Vaccine for brain tumor may double survival: study


04 jun 2008--An experimental vaccine designed to treat the most common and deadly brain tumor has more than doubled the survival of patients, according to results of a small clinical study released on Monday.
The vaccine, produced by the US firm Avant Immunotherapeutics Inc, stimulates the immune system to attack the glioblastoma multiforme (GBM) tumor.
The clinical trial involved 23 patients with large GBM tumors.
The patients treated with the vaccine lived an average of 33 months while those receiving standard treatment typically live for an average of 14 months, said Dr John Sampson, of Duke University in North Carolina who presented the results at the annual conference of the American Society of Clincial Oncology in Chicago.
The study also showed the vaccine slowed the return of the tumor after surgery. The tumor for those treated with the vaccine reappeared in 16.6 months compared to the usual six months.
The GBM is an aggressive cancer with a poor prognosis, brain specialist Mark Gilbert of the M.D. Anderson Cancer Center in Texas told reporters.
The tumor kills 50 percent of patients during the first year after diagnosis and few live beyond three years. Without treatment the tumor grows back between two to three months after being surgically removed.
The GBM tumor is the same that afflicts longtime US Senator Edward Kennedy who underwent surgery on Monday in Durham, North Carolina.
When asked about Kennedy's case which has generated national media attention, Gilbert said that the senator could possibly benefit from the vaccine if surgery succeeds in completely removing his tumor.
The experimental vaccine, administered with chemotherapy to stimulate an immune response, is aimed at proteins linked to tumor cells.
A much larger clinical trial was planned for later this year, Gilbert said.
About 22,000 cases of malignant tumors of the brain and bone marrow will be diagnosed in 2008 in the United States and 13,000 people will die, according to the American Cancer Society.

Noninfectious Illnesses Are Expected to Become Top Killers

By Donald G. McNeil Jr.
03 jun 2008--As the world’s population ages, gets richer, smokes more, eats more and drives more, noncommunicable diseases will become bigger killers than infectious ones over the next 20 years, the World Health Organization is reporting.
The report, World Health Statistics 2008, shows that diseases like diarrhea, AIDS, tuberculosis, neonatal tetanus and malaria will become less important causes of death as heart disease, cancer, stroke, diabetes and traffic accidents claim greater percentages of victims. There will still be wide disparities, the report says. Infectious diseases will remain major killers in Africa but should decrease in Asia.
Dr. Ties Boerma, director of health statistics for the agency, said he had seen more obese people and more smokers in capitals around the developing world.
“We tend to associate developing countries with infectious diseases,” he said, but heart disease and stroke are becoming “the chief causes of death in more and more countries.”
Annual deaths from AIDS are expected to fall to 1.8 percent of all deaths in 2030 from more than 3 percent now, the report said.
Tobacco companies are aggressively marketing to young people in poor countries. Almost a quarter of smokers started before age 10, the W.H.O. said, and one of its surveys of teenagers found that 20 percent owned clothing with cigarette brand logos. Citing freedom of choice, the companies work to break down traditions preventing women from smoking.
Worldwide, 100 million people each year are impoverished by paying for health care, the report said. And 40 percent of pregnant women and infants do not get basic health care or immunizations.

Earlier diagnosis giving Alzheimer's a new voice


03 jun 2008-- Don Hayen has a handy way of deflecting the instant pity that comes when he reveals his Alzheimer's disease: ''But I haven't lost my keys all day,'' he quickly jokes. Hayen is part of a growing new movement in Alzheimer's: Patients diagnosed early enough to still be articulate and demand better care and better research.
They are giving a voice to a disease whose victims until now have remained largely silent, and powerless.
It's a shift with big ramifications.
Alzheimer's patients are joining their counterparts with cancer and HIV to lobby Congress for more money to hunt treatments. Some are advising top scientists to push for higher-stakes research even if it means higher risks. They're even offering unprecedented glimpses into how a mind slowly unravels as they blog about their dementia.
''It's labeled incurable and you end up being a vegetable. People think as soon as you're labeled that way, you are. A lot of us aren't,'' says Hayen, 74, a retired San Diego physician who joined about 30 other early-stage Alzheimer's patients last month for a lobbying blitz at the nation's capital.
''I can still speak for those who can't.''
More than 5 million Americans are estimated to be living with Alzheimer's disease, although no one knows how many have been diagnosed. But research suggests as many as half of Alzheimer's sufferers may be in the disease's early stages. Doctors say they've begun diagnosing far more people who still have years of independent living ahead them than they did just a few years ago.
And this week, the Alzheimer's Association begins pilot-testing a campaign in three cities -- Richmond, Va., Minneapolis and Oklahoma City -- aimed at increasing early diagnosis. ''Know the signs -- early detection matters,'' advertising will urge.
Diagnosis can be difficult. There is no single test for dementia. Memory problems aren't always even the obvious first symptom; Hayen cites unprovoked anger and disorientation.
But early detection gives people a chance to plan for their future care while they still have the mental capacity to do so.
It also highlights some harsh unknowns. For example, do you medicate right away? Today's drugs merely alleviate symptoms for a temporary period.
''It's going to work a year or two and for whatever reason, it fades out. The question becomes, 'Do you want to use it now or wait until you become more symptomatic and maybe people are talking about your driving privileges?''' says Dr. Ronald Petersen, an Alzheimer's specialist at the Mayo Clinic.
Nor are there many support groups or research studies for high-functioning patients. Even the Alzheimer's Association acknowledges that until recently, its main focus in education and even legislative efforts for such things as respite care has been aimed at caregivers, not patients directly.
''What we're hearing from people with early-stage is they want that same level of attention,'' says program director Dr. Peter Reed, who monitored four meetings around the country that gathered about 300 such patients to advise the association about their needs.
One message: A huge hurdle is the stigma of a disease known mostly for its devastating end stage.
''Automatically people look at you like you're stupid,'' fumes Kris Bakowski, 52, of Athens, Ga., who was diagnosed at the unusually young age of 46 and had to sue to keep her job for almost two extra years, until her symptoms worsened. ''Five minutes ago, you were carrying on a conversation. Now they see a big 'A' on your forehead.''
But dealing with that hurdle is timely -- because increasing early detection also is key to better research into ways to prevent Alzheimer's or at least slow its worsening, several dozenof the disease's top specialist wrote in last month's journal Alzheimer's & Dementia.
Treating memory symptoms is ''like waiting until somebody with heart disease develops chest pains and then treating them,'' says Petersen, who co-authored the report with specialists gathered by the Lou Ruvo Brain Institute to identify research barriers.
A handful of experimental drugs are being tested for their potential to slow Alzheimer's by fighting the buildup of its hallmark brain plaque, called amyloid; some anxiously awaited study results are due out in July. Perhaps more important is testing the brains of healthy elderly people and those with mild memory problems to determine what changes signal impending Alzheimer's -- so-called biomarkers that remain a critical gap in scientific understanding.
Meanwhile, early-diagnosed patients are filling some other gaps, as they share intimate details of how Alzheimer's stealthily infiltrates lives they're struggling to keep as normal as possible.
Take Bakowski, the Georgia woman. She handled flying on an airplane alone to last month's Washington lobbying trip, albeit with a brief panic attack when she had to ask for directions in the airport.

Progress Has Been Made in Fight Against AIDS, but Not Enough, U.N. Report Says

By CELIA W. DUGGER
JOHANNESBURG, 03 jun 2008 — The good news on AIDS: Nearly a million people began life-prolonging drug treatment in developing countries last year. The bad news: 2.5 million people were newly infected with H.I.V.
As new infections continue to far outstrip efforts to treat the sick, the United Nations released a progress report on Monday that highlighted both the notable gains in combating the AIDS epidemic and the daunting scale of what remains to be done.
Unaids and the World Health Organization, two United Nations agencies, had initially set a 2005 deadline for getting three million people in developing countries onto treatment regimens, but that goal was not achieved until last year. In 2007 alone, the number of people receiving antiretroviral therapy rose by 54 percent. Still, that is less than a third of those believed to need the treatment.
There was also significant headway in providing antiretroviral treatments to help prevent women from infecting their babies with H.I.V., the virus that causes AIDS, during pregnancy and childbirth. About a third of H.I.V.-positive pregnant women got the treatments last year, compared with 10 percent in 2004, with the greatest gains in West and Central Africa, the report found.
“It demonstrates our efforts have started to bear fruit,” Patricia Doughty, a program officer at Unicef, said in a telephone briefing.
But even as health systems geared up to prevent mothers from passing on the disease to their children, the needs of the mothers themselves were neglected. Only 12 percent of H.I.V.-positive pregnant women were assessed for whether they needed treatment themselves. When mothers die of AIDS and their children are orphaned, the opportunities and even survival of the babies who were saved from infection are undermined.
The statistics were laid out in “Towards Universal Access: Scaling up Priority H.I.V./AIDS Interventions in the Health Sector,” a collaboration of Unaids, the World Health Organization and Unicef. It is the annual report that documents the provision of prevention, care and treatment services for H.I.V. and AIDS.
More than a year after clinical trials in Africa found that male circumcision reduced the risk of heterosexual men contracting H.I.V. by about 60 percent, “many high burden countries are exploring how and whether to scale up male circumcision programs,” the report said.
Experts estimate that male circumcision, if widely applied in Africa, could avert two million infections and prevent 300,000 deaths over the next decade.
Dr. Kevin M. De Cock, who heads the World Health Organization’s H.I.V./AIDS department, said performing circumcisions on a large scale was no simple task for overstretched health care systems in southern African countries, where the approach was most needed. He acknowledged that adoption of the strategy had been “relatively slow.”
“There has been progress, but it would be nice to see it faster,” he said.

Drug May Cut Tremors Associated With Parkinson's

03 jun 2008-- A new drug may help people with Parkinson's disease combat the tics, spasms and tremors they experience when their main medications wear off, a new study suggests.
Istradfeylline works by helping nerve and brain signals bypass the damaged dopamine system in the brain that leads to Parkinson's. A study of 395 Parkinson's patients on levodopa, a popular Parkinson's drug, found those using istradefylline experienced 24 percent less "off" time, defined as when the physical symptoms appear after levodopa wears off. A group of those studied who took a placebo showed a 10 percent decrease in "off" time.
"These results suggest that istradefylline is effective as an add-on therapy to other drugs that treat symptoms of Parkinson's disease. More importantly, this medication seems to improve 'off' time in a population in which more than 90 percent of patients are already being treated with two or more drugs," study author Dr. Mark Stacy, of Duke University Medical Center in Durham, N.C., said in a prepared statement.
The findings, published in the June 3 issue of Neurology, may not mean relief is coming soon for Parkinson's sufferers, at least in the United States. In March, the U.S. Food and Drug Administration refused to approve the drug, calling evidence of its effectiveness insufficient. The drug's manufacturer, Kyowa Pharmaceuticals Inc., has suspended development of istradefylline in North America.
The study was supported by Kyowa Pharmaceutical.
Istradefylline is a novel drug approach to Parkinson's. The disease is usually treated with medications that work on dopamine, but their effectiveness wears off after time. Istradefylline appears to connect with receptors other than dopamine to open communication with the brain.
"Istradefylline and other agents in the same class that work in a different area of the brain are an important step forward when treating patients who experience this wearing off phenomenon and side effects related to dopaminergic drugs," Stacy said.

Combo Therapy Knocks Out Melanoma Tumors

03 jun 2008-- Chemotherapy may be more effective on melanoma tumors if a protein frequently found in the growth can first be disabled, a new study reports.
Researchers at the Duke Comprehensive Cancer Center found the drug ADH-1, which makes it difficult for cells to properly bind to one another, helped chemotherapy completely destroy the tumors in twice as many patients than with chemo alone. Sixteen people with regionally advanced melanoma, in which the cancerous growths appear and spread mainly on the limbs, participated in the pilot study.
"Eight of the patients in the study had complete responses to therapy, meaning their tumors completely disappeared," study lead investigator Dr. Georgia Beasley, a medical student at Duke, said in a prepared statement. "This is very encouraging, and we look forward to continuing this study and then eventually moving on to a phase III trial."
Without ADH-1, patients generally have complete responses about 25 percent to 35 percent of the time.
"When chemotherapy was applied to the tumor in this weakened state, it was much more effective compared to conventional therapy alone," study senior investigator Dr. Douglas Tyler, a surgeon at Duke and the Durham Veterans Affairs Medical Center, said in a prepared statement.
The researchers were expected to present their findings Sunday at the American Society of Clinical Oncology annual meeting, in Chicago.
"These early results really speak to the importance of developing combination therapies," Beasley said. "Earlier animal results showed that using ADH-1 alone was not an effective treatment, but in combination with chemotherapy, the results, both pre-clinically and clinically, have been very exciting."
Malignant melanoma is increasing at a rate faster than any other cancer -- 60,000 new cases are expected to be diagnosed this year in the United States alone. When the growths spread beyond the primary site, the disease is rarely curable, and treatment is limited.

For People With Down Syndrome, Longer Life Has Complications

By SALLY SARA
02 jun 2008--His Superman T-shirt was bold and bright, but his face was creased with confusion. Gerry Thomas was stumped by a question most men can answer in an instant.
“What’s your favorite beer?” asked his sister, Beth Thomas.
Mr. Thomas, 50, sitting in the house he and his sister share in Queens, squinted with intense concentration. He struggled to unravel the question, let alone remember the answer. Finally, he gave his sister an apologetic smile and shook his head. “I think I’m losing it,” he said.
Doctors had predicted that Mr. Thomas, born with Down syndrome, would be lucky to reach his 10th birthday. His longevity has come at a price, though.
Two years ago, it was determined that Mr. Thomas, at 48, had early-onset Alzheimer’s disease, adding new challenges of dementia to his already significant disabilities.
In a cruel coincidence that scientists do not yet fully understand, research has shown that people with Down syndrome, a chromosomal abnormality, have a much higher incidence of Alzheimer’s disease at an early age. Some studies have said that 60 to 75 percent of people over age 60 with Down syndrome will have Alzheimer’s, though Dr. Ira Lott, who is in charge of the Down syndrome program at the School of Medicine at the University of California, Irvine, said those studies have been limited in scope.
So as advances in health care have extended the average life expectancy of people with Down syndrome to more than 50 years today from 25 in 1983, doctors and family members are now struggling to cope with a double dose of disability.
Dr. Philip Levy, president of the Manhattan-based YAI/National Institute for People with Disabilities, said Alzheimer’s theft of memory and communication skills is particularly devastating for people with Down syndrome, who have a lower-than-average I.Q. but can make friends easily.
“Their social skills are one of the things that makes them feel very important; they get a lot of positive attention for that,” Dr. Levy noted. “So, when that is taken away, it is very, very cruel.”
Researchers at Columbia University, the New York Institute for Basic Research in Developmental Disabilities and the Kennedy Krieger Institute in Baltimore are trying to untangle the connection between Down syndrome and the early onset of Alzheimer’s disease. They are studying how age, sex, mental ability, cholesterol and estrogen levels may relate to the propensity for Down syndrome patients to develop symptoms of Alzheimer’s, using data from 20 years of assessments of 500 people with Down syndrome on things like whether they can use a toothbrush or comb, dress themselves, do basic math, remember lists of common words or copy drawings of geometric patterns.
There is the hope, too, that the research could have broader implications. “Is there something there that we may actually learn about that may actually prevent Alzheimer’s disease in other people as well?” said Dr. Brian Chicoine, medical director of the Adult and Teen Down Syndrome Center at the Lutheran General Hospital in Chicago.
At the same time, community groups are scrambling to provide services for the expanding population of those with Down syndrome and Alzheimer’s. Chapters of the Alzheimer’s Association nationwide have expressed interest in replicating a program pioneered in Rochester in 2006 that has served about 60 people who have both Down syndrome and Alzheimer’s.
The Rochester program provides workshops on things like changing the lighting and layout of a room to make it more comfortable for people with Alzheimer’s, grief counseling for relatives, and training for caregivers in how to bathe and feed patients in a calm, predictable way.
“There’s growing interest among the Alzheimer’s Association to meet the needs of this unique population,” said Paula Casselman, resource center director of the Rochester Alzheimer’s group.
There is no program like the Rochester one near Queens Village, where Ms. Thomas, 56, and her brother live in a small, cluttered house where they grew up. In fact, she said that she had decided to share her brother’s story in part because she did not know anybody else caring for someone at home who has both Down syndrome and Alzheimer’s.
She had no idea her brother was at a higher risk for Alzheimer’s until the diagnosis was made. Since their mother died a year ago, Ms. Thomas, who used to work part time as a nurse, now looks after her brother full time. She said she managed to build up some savings before quitting; her brother also receives $620 a month from a Social Security program.
“I am the psychologist, the chauffeur, mother, father, sister, friend, whatever,” she said in an interview. “And he’s my heart.”
When her brother was born in the Bronx, Ms. Thomas recalled, his family was told he was a “Mongolian idiot” and should be put in an institution. Instead, his parents took him home to their apartment, where he was welcomed by his older sister.
“I put my arms around him on the bed and I said, ‘This baby is mine, and you guys can go back to the hospital and get yourselves another baby.’ ” Ms. Thomas recalled. “He brings great joy to my life.”
But two years ago, lapses in memory and concentration started disrupting Mr. Thomas’s daily routine. He would become tangled in his sweat pants as he tried to dress in the morning, unable to tell back from front and unsure whether he was taking them on or off. On the volleyball court, he would forget when it was his turn to serve or how to switch positions.
Ms. Thomas went to her computer to research Alzheimer’s and was surprised to discover its deep connection to Down syndrome. “I was apprehensive about what I could do to manage him at home, because Alzheimer’s to me was just an old person’s disease,” she said. “I didn’t know how fast it was going to take him.”
Now, before any family gathering, Ms. Thomas walks her brother through old photographs to remind him who is who. She guides him step by step through simple tasks, like putting milk into his coffee, that he used to handle himself.
Grabbing a cup of coffee one recent morning, he scrunched up his face, straining to remember what to do. He looked pleadingly into her eyes, seeking help. Then he made a cartoon-style laugh, poking fun at himself, to end the tension. But he seemed frustrated and embarrassed.
“It makes you frus-ter-a-ted,” Ms. Thomas said, overemphasizing each syllable. “It’s just the Alzheimer’s.”
Mr. Thomas disagreed. “I don’t have that,” he said emphatically.
He was reluctant to discuss the disease, looking down when it was mentioned. He said he only has “a smidge” of the disease.
The genetic link between Down syndrome and Alzheimer’s has been known for decades, but has garnered attention only recently as many more Down patients began living long enough to develop Alzheimer’s.
There are about 350,000 people with Down syndrome in the United States. They have an extra copy of the 21st chromosome, which carries genes for the production of a protein, beta-amyloid. Overproduction of that protein results in what are known as amyloid plaques in the brain, which can manifest as Alzheimer’s disease and alter memory and brain function.
By age 40, all people with Down syndrome have the amyloid plaques in their brains, though not all develop Alzheimer’s symptoms immediately. Some people with Down syndrome live into their 50s, 60s and even 70s without ever actually contracting the disease.
“I think the hardest part is you just don’t know if Alzheimer’s is going to affect your child or not,” said Betsy Goodwin, founder and a board member of the National Down Syndrome Society, who has a 30-year-old daughter with Down syndrome. “It’s very difficult to make any long-term plans.”
For relatives of people with Down syndrome, the joy of watching them live long beyond expectations is sometimes mitigated by sorrow at seeing them disintegrate. And often the parents who dedicated themselves to raising a disabled child have died or have become too frail to handle the needs of a disabled adult with dementia.
Maryann Slattery, who lost her 80-year-old mother to Alzheimer’s eight years ago, is now watching her 45-year-old sister, Michele Stabile, who has Down syndrome, deteriorate from the disease.
Before her Alzheimer’s diagnosis two years ago, Ms. Stabile used to watch wrestling on television and sort her collection of wrestling cards. Now she can no longer tell one card from another. One recent afternoon, she sat at the kitchen table of a group home for people with disabilities in Cobble Hill, Brooklyn, shuffling through a box littered with brittle, broken rubber bands that once held the cards in neat piles. She still likes to hold the cards; they still feel smooth on her fingers.
“You just see a little bit of her dying all the time,” Ms. Slattery said. “With Alzheimer’s, it’s not just the person who has it. It’s the family.”
Five years ago, celebrating her 40th birthday, Ms. Stabile had a boyfriend, Freddie Goldstein, who was also developmentally disabled. She would give him a kiss when he caught the bus on his way to dialysis treatment several times a week. “Freddie was the love of her life,” Ms Slattery said. “She would be pretending to pick out engagement rings.”
But Ms. Stabile began to withdraw, no longer talking to people she met in the elevator or to her friends she saw in the day program she attended. And her behavior became unpredictable.
“She was laughing one minute and crying the next,” Ms. Slattery said. “It was like the pendulum swinging back and forth.” Now, the volatility has gone and Ms. Stabile is quiet and hauntingly calm, with the gait and slow, deliberate movements of a woman twice her age.
If Ms. Stabile is asked a question, she politely answers “yes,” even if she doesn’t fully understand it.
Her family is caught between gratitude and grief. Ms. Stabile has lived well beyond their expectations, but they want her future years to be good ones.
Ms. Slattery said that watching her sister struggle with Alzheimer’s is even harder than it had been living through her mother’s ordeal.
“My mom was in her late 70s, she was 80 years old,” she said. “It was difficult, but it’s more difficult with Michele because she was such a vibrant, outgoing person.”
Ms. Thomas is doing what she can to extend her brother’s ability to remember things and to act independently, and counts each day that she can joke and laugh with him as increasingly precious. She plans to take him on a cruise to the Caribbean.
Holding hands on the sofa in a living room decorated with certificates of Mr. Thomas’s sporting and community achievements, she teased him, “You’re getting to be an old, old man.”
“You can’t just hang out for the rest of your days. You have to get out and see how the rest of the world looks like,” she said. “There are a lot of things out there to see. I want him to see them all. If he remembers them, O.K.. If not, O.K.”

Bone drug Zometa helps fight breast cancer spread

By MARILYNN MARCHIONE
02 jun 2008--A drug to prevent bone loss during breast cancer treatment also substantially cut the risk that the cancer would return, results that left doctors excited about a possible new way to fight the disease.
It is the first large study to affirm wider anti-cancer hopes for Zometa and other bone-building drugs called bisphosphonates. Zometa, made by Novartis AG, is used now for cancers that have already spread to the bone.
The new study involved 1,800 premenopausal women taking hormone treatments for early-stage breast cancer. Zometa cut by one-third the chances that cancer would recur — in their bones or anywhere else.
"This is an important finding. It may well change practice," said Dr. Claudine Isaacs, director of the clinical breast cancer program at Georgetown University's Lombardi Cancer Center.
About three-fourths of breast cancers occur in women after menopause. Zometa may help them, too, but it hasn't been tested yet in that age group.
The study was led by Dr. Michael Gnant of the Medical University of Vienna and reported Saturday at an American Society of Clinical Oncology conference in Chicago.
If a second, ongoing study also finds a benefit, doctors predict that Zometa will quickly be tested against other cancers that tend to spread, or metastasize, to bones, such as prostate and kidney cancer.
"Hugely important is whether this has to do with the fact that it just makes the bone hostile, somehow, to metastasis or if there is a more global anti-metastasis effect," said the oncology group's president, Dr. Nancy Davidson of Johns Hopkins University.
"Either of those would be good and would teach us a lot about what to do next."
Breast cancer is the most common cancer in women. About 184,450 cases and 40,930 deaths from the disease are expected in the United States this year.
Standard treatments are surgery, chemotherapy, radiation and hormone-blocking drugs if the tumors are like those in the study — helped to grow by estrogen or progesterone.
The hormone-blockers often weaken bones, so bisphosphonates like the osteoporosis pill Fosamax have become increasingly popular to treat this side effect. However, using them to treat the cancer itself is a very different approach.
Lab studies hinted it would work, and Gnant's is the first to test it in a large group of breast cancer patients.
All had surgery to remove their tumors and were taking hormone-blocking drugs — goserelin plus either tamoxifen or anastrozole — treatments that made them menopausal. Half also were given infusions of Zometa once every six months.
The women were treated for three years and studied for two more. By then, only 6 percent of those given Zometa had suffered a relapse or died, compared to 9 percent of the others. That translated to a 36 percent decline in risk.
Sixteen women given Zometa died versus 26 of the others — a difference that could have occurred by chance alone but an encouraging trend that doctors hope will mean better survival as the groups are followed for a longer time.
There were no big differences in serious side effects, though minor ones like fever and bone and joint pain were more common among women given Zometa. Two percent of all study participants developed a rapid heartbeat, but only three were hospitalized — two on Zometa and one of the others.
The study was sponsored by Zometa's maker, Swiss-based Novartis, and British-based AstraZeneca PLC, which makes Arimidex, the brand name of anastrozole. Gnant consults for the companies and several other breast cancer drugmakers.
With doctor fees for the infusion, a Zometa treatment can run more than $1,200. The other large study is testing it in 3,360 pre- and postmenopausal women with cancer that has spread but not extensively.
Experts stressed that the results so far are only in women who were made menopausal by hormone-blocking treatments — not women who develop breast cancer after natural menopause.
For now, using Zometa to prevent breast cancer recurrence should be confined to those who develop breast cancer before menopause, said Dr. Eric Winer of Dana-Farber Cancer Center in Boston.
"This is a treatment that doctors should talk to a patient about" because of these encouraging new results, Winer said.
In other news at the conference, women with advanced breast cancers who were given Avastin plus Taxotere were a little less likely to have their cancers progress than women given Taxotere alone. However, side effects including high blood pressure were more common for those taking both drugs. Taxotere treatment is more common in Europe and Asia; in the United States, doctors are more likely to use Taxol.
In the study of 736 women, 44 percent of those given just Taxotere had their tumors shrink versus 55 percent of those also given a lower dose of Avastin and 63 percent of those given a higher dose.
Avastin, marketed by California-based Genentech and Swiss-based Roche Holding AG, recently won federal approval for breast cancer — against the recommendations of outside advisers. The approval was based on measurements like those in this study — cancer progression, rather than overall survival. The new study was too short to show any differences in survival.

Erbitux slightly boosts survival in cancer study

By MARILYNN MARCHIONE
02 jun 2008--Adding the novel cancer drug Erbitux to standard chemotherapy helped advanced lung cancer patients live just a month longer than chemo alone, a study found.
Although this is the first study to find a survival benefit from a newer, more targeted cancer drug as initial treatment for lung cancer patients, the results left doctors mostly disappointed.
"It's a very small benefit. No one should try to make any more of it than that," said Dr. Roy Herbst, lung cancer chief at the University of Texas M.D. Anderson Cancer Center in Houston.
He consults for Erbitux's makers but had no role in the study, which is to be presented Sunday at a meeting in Chicago of the American Society of Clinical Oncology.
Results were released Saturday because a news release was inadvertently published early.
Lung cancer is the world's top cancer killer, claiming 1.3 million lives each year. In the United States, 215,000 new cases and 162,000 deaths from the disease are expected this year.
Most are non-small cell — the type in the new study. Five-year survival is only 15 percent, mostly because the cancer usually has already spread by the time it is diagnosed.
Erbitux is already used to treat advanced colon cancer, and is best known for embroiling homemaking queen Martha Stewart in an insider trading scandal several years ago.
The new study tested it in 1,125 people with lung cancer that had already spread widely. Average survival was just over 11 months for those given Erbitux on top of standard chemotherapy, versus just over 10 months for those on chemo alone.
The study was led by Dr. Robert Pirker at the University of Vienna in Austria. It was sponsored by Germany's Merck KGaA, which markets Erbitux with the drug's initial developer, ImClone Systems Inc., and Bristol-Myers Squibb Co.
The companies announced last fall that the study had met its main goal of improving survival, but no numbers were released until now.
Several other targeted drugs are used to treat advanced lung cancer but not as initial treatment. Erbitux is another possibility "in a field that needs all the help it can get," because the cancer is so lethal, said Dr. Nancy Davidson, a cancer specialist at Johns Hopkins University who is president of the oncology society.

Avastin slows progress of breast cancer in trial

By Deena Beasley
02 jun 2008--The addition of Genentech Inc's cancer drug Avastin to chemotherapy slows the progress of breast cancer at two different doses, according to results of a large international trial released on Saturday.
The trial showed that after 11 months, patients treated with a high dose of Avastin were 28 percent less likely to have their disease get worse compared with patients on chemotherapy alone. Those given a low dose of the drug were 21 percent less likely to have tumor growth compared to chemotherapy alone.
The results suggest that "the jury is still out" on whether a lower, and much less expensive, dose of Avastin would be an effective option for breast cancer patients, said Dr. Eric Winer, director of the oncology center at Dana-Faber Cancer Institute in Boston.
Dr. David Miles, of Mount Vernon Cancer Center in the United Kingdom and the study's lead investigator, said "the tendency is to think that the higher dose is best for our patients."
Avastin costs more than $4,000 a month at the low dose and double that for the high dose.
"The general message here is that Avastin has a role in breast cancer, but based on the scientific data it has not become the standard of care," Dr. Winer said.
Under U.S. Food and Drug Administration protocols -- which take into account differences in prognostic indicators and other changes -- the trial showed that progression-free survival was 39 percent better for patients on high-dose Avastin, and 31 percent better for the low-dose group, according to the researchers.
The results "were in-line with expectations. The fear was that the high dose would look inferior," said Eric Schmidt, an analyst at Cowen & Co.
The data "are likely to provide a tailwind to a launch that we believe will be above expectations," JP Morgan analyst Geoffrey Meacham said in a research note, referring to pending regulatory approval of Genentech's marketing materials.
Avastin, known chemically as bevacizumab, is already approved in the United States -- at the higher dose of 15 mg per kilogram and in combination with paclitaxel chemotherapy -- as an initial treatment for patients diagnosed with advanced breast cancer. U.S. sales totaled $2.3 billion last year.
The 736-patient trial presented at a meeting of the American Society of Clinical Oncology in Chicago involves treatment with another taxane chemotherapy agent, docetaxel, sold under the brand name Taxotere.
Taxotere is more commonly used in Europe, Asia and Australia, while U.S. oncologists are more likely to use paclitaxel, or Taxol.
Swiss drugmaker Roche Holding AG, which sells Avastin outside of the United States and holds a majority stake in Genentech, conducted the European trial.
"This is the second confirmation of efficacy in breast cancer patients," said David Schenkein, senior vice president of clinical hematology/oncology at Genentech.
He noted that the trial, which was not designed to compare the two doses of Avastin, is continuing and results of overall survival are expected late next year.
Early survival results, based on just 15 percent to 20 percent of patients, show that the high dose of Avastin plus chemotherapy improved survival by 47 percent compared to placebo plus chemotherapy, while the low dose of the drug raised survival by 9 percent, according to Schenkein.
Results at 11 months showed that breast cancer tumors shrank in 63.1 percent of patients on high-dose Avastin, 55.2 percent on low-dose Avastin and 44.4 percent in the placebo plus chemotherapy group.
Severe side effects, such as high blood pressure, were seen in 74.1 percent of patients in the high-dose group, 74.8 percent of the low-dose group and 67 percent of the chemotherapy-alone group.
Bowel perforations occurred in two patients in the placebo group and one patient in each of the Avastin groups.
Schenkein said there were no differences in the rate of severe side effects between the two doses.

Mediterranean Diet May Ward Off Type 2 Diabetes

By Steven ReinbergHealthDay Reporter
01 jun 2008-- Adhering to the so-called Mediterranean diet, which is rich in fruits and vegetables and low in animal products, may protect you against developing type 2 diabetes, a Spanish study suggests.
A Mediterranean diet is often recommended as a way to guard against cardiovascular disease, but whether it protects against diabetes hasn't been established. The diet emphasizes olive oil, vegetables, fruits, nuts, cereals, legumes and fish, and deemphasizes meat and dairy products.
"The Mediterranean diet is a healthful eating plan that seems to help in the prevention of heart disease," said Connie Diekman, director of university nutrition at Washington University in St. Louis, who was not involved with the study. "Consumption of the Mediterranean diet will support health and may aid in the prevention of several diseases," she added.
For the study, published online May 30 in the British Medical Journal, researchers tracked the diets of 13,380 Spanish university graduates with no history of diabetes. Participants filled out a 136-item food questionnaire, which measured their entire diet (including their intake of fats), their cooking methods and their use of dietary supplements.
During an average of 4.4 years of follow-up, the team found that people who adhered to a Mediterranean diet had a lower risk of developing type 2 diabetes. In fact, those who stuck very closely to the diet reduced their risk by 83 percent.
Moreover, the people who tended to stick closest to the diet were those with factors that put them at the highest risk for developing diabetes, such as being older, having a family history of diabetes and being an ex-smoker. These people were expected to have a higher rate of diabetes, but when they adhered to the Mediterranean diet this was not the case, the researchers noted.
Type 2 diabetes is typically brought on by poor eating habits, too much weight and too little exercise.
The researchers suggested that one key factor that might be responsible for the protective effect of the Mediterranean diet is its emphasis on olive oil for cooking, frying, putting on bread and mixing in salad dressings.
"Our prospective cohort study suggests that substantial protection against diabetes can be obtained with the traditional Mediterranean diet, rich in olive oil, vegetables, fruits, nuts, cereals, legumes, and fish but relatively low in meat and dairy products," the researchers concluded.
Diekman said the study does have some limitations. "The use of food-frequency questionnaires is a limitation to actual intake, since most people don't know their real eating patterns and tend to 'guess' rather than provide real data," she said.
The low number of cases of diabetes identified in the study is another concern because typical demographic trends would suggest a higher number, she said.
"Finally, since the study is observational, it is hard to determine if other factors may have had an impact," Diekman said. "Self-reporting of study factors always compounds outcomes."
Still, another nutrition expert said the findings seem to confirm the benefits of a Mediterranean diet for overall health.
"This study reminds me of a comment I once heard someone else say -- 'Research simply confirms what we already know or suspect,' " said Lona Sandon, an assistant professor of clinical nutrition at the University of Texas Southwestern Medical Center at Dallas and a spokeswoman for the American Dietetic Association.
"There are reams of epidemiological studies that have shown an association of the Mediterranean eating pattern with better health overall," Sandon said. "This study adds more fuel to the argument to make better choices in the types of fats we choose to eat and adding more vegetables to our plates."

In New York City, Two Versions of End-of-Life Care

By ANEMONA HARTOCOLLIS
01 jun 2008--There are two starkly different paths toward death in New York City’s hospitals, one for patients at elite private institutions, another for those at public hospitals, according to new data compiled as part of a consumer rating system.
Most elderly patients in their last two years of life have more intensive treatment, more tests, more days of hospitalization — and more out-of-pocket costs — at private teaching hospitals like N.Y.U. and Lenox Hill than their counterparts at Bellevue and the city’s other municipal hospitals, which have historically served the neediest New Yorkers.
The city’s private hospitals were among the most aggressive of about 3,000 hospitals studied across the nation, ranking in the 94th percentile as a group, while the public hospitals landed in the 69th percentile, still significantly above the national average.
The rankings, compiled by Consumer Reports from a 15-year research project based at Dartmouth College, have huge implications for administrators, doctors and patients as they consider which model of care is best for those suffering from chronic, fatal illnesses like cancer, congestive heart failure, lung disease and dementia.
The study does not address the question of whether longer stays and more intervention prolong patients’ lives, and the Dartmouth researchers argue, in general, that less-aggressive treatment does not change the outcome, but spares patients the agony of unnecessary tests and reduces the risk of hospital-borne infections.
“The general principle is that greater intensity of care is not better, and at the high end can actually be harmful,” Dr. David Goodman, a co-author of the Dartmouth Atlas of Health Care, as the database is called, said in an interview on Thursday. Saying that New York’s healthcare system was “full of ironies,” Dr. Goodman suggested that the dichotomy of treatment might illustrate how a city with an abundance of sophisticated doctors and wide disparities in patients’ income and education could result in unfair distribution of resources.
“You have some of the most expensive and high-intensive care in the nation, and yet we know that there are populations that are not getting the care that they need,” Dr. Goodman said. “So this robs it, drains resources from places where it’s really necessary.”
The level of care was most intensive at New York University Medical Center, on First Avenue in the 30s in Manhattan, where 65 percent of patients saw 10 or more physicians in their last six months of life and paid an average of $5,500 beyond what Medicare — the federal insurance program for the elderly — pays for in the last two years of life. N.Y.U. ranked in the 99th percentile nationally.
In contrast, at Bellevue Hospital Center, on First Avenue in the 20s, 7 percent of patients saw 10 or more physicians, and patients averaged $1,380 in out-of-pocket expenses.
Dr. Elliott Fisher, another co-author of the Dartmouth Atlas, said that some people, but not all, were eager for every possible intervention to delay death. “Many patients say, ‘If I’m 85 and this is a choice between being in the hospital and being at home, I’d rather be home,’” he explained.
Kenneth Raske, president of the Greater New York Hospital Association, which includes public and private institutions, said the data was flawed because it worked backward from patients who died, rather than looking at the outcomes for patients who had the same treatment but survived.
He attributed the aggressiveness of private hospitals in New York simply to the sophistication of the patients and their families and the desire of doctors to give them the best possible care.
“The patients and physicians and their families, of course, are trying to live longer and beat whatever malady they have,” Mr. Raske said, “and that’s a reflection of the New York culture that we have.”
Dr. Eric Manheimer, who is the medical director at Bellevue and on the faculty at N.Y.U., said that having a foot in both the public and private systems gave him a unique perspective on the discrepancies. He said that care was less aggressive at public hospitals because most of their doctors — he estimated 75 to 85 percent — were salaried physicians with little financial incentive to order tests or other interventions. At private hospitals, he said, supply can create its own demand: There is often an abundance of beds and an endless list of specialists who can be called.
“You end up with the phenomenon of specialists referring to other specialists, with nobody coordinating, which results in confused messages, more referrals, more hospitalizations, deterioration in health care and a more anxious patient,” Dr. Manheimer said.
The city’s public hospitals, he said, offered a more collegial, intimate culture of care because many of their staff members came from the same community as their patients.
“We’re not smarter or better than the private doctors,” Dr. Manheimer said. “But when you have a salaried physician staff that’s cohesive, that works together, with no incentive to do additional health care, that’s a different mental model.”
He noted that the Mayo Clinic in Rochester, Minn., a prestigious private hospital where doctors also work on salary, ranked in the 28th percentile for aggressiveness of care.
The Dartmouth Atlas, from which the data is drawn, includes 46 New York City hospitals: 8 public and 38 private.
The Consumer Reports rankings allow consumers to look at data from hospitals across the country, and examine the intensity of care during the last two years of life. Intensity is measured by how many days the average patient spent in the hospital, how many times a doctor visited that patient and how much the patient or private insurer spent for doctors beyond what Medicare covered.
Patients in the city’s private hospitals averaged 54 visits from doctors, while those in public hospitals averaged 24 visits during the final six months. In private hospitals, 56 percent of patients saw 10 or more physicians, compared with 32 percent in public hospitals.
And private patients paid an average of $4,000 out-of-pocket over two years, nearly double the $2,200 per patient at the city-run institutions. But in terms of the ultimate outcome, there was little difference.
The Dartmouth Atlas showed that 58 percent of the public-hospital patients died in the hospital as opposed to at home or in hospice care, compared with 57 percent for private hospitals. Thirty percent of patients in public hospitals had been admitted to intensive care units before their death, compared with 27 percent in private hospitals.
Many fewer patients from public hospitals — 7 percent — were enrolled in a hospice than patients from private hospitals, where the rate was 12 percent, according to the Dartmouth data.

Periodontal disease, tooth loss, and cancer risk in male health professionals: a prospective cohort study

Dr Dominique S
01 jun 2008--Studies suggest that tooth loss and periodontal disease might increase the risk of developing various cancers; however, smoking might have confounded the reported associations. We aimed to assess whether periodontal disease or tooth loss is associated with cancer risk.
Methods
The analysis was done in a prospective study (the Health Professionals Follow-Up Study [HPFS]), which was initiated in 1986 when US male health professionals aged 40–75 years responded to questionnaires posted by the Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA. In addition to the baseline questionnaires, follow-up questionnaires were posted to all living participants every 2 years and dietary questionnaires every 4 years. At baseline, participants were asked whether they had a history of periodontal disease with bone loss. Participants also reported number of natural teeth at baseline and any tooth loss during the previous 2 years was reported on the follow-up questionnaires. Smoking status and history of smoking were obtained at baseline and in all subsequent questionnaires. Additionally at baseline, participants reported their mean frequency of food intake over the previous year on a 131-item semiquantitative food-frequency questionnaire. Participants reported any new cancer diagnosis on the follow-up questionnaires. Endpoints for this study were risk of total cancer and individual cancers with more than 100 cases. Multivariate hazard ratios (HRs) and 95% CIs were calculated by use of Cox proportional hazard models according to periodontal disease status and number of teeth at baseline.
Findings
In the main analyses, 48 375 men with median follow-up of 17·7 years (1986 to Jan 31, 2004) were eligible after excluding participants diagnosed with cancer before 1986 (other than non-melanoma skin cancer, n=2076) and those with missing data on periodontal disease (n=1078). 5720 incident cancer cases were documented (excluding non-melanoma skin cancer and non-aggressive prostate cancer). The five most common cancers were colorectal (n=1043), melanoma of the skin (n=698), lung (n=678), bladder (n=543), and advanced prostate (n=541). After adjusting for known risk factors, including detailed smoking history and dietary factors, participants with a history of periodontal disease had an increased risk of total cancer (HR 1·14 [95% CI 1·07–1·22]) compared with those with no history of periodontal disease. By cancer site, significant associations for those with a history of peridontal disease were noted for lung (1·36 [1·15–1·60]), kidney (1·49 [1·12–1·97]), pancreas (1·54 [1·16–2·04]; findings previously published), and haematological cancers (1·30 [1·11–1·53]). Fewer teeth at baseline (0–16) was associated with an increase in risk of lung cancer (1·70 [1·37–2·11]) for those with 0–16 teeth versus those with 25–32 teeth. In never-smokers, periodontal disease was associated with significant increases in total (1·21 [1·06–1·39]) and haematological cancers (1·35 [1·01–1·81]). By contrast, no association was noted for lung cancer (0·96 [0·46–1·98]).
Interpretation
Periodontal disease was associated with a small, but significant, increase in overall cancer risk, which persisted in never-smokers. The associations recorded for lung cancer are probably because of residual confounding by smoking. The increased risks noted for haematological, kidney, and pancreatic cancers need confirmation, but suggest that periodontal disease might be a marker of a susceptible immune system or might directly affect cancer risk.

Dialysis more often doesn't help patients


BY ANGELA STEWART
01 jun 2008--Giving critically ill kidney patients dialysis more than the standard three times a week does not improve their survival, a study has found.
The research was based on outcomes of 1,124 patients who were randomly assigned to receive either conventional thrice-weekly treatment or a more intensive regimen involving an average of 5.4 treatments per week. The death rate for patients who received the more intense treatment was about the same as that of patients receiving the standard dose, the study found.
"There will need to be new directions pursued because merely ramping up the dose of dialysis is not going to be the answer to improving outcomes," said study co-author Paul Palevsky, chief of the renal section for the VA Pittsburgh Healthcare System.
The study, funded by the U.S. Department of Veterans Affairs and the National Institute of Diabetes and Digestive and Kidney Diseases, is scheduled to be published in the July 3 New England Journal of Medicine. It was released yesterday to coincide with the International Conference of the American Thoracic Society.
Unlike chronic kidney disease, a long-term illness associated with high blood pressure and diabetes, acute kidney failure comes on suddenly. It affects more than 35 percent of critically ill hospitalized patients and is often linked with severe sepsis, a systemic bodily infection that can lead to organ failure.
Mortality rates for hospitalized patients suffering from chronic kidney disease can range from 50 to 80 percent. Some smaller studies conducted at single institutions have suggested that more intense dialysis produces better outcomes in these very sick patients. The latest study, involving a far larger number of patients and conducted at 27 centers around the country, contradicted those findings.
"This study now confirms that as long as the dialysis treatments are well designed and effective, three times a week is adequate," agreed Joseph Bonventre, a physician at Brigham and Women's Hospital Boston who wrote an editorial accompanying the study.
In the study, Palevsky's team randomly assigned 1,124 patients with acute kidney disease to receive intensive or less intensive dialysis. The researchers found that the rate of death was 53.6 percent among patients receiving intensive renal therapy and 51.5 percent among patients receiving less intensive therapy.
Palevsky and his team concluded that the findings represented "no significant difference in mortality." Nor was any significant difference seen between the two groups in recovery of kidney function or the rate of other organs failing.
"It doesn't mean that the dose of dialysis isn't important, but once you achieve what would be the standard dose, going beyond that, there is no science to support it," said James McAnally, chief of nephrology at Trinitas Hospital in Elizabeth, who was not involved with the study.
Others, however, cautioned that the results should not be overinterpreted, citing instances such as with congestive heart failure patients when standard treatment may be inadequate.
"Many of our patients are so ill, they may require a fourth treatment just to remove fluid or control the level of poisons," said Neil Lyman, chief of nephrology and director of dialysis at Saint Barnabas Medical Center in Livingston.
"You have to make allowances for each clinical circumstance of the patient being managed," added Stanley Harris, medical director for Horizon Blue Cross Blue Shield of New Jersey, which leaves the decision up to doctors.

Heart failure guidance 'ignored'

01 jun 2008--Many GPs, and even some hospital specialists, are failing to follow guidelines for managing heart failure, a Europe-wide survey suggests.
British GPs frequently did not use recommended tests or drugs, which the researchers said could be unsafe.
The European Heart Journal report said the results were "very worrying".
However, one specialist GP disputed whether the survey answers were clear evidence of poor practice among family doctors in the UK.
I find these figures very worrying as guidelines are the only source of information which gives management advice in a complete and unbiased way Professor Willem Remme Study author
Heart failure is a common disease of old age, with approximately 67,000 new cases diagnosed in the UK every year.
The study found that while 94% of UK hospital cardiologists would use an echocardiograph test, 69% of GPs said that they could make the diagnosis on symptoms and other signs alone.
Only half the GPs who answered the survey said they often needed other tests to confirm the diagnosis, the team led by the Sticares Cardiovascular Research Foundation in the Netherlands reported.
Only a quarter of GPs said they could get echocardiography tests for their patients within a month - compared to three quarters of French primary care doctors, 90% in Germany, and 51% in Italy.
Drug mistakes
Having made their diagnosis, just over a third of UK GPs opted for a treatment using ACE inhibitors, with well over half appearing to choose diuretic drugs alone, a practice described as "unsafe" by the study authors.
No-one is going to turn around and say that heart failure care in the UK is perfect, but I don't think that we are performing that badly Dr Terry McCormack Primary Care Cardiovascular Society
However, Dr Terry McCormack, a Yorkshire GP and chairman of the UK Primary Care Cardiovascular Society, said that European guidelines did not exactly match those in the UK, and there were reasonable arguments for using diuretics as a first step while awaiting test results.
"No-one is going to turn around and say that heart failure care in the UK is perfect, but I don't think that we are performing that badly.
"We are pretty good for getting echocardiagrams, and pretty good for the use of ACE inhibitors and beta blockers."
Among the specialists, ACE inhibitors were more commonly prescribed, with 85% of UK cardiologists saying they used them in at least nine out of 10 patients, well above the European average.
Professor Willem Remme, who led the study, said that many doctors were aware that the guidelines existed, but had not read them, or chose not to follow them.
"I find these figures very worrying as guidelines are the only source of information which gives management advice in a complete and unbiased way, based on data from controlled studies or real expert opinion."
Professor Peter Weissberg, medical director for the British Heart Foundation, said: "The main message from this study is that heart failure patients get better treatment if they are managed by a specialist."

Death of spouse ups odds of nursing home care

By Megan Rauscher

31 may 2008--An older person's likelihood of entering a nursing home or other long-term care facility is particularly high immediately after the death of a spouse, new research indicates.
There could be various reasons for this, Elina Nihtila, of the department of sociology at the University of Helsinki, Finland, who led the research, told Reuters Health.
"It may be related to the loss of social and instrumental support, in the form of care and help with daily activities such as help in cooking, cleaning, and shopping formerly shared with the deceased spouse," Nihtila said.
"Second, grief and spousal loss may cause various symptoms, such as depression and anxiety, loss of appetite, sleep disturbances, fatigue and loss of concentration that could increase the need for institutional care." She added. "Furthermore, grief may cause increased susceptibility to physical diseases."
The research team analyzed how the death of a spouse affects the likelihood of entering institutionalized care among nearly 141,000 Finnish adults aged 65 and older. All of them were living with a spouse at the beginning of the study and were followed for five years.
"The data were unique in that they covered a large number of persons bereaved during the follow-up and gave the dates of bereavement and of first admission into institutional care," Nihtila and colleagues explain in the American Journal of Public Health.
Results showed that the risk of entering long-term institutional care was higher among older adults who had lost their spouse than among those living with their spouse. "The excess risk of institutionalization was highest during the first month after the spouse's death -- more than three times higher among both men and women -- and decreased with time from bereavement, stabilizing at approximately 20% to 50% higher over 1 to 5 years," Nihtila noted.
The researcher thinks home help services "should be targeted to the bereaved immediately after a spouse's death to reduce the need for institutional care."
SOURCE: American Journal of Public Health, July 2008 (online May 29, 2008).

Airborne Fine Particulate Matter Linked to Stroke Risk

By Todd Neale
ANN ARBOR, Mich., 31 may 2008Even low levels of airborne fine particulate matter appear to be associated with an increased risk of cerebrovascular events, researchers found.Levels of particulate matter in a southeast Texas county were associated with "borderline significant" increases in the risk of ischemic stroke and transient ischemic attack, Lewis Morgenstern, M.D., of the University of Michigan, and colleagues reported online in the Annals of Neurology.When levels of fine particulate matter rose by 5.1 mg/m3 the risk of suffering one of the events increased by 3% that day (RR 1.03, 95% CI 0.99 to 1.07) and the day after (RR 1.03, 95% CI 1.00 to 1.07).
"Although the magnitude of increased risk for stroke/[transient ischemic attack] because of [particulate matter] exposure was relatively small," the researchers said, "most of the public is exposed to ambient air pollution at the levels observed in this community or greater every day, suggesting a potentially large public health impact."
The median particulate matter level was 7.0 mg/m3, less than half the standard set by the Environmental Protection Agency (15 mg/m3).
The results, therefore, "call into question current standards for fine particulate matter and whether these standards are sufficient to protect the public from stroke," the researchers said.
Past studies have found a link between air pollution and cardiovascular disease in general but data on the association with stroke have been more limited, the researchers said.
Fine particulate matter -- a diameter less than 2.5 mm -- can penetrate airways and alveoli and enter the circulation because of its smaller size and chemical activity, they said.
The particles may raise the risk for cerebrovascular events by inducing arterial vasoconstriction or acute increases in blood pressure and plasma viscosity, they said.
To explore the issue, Dr. Morgenstern and colleagues turned to the Brain Attack Surveillance in Corpus Christi Project, which is designed to capture all strokes in Nueces County, Tex. There are a large number of oil refineries, chemical plants, and other sources of particulate matter pollution in this area.
Nevertheless, the level of particulate matter during the study was low, most likely because of the prevailing winds and coastal location, they said.
Air pollution and meteorological data were obtained from the Texas Commission on Environmental Quality.
From Jan. 1, 2001 through Dec. 31, 2005, the researchers identified 2,350 ischemic strokes and 1,158 transient ischemic attacks in patients ages 45 and older (median age 72). Half of the patients were Mexican-American, 44% were white, and 5% were African American.
The increased risk of suffering a stroke or transient ischemic attack was independent of ozone levels after accounting for temperature, day of the week, and temporal trends in cerebrovascular events.
Season did not modify the association.
"These data contribute to the literature because there is currently a scarcity of data on the effect of environmental exposures on risk for stroke in the United States," the researchers said.
Future studies on the effects of particulate air pollution on the risk for subtypes of ischemic stroke could reveal the biological mechanisms at work, they said.
The authors acknowledged some limitations to the study, including the fact that, as an ecological study, it should be used primarily for generating hypotheses. The results should be replicated, they said, and future studies should take into account any unmeasured confounders.
In addition, measurement of particulate matter is subject to error. The values obtained in this study may not be generalizable over a wider geographic area, they said.
Finally, they said, residual confounding by other pollutants may have occurred.
The study was funded by a grant from the National Institute of Neurological Disorders and Stroke.
The authors made no disclosures.
Primary source: Annals of NeurologySource reference:Lisabeth L, et al "Ambient air pollution and risk for ischemic stroke and transient ischemic attack" Ann Neurol 2008; DOI: 10.1002/ana.21403.

Gene variant worsens chances for women with breast cancer

31 may 2008--European doctors said Friday they had identified a genetic characteristic that strongly worsens survival chances for women with breast cancer who are treated with a common form of chemotherapy.
The telltale sign is a variant of a gene called NQO1, which in its normal form produces an enzyme that protects cells against oxidative stress -- a key factor in the spread of cancer.
The variant of NQ01, called NQ01*2, stops production of this protective enzyme. It is present in between four and 20 percent of the world's population, with a preponderance in Asia, according to figures presented in the study.
The researchers -- led by Heli Nevanlinna of the University of Helsinki and Jiri Bartek, a Czech scientist with the Danish Cancer Society -- found that women who had a double copy of NQ01*2 in their genome had only a 17-percent survival rate when treated with an anthracyclin-based chemotherapy.
Those who had only a single copy of NQ01*2, or did not have the variant at all, had a survival rate of 75 percent.
The paper, published online by the specialised British journal Nature Genetics, is based on DNA data from more than 2,000 Finnish women treated for breast cancer.

SAEM: AHA Guidelines for Cardiac Arrest Treatment Increase Survival

By Todd Neale
WASHINGTON, 31 may 2008-- The rate of resuscitation after out-of-hospital cardiac arrests jumped nearly four-fold when new guidelines on CPR were fully implemented in a North Carolina county, according to researchers here.The 2005 American Heart Association guidelines outlined a protocol calling for simple, continuous chest compressions, controlled ventilation, and early use of induced hypothermia.When the guidelines were fully implemented in Wake County, which has urban and suburban areas and a population of about 815,000, cardiac arrest survival increased 3.99-fold (95% CI 2.19 to 7.27), Brent Myers, M.D., M.P.H., medical director of the Emergency Medical Services System in Raleigh, N.C., reported at the Society for Academic Emergency Medicine meeting here.
Overall survival increased from 2.4% using older guidelines to 6.7% after introduction of the full 2005 AHA protocol.
He said that "the neurologic improvement was at least as robust as the survival improvement."
The entire protocol was introduced for less than $200 per patient, he said.
"All of these changes are simple, they are inexpensive, and they are incredibly effective," he said. From January 2004 through October 2007, there were 2,594 out-of-hospital cardiac arrests in patients ages 15 and older (mean age 65; 58% male).
More than a third (36%) were witnessed and received CPR from a bystander before emergency medical services arrived and 26% had ventricular fibrillation/ventricular tachycardia rhythm.
From January 2004 through April 2005, the emergency medical services system followed the older AHA guidelines, which mandated a 15:2 compression-to-ventilation ratio without a focus on interruption of compressions and with an emphasis on intubation.
Survival rates during this period were 2.4% overall and 12.1% for patients with ventricular fibrillation-ventricular tachycardia rhythm.
In April 2005 the system started following the new recommendation for continuous cardiac compression with a 30:2 compression-to-ventilation ratio with minimal interruption. After 12 months, the survival rates had increased to 4% overall and 21.8% for patients with ventricular fibrillation-ventricular tachycardia rhythm.
In April 2006, use of an impedance threshold device, a ResQPod, was introduced to better control ventilation and avoid over-ventilation. The device also helps improve the effectiveness of chest compression by enhancing blood flow to the coronary arteries.
This change was associated with another rise in survival -- 4.5% overall and 28.5% for patients with ventricular fibrillation-ventricular tachycardia rhythm.
Six months later, the system began early induction of hypothermia, the final stage of the protocol. Ice packs and chilled IV fluids were applied within two to three minutes of receiving a pulse and after the patient was found to be unresponsive neurologically.
Survival rates after a year of following the entire protocol were 6.7% overall and 37.4% for patients with ventricular fibrillation-ventricular tachycardia rhythm.
The odds of overall survival increased three-fold (95% CI 1.7 to 5.0) and the odds of survival for patients with ventricular fibrillation-ventricular tachycardia rhythm rose 4.3-fold (95% CI 2.2 to 8.6) from the beginning of the study.
In a multivariate analysis, the odds ratios for survival for each phase of implementation were as follows:
New CPR protocol: 2.13 (95% CI 1.12 to 4.04)
Addition of impedance threshold device: 2.33 (95% CI 1.09 to 5.00)
Addition of early hypothermia: 3.99 (95% CI 2.19 to 7.27)
Patients who received CPR from a bystander were 1.79-fold (95% CI 1.18 to 2.72) more likely to survive.
Dr. Myers defended the decision not to conduct a randomized trial, saying it would be unethical to do so.
"We felt that at each stage the evidence was so compelling to do what we were doing that we shouldn't randomize," he said.
He concluded, "Our findings not only demonstrate beneficial outcomes for victims of cardiac arrest, but also suggest the possibility that such treatment plans can be implemented for other medical conditions."
Dr. Myers and one of his co-authors are on the speaker's bureau for Alsius.
Primary source: Society for Academic Emergency MedicineSource reference:Hinchey P, et al "Out-of-hospital cardiac arrest survival after the sequential implementation of 2005 AHA guidelines for compressions, ventilations, and induced hypothermia" SAEM Meeting 2008; Abstract 167.

Nonalcoholic Fatty Liver Linked to Kidney Disease in Diabetic Patients

By Judith Groch
VERONA, 31 may 2008-- For patients with type 2 diabetes, non-alcoholic fatty livers may lead to chronic kidney disease, an observational study found.
The risk for chronic kidney disease was 69% higher for diabetic patients with non-alcoholic fatty liver disease than for diabetic patients without the liver disorder, Giovanni Targher, M.D., of the University of Verona, and colleagues here and at the University of Colorado reported online in the Journal of the American Society of Nephrology.
Non-alcoholic fatty liver prevalence has been estimated to be in the 15% to 30% range in the general population in various countries and appears to be increasing, the researchers said. However, there has been little information about the association between the fatty liver disease and the risk of developing diabetic nephropathy.
Treating earlier stages of nephropathy in diabetic patients could slow the progression of the kidney disorder to end-stage renal disease. Thus, early detection of precursors and risk factors for chronic kidney disease is very important, Dr. Targher and colleagues wrote.
Their study included 1,760 outpatients with type 2 diabetes and normal or near-normal kidney function and without overt proteinuria.
Patients were followed for 6.5 years (through December 2006) for the occurrence of chronic kidney disease (overt proteinuria and/or estimated GFR< 60 ml/min per 1.73 m2).
The participants were recruited from the Valpolicella Heart Diabetes Study cohort, a prospective observational study to evaluate associations between diabetes and chronic vascular complications.
Patients with other common causes of fatty liver, such as alcohol abuse, chronic viral hepatitis, and use of potentially liver-toxic medications were excluded.
During follow-up, 547 participants developed incident chronic kidney disease, with a yearly risk of about 4.5%, the researchers said.
Nonalcoholic fatty liver disease, diagnosed by liver ultrasound and exclusion of other common causes of chronic liver disease, was associated with a moderately increased risk for the kidney disorder (hazard ratio 1.69, 95% confidence interval 1.3 to 2.6, P<0.001).
Adjustments for gender, age, BMI, waist circumference, blood pressure, smoking, diabetes duration, glycosylated hemoglobin, lipids, baseline estimated GFR, microalbuminuria, and medications (hypoglycemic, lipid-lowering, antihypertensive, or antiplatelet drugs) did not appreciably attenuate this association (HR 1.49, 95% CI 1.1 to 2.2, P < 0.01).
The annual cumulative incidence of 4.5% per year was comparable to that previously described in other Italian and European populations with diabetes and similar baseline characteristics.
The underlying biologic mechanisms by which fatty liver disease may increase the risk for chronic kidney disease in type 2 diabetes are poorly understood, the investigators said. The most obvious explanation is that the findings simply reflect the coexistence of underlying known risk factors.
However, they said, the findings were independent of numerous baseline risk factors, so that it is conceivable that nonalcoholic fatty liver may confer an excess risk beyond these known risk factors and that fatty liver itself in diabetic patients may be involved in the pathogenesis of chronic kidney disease.
The possible molecular mediators may include the release of some pathogenic factors from the liver, including elevated advanced glycosylated end products, increased reactive oxygen species, elevated C-reactive protein, TNF-α, TGF-β1, and other proinflammatory cytokines.
Importantly, several studies have shown that these potential mediators of vascular and/or renal injury are remarkably higher in diabetic or obese patients with fatty liver disease and are thought to be pathogenic factors for the progression of chronic kidney disease.
In addition, they said, the liver disease may worsen whole-body insulin resistance and hyperglycemia, which may in turn contribute to the progression of kidney disease. This was supported by the observation in this study that HbA1c was higher in patients with fatty liver than in those without it.
Study limitations included the use of an estimated GFR to define chronic kidney disease. Also, the fatty liver diagnosis was based on ultrasound diagnosis and exclusion of secondary causes of chronic liver disease but was not confirmed by biopsy. Whether these observations can be extended to nonwhite patients and other ethnic groups remains to be determined.
It is not known whether treating fatty liver disease will ultimately prevent progression to chronic kidney disease, the researchers said.
However, they wrote, it is notable that interventions effective in preventing or delaying the progression to chronic kidney disease in patients with diabetes, such as weight reduction or treatment with angiotensin receptor blockers or insulin-sensitizing agent, may also be effective for fatty liver disease.
Further prospective studies are required to confirm the reproducibility of these results and whether the findings can be extended to nonwhite ethnic groups, they concluded.
No financial conflicts were reported.
Primary source: Journal of the American Society of NephrologySource reference:Targher G, et al "Increased risk of CKD among type 2 diabetics with nonalcoholic fatty liver disease" J Am Soc Nephrol 2008; DOI: 10.1681/ASN.2007101155.