Four deaths in patients using painkiller
Thu, 13 Sep 2007 20:06:56 GMT
WASHINGTON - The deaths of two patients prescribed a powerful painkiller as a headache treatment were among four fatalities linked to the recently approved drug, its manufacturer reported Thursday.
All four deaths apparently involved improper use of the drug, called Fentora, manufacturer Cephalon Inc. said. The Food and Drug Administration was monitoring the situation, a spokeswoman said.
The FDA approved the drug in September for use only by cancer patients already taking morphine or other prescription narcotics for their pain. Fentora contains fentanyl, which is similar to morphine, but far more potent.
Besides the two headache patients, the other deaths involved a suicide and a patient administered the drug outside the recommended dosing.
"None of the reports were in cancer patients, which leads us to believe they were inappropriate candidates for the product," Cephalon spokeswoman Candace Steele said.
Cephalon reminded doctors and pharmacists, in letters dated Monday but released Thursday by the FDA, of who should take the drug, and in what quantities and how often. The company also warned not to substitute Fentora on a one-for-one basis for another, older fentanyl drug called Actiq that it also makes, because the newer drug is stronger.
"The FDA takes this very seriously, and is working with the company to assure the safest possible use of this medication," agency spokeswoman Susan Cruzan said.
Steele said the deaths were not linked to allegations subject to investigation that Cephalon engaged in improper promotion of Fentora and other drugs for uses other than those outlined in their FDA-approved labels. While it's not illegal for doctors to prescribe drugs for so-called "off-label" uses, companies are prohibited from marketing medicines for those purposes.
Last month, Frazer, Pa.-based Cephalon said it was cooperating with the investigations by Congress, the U.S. attorney's office in Philadelphia and Connecticut attorney general.
Doctors have written about 78,000 prescriptions for Fentora tablets since October, Steele said.
___
On the Net: FDA medical product safety alerts:
http://www.fda.gov/medwatch/safety/2007/safety07.htm#Fentora
MDs use experimental cooling on Everett
Thu, 13 Sep 2007 08:49:20 GMT
By MARILYNN MARCHIONE, AP Medical Writer
Doctors are following the playbook in treating Buffalo Bills football player Kevin Everett's severe spinal cord injury except in one notable regard: pumping icy cold saline into his veins to try to prevent further damage.
Although the treatment is experimental, it is more science than science fiction, and also is being tried on stroke and brain injury patients.
"There are compelling reasons why one might want to try it" in a case like this, said Dr. Gary Steinberg, chairman of neurosurgery at Stanford University. He had no role in Everett's case but has tested the body cooling treatment.
Everett's prognosis remains uncertain. His doctors were encouraged by signs on Tuesday that he could move his legs and arms — a day after saying he stood little chance of making a full recovery. They also have said that his spinal cord was intact rather than severed — a very good sign.
Doctors say that it is far too soon to know whether he will be left with any paralysis or its extent.
"Walking out of this hospital is not a realistic goal, but walking may be," Dr. Andrew Cappuccino, the team's orthopedic surgeon, said at a news conference in Buffalo on Wednesday.
That does not mean a return of his career, though, said Dr. Joseph Maroon, team neurosurgeon for the Pittsburgh Steelers and a University of Pittsburgh Medical Center specialist who was consulted on Everett's case.
"If he ever does regain function, no neurosurgeon would ever permit him to play football," Maroon said.
Everett suffered a fracture and dislocation of his spinal cord in the neck area during a game Sunday night against the Denver Broncos. Watching it on television from home was Dr. W. Dalton Dietrich, scientific director for the Miami Project, a spinal cord program affiliated with the University of Miami Miller School of Medicine.
The program is among several in the United States that has led research into moderate hypothermia, or cooling the body a few degrees to try to limit swelling, inflammation and the cascade of events and chemicals that cause further damage after an initial neurological injury.
Dietrich sent an urgent e-mail to fellow neurosurgeon Dr. Barth Green, who knows Buffalo Bills owner Ralph Wilson.
Who did what next is unclear, but doctors say Everett received the experimental cooling therapy in the ambulance, even before X-rays and other tests could show the extent of his injury and the treatment he would need.
The goal of the treatment is "to cool the tissue a few degrees to reduce its need for oxygen and to reduce its metabolic rate" and limit secondary damage from chemicals the body releases after the initial injury, said Dr. Elad Levy, a University of Buffalo neurosurgeon who treated Everett.
On Monday, as Everett's temperature began to rise, doctors decided to try cooling his body again, using a slightly different system. This time, a hollow tube called a catheter was inserted into the femoral vein in the leg near the groin. Cold saline was circulated inside the catheter, indirectly cooling the blood as it flowed through the vein.
"We did this here at the University of Pittsburgh in the 70s," but with a different method of threading a catheter directly over the spinal cord, Maroon said. The treatment had to be done within three hours of injury to have any benefit and was extremely cumbersome, he said. For that and other reasons, it was largely abandoned until recently, when doctors have resumed testing it through different cooling methods for stroke and brain injury patients.
"Not a lot is known about it for spinal cord injury," said Steinberg at Stanford, where it mostly is done in some stroke and head injury cases under an experimental protocol.
Other aspects of Everett's care are more routine.
He received large intravenous doses of methylprednisolone, a steroid to limit inflammation and swelling, and had decompression surgery to relieve pressure on his spinal cord.
Doctors initially operated from the front of his neck, removing the injured disk and bone impinging on the spinal cord, and realigned it. They filled the space where the disk had been with a bone graft — whether from a cadaver or his hip isn't known — and put in a titanium plate to stabilize the neck area.
Surgeons then turned him over and operated from the back of his neck, fusing the vertebrae above and below the fracture, and putting in four screws and two small rods.
Long-term results from such operations can vary widely, said Maroon, the Steelers' surgeon who published a paper in the April issue of Journal of Neurosurgery on this topic. He has operated on about 30 athletes.
On Wednesday, Everett was successfully removed from the respirator though doctors say it could be a struggle to keep him breathing on his own. A stroke and blood clots in his legs are other possible complications they are trying to prevent.
He showed more ability to move his legs and a little more in his arms, but has no movement or function at all of his hands. He is getting nourishment from a feeding tube, and his mother is at his side.
"She understands that this is a life-changing event," and that "the story will change over months to years," said Dr. Kevin Gibbons, another University of Buffalo neurosurgeon who has been treating Everett.
___
On the Net:
Spinal cord center: http://www.themiamiproject.org/
Body cooling system: http://www.alsius.com/
Study Pollution raises exercise risks
Thu, 13 Sep 2007 01:08:12 GMT
By LINDA A. JOHNSON, Associated Press Writer
People with heart disease may want to steer clear of heavy traffic when exercising or simply take their workout indoors to avoid breathing polluted air.
Exercising in areas with high levels of diesel exhaust and microscopic soot particles is especially risky for people with heart disease, according to the first study in which heart patients were directly exposed to pollution.
European researchers found that brief exposure to diluted diesel exhaust during exercise reduced a key anticlotting substance in the blood and worsened exercise-induced ischemia, or insufficient flow of blood and oxygen to the heart — changes that can trigger a heart attack and even death.
"We now have evidence that being exposed to diesel fuel during exercise will cause cardiac ischemia and that if you have heart disease, it can only make things worse," said Dr. Abraham Sanders, a lung specialist at New York-Presbyterian Hospital who was not involved in the study.
The results have big implications: About 16 million Americans have heart disease, according to the American Heart Association. In addition, people with asthma, bronchitis and chronic obstructive pulmonary disease also should use caution and avoid polluted air when exercising, Sanders recommended. But heart and respiratory patients should keep exercising regularly because it is so beneficial to overall health, doctors stress.
Numerous studies have shown a link between short-term and long-term exposure to air pollution and higher rates of hospitalizations and deaths due to poor blood supply to the heart, abnormal heart rhythms, gradual heart failure and stroke.
This study adds to that knowledge about how air pollution harms people and aims to show what pollution is doing in the body, information that might eventually give clues for preventing such problems, said Dr. Howard M. Kipen, director of clinical research at Rutgers University's Environmental and Occupational Health Sciences Institute.
"It's quite amazing, what they found," but not a surprise, he said. Still, "most doctors aren't aware that little bits of pollution can cause heart attacks."
The European study was reported in Thursday's New England Journal of Medicine.
Researchers in Sweden and the United Kingdom tested 20 men aged about 60 who had survived a heart attack at least six months earlier, had blockages cleared and propped open with a stent, and were getting treatment to prevent a second heart attack. The researchers noted they only tested men with stable heart disease and good tolerance for exercise, and monitored each closely to ensure none suffered any health problems.
On two separate occasions, each man was put in an enclosed chamber for an hour and exposed to either diluted diesel exhaust or clean, filtered air. They rode an exercise bike for two 15-minute periods and rested in between. The men had electrodes attached to their bodies to monitor the heart's electrical activity, like what happens in a standard heart stress test.
While exercising and exposed to diesel exhaust, the men experienced drops in the heart's electrical activity two to six times greater than when they were breathing filtered air. Those reductions indicated the heart muscles were not getting enough blood.
While diesel exhaust contains many harmful chemicals, the researchers said they believe that particulates in the exhaust are the main harm to the heart patients.
A 2000 study in six U.S. cities found the strongest association between risk of death in heart patients and air pollution exposure was for microscopic air particulates, such as those in diesel exhaust.
The European researchers noted particulate concentrations can regularly hit 300 micrograms per cubic meter — the level to which the study participants were exposed — in heavy traffic, workplaces such as factories and refineries and in the world's largest cities. Levels of some of the pollutants in the diesel exhaust were far above the limits recommended by the World Health Organization, they noted.
This study only included men, but Sanders said he thinks the findings probably apply to women. A recent report from the federal Women's Health Initiative found exercise in polluted environments causes a temporary reduction in blood flow to the heart muscle.
In an editorial, Dr. Murray A. Mittleman of Beth Israel Deaconess Medical Center in Boston wrote, "these findings may represent the tip of an iceberg" on how spikes in air pollution levels affect cardiovascular risk.
Kipen said his institute also studies health effects of diesel exhaust, generally on healthy people under age 45, but they use a more natural setting rather than an exposure chamber.
"We put them in a car and drive them around on the turnpike at rush hour for two hours," Kipen said.
___
On the Net:
New England Journal: http://www.nejm.org
American Heart Association: http://www.americanheart.org/presenter.jhtml?identifier4419
Report Number of U.S. deaths up in 2005
Thu, 13 Sep 2007 08:51:40 GMT
By MIKE STOBBE, AP Medical Writer
ATLANTA - The number of deaths in the United States rose in 2005 after a sharp decline the year earlier, a disappointing reversal that suggests the 2004 numbers were a fluke. Cancer deaths were also up.
U.S. health officials said they believe the drop in deaths seen earlier may have been due to 2004's unusually mild flu season. Deaths from flu and lower respiratory disease jumped in 2005.
The new mortality data was released Wednesday in a report by the National Center for Health Statistics. It was a preliminary report, based on about 99 percent of the death records reported in all 50 states and the District of Columbia for 2005.
Last year, statistics from 2004 showed U.S. deaths fell to 2,397,615. It was a decline of about 50,000 from 2003, and was the largest drop in deaths in nearly 70 years. Some experts saw it as a sign of the triumph of modern medicine.
But the preliminary 2005 death count was up more than 50,000 — about 2,447,900 — almost back to the 2003 level.
"The best way to look at this is in five-year groupings, because every once in a while you are going to have an aberration," said Ken Thorpe, an Emory University health policy professor.
An unusually mild flu season in 2004 cut the flu death rate — deaths per 100,000 population — by 7 percent. And it likely had a ripple effect by not worsening the condition of frail patients who ultimately died of something else, government health scientists said.
The 2005 flu season was closer to normal, and deaths from the virus rose by more than 3,000 from 2004. Deaths from chronic lower respiratory diseases increased by nearly 9,000.
Heart disease and stroke — the No. 1 and No. 3 killers — killed fewer people in 2005 than 2004. But the No. 2 cause of death, cancer, rose to about 559,000 from 554,000, according to the report.
The overall age-adjusted rate for all deaths in 2005 fell to 799 per 100,000 population, down from 801 per 100,000 in 2004. The 2005 rate was an all-time low, but the rate has been in a general decline for more 50 years, according to government data.
The death rates for heart disease, stroke and cancer all declined too. The death rate was 210 per 100,000 for heart disease; 184 for cancer; and 46.5. for stroke.
The success against heart disease is at least partly due to better treatments, which overcame the impact of an aging, growing population, Thorpe said.
But with total cancer deaths, there was no such offset in 2005. "That's unfortunate news," he said.
"You continue to hope with earlier detection diagnosis and treatment, we will pick these things up faster" and prevent deaths. But because a growing number of Americans lack health insurance, many may not be getting those services, Thorpe said.
U.S. life expectancy inched up to 77.9 from the previous record, 77.8, recorded for 2004. The increase was more dramatic in contrast with 1995, when life expectancy was 75.8, and 1955, when it was 69.6.
A final report will be released later, and the numbers may change a little. Last year, when releasing its preliminary death data for 2004, the government reported a 77.9 life expectancy. That figure later dropped to 77.8 in the final report.
"If death rates from certain leading causes of death continue to decline, we should continue to see improvements in life expectancy," said study co-author Hsiang-Ching Kung, in a prepared statement.
Researchers also noted continued differences by race and sex. Life expectancy for whites in 2005 was 78.3, the same as in 2004. Black life expectancy rose from 73.1 in 2004 to 73.2 in 2005, but it was still nearly five years lower than the white figure.
Life expectancy for women continues to be five years longer than for men, the report also found. The infant mortality rate remained roughly the same as the previous year, about 6.9 per 1,000 live births.
Also, there were 5 percent increases in the rates for Alzheimer's disease, the No. 7 leading cause of death, and for Parkinson's disease, which was No. 14.
The United States continues to lag at least 40 other nations. Andorra, a tiny country in the Pyrenees mountains between France and Spain, has the longest life expectancy, at 83.5 years, according to a U.S. Census Bureau analysis of 2004 international data. It was followed by Japan, Macau , San Marino and Singapore.
___
On The Net:
National Center for Health Statistics: http://www.cdc.gov/nchs
Obesity may raise the risk of stillbirth
Thu, 13 Sep 2007 16:37:32 GMT
By Amy Norton
NEW YORK -
Obese pregnant women may have
an increased risk of losing their baby relatively late in
pregnancy, and black women appear particularly at risk, a large
study suggests.
Researchers found that obese women were 40 percent more
likely than normal-weight and overweight women to have their
pregnancy end in stillbirth -- defined as fetal death in the
20th week of pregnancy or later.
African-American women were especially at risk. Compared
with obese white women, their rate of stillbirth was 90 percent
higher, the study authors report in the journal Obstetrics &
Gynecology.
Part of the reason for the obesity-stillbirth link may rest
in the fact that obese women are more prone to diabetes and
high blood pressure in pregnancy, explained Dr. Hamisu Salihu,
an associate professor at the University of South Florida in
Tampa and the study's lead author.
Because black women have higher rates of these pregnancy
complications than white women do, this may also help explain
the racial gap, according to the researchers.
However, diabetes and high blood pressure are not the whole
story, Salihu told Reuters Health, and other factors must be at
work.
For example, he explained, obese women also have higher
levels of lipids -- blood fats such as cholesterol. These fats
suppress a substance called prostacyclin, which can narrow the
blood vessels and promote blood clotting in vessels supplying
the fetus.
Whatever the reason for the higher risk of stillbirth, the
best way to reduce these odds is for obese women to shed weight
before getting pregnant, according to Salihu.
&;Weight reduction before becoming pregnant should be the
cornerstone of any strategy that aims to reduce the high level
of risk for stillbirth among obese mothers,&; he said.
The findings are based on pregnancy outcomes of more than
1.5 million Missouri women who were pregnant between 1978 and
1997. Salihu's team found not only that obesity raised the risk
of stillbirth, but also that the odds continued to climb with
the degree of obesity.
Women who were classified as extremely obese had nearly
double the risk of stillbirth as women who were normal-weight
or overweight before becoming pregnant.
While weight loss before pregnancy may be the best way to
prevent these stillbirths, this is clearly not possible for all
women. According to Salihu, researchers still need to determine
the best way to manage obese women's pregnancies in order to
lower the risk of stillbirth.
Obesity itself has only recently been recognized as a risk
factor for stillbirth, he noted, and there are no standard
recommendations on how doctors should address the problem.
SOURCE: Obstetrics & Gynecology, September 2007.
Salmon spawn baby trout in experiment
Thu, 13 Sep 2007 20:56:34 GMT
By LAURAN NEERGAARD, Associated Press Writer
WASHINGTON - Papa salmon plus mama salmon equals ... baby trout? Japanese researchers put a new spin on surrogate parenting as they engineered one fish species to produce another, in a quest to preserve endangered fish.
Idaho scientists begin the next big step next month, trying to produce a type of salmon highly endangered in that state — the sockeye — this time using more plentiful trout as surrogate parents.
The new method is "one of the best things that has happened in a long time in bringing something new into conservation biology," said University of Idaho zoology professor Joseph Cloud, who is leading the U.S. government-funded sockeye project.
The Tokyo University inventors dubbed their method "surrogate broodstocking." They injected newly hatched but sterile Asian masu salmon with sperm-growing cells from rainbow trout — and watched the salmon grow up to produce trout.
The striking success, published in Friday's edition of the journal Science, is capturing the attention of conservation specialists, who say new techniques are badly needed. Captive breeding of endangered fish is difficult, and attempts to freeze fish eggs for posterity so far have failed.
"They showed nicely that ... they produced the fish they were shooting for," said John Waldman, a fisheries biologist at Queens College in New York.
"Future work should look to expand this approach to other fishes in need of conservation, in particular, the sturgeons and paddlefish," he added. "We have a lot of species of fish around the world that are really in danger of becoming extinct."
The Japanese researchers' ultimate goal: Boost the rapidly dwindling population of bluefin tuna, a species prized in a country famed for its tuna appetite.
"We need to rescue them somehow," said Goro Yoshizaki, a Tokyo University marine scientist who is leading the research.
First, Yoshizaki's team started with "salmonids," a family that includes both salmon and trout, and one of concern to biologists because several species are endangered or extinct.
Initial attempts to transplant sperm-producing cells into normal masu salmon mostly produced hybrids of the two species that didn't survive.
This time, Yoshizaki engineered salmon to be sterile. He then injected newly hatched salmon with stem cells destined to grow into sperm that he had culled from male rainbow trout.
Once they were grown, 10 of 29 male salmon who got the injections produced trout sperm, called milt.
Here's the bigger surprise: Injecting the male cells into female salmon sometimes worked, too, prompting five female salmon to ovulate trout eggs. That's a scientific first, Yoshizaki said.
The stem cells were still primitive enough to switch gears from sperm-producers to egg-producers when they wound up inside female organs, explained Idaho's Cloud.
Then Yoshizaki used the salmon-grown trout sperm to fertilize both wild trout eggs and the salmon-grown trout eggs. DNA testing confirmed that all of the dozens of resulting baby fish were pure trout, he reported.
Moreover, those new trout grew up able to reproduce.
Those first experiments, funded by a Japanese research institute, used still fairly plentiful species to develop the technique. Now comes Idaho's attempt to prove if the method is really useful in trying to produce the endangered sockeye salmon.
Last January, Yoshizaki helped University of Idaho scientists collect and freeze immature sperm tissue from young sockeye salmon being raised at a state-run hatchery. Next month, he'll be back to help Cloud thaw the tissue and implant it into sterile rainbow trout.
In Japan, Yoshizaki is focused on bluefin tuna, noting that standard "marine ranching" techniques are difficult for tuna that can reach man-size.
He has begun experiments into how to produce baby tuna from mackerel, which are nearly a thousand times smaller than adult tuna. If it works, "we can save space, cost and labor," he predicted in an e-mail interview.
Mediterranean diet extends life in Alzheimer39s
Thu, 13 Sep 2007 17:58:10 GMT
NEW YORK -
Add yet another health benefit
to eating the Mediterranean way -- the veggie-rich, meat-poor
diet may slow the progress of Alzheimer's disease, a study
hints.
The more closely Alzheimer's patients adhered to the
Mediterranean diet ideal, the longer their lives, Dr. Nikolaos
Scarmeas of Columbia University Medical Center in New York City
and colleagues found.
&;The magnitude of the effect was considerable,&; they write
in the September 11 issue of Neurology.
The researchers had previously shown that eating a
Mediterranean-style diet consisting of lots of fruits,
vegetables, legumes and cereals; plenty of unsaturated fatty
acids, chiefly olive oil; few dairy products or meat and
poultry; a &;moderately high&; intake of fish; and wine during
meals reduced the risk of Alzheimer's disease.
In the current study, they followed 192 people who had been
diagnosed with the disease to determine if the diet would
affect its progression. Study participants were divided into
three groups based on how close their eating habits mirrored
the Mediterranean ideal, and were then followed for 4.4 years,
during which time 85 percent died.
People in the middle group of Mediterranean diet adherence
were 35 percent less likely to die during follow-up than those
in the bottom group, which translated to 1.33 more years of
life. Those in the highest group for adherence were at 73
percent lower risk of death, and lived nearly four years
longer.
&;New benefits of this diet keep coming out,&; Scarmeas noted
in a press release accompanying the study. &;We need to do more
research to determine whether eating a Mediterranean diet also
helps Alzheimer's patients have slower rates of cognitive
decline, maintain their daily living skills, and have a better
quality of life&; the investigator added.
SOURCE: Neurology, September 11, 2007.
Targeted drug combos could outsmart cancer
Thu, 13 Sep 2007 20:42:37 GMT
By Julie Steenhuysen
CHICAGO -
Cancer cells often have a way of
outsmarting new targeted drug therapies, but U.S. researchers
said on Thursday a combination of targeted drugs could shut
down a tumor's backup plan, resulting in much more effective
treatments.
A number of these so-called targeted cancer drugs -- such
as Roche's Tarceva and Novartis' Gleevec -- work by blocking
the activity of various protein switches that tell the cell to
grow. They are known as receptor tyrosine kinases or RTKs.
&;They essentially allow the cell to communicate with the
external world to sense growth factors that could maintain the
survival of a cancer cell,&; said Dr. Ronald DePinho of the
Dana-Farber Cancer Institute and Harvard Medical School, whose
study appears in the journal Science.
These protein switches are on the surface of all cells, and
they go haywire in a number of cancers.
Drugs that target a single switch have transformed the
treatment of some patients with certain cancers -- for
instance, Gleevec and chronic myelogenous leukemia.
But they only work in a small percentage of people. And
certain tumors, including the aggressive brain cancer
glioblastoma multiforme, respond poorly to such drugs.
DePinho and colleagues now believe they know why. His team
studied 20 different batches of glioblastoma cells in the lab
and found that many growth switches were flipped on at once.
In 19 of the 20 cell lines, three or more were switched on.
They tested tumor samples from newly diagnosed cancer patients
and got a similar result.
&;We found there was a multitude of activated receptor
tyrosine kinases,&; DePinho said in a telephone interview. &;When
you would extinguish one with a specific targeted agent, the
other ones would simply step in.&;
'BROADLY APPLICABLE'
When they tried Gleevec, known generically as imatinib, it
had little effect on the cells. But when they combined it with
two other drugs -- Tarceva, known generically as erlotinib, and
Pfizer's SU-11274 -- the growth signal was shut down and the
cancer cells died.
&;It's a very important observation scientifically and it
has immediate clinical implications,&; DePinho said. &;This is
broadly applicable. This paradigm is true for virtually all
solid tumors that we've looked at.&;
He and colleagues hope to start testing combinations of
these targeted therapies in patients.
A person's tumors would be profiled first to determine
which signals are active, and then doctors would pick a drug
combination that would work best.
DePinho said it would take some time to get these therapies
to cancer patients because the drugs used in combination might
turn out to be toxic.
He agreed that a cocktail of targeted drugs would be
costly. Tarceva -- approved to treat lung and pancreatic cancer
-- costs around $3,000 for a 30-day supply.
But he said one of the reasons for the drugs' current high
cost is the high failure rate of drug development.
&;If we can use science ... to design better clinical
trials, the costs will be a lot less,&; DePinho said.