Media coverage of drug studies lacking

by Elizabeth Cooney
05 oct 2008--The news media isn't doing a very good job when it comes to reporting on drug studies published in leading scientific journals, Cambridge researchers report. Journalists too often let readers down by leaving out information that might reflect bias in the results, and use brand names that might implicitly promote the drug in question, the researchers conclude.
Almost half of the stories in newspapers and on online news sites neglected to mention pharmaceutical company funding for drug trials whose results were published in high-impact medical journals, according to a review of more than 300 news articles conducted by Dr. Michael Hochman and colleagues from Cambridge Health Alliance and Harvard Medical School. Their study was paid for by Cambridge Hospital. Hochman, a third-year resident in internal medicine, is a contributor to The Boston Globe.
More than a third of the news stories used only the brand name of the drug, the review also found.
"As a doctor I've become increasingly worried in recent years that company-funded research, to put it simply, can't be trusted. The rofecoxib scandal -- better known as the Vioxx scandal -- is one example of this," Hochman said in an interview. "I am worried that lay readers and patients don't always look at it this way and I think it's very important when patients or readers read a medical story that they are at least aware of who sponsored it and what the motives are of who sponsored it."
All the trials in question were paid for by drug companies and all had their funding sources included in the journal articles. A growing number of scientific journals require authors to make disclosures in order to reveal potential conflicts of interest.
Despite this showing, when editors at the top 100 newspapers were surveyed about their coverage, 82 of the 93 who responded said their stories always or often indicated drug-company funding, and 71 editors said they used generic names rather than brand names. Only three newspapers had written policies requiring reporters to include company funding of drug studies in their stories. Only two newspapers had written policies mandating the use of generic names rather than brand names for drugs.
The Boston Globe's written policy states that health/science reporters must always ask the doctors and scientists they interview whether they have any financial stake in a study, even if they have already made a disclosure to the journal in which their work is published. Conflicts should be included in the news story, the policy says, as well as whether a researcher or physician declined to answer questions about it. Reporters must also always determine who paid for a study and what control they had over how it was conducted or described in a paper.
The Globe's policy does not address using generic vs. brand names in its stories.
Hochman's article appears in the Journal of the American Medical Association, one of the five journals the Cambridge researchers reviewed from 2004 through 2008. The others are the New England Journal of Medicine, The Lancet, Annals of Internal Medicine and Archives of Internal Medicine. Studies have shown that company-funded research is more likely to have favorable results than non company-funded research, Hochman said.
"If a company sponsors a study, they are doing it so that it promotes the product," he said. "When I read a newspaper, I see a lot of times they don't do a very good job of indicating how the study was funded."
Journals could make funding disclosures more prominent, Hochman said, including them in scientific paper abstracts, the short descriptions that may be all a reader sees. Press releases sent to news outlets should --- but almost never do -- include information on who funded a study, Hochman's team also found.
Reporters aren't alone in using brand names, Hochman said.
"I think all of us -- doctors, patients, and the news media -- have gotten into what I would consider to be bad habit of referring to medications by brand name rather than generic name," he said. "The commercial interest should be as separate as possible from medical decision making."

Merck Discontinues Development of Investigational Medicine Taranabant for Obesity

WHITEHOUSE STATION, N.J., 05 oct 2008 - Merck & Co., Inc. will not seek regulatory approval for taranabant, an investigational medicine, to treat obesity and is discontinuing its Phase III clinical development program for taranabant for obesity. "Available Phase III data showed that both efficacy and adverse events were dose related, with greater efficacy and more adverse events in the higher doses. Therefore, after careful consideration, we determined that the overall profile of taranabant does not support further development for obesity," said John Amatruda, M.D., senior vice president and research head, diabetes and obesity, Merck Research Laboratories. "We thank the patients and investigators around the world who collaborated with us on the research program for taranabant and look forward to developing new medicines for obesity to address the significant medical need posed by this disease."

CT Screening for Lung Cancer: Update 2007

Claudia I. Henschke
05 oct 2008--Screening is the pursuit of the early diagnosis of cancer before symptoms occur. The purpose of early diagnosis is to provide early treatment, which potentially prevents death from the cancer. The usefulness of screening depends on how early the cancer can be diagnosed and how many deaths can be prevented by early treatment as compared with later symptom-prompted diagnosis and treatment.
The goal of the Early Lung Cancer Action Project investigators was to develop an efficient methodology that would provide an ever-accumulating, continually updated body of evidence for evaluation of emerging new technologies for screening for cancer. This methodology recognizes that screening is a sequential process that starts with the pursuit of the early diagnosis of cancer followed by early treatment. It also recognizes that diagnostic research is fundamentally different from treatment research. To fully understand the current discussions on the evidence for lung cancer screening, key definitions are provided, including the differentiation between the first, baseline round of screening and all subsequent rounds of repeat screening and baseline and repeat cancers and their distribution by cell type. These definitions are critical in analyzing the results of various screening reports as they are not used by all.
To provide optimal screening, a regimen for the diagnostic workup must be specified starting with the definition of the initial test, its positive result, and the workup for a positive result leading to a diagnosis of cancer. Assessment of diagnostic performance does not require a control group, but does require confirmation of the diagnosis.
For assessment of the effectiveness of early treatment, a comparison group is needed. The comparison group may be formed by randomly assigning people with screen-diagnosed lung cancer to immediate or delayed treatment, as has been done for prostate cancer. This provides a direct assessment of any potential overdiagnosis of the cancer resulting from screening. Alternatively, a quasiexperimental control group can be used consisting of participants diagnosed with the cancer who have refused or delayed their treatment even though they are candidates for it.

Supplements no better than placebo in slowing cartilage loss in knees of osteoarthritis patients

SALT LAKE CITY, 04 oct 2008 – In a two-year multicenter study led by University of Utah doctors, the dietary supplements glucosamine and chondroitin sulfate performed no better than placebo in slowing the rate of cartilage loss in the knees of osteoarthritis patients.
This was an ancillary study concurrently conducted on a subset of the patients who were enrolled in the prospective, randomized GAIT (Glucosamine/chondroitin Arthritis Intervention Trial). The primary objective of this ancillary study was to investigate whether these dietary supplements could diminish the structural damage of osteoarthritis. The results, published in the October issue of Arthritis & Rheumatism, show none of the agents had a clinically significant effect on slowing the rate of joint space width loss —the distance between the ends of joint bones as shown by X-ray.
However, in line with other recent studies, the researchers observed that all the study's participants had a slower rate of joint space width loss than expected, making it more difficult to detect the effects of the dietary supplements and other agents used in the study.
Rheumatologist Allen D. Sawitzke, M.D., associate professor of internal medicine at the University of Utah School of Medicine, was lead investigator. "At two years, no treatment achieved what was predefined to be a clinically important reduction in joint space width loss," Sawitzke said. "While we found a trend toward improvement among those with moderate osteoarthritis of the knee in those taking glucosamine, we were not able to draw any definitive conclusions."
More than 21 million Americans have osteoarthritis, with many taking glucosamine and chondroitin sulfate, separately or in combination, to relieve pain. The original GAIT, led by University of Utah rheumatologist Daniel O. Clegg, M.D., professor of internal medicine, was a multicenter, randomized, national clinical trial that studied whether these dietary supplements provided significant pain relief to people with osteoarthritis in the knees. GAIT found that the supplements produced no more pain relief than placebo (New England Journal of Medicine, February 2006), although a subset of the original GAIT participants with moderate to severe osteoarthritis knee pain appeared to receive significant pain relief when they took a combination of glucosamine and chondroitin sulfate.
In this ancillary study, GAIT patients were offered the opportunity to continue their original study treatment for an additional 18 months, for a total of two years. Participants remained on their originally assigned GAIT treatment: 500 mg of glucosamine three times a day; or 400 mg of chondroitin sulfate three times a day; or a combination of the two supplements; or 200 mg of celecoxib daily; or a placebo.
X-rays were obtained at study entry and again at one and two years. Joint space width was measured on 581 knees from 357 patients. None of the trial groups showed significant improvement. The group taking glucosamine had the least change in joint space width, followed by the groups taking chondroitin sulfate, celecoxib, placebo and the combination of both dietary supplements.
The total joint space width loss over two years for each group was:
0.013mm (glucosamine)
0.107mm (chondroitin sulfate)
0.111mm (celecoxib)
0.166mm (placebo)
0.194mm (glucosamine and chondroitin sulfate)
The interpretation of the results was problematic because the placebo group's joint space width loss was much less at two years than the 0.4mm the researchers' expected. Based on other large studies published in scientific journals, the researchers hypothesized that a loss of 0.2mm or less at two years would mean a slowed rate of cartilage loss. However, because the reduction in rate of joint space loss for all the groups was under the 0.2mm threshold, the researchers concluded none of the agents significantly slowed the loss of joint space width.
Josephine P. Briggs, M.D., director of the National Center for Complementary and Alternative Medicine, one of the study's funders, said although no definitive conclusions can be drawn about the two dietary supplements yet, "the results of the study provide important insights for future research."
Clegg said the trial shed light on osteoarthritis progression, techniques that can more reliably measure joint space width loss, possible effects of glucosamine and chondroitin sulfate, and on identifying patients who may respond best as further studies are pursued.
###
The other centers in the study were: The Arthritis Research and Clinical Centers, Wichita, Kan.; University of Arizona, Tucson; Case Western Reserve University, Cleveland; Cedars-Sinai Medical Center; Los Angeles; Indiana University, Indianapolis; University of California, Los Angeles; University of California, San Francisco; University of Pittsburgh.

Study looks at psychological impact of gene test for breast cancer

DNA testing for hereditary breast cancer: Many women have inconclusive results -- how do they adjust?

04 oct 2008--Personal beliefs about inconclusive DNA testing for hereditary breast cancer are associated with cancer-related worry, and such beliefs are an especially strong predictor of whether women had been able to leave the period of DNA-testing behind, reports a study in the October issue of Genetics in Medicine, official journal of the American College of Medical Genetics (ACMG). The journal is published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health.
Published during National Breast Cancer Awareness Month, the study lends new insights into how women cope with the results of BRCA testing for hereditary breast cancer—an increasingly used genetic test in which an "inconclusive" result is common.
Sandra van Dijk, M.A., Ph.D., of Leiden University Medical Center, The Netherlands, assessed psychological adjustment in 215 women who underwent DNA testing for BRCA gene mutations associated with hereditary breast cancer. Of these, 147 women—more than two-thirds of the total—had inconclusive results. The results were positive in 37 women and "true negative" in 31.
Several Factors Affect Adjustment to Uncertainty
An inconclusive result on BRCA testing means the woman carries no genetic mutation currently known to increase breast cancer risk. However, she may still be at increased risk because of unrecognized mutations, or because of other risk factors associated with familial breast cancer. Of women in the study with inconclusive results, about half were still considered to have more than a 30 percent residual risk of a cancer-causing mutation.
When re-evaluated after four years, none of the three groups had "adverse psychological consequences" of BRCA testing, the researchers write. Not surprisingly, women with negative results had the lowest rates of worry and cancer-related distress. For women with inconclusive results, levels of worry and distress were similar to those who tested positive for a BRCA mutation. In all three groups, the women were less worried than before they were tested.
The study found that the women's beliefs about their inconclusive result had an important impact on their psychological adjustment. "For example, women who report feeling uncertain or ambivalent about their inconclusive DNA test result reported higher levels of worry and distress," Drs. Van Dijk and colleagues write. The women's beliefs about their inconclusive results were "very strongly related" to whether they had come to terms with their result and its implications for breast cancer risk.
The link between beliefs and psychological adjustment remained strong even after accounting for the women's levels of worry and distress. "Cancer-related worries and distress may provide an important but incomplete picture on how women adapt to their inconclusive result," according to the researchers. "[W]omen differ in whether they can cope with the uncertainty of an inconclusive result."
Other important factors included whether the women were actually tested themselves or had received inconclusive results from an affected relative who was tested. Women who were not personally tested were more likely to believe they might have inherited a BRCA mutation, which in turn was related to lower psychological adjustment.
Implications for Genetic Counseling
As in other genetic tests, the psychological impact of BRCA testing is an important consideration. Previous research has found that BRCA testing does not generally lead to high levels of psychological distress. However, few studies have focused on adjustment in the large number of women with inconclusive results.
Dr. van Dijk and colleagues believe their results highlight the role played by genetic counselors in ensuring that women accurately understand their BRCA test—including the uncertainty associated with inconclusive results. They write, "Not only must women's expectations before BRCA testing be addressed, but also the issue of how women are planning to come to terms with an inconclusive result."
"Over 200,000 women will be diagnosed in the U.S. this year with breast cancer and a significant minority of them will have developed cancer because they harbor a BRCA1 or BRCA2 mutation," comments Dr. James P. Evans, Editor-in-Chief of Genetics in Medicine. "Sequencing of these genes has been a boon to patient management and to their family members but such testing comes with a psychological price. In the current issue of GIM, van Dijk et al. explore the psychological effect of discovering such ambiguous and potentially disturbing results."
###
Note to editors: Interviews with the lead authors available upon request by contacting Kathy Beal, Media Relations Officer for the ACMG: phone 301-238-4582 or e-mail kbeal@acmg.netAbout the American College of Medical Genetics
Founded in 1991, the ACMG (www.acmg.net) provides education, resources and a voice for the medical genetics profession. To make genetic services available to and improve the health of the public, the ACMG promotes the development and implementation of methods to diagnose, treat and prevent genetic disease. Members include biochemical, clinical, cytogenetic, medical and molecular geneticists, genetic counselors, and other health care professionals committed to the practice of medical genetics. Genetics in Medicine, now published monthly, is the official journal of the ACMG.

Breast cancer cells recycle to escape death by hormonal therapy

Dr. Patricia V. Schoenlein, cancer researcher in the Medical College of Georgia Schools of Medicine and Graduate Studies.

04 oct 2008--Many breast cancer cells facing potentially lethal antiestrogen therapy recycle to survive, researchers say.
About 70 percent of breast cancer cells have receptors for the hormone estrogen, which acts as a nutrient and stimulates their growth. Patients typically get an antiestrogen such as tamoxifen for five years to try to starve them to death, says Dr. Patricia V. Schoenlein, cancer researcher in the Medical College of Georgia Schools of Medicine and Graduate Studies.
"About 50 to 60 percent of these women really benefit from hormonal therapy," says Dr. Schoenlein. Why others don't has been asked for at least two decades.
One reason may be breast cancer cells switch into a survival mode that normal cells also use when faced with starvation, according to research published in the September issue of Molecular Cancer Therapeutics. Dr. Schoenlein also is reporting on the research during the 2nd World Conference on Magic Bullets (Ehrlich II) Oct. 3-5 in Nürenberg, Germany.
It's called macroautophagy – autophagy means "self eating" – and within a week, breast cancer cells can reorganize component parts, degrade non-essentials and live in this state until antiestrogen therapy is stopped or the cells mutate and resume proliferation in the presence of tamoxifen. "It's like taking your foot off of the gas pedal of your car," says Dr. Schoenlein, corresponding author on the study. "The cancer cell is in idle, unable to grow or replicate. But the cell is smart enough to use component parts generated by macroautophagy for the most necessary things required for survival." She notes that macroautophagy can't be maintained indefinitely; cells can actually self-digest. "This is a time-buying strategy."
Chemotherapeutic drugs are more direct killers but also kill healthy cells and can be tolerated by patients only for relatively short periods. Antiestrogen therapy is more specific, targeting breast cancer cells that express estrogen receptors.
In the laboratory, 20-25 percent of breast cancer cells died when Dr. Schoenlein and colleagues gave antiestrogen continuously over time – similar to how patients get it. More typically, the cells expressed increasing levels of macroautophagy and survived. "They don't grow, but they survive the therapy. They will grow if you take away the therapy." Adding a macroautophagy inhibitor promoted robust cell death.
"We believe targeting the autophagosome function will significantly improve the efficacy of hormonal treatment for estrogen-positive breast cancer," says the researcher. She recently received a three-year, $1.1 million National Cancer Institute grant to pursue that strategy.
She'll now look for ways to block macroautophagy in an animal model, including using chloroquine, a drug used to treat malaria. "We know patients can take it with few side effects," she says. If it works in animals, the drug, in combination with an antiestrogen, could move relatively quickly into human testing.
During autophagy, the internal pH for the recycling center of the reorganized cell gets acidic and chloroquine increases pH. "If you add this particular inhibitor of the recycling center, you alter the pH and block its ability to do what it is supposed to do," says Dr. Schoenlein.
A University of Pennsylvania team led by Dr. Craig Thompson reported in 2007 in The Journal of Clinical Investigation that chloroquine increased death of suicide-resistant lymphoma cells being treated with chemotherapy. Dr. Schoenlein will give chloroquine along with an antiestrogen and measure cell death.
"Most cancers probably use autophagy as a survival mechanism. You can either block the autophagosome with your therapy or you can make the cell eat itself to the point of no return and the cell self-destructs. You have to push it either way," she says. Although there are no known compounds in clinical use to induce self-destruction by autophagy, there is some evidence arsenic trioxide, a compound used in China to treat some aggressive cancers, prompts cancer cells to die from self digestion, she says. That and other compounds will no doubt be studied further, she says.
Dr. Schoenlein believes breast cancer survival during macroautophagy requires high activity of the tumor suppressor protein Rb and low levels of the lipid ceramide. Ceramide is vital but causes cell death at high levels. MCG researcher Erhard Bieberich and colleague Dr. Brian G. Condie at the University of Georgia showed in 2003 that high levels of ceramide kill cells that are unnecessary to the developing brain. The new studies will further explore the roles of Rb and ceramide in breast cancer survival during macroautophagy and determine if chloroquine can change their balance.

Steps could get more seniors into clinical trials

By Joene Hendry
04 oct 2008--Various strategies could encourage elderly people to participate and stay in clinical trials -- a pressing issue as the population ages -- researchers suggest.
"No one is ever too old to make a meaningful contribution to research," said Dr. Patricia S. Goode, of the University of Alabama at Birmingham.
Nevertheless, "Older participants are often specifically excluded from clinical trials, even those testing therapies that will be prescribed for older persons," Goode told Reuters Health.
She and her colleagues note in the Journal of the American College of Surgeons that trials testing different medical treatments need to recruit participants representing the people for whom the treatment is intended.
To assess potential reasons why the elderly are often excluded from research studies, the team examined the recruitment and retention of older women participating in two trials assessing surgical procedures for pelvic organ prolapse.
The investigators developed a questionnaire that addressed factors that either facilitated or impeded trial enrollment and completion, then assessed responses from 23 physicians and 11 nurses involved in research studies.
These responses show a third of the doctors and nurses felt it is harder to recruit older study participants and more than half cited difficulties obtaining informed consent.
Other hurdles for elderly participants included caregiver involvement, having several health disorders, fatigue, and cognitive impairment.
However, when Goode and colleagues assessed actual retention rates of the 512 women enrolled in the two surgical trials -- of whom about 221 were 70 years and older -- they found older participants did not have higher drop-out rates than younger participants. The investigators also noted no age-group differences in missed follow-up visits.
"Recruitment and retention of older women for research studies can equal that of younger women if special measures are taken," Goode said.
She and her colleagues list numerous steps that can be taken to overcome barriers faced by elderly participants. These include, for example, allocating time to explain study procedures clearly, ensuring participants have transportation assistance to and from study visits, buying a lightweight amplifying headset for the clinic to help people with hearing impairment, and using large print on questionnaires.
Although these strategies haven't been tested, the researchers say they could help investigators successfully enroll and retain older subject in their clinical trials.
SOURCE: Journal of the American College of Surgeons, September 2008.

Could Chinese Herb Be a Natural Viagra?

By Amanda Gardner
04 oct 2008-- A Chinese herbal remedy known as "horny goat weed" may indeed live up to its name as a natural version of Viagra.
Italian researchers report that laboratory studies show that the compound has the potential to treat erectile dysfunction, and possibly with fewer side effects than its pharmaceutical cousin.
"No in-vivo studies in an animal model have been performed at this regard, so a lot of work must be done. We would like to test in vivo [with animals] the molecule to understand if it really works in humans," said study lead author Mario Dell'Agli, of the University of Milan's laboratory of pharmacognosy. "At this stage of the research, we cannot say if the molecule we have synthesized possesses less side effects with respect to Viagra. However, this derivative seems to be in vitro [in lab tests] more selective than Viagra, because it targets [an enzyme involved in blood flow to the penis] more precisely."
The study was expected to be published in the Oct. 24 issue of the Journal of Natural Products, a publication of the American Chemical Society.
Viagra (sildenafil) is one of several prescription medications available and widely prescribed for erectile dysfunction, a condition that affects an estimated 18 million men in the United States. Viagra and other drugs like it can cause side effects such as headache, stomach problems and visual disturbances.
Horny goat weed, hailing primarily from southern China, has a long history as an aphrodisiac.
As part of a new screening program to find natural alternatives to Viagra, the study authors analyzed a number of herbal extracts long used for male impotence, including Ferula hermonis or Lebanese Viagra; Cinnamomum cassia or Chinese cinnamon; as well as Epimedium brevicornum aka horny goat weed. All three extracts are reputed to improve sexual performance.
The main active component of each extract was tested against an enzyme known as phosphodiesterase-5A1 (PDE5A1), which regulates blood supply to the penis. Inhibition of this enzyme results in more blood flow to the penis, resulting in an erection.
Icariin, the active ingredient of horny goat weed, inhibited PDE5A1 to a greater degree than the other compounds tested.
"The novelty of this work is the new molecule we have synthesized by icariin," Dell'Agli said. "It is derived by chemical modifications of the structure of icariin, which is the active ingredient purified from E. brevicornum (horny goat weed). The mechanism by which the molecule we have found might work in humans is the inhibition of phosphodiesterase 5 (PDE 5) in the corpus cavernosum [erectile tissue in the penis], which is the mechanism by which Viagra works. This is an in vitro study. It can be considered a pre-clinical study."
More information
The National Institutes of Health has more on erectile dysfunction.

Palliative care access varies widely in the US according to new study in J Palliative Medicine

New Rochelle, NY, 03 oct 2008— There has been rapid growth of new, innovative palliative care consultation services in the nation's hospitals. More than half of the 50-bed or larger hospitals in the U.S. offer palliative care services to ease pain and suffering for seriously ill patients and their families. However, the availability of these services varies widely across geographic regions, according to a study published in the October 2008 issue of the peer-reviewed, Journal of Palliative Medicine. The study is available online at www.liebertpub.com/jpm
Whereas in 2000 only a few hospitals in the U.S. provided palliative care services, this report documents a steady overall increase in adoption of palliative care, with 52.8% of hospitals surveyed offering services aimed at alleviating pain and suffering. The number of large hospitals (>249 beds) with palliative care programs has increased to 72.2%, while fewer small hospitals (>50 beds) reported offering these services. Growth in palliative care has occurred mainly in not-for-profit hospitals and has been most notable in the midwestern and western regions of the U.S.
Benjamin Goldsmith, Jessica Dietrich, MPH, Qingling Du, MS, and R. Sean Morrison, MD, from the National Palliative Care Research Center, and Center to Advance Palliative Care in New York, report these findings in a paper entitled, "Variability in Access to Hospital Palliative Care in the United States."
"This paper documents the success and applicability of this new field of medicine in American health care. I hope it leads to the patient expectation that the expert relief of suffering will be as routine in hospitals as cardiology or surgery," says Charles F. von Gunten, MD, PhD, Editor-in-Chief of the Journal and Provost, Institute for Palliative Medicine at San Diego Hospice.
Importantly, the study found that 84% of medical schools were associated with at least one hospital that has a palliative care program. This positive finding implies that future doctors will have access to training in palliative care, facilitating its incorporation into their daily patient care routines.
Additionally, the authors observed that the availability of palliative care services is inversely related to Medicare expenditures. "This implies that palliative care is consistent with other innovations—when the right care is applied to the right patient at the right time, overall costs go down because futile or ineffective approaches are abandoned in favor of the effective new intervention," says von Gunten.
###
About the Journal of Palliative Medicine
Journal of Palliative Medicine, published 10 times per year in print and online, is an interdisciplinary journal that reports on the clinical, educational, legal, and ethical aspects of care for seriously ill and dying patients. It includes coverage of the latest developments in drug and non-drug treatments for patients with life-threatening diseases including cancer, AIDS, cardiac disease, pulmonary, neurologic, respiratory conditions, and other diseases. The Journal reports on the development of palliative care programs around the United States and the world, and on innovation in palliative care education. Journal of Palliative Medicine is the Official Journal of the American Academy of Hospice and Palliative Medicine (http://www.aahpm.org/). JPM is published by Mary Ann Liebert, Inc. (http://www.liebertpub.com/).

New study proves that pain is not a symptom of arthritis, pain causes arthritis

New treatments will seek to interrupt 'crosstalk' between joints and the spinal cord

03 oct 2008--Pain is more than a symptom of osteoarthritis, it is an inherent and damaging part of the disease itself, according to a study published today in journal Arthritis and Rheumatism. More specifically, the study revealed that pain signals originating in arthritic joints, and the biochemical processing of those signals as they reach the spinal cord, worsen and expand arthritis. In addition, researchers found that nerve pathways carrying pain signals transfer inflammation from arthritic joints to the spine and back again, causing disease at both ends.
Technically, pain is a patient's conscious realization of discomfort. Before that can happen, however, information must be carried along nerve cell pathways from say an injured knee to the pain processing centers in dorsal horns of the spinal cord, a process called nociception. The current study provides strong evidence that two-way, nociceptive "crosstalk" may first enable joint arthritis to transmit inflammation into the spinal cord and brain, and then to spread through the central nervous system (CNS) from one joint to another.
Furthermore, if joint arthritis can cause neuro-inflammation, it could have a role in conditions like Alzheimer's disease, dementia and multiple sclerosis. Armed with the results, researchers have identified likely drug targets that could interfere with key inflammatory receptors on sensory nerve cells as a new way to treat osteoarthritis (OA), which destroys joint cartilage in 21 million Americans. The most common form of arthritis, OA eventually brings deformity and severe pain as patients loose the protective cushion between bones in weight-bearing joints like knees and hips.
"Until relatively recently, osteoarthritis was believed to be due solely to wear and tear, and inevitable part of aging," said Stephanos Kyrkanides, D.D.S., Ph.D., associate professor of Dentistry at the University of Rochester Medical Center. "Recent studies have revealed, however, that specific biochemical changes contribute to the disease, changes that might be reversed by precision-designed drugs. Our study provides the first solid proof that some of those changes are related to pain processing, and suggests the mechanisms behind the effect," said Kyrkanides, whose work on genetics in dentistry led to broader applications. The common ground between arthritis and dentistry: the jaw joint is a common site of arthritic pain.
Study Details
Past studies have shown that specific nerve pathways along which pain signals travel repeatedly become more sensitive to pain signals with each use. This may be a part of ancient survival skill (if that hurt once, don't do it again). Secondly, pain has long been associated with inflammation (swelling and fever).
In fact, past research has shown that the same chemicals that cause inflammation also cause the sensation of pain and hyper-sensitivity to pain if injected. Kyrkanides' work centers around one such pro-inflammatory, signaling chemical called Interleukin 1-beta (IL-1β), which helps to ramp up the bodies attack on an infection.
Specifically, Kyrkanides' team genetically engineered a mouse where they could turn up on command the production of IL-1β in the jaw joint, a common site of arthritis. Experiments showed for the first time that turning up IL-1β in a peripheral joint caused higher levels of IL-1β to be produced in the dorsal horns of the spinal cord as well.
Using a second, even more elaborately engineered mouse model, the team also demonstrated for the first time that creating higher levels of IL-1β in cells called astrocytes in the spinal cord caused more osteoarthritic symptoms in joints. Past studies had shown astrocytes, non-nerve cells (glia) in the central nervous system that provide support for the spinal cord and brain, also serve as the immune cells of CNS organs. Among other things, they release cytokines like IL-1β to fight disease when triggered. The same cytokines released from CNS glia may also be released from neurons in joints, possibly explaining how crosstalk carries pain, inflammation and hyper-sensitivity back and forth.
In both mouse models, experimental techniques that shut down IL-1β signaling reversed the crosstalk effects. Specifically, researchers used a molecule, IL-1RA, known to inhibit the ability of IL-1β to link up with its receptors on nerve cells. Existing drugs (e.g. Kineret® (anakinra), made by Amgen and indicated for rheumatoid arthritis) act like IL-1RA to block the ability IL-1β to send a pain signal through its specific nerve cell receptor, and Kyrkanides' group is exploring a new use for them as osteoarthritis treatment.
The implications of this process go further, however, because the cells surrounding sensory nerve cell pathways too can be affected by crosstalk. If 10 astrocytes secrete IL-1β in response to a pain impulse, Kyrkanides said, perhaps 1,000 adjacent cells will be affected, greatly expanding the field of inflammation. Spinal cord astrocytes are surrounded by sensory nerve cells that connect to other areas of the periphery, further expanding the effect. According to Kyrkanides' model, increased inflammation by in the central nervous system can then send signals back down the nerve pathways to the joints, causing the release of inflammatory factors there.
Among the proposed, inflammatory factors is calcitonin gene related peptide (CGRP). The team observed higher levels calcitonin-gene related peptide (CGRP) production in primary sensory fibers in the same regions where IL-1β levels rose, and the release of IL-1β by sensory neurons may cause the release of CGRP in joints. Past studies in Kyrkanides reveal that CGRP can also cause cartilage-producing cells (chondrocytes) to mature too quickly and die, a hallmark of osteoarthritis.
Joining Kyrkanides in the publication from the University of Rochester School of Medicine and Dentistry were co-authors M. Kerry O'Banion, M.D., Ph.D., Ross Tallents, D.D.S., J. Edward Puzas, Ph.D. and Sabine M. Brouxhon, M.D. Paolo Fiorentino was a student contributor and Jennie Miller was involved as Kyrkanides' technical associate. Maria Piancino, led a collaborative effort at the University of Torino, Italy. This work was supported in part by grants from the National Institutes of Health.
"Our study results confirm that joints can export inflammation in the form of higher IL-1β along sensory nerve pathways to the spinal cord, and that higher IL-1β inflammation in the spinal cord is sufficient in itself to create osteoarthritis in peripheral joints," Kyrkanides said. "We believe this to be a vitally important process contributing to orthopaedic and neurological diseases in which inflammation is a factor."

Logging On for a Second (or Third) Opinion

By JOHN SCHWARTZ
03 oct 2008--When Terri Nelson learned she had a large fibroid tumor in her uterus, she went online.
There is nothing new in that, of course. The intrepid and the adept were going to the Web for health information as long ago as the 1980s, well before Google and other search engines made it accessible to a wider audience.
These days, that is pretty much everyone. At least three-quarters of all Internet users look for health information online, according to the Pew Internet and American Life Project; of those with a high-speed connection, 1 in 9 do health research on a typical day. And 75 percent of online patients with a chronic problem told the researchers that “their last health search affected a decision about how to treat an illness or condition,” according to a Pew Report released last month, “The Engaged E-Patient Population.”
Reliance on the Internet is so prevalent, said the report’s author, Susannah Fox, the associate director at Pew, that “Google is the de facto second opinion” for patients seeking further information after a diagnosis.
But paging Dr. Google can lead patients to miss a rich lode of online resources that may not yield to a simple search. Sometimes just adding a word makes all the difference. Searching for the name of a certain cancer will bring up the Wikipedia entry and several information sites from major hospitals, drug companies and other providers. Add the word “community” to that search, Ms. Fox said, and “it’s like falling into an alternate universe,” filled with sites that connect patients.
As a result, said Dr. Ted Eytan, medical director for delivery systems operations improvement at the Permanente Federation, “patients aren’t learning from Web sites — they’re learning from each other.” The shift is nothing less than “the democratization of health care,” he went on, adding, “Now you can become a national expert in your bedroom.”
These expanded capabilities allow people to share information easily, upending the top-down path of information between doctors and patients. Today, said Clay Shirky, an expert in the evolving online world, patients are “full-fledged actors in the system.”
And they have plenty of company. Benjamin Heywood, the president of PatientsLikeMe.com, a site that allows patients to track and document their conditions and compare notes with other patients, says that with a growing online population, it becomes possible to research highly specific conditions — say, being a 50-year-old with multiple sclerosis who has leg spasms and is taking a certain combination of drugs.
“We are really about measuring value in the real world,” he said.
There are so many sites today and the landscape is changing so rapidly that it would take an encyclopedia rather than a newspaper to list them. But they can be grouped into five broad, often overlapping, categories:
GENERAL INTEREST Sites like WebMD (webmd.com), Discovery Health (health.discovery.com) and The New York Times (nytimes.com/health) provide information about disease, news and lifestyle advice, as do medical institutions like the Mayo Clinic (mayoclinic.com).
MEDICAL RESEARCH SITES offer access to the published work of scientists, studies and a window into continuing research. Examples include PubMed (ncbi.nlm.nih.gov/pubmed) from the National Library of Medicine; clinicaltrials.gov, which tracks federally financed studies; psycinfo (apa.org/psycinfo), with its trove of psychological literature; and the National Center for Complementary and Alternative Medicine (nccam.nih.gov), the government’s registry on alternative medicine research.
PATIENT SITES for groups and individuals are booming — so much so that they are increasingly used by researchers to find patients for studies. These include the Association of Cancer Online Resources (acor.org) and e-patients (e-patients.net), as well as Patients Like Me and Trusera (trusera.com), which provide a bit of Facebook-style social connectivity for patients, along with the ability to share their stories in clinical, data-laden detail.
DISEASE-SPECIFIC SITES focus on a particular condition and are often sponsored by major organizations like the American Heart Association (americanheart.org), the American Cancer Society (cancer.org) and the American Diabetes Association (diabetes.org). But smaller groups can put together extensive resources as well, with sites like breastcancer.org and Diabetes Mine (diabetesmine.com), which calls itself the “all things diabetes blog.”
WEB TOOLS These sites help people manage their conditions — for example, sugarstats.com for diabetes, Destination Rx (drx.com) for comparing drug prices, and YourDiseaseRisk.com, a service of the Washington University school of medicine that helps patients determine their risk for various problems.
All of the changes in the Internet and the ways people use it help explain why Terri Nelson’s experience in 2008 is very different from what it might have been in 1998.
Ms. Nelson, who lives in Portland, Ore., received her diagnosis on Aug. 11. She had two weeks before a follow-up visit with her surgeon. Ms. Nelson and her husband, Stewart Loving-Gibbard, used the time to research fibroids and the most common treatments.
Ms. Nelson started with straightforward information gathering, checking the articles on fibroid tumors at sites that included the Mayo Clinic and PubMed. Then she reached out to the community of people with fibroid tumors at ACOR and other sites. (“Those had to be evaluated carefully,” she said, “to find the nuggets of valid information in the vast sea of online hypochondria.”)
Having spent many years trolling roisterous online forums, however, she had developed that essential Internet tool: what might be called a personal baby/bathwater algorithm that helps people to sift through mountains of information to find what is relevant. She found a blog for the layperson, “Inquisitive Geek With Fibroid Tumors,” that featured wide-ranging discussions and, she said, “was really useful” and specific to her condition.
By the time she went into the consultation with her surgeon, she knew that the old-school way of dealing with her grapefruit-size tumor would probably have been a hysterectomy. But that can impair sexual response, among other side effects; a growing number of doctors prefer abdominal myomectomy, which leaves the uterus intact. The surgeon laid out the options and recommended that approach as well, confirming Ms. Nelson’s research.
During the surgery and recovery, Mr. Loving-Gibbard used Twitter, the short-message communication service, to keep friends and family apprised of her condition. Twittering an operation might seem frivolous, but when Ms. Nelson’s teeth began chattering after the procedure, a friend following the updates suggested it could be a potentially hazardous side effect, tardive dyskinesia, that can occur with one of the antinausea drugs Ms. Nelson was taking. Mr. Loving-Gibbard, who had been researching that very point when the message from the friend, Ken Yee, came in, was able to get the medication changed.
After the procedure, they posted photographs of the surgery and tumor on the photo-sharing site Flickr.com under the heading “Extracting a Pound of Flesh” (flickr.com/photos/littlecrumb/sets/72157607218121711/).
They are not for the squeamish, but as Ms. Nelson said, “My husband’s family is mostly doctors, so they were all interested in seeing the photos, and most of my friends are morbidly fascinated.”
As patients go online to share information and discuss their care, they are becoming something more: consumers. Amy Tenderich, the creator of Diabetes Mine has turned her site into a community for diabetes patients and an information clearinghouse for treatments and gadgets — even going so far as to publish an open letter last year to Steven Jobs, the Apple Computer co-founder, challenging him to design medical devices like insulin pumps that are as sleek and easy to use as an iPod.
Dr. Talmadge E. King Jr., chairman of the department of medicine at the University of California, San Francisco, says doctors are coming around to seeing the value of a patient who has gone online for information.
Patients in his pulmonary practice, he said, sometimes come into his office holding medical journal articles he has written “and quiz me.” The better-educated patient might stump the doctor, he went on, but these days “it’s much easier for me to look them straight in the eye and say, ‘I don’t know’ ” and promise to get back to them. “Patients know you’re not all-knowing,” he said. “They’re not upset by that.”
Can online information be trusted? The answer, increasingly, is yes. In a study earlier this year, a report in the journal Cancer looked at 343 Web pages about breast cancer that came up in online searches. The researchers found 41 inaccurate statements on 18 sites — an error rate of 5.2 percent. Sites promoting alternative medicine were 15 times as likely to offer false or misleading health information as those sites that promoted conventional medicine, the study found.
Matthew Holt, who with Indu Subaiya created a conference, Health 2.0, that showcases innovation, says the marketplace in information can correct itself over time.
“In the end,” he said, “the more people you have in the conversation, the better information drives out the worse information.”

Computers help docs spot breast cancer on X-rays

By STEPHANIE NANO
03 oct 2008--A computer is as good as a second pair of eyes for helping a radiologist spot breast cancer on a mammogram, one of the largest and most rigorous tests of computer-aided detection found.
Like spell-checkers looking for mistakes, the computers flag suspicious areas on X-rays for a closer look by a radiologist. Mammograms are used to screen women for early signs of breast cancer but the tests aren't perfect. In the U.S., the X-rays are read by a single radiologist and cancers are sometimes missed.
Computer-aided detection, or CAD, was developed to help radiologists pick up more cancers. Approved a decade ago, these computer programs are now used for about a third of the nation's mammograms. But the value and accuracy of the technology has continued to be debated.
Now, British researchers are reporting results from a randomized study of 31,000 women. Mammograms in Britain are routinely checked by two radiologists or technicians, which is thought to be better than a single review. Researchers wanted to know if a single expert aided by a computer could do as well as two pairs of eyes.
They found that computer-aided detection spotted nearly the same number of cancers, 198 out of 227, compared to 199 for the two readers.
In places like the United States, "Where single reading is standard practice, computer-aided detection has the potential to improve cancer-detection rates to the level achieved by double reading," the researchers said. Their findings were published online Wednesday by the New England Journal of Medicine,
The study was done at three centers in England that do a large number of routine mammograms. Most of the women in the study were assigned to have their mammograms reviewed twice — once by a pair of experts and a second time by a single reviewer aided by a computer.
"What we demonstrated was that one reader using CAD could pick up as many cancers as the two readers could," said radiologist Fiona J. Gilbert of the University of Aberdeen, lead author of the study.
She said computer-aided detection could be used to expand screening by Britain's national health service, which now offers the test every three years to women 50 to 70. The cost-effectiveness will have to be determined first, she said.
The new findings are encouraging, said Dr. Carol H. Lee, a radiologist at Memorial Sloan-Kettering Cancer Center in New York.
"In the United States, it's just not practical in most practices to do double readings by physicians," said Lee, who is head of the American College of Radiology's Breast Imaging Commission. "These results are reassuring to me that single reading with CAD can achieve that same sensitivity."
The U.S. government recommends mammograms every one or two years starting at age 40. Experts said there aren't enough radiologists to give mammograms two readings, and insurers don't pay for a second look. Medicare does pay an additional $15 for computer-aided detection.
That extra money helped spur the adoption of the computer checks, said Dr. Ferris M. Hall, a radiologist at Boston's Beth Israel Deaconess Medical Center, where computers are used. He expects more places to use them as they switch to digital images from film X-rays, which eliminates a step in the process.
The research was funded by the British government and Cancer Research UK, a charity. Two of the researchers have received fees from the maker of a computer system and served as unpaid consultants to another.

Hypnosis eases post-breast cancer hot flashes

By Anne Harding
03 oct 2008--Hypnosis can help reduce hot flashes among breast cancer survivors, new research published in the Journal of Clinical Oncology shows.
The authors of the report note that "hot flashes are a significant problem for many breast cancer survivors." The new findings are particularly important because the current best treatment for hot flashes, estrogen therapy, is off limits for most women who have had breast cancer.
Furthermore, many women must take estrogen-blocking drugs like tamoxifen for years after breast cancer treatment, but "hot flashes can be so severe that some women make a decision to not continue those medications," Dr. Gary Elkins told Reuters Health.
Based on some small studies that found hypnosis benefited women suffering from hot flashes, Elkins of Baylor University in Waco, Texas, and his team randomly assigned 60 breast cancer survivors to hypnosis once a week for five weeks or no treatment.
The hypnosis sessions, which lasted about 50 minutes, involved helping the patient to reach a deeply relaxed state, and then offering suggestions for mental imagery to help her relax and feel cool. This could mean having a woman imagine herself walking down a cool mountain path, for example. Women also received instructions on how to practice hypnosis on their own.
Among the 51 women who completed the study, those who had hypnosis reported a 68% reduction in the severity and frequency of their hot flashes. This translated to 4.39 fewer hot flashes a day, on average, for women in the hypnosis group, while there was little change in the control group.
In an editorial accompanying the study, Dr. Nancy E. Avis of the Wake Forest University School of Medicine in Winston-Salem, North Carolina, calls the reduction in hot flashes seen by Elkins and his team "impressive," but points to the need to compare hypnosis to some type of placebo, rather than no treatment at all.
In fact, Elkins said, he and his colleagues are now launching a National Institutes of Health-funded study to address this issue, which will enroll 180 postmenopausal women and will compare hypnosis to another type of mind-body intervention.
The mechanism behind hot flashes is still poorly understood, Elkins noted. "We know that they are related to decreases in estrogen, however that relationship is not direct in the sense that hot flashes lessen over time even though estrogen levels remain low," he explained.
Hot weather, spicy food and stress can also trigger hot flashes, he added, so it's possible that women undergoing menopause may have a more difficult time regulating their body temperature in response to these triggers. Hypnosis treatment can reduce stress by helping women to relax, Elkins explained, and may also give them a sense of control that allows them to keep their body temperature more stable.
SOURCE: Journal of Clinical Oncology, online September 22, 2008.

Workouts for elders work in real world

02 oct 2008--Physical activity programs for aging baby boomers and seniors, developed and tested in research settings, can be successfully implemented on a large scale through community organizations, according to results from the "Active for Life" program.
The program used two lifestyle interventions aimed at older adults: Active Choices, a telephone coaching program, and Active Living Every Day, a group-based program.
"Many programs shown to be effective in research studies are never disseminated more widely and thus, don't impact public health," Dr. Sara Wilcox, from the University of South Carolina, who was involved in the research, noted in a university-issued statement. "This initiative was different because it showed that community-based organizations could put these two programs in place, reach a large number of older adults, and produce meaningful changes."
The Active for Life program was established in 2003 at the Texas A&M Health Science Center School of Rural Public Health with funding from the Robert Wood Johnson Foundation. The goals of the program were to learn how research-based programs need to be adapted for broader implementation in real-world settings.
The Active Choices program is a 6-month program consisting of one face-to-face meeting between a participant and a health educator during which a physical activity plan is generated and activity goals are set. The participant is given a pedometer and exercise log and follow-up telephone pep talks.
The Active Living Every Day program is a 12-week physical activity intervention delivered in small groups with the goal of accumulating 30 minutes of moderate intensity physical activity on most days.
Wilcox and her colleagues looked at data on almost 6,000 people who participated in the programs between 2003 and 2007 at 12 sites. Those in the Active Choices program averaged 65 years of age while those in the Active Living Every Day program were around 70 years old on average.
The researchers report in the American Journal of Preventive Medicine that the programs produced significant increases in total physical activity, as well as increases in moderate to vigorous intensity, in particular.
The programs helped the participants lose weight and feel better about how they looked physically and how their body functioned. Participants in the Active Living Every Day program also reported a decrease in stress and depressive symptoms.
Wilcox said this study is noteworthy because it shows that community organizations and health care networks can partner and successfully deliver research-based programs in their community.
SOURCE: American Journal of Preventive Medicine, October 2008.

Occupational therapy gets people with osteoarthritis moving

U-M pilot study finds occupational therapy approach combined with exercise increases physical activity for most patients with hip and knee osteoarthritis

Ann Arbor, 02 oct 2008 – Physical activity is the cornerstone of any healthy lifestyle – and especially for people with osteoarthritis as exercise helps maintain good joint health, manage their symptoms, and prevent functional decline. Osteoarthritis, however, often makes physical activity, such as exercise, and even performing daily activities, a challenge.
But an occupational therapist-led approach – called activity strategy training – could provide patients with knee and hip osteoarthritis the opportunity to lead more active lives and even improve their overall health, according to a new study led by researchers at the University of Michigan Health System.
In the pilot study, the researchers found that patients who engaged in activity strategy training along with regular exercise increased their physical activity, more so than those patients who only took part in exercise and health education sessions. Study results are now online and are set to appear in the October issue of Arthritis & Rheumatism.
"Occupational therapy is really the missing link in promoting wellness of people with hip and knee osteoarthritis," says study lead author Susan L. Murphy, Sc.D., OTR, assistant professor in the Department of Physical Medicine and Rehabilitation at the U-M Medical School and Research Health Science Specialist at the VA Ann Arbor Healthcare System.
"Most people with osteoarthritis want to be active, but often find that there are personal or physical barriers in the way. For instance, people with osteoarthritis often deal with pain and fatigue, which makes engaging in regular physical activity more difficult. In addition, there are often barriers in people's homes and communities that make physical activity difficult," she continues.
For that reason, Murphy says the pilot study used activity strategy training in groups and in places – such as senior housing facilities – where barriers could be addressed and potential solutions discovered.
Taught by occupational therapists, this structured rehabilitation program is designed to educate patients about joint protection, proper body mechanics, activity pacing, and environmental barriers. For example, patients with joint pain caused by osteoarthritis learn techniques for walking around the house or outdoors, or even getting in and out of a car. For the pilot study, the activity strategy training included education, group discussion, a home visit, and demonstration and practice of techniques to facilitate activity.
Activity strategy training, however, is not commonly prescribed to patients with hip or knee osteoarthritis, a degenerative disease that causes the breakdown of the cartilage in joints. Most physical activity programs for these patients only offer structured exercise, which has been shown to have short-term positive effects on arthritis pain and physical disability. But these effects usually fade soon after participation in the program ends.
In this study, both groups participated in the same structured exercise program. However, only participants who received the activity strategy training were found to have increased the intensity of their physical activity at the end of the study compared to those who received health education.
While the results are promising, Murphy says more research needs to be conducted to replicate with larger groups and to examine long-term effects before this technique can be applied to patient care.
Regardless, Murphy encourages patients with hip or knee osteoarthritis to seek out opportunities now to enhance and expand their daily physical activity, and improve overall health behaviors.
"People with osteoarthritis tend to know more about surgical options, and less about how they can take an active role in promoting their own health and well-being," Murphy explains. "People with osteoarthritis need to be their own agents of change. They can do so much to manage symptoms and stave off functional decline caused by osteoarthritis just by being physically active. The bottom line is to find ways to help people create and maintain these healthy habits."

Depression linked to higher death rates from all causes among elderly with diabetes

02 oct 2008--2-year study looked at more than 10,000 Medicare beneficiaries with diabetes
In a large group of Medicare beneficiaries with diabetes, depression was associated with a higher death rate from all causes during a two-year study period. The findings are published in the October 2008 Journal of General Internal Medicine.
Lead author Dr. Wayne Katon, professor of psychiatry and behavioral sciences at the University of Washington (UW), noted that previous research indicates that depression and diabetes is a potentially lethal mix among young to middle-aged patients. Depression also puts patients at greater risk of complications from their diabetes. This more recent study suggests that depression is also a risk factor for mortality in older patients with diabetes. Most Medicare beneficiaries, like the ones in this study, are over age 65. The mean age of the participants was 75.6 years.
The study tracked 10,704 Medicare beneficiaries with diabetes who were enrolled in a disease management program in Florida. They were surveyed at the start of the study with a health assessment questionnaire. Evidence of depression among members of the group came from physician diagnosis, patient reports of having a prescription for an antidepressant in the year before the survey, or patient answers to a brief screening test. For the next two years, the research team recorded the death and cause of death of participants through bi-monthly checks of Medicare claims and eligibility files, or from phone calls with the participants' families.
The research team found that patients with both diabetes and depression had an increased risk of about 36 percent to 38 percent of dying from any cause during the two-year follow-up. Participants with a physician diagnosis of depression were significantly younger than their cohorts, more likely to be female, had more severe medical illness, were less likely to be African-American, and more likely to be Hispanic. These variables were controlled for in the analysis of increased risk. A total of 12.1 percent of participants who had both disorders died during that period. Among those without depression, 10.4 percent died.
Participants who had been treated with one or more antidepressant medications in the year before the study had a 24 percent increased risk of mortality, compared to non-depressed participants. According to the study authors, those patients may have been treated with antidepressants because their depressive symptoms were more severe and persistent than those of more mildly depressed patients who weren't prescribed antidepressants.
There was no difference in the rate of cardiovascular or cerebrovascular events between those treated with antidepressants and those who had no indication of depression.
"Rates of mortality from vascular disease may be decreasing in recent years among patients with diabetes due to more aggressive treatment of high blood pressure, cholesterol, and glucose levels," the researchers surmised, "as well as widespread use of preventative medications such as aspirin and beta blockers."
According to the authors, there may be several reasons why depression worsens chronic diseases such as diabetes. Depression has been associated with inadequate self-care and harmful habits like smoking or overeating. Depression is also associated with nervous system and endocrine system problems, and with inflammatory markers.
The authors noted their study's limitations: the participants were from one geographic region of the United States, and the follow-up period was relatively short. Defining depression in part by physician diagnosis and treatment, they added, may have selected for participants with more severe illness. The study was also not able to obtain information on education, income, weight, smoking habits, physical activity, or compliance in taking medication.
###
In addition to Katon, the researchers included Drs. Ming-Yu Fan and Jurgen Unutzer from the UW, Dr. Jennifer Taylor from Green River Health in Tampa, Fl.; Dr. Harold Pincus from Columbia University and the Rand Corporation; and Michael Schoenbaum from the National Institutes of Health (NIH) in Bethesda, Md.
Grants from the National Institute of Mental Health of the NIH funded the study

Facet joint effusion and interspinal ligament edema: major sources of lower back pain

02 oct 2008--New MR techniques show that facet joint effusion (the collection of fluid in the spinal joints) and interspinal ligament edema (swelling of the interspinal ligaments) are major sources of lower back pain, according to a study performed at Baskent University Hospital in Ankara, Turkey and Alanya Research Center in Antalya, Turkey.
During the study 372 patients with lower back pain and 249 healthy patients underwent MRI accompanied by STIR (short inversion time inversion recovery) sequences. "The most common imaging findings in patients with lower back pain were soft tissue changes, mainly facet joint effusion, 85.5%, and interspinal ligament swelling, 80.6%," according to Nefise Cagla Tarhan, MD, lead author of the study.
"Soft tissue changes are important in the understanding of lower back pain and prevention and treatment options should focus more on these changes. A lot of patients (mostly younger) come to me with complaints of bad, lower back pain; it is a very common community problem," said Dr. Tarhan. "With this new MR technique, prevention and treatment options for lower back pain can focus more on soft tissue degenerative changes that cause facet joint effusion and interspinal ligament swelling," said Dr. Tarhan.
###
This study appears in the October issue of the American Journal of Roentgenology. For a copy of the full study, please contact Heather Curry via email at hcurry@arrs.org.

Getting help for depression and anxiety has significant long-term benefits

02 oct 2008--According to the Mood Disorder Society of Canada, about 1.3 million Canadians suffer from depression.
University of Alberta researcher Ian Colman says most people are not getting the type of treatment they need.
Colman, an assistant professor from the School of Public Health, and his research team decided to perform a study to see the long term effects of taking antidepressants or anti-anxiety medications.
The team studied a group of 200 people who were diagnosed with either depression or anxiety. Of that group, 45 were on medication.
The group of 200 had their mental health assessed in 1989 through a series of questions in a survey asking about their illness and what, if any, treatments they were on. Ten years later the group took a similar questionnaire.
Colman says they were surprised to find those who were not using antidepressants or anti-anxiety medications were three times more likely to be suffering from depression or anxiety 10 years later.
"This is a significant find," said Colman. "What this tells us is that, if people get treated initially, they are less likely to have a relapse in the future. This could be a significant benefit, not only for the patient but also for the health-care system as it's estimated the economic costs in Canada associated with depression are $14 billion per year."
Colman says depression and anxiety have a stigma attached to them and that people are often afraid to admit they have a mental disorder. But he hopes this new information will help people realize the long-term benefits of getting help right away.
###
Colman's research is being published October 1st in The British Journal of Psychiatry. He is available for interviews October 2nd, and can be reached at either ian.colman@ualberta.ca or 780-492-8578.

Restless nights put older adults at risk for depression recurrence

01 oct 2008--Nearly 60 percent of the nation's elderly have trouble sleeping, whether it's a lot of tossing and turning or outright bouts of insomnia. While for most people sleeplessness can be annoying at best or unhealthy at worst, for elderly individuals who have suffered from depression in the past, poor sleep may be the first sign that a new bout of depression is coming on.
In a study to be published in an upcoming issue of the American Journal of Psychiatry and currently available online, UCLA professor of psychiatry Dr. Michael Irwin and his colleagues posed three hypotheses: risk for depression would be higher among older people with a prior history of the disorder; among those with prior depression, sleep disturbance could predict a relapse or recurrence; and sleep disturbances could act as a risk factor for depression recurrence separate from other depressive symptoms. The study confirmed all three hypotheses.
"Insomnia is the most frequent sleep disturbance in depressed patients and is viewed as a symptom of current depression," said Irwin, who also directs the Cousins Center for Psychoneuroimmunology at UCLA's Semel Institute for Neuroscience and Human Behavior. "But when sleep disturbances begin to emerge in an otherwise healthy adult who has experienced depression in the past, we found that it may serve as a precursor to another attack of depression."
The study looked at 351 adults, age 60 and older. Of that number, 145 had a prior history of major or non-major depression that was in full remission, while 206 had no prior history of depression or other mental illness. The participants were assessed at four different times over a two-year period for depressive episodes, depressive symptoms, sleep quality and chronic medical disease.
The researchers found that of the subjects with prior depression, 23 had a relapse, compared with only one person in the group without prior mental illness. With the first group, researchers were able to predict depression recurrence based on individuals' sleep disturbance. Irwin noted that this association was established independently of other depressive symptoms, chronic medical disease or any use of antidepressants.
The study, Irwin said, is the first to demonstrate that sleep disturbances act as an independent risk factor for depression recurrence in older adults.
"Unfortunately, sleep difficulties are often considered to be a part of normal aging, and asking about and assessing the quality of an older person's sleep is frequently overlooked during routine doctor visits," Irwin said. "The omission is particularly striking, since we know that sleep disturbance is associated with declines in health functioning and with increases in all causes of mortality in older adults.
"And now, this study shows that sleep disturbance is often related to depressive disorders in late life, which carry further considerable risks for morbidity and mortality."
To identify older adults at risk for depression, Irwin said, a two-step strategy can be employed. One step involves assessment of whether individuals have had a prior episode of depression, the other whether they have current and ongoing sleep disturbance.
"Given that sleep disturbance is a modifiable risk factor," he said, "these findings tell us that we need to develop treatments that target sleep disturbances for the prevention of depression recurrence in older adults."

You’re Sick. Now What? Knowledge Is Power.

By TARA PARKER-POPE
01 oct 2008--Are patients swimming in a sea of health information? Or are they drowning in it?
The rise of the Internet, along with thousands of health-oriented Web sites, medical blogs and even doctor-based television and radio programs, means that today’s patients have more opportunities than ever to take charge of their medical care. Technological advances have vastly increased doctors’ diagnostic tools and treatments, and have exponentially expanded the amount of information on just about every known disease.
The daily bombardment of news reports and drug advertising offers little guidance on how to make sense of self-proclaimed medical breakthroughs and claims of worrisome risks. And doctors, the people best equipped to guide us through these murky waters, are finding themselves with less time to spend with their patients.
But patients have more than ever to gain by decoding the latest health news and researching their own medical care.
“I don’t think people have a choice — it’s mandatory,” said Dr. Marisa Weiss, a breast oncologist in Pennsylvania who founded the Web site breastcancer.org. “The time you have with your doctor is getting progressively shorter, yet there’s so much more to talk about. You have to prepare for this important meeting.”
Whether you are trying to make sense of the latest health news or you have a diagnosis of a serious illness, the basic rules of health research are the same. From interviews with doctors and patients, here are the most important steps to take in a search for medical answers.
Determine your information personality.
Information gives some people a sense of control. For others, it’s overwhelming. An acquaintance of this reporter, a New York father coping with his infant son’s heart problem, knew he would be paralyzed with indecision if his research led to too many choices. So he focused on finding the area’s best pediatric cardiologist and left the decisions to the experts.
Others, like Amy Haberland, 50, a breast cancer patient in Arlington, Mass., pore through medical journals, looking not just for answers but also for better questions to ask their doctors.
“Knowledge is power,” Ms. Haberland said. “I think knowing the reality of the risks of my cancer makes me more comfortable undergoing my treatment.”
Dr. Michael Fisch, interim chairman of general oncology for the University of Texas M. D. Anderson Cancer Center, says that before patients embark on a quest for information, they need to think about their goals and how they might react to information overload.
“Just like with medicine, you have to ask yourself what dose you can take,” he said. “For some people, more information makes them wackier, while others get more relaxed and feel more empowered.”
The goal is to find an M.D., not become one.
Often patients begin a medical search hoping to discover a breakthrough medical study or a cure buried on the Internet. But even the best medical searches don’t always give you the answers. Instead, they lead you to doctors who can provide you with even more information.
“It’s probably the most important thing in your cancer care that you believe someone has your best interests at heart,” said Dr. Anna Pavlick, director of the melanoma program at the New York University Cancer Institute. “In an area where there are no right answers, you’re going to get a different opinion with every doctor you see. You’ve got to find a doctor you feel most comfortable with, the one you most trust.”
Keep statistics in perspective.
Patients researching their health often come across frightening statistics. Statistics can give you a sense of overall risk, but they shouldn’t be the deciding factor in your care.
Jolanta Stettler, 39, of Denver, was told she had less than six months to live after getting a diagnosis of ocular melanoma, a rare cancer of the eye that had spread to her liver.
“I was told there is absolutely nothing they could help me with, no treatment,” said Ms. Stettler, a mother of three. “I was left on my own.”
Ms. Stettler and her husband, a truck driver, began searching the Internet. She found Dr. Charles Nutting, an interventional radiologist at Swedish Medical Center in Englewood, Colo., who was just beginning to study a treatment that involves injecting tiny beads that emit small amounts of radiation. That appeared to help for about 18 months.
When her disease progressed again, Ms. Stettler searched for clinical trials of treatments for advanced ocular melanoma, and found a National Institutes of Health study of “isolated hepatic perfusion,” which delivers concentrated chemotherapy to patients with liver metastases. After the first treatment, Ms. Stettler’s tumors had shrunk by half.
“I don’t like statistics,” she said. “If this study stops working for me, I’ll go find another study. Each type of treatment I have is stretching out my life. It gives me more time, and it gives more time to the people who are working really hard to come up with a treatment for this cancer.”
Don’t limit yourself to the Web.
There’s more to decoding your health than the Web. Along with your doctor, your family, other patients and support groups can be resources. So can the library. When she found out she had Type 2 diabetes in 2006, Barbara Johnson, 53, of Chanhassen, Minn., spent time on the Internet, but also took nutrition classes and read books to study up on the disease.
“I was blindsided — I didn’t know anybody who had it,” said Ms. Johnson, who told her story on the American Heart Association’s Web site, IKnowDiabetes.org. “But this is a disease you have to manage yourself.”
Tell your doctor about your research.
Often patients begin a health search because their own doctors don’t seem to have the right answers. All her life, Lynne Kaiser, 44, of Plano, Tex., suffered from leg pain and poor sleep; her gynecologist told her she had “extreme PMS.” But by searching the medical literature for “adult growing pains,” she learned about restless legs syndrome and a doctor who had studied it.
“I had gone to the doctors too many times and gotten no help and no results,” said Ms. Kaiser, who is now a volunteer patient advocate for the Web site WhatIsRLS.org. The new doctor she found “really pushed me to educate myself further and pushed me to look for support.”
Although some doctors may discourage patients from doing their own research, many say they want to be included in the process.
Dr. Fisch of M. D. Anderson recalls a patient with advanced pancreatic cancer who decided against conventional chemotherapy, opting for clinical trials and alternative treatments. But instead of sending her away, Dr. Fisch said he kept her in the “loop of care.” He even had his colleagues use a mass spectroscopy machine to evaluate a blue scorpion venom treatment the patient had stumbled on. It turned out to be just blue water.
“We monitored no therapy like we would anything else, by watching her and staying open to her choices,” Dr. Fisch said. “She lived about a year from the time of diagnosis, and she had a high quality of life.”
Dr. Shalom Kalnicki, chairman of Radiation Oncology at the Montefiore-Einstein Cancer Center, says he tries to guide his patients, explaining the importance of peer-reviewed information to help them filter out less reliable advice. He also encourages them to call or e-mail him with questions as they “study their own case.”
“We need to help them sort through it, not discourage the use of information,” he said. “We have to acknowledge that patients do this research. It’s important that instead of fighting against it, that we join them and become their coaches in the process.”

How a Patient Can Help a Doctor Give the Best Care

By JANE E. BRODY
01 oct 2008--As primary care doctors become increasingly pressed for time, here are 10 tips to help maximize the benefits you get from modern medical care.
1. Write down your questions before calling or seeing the doctor. Don’t wait until the end of a visit to mention a pressing health concern.
2. Keep a diary of your symptoms and the circumstances under which they occur, and bring it with you to the appointment.
3. Maintain an up-to-date list of all the medications and over-the-counter drugs and supplements you take and their dosages. Bring that with you.
4. Write down what the doctor says about your condition and how to treat it.
5. Know your personal and family medical history, including illnesses and operations you had and diseases or causes of death of your parents, grandparents and siblings.
6. Be honest about your lifestyle. If you smoke, drink alcohol or take recreational drugs, reveal how often or how much.
7. Be willing to see a physician’s assistant or nurse practitioner for routine care like wellness checkups and immunizations.
8. Ask if the doctor uses e-mail and checks it daily. If so, use e-mail messages to discuss nonurgent matters or lingering concerns, to clarify treatment instructions and to report an improvement in symptoms. But call immediately if your symptoms fail to improve as expected or suddenly get worse.
9. If you call about a worrisome symptom and the doctor tells you to go to the emergency room, don’t wait. If you are told to go by ambulance, do it; you’ll be seen right away, which could make a life-or-death difference.
10. Get an independent second opinion if you are told that you have a life-threatening condition or that surgery is needed to correct a problem, or if you are doubtful about the quality of tests that were done.

Radiosurgery for brain cancer OK for elderly

01 oct 2008--People 75 years of age and older with cancer that has spread to the brain respond about as well as younger patients to stereotactic radiosurgery, according to a recent report.
The treatment focuses multiple beams of radiation from different directions on the tumor, so that normal tissues are spared damaging doses.
Several studies have shown that using stereotactic radiosurgery to treat cancer that has metastasized to the brain from other sites improves survival rates, but there has been no detailed study in patients over 65 years old, explain the authors of the report in the medical journal Cancer.
Dr. Se-Hyuk Kim from the Cleveland Clinic Foundation, Ohio, and colleagues examined the outcomes of a series of 44 patients at least 75 years old with brain metastases treated with stereotactic radiosurgery and followed for up to 2.5 years.
Survival rates were of 86 percent at 3 months, 68 percent at 6 months, 45 percent at 9 months, and 34 percent at 12 months.
Average survival times were longer in patients with a single brain metastasis (10.1 months) than in those with two or more brain metastases (6.6 months), the report indicates.
Some patients who developed a new brain metastasis were successfully treated again with stereotactic radiosurgery.
The treatment in patients aged 75 years and older "has an excellent functional outcome, and provides results that are similar to those noted in younger patients," Kim's team concludes.
"Based on our outcomes," they add, "we will continue to offer stereotactic radiosurgery for patients with brain metastases who are aged 75 years and older."
SOURCE: Cancer, August 15, 2008.

Study finds link between genes, obesity and colon cancer

01 oct 2008--The discovery of a genetic link between obesity and colon cancer may pave the way for more effective screening tests for the disease, according to a study published Tuesday.
Researchers found that people who inherit a variation of a gene called ADIPOQ, which results in the formation of a fat hormone called adiponectin, are 30 percent less likely to develop colon cancer.
People identified without this gene variant, or who have excessive blood levels of the fat hormone, would therefore benefit from early colon examinations, said Boris Pasche, professor at the University of Alabama Comprehensive Cancer Center and lead author of the study.
"Our hope is that we can significantly improve the screening and early detection for this disease, and open new avenues for better understanding the genetic and lifestyle factors that influence colon cancer risk," said Pasche.
A third of people with colon cancer have a family history of the disease, he said.
Scientists have already proven a link between obesity and genetics, and that colon cancer is influenced by genetics.
The latest study, published in the Journal of the American Medical Association, is the first to prove a three-way connection between genetics, obesity and colon cancer risk.
The study showed that test subjects who did not have the genetic variation could reduce their risk through physical exercise and dieting to lose weight.
Colon cancer is the third deadliest cancer in the United States.
Nearly 150,000 Americans are diagnosed each year, and 50,000 of those diagnosed die from the disease, according to estimates from the American Cancer Society.