Category Archives: P4 Medicine Update 10/5/11

Personalized Screening for Athletes at High Risk for ACL Injuries

Timothy Hewett, PhD, FACSM; Director of Research, The Ohio State University Sports Health and Performance Institute. Dr. Hewitt specializes in researching ways to prevent ACL injuries in young women.

100,000 – 250,000 ACL injuries occur each year in the U.S. Females are between 2 and 10 times more likely to tear their ACL than men, especially women participating in high-risk landing/cutting/jumping activities. The ACL is a sensor full of mechano-receptors and the tissue senses the positioning of the knee joint in three-dimensional space. Once the ACL is torn, this sensor does not work properly. Deficient neuromuscular control may contribute to ACL injury risk.  Following an ACL tear, the ability to generate power is significantly reduced. The female athletes have a lot more force, with less power to control that force. Women have significantly less ability to balance on a single limb after ACL tear/surgery than men in a similar situation.

Once you tear one ACL, your risk of tearing another ACL is much more likely. Neuromuscular repair is limited once an ACL tear occurs. When athletes return to sports, post-ACL reconstruction, their landing force profiles are abnormal. Force on non-operated limb is reduced. 23% (1 in 4) women will tear a second ACL. Five times higher risk in women than in men for a second ACL tear.

Those with a second ACL injury had an internal hip turn when jumping and landing. A neuromuscular control loss will cause the non-injured side of your body to drop to equalize.

Coupled biomechanical studies identify risk of ACL tears in women. We need to evaluate a greater number of athletes to get more data. After evaluation, athletes go out and play as usual and follow-up is done with athletes if they at some point tear their ACL.

Physical therapy is changing to try and address potential issues in advance. Move toward technique progression, stability progression, single leg lateral progression, symmetry side to side, single leg rotator progression and lateral trunk progressions are being done with athletes in this study. The goal is to get athletes back to their sport, while also evaluating their movements.

ACL injuries are genetically based. Filing information in web portals is helping keep data in one place. “Understanding and Preventing ACL Injuries” is a great resource for additional information about preventing ACL injuries.

Would this screening ever be incorporated into school physicals?

Yes. We are hoping to get these studies incorporated into PPEs (already being done). Encourage your local study reviewer to support the grant to help get this incorporated into pre-sports physicals.

Ohio as a Center of Healthcare Reform

Steve Allen, MD; CEO, Nationwide Children’s Hospital, Steven G. Gabbe, MD; CEO, The Ohio State University Medical Center and Gerald McDougall, head of the health practice for PricewaterhouseCoopers discuss the impact of healthcare reform.

In this time of health care reform, where in many ways providers are getting pressure to reduce spending with an expectation for more durable outcomes, what are our system needs to deal with this? What changes do you see on the horizon?

 Allen: In pediatric health care, the pressures are a little different from adult population. So much of what we do is related to Medicaid – in most pediatric hospitals more than 50 percent of patients are covered by Medicaid. Where we see challenges: We have to figure out how to provide care for a lower cost. We go through an initiative every year to cut our expenses so we can continue to support our mission. We have to learn how to manage the population’s health better. I feel very strongly that whatever direction health reform takes, we will be compensated on how well we manage clinical outcomes over a long period of time, not just acute episodes.

 Gabbe: The Affordable Care act is going to force us to do the right thing: look at health care longitudinally provide care of the highest quality and highest safety, while also reducing readmissions and assessing those patients at the highest risk. Another challenge in academic medical centers is that our bottom line is what we have used traditionally to fund our education, research and new program missions. That bottom line is going to be constrained. We’re going to get paid less for what we don’t do well, perhaps a little bit more for what we do well, but we’re going to have to find other sources of financial support for research, education and unique and innovative programs that we have developed and want to develop. Patient care itself, the pillar for funding sources, is not going to be there as it has in the past.

 McDougall: No matter what happens in political dynamics, structural shifts will occur and evolve. It’s important for policymakers and the public to understand the context of academic medical centers. Does Washington understand they approach $600 billion in our economy? What would Columbus be without Ohio State Medical Center as an economic driver? Sometimes the value of education and research is not realized as a unique asset.

 Gabbe: Columbus health care provides 36,000 jobs.

We hear about the need for better care coordination. How does that play out in improving the health of our population?

 Allen: We have 300,000 children for whom we are responsible for their clinical and economic outcomes. That has allowed us to change our behavior so we do more things to prevent them from going into the hospital and produce better outcomes. Infant mortality in this country is higher than in most developed countries and the No. 1 thing driving that is prematurity. It’s big business for children’s hospitals across the country. But it would be so much better for those babies and their families and our society if those babies didn’t arrive so early. We are partnering to prolong pregnancies and decrease NICU utilization. That is counter to economic interests of hospitals, but it is the right thing to do with society’s dollars allocated to health care.

 Gabbe: Most care we deliver has been episodic with very little interaction with the health system between those episodes. EMR is changing our ability to coordinate care. At Ohio State most patients we see for hospitalization are outside Franklin County. We need to make sure when they’re hospitalized that spend as much time planning for their discharge as we do providing their care. Patients need to go home to a welcoming health care environment. We should coordinate our efforts with the primary care community, make sure patients go home with right medications and know how to take them, ensure they see their primary care physician in a timely way. That’s how we’re going to impact readmissions and wellness once that patient goes home.

McDougall: Behavioral health is a big component of costs. We need to do a better job in behavioral health that I think we’ve been grossly underfunding for the longest time. Now we’re paying for it.

Governor Kasich is very interested in commercialization and owning the technology-based economy for the state of Ohio. How do you see this fitting into our plans? What types of partnerships might we see in the future, because revenue streams from the past may not be there as much as they have been in the past.

Gabbe: Ohio has seven medical schools, three of them have clinical and translational science awards from the NIH. Linking medical schools and medical centers to develop common IRBs, shared use of biorepositories and electronic medical records will help create clinical research organizations. Governor Kasich and we (at OSU) believe that we have a great opportunity to develop clinical research organizations in the state that can be the research basis for new drug development and technology transfer and new revenue sources for our medical schools.

McDougall: Need to have an organic strategy (very costly with great barriers to entry). This is still very important.

Retention – create an environment where companies are grown and retained.

Recruitment – Recruit companies at a global level. Role of the academic medical center in knowledge is a huge opportunity where a multitude of different funding sources that didn’t exist five years ago, exist today. Opportunities are endless. Execution of those opportunities is challenging. This takes a lot of patience, planning and alignment.

Gabbe: First Customer Concept – Agreement by a group of academic medical centers, that when an inventor comes up with new technology, we as a group of academic medical centers will do whatever we can to evaluate, refine and implement the new technology, leading to improved patient care.

Because of accountable care act and other requirements, we have a lot of hospital systems asking for assistance to develop efficiencies. Will we see more hospital mergers between academic centers moving forward to address these issues?

Jerry: Identifying how to develop coordinated care and also the health economics situation is a work in progress.

How do we cut our spending instead of preserving it?

Gabbe: We have to practice evidence-based medicine. We need to have difficult conversations about end of life care. 25% of medicare costs surround end of life care. There will be a big change around people’s expectations overall.

Where do you see things going?

Gabbe: Healthcare continues to attract the best and brightest people. Medicine has great rewards. Every day you pick up the newspaper and hear a story about healthcare, because that’s how we’re going to make this better and keep the conversation going. The future of medicine is very bright.


Making Connections to the Whole Patient

Ann Pendleton-Jullian; Walter H.Kidd Professor, Austin E. Knowlton School of Architecture, The Ohio State University, discusses the importance of creating complex and adaptive systems in health care.

Conflict exists between patient needs and insurance companies. Because of this, we need a new set of approaches and models different than what we have had up to this point. We are in a system of change and you cannot engineer for change because each moment of the system, changes the system.

Design has generally been deployed for designing things (content) and we need to begin thinking about designing contexts for human life to play out inside of it. Instead of just building spaces, buildings, cities, territories, we need to focus on building ecosystems. Design to date has been seen as embedded in business. Design sits inside of business, culture and nature. We have a responsibility to take on big problems whether they are environmental, poverty or healthcare.

Design by nature works on complex problems. In a learning healthcare system, you work and then calibrate, do some more work and then re-calibrate. You can try multiple paths and work on several things at once.

Disease is maladaptive aging. Medicine focuses on designing for change. Health is dynamic and is a complex, evolving condition. Ecosystems are alive and they are environments – everything feeds back into the system and affects the entire system.

Personalized healthcare must be a complex, adapting system.

Language is a socio-technical phenomenon. It is technical in nature – has science and linguistics structure, but serves the social function.

When defining complex systems, chaos is on one side and order is on the other side. Order can be 100% knowable and planned, but chaos cannot be. Complexity lies between order and chaos. Everything that is done, feeds back in and affects the entire system. For example: Every time you make a move in chess, you’ve changed the rest of the game.

You can do things to complex problems and move them to be just “complicated.” Some things will always stay chaotic, so you must move them before you do anything else, so they can be moved to a place where you can work on them. You cannot solve complexity or even model complex systems, because the system is the model.

Hotspotting Heart Health

600 of 65,000 people at OSU take up $80M of $250M (1/3 of the money, which is significant).

Work on the short term (the patients we actually see) to help patients work toward good health long-term.  Identify core principles, metrics, new mechanisms and means.

We need to identify new ways to look at the social side and new mechanisms of discovery and action for impact. Participatory is the most difficult of the 4 Ps. We need intrinsic motivations from birth throughout life. If you cannot solve the problem, then work toward positive change.

Things can be placed in the system to read the system, including genetic and epigenetic data, and implantable devices.

Micro-narratives are not about surveys or social scientists, but about the person giving you their story in their own words, from their perspective.

Methodological logic:

  • Start with a prompting question
  • Listen to the story
  • Doesn’t matter if story was true or not, because the person will act in accordance with the story they believe
  • Act on the signals

Our social networks have a lot to do with our own behavior. If the people in your network are obese, there’s a good chance you will be also.

How does your social network scaffold you?


Modulators  are things you put in the system to affect change in the system.

Games and gamification provide a powerful, intrinsic motivation. How do you harness your social network and create a network of people regularly feeding into your system to help you get better (after brain injury, for example)?

Building a game layer on top of the world begins to be about influence and how to influence behavior. For example, World of Work Craft  is a motivational device to help people get healthier in the workplace.

The capacity to adapt and change to changing technological circumstances is critical. Technology has to be very sophisticated and very simple for users at the same time.

Q & As:

How will we recognize when we see core things coming out and identifying the core parts of this?

Certain things that scale. Things that scale are really valuable. Things within heart health will work with other things as well.

Principles behind gamification

Gamification often talked about as reward programs. Leveraging up is important, so you’re leveraging accomplishmenet and using it to move people forward. The “fun” factor is also important.

Where will change come from and what is the role of resources?

Change can be affected in several different ways. Understand the system you’re working on. Change needs to come from the top. The things ysou do begin to be exemplary for others. Work on the things people care least about first, so fewer people will be focusing on you. Many patients don’t feel empowered, so you need to create mechanisms that allow better comprehension and a feeling of empowerment for patients. You learn from every patient and every patient visit.

Ohio State’s P4 Medicine Update, Oct. 5, 2011

Captured by Sherri Kirk

Researchers Find Promising New Target in Treating and Preventing Progression of Heart Failure

Captured by Mount Sinai Medical Center 

Researchers at Mount Sinai School of Medicine have identified a new drug target that may treat and/or prevent heart failure. The team evaluated failing human and pig hearts and discovered that SUMO1, a so-called “chaperone” protein that regulates the activity of key transporter genes, was decreased in failing hearts. When the researchers injected SUMO1 into these hearts via gene therapy, cardiac function was significantly improved. This research indicates that SUMO1 may play a critical role in the pathogenesis of heart failure. The data are published online in Nature.

Led by Roger J. Hajjar, MD, Director of Mount Sinai’s Wiener Family Cardiovascular Research Laboratories, and the Arthur and Janet C. Ross Professor of Medicine, Mount Sinai School of Medicine, the team has been evaluating the transporter gene SERCA2a in patients with severe heart failure as part of the CUPID (Calcium Up-regulation by Percutaneous administration of gene therapy In cardiac Disease) trial. When delivered via an adeno-associated virus vector—an inactive virus that acts as a medication transporter—into cardiac cells, SERCA2a demonstrated improvement or stabilization with minimal side effects. However, they found that while injection with SERCA2a restored cardiac function, over time the new SERCA2a became dysfunctional. This indicated that something else upstream from SERCA2a was causing the dysfunction in the heart.

Changwon Kho, PhD and Ah Young Lee, PhD, two postdoctorate students in the study of cardiac proteins at Mount Sinai School of Medicine, identified SUMO1 as the regulator of SERCA2a, showing that it enhanced its function and improved its stability and enzyme activity. Dr. Hajjar and his team studied human and animal models and found that when SUMO1 was decreased, SERCA2a became dysfunctional, showing that SUMO1 plays a protective role. When the team injected SUMO1 as a gene therapy, they found that it protected SERCA2a from the oxidative stresses and dysfunction that are prevalent in heart failure.

“Our experiments over the last four years beginning with the discovery of SUMO1 as an interacting protein of SERCA2a have shown that it plays a critical role in the development of heart failure,” said Dr. Hajjar. “In fact, SUMO1 may be a therapeutic target at the earliest signs of development, and may be beneficial in preventing its progression, a much-needed advance for the millions suffering from this disease.” Read more…

Stroke Prevention Trial Has Immediate Implications for Treating Patients

Captured by Houston Methodist Hospital 

People who received intensive medical treatment following a first stroke had fewer second episodes and were less likely to die than people who received brain stents in addition to medical treatment, according to a new report in the New England Journal of Medicine, to be published online Sept. 7. All patients in the study had experienced one stroke and were considered at high risk for a second one.

Two co-authors on the paper were Methodist Neurological Institute investigators involved in the NIH-funded trial – Dr. David Chiu, principal investigator and medical director of Methodist’s Eddy Scurlock Stroke Center, and Dr. Richard Klucznik, co-investigator and interventional neuro-radiologist.

“This study is important because it will impact the way we treat stroke patients with arterial blockage in the brain,” said Chiu. “Over the past several years, we have improved treatments for intracranial atherosclerosis, and this research shows that intensive medical management is the key to preventing stroke recurrence.”

The Stenting vs. Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) study enrolled more than 450 patients at 50 sites across the United States

Co-authors say stroke patients with recent symptoms and intracranial arterial blockage of 70 percent or greater should be treated with an aggressive medical therapy that mirrors the regimen used in this trial. The regimen used in the study included daily blood-thinning medications and the aggressive control of blood pressure and cholesterol.

The Methodist Neurological Institute had the fourth largest patient enrollment nationwide (20). New enrollment in the study was stopped in April because early data showed significantly more strokes and deaths occurred among the stented patients at the 30-day mark compared to the group who received the medical management alone. All patients will continue to be followed for two years to determine the long term effects of both interventions.

In addition to the intensive medical program, half of the patients in the study received an intervention of a self-expanding stent called a Gateway-Wingspan that widens a major artery in the brain and facilitates blood flow. The study patients at Methodist who received a stent (10) suffered no complications from stenting. Read more…


GE Healthcare to Invest $1B in Cancer R&D Including Biomarker Development

Capture by GenomeWeb 

GE Healthcare today announced plans to dedicate $1 billion in research and development spending over the next five years to expand its cancer diagnostic and molecular imaging capabilities, technologies for manufacturing biopharmaceuticals, and cancer research.

In line with those plans, its Clarient business is furthering development of a biomarker to identify patients who do not respond to taxane therapies for certain cancers. GE purchased Clarient last year for around $580 million with an eye toward combining Clarient’s biomarker efforts with its existing imaging capabilities.

“[W]ith a disease as complex and multifaceted as cancer, solutions need to be equally multifaceted and even more integrated, combining imaging, molecular diagnostics, and healthcare IT,” GE Healthcare President and CEO John Dineen said in a statement.

GE also announced a $100 million open innovation challenge “to find and fund ideas to accelerate detection of breast cancer and enable more personalized treatment.” The new investments, it said, will “focus on developing new oncology solutions and build on advanced technologies and research already in progress.”

One area of research focuses on a new biomarker, TLE3, which is being developed to help clinicians exclude patients least likely to benefit from taxane therapy. The biomarker is being developed by GE Clarient for breast cancer, lung cancer, and ovarian cancer.

In addition to improving patient outcomes, the work could save the healthcare system millions of dollars each year, GE said, adding it hopes to have a test based on the biomarker launched in 2013.

GE also plans to invest in molecular pathology for the development of cancer diagnostic technologies for “a clearer picture of pathways driving specific tumors,” as well as research that advances understanding of the molecular mechanisms of cancer.