Wednesday, December 31, 2008

Electronic Health Record

Dr. Theodore A. Praxel, Marshfield’s director of quality improvement and care management.


Darren Hauck for The New York Times
Claire Critelli, 6, and her mother, Marilee, left, with Dr. Edna O. DeVries at the Marshfield Clinic in Wisconsin.










December 27, 2008
The Evidence Gap
Health Care That Puts a Computer on the Team
By STEVE LOHR
MARSHFIELD, Wis. — Joseph Calderaro, 67, is one of health care’s quiet success stories. Over the last four years, he has carefully managed his diabetes by lowering his blood sugar, blood pressure and cholesterol with diet, exercise and medication.
To keep on track, Mr. Calderaro visits his doctor, attends meetings for diabetes patients and gets frequent calls from a health counselor. It is a team effort, orchestrated by the Marshfield Clinic here. And it is animated by technology, starting with Mr. Calderaro’s computerized patient record — a continuously updated document that includes his health history, medications, lab tests, treatment guidelines and doctors’ and nurses’ notes.
To visit the Marshfield Clinic, a longtime innovator in health information technology, is to glimpse medicine’s digital future. Across the national spectrum of health care politics there is broad agreement that moving patient records into the computer age, the way Marshfield and some other health systems have already done, is essential to improving care and curbing costs.
A paper record is a passive, historical document. An electronic health record can be a vibrant tool that reminds and advises doctors. It can hold information on a patient’s visits, treatments and conditions, going back years, even decades. It can be summoned with a mouse click, not hidden in a file drawer in a remote location and thus useless in medical emergencies.
Modern computerized systems have links to online information on best practices, treatment recommendations and harmful drug interactions. The potential benefits include fewer unnecessary tests, reduced medical errors and better care so patients are less likely to require costly treatment in hospitals.
The widespread adoption of electronic health records might also greatly increase evidence-based medicine. Each patient’s records add to a real-time, ever-growing database of evidence showing what works and what does not. The goal is to harness health information from individuals and populations, share it across networks, sift it and analyze it to make the practice of medicine more of a science and less an art.
The Bush administration has left it mainly to advocacy and the private sector to introduce digital medicine. But President-elect Barack Obama apparently plans to make a sizable government commitment. During the campaign, Mr. Obama vowed to spend $50 billion over five years to spur the adoption of electronic health records and said recently that a program to accelerate their use would be part of his stimulus package.
The Marshfield Clinic, a large doctors’ group in Wisconsin, shows that computerized records can indeed improve the quality and efficiency of medicine. Yet the Marshfield experience suggests that the digital record becomes truly useful only when patient information is mined to find patterns and answer questions: What treatments work best for particular categories of patients? What practices or procedures yield the best outcome?
The Marshfield Clinic “understands that it’s a system of improvement that technology makes possible that really matters, and the electronic health record itself is no silver bullet,” said Dr. Carolyn M. Clancy, director of the federal Agency for Healthcare Research and Quality.
For the Obama presidency and the administrations that follow it, the challenge will be to somehow link electronic medical islands into a network that begins to approach on a national scale what organizations like Marshfield have achieved regionally. Ideally, a lone physician in a rural community could tap into the national health information network and be as well informed on treatments and research for patients with certain conditions as a specialist at Marshfield.
Some experts caution that such a broad capacity for record-sharing could take decades to achieve — if it is even possible in the decentralized American marketplace of medical competitors.
Marshfield Clinic, a nonprofit organization founded in 1916, has a long history of using information technology to further research and improve care. In the 1960s, the clinic bought the digital breakthrough of its day — a mainframe computer — and used punched cards to feed it information on diagnoses and procedures. In 1985, the clinic introduced its first basic electronic health records, kept refining them and by 1994 mandated that its doctors all use them. In 2003, it introduced wireless tablet computers, whose screen can written on like digital paper or flipped up, exposing a keyboard, and used as a conventional laptop PC.
Today, Marshfield’s 790 doctors and their support staff at 43 locations in Wisconsin all use the tablet PCs. At the end of last year, the group eliminated paper charts for the more than 365,000 patients its doctors see each year, freeing up storage space the size of a football field at the main clinic in Marshfield. At each step toward a fully digital system, physicians were consulted and involved in the design process.
“It’s been a fabulous journey from physicians being reluctant to now being unable to live without this technology,” observed Dr. Karl J. Ulrich, the clinic’s chief executive. Marshfield is one of a few dozen medical groups across the country that are aggressively embracing information technology. The organizations tend to be big — ranging from providers with thousands of physicians like Kaiser Permanente and the Department of Veterans Affairs to ones with hundreds like Marshfield and Geisinger Health Systems in central Pennsylvania. They are typically responsible for most or all aspects of a patient’s care. They are often insurers, as well.
Those groups, in other words, have the scale and economic incentives to invest in information technology to capture the gains from improved quality and efficiency. In that regard, they lie outside the mainstream of America’s health care economy, a fee-for-service system in which providers are typically paid for doing more, not necessarily doing better. It is a system that encourages more doctor visits, more tests, more surgical procedures, more pills.
For most doctors, who work in small practices, an investment in electronic health records looks simply like a cost for which they will not be reimbursed. That is why policy experts say any government financial incentives to use electronic records — matching grants or other subsidies — should be focused on practices with 10 or fewer doctors, which still account for three-fourths of all doctors in this country. Only about 17 percent of the nation’s physicians are using computerized patient records, according to a government-sponsored survey published in The New England Journal of Medicine.
Even for the large doctor groups, there is no crisp, conclusive cost-benefit arithmetic. Marshfield can point to various measurable savings, but has scant proof they outweigh the millions spent in the past and the $50 million-a-year technology budget.
“People ask about return on investment, but that’s the wrong question,” said Dr. John W. Melski, the medical director of clinical informatics at Marshfield. “This requires the usual leap of faith that knowledge will yield good things — better care, doing things smarter and, yes, saving money in the long run.”
Aided by their growing database, Marshfield’s physician-researchers are working on ambitious projects in personalized medicine that use genetic markers to tailor drug dosages. For example, the clinic recently began a clinical test on 250 patients that uses three gene markers to personalize their doses of Coumadin, or warfarin as the generic drug is known. The blood-thinning drug is widely prescribed for heart patients. But it is often difficult to calibrate the right dose for individuals, and the consequences of internal bleeding or blood clots can be life-threatening. In this case, the electronic health record is the starting point for research, feeding information into the database from which the clinic’s scientists appropriate patients. The digital record holds the patient-specific information used in the Coumadin calculation of tailored doses for individuals.
Marshfield is also researching “predictive” medicine that combines genetics, family histories and lab tests to warn patients about looming health risks. It has a voluntary DNA database on nearly 20,000 people, whose health care information goes back 30 years on average — and the electronic record is the vehicle for collecting and conveying that information. The researchers are looking for patterns in family history, lifestyle, environmental factors, lab test results and selected genetic markers that might predict the onset of conditions like diabetes and Alzheimer’s disease years in advance.
“Better health information technology is needed every step of the way,” said Catherine A. McCarty, director of Marshfield’s center for human genetics and principal investigator for its personalized medicine research project. “We could not do this without the electronic health record.”
The more immediate target, though, is harnessing the digital technology to help manage chronic illnesses like diabetes, heart disease, cancer and asthma. Seventy-five percent of America’s health care spending goes to people with one or more chronic conditions. And as the population ages that percentage is rising.
Marshfield’s progress in recent years with its more than 18,000 diabetes patients, including Mr. Calderaro, points to the potential. The gains are a byproduct of being able to constantly measure and manage health outcomes, a process of efficiently gathering and monitoring patient information that is made possible by the electronic health record. Besides the doctor visits, group meetings and monthly calls from a diabetes counselor, Mr. Calderaro has used all the information to take responsibility for controlling his diabetes. He not only monitors his blood sugar and blood pressure readings, but he could recite the carbohydrate grams in each of the foods he ate one day recently. A three-mile walk is often part of his daily regimen. He was never really heavy, but he has a sister with diabetes and had a maternal grandmother who suffered from the disease.
“If I had known when I was 40 years old what I know now, I would have done things differently,” Mr. Calderaro said.
From mid-2004 through the third quarter of this year, the percentage of the clinic’s diabetic patients with blood cholesterol at or below the recommended level rose to 61 percent, from 40 percent earlier. The percentage with satisfactory blood pressure increased to 52 percent, up from 32 percent.
Over the same span, hospital admissions among Marshfield’s diabetic population fell — to 311 per 1,000 patients a year, from 360. Because a hospital stay for a diabetes patient ranges from $8,000 to $22,500, according to national statistics, Marshfield’s results translate into an annual cost saving of $7.3 million to $20.5 million.
More important may be the suffering avoided. Complications from diabetes include kidney failure, blindness and amputations. “Those are the things that really scare you,” Mr. Calderaro, the patient, said. “But it doesn’t have to be. You can manage it.”
Marshfield is striving to help more of its diabetes patients to do as well as Mr. Calderaro, and the federal Medicare agency has recognized Marshfield’s progress.
In a continuing pilot project, Medicare has selected the clinic and nine other large doctor groups and arranged to pay them for the quality of care they deliver. Last year, on the basis of how well diabetes patients had fared, by various measures, Marshfield was one of only two groups that did well enough to earn bonus payments.
The Medicare pilot prompted Marshfield to take a fresh look at how it cares for various chronic conditions, including heart disease and hypertension. That led to a new software tool, called the iList, which has proved a big help, said Dr. Theodore A. Praxel, Marshfield’s medical director of quality improvement and care management.
The iList (for “intervention list”) culls the patient records of a primary care physician, and ranks and flags patients by conditions not met, including uncontrolled blood pressure and cholesterol, overdue lab tests and vaccinations missed. Nurses and medical assistants then “work the iList,” calling patients with reminders and scheduling them for exams and lab work.
In medicine, the computer is to memory what the X-ray machine is to vision — a technology that vastly surpasses human limitations. The benefits of a computer-helper, doctors say, become quickly evident in everyday practice.
When a doctor electronically prescribes a new drug, for example, an on-screen warning appears if the medication is on the patient’s allergy list or could cause a potentially dangerous interaction with another drug the person is taking. In the New England Journal of Medicine survey, 71 percent of physicians using electronic health records with that feature said they had received a computer alert that helped them avoid a harmful prescription mistake.
“It absolutely happens,” said Dr. Edna O. DeVries, a pediatrician at Marshfield. “You’re distracted and talking to the parents. You’re on autopilot.”
Dr. DeVries, who joined the clinic in 1989, was the medical director nearly a decade ago on a database, created by Marshfield, to track early childhood immunizations in central Wisconsin. Over the next two years, the immunization rates for children in the area rose to 93 percent, from 67 percent, as a result of the tracking and follow-up reminders.
“The quality of care goes up dramatically just by having information instantly,” Dr. DeVries said. Yet, as her colleague and veteran of computer medicine Dr. Melski notes, there is no payoff to technology alone — only in people using technology wisely.
“We have to restructure our medical culture,” he said. “We have to promote a culture that believes in the evidence and is trained in analyzing the evidence. It’s the only long-run answer to the challenges we face in health care — evidence-based medicine.”

No Mug? Drug Makers Cut Out Goodies for Doctors

Just a few of the free pens in Dr. Jeffrey F. Caren’s collection.




Dr. Jeffrey F. Caren, a cardiologist at Cedars-Sinai Medical Center in Los Angeles, has collected more than 1,200 pens and mounted them on a pillar in his office.
December 31, 2008
No Mug? Drug Makers Cut Out Goodies for Doctors
By NATASHA SINGER
To Lehman Brothers, Linens ’n Things and the blank VHS tape, add another American institution that expired in 2008: drug company trinkets.
Starting Jan. 1, the pharmaceutical industry has agreed to a voluntary moratorium on the kind of branded goodies — Viagra pens, Zoloft soap dispensers, Lipitor mugs — that were meant to foster good will and, some would say, encourage doctors to prescribe more of the drugs.
No longer will Merck furnish doctors with purplish adhesive bandages advertising Gardasil, a vaccine against the human papillomavirus. Banished, too, are black T-shirts from Allergan adorned with rhinestones that spell out B-O-T-O-X. So are pens advertising the Sepracor sleep drug Lunesta, in whose barrel floats the brand’s mascot, a somnolent moth.
Some skeptics deride the voluntary ban as a superficial measure that does nothing to curb the far larger amounts drug companies spend each year on various other efforts to influence physicians. But proponents welcome it as a step toward ending the barrage of drug brands and logos that surround, and may subliminally influence, doctors and patients.
“It’s not just the pens — it’s the paper on the exam table, the tongue depressor, the stethoscope tags, medical calipers that might be used to interpret an EKG, penlights,” said Dr. Robert Goodman, a physician in internal medicine at Montefiore Medical Center in the Bronx.
In 1999, Dr. Goodman started No Free Lunch, a nonprofit group that encourages doctors to reject drug company giveaways. “Practically anything you can put a name on is branded in a doctor’s office, short of branding, like a Nascar driver, on the doctor’s white coat,” Dr. Goodman said.
The new voluntary industry guidelines try to counter the impression that gifts to doctors are intended to unduly influence medicine. The code, drawn up by Pharmaceutical Research and Manufacturers of America, an industry group in Washington, bars drug companies from giving doctors branded pens, staplers, flash drives, paperweights, calculators and the like.
The guidelines also reiterate the group’s 2002 code, which prohibited more expensive goods and services like tickets to professional sports games and junkets to resorts. And it asks companies that finance medical courses, conferences or scholarships to leave the selection of study material and scholarship recipients to outside program coordinators.
Diane Bieri, the executive vice president of Pharmaceutical Research and Manufacturers of America, said the updated guidelines were not an admission that gifts could influence doctors’ prescribing habits. Instead, she said, they were meant to emphasize the educational nature of the relationship between industry and doctors.
“We have never said and would never say that a pharmaceutical pen or notebook has influenced any prescription,” Ms. Bieri said.
But some critics said the code did not go far enough to address the influence of drug marketing on the practice of medicine. The guidelines, for example, still permit drug makers to underwrite free lunches for doctors and their staffs or to sponsor dinners for doctors at restaurants, as long as the meals are accompanied by educational presentations.
“Pens or no pens, their influence is not going to be diminished,” said Dr. Larry M. Greenbaum, a rheumatologist in Greenwood, Ind. He has made a point of collecting ballpoint pens advertising formerly heavily promoted medications, like the painkiller Vioxx, that were later withdrawn after reports of dangerous side effects.
Last year, besides giving away nearly $16 billion in free drug samples to doctors, pharmaceutical companies spent more than $6 billion on “detailing” — an industry term for the sales activities of drug representatives including office visits to doctors, meal-time presentations and branded pens and other handouts, according to IMS Health, a health care information company.
The industry code also permits drug makers to pay doctors as consultants “based on fair market value” — which critics say means that companies can continue to pay individual doctors tens of thousands of dollars or more a year.
“We have arrived at a point in the history of medicine in America where doctors have deep, deep financial ties with the drug makers and marketers,” said Allan Coukell, the director of policy for the Prescription Project, a nonprofit group in Boston working to promote evidence-based medicine. “Financial entanglements at all the levels have the potential to influence prescribing in a way that is not good.”
About 40 drug makers, including Eli Lilly & Company, Johnson & Johnson and Pfizer, have signed on to the code. Representatives of several pharmaceutical makers said their companies intended to comply with the guidelines, but they declined to discuss past marketing programs involving branded gifts.
The restrictions come as a blow to the makers and distributors of promotional products, an industry with an annual turnover of about $19 billion, according to Promotional Products Association International, a trade group. Such companies, accustomed to orders of up to a million pens a drug, stand to lose around $1 billion a year in sales as a result of the drug industry’s voluntary ban, the group said.
The sudden scarcity of free goodies, though, could enhance the cachet of collections that some doctors have assembled over the years as a mocking countermeasure to drug marketing. Dr. Nathan Anderson, a resident in internal medicine at a hospital in Texas, has posted photographs of the various items he has received on his blog, drugreptoys.blogspot.com.
Dr. Jeffrey F. Caren, a cardiologist at Cedars-Sinai Medical Center in Los Angeles, has collected more than 1,200 pens and mounted them on a pillar in his office.
While some doctors applaud the gift ban, others seem offended by the insinuation that a ballpoint pen could turn their heads. “It seems goofy to us; we like getting our pens,” Dr. Susan B. Hurson, an obstetrician and gynecologist in Washington, said in a telephone interview.
Dr. Hurson said she paid no attention to the logos on the pens she carries around in her doctor’s coat.
Prompted by a reporter’s question, she pulled out a handful of pens from her pocket and read off the drugs advertised: Clindesse, a cream for vaginal infection; Halo, a system for detecting breast cancer, and Evamist, an estrogen spray. “It’s hard for me to believe it influences what you prescribe.”
But Dr. Phillip Freeman, a psychiatrist in Boston, said that physicians who contended that the giveaways were benign might be suffering from denial.
“The need to deny influence is damaging to the soul,” Dr. Freeman said. He suggested that doctors would feel less conflicted if they simply wore drug company patches on their white coats.

Living Better With Rheumatoid Arthritis

Personal Health
Living Better With Rheumatoid Arthritis

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new_york_times:http://www.nytimes.com/2008/08/12/health/12brod.html

By JANE E. BRODY
Published: August 11, 2008

Alan Moore was 52 years old, teaching statistics at the University of Wyoming, playing the violin in the university’s symphony and accompanying soloists on the piano when his health took a nosedive in April 2001.

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“I felt like I had the flu,” Mr. Moore recalled in an interview last month. “I was very weak and fatigued. I had extreme pain and swelling in a lot of my joints. I was in agony when I got up in the morning, so stiff I had to shuffle to the bathroom. I couldn’t peel a banana, turn the key in the ignition or even pull the tab of a tea bag. My wife, Cindy, had to help me with the simplest of tasks. Needless to say, I couldn’t play the violin or piano or use the computer.”
Doctors diagnosed it as rheumatoid arthritis.
“And I thought that my life as I knew it was over,” said Mr. Moore, now 59, of Laramie, Wyo.
But by enrolling in a clinical trial of one of the drugs and drug combinations that are revolutionizing the treatment of the disease, Mr. Moore got his life back.
Rheumatoid arthritis is the world’s most common autoimmune disease, striking up to 1 in 100 in the course of a lifetime. It is most often diagnosed in people ages 30 to 60 but it can occur at any time, including childhood.
As with other autoimmune diseases, women are three to four times likelier than men to develop rheumatoid arthritis. About 80 percent of Caucasians with the disease have a genetic marker, a gene sequence in the HLA-D region of chromosome 6 that is found in only about 35 percent of the general population.
The disease causes chronic joint inflammation and progressive destruction of the cartilage at the ends of bones, which can result in an inability to use the affected joints. Other effects include fatigue, malaise, anemia and damage to organs throughout the body, including the cardiovascular system.
Untreated, 20 to 30 percent of people become permanently disabled within three to five years of diagnosis. Life expectancy may be reduced by as much as 15 years, with half of patients succumbing to cardiovascular disease.

A Therapeutic Revolution
Doctors traditionally treated the symptoms of rheumatoid arthritis, usually with anti-inflammatory and pain-relieving medications. But the underlying destruction of tissues continued, leading to chronic disability and premature death.
The goal today is suppression of the disease and prevention of progressive joint destruction by treating patients early with synthetic or biologic agents called disease-modifying antirheumatic drugs.
Though he did not know it at the time, Mr. Moore was randomly assigned to the study group that every two weeks self-injected a biologically derived drug called Humira, which acts to block a protein involved in the inflammation associated with rheumatoid arthritis. Humira is one of six federally approved biologic treatments for the disease. Three other biologic remedies are nearing approval by the Food and Drug Administration.
“Within days my symptoms declined to nearly zero,” Mr. Moore said, “and I’ve had no symptoms since.” He has continued the injections of Humira and participates in a registry of patients to help assess the drug’s long-term benefits and potential risks.

Combining Treatments
The costly biologic drugs are often used in combination with much cheaper synthetic disease-modifying drugs taken orally, like methotrexate. In some cases, oral medications are all that patients need to keep symptoms and joint destruction under control.
But well-designed clinical trials have typically shown that in patients facing moderate to severe disease, combining the treatments often results in fewer symptoms and less destruction of joints, especially if therapy begins early.
In a study published July 16 in The Lancet, researchers in Leeds, England, reported that among 542 patients randomly assigned to receive either methotrexate alone or in combination with Enbrel, another biologic agent, those receiving the combination were almost twice as likely to become symptom free and more likely to show no X-ray signs of progressive joint destruction a year later.
In a commentary with the Lancet report, Dr. Joel M. Kremer, a rheumatologist at Albany Medical College, said it was important to consider the long-term consequences and costs of the disease when deciding how much to spend on therapy.
“Most of the biologic agents cost in the range of $16,000 to $18,000 a year, whereas the oral medications cost only about a tenth that,” Dr. Kremer said in an interview.
But, he added, inadequately treated rheumatoid arthritis typically leads to a need for multiple joint replacements, lost productivity, lost tax revenue and a greatly diminished quality of life, as well as an increased risk of life-threatening infections and cardiovascular disease.
“Most patients diagnosed at age 45 will be disabled in five or six years,” Dr. Kremer said. “You have to consider what it costs to fix a bridge against what it will cost when the bridge collapses.”
Before the use of disease-modifying drugs, direct medical costs from rheumatoid arthritis were estimated at $5.5 billion, and that did not include the indirect costs of lost wages and productivity, the need for custodial care and the emotional and social consequences of chronic disability.

A Tailored Approach
While not everyone with rheumatoid arthritis responds to the new treatments as vividly as Mr. Moore did, many large studies have shown there is no longer any reason for pessimism about the diagnosis. But it is vitally important to begin treatment early.
The recent therapeutic developments, Dr. Kremer said, mean doctors in general practice need to remain alert to symptoms of the disease in its early stages and quickly refer patients to rheumatologists who can confirm the diagnosis and prescribe up-to-date treatment before irreparable damage to joints occurs. Treatment is most effective if begun within one year after symptoms appear.
There is no one treatment approach that works for everyone. Rather, studies have indicated that treatment should be tailored to individual patients: the nature and extent of their disease, their other health issues and how they respond to various therapies.
Dr. Kremer said many patients could be started on a single, low-cost drug like methotrexate, as long as their condition was closely monitored and the treatment adjusted if there are signs of progressive disease.
Regular exercise and physical and occupational therapy, along with medication, can help patients maintain function. In addition to antirheumatic drugs to reduce inflammation, Dr. Kremer recommends fish oil at a daily dose of 2 grams of EPA and DHA — about six capsules as they are currently formulated.

http://www.nytimes.com/2008/08/12/health/12brod.html?_r=1&fta=y

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Patient’s DNA May Be Signal to Tailor Medication

Jody Uslan, who took the drug Tamoxifan for two and a half years to prevent a recurrence of breast cancer, recently found out through newly available genetic testing that the drug had no effect on her.

Dr. David Flockhart discovered how the body converted the medication tamoxifen.


The Evidence Gap
Patient’s DNA May Be Signal to Tailor Medication
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new_york_times:http://www.nytimes.com/2008/12/30/business/30gene.html

By ANDREW POLLACK
Published: December 29, 2008

The Evidence GapThe Genetic Factor
Articles in this series are exploring medical treatments used despite scant proof that they work and are examining steps toward medicine based on evidence.


For more than two years, Jody Uslan had been taking the drug tamoxifen in hopes of preventing a recurrence of breast cancer. Then a new test suggested that because of her genetic makeup, the drug was not doing her any good.
“I was devastated,” said Ms. Uslan, 52, who stopped taking tamoxifen and is now evaluating alternative treatments. “You find out you’ve been taking this medication for all of this time, and find out you are not getting benefit.”
Ms. Uslan’s situation is all too common — and not just among the hundreds of thousands of women in this country taking tamoxifen.
Experts say that most drugs, whatever the disease, work for only about half the people who take them. Not only is much of the nation’s approximately $300 billion annual drug spending wasted, but countless patients are being exposed unnecessarily to side effects.
No wonder so much hope is riding on the promise of “personalized medicine,” in which genetic screening and other tests give doctors more evidence for tailoring treatments to patients, potentially improving care and saving money.
Many policy experts are calling for more studies to compare the effectiveness of different treatments. One drawback is that such studies tend to be “one size fits all,” with the winning treatment recommended for everybody. Personalized medicine would go beyond that by determining which drug is best for which patient, rather than continuing to treat everyone the same in hopes of benefiting the fortunate few.
The colon cancer drugs Erbitux and Vectibix, for instance, do not work for the 40 percent of patients whose tumors have a particular genetic mutation. The Food and Drug Administration held a meeting this month to discuss whether patients should be tested to narrow use of the drugs, which cost $8,000 to $10,000 a month.
And a genetic test might help doctors determine the optimal dose of warfarin, a blood thinner used by millions of Americans.
Tens of thousands of them are hospitalized each year because of internal bleeding from an overdose or a blood clot from an inadequate dose.
“If you save one hospitalization for every 100 new warfarin users, you more than offset the cost of testing all 100,” said Dr. Robert S. Epstein, the chief medical officer of Medco Health Solutions, which manages prescription plans for employers. The test typically costs $100 to $600.
For all the potential, experts see some formidable obstacles on the path to the promised land of personalized medicine.
“It’s going to take 20 to 30 years for all this to fall into place,” said Dr. Gregory Downing, who heads efforts by the Department of Health and Human Services to spur personalized health care.
The hurdles include




  • drug makers, which can be reluctant to develop or encourage tests that may limit the use of their drugs.


  • Insurers may not pay for tests, which can cost up to a few thousand dollars.


  • For makers of the tests, which hope their business becomes one of health care’s next big growth industries, a major obstacle is proving that their products are accurate and useful.


While drugs must prove themselves in clinical trials before they can be sold, there is no generally recognized process for evaluating genetic tests, many of which can be marketed by laboratories without F.D.A. approval.
Genentech, a developer of cancer drugs, petitioned the F.D.A. this month to regulate such tests. It warned of “safety risks for patients, as more treatment decisions are based in whole or in part on the claims made by such test makers.”
A cautionary case is Herceptin, a Genentech breast cancer drug that is considered the archetype of personalized medicine because it works only for women whose tumors have a particular genetic characteristic. But now, 10 years after Herceptin reached the market, scientists are finding that the various tests — some approved by the F.D.A., some not — can be inaccurate.
Moreover, doctors do not always conduct the tests or follow the results. The big insurer UnitedHealthcare found in 2005 that 8 percent of the women getting the drug had tested negative for the required genetic characteristic. An additional 4 percent had not been tested at all, or their test results could not be found.
Tamoxifen, the drug Ms. Uslan took, illustrates the promise and current limitations of genetic testing. In 2003, more than 25 years after tamoxifen was introduced, researchers led by Dr. David A. Flockhart at Indiana University School of Medicine figured out that the body coverts tamoxifen into another substance called endoxifen. It is endoxifen that actually exerts the cancer-fighting effect. The conversion is done by an enzyme in the body called CYP2D6, or 2D6 for short.
But variations in people’s 2D6 genes mean the enzymes have different levels of activity. Up to 7 percent of people, depending on their ethnic group, have an inactive enzyme, Dr. Flockhart said, while another 20 to 40 percent have an only modestly active enzyme.
The implications were “scary,” Dr. Flockhart said. Many women were apparently not being protected against cancer’s return because they could not convert tamoxifen to endoxifen.
The economic implications could be just as scary to big pharmaceutical companies.
Tamoxifen, now a generic drug, costs as little as $500 for the typical five-year treatment. But most patients in the United States are currently treated with a newer, much more expensive class of drugs, called aromatase inhibitors, that cost about $18,000 over five years. Those drugs — made by AstraZeneca, Novartis and Pfizer — performed better than tamoxifen in clinical trials before the role of 2D6 was generally understood.
If only women with active 2D6 had been assessed, tamoxifen might have worked as well or better than the newer drugs, according to researchers at the Dana-Farber Cancer Institute in Boston.
But proving these suppositions and having them incorporated into medical practice have not been easy.
The F.D.A., in its meeting this month, said clinical trials were the ideal way to validate a test. But many test developers argue that trials would be too costly and time-consuming, so many tests are validated by reanalyzing patient data from old trials.
In the case of tamoxifen, Dr. Matthew P. Goetz of the Mayo Clinic and colleagues went back to an old trial and used stored tumor samples to test the 2D6 genes of each patient. The researchers reported in 2005 that 32 percent of the women with inactive 2D6 enzyme had relapsed or died within two years, in contrast to only 2 percent of the other women.
But while some subsequent studies have backed those conclusions, two had contradictory results. That leaves many experts hesitant to use the test, which costs about $300.
There are other complications. Dozens of variants of the 2D6 gene exist, and laboratories can differ in their interpretation of test results. And it is not always clear how to act upon the information the test provides.
Ms. Uslan, who lives in the Woodland Hills neighborhood of Los Angeles, is in a predicament since she stopped taking tamoxifen. The newer alternative, aromatase inhibitors, work only for postmenopausal women and she has not yet completed menopause. To take an aromatase inhibitor, she must have her ovaries removed or take a drug to induce menopause. Because both options are unattractive, many experts say there is no point testing premenopausal women for 2D6.
Such complexities are not confined to tamoxifen testing. The labels of about 200 drugs now contain some information relating genes to drug response, said Lawrence J. Lesko, the F.D.A.’s head of clinical pharmacology. But in many cases, he said, doctors are not told specifically enough what to do with the test results, such as how much to change the dose.
Despite all the obstacles, personalized medicine is coming. Even the drug companies, which have been worried that testing would reduce their sales, are starting to realize that their medicines might not be approved or paid for without better evidence that they work.
Last year, for instance, European regulators said Amgen’s colon cancer drug Vectibix did not provide enough benefit to patients to be approved.
So Amgen reanalyzed the data from its clinical trial. After the results showed Vectibix worked better in patients whose tumors did not have a mutation in a gene called KRAS, the drug was approved for those patients only.
As for tamoxifen, an F.D.A. advisory panel recommended two years ago that the 2D6 test be mentioned in the drug’s label.
But the agency itself was not persuaded there was enough evidence until just recently, Dr. Lesko said. “There’s no ‘one size fits all’ for evidence that everybody buys into.”
More Articles in Business » A version of this article appeared in print on December 30, 2008, on page A1 of the New York edition.






Tuesday, December 30, 2008

Cyberknife boost to cancer care

Professor Eric Lartigau is impressed by the technology


The cyberknife minimises damage to healthy tissue



Page last updated at 06:00 GMT, Tuesday, 30 December 2008
Cyberknife boost to cancer care
By Fergus Walsh BBC News medical correspondent
Dr Nick Plowman says the cyberknife can target cancer cells with 'high exactitude'
A robot radiotherapy machine to treat cancer is to be available in the UK for the first time from February.
Called the Cyberknife, it moves with a patient's breathing so tumours can be targeted with greater accuracy, and damage to healthy tissue is reduced.
The machine will be at the private Harley Street Clinic in London.
More than a dozen countries worldwide already use the machine, including France, which has three under clinical trial.
At first sight the Cyberknife looks like one of those robots used in the TV car commercials.
It is a compact linear accelerator mounted on a robot arm.

The cyberknife minimises damage to healthy tissue
The cyberknife works by delivering multiple beams of high dose radiation from a wide variety of angles using a robotic arm.
X-ray cameras monitor the patient's breathing and re-position the radiotherapy beam in order to minimise damage to healthy tissue.
This accuracy enables tumours to be treated that are in difficult or dangerous to treat positions, such as near the spinal cord.
Good results
The French National Cancer Institute has paid for three Cyberknife machines to be trialled at hospitals in Nice, Nancy and Lille.
Professor Eric Lartigau from the Centre Oscar Lambret in Lille said he was very impressed.
He said: "We have treated just over 200 patients in 18 months and all couldn't have been treated with conventional radiotherapy so it is a big plus for our patients."
One of those patients is Helen O'Doherty from Limerick in Ireland.
She has liver cancer and was told by her doctors that conventional treatment, like surgery, was not possible, so she was referred to Lille for radiotherapy with the Cyberknife.

Professor Eric Lartigau is impressed by the technology
The Irish health service is paying for her treatment and she has made several trips to Lille with her husband.
She said: "I feel very privileged and excited to be here because I know it's the best and I'm so grateful to have another chance."
Conventional radiotherapy involves twenty or more short sessions with low-dose radiation.
But because the Cyberknife can deliver high dose beams with greater accuracy, it means Helen can have all her treatment in just three sessions.
Fifteen countries including the USA, Germany, Italy and Japan have the Cyberknife.
It is also installed in hospitals in Vietnam, Turkey and Greece.
In early February, the first Cyberknife in the UK will begin treating patients at the private Harley Street Clinic in London.
Clinical director Dr Nick Plowman, who is also a consultant oncologist at Barts Hospital, does not believe that Britain is lagging behind.
He said: "It is only in the past couple of years that the software has got to the stage where we believe it is right for introduction to our clinical service.
"So we don't believe we have been tardy; we have been waiting for the improvements to come and now they're here we are happy to introduce the machine."
Treatment will cost between £20,000 and £25,000.
Although most will be private, the clinic says it expects to treat some NHS patients.
Dr Plowman is keen to stress that conventional radiotherapy works well for most patients.
But for patients with some hard to treat tumours the Cyberknife will present another potential therapy.


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Cholera deaths soar in Zimbabwe

This is the reality of Zimbabwe’s cholera epidemic, aid workers say. Dehydrated patients lie motionless on makeshift beds. Nurses work day and night with barely any medical supplies.






This clinic had 15 cholera patients, a nearby clinic was said to have 600





The UN has warned the total number of cases could reach 60,000





Page last updated at 11:50 GMT, Monday, 29 December 2008
Cholera deaths soar in Zimbabwe

The UN has warned the total number of cases could reach 60,000
The latest figures from the UN and Zimbabwe's health ministry reveal that two-thirds of the victims of the cholera outbreak have died this month.
The death toll at the end of last week stood at 1,564, with 29,131 suspected cases since August, the UN said.
Figures from the health ministry on 1 December put cholera deaths at 484.
The UN has warned it could take six months to control the outbreak that has been fuelled by the collapse of the health, sanitation and water services.
No food
According to the World Health Organization, cases have been reported in all 10 of Zimbabwe's provinces.
CHOLERA FIGURES SINCE AUGUST
25 December



Deaths: 1,564



Cases: 29,131
1 December



Deaths: 484



Cases: 11, 735
Cases in December 68%
"The overall Case Fatality Rate (CFR) has risen to 5.7% - far above the 1% which is normal in large outbreaks - and in some rural areas it has reached as high as 50%," the WHO said in a statement.
Last Tuesday, Unicef put the number of cholera deaths at 1,174.
Aid agencies say so many clinics and hospitals have closed that large sections of the population have no access to medical care.
The suburb of Budiriro in Harare's capital, has been worst hit by the outbreak, followed by Beitbridge on the border with South Africa.
South Africa has recorded 1,279 cases and 12 deaths - the bulk of these in the border region, the WHO says.
Over the weekend, Save the Children said some five million people in Zimbabwe - or about 50% of the country's population - were now in need of food aid.
President Robert Mugabe has been facing intensified criticism over the dire economic and humanitarian situation in Zimbabwe.
He signed a power-sharing deal with his rival, Morgan Tsvangirai, in September, intended to rescue the collapsing economy but progress has since stalled over who should control key ministries.
Mr Tsvangirai has threatened to pull out of power-sharing talks unless abductions of his supporters stop.
According to his Movement for Democratic Change, about 40 human rights activists and opposition supporters have been abducted in the past two months.
Meanwhile, the US envoy to Africa, Jendayi Frazer, has warned that last week's military coup in Guinea should serve as a warning of what could happen in Zimbabwe, if Mr Mugabe is allowed to cling to power and die in office.

http://news.bbc.co.uk/2/hi/africa/7802943.stm






CHOLERA CRISIS



Blood pressure cases 'to top 1bn'

Last Updated: Thursday, 16 August 2007, 23:16 GMT 00:16 UK
Blood pressure cases 'to top 1bn'

High blood pressure is generally accepted as a reading above 140/80mmHgHigh blood pressure is out of control around the world, with the number of sufferers expected to exceed a billion within 20 years, experts warn.
One in four adults already has the condition, which increases the risk of heart disease, stroke and death.
But unhealthy modern lifestyles mean the toll could hit 1.56 billion by 2025, up from 972 million in 2000, The Lancet medical journal reports.
The biggest problem is poor compliance with treatment, an editorial claims.
Time bomb
Despite very effective and cost-effective treatments, target blood pressure levels are very rarely reached, even in countries where cost of medication is not an issue, says the editorial.
"Many patients still believe that hypertension is a disease that can be cured, and stop or reduce medication when blood pressure levels fall.
"Physicians need to convey the message that hypertension is the first, and easily measurable, irreversible sign that many organs in the body are under attack.
"Perhaps this message will make people think more carefully about the consequences of an unhealthy lifestyle and give preventative measures a real chance," it says.
High blood pressure is a ticking time bomb and should be taken seriously
Professor Gareth Beevers of the Blood Pressure Association
Currently, a person in the Western world has a greater than 90% lifetime risk of developing high blood pressure or hypertension.
But lifestyle factors, such as physical inactivity, a salt-rich diet with high processed and fatty foods, and alcohol and tobacco use, mean the problem is spreading at an alarming rate from developed countries to emerging economies, such as India and China, says The Lancet.
Professor Gareth Beevers of the Blood Pressure Association said: "This shows that high blood pressure is a ticking time bomb and should be taken seriously.
"This is preventable, if people of all ages start looking at their lifestyles and start taking the right action to reduce their risk."
Prevention
Dr Isabel Lee, of The Stroke Association, said: "Every five minutes someone in the UK has a stroke - that's 150,000 every year. Yet, over 40% of these strokes could be prevented by the control of high blood pressure.
"Whilst it is important to get your blood pressure measured regularly, it is equally important that people who are prescribed blood pressure medication continue to take it even once their blood pressure is back under control.
"GPs need to ensure that patients are made fully aware of the importance of continuing with their blood pressure medication."
People can also take additional steps to help improve their lifestyles and reduce their risk of high blood pressure by stopping smoking, having a healthy diet and exercising regularly, she said.
A British Heart Foundation spokeswoman said high blood pressure often remained undiagnosed until a person encountered something as serious, and potentially fatal, as a heart attack or stroke.
"That's why it's vital that people know what their blood pressure is and how they can reduce it if it is high.
"Everyone over 40 years of age should talk to their GP or practice nurse about having a full risk assessment for heart and circulatory disease carried out."

http://news.bbc.co.uk/2/hi/health/6949526.stm

Blood pressure 'link to dementia'

High blood pressure can be a warning of ill health


Blood pressure 'link to dementia'

High blood pressure can be a warning of ill health
Controlling blood pressure from middle-age onwards may dramatically reduce the chances of developing dementia, researchers have said.
Two studies support a link between high blood pressure and dementia risk - with one by an Imperial College London team suggesting treatment could cut this.
This study, by published in the Lancet Neurology journal, found blood pressure drugs reduce dementia by 13%.
The Alzheimer's Society said better control could save 15,000 lives a year.
Only half of people over 65 receive effective treatment, yet we know treatment works
Professor Clive BallardAlzheimer's Society
As many as one in four people has high blood pressure, in many cases undiagnosed or untreated.
The precise reasons why high blood pressure might increase the risk of dementia are not fully understood although many scientists believe that it can starve the brain of bloodflow and the oxygen it carries.
Patients suffering this restricted bloodflow are often described as having "vascular dementia", and account for approximately a quarter of dementia patients.
Other types of dementia, such as Alzheimer's disease, have no obvious link to bloodflow, but some experts think that blood pressure may still be somehow contributory in some cases.
The Lancet Neurology study looked at a trial of elderly patients with high blood pressure to see if those who were receiving treatment were less likely to develop any form of dementia compared with those left untreated.
Clear benefit
The trial was stopped early after the benefits of treatment in terms of reducing strokes and heart disease were so obvious it became unethical to deny them to everyone.
Although this meant that no benefits in terms of dementia could be found, when these results were combined with other similar studies in different age groups, the incidence of dementia was 13% lower in the treated groups.
Dr Ingmar Skoog, from the Institute of Neurosciences at Sweden's Goteburg University, said that the need to treat high blood pressure, reducing heart attacks and strokes, was clear, even without the additional results on dementia.
Rebecca Wood, from the Alzheimer's Research Trust, said the finding was an "exciting development", which, if repeated, could offer hope to the 700,000 people in the UK with dementia.
Healthy living
The Alzheimer's Society, however, stressed the need to try to prevent the disease.
Its own unpublished research suggested that vascular dementia was six times more likely to develop in people who had high blood pressure in their 40s and 50s.
If "best practice" in blood pressure treatment was applied to the UK population, it said, with every case detected and treated appropriately, this would save 15,000 lives a year.
Professor Clive Ballard, its director of research, said: "Only half of people over 65 receive effective treatment, yet we know treatment works."
The charity's chief executive, Neil Hunt, urged everyone, even those in middle age, to have regular blood pressure and cholesterol checks.

Drug adherence poor in women with urinary trouble

Drug adherence poor in women with urinary trouble

Thu Dec 25, 4:32 pm ET
NEW YORK (Reuters Health) – The odds are high that a woman who is prescribed an "anticholinergic" drug to relieve urinary incontinence or other lower urinary tract symptom will discontinue the medication not long after starting it, a study suggests. This is true regardless of the class of medication used.
Two examples of anticholinergic drugs that are often prescribed for urinary incontinence are oxybutynin (Ditropan) and tolterodine (Detrol).
"Our high discontinuation rates across all anticholinergic drug classes...highlight the need for more effective therapies for lower urinary tract symptoms," Dr. Manish Gopal from Saint Peter's University Hospital, New Brunswick, New Jersey and colleagues conclude.
Using a large database, Gopal and colleagues analyzed 29,369 women aged 18 and older who were initially prescribed an anticholinergic medication, such as Ditropan or Detrol, between 1991 and 2005.
They found that half of women prescribed an anticholinergic stopped taking it by 6 months, and 3 out of 4 women discontinued therapy by 1 year. The median time to discontinuation for all 9 different anticholinergic drugs was about 4 months after initial use.
In a report in the journal Obstetrics and Gynecology, the investigators note that rates of discontinuation increased with duration of use, and "very few women" switched to another drug after initial prescribed treatment before stopping the drug.
Because of the high discontinuation rates of anticholinergic therapy for lower urinary tract symptoms, health care providers "must be vigilant" regarding alternative forms of treatment, such as bladder training and pelvic floor rehabilitation, for overactive bladder "and increase our awareness that this group of women is being treated inadequately," the investigators conclude.
SOURCE: Obstetrics and Gynecology, December 2008.

http://news.yahoo.com/s/nm/20081225/hl_nm/us_drug_adherence_poor_women_with_urinary_tr;_ylt=Aq.VdxUGMew7lCQNa4w0qE7VJRIF
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Teens may not know risk factors for infertility

Teens may not know risk factors for infertility

By Joene Hendry Joene Hendry – Mon Dec 29, 5:17 pm ET
NEW YORK (Reuters Health) – Canadian high school students may lack important knowledge about risk factors for infertility, survey findings suggest. For example, most students were unaware that some sexually transmitted infections can cause infertility.
"About 80 percent of students said they were familiar with the term infertility," Susan Quach, of Sunnybrook and Women's College Hospital Fertility Center in Toronto, told Reuters Health. But when asked more specific infertility-related questions, fewer students answered correctly, indicating a lack of knowledge that may increase their risk of infertility later in life, Quash said.
For example, more than 94 percent of the students did not know that sexually transmitted infections, such as chlamydia or gonorrhea can lead to infertility, Quash and co-investigator Dr. Clifford Librach at the University of Toronto report in the journal Fertility and Sterility.
The researchers asked 772 ethnically diverse high school students to complete a written questionnaire designed to determine their knowledge of and attitudes about infertility. The students were 17.5 years old, on average, and 49 percent were female.
A total of 608 students completed the questionnaire and, as noted, the vast majority did not know that chlamydia and gonorrhea can lead to infertility. About 25 percent thought fertility problems only occurred among women 40 years or older.
The researchers found that students from schools with low socioeconomic status more frequently gave incorrect answers and were significantly less aware of associations between sexually transmitted diseases and infertility.
Overall, about 73 percent of female and 67 percent of male respondents said protecting their fertility was important to them. Most also reported that their fertility was important to them. Fifty-five percent of the students said they were open to screening for sexually transmitted diseases as a means of protecting their fertility.
These findings highlight the importance of educating young people about modifiable risk factors for infertility, such as body fat, smoking, caffeine consumption, excessive exercise, drug use, and sexually transmitted infections, Quash and Librach note.
To assist the development of targeted and appropriate infertility prevention education, the investigators suggest that further infertility knowledge assessments should be conducted among students in rural or less ethnically diverse schools.
SOURCE: Fertility and Sterility, December 2008.

http://news.yahoo.com/s/nm/20081229/hl_nm/us_teens_infertility;_ylt=Av6RSFbKb2vXMM8Yv3WKGejVJRIF
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