DHA 'fish oil' supplements do not seem to slow cognitive, functional decline in Alzheimer's disease

Patients with mild to moderate Alzheimer's disease (AD) who received supplementation with the omega-3 fatty acid docosahexaenoic acid (DHA), believed to possibly reduce the risk of AD, did not experience a reduction in the rate of cognitive and functional decline, compared to patients who received placebo, according to a study in the November 3 issue of JAMA, a theme issue on aging.

06 nov 2010--"Several studies have found that consumption of fish, the primary dietary source of omega-3 fatty acids, is associated with a reduced risk of cognitive decline or dementia. Some studies have found that consumption of DHA, but not other omega-3 fatty acids, is associated with a reduced risk of Alzheimer disease," the authors write. However, those studies were observational and did not control who received DHA. Animal studies that used DHA showed reductions in Alzheimer-like brain pathology.

Dr. Quinn and colleagues conducted a randomized, controlled trial to examine whether DHA supplementation would slow the rate of cognitive and functional decline in individuals with Alzheimer's disease. The study, which was conducted between November 2007 and May 2009 at 51 U.S. clinical research sites, included 402 individuals with mild to moderate Alzheimer's disease. Participants were randomly assigned to DHA at a dose of 2 grams/day or to identical placebo (60 percent were assigned to DHA and 40 percent were assigned to placebo). Duration of treatment was 18 months. Changes in cognitive and functional abilities were assessed with the Alzheimer's Disease Assessment Scale

(ADAS-cog) and the Clinical Dementia Rating (CDR) sum of boxes. Rate of brain atrophy was also determined by volumetric magnetic resonance imaging (MRI) in a subsample of participants.

A total of 295 participants completed the trial while taking study medication (DHA: 171; placebo: 124). The researchers found that supplementation with DHA had no beneficial effect on rate of change on ADAS-cog score, with the rate of average change in the score over 18 months being 8.27 points for the placebo group and 7.98 points for the DHA group. The rate of points change on CDR sum of boxes over 18 months was 2.93 for the placebo group compared with 2.87 for the DHA group.

Among the individuals participating in the MRI substudy (102 had MRIs at the beginning of the study and at 18 months [DHA group: 53; placebo group: 49]), an analysis showed no effect of DHA treatment on total brain volume change during 18 months.

"In summary, these results indicate that DHA supplementation is not useful for the population of individuals with mild to moderate Alzheimer disease," the authors write.

The researchers add that "because part of the rationale for the trial was epidemiological evidence that DHA use before disease onset modifies the risk of Alzheimer disease, it remains possible that an intervention with DHA might be more effective if initiated earlier in the course of the disease in patients who do not have overt dementia."

More information: JAMA. 2010;304[17]:1903-1911.

Provided by JAMA and Archives Journals

Helical CT scans reduce lung cancer mortality by 20% compared to chest X-rays


In a major new study announced today by the National Cancer Institute, researchers including Brown University biostatistian Constantine Gatsonis and his colleagues found that screening for lung cancer using helical CT scanning reduced lung cancer deaths by 20 percent compared to using chest X-rays.

05 nov 2010--"The findings we're announcing today offer the first definitive evidence for the effectiveness of helical CT screening smokers for lung cancer " said Gatsonis, a lead biostatistician in the study and director of the American College of Radiology Imaging Network's (ACRIN) Biostatistics and Data Management Center, based at Brown's Center for Statistical Sciences. "This is a major step in the formulation of appropriate screening strategies for this deadly disease."

The National Lung Screening Trial (NLST) was conducted by a consortium consisting of ACRIN and the Lung Screening Study (LSS). The consortium enrolled more than 53,000 current and former heavy smokers ages 55 to 74 into the NLST at 33 sites across the United States. Starting in August 2002, participants were enrolled during a 20-month period and randomly assigned to receive three annual screens with either low-dose helical CT (often referred to as spiral CT) or standard chest X-ray. A manuscript reporting on the design of the study appeared yesterday on the Web site of the journal Radiology.

"Everyone who participated in this trial has played an important role in providing hard evidence of a mortality benefit from CT screening for lung cancer as well as a road map for public policy development in the future," said Denise R. Aberle, M.D., the national principal investigator for NLST ACRIN, site co-principal investigator for the UCLA NLST team, and a deputy chair of ACRIN.

Helical CT uses X-rays to obtain a multiple-image scan of the entire chest compared to a standard chest X-ray that produces a single image of the whole chest in which anatomic structures overlie one another.

A secondary finding in the study showed overall deaths due to any factor, including lung cancer, were 7 percent lower in those screened with low-dose helical CT than in those screened with chest X-ray. Approximately 25 percent of deaths in the NLST were due to lung cancer, while other deaths were due to factors such as cardiovascular disease.

"The combined findings of a reduction in mortality due to lung cancer and in overall mortality are important for the overall interpretation and impact of the results from this study," Gatsonis said.

Today's announcement addresses only the primary objective of the NLST study: the lung cancer mortality comparison between helical CT and chest X-rays. Intensive analysis of the data collected in the study is now under way to address a host of questions, including the health care required to follow up screening findings, the impact of screening on quality of life, and the cost and cost-effectiveness of screening for lung cancer, Gatsonis said. The results of these analyses will provide crucial information for the eventual development of guidelines for screening for lung cancer.

Faculty and staff at the Brown Center for Statistical Sciences contributed methodologic expertise and leadership throughout the study, in collaboration with other ACRIN and LSS investigators, Gatsonis said. They collaborated on the original design and implementation of the study, worked on the collection and monitoring of the data, and prepared in-depth reports for the independent Data and Safety Monitoring Committee. Now they are doing the final analysis of the data and contributing to the interpretation of the findings.

Faculty and staff at the center also organized and carried out the data collection on the impact of screening on quality of life and smoking cessation. Ilana Gareen, research assistant professor of community health, is leading this effort.

"Many, many people across the country dedicated years of their lives to bring this study to its successful conclusion," Gatsonis said. "They should take pride in the results of their efforts announced today."

Provided by Brown University

Pain is common in the last two years of life, study find

In the first study to look at the prevalence of pain experienced among older people during the last two years of life, researchers at the San Francisco VA Medical Center found that 46 percent of study participants suffered moderate to severe pain during their final four months of life.

04 nov 2010--The researchers also found that more than one quarter of the participants had moderate to severe pain during the last two years of life, and that arthritis was the biggest single predictor of pain, outweighing all eventual causes of death, including cancer.

“The impact of arthritis on the experience of pain among older adults has not been recognized to the extent it should be,” says lead author Alexander K. Smith, MD, MS, MPH, a palliative medicine physician at SFVAMC. He notes that the prevalence of pain in the last month of life was 60 percent among patients with arthritis and 26 percent among patients without arthritis.

“This research tells us that physicians should anticipate that pain will increase among their elderly and dying patients, assess their patients for pain frequently, and prescribe appropriate pain medications at appropriate levels,” says Smith, who is also an assistant professor of medicine in the Division of Geriatrics at the University of California, San Francisco.

Smith recommends that physicians regularly assess and treat pain in their older patients with chronic diseases who are not obviously nearing death. “In other words,” he says, “pain management is not just for hospice patients.” The study appears in the November 2, 2010 issue of the Annals of Internal Medicine.

The authors analyzed data from interviews conducted with 4,703 men and women age 50 and older who died while enrolled in the Health and Retirement Study, an ongoing nationally representative longitudinal study of health, retirement, and aging sponsored by the National Institute on Aging. The interviews were conducted during each participant’s last 24 months of life.

“As physicians, we need to recognize the high burden of pain among our older patients,” says Smith.

Provided by University of California, San Francisco

New study tracks factors leading to physical decline in older adults

A study by Yale School of Medicine researchers reveals that the illnesses and injuries that can restrict the activity of older adults or land them in the hospital are linked to worsening functional ability, especially among those who are physically frail. The report appears in JAMA's November 3 theme issue on aging.

03 nov 2010--Thomas M. Gill, M.D., the Humana Foundation Professor of internal medicine (geriatrics), investigative medicine and epidemiology and public health at Yale, will present the findings at a JAMA media briefing today.

"We now have a much better understanding of the complex and highly dynamic disabling process," said Gill, who is also an attending physician at Yale-New Haven Hospital.

Among older adults, disability in essential activities of daily living, such as bathing, and dressing, is common and associated with an increased rate of death, institutionalization, and greater use of formal and informal home services. But many older adults also recover from disabilities. Gill points to high rates of recovery and frequent transitions between states of disability, but he said the role of intervening illnesses and injuries on these transitions was little understood until this study shed some light on it.

Gill and his co-authors followed 754 adults age 70 and older living in the Greater New Haven area, with monthly phone interviews for over 10 years starting in 1998. The team assessed disability and ascertained exposure to intervening illnesses and injuries. Physical frailty—slow walking speed—was assessed every 18 months for nine years. The team evaluated the relationship between two types of intervening events—hospitalization and restricted activity, and transitions between no disability, mild disability, severe disability and death.

The team found that among the 637 participants, who had at least one functional transition, 90.7 percent had at least one hospital admission and 94.3 percent had at least one month of restricted activity. Hospitalization was associated with disability for eight of the nine transitions.

Among the possible reasons for hospitalization or restricted activity, fall-related injury led to the highest likelihood of developing new or worsening disability.

Gill notes that despite the reductions observed in the prevalence of disability over the past two decades, the number of disabled older Americans could increase substantially in the coming years with the aging of the baby boom generation. "To address this increase, more aggressive efforts will be needed to prevent and manage intervening illnesses and injuries, given their apparent role in precipitating and perpetuating the disabling process," said Gill.

More information: JAMA. 2010;304[17]:1919-1928.

Patients who survive sepsis are more than 3 times as likely to have cognitive problems


Older adults who survive severe sepsis are at higher risk for long-term cognitive impairment and physical limitations than those hospitalized for other reasons, according to researchers from the University of Michigan Health System.

02 nov 2010--Research to be published Oct. 27 in the Journal of the American Medical Association showed that 60 percent of hospitalizations for severe sepsis were associated with worsened cognitive and physical function among surviving older adults. The odds of acquiring moderate to severe cognitive impairment were 3.3 times higher following an episode of sepsis than for other hospitalizations.

Severe sepsis also was associated with greater risk for the development of new functional limitations following hospitalization, says lead author, Theodore (Jack) Iwashyna, M.D., Ph.D., assistant professor of internal medicine at U-M.

Among patients who had no limitations before sepsis, more than 40% developed trouble with walking. Nearly 1 in 5 developed new problems with shopping or preparing a meal. Patients often developed new problems with such basic things as bathing and toileting themselves.

"We used to think of sepsis as just a medical emergency, an infection that you get sick with and then recover," said Iwashyna, "But we discovered a significant number of people face years of problems afterwards.

"Those problems are bigger and more common than we expected. Most older Americans suffer real brain and body problems. We need new treatments, not just for the sepsis infection, but to prevent these new disabilities afterwards."

Sepsis is an overwhelming infection that can result in failure of multiple organ systems. The initial infections are often common problems, such as pneumonia or a urinary tract infection. About 40 percent of those with severe sepsis die from the infection.

Anyone can get sepsis, but older people and those with weakened immune systems are most vulnerable. Sepsis is probably the most common cause of critical illness in the United States.

The best data available are from the 1990s, when it was estimated that 750,000 people each year were diagnosed with sepsis. Researchers believe that number has doubled each decade.

"These new data show a majority of older patients suffer with real life-changing burdens after beating sepsis. This is an underrecognized public health problem with major implications for patients, families and the health care system," Iwashyna says.

"We need to make sure families have the resources they need to care for survivors of sepsis when they go home. It's not enough just to get them through the acute episode. We need to start preparing them for the years of problems they may have afterwards."

"This research underscores the need for physicians who care for older adults to focus early on preventing infections that can lead to sepsis," says study co-author Kenneth M. Langa, M.D., Ph.D., a core investigator for the Ann Arbor Veterans Administration Health Services Research and Development Service's Center of Excellence and professor of internal medicine at U-M.

Older patients need to get their flu and pneumonia vaccines in order to decrease their risk for infections, and physicians need to be aware of the long-term risk for cognitive and physical disabilities that many patients may face, Langa said.

"In contrast to Alzheimer's disease and other forms of dementia, the cognitive impairment associated with sepsis is likely at least partially preventable through better acute care of the sepsis episode and better rehabilitation efforts afterwards," Langa says.

"We need to start working early – from the beginning of the hospitalization – to make sure patients do not develop new disability. There are innovative new ways to care for people that might help prevent this disability," Iwashyna says.

The research was supported primarily by the National Institute on Aging and the National Heart, Lung and Blood Institute.

The researchers used data from the NIA-supported Health and Retirement Study , a long-term study that collects information on the health, economic, and social factors influencing the health and well-being of a nationally representative sample Americans over age 50.

"This research makes clearer how acute medical problems in older adults may have an important lasting impact and contribute to a downward trajectory in both cognitive and physical function," says Richard Suzman, Ph.D., director of the NIA's Division of Behavioral and Social Research, which supports the HRS.

"The unique nature of the rich HRS dataset that links both survey data and Medicare administrative data made this innovative study possible and will also facilitate future studies of the long-term impact of critical illness on older adults and the family members that care for them."

More information: Journal of the American Medical Association, 2010; 304(16): 1787-1794.

More Older Americans Living With HIV

01 nov 2010-- Better treatments are extending the lives of people with HIV, but aging with the AIDS-causing virus takes a toll that will challenge the health care system, a new report says.

A survey of about 1,000 HIV-positive men and women ages 50 and older living in New York City found more than half had symptoms of depression, a much higher rate than others their age without HIV.

And 91 percent also had other chronic medical conditions, such as arthritis (31 percent), hepatitis (31 percent), neuropathy (30 percent) and high blood pressure (27 percent). About 77 percent had two or more other conditions. About half had progressed to AIDS before they got the HIV diagnosis, the report found.

"The good news is antiretroviral therapies are working and people are living. If all goes well, they will have life expectancies similar to those without HIV," said Daniel Tietz, executive director of the AIDS Community Research Initiative of America.

"But a 55-year-old with HIV tends to look like a 70-year-old without HIV in terms of the other conditions they need treatment for," he said Wednesday at a meeting of the Office of National AIDS Policy at the White House in Washington, D.C.

The research included interviews with 640 men, 264 women and 10 transgender people. Dozens of experts on HIV and aging attended the meeting, which was intended to identify the needs of older adults with HIV and to explore ways to improve services to them.

Currently, about 27 percent of those with HIV are over 50. By 2015, more than half will be, said the report.

Because of their special needs, this poses challenges for public health systems and organizations that serve seniors and people with HIV, Tietz said.

HIV can be isolating, Tietz said. Seventy percent of older Americans with HIV live alone, more than twice the rate of others their age, while about 15 percent live with a partner, according to the report.

The survey found that loneliness was higher among HIV-positive adults than for other older Americans. One reason is that many men and women conceal the condition from friends and family for fear of stigma or rejection, both real and imagined, Tietz said.

Lack of social and family support increases the likelihood of needing costly health care, such as home health aides and nursing homes as they get older, Tietz said.

Dr. Amy Justice, an HIV researcher who also attended the meeting, spoke of the need for health care professionals to learn about specific issues facing HIV-positive seniors.

HIV organizations tend to gear messages toward younger people, and senior services organizations often don't know much about the needs of HIV-positive seniors, said Justice, principal investigator of the Veterans Aging Cohort Study. This ongoing study involves some 40,000 veterans with HIV and 80,000 without HIV from 10 Veterans Affairs medical centers nationwide.

"There are a lot of people with HIV who are 60 or 65 and even 80 or 85," Justice said. "Those individuals feel older than their stated age and may have some of the same problems people 10 or 15 years older would normally experience."

Many older Americans with HIV are still sexually active and should be encouraged to practice safe sex, Justice said. While 57 percent of older Americans with HIV said they disclosed their HIV status to sexual partners, about 16 percent didn't, the report found.

About half the survey participants were black, one-third were Hispanic and 14 percent were white. About 67 percent considered themselves heterosexual, 24 percent were gay and 9 percent bisexual.

Why people with HIV are more likely to have other chronic diseases is still unclear, Tietz said. The cause could be the HIV itself or long-term side effects from taking multiple medications, he said. Early HIV drugs were especially toxic, he added.

Stress may have only small impact on weight

NEW YORK , 31 oct 2010-- Despite the common belief that stress causes people to pack on the pounds, a new research review finds that, on average, stress has little long-term effect on weight.

The results are surprising, researchers say, given the widespread notion that stress - by causing people to reach for junk food or skimp on exercise, for example -- is an important factor in weight gain.

When the investigators pulled together 32 previously published studies on the question, however, they found the majority showed no association between people's stress levels and their weight gain over several years.

When the researchers combined the studies' results -- in what is known as a meta-analysis -- there was only a modest association overall between stress and weight gain.

"When we started this meta-analysis, we assumed that there would be a substantial association between stress and obesity, since the popular view is that stress contributes to weight gain," co-researcher Dr. Andrew Steptoe, of University College London in the UK, told Reuters Health in an e-mail.

"But when we looked carefully at well-controlled scientific studies," he said, "effects were surprisingly small."

That does not necessarily mean that stress cannot have a significant influence on some people's weight, according to Steptoe. The average effect of stress on weight might be small, but there could be wide variations among individuals, he said.

Citing diet as one example, Steptoe noted that "some people may increase their food consumption under stress, while others may stop eating and lose their appetites."

In addition, he said, different types of stress - whether associated with work, caregiving or specific life events -- might have different effects on weight gain.

Examining those questions was beyond the scope of the data Steptoe and his colleagues had.

For the study, the researchers, led by Dr. Jane Wardle, also of University College London, analyzed 32 international studies conducted mainly in the 1990s and 2000s.

All of the studies assessed participants' stress levels, then followed the subjects over time to see whether there was a relationship between stress and subsequent weight gain. Most followed participants for one to seven years, but a few were longer term projects that followed people for up to 38 years.

Some of the studies focused on participants' levels of work stress, while others gauged "general life stress," which includes anything from major traumas like experiencing a serious illness or a divorce, to feeling overwhelmed by daily hassles.

Overall, the researchers found, 69 percent of the studies uncovered no clear association between stress levels and weight gain. One-quarter linked higher stress levels to greater weight gain, and the remaining 6 percent found that greater stress was related to less weight gain over time.

When Wardle's team pooled the results of all the studies, they found a modest association between higher stress levels and greater weight gain.

In general, the connection was stronger among men than among women -- an interesting finding, Steptoe said, since it is "popular belief" that stress has a greater impact on women's weight.

One of the limitations of this review, according to the researchers, was that it could not examine the role of psychological disorders - the included studies focused on exposure to stress, and not, for example, whether a person developed depression in response to that stressor.

"The general message," Steptoe said, "is that, based on the best current scientific research, stress is not likely to play a major role in increasing body weight or obesity for most people."

"It could be that some people are more affected than others," he added, "but rather little is known about this at present."

He and his colleagues call for more research into the factors that might explain why one person puts on pounds in response to stress and another does not.

Getting older leads to emotional stability, happiness: study

"As people get older, they're more aware of mortality," researcher Laura Carstensen said. "So when they see or experience moments of wonderful things, that often comes with the realization that life is fragile and will come to an end. But that's a good thing. It's a signal of strong emotional health and balance."

30 oct 2010--As people age, they're more emotionally balanced and better able to solve highly emotional problems, says psychology professor and longevity expert Laura Carstensen.

It's a prediction often met with worry: In 20 years, there will be more Americans over 60 than under 15. Some fear that will mean an aging society with an increasing number of decrepit, impaired people and fewer youngsters to care for them while also keeping the country's productivity going.

The concerns are valid, but a new Stanford study shows there's a silver lining to the graying of our nation. As we grow older, we tend to become more emotionally stable. And that translates into longer, more productive lives that offer more benefits than problems, said Laura Carstensen, the study's lead author.

"As people age, they're more emotionally balanced and better able to solve highly emotional problems," said Carstensen, a psychology professor and director of the Stanford Center on Longevity. "We may be seeing a larger group of people who can get along with a greater number of people. They care more and are more compassionate about problems, and that may lead to a more stable world."

Between 1993 and 2005, Carstensen and her colleagues tracked about 180 Americans between the ages of 18 and 94. Over the years, some participants died and others aged out of the younger groups, so additional participants were included.

For one week every five years, the study participants carried pagers and were required to immediately respond to a series of questions whenever the devices buzzed. The periodic quizzes were intended to chart how happy, satisfied and comfortable they were at any given time.

Carstensen's study – which was published online Monday in the journal Psychology and Aging – was coauthored by postdoctoral fellows Bulent Turan and Susanne Scheibe as well as Stanford doctoral students and researchers at Pennsylvania State, Northwestern, the University of Virginia and the University of California's campuses in San Francisco and Los Angeles.

While previous research has established a correlation between aging and happiness, Carstensen's study is the first to track the same people over a long period of time to examine how they changed.

The undertaking was an effort to answer questions asked over and over again by social scientists: Are seniors today who say they're happy simply part of a socioeconomic era that predisposed them to good cheer? Or do most people – whether born and reared in boom times or busts – have it within themselves to reach their golden years with a smile? The answer has important implications for future aging societies.

"Our findings suggest that it doesn't matter when you were born," Carstensen said. "In general, people get happier as they get older."

Over the years, the older subjects reported having fewer negative emotions and more positive ones compared with their younger days. But even with the good outweighing the bad, older people were inclined to report a mix of positive and negative emotions more often than younger test subjects.

"As people get older, they're more aware of mortality," Carstensen said. "So when they see or experience moments of wonderful things, that often comes with the realization that life is fragile and will come to an end. But that's a good thing. It's a signal of strong emotional health and balance."

Carstensen (who is 56 and says she's happier now than she was a few decades ago) attributes the change in older people to her theory of "socio-emotional selectivity" – a scientific way of saying that people invest in what's most important to them when time is limited.

While teenagers and young adults experience more frustration, anxiety and disappointment over things like test scores, career goals and finding a soul mate, older people typically have made their peace with life's accomplishments and failures. In other words, they have less ambiguity to stress about.

"This all suggests that as our society is aging, we will have a greater resource," Carstensen said. "If people become more even-keeled as they age, older societies could be wiser and kinder societies."

So what, then, do we make of the "grumpy old man" stereotype?

"Most of the grumpy old men out there are grumpy young men who grew old," Carstensen said. "Aging isn't going to turn someone grumpy into someone who's happy-go-lucky. But most people will gradually feel better as they grow older."

The perils of taking experimental cancer drugs

NEW YORK 29 oct 2010-- Trying a new, experimental cancer drug may offer a glimpse of hope for very sick patients, but often does more harm than good, a new study shows.

Researchers said cancer doctors regularly resort to drugs still undergoing testing, as long as they have been approved for other diseases or in different combinations or doses.

But because the science is still up in the air, nobody really knows what the consequences of taking such drugs are.

"Many of these drugs end up not being the tremendous improvement that we hoped they would be," said Dr. Otis Brawley, chief medical officer of the American Cancer Society, who was not involved in the new study.

"People need to realize that because the trials have not been completed there is a great deal that is not known about the treatments," he told Reuters Health. "There are people who get these treatments and get hurt."

The new study, published in the Journal of Clinical Oncology, looked at 172 clinical trials published over two years.

Less than a third of the clinical trials showed the experimental drugs improved patient survival, and less than half found the drugs helped other clinical outcomes.

Those numbers could even be too high, researchers say, because negative findings tend not to be published.

On the other hand, two thirds of the trials reported increases in at least one severe or life-threatening side-effect.

Most of the drugs under scrutiny had already been approved in different doses or combinations -- or for different diseases -- and were available on the U.S. market.

It's unclear if doctors were prescribing them for unapproved indications, but it's entirely possible as one-fifth of US drugs are prescribed in such a way -- a legal practice known as off-label prescription.

"We know there is a high demand for new treatments in oncology," said Dr. Jeffrey Peppercorn, a cancer doctor at Duke University Medical Center in Durham, North Carolina, who led the new research.

In an earlier survey, he said, he had found that more than eight in 10 cancer doctors prescribe medications that are being tested.

"This sounds a cautionary note," Peppercorn said about his new findings. "In most cases, we should refrain from using experimental drugs outside of clinical trials."

And it's not only patients taking the experimental drugs that may feel the impact.

Clinical trials done in the US, the researchers found, had trouble recruiting participants and took nearly twice as long to complete when the drug under scrutiny was already on the market.

"The concern is that you have fewer people choosing to enter the trial if the drug is already available," Peppercorn said, cautioning that the trial didn't prove that to be the case.

Trials are designed to compare new drugs with existing ones that have been deemed safe and effective by the US Food and Drug Administration.

Signing a patient up for a trial therefore often means only a 50-50 chance that he or she will get the new drug. So doctors may choose to prescribe it off label instead, and insurance companies often pay for it.

"Most of the doctors who do this are thinking that they are doing something in the best interest of the patients," said Brawley. But in reality, he added, they end up slowing down the development of new drugs.

Dr. Steven Joffe, an ethicist at Dana-Farber Cancer Institute in Boston who has worked with Peppercorn on earlier studies, agreed.

"I perfectly understand why a patient with a poor prognosis might want to have access to these drugs and why doctors would give them the drugs," he told Reuters Health.

"They may think they know that it works," he said. "But the fact is, somebody is running a study to find out if it does. Almost by definition it hasn't been proved safe and effective."

As an example of how doctors and patients can be fooled, Joffe mentioned that scores of women were treated for breast cancer with stem cells in the 1990s, when the treatment was still in clinical trials.

"It took about ten years to do the trial because it was so hard to get women to enroll," said Joffe. And when the results finally came, the treatment turned out to be a dud -- a toxic and expensive one, too.

Joffe said prescribing drugs when they are still in clinical trials might not only slow the development of good medical evidence, but could even halt it.

"We know that many studies fail to ever get completed," he explained. "These data suggest that the use of drugs outside of trial protocols could contribute to the failure of studies ever to get completed."

Sometimes, of course, new drugs do work, and no one argues that doctors shouldn't be allowed to prescribe medications they think will help patients.

But doctors should be very clear about the high risks involved. One way to do that, said Peppercorn, would be to require that cancer doctors get informed consent from patients before they start them on experimental drugs.

In the end, Brawley said, the decision to use such treatment should be left to the patient and his or her doctor.

"There are times when it can be justified," he noted, "but it is done far more often than it should be."

Glucosamine causes the death of pancreatic cells

Quebec City, 28 oct 2010—High doses or prolonged use of glucosamine causes the death of pancreatic cells and could increase the risk of developing diabetes, according to a team of researchers at Université Laval's Faculty of Pharmacy. Details of this discovery were recently published on the website of the Journal of Endocrinology.

In vitro tests conducted by Professor Frédéric Picard and his team revealed that glucosamine exposure causes a significant increase in mortality in insulin-producing pancreatic cells, a phenomenon tied to the development of diabetes. Cell death rate increases with glucosamine dose and exposure time. "In our experiments, we used doses five to ten times higher than that recommended by most manufacturers, or 1,500 mg/day," stressed Professor Picard. "Previous studies showed that a significant proportion of glucosamine users up the dose hoping to increase the effects," he explained.

Picard and his team have shown that glucosamine triggers a mechanism intended to lower very high blood sugar levels. However, this reaction negatively affects SIRT1, a protein critical to cell survival. A high concentration of glucosamine diminishes the level of SIRT1, leading to cell death in the tissues where this protein is abundant, such as the pancreas.

Individuals who use large amounts of glucosamine, those who consume it for long periods, and those with little SIRT1 in their cells are therefore believed to be at greater risk of developing diabetes. In a number of mammal species, SIRT1 level diminishes with age. This phenomenon has not been shown in humans but if it were the case, the elderly—who constitute the target market for glucosamine—would be even more vulnerable.

"The key point of our work is that glucosamine can have effects that are far from harmless and should be used with great caution," concluded Professor Picard.

The results obtained by Picard and his team coincide with recent studies that cast serious doubt on the effectiveness of glucosamine in treating joint problems.

###

This study was co-authored by Mathieu Lafontaine-Lacasse and Geneviève Doré.

Information:
Frédéric Picard
Faculty of Pharmacy
Université Laval
418-656-8711 ext. 3737

New guideline from ASH and ASCO recommends caution regarding ESA use in cancer patients

WASHINGTON, 27 oct 2010– An updated joint guideline by the American Society of Hematology (ASH) and the American Society of Clinical Oncology (ASCO) advises physicians about the appropriate use of erythropoiesis-stimulating agents (ESAs), a class of drugs that stimulate the bone marrow to produce more red blood cells, to treat cancer patients with chemotherapy-induced anemia. While the guideline cautions that ESAs are associated with shorter survival and increased risk of thromboembolism — blood clots — and tumor progression, it also recognizes their major benefit of reducing the need for red blood cell transfusions, which can potentially cause serious infections and adverse reactions in the immune system.

"This updated guideline offers clinicians the latest synthesis of the medical evidence surrounding use of ESAs in patients with cancer, including appropriate cautions where evidence is lacking or where risks may outweigh the use of ESAs," said J. Douglas Rizzo, MD, MS, Co-Chair of the guideline panel and Professor of Medicine at the Medical College of Wisconsin.

Those risks may include thromboembolism or even death, according to new data cited in the guideline, which suggests that physicians avoid the use of ESAs in cancer patients who are not receiving chemotherapy, except for those with myelodysplastic syndrome (MDS). At the same time, the guideline confirms the effectiveness of ESAs in sparing patients the need for transfusions, which can substantially impact quality of life. By recommending that physicians discuss individual risks and benefits of ESAs and blood transfusion with patients prior to therapy, the guideline recognizes the critical role of shared decision-making between the patient and the physician.

In addition to outlining the clotting risks of ESAs, the guideline makes specific recommendations on usage and provides insights into disease progression and patient survival. The guideline also details new thresholds for initiation and modification of ESAs, which are consistent with current FDA labeling.

Originally published in 2002 and last updated in 2007, the guideline was derived from analysis of individual patient data, various medical literature, and systematic reviews of published clinical trials. In developing the update, panel members considered all relevant literature published between January 2007 and January 2010. Additional evidence was considered when it was considered pertinent to each section of the updated guideline.

"These guidelines touch on almost all aspects of the use of ESAs in patients with cancer and MDS, as well as secondary issues, such as the role of iron supplementation," said Samuel Silver, MD, a member of ASH's Committee on Practice and Professor of Internal Medicine at the University of Michigan. "These are issues that confront practicing hematologists and oncologists on a daily basis, and we hope that these evidence-based recommendations will influence practice standards and result in better care for patients."

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The guideline will be published ahead of print on the websites of Blood (bloodjournal.org), ASH's scientific journal, and ASCO's Journal of Clinical Oncology (jco.org) at 4:00 p.m. on October 25. The guideline will be published in print in Blood on November 18 and in the Journal of Clinical Oncology on November 20.

Heavy Smoking Linked to Alzheimer's in Study

26 oct 2010-- Heavy smoking in middle age seems to increase the risk for developing Alzheimer's disease or another dementia, a large new study suggests.

"We found that people who reported heavy smoking in midlife had more than a 100 percent increase in risk of Alzheimer's disease and vascular dementia," said lead researcher Rachel A. Whitmer, a research scientist in Kaiser Permanente's Division of Research in Oakland, Calif.

"We have known that smoking is a risk factor for cancer, stroke and cardiovascular disease," she said. "This adds to the evidence that what is bad for the heart is bad for the brain."

The report is published in the Oct. 25 online edition of the Archives of Internal Medicine.

For the study, Whitmer's group collected data on 21,123 ethnically diverse people in the Kaiser Permanente health care system who were surveyed between 1978 and 1985, when they were 50 to 60 years old.

During an average follow-up of 23 years, the researchers found that 25.4 percent were diagnosed with dementia, including Alzheimer's (1,136 people) or vascular dementia (416 people), which is the second most common form of dementia after Alzheimer's disease. Vascular dementia is caused by damage to the arteries in the brain.

Compared with non-smokers, those who smoked more than two packs of cigarettes a day in midlife had a "dramatic increase" in the incidence of dementia -- more than a 157 percent increased risk of developing Alzheimer's disease and a 172 percent increased risk of developing vascular dementia, Whitmer's team found.

Former smokers and people who smoked less than half a pack a day did not appear to be at increased risk of Alzheimer's or vascular dementia, the researchers note.

The associations between smoking and dementia did not change even after adjusting for race or gender, high blood pressure, high cholesterol or heart attack, stroke or weight, they add.

A link between Alzheimer's and smoking has been shown before, but this new study pinpoints the specific risk for middle-age smokers for developing both Alzheimer's and vascular dementia, the researchers say.

Smoking, an established risk factor for stroke, may contribute to the likelihood of vascular dementia by causing small clots in the brain. Smoking also contributes to oxidative stress and inflammation, which may be linked to the risk of developing Alzheimer's disease, the researchers say.

"The brain is not immune to long-term damage from smoking," Whitmer said.

Two smaller studies of predominantly white participants also suggested that mid-life smoking raised the risk of developing Alzheimer's, researchers noted.

Commenting on the new study, William Thies, chief medical and scientific officer at the Alzheimer's Association, said "this is a sound confirmation of something that's been known for a while."

Another expert, Dr. Samuel E. Gandy, the Mount Sinai Professor of Alzheimer's Disease Research at Mount Sinai School of Medicine in New York City, said the findings are promising.

"Environmental factors in Alzheimer's disease have been long sought, and, until now, only head injury has emerged," Gandy said. "Unlike head injury, a tobacco smoking association is especially important because that is a risk that can be modified."

Yoga alleviates pain and improves function in fibromyalgia patients

According to new study published in Pain

Philadelphia, PA, 25 oct 2010– Fibromyalgia (FM) is a debilitating condition affecting 11 million individuals in the US alone. FM carries an annual direct cost for care of more than $20 billion and drug therapies are generally only 30% effective in relieving symptoms and 20% effective in improving function. Standard care currently includes medications accompanied by exercise and coping skills approaches. In a study published in the November issue of PAIN, researchers report patients participating in a "Yoga of Awareness" program showed significantly greater improvement in FM symptoms and functioning compared to patients on a standard FM care program.

"Although yoga has been practiced for millennia, only recently have researchers begun to demonstrate yoga's effects on persons suffering from persistent pain," commented lead investigator James W. Carson, PhD, Oregon Health & Science University. "The Yoga of Awareness program stands in contrast to previous multimodal interventions with FM patients in that it integrates a wide spectrum of yoga-based techniques – postures, mindfulness meditation, breathing exercises, application of yogic principles to optimal coping, and group discussions.…the findings of this pilot study provide promising preliminary support for the beneficial effects of yoga in patients with FM."

Given the much higher prevalence of FM in females (80%), researchers chose to include only women in this study. 53 women at least 21 years of age participated. To be eligible, patients had to meet the following criteria: be diagnosed with FM by American College of Rheumatology (ACR) criteria for at least 1 year and be on a stable regimen of pharmacologic and/or non-pharmacologic treatment for FM for at least 3 months. The patients were randomized; 25 participated in the Yoga of Awareness program, while 28 received standard care.

Yoga of Awareness is an innovative, comprehensive yoga program, which for the purposes of this study was tailored to address pain, fatigue, sleep disturbance, and emotional distress in FM. Each Yoga of Awareness class included approximately 40 minutes of gentle stretching poses, 25 minutes of mindfulness meditation (e.g., awareness of breath, awareness of awareness itself), 10 minutes of breathing techniques (e.g., full yogic breath, breathing into sensation), 20 minutes of didactic presentations on the application of yogic principles to optimal coping, and 25 minutes of group discussions (e.g., experiences while practicing yoga at home).

After the yoga program was completed, both groups were assessed for fibromyalgia symptoms and functional deficits, overall improvement in fibromyalgia symptoms, physical tests of fibromyalgia symptoms and functional deficits such as tender points, strength and balance deficits, and a number of pain coping strategies.

Following treatment, women assigned to the yoga program showed significantly greater improvements on standardized measures of FM symptoms and functioning, including pain, fatigue, and mood, and in pain catastrophizing, acceptance, and other coping strategies.

Dr. Carson and colleagues observed, "In addition, the results suggested the yoga intervention led to a beneficial shift in how patients cope with pain, including greater use of adaptive pain coping strategies (i.e., problem solving, positive reappraisal, use of religion, activity engagement despite pain, acceptance, relaxation) and less use of maladaptive strategies (i.e., catastrophizing, self-isolation, disengagement, confrontation)."

One-Third of U.S. Adults Could Have Diabetes by 2050: CDC

24 oct 2010-- The number of American adults with diabetes could double or triple by 2050 if current trends continue, warns a federal government study released Friday.

The number of new diabetes cases a year will increase from 8 per 1,000 in 2008 to 15 per 1,000 in 2050, predicts the U.S. Centers for Disease Control and Prevention. By 2050, between one-fifth and one-third of all adults could have diabetes -- with virtually all the increase attributed to type 2 diabetes, which is largely preventable.

An aging population, an increase in minority groups at higher risk for diabetes, and the fact that diabetes patients are living longer are among the reasons for the steep projected rise.

"These are alarming numbers that show how critical it is to change the course of type 2 diabetes," Ann Albright, director of CDC's Division of Diabetes Translation, said in an agency news release. "Successful programs to improve lifestyle choices on healthy eating and physical activity must be made more widely available, because the stakes are too high and the personal toll too devastating to fail."

Another expert agreed.

"These data are accurate and reflect reality," said Dr. Mary Ann Banerji, professor of medicine and director of the Diabetes Treatment Center at SUNY Downstate Medical Center, New York City. "Taking into consideration minorities and longer life expectancy, the real burden of diabetes is much greater than many people thought."

Banerji believes that "we need to act now. Immediate changes in diet, physical activity, stress and sleep are known to decrease diabetes and obesity. We can make changes in our physical environment to promote greater physical activity and we should consider changes in national food policy."

Diabetes remains the leading cause of new cases of blindness under age 75, kidney failure, and preventable leg and foot amputation among adults in the United States, according to the CDC.

In addition, people diagnosed with diabetes have medical costs that are more than twice that of those without the disease, the agency reports. The total costs of diabetes in the United States are an estimated $174 billion annually, including $116 billion in direct medical costs.

The study appears in the journal Population Health Metrics.

The projected increase in U.S. diabetes numbers reflects the global growth of the disease. About 285 million people worldwide had diabetes in 2010, and the number could swell to as many as 438 million by 2030, according to the International Diabetes Federation.

About 24 million Americans have diabetes, but one-quarter of them don't know it. Older age, obesity, a sedentary lifestyle, family history, developing diabetes while pregnant, and race/ethnicity are risk factors for type 2 diabetes. Racial/ethnic groups at increased risk are African Americans, Hispanics, American Indians/Alaska Natives, and some Asian-Americans and Pacific Islanders.

"The incidence of diabetes over the last few decades has progressively increased," notes diabetes expert Dr. Jacob Warman, chief of endocrinology at The Brooklyn Hospital Center, New York City. "It is not surprising that with a flourishing of fast food chains and use of Internet and cable television, the population has become more sedentary and overweight."

However, regular physical activity and proper nutrition can reduce the risk of type 2 diabetes and help control the disease. To that end, the CDC has launched a campaign to reduce such risks in overweight and obese people, stressing dietary changes, coping skills and group support to help participants lose 5 percent to 7 percent of their body weight and get at least 150 minutes per week of moderate physical activity.

Prevention programs that target at-risk groups can help reduce -- but not eliminate -- future increases in type 2 diabetes prevalence, the study said.

Studies: Pneumonia is misdiagnosed on patient readmissions

DETROIT23 oct 2010 – Patients were misdiagnosed with pneumonia at an alarming rate when they were readmitted to the hospital shortly after a previous hospitalization for the same illness, according to two Henry Ford Hospital companion studies.

Researchers say the misdiagnoses led to overuse of antibiotics and increased health care costs. Pneumonia ranks second to congestive heart failure as the reason for readmission within 30 days of a previous hospitalization.

Led by Henry Ford Infectious Diseases physicians Hiren Pokharna, M.D., and Norman Markowitz, M.D., researchers found that:

• 72 percent of patients were misdiagnosed with pneumonia upon readmission to the same hospital.
• African-Americans were twice more likely than Caucasians to be misdiagnosed with pneumonia.
• Patients who smoke or have lung disease were likely to be misdiagnosed with pneumonia.
• 72 percent of the misdiagnoses occurred in the Emergency Department.
• Fewer than 33 percent of patients had any outpatient follow-up care prior to their readmission.

Results of the two companion studies will be presented Friday at the 48th annual meeting of the Infectious Diseases Society of America Oct. 21-24 in Vancouver.

"These studies show that we need to increase awareness among physicians about using the diagnostic standards and criteria set forth in the Centers for Disease Control and Prevention's National Healthcare Safety Network for diagnosing pneumonia at the time of readmission," says Dr. Pokharna, a fellow at Henry Ford and the lead author of the companion studies.

"This also points to the importance of using X-ray for ruling out pneumonia. And once pneumonia is ruled out, the antibiotics can be discontinued."

In seeking to explain the difficulty of diagnosing pneumonia and high prevalence of misdiagnoses, Henry Ford researchers examined medical records of 127 patients diagnosed with pneumonia between December 2008 and December 2009 and readmitted within 30 days of a previous hospitalization.

Researchers found that 92 of the 127 patients were misdiagnosed with health care associated pneumonia using CDC/National Healthcare Safety Network criteria. Health care associated pneumonia is a newly recognized form of pneumonia in patients who had recent close contact with a health care system, either through a hospital, outpatient dialysis center, nursing home or long-term care facility. The classification was added with the shift from hospital-based care to home-based care.

Researchers cited several reasons for the misdiagnoses, including pre-existing lung disease and abnormalities on chest X-rays.

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The studies were funded by Henry Ford Hospital.

Hormone therapy linked to increased cancer risk

WASHINGTON, 22 oct 2010 – Menopausal women taking combined hormone therapy have an elevated risk of being diagnosed with a more advanced stage of breast cancer and dying from it, according to a new US study.

Researchers conducted a new analysis of a landmark, federally funded clinical trial known as the Women's Health Initiative (WHI), which was halted in 2002 after data suggested women who took a combination of estrogen and progestin hormones faced a higher risk of breast cancer.

The study, published in this week's edition of the Journal of the American Medical Association, also found that women who previously used hormone therapy and discontinued it after the WHI was terminated still faced a slightly higher breast cancer mortality rate than women not taking hormones.

For their analysis, Rowan Chlebowski of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and colleagues observed 16,608 postmenopausal women ages 50 to 79 years with no prior hysterectomy from 40 US clinical centers.

Their follow-up of about 11 years of WHI participants found that 385 women receiving hormones for an average of 5.6 years, or 0.42 percent, developed invasive breast cancer, compared with 293 women who received a placebo, or 0.34 percent.

A significantly larger fraction of the women in the hormone therapy group -- 81, or 23.7 percent -- were diagnosed after their breast cancer had spread to lymph nodes. In the placebo group, only 43 women, or 16.2 percent, were diagnosed at that stages.

Twenty-five of the women who received the hormone therapy died from breast cancer, compared to 12 deaths among those who received a placebo. That translated to one to two extra deaths from breast cancer each year for every 10,000 women who used hormone therapy rather than a placebo.

Researchers noted that in the WHI trial, unlike most observational studies, combined hormone therapy both increased the risk of breast cancer and interfered with breast cancer detection, hindering the detection of breast cancer and thus leading to diagnoses at more advanced stages.

"Now, with longer follow-up results available, there remains a cumulative, statistically significant increase in breast cancers in the combined hormone therapy group, and the cancers more commonly had lymph node involvement," the researchers said.

"The observed adverse influence on breast cancer mortality of combined hormone therapy can reasonably be explained by the influence on breast cancer incidence and stage."

They noted that the incidence of breast cancer substantially decreased in the United States after the WHI trial's results were initially reported eight years ago, which was attributed to a marked decrease in postmenopausal hormone therapy use.

"The adverse influence of estrogen plus progestin on breast cancer mortality suggests that a future reduction in breast cancer mortality in the United States may be anticipated as well," the researchers added.

In an accompanying editorial, Peter Bach of Memorial Sloan-Kettering Cancer Center in New York said "the available data dictate caution in the current approach to use of hormone therapy," namely because physicians are "ill-equipped" to anticipate its effects on long-term health.

"Clinicians who prescribe brief courses of hormone therapy for relief of menopausal symptoms should be aware that this approach has not been proven in rigorous clinical trials and that the downstream negative consequences for their patients are of uncertain magnitude," Bach added.

Devastating impact of spinal osteoporotic fractures revealed on World Osteoporosis Day

A new report issued by the International Osteoporosis Foundation (IOF) for World Osteoporosis Day puts the spotlight on the severe impact of spinal fractures and calls on health professionals to recognize the signs of these fractures in their patients.

21 oct 2010--"The widespread under–diagnosis and lack of treatment of spinal fractures, leaves millions of people around the world with chronic pain, deformity, disability and at high risk of future fractures," says Professor John Kanis, President of the IOF.

As many as two-thirds of spinal osteoporotic fractures are not recognized by doctors. Untreated, as many as one in five women with a spinal fracture will sustain another within twelve months.

'The Breaking Spine', authored by Professor Harry K. Genant of the University of California and Dr. Mary Bouxsein of Harvard Medical School, reveals the serious impact of these fractures and calls on health professionals to take action to diagnose patients and refer them for treatment. "Doctors must look out for evidence of spinal fractures, especially in their patients over 50 – stooped back, loss of height, and sudden, severe back pain are the three tell-tale signs, says Professor Genant. "It is essential that doctors refer these patients for further testing and that radiology reports clearly identify spinal fractures as 'FRACTURED' to avoid ambiguity." Currently, only about 40% of older women with spinal fractures visible on X-ray are tested for osteoporosis. The figure is even lower in men (less than 20%).

The IOF urges health professionals and the public to recognize the signs of spinal fractures. The repercussions of these common fractures can be severe, resulting in stooped back, acute and chronic back pain, loss of height, immobility, depression, increased number of bed days, reduced pulmonary function and even premature death.

Globally, spinal fractures represent a huge socio-economic burden. It is estimated that one spinal fracture occurs every 22 seconds worldwide. Studies have shown that as many as 20-25% of Caucasian women and men over 50 years of age have a current spinal fracture. Costs associated with all osteoporotic fractures are predicted to rise markedly over the next few decades as the population ages.

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The new IOF report, The Breaking Spine, can be downloaded on http://www.iofbonehealth.org/publications/the-breaking-spine.html

Survey Reveals Alzheimer's Caregivers' Top Concerns

20 oct 2010-- Family caregivers' greatest concerns about the progression of a loved one's Alzheimer's disease are memory loss (41 percent), personal safety (33 percent) and confusion (27 percent), finds a new survey.

The poll of 524 caregivers also found that 67 percent named at least one cognitive (or thinking skills') change in their loved one as a main concern; 55 percent said caring for a loved one with Alzheimer's has taken a toll on their own health; and 60 percent said they felt overwhelmed.

Male caregivers were more concerned about memory loss than women -- 50 percent versus 37 percent.

The survey was conducted by Harris Interactive in September for drug makers Eisai Inc. and Pfizer Inc., in partnership with the Alzheimer's Foundation of America (AFA).

Among the other findings about issues caregivers face:

• Women were more likely than men to "worry all the time" (13 percent versus 3 percent) and less likely than men to feel that they have enough support to take care of themselves and their own needs (60 percent versus 76 percent).
• Women were more likely than men to find it challenging to maintain relationships with family or friends -- 47 percent versus 31 percent.
• People looking after loved ones with severe Alzheimer's disease were more likely (84 percent) to say that caregiving frequently prevents them from doing activities they enjoy, compared to caregivers of loved ones with moderate (68 percent) or mild (67 percent) Alzheimer's disease.
• Men were more likely than women to be satisfied with communication with their loved one's health care professional (84 percent versus 70 percent) and more likely to regularly discuss options for support or information (26 percent versus 14 percent).
• Dissatisfaction with a loved one's treatment was expressed by 53 percent of caregivers who had little or no involvement in discussions with health care providers, compared with 31 percent of caregivers who were involved.

"These survey results reveal that changes in cognition as the disease progresses were an important concern among caregivers. We encourage caregivers and health care professionals to discuss these changes and any others during regular visits," Eric J. Hall, president and CEO of the AFA, said in a Harris Interactive news release.

More information

The U.S. National Institute on Aging has more about Alzheimer's disease.

Coronary Artery Calcium Aids Risk Classification in Elderly

Adding CAC to risk classification model most appropriate for those at intermediate risk

19 oct 2010-- Coronary artery calcium (CAC) levels can be used to fine-tune coronary heart disease (CHD) risk assessment in elderly people with no disease symptoms, according to a study in the Oct. 19 issue of the Journal of the American College of Cardiology.

Suzette E. Elias-Smale, M.D., of Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues followed 2,028 elderly subjects without CHD symptoms for a median 9.2 years, during which 135 nonfatal myocardial infarctions and CHD deaths occurred. First the subjects were classified into low-, intermediate-, and high-risk categories in accordance with a Framingham risk model, and then the researchers added CAC levels (measured in Agatston units) to the risk model, assessed the impact of CAC on risk recalculation, and computed CAC cutoff values for risk reclassification.

Fifty-one percent of men and 53 percent of women initially classified as intermediate-risk were reclassified as a result of the inclusion of CAC levels. Among men, 30 percent of those initially at intermediate risk were moved to the low-risk category, and 21 percent were moved to the high-risk category. Among women, 29 percent of those initially at intermediate risk were moved to a lower-risk category and 24 percent were moved to a higher-risk category.

"In a general population of elderly patients at intermediate CHD risk, CAC scoring is a powerful method to reclassify persons into more appropriate risk categories. Empirically derived CAC cut-off values at which persons at intermediate risk reclassified to either high or low risk were 615 and 50 Agatston units, respectively," the authors write.

Abstract
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TTF and chemotherapy increase survival for patients with advanced non-small cell lung cancer

Novocure reported that patients with advanced non-small cell lung cancer (NSCLC) achieved a significant increase in survival time when tumor treating fields (TTF) therapy was added to chemotherapy, as compared to previously reported outcomes for patients receiving chemotherapy alone. Dr. Miklos Pless, head of medical oncology at the Winterthur Hospital Cancer center in Switzerland, presented the data at the European Society for Medical Oncology Congress (ESMO).

18 oct 2010--Physicians delivered TTF Therapy to patients in the study using the NovoTTF-100L—a portable, non-invasive medical device. Investigators conducted this single arm, phase II study at four centers in Switzerland, enrolling 42 patients with locally advanced and metastatic NSCLC (stage IIIb-IV) who had failed prior treatments with chemotherapy. Patients in the study received TTF Therapy for 12 hours a day in combination with pemetrexed (Alimta; Eli Lilly) until disease progression.

Advanced NSCLC is the second cancer in which TTF Therapy has shown clinical efficacy in human trials. Novocure reported a successful phase III clinical trial of TTF monotherapy in patients with recurrent glioblastoma, an aggressive form of brain cancer, at the American Society for Clinical Oncology Conference (ASCO) earlier this year. Results of this phase III trial have been filed with the U.S. Food and Drug Administration (FDA).

"We were pleased to report on the results of this multi-center trial of TTF Therapy in a non-brain tumor indication," said Dr. Pless. "We believe this study has shown TTF Therapy to be completely non-toxic and to have the potential to act as a significant adjunct to chemotherapy in the treatment of NSCLC and other solid tumor indications."

Patients treated with TTF Therapy in combination with pemetrexed had a median overall survival time of 13.8 months compared with the 8.3 months reported for pemetrexed alone. The one-year survival rate for the combination was 57 percent compared with the 30 percent reported for pemetrexed alone. Progression-free survival more than doubled when TTF Therapy was added to pemetrexed, to 22-28 weeks versus the 12 weeks previously reported for pemetrexed alone1. The only reported adverse event for TTF Therapy was mild to moderate skin irritation at the treatment site.

"These NSCLC data further validate TTF Therapy as a viable approach to treating deadly cancers," said Asaf Danziger, chief executive officer of Novocure. "We have seen positive clinical success in both phase II and phase III studies, alone and in combination with chemotherapy, and believe TTF Therapy has the potential to be effective in a range of solid tumors."

TTF Therapy slows and reverses tumor cell proliferation by inhibiting mitosis, the process by which cells divide and replicate themselves. The NovoTTF-100L device, which weighs about six pounds (three kilograms), creates a low-intensity, alternating electric field within the tumor that exerts physical forces on electrically charged cellular components, preventing the normal mitotic process and causing cancer cell death prior to division.

Novocure’s NovoTTF-100A device has received its CE Mark and is approved for sale in six European countries as a treatment for glioblastoma brain tumors. The NovoTTF-100L device has received its CE Mark as a treatment for NSCLC and will be launched in Europe in the near future. Novocure is also planning to file an investigational device application with the FDA for a phase III study of TTF Therapy in early stage NSCLC in the near future.

More information: Nasser Hanna et al; "Randomized Phase III Trial of Pemetrexed versus Docetaxel in Patients with Non-Small-Cell Lung Cancer Previously TreatedWith Chemotherapy," Journal of Clinical Oncology 22.9 (2004): pp 1589-1597