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Sustained Cardiac Atrial Fibrillation: Management Strategies by Director of the Arrhythmia Service and Electrophysiology Lab at The Johns Hopkins Hospital

Posted in Bio Instrumentation in Experimental Life Sciences Research, Cardiac & Vascular Repair Tools Subsegment, Cell Biology, Signaling & Cell Circuits, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Frontiers in Cardiology and Cardiovascular Disorders, Health Economics and Outcomes Research, HTN, Medical Devices R&D Investment, Pharmaceutical R&D Investment, Pharmacotherapy of Cardiovascular Disease, Technology Transfer: Biotech and Pharmaceutical, tagged , , , , , , , , , , , on October 16, 2012| 2 Comments »

Atrial Fibrillation: The Latest Management Strategies

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 8/5/2013

Ischemic strokes are the most common type of AFib-related stroke5 and can be extremely debilitating.6,7 It’s important to help your patients understand the risk of ischemic stroke and how you can help lower that risk.

Nearly 9 out of 10 AFib-related strokes are ischemic, and most are cardioembolic5,8,9

  • Cardioembolic strokes are most commonly caused by AFib9,10
  • Hemorrhagic strokes account for approximately 10% of AFib-related strokes5
  • AFib-related ischemic strokes are primarily caused by an embolus formed in the left atrial appendage of the heart11

Ischemic strokes can be devastating, often resulting in irreversible brain damage2

  • Debilitating effects of a stroke include paralysis, slurred speech, and memory loss12
    • Every second, ≈32,000 brain cells can die due to hypoxia from lack of blood flow4
    • In 1 minute, nearly 2 million brain cells can die—increasing the risk of disability or death2-4
  • Severely disabling stroke is frequently rated by patients as equivalent to or worse than death13

Strokes are a leading cause of disability in the US14

The good news is you can significantly reduce your AFib patients’ risk of ischemic stroke with anticoagulation therapy.11,15,16 By keeping them appropriately anticoagulated, you can help your patients avoid the devastation of ischemic stroke.11

AFib=atrial fibrillation.

References

  1. Types of stroke. Johns Hopkins Medicine Web site. http://www.hopkinsmedicine.org/healthlibrary/printv.aspx?d=85,P00813. Accessed August 9, 2012.
  2. Maas MB, Safdieh JE. Ischemic stroke: pathophysiology and principles of localization. Hospital Physician Neurology Board Review Manual. 2009;13:1-16.http://www.turner-white.com/pdf/brm_Neur_V13P1.pdf. Accessed February 1, 2013.
  3. Rosamond WD, Folsom AR, Chambless LE, et al. Stroke incidence and survival among middle-aged adults: 9-year follow-up of the Atherosclerosis Risk in Communities (ARIC) cohort. Stroke. 1999;30:736-743.
  4. Saver JL. Time is brain—quantified. Stroke. 2006;37:263-266.
  5. Mercaldi CJ, Ciarametaro M, Hahn B, et al. Cost efficiency of anticoagulation with warfarin to prevent stroke in Medicare beneficiaries with nonvalvular atrial fibrillation. Stroke. 2011;42:112-118.
  6. Vemmos KN, Tsivgoulis G, Spengos K, et al. Anticoagulation influences long-term outcome in patients with nonvalvular atrial fibrillation and severe ischemic stroke. Am J Geriatr Pharmacother. 2004;2:265-273.
  7. Lin HJ, Wolf PA, Kelly-Hayes M, et al. Stroke severity in atrial fibrillation. The Framingham Study. Stroke. 1996;27:1760-1764.
  8. Grau AJ, Weimar C, Buggle F, et al. Risk factors, outcome, and treatment in subtypes of ischemic stroke: the German Stroke Data Bank. Stroke. 2001;32:2559-2566.
  9. Bogousslavsky J, Van Melle G, Regli F, Kappenberger L. Pathogenesis of anterior circulation stroke in patients with nonvalvular atrial fibrillation: the Lausanne Stroke Registry. Neurology. 1990;40:1046-1050.
  10. Freeman WD, Aguilar MI. Prevention of cardioembolic stroke. Neurotherapeutics. 2011;8:488-502.
  11. Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation—executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. 2006;114:700-752.
  12. Effects of stroke. American Stroke Association Web site. http://www.strokeassociation.org/STROKEORG/AboutStroke/EffectsofStroke/Effects-of-Stroke_UCM_308534_SubHomePage.jsp. Accessed December 8, 2012.
  13. Gage BF, Cardinalli AB, Owens DK. The effect of stroke and stroke prophylaxis with aspirin or warfarin on quality of life. Arch Intern Med. 1996;156:1829-1836.
  14. Centers for Disease Control and Prevention (CDC). Prevalence of Stroke—United States, 2006-2010. MMWR Morb Mortal Wkly Rep. 2012;61:379-382.
  15. Singer DE, Chang Y, Fang MC, et al. The net clinical benefit of warfarin anticoagulation in atrial fibrillation. Ann Intern Med. 2009;151:297-305.
  16. Lip GYH, Andreotti F, Fauchier L, et al. Bleeding risk assessment and management in atrial fibrillation patients: a position document from the European Heart Rhythm Association, endorsed by the European Society of Cardiology Working Group on Thrombosis. Europace. 2011;13:723-746.

SOURCE

http://www.medscape.com/infosite/afib/public/

Straightforward, informed answers to your most important questions about living

with atrial fibrillation – the most common sustained cardiac arrhythmia.

Written by

Hugh G. Calkins, M.D., Director of the Arrhythmia Service

and Electrophysiology Lab at The Johns Hopkins Hospital,

and Ronald Berger, M.D.,

If you’ve ever run up a flight of stairs, chased a tennis ball across the court, or reacted in fright at a scary movie, you know what a pounding heart feels like…

But for the 2.3 million Americans who suffer from atrial fibrillation (AF or AFib), a racing heart is a way of life. Simple tasks like getting out of bed in the morning or rising from a chair can cause dizziness, weakness, shortness of breath, or heart palpitations. For these people, AF severely impairs quality of life – and even when symptoms stemming from AF are mild, the disorder can seriously impact health, increasing the risk of stroke and heart failure.

AF can be a debilitating even deadly condition. Fortunately, it can be successfully managed – but there are various approaches for treating AF or preventing a recurrence. How do you and your doctor choose which approach is right for you?

If you or a loved one has AF, there are so many questions: Do I need an anticoagulant… should I be taking medication to control my heart rate… will my symptoms respond to cardioversion… if I need an antiarrhythmic drug to control AF episodes, which one should I take… when is an ablation procedure appropriate… and more.

It’s critically important to learn everything you can now — so you can partner with your doctor effectively, ask the right questions, and understand the answers.

To help you, we asked two eminent experts at Johns Hopkins to share their expertise and hands-on experience with arrhythmia patients in an important new report, Atrial Fibrillation: The Latest Management Strategies.

Dr. Hugh Calkins and Dr. Ronald Berger are ideally positioned to help you understand and manage your AF. Together with their colleagues at Johns Hopkins, they perform approximately 2,000 electrophysiology procedures and 200 pulmonary vein isolation procedures for atrial fibrillation each year.

Hugh Calkins, M.D. is the Nicholas J. Fortuin, M.D. Professor of Cardiology, Professor of Pediatrics, and Director of the Arrhythmia Service, the Electrophysiology Lab, and the Tilt Table Diagnostic Lab at The Johns Hopkins Hospital. He has clinical and research interests in the treatment of cardiac arrhythmias with catheter ablation, the role of device therapy for treating ventricular arrhythmias, the evaluation and management of syncope, and the study of arrhythmogenic right ventricular dysplasia.

Ronald Berger, M.D., Ph.D., a Professor of Medicine and Biomedical Engineering at Johns Hopkins, is Director of the Electrophysiology Fellowship Program at The Johns Hopkins Hospital. He serves on the editorial board for two major journals in the cardiovascular field and has written and coauthored more than 100 articles and book chapters.

Atrial Fibrillation: The Latest Management Strategies is now available to you in a digital PDF download and print version.

“I feel like my heart is going to jump out of my chest…” 

An arrhythmia is an abnormality in the timing or pattern of the heartbeat, causing the heart to beat too rapidly, too slowly, or irregularly. Sounds pretty straightforward, but there’s a lot we don’t know about why the heart rhythm goes awry… or the best way to treat it.

In Atrial Fibrillation: The Latest Management Strategies, we focus on what we DO know. In page after page of this comprehensive report, we address your most serious concerns about living with AF, such as:

  • I don’t have any symptoms. Is my problem definitely AF?
  • Can drinking alcohol trigger or worsen AF?
  • Is every person who has AF at risk for a stroke?
  • If my doctor suspects AF, will I have to wear an implantable or event monitor to be sure?
  • Why does AF often show up later in life?
  • What would you recommend to the older patient – 75 and older – who has AF but no bothersome symptoms?
  • What do you recommend for the person with longstanding persistent AF?
  • Is the AF experienced by an otherwise healthy person different from that of a person with underlying heart disease or other health issues?
  • What are the differences among: paroxysmal AF, persistent AF, and longstanding persistent AF?
  • What is the “pill-in-the-pocket” approach to AF?

Anticoagulation Therapy: What You Should Know

While AF is generally not life threatening, for some patients it can increase the likelihood of blood clots forming in the heart. And if a clot travels to the brain, a stroke will result. Anticoagulation therapy is used to prevent blood clot formation in people with AF…

  • Why is anticoagulation therapy with warfarin (Coumadin) needed for some people with AF?
  • How is the use of warfarin monitored?
  • How does a doctor determine if a patient with AF needs to take warfarin?
  • What’s the CHADS2 score and how is it used?
  • If a patient’s CHADS2 score is 1, how do you decide between aspirin and warfarin, or nothing at all?
  • Why is it so difficult to keep within therapeutic range with warfarin?
  • Can I test my INR (a test measuring how long it takes blood to clot) at home?
  • What happens if my INR is too high?
  • What options are available if a patient cannot take warfarin?
  • What are the benefits of dabigatran, a new blood-thinning alternative to warfarin therapy?

Symptom Control: The Art of Rate and Rhythm Control

For many patients and their doctors, it’s difficult to achieve and maintain heart rhythm. Two key management strategies are used: heart rate and heart rhythm control. In Atrial Fibrillation: The Latest Management Strategies, you’ll read an in-depth discussion of the benefits of rate versus rhythm control for AF:

  • What have we learned from the AFFIRM study, and how has this knowledge affected the management of AF?
  • What is catheter ablation of the AV (atrioventricular) node?
  • Why is cardioversion needed?
  • Are there different types of cardioversion?
  • What is chemical cardioversion? What is electrical cardioversion?
  • Can medication be used to convert the heart back to normal sinus rhythm?
  • Which antiarrhythimic drugs are used to treat AF?
  • How is catheter ablation for AF performed?
  • What is pulmonary vein antrum isolation (PVAI) and how is it performed?
  • Who are the best candidates for PVAI?

There’s more to Atrial Fibrillation: The Latest Management Strategies, much more.

We explain surgical ablation of AF, a procedure performed through small incisions in the chest wall… discuss when it’s appropriate to seek a second opinion… take a close look at strokes and explain the warning signs and differences among ischemic, thrombotic, embolic, and hemorrhagic strokes… and provide an arrhythmia glossary of key AF terms used by electrophysiologists and cardiologists.

Direct to You From Johns Hopkins

Atrial Fibrillation: The Latest Management Strategies is designed to give you unprecedented access to the expertise of the hospital ranked #1 of America’s Best Hospitals for 21 consecutive years 1991-2011 by U.S. News & World Report. You simply won’t find a more knowledgeable and trustworthy source of the medical information you require. A tradition of discovery and medical innovation is the hallmark of Johns Hopkins research. Since its founding in 1889, The Johns Hopkins Hospital has led the way transferring the discoveries made in the laboratory to the administration of effective patient care. No one institution has done more to earn the trust of the men and women diagnosed with AF and other cardiovascular conditions.

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Biotech’s No.1 Cluster: Boston — San Francisco is called to “Watch Out”

Posted in Bio Instrumentation in Experimental Life Sciences Research, Pharmaceutical Analytics, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, tagged on October 8, 2012| 1 Comment »

Reporter: Aviva Lev-Ari, PhD, RN

Watch Out SF, Boston Is Turning Into Biotech’s No. 1 Cluster

http://www.xconomy.com/national/2012/10/08/watch-out-sf-boston-is-becoming-biotechs-no-1-cluster/2/

10/8/12Follow @ldtimmerman
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Luke Timmerman is the National Biotech Editor of Xconomy. E-mail him at

ltimmerman@xconomy.com

Follow @ldtimmerman

Biotech has never concentrated in just one place. This industry tends to grow up in geographic clusters, but it will always be spread around the map, partly because great science comes from hundreds of academic hotspots around the world.

But there have always been two places—San Francisco and Boston—that have stood out way above all the other hubs of biotech. And something truly special is happening now in Boston’s biotech cluster, and it’s a long-term mega-trend. Boston, I’m convinced, is very close to taking the title as the world’s No. 1 biotech hub, and holding onto that distinction for a generation.

Before going too much further, I should say a little bit about where I come from on this question. I started covering biotech 11 years ago in Seattle, which is where I call home. But a few years ago, I spent an academic year on a fellowship in Cambridge, MA, that gave me freedom to attend classes and meet innovators at Harvard, MIT, and the Longwood Medical Area. Then I moved to San Francisco for a little more than a year to cover biotech’s biggest companies for Bloomberg News. Four years ago, I made the startup leap to Xconomy, where my job has been to build up our biotech coverage in Boston, Seattle, San Francisco, and San Diego. I’ve spent a lot of time meeting and interviewing people in those places, and writing about life sciences innovation at startups as well as big companies like Amgen and Genentech.

San Francisco, as I think most people in the industry would agree, is still an amazing place for life sciences and has earned its ranking as the No. 1 cluster of biotech. This dates back to the late ‘70s and the formation of Genentech. Even today, if you look at the categories Ernst & Young uses to rank geographic clusters in its most recent “Beyond Borders” report, the San Francisco Bay Area ranks No. 1 in six of the seven. The Bay Area is tops in number of public biotech companies, public company revenue, R&D spending, profits, cash balances, and total assets. Boston was No. 1 in public company market valuations (a number that fluctuates daily), and was second in every other category.

Those numbers tell a much of the story at public companies, but not the whole story, because it leaves out private companies and Big Pharma investment. If you think that private companies and startup funding are an important part of the story, and a leading indicator of future success, Boston has the edge. New England surpassed the Bay Area in seed/early stage biotech financing, and the number of startup companies in 2009/2010. New England had 124 seed/early stage companies that pulled in $1.17 billion in financing that fiscal period, compared with 99 companies that got $938 million that fiscal year, according to figures from PricewaterhouseCoopers and the National Venture Capital Association.

While plenty of people in Boston can scratch the startup itch, quite a few others can find steady work and experience in Big Pharma. Those companies have decided over the last decade to invest big money, and hire a lot of people, in Boston. There’s Novartis, Merck, Pfizer, GlaxoSmithKline, and more. When Paris-based Sanofi bought Cambridge, MA-based Genzyme for $20 billion last year, at a point when it was closing R&D centers around the world, it created combinedoperations in Boston. When Tokyo-based Takeda Pharmaceuticals bought Cambridge, MA-based Millennium Pharmaceuticals a few years ago for $8.8 billion, it didn’t just pick up the company’s crown jewel and leave. It consolidated its global cancer drug R&D operation in Boston, instead a lot more money there, and charged CEO Deborah Dunsire and her team with creating more products like bortezomib (Velcade).

Now look at the independent biotech companies based there. Biogen Idec (NASDAQ: BIIB) has undergone a resurgence the past couple years under a new management team. Vertex Pharmaceuticals (NASDAQ: VRTX) has broken out to become a regional anchor, and regional role model for dozens of startups, thanks to two important new FDA approved drugs. And during a time when manyVCs are cutting back investment or going out of business, Third Rock Ventures has burst on the Boston biotech scene, injecting big money into bold new startup ideas coming out of Boston’s research institutions. Companies like Agios Pharmaceuticals, Constellation Pharmaceuticals, Foundation Medicine, Bluebird Bio, Warp Drive Bio, and Zafgen are a few of these high-impact kind of opportunities that you rarely see sprouting up anywhere else. It will take a few more years to see if this strategy really pays off, but the early indications are encouraging, and have emboldened Third Rock to expand this model to San Francisco.

Cutting-edge science at Harvard University and MIT put Boston on the map in the first place, and Boston is always working hard to keep its edge in fields like genomics, where the Broad Institute rules. But what is interesting to me is how many visionary decisions about transportation and land use—intentional or not—have been made to support that science, and that will pay dividends for generations. Without question, Kendall Square in Cambridge is the most

highly concentrated place in the world for life sciences innovation, in terms of bright people and bright ideas per square foot. There’s no other place in the world with biotech companies big and small, Big Pharma, world-class biomedical researchers, top clinical collaborators, thousands and thousands of talented employees, and venture capitalists all within walking distance.

When I travel to Boston, all I need is a hotel room, a subway pass, and good walking shoes to pack an amazingly efficient day of meetings with innovators. If I need to go to meet companies along Route 128, I’ll just rent a Zipcar from Kendall Square for a day. Travel to San Francisco or San Diego, and you have to rent a car (often way overpriced) and spend a fair amount of time traveling around suburban office parks, sitting in traffic.

The difference in land use and transportation has helped turn Boston into a tight-knit community. When it’s easy for a bench scientist, a business development director, or a CEO from different companies to talk shop or commiserate, they do. And they help each other. “When you are struggling with some kind of issue, you call up five of your friends at other companies and ask how they dealt with something like that,” says Adelene Perkins, CEO of Cambridge-based Infinity Pharmaceuticals (NASDAQ: INFI).

Adelene Perkins, CEO of Infinity Pharmaceuticals

David Schenkein, the CEO of Cambridge, MA-based Agios Pharmaceuticals, has had the experience of living in both the East and West Coast’s top biotech hubs, and he says the density of Boston translates into a competitive advantage. He joined the biotech industry in 2001 at Cambridge-based Millennium Pharmaceuticals, moved to Genentech from 2006 to 2009, and returned to Boston to run Agios. He says Genentech was an amazing place that lived up to its reputation for excellence, but it’s also geographically isolated at its campus on a hilltop in South San Francisco. That isolation doesn’t help foster the kind of company-to-company networking and cross-pollination of ideas that happens when so many people in the industry are within walking distance.

David Schenkein, CEO of Agios Pharmaceuticals

“The thing in Boston is proximity,” Schenkein says. “At least twice a week, somebody from the Broad Institute, the Whitehead Institute, or Harvard walks to our building to share some data they want to review with us, or I just walk over to their building. It makes life a whole lot easier to not have to get in your car.”

OK, you might say, getting in a car for 20-30 minutes and finding a place to park is no big deal. And people often argue that the West Coast has greater recreation/outdoor/quality of life opportunities that Boston can’t compete with. But the Bay Area also has some real problems with stratospheric housing costs that discourage young people getting started in their careers. Bad transportation and land use policies from decades ago tend to isolate people, keeping them walled off in their professional silos. That isolation keeps people from gaining that kind of peer-to-peer understanding that Perkins says she can get in the Boston network.

Having such a tight-knit industrial community creates a lasting competitive advantage. When people feel connected to a community, they tend to put down roots, knowing that while their company might be risky, they will easily find another job down the street without having to move their families. And they can easily diversify their skill sets in Boston by moving around a few times in their career to different kinds of organizations.

“The biggest advantage I can see building Agios in Boston rather than San Francisco or New York or Boulder is my ability to go from 15 employees to 75 employees in two years, and keep getting A-players,” Schenkein says.

Of course, once a place attracts this many smart people and gets this much critical mass, the advantage tends to create a virtuous cycle. Look at Sarepta Therapeutics (NASDAQ: SRPT). This company recently nailed an important clinical trial with a drug for Duchenne Muscular Dystrophy. It needed to recruit a bunch of new people with expertise in rare diseases. When it couldn’t get the people it said it wanted to move to its headquarters in Seattle, the companymoved its headquarters where the recruits were—Boston.

One other advantage, not to be underestimated, is Boston biotech’s edge in status and clout. When I traveled to the Biotechnology Industry Organization’s conference in Boston in June, I was amazed that the hometown paper, the Boston Globe, considered BIO’s convention to be front-page, above-the-fold news in the Sunday paper. Flipping channels that evening in the hotel, I saw the CEO of the Massachusetts Biotechnology Council being interviewed on New England Cable News about what the Bay State can do to flex even more biotech muscle.

Coming from the West Coast, this amount of attention for biotech is eye-opening. Unless anti-industry activists raise an enormous stink about biotech, it doesn’t make mainstream news. If you live in the Bay Area, your town is dominated by Apple, Google, Facebook, etc.—and unless you work in the industry, you may never have heard of Gilead Sciences (NASDAQ: [[ticker:GILD]). San Diego has some good biotech assets, but most folks think of it first as a military town, or as a wireless infrastructure (Qualcomm) town. Seattle has Boeing, Microsoft, Amazon, Starbucks, Nordstrom, Costco, and no flagship biotech company.

In Boston, if you define healthcare loosely to include all the hospitals, biomedical research, and biotech and Big Pharma, then healthcare is the state’s undisputed No. 1 industry. As Millennium’s Dunsire said at an Xconomy event last week, there are 450,000 people working in healthcare in Massachusetts. That many people in one group creates clout. In Massachusetts, elected officials know this and want to do what they can to help biotech. Even though elected officials can’t always throw big bucks into the industry, this support can mean the difference when a company needs a permit or some smaller issue. And it provides a psychological boost to the companies who know they will be heard, and not just get a cold shoulder from their elected officials.

Aveo Oncology CEO Tuan Ha-Ngoc

One last point about culture. There’s always been some cultural divide between the coasts, and I suppose people will probably never stop arguing about it. People on the West Coast sometimes like to trot out stereotypes about the sharp-elbowed competitors in Boston, how they just can’t collaborate as well as us laid-back West Coasters. That’s just not consistent with the Boston I’ve experienced. If anything, there’s more of a tight-knit collaborative community in Boston than in San Francisco. There’s a can-do spirit, an energy in Boston that is palpable. It will endure. Boston is reaping what it has sown for decades.

“You can feel the sense of common purpose,” says Tuan Ha-Ngoc, the CEO of Cambridge-based Aveo Oncology (NASDAQ: AVEO), who started his biotech career at Genetics Institute in Boston in 1984. “We are all here, we run scientific organizations, we run hospitals, we run companies. We know the future is out there for us.”

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A new treatment for depression and epilepsy – Approval of external Trigeminal Nerve Stimulation (eTNS) in Europe

Posted in Bio Instrumentation in Experimental Life Sciences Research, Innovations in Neurophysiology & Neuropsychology, Medical Devices R&D Investment, tagged , , , , , , on October 7, 2012| 2 Comments »

The eTNS System. (PRNewsFoto/NeuroSigma)

Reporter: Howard Donohue, PhD (EAW)

Following the arrival in the 1990s of a drug for treating depression called fluoxetine (better known by its brand name, Prozac) – a “selective serotonin reuptake inhibitor” (SSRI) – it’s probably fair to say that not many drugs have become as deeply engrained in the public’s general awareness as those of this type. Perhaps one reason for this could be the sheer number of people affected by depression and to whom SSRIs are relevant as a possible treatment (one study has estimated that depression affected upwards of 30 million Europeans in the year 2010 [1]). Perhaps another reason could be the various controversies that have surrounded SSRIs over the years, from stories of increased suicide risk in children [2] to evidence of biases and the “selective” publishing of clinical data favoring the effectiveness of these drugs [3]. Of course, despite the controversies, SSRIs (along with other classes of antidepressant drug) continue to be a mainstay, but let’s not forget, amid their popularity, that there are other ways to treat depressive illnesses. And in maximizing the benefits of treatment for the individual, it’s important to realize that any one of these approaches might work well for one person, but not for another. Among the non-pharmacologic ways to treat depression are psychological approaches, for example cognitive behavioral therapy, or alternatively, “brain stimulation” approaches such as electroconvulsive therapy (ECT). ECT is a method to induce a mild seizure in the patient by means of electrical activity applied to the brain via electrodes connected to the temples.

On the subject of ECT; you could be forgiven for thinking that it’s not very nice, especially if you’ve seen the plights of characters like Randle Patrick “Mac” McMurphy, portrayed by Jack Nicholson in One Flew Over the Cuckoo’s Nest or Russell Crowe’s portrayal of Dr. John Nash (based on the real-life Nobel Laureate in Economics by the same name) in A Beautiful Mind. Nonetheless, despite the treatment in Hollywood of ECT as a sinister, repressive, and even brutal procedure, the reality is obviously different and it continues to have a place in medical practice for the treatment of severely depressed patients to this day. This isn’t to say that controversies don’t exist within the medical community concerning certain side effects (such as memory loss), but in balancing this, we should remember that many – if not most – medical procedures have their drawbacks (hopefully, the benefits will far outweigh the drawbacks). Putting aside any thoughts on whether ECT is good or bad, it is recognition and consideration of the drawbacks that helps drive the evolution of medical technologies.

So, in illustrating the evolution that is happening in the field of brain stimulation for treating neurological disorders (in this case, depression and also epilepsy), the recent approval in Europe of an “external Trigeminal Nerve Stimulation” (eTNS) technique provides an excellent example. The technique, called the MonarchTM and exclusively licensed to Neurosigma Inc. (a Los Angeles-based medical device company) “for the adjunctive treatment of epilepsy and major depressive disorder, for adults and children 9 years and older”, is a non-invasive form of neuromodulation therapy [4]. It was invented at the University of California, Los Angleles (UCLA) and has been in development for over 10 years [4]. It works by using a low-energy stimulus to stimulate branches of the trigeminal nerve, a nerve that can affect the activity of several key brain regions believed to be involved in depression and epilepsy. In contrast to ECT, the stimulus is restricted to the soft tissues of the forehead without direct penetration to the brain, which thereby facilitates a non-invasive form of neuromodulation [4]. Following European approval, Neurosigma affirmed in a press release that eTNS is “supported by years of safety and compelling efficacy data generated in clinical trials conducted at UCLA and the University of Southern California (USC)” [4]. In realizing the future potential of eTNS, Neurosigma’s business strategy is now geared toward steps for its adoption at major epilepsy and depression centers in the EU, as well as endeavors to make it available to patients in the US and other countries [4].

To answer the question of whether eTNS will rise to prominence as an effective treatment in the fight against depression and epilepsy, only time will tell. But if it does, as well as being a valuable addition to the armamentarium against these debilitating diseases, maybe its non-invasive nature will mean that the film directors have a harder time in “demonizing” it for dramatic effect. Well anyway, let’s hope so.

References

  1. Wittchen et al. Eur Neuropsychopharmacol 2011: 21:655-79.
  2. http://news.bbc.co.uk/2/hi/health/3656110.stm
  3. Turner et al. N Engl J Med 2008; 358:252-60.
  4. http://www.prnewswire.com/news-releases/neurosigma-receives-ce-certification-168578146.html

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Inhibition of ET-1, ETA and ETA-ETB, Induction of NO production, stimulation of eNOS and Treatment Regime with PPAR-gamma agonists (TZD): cEPCs Endogenous Augmentation for Cardiovascular Risk Reduction – A Bibliography

Posted in Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, BioSimilars, Cell Biology, Signaling & Cell Circuits, Chemical Biology and its relations to Metabolic Disease, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Frontiers in Cardiology and Cardiovascular Disorders, HTN, Nitric Oxide in Health and Disease, Origins of Cardiovascular Disease, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Pharmacotherapy of Cardiovascular Disease, Resident-cell-based, Stem Cells for Regenerative Medicine, tagged , , , , on October 4, 2012| 14 Comments »

Curator of an Investigator Initiated Study: Aviva Lev-Ari, PhD, RN

Inhibition of ET-1, ETA and ETA-ETB, Induction of NO production,  stimulation of eNOS and Treatment Regime with PPAR-gamma agonists (TZD): cEPCs Endogenous Augmentation for Cardiovascular Risk Reduction – A Bibliography

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Benowitz, NL., (2004). Antihypertensive Agents. Chapter 11 in Katzung, BG., Basic & Clinical Pharmacology. McGraw-Hill, 9th Edition, pp. 160-183.

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Increased risks of obesity and cancer, Decreased risk of type 2 diabetes: The role of Tumor-suppressor phosphatase and tensin homologue (PTEN)

Posted in Bio Instrumentation in Experimental Life Sciences Research, Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, CANCER BIOLOGY & Innovations in Cancer Therapy, Cell Biology, Signaling & Cell Circuits, Chemical Biology and its relations to Metabolic Disease, Chemical Genetics, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Genome Biology, Genomic Testing: Methodology for Diagnosis, Human Immune System in Health and in Disease, Liver & Digestive Diseases Research, Medical and Population Genetics, Metabolomics, Molecular Genetics & Pharmaceutical, Personalized and Precision Medicine & Genomic Research, Pharmaceutical R&D Investment, Technology Transfer: Biotech and Pharmaceutical, tagged , , , , , , , , , on October 1, 2012| 2 Comments »

Reporter: Aviva Lev-Ari, PhD, RN

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PTEN Mutations as a Cause of Constitutive Insulin Sensitivity and Obesity

Aparna Pal, M.R.C.P., Thomas M. Barber, D.Phil., M.R.C.P., Martijn Van de Bunt, M.D., Simon A. Rudge, Ph.D., Qifeng Zhang, Ph.D., Katherine L. Lachlan, M.R.C.P.C.H., Nicola S. Cooper, M.R.C.P., Helen Linden, M.R.C.P., Jonathan C. Levy, M.D., F.R.C.P., Michael J.O. Wakelam, Ph.D., Lisa Walker, D.Phil., M.R.C.P.C.H., Fredrik Karpe, Ph.D., F.R.C.P., and Anna L. Gloyn, D.Phil.

N Engl J Med 2012; 367:1002-1011  September 13, 2012DOI: 10.1056/NEJMoa1113966

BACKGROUND

Epidemiologic and genetic evidence links type 2 diabetes, obesity, and cancer. The tumor-suppressor phosphatase and tensin homologue (PTEN) has roles in both cellular growth and metabolic signaling. Germline PTEN mutations cause a cancer-predisposition syndrome, providing an opportunity to study the effect of PTENhaploinsufficiency in humans.

METHODS

We measured insulin sensitivity and beta-cell function in 15 PTENmutation carriers and 15 matched controls. Insulin signaling was measured in muscle and adipose-tissue biopsy specimens from 5 mutation carriers and 5 well-matched controls. We also assessed the effect of PTEN haploinsufficiency on obesity by comparing anthropometric indexes between the 15 patients and 2097 controls from a population-based study of healthy adults. Body composition was evaluated by means of dual-emission x-ray absorptiometry and skinfold thickness.

RESULTS

Measures of insulin resistance were lower in the patients with aPTEN mutation than in controls (e.g., mean fasting plasma insulin level, 29 pmol per liter [range, 9 to 99] vs. 74 pmol per liter [range, 22 to 185]; P=0.001). This finding was confirmed with the use of hyperinsulinemic euglycemic clamping, showing a glucose infusion rate among carriers 2 times that among controls (P=0.009). The patients’ insulin sensitivity could be explained by the presence of enhanced insulin signaling through the PI3K-AKT pathway, as evidenced by increased AKT phosphorylation. The PTEN mutation carriers were obese as compared with population-based controls (mean body-mass index [the weight in kilograms divided by the square of the height in meters], 32 [range, 23 to 42] vs. 26 [range, 15 to 48]; P<0.001). This increased body mass in the patients was due to augmented adiposity without corresponding changes in fat distribution.

CONCLUSIONS

PTEN haploinsufficiency is a monogenic cause of profound constitutive insulin sensitization that is apparently obesogenic. We demonstrate an apparently divergent effect of PTEN mutations: increased risks of obesity and cancer but a decreased risk of type 2 diabetes owing to enhanced insulin sensitivity. (Funded by the Wellcome Trust and others.)

Supported by grants from the Wellcome Trust (095101/Z/10Z, to Dr. Gloyn), the Medical Research Council (G0700222, to Dr. Gloyn; and G0800467, to Drs. Pal and Gloyn), the National Institute for Health Research Oxford Biomedical Research Centre (to Drs. Pal, Karpe, and Gloyn), the Biotechnology and Biological Sciences Research Council (to Drs. Rudge, Zhang, and Wakelam), and the European Union Seventh Framework Program LipodomicNet (202272, for adipocyte signaling work, to Drs. Wakelam and Karpe).

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

We thank the clinicians Trevor R.P. Cole, Louise Izatt, Carole McKeown, Eamonn R. Maher, and Mary Porteous for referring patients for this study; the research nurses Beryl Barrow and Jane Cheeseman for assistance with collecting clinical data; Amy Barrett for analysis of PTEN expression; Sandy Humphries for analysis of apolipoprotein B; Tim James and colleagues at the John Radcliffe Hospital, Oxford, for analysis of glucose and insulin; the NIHR Cambridge Biomedical Research Centre Core Biochemical Assay Laboratory for analysis of leptin and adiponectin; Leanne Hodson and Barbara Fielding for access to control dual-emission x-ray absorptiometry scans and phenotypic data on postmenopausal controls; and Jonathan Clark and Izabella Niewczas for providing lipid standards for the mass-spectrometry analysis.

SOURCE INFORMATION

From the Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford (A.P., T.M.B., M.V.B., J.C.L., F.K., A.L.G.); the Oxford National Institute for Health Research Biomedical Research Centre (A.P., J.C.L., F.K., A.L.G.) and the Oxford Regional Genetics Centre (H.L., L.W.), Churchill Hospital, Oxford; the Inositide Laboratory, the Babraham Institute, Babraham, Cambridge (S.A.R., Q.Z., M.J.O.W.); Wessex Clinical Genetics Service, University Hospital Southampton, Southampton (K.L.L.); the Department of Human Genetics and Genomic Medicine, Faculty of Medicine, University of Southampton, Southampton (K.L.L.); and West Midlands Regional Clinical Genetics Service, Birmingham Women’s Hospital, Birmingham (N.S.C.) — all in the United Kingdom.

Address reprint requests to Dr. Gloyn at the Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Headington, Oxford OX3 7LE, United Kingdom, or atanna.gloyn@drl.ox.ac.uk.

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FDA Approval for Under-Skin Defibrillator goes to Boston Scientific Corporation

Posted in Bio Instrumentation in Experimental Life Sciences Research, Cardiac & Vascular Repair Tools Subsegment, Ecosystems & Industrial Concentration in the Medical Device Sector, FDA Regulatory Affairs, Frontiers in Cardiology and Cardiovascular Disorders, Health Law & Patient Safety, Massachusetts Niche Suppliers and National Leaders, Medical Devices R&D and Inventions, Medical Devices R&D Investment, Origins of Cardiovascular Disease, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Technology Transfer: Biotech and Pharmaceutical, tagged , , , , , , , on October 1, 2012| Leave a Comment »

FDA Approval for Under-Skin Defibrillator goes to Boston Scientific Corporation

Reporter: Aviva Lev-Ari, PhD, RN

 

Boston Scientific Corporation (BSX) Wins FDA Approval for Under-Skin Defibrillator

 

10/1/2012 7:09:13 AM

 

NATICK, Mass., Sept. 28, 2012 /PRNewswire/ — The U.S. Food and Drug Administration has granted Boston Scientific Corporation (NYSE: BSX) regulatory approval for its S-ICD® System, the world’s first and only commercially available subcutaneous implantable defibrillator (S-ICD) for the treatment of patients at risk for sudden cardiac arrest (SCA). The S-ICD System sits entirely just below the skin without the need for thin, insulated wires — known as electrodes or ‘leads’ — to be placed into the heart. This leaves the heart and blood vessels untouched, offering patients an alternative to transvenous implantable cardioverter defibrillators (ICDs), which require leads to be placed in the heart itself.

 

“The S-ICD System establishes the first new category of cardiac rhythm management devices since the introduction of cardiac resynchronization therapy,” said Raul Weiss, M.D., Associate Professor-Clinical, Cardiovascular Medicine at The Ohio State University. “Doctors now have a breakthrough treatment option that provides protection from sudden cardiac arrest without touching the heart.”

Approval of the S-ICD System was based on data from a 330-patient, prospective, non-randomized, multicenter clinical study, which evaluated the safety and effectiveness of the system in patients at risk of SCA. The S-ICD System met the primary endpoints of the study, and results were presented earlier this year at the Heart Rhythm Society 33rd Annual Scientific Sessions. The study results support that the S-ICD System is an important new treatment option for a wide range of primary and secondary prevention patients.

“With the addition of the S-ICD System, we believe Boston Scientific has a compelling and highly differentiated portfolio that will help fuel our growth strategy,” said Hank Kucheman, chief executive officer, Boston Scientific. “We are the only company to offer an FDA-approved subcutaneous implantable defibrillator and expect this to be the case for several years. The S-ICD System, coupled with our numerous recent regulatory approvals and our other innovative products, such as the WATCHMAN® Left Atrial Appendage Closure Device and Alair® Bronchial Thermoplasty System for the treatment of severe asthma, demonstrates our continued commitment to developing and bringing to market innovative products for physicians and their patients.”

Sudden cardiac arrest is an abrupt loss of heart function. Most episodes are caused by the rapid and/or chaotic activity of the heart known as ventricular tachycardia or ventricular fibrillation. Recent estimates show that approximately 850,000 people in the United States are at risk of SCA and indicated for an ICD device, but remain unprotected.

“Each year, thousands of patients indicated for an ICD are not referred to a specialist and remain untreated,” said William T. Abraham, MD, FACC, Director, Division of Cardiovascular Medicine at The Ohio State University Heart Center. “The S-ICD System is an important new treatment option that has the potential to improve patient acceptance of ICD therapy.”

The S-ICD System is designed to provide the same protection from sudden cardiac arrest as transvenous ICDs. The system has two main components: (1) the pulse generator, which powers the system, monitors heart activity, and delivers a shock if needed, and (2) the electrode, which enables the device to sense the cardiac rhythm and deliver shocks when necessary. Both components are implanted just under the skinthe generator at the side of the chest, and the electrode beside the breastbone. Unlike transvenous ICDs, the heart and blood vessels remain untouched. Implantation with the S-ICD System is straightforward using anatomical landmarks, without the need for fluoroscopy (an x-ray procedure that makes it possible to see internal organs in motion). Fluoroscopy is required for implanting the leads attached to transvenous ICD systems.

Boston Scientific expects to begin a phased launch of the S-ICD System that will expand over time as medical professionals are trained on the safe and effective use of the system. The company acquired the S-ICD System earlier this year when it completed the acquisition of Cameron Health, Inc. The S-ICD System received CE Mark in 2009 and is commercially available in many countries in Europe as well as in New Zealand. To date, more than 1,400 devices have been implanted in patients around the world. To download a high-resolution image of the S-ICD System go to: http://bostonscientific.mediaroom.com/home.

The S-ICD System is intended to provide defibrillation therapy for the treatment of life-threatening ventricular tachyarrhythmias in patients who do not have symptomatic bradycardia, incessant ventricular tachycardia, or spontaneous, frequently recurring ventricular tachycardia that is reliably terminated with anti-tachycardia pacing.

The WATCHMAN device is an investigational device in the United States. It is limited by applicable law to investigational use and not available for sale.

About Boston Scientific
Boston Scientific is a worldwide developer, manufacturer and marketer of medical devices that are used in a broad range of interventional medical specialties. For more information, please visit: www.bostonscientific.com.

Cautionary Statement Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Forward-looking statements may be identified by words like “anticipate,” “expect,” “project,” “believe,” “plan,” “estimate,” “intend” and similar words. These forward-looking statements are based on our beliefs, assumptions and estimates using information available to us at the time and are not intended to be guarantees of future events or performance. These forward-looking statements include, among other things, statements regarding our business plans and growth strategy, markets for our products, regulatory approvals, the importance of the S-ICD System, our technology, clinical trials, product launches, product performance and competitive offerings. If our underlying assumptions turn out to be incorrect, or if certain risks or uncertainties materialize, actual results could vary materially from the expectations and projections expressed or implied by our forward-looking statements. These factors, in some cases, have affected and in the future (together with other factors) could affect our ability to implement our business strategy and may cause actual results to differ materially from those contemplated by the statements expressed in this press release. As a result, readers are cautioned not to place undue reliance on any of our forward-looking statements.

Factors that may cause such differences include, among other things: future economic, competitive, reimbursement, legal and regulatory conditions; clinical trials and outcomes; new product introductions; product performance; demographic trends; intellectual property; litigation; financial market conditions; and future business decisions made by us and our competitors. Such factors are difficult or impossible to predict accurately and many of them are beyond our control. For a further list and description of these and other important risks and uncertainties that may affect our future operations, see Part I, Item 1A Risk Factors in our most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission, which we may update in Part II, Item 1A Risk Factors in Quarterly Reports on Form 10-Q we have filed or will file hereafter. We disclaim any intention or obligation to publicly update or revise any forward-looking statements to reflect any change in our expectations or in events, conditions or circumstances on which those expectations may be based, or that may affect the likelihood that actual results will differ from those contained in the forward-looking statements. This cautionary statement is applicable to all forward-looking statements contained in this document.

CONTACT: Denise Kaigler
508-650-8330 (office)
Media Relations
Boston Scientific Corporation
denise.kaigler@bsci.com
Michael Campbell
508-650-8023 (office)
Investor Relations
Boston Scientific Corporation
investor_relations@bsci.com

SOURCE Boston Scientific Corporation

www.bostonscientific.com

 

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NGS Cardiovascular Diagnostics: Long-QT Genes Sequenced – A Potential Replacement for Molecular Pathology

Posted in Bio Instrumentation in Experimental Life Sciences Research, Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, Cardiovascular Pharmacogenomics, Chemical Genetics, Computational Biology/Systems and Bioinformatics, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, Genomic Testing: Methodology for Diagnosis, Molecular Genetics & Pharmaceutical, Personalized and Precision Medicine & Genomic Research, Population Health Management, Genetics & Pharmaceutical, Technology Transfer: Biotech and Pharmaceutical, tagged , , , , , , , , , on October 1, 2012| 3 Comments »

 

Reporter: Aviva Lev-Ari, PhD, RN

J Cardiovasc Transl Res. 2012 Sep 7. [Epub ahead of print]

Next Generation Diagnostics in Inherited Arrhythmia Syndromes : A Comparison of Two Approaches.

Ware JS, John S, Roberts AM, Buchan R, Gong S, Peters NS, Robinson DO, Lucassen A, Behr ER, Cook SA.

Source

MRC Clinical Sciences Centre, Imperial College London, London, UK, j.ware@imperial.ac.uk.

Abstract

Next-generation sequencing (NGS) provides an unprecedented opportunity to assess genetic variation underlying human disease. Here, we compared two NGS approaches for diagnostic sequencing in inherited arrhythmia syndromes. We compared PCR-based target enrichment and long-read sequencing (PCR-LR) with in-solution hybridization-based enrichment and short-read sequencing (Hyb-SR). The PCR-LR assay comprehensively assessed five long-QT genes routinely sequenced in diagnostic laboratories and “hot spots” in RYR2. The Hyb-SR assay targeted 49 genes, including those in the PCR-LR assay. The sensitivity for detection of control variants did not differ between approaches. In both assays, the major limitation was upstream target capture, particular in regions of extreme GC content. These initial experiences with NGS cardiovascular diagnostics achieved up to 89 % sensitivity at a fraction of current costs. In the next iteration of these assays we anticipate sensitivity above 97 % for all LQT genes. NGS assays will soon replace conventional sequencing for LQT diagnostics and molecular pathology.

PMID: 22956155 [PubMed]
Source: 
http://www.ncbi.nlm.nih.gov/pubmed/22956155

Researchers in the UK have compared a PCR-based and a capture hybridization-based assay for sequencing panels of inherited cardiovascular disease genes and have found both to be suitable for diagnostics in principle, though their sensitivity needs to be optimized.

According to James Ware, a clinical lecturer at Imperial College London, the purpose of the study, published online this month in the Journal of Cardiovascular Translational Research, was to evaluate different approaches for sequencing cardiovascular disease genes, both for molecular diagnosis and for large-scale resequencing research studies.

His group, in the National Institute for Health Research Royal Brompton Cardiovascular Biomedical Research Unit, is interested in a range of inherited heart disease types, including cardiomyopathies and inherited arrhythmia syndromes such as long QT syndrome.

For their study, they compared two next-gen sequencing assays: a PCR-based approach that uses Fluidigm’s Access Array to amplify 96 amplicons in five LQT genes and one other gene, followed by sequencing on the 454 GS Junior; and an in-solution hybridization approach that uses Agilent’s SureSelect to target 49 inherited arrhythmia genes and sequences them on Life Technologies’ SOLiD 4.

The study focused on the sensitivity of the assays, or how well they were able to capture their intended targets, rather than their specificity, or their ability to avoid false positives.

Ware said that at the time of the study, PCR and in-solution capture were the two main target selection methods available. The researchers are still using both approaches but are now employing “a wide range of sequencers” from various providers for both types of assays, including Illumina instruments and Life Tech’s Ion Torrent.

For their comparison, they analyzed 48 samples, of which they sequenced 33 with both approaches and 15 using either one or the other.

The samples included 19 known variants in three disease genes, of which the hybridization-SOLiD method detected 17 and the PCR-454 method 14. Undetected variants were generally in areas that were not well covered, either due to a failure in enrichment, sequencing, or because the alignment was not unique. One variant that was missed by both approaches fell in a very GC-rich region.

Consumables costs for both assays were considerably lower than with Sanger sequencing: While sequencing five genes by Sanger costs more than $700 in consumables, the five-gene PCR/454 assay cost about $55 and the 49-gene hybridization/SOLiD assay cost about $200, according to the study.

Turnaround time is the shortest for Sanger sequencing, which, according to the study, can be done in one day for five genes and 17 samples, not including sample prep. The PCR/454 assay takes about two days for target enrichment and sequencing 48 samples, and the hybridization/SOLiD assay takes about two weeks for sequencing alone, they wrote.

Overall, Ware said, both sequencing approaches performed “reasonably well” and are significantly cheaper than Sanger sequencing. He said that in the UK, molecular diagnosis for inherited cardiovascular disease has traditionally been performed by Sanger, at a cost of approximately £500 to £1,000 ($800 to $1,600) for several genes involved in a clinical condition. However, for cost reasons, not all relevant genes are usually sequenced.

Target selection was the performance-limiting step for both approaches, a result the researchers expected. “It sounds obvious, but not all genes are equally easy to target,” Ware said. For example, in the hybridization assay, the overall target coverage was about 98 percent, but for some genes, it was only 80 percent or 90 percent. The two most important genes in long QT syndrome, KCNQ1 and KCNH2, “proved to be the hardest to sequence.”

Thus, for diagnostic use of NGS gene panels, “it’s important to know not just how the system performs overall but really how it’s performing for the specific genes you’re interested in,” he said.

To use either approach in diagnostics, the target selection step would need to be optimized. Ware’s team has already improved both assays and is now trying them in a number of fully Sanger-sequenced samples to study both sensitivity and specificity.

Longer term, the sensitivity of next-gen sequencing could approach that of Sanger sequencing, he said. And even if it does not reach 100 percent, because NGS approaches can target so many more genes, “maybe you can afford a very slight tradeoff in the per-gene sensitivity if the overall diagnostic sensitivity of the panel goes up,” he said. “At the moment, because we don’t have that much experience in sequencing the less-common genes, we don’t exactly know where that tradeoff lies.” In addition, any gaps could be filled by Sanger sequencing, while the test would probably still be cost effective.

Each approach also has some features that make it more suitable for certain applications. The PCR-based method has a fast turnaround and an “extremely user-friendly workflow,” Ware said, but it can only accommodate a small number of genes at the moment. His team also found it to be easier to optimize and improve. Thus, in the short term, PCR and sequencing “is probably closer to providing a diagnostic solution,” he said, especially for conditions where only a few genes are causative.

The hybridization-based approach, on the other hand, has much greater capacity, and there are advantages in “having a single assay that covers everything,” he said. It might also be possible to detect copy number variants using this approach, but not the more limited PCR method, he added.

Ware and his colleagues are currently using the hybridization approach to study a large panel of genes in 2,000 well-phenotyped volunteers, both healthy individuals and heart disease patients.

They have also started to use the hybridization method to sequence the TTN gene, truncating mutations in which were recently found to be a common cause of dilated cardiomyopathy. They are running the TTN test routinely for patients consented for research diagnostic testing that is not available anywhere else. Because this gene is so large, it is “completely impractical to be sequenced by conventional Sanger,” Ware said.

Julia Karow tracks trends in next-generation sequencing for research and clinical applications for GenomeWeb’s In Sequenceand Clinical Sequencing News. E-mail her here or follow her GenomeWeb Twitter accounts at @InSequence and@ClinSeqNews.

 

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Imaging-guided biopsies: Is there a preferred strategy to choose?

Posted in Bio Instrumentation in Experimental Life Sciences Research, CANCER BIOLOGY & Innovations in Cancer Therapy, Imaging-based Cancer Patient Management, Medical Devices R&D Investment, tagged , , , , , , , , , , , , , , , , , , , , , , , on September 29, 2012| 7 Comments »

Imaging-guided biopsies: Is there a preferred strategy to choose?

Author: Dror Nir, PhD

Article 11.3.3 Imaging guided biopsies Is there a preferred strategy to choose

The most stressful period in a cancer patients’ pathway is from the moment they fail a screening test or present with suspicious symptoms to the moment they are diagnosed. Today’s medical guidelines require histopathology findings as the only acceptable proof: positive results  mean you are a cancer patient, negative results mean, well…maybe you are and maybe you are not. You now enter into what might be a very long period, sometime years, of uncertainty regarding your health and prospects. And why?

Because the substance for histopathology is acquired by biopsies, and biopsies are known to be inaccurate. For example, breast and prostate biopsies  fail to find 25% to 35% of the cancer lesions at the first biopsy session.

Therefore, it is not surprising that from the beginning of this procedure,  medical practitioners look for ways to incorporate imaging into the workflow. In the last decade, significant progress has been made in the introduction of imaging-guided biopsies. The most common modalities were ultrasound and CT/mammography. Recently, as the industry solved the issues of magnetic field compatibility for biopsy needles and the introduction of open MRI systems, MRI-guided biopsies were also made  possible.

Ultrasound-guided biopsies are  by far the most commonly used procedure. Why? Because they  can be often performed as an office-based procedure. Here are some interesting links to YouTube videos describing such procedures:

  • Prostate

Prostate Ultrasound and Prostate Biopsy by Dr. Neil Baum

Transrectal ultrasound (Trus) Biopsy of the prostate

  • Breast

Ultrasound-Guided Breast Biopsy

Breast Tissue Biopsy

The main advantages: they are easily accessible, low cost and quick. The disadvantages of these procedures are  that they are very much operator dependent, rather than standardized, and there are no quality assurance guidelines attached. Efforts to standardize ultrasound-based biopsies and increase their efficiency are evident by recent introductions of ultrasound systems into the market ,  which support real-time guided biopsies and ultrasound applications that perform real-time biopsy tracking. But these systems are still far from being widely available. I will touch on this issue in my upcoming posts as I am part of these efforts.

CT and Mammography guided biopsies require more sophisticated equipment and well-trained operators. As an example:

Breast Biopsy – What To Expect

The main advantage: if you return to the same operator, the process is likely to be reproducible. The disadvantages are identical to that of ultrasound-based biopsies. It is worthwhile to note that, recently, radiologists who perform biopsies are required to go through a certification process. Still, such certification demands vary between the various radiology societies.

MRI-guided biopsies are an even more sophisticate and complex procedure:

  • Prostate:

DynaTRIM Video

DynaTRIM Intervention

An interesting quote from Dr. Hashim U. Ahmed, M.D., MRCS, Division of Urology  Department of Surgery, University College of London (https://mail.google.com/mail/u/1/?shva=1#label/Work%2FLinks%2FAuntMinnie/139d9c5bc6bda842): “Advocating the widespread use of MRI before biopsy in a population of men with risk parameters for harboring prostate cancer has a number of advantages, which might ultimately benefit the care these men undergo. Increasing the detection of prostate cancer that requires treatment while avoiding biopsy – and hence unnecessary treatment – in those with insignificant or no cancer are compelling arguments for this approach.”

  • Breast

MRI Breast Biopsy – Diagnostic and Biopsy Services for Breast Evaluation

I recommend reading the following article regarding the use of Open MRI to guide freehand biopsies of breast lesions. Especially interesting is the discussion where the authors give a good description of the difficulties in breast biopsies they are trying to overcome in order to achieve good lesion sampling.

MR-guided Freehand Biopsy of Breast Lesions in a 1.0-T Open MR Imager with a Near-Real-time Interactive Platform: Preliminary Experience Frank Fischbach, MD, et. al

http://radiology.rsna.org/content/early/2012/08/14/radiol.12110981.full?sid=bd45ceb4-9c8d-4ffc-b80b-0345ee679b4e

The question remains: which biopsy procedure is the best? And does this question have one coherent answer, i.e. one that will satisfy the patients, the doctors and the health-care insurers?  Will the answer to this question remain the subject of endless uncoordinated clinical studies?

If anyone who reads this post knows on methodological scientific or regulatory initiatives aimed at answering this question on a level of global guide lines  I would appreciate his comment.

Written by: Dror Nir, PhD.

 

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Imaging: seeing or imagining? (Part 2)

Posted in Bio Instrumentation in Experimental Life Sciences Research, CANCER BIOLOGY & Innovations in Cancer Therapy, Health Economics and Outcomes Research, Imaging-based Cancer Patient Management, Medical Devices R&D Investment, tagged , , , , , , , , , , , , , , , , , , , , on September 29, 2012| 7 Comments »

Imaging: seeing or imagining? (Part 2)

Author and Curator: Dror Nir, PhD

Article 11.3.2 Imaging seeing or imagining Part 2

This post is a continuation of

Imaging: seeing or imagining? (Part 1)

http://pharmaceuticalintelligence.com/2012/09/10/imaging-seeing-or-imagining-part-1/

That is the question…

Anyone who follows healthcare news, as I do , cannot help being impressed with the number of scientific and non-scientific items that mention the applicability of Magnetic Resonance Imaging (‘MRI’) to medical procedures.

A very important aspect that is worthwhile noting is that the promise MRI bears to improve patients’ screening – pre-clinical diagnosis, better treatment choice, treatment guidance and outcome follow-up – is based on new techniques that enables MRI-based tissue characterisation.

Magnetic resonance imaging (MRI) is an imaging device that relies on the well-known physical phenomena named “Nuclear Magnetic Resonance”. It so happens that, due to its short relaxation time, the 1H isotope (spin ½ nucleus) has a very distinctive response to changes in the surrounding magnetic field. This serves MRI imaging of the human body well as, basically, we are 90% water. The MRI device makes use of strong magnetic fields changing at radio frequency to produce cross-sectional images of organs and internal structures in the body. Because the signal detected by an MRI machine varies depending on the water content and local magnetic properties of a particular area of the body, different tissues or substances can be distinguished from one another in the scan’s resulting image.

MRI scan of a breast lesion (Source Radiology.com)

The main advantages of MRI in comparison to X-ray-based devices such as CT scanners and mammography systems are that the energy it uses is non-ionizing and it can differentiate soft tissues very well based on differences in their water content.

In the last decade, the basic imaging capabilities of MRI have been augmented for the purpose of cancer patient management, by using magnetically active materials (called contrast agents) and adding functional measurements such as tissue temperature to show internal structures or abnormalities more clearly.

In order to increase the specificity and sensitivity of MRI imaging in cancer detection, various imaging strategies have been developed. The most discussed in MRI related literature are:

  • T2 weighted imaging: The measured response of the 1H isotope in a resolution cell of a T2-weighted image is related to the extent of random tumbling and the rotational motion of the water molecules within that resolution cell. The faster the rotation of the water molecule, the higher the measured value of the T2 weighted response in that resolution cell. For example, prostate cancer is characterized by a low T2 response relative to the values typical to normal prostatic tissue [5].

T2 MRI pelvis with Endo Rectal Coil ( DATA of Dr. Lance Mynders, MAYO Clinic)

  • Dynamic Contrast Enhanced (DCE) MRI involves a series of rapid MRI scans in the presence of a contrast agent. In the case of scanning the prostate, the most commonly used material is gadolinium [4].

Axial MRI Lava DCE with Endo Rectal ( DATA of Dr. Lance Mynders, MAYO Clinic)

  • Diffusion weighted (DW) imaging: Provides an image intensity that is related to the microscopic motion of water molecules [5].

DW image of the left parietal glioblastoma multiforme (WHO grade IV) in a 59-year-old woman, Al-Okaili R N et al. Radiographics 2006;26:S173-S189

  • Multifunctional MRI: MRI image overlaid with combined information from T2-weighted scans, dynamic contrast-enhancement (DCE), and diffusion weighting (DW) [5].
  • Blood oxygen level-dependent (BOLD) MRI: Assessing tissue oxygenation. Tumors are characterized by a higher density of micro blood vessels. The images that are acquired follow changes in the concentration of paramagnetic deoxyhaemoglobin [5].

In the last couple of years, medical opinion leaders are offering to use MRI to solve almost every weakness of the cancer patients’ pathway. Such proposals are not always supported by any evidence of feasibility. For example, a couple of weeks ago, the British Medical Journal published a study [1] concluding that women carrying a mutation in the BRCA1 or BRCA2 genes who have undergone a mammogram or chest x-ray before the age of 30 are more likely to develop breast cancer than those who carry the gene mutation but who have not been exposed to mammography. What is published over the internet and media to patients and lay medical practitioners is: “The results of this study support the use of non-ionising radiation imaging techniques (such as magnetic resonance imaging) as the main tool for surveillance in young women with BRCA1/2 mutations.”.

Why is ultrasound not mentioned as a potential “non-ionising radiation imaging technique”?

Another illustration is the following advert:

Advert in favour of MRI termal imaging of breast

An MRI scan takes between 30 to 45 minutes to perform (not including the time of waiting for the interpretation by the radiologist). It requires the support of around 4 well-trained team members. It costs between $400 and $3500 (depending on the scan).

The important question, therefore, is: Are there, in the USA, enough MRI  systems to meet the demand of 40 million scans a year addressing women with radiographically dense  breasts? Toda there are approximately 10,000 MRI systems in the USA. Only a small percentage (~2%) of the examinations are related to breast cancer. A

A rough calculation reveals that around 10,000 additional MRI centers would need to be financed and operated to meet that demand alone.

References

  1. Exposure to diagnostic radiation and risk of breast cancer among carriers of BRCA1/2 mutations: retrospective cohort study (GENE-RAD-RISK), BMJ 2012; 345 doi: 10.1136/bmj.e5660 (Published 6 September 2012), Cite this as: BMJ 2012;345:e5660 – http://www.bmj.com/content/345/bmj.e5660
  1. http://www.auntminnieeurope.com/index.aspx?sec=sup&sub=wom&pag=dis&itemId=607075
  1. Ahmed HU, Kirkham A, Arya M, Illing R, Freeman A, Allen C, Emberton M. Is it time to consider a role for MRI before prostate biopsy? Nat Rev Clin Oncol. 2009;6(4):197-206.
  1. Puech P, Potiron E, Lemaitre L, Leroy X, Haber GP, Crouzet S, Kamoi K, Villers A. Dynamic contrast-enhanced-magnetic resonance imaging evaluation of intraprostatic prostate cancer: correlation with radical prostatectomy specimens. Urology. 2009;74(5):1094-9.
  1. Advanced MR Imaging Techniques in the Diagnosis of Intraaxial Brain Tumors in Adults, Al-Okaili R N et al. Radiographics 2006;26:S173-S189 ,

http://radiographics.rsna.org/content/26/suppl_1/S173.full

  1. Ahmed HU. The Index Lesion and the Origin of Prostate Cancer. N Engl J Med. 2009 Oct; 361(17): 1704-6

Writer: Dror Nir, PhD.

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

Posted in Bio Instrumentation in Experimental Life Sciences Research, Cardiac & Vascular Repair Tools Subsegment, Ecosystems & Industrial Concentration in the Medical Device Sector, Exec Compensation in the Cardiac & Vascular Repair Tools Subsegment, FDA Regulatory Affairs, Frontiers in Cardiology and Cardiovascular Disorders, Health Economics and Outcomes Research, Health Law & Patient Safety, HTN, Massachusetts Niche Suppliers and National Leaders, Medical Devices R&D and Inventions, Medical Devices R&D Investment, Origins of Cardiovascular Disease, PCI, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Pharmacotherapy of Cardiovascular Disease, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Stents & Tools, Technology Transfer: Biotech and Pharmaceutical, tagged , , , , , on September 29, 2012| 6 Comments »

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

Reporter: Aviva Lev-Ari, PhD, RN

 

Abbott Laboratories (ABT) Announces International Launch of the Absorb™ Bioresorbable Vascular Scaffold

9/25/2012 10:26:30 AM

ABBOTT PARK, Ill., Sept. 25, 2012 /PRNewswire/ — Abbott (NYSE: ABT) announced today that Absorb, the world’s first drug eluting bioresorbable vascular scaffold (BVS), is now widely available across Europe and parts of Asia Pacific and Latin America. Absorb is a first-of-its-kind device for the treatment of coronary artery disease (CAD). It works by restoring blood flow to the heart similar to a metallic stent, but then dissolves into the body, leaving behind a treated vessel that may resume more natural function and movement because it is free of a permanent metallic stent. Absorb is made of polylactide, a naturally dissolvable material that is commonly used in medical implants such as dissolving sutures.

The potential long-term benefits of a scaffold that dissolves are significant. The vessel may expand and contract as needed to increase the flow of blood to the heart in response to normal activities such as exercising; treatment and diagnostic options are broadened; the need for long-term treatment with anti-clotting medications may be reduced; and future interventions would be unobstructed by a permanent implant.

“This innovation represents a true paradigm shift in how we treat coronary artery disease. With the launch of Absorb, a scaffold that disappears after doing its job is no longer a dream, but a reality,” said Patrick W. Serruys, M.D., Ph.D., professor of interventional cardiology at the Thoraxcentre, Erasmus University Hospital, Rotterdam, the Netherlands. “Patients are excited about Absorb since it may allow blood vessels to return to a more natural state and expand long-term diagnostic and treatment options.”

The international launch of Absorb is supported by a robust clinical trial program that encompasses five studies in more than 20 countries around the world. Study data indicate that Absorb performs similar to a best-in-class drug eluting stent across traditional measures such as major adverse cardiovascular events (MACE) and target lesion revascularization (TLR), while providing patients with the added benefits associated with a device that dissolves over time. As the Absorb scaffold dissolves, vascular function is potentially restored to the blood vessel, allowing more blood to flow through the vessel as the body requires.

“Absorb is a leading example of Abbott’s dedication to advancing patient outcomes through innovative technology. Abbott has remained committed to meeting the growing physician and patient demand for a bioresorbable vascular scaffold from the initial device developed nearly 10 years ago to the expansion of our manufacturing capabilities to support this international launch,” said John M. Capek, executive vice president, Medical Devices, Abbott. “We are proud to be the first company to commercialize a drug eluting bioresorbable vascular scaffold, which has the potential to revolutionize the way physicians treat their patients with coronary artery disease.”

Heart disease is the leading cause of death for men and women around the world, and CAD is the most common type of heart disease.1,2 CAD occurs when arteries that supply blood to the heart become narrowed or blocked, leading to chest pain or shortness of breath and increased risk of heart attack.

About the Absorb Bioresorbable Vascular Scaffold

Absorb is now available in a broad size matrix to support the needs of physicians treating patients with CAD.

The Absorb bioresorbable vascular scaffold, similar to a small mesh tube, is designed to open a blocked heart vessel and restore blood flow to the heart. Absorb is referred to as a scaffold to indicate that it is a temporary structure, unlike a stent, which is a permanent implant. The scaffold provides support to the vessel until the artery can stay open on its own, and then dissolves naturally. Absorb leaves patients with a vessel free of a permanent metallic stent and may allow the vessel to resume more natural function and movement, enabling long-term benefits.3,4

Abbott’s BVS delivers everolimus, an anti-proliferative drug used in Abbott’s XIENCE coronary stent systems. Everolimus was developed by Novartis Pharma AG and is licensed to Abbott by Novartis for use on its drug eluting vascular devices. Everolimus has been shown to inhibit in-stent neointimal growth in the coronary vessels following stent implantation, due to its anti-proliferative properties.

Absorb is neither approved nor authorized for sale and currently is in development with no regulatory status in the United States. Absorb is authorized for sale in CE Mark countries. Absorb is now available in Europe, the Middle East, parts of Asia Pacific, including Hong Kong, Singapore, Malaysia and New Zealand, and parts of Latin America.

About Abbott Vascular

Abbott Vascular is the world’s leader in drug eluting stents. Abbott Vascular has an industry-leading pipeline and a comprehensive portfolio of market-leading products for cardiac and vascular care, including products for coronary artery disease, vessel closure, endovascular disease and structural heart disease.

About Abbott

Abbott is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs approximately 91,000 people and markets its products in more than 130 countries.

Abbott’s news releases and other information are available on the company’s Web site at www.abbott.com.

1The top 10 causes of death, World Health Organization. June 2011 Available at: http://www.who.int/mediacentre/factsheets/fs310/en/index.html 2 Coronary Artery Disease. National Heart, Lung and Blood Institute. May 2011 Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/cad/ 3Absorb completely dissolves except for two pairs of tiny metallic markers, which help guide placement and remain in the artery to enable a physician to see where the device was placed.4Early evidence indicates natural vessel function is possible to achieve improved long term outcomes. Absorb is a trademark of the Abbott Group of Companies.

On this Scientific Web Site the, Cardiovascular Medical Devices are addressed in the following posts:

Lev-Ari, A. (2012U). 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/

 

Lev-Ari, A. (2012R). Coronary Artery Disease – Medical Devices Solutions: From First-In-Man Stent Implantation, via Medical Ethical Dilemmas to Drug Eluting Stents http://pharmaceuticalintelligence.com/2012/08/13/coronary-artery-disease-medical-devices-solutions-from-first-in-man-stent-implantation-via-medical-ethical-dilemmas-to-drug-eluting-stents/

 

Lev-Ari, A. (2012K). Percutaneous Endocardial Ablation of Scar-Related Ventricular Tachycardia

http://pharmaceuticalintelligence.com/2012/07/18/percutaneous-endocardial-ablation-of-scar-related-ventricular-tachycardia/

 

Lev-Ari, A. (2012C). Treatment of Refractory Hypertension via Percutaneous Renal Denervation

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

 

Lev-Ari, A. (2012D). Competition in the Ecosystem of Medical Devices in Cardiac and Vascular Repair: Heart Valves, Stents, Catheterization Tools and Kits for Open Heart and Minimally Invasive Surgery (MIS)

http://pharmaceuticalintelligence.com/2012/06/22/competition-in-the-ecosystem-of-medical-devices-in-cardiac-and-vascular-repair-heart-valves-stents-catheterization-tools-and-kits-for-open-heart-and-minimally-invasive-surgery-mis/

 

Lev-Ari, A. (2012E). Executive Compensation and Comparator Group Definition in the Cardiac and Vascular Medical Devices Sector: A Bright Future for Edwards Lifesciences Corporation in the Transcatheter Heart Valve Replacement Market

http://pharmaceuticalintelligence.com/2012/06/19/executive-compensation-and-comparator-group-definition-in-the-cardiac-and-vascular-medical-devices-sector-a-bright-future-for-edwards-lifesciences-corporation-in-the-transcatheter-heart-valve-replace/

 

Lev-Ari, A. (2012F). Global Supplier Strategy for Market Penetration & Partnership Options (Niche Suppliers vs. National Leaders) in the Massachusetts Cardiology & Vascular Surgery Tools and Devices Market for Cardiac Operating Rooms and Angioplasty Suites

http://pharmaceuticalintelligence.com/2012/06/22/global-supplier-strategy-for-market-penetration-partnership-options-niche-suppliers-vs-national-leaders-in-the-massachusetts-cardiology-vascular-surgery-tools-and-devices-market-for-car/

 

Lev-Ari, A. (2012G).  Heart Remodeling by Design: Implantable Synchronized Cardiac Assist Device: Abiomed’s Symphony

http://pharmaceuticalintelligence.com/2012/07/23/heart-remodeling-by-design-implantable-synchronized-cardiac-assist-device-abiomeds-symphony/

 

SOURCE Abbott

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