Wednesday, May 20, 2009

Vital Signs: Fishy Food

Ronnie Martin, the hardworking creator of a popular TV sitcom, loved her tropical getaways. By all rights, her seventh visit to Bora-Bora should have been a breeze. Lucky seven, right? Then came her unlucky visit to the Rainbow Reef bar. Along with her afternoon Bloody Mary, she sampled a raw fish seviche. Her husband Tom did not. It was a snack she would always remember with regret.

A few hours later, Ronnie lay moaning on the floor of her beachfront suite, desperately ill. The pain in her lower abdomen felt like a thousand stabbing knives. She had also vomited several times. Tingling, trembling, and unable to stand, she had just one thought: Need help—fast!

Soon, with Tom propping her up, she entered the only hospital within miles, a crowded sick bay far more rustic than what either of them had pictured when directed there by the hotel concierge. After receiving a liter of intravenous fluid, an unknown injection, and a working diagnosis of “kidney stone,” Ronnie had had enough. “Kidney stone, my a**!” she said to herself. She ripped the IV from her arm, got up, and staggered to a waiting taxi. Somehow she survived the ride back to the hotel and her flight home to Los Angeles the next day.

But her misery didn’t end there. Over the next several months, Ronnie suffered ongoing abdominal pain, recurrent bouts of diarrhea, numbing fatigue, and an inflamed nerve in her arm. She also dropped 15 pounds, reaching a weight she had not seen since joining the Martha Graham Dance Company in her twenties.

Throughout her mystery illness, one question never left her mind: What the heck was in that seviche?

I’m a tropical medicine specialist. When I received Ronnie’s SOS call three months after her trip, she was still profoundly fatigued. Instead of her usual 12-hour workdays, she spent what little energy she had visiting medical specialists. Ronnie found me after her gastroenterologist hazarded a guess that an exotic fishborne parasite had triggered her blight. Before long Ronnie had me on the phone.

Within minutes I had heard enough tantalizing clues—South Pacific, seafood, and strange, sporadic symptoms—to reach my own conclusion. What had hit Ronnie like a ton of bricks was not a parasite but a toxin. But could I prove it?

Many of us have heard of tropical fish poisoning, yet few people —medical folks included—know much about it. Adding to the confusion is the fact that the term covers a host of ills. These include scombroid poisoning, a syndrome resulting from the overgrowth of normal bacteria in warm or improperly refrigerated fish that has begun to spoil. The bacteria convert histidine into histamine, which triggers allergic reactions such as hives, asthma, diarrhea, and plummeting blood pressure. There is also poisoning by tetrodotoxin, a nerve poison 100 times more potent than curare and strychnine. Although several varieties of fish can harbor tetrodotoxin in their liver and other organs, the most notorious source of the sodium channel–blocking toxin is the Japanese delicacy fugu (also called blowfish or puffer fish). In Japan this fish can be prepared and served only by government-licensed cooks who have completed a stringent food-safety course. Puffer fish are themselves impervious to tetrodotoxin because of a point mutation in their sodium channel receptors.

Shellfish containing stowaway dinoflagellates—a diverse group of plankton—are another cause of sickness or occasionally death by seafood. Saxitoxin, the most fearsome dinoflagellate by-product, is similar to tetrodotoxin. A single mussel or handful of clams containing less than 5 milligrams of the compound can be lethal. The usual cause of death is paralysis and respiratory failure.

In addition to noxious toxins, fish can also harbor worms; just ask any sushi chef. Sushi restaurants typically avoid fish cuts and species prone to worms, but if something wriggles in raw fish flesh, sushi chefs are trained to spot it and remove it. The most common culprits they see in marine fish are anisakid roundworm larvae. If consumed by humans, these tiny creatures often burrow into the stomach or small intestine of their victims, causing excruciating pain that is alleviated only by meticulous extraction of the larvae via a fiber-optic endoscope. Worms carried by freshwater fish may infect humans as well. These include leaflike flukes and the giant fish tapeworm Diphyllobothrium latum, which when fully grown can measure an unnerving 3 to 12 meters (about 10 to 40 feet) in the human intestinal tract.

Even before meeting Ronnie, I knew a simple worm was not to blame for her lightning-quick illness and lingering multisystem distress.

Back to Ronnie Martin. Call it gut instinct, but even before meeting her and reviewing her lengthy medical record, I knew that a simple worm was not to blame for her lightning-quick illness and lingering multisystem distress. Since she had eaten seviche as opposed to shellfish or fugu, I also knew she had not fallen prey to one of the rarest and deadliest of seafood toxins, such as tetrodotoxin or saxitoxin. By a process of elimination, I decided that the likely cause of her illness was the tasteless, odorless, highly stable ciguatera fish toxin.

Ciguatera was named, according to historical lore, by a 19th-century Englishman who became violently ill after dining on barracuda from Cuba. (Ciguatera, a Spanish reworking of the English “seawater,” was the word he used when implicating the fish.) It is present in the muscles and organs of more than 400 species of tropical reef–dwelling fish, especially those at the top of the food chain, such as grouper, red snapper, amberjack, and barracuda. Once again a unicellular microalga—in this case, Gambierdiscus toxicus—previously ingested by the fish is the ultimate source of the injurious toxin.

Within two to six hours of eating a ciguatoxin-tainted fish, most people develop a host of intestinal and neurological symptoms ranging from nausea, vomiting, diarrhea, and abdominal pain to shortness of breath, profuse sweating, staggering gait, vertigo, blurred vision, and abnormal sensations in the hands and feet. In some patients the symptoms disappear after 24 hours. In others they last for months.

Cases like Ronnie’s are far from rare. Experts in foodborne diseases know that ciguatera fish toxin is widely distributed throughout the South Pacific, the Caribbean, and other warm tropical waters. In fact, ciguatera is thought to be the most common form of seafood poisoning in the world, causing up to a million cases a year. But what is familiar to toxicologists is less well-known to medical practition­ers. The challenge to clinicians, therefore, is to connect the dots in a given patient and reach the diagnosis on the basis of clinical and circumstantial evidence. Chemical assays are available to detect ciguatoxin in fish, but few if any doctors and nurses—especially in poor small towns—have access to such tests. Moreover, there are no specific tests to confirm the condition in humans.

In the end, Ronnie accepted my diagnosis. She was not happy to learn there is no “magic bullet” for ciguatera—I and other doctors would simply have to nurse her through her lingering symptoms—but she took comfort in knowing that the toxin would not cause permanent harm. Sure enough, over time she bounced back.

Today, despite the many healthful benefits of seafood, does Ronnie still eat fish? Not on your life. Cholesterol be damned; she’d rather take her chances with a steak.

Claire Panosian Dunavan is an infectious diseases specialist at UCLA Medical Center and past president of the American Society of Tropical Medicine and Hygiene. The cases in Vital Signs are real, but names and certain details have been changed.

Friday, May 15, 2009

Lab-Grown Blood Vessels Could Provide Safe Docking Station for Dialysis


Blood vessels grown from patients’ own skin cells have been used to make the process of dialysis safer and easier for people with failing kidneys, and researchers say the process may one day be used to custom-produce blood vessels for patients with circulatory problems in their hearts or legs [AP].

Kidney patients need frequent dialysis to filter their blood, and that requires a vessel, or shunt, to connect them to dialysis machines. This can be made from their own vessels. But because dialysis is done so regularly, kidney patients often run out of healthy vessels and need an artificial one, often made out of [Gore-Tex]. Those are prone to infection and inflammation [AP].

For the new study, published in The Lancet, researchers took small snips of skin from the backs of ten patients’ hands and extracted two cell types — fibroblasts from the skin which provide the structural backbone of the vein, and endothelial cells to form the lining of the vein [Reuters]. In the lab, those cells were grown into sheets of tissue that were then rolled into tubes measuring about six inches long, which then fused at the seams. Those tubes were essentially new blood vessels. The whole process took between six to nine months.

The new blood vessels were implanted in the arms of the ten patients, all of whom had advanced kidney disease. Three of the patients suffered a failure during the first three months of the trial — a not-unexpected result considering the patients’ risk factors, [lead researcher Todd] McAllister said. Another withdrew from the study and a fifth died of unrelated causes. The rest of the grafts have functioned for as long as 20 months [Los Angeles Times].

Researchers say the new procedure is very promising, and could be useful for a wide range of people with circulation problems. “It’s basically a piece of plumbing to bypass blockages” [AP], says McAllister. For now, cost is the main obstacle to overcome. Growing replacement blood vessels is expected to cost between $15,000 and $20,000.

Related Content:
80beats: Researchers Could Grow Replacement Tissue to Patch Broken Hearts
80beats: Researchers Grow a Blood Vessel Network From a Few “Progenitor” Cells

Wednesday, May 13, 2009

What do patients really want from you?

A national survey tracks patients' consumer habits, from "content and compliant" to "sick and savvy."

By Emily Berry, AMNews staff. Posted April 27, 2009.


View in PDF
Click to see data in PDF.

After 23 years in family practice in Topeka, Kan., Douglas Iliff, MD, said that despite what he reads about consumerism being the wave of the future -- or the present -- patients usually want him to tell them what to do.

Even the patients who ask the most questions -- typically those who have high-deductible plans paired with health savings accounts -- honestly want his recommendation, not just coaching or a list of options, he said.

"Since the Internet revolution came along, yes, patients ask more questions, and ask more intelligent questions. But they'll come to me with those questions asking what I think."

Research by consulting firm Deloitte supports Dr. Iliff's observation that most patients do like what it terms an "authoritarian" or "traditional" physician. But it also suggests that a growing number of patients is seeking more details from doctors, in terms of both costs and treatment.

Paul H. Keckley, PhD, is executive director of the Deloitte Center for Health Solutions, which conducted the nationwide survey of 4,001 adults in the fall of 2008. He said the survey, released this spring, supports his contention that physicians need to adjust to patients who are more likely to want choices and detailed information from doctors, not just a prescription or a referral.

"The good news is, most consumers are generally happy with the physicians they see, and they are still trusting in the recommendations of those physicians," Keckley said. "The challenging news would be they're becoming a bit uncomfortable with the lack of information they'd like to get from physicians."

Patient personality types

As in Deloitte's first consumer health care survey, released a year ago, respondents were split into six personality segments based on their answers.

The largest group, 28.5% of respondents, was "content and compliant," characterized by satisfaction with the current health care system and preference for traditional approaches in medicine. Nearly as common, 27.6% of the respondents were defined as "casual and cautious," defined by disengagement in health and treatment, disinterest in options and a weak sense of quality differences.

Another 25.3% of respondents, however, were "sick and savvy" -- very aware of quality differences and likely to participate in health care decisions.

"Out and about" patients, who made up 8.2% of respondents, were interested in nontraditional medicine and were least likely to trust doctors' advice. The 8% of patients described as "online and onboard" were characterized as most likely to shop around for doctors, ask for drugs by name and to participate in wellness activities. The smallest category, "shop and save," encompassed 2.4% of respondents. These patients were likely to change physicians or health plans to save money, but also likely to not fill a prescription because of cost.

Although nearly a third of respondents remain in the "content and compliant" category, Keckley said those patients are older. He said that population is, to put it bluntly, dying out.

The respondents in the most recent survey were incrementally more likely than those in the 2008 survey to be in the "sick and savvy," "online and onboard" or "shop and save" categories. Those patients are active and engaged in choosing physicians and hospitals, asking for reliable medical advice, and seeking quality and cost information.

Keckley said physicians need to change their practices now to be ready for the future.

"For a patient to leave the doctor's office newly diagnosed with a condition without a referral to a trusted Web site to find more information is simply a mistake," Keckley said. Physicians who want to get ahead in their markets need to use the Web to interact with patients between visits via a personal health record connected to patients' homes, he added. Physicians who "are not tech-savvy are physicians who are going to be paid less, and they're going to regret it."

Adopting the patient-centered medical home model is one way physicians can create a practice that caters to different types of patients, like those in the "complex mosaic" outlined by Deloitte, said Lori Heim, MD, president-elect of the American Academy of Family Physicians.

The medical home is generally defined as a base from which health care is coordinated. A physician has an ongoing relationship with a patient and helps coordinate the patient's health and treatments across the entire health care system.

Dr. Heim said running a practice as a patient-centered medical home would help a physician care for every patient, whether they are "content and compliant" or "shop and save" patients.

"I think the successful physician, just like the successful person, is someone who can adapt their style to be the most effective with the patient," she said.

Cultural shift on costs

The Deloitte report also suggested that the cost of seeing doctors and getting treated for illnesses or injuries could be behind a continuing shift from a more passive patient population to a more active one. Sometimes patients decide to ignore a doctor's advice altogether if it's deemed too expensive.

So what can physicians do to keep savvy patients engaged but also discourage them from skipping needed care?

David C. Scroggins, a Cincinnati-based practice management consultant and principal with Clayton L. Scroggins Associates, said physicians should talk to patients about what can and cannot be postponed when money is tight, and they should remind patients that even cut-rate insurance plans often cover preventive visits.

"Then, when they have to make choices when they've got money to spend, they think, 'Maybe I will spend it on my health,' " he said.

Dr. Iliff said he is skeptical of surveys like Deloitte's that ask consumers what they want in an ideal world, or what they would do under certain circumstances. What matters to his practice, and where he said "the system is falling apart," is what people actually do, not their intentions or wishes.

This content was published online only.

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 ADDITIONAL INFORMATION: 

Searching for cost, quality

A Web-based survey by Deloitte finds patients are increasingly seeking information about both cost and quality of care. Among the 4,001 respondents:

13% looked online, in the previous 12 months, for cost information.

27% looked online, in the previous 12 months, for information about the quality of care provided by specific doctors.

57% would use quality rankings to compare doctors and hospitals in their community.

58% are interested in using cost information.

Source: Deloitte, "2009 Survey of Health Care Consumers: Key Findings, Strategic Implications" (www.deloitte.com/dtt/article/0,1002,sid%253d80772%2526cid%253d252396,00.html)

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6 kinds of consumers

As part of its most recent public survey, consulting firm Deloitte broke down respondents into six categories, based on their satisfaction with the health care system, use of health services and behaviors around health care. The categories that exemplify health care consumerism grew slightly since the 2008 survey, while those representing more passive, less engaged patients shrank. Here's how the 4,001 respondents filled out the Deloitte-named categories:

CONTENT & COMPLIANT

2008: 29.3% of respondents
2009: 28.5% of respondents
System use: Medium
Care preferences: Traditional, most likely to prefer authoritarian doctors 
Satisfaction: Most satisfied 
Adherence: Most compliant 
Information: Least likely to seek information and compare alternatives
Switching: Least likely to switch physicians or plans
Innovation: Most likely to prefer standard approach
Other: Most confident in effectiveness of medications

SICK & SAVVY

2008: 24.3% of respondents
2009: 25.3% of respondents
System use: Highest
Care preferences: Traditional, but want to be engaged in decision-making
Satisfaction: Satisfied
Adherence: Compliant
Information: Strongest sense of quality differences; likely to seek coverage details, trust Web sites, have personal health record
Switching: Likely to ask for drug by name, less likely to switch physicians, plans
Innovation: Most receptive to new treatments and devices
Other: Most prepared financially; mental/behavioral health coverage is important; want enhanced plan

ONLINE & ONBOARD

2008: 7.3% of respondents
2009: 8% of respondents
System use: High
Care preferences: Traditional, but open to nonconventional (e.g., retail clinics)
Satisfaction: Satisfied
Adherence: Compliant
Information: Most likely to compare doctors, use cost/quality info, trust Web sites, have personal health record
Switching: Likely to ask for drugs by name, switch plans, switch doctors
Innovation: High interest in innovative devices 
Other: Likely to participate in wellness and contact plan for advice; want enhanced plan and mental/behavioral health coverage

SHOP & SAVE

2008: 1.6% of respondents
2009: 2.4% of respondents 
System use: Medium
Care preferences: Traditional, but open to nonconventional, seek lower-cost doctors
Satisfaction: Less satisfied 
Adherence: Less compliant 
Information: Likely to compare doctors, use cost/quality and coverage info, have personal health record 
Switching: Most likely to switch plans, change insurance, switch doctors 
Innovation: No strong preference 
Other: Likely to participate in wellness, not fill prescriptions due to costs, contact plan with question or complaint

OUT & ABOUT

2008: 9.1% of respondents
2009: 8.2% of respondents 
System use: Medium 
Care preferences: Alternative, prefer holistic approaches and natural remedies, open to nonconventional 
Satisfaction: Least satisfied 
Adherence: Least compliant 
Information: Least likely to trust doctor's advice 
Switching: Likely to switch doctors
Innovation: Receptive to new treatments
Other: Likely to delay doctor's recommendation, most open to traveling out of U.S., want enhanced plan

CASUAL & CAUTIOUS

2008: 28.4% of respondents
2009: 27.6% of respondents
System use: Lowest
Care preferences: Disengaged, but lean toward traditional, seek lower-cost doctors
Satisfaction: Less satisfied 
Adherence: Less compliant 
Information: Weakest sense of quality differences, less likely to seek information 
Switching: Less likely to switch physicians or plans
Innovation: Likely to prefer standard approach
Other: Least prepared financially for future costs

Source: Deloitte, "2009 Survey of Health Care Consumers: Key Findings, Strategic Implications" (www.deloitte.com/dtt/article/0,1002,sid%253d80772%2526cid%253d252396,00.html)

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Costs count

A survey of health care consumers found that financial concerns were changing their behaviors, pushing them to delay care or, in some cases, to not follow doctors' advice or not fill prescriptions. Among the respondents to Deloitte's survey:

84% believe current economic conditions will make it harder for consumers to pay medical bills.

35% of those who skipped filling a prescription did so because of cost concerns.

30% would be likely to use a retail clinic if it cost them 50% or less than a visit to a doctor's office.

28% had problems paying medical bills in the past year.

24% decided not to see a doctor or get health care services when they were sick or injured. These decisions occurred most often among people who were uninsured or age 18-28. Among those who skipped care, 38% cited cost concerns.

15% delayed or decided against treatments recommended by their doctor; among those, 2 in 5 said costs were too high.

Source: Deloitte, "2009 Survey of Health Care Consumers: Key Findings, Strategic Implications" (www.deloitte.com/dtt/article/0,1002,sid%253d80772%2526cid%253d252396,00.html)

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Copyright 2009 American Medical Association. All rights reserved.

Saturday, May 9, 2009

AMA letter backs Obama's broad principles for health system reform

The Association outlines the next steps Congress and the White House should take to turn the tenets into policy changes.

By Chris Silva, AMNews staff. Posted April 27, 2009.


The American Medical Association earlier this month further fleshed out what it will push for in this year's landmark health system reform debate, aligning itself with several core principles from President Obama and offering more specifics about how to achieve them.

In an April 13 letter to the White House, the AMA announced its strong support for eight guiding principles against which Obama has said he will gauge the health reform effort as he works with Congress. The AMA made the statement in an effort to show it is backing this "historic opportunity to improve the system," while also highlighting more specific issues the organization wants Congress to address this year, said AMA President Nancy H. Nielsen, MD, PhD. She co-signed the letter with AMA President-elect J. James Rohack, MD.

"We are committed to reform, and we want to expand access to care for all Americans," Dr. Nielsen said. "This is an important year, because more people may lose their jobs and their health insurance, and we have grave concerns about that and the loss of preventive services."

The eight basic principles -- including guaranteeing patient choice and aiming for universal health care coverage -- lack details, although Obama further outlined his long-term vision in his budget proposal released Feb. 26. The AMA letter indicates that the standards dovetail with more expansive policy changes for which the Association already is pushing.

But embracing the eight principles does not mean the AMA necessarily backs every idea on health reform that Obama has revealed so far. For instance, the president has called for creating a public health plan option linked with a national health insurance exchange to serve as competition for private plans. In its letter to the White House, the AMA says it supports a health insurance exchange to ensure coverage choice and portability, but it does not weigh in on the public plan option. To move toward universal coverage, Congress should build on the employer-based system and strengthen the safety net provided by publicly financed programs such as Medicare, Medicaid and the Children's Health Insurance Program, Dr. Nielsen and Dr. Rohack wrote.

Dr. Nielsen stressed that the organization is mindful of the need to watch the dollar signs as policymakers work toward the goal of universal coverage. "It's very important for us that all Americans have health care coverage that's affordable. But we do understand that we can't afford everything for everybody, so we need to have fiscally responsible conversations."

The letter proposes expanding on Obama's principles in a number of ways, including:

  • Reforming and improving the insurance market through the use of modified community rating, guaranteed renewability and fewer benefit mandates.
  • Assisting low-income individuals through premium subsidies and cost-sharing assistance.
  • Promoting medical home models to reduce system fragmentation and improve care coordination.
  • Establishing antitrust reforms that would allow groups of physicians to contract jointly with payers as long as the doctors certify they are collaborating on health information technology and quality improvement initiatives.
  • Easing the effect of liability pressure on the practice of defensive medicine through innovative approaches, such as health courts, early disclosure and compensation programs, and expert witness qualification standards.

Some signs of progress

Dr. Nielsen said she is encouraged by the progress already made in talks about Medicare physician payment reform, a key part of the AMA's broader health system reform agenda. Physicians soon may begin to see pilot programs testing various payment models in an attempt to find long-term alternatives to the current system, she said. "It's early, but there's no question that's on the table."

In his fiscal 2010 budget proposal, Obama said Medicare's physician pay cuts as mandated by law are not practical. He said Congress should plan on spending $330 billion over the next decade to repeal the current pay system instead of simply patching it year after year.

The next steps on the issue are up to lawmakers. The AMA was one of more than 70 medical organizations that signed an April 13 letter to the House Budget Committee asking Congress to retain a section in the House budget proposal that could make it easier for lawmakers to approve a payment overhaul. By suspending "pay as you go" rules for a large initial portion of a physician pay proposal, the House budget would obviate the need to find hundreds of billions of dollars in offsets otherwise needed to prevent the overhaul from running up deficit spending. At this article's deadline, lawmakers were still negotiating over the differences between the House budget blueprint and the Senate version, which does not include the pay-go exemption.

At least two key Senate leaders think Congress can move quickly, even though it is contemplating the largest health system overhaul proposed in 15 years. "We have jointly laid out an aggressive schedule to accomplish our goal" of enacting comprehensive health system reform, said an April 20 letter to Obama from Senate Finance Committee Chair Max Baucus (D, Mont.) and Senate Health, Education, Labor and Pensions Committee Chair Edward Kennedy (D, Mass.). Both committees plan to mark up legislation in early June.

This content was published online only.

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 ADDITIONAL INFORMATION: 

Obama's 8 principles

The American Medical Association has aligned itself with President Obama's eight basic health system reform principles and provided ideas about how Congress and the administration can achieve them. Here are the original principles for a reform plan as the White House describes them:

Guarantee choice: The plan should provide Americans a choice of health plans and physicians. People will be allowed to keep their own doctor and their employer-based health plan.

Make health coverage affordable: The plan must reduce waste and fraud, high administrative costs, unnecessary tests and services, and other inefficiencies that drive up costs with no added health benefits.

Protect families' financial health: The plan must reduce the growing premiums and other costs American citizens and businesses pay for health care. People must be protected from bankruptcy due to catastrophic illness.

Invest in prevention and wellness: The plan must invest in public health measures proven to reduce cost drivers in our system -- such as obesity, sedentary lifestyles and smoking -- as well as guarantee access to proven preventive treatments.

Provide portability of coverage: People should not be locked into their jobs just to secure health coverage, and no American should be denied coverage because of preexisting conditions.

Aim for universality: The plan must put the United States on a clear path to cover all Americans.

Improve patient safety and quality care: The plan must ensure the implementation of proven patient safety measures and provide incentives for changes in the delivery system to reduce unnecessary variability in patient care. It must support the widespread use of health information technology with rigorous privacy protections and the development of data on the effectiveness of medical interventions to improve the quality of care delivered.

Maintain long-term fiscal sustainability: The plan must pay for itself by reducing the level of cost growth, improving productivity and dedicating additional sources of revenue.

Source: The White House, AMA letter (www.ama-assn.org/ama/pub/news-events/news-events/obama-principles-health-care.shtml)

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DeParle weighs in on health system reform

With the expectation of an eventful year ahead on health system reform, the new leader of the reform effort within the White House started working more than a month before her new office was officially created.

Nancy-Ann DeParle, the first head of the newly minted White House Office for Health Reform, said during an April 15 briefing with reporters in Washington, D.C., hosted by the Kaiser Family Foundation, that she has been plugging away since her appointment was announced March 2. Obama created the new office by executive order on April 8.

Most of her time has been spent meeting with various lawmakers and their staffs on the reform issue, DeParle said. But she reported that she also met with the American Medical Association, the American Hospital Assn. and "various groups who I have reached out to or who have reached out to me to talk about how we get this done this year."

The efforts have already borne fruit, DeParle said. Meetings with state leadership in rural areas of the country, for instance, have highlighted the need for policymakers to help small business owners and their workers, many of whom have been denied coverage or have seen steep increases in their premiums because of preexisting conditions.

"The stories are heartbreaking, and I think they're the reason why this president ... has made it clear that health reform must not wait, cannot wait and will not wait another year."

DeParle took reporters' questions, including several on Obama's plan to save $180 billion over 10 years by requiring private Medicare plans to bid competitively for contracts, with the federal government paying the average of all bids. Confronting payment disparities between Medicare Advantage and the traditional fee-for-service program allows the White House to set the stage for broader Medicare payment reforms, she said.

"Everyone acknowledges that the Medicare Advantage plans, particularly the private fee-for-service plans, nationwide have been paid something like a 12% to 14% premium above what traditional fee-for-service Medicare has been paid to provide the same services," DeParle said.

DeParle also discussed plans to promote the medical home model in an effort to reduce system fragmentation, comparative effectiveness research to determine the best treatments and incentives to help address the growing shortage of primary care physicians.

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Copyright 2009 American Medical Association. All rights reserved.

Friday, May 8, 2009

Promising New Malaria Vaccine Is Extracted From Irradiated Mosquito Spit


The U.S. Food and Drug Administration has approved human trials of a new malaria vaccine: it is made from a weakened form of the entire malaria-causing parasite, Plasmodium falciparum, extracted from irradiated mosquito spit. Sanaria, the company producing the vaccine, has been working with a particular stage of the P. falciparum parasite called a sporozoite. This is the stage when it leaves the mosquito’s salivary glands to enter the human bloodstream [Reuters].

To produce the vaccine, Sanaria weakens the parasite by feeding human, infected blood to mosquitoes, then [exposes] the mosquitoes to enough irradiation to cripple the parasite [New Scientist]. The mosquitoes are then killed and their saliva is extracted by hand, with each of six laboratory workers averaging a rate of 100 mosquitoes per hour. With every mosquito containing about two doses in its spit, Sanaria founder Stephen Hoffman estimates that about 1,200 doses are produced per hour.

The vaccine uses a model similar to others that prevent diseases like measles and polio, in which weakened bacteria is injected, creating an immune response without causing illness. In the Sanaria vaccine, the body recognizes the malaria parasite as a foreign material [CNN], but it does not pose a threat of disease because the mosquito was irradiated. The theory is that by exposing the body to something that looks exactly like the dangerous parasite but is actually harmless, the body’s immune system will develop much stronger resistance than if it encounters vaccines based only on tiny elements of the parasite. In earlier trials of the spit vaccine, before the manufacturing process was perfected, recipients received virtually full protection against malaria for at least 42 months [New Scientist]. That’s an improvement on another vaccine being tested by GlaxoSmithKline, which was based on a fragment of the parasite; that vaccine has been shown to reduce infections in children by about 50 percent.

Starting in May, the vaccine will be tested on volunteers in Maryland. They will receive the vaccine and will then sit in booths filled with malaria-infected mosquitoes until they’re bitten and infected. Researchers believe the vaccine will protect the volunteers, but if any do come down with malaria researchers say they can be treated easily and safely. If these trials are successful, researchers will initiate trials on adults in Africa, and then children [CNN].

Related Content:
80beats: Experimental Malaria Vaccine Could Start Saving Lives by 2011
80beats: Researchers Decode the Genomes of Two Malaria Parasites

Thursday, May 7, 2009

Alzheimer's 'is brain diabetes'

The most common form of dementia may be closely related to another common

 disease of old-age - type II diabetes, say scientists.

Treating Alzheimer's with the hormone insulin, or with drugs to boost its effect, may help patients, they claim.

The journal Proceedings of the National Academ

y of Sciences reports insulin could protect against damage to brain cells key to memory.

UK experts said the find could be the basis of new drug treatments.


 The most exciting implications are that some diabetes drugs have the potential to be developed as Alzheimer's treatments 
Spokesman, Alzheimer's Research Trust



The relationship between insulin 
and brain disease has been under scrutiny since doctors found evidence that the hormone was active there.

The latest study, joint research betw

een Northwestern University in the US and the University of Rio de Janeiro in Brazil, looked at the effects of insulin on proteins called ADDLs, which build up in the brains of Alzheimer's patients and cause damage

.

They took neurons - brain cells - from the hippocampus, a part of the brain with a pivotal role in memory formation.

These were treated with insulin and a drug called rosiglitazone, given to type II diabetics to increase the effect of the hormone on cells.

After this, the cells were far less susceptible to damage when exposed t

o ADDLs, suggesting that insulin was capable of blocking their effects.

Treatment hope

Professor William Klein, from Northwestern, said that drugs to boost the brain's sensitivity to insulin could

 provide "new avenues" for treating Alzheimer's disease.

"Sensitivity to insulin can decline with aging, which presents a novel risk factor for Alzheimer's disease - our results demons

trate that bolstering insulin signalling can protect neurons from harm."

His colleague, Professor Sergio Ferreira, from Rio de Janeiro, said: "Recognising that Alzheimer's disease is a type of brain di

abetes points the way to novel discoveries that may finally result in disease-modifying treatments for this devastating disease."

A spokesman for the Alzheimer's Research Trust said that the study shed light on how insulin i

nteracted with toxic proteins linked to the disease.

"People with diabetes are at higher risk of developing Alzheimer's. It is well known that insulin affects how the brain works, and this research adds more evidence to the possibility that 

Alzheimer's could be a type of brain diabetes.

"The most exciting implications are that some diabetes drugs have the potential to be developed as Alzheimer's treat

ments."

Dr Victoria King, of the charity Diabetes UK, said: "We already know that people with Type 2 diabetes are at a higher risk of developing Alzheimer's disease.

"This study is in its early stages but it is 

interesting because it suggests that insulin, alongside drugs that help the body use insulin more effectively, may protect against the underlying biological mechanisms associated with

 the development of Alzheimer's disease.

"This is very intriguing and could potentially help with new treatments for Alzheimer's disease and shed further light on its links with diabetes. We 

would certainly welcome more research in this area." 

Wednesday, May 6, 2009

As Swine Flu Spreads, Focus Shifts to a Potential Vaccine


As the swine flu outbreak continues to spread, with Russia, South Korea, and Australia joining the list of countries with suspected cases and the death toll climbing in Mexico, attention has turned to the potential of a swine flu vaccine that could protect populations from infection. But a new vaccine takes some months to develop. Says Iain Stephenson, an expert on flu vaccines: “We are in a position where if a swine flu virus becomes a pandemic we don’t currently have a vaccine for it…. I think that it is unlikely there will be widespread vaccine in less than six to eight months” [Telegraph]. In the meantime, says Stephenson, patients can be treated with antiviral drugs.

International health officials haven’t yet decided whether the swine flu poses a serious worldwide threat that would call for the immediate prioritizing of a vaccine. The pharmaceutical company Novartis said it had received the genetic code of the new virus strain, enabling it to start work on evaluating production, and it hoped to receive the actual virus in its laboratories “in the near future.” … But the World Health Organisation (WHO) said it would only call for large-scale production of such a pandemic vaccine if it strongly believed the world was on the edge of an unstoppable global outbreak of flu [Reuters]. Vaccine companies are currently producing the seasonal flu vaccine, and health officials worry that calling them off that task could lead to shortages of the common flu shot.

If drug companies are given the green light to start production of the new vaccine, most will use a traditional method called the attenuated method, in which scientists grow the new strain of virus in chicken eggs. The virus is then killed to make it safe. Upon injection, the dead virus acts as an antigen that trains the immune system to recognize the virus, so that a real infection would trigger an immediate immune response. But even though vaccine is more efficiently produced than in the past, say WHO officials, some infectious-disease experts say eggs can be unreliable. “They can go bad, the strain might not grow fast enough, or at all” [USA Today], says vaccine expert Brian Currie. Growing the virus is cell cultures is a slightly faster process, although some experts argue that both egg and cell culture approaches are outdated.

If the swine flu spreads rapidly, the government may turn to companies whose experimental technologies promise to yield large batches of vaccines more quickly. [Start-up company] Vaxart makes vaccines by combining an antigen – in this case, the swine-flu DNA – with a non-replicating viral vector and an adjuvant that boosts the immune response. This “modular” approach is about two months faster than egg or cell-culture systems, said Chief Executive Mark Backer. If swine flu becomes a large problem, U.S. regulators may permit Vaxart and others to move rapidly from animal research to human studies, he said [The Wall Street Journal].

Related Content:
80beats: Fears of a Swine Flu Pandemic Increase as the Virus Goes Global
80beats: Deadly Swine Flu Outbreak in Mexico City Prompts Fears of a Pandemic
80beats: Bird Flu in Egypt and Swine Flu in California Raise Guarded Concerns

Monday, May 4, 2009

Volunteers and the Great Unknown: Interview with Clinical-Trial Participants

Amanda Redig

Don’t think, try.
—William Harvey, physician (1578-1657)

In one of the earliest recorded clinical trials, British physician Edward Jenner decided to test his theory that infection with the cowpox virus provided protection from the more deadly scourge of smallpox. Jenner’s approach, however, is also a bioethicist’s worst nightmare. In the waning days of the 18th century, there was no such thing as informed consent, institutional review boards, or human-subjects protection. So, without much fanfare, Jenner simply transferred pus from a cowpox pustule to an incision he created on the arm of his 8-year-old test subject, James Phipps, and subsequently exposed the boy to smallpox. Luckily for Phipps, Jenner’s idea did not prove fatal: cowpox exposure did offer smallpox protection. When the Royal Society of London declined to publish his findings, Jenner simply turned to more pediatric subjects to prove his point. As legend has it, this included his own infant son [1].

LEARNING OBJECTIVELearn from first-person reports why individuals—both healthy and ill—agree to participate in human-subjects research.

In the end, Jenner’s ideas—if not his methods—were not as far-fetched as first imagined. While his discoveries were responsible for the first smallpox vaccine and earned him a place in medical history as the father of immunology, much has changed in the way physicians interact with patient research subjects since Jenner’s time. After the trials at Nuremberg and the Declaration of Helsinki, the rights and protection of the patient-subject are at the forefront of any modern research trial [2].

What motivates people to participate in research protocols today? Entire departments and layers upon layers of federally mandated paperwork exist to protect both the scientific integrity of research as well as the health and well-being of human test subjects. One fundamental detail, however, has not changed in the days since Jenner exposed neighborhood children to smallpox: clinical research must necessarily contain an element of the unknown. Yet people still participate.

I decided to interview some clinical-study participants to see what they had to say about their decision to participate in a study and whether or not they would do so again. The studies represented were a trial that compared a new cancer drug to existing therapy and two preclinical research studies in which normal (non-sick) volunteers underwent neurological imaging or donated bone marrow for laboratory studies. Given the diversity of study aims, the answers of study participants may surprise you. And in a way, their thoughts about participating in clinical-research projects embody the same spirit of inquiry that first set Jenner on his way over 200 years ago.

In their own words. “Why would anyone want to do that?” This is one of the first questions that comes to mind when one considers the uncharted waters of a clinical protocol. Yet as those close to patient-subjects make clear, sometimes it is the promise of something new and different that makes a study appealing. “My mom participated in the study because we were out of options at that point,” a family member said, referring to a study that was designed to test the efficacy of a new medication to treat a particular kind of cancer.

The drug she had been taking…stopped working, and the side effects of interferon were nearly killing her. We heard about Gleevec and weren’t sure she would qualify for the clinical trial…but we thought, if she qualified, then why not? We had nothing to lose. She wasn’t paid, but the promise of a new drug gave us hope when we were already expecting the worst.

This particular patient-participant’s disease was so advanced at the time of therapy initiation that she eventually succumbed to it. The drug she received, however, is now standard therapy for this type of leukemia (chronic myelogenous leukemia) and has had a profound influence on pharmaceutical drug design. “Ultimately my mom knew she was fighting a losing battle,” her daughter noted. But, “I think she would have done it again, especially to be on the trial for a drug that revolutionized the therapy of CML as we know it.”

The same thread of hope is also a part of the motivation for a normal volunteer who participated in a different study that involved donating bone marrow for laboratory research. “If I truly believe in the utility and promise of clinical studies,” he said, “then I feel obligated to participate in whatever way I can to further the research goals of others, even if it means enduring slight discomfort.” This thought is echoed by a participant in the same trial who, even though she initially thought the bone-marrow-donation process was too painful to consider doing again, decided the right trial might change her mind. “Well, actually maybe I would do it again if it was something to help children or a disease like cancer or MS,” she said.  “Clinical research is a wonderful thing, and it should be funded more,” she said.

Financial reward. The promise of hope is indeed a powerful motivation. Yet the question of financial remuneration is also powerful and one of the most complex issues involved in clinical studies. To avoid coercion, money offered to participants cannot be deemed excessive. Yet, particularly for the non-sick volunteers needed to serve as healthy controls for many types of studies, shouldn’t there be some payback for donation of time and the experience of undergoing unpleasant and often painful procedures? Who is to say how much is enough (or too much)? And does money of any kind make people more likely to participate? The answer appears to be more convoluted than one might imagine. As one participant stated,

I donated bone marrow for a friend’s PhD research project. The money was nice (I was paid $150), but I mostly donated because I liked the idea of being included in my friend’s project. As a future physician, I wanted to know what it was like to donate bone marrow, so I would understand what patients experience during bone-marrow biopsies.

This thought was echoed by another participant in the same study who remarked,

While I was compensated for my time and discomfort, this was not the primary motivation for participation. Knowing that part of me might be used to help better understand disease and perhaps lead to an improved diagnostic method or therapy was rewarding enough.

A third participant who also donated bone marrow concurred. “Well, for the money, yes,” she said, when asked why she participated. “But also for the science factor. Depending on what it was for, I wouldn’t need to be paid to consider it.”

Sometimes, this same sense of curiosity leads people to participate in multiple studies. Another participant in the bone-marrow study remarked, “While a laboratory technician…I participated in several studies that involved transcranial magnetic stimulation (TMS) and MRIs. I was not compensated for the studies, but I participated because I was fascinated by the science and really interested in seeing the scans of my own brain.”

Would you do it again? Repeat participation in future studies is—of course—the best way to gauge a clinical subject’s overall experience on a research protocol. For the volunteers interviewed here who were not sick, the overwhelming answer seems to be affirmation of the promise of clinical research. As one participant put it,

I would definitely do it [donate bone marrow] again. Since then, I have donated blood for basic science research….The first time I did it, the guy unfortunately missed three veins and couldn’t get any blood. I would still go back. I love the idea that I can contribute to science.

Another volunteer on the bone-marrow protocol added, “I hope to continue in whatever way I can to help researchers pursue their studies.”

Yet participation in a clinical study of any kind is not an entirely benign experience. It is sometimes difficult to tell whether the new drugs and devices being tested are working. “She did start to feel better,” a family member noted about a cancer patient participating in a trial evaluating a new medication. “But the course of the illness…and her death were about the amount of time the doctor had predicted, regardless of the [drug].” Furthermore, the time commitment required for evaluation of new therapies can be exhausting for people who are already sick. As the daughter of one participant put it: “I think my mom was getting frustrated with the constant appointments.” Even for normal volunteers who participate in studies that do not involve long-term follow-up, there is still the upfront commitment of time, not to mention sometimes unpleasant procedures. “No, I wouldn’t do it again. It was too painful,” remarked a study participant in reference to a bone-marrow donation.

Much has changed since the early days of medical research, but what will never go away is the challenge of finding a way to pursue progress when that progress requires human experimentation. Participation in a clinical study of any kind is a significant commitment. Yet it seems that such studies will continue to move ahead thanks to the sense of purpose felt by patients and normal volunteers alike. This general optimism is perhaps best summarized by an individual who lost her mother to cancer: “…I knew the medicine probably wasn’t going to make a miracle happen, but at least the [experimental] drug gave us all something new to have hope and faith in. And even if [it] didn’t help my mom, we were at least playing a part in something that maybe would work for someone else’s mother. I am sure my mom would agree.”


References

  1. BBC. Historic figures: Edward Jenner (1749-1823). http://www.bbc.co.uk/history/historic_figures/jenner_edward.shtml. Accessed February 24, 2009.
  2. The World Medical Association. World Medical Association Declaration of Helsinki. 2008. http://www.wma.net/e/policy/b3.htm. Accessed February 24, 2009.

Amanda Redig is an MD/PhD student at Northwestern University’s Feinberg School of Medicine in Chicago. She will defend her doctoral thesis in April 2009 and graduate from medical school in May 2010, at which time she plans to pursue a career in academic hematology-oncology. As a research scientist, future physician, and prior patient-research subject, Ms. Redig is committed to clinical research that is medically exciting and ethically sound.

Politics of Participation: Walter Reed’s Yellow-Fever Experiments, April 2009

Enrollment of Economically Disadvantaged Participants in Clinical Research, January 2009

Helping Patients Decide whether to Participate in Clinical Trials, January 2007