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History > 2006 > USA > Health (III)

F.D.A. Says Bayer Failed

to Reveal Drug Risk Study

September 30, 2006
The New York Times
By GARDINER HARRIS

WASHINGTON, Sept. 29 — Bayer A.G., the German pharmaceutical giant, failed to reveal to federal drug officials the results of a large study suggesting that a widely used heart-surgery medicine might increase the risks of death and stroke, the Food and Drug Administration announced Friday.

Bayer scientists even appeared at a public meeting called by the F.D.A. on Sept. 21 to discuss the possibility that the drug, Trasylol, might have serious risks. But they did not mention the study or its worrisome results.

In a highly unusual move, the food and drug agency released a public health advisory saying it had learned of the study’s existence only on Wednesday. Preliminary results of the study demonstrate “that use of Trasylol may increase the chance for death, serious kidney damage, congestive heart failure and strokes,” the advisory said.

Nevertheless, the agency did not change its advice about whether patients should be given the drug. Instead, it restated previous warnings that Trasylol’s use should be limited to patients in whom the risks of blood loss outweighed the drug’s risks.

The disclosure comes exactly two years after Merck announced it was withdrawing its arthritis drug, Vioxx, after a study showed that it doubled the risks of heart attacks. Since then, members of Congress and even top scientific advisers have concluded that the F.D.A. lacks the regulatory authority and the money needed to detect and protect against drug dangers.

Drug companies have also been sharply criticized for failing to make public the results of some human trials of their drugs that suggest that the drugs are either ineffective or dangerous. Some lawmakers have proposed legislation that would require that nearly all human drug trials must be announced and their results disclosed publicly.

A top F.D.A. official said the agency learned of the Trasylol study on Wednesday only after a getting a tip from a researcher involved in it. The official insisted on anonymity because of the sensitive nature of the information.

In a written statement, Bayer said “that it mistakenly did not inform” the F.D.A. of the study and added, “This data was not shared immediately with the agency because it was preliminary in nature.”

Staci Gouveia, a Bayer spokeswoman, said the company nonetheless stood behind the safety of Trasylol, which has become one of Bayer’s fastest sellers. Sales last year were $200 million and were expected to nearly triple this year.

Several members of the advisory committee that met last week said they were shocked that Bayer failed to inform them of the study.

“For them not to mention that it was under way, that it was being analyzed or that results were available is appalling and will do significant harm to their reputation for transparency,” said Dr. John Teerlink, an associate professor of medicine at the University of California, San Francisco, and a member of the advisory committee.

Steven Findlay, a health care analyst at Consumers Union and another committee member, said the agency needed to investigate whether Bayer knowingly withheld the information from the advisory committee.

“The safety of this drug is called into further question now,” Mr. Findlay said.

Doctors give Trasylol to patients before surgery to reduce the risks of blood loss. It can also reduce the need for transfusions in patients undergoing heart bypass surgery. Trasylol, also known as aprotinin, has been on the market for 13 years.

But two recent studies suggested that the drug might have serious risks. One of the articles, published in January in The New England Journal of Medicine, found that the drug increases the risks of kidney failure, heart attack and stroke. The study concluded that halting the drug’s use would prevent 10,000 to 11,000 cases of kidney failure a year and save more than $1 billion a year in dialysis costs, as well as nearly $250 million spent on the drug itself.

There are other, cheaper drugs that can be used in Trasylol’s place.

Still, the advisory panel concluded that Trasylol’s risks were worth taking in some patients. Dr. Teerlink said that despite the results of the new study, that might still be true.

Bayer’s study was performed by a contract research organization. But Bayer did not inform the F.D.A. that the study was being done, even though that is routine practice.

It examined hospital records of 67,000 patients, 30,000 of whom received Trasylol. The rest got other drugs. It concluded that the patients given Trasylol were at greater risk.

Such studies, however, are fraught with statistical and other problems. Patients given Trasylol may have been sicker than those given other drugs. Their worse outcomes would be explained not by problems with Trasylol but by their own illness.

Susan Bro, an F.D.A. spokeswoman, said it was evaluating the new study and would decide soon whether the results merit changing the agency’s advice about use of the drug.

“It is regrettable that the F.D.A. advisory board did not have the benefit of a frank scientific dialogue based on the totality of available data,” she said.

Senator Charles E. Grassley, Republican of Iowa and chairman of the Senate Finance Committee and a longtime critic of the F.D.A., said Bayer’s behavior proved that the agency was largely toothless.

“The remedy is mandatory reporting of all clinical trials and real teeth for the F.D.A. to do its job in holding drug companies accountable,” Mr. Grassley said.

F.D.A. Says Bayer Failed to Reveal Drug Risk Study, NYT, 30.9.2006, http://www.nytimes.com/2006/09/30/health/30fda.html

Economix

The Choice: A Longer Life or More Stuff

September 27, 2006
The New York Times
By DAVID LEONHARDT

The most authoritative report on the cost of health insurance came out yesterday, and it’s sure to cause some new outrage.

The average cost of a family insurance plan that Americans get through their jobs has risen another 7.7 percent this year, to $11,500, according to the Kaiser Family Foundation. In only seven years, the cost has doubled, while incomes and company revenue, which pay for health insurance, haven’t risen nearly as much.

These spiraling costs — a phrase that has virtually become a prefix for the words “health care” — are slowly creating a crisis. Many executives have decided that they cannot afford to keep insuring their workers, and the portion of Americans without coverage has jumped 23 percent since 1987.

An industry that once defined the American economy, meanwhile, is sinking in large measure because of the cost of caring for its workers and retirees. For every vehicle that General Motors sells, fully $1,500 of the purchase price goes to pay for medical care. “We must all do more to cut costs,” G.M.’s chief executive, Rick Wagoner, said on Capitol Hill this summer while testifying about health care.

Mr. Wagoner’s argument has become the accepted wisdom about the crisis: the solution lies in restraining costs. Yet it’s wrong. Living in a society that spends a lot of money on medical care creates real problems, but it also has something in common with getting old. It’s better than the alternative.

To understand why, it helps to look back to a time when Americans didn’t worry much about health care costs. In 1950, the country spent less than $100 a year — or $500 in today’s dollars — on the average person’s medical care, compared with almost $6,000 now, notes David M. Cutler, an economist who wrote a wonderful little book in 2004 titled, “Your Money or Your Life.”

Most families in the 1950’s paid their medical bills with ease, but they also didn’t expect much in return. After a century of basic health improvements like indoor plumbing and penicillin, many experts thought that human beings were approaching the limits of longevity. “Modern medicine has little to offer for the prevention or treatment of chronic and degenerative diseases,” the biologist René Dubos wrote in the 1960’s.

But then doctors figured out that high blood pressure and high cholesterol caused heart attacks, and they developed new treatments. Oncologists learned how to attack leukemia, enabling most children who receive a diagnosis of it today to triumph over a disease that was almost inevitably fatal a half-century ago. In the last few years, orphan drugs that combat rare diseases and medical devices like the implantable defibrillator have extended lives. Human longevity still hasn’t hit the wall that was feared 50 years ago.

Instead, a baby born in the United States this year will live to age 78 on average, a decade longer than the average baby born in 1950. People who have already made it to their 40’s can now expect to reach age 80. These gains are probably bigger than the ones the British experienced in the entire millennium leading up to 1800. If you think about this as the return on the investments in medicine, the payoff has been fabulous: Would you prefer spending an extra $5,500 on health care every year — or losing 10 years off your lifespan?

Yet we often imagine that the costs and benefits are unrelated, that we can somehow have 2006 health care at 1950 (or even 1999) prices. We think of health care as if it were gasoline, a product whose price and quality have nothing to do with each other.

There is no question that the American medical system does suffer from a lot of waste, be it insurance industry bureaucracy or expensive procedures that haven’t been proven effective. But the No. 1 cause of the cost increases is still the one you can see at the hospital and in your medicine cabinet — defibrillators, chemotherapy, cholesterol drugs, neonatal care and other treatments that are both expensive and effective.

Not even most forms of preventive care, like keeping diabetes under control, usually save money, despite what many people think. The care itself has some costs, and, more important, patients then live longer than they otherwise would have and rack up medical bills. “When I make this point, people accuse me of wanting people to die earlier. But it’s exactly the opposite,” Dr. Jay Bhattacharya, a researcher at Stanford Medical School, told me. “If these expenditures are keeping people alive, it’s money well spent.”

As Dr. Mark R. Chassin of the Mount Sinai School of Medicine in New York says, “You almost always spend money to gain health.” Of course, the opposite is also true: the best way to reduce health care spending is to reduce health care itself.

Which is exactly what we’re starting to do. The growing number of families without health insurance are, in effect, families who have been kicked off the country’s health care rolls. Many will go without available treatment, will get sicker than they need to get — and will thereby save the rest of us money. They are what now passes for a solution to the health care mess.

The current situation is indeed unsustainable, a point that the conventional wisdom has right. The cost of health insurance can’t keep doubling every seven years, and wasteful spending — the brand-name drugs that are no better than generics, the treatments that haven’t been proved to extend lives or improve health — does need to be reined in.

But far too much of the discussion has been centered on this narrow idea. Somehow, going to the mall to buy clothes has come to be seen as a vaguely patriotic way to keep the economy humming, and taking out a risky mortgage is considered to be an investment in one’s future. But medical care? That’s just a cost.

It’s easy to be against high costs, and it will no doubt be hard to come up with a broad health care solution. But the way to start is by acknowledging that an affluent society should devote an ever-growing share of its resources to the health of its citizens. “We have enough of the basics in life,” Mr. Cutler, the economist and author, points out. “What we really want are the time and the quality of life to enjoy them.”

The Choice: A Longer Life or More Stuff, NYT, 28.9.2006, http://www.nytimes.com/2006/09/27/business/27leonhardt.html

Life Expectancy Data

September 27, 2006
The New York Times
By DAVID LEONHARDT

For most of human history, the average lifespan was considerably less than 50 years. It began to rise markedly in the 19th century, hitting 49 in the United States in 1900, and then took off in the 20th century.

“Life expectancy increased only very slowly for two millennia,” said Richard Suzman, director of the Social and Behavioral Research Program at the National Institute on Aging, “and then almost doubled since 1800.”

Today, the average baby born in this country will live to 78. The average 35 year old will live to about 80. And the average 65 year old will live past 83.

For detailed data going back to 1900, click here and then go to Table 11, which appears on page 30 of the document.

Life Expectancy Data, NYT, 28.9.2006, http://www.nytimes.com/2006/09/27/business/27leonhardt_sidebar.html

Best cardiac care

found in wealthiest areas,

GNS analysis shows

Updated 9/27/2006 10:42 PM ET
By Robert Benincasa and Jennifer Brooks,
Gannett News Service
USA Today

WASHINGTON — Heart patients in wealthier communities have a better chance of getting recommended treatments at their local hospitals than patients in lower-income areas.

A Gannett News Service analysis of how frequently U.S. hospitals gave recommended treatments to those suffering from heart attacks and heart failure found that the best-performing hospitals are much more concentrated in the nation's higher-income counties.

In low-income counties, top-performing hospitals are scarce. In counties ranking in the lowest 20% for median household income, only 5% of the hospitals were in the highest of five performance rankings for heart attack patients. Nearly half of them fell into the lowest category.

In high-income counties, a quarter of the hospitals were top performers.

"Hospitals serving poor populations have very limited resources, and they simply cannot provide the high-quality care delivered in your mainstream hospitals," said Dr. Ernest Moy, who leads the team that writes the federal government's National health care Disparities Report.

Moy said the GNS findings are consistent with other disparities researchers have documented in American health care. "In almost everything we track, there's a very large socioeconomic effect, and it's as large or larger than the racial or ethnic effect," he said.

The most recent report from Moy's group looked at 13 key measures of health care quality and found poor people got lower quality care than high-income people on 11 of them.

Using data provided by hospitals to the federal Centers for Medicare and Medicaid Services and covering the period of October 2004 through September 2005, GNS rated the nation's hospitals on heart care. The ratings show how often they gave standard treatments to heart attack and heart failure patients who were supposed to get them.

Treatments included giving heart attack patients aspirin, which reduces the tendency of blood to clot, and beta-blocker drugs, which reduce the stress on the heart.

Based on how hospitals ranked in comparison to other hospitals, GNS awarded them from one to five stars for heart attack and heart failure treatments, both nationally and within their states. Hospitals with very few heart patients weren't included. Some 3,100 U.S. hospitals, or about three-quarters of those in a federal government database, received GNS heart attack ratings, and 3,600 received heart failure ratings.

The heart treatment data come from a government and industry consortium aimed at measuring and improving hospital quality. The group chose heart measures among its first indicators because heart attacks and heart failure are common, serious problems that are relatively easy to track. Hospitals around the country have improved on the indicators since the consortium began systematically collecting and publishing the data.

In 2006, an estimated 1.2 million Americans will have a heart attack, and heart disease will kill more U.S. adults than any other single cause.

Other indicators of quality

In addition to the household income of a hospital's home county, there were other powerful indicators associated with hospital performance. Among them:

- Medical school affiliation. This made a dramatic difference in following guidelines, particularly for heart attack patients. Among larger teaching hospitals, those with 500 beds or more, more than a third earned top ratings for heart attack treatments. Very few of those facilities — 3% — were in the lowest performance category.

Advocates for teaching hospitals say the variety of specialized personnel and educational emphasis adds up to more attention to patients and more cutting edge science.

- Urban vs. rural. Only about one in nine rural hospitals fell into the top-scoring category for treating heart attack patients. More than a third were in the lowest category. Urban hospitals were unlikely to be in the lowest category, with about 13%. For heart failure patients, nearly a third of rural hospitals fell into the lowest performance category.

The reason is likely linked to the disadvantages rural hospitals may face when trying to improve quality: limited resources, small staffs, low patient volume and lagging information technology. Rural hospitals also face shortages of specialty doctors and other providers, according to the National Advisory Committee on Rural Health and Human Services.

- Geography. On average, hospitals in Southern states provided standard treatments for heart attack patients about 87% of the time. In other regions, the average was more than 90%. Western states lagged in standard treatments for heart failure patients, with a 67% average rate, below a national average of 72%.

- Accreditation. Nearly half of the hospitals without a current accreditation from the Joint Commission on Accreditation of health care Organizations were bottom-tier performers for heart failure patients. For treating heart attacks, 40% were bottom-tier performers.

- Ownership type. Government-owned and for-profit hospitals generally performed poorly in comparison to hospitals with other ownership arrangements. Church-owned facilities performed well for both types of heart patients studied.

Public hospitals tend to get less revenue from their patients, many of whom are uninsured. And with typically small operating margins, they may find it harder to fund quality improvement programs and computer systems.

"They're always going to be stretched thin," said Dr. Benjamin Chu, a former head of New York City's public hospital corporation who is credited with improving quality there.

Making an informed choice

Kim Miller, a 48-year-old single mom and businesswoman, thought through her hospital choice, despite being in the throes of an attack.

Doubled over with chest pains and nausea — symptoms of a heart attack — Miller had two hospitals to choose from in her hometown of Poughkeepsie, N.Y., one night in December 2003, as she telephoned a friend for a ride to the emergency room.

One of the hospitals, Vassar Brothers, is the city's heart center and performs cardiac surgery.

"I knew that Vassar has the cardiac center," said Miller, who directed her friend to drive her to that hospital, rather than the emergency room at St. Francis Hospital.

In 2004-05, Vassar Brothers performed above the state and national medians for providing correct care to heart attack patients, and earned five stars in the GNS analysis for landing in the top category nationally and within New York state.

The other hospital, St. Francis, performed below the medians and earned one star.

Miller is happy about her choice and the treatment she received at Vassar Brothers. But St. Francis President and CEO Bob Savage said it wouldn't have made a difference if she had chosen his hospital instead.

"All hospitals really can treat an acute myocardial infarction, a heart attack. The difference in Vassar Brothers and St. Francis at this point is they do have the cardiac catheterization lab, and cardiac catheterization is the ultimate diagnostic tool."

With catheterization, doctors thread a thin tube into the heart through an intravenous line, and use it to check heart functions.

Savage said the hospital's scores were low because of a charting problem. "Basically we were not doing a good job of documenting exclusions," he said. "There really are reasons why some people should not receive aspirin or beta blockers."

The next batch of numbers on heart treatments, Savage said, will be much improved, reflecting better documentation as well as an improvement in care.

Still, says disparities researcher Moy, "The average consumer should look at how their local hospital is doing and consider going to another hospital if their hospital is in the bottom (group)."

Best cardiac care found in wealthiest areas, GNS analysis shows, UT, 27.9.2006, http://www.usatoday.com/news/health/2006-09-27-hospitals-analysis-main_x.htm

The Last Holdout

Reconsiders a Program to Curb H.I.V.

September 25, 2006
The New York Times
By RICHARD G. JONES

CAMDEN, N.J., Sept. 21 — On most days, the fringe workers in this city’s stunningly vibrant drug trade shout and gesticulate from street corners like hot dog vendors at a ballpark, hawking hypodermic needles they claim are clean.

“Works for sale! Works for sale!”

But the shouting stopped at one corner recently after one of those dealers died of a drug overdose. For his loyal customers, it was a disaster, however briefly.

“It was a drought of works,” said Maria Lugo, 26, who said that she injects heroin eight times a day. “People were picking up old needles off the street. They didn’t care. They just wanted to get off.”

That mix of apathy and addiction has led to what health officials say is a public health crisis in New Jersey, where state figures show that more than 4 in 10 cases of H.I.V. infection result from injecting illegal drugs with contaminated needles. Even so, New Jersey remains the one state that prohibits the distribution of hypodermic needles in government-sanctioned programs.

That may soon change. In a reversal that even supporters acknowledge would have been unexpected as recently as six months ago, lawmakers may well pass a bill soon to allow needle exchanges in New Jersey.

The legislation, to be considered this week, appears finally to have enough support to win passage, 14 years after it was first introduced, and Gov. Jon S. Corzine has said he would sign it.

To supporters, the bill is long overdue, and the Legislature’s refusal to approve it has contributed to the deaths of an untold number of drug users.

To opponents, including State Senator Thomas H. Kean Jr., the Republican nominee for the United States Senate, the measure would mean nothing less than a government endorsement of illegal drug use.

One of the bill’s most vocal critics, State Senator Ronald L. Rice, a former Newark police officer who represents a district in Essex County, has compared legal needle exchanges to the notorious Tuskegee Syphilis Study, an experiment in Alabama from 1932 until 1972 in which proper treatment was withheld from African-Americans infected with venereal disease.

Mr. Rice has argued that exchange programs contribute to a cycle of social and economic inertia for minorities and the poor.

A better use of state money, he says, would be to create more programs providing drug education and treatment.

“Those who want a syringe access program are saying that it’s O.K. for drug users to continue using drugs and kill themselves because it’s cheaper for the government,” he said.

It was Mr. Rice, a Democrat, who negotiated an alliance with the Republican minority in the Senate to prevent the needle exchange bill from getting out of committee as recently as last spring.

But last Monday, committee members reached a compromise that would allow pilot needle exchange programs in six cities. The program would be re-evaluated in five years under the bill, which would also provide $10 million for drug treatment programs.

State Senator Nia H. Gill, a Democrat from Essex County who sponsored the original legislation, cited statistics that show New Jersey is the state with the third-highest rate of H.I.V. infection among children, and the highest rate among women.

Nearly 33,000 residents of New Jersey have AIDS, according to state health officials, and, in a statement, Ms. Gill noted that almost as many — about 30,000 — have died of the disease.

“If there were any other cause of hundreds of deaths of children, thousands of deaths of women and the orphaning of tens of thousands of children — our Legislature would act on an emergency basis to reduce that cause,” she said.

To those who see the consequences of the drug trade in neighborhoods like South Camden, an exchange program cannot come too soon.

Several times a week, Jose Quann and Johnny Brown, workers with the Camden Area Health Education Center, drive a modified recreational vehicle through some of the bleakest parts of the city to do street-level prevention and education concerning H.I.V. and AIDS.

They hand out free condoms to prostitutes. They give intravenous-drug users bleach kits to sterilize syringes. And they offer health services like free blood pressure screenings and new oral H.I.V. tests that yield results in 20 minutes.

Bouncing over the uneven asphalt along Broadway in South Camden the other day, Mr. Brown, a burly 51-year-old, said that he did not believe free needles would encourage drug abuse.

“When they take part in needle exchange, it means they’re starting to take an interest in their health,” Mr. Brown said. “That’s the first step.”

Mr. Quann, 46, agreed. “It’s a win-win for everybody,” he said. “Right now, they’re disposing of these things in our back alleys, in our playground where our kids are getting pricked.”

Although the six cities in the proposed pilot program have not been chosen, both men hope that Camden, whose 75,000 residents, according to city figures, include an estimated 800 people with H.I.V. or AIDS, will be one of them.

So did a half-dozen visitors to their bus.

One of them, a 30-year-old prostitute who said her first name was Summer, sneered at the idea that providing free needles would promote drug use.

“Users are going to use anyway,” she said. “But you’d have less people infected with H.I.V., hepatitis.”

The Last Holdout Reconsiders a Program to Curb H.I.V., NYT, 25.9.2006, http://www.nytimes.com/2006/09/25/nyregion/25needles.html

Lung Patients See a New Era of Transplants

NYT 24.9.2006

http://www.nytimes.com/2006/09/24/health/24lung.html

Lung Patients

See a New Era of Transplants

September 24, 2006
The New York Times
By DENISE GRADY

A quiet revolution in the world of lung transplants is saving the lives of people who, just two years ago, would have died on the waiting list.

In the past 16 months, waits have shortened, lists have shrunk, and the number of lung transplants has gone up. Further improvements are expected this year.

The changes have all but erased the need for transplants from live donors — desperate, last-ditch operations requiring two donors per patient, usually relatives and friends who risk major surgery in hopes of rescuing a loved one whose time is running out.

“It’s almost as if it’s a whole new day for lung transplantation,” said Dr. Cynthia Herrington, a surgeon at the University of Minnesota Medical Center, Fairview, in Minneapolis. “It’s amazing.”

Nationwide, it is too soon to tell what the impact of the transplant changes will be.

“Are we actually improving overall survival?” asked Dr. Selim Arcasoy, the medical program director for lung transplantation at New York-Presbyterian Hospital/Columbia University. “Or are we transplanting sicker people who don’t last as long?”

Transplants are given to people whose lungs fail because of emphysema, cystic fibrosis or other, less common diseases. Since demand exceeds supply, patients must join regional waiting lists that are part of a national network.

Recent changes have revitalized lung transplantation. Starting in May 2005, new rules nationwide put patients who needed transplants most at the top of the list — people who would soon die without a transplant, but who had a good chance of surviving after one.

Previously, lungs went to whoever had been waiting longest, even if another patient needed them more. The waiting time was often two years or more, so there was little hope for people with lung diseases that came on suddenly or progressed rapidly.

Another major change is that more lungs from cadavers have become available, for two reasons: more people are becoming organ donors, and doctors have figured out ways to salvage lungs that previously would have been considered unusable. The new methods use drugs, respirator settings and other techniques to prevent damage to the lungs and keep their tiny air sacs open in brain-dead patients.

In the past, lungs could be retrieved from only about 15 percent of organ donors, but at some centers the rates have risen to 40 percent. Dr. Herrington said that in Minnesota, the number of lungs retrieved went to 97 from 25 in a single year.

“Good organs 5 or 10 years ago were probably being buried” because doctors did not know how to save them, said Dr. Kenneth R. McCurry, director of heart and lung transplantation at the University of Pittsburgh.

The number of lung transplants has risen to 1,405 in 2005, 248 more than the year before. Fewer people are dying on the waiting list: 360 in 2005, down from 488 in 2004.

The new rules made the difference between life and death for Hannah Olson, 20, a college student from Waukon, Iowa, with cystic fibrosis, a genetic disease that affects the lungs and digestive system. Ms. Olson was well enough to start college in 2004, but by January 2006, she was on the transplant list. Her status, though, was not yet listed as “active,” because her condition seemed stable and she needed to gain weight.

But in mid-February her lungs gave out. Unable to breathe, Ms. Olson was put on a respirator, and her waiting list status changed to active. Without a transplant, she probably would have died within days. Her desperate condition translated into a numerical score that shot her to the top of the list. Twelve hours later, lungs became available, and she received her transplant at the Fairview center in Minneapolis, one day after being put on the active list.

“I’d probably be gone if the list was the way it was before,” Ms. Olson said.

Her surgeon, Dr. Herrington, agreed, saying, “In the old system she would not have even been listed, because she would have had years to wait.”

Ms. Olson is back in college now, hoping to earn a degree in social work. “I’d kind of like to work with transplant patients,” she said.

Lungs have always been “the bad stepchild” of organ transplants — harder to get, harder to transplant, more prone to rejection and complications than other organs, said Dr. Scott Palmer, the medical director of Duke University’s lung transplant program. Lung transplants were not consistently successful until the mid-1980’s, lagging far behind those of kidneys, livers and hearts. From the start, lungs have been offered first to whoever had spent the most time on the waiting list, in the donor’s geographic region.

Changes in the system came about partly because of a 1998 federal regulation requiring that all organ transplants go to patients with the greatest medical need. The intention was to even out waiting times around the country and decrease deaths on the waiting list. Changes have been gradual.

Livers and hearts are already allocated according to patients’ needs. Kidneys still depend on waiting time, but the rules may change to factor in patients’ odds for survival, according to Annie Moore, a spokeswoman for the United Network for Organ Sharing, or UNOS, the nonprofit organization that manages the transplant network in the United States.

For lungs, figuring out how to measure medical need and rank patients with different diseases took time.

“Our concern was that if we used just severity of illness, we might waste a lot of lungs on patients who were so sick they were unlikely to survive anyway,” said Dr. Thomas Egan, a cardiothoracic surgeon at the University of North Carolina, Chapel Hill, who led a UNOS panel that spent several years developing new rules for lung allocation.

The panel studied medical records to figure out which patients were most or least likely to survive after a transplant, and worked that into the scoring system. As a result, lungs are now the only organs with transplant rules that consider the recipient’s survival odds.

Almost immediately, the new system cut the waiting list in half. Because waiting time no longer mattered, people who had been listed early in their illness just to hold a place in line dropped in rank or were deleted (unless they needed a transplant right away) but could rejoin the list later if they became sicker.

Overnight, some patients who had waited for years to reach the top of the list suddenly found themselves at the bottom, or even crossed off. Nobody was grandfathered in.

“We tried our best to educate and communicate, but many felt they had been cheated,” Dr. McCurry said. But at his center in Pittsburgh there were no deaths among those who lost their places in line, he said, adding that many still received transplants.

Those who remained on the list needed transplants soon. As a result, it became much easier to find recipients quickly, which was a huge improvement, because once an organ donor is brain dead, organs start to deteriorate. The lungs are especially fragile.

In the past, transplant coordinators might have spent hours calling hospitals, only to hear again and again that the patient at the top of the lung list was not sick enough for a transplant. Meanwhile the clock would be ticking; patients would have been found who needed the heart, kidneys and liver; and surgeons would be standing by, ready to remove them. Doctors say some lungs were probably wasted because recipients simply could not be found fast enough.

“Placement is easier now,” Dr. Egan said. “It takes four or five calls. It used to be 16.”

The new system has also changed the types of patients who receive the most transplants. Before, a majority had emphysema, a lung disease nearly always brought on by smoking. They received transplants because the disease moves slowly and they could wait, outlasting patients — often younger ones — with other lung diseases.

“People with pulmonary fibrosis or pulmonary hypertension can be diagnosed and go downhill very, very rapidly,” said Dr. G. Alexander Patterson, a surgeon at Washington University in St. Louis, which has one of the country’s largest lung transplant programs, with about 55 to 60 adult patients and 25 to 30 children a year.

Pulmonary fibrosis causes extensive lung scarring, and its cause is often unknown. Patients can die within a year of the diagnosis. But patients with emphysema can often live for a long time. As a result, Dr. Patterson said, many people thought the old system gave an unfair advantage to emphysema patients.

On the waiting list, 5 to 10 percent with emphysema died each year, compared with 30 to 40 percent among those with cystic fibrosis or pulmonary fibrosis.

“It was an ethical dilemma,” Dr. Patterson said, adding that some doctors were troubled to see so many transplants go to people with emphysema, which is caused by smoking, whereas “others have disease they didn’t produce.”

Now, at most centers, more patients with pulmonary fibrosis are getting transplants.

Dr. Jonathan B. Orens, medical director of the lung transplant program at Johns Hopkins, said that in the past year, more than half the 28 recipients there were people who, under the old system, would have died on the waiting list.

Dr. Orens said he and his colleagues had just performed a preliminary analysis of the nationwide data on the first patients treated under the new system, and found that so far, one-year survival rates appeared to have dropped, to about 70 percent, from about 80 percent over all.

“At first blush, that may seem like a bad thing,” he said. But, he said, it may mean that the new system is doing exactly what was intended: giving transplants to the patients who need them most, rather than to people who do not need them yet.

Past survival rates might have been higher because the recipients were healthier. But a transplant might not have prolonged those patients’ lives because they might have survived just as long without it. Sicker patients may not live as long as others after a transplant but may still live longer than they would have without it.

“You get only a limited longevity from a lung transplant,” Dr. Orens said. “In the old system, the average survival was a little under five years.”

Earlier studies suggested that although people with emphysema might have felt better after transplants, they did not necessarily gain time, whereas those with pulmonary fibrosis or cystic fibrosis did. That finding means that the emphysema patients may have been getting transplants too soon, Dr. Orens said.

“This is important,” he said. “If you transplant patients prematurely, you may shorten their lives.”

Slightly lower survival rates under the new system, he said, “may be the best we can do with lung transplants when patients are this sick.”

The rates may still represent a net benefit, he said, “compared to shortening the lives of patients who did not quite need the transplant.”

As more data comes in, the rules may need to be adjusted, Dr. Orens said. “We’re trying to capture just the right patients at just the right time.”

Lung Patients See a New Era of Transplants, NYT, 24.9.2006, http://www.nytimes.com/2006/09/24/health/24lung.html

As Children Suffer,

Parents Agonize Over Spinach

September 24, 2006
The New York Times
By MONICA DAVEY

MILWAUKEE, Sept. 22 — The hardest moment came when Elaine and Dennis Krause’s 9-year-son, who had stoically undergone kidney dialysis, blood transfusions and drug treatments that made him hallucinate that spiders were all around him, quietly asked his parents whether he was going to die.

“What do you say when your child asks you, am I going to die?” asked Elaine Krause, who has spent nearly all of this month beside her son’s bed at a hospital here, watching his skinny, lanky body do battle with E. coli. “I told him, ‘These people are trying to help you, and you are getting good care.’ But the truth is, I couldn’t answer him directly. We didn’t know.”

By this weekend, a national outbreak of E. coli linked to fresh spinach grown in California had sickened 170 people in 25 states and killed at least one here in Wisconsin, where more people have grown ill than in any other state. The authorities in Idaho and Maryland were investigating the deaths of two others, including a toddler whose parents said they gave him a fruit smoothie with spinach days earlier, trying to determine whether their deaths, too, were linked to the outbreak.

But beyond the raw statistics were individual stories of a sudden, mysterious, life-threatening illness, one that struck most often in the homes of those who viewed themselves as more health conscious than many other Americans.

In many cases, it crept up with frightening force after what had seemed a harmless, even healthful meal — a spinach salad with walnuts, a sandwich layered with spinach or, as for the Krause family, a baked, boneless, skinless piece of chicken on a small bed of spinach. Then what had seemed a simple bout of diarrhea in the morning often led to a harrowing, bloody race to the emergency room by midnight.

And around the country, some families still wait by bedsides, wondering which foods they could ever again feel safe giving their children, what the government or the spinach industry could have done to protect them, and, most of all, whether their loved ones will ever fully recover.

“Here you think you’re feeding your child a great, healthy meal,” Dennis Krause said sadly. “But here I was, poisoning him.”

Not all E. coli is harmful to humans, but certain strains produce toxins that kill cells in the gut and in the blood vessels, leading to abdominal cramps and watery to bloody diarrhea, said Dr. John Flaherty, associate chief of the division of infectious disease at the Feinberg School of Medicine at Northwestern University.

One area where the toxins can wreak particular havoc is in the kidneys; when it happens, Dr. Flaherty said, the inflamed cells lining the blood vessels get “roughed up,” causing red blood cells to break open as they pass by and jam blood flow to the kidneys.

“In the course of one week, he went from this healthy, lively little boy to a boy in a hospital bed fighting for his life,” said Anne Grintjes, of Brookfield, Wis., whose 7-year-old son developed a dangerous form of kidney failure linked to E. coli, called hemolytic uremic syndrome. “He turned yellow and gray, literally. It was shocking and terrifying and unbelievable to watch.”

Of the 171 cases that have been confirmed as part of the spinach outbreak, more than half required hospitalization, and about 16 percent developed the dangerous hemolytic uremic syndrome.

Doctors say they cannot be certain what long-term effects the syndrome may have; it varies from person to person. Many patients recover entirely, they say, while others may suffer from chronic kidney problems and other health risks.

Although the youngest children and the oldest adults are considered most vulnerable to getting sick from the bacteria and to struggling to recover from its effects, more than 70 percent of those who grew ill in this outbreak were somewhere in between: older than 4 and younger than 65.

At 27, Gwyn Wellborn of Salem, Ore., described a sudden onslaught of slicing, stabbing abdominal pain and bloody diarrhea in late August, days after eating baby spinach at work, thinking she was being especially virtuous. At first, doctors sent her home, Ms. Wellborn said, with a painkiller and a diagnosis of food poisoning. Hours later, though, the pain became so excruciating and the bleeding so constant, she said, that her husband rushed her back to a hospital.

From there, she quickly deteriorated. Her kidneys began failing. “At one point, the doctors told my family there was nothing they could do, that that was it,” she recalled. But after three transfusions and several weeks in a hospital, Ms. Wellborn went home.

Hers is one of at least four lawsuits filed in courts around the country by William D. Marler, a Seattle lawyer, in connection with the outbreak. Ms. Wellborn said she would not consider eating spinach anytime soon. “Not in a million years,” she said.

Marion Graff, 77, a former bank clerk and widow from Manitowoc, Wis., is the nation’s only confirmed fatality in the outbreak, but deaths in Maryland and Idaho are also considered “suspect” cases, federal authorities said on Friday.

Kyle Allgood, 2, of Chubbuck, Idaho, died at a Utah hospital from cardiac arrest after contracting hemolytic uremic syndrome, his family said, a case Idaho authorities said was “probably connected” to the tainted spinach, although laboratory tests have been inconclusive. Kyle’s mother, Robyn Allgood, said she had mixed vegetables into blended fruit and juice smoothies, as a way to get Kyle and her two daughters to eat vegetables, and had given him such a drink on Sept. 12.

Three days later, she said, Kyle had flu-like symptoms, including severe diarrhea.

On Wednesday, despite specialized treatment at a hospital in Salt Lake City, Kyle died, hours after his father, Jeff, said he had urged the boy “to fight for me.”

Relatives tearfully recalled Kyle as generous and good-natured though mischievous — a boy known as the “stuntman” for his antics, which inspired fear and awe in adults.

He liked to twirl his hair into knots, dance wildly to the music of Jack Johnson and give lingering kisses to his aunts, the family said. He was also impish; at Primary Children’s Medical Center in Salt Lake City, Kyle was pinching his nurses and ripping at his IV’s until near his final moments, they said.

In Maryland, an elderly woman died of E. coli on Sept. 13 after eating fresh spinach, state health officials confirmed, but because of a lack of DNA specimens from the victim, officials have yet to determine whether it was the same strain of E. coli that infected others who ate spinach. Family members identified the woman as June E. Dunning, 86, of Hagerstown.

Warren Swartz, Ms. Dunning’s son-in-law, said she had eaten steamed spinach from a package on Aug. 30 and Sept. 1 and baby spinach from a bag on Aug. 30. She had signs of E. coli, including rectal bleeding and bloody diarrhea, on Sept. 1 and went to the hospital the next day.

For the Krause family, of McFarland, Wis., the illness began a few days after a family dinner on Aug. 24. First, their 15-year-old daughter grew ill. Then their 9-year-old, who was healthy enough that he had a perfect attendance record last year in third grade, grew even more ill, and has suffered debilitating effects, including acute renal failure, fluid buildup near the heart, raised blood pressure, soaring blood sugar.

In a hospital cafeteria here, miles from their home, the Krauses at first could only bring themselves to eat peanut butter and jelly sandwiches. Everything else — lunch meats , salads, everything — scared them.

“For me, there’s anger and paranoia and fear for others — for the safety of food we get that’s supposed to be monitored,” Ms. Krause, 47, said. “I don’t know what to trust. Should we grow it all ourselves?”

On Friday, their strawberry-blond boy lay weakly in his hospital bed, surrounded by balloons and cards from the school where he says he fears falling behind his class. He had physical therapy, then occupational therapy to begin rebuilding his body. He told his father he only wanted to be well, to somehow rewind to the day before the spinach.

A few days ago, his body seemed to turn a corner and doctors removed him from the dialysis machine, a crucial step toward recovery. His parents have not asked when he might be well enough to go home; they said it was too early to look ahead.

“I keep thinking we will at some point go home and it’ll all be like it was,” said Mr. Krause, 52. “But we don’t know yet what the long-term effects are. He will be monitored probably for the rest of his life. It’ll never be the same.”

Libby Sander contributed reporting from Chicago; Martin Stolz from Bountiful, Utah; and Gary Gately from Baltimore.

As Children Suffer, Parents Agonize Over Spinach, NYT, 24.9.2006, http://www.nytimes.com/2006/09/24/us/24spinach.html

Study Condemns

F.D.A.’s Handling of Drug Safety

September 23, 2006
The New York Times
By GARDINER HARRIS

WASHINGTON, Sept. 22 — The nation’s system for ensuring the safety of medicines needs major changes, advertising of new drugs should be restricted, and consumers should be wary of drugs that have only recently been approved, according to a long-anticipated study of drug safety.

The report by the Institute of Medicine, part of the National Academy of Sciences, is likely to intensify a debate about the safety of the nation’s drug supply and the adequacy of the government’s oversight. The debate heated up in September 2004 when Merck withdrew its popular arthritis drug Vioxx after studies showed that it doubled the risks of heart attacks.

Several senators have already proposed significant changes, some of which the report seems to endorse.

The report’s conclusions are often damning. It describes the Food and Drug Administration as rife with internal squabbles and hobbled by underfinancing, poor management and outdated regulations.

“Every organization has its share of dysfunctions, unhappy staff members and internal disputes,” the report said. But panel members said that they were deeply concerned about the agency’s “organizational health” and its ability to ensure the safety of the nation’s drug supply.

The report made these recommendations, most of which would require Congressional authorization:

¶Newly approved drugs should display a black triangle on their labels for two years to warn consumers that their safety is more uncertain than that of older drugs.

¶Drug advertisements should be restricted during this initial period.

¶The F.D.A. should be given the authority to issue fines, injunctions and withdrawals when drug makers fail — as they often do — to complete required safety studies.

¶The F.D.A. should thoroughly review the safety of drugs at least once every five years.

¶The F.D.A. commissioner should be appointed to a six-year term.

¶Drug makers should be required to post publicly the results of nearly all human drug trials.

In a telephone conference with reporters on Friday, top F.D.A. officials struck an awkward balance between thanking the institute for its work and defending their own leadership. They said they needed to study the report before deciding which of its recommendations to endorse.

“While considerable work has been done over the past two years to improve our approach to drug safety, work still needs to be done,” said Dr. Andrew C. von Eschenbach, the acting commissioner of the agency and the nominee for commissioner.

An internal e-mail message sent Friday to agency staff members by Dr. Sandra L. Kweder, deputy director of the Office of New Drugs, was blunter, bemoaning the report’s criticism of what it described as the agency’s dysfunctional culture.

“It is a long, inflammatory section of the report that will certainly generate the most public attention and hit our people hard,” Dr. Kweder wrote, according to a copy provided to The New York Times.

Agency critics were elated.

“The new report validates what the watchdog community has been saying for the last two years,” said Senator Charles E. Grassley, Republican of Iowa, who as chairman of the Senate Finance Committee has overseen investigations into drug safety problems. “Problems are systemic, and solutions must reflect a new mind-set by the agency leadership.”

The drug industry, through its trade organization, reacted warily. “Though there is always room for improvements, it would be a mistake to accept the notion that the F.D.A. drug safety system is seriously flawed,” said Caroline Loew, senior vice president of the Pharmaceutical Research and Manufacturers of America.

The Institute of Medicine is a nonprofit organization created by Congress to advise the federal government on health issues. The report was issued by the Committee on the Assessment of the United States Drug Safety System, led by Sheila P. Burke, deputy secretary and chief operating officer of the Smithsonian Institution.

The report described fierce disagreements between those who approve drugs and those who study their effects after approval, disputes that repeated F.D.A. efforts have not resolved. Indeed, managers’ failure to address such disagreements competently “has played an important role in damaging the credibility” of the agency, it said.

Critics of the food and drug agency have long been divided into two warring camps. Some say the agency fails to approve life-saving medicines quickly enough, while others say that it is so intent on rapid approvals that it fails to ensure the safety of the drugs.

The institute’s report champions the latter view by calling for greater caution. It suggests that one of the agency’s biggest problems is a deal struck in 1992 between Congress and the drug industry in which drug makers agreed to pay millions in fees to speed reviews. This deal has increased pressures on drug reviewers to act quickly, and it has limited “the ability of reviewers to examine safety signals as thoroughly as they might like,” the report said.

“Some also have serious concerns that the regulator has been ‘captured’ by industry it regulates, that the agency is less willing to use the regulatory authority at its disposal,” the report said, criticizing the agency’s regulatory tools as “all-or-nothing.”

“The agency needs a more nuanced set of tools to signal uncertainties, to reduce advertising that drives rapid uptake of new drugs, or to compel additional studies in the actual patient populations who take the drug after its approval,” it said.

The pharmaceutical industry is likely to fight at least some of the proposals, said Charlie Cook, a Washington political analyst.

“One should never underestimate the influence of the drug industry,” Mr. Cook said. “But I would think that at least the outlines of many of these recommendations would have a decent chance of getting through Congress.”

Senators Michael B. Enzi, Republican of Wyoming and chairman of the Health, Education, Labor and Pensions Committee, and Edward M. Kennedy of Massachusetts, the ranking Democrat on the committee, have jointly proposed a bill that would undertake at least some of the changes advocated by the report.

Another bill, sponsored by Senator Grassley and Senator Christopher J. Dodd, Democrat of Connecticut, offers similar proposals.

There is little chance that Congress will act on any of these proposals before next year, when it must reauthorize the 1992 financing deal with the drug industry. Negotiations between the drug industry and agency about the parameters of that deal are already under way.

Despite its fierce criticisms, the report may bolster the confirmation prospects of Dr. von Eschenbach. A Senate committee approved his nomination on Wednesday, but two Republican senators have vowed to block it.

Over the past 10 years, no commissioner has served more than two years, though the term is open-ended. The report deplored this “lack of stable leadership.”

“Without stable leadership strongly and visibly committed to drug safety, all other efforts to improve the effectiveness of the agency or position it effectively for the future will be seriously, if not fatally, compromised,” the report states.

It recommends that the commissioner be nominated for a six-year term, but such a change may not solve the problem of early exits. President Bush has nominated two past commissioners. The first left for another job within the administration; the second left amid accusations of financial improprieties.

The report recommends that Michael O. Leavitt, the secretary of health and human services, appoint an independent board to advise the commissioner “to implement and sustain the changes necessary to transform” the agency’s culture.

It rejects suggestions by Mr. Grassley and others that the F.D.A. create a center for drug safety to monitor drugs after approval.

“Achieving a balanced approach to the assessment of risks and benefits would be greatly complicated, or even compromised, if two separate organizations were working in isolation from one another,” the report concludes.

The F.D.A. asked the Institute of Medicine to review its drug safety system shortly after the Vioxx withdrawal in 2004, and the agency has agreed to pay $3 million for the study.

Study Condemns F.D.A.’s Handling of Drug Safety, NYT, 23.9.2006, http://www.nytimes.com/2006/09/23/health/policy/23fda.html

U.S. Urges

H.I.V. Tests for Adults and Teenagers

September 22, 2006
The New York Times
By DONALD G. McNEIL Jr.

In a major shift of policy, the federal government recommended yesterday that all teenagers and most adults have H.I.V. tests as part of routine medical care because too many Americans infected with the AIDS virus don’t know it.

The recommendation, by the Centers for Disease Control and Prevention, urges testing at least once for everyone aged 13 to 64 and annual tests for those with high-risk behavior.

The proposal is a sharp break from the early days of the AIDS epidemic, when the stigma of the disease and the fear of social ostracism caused many people to avoid being tested.

That led to heated debate about whether positive test results could be shared by medical and governmental authorities in their effort to contain the epidemic by reaching out to partners of those who might be infected.

Under the agency’s plan, which states can adopt or modify if they choose, patients would be advised they were being tested, but the tests would be voluntary.

So that the tests could be easily administered, however, the agency urged the removal of two major barriers that some states now have: separate signed consent forms and lengthy counseling before each test.

That would require new laws in some states, however, which could take years because some civil liberties groups and lobbyists for people with AIDS oppose the changes.

Many doctors are expected to welcome the changes.

“These recommendations are important for early diagnosis and to reduce the stigma still associated with H.I.V. testing,” said Dr. Nancy Nielsen, a board member of the American Medical Association, which endorsed the new guidelines.

Dr. Julie Gerberding, the disease control agency’s director and a doctor who treated some of the first San Francisco AIDS patients in 1981, said: “Our traditional approaches have not been successful. People who don’t know their own H.I.V. status account for 50 to 70 percent of all new infections. If they knew, they would take steps to protect themselves and their partners.”

The new guidelines, if adopted, would move the agency toward its “ultimate goals,” which Dr. Gerberding described as: no more H.I.V.-infected children, no one living for years without antiretroviral treatment and, eventually, no more new cases of the disease.

About 40,000 Americans are newly infected each year, a number that has been remaining steady. In contrast to the early days of the epidemic, which struck gay men the hardest, many of those now infected are black or Hispanic, are teenagers and were infected by heterosexual sex. The agency estimates that 250,000 Americans, a quarter of those with the disease, do not know they are infected.

Moreover, 42 percent of those who find out they are infected are tested only because they are already seriously ill — which means they have been infected for up to 10 years and may have been passing the infection on all that time, Dr. Gerberding said.

The American Academy of H.I.V. Medicine, a group for AIDS specialists, gave a qualified endorsement of the guidelines, agreeing with the need for more testing but arguing that they gave counseling short shrift.

“Counseling just naturally goes with testing, as diet does to exercise,” said Dr. Jeff Schouten, the academy’s chairman.

Some civil liberties organizations and those representing people with AIDS, while favoring more testing, have lobbied against removing signed consent forms or pretest counseling for fear that such changes will make testing less voluntary.

Some states, including New York, have laws requiring such counseling and consent forms. They were passed in the early days of the AIDS epidemic, when having the virus amounted to a death sentence, the disease’s stigma often led to denial of jobs or housing, and testing was done primarily to protect the blood supply.

Dr. Thomas R. Frieden, New York City’s health commissioner, said yesterday that he “absolutely” agreed with the new guidelines and had been lobbying the state Legislature for a law incorporating them.

A bill he supported was introduced late last year, Dr. Frieden said, but opponents kept it from coming up for a vote.

“I am optimistic that it will make it through this year,” he said.

Rose A. Saxe, a staff lawyer with the AIDS Project of the American Civil Liberties Union, said her group opposed the recommendation because it would remove the requirement for signed consent forms and pretest counseling. In settings like emergency rooms where doctors are strapped for time, Ms. Saxe said, “we’re concerned that what the C.D.C. calls routine testing will become mandatory testing.”

Patients, particularly teenagers, she said, “will be tested without an opportunity for understanding the magnitude of having a positive result.”

David Ernesto Munar, associate director of the AIDS Foundation of Chicago and a board member of the National Association of People With AIDS, said he favored more testing and faster counseling to encourage it.

“But our fear,” Dr. Munar said, “is that on the ground, the rush to get more blood samples is going to railroad right over any consent.”

Illinois, like New York, requires written consent before a test, he said.

Disease control agency experts deny that their guidelines would encourage such problems.

They oppose mandatory testing, secret testing or testing without informing patients, at least orally, that such a test will be done. They suggest that whatever general consent for routine medical care a state law requires include consent for H.I.V. testing.

They also want anyone who tests positive to be counseled that AIDS is a serious disease and taught where to get treatment and how to keep from infecting others.

As an example of success in a related program, Dr. Timothy Mastro, acting director of the agency’s AIDS prevention division, pointed to the agency’s guidelines to prevent infection of newborns.

The guidelines say that all pregnant women should be tested unless they refuse and that oral consent is acceptable. They also recommend tests again in late pregnancy for women who inject drugs, have sex with many men, have sex for money or live in neighborhoods where AIDS is common.

The number of babies born infected dropped to fewer than 240 a year now from 1,650 in 1991, Dr. Mastro said.

Laws for prisoners, which Dr. Mastro described as “a tricky area,” might also need revision. In some states, testing is mandatory for all prisoners. In New York, it is voluntary.

Health officials in other states appeared to welcome the new guidelines. Steve Huard, spokesman for the Hillsborough County Health Department, which includes Tampa, Fla., said: “We strongly believe in universal H.I.V. testing through anonymous and confidential testing. With the recommendations, it would be more widespread. It would go out to private physicians and we should see infection rates going down.”

Some states with few AIDS patients, like Wyoming, may be reluctant to adopt the guidelines on the ground that routine H.I.V. tests would be unnecessarily burdensome for doctors and patients.

To compensate for that, the guidelines suggest that routine tests might not be required in areas where fewer than 1 in 1,000 people test positive. But health care practitioners are not very good at guessing what rate will be found among their patients, said Dr. Bernard Branson, the C.D.C.’s associate director for laboratory diagnostics, so there should first be a period of routine testing.

The wholesale cost is about $1 for each test run in batches and about $8 for rapid tests done individually. Each positive test would require a second confirmation test and then counseling, which would raise the cost to about $80, Dr. Branson said.

That is far cheaper than many other routine screening tests like colonoscopies or mammograms, and Dr. Branson said most such tests were paid for by insurers because it was usually cheaper to treat diseases when they were caught early.

U.S. Urges H.I.V. Tests for Adults and Teenagers, NYT, 22.9.2006, http://www.nytimes.com/2006/09/22/health/22hiv.html

Spinach Pulled From Stores Across U.S.

September 17, 2006
By THE ASSOCIATED PRESS
Filed at 4:45 a.m. ET
The New York Times

LOS ANGELES (AP) -- Shoppers changed their buying habits Saturday as spinach was pulled from grocery store shelves because of the outbreak of E. coli bacteria that had killed one person and sickened more than 100 others.

The U.S. Food and Drug Administration warned consumers not to eat fresh spinach and Natural Selection Foods LLC recalled its packaged spinach throughout the United States, Canada and Mexico. The move came as a precaution after federal health officials said some of those hospitalized reported eating brands of prepackaged spinach distributed by the company.

The officials stressed that the bacteria had not been isolated in products sold by the holding company, based in San Juan Bautista, Calif., and known for Earthbound Farm and other brands. As the investigation continues, other brands may be implicated, officials said.

At a Safeway grocery in San Francisco's Potrero Hill neighborhood, many of bagged produce shelves were empty Saturday. Anna Cairns said she had to settle for bags of iceberg green lettuce and Caesar salad, instead of her normal salad mix, which contained spinach.

''I have a bag of spinach in my refrigerator I need to throw away,'' said Cairns, 59, of San Francisco.

Marina Zecevic, 49, of West Los Angeles, shopping at a Trader Joe's, said she made the mistake of serving creamed spinach to her kids the day the story broke.

''My sons started accusing me of premeditated murder,'' she said.

She felt the contamination issue was overblown.

''The minute we get the all clear, the spinach is back on the table,'' she said.

The spinach, grown in California, could have been contaminated in the field or during processing, according to the Centers for Disease Control and Prevention.

About 74 percent of the fresh market spinach grown in the U.S. comes from California, according to the California Farm Bureau Federation. There have been previous bacterial contamination outbreaks linked to spinach and lettuce grown in the state.

Wisconsin accounted for nearly a third of the 102 reported illnesses, including the lone death, a 77-year-old woman who died of kidney failure.

Other states reporting cases were California, Connecticut, Idaho, Indiana, Kentucky, Maine, Michigan, Minnesota, New Mexico, Nevada, New York, Ohio, Oregon, Pennsylvania, Utah, Virginia, Washington and Wyoming, according to the CDC.

''We are very, very upset about this. What we do is produce food that we want to be healthy and safe for consumers, so this is a tragedy for us,'' Natural Selection spokeswoman Samantha Cabaluna said.

The FDA advised consumers not to eat fresh spinach or fresh spinach-containing products until further notice. Some restaurants and retailers may be taking spinach out of bags before selling it, so consumers shouldn't buy it at all, the FDA said.

Boiling contaminated spinach can kill the bacteria but washing won't eliminate it, the CDC warned.

At a Stop and Shop supermarket in Meriden, Conn., Michelle Bookey said she frequently buys spinach for salads for her dieting husband but plans to cook it from now on.

''It worries me. I don't even want to buy lettuce,'' said Bookey, 36.

Earthbound Farm, which claims it pioneered the retail market in pre-washed, bagged salads in 1986, says its spinach and other products are in 74 percent of U.S. grocery stores.

It also sells spinach to restaurants and other establishments that serve food. The National Restaurant Association said members were pulling spinach from their menus.

The recall earned the praise of Tom Stenzel, president and chief executive officer of the United Fresh Produce Association.

''The FDA investigation and the voluntary action taken by Natural Selection Foods LLC help narrow concern about any continuing risk, and begins to ensure that product that may be potentially contaminated is removed completely from the food supply,'' Stenzel said in a statement.

A Seattle law firm said it planned to add Natural Selection Foods on Monday to federal lawsuits previously filed in Wisconsin and Oregon that named other spinach producers.

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Associated Press writers Andrew Bridges in Washington, Justin M. Norton in San Francisco, Ryan J. Foley in Madison, Wis., and Shelley Wong of Hartford, Conn., contributed to this story.

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On the Net:

Center for Food Safety and Applied Nutrition: http://www.cfsan.fda.gov/

Spinach Pulled From Stores Across U.S., NYT, 17.9.2006, http://www.nytimes.com/aponline/us/AP-Tainted-Spinach.html

For Insurance, Adult Children Ride Piggyback

NYT 17.9.2006

http://www.nytimes.com/2006/09/17/us/17insure.html

For Insurance,

Adult Children Ride Piggyback

September 17, 2006
The New York Times
By JENNIFER 8. LEE

Not only are children moving back home after college and asking Mom and Dad for monthly subsidies, but in a growing number of states children can now stay on their parents’ health insurance plans well into their 20’s.

Call it another example of adultescence. With 18- to 34-year-olds the fastest growing group of uninsured, states are extending the time that children can be a dependent for insurance purposes.

In New Jersey, which this year enacted the highest age limit, children can “piggyback” until they turn 30, as long as they live in the state and don’t have their own children.

The trend stems from a concern that a healthy — and profitable — segment of the population is dropping out of the insurance pool. About half of all states have studied such proposals, and at least nine have passed laws, eight of them since 2003 and three just this year, according to the National Conference of State Legislatures.

Hilary Shinn, 23, of Wall Township, N.J., who likes competitive surfing and snowboarding, was graduating from Rutgers University last spring and had not decided whether she would have health insurance.

“I’m a little accident-prone,” said Ms. Shinn, who had a skateboarding accident on her way to her last class in May. “It didn’t really hit me until my mom brought it up: ‘Hey, you are not going to be covered when you graduate. Let’s figure something out.’ ”

The New Jersey law allowed Ms. Shinn, who started graduate school at Monmouth University this semester, to stay on her father’s plan, for an additional premium.

In contrast, a number of her friends are now without health insurance. “If they get sick, they just don’t address it, on the hope it will go away,” she said.

About 30 percent of adults ages 18 to 24, and more than one-quarter of adults 25 to 34, are uninsured, though the average for all age groups is 16 percent, according to figures released by the Census Bureau in late August.

It is not known how many people have taken advantage of extended coverage, because policies are administered by private companies and most of the changes have only recently taken effect.

The rise of uninsured young adults results from two main economic forces, analysts say. Changes in the workplace mean that fewer jobs now have full benefits, which disproportionately affects the newest workers. In addition, the rising cost of premiums, whether shared with an employer or paid individually, makes insurance less attractive to a relatively healthy population.

“It’s different from a generation ago,” said Katherine Swartz, a professor of health policy at Harvard University who is the author of “Reinsuring Health,” a new book on the uninsured population. “We have so many people not used to having health insurance.”

For years, children have been allowed to stay on their parents’ health insurance until they turned 19, or until they turned 22 or 23 if they remained full-time students.

Some of the laws extending the age of coverage allow insurers to charge extra premiums, which vary depending on the plan. They also have various restrictions, sometimes requiring that the child be a full-time student, be unmarried, reside in the state or even live with the parents.

In general, these laws do not apply to insurance plans financed by the employer — as opposed to plans in which the employer buys coverage from an insurance company — because self-insured plans, favored by some larger companies, are shielded from state rules and laws under the 1974 federal Employee Retirement Income Security Act.

Ms. Shinn’s family pays several hundred dollars a month to add her to her father’s plan, which is through his employer, Systems Technology, a satellite communications company. She could have bought insurance on her own for a similar price, but her father’s plan provides better coverage, said Deborah Shinn, her mother.

“I know that our children, if they didn’t have family behind them, would never have an affordable choice,” said Mrs. Shinn, who has four children. “Between car insurance and just buying books for schools and normal day-to-day expenses, I really feel that she would never be able to earn enough income to cover the things that are important for us to have in place for her.”

Before this year, laws extending health coverage were passed in Colorado, Massachusetts, New Mexico, South Dakota and Texas. Utah, where young Mormon men commonly complete two years of missionary work, passed the first law, in 1994. The governors of Delaware and Rhode Island signed such laws last July.

New York State has three bills in legislative committees to raise the age limit for children to 25, with various restrictions. Connecticut has a similar proposal in committee.

The availability of health insurance in the workplace has become a problem for young adults. One reason employers are reluctant to hire full-time employees is the rising cost of health insurance and other benefits. The percentage of employers offering health insurance dropped to 60 percent in 2005, down from 66 percent in 2000, according to a survey of employers conducted by the Kaiser Family Foundation.

Thus, new graduates, from both high school and college, are entering a job market that is increasingly characterized by consulting, freelance and contract jobs.

And many employers that still offer insurance are asking employees to shoulder a higher share of the premiums, another reason young adults decline coverage, said Laura Tobler, a health policy analyst for the National Conference of State Legislatures. “It’s a cost-benefit analysis,” she said.

As a result, she said, states are “looking for ways to reach out to these folks and doing it in the least expensive way possible.”

Brian Merritt, a freelance technology consultant for a Fortune 500 company in New York City, checked on buying his own health insurance from the Freelancers Union but decided it was not worth the cost of nearly $200 a month.

“Basically, I’m a healthy 31-year-old male,” he said. “The last three times I went to the doctor, everything was O.K. So I haven’t felt the need for insurance.”

He acknowledged the risk. “If I trip on the sidewalk and fall and break my arm, I guess I am out of luck,” Mr. Merritt said. “Not only am I out medical costs, I can’t work.”

Other young adults said they had more pressing financial priorities. Tom Donatelli, a 29-year-old freelance cameraman from Brooklyn, is eager to reduce his credit-card and other debt. “If I have extra money, then it’s going to go toward debt that I already have, not debt that I might have,” he said.

Health insurance companies have been supportive of the age extensions that funnel additional premiums into the system, because they are looking for ways to keep young adults in the insurance pool, said the assemblyman who sponsored New Jersey’s bill, Neil M. Cohen. “They can use that new revenue to make adjustments in the rest of the market,” said Mr. Cohen, a Democrat of Roselle.

Susan Pisano, a spokeswoman for America’s Health Insurance Plans, an industry group, said that while insurance companies generally did not oppose laws that extend the age limit by a couple of years, New Jersey’s law, with the age ceiling of 30, might take it too far.

“The law in New Jersey has the potential to drive up health care costs for employers, whereas the other ones do not depart as radically from the current situation in those states,” Ms. Pisano said. “Our members have been comfortable with what is going on elsewhere.”

In Colorado, however, Leo Tokar, vice president for marketing and sales for Kaiser Permanente Colorado, said the added expense from that state’s new law created a “perverse incentive” for companies to reduce insurance benefits. Employers there can either pass along additional premiums for the adult children — who can stay on health plans until they reach age 25 — to their parents or spread the extra cost among all employees.

“Our opinion is it was absolutely the right direction to go, but it was the wrong way to go about doing it,” Mr. Tokar said.

He said it was inappropriate to make employers that offer insurance serve “as a conduit to address broader social issues.”

For Insurance, Adult Children Ride Piggyback, NYT, 17.9.2006, http://www.nytimes.com/2006/09/17/us/17insure.html

Washing spinach won't help;

health officials struggle

to find source of E. coli

Updated 9/15/2006 11:46 PM ET
AP
USA Today

WASHINGTON (AP) — Even if you wash the spinach, you still could be at risk.

Sober warnings for salad lovers came from federal health officials Friday as they focused on a possible source of a multistate E. coli outbreak that killed one person and sickened nearly 100 more. Twenty-nine people have been hospitalized, 14 of them with kidney failure.

The outbreak was traced to Natural Selection Foods, a holding company based in San Juan Bautista, Calif., known for Earthbound Farm and other brands. The company has voluntarily recalled products containing spinach.

Food and Drug Administration officials stressed that the bacteria had not been isolated in products sold by Natural Selection Foods but that the connection was established by patient accounts of what they had eaten before becoming ill.

The investigation was continuing.

"It is possible that the recall and the information will extend beyond Natural Selection Foods and involve other brands and other companies, at other dates," said Dr. David Acheson, the chief medical officer with the FDA's Center for Food Safety and Applied Nutrition.

Natural Selection Foods LLC said in a statement that it was cooperating with federal and state health officials to identify the source of the contamination and had stopped shipping all fresh spinach products. They are sold under many brand names, including Earthbound Farm, Dole, Green Harvest, Natural Selection Foods, Rave Spinach, Ready Pac and Trader Joe's.

"We are very, very upset about this," Natural Selection Foods spokeswoman Samantha Cabaluna said Friday night. "What we do is produce food that we want to be healthy and safe for consumers, so this is a tragedy for us."

Meanwhile, the FDA warned people nationwide not to eat any prepackaged spinach, whether sold in bags or clamshell boxes. Officials don't know how much contaminated spinach may be out there, but consumers buy more than 500 million pounds of it each year.

Washing contaminated spinach won't get rid of the tenacious bug, though thorough cooking can kill it. Supermarkets across the country pulled spinach from shelves, and consumers tossed out the leafy green.

"We're waiting for the all-clear. In the meantime, Popeye the Sailor Man and this family will not be eating bagged spinach," said Dr. William Schaffner, chairman of preventative medicine at Vanderbilt University. The Tennessee university's medical center was treating a 17-year-old Kentucky girl for E. coli infection. That case originally was listed as being from Tennessee, but federal health officials changed it to Kentucky.

By Friday, the outbreak had grown to include at least 19 states: California, Connecticut, Idaho, Indiana, Kentucky, Maine, Michigan, Minnesota, New Mexico, Nevada, New York, Ohio, Oregon, Pennsylvania, Utah, Virginia, Washington, Wisconsin and Wyoming, according to the Centers for Disease Control and Prevention. Wisconsin accounted for about half the cases, including the lone death, Gov. Jim Doyle said.

"We are telling everyone to get rid of fresh bagged spinach right now. Don't assume anything is over," Doyle said.

In all, the bug is known to have sickened at least 94 people.

FDA officials said they issued the nationwide consumer alert before they could confirm the source of the tainted spinach.

"Early is good," said Caroline Smith DeWaal, food safety director for the Center for Science in the Public Interest, adding that the alert may have prevented hundreds more cases.

An industry spokeswoman said public health concerns justified the blanket warning: "It needed to happen this way," said Kathy Means, a spokeswoman for the Produce Marketing Association. "Public health has to trump economics at this time."

Farmers in California's Monterey County grow more than half the nation's 500 million-pound spinach crop, according to the Agriculture Department.

"We're trying to get to the bottom of this and figure out what happened. Everybody is terribly concerned," said Dave Kranz, a spokesman for the California Farm Bureau Federation.

Even before the latest outbreak, a joint state and federal effort has been underway in the California county to find and eliminate any possible sources of E. coli contamination.

"We need to strive to do even better so even one life is not lost," said Dr. Andrew von Eschenbach, FDA's acting commissioner.

The FDA's top food expert stressed the importance of stopping the bacterium at its source, since rinsing spinach won't eliminate the risk. "If you wash it, it is not going to get rid of it," said Robert Brackett, director of the agency's Center for Food Safety and Nutrition.

E. coli lives in the intestines of cattle and other animals and typically is spread through contamination by fecal material. Brackett said the use of manure as a fertilizer for produce typically consumed raw, such as spinach, is not in keeping with good agricultural practices. "It is something we don't want to see," he told a food policy conference.

Meanwhile, Wal-Mart Stores Inc., Safeway Inc., SuperValu Inc. and other major grocery chains stopped selling spinach, removing it from shelves and salad bars.

"We pulled everything that we have spinach in," said Dan Brettelle, manager of a Piggly Wiggly store in Columbia, S.C.

State health officials became aware of the first E. coli poisoning cases on Aug. 25, Acheson said. The FDA was alerted about the outbreak at midweek.

Consumer activist Barb Kowalcyk said fixing the nation's "fractured network" of food safety agencies could save lives. In 2001, her 2-year-old son, Kevin, died of E. coli, possibly after eating tainted ground beef.

"How can we improve communication between agencies? That needs to happen," the Loveland, Ohio, resident said.

Rep. Rosa DeLauro, D-Conn., and other lawmakers seek a hearing on legislation that would consolidate all federal food safety agencies and establish the Food Safety Administration, her spokeswoman said. Staff members of the House Energy and Commerce committee will examine the situation and current government policy, deputy staff director Larry Neal said.

Not all strains of E. coli cause illness: E. coli O157:H7, the strain involved in the current outbreak, was first recognized as a cause of illness in 1982. That strain causes an estimated 73,000 cases of infection, including 61 deaths, each year in the United States, according to the CDC.

When ingested, the bug can cause diarrhea, often with bloody stools. Most healthy adults can recover completely within a week, although some people — including the very young and old — can develop a form of kidney failure that often leads to death.

Sources of the bacterium include uncooked produce, raw milk, unpasteurized juice, contaminated water and meat, especially undercooked or raw hamburger.

Anyone who has gotten sick after eating raw packaged spinach should contact a doctor, officials said. Other bagged vegetables, including prepackaged salads, apparently are not affected.

"At this point, we are focused on the issue of the spinach. As we learn more, as we go further, we will alter or change that recommendation," von Eschenbach said.

Washing spinach won't help; health officials struggle to find source of E. coli, UT, 15.9.2006, http://www.usatoday.com/news/health/2006-09-14-ecoli_x.htm

Battle Lines in Treating Depression

September 10, 2006
The New York Times
By BARNABY J. FEDER

TAMARA KNIGHT remembers little of the summer of 2004 beyond a numbing despair that resisted 16 different antidepressant drugs. She dreaded a return to electroshock therapy, which she had tried periodically for years, because it brightened her mood for only a few weeks, at best, while progressively destroying her memory.

“She was in as dark and low a place as you can ever imagine a person living,” said Don Knight, her husband. So Ms. Knight drove to a drugstore in her hometown of Columbus, Ga., bought two large bottles of extra-strength Excedrin and two boxes of sleeping pills. She said she swallowed as many of the pills as she could before she passed out.

Katherine V. Coram, another depression sufferer with a history of attempted suicide, was in relatively better shape that same summer. She had managed to cling to a job at the National Archives in Washington, where an understanding boss gave her a light workload. But Ms. Coram felt defeated. Her three years in a clinical trial to see if an implanted nerve stimulator could control her illness had ended with hellish results.

“I was hospitalized three times in the year after I got it for anxiety, panic and other problems — after having gone 15 years without hospitalization,” said Ms. Coram, who lives alone in Silver Spring, Md. “Once I even hit a stranger in a restaurant after I got mad. It was totally out of character for me.”

The summer of 2004 was also trying for Cyberonics, a small Houston company that made Ms. Coram’s stimulator, and Robert P. Cummins, known as Skip, the company’s combative chief executive. A Food and Drug Administration panel recommended in June that the agency approve the device — a pocket-watch-sized generator implanted in the chest that transmits electronic pulses to a major nerve pathway in the neck — for treating the most intractable forms of depression. But about two months later, the F.D.A. ignored its own panel’s recommendation and decided to withhold approval after weighing criticisms from groups opposed to the controversial treatment.

Since 2004, Ms. Knight and Ms. Coram have continued their struggles with depression, their fates intersecting with Cyberonics’ own battles with the F.D.A. and insurers, as well as medical skeptics and public interest groups who argue that the company is peddling false hopes built on a still unproved technology.

The struggle over the future of the $15,000 device, which costs another $10,000 or more to implant, is being played out against that most tender of landscapes: the human psyche and the unpredictable and poorly mapped fault lines that cause depression and separate people from themselves and the world around them.

IT is a very promising avenue of research, and the long-term data they are pushing are encouraging,” said Dr. Christopher Gorton, chief medical officer of APS Healthcare, a consulting firm that was hired by the state of South Carolina to review Cyberonics’ research results. “But people have a legitimate need to be cautious. Even the sponsors admit they don’t know exactly how it works. The psychiatric literature is full of people clutching at straws.”

Some 21 million American adults suffer from depression, according to the National Institute of Mental Health, a federal research agency. While doctors as far back as the Renaissance speculated that mood disorders had medical roots, it was not until the end of the 19th century that such views were widely accepted. Since then, mental health care has seen innovations in talk therapy, electroshock, surgical procedures, drugs and, most recently, implanted devices.

Along the way, there have been notorious examples of misplaced medical enthusiasm, including adoption of lobotomies to treat depression. Currently, critics complain about frequent misuse of electroshock therapy and the virtually unregulated mixing of potent antidepression and antipsychotic drugs.

Cyberonics, which finally secured F.D.A. approval to market its implant last year, has ventured into the most difficult corner of depression treatment. It says its stimulator can provide relief for many of the four million or so people who suffer from “treatment resistant depression,” or T.R.D., a form so severe that patients fail to respond to drugs and traditional shock therapy. No other product has ever been designed for — and tested exclusively on — such a severely depressed population.

During the last month, some 1,300 doctors, patients and Cyberonics employees have written to the Centers for Medicare and Medicaid Services, asking that the agency grant Cyberonics’ recent petition for Medicare coverage. Public Citizen, a consumer advocacy group in Washington, filed a competing request on Wednesday, asking the agency to deny coverage. The group contends that Cyberonics has relied on misleading advertising and clinical trial write-ups, among other tactics, to secure federal approvals.

“With substantial constraints on the Medicare budget and so many clear needs going unmet, it seems absurd to flush away millions of dollars on this unproven device,” wrote Dr. Peter Lurie, deputy director of health research for Public Citizen, in the group’s petition. Other problems loom over the company. Federal prosecutors and regulators are investigating its pay practices, according to recent securities filings. Earnings disappointments over the last year have also caused Cyberonics’ stock to drop to $17.30 from a 52-week high of $40.69. Mr. Cummins declined to comment on the investigations, which are continuing.

But in an e-mail message last week, he scornfully dismissed Public Citizen’s criticisms as “shrill” and questioned Dr. Lurie’s expertise. “I look forward to the day when T.R.D. patients and fully qualified psychiatrists have the right to make treatment decisions regarding the ONLY treatment ever studied, proven safe and effective and F.D.A. approved for the long-term treatment of T.R.D!” he wrote.

The Cyberonics implant, like so many modern medical devices born of recent technological advances, would have been unimaginable only a generation ago. After being implanted in a patient’s chest, the device is surgically wired to the neck’s left vagus nerve, a major pathway for nerve signals to the brain from the heart and torso. Research suggests that repeated electronic stimulation of the vagus nerve can help treat severe depression by altering chemical and electrical functions in areas of the brain linked to mood disorders.

Cyberonics, which was founded in 1987, initially developed the stimulator to help epileptics control seizures. The F.D.A. approved that use in 1997. In 1998, based on animal tests and reports that many epileptics with the implant experienced mood improvements, Mr. Cummins gambled Cyberonics’ future on the idea that the device could also help treat patients with T.R.D. — people like Ms. Knight and Ms. Coram.

Mr. Cummins forecast, to Wall Street’s delight, that the T.R.D. market might be 10 times bigger than the epilepsy market. But his zeal also reflected his own family’s experience with depression, an affliction he says drove his mother and his grandfather to suicide. “My mother was my object lesson in wasted potential,” he said.

A squarely built, 6-foot-2-inch former college linebacker, Mr. Cummins, 52, says his mantra is, “Maybe wrong but never in doubt.” His shaved head and nonstop intensity seem well suited to someone whose idea of relaxation is competing in Nascar-affiliated car racing events. He now owns a Daytona Prototype race car — named Cyberspeed in honor of his company.

A native of Grove City, Pa., Mr. Cummins is the youngest of three children born into a dysfunctional family that he said was ripped apart by the periodic absences of his father, a steelworker, and his mother’s depression, alcohol and drug addictions. A decent student and a star athlete, he won a scholarship to Dartmouth, where he majored in government affairs.

After earning an M.B.A. at the University of Illinois at Urbana-Champaign Mr. Cummins eventually became a venture capitalist, joining Cyberonics’ board in 1988. Cyberonics was the brainchild of Reese S. Terry Jr., a veteran of the medical device industry, who set up the company to develop nerve-stimulation technology invented by Dr. Jacob Zabara at Temple University.

Dr. Zabara was one of many researchers exploring how electrical stimulation of the nervous system and the brain could affect a range of mental and physical ailments. The neurostimulation market as a whole now generates $1 billion annually in revenue, according to Wall Street analysts, and includes devices like spinal-cord stimulators that mask pain and deep brain implants that control some symptoms of Parkinson’s disease.

Wall Street and leading device companies see neurostimulation growing into a $10 billion business in the next decade, thanks to rapid advances in microchips and sensors. Executives at Cyberonics say that focusing on the vagus nerve makes its implants as effective but less risky and invasive than those that stimulate the brain and spinal cord.

Mr. Cummins became Cyberonics’ chief executive in 1995, when the company was struggling to stay afloat financially while seeking regulatory approval of its epilepsy therapy. He took over about the same time that Tamara Knight began a seemingly irreversible slide into severe depression.

Ms. Knight began suffering from depression as a teenager, a struggle that led to an early suicide attempt. Several years ago, drugs that had helped her recover stopped working. She began to neglect housework and her three children. In the fall of 1998, after several incidents in which she became outraged with co-workers, she lost her job. That winter, she began electroshock therapy.

What followed, she said, were more than 30 such treatments and more hospitalizations than she can recall. The number of drugs she took kept increasing, along with her weight. At one point, Ms. Knight, who is 5-foot-6 and had struggled with anorexia as a teenager, weighed more than 200 pounds. By 2004, she was depressed and was suffering from a common side effect of the electroshock therapy required to control her suicidal impulses: a steady erosion of her memory.

“Moneywise, insurance and Medicare paid for them,” Ms. Knight said of her treatments. “But it cost 30 years of my life in memory loss.”

As often happens in cases of severe depression, the family says it also lost the support of outsiders, including its local church. “If Tamara had had cancer, our church would have had people visiting all the time,” Mr. Knight said. “One older man visited us as long as he was able. That was it. It was a real blow to our faith.”

When Ms. Knight’s psychiatrist recommended a Cyberonics implant shortly after the F.D.A. approved the device in 2005, she became enthusiastic. Mr. Knight, who said he thought that V.N.S. therapy — Cyberonics’ trademarked name for “vagus nerve stimulation” — sounded far-fetched when he heard about it a few years earlier, now agreed that it was a chance they had to take.

HE was worried, though, that public information about V.N.S. came largely from Cyberonics and highlighted favorable aspects of clinical data. Negative experiences of clinical-study patients like Katherine Coram were not readily available, outside of commentaries that epilepsy patients posted on a Cyberonics Web site.

Ms. Coram recalls feeling better in the first six months after her Cyberonics stimulator first turned on in 2001.

But when researchers ramped up her implant’s power to enhance its long-term performance, Ms. Coram began suffering nausea, sleeplessness and panic attacks that sent her to the hospital. She lost track of her finances. Like many victims of severe depression, she also began to experience distressingly peculiar setbacks, including an inability to load her dishwasher. Ms. Coram said doctors raised and lowered the implant’s power level several times before she asked them to turn it off temporarily.

“I was trusting the people in the study to figure out how to use the device but they didn’t have a clue,” Ms. Coram said.

The experiences of individuals like Ms. Coram and inconclusive data were not enough, though, for the F.D.A. to shut its doors to Cyberonics. In June 2004, an advisory panel recommended that the agency allow Cyberonics to market its stimulator.

That same night, Cyberonics’ board granted Mr. Cummins a bonus of 150,000 stock options. The next day, as the stock market reacted to the F.D.A. panel’s recommendation, Cyberonics shares leapt 77 percent, laying the groundwork for what, two years later, would become inquiries by the Securities and Exchange Commission and the Justice Department into whether Mr. Cummins’s options grant was legal.

But in 2004, Mr. Cummins had more immediate problems. By early August, critics inside and outside the F.D.A. had talked the agency into the unusual step of disagreeing with its advisory panel. True, there were success stories from patients who achieved almost complete recoveries (nearly 20 percent, according to Cyberonics). Data also suggested that patients who benefited — over 50 percent to one degree or another — were more likely to avoid relapses, expensive hospitalizations and suicide than a similar group of patients who received conventional therapy.

Still, in the most carefully controlled trial, a group that had the device implanted but not turned on fared nearly as well as the group being stimulated. Critics also pointed out that long-term results indicated that 30 percent of the patients reported worsening depression similar to Ms. Coram’s, creating unanswered questions about potential harm.

Mr. Cummins said in a press release that Cyberonics was “shocked” by the agency’s rejection. He denigrated the F.D.A. request for more randomized testing, arguing that other antidepression therapies had been subjected to far less challenging scrutiny. And he suggested to analysts that the agency’s decision would leave many patients feeling that they had no option other than suicide. In September, the F.D.A. accepted an amended application from Cyberonics that contained more long-term performance data and comparisons to other therapies.

Still, it came as something of a surprise on Wall Street and in the medical device industry when the F.D.A. decided early in February 2005 to approve V.N.S. as a depression treatment if Cyberonics met certain conditions. Most of the new requirements dealt with follow-up studies aimed at figuring out how the device could be used most effectively. Mr. Cummins forecast that all of the conditions could be met by the end of May. Shares of Cyberonics soared, and the company went on a hiring spree.

Mr. Cummins cast the decision as a victory for patients but also heralded the financial upside, projecting that Cyberonics’ sales could reach $1 billion by 2010. In the weeks after the F.D.A.’s announcement, he responded to Cyberonics’ stock run-up by exercising options on 350,000 shares, which netted him about $10.75 million. (The sales left him holding just over 36,000 Cyberonics shares, a stake he has since raised to 173,750 shares, according to federal filings.)

The long-awaited marketing approval from the F.D.A. came in July, but new problems emerged. A prominent board member resigned, citing disagreements with other directors over compensation policies and lack of a succession plan for Mr. Cummins.

The Senate Finance Committee, which began investigating the F.D.A.’s handling of the implant that spring, issued a staffreport in February of this year criticizing Dr. Daniel G. Schultz, a senior F.D.A. official, for overruling agency experts opposed to the device. An F.D.A. spokeswoman said that the agency acted carefully and that for “the small number of patients with severe depression who have failed all other treatments, data shows this may be the difference between being able to live a more productive life or suffer from debilitating illness.”

The Senate report also put Medicare officials on notice that decisions to cover V.N.S. would invite further scrutiny.

Continued uncertainty surrounding V.N.S. and Mr. Cummins’s us-against-the-world attitude have taken their toll on Cyberonics’ stock price and on Wall Street’s faith in the company. “There are institutional investors who won’t touch the company as long as Skip is at the helm,” said Jan Wald, an analyst at A. G. Edwards & Sons.

To hear Mr. Cummins tell it, what really matters is that a growing number of depression patients now credit the device with saving their lives. They include Ms. Knight, who got her Cyberonics implant last October, and quickly proved to be the kind of patient the company treasures.

“My family could see subtle differences right away,” Ms. Knight recalled in the letter of support for V.N.S. she sent to Medicare regulators last month. “I was out of bed more often and started taking an interest in how the house looked.”

While Ms. Knight, now 47, talks about “having my life back,” the legacy of severe depression remains with her. After spending so much time for so many years in bed, her body cannot keep up with all the things she now wants to do around the house, often leaving her in pain. She continues to lose her way around her hometown and mourns the loss of so much of her long-term memory. But she has been able to cut back to using just three medications, a change she credits with helping her shed 40 pounds.

MS. CORAM is also on the mend, but not because of V.N.S. or Cyberonics. After enduring numerous futile adjustments to her implant and having it temporarily turned off, she asked her doctors to try one last time in March 2004. Three months later, she stopped using the implant for good and then had it removed from her chest. Her doctors left the metal leads wrapped around her vagus nerve, saying it was too risky to try to remove them.

She said she is slowly regaining the ability to do household tasks — like paying bills — that had been impossible during her V.N.S. treatment. “I feel like I’m just beginning to get my life back,” she said recently.

Mr. Cummins remains as driven as ever. Cyberonics says 1,810 patients have received the implants since the product was approved, out of 13,313 identified candidates. Thousands have been caught up in lengthy and often unsuccessful appeals for insurance coverage, since only a few small insurers routinely pay for the device.

Seeking the traction it desperately needs with insurers, Cyberonics decided in May to narrow the company’s focus to the subset of T.R.D. patients whose problems are the most costly for health care providers. Cyberonics contends that V.N.S. treatment for that group would save hospitals $4,800 to $8,200 a patient annually, based on an estimate of the implant’s cost and follow-up visits over eight years. But Cyberonics’ calculation is based on optimistic presumptions, including aggressive estimates about the pace and nature of patients’ recovery.

Because the presumptions are also based primarily on results from earlier trials, critics like Public Citizen say the new focus has all the flaws of the old one.

However the controversy is resolved, depression victims who finally get an implant will find themselves entering a medical lottery. Many, like Joe Marhefka, 49, of Colchester, Conn., are too depressed to be optimistic about the procedure.

Mr. Marhefka, who ended up in the hospital last fall after attempting suicide, said that he masked his depression most of his life by drinking. When he gave up alcohol eight years ago, the depression seemed to intensify. He said electroshock therapy two years ago destroyed most of his memories of his adolescence, and younger adult years. He lost his job as a high school math teacher shortly before his suicide attempt.

“When I had the implant last month, I was hoping I wouldn’t wake up,” Mr. Marhefka said in July, before entering the New London, Conn., office of Dr. Kathleen R. Degen to have his stimulator activated. “I don’t have any hopes this is going to work. I’m doing this because my wife deserves a husband and my two daughters deserve a Dad. They have hope. I’m just going along with the doctors.”

Dr. Degen used a hand-held computer to program a wand that Mr. Marhefka held over the spot on his chest where his implant was located. A 30-second-long pulse surged into his vagus nerve, reducing Mr. Marhefka’s voice to a barely audible rasp. When the pulse stopped, his voice returned to normal and he conversed briefly with Dr. Degen. He asked about reducing his medications; Dr. Degen said the request was common, but that it was too early to consider it.

Five minutes later, just as Mr. Marhefka asked whether his implant was still on, it delivered its second pulse — again taking away his voice and leaving him with what he said was a mild strangling feeling. Dr. Degen let the pulse pass and explained how she would gauge his future progress.

But Mr. Marhefka plans to measure his progress with his own yardstick.

“If I start smiling again, maybe even laughing sometimes, that’s how I’ll know,” he had said just before entering Dr. Degen’s office. So far, Mr. Marhefka said in a phone call last week, he is still waiting.

Battle Lines in Treating Depression, NYT, 10.9.2006, http://www.nytimes.com/2006/09/10/business/yourmoney/10cyber.html

Mental Activity

Seen in a Brain Gravely Injured

September 8, 2006
The New York Times
By BENEDICT CAREY

A severely brain-damaged woman in an unresponsive, vegetative state showed clear signs on brain imaging tests that she was aware of herself and her surroundings, researchers are reporting today, in a finding that could have far-reaching consequences for how unconscious patients are cared for and how their conditions are diagnosed.

In response to commands, the patient’s brain flared with activity, lighting the same language and movement-planning regions that are active when healthy people hear the commands. Previous studies had found similar activity in partly conscious patients, who occasionally respond to commands, but never before in someone who was totally unresponsive.

Neurologists cautioned that the new report characterized only a single, perhaps unique case and that it did not mean that unresponsive brain-damaged people were more likely to recover or that treatment was possible. The woman in the study could not communicate with the researchers, and there was no way to know whether her subjective experience was anything like what healthy people call consciousness. The woman was injured in a traffic accident in England last year.

Yet the study so drastically contradicted the woman’s diagnosed condition that it exposed the limitations of standard methods of bedside diagnosis. And its findings are bound to raise hopes for tens of thousands of families caring for unresponsive, brain-damaged patients around the world — whether those hopes are justified or not, experts said.

“One always hesitates to make a lot out of a single case, but what this study shows me is that there may be more going on in terms of patients’ self-awareness than we can learn at the bedside,” said Dr. James Bernat, a professor of neurology at the Dartmouth Medical School, who was not involved in the study. “Even though we might assume some patients are not aware, I think we should always talk to them, always explain what’s going on, always make them comfortable, because maybe they are there, inside, aware of everything.”

Dr. Bernat added that brain imaging promised to improve the diagnosis of unconscious states in certain patients, but that the prospect of imaging could also raise false hopes in cases like that of Terri Schiavo, the Florida woman who was removed from life support and died last year after a bitter national debate over patients’ rights.

Ms. Schiavo suffered far more profound brain damage than the woman in the study and was unresponsive for some 15 years, according to neurologists who examined her.

The journal that published the new paper, Science, promoted the finding in a news release, but added a “special note” citing the Schiavo case and warning that the finding “should not be used to generalize about all other patients in a vegetative state, particularly since each case may involve a different type of injury.”

The brain researchers, led by Adrian Owen at the Medical Research Council Cognition and Brain Sciences Unit in Cambridge, England, performed scans on the patient’s brain five months after her accident. The imaging technique, called functional M.R.I., reveals changes in activity in specific brain regions. When the researchers spoke sentences to the patient, language areas in her brain spiked in the same way healthy volunteers’ did.

When presented with sentences containing ambiguous words, like “The creak came from a beam in the ceiling,” additional language processing areas also became active, as in normal brains. And when the researchers asked the woman to imagine playing tennis or walking through her house, they saw peaks of activity in the premotor cortex and other areas of her brain that mimicked those of healthy volunteers.

“If you put her scans together with the other 12 volunteers tested, you cannot tell which is the patient’s,” Dr. Owen said in an interview. Doctors from the University of Cambridge and the University of Liège in Belgium collaborated on the research.

Dr. Nicholas Schiff, a neuroscientist at Weill Cornell Medical College in New York, said that the study provided “knock-down, drag-out” evidence for mental awareness, but that it was not clear “whether we’ll see this in one out of 100 vegetative patients, or one out of 1,000, or ever again.”

In a more recent exam, more than 11 months after her injury, the patient exhibited a sign of responsiveness: she tracked with her eyes a small mirror, as it was moved slowly to her right, and could fixate on objects for more than five seconds, said Dr. Steven Laureys, a neurologist at the University of Liège and an author of the study. This means by definition that the young woman has transitioned from an unresponsive, vegetative state to a sometimes responsive condition known as a minimally conscious state, Dr. Laureys said in an interview. An estimated 100,000 Americans exist in this state of partial consciousness, and some of them eventually regain full awareness.

The chances that an unresponsive, brain-damaged patient will eventually emerge depend on the type of injury suffered, and on the length of time he or she has been unresponsive. Traumatic injuries to the head, often from car accidents, tend to sever brain cell connections and leave many neurons intact. About 50 percent of people with such injuries recover some awareness in the first year after the injury, studies find; very few do so afterward. By contrast, brains starved of oxygen — like that of Ms. Schiavo, whose heart stopped temporarily — often suffer a massive loss of neurons, leaving virtually nothing unharmed. Only 15 percent of people who suffer brain damage from oxygen deprivation recover some awareness within the first three months. Very few do after that, and a 1994 review of more than 700 vegetative patients found that none had done so after two years.

The imaging techniques used in the new study could help identify which patients are most likely to emerge — once the tests are studied in larger numbers of unconscious people, said Dr. Joseph Fins, chief of the medical ethics division of New York Presbyterian Hospital-Weill Cornell Medical Center.

Without this context, Dr. Fins said, the imaging tests could create some confusion, because like any medical tests they may occasionally go wrong, misidentifying patients as exhibiting consciousness or lacking it. “For now I think what this study does is to create another shade of gray in the understanding of gray matter,” he said.

Mental Activity Seen in a Brain Gravely Injured, NYT, 8.9.2006, http://www.nytimes.com/2006/09/08/science/08brain.html

Gene Called Link

Between Life Span and Cancers

September 7, 2006
The New York Times
By NICHOLAS WADE

Biologists have uncovered a deep link between life span and cancer in the form of a gene that switches off stem cells as a person ages.

The critical gene, well known for its role in suppressing tumors, seems to mediate a profound balance between life and death. It weighs the generation of new replacement cells, required for continued life, against the risk of death from cancer, which is the inevitable outcome of letting cells divide.

To offset the increasing risk of cancer as a person ages, the gene gradually reduces the ability of stem cells to proliferate.

The new finding, reported by three groups of researchers online yesterday in Nature, was made in a special breed of mice that lack the pivotal gene, but is thought likely to apply to people, as well.

The finding suggests that many degenerative diseases of aging are caused by an active shutting down of the stem cells that renew the body’s various tissues and are not just a passive disintegration of tissues under daily wear and tear. “I don’t think aging is a random process — it’s a program, an anticancer program,” said Dr. Norman E. Sharpless of the University of North Carolina, senior author of one of the three reports.

The other senior authors are Drs. Sean J. Morrison of the University of Michigan and David T. Scadden of the Harvard Medical School.

The full implications are far from clear, but the finding that the cells are switched off with age does not seem too encouraging for researchers who hope to use a patient’s own adult stem cells to treat disease. That result may undercut opponents of research on human embryonic stem cells who argue that adult stem cells are enough to build new tissue.

Dr. Sharpless said his finding showed the need to pursue both types of research. The gene in the finding has the unmemorable name of p16-Ink4a. It plays a central role in the body’s defenses against cancer, and it produces two quite different proteins that interact with the two principal systems for deciding whether a cell will be allowed to divide.

One of the proteins had also been noted to increase substantially with age. The cells of a 70-year-old produce 10 times as much of the Ink4 protein as those of a 20-year-old, Dr. Sharpless said.

To help understand that Dr. Sharpless genetically engineered a mouse strain with the gene knocked out. He set out to see whether losing the gene would affect the blood-making stem cells. Learning that Dr. Morrison was interested in that with brain cells and Dr. Scadden with the insulin-making cells of the pancreas, he shared his mice with them.

The teams agreed to publish their findings together, a departure from usual researchers’ competitiveness.

All three teams report essentially the same results, that in each type of tissue the cells have extra ability to proliferate when the Ink4 protein can no longer be made.

At the same time, the Ink-less mice are highly prone to cancer, which they start to develop as early as 1 year of age.

The researchers assume, but have not yet proved, that the increasing amounts of Ink4 as a person ages will thrust the stem cells into senescence, meaning that they can never divide again. The evolutionary purpose is evidently to avert the risk that a damaged stem cell might evade controls and proliferate into a tumor.

One implication is that therapists who hope to increase longevity have to tackle a system that may be hard to cheat. An intervention that reduces Ink4 production to prevent the age-related decline of stem cells will also increase the risk of cancer.

“There is no free lunch,’’ Dr. Sharpless said. “We are all doomed.”

He quickly modified that by noting that a calorically restricted diet is one intervention that is known to increase life span and reduce cancer, at least in laboratory mice. The reason, he said, is probably because such diets reduce cell division, the prime source of cancer risk.

For cell therapists, the dual activity of Ink4 may be “a hard box to get out of,” he said, unless they use cells that are somehow much younger than the patient.

Dr. Scadden, however, said he hoped that there would turn out to be some sloppiness in the Ink4 gene’s balancing trick, allowing it to be switched off temporarily with yet-to-be invented drugs in a way that would promote stem cell proliferation without greatly increasing the risk of cancer. “There is clearly a dark side to the finding, but whether or not we can exploit it, that’s the challenge,” he said.

Some proposals for stem cell therapy with adult stem cells envisage taking a patient’s stem cells, making them divide in the laboratory and putting them back in the patient to build new tissue.

“The notion that adult stem cells are infinite in proliferative capacity is seriously undermined by this work,” Dr. Sharpless said.

Dr. Morrison said it had long been known that older patients did not do as well in bone marrow transplants as younger ones, and the new finding might explain why.

“I don’t think any of these findings dims the promise of stem cell research at all,” he said, because the greater robustness of younger people’s cells was already well known.

The researchers said they did not yet know what stimulus makes cells increase their production of the Ink4 protein as a person grows older. Their suspicion is that the usual factors implicated in aging like mutation and oxidative damage to tissues would turn out to have a role in making cells produce more Ink4.

Dr. Ronald A. DePinho, an expert on cellular aging and a co-author of Dr. Scadden’s report, said the new finding, in showing how the renewal capacity of stem cells was governed, might enable drugs to be made that would improve cell transplants.

Dr. Scott Lowe, a cancer gene expert at the Cold Spring Harbor Laboratory on Long Island who was not involved in the three papers, said the results were interesting because they linked to aging a gene of central importance in cancer.

Press releases by the University of North Carolina School of Medicine and the University of Michigan attributed the advance to all three teams equally. But the press release issued by the Harvard Stem Cell Institute, where Dr. Scadden has an appointment, described him as the leader of the multi-institutional team, with the other two teams confirming his work. Dr. Scadden made no such claim in an interview, and acknowledged Dr. Sharpless’s generosity in lending his mice.

Gene Called Link Between Life Span and Cancers, NYT, 7.9.2006, http://www.nytimes.com/2006/09/07/science/07stem.html

NYT 2.9.2006

Seeking Healthy Children, Couples Cull Embryos NYT 3.9.2006

http://www.nytimes.com/2006/09/03/health/03gene.web.html

The DNA Age

Seeking Healthy Children,

Couples Cull Embryos

September 3, 2006
The New York Times
By AMY HARMON

As Chad Kingsbury watches his daughter playing in the sandbox behind their suburban Chicago house, the thought that has flashed through his mind a million times in her two years of life comes again: Chloe will never be sick.

Not, at least, with the inherited form of colon cancer that has devastated his family, killing his mother, her father and her two brothers, and that he too may face because of a genetic mutation that makes him unusually susceptible.

By subjecting Chloe to a genetic test when she was an eight-cell embryo in a petri dish, Mr. Kingsbury and his wife, Colby, were able to determine that she did not harbor the defective gene. That was the reason they selected her, from among the other embryos they had conceived through elective in vitro fertilization, to implant in her mother’s uterus.

Prospective parents have been using the procedure, known as preimplantation genetic diagnosis, or P.G.D., for more than a decade to screen for genes certain to cause childhood diseases that are severe and largely untreatable.

Now a growing number of couples like the Kingsburys are crossing a new threshold for parental intervention in the genetic makeup of their offspring: They are using P.G.D. to detect a predisposition to cancers that may or may not develop later in life, and are often treatable if they do.

For most parents who have used preimplantation diagnosis, the burden of playing God has been trumped by the near certainty that diseases like cystic fibrosis and sickle cell anemia will afflict the children who carry the genetic mutation that causes them. The procedure has also been used to avoid passing on Huntington’s disease, a severe neurological disease that typically doesn’t surface until middle age but spares no one who carries the mutation that causes it.

Couples like the Kingsburys, by contrast, face an even more complex calibration. They must weigh whether their desire to prevent suffering that is not certain to occur justifies the conscious selection of an embryo and the implicit rejection of those that carry the defective gene.

As doctors and genetic counselors at leading cancer centers like Memorial Sloan-Kettering in New York start to suggest the possibility of P.G.D., more young patients are finding that their answer lies in trading natural conception for the degree of scientific control offered by the procedure. And if the growing interest in screening for cancer risk signals an expanded tolerance for genetic selection, geneticists and fertility experts say it may well be accompanied by the greater use of preimplantation diagnosis to select for characteristics that range from less serious diseases to purely matters of preference.

Already, it is possible to test embryos for an inherited form of deafness or a mild skin condition, or for a predisposition to arthritis or obesity. Some clinics test for gender. As scientists learn more about the genetic basis for inherited traits, and as people learn more about their genetic makeup, the embryo screening menu and its array of ethical dilemmas are only expected to grow.

“From a technology perspective we can test anything,” said Mark Hughes, director of the Genesis Genetics Institute in Detroit, who is performing P.G.D. this month for two couples who want to avoid passing on a susceptibility to breast cancer. “The issue becomes what is considered serious enough to warrant such testing and who decides that.”

The process is also difficult and expensive. P.G.D., which requires in vitro fertilization, can cost tens of thousands of dollars. While insurance companies often pay for the more traditional uses of the procedure, they have not done so for cancer-risk genes, fertility experts say. The barrier to affordability, some critics fear, could make preimplantation diagnosis for cancer risk the first significant step toward a genetic class divide in which the wealthy will become more genetically pure than the poor.

Knowing that Mr. Kingsbury had tested positive for the colon cancer mutation, the Kingsburys started with the basic laws of genetics: because children randomly inherit half of each parent’s genes, he had a 50 percent chance of passing it on. Since the mutation raises the risk of developing the cancer by about twentyfold, that means any child of theirs conceived the traditional way would have about a one in three chance of getting it, usually around age 45. Those who did develop the cancer would also have a nearly 90 percent chance of surviving it, but only if it was caught early.

The jumble of odds meant little to the Kingsburys as they tried to think about starting a family while the cancer claimed Mr. Kingsbury’s second uncle. Then, from a cousin of Mr. Kingsbury’s who had also fought colon cancer, they heard about P.G.D., the technology that offered them a way to reload the genetic dice.

To do it, they had to overcome their own misgivings about meddling with nature. They had to listen to the religious concerns of Mr. Kingsbury’s family and to the insistence of Ms. Kingsbury’s that the expense and physical demands of in vitro fertilization were not worth it, given that the couple could probably get pregnant without it. They had to stop asking themselves the unanswerable question of whether a cure would be found by the time their child grew up.

It took them two months to make the decision. But every time Mr. Kingsbury looks at Chloe, with her blue saucer eyes and her tantrums that turn abruptly to laughter — and back — he knows it was worth it.

“I couldn’t imagine them telling me my daughter has cancer,” he said, “when I could have stopped it.”

Shifting Medical Advice

Cancer-prone families are only just beginning to hear about P.G.D. in part because the procedure falls through the cracks in medicine. Oncologists tend not to think about family planning, and obstetricians tend not to think about cancer genetics. Doctors may also shy from raising the prospect of what some critics call “unnatural selection.”

For many couples, going to such lengths to ensure that a child will be born free of a predisposition to a certain kind of cancer is anathema. Breast and colon cancer, the two most common cancers for which genetic susceptibility tests are available, can be detected early and are often treatable, and even those who die of them often lead long and productive lives.

Many people without the risk-raising genes still get one of the cancers, and those who do carry the genetic mutations are just as likely as anyone else to develop other forms of the disease.

Prospective parents who want to avail themselves of P.G.D. must first undergo the same in vitro fertilization process often used to assist infertile couples, in which eggs are extracted from the mother and fertilized with the father’s sperm in a petri dish. When the resulting embryos are three days old, doctors remove a single cell from each and analyze its DNA. Only embryos without the defective gene are then considered candidates to implant in the mother’s uterus.

The out-of-pocket costs often exceed $25,000, depending on how many in vitro cycles are required. Because embryos are selected for their genetic status, rather than solely by which look the healthiest, the chance that they will fail to develop after implantation is higher. And despite the birth of thousands of apparently healthy babies after P.G.D., there is still concern that the long-term effects of removing a cell from an eight-cell embryo have not been studied enough.

That has not stemmed the rising demand to screen embryos for cancer-risk genes. No one tracks the number of such procedures in the United States, but an article in next month’s issue of The Journal of Clinical Oncology reports that clinics around the country have been quietly performing P.G.D. for hereditary cancers of the breast and the colon. The article, written by Dr. Kenneth Offit, chief of clinical genetics at Memorial Sloan-Kettering Cancer Center, suggests there would be even more interest in P.G.D. if oncologists were to begin informing prospective patients of the option.

About one in every 200 Americans carry a genetic mutation that makes them more susceptible to breast or colon cancer. The half-million or so who carry mutations in several genes associated with colon cancer have up to a 70 percent chance of developing the disease, compared with 6 percent for those with normal copies of the genes. One in eight American women will develop breast cancer in their lifetimes, but for those who carry mutant forms of the BRCA1 or BRCA2 genes, the risk jumps to one in two.

Until the last year or so, Dr. Offit said in an interview, he questioned the utility of P.G.D. for his patients, focusing instead on the increasingly effective prevention and treatment options for anyone born with an elevated cancer risk. Genetics, he said, is not necessarily destiny.

But learning of its existence, Dr. Offit noticed, could make many young patients less fatalistic about their genes and more optimistic about starting a family. The sense of relief it offered was especially strong among those who had seen a parent or a sibling die of cancer.

“Having seen so many children from cancer-prone families, I’m more sensitive to the sentiment that they would rather avoid the syndrome altogether,” Dr. Offit said. “Our genetic counselors now try to bring up the potential of this technology in circumstances where we think it may be empowering to young couples.”

Too Late for Some Carriers

If other cancer centers follow Sloan-Kettering’s lead, the shift will still come too late for some cancer gene carriers. One woman, a professional in New York, said she blamed bad medical advice for her having possibly passed to her 4-year-old daughter a chance of developing breast cancer this is five times as great as that of women in the general population.

Unaware of P.G.D., she followed the counsel given to most women with a family history of breast cancer and had her children before getting tested for the gene. The logic is that women ought not worry about their genetic status until they can consider the most effective prophylactic measures, removing their breasts and ovaries.

But in postings to an online breast cancer support group, facingourrisk.org, the woman said she suspected that the prevailing unease over genetic selection and the question of when life begins also kept doctors from suggesting P.G.D.

“Those values should not be dictating recommendations by doctors,” said the woman, 40, who declined to be identified by name because her words might be hurtful to her family. “That’s what I resent. I feel like the choice was taken away from me.”

In Europe, divergent values are quite explicitly shaping different P.G.D. policies. This spring, England approved the use of preimplantation diagnosis for the breast and colon cancer risk genes. In Italy, the procedure has been effectively banned for any condition.

In the United States, where the technology is not regulated, decisions about when it is appropriate are left largely to fertility specialists and their patients. Reflecting the growing demand for the procedure, the company that owns the tests for the breast cancer genes recently licensed the right to use them to three fertility centers.

“We decided we don’t want to do it here,” said William Hockett, a spokesman for the company, Myriad Genetics of Salt Lake City, citing both moral preferences and a disinclination to invest in the technique for business reasons. “But we don’t want to impose our values on society, so we felt we should allow others to do it if they wished.”

The interest in embryo testing is being driven largely by a greater knowledge of genetics among cancer patients and their family members. In the last five years, nearly 10 times as many Americans have been tested for the breast-cancer risk genes as in the previous five, according to Myriad, surpassing a total of 100,000 since the test was made available in 1996.

Familiarity with their own genetic profile makes some people more comfortable with intervening to alter their children’s. For them, genetic traits can seem less like destiny and more like any other part of their lives that can be improved by technology.

Many of those exploring P.G.D. are the first generation of women to have reached reproductive age after their mothers developed cancer and tested positive for one of the breast cancer mutations. They see it as saving not just their children but generations of descendants from the same fate.

“I was very relieved to know that I would not have to pass this gene on to my children,” said Michaela Walsh, 20, a junior at Susquehanna University in Selinsgrove, Pa., who found out she carries a BRCA mutation. She has already decided she wants to use P.G.D. when she has children. “My mother told me that the only worse thing than having cancer twice was having to give the gene to me.”

But the same knowledge makes others who carry the mutations take particular offense at the selection procedure, which they say implies that they themselves, and many members of their family, should never have existed. It raises the specter of eugenics, they say, in the most personal terms.

“It’s like children are admitted to a family only if they pass the test,” said Denise Toeckes, 32, a teacher who tested positive for a BRCA mutation. “It’s like, ‘If you have a gene, we don’t want you; if you have the potential to develop cancer, you can’t be in our family.’ ”

Other critics oppose preimplantation diagnosis on the grounds that it could be used to select against homosexuals, women or people with disabilities. It reduces people to their genes, they say, and paves the way for the pursuit of children designed to suit parental ideals and for discrimination against those born with perceived imperfections.

Proponents of the technology say that confusing the concept of “designer babies” with people trying to avoid deadly illnesses is hurtful and misleading. No one, they say, would endure the substantial physical and emotional difficulty posed by the process to make a baby with blue eyes and a wicked curveball. Still, the hostility couples have encountered from friends, family, colleagues and even medical professionals caused several of those interviewed for this article to request that their names be withheld.

One prospective father, a medical resident at Johns Hopkins Hospital in Maryland, said the Shady Grove Fertility Center, the local fertility clinic, required that he and his wife, also a resident at Hopkins, write a letter justifying their request for P.G.D. to the clinic’s ethics committee.

The doctor’s own father continually warned that in trying to prevent cancer, removing a cell from the embryo would create a mentally retarded child — no matter how many times his son cited studies to the contrary. Reactions from colleagues made the couple worry that if they allowed their names to be used, it might hurt their chances when applying for jobs at medical or research institutions.

“It became such a negative topic of conversation that my wife and I decided, ‘We’re not talking about this to anyone,’ ” said the doctor, 30, whose mother has had her breasts, uterus and ovaries removed to combat her cancer, in addition to undergoing dozens of chemotherapy sessions.

The couple held firm in their belief that there was no virtue in letting nature take its course when its outcome was so potentially damaging. “We hope to look back on this as really the first decision we made as parents,” they wrote in a letter to the ethics committee that persuaded the clinic to let them move ahead.

Multiplying Decisions

Even for those who choose it, the burden of selection weighs heavily. Kim Surkan, who carries the BRCA1 breast cancer mutation, said her partner had initially described preimplantation diagnosis as a “pact with the devil.” As Ms. Surkan prepares for her eggs to be extracted next month, she has nightmares that the child she selects will drown in a swimming pool, as opposed to a child chosen by fate, who might carry the cancer-risk gene but would have been a good swimmer.

“At least I know I’ve done whatever I can do with the information I have,” said Ms. Surkan, an adjunct lecturer in women’s studies at the Massachusetts Institute of Technology. “I can’t control everything.”

Like many people who want to take advantage of P.G.D. but cannot easily afford it, Ms. Surkan had to first convince her insurance company that she was infertile so that it would pay for the in vitro fertilization process. Because she is in a same-sex couple, that meant she had to undergo several cycles of insemination, hoping that she would in fact not get pregnant, so that she could proceed with preimplantation diagnosis.

Now more decisions are coming. What if, she wonders, she is unlucky, and all her embryos have disease genes? Should she implant a male one, since men rarely develop breast cancer, even if she is opposed to selection based on gender?

If she does get pregnant with an embryo found to be free of the gene, should she test the fetus at 16 weeks, since there is up to a 3 percent chance that P.G.D. will fail to detect an unwanted mutation? If she has two embryos implanted, and one has the defective gene, should she terminate it?

For many couples, preimplantation diagnosis is an appealing option precisely because it does not require terminating a pregnancy, a step that is common after an amniocentesis reveals that a fetus has a severe genetic disease but is essentially unheard of for predisposition to common cancers.

Danielle Jamond, who carries a gene for a severe form of inherited colon cancer, said she and her husband were considering that option a year ago. But she was saved from making the choice when she heard of a doctor who had developed a P.G.D. procedure for her form of the disease.

“At that point, the choice was obvious,” said Ms. Jamond, a human resources manager in a suburb of Paris, who has had her large intestines removed to avoid getting the cancer, a prophylactic measure for people with her genetic mutation.

Four embryos were created from her 12 eggs, and three did not have the genetic mutation. One died, the other two were implanted, and one survived. She is now six months pregnant with the surviving one, a girl.

But some people who believe life begins with conception think P.G.D. is as unethical as abortion and perhaps more pernicious because it is psychologically less burdensome. Unused embryos may be frozen indefinitely, skirting one moral issue, but at a cost of several hundred dollars a year. Reproductive Genetics Institute, a leading P.G.D. lab in Chicago that performed the preimplantation diagnosis for the Kingsburys, said about half the embryos containing the unwanted genetic profile were discarded and half donated to research.

‘Is This Genetic Engineering?’

Already, thousands of couples who are undergoing in vitro fertilization to overcome infertility use P.G.D. to weed out embryos that harbor common chromosomal disorders that would otherwise be screened for by amniocentesis. Fertility experts say they may be the first to take advantage of the procedure for a range of other genetic conditions.

Dr. Ina N. Cholst, a reproductive endocrinologist at Weill Medical College of Cornell University, said a fertility patient of hers who suffers from an inherited arthritic condition called ankylosing spondylitis was planning to add genetic diagnosis to her in vitro procedure. She has a 50 percent chance of passing the gene to a child. Of those who carry it, four of five will be unaffected. The others will have arthritis, sometimes mild and sometimes quite severe, but increasingly treatable.

“We brought it up,” said Dr. Cholst, who consulted with the patient’s rheumatologist. “At the same time, I am thinking, ‘Is this a wonderful thing, or is this genetic engineering?’ ”

In the future, many specialists believe, most in vitro fertilizations will be performed for fertile couples seeking genetic diagnosis, not as a treatment for infertility. But as it becomes easier to identify the possible consequences of more kinds of genes, the decisions for parents may become harder. Having passed over 4 embryos with the defective gene and identified 10 healthy ones, the Kingsburys were asked if they wanted to pay $2,000 extra to test them for Down syndrome. That test eliminated two more.

“You kind of feel like you shouldn’t be doing it,” Ms. Kingsbury said. “But then why would we go through all of this and not take those extra precautions?”

Soon, experts say, prospective parents may be able to choose between an embryo that could become a child with a lower risk of colon cancer who is likely to be fat, or one who is likely to be thin but has a slightly elevated risk of Alzheimer’s, or a boy likely to be short with low cholesterol but a significant risk of Parkinson’s, or a girl likely to be tall with a moderate risk of diabetes.

For the Kingsburys, the choice is still clear. Like any parents, they plan to tell Chloe the story of her birth. And if all goes well, they say, she will soon have a sibling who shares a similar tale.

Seeking Healthy Children, Couples Cull Embryos, NYT, 3.9.2006, http://www.nytimes.com/2006/09/03/health/03gene.web.html

Clarification Issued on Stem Cell Work

September 2, 2006
The New York Times
By NICHOLAS WADE

The scientific journal Nature has corrected a press release and is considering whether to add further information to an article published last week reporting that human embryonic stem cells could be generated without destroying an embryo.

The article has political consequences because destruction of embryos, which is unavoidable with present methods, is the main stated objection of many who oppose embryonic stem cell research.

The journal’s action follows numerous news reports on the article and criticism from the United States Conference of Catholic Bishops, which pointed out that embryos used in the research were being destroyed, a fact made clear in the scientific paper but not the press release.

Both the journal and the principal author of the article, Dr. Robert Lanza of Advanced Cell Technology, say that the scientific report is correct and that any addition would be solely for purposes of clarification.

“We’re looking to see if the description is clear, but there is nothing wrong with the paper,” a Nature press officer, Ruth Francis, said yesterday.

For about 10 years, fertility clinics have sometimes used a genetic diagnostic test in which a single cell is removed from an embryo at the eight-cell stage to be tested for abnormalities like Down syndrome. If no defect is found, the embryo with its remaining seven cells is implanted in the womb and grows to term. Babies born from seven-cell embryos seem as healthy as others born after in vitro fertilization.

Dr. Lanza noted in his article that the cell removed in this test, known as preimplantation genetic diagnosis, or P.G.D., could be used, after growing and dividing, both for testing and, with his new technique, to derive human embryonic stem cells. Since the original embryo would be unharmed, a principal objection to the research would be removed, he said.

Dr. Lanza’s article in Nature made clear that he had not saved the embryos in his own experiments, in which he used as many as eight cells from each of some 16 donated embryos. Had he taken only a single cell from each, many more embryos would have been needed. The press release issued by Nature, however, incorrectly implied that he had removed just a single cell.

After news accounts based on the press release drew criticism from the bishops conference, which opposes in vitro fertilization and human embryonic stem cell research, Nature corrected its statement to make clear that Dr. Lanza’s embryos had been destroyed. But the revised statement said other researchers, as he had noted, could use his technique to derive stem cells from cells removed in P.G.D.

Dr. Lanza said yesterday that Nature had not shown him the original press release before publication.

Clarification Issued on Stem Cell Work, NYT, 2.9.2006, http://www.nytimes.com/2006/09/02/science/02stem.html