need to do. Such a workflow can automatically schedule tasks, remind and alert, thus triggering better compliance to the quality system and at the same time automatically creating the required records. This is a double win. JIRA® is our tool of choice and it provides a state-of-the-art solution to everything related to forms and workflows.

3. Design control: Some of the issues covered by section 7 of the ISO 13485 require quite advanced control along several phases of design and development. The risk mitigation measures and the product requirements should be, for example, verified in the product verification stage. This verification, or the test file, could be written as a simple Word or Excel document, but a far better implementation is to create it within JIRA. The advantage of JIRA here is the various reporting that it allows once the data is in and the fact that it can connect directly into the work scheduling of the various team members. JIRA is the principal tool we use for design control. Confluence can be used in some advanced implementations. If the medical device involves software, then the development suite from Atlassian can be implemented to provide a complete software life cycle management suite.
4. Manufacturing and product traceability: Some requirements relate to your manufacturing setup. Depending on the scale and type of manufacturing, specialized ERP may be the best option. When manufacturing is more basic and does not call for a full blown manufacturing facility, JIRA can handle the requirements of the standard.
5. Monitoring and improving: A key theme of the standard is the need of the organization to measure and improve (for example, section 8.2.3). The nice thing is that the framework we have put in place to support the other categories, if done correctly, should provide us with the reports, alerts, and statistics we need. Indeed, all the processes we have implemented in JIRA, as well as the various elements we have implemented in Confluence, may easily be collected and displayed in practically endless variations of reports and dashboards.

Requirement (Article)	Requirement type
4.Quality management system – 1.General requirements	Non specific
4.Quality management system – 2.Documentation requirements – 1.General	Document management
4.Quality management system – 2.Documentation requirements – 2.Quality manual	Document management
4.Quality management system – 2.Documentation requirements – 3.Control of documents	Document management
4.Quality management system – 2.Documentation requirements – 4.Control of records	Procedures and records
5.Management responsibility – 1.Management commitment	Document management
5.Management responsibility – 2.Customer focus	Non specific
5.Management responsibility – 3.Quality policy	Monitoring and ongoing improvement
5.Management responsibility – 4.Planning – 1.Quality objectives	Monitoring and ongoing improvement
5.Management responsibility – 4.Planning – 2.Quality management system planning	Monitoring and ongoing improvement
5.Management responsibility – 5.Responsibility, authority and communication – 1.Responsibility and authority	Document management
5.Management responsibility – 5.Responsibility, authority and communication – 2.Management representative	Monitoring and ongoing improvement
5.Management responsibility – 5.Responsibility, authority and communication – 3.Internal communication	Monitoring and ongoing improvement
5.Management responsibility – 6.Management review – 1.General	Monitoring and ongoing improvement
5.Management responsibility – 6.Management review – 2.Review input	Monitoring and ongoing improvement
5.Management responsibility – 6.Management review – 3.Review output	Monitoring and ongoing improvement
6.Resource management – 1.Provision of resources	Non specific
6.Resource management – 2.Human resources – 1.General	Procedures and records
6.Resource management – 2.Human resources – 2.Competence, awareness and training	Procedures and records
6.Resource management – 3.Infrastructure	Manufacturing and product traceability
6.Resource management – 4.Work environment	Non specific
7.Product realization – 1.Planning of product realization	Design control
7.Product realization – 2.Customer-related processes – 1.Determination of requirements related to the product	Design control
7.Product realization – 2.Customer-related processes – 2.Review of requirements related to the product	Design control
7.Product realization – 2.Customer-related processes – 3.Customer communication	Design control
7.Product realization – 3.Design and development – 1.Design and development planning	Design control
7.Product realization – 3.Design and development – 1.Design and development input	Design control
7.Product realization – 3.Design and development – 3.Design and development outputs	Design control
7.Product realization – 3.Design and development – 4.Design and development review	Design control
7.Product realization – 3.Design and development – 5.Design and development verification	Design control
7.Product realization – 3.Design and development – 6.Design and development validation	Design control
7.Product realization – 3.Design and development – 7.Control of design and development changes	Design control
7.Product realization – 4.Purchasing – 1.Purchasing process	Procedures and records
7.Product realization – 4.Purchasing – 2.Purchasing information	Procedures and records
7.Product realization – 4.Purchasing – 3.Verification of purchased product	Procedures and records
7.Product realization – 5.Production and service provision – 1.Control of production and service provision – 1.General requirements	Procedures and records
7.Product realization – 5.Production and service provision – 1.Control of production and service provision – 2.Control of production and service provision: Specific requirements – 1.Cleanliness of product and contamination control	Manufacturing and product traceability
7.Product realization – 5.Production and service provision – 1.Control of production and service provision – 2.Control of production and service provision: Specific requirements – 2.Installation ativities	Procedures and records
7.Product realization – 5.Production and service provision – 1.Control of production and service provision – 2. – 3.Servicing activities	Procedures and records
7.Product realization – 5.Production and service provision – 1.Control of production and service provision – 3.Particular requirements for sterile medical devices	Manufacturing and product traceability
7.Product realization – 5.Production and service provision – 2.Validation of processes for production and service provision – 1.General requirements	Manufacturing and product traceability
7.Product realization – 5.Production and service provision – 2.Validation of processes for production and service provision – 2.Particular requirements for sterile medical devices	Manufacturing and product traceability
7.Product realization – 5.Production and service provision – 3. Identification and traceability – 1.Identification	Manufacturing and product traceability
7.Product realization – 5.Production and service provision – 3. Identification and traceability – 2.Traceability – 1.General	Manufacturing and product traceability
7.Product realization – 5.Production and service provision – 3. Identification and traceability – 2.Particular requirements for active implantable medical devices and implantable medical devices	Manufacturing and product traceability
7.Product realization – 5.Production and service provision – 3. Identification and traceability – 3.Status identification	Manufacturing and product traceability
7.Product realization – 5.Production and service provision – 4.Customer property	Non specific
7.Product realization – 5.Production and service provision – 5.Preservation of product	Procedures and records
7.Product realization – 6.Control of monitoring and measuring devices	Manufacturing and product traceability
8.Measurement, analysis and improvement – 1.General	Monitoring and ongoing improvement
8.Measurement, analysis and improvement – 2.Monitoring and measurement – 1.Feedback	Monitoring and ongoing improvement
8.Measurement, analysis and improvement – 2.Monitoring and measurement – 2.Internal audit	Procedures and records
8.Measurement, analysis and improvement – 2.Monitoring and measurement – 3.Monitoring and measurement of processes	Monitoring and ongoing improvement
8.Measurement, analysis and improvement – 2.Monitoring and measurement – 4.Monitoring and measurement of product – 1. General requirements	Design control
8.Measurement, analysis and improvement – 2.Monitoring and measurement – 4.Monitoring and measurement of product – 2.Particular requirement for active implantable medical devices and implantable medical devices	Procedures and records
8.Measurement, analysis and improvement – 3.Control of nonconforming product	Procedures and records
8.Measurement, analysis and improvement – 4.Aalysis of data	Monitoring and ongoing improvement
8.Measurement, analysis and improvement – 5.Improvement – 1.General	Monitoring and ongoing improvement
8.Measurement, analysis and improvement – 5.Improvement – 2.Corrective action	Procedures and records
8.Measurement, analysis and improvement – 5.Improvement – 3.Preventive action	Procedures and records

Share this:

• X
• LinkedIn
• Facebook
• Print
• Email

Like this:

Like Loading…

Read Full Post »

The Cost to Value Conundrum in Cardiovascular Healthcare Provision

Posted in Accountable Care Organizations, Affordable Care Act, Anemia, Atherogenic Processes & Pathology, Best evidence, Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, Ca2+ triggered activation, Ca2+ triggered activation, Calcium Signaling, Cardiac & Vascular Repair Tools Subsegment, Cardiac and Cardiovascular Surgical Procedures, Cardiac muscle regeneration, Cardiomyopathy, Cardiovascular Pharmacogenomics, Coagulation Therapy and Internal Bleeding, Computational Biology/Systems and Bioinformatics, Curation, Curation methodology, Cytoskeleton, Diabetes Mellitus, Electrophysiology, Evidence-based decision-making, Experimental validation, Federal Budget Appropriations, Frontiers in Cardiology and Cardiovascular Disorders, Health Economics and Outcomes Research, Health Law & Patient Safety, Healthcare costs and reimbursement, Healthcare Reform, Historical relevance, HTN, HTN in Youth, Indigent Nutrition, Interviews with Scientific Leaders, Ionic Transporters Na+, K, Medical Devices R&D and Inventions, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Medicare and Medicaid, Na-K transport, Na-K-ATPase, Nephrology, Nitric Oxide in Health and Disease, Nutrition, Nutritional Supplements: Atherogenesis, lipid metabolism, Origins of Cardiovascular Disease, Pharmaceutical Analytics, Pharmacogenomics, Pharmacologic toxicities, Pharmacotherapy of Cardiovascular Disease, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Prescription Drugs Costs, Regenerative Biology and Medicine, Resident-cell-based, Skilled Nursing Facilities, Stem Cells for Regenerative Medicine, Stents & Tools, Synaptic vesicle, Systematic Error (Bias), Systemic Inflammatory Response Related Disorders, Technology Advance Assessment of, Technology Capital Expenses, Technology Transfer: Biotech and Pharmaceutical, Translational Effectiveness, Translational Science, Uninsured and Underinsured, Valves & Tools, tagged acute myocardial infarct, American College of Cardiology ACC, Antiarrhythmic drugs, arrythmias, Artificial Biosensor, Artificial cardiac pacemaker, Artificial heart, Bare-metal stent, Cardiac & Vascular Repair, cardiac myocyte regeneration, Cardiogenic Shock, Cardiology, Cardiometabolic Syndrome, CHF, Content Curation, Coronary artery disease, Coronary stent, Curation methodology, Drug-eluting stents, gene expression, Hypertension, myocardial hypertrophy, nitric oxide, Nitric oxide synthase, RNA, Stem cell on January 1, 2014| Leave a Comment »

The Cost to Value Conundrum in Cardiovascular Healthcare Provision

Author: Larry H. Bernstein, MD, FCAP

Article ID #98: The Cost to Value Conundrum in Cardiovascular Healthcare Provision. Published on 1/1/2014

WordCloud Image Produced by Adam Tubman

I write this introduction to Volume 2 of the e-series on Cardiovascular Diseases, which curates the basic structure and physiology of the heart, the vasculature, and related structures, e.g., the kidney, with respect to:

1. Pathogenesis
2. Diagnosis
3. Treatment

Curation is an introductory portion to Volume Two, which is necessary to introduce the methodological design used to create the following articles. More needs not to be discussed about the methodology, which will become clear, if only that the content curated is changing based on success or failure of both diagnostic and treatment technology availability, as well as the systems needed to support the ongoing advances.  Curation requires:

• meaningful selection,
• enrichment, and
• sharing combining sources and
• creation of new synnthesis

Curators have to create a new perspective or idea on top of the existing media which supports the content in the original. The curator has to select from the myriad upon myriad options available, to re-share and critically view the work. A search can be overwhelming in size of the output, but the curator has to successfully pluck the best material straight out of that noise.

Part 1 is a highly important treatment that is not technological, but about the system now outdated to support our healthcare system, the most technolog-ically advanced in the world, with major problems in the availability of care related to economic disparities.  It is not about technology, per se, but about how we allocate healthcare resources, about individuals’ roles in a not full list of lifestyle maintenance options for self-care, and about the important advances emerging out of the Affordable Care Act (ACA), impacting enormously on Medicaid, which depends on state-level acceptance, on community hospital, ambulatory, and home-care or hospice restructuring, which includes the reduction of management overhead by the formation of regional healthcare alliances, the incorporation of physicians into hospital-based practices (with the hospital collecting and distributing the Part B reimbursement to the physician, with “performance-based” targets for privileges and payment – essential to the success of an Accountable Care Organization (AC)).  One problem that ACA has definitively address is the elimination of the exclusion of patients based on preconditions.  One problem that has been left unresolved is the continuing existence of private policies that meet financial capabilities of the contract to provide, but which provide little value to the “purchaser” of care.  This is a holdout that persists in for-profit managed care as an option.  A physician response to the new system of care, largely fostered by a refusal to accept Medicaid, is the formation of direct physician-patient contracted care without an intermediary.

In this respect, the problem is not simple, but is resolvable.  A proposal for improved economic stability has been prepared by Edward Ingram. A concern for American families and businesses is substantially addressed in a macroeconomic design concept, so that financial services like housing, government, and business finance, savings and pensions, boosting confidence at every level giving everyone a better chance of success in planning their personal savings and lifetime and business finances.

http://macro-economic-design.blogspot.com/p/book.html

Part 2 is a collection of scientific articles on the current advances in cardiac care by the best trained physicians the world has known, with mastery of the most advanced vascular instrumentation for medical or surgical interventions, the latest diagnostic ultrasound and imaging tools that are becoming outdated before the useful lifetime of the capital investment has been completed.  If we tie together Part 1 and Part 2, there is ample room for considering  clinical outcomes based on individual and organizational factors for best performance. This can really only be realized with considerable improvement in information infrastructure, which has miles to go.  Why should this be?  Because for generations of IT support systems, they are historically focused on billing and have made insignificant inroads into the front-end needs of the clinical staff.

Share this:

• X
• LinkedIn
• Facebook
• Print
• Email

Like this:

Like Loading…

Read Full Post »

Physiologist, Professor Lichtstein, Chair in Heart Studies at The Hebrew University elected Dean of the Faculty of Medicine at The Hebrew University of Jerusalem

Posted in Bio Instrumentation in Experimental Life Sciences Research, Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, BioSimilars, Cardiovascular Pharmacogenomics, Cardiovascular Research, Cell Biology, Signaling & Cell Circuits, Cerebrovascular and Neurodegenerative Diseases, Chemical Biology and its relations to Metabolic Disease, Chemical Genetics, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Drug Delivery Platform Technology, Electrophysiology, Frontiers in Cardiology and Cardiovascular Disorders, Human Sensation and Cellular Transduction: Physiology and Therapeutics, Ionic Transporters Na+, Na-K transport, Origins of Cardiovascular Disease, Pharmacotherapy and Cell Activity, Pharmacotherapy of Cardiovascular Disease, Scientist: Career considerations, Technology Transfer: Biotech and Pharmaceutical, Translational Research, Translational Science, Water Transporters, tagged Hebrew University of Jerusalem, pharmacology, Roche Institute of Molecular Biology on December 18, 2013| Leave a Comment »

Physiologist, Professor Lichtstein, Chair in Heart Studies at The Hebrew University elected Dean of the Faculty of Medicine at The Hebrew University of Jerusalem

Reporter: Aviva Lev-Ari, PhD, RN

Professor David Lichtstein Elected Dean of Hebrew University’s Faculty of Medicine

December 2, 2013

Jerusalem — Professor David Lichtstein has been elected dean of the Faculty of Medicine at The Hebrew University of Jerusalem. Professor Lichtstein is the Walter & Greta Stiel Chair in Heart Studies at The Hebrew University. He replaces Professor Eran Leitersdorf, who recently completed his four-year term as dean.

According to Professor Lichtstein, “The Hebrew University’s Faculty of Medicine is devoted to creating innovative teaching, research and patient care programs that will meet the demands of 21st century health care. As global health care moves toward prevention, wellness and cost effectiveness, we are adapting how we train the next generation of physicians, nurses, pharmacists and biomedical researchers. Through fruitful collaborations between preclinical and clinical faculty, we are also translating basic biomedical insights into clinical treatments. Thus, the Faculty of Medicine is well-positioned to maintain its leading role in the scientific community of Israel and the world.”

Professor Lichtstein was born in Lodz, Poland, and immigrated to Israel with his family in 1957. As a student at The Hebrew University, he completed a Bachelor’s degree in Physiology and Zoology in 1970, followed by a Master’s degree in Physiology in 1972 and a Ph.D. in Physiology in 1977. He joined the Department of Physiology of The Hebrew University-Hadassah Medical School in 1980 as a lecturer, and received full professorship in 1994. Prof. Lichtstein has held many roles at The Hebrew University and its Faculty of Medicine, including Chairman of the Neurobiology Teaching Division, Chairman of the Department of Physiology, Chairman of the Institute for Medical Sciences and, until recently, Chairman of the Faculty of Medicine. From 2007 to 2011, Professor Lichtstein was the Jacob Gitlin Chair in Physiology at The Hebrew University. In 2011 he was named the Walter & Greta Stiel Chair in Heart Studies at The Hebrew University. He also served as the President of the Israel Society for Physiology and Pharmacology from 1996 to 1999.

From 1977-1979 Professor Lichtstein was a Postdoctoral Fellow at the Roche Institute of Molecular Biology in New Jersey. He was a visiting scientist at the National Institute of Child Health and Human Development (1985-1986) and the Eye Institute (1997-1998) at the National Institutes of Health in Maryland, and a visiting professor at the Toledo School of Medicine in Ohio (2007).

Professor. Lichtstein’s main research focus is the regulation of ion transport across the plasma membrane of eukaryotic cells. His work led to the discovery that specific steroids that were known to be present in plants and amphibians are actually normal constituents of the human body and have crucial roles, such as the regulation of cell viability, heart contractility, blood pressure and brain function. His research has implications for the fundamental understanding of body functions, as well as for several pathological states such as heart failure, hypertension and neurological and psychiatric diseases.

SOURCE

http://www.afhu.org/professor-david-lichtstein-elected-dean-hebrew-universitys-faculty-medicine

Field of Study

Regulation of ion transport across the plasma membrane:

The primary focus of the research in my laboratory is the regulation of ion transport across the plasma membrane of eukaryotic cells. In particular, we study the main transport system for sodium and potassium, the sodium-potassium-ATPase, and its regulation by cardiac steroids.

Specific areas of interest:

Identification of endogenous cardiac steroids in mammalian tissue; The biological consequences of the interaction of cardiac steroids with the sodium-potassium-ATPase; Biosynthesis of the cardiac steroids in the adrenal gland; Effects of endogenous sodium-potassium-ATPase inhibitors on cell differentiation; Determination of the levels of endogenous sodium-potassium-ATPase inhibitors in pathological states, including hypertension, preeclampsia; malignancies (cancer) and manic depressive illnesses; Involvement of the sodium-potassium–ATPase/cardiac steroids system in depressive disorders; Involvement of the sodium-potassium-ATPase/cardiac steroids system in cardiac function; Involvement of intestinal signals in the regulation of phosphate homeostasis; Volume regulation and its involvement in the mitogenic response.

Cardiac Steroids and the Na+, K+-ATPase and Cardiac Steroids

Cardiac steroids, such as ouabain, digoxin and bufalin are hormones synthesized by and released from the adrenal gland and the hypothalamus. These compounds, the structure of which resembles that of plant and amphibian and butterfly steroids, interact only with the plasma membrane Na+, K+-ATPase (Figure 1). This interaction elicits numerous specific biological responses affecting the function of cells and organs.

Topics Currently under investigation include

Cardiac Steroids

• Ouabain
• Bufalin
• Dogoxin

Involvement of the sodium-potassium–ATPase/cardiac steroids system in depressive disorders

Depressive disorders, including major depression, dysthymia and bipolar disorder, are a serious and devastating group of diseases that have a major impact on the patients’ quality of life, and pose a significant concern for public health. The etiology of depressive disorders remains unclear. The Monoaminergic Hypothesis, suggesting that alterations in monoamine metabolism in the brain are responsible for the etiology of depressive disorders, is now recognized as insufficient to explain by itself the complex etiology of these diseases. Data from our and other laboratories has provided initial evidence that endogenous cardiac steroids and their only established receptor, the Na+, K+-ATPase, are involved in the mechanism underlining depressive disorders, and BD in particular. Our study (Biol. Psychiatry. 60:491-499, 2006) has proven that Na+, K+-ATPase and DLC are involved in depressive disorders particularly in manic-depression. We have also shown that specific genetic alterations in the Na+, K+-ATPase α isoforms are associated with bipolar disorders (Biol. Psychiatry, 65:985-991, 2009). Our recent study in this project (Eur. Neuropsychopharmacol. 22:72-729, 2012) showed that drugs affecting the Na+, K+-ATPase/cardiac steroids system are beneficial for the treatment of depression. Hence our work is in accordance to the proposition that mal functioning of the Na+, K+-ATPase/cardiac steroids system may be involved in manifestation of depressive disorders and identify new compounds as potential drug for the treatment of these maladies.

Involvement of the sodium-potassium-ATPase/cardiac steroids system in cardiac function

The classical and best documented effect of cardiac steroids, as their name implies, is to increase the force of contraction of heart muscle. Indeed, cardiac steroids were widely used in Western and Eastern clinical practices for the treatment of heart failure and atrial fibrillation. Despite extensive research, the mechanism underlying cardiac steroids actions have not been fully elucidated. The dogmatic explanation for cardiac steroids-induced increase in heart contractility is that the inhibition of Na+, K+-ATPase by the steroids causes an increase in intracellular Na+ which, in turn, attenuates the Na+/Ca++ exchange, resulting in an increased intracellular Ca++ concentration, and hence greater contractility. However, recent observations led to the hypothesis that the ability of cardiac steroids to modulate a number of intracellular signaling processes may be responsible for both short- and long-term changes in CS action on cardiac function. We are addressing this hypothesis using the zebrafish model and our ability to quantify heart function in-vivo. Heart contractility measurements were performed using a series of software tools for the analysis of high-speed video microscopic images, allowing the determination of ventricular heart diameter and perimeter during both diastole and systole. The ejection fraction (EF) and fractional area changes (FAC) were calculated from these measurements, providing two independent parameters of heart contractility (see attached movie bellow). We are currently testing the effect of cardiac steroids in the presence and absence of intracellular signaling pathways (MAP, AKT, IP3R) inhibitors. Reduction in the steroids ability to increase the force of contraction will serve as the first evidence, in-vivo, for the participation of the signaling processes in the molecular mechanisms responsible for the action of cardiac steroids on heart muscle.

Laboratory Techniques

We employ a broad range of preparations and techniques. These include isolated organs (arterial rings, smooth and cardiac muscle strips) and isolated nerve endings, as well as primary and established tissue-cultured cells. Our studies involve the application of biochemical and immunological techniques (transport and enzymatic activity measurements, RIA, ELISA), molecular biological techniques (e.g., Western and Northern blotting, and PCR), protein purification (HPLC), cellular techniques muscle contractility, cell proliferation and differentiation’ in-vivo measurements of heart contractility and blood flow in Zebrafish and behavior measurements in rodents.

Biography

Education

1970	B.Sc. in Physiology and Zoology, The Hebrew University, Jerusalem, Israel
1970-1972	M.Sc. in Physiology, Department of Physiology, The Hebrew University, Hadassah Medical School, Jerusalem, Israel.
1973-1977	Ph.D., Department of Physiology, Hebrew University Hadassah Medical School, Jerusalem, Israel. (Thesis: “Increased Production of Gamma Aminobutyryl choline in Cerebral Cortex Caused by Afferent Electrical Stimulation” (Thesis Advisors: Prof. J. Dobkin and Prof. J. Magnes).
1977-1979	Postdoctoral Fellow, Department of Physiological Chemistry and Pharmacology, Roche Institute of Molecular Biology, Nutley, New Jersey, U.S.A.

Positions held

1970-1972	Teaching and Research Assistant, Department of Physiology, The Hebrew University, Hadassah Medical School, Jerusalem, Israel
1972-1974	Assistant Instructor, Department of Physiology, The Hebrew University, Hadassah Medical School, Jerusalem, Israel
1975-1977	Instructor, Department of Physiology, The Hebrew University, Hadassah Medical School, Jerusalem, Israel
1977-1979	Postdoctoral Fellow, Department of Physiological Chemistry and Pharmacology, Roche Institute of Molecular Biology, Nutley, New Jersey, U.S.A.
1979-1983	Lecturer, (REVSON fellowship) Department of Physiology, The Hebrew University, Hadassah Medical School, Jerusalem, Israel
1981 (summer)	Visiting Scientist, Department of Physiological Chemistry and Pharmacology, Roche Institute of Molecular Biology, Nutley, New Jersey, USA
1983-1987	Senior Lecturer, Department of Physiology, The Hebrew University Hadassah Medical School, Jerusalem, Israel.
1985-1986	Visiting Scientist, Laboratory of Theoretical and Physical Biology, NICHD, National Institutes of Health, Bethesda, Maryland, USA
1988-1994	Associate Professor, Department of Physiology, The Hebrew University Hadassah Medical School, Jerusalem, Israel
1994-present	Professor of Physiology, Department of Physiology, The Hebrew University Hadassah Medical School, Jerusalem, Israel
1997-1998	Visiting Scientist, Laboratory of Mechanisms of Ocular Diseases, NEI, National Institutes of Health, Bethesda, Maryland, USA
2007 (summer)	Visiting Professor, Department of Physiology, Pharmacology, Metabolism and cardiovascular Sciences, Medical Center University of Toledo, Toledo, Ohio, USA
2007-2011	Jacob Gitlin Chair in Physiology, The Hebrew University, Jerusalem, Israel
​2011-present	​Walter & Greta Stiel Chair in Heart Studies, The Hebrew University, Jerusalem

Professional Membership

1979-present	International Society of Neurochemistry
1979-present	Israel Society for Physiological and Pharmacological
1980-present	Society of Neurosciences (Europe)
1986-present	The American Society of Hypertension
1992-present	Israeli Society for Neurosciences
1999-present	The American Physiological Society

Editorial Tasks

Serving as a Reviewer for the scientific journals:
•	American Journal of Hypertension		•	Journal of Neural Transmission
•	American Journal of Physiology		•	Journal of Neurochemistry
•	Apoptosis		•	Journal of Pharmacology and Experimental Therapeutics
•	Biochemical and Biophysical Research Communications		•	Life Sciences
•	Basic Journal of Physiology and Pharmacology		•	NANO
•	Brain Research		•	Neurochemistry International
•	Bioconjugate Chemistry		•	Neuroscience
•	Cell Calcium		•	Neurotoxicity Research
•	Clinical Science		•	Pathophysiology
•	Endocrinology		•	Physiology and Behavior
•	European Neuropsychopharmacology		•	PNAS
•	General and Comparative Endocrinology		•	Psychiatry Research
•	Hypertension		•	Translational Research
•	Journal of Cell Sciences

University and Other Activities

1982-1985	Chairman of the Neurobiology Teaching Division, The Hebrew University, Jerusalem
1988-1994	Elected representative of the Senior Lecturers and Associate Professors for the University Senate
1989-1997	Member of the admission committee of the Medical School, The Hebrew University, Jerusalem
1990-1996	Member of the Committee for cellular biology of the graduate studies, The Hebrew University, Jerusalem
1992-1996	Member of the Teaching Committee, Faculty of Medicine, The Hebrew University, Jerusalem
1992-1996	Chairman, Department of Physiology, The Hebrew University, Hadassah Medical School, Jerusalem
1994-1997	Member of the Committee for graduate studies, The Hebrew University, Jerusalem
1992-2002	Member of the Management Committee of The Institute for Medical Sciences, Faculty of Medicine, The Hebrew University, Jerusalem
1996-1999	President of the Israel Society for Physiology and Pharmacology
1998- 2002	Chairman, Institute of Medical Sciences, The Hebrew University, Hadassah Medical School, Jerusalem
1999-2002	Member of the Planning and Development Committee of the Faculty of Medicine, The Hebrew University, Jerusalem
2007–Present	Elected representative of the Professors for the executive University Senate
2008-2012	Member of the Planning and Development Committee of the Faculty of Medicine, The Hebrew University, Jerusalem
2008-2012	Chairman, Institute for Medical Research Israel-Canada, The Hebrew University, Hadassah Medical School, Jerusalem
2009 – Present	Elected member of the Senate to the Executive Committee of the Hebrew University

 https://medicine.ekmd.huji.ac.il/En/Publications/ResearchersPages/pages/davidli.aspx

PUBLICATIONS 2006 – 2012

Use link below for earlier publications

https://medicine.ekmd.huji.ac.il/En/Publications/publications/Pages/default.aspx?aut=Lichtstein,%20D

Search By:  Author Abeles, M Abramovitch, R Allweis, C Altuvia, S Amedi, A Amster-Choder, O Anglister, L Aqeilan, RI Aronovitch, Y Bachrach, U Baniyash, M Barak, V Barenholz, Y Bar-Shalita, T Bar-Shavit, R Bar-Shavit, Z Bar-Tana, J Becker, Y Behar, O Ben-Ishay, Z Benita, S Ben-Neriah, Y Benny, O Ben-Or, S Ben-porath, I Ben-Sasson, S Ben-Sasson, SZ Ben-Shaul, Y Ben-Yehuda, S Bercovier, H Berger, M Bergman, H Bergman, Y Berry, E Bialer, M Binshtok, AM Blum, G Brandes, R Brautbar, C Breuer, E Cedar, H Chevion, M Chinitz, D Citri, N Cohen, A Cohen, E Deutsch, J Dikstein, S Domb, A Dor, Y Dror, OE Dzikowski, R Elkin, M Engelberg-Kulka, H Even-Ram, S Eyal, S Fainsod, A Feintuch, U Friedlander, y Friedman, M Gallily, R Gatt, S Gerlitz, O Gertz, SD Gibson, D Glaser, G Goelman, G Goldberg, I Goldberg, JA Goldblum, A Golenser, J Golomb, G Golos, A Gordon, A Gorinstein, S Gorodetsky, R Granot, Z Greenblatt, CL Greenwald, T Gross, E Grover, N Gutman, Y Hahn-Markowitz, J Hamburger, J Hanani, M Hanski, E Hartman-Maeir, A Hellman, A Hochner, H Hoffman, A Honigman, A Horowitz, M Ilani, A Inbal, A Jaffe, CL Jarrous, N Kaempfer, R Kalcheim, C Kanner, BI Kapitulnik, J Karni, R Katz, E Katzav, S Katz-Brull, R Katzhendler, J Kedar, E Keren, N Keshet, E Klar, A Kohen, R Konijn, A Kotler, M Langer, D Laskov, R Lazarovici, P Levi-Schaffer, F Lev-Tov, A Lichtstein, D Liebergall, M Lorberboum-Galski, H Magen, H Mandelboim, O Manor, O Margalit, H Matok, I Mechoulam, R Meiri, H Melloul, D Meyuhas, O Minke, B Mishani, E Mitrani-Rosenbaum, S Mumcuoglu, K Naor, D Naveh-Many, T Neumark, Y Nussinovitch, I Oppenheim, A Ornoy, A Panet, A Paroush, Z Parush, S Peled, A Pikarsky, E Pines, O Priel, A Prut, Y Rachmilewitz, J Rahamimoff, H Ravid, S Razin, A Razin, E Razin, S Reich, R Reshef, L Richter, E Ringel, I Rokem, JS Rom, M Ron, A Rosen, H Rosenshine, I Rotenberg-Shpigelman, S Rotshenker, S Rottem, S Rubinstein, A Samueloff, S Samuni, A Sasson, S Schlein, Y Schlesinger, M Schueler-Furman, O Sharon, D Sharon, R Shaulian, E Shlomai, J Shmueli, A Shohami, E Shtarkshall, R Shurki, A Simon, I Smith, P Sohmer, H Sperling, D Steinitz, M Stern-Bach, Y Tal, M Taraboulos, A Ta-Shma, R Tirosh, B Touitou, E Trachtenberg, S Traub, R Treinin, M Tsvelikhovsky, D Vaadia, E Warburg, A Weinstock, M  Weintraub, N Weiss, D Weiss, R Wiener, R Wormser, U Yaari, Y Yagen, B Yaka, R yanai, J Yavin, E Yedgar, S Yefenof, E Yisraeli, JK Yochman, A Yogev, D Yosselson-Superstine, S Zajicek, G Zakay-Rones, Z  Sort By:  Year Descending Year Ascending  Text: Dvela, M., Rosen, H., Ben-Ami, H. C., Lichtstein, D. Endogenous ouabain regulates cell viability American journal of physiology. Cell physiology, 302(2), C442-52, 2012 JCR Impact FactorAbstract Goldstein, I., Lax, E., Gispan-Herman, I., Ovadia, H., Rosen, H., Yadid, G., Lichtstein, D. Neutralization of endogenous digitalis-like compounds alters catecholamines metabolism in the brain and elicits anti-depressive behavior European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 22(1), 72-9, 2012 JCR Impact FactorAbstract Feldmann, T., Shahar, M., Baba, A., Matsuda, T., Lichtstein, D., Rosen, H. The Na(+)/Ca(2+)-exchanger: an essential component in the mechanism governing cardiac steroid-induced slow Ca(2+) oscillations Cell calcium, 50(5), 424-32, 2011 JCR Impact FactorAbstract Nesher, M., Shpolansky, U., Viola, N., Dvela, M., Buzaglo, N., Cohen Ben-Ami, H., Rosen, H., Lichtstein, D. Ouabain attenuates cardiotoxicity induced by other cardiac steroids British journal of pharmacology, 160(2), 346-54, 2010 JCR Impact FactorAbstract Guttmann-Rubinstein, L., Lichtstein, D., Ilani, A., Gal-Moscovici, A., Scherzer, P., Rubinger, D. Evidence of a parathyroid hormone-independent chronic effect of estrogen on renal phosphate handling and sodium-dependent phosphate cotransporter type IIa expression Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 42(4), 230-6, 2010 JCR Impact FactorAbstract Jaiswal, M. K., Dvela, M., Lichtstein, D., Mallick, B. N. Endogenous ouabain-like compounds in locus coeruleus modulate rapid eye movement sleep in rats Journal of sleep research, 19(1 Pt 2), 183-91, 2010 JCR Impact FactorAbstract Nesher, M., Dvela, M., Igbokwe, V. U., Rosen, H., Lichtstein, D. Physiological roles of endogenous ouabain in normal rats American journal of physiology. Heart and circulatory physiology, 297(6), H2026-34, 2009 JCR Impact FactorAbstract Goldstein, I., Lerer, E., Laiba, E., Mallet, J., Mujaheed, M., Laurent, C., Rosen, H., Ebstein, R. P., Lichtstein, D. Association between sodium- and potassium-activated adenosine triphosphatase alpha isoforms and bipolar disorders Biological psychiatry, 65(11), 985-91, 2009 JCR Impact FactorAbstract Nesher, M., Vachutinsky, Y., Fridkin, G., Schwarz, Y., Sasson, K., Fridkin, M., Shechter, Y., Lichtstein, D. Reversible pegylation prolongs the hypotensive effect of atrial natriuretic peptide Bioconjugate chemistry, 19(1), 342-8, 2008 JCR Impact FactorAbstract Dvela, M., Rosen, H., Feldmann, T., Nesher, M., Lichtstein, D. Diverse biological responses to different cardiotonic steroids Pathophysiology : the official journal of the International Society for Pathophysiology / ISP, 14(3-4), 159-66, 2007 JCR Impact FactorAbstract Feldmann, T., Glukmann, V., Medvenev, E., Shpolansky, U., Galili, D., Lichtstein, D., Rosen, H. Role of endosomal Na+-K+-ATPase and cardiac steroids in the regulation of endocytosis American journal of physiology. Cell physiology, 293(3), C885-96, 2007 JCR Impact FactorAbstract Chirinos, J. A., Corrales-Medina, V. F., Garcia, S., Lichtstein, D. M., Bisno, A. L., Chakko, S. Endocarditis associated with antineutrophil cytoplasmic antibodies: a case report and review of the literature Clinical rheumatology, 26(4), 590-5, 2007 JCR Impact FactorAbstract Nesher, M., Shpolansky, U., Rosen, H., Lichtstein, D. The digitalis-like steroid hormones: new mechanisms of action and biological significance Life sciences, 80(23), 2093-107, 2007 JCR Impact FactorAbstract Lichtstein, D. M., Arteaga, R. B. Rhabdomyolysis associated with hyperthyroidism The American journal of the medical sciences, 332(2), 103-5, 2006 JCR Impact FactorAbstract Morla, D., Alazemi, S., Lichtstein, D. Stauffer’s syndrome variant with cholestatic jaundice: a case report Journal of general internal medicine, 21(7), C11-3, 2006 JCR Impact FactorAbstract Chirinos, J. A., Corrales, V. F., Lichtstein, D. M. ANCA-associated large vessel compromise Clinical rheumatology, 25(1), 111-2, 2006 JCR Impact FactorAbstract Deutsch, J., Jang, H. G., Mansur, N., Ilovich, O., Shpolansky, U., Galili, D., Feldman, T., Rosen, H., Lichtstein, D. 4-(3’alpha15’beta-dihydroxy-5’beta-estran-17’beta-yl)furan-2-methyl alcohol: an anti-digoxin agent with a novel mechanism of action Journal of medicinal chemistry, 49(2), 600-6, 2006 JCR Impact FactorAbstract Goldstein, I., Levy, T., Galili, D., Ovadia, H., Yirmiya, R., Rosen, H., Lichtstein, D. Involvement of Na(+) Biological psychiatry, 60(5), 491-9, 2006 JCR Impact FactorAbstract Chirinos, J. A., Garcia, J., Alcaide, M. L., Toledo, G., Baracco, G. J., Lichtstein, D. M. Septic thrombophlebitis: diagnosis and management American journal of cardiovascular drugs : drugs, devices, and other interventions, 6(1), 9-14, 2006 JCR Impact FactorAbstract Rosen, H., Glukmann, V., Feldmann, T., Fridman, E., Lichtstein, D. Short-term effects of cardiac steroids on intracellular membrane traffic in neuronal NT2 cells Cellular and molecular biology (Noisy-le-Grand, France), 52(8), 78-86, 2006 JCR Impact FactorAbstract

SOURCE

https://medicine.ekmd.huji.ac.il/En/Publications/publications/Pages/default.aspx?aut=Lichtstein,%20D

 

Share this:

• X
• LinkedIn
• Facebook
• Print
• Email

Like this:

Like Loading…

Read Full Post »

St. Jude’s CEO is still betting on EnligHTN IV Study Renal Denervation System, despite Medtronic’s setback related to SYMPLICITY Phase IV

Posted in Bio Instrumentation in Experimental Life Sciences Research, Biomedical Measurement Science, Cardiac & Vascular Repair Tools Subsegment, Cardiac and Cardiovascular Surgical Procedures, Cardiovascular Research, Ecosystems & Industrial Concentration in the Medical Device Sector, FDA Regulatory Affairs, FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, GLP, ISO 14155, Frontiers in Cardiology and Cardiovascular Disorders, HTN, Interviews with Scientific Leaders, Medical Devices R&D and Inventions, Medical Devices R&D Investment, Origins of Cardiovascular Disease, Peripheral Arterial Disease & Peripheral Vascular Surgery, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Renal Denervation, Technology Transfer: Biotech and Pharmaceutical, tagged Boston Scientific, Clinical trial, Food and Drug Administration, Hypertension, Medtronic, Renal denervation medical devices, Renal denervation procedure, St. Jude Medical on December 10, 2013| Leave a Comment »

St. Jude’s CEO is still betting on EnligHTN IV Study Renal Denervation System, despite Medtronic’s setback related to SYMPLICITY Phase IV

Reporter: Aviva Lev-Ari, PhD, RN

Article ID #92: St. Jude’s CEO is still betting on EnligHTN IV Study Renal Denervation System, despite Medtronic’s setback related to SYMPLICITY Phase IV. Published on 12/10/2013

WordCloud Image Produced by Adam Tubman

UPDATED on 1/14/2014

This is in continuation to our 1/9/2014 article:

Market Impact on Global Suppliers of Renal Denervation Systems by Pivotal US Trial: Metronics’ Symplicity Renal Denervation System FAILURE at Efficacy Endpoint

http://pharmaceuticalintelligence.com/2014/01/09/market-impact-on-global-suppliers-of-renal-denervation-systems-by-pivotal-us-trial-metronics-symplicity-renal-denervation-system-failure-at-efficacy-endpoint/

In the short term, the company, St. Jude suspended enrollment in three other related trials and announced plans to gather an independent panel of experts to plot a future course. 

St. Jude Medical won a CE mark for its next-gen EnligHTN IV renal denervation system over the summer, but halted its own U.S. trial in December. Minnesota-based St. Jude said it had struggled to recruit viable candidates for the 590-patient trial, and was concerned that Medtronic’s Symplicity might siphon off viable patients needed for its own study. At the time, St. Jude said it would work to develop a new protocol to address trial enrollment challenges.

According to Mark Hollmer:

Symplicity’s setbacks may make that job much easier for St. Jude. They also create new opportunities for other rivals focused on developing similar technology, such as Boston Scientific ($BSX) and Covidien ($COV).

Curator of this article has expressed a different view in 

http://pharmaceuticalintelligence.com/2014/01/09/market-impact-on-global-suppliers-of-renal-denervation-systems-by-pivotal-us-trial-metronics-symplicity-renal-denervation-system-failure-at-efficacy-endpoint/

St. Jude’s CEO is still betting on renal denervation, despite Medtronic’s setback

By Mark Hollmer

Medtronic’s Symplicity renal denervation device

If Medtronic’s ($MDT) recent U.S. clinical trial failure for its Symplicity renal denervation device throws the door wide open for its competitors, St. Jude Medical ($STJ) will likely waste no time walking through.

As MassDevice reported, St. Jude CEO Daniel Starks told an audience at the JPMorgan Healthcare conference in San Francisco that the company plans to keep plowing ahead with the development of its own technology.

“The fact that we had and that there have been favorable early clinical results in numerous other experiences is still valid,” MassDevice quoted Starks as saying. “There is open surgical data dating back several decades that was favorable to the impact of surgical renal denervation to treat hypertension.

That said, he also expressed genuine surprise about Medtronic’s trial setback.

“This was unexpected for us, to have a negative result from Medtronic’s trial, and it’s too soon for us to know what to make of that,” Starks said in the story.

Medtronic’s Symplicity device, which has a CE mark and is a market leader, had done well in previous trials in patients with different forms of hypertension and was on track to win FDA approval in 2015–potentially the first renal denervation device to reach that point.

The Minnesota device giant announced a few days ago that Symplicity proved safe in a 535-patient trial but failed to significantly lower blood pressure for drug-resistant hypertension.

This was a trial that mattered, designed to help fuel FDA approval.

Related Articles:

Medtronic’s flunked trial throws its hypertension program into doubt

St. Jude Medical will try again another day for a U.S. renal denervation study

St. Jude bags EU approval for next-gen renal denervation

 SOURCE

From: FierceMedicalDevices <editors@fiercemedicaldevices.com>
Date: Tue, 14 Jan 2014 18:14:06 +0000 (GMT)
To: <avivalev-ari@alum.berkeley.edu>

Renal Denervation: EnligHTN IV Study Called Off and Potential Novel Indications – Diastolic Heart Failure

Reporter: Aviva Lev-Ari, PhD, RN

This Open Access Scientific Journal has covered all the major developments reported on Renal Denervation since its inception

The Archive for Renal denervation

http://pharmaceuticalintelligence.com/category/cardiac-and-cardiovascular-surgical-procedures/renal-denervation/

Search Results for Renal Denervation

http://pharmaceuticalintelligence.com/?s=Renal+denervation

Heartwire Reported on December 09, 2013

EnligHTN IV Renal Denervation Study Called Off

Michael O’Riordan

EDITORS’ RECOMMENDATIONS

• EnligHTN-1 12-Mo Results as Renal Denervation Booms
• Multielectrode Renal-Denervation Device Appears Safe
• New Renal-Denervation Systems Debut Amid Excitement, Caution

ST PAUL, MN – The EnligHTN IV study (St Jude Medical, St Paul, MN), testing the multielectrode renal-denervation system in patients with resistant hypertension, has been stopped almost before it even began. The trial, which was announced in June and began enrolling a small number of patients this fall, was canceled because of concerns about slow enrollment.

To heartwire ,

Denise Perkins-Landry, a spokesperson for St Jude Medical, said the decision to discontinue the study was based on “anticipated recruitment challenges” and is not the result of any safety or efficacy issues with the device. “A US clinical trial for EnligHTN remains a very high priority for St Jude Medical, and we will be working with the FDA to develop a new protocol that will address anticipated enrollment challenges,” she stated in an email.

The full results of the SYMPLICITY HTN-3 trial, a study similar to the EnligHTN IV study, which is sponsored by Medtronic (Minneapolis, MN), are expected in early 2014. While neither device is approved for clinical use in the US, it is expected that the Medtronic renal-denervation system will be first. As a result, it might be difficult to enroll patients to a sham procedure if there is another commercially available system for treating resistant hypertension, according to St Jude.

EnligHTN IV was to be a randomized, single-blind, controlled study with patients randomized from as many as 80 clinical centers in the US and Canada. It was intended to show the safety and effectiveness of the renal-denervation system in the reduction of systolic blood pressure in 590 patients with an office blood pressure >160 mm Hg despite taking three or more antihypertensive medications, including a diuretic.

Abrupt Decision to Stop the Study

Dr William White (University of Connecticut Medical Center, Farmington), one of the cochairs of the EnligHTN IV steering committee, told heartwire the decision to cancel the study was made just last week. In fact, there were clinical centers already up and running in terms of enrollment, although these were pilot centers where any “bugs could be worked out.” The meeting for training investigators participating in the trial was scheduled for Saturday in Chicago, IL, although that is now off.

“In the grander scheme of things, I can tell you that the decision was not made because of any problem with the catheter or any safety issues,” said White. “Outside the US, the development is continuing as planned, but the biggest concern is that it might be very difficult, if not impossible, to continue doing a sham-controlled study a year from now if there were a commercially available renal-denervation catheter in the US, which there very well could be with Medtronic.”

Still, White said that it’s not even known if the SYMPLICITY HTN-3 study is positive or if the FDA will be satisfied with the trial and its outcomes. He said a lot of assumptions are being made by St Jude Medical in stopping the trial, and it could turn out to be a bad decision. In addition, reimbursement remains an open question.

“Commercially available doesn’t mean there’s going to be a payer,” White told heartwire . “If that happens, it will be doubly unfortunate for the patients that are out there because they might be willing and able to go into a clinical trial but they won’t have that opportunity.”

As a scientist, White said that he would have preferred the trial be pursued, regardless of what happens with Medtronic. He believes the EnligHTN catheter is “outstanding,” as it has multiple electrodes to enable physicians to thoroughly ablate the renal arteries within a couple of minutes. “The clinical scientist in me would have preferred that we go ahead as planned,” he said. “I think we would have gained a great deal of knowledge. And just because one study shows a p value of 0.05 doesn’t mean a second study will.”

The Medtronic SYMPLICITY renal-denervation system was launched in 2010 and is available in parts of Europe, Asia, Africa, and South America. The first-generation EnligHTN device has had CE Mark approval in Europe since 2012 while the updated second-generation system with multiple electrodes received European approval this past summer.

News of the halting of EnligHTN IV was first reported by Wells Fargo analyst Larry Biegelsen.

SOURCE

http://www.medscape.com/viewarticle/817482?nlid=41903_2105&src=wnl_edit_medp_card&uac=93761AJ&spon=2

On December 06, 2013 Marlene Busko reported to Heartwire on

Renal Denervation’s Structural, Functional Heart Benefits May Be Independent of BP

HAMBURG, GERMANY — In a small study of patients undergoing renal denervation for resistant hypertension, left-ventricular hypertrophy and diastolic function improved independently of changes in blood pressure and heart rate ^[1].

“The novelty of our findings is the independence of morphologic improvements [regression of LV hypertrophy] from hemodynamic changes (reduction of blood pressure and heart rate),” Dr Stephan H Schirmer (University of Saarland, Hamburg, Germany) told heartwire in an email. “If this is confirmed in larger trials, it might open up novel indications for the use of renal denervation, for example, in [diastolic] heart-failure patients, independent of blood pressure.”

Dr Deepak L Bhatt (Harvard Medical School, Boston, MA) told heartwire that the study observations are “provocative” and “exciting” but stressed that they need to be confirmed in a blinded, larger, multicenter study before they could be accepted into clinical practice. Bhatt and Dr George Bakris (University of Chicago, IL) are co–principal investigators for the ongoing SYMPLICITY HTN-3 trial of bilateral renal denervation in patients with uncontrolled hypertension.

The study was published online December 4, 2013 in the Journal of the American College of Cardiology.

Are Renal Denervation Effects Always Tied to BP Change?

Renal denervation reduces heart rate and blood pressure in patients with resistant hypertension, and as reported by heartwire , a recent small study suggested that the procedure also reduces left-ventricular mass and improves diastolic function in such patients, Schirmer and colleagues write.

They hypothesized that renal denervation might affect cardiac structure and function, independent of the effect on blood pressure.

They enrolled 66 consecutive patients who underwent renal denervation using the Flex catheter system (Medtronic) at their center during 2010 and 2011 for treatment of resistant hypertension (office systolic blood pressure >140 mm Hg). Patients had a mean age of 64 years, and 55% were men. They were on a mean of 4.3 antihypertensive drugs. All were taking a diuretic, 89% were taking a beta-blocker, and 55% were taking an angiotensin-receptor blocker.

Six months after renal denervation,

• Mean blood pressure decreased from 172.9/92.5 to 151.3/85.5 mm Hg, confirmed by 24-hour ambulatory monitoring, if available (n=50).
• Mean heart rate decreased from 67.7 to 60.5 bpm.
• Mean left-ventricular mass index decreased from 61.5 to 53.4 g/m².
• Measures of diastolic function also improved.

The changes in cardiac function and ventricular size were not tied to the magnitude of the blood-pressure reduction, which “suggest[s] a direct effect of the sympathetic nervous system on myocardial morphology and function,” Schirmer and colleagues write. They call for further research to investigate functional cardiovascular benefits of renal denervation beyond blood-pressure reduction.

Promising Early Benefit, Needs Confirmation

In an accompanying editorial ^[2], Bakris and Dr Sandeep Nathan (University of Chicago) commend Schirmer and colleagues “for providing promising early benefit of catheter-based renal denervation and for highlighting a possible blood-pressure–independent facet of this technique.” However, they caution that although the findings are “intriguing,” the study’s limitations include that it was

• relatively small,
• conducted at a single center,
• lacked a sham control, and
• relied on echocardiography rather than magnetic resonance imaging.

Therefore, “these observations need confirmation before acceptance in clinical practice . . . and can only be applied to those with inclusion criteria used in their study,” the editorialists conclude.

“It’s an exciting, provocative result, and there’s a good chance that it will stand the test of time, but I still think in general, it’s best to be cautious about new technologies and relatively small studies, because time typically shows that they provide an overestimate of what the true effects will be,” Bhatt commented when interviewed.

“Whether the reduction in left-ventricular mass is beyond what would be anticipated with blood-pressure and heart-rate reduction—certainly this analysis suggests that is a possibility—needs to be confirmed in larger studies,” he added, echoing the authors and editorialists.

Potentially referring physicians, in the United States where the procedure is investigational, and even in Europe where it’s approved, appear to be waiting for the results of SYMPLICITY HTN-3, Bhatt said. This blinded, randomized, multicenter trial will provide a clearer picture of what sort of blood-pressure reductions are achievable in patients with resistant hypertension who undergo renal denervation. Results are expected by mid-2014.

References

1. Schirmer SH, Sayed M, Reil J-C, et al. Improvements of left-ventricular hypertrophy and diastolic function following renal denervation – Effects beyond blood pressure and heart rate reduction. J Am Coll Cardiol 2013; DOI:10.1016/j.jacc.2013.10.073. Abstract
2. Bakris G, Nathan S. Renal denervation and left ventricular mass regression: A benefit beyond blood pressure reduction? J Am Coll Cardiol 2013; DOI:10.1016/j.jacc.2013.11.015. Editorial

SOURCE

http://www.medscape.com/viewarticle/817397?nlid=41903_2105&src=wnl_edit_medp_card&uac=93761AJ&spon=2

This Open Access Scientific Journal has covered all the major developments reported on Renal Denervation since its inception

The Archive for Renal denervation

http://pharmaceuticalintelligence.com/category/cardiac-and-cardiovascular-surgical-procedures/renal-denervation/

Search Results for Renal Denervation

http://pharmaceuticalintelligence.com/?s=Renal+denervation

For the ORIGINAL work on 

Renal Sympathetic Denervation: Updates on the State of Medicine

the Readers is called to go to the ORIGINAL SOURCES listed below:

Intravascular Stimulation of Autonomics: A Letter from Dr. Michael Scherlag

http://pharmaceuticalintelligence.com/2012/09/02/intravascular-stimulation-of-autonomics-a-letter-from-dr-michael-scherlag/

Imbalance of Autonomic Tone: The Promise of Intravascular Stimulation of Autonomics

http://pharmaceuticalintelligence.com/2012/09/02/imbalance-of-autonomic-tone-the-promise-of-intravascular-stimulation-of-autonomics/

Interaction of Nitric Oxide and Prostacyclin in Vascular Endothelium

http://pharmaceuticalintelligence.com/2012/09/14/interaction-of-nitric-oxide-and-prostacyclin-in-vascular-endothelium/

Absorb™ Bioresorbable Vascular Scaffold: An International Launch by Abbott Laboratories

http://pharmaceuticalintelligence.com/2012/09/29/absorb-bioresorbable-vascular-scaffold-an-international-launch-by-abbott-laboratories/

The Molecular Biology of Renal Disorders: Nitric Oxide – Part III

http://pharmaceuticalintelligence.com/2012/11/26/the-molecular-biology-of-renal-disorders/

Treatment of Refractory Hypertension via Percutaneous Renal Denervation

http://pharmaceuticalintelligence.com/2012/06/13/treatment-of-refractory-hypertension-via-percutaneous-renal-denervation/

Renal Denervation Technology of Vessix Vascular, Inc. been acquired by Boston Scientific Corporation (BSX) to pay up to $425 Million

http://pharmaceuticalintelligence.com/2012/11/08/renal-denervation-technology-of-vessix-vascular-inc-been-acquired-by-boston-scientific-corporation-bsx-to-pay-up-to-425-million/

Share this:

• X
• LinkedIn
• Facebook
• Print
• Email

Like this:

Like Loading…

Read Full Post »

« Newer Posts - Older Posts »

• Follow Blog via Email

  Enter your email address to follow this blog and receive notifications of new posts by email.

  Email Address

  Follow

  Join 2,038 other subscribers

• Recent Posts

  • Novartis and Bristol Myers Squibb halt CAR-T trial for autoimmune diseases over patient deaths: a potential issue with cell-based manufacturing September 15, 2026
  • FDA Contemplates Changes in Trial Design, Drug Development, and Use of AI in Clinical Trials September 15, 2026
  • FDA Moves Forward With Its Guidance Framework for Rare Disease Trials: 2026 August 3, 2026
  • Artificial Intelligence TRANSFORMS Medicine, Biotech and Healthcare, How? August 3, 2026
  • In Memoriam: Nobel Laureate J. Michael Bishop for discovery of Retroviral Oncogenes July 31, 2026
  • Companies Actively Engaging Artificial Intellegence for Drug Design: 2026 July 31, 2026
  • AI-Native Drug Discovery Landscape 2026 – How LPBI Group Differentiates in the New Era of Foundation Models July 19, 2026
  • In Memoriam: In Remembrance of Cancer Researchers who passed in 2026 July 13, 2026
  • Urgent Request for Action on Proposed Rule Affecting Federal Funding Grant Review July 7, 2026
  • 2026 Tang Prize in Biopharmaceutical Science Awarded to Three Pioneers of Cellular Immunotherapy Revolutionizing Treatments for Blood Cancers and Solid Tumors July 5, 2026

• Archives

  Archives Select Month September 2026  (2) August 2026  (2) July 2026  (6) June 2026  (4) May 2026  (1) January 2026  (10) December 2025  (8) November 2025  (8) October 2025  (12) September 2025  (2) July 2025  (4) June 2025  (8) May 2025  (4) April 2025  (2) March 2025  (1) February 2025  (2) January 2025  (3) December 2024  (1) November 2024  (5) October 2024  (7) September 2024  (7) August 2024  (1) June 2024  (1) May 2024  (2) April 2024  (2) January 2024  (1) November 2023  (1) October 2023  (3) September 2023  (3) August 2023  (2) July 2023  (2) June 2023  (7) May 2023  (4) April 2023  (2) March 2023  (5) February 2023  (2) January 2023  (3) December 2022  (2) October 2022  (6) September 2022  (2) August 2022  (1) July 2022  (3) June 2022  (3) May 2022  (8) April 2022  (10) March 2022  (7) February 2022  (7) January 2022  (3) December 2021  (3) November 2021  (4) October 2021  (11) September 2021  (5) August 2021  (8) July 2021  (21) June 2021  (8) May 2021  (10) April 2021  (8) March 2021  (15) February 2021  (17) January 2021  (20) December 2020  (10) November 2020  (12) October 2020  (26) September 2020  (17) August 2020  (22) July 2020  (27) June 2020  (33) May 2020  (26) April 2020  (42) March 2020  (22) February 2020  (11) January 2020  (7) December 2019  (20) November 2019  (13) October 2019  (11) September 2019  (3) August 2019  (8) July 2019  (25) June 2019  (47) May 2019  (40) April 2019  (27) March 2019  (29) February 2019  (17) January 2019  (50) December 2018  (14) November 2018  (17) October 2018  (18) September 2018  (17) August 2018  (8) July 2018  (20) June 2018  (22) May 2018  (17) April 2018  (12) March 2018  (20) February 2018  (26) January 2018  (16) December 2017  (6) November 2017  (20) October 2017  (13) September 2017  (16) August 2017  (16) July 2017  (19) June 2017  (20) May 2017  (32) April 2017  (21) March 2017  (10) February 2017  (24) January 2017  (21) December 2016  (43) November 2016  (8) October 2016  (40) September 2016  (67) August 2016  (59) July 2016  (75) June 2016  (37) May 2016  (95) April 2016  (152) March 2016  (175) February 2016  (196) January 2016  (139) December 2015  (90) November 2015  (287) October 2015  (237) September 2015  (115) August 2015  (96) July 2015  (63) June 2015  (44) May 2015  (53) April 2015  (76) March 2015  (95) February 2015  (83) January 2015  (75) December 2014  (75) November 2014  (88) October 2014  (135) September 2014  (117) August 2014  (88) July 2014  (88) June 2014  (109) May 2014  (60) April 2014  (85) March 2014  (58) February 2014  (72) January 2014  (107) December 2013  (104) November 2013  (136) October 2013  (62) September 2013  (32) August 2013  (46) July 2013  (74) June 2013  (110) May 2013  (112) April 2013  (86) March 2013  (92) February 2013  (63) January 2013  (63) December 2012  (46) November 2012  (71) October 2012  (84) September 2012  (82) August 2012  (122) July 2012  (59) June 2012  (34) May 2012  (46) April 2012  (2)

• Categories

  Categories Select Category 3D Printing for Medical Application  (240)    3D Plotting Scaffolds  (44)    BioInks  (34)       Biopolymer Blend Open Porous  (18)       Dental Applications  (10)    BioPrinting in Regenerative Medicine  (77)       Cell Level  (16)       MicroEngineering Cell-Tissue & Systems  (31)       Tissue Engineering  (37)    Cardiovascular and Vascular Systems  (30)       Artificial Vascular Structures  (9)       Cardiovascular Tissue  (8)    Drug Development using MultiOrgan Chip  (12)    Drug Development/Formulation using 3D Printing  (10)    MEMS  (16)       Bio-MEMS  (12)    Organ-on-a-Chip  (11)    Programmable Sensors (Carbon Nano Tubes)  (5) 3rd Party IP: Drug DIscovery  (1) 4D Printing and Meta Materials  (10) Academic Publishing  (223)    Key Opinion Leaders in eScientific Publishing – Interviews with  (8) Advanced Drug Manufacturing Technology  (97)    Antimalarial Preparation  (8)    Autologous Cell Therapy  (14)    Automated Cell Processing  (13) Allergy and Infectious Diseases  (12) Alzheimer’s Disease  (163)    Etiology  (77)    Medical Device Therapies for Altzheimer’s Disease  (15)    Pharmacotherapy and Cell Activity  (51) Anticancer Resistance  (31) Art Exhibits on the Human Condition  (1) Art Inspires Science  (4) Article Type  (2)    Authored  (1)    Curated  (2)    Scientific report  (1) Artificial Heart  (2) Artificial Intelligence – General  (240)    An executive’s guide to AI  (11)    Artificial Intelligence – Breakthroughs in Theories and Technologies  (119)    Artificial Intelligence Applications in Health Care  (131)       Artificial Intelligence in CANCER  (42)       Artificial Intelligence in Health Care – Tools & Innovations  (77)    Artificial Intelligence in Medicine – Application for Diagnosis  (72)       Artificial intelligence applications for cardiology  (33)          AI-assisted Cardiac MRI  (10)       Artificial Intelligence in Psychiatry  (7)       Deep Learning in Pathology  (19)    Artificial Intelligence in Medicine – Applications in Therapeutics  (71)    ChatGPT, GPT-4  (7)       ChatGPT at LPBI Group  (3)       ChatGPT in Academic Education  (3)    Machine Learning  (73)       Deep Learning  (26)       Natural Language Processing (NLP)  (45)    Machine learning in predicting type 2 diabetes  (6) Auditory and vision  (13) Autism Spectrum Disorders  (10) Autoimmune Inflammatory DIseases  (25)    Crohn’s disease  (5)    Tolerance-inducing Autoimmune Disease Therapeutics  (7)    Ulcerative Colitis  (3) Autophagosome  (4) Bacterial Resistance  (25) Behavior  (26) Behavioral Genetics  (21) Big Data  (88)    Intelligent Information Systems  (51) Bio Instrumentation in Experimental Life Sciences Research  (368)    Analytical Instruments Industry  (5)    Microfuidics  (8) Bio-Ethics  (16) BioBanking  (36) Biodegradable Drug-eluting Material  (8) Bioengineering & reverse engineering design  (43) BioIT: BioInformatics  (147) BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics  (135)    Advanced Computing Platform  (32)       Blockchain Transactions System  (6)          Platform for Content Monetization embedded Content Promotion  (1)    Pancreatic adenocarcinoma classifier  (4)    Simulation Modeling in NGS  (5) Biological Engineering  (43) Biological Networks  (193) Biological Networks, Gene Regulation and Evolution  (479)    Virology  (10) Biomarkers & Medical Diagnostics  (572)    VOC – Volatile Organic Compounds as BioMarkers  (2) Biomedical Measurement Science  (173) BioSimilars  (112) BioTechnology – Venture Creation  (133)    Foundations for supporting Science and Education  (14)    Philanthropy to Academic Institution  (3) BioTechnology – Venture Creation, Venture Capital  (110)    Seeking Talent  (3) BiVAD  (1) Blindness  (6) Bone Disease and Musculoskeletal Disease  (82) Brain Basis of Emotion  (5) Business Career Consideration  (1) Ca2+ triggered activation  (61) Calcium  (21) Calcium Signaling  (71) Calmodulin Kinase and Contraction  (36) Cancer – General  (186) Cancer and Current Therapeutics  (412)    interventional oncology  (49)       Breast Cancer – impalpable breast lesions  (20)       Prostate Cancer: Monitoring vs Treatment  (9) CANCER BIOLOGY & Innovations in Cancer Therapy  (1,127)    Anaerobic Glycolysis  (51)    Cachexia  (18)    Cancer Genomics  (85)       Circulating Tumor Cells (CTC)  (27)          Liquid Biopsy Chip detects an array of metastatic cancer cell markers in blood  (17)             mRNA  (6)          MagSifter chip  (1)       KRAS Mutation  (9)       Li-fraumeni syndrome.  (4)       TP53 – Germline mutations  (9)    cancer metabolism  (28)    Funding Opportunities for Cancer Research  (13)    Genomic Expression  (150)    Glioblastoma  (7)    Hexokinase  (14)    Loss of function gene  (18)    Metabolic Immuno-Oncology  (21)    Metastasis Process  (15)    Methylation  (33)    Microbiome and Responses to Cancer Therapy  (10)    Monoclonal Immunotherapy  (29)    mtDNA  (13)    Oxidative phosphorylation  (56)    Pancreatic cancer  (10)    Pyruvate Kinase  (27)    The NCI Formulary  (1)    tumor microenvironment  (16)    Warburg effect  (50) Cancer Informatics  (104) Cancer Prevention: Research & Programs  (132) Cancer Screening  (108) Cancer Vaccines: Targeting Cancer Genes for Immunotherapy  (30)    Engineering Enhanced Cancer Vaccines  (3) cancer-general  (7) Cardiac and Cardiovascular Surgical Procedures  (328)    Aortic Valve: TAVR, TAVI vs Open Heart Surgery  (91)       Prosthesis-Patient Mismatch (PPM) in TAVI vs SAVR  (2)       TAVI vs Open Heart Surgery  (6)       Transcatheter Aortic Valve Replacement via the Transcarotid Access  (3)       Transcaval TAVR Procedure  (3)       Valve-in-Valve Procedure  (5)    Atrial Fibrilation (a-Fib), Cardiac Pacing and Arrhythmias  (18)    BackBeat’s Cardiac Neuromodulation Therapy (CNT) bioelectronic therapy  (1)    CABG  (47)    Cancer Surgery of the Heart  (10)    Cardiovascular Fluid Management: algorithms  (1)    Heart Transplant  (16)    Heart-Lung Transplant  (11)    Implantation  (3)    Left Main Coronary Artery Disease (LMCAD)  (3)    Mechanical Assist Devices: LVAD, RVAD, BiVAD, Artificial Heart  (22)    Mitral Valve: Repair and Replacement  (64)       TMVR – Transcatheter Mitral Valve Repair  (5)    PCI  (108)       Bioresorbable Vascular Scaffold (BVS)  (4)       Invasive FFR for PCI  (2)       Multivessel PCI FFR Guidance  (1)       Robotic-assisted percutaneous coronary intervention  (2)       Stent Retriever in endovascular thrombectomy  (3)    Peripheral Arterial Disease & Peripheral Vascular Surgery  (65)       Abdominal Aorta  (20)       Carotid Artery  (15)       Limb ischemia  (4)       Thoracic Aorta  (16)    Pulmonary Valve Replacement and Repair  (3)    Renal Denervation  (20)    Replacement  (1)    Robotically assisted Cardiothoracic Surgery  (2)    Tricuspid Valve Repair  (7)    Vena Caval Filters: Device for Prevention of Pulmonary Embolism and Thrombosis  (2) Cardiovascular Pharmacogenomics  (171) Cargo  (3) Cell Biology  (323) Cell Biology, Signaling & Cell Circuits  (673)    Apoptosis  (17)    Autophagy-Modulating Proteins  (6)    “Antibody–enzyme conjugates”  (6)    Cell Processing System in Cell Therapy Process Development  (28)    Endoplasmic reticulum  (3)    Enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP)  (3)    Ubiquitin  (11) Cerebrovascular and Neurodegenerative Diseases  (123)    Stroke  (9) Chemical Biology and its relations to Metabolic Disease  (464)    #BIGAxisSummit  (1)    Gut Microbiome and Obesity  (8) Chemical Genetics  (350) Child and Adolescent Psychiatry  (13) Childhood cancer  (17) Childhood malnutrition  (3) children  (4) Circulating Progenitor Cells  (27)    Bone marrow derived cells  (17)    Endothelial cells  (7)    Umbilical cord cells  (6) Clinical & Translational  (239) Clinical Diagnostics  (220)    Mass automation of plasma proteins  (13) Clinical Genomics  (144) Coagulation Therapy and Internal Bleeding  (83) Cognition  (47) Commercialization  (20) Components and IRB related issues  (4) Computational Biology/Systems and Bioinformatics  (471)    Computational Histopathology  (3)    Meta-analysis of transcriptome data  (10) Conference Coverage with Social Media  (494)    MassBio  (3) coronavirus  (18) COVID-19  (20) CRISPR/Cas9 & Gene Editing  (192)    CRISPR alternative for editing genes without cutting  (14)       CAST – Alternative to CRISPR/Cas9  (3)       Transposon-encoded CRISPR–Cas systems direct RNA-guided DNA integration  (4)    CRISPR applied to Human Germ Line  (13)       Gene Editing Impact on Longevity  (6) CT  (20) Cytokines  (21) Cytoskeleton  (85) Developmental biology  (107) Diabetes Mellitus  (146)    Artificial Pancreas for Type 2 Diabetes  (4)    Artificial Pancreas for Type1 Diabetes  (8)    Gestational diabetes  (5) Diagnostic Immunology  (61) Diagnostics and Lab Tests  (128)    Liquid Biopsy: Circulating Tumor Cells in Urine and Blood  (9) Digital HealthCare – biotech & internet joint ventures  (47) Disease Biology  (334) Disease Biology, Small Molecules in Development of Therapeutic Drugs  (488) DNA repair  (73)    Apoptosis  (13)    Autophagy  (13)    Cell death pathways  (19)    Proteolysis  (8)    Proteosome  (8) Drug Delivery Platform Technology  (159)    Drug Carrier Design  (21)       Medication Remote Compliance Monitoring  (3)    Exosomes: Natural Carriers for siRNA Delivery  (9) Drug Toxicity  (74) Ecosystems & Industrial Concentration in the Medical Device Sector  (172)    Cardiac & Vascular Repair Tools Subsegment  (128)    Exec Compensation in the Cardiac & Vascular Repair Tools Subsegment  (14)    Massachusetts Niche Suppliers and National Leaders  (20) Electronic Health Record  (10) Embryology  (24) Empathy  (6) Endocrine Diseases  (60) Enzyme Induction  (46)    ion-transporting enzyme  (2)    K + -ATPase.  (1)    Na +  (2) Epigenetics and Environmental Factors  (35) Ethics and Leadership  (10) Executive Compensation – Big Pharma  (3) Fat soluble vitamins  (4) FDA  (73) FDA Regulatory Affairs  (360)    FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning – GCP, GLP, ISO 14155  (52)    ISO 10993 for Product Registration: FDA & CE Mark for Development of Medical Devices and Diagnostics  (30) Fetal Ultrasound  (2) Fiction and medicine  (5) Frontiers in Cardiology and Cardiovascular Disorders  (929)    Acute Myocardial Infarction  (63)       Cardiogenic Shock  (5)    Anemia in CVD Patients  (6)    Cardio-Oncology  (4)    Cardiomyopathy  (57)    Cardiovascular Research  (187)       Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism  (64)       Pre-Clinical Animal Model Development  (23)    Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Pulmonary Arterial Hypertension (PAH)  (20)    Cost of Inpatient Stay for Cardiovascular Diagnosis for Admission  (1)    Electrophysiology  (111)       Ablation Procedure vs Drug Therapy  (2)       Arrhythmia Detection with Machine Learning Algorithms  (7)       Cardiotoxic Risks of Immune Checkpoint Inhibitors  (1)       Genomic Analysis of EKG Electrophysiology Genomics  (3)       implantable cardioverter defibrillator (ICD) and External Defibrillation  (1)       implantable pacemaker  (2)       Rare heart rhythm disorders and Long QT syndrome (LQTS)  (7)    Epigenetics and Cardiovascular Risks  (57)    Heart Failure (HF)  (51)       Acute coronary syndrome  (7)       congestive heart failure  (19)       Hypertensive Disorders of Pregnancy  (1)    Medical Devices R&D and Inventions  (212)       Assist Devices: LV  (3)       RV  (1)       Stents & Tools  (90)       Valves & Tools  (67)    Origins of Cardiovascular Disease  (422)       Atherogenic Processes & Pathology  (180)       Congenital Heart Disease  (34)          Genetic Mutations in Congenital Heart Disease  (4)       inflammation independent of lipid levels  (13)       Systemic Inflammatory Diseases as CVD Risk  (12)    Pharmacotherapy of Cardiovascular Disease  (356)       HTN  (176)       HTN in Youth  (8)       Resident-cell-based  (43)       Subarachnoid Hemorrhage (SAH)  (1)       Transthyretin amyloid cardiomyopathy (ATTR-CM)  (1)    Spontaneous Coronary Artery Dissection (SCAD)  (6)    Stroke  (15)       endovascular thrombectomy  (6)    Vascular Diseases  (21)       mesenteric ischemia  (3) Future Pandemics Inform-graphics  (1) Gastroenterology  (38) Gene Regulation  (233) Gene Regulation and Evolution  (137) Genetics & Innovations in Treatment  (176) Genetics & Pharmaceutical  (204) Genome Biology  (967)    Exosomes  (25)    Gene Therapy & Gene Editing Development  (42)    mRNA Therapeutics  (20)    Mutagenesis  (27)    Single Cell Genomics  (25)    Single-cell sequencing  (20)    Variation in human protein-coding regions  (35) Genomic Endocrinology  (42) Genomic Testing: Methodology for Diagnosis  (416) Genomics Pharmacy  (40) Global Market of Medical Devices Technology  (3) Global Medical Publishers by Country  (3) Global Partnering & Biotech Investment  (48) GLP  (4) Glycobiology: Biopharmaceutical Production  (16) Glycobiology: Biopharmaceutical Production, Pharmacodynamics and Pharmacokinetics  (28) Health Care System by Country  (58)    AI Models in Healthcare  (12)    Centers for Medicare & Medicaid Services  (8)    Health in Israel  (2)    India  (1)    United States  (27)       Hospital-based Medical Innovations  (10)       Medical Recertification and Maintenance of Certification (MOC)  (1) Health Economics and Outcomes Research  (384)    Women Health  (18)       Heart and Brain Disease in Women  (3) Health Law & Patient Safety  (165)    and Bioethics  (14)    Biotechnology  (12)    Health Law Policy  (13) HealthCare IT  (139) Healthcare Reform  (118)    Accountable Care Organizations  (26)    Affordable Care Act  (29)       Repair  (1)       Repeal ACA  (1)       Replace  (1)    Federal Budget Appropriations  (27)    Healthcare costs and reimbursement  (59)    Indigent Nutrition  (14)    Medicare and Medicaid  (20)    Prescription Drugs Costs  (21)    Skilled Nursing Facilities  (6)    Technology Capital Expenses  (15)    Uninsured and Underinsured  (20) Hematology  (100)    Acute lymphocytic leukemia  (18)    Acute myelocytic leukemia  (21)    Hematopoiesis  (48)    Lymphoma  (21) History and physical exam  (6) Human aging  (27) Human Immune System in Health and in Disease  (246) Human Sensation and Cellular Transduction: Physiology and Therapeutics  (21) Image Processing/Computing  (41) Imaging-based Cancer Patient Management  (116) Immuno-Oncology & Genomics  (133)    mRNA platform in Drug DIscovery  (6) Immunodiagnostics  (141)    Cancer-Immune Interactions  (31)    CNS-Immune Interface  (5)    Neuronal Circuits  (4) Immunology  (123)    Adaptive Immune Response to Biomaterials and Tissue Repair  (13)    Antibody Responses Predict Antigen Exposure  (17)    Cytokine Receptor Structure  (8)    Human Antibody Response  (18)    Human Circulating Antibody Repertoire  (11)    Human Naive B Cell Repertoire  (8)    MHC Repertoires for Antigen Prediction  (8)    Protection Against Autoimmune Disease  (11)    Synthetic Immunology: Hacking Immune Cells  (15) Immunotherapy  (137)    CAR-T  (16)    combination immunotherapies.  (15)    Efficacy of Anti-Tumor T Cells  (15)    Engineering Better T Cells  (11)    Immune Engineering  (18)    Immune Modulatory  (16)    Integrin-targeted Combination Immunotherapy  (6)    Modulating Macrophages in Cancer Immunotherapy  (17)    NK Cell-Based Cancer Immunotherapy  (20)    Synergistic Innate and Adaptive Immunotherapy  (14) Income Disparity  (2) Infectious Disease & New Antibiotic Targets  (162)    Antibiotic resistance  (7)    Viral diseases  (37)       Myocarditis  (1) Infectious Disease Immunodiagnostics  (58)    Virology – Vector-borne DIsease  (17) Inflammasome  (29)    Anti-tumor necrosis factor drugs (TNF inhibitors)  (3) Innovation in Immunology Diagnostics  (111)    Universal Immune Cell Therapies (uICT)  (11) Innovations  (186)    R&D Expenditure  (8) Innovations in Neurophysiology & Neuropsychology  (145)    Age and Life Expectancy  (3)    autism spectrum disorder  (1)    Circadian Rhythm and Sleep  (6)    hNPCs  (1)    Nervous System Function  (2)    Relapsing Multiple Sclerosis  (1) Intellectual Property  (85)    Disputes and Settlements  (9)    IP Valuation Models – Pricing Intangible Assets  (7)    Patent Law in Biotech  (12) Intellectual Property, Innovations, Commercialization, Investment in technological breakthrough  (121) International Global Work in Pharmaceutical  (191) Interventional Oncology: Radiofrequency Ablation, Transarterial Chemoembolization, Microwave Ablation and Irreversible Electroporation (IRE)  (12) Interviews with Scientific Leaders  (319)    Albany Medical Center Prize in Medicine and Biomedical Research  (3)    Annual Breakthrough Prize  (4)    Annual Lewis S. Rosenstiel Award  (2)    Awards in Cardiology and Cardiovascular Medicine  (6)    CEOs of Biotech Companies  (3)    Gerald D Aurbach Award for Outstanding Translational Research  (2)    Interviews with Key Opinion Leaders (KOLs)  (11)    James Prize in Science and Technology Integration  (2)    Jessie Stevenson Kovalenko Medal – Medical Sciences  (2)    Lemelson-MIT Prize  (2)    Life Sciences Breakthrough Prize  (6)    Mosteller Statistician of the Year Award  (2)    Mourning the Loss of a Scientific Leader  (6)    National Academy of Sciences AWARDS  (4)    Nobel Prize Winners  (30)    Noble Prize (Not Nobel Prize)  (2)    Paul Marks Prize for Cancer Research  (2)    Russ Prize recognizes bioengineering achievements worldwide  (2)    The Dan David Prize  (6)    Warren Alpert Foundation Prize Recipients  (4)    Wolf Prize  (2)    Wolf Prize in Medicine  (2)    women in science  (5) Investment in Technological Breakthrough  (60) Ionic Transporters Na+  (25) IP Development by LPBI Group Team  (14) IP Development by LPBI Group Team & Other Organizations  (8) ISO 14155  (3) Joint Venture – SBH & M3DP: SOP and Arrangements  (1) Justice & Law  (1) K  (15) Lab-on-a-chip  (2) Landscape  (1) Lasers and photonics  (18)    Midrange IR spectroscopy  (1) Law and Medicine Conflicts  (15) Leadership, Power, Social Interlocking Connections  (13) Lipid metabolism  (109)    Fatty acids  (38)    Lipids  (38)    PCSK9 Inhibitor Therapy  (19) Lipidomics  (11) Liposome  (4) Liver & Digestive Diseases Research  (122) LPBI Group, e-Scientific Media, DFP, R&D-M3DP, R&D-Drug Discovery, US Patents: SOPs and Team Management  (143)    Award Nominations  (5)    BioMed e-Books e-Series by LPBI Group  (9)    Feedback from Investors: LPBI Portfolio of Five Businesses  (2)    LPBI Group Founder – Aviva Lev-Ari  (27)    PhD  (1)    RN  (1) LPBI Management  (23) Massachusetts Academy of Sciences (MAS)    (2) Materials Science & Engineering  (37)    Organic BioElectronics  (2) Math  (13)    Great Discoveries  (7) Mechanical Assist Devices: LVAD  (4) Medical and Population Genetics  (193) Medical Devices R&D Investment  (242)    21st Century Cures Act  (2)    CE Mark & Global Regulatory Affairs: process management and strategic planning – GCP  (14)    Rhythm management device hardware: dual-chamber pacemakers  (1)       Systolic HTN  (1) Medical Imaging Technology  (59) Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound  (164)    Circumferential-Intravascular-Radioluminescence-Photoacoustic-Imaging (CIRPI)  (3)    Echocardiography  (3)    MRI  (18)    Noninvasive Diagnostic Fractional Flow Reserve (FFR) CT  (6)    Ultra Sound  (10) Melatonin & Circadian Regulation  (9) memory loss  (1) Metabolism  (239)    Biochemical pathways  (144)       Enzymes and isoenzymes  (73)          Dehydrogenase  (16)          Kinase  (28)          Phosphatase  (9)          Phosphorylase  (22)          tyrosine decarboxylases  (3)    Inosine nucleotides  (9)    Leloir pathway  (6)    microbiome  (7)    Pentose monophosphate shunt  (14)    Pyridine nucleotides  (28)       Pyridine nucleotide transhydrogenase  (7) Metabolomics  (321) Methods  (37) Mg++  (10) Microbiologial genetics  (36) Microbiology  (68)    Virology  (14) Micronutrients  (16) Microvesicle  (7) Microwave Ablation and Irreversible Electroporation (IRE)  (1) Mobile Healthcare  (5) Molecular Genetics & Pharmaceutical  (377)    Organoids  (3) Monoclonal antibody therapy  (14) Mutant Gene Expression  (42) Myocardial adenine nucleotide metabolism  (6) Myocardial Ischemia  (26) Myocardial Metabolism  (36) Na-K transport  (40) Na-K-ATPase  (27) Nanotechnology for Drug Delivery  (99) Nephrology  (46) Nephrology & Regenerative medicine  (9) Neurodegenerative Diseases  (89)    hNPCs  (3)    MS  (5) Neurohumoral Transmission  (68)    Ca2+ triggered activation  (21)    Calmodulin  (13)    Parkinson’s disease dyskinesia levodopa  (3)    PKC  (13)    Synaptic vesicle  (20) Neurological Diseases  (121) Neuroscience  (126) Next Generation Sequencing (NGS)  (27)    Nanopore sequencing  (1) NIH Common Fund  (1) Nitric Oxide in Health and Disease  (136) Nuclear Medicine  (11) Nutrigenomics  (68) Nutrition  (195)    Nutritional Supplements: Atherogenesis, lipid metabolism  (50) Nutrition and Phytochemistry  (62)    Minerals in Medicine  (4)    Plant extract  (22) Nutrition Disorders  (31) Nutritional Supplements: Atherogenesis  (31) Obesity  (19) Oligonucleotide Therapeutics & Delivery  (7) Oncolytic virus & OncoViro-Therapy  (23)    Synthetic Virology  (1) Organ-on-a-Chip & 3D Printing in Life Sciences  (7) Pain: Etiology, Genetics & Innovations in Treatment  (24) Parasitology  (5)    Malaria  (4)    Tropical diseases  (1) Patents  (35) Patient Experience  (66)    Art therapy  (1)    Hospital reputation  (7)    Humor  (1)    Music therapy  (2)    Pain Alleviation  (7)    Patient Outlook  (28)    Reputation of Interventionist  (4)    Support Staff  (13)    Supportive therapies  (6)       laughfter  (1)    Surgical Procedure  (9) Patient Experience: Personal Memories of Invasive Medical Intervantion  (30) Patient’s Voice: Personal Experience with Invasive Medical Procedures  (18) Perioperative Statins at Noncardiac Surgery  (2) Personal Health Applications: Tech Innovations serves HealhCare  (43) Personalized and Precision Medicine & Genomic Research  (740)    Longevity  (3)    New Drug Approval  (7)    Patient-centered Medicine  (39)       cell-based therapy  (9)       stem cell biology and patient-specific  (7)    Personalized Medicine Coalition  (10)    Precision Cancer Medicine  (33) Phagophore  (2) Pharmaceutical Analytics  (262)    Pharmacologic toxicities  (63) Pharmaceutical Discovery  (112)    Rapid automation of plasma protein pools  (18) Pharmaceutical Drug Discovery  (207)    Drug Development Process  (62)       Drug Discovery Chemistry  (33)    drug repurposing  (11) Pharmaceutical Industry Competitive Intelligence  (347)    Pharmacovigilance  (8)    Value-based Drug Pricing  (8) Pharmaceutical R&D Informatics  (45) Pharmaceutical R&D Investment  (301) Pharmacodynamics and Pharmacokinetics  (24) Pharmacogenomics  (161) Photography Collection  (1) Physics  (12) Placenta  (7) Population genetics  (27) Population Health Management  (205)    Evolution of Biology Through Culture  (14)    U.S. Employment-to-Population Ratio  (8) Population Health Management, Genetics & Pharmaceutical  (643)    COVID-19  (157)       Biomarkers: Inflammation  (37)       Cancer Researchers Fighting COVID-19  (14)       COVID-19 effects on Human Heart  (15)       COVID-19: Pandemic Surgery Guidance  (19)       Economic Impact of Coronavirus Pandemic  (41)       number of asymptomatic infections  (27)       Treatment Protocols for COVID-19  (62)    SARS-CoV-2  (141)       Coronavirus Gene Expression  (66)          SARS-CoV-2 circulating variants   (14)          SARS-CoV-2 Viral Variants  (19)       Glycosylation and its Role in SARS-CoV-2 Viral Pathogenesis  (2)       Immune-Mediation (independent immunopathology: lung and reticuloendothelial system)  (30)       Mechanisms of infection by SARS-CoV-2  (21)       SAR-Cov-2 a vasculotropic (blood vessels) RNA Virus  (35)          SARS-COV2 Hijacking the Complement and Coagulation Systems  (19)       Seasonality & Environmental Factors in Resurgence  (26)       Serology tests for coronavirus antibodies  (44)       T-cell response to SARS-CoV-2 infection  (14)       Vaccinology  (51)          Mechanism of Thrombosis with AZ & J&J COVID-19 Vaccines  (5)       Virtual Drug Molecule Screening targeting SAR-CoV-2 proteins  (8)    Virus Infective Acute Respiratory Syndrome: SARS-CoV  (92) Population Health Management, Nutrition and Phytochemistry  (162) Preimplantation Genetic Diagnosis and Reproductive Genomics  (13) Protein-energy malnutrition  (12) Proteomics  (367)    Amino acids  (54)    Proteins  (138) Pulmonary diseases  (16)    Lung and pulmonology  (15) Pulmonary pathology  (8) Radio Frequency (RF)-based Surgical Solutions  (2) REAL TIME Conference Coverage Twitter’s Hashtags and Handles per Presentation/session  (50) Regenerative Biology and Medicine  (92) Regulated Clinical Trials: Design, Methods, Components and IRB related issues  (265) Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics  (113) Reproductive Biology & Bio Instrumentation  (78) RNA Biology  (81)    RNA interference (RNAi) therapeutic  (4) RNA Biology, Cancer and Therapeutics  (64) RVAD  (1) SBIR, SBA, NIH, NSF  (3) Schizophrenia  (16) Scientific & Biotech Conferences: Press Coverage  (182) Scientific Publishing  (609)    Curation  (585)       Curation methodology  (40)       De novo synthesis  (16)       Dialectic  (17)       Discovery process  (72)       Evolutionary cognition  (52)       Experimental validation  (91)       Explanatory  (91)       Historical relevance  (71)       Technology Advance Assessment of  (69)       Theoretic convergence  (27)    Open Access Journals  (37) Scientist: Career considerations  (198)    Big Data & Analytics  (17)    Data Science  (13)    Women in Life Sciences  (12) Scoop.it  (19) Sensors & Analytics  (18) Sepsis  (2) Severe Autism  (3) Signaling  (102)    Phosphorylation  (43)    S-nitrosylation  (13)    Ubiquitinylation  (34) Signaling & Cell Circuits  (130) single cell sequencing  (3) Small Molecules in Development of Therapeutic Drugs  (71) Social Development  (15) Specialized 3D BioPrinters (Cornea  (1) Statistical Methods for Research Evaluation  (137) Stem Cells for Regenerative Medicine  (177)    Cardiac muscle regeneration  (19)    Competition in regenerative stem cell science  (18)    Human neural progenitor cells  (8)    Skeletal muscle regeneration  (9) STORM  (2) Stress Disorders  (19) Substance Abuse  (4) Systemic Inflammatory Response Related Disorders  (161)    Inflammatory Pathophysiology  (9) Technology Transfer: Biotech and Pharmaceutical  (354) therapeutics  (3) Tissue Engineering and Regenerative Medicine  (22) Tissue Microenvironment  (5) Transarterial Chemoembolization  (2) Transcriptomics  (47) Transformative Technologies in Healthcare  (23) Translational Science  (230)    Best evidence  (52)    Bias measurement tools  (2)    Evidence-based decision-making  (29)    Inferential analysis  (25)    Intra-rater error  (1)    Quality Assurance  (8)    Random Error  (2)    Systematic Error (Bias)  (6)    Total error  (2)    Translational Effectiveness  (49)    Translational Research  (92) Trends in Global Economy  (6) Uncategorized  (1,019) Unfolded Protein Response (UPR)  (6) US and Global Economy: Trends and Findings  (9) Venture Capital  (47)    Income Geographic Distribution  (3)    Institutional Capital Raised by Female Founders  (6) virology  (10) Vision  (7) Voices of Patients and Healthcare Providers  (22) Water Transporters  (8) Wearable Tech + Digital Health  (5) Anemia  (22) Neutropenia  (8) Neutrophilia  (9) Platelet count disorder  (9) Folate and B12  (7) Iron deficiency  (5) Myelodysplasia  (13) Myelofibrosis  (10)

• Meta

  • Log in
  • Entries feed
  • Comments feed
  • WordPress.org

• • 2012pharmaceutical
  • sjwilliamspa