Posts Tagged 'research'

SNI Communication Tools

John W. Henson, MD, Swedish Neuroscience Institute     

 

SNI is leveraging communication tools that deliver information to patients, referring physicians and the public as a crucial part of providing care at the advancing edge of neu­rological knowledge. The goals of these tools are two-fold. One goal is to update established patients and their doctors regarding the latest developments in our programs and centers. The other is to lower the barrier for patients and physicians who are facing a new neuro­logical problem to discover tertiary subspe­cialty care.

A new SNI communication tool

Dan Rizzuto, Ph.D., director of SNI research, and John Henson, M.D., recently launched SNIblog.com to complement other commu­nication efforts and to provide a communication outlet for the staff of SNI. SNIblog.com offers brief notes about advances in neurological care provided in SNI’s centers, as well as news items about the institute that are of interest to our patients and referring physicians.

Blog content is more dynamic than Web content. Search engines are able to detect targeted key words within each entry, which helps direct highly relevant Web traffic to the blog. This aids in the dissemination of infor­mation to patients and physicians. Viewers also can subscribe to an e-mail notification system that will alert them to newly posted material.

As is the case with any communication tool, however, blogs also have limitations. For example, blogs are not able to incorpo­rate the interactive features of social media that exponentiate information transfer to a selected audience. Therefore, SNI will build upon its existing menu of communication tools by launching social media outlets in the near future.

Other SNI communication tools

At SNI we provide print and electronic options to meet the needs of various audi­ences.

BrainWaves. This print news letter is de­signed to be an educa­tional resource about neurological topics for physicians in thePacific Northwest. Each issue focuses on conditions treated at SNI. Staff members au­thor the articles.

Physicians Practice. Swedish has the exclu­sive contract with this practice management journal to customize content in six issues annually. Although the journal is not exclu­sively used for SNI in­formation, many neu­rological topics have been covered in recent issues. Swedish maintains an online library of past content in the Health Professionals sec­tion of its website at www.swedish.org.

Swedish Neuroscience Institute website. Earlier this year the SNI website took on a new look as part of a project to redesign the entireSwedishMedicalCenter website. SNI members are now able to directly update information about their programs, and are actively developing online patient resources for each of SNI’s programs. The SNI website is a repository of information about our neurological services, research, clin­ical trials and professional expertise.

Our goal is to continuously improve ac­cess to neurological information and the de­livery of that information to interested groups of patients and referring physicians.

PFO closure for migraine

Mark Reisman, MD, Director of Cardiovascular Research and Education

 

Migraine is a primary headache dis­order that causes significant suffering in approximately 13 percent of the popula­tion of the United States. It accounts for an estimated $23 billion in annual cost to the economy through health-care expenses and lost productivity.

Two major features of migraine are migraine aura (MA) and headache. MA occurs in nearly one-third of migraine pa­tients and consists of one or more focal neurological symptoms that develop gradually over 5-20 minutes and persist for less than 60 minutes. MA typically precedes development of migraine headache.

Several years ago single-center retrospective analyses first reported an apparent association between partial or complete relief of migraine symptoms and transcatheter clo­sure of patent foramen ovale (PFO) for secondary stroke prevention (Reisman M, et al., 2005). The fora­men ovale normally serves as a one-way valve in the interatrial septum for physiologic right-to-left shunt in utero. Complete fusion of interatrial septae normally occurs by two years of age. When septae fail to fuse, how­ever, the PFO is a potential tunnel that can be opened by reversal of the interatrial pressure gradient. PFO is the most common form of right-to-left circulatory shunt (RLS).

Studies have shown that as many as 50 percent of individuals with MA will have a PFO, whereas PFO is present in about 25 percent of the general population and in migraineurs without aura (MO). In analy­ses performed by Swedish researchers, MA patients had a larger RLS than patients with MO, despite similar interatrial anat­omy (Jesurum JT, et al., 2007), and were about 4.5 times more likely to have greater than 50 percent reduction in migraine fre­quency following PFO closure (Jesurum JT, et al., 2008). These observations indicated a potential pathophysiological relationship between migraine and PFO.

The mechanism for this potential re­lationship is not understood, but investi­gators have focused on possible interatrial transit of vasoactive chemicals that bypass the pulmonary capillary bed, or on micro­emboli from the venous circulation which might trigger cortical spreading depres­sion and transient regional hypoperfu­sion. Migraineurs may have higher plate­let reactivity (Jesurum JT et al., 2010) or pro-coagulant state (e.g., protein C or S deficiency) than non-migraineurs, possibly resulting in greater load of microemboli in the arterial circula­tion. The brains of migraineurs may be more sensitive to circulatory changes than are the brains of those without migraine. The combination of potential triggers and susceptible neuronal substrate may result in an enhanced risk of MA among pa­tients with PFO.

The Migraine Intervention with STARFlex Technology (MIST) trial was a randomized trial of PFO clo­sure in migraine (Dowson A et al.). The failure of the trial to meet its primary endpoint (cessation of headache) and secondary endpoint (>50-percent re­duction in headache frequency and days) was surprising. Eligibility criteria for the trial may have excluded those patients who were most likely to benefit from PFO clo­sure. For instance, patients were excluded from MIST if they had a history of stroke or hypercoagulability, and subjects had to fit within a narrow range of headache fre­quency. If patients with a greater migraine burden or hypercoagulability were more likely to achieve meaningful reductions in headache frequency and severity, these exclusion cri­teria could have altered the study outcome.

Other trials are in progress or in the pipeline that may better elu­cidate the effect of PFO closure on migraine. The migraine-PFO asso­ciation offers opportunities for col­laboration between scientists and clinicians in both neurology and cardiology. The long-term goals of collaborative trials are improved quality of life and reduced cerebro­vascular sequelae for individuals who suffer from migraine.

 

Winter Issue of BrainWaves Now Available

The Winter 2010 edition of BrainWaves is now available online.  

BrainWaves is the newsletter of the Swedish Neuroscience Institute. Published quarterly, BrainWaves provides information about neurological conditions treated at the Institute, and also profiles the programs, services, and new initiatives of the institute and its staff.

 

Also check out our past editions of the BrainWaves newsletter.

SNI Fellowship Opportunities

The Swedish Neuroscience Institute (SNI) at Swedish Medical Center in Seattle, Washington, is committed to improving the delivery of neurologic care through evidence-based protocols, research and education.

SNI offers advanced training through five fellowships:

Applications are reviewed as received, with fellowships beginning bi-annually on January 1 and July 1.

For one hundred years Swedish has been the premier health-care provider in the Pacific Northwest and a trusted resource for people when it truly counts. As a high-volume, urban medical center located at the epicenter of the Puget Sound area, Swedish attracts nationally recognized physicians and scientists, and provides a broad population base that enhances the patient care, research and education efforts at SNI.

Applying for an SNI fellowship

You can also email your inquiries to SNIFellowships@swedish.org

Creating the future through research at SNI

Dan Rizzuto, PhD, Research Manager, Swedish Neuroscience Institute

Clinical research is an essential component of Swedish Neuroscience Institute (SNI). It provides our patients therapeutic options that would otherwise be unavailable to them and places our staff at the forefront of medical knowledge as they evaluate leading-edge drugs and medical devices. The majority of SNI investigations assess the safety and efficacy of new drugs and devices. These studies are typically sponsored by the federal government, or pharmaceutical and medical device companies, with oversight provided by the U.S. Food and Drug Administration. Investigator-initiated trials at SNI answer questions about current standard-of-care therapies. These trials play an important role in supporting evidence-based medicine and advancing patient care.

Initiating a research study at SNI begins with a physician identifying a research question or a sponsor asking a physician to investigate a new therapy. After the physician defines the study protocol, he or she presents an overview to the SNI Research Committee to ensure sufficient patient access, financial support and staffing resources are available. After the committee has approved the protocol, the Swedish Institutional Review Board performs its federally-required review, which is designed to protect the welfare of research participants.

As research manager, I oversee the financial and regulatory aspects of clinical research at SNI, including budget, contract negotiations with study sponsors and the assignment of study coordinators to assist with IRB submissions and patient visits. This allows the investigator to focus on providing patient care, overseeing patient safety and collecting efficacy data.

Research at SNI currently includes 54 active investigations across nine programs, and is supported by more than $2 million dollars in annual funding. Thirty-seven of these studies are sponsored and financially supported by pharmaceutical and device companies, eight are investigator-initiated and nine are funded by the federal government or other non-profit organizations.

Research at SNI has a very bright future with many new and exciting trials on the horizon. The movement disorders program has ramped up its first clinical trial of a Parkinson’s disease treatment, and the Ivy Center for Advanced Brain Tumor Treatment is at the forefront of developing personalized medicine for brain cancer patients. One of the most exciting developments involves the bridging of two disciplines: deep brain stimulation (DBS) and psychiatry. The DBS program and the Swedish psychiatry program are evaluating clinical trials that use DBS for treatment resistant obsessive compulsive disorder and major depression. DBS offers hope for the most severely affected of these patients who continue to exhibit severe symptoms even after adequate trials of currently available therapies.

As a neuroscience center of excellence, SNI is uniquely designed to meet the healthcare challenges of the 21st century and beyond. We pursue evidence-based medicine by combining an academic focus on learning and research with high-quality clinical programs. The power to meet these challenges resides within each of us, and I encourage you to think about how you can be a pioneer in the advancement of medicine through clinical research.

If you would like to participate in clinical research activities at SNI, please contact:

Dan Rizzuto, Ph.D.

dan.rizzuto@swedish.org

Desmoteplase may hold the key for stroke patients

Dan Rizzuto, PhD, Research Manager, Swedish Neuroscience Institute

Acute stroke is the third leading cause of mortality and the major cause of long-term disability in the developed world. Ischemic strokes account for about 85 percent of all acute strokes and are caused by clots that block blood vessels in the brain, stopping the flow of blood to crucial brain areas.

The main approach to treating acute ischemic stroke is thrombolysis, which degrades the clot causing the stroke and provides significant clinical improvements. The only thrombolytic intervention for acute ischemic stroke that is currently approved by the U.S. Food and Drug Administration (FDA) is alteplase. However, alteplase must be administered within three hours after symptom onset to avoid the risk of inducing a hemorrhage in the brain. (More recent evidence supports delivering alteplase up to 4.5 hours.) Because of this time limitation, it is estimated that alteplase is currently administered to less than five percent of acute stroke patients. While this time limitation is a large factor, a high proportion of patients arriving within the appropriate time window still do not receive alteplase due to contraindications (e.g. age, severity, hypertension etc.) or due to the unfavorable risk-benefit ratio.

Recently a new thrombolytic agent, desmoteplase, has been developed that is based upon a protein found in the saliva of the Desmodus rotundus, better known as the common vampire bat. Studies conducted so far suggest desmoteplase breaks down clots efficiently and elicits few side effects, indicating the potential for better clinical outcomes. Importantly, it is possible to administer desmoteplase up to nine hours after symptom onset. Swedish Medical Center is participating in DIAS-4, a new study to assess the safety and effectiveness of desmoteplase.

“This new agent holds great promise,” said William Likosky, M.D., principle investigator for the clinical trial and medical director of the Swedish Acute Telestroke Program. “Currently, we are fortunate to have a network of emergency departments in which alteplase can be administered within an early window. If stroke patients have an initial treatment window up to nine hours, however, we can consider transferring them to medical centers that can provide thrombolysis beyond that available for alteplase.”

This clinical research study to test desmoteplase is being carried out under strict oversight by the FDA. By participating in this study, Swedish continues its tradition of offering the most advanced therapies available to patients who have few other options. In addition, the Swedish Acute Telestroke Program is able to offer this trial to patients outside the Seattle area who are brought emergently to Swedish for treatment.

Unfundable: Clinical trials for rare diseases and orphan drugs


John W. Henson, M.D., FAAN, Director, Neurology, Swedish Neuroscience Institute

The study of acetazolamide for idiopathic intracranial hypertension described on page 9 of the Spring issue of BrainWaves raises an important question about a neglected aspect of clinical trials: How do investigators obtain funding to study the efficacy of a drug that has no commercial potential?

Only 300 of the approximately 7,000 known human diseases are of interest to the biopharmaceutical industry from the standpoint of prevalence or commercial potential, according to the Office of Rare Diseases Research (ORDR) at the National Institutes of Health (NIH). The Orphan Drug Act of 1983 sought to use patent protection and tax incentives to promote development of drugs for diseases with a small market. In this context, the word “orphan” refers to a condition or drug that has not been “adopted” by the pharmaceutical industry because of limited commercial potential and a rare disease is one that affects 200,000 or fewer Americans. In the twenty years following enactment of the ODA, 249 orphan drugs received marketing authoriza¬tion, compared to 10 in the preceding decade, with the most notable being Amgen’s erythropoietin.

Commercial potential alone does not determine value

Low prevalence does not equate to limited commercial potential, of course, because pricing must also be considered. The vigorous development of expensive new treatments for diseases of moderate or low prevalence, such as temozolomide for malignant gliomas and natalizumab for multiple sclerosis, are good examples. But when the condition is rare or the treatment of interest is post-patent, as with the study of acetazolamide for idiopathic intracranial hypertension (IIH), there is double jeopardy against much needed advances for patients with such disorders.

A survey of the NIH clinical trials registration web site, reveals that acetazolamide is under evaluation as a single agent in three clinical trials in the United States. All three are sponsored by the NIH. The four-year, $1.5- million study of acetazolamide for IIH is one of two studies funded by the National Eye Institute. The other study is funded through the NIH Office of Rare Diseases Research.

The biopharmaceutical industry has been spectacularly successful in developing new treatments for many of the most important human diseases, but the study of acetazolamide for IIH is a reminder that new treatments for orphan diseases usually require federal or private foundation funding.