Folic acid, vitamins B6, B12 don't prevent cancer in women: study

WASHINGTON, 05 nov 2008– Folic acid and vitamins B6 and B12 play no significant role in preventing cancer in women at high risk for cardiovascular disease, said a study published Tuesday in the Journal of the American Medical Association.
The study contradicts a prevalent belief in the medical community about cancer prevention through intake of folic acid and vitamins B6 and B12.
Since 1998, many food items in the United States have been enriched with synthetic folic acid chiefly to reduce the risk of neural tube birth defects.
Around one third of the United States' adult population currently take multivitamin complexes that include folic acid and vitamins B6 and B12, the study said.
However, there are few clinical test results linking folic acid alone or in combination with vitamin B to the risk of cancer. Furthermore, the test results are not coherent and one of them even showed harmful effects, the researchers said.
"Combined folic acid, vitamin B6, and vitamin B12 treatment had no significant effect on overall risk of total invasive cancer or breast cancer among women during the folic acid fortification era," the study said.
The latest study was carried out among 5,442 female health professionals aged 42 years or older at high risk of cardiovascular disease.
Half the participants were randomly assigned to receive a daily combination of folic acid (2.5 milligrams), vitamin B6 (50 mg) and vitamin B12 (1.0 mg), while the rest were administered a placebo.
The clinical trial lasted from April 1998 to July 2005.

An anti-frailty pill for seniors?

University of Virginia study shows new drug increases muscle mass in arms and legs of older adults

05 nov 2008--Researchers at the University of Virginia Health System report that a daily single oral dose of an investigational drug, MK-677, increased muscle mass in the arms and legs of healthy older adults without serious side effects, suggesting that it may prove safe and effective in reducing age-related frailty.
Published in the November 4, 2008 issue of Annals of Internal Medicine, the study showed that levels of growth hormone (GH) and of insulin-like growth factor I (IGF- I) in seniors who took MK-677 increased to those found in healthy young adults. The drug restored 20 percent of muscle mass loss associated with normal aging.
"Our study opens the door to the possibility of developing treatments that avert the frailty of aging," explains Dr. Michael O. Thorner, a nationally recognized researcher of growth hormone regulation and a professor of internal medicine and neurosurgery at UVA. "The search for anti-frailty medications has become increasingly important because the average American is expected to live into his or her 80s, and most seniors want to stay strong enough to remain independent as they age."
Funded by the National Institutes of Health, the two-year, double-blind, placebo-controlled, modified-crossover study involved 65 men and women ranging in age from 60 to 81.
The study drug, MK-677, mimics the action of ghrelin, a peptide that stimulates the growth hormone secretagogue receptor (GHSR). Drug developers are focusing on GHSR because it plays an important role in the regulation of growth hormone and appetite. They think it may prove to be an excellent treatment target for metabolic disorders such as those related to body weight and body composition.
According to Dr. Thorner, the UVA research was a "proof-of-concept" study that sets the stage for a larger and longer clinical trial to determine whether MK-677 is effective in people who are frail and to assess its long term safety

Drug mimics low-cal diet to ward off weight gain, boost running endurance

05 nov 2008--A drug designed to specifically hit a protein linked to the life-extending benefits of a meager diet can essentially trick the body into believing food is scarce even when it isn't, suggests a new report in the November Cell Metabolism.
The drug called SRT1720, which acts through the protein SIRT1, enhances running endurance in exercised mice and protects the animals against weight gain and insulin resistance even when they eat a high-fat diet, the researchers report. The drug works by shifting the metabolism to a fat-burning mode that normally takes over only when energy levels are low.
The findings bolster the notion that SIRT1 may be a useful target in the fight again metabolic disorders, including obesity and type 2 diabetes. It also helps lay to rest a long-standing controversy in the scientific world over the metabolic benefits of the red wine ingredient known as resveratrol. Resveratrol also acts on SIRT1, but its influence on other metabolic actors had left room to question exactly how it works.
" There has been a lot of controversy in the field about resveratrol action," said Johan Auwerx of Ecole Polytechnique Fédérale de Lausanne. "We find that the majority of the biology of resveratrol can be ascribed to SIRT1." While SIRT1 might not explain all of resveratrol's effects, the new results suggest that the central metabolic protein is responsible for about "80 percent of the picture," he said.
The researchers had conducted earlier studies to demonstrate many of the benefits of resveratrol. To further explore the underlying pathways responsible in the new study, they ran essentially the same experiments with the more potent and specific SIRT1-activating compound SRT1720 developed by the company Sirtris Pharmaceuticals, Inc.
The researchers found that a low dose of SRT1720 partially protected mice from gaining weight on a high-fat diet after 10 weeks of treatment. At higher doses, the drug completely prevented weight gain in the animals. SRT1720 also improved blood sugar tolerance and insulin sensitivity and endowed the animals with greater athletic ability.
" SIRT1720 made the animals run twice as long," Auwerx said. That improvement was seen only when the researchers specifically exercised the animals. Their voluntary activity actually declined in the study as they hunkered down to save energy.
They found further evidence that the SIRT1 activator acts as a calorie-restriction mimetic that favors the use of fat stores by promoting the direct modification of multiple SIRT1 targets. It also induces chronic metabolic adaptations that involve the indirect activation of AMPK, an enzyme that regulates skeletal muscle glucose and the metabolism of fatty acids.
The major advantage of SRT1720 or any specific SIRT1 activator over resveratrol is that it is likely to come with fewer side effects, Auwerx said.
That said, SRT1720 does have some limitations, Auwerx noted, in that the effects they observed came only at fairly high doses. He speculates that SRT1720 derivatives might get around this potential stumbling block for the drug's therapeutic promise.
While the researchers did not observe any significant side effects of the drug in their study, they said further studies are needed to adequately address that question.
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The researchers include Jerome N. Feige, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/Universite´ Louis Pasteur, Illkirch, France; Marie Lagouge, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/Universite´ Louis Pasteur, Illkirch, France; Carles Canto, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/Universite´ Louis Pasteur, Illkirch, France; Axelle Strehle, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/Universite´ Louis Pasteur, Illkirch, France; Sander M. Houten, University of Amsterdam, Amsterdam, The Netherlands; Jill C. Milne, Sirtris Pharmaceuticals Inc., Cambridge, MA; Philip D. Lambert, Sirtris Pharmaceuticals Inc., Cambridge, MA; Chikage Mataki, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/Universite´ Louis Pasteur, Illkirch, France; Peter J. Elliott, Sirtris Pharmaceuticals Inc., Cambridge, MA; and Johan Auwerx, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/Universite´ Louis Pasteur, Illkirch, France, Institut Clinique de la Souris, Illkirch, France, Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne, Switzerland.

Risk of sudden cardiac death appears increased within 30 days of heart attack

The risk of sudden cardiac death following a heart attack has declined significantly in the past 30 years, although patients appear to be at elevated risk for sudden cardiac death for the first month after having a heart attack, after which time their risk decreases unless they develop heart failure, according to a study in the November 5 issue of JAMA.
"Sudden cardiac death is a devastating complication of myocardial infarction [heart attack]," the authors write as background information in the article. Determining which patients are at risk for this complication remains challenging, they note. Currently, risk prediction approaches are based on characteristics assessed shortly after heart attack—a strategy that may be insufficient. Other factors that occur in the days to weeks following heart attack, such as heart failure or recurrent ischemia (which may cause chest pain from narrowed or blocked coronary arteries), may be associated with risk of sudden cardiac death.
A. Selcuk Adabag, M.D., M.S., of Veterans Affairs Medical Center, Minneapolis, and colleagues at Mayo Clinic, Rochester, Minn., studied 2,997 residents (average age 67, 59 percent men) who had a heart attack in Olmsted County, Minn., between 1979 and 2005. Patients were followed through medical records for a median (midpoint) of 4.7 years, through Feb. 29, 2008.
During this time, 1,160 patients died, including 282 (24 percent) from sudden cardiac death. The 30-day cumulative incidence of sudden cardiac death was 1.2 percent, which is four times higher than expected. For each following year, however, the rate of sudden cardiac death was constant at 1.2 percent per year—lower than the rate among the general population. The cumulative five-year incidence of sudden cardiac death among heart attack patients was 6.9 percent.
A total of 842 patients developed recurrent ischemia, 365 developed heart failure and 873 developed both. Recurrent ischemia was not associated with sudden cardiac death. However, compared with patients who did not experience heart failure during follow-up, those who did had a 2.5 percent higher risk of sudden cardiac death within 30 days of heart attack and in each year thereafter.
"The risk of sudden cardiac death has declined significantly over time for myocardial infarctions that occurred between 1997 and 2005 compared with between 1979 and 1987," the authors write—a decline of more than 40 percent over the past 25 years. This decline predates the widespread use of defibrillators but coincides with other drastic changes in therapy for heart attacks, including secondary prevention and reperfusion therapy, which re-opens blocked arteries.
"In the community, the risk of sudden cardiac death is the highest during the first month after myocardial infarction when it markedly exceeds the rate in the general population," the authors conclude. "Among 30-day survivors, the risk of sudden cardiac death declines rapidly but it is markedly increased by the occurrence of heart failure during follow-up. This underscores the importance of continued surveillance of patients after myocardial infarction and the dynamic nature of risk stratification."
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(JAMA. 2008;300[17]:2022-2029. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: This study was supported by a grant from the Public Health Service and grants from the National Institutes of Health. Dr. Adabag is supported, in part, by a VA Clinical Science R&D Service Grant. Co-author Dr. Roger is an established investigator of the American Heart Association. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Response rates to antidepressants differ among English- and Spanish-speaking Hispanics

LA BioMed study suggests additional treatment may be necessary

TORRANCE , 05 nov 2008--In the first-ever study of its kind, a team led by researchers at Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed) report in November's Psychiatric Services journal that Spanish-speaking Hispanics took longer to respond to medication for depression and were less likely to go into remission than English-speaking Hispanics.
Using data from the nation's largest real-world clinical study of depression, the researchers found the Spanish-speaking participants in the study were older and were more likely to be women than the English speakers. The Spanish speakers also had less education and lower income, more medical issues and were more likely than English speakers to be seen in primary care than psychiatric clinics.
"Once we adjusted for these differences in their socioeconomic status, both groups responded about the same to medication for depression," said Ira Lesser, M.D., a LA BioMed investigator who authored the report. "These results are important for clinicians and patients to be aware that Spanish-speaking Hispanics with depression who come from lower social economic groups may need more than medication for depression."
Funded by the National Institute of Mental Health, the study surveyed the treatment records of 195 Spanish-speaking and English-speaking Hispanics who had sought care at the Los Angeles and San Diego sites from among the more than 4,000 patients who participated in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, the nation's largest real-world study of depression.
"Hispanics are the nation's largest ethnic minority and its fastest-growing population group," said Dr. Lesser. "As clinicians ourselves, we always are seeking information on the best treatments for our patients, taking into account the differences among them."
Hispanics comprise about 15% of the U.S. population, and 40% are born outside the country. In the 2000 Census, 32% of Hispanic respondents who said they spoke Spanish at home also said they spoke English "not well" or "not at all." Depression is the nation's most prevalent psychiatric disorder, with approximately 16 out of 100 Americans suffering from it at some point in their lives.
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About LA BioMed
Founded 56 years ago, LA BioMed is one of the country's largest not-for-profit independent biomedical research institutes. It conducts biomedical research, trains young scientists and provides community services, including childhood immunization, nutrition assistance and anti-gang violence programs. The institute's researchers conduct studies in such areas as cardiovascular disease, emerging infections, cancer, diabetes, kidney disease, dermatology, reproductive health, vaccine development, respiratory disorders, inherited illnesses and neonatology.
LA BioMed is an independent institute that is academically affiliated with the David Geffen School of Medicine at UCLA. The institute is located on the campus of Harbor-UCLA Medical Center near Torrance. It contributes to Los Angeles County's economic viability while inventing the future of health care through its ground-breaking research, its training of the scientists of tomorrow and its service to the local community. Please visit our website at www.LABioMed.org

Diabetes, Hypertension Hasten Death in Alzheimer's Patients

04 nov 2008 -- Having diabetes or high blood pressure may hasten the death of people with Alzheimer's disease, new research suggests.
According to the study, published in the Nov. 4 issue of Neurology, Alzheimer's patients with diabetes were twice as likely to die sooner than those with the dementia condition but no diabetes. Those with Alzheimer's and high blood pressure were two-and-a-half times more like to die sooner than those with normal blood pressure.
"Studies show that the average life span of a person diagnosed with Alzheimer's can be anywhere from three to nine years. For that person and their caregiver, every minute counts. Here we have two controllable factors that may drastically affect how long that person can survive," study author Yaakov Stern, director of the Cognitive Neuroscience Division of Gertrude H. Sergievsky Center at Columbia University Medical Center in New York, said in an American Academy of Neurology news release.
The study, involving more than 300 people, also found Hispanics live longer after an Alzheimer's diagnosis than either non-Hispanic whites or blacks. Hispanics lived for eight years after diagnosis, blacks lived an average of five years and non-Hispanic whites about four years.
However, after adjusting for gender and other factors, the results were no longer significant.
"Though these findings were not significant, they are intriguing and warrant further research as to whether race affects survival time in people with Alzheimer's disease," Stern said.

Hip resurfacing is not for everyone

Rush University Medical Center study finds more complications in women and in males over the age of 55

CHICAGO, 04 nov 2008—Hip resurfacing is often seen as a modern alternative to the more conventional total hip replacement, but new data from a study led by Rush University Medical Center suggest that a patient's age and gender are key to the operation's success.
In a review of over 500 surgeries performed in the U.S. using a hip resurfacing device recently approved by the Food and Drug Administration (FDA), the researchers found that the majority of serious complications occurred in women of all ages and men over the age of 55. The most common complication, and the most serious, was a fracture of the femoral neck, the slender area of bone just beneath the head of the femur.
The study has just been published online and will appear in the January 2009 issue of Clinical Orthopaedics and Related Research.
"The ideal patients for hip resurfacing are males under the age of 55. They have the fewest, and the least serious, complications," said Dr. Craig Della Valle, lead author and a specialist in joint reconstruction at Rush University Medical Center. "Patients may be eager to take advantage of technological innovations, but for older individuals, a conventional hip replacement is generally more appropriate."
The researchers analyzed data for the first 537 hip resurfacing surgeries performed in the U.S. after the Birmingham Hip Resurfacing implant, manufactured by Smith & Nephew, was approved by the FDA in October 2006. The majority of the patients suffered from severe osteoarthritis. All 89 orthopedic surgeons involved in the procedures had undergone training required by the FDA before conducting their first cases. Their level of experience with hip surgery varied. Some were joint replacement specialists; others were general orthopedic surgeons.
Serious complications occurred in 32 of the 537 cases, including 10 cases in which the femoral neck fractured after surgery, a problem not seen with conventional hip replacements. Such fractures require additional surgery.
Nine of the fractures in the study occurred in patients who were either female or older than 55 at the time of the implant. Eight of the fractures occurred when the surgeon was relatively inexperienced with the procedure (within the surgeon's first 10 cases).
According to Della Valle, age and sex are probably linked to the incidence of such fractures because of bone quality and quantity.
"Patients who are older or who are female tend to have softer bone," he said. "Also, men on average have larger bone structures, with a greater surface area for securing the implant."
The study identified several other serious complications, including nerve injury, joint dislocation, fracture of the proximal femur (just below the femoral neck), loosening of the metal component in the joint socket, and deep infection.
The rate of complications, however, was similar to that found in other studies involving only orthopedic surgeons who had extensive experience with hip resurfacing. As a result, the authors concluded that the FDA-mandated training succeeded in teaching generalists the skills needed to perform the technically challenging hip resurfacing procedure, alerting them to possible complications and ways to avoid those problems.
In a conventional total hip replacement, orthopedic surgeons remove the head of the femur, or the ball of the hip joint, and replace it with a metal stem inserted into the thigh bone. They fit the socket of the joint with a metal shell that typically includes a plastic liner. In hip resurfacing, the femoral head remains, but its surface is reshaped to accept a rounded cap with a short stem that sits in the femur. A thin metal cup is pressed into the hip socket. Both components are made entirely of cobalt chrome, a metal.
Hip resurfacing is generally recommended for younger, more active patients out of concern that the traditional artificial hip might wear out during their lifetime and require a second replacement, a far more complicated surgery.
"Hip resurfacing has certain advantages over the conventional total hip replacement," said Della Valle. "It preserves more bone because the head of the femur is retained. It enables the patient to return to high-impact sports because the metal components of the implant resist wear and tear and can withstand the forces associated with activities like running. Some studies have also shown that hip resurfacing carries a lower risk of dislocation because the size of the ball component is larger."
"But despite its benefits, risks remain," Della Valle added. "Our findings suggest that we need to be cautious. This procedure is not ideal for everyone."
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Rush University Medical Center's orthopedics program ranks tenth in the nation, according to U.S. News & World Report. Physicians from Rush serve as the team physicians for the Chicago Bulls and the Chicago White Sox. For more information on orthopedics at Rush, visit http://www.rush.edu/rumc/page-R11726.html or call (888) 352-RUSH.
Rush University Medical Center is an academic medical center that encompasses the more than 600 staffed-bed hospital (including Rush Children's Hospital), the Johnston R. Bowman Health Center and Rush University. Rush University, with more than 1,270 students, is home to one of the first medical schools in the Midwest, and one of the nation's top-ranked nursing colleges. Rush University also offers graduate programs in allied health and the basic sciences. Rush is noted for bringing together clinical care and research to address major health problems, including arthritis and orthopedic disorders, cancer, heart disease, mental illness, neurological disorders and diseases associated with aging.

Surgical removal of small colon polyps is costly and unnecessary

04 nov 2008--Polypectomy (the surgical removal of polyps by colonoscopy) of small polyps found during CT colonography is costly and unnecessary according to a study performed at the University of Wisconsin School of Medicine and Public Health in Madison, WI.
A decision analysis model was constructed to represent the clinical and economic consequences of performing three year colorectal cancer surveillance, immediate colonoscopy with polypectomy, or neither on patients who have 6-9 mm polyps found on CT colonography (CTC). The analysis model was accompanied by a hypothetical population of 100,000 60-year-old adults with 6- to 9-mm polyps detected at CTC screening. Results showed that, "by excluding large polyps and masses, CTC screening can place a patient in a very low risk category making colonoscopy for small polyps probably not warranted," said Perry J. Pickhardt, MD, lead author of the study. "Approximately 10,000 colonoscopy referrals would be needed for each theoretical cancer death prevented at a cost of nearly $400,000 per life-year gained. We would also expect an additional 10 perforations and probably one death related to these extra colonoscopies. There may be no net gain in terms of lives—just extra costs," said Dr. Pickhardt.
"The clinical management of small polyps detected at colorectal cancer screening has provoked controversy between radiologists and gastroenterologists. Patients should be allowed to have the choice between immediate colonoscopy and imaging surveillance for one or two isolated small polyps detected at colorectal cancer screening," said Dr. Pickhardt.
CT colonography is now a recommended test for colorectal cancer screening by the American Cancer Society. "If patients with small polyps are monitored, only five percent of adults undergoing CTC screening will need to undergo immediate invasive colonoscopy," said Dr. Pickhardt.
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This study appears in the November issue of the American Journal of Roentgenology. For a copy of the full study, please contact Heather Curry via email at hcurry@arrs.org.
About ARRS
The American Roentgen Ray Society (ARRS) was founded in 1900 and is the oldest radiology society in the United States. Its monthly journal, the American Journal of Roentgenology, began publication in 1906. Radiologists from all over the world attend the ARRS annual meeting to participate in instructional courses, scientific paper presentations and scientific and commercial exhibits related to the field of radiology. The Society is named after the first Nobel Laureate in Physics, Wilhelm Röentgen, who discovered the x-ray in 1895.

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Fibromyalgia can no longer be called the 'invisible' syndrome

Molecular imaging uncovers evidence that symptoms are related to functional brain abnormalities, according to article in the Journal of Nuclear Medicine

Reston, Va., 04 nov 2008—Using single photon emission computed tomography (SPECT), researchers in France were able to detect functional abnormalities in certain regions in the brains of patients diagnosed with fibromyalgia, reinforcing the idea that symptoms of the disorder are related to a dysfunction in those parts of the brain where pain is processed.
"Fibromyalgia is frequently considered an 'invisible syndrome' since musculoskeletal imaging is negative," said Eric Guedj, M.D., and lead author of the study. "Past imaging studies of patients with the syndrome, however, have shown above-normal cerebral blood flow (brain perfusion) in some areas of the brain and below-normal in other areas. After performing whole-brain scans on the participants, we used a statistical analysis to study the relationship between functional activity in even the smallest area of the brain and various parameters related to pain, disability and anxiety/depression."
In the study, which was reported in the November issue of The Journal of Nuclear Medicine, 20 women diagnosed with fibromyalgia and 10 healthy women as a control group responded to questionnaires to determine levels of pain, disability, anxiety and depression. SPECT was then performed, and positive and negative correlations were determined.
The researchers confirmed that patients with the syndrome exhibited brain perfusion abnormalities in comparison to the healthy subjects. Further, these abnormalities were found to be directly correlated with the severity of the disease. An increase in perfusion (hyperperfusion) was found in that region of the brain known to discriminate pain intensity, and a decrease (hypoperfusion) was found within those areas thought to be involved in emotional responses to pain.
In the past, some researchers have thought that the pain reported by fibromyalgia patients was the result of depression rather than symptoms of a disorder. "Interestingly, we found that these functional abnormalities were independent of anxiety and depression status," Guedj said.
According to Guedj, disability is frequently used in controlled clinical trials to evaluate response to treatment. Because molecular imaging techniques such as SPECT can help predict a patient's response to a specific treatment and evaluate brain-processing recovery during follow-up, it could prove useful when integrated into future pharmacological controlled trials.
"Fibromyalgia may be related to a global dysfunction of cerebral pain-processing," Guedj added. "This study demonstrates that these patients exhibit modifications of brain perfusion not found in healthy subjects and reinforces the idea that fibromyalgia is a 'real disease/disorder.'"
According to the National Institute of Arthritis and Musculoskeletal and Skin Diseases, fibromyalgia syndrome is a common and chronic disorder characterized by widespread muscle pain, fatigue and multiple tender points. Tender points are specific places—for example, on the neck, shoulders, back, hips, and upper and lower extremities—where people with fibromyalgia feel pain in response to slight pressure. The syndrome is one of the most common causes of musculoskeletal pain and disability and affects three to six million, or as many as one in 50, Americans. Between 80 and 90 percent of those diagnosed are women.
Although fibromyalgia is often considered an arthritis-related condition, it does not cause inflammation or damage to the joints, muscles or other tissues. Like arthritis, however, the significant pain and fatigue caused by fibromyalgia can interfere with a person's ability to carry out daily activities.
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Coauthors of "Clinical Correlate of Brain SPECT Perfusion Abnormalities in Fibromyalgia" include Eric Guedj, Serge Cammilleri and Olivier Mundler, Service Central de Biophysique et de Médecine Nucléaire, AP-HM Timone; Jean Niboyet, Patricia Dupont, Eric Vidal and Jean-Pierre Dropinski, Unité d'Etude et de Traitement de la Douleur, Clinique La Phocéanne, all of Marseille, France.
About SNM
SNM is an international scientific and medical organization dedicated to raising public awareness about what molecular imaging is and how it can help provide patients with the best health care possible. SNM members specialize in molecular imaging, a vital element of today's medical practice that adds an additional dimension to diagnosis, changing the way common and devastating diseases are understood and treated.
SNM's more than 17,000 members set the standard for molecular imaging and nuclear medicine practice by creating guidelines, sharing information through journals and meetings and leading advocacy on key issues that affect molecular imaging and therapy research and practice. For more information, visit www.snm.org.

New evidence for homeopathy

Two new studies conclude that a review which claimed that homeopathy is just a placebo, published in The Lancet, was seriously flawed.

04 nov 2008--George Lewith, Professor of Health Research at Southampton University comments: 'The review gave no indication of which trials were analysed nor of the various vital assumptions made about the data. This is not usual scientific practice. If we presume that homeopathy works for some conditions but not others, or change the definition of a 'larger trial', the conclusions change. This indicates a fundamental weakness in the conclusions: they are NOT reliable.'
The background to the ongoing debate is as follows:
In August 2005, The Lancet published an editorial entitled 'The End of Homeopathy', prompted by a review comparing clinical trials of homeopathy with trials of conventional medicine. The claim that homeopathic medicines are just placebo was based on 6 clinical trials of conventional medicine and 8 studies of homeopathy but did not reveal the identity of these trials. The review was criticised for its opacity as it gave no indication of which trials were analysed and the various assumptions made about the data.
Sufficient detail to enable a reconstruction was eventually published and two recently published scientific papers based on such a reconstruction challenge the Lancet review, showing that:
Analysis of all high quality trials of homeopathy yields a positive conclusion.
The 8 larger higher quality trials of homeopathy were all for different conditions; if homeopathy works for some of these but not others the result changes, implying that it is not placebo.
The comparison with conventional medicine was meaningless.
Doubts remain about the opaque, unpublished criteria used in the review, including the definition of 'higher quality'.
The Lancet review, led by Prof Matthias Egger of the Department of Social and Preventive Medicine at the University of Berne, started with 110 matched clinical trials of homeopathy and conventional medicine, reduced these to 'higher quality trials' and then to 8 and 6 respectively 'larger higher quality trials'. Based on these 14 studies the review concluded that there is 'weak evidence for a specific effect of homoeopathic remedies, but strong evidence for specific effects of conventional interventions'.
There are a limited number of homeopathic studies so it is quite possible to interpret these data selectively and unfavourably, which is what appears to have been done in the Lancet paper. If we assume that homeopathy does not work for just one condition (Arnica for post-exercise muscle stiffness), or alter the definition of 'larger trial', the results are positive. The comparison with conventional medicine was meaningless: the original 110 trials were matched, but matching was lost after they were reduced to 8 and 6. But the quality of homeopathic trials was better than conventional trials.
This reconstruction casts serious doubts on the review, showing that it was based on a series of hidden judgments unfavourable to homeopathy. An open assessment of the current evidence suggests that homeopathy is probably effective for a number of conditions including allergies, upper respiratory tract infections and 'flu, but more research is desperately needed.
Prof Egger has declined to comment on these findings.
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References Lüdtke R, Rutten ALB. The conclusions on the effectiveness of homeopathy highly depend on the set of analyzed trials. J Clin Epidemiol 2008. doi:10.1016/j.jclinepi.2008.06.015 Rutten ALB, Stolper CF. The 2005 meta-analysis of homeopathy: the importance of post-publication data. Homeopathy 2008. doi:10.1016/j.homp.2008.09.008.

Falls Are Leading Cause of Injury to Seniors

03 nov 2008-- Former first lady Nancy Reagan and Democratic presidential candidate Barack Obama's grandmother have suffered recent pelvic and hip injuries. And on Friday, author Studs Terkel died, following reports that a fall two weeks ago had hastened his decline.
Such news, experts say, should be a reminder to all about the need to help the elderly protect themselves against their increased risk of falls and bone injuries.
According to the American Academy of Orthopaedic Surgeons, one in every three Americans older than 65 experiences a fall, making it the leading cause of injuries to seniors.
To help prevent falls and bone fractures, the academy recommends that seniors:
Have an annual physical and eye examination. Make sure any cardiac and blood pressure problems are fully evaluated.
Consume a diet with adequate dietary calcium and vitamin D for good bone health. Do not smoke, and avoid excessive use of alcohol.
Participate in an exercise program to maintain agility, strength, balance, and coordination.
Maintain a clutter-free home with clear walking paths through rooms. Eliminate tripping hazards and install grab bars, handrails and other safety devices in appropriate areas, such as bathrooms and bedrooms.
Wear properly fitting shoes with nonskid soles. Never walk about with only socks or stockings on your feet.
Have adequate lighting in the home. Use nightlights between bedrooms and bathrooms. Make sure light switches are easily accessible by doorways.

Foods to prevent disease?

by Christine Courcol
PARIS, 03 nov 2008– Eating tomatoes to help prevent cancer, garlic to prevent AIDS or drinking fruit juice to ward off Alzheimer's? Despite a bevy of research, the impact of food on killer diseases remains to be proved.
Scientists agree that a balanced quality diet is key to good health, and most governments in past years have urged citizens to adopt a daily diet of five portions of fruit and veg, and three each of dairy products and starch, while cutting back fats, sugar and alcohol.
Watching what you eat, experts say, does help prevent illnesses such as diabetes, hypercholesterolaemia -- which leads to cardio-vascular disease -- or osteoporosis.
But researchers are in disagreement over illnesses not directly related to nutrition, such as cancer, AIDS or neurodegenerative diseases -- though again all recommend a balanced diet.
Among the thousands of studies on hand, one European investigation concluded that eating fruit and vegetable fibre might limit the risk of colorectal cancer.
Fruit was tipped as a possible protection against cancer of the lung, and to ward off prostate cancer, the study recommended five cups a day of catechin-rich green tea -- catechins are polyphenolic antioxidant plant metabolites.
Industrial -- or processed -- fats, already known to be harmful for the cardiovascular system, could double the risk of breast cancer while soybeans reduced the risk threefold.
But soybeans, which are rich in anti-oxydants that help cells survive, could increase the risk of infertility.
Lycopene, the bright red anti-oxydant pigment found in tomatoes and other red fruits, also was found by some researchers to reduce the risk of cancer, but the US Food and Drug Administration (FDA) says there is no solid proof for the claim.
Alzheimer's on the other hand could be kept at bay by pomegranate juice, as well as the polyphenols in a glass of red wine.
But while fish are hailed for their omega-3, a family of unsaturated fatty acids, fish are also rich in mercury and toxic PCBs, or polychlorinated biphenyls.
"There are no good or bad foods," said France's Afssa food security agency.
But eating five fruit and veggies a day and little animal fat "is plain common sense", said oncologist Dominique Belpomme.
Experts at France's national food and cancer research centre, NACRe, said a varied diet of mainly fruit and vegetables with not too much alcohol would help prevent cancers of the mouth, pharynx, oesophagus, lung, stomach, pancreas, colon-rectum and bladder.
After leafing through 7,000 studies from across the globe, the World Cancer Research Fund (WCRF) recommends avoiding food and drinks high in sugar, salt or fats and low in fibres, and instead eating fruit, vegetables, wholegrain cereals and pulses.
Eating well is also key to treating HIV-positive patients as malnutrition weakens the immune system, lowering resistance to secondary effects.
But good food cannot replace antiretrovirals despite claims to the contrary by South Africa's controversial health minister -- "Dr Beetroot" -- on fighting AIDS with garlic, lemons and veggies.

Excess Weight Seems to Boost Breast Cancer Risk

By Dennis Thompson

03 nov 2008-- Obesity can wreck a person's health for many reasons. But for women, too much weight tacks on an additional danger: Studies have linked obesity and breast cancer in a variety of ways.
Doctors aren't sure why this link exists and are trying to figure out what ties weight gain to breast cancer. But they are more and more convinced the link is there, and they are urging women to watch their weight and increase their exercise to help stave off what is the most common cancer among females, nonmelanoma skin cancer aside.
"There are a lot of factors we need to figure out," said Dr. Jennifer A. Ligibel, of the Dana-Farber Cancer Institute in Boston. "There are a lot of things we don't know."
An estimated 182,500 women in the United States will be found to have invasive breast cancer in 2008, according to the American Cancer Society, and about 40,480 women will die from the disease this year. Currently, there are about 2.5 million breast cancer survivors in the United States.
Studies have found that, in general, obesity is linked to cancer. The higher a person's body-mass index (BMI, a ratio of weight to height), the more likely she or he will develop cancer, according to recent research by scientists at the University of Manchester in England. Other studies have found similar links to increased body fat.
Still other studies have found that women with breast cancer are more likely to live shorter lives and suffer a recurrence of their cancer if they are overweight.
For example, in a recent study conducted at the University of Texas M.D. Anderson Cancer Center in Houston, more than two-thirds of women with stage III locally advanced breast cancer were either overweight or obese. The study also found that a greater proportion of obese patients were likely to be diagnosed with a rare and more deadly form of breast cancer, known as inflammatory breast cancer.
Scientists vary in their opinions on why this link exists, and what it means.
Some believe that obesity may make tumors harder to detect, so a woman's breast cancer will be further developed before it is discovered.
"It could be because there's more breast tissue, a lump would be less evident," Ligibel said.
Researchers also believe that the systemic effects of obesity might do something to spur cancer on. For example, obesity or overweight can lead to fluctuations in hormone levels in the body.
"When women are heavier, their estrogen levels are higher," Ligibel said. "That could be a pathway through which weight affects breast cancer. Other studies have shown that when insulin levels are high, there's more chance a cancer will come back."
Another link to obesity was found in a study from the University of North Carolina at Chapel Hill that showed that obese women are more likely to skip screenings for breast and cervical cancer. Without those screenings, women are less likely to catch breast cancer at a more treatable stage.
Debbie Saslow, director of breast and gynecologic cancer at the American Cancer Society, said it's not completely clear what role obesity plays in breast cancer risk.
"For obesity, which is independent of breast size, I would think two factors would come into play," Saslow said. "One, a positive, is that the breasts may be fattier, which would make a mammogram easier to read. The second, a negative, is indirect: Obese women are less likely to go to a doctor."
Menopause appears to be a critical time, Ligibel said. Obesity creates a greater risk for breast cancer post-menopause, while pre-menopausal women actually have a reduced risk.
"Gaining weight around the time of menopause is a risk factor in developing breast cancer," Ligibel said.
The increased risk of developing breast cancer and dying of it after menopause is believed due to increased levels of estrogen in obese women, said Colleen Doyle, director of nutrition and physical activity with the American Cancer Society.
There is good news. Studies have shown that exercise -- 30 minutes to 60 minutes a day of moderate-to-high intensity physical activity -- decreases breast cancer risk, Doyle said.
"Physical activity reduces breast cancer risk both directly, by decreasing circulating estrogens, and also indirectly, by helping with weight control," she said. "Women are so concerned about breast cancer risk. Communicating that there are key things you can do to reduce risk -- watch your weight and be more active -- are valuable messages."
Ligibel agreed, noting that exercise might be valuable enough to counteract the strain on the body caused by obesity.
"You might not need to lose weight if you exercise," Ligibel said. "Exercise could affect the hormone levels and help keep cancer from occurring or recurring."

Study links primary insomnia to a neurochemical abnormality in young and middle-aged adults

The study is the first to show a specific neurochemical difference in the brains of adults with primary insomnia

Westchester, Ill, 03 nov 2008 — A study in the Nov. 1 issue of the journal Sleep is the first demonstration of a specific neurochemical abnormality in adults with primary insomnia, providing greater insight to the limited understanding of the condition's pathology.
Results indicate that gamma-aminobutyric acid (GABA), the most common inhibitory transmitter in the brain, is reduced by nearly 30 percent in individuals who have been suffering from primary insomnia for more than six months. These findings suggest that primary insomnia is a manifestation of a neurobiological state of hyperarousal, which is present during both waking and sleep at physiological and cognitive levels.
"GABA is reduced in the brain of individuals with insomnia, suggesting overactivity is present not only at the level of excessive thoughts and emotions, but can also be detected at the level of the nervous system," said principal investigator Dr. John Winkelman of Brigham and Women's Hospital, which is a teaching affiliate of Harvard Medical School in Boston, Mass.
GABA decreases overall activity in many brain areas, helping the brain to "shut down." Having a "racing mind" and an inability to shut down at night is a common complaint of people with primary insomnia.
Chronic insomnia, or symptoms that last for at least a month, affects about 10 percent of all adults in industrialized countries and is the most common sleep disorder. Most often insomnia is a "comorbid" disorder, present with another medical illness, mental disorder or sleep disorder, or associated with certain medications or substances. Approximately 25 percent of people suffering from insomnia are considered to have primary insomnia, which is defined as a difficulty falling asleep or maintaining sleep in the absence of coexisting conditions.
According to Winkelman, the recognition that primary insomnia is associated with a specific neurochemical deficiency helps validate the often misunderstood complaint of insomnia.
"Recognition that insomnia has manifestations in the brain may increase the legitimacy of those who have insomnia and report substantial daytime consequences," he said. "Insomnia is not just a phenomenon observed at night, but has daytime consequences for energy, concentration and mood."
This preliminary study included 16 participants (eight men and eight women) who were screened to be free of medical and sleep disorders, as well as anxiety and mood disorders, and who were not taking prescription medication. Ages ranged from 25 to 55 years. Researchers recruited people who had difficulty initiating or maintaining sleep with resulting daytime distress or dysfunction for a period of at least six months. The average duration of participants' symptoms was 10 years. Objective data were collected by actigraphy and overnight polysomnography. Proton magnetic resonance spectroscopy (1H-MRS) was used to non-invasively determine GABA levels. For statistical comparison the study included a well-matched control group consisting of seven women and nine men.
Significant correlations were found between GABA levels and both subjective and objective sleep measures after adjusting for age, body mass index (BMI) and gender. In subjects with primary insomnia, sleep continuity, as measured by minutes of wake after sleep onset (WASO) on sleep study, was strongly associated with GABA levels.
According to the study, reductions in brain GABA levels also have been observed with 1H-MRS in major depressive disorder (MDD) and anxiety disorders. Primary insomnia shares many features with anxiety and depressive disorders, including sleep disturbance, elevation in anxiety, and impairments in concentration and energy. In addition, primary insomnia is an important risk factor for incident mood and anxiety disorders. The study raises the possibility that GABA deficiencies seen in people with mood and anxiety disorders may be based on disturbances in sleep.
The study also reports that many of the hypnotic medications that are most effective in treating insomnia are benzodiazepine receptor antagonists (BzRAs), which increase activity at the GABA neurons. According to a new clinical guideline for the evaluation and management of chronic insomnia in adults, which was published by the American Academy of Sleep Medicine in the Journal of Clinical Sleep Medicine, hypnotic treatment should be supplemented with behavioral and cognitive therapies whenever possible.
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A media fact sheet about insomnia is available from the AASM at http://www.aasmnet.org/Resources/FactSheets/Insomnia.pdf, and information for patients and the public is available at http://www.sleepeducation.com/Disorder.aspx?id=42.
Sleep is the official journal of the Associated Professional Sleep Societies, LLC (APSS), a joint venture of the American Academy of Sleep Medicine and the Sleep Research Society. The APSS publishes original findings in areas pertaining to sleep and circadian rhythms. Sleep, a peer-reviewed scientific and medical journal, publishes 12 regular issues and one issue comprised of the abstracts presented at the SLEEP Meeting of the APSS.
For a copy of the study, "Reduced Brain GABA in Primary Insomnia: Preliminary Data from 4T Proton Magnetic Resonance Spectroscopy (1H-MRS)," or to arrange an interview with an AASM spokesperson, please contact Kelly Wagner, AASM public relations coordinator, at (708) 492-0930, ext. 9331, or kwagner@aasmnet.org.
Principal Investigator Contact Information: Dr. John Winkelman, MD, PhD Brigham and Women's Hospital Harvard Medical School 1505 Commonwealth Avenue Brighton, MA Telephone: (617) 783-1441 JWWinkelman@partners.org
Additional Information on Insomnia
Approximately 30 percent of adults have symptoms of insomnia.
Insomnia is more common among women and elderly people. Some medical conditions cause insomnia, or symptoms may be a side effect of a medication.
The essential feature of primary insomnia, or pscyhophysiological insomnia, is heightened arousal and learned sleep-preventing associations that result in a complaint of insomnia and associated decreased functioning during wakefulness.
Psychophysiological insomnia is associated with excessive worrying about sleep. As a result, they may engage in bad behaviors that include taking sleeping pills, drinking alcohol or spending too much time in bed hoping to get more sleep.
Individuals with persistent pscyophysiological insomnia tend to note decreased feelings of well-being during the day. The sleep difficulty often leads to deteriorated mood and motivation; decreased attention, vigilance energy and concentration. Despite these symptoms many report an inability to take intentional daytime naps.

Landmark UCLA study finds aggresive, personalized treatment increases kidney cancer patient survival

Study will allow doctors to better predict which patients will do well and select those who may respond to targeted therapies

03 novc 2008--A study of nearly 1,500 patients treated for kidney cancer at UCLA in the last 15 years shows that an aggressive, tailored treatment approach results in better survival rates and uncovered subsets of kidney cancer that behave differently and need to be treated accordingly.
The one-size-fits-all approach traditionally used in kidney cancer treatment should be changed based on the results of the study, the longest to date to analyze kidney cancer patients and their outcomes, said Dr. Arie Belldegrun, senior author of the study, a professor of urology and a researcher at UCLA's Jonsson Comprehensive Cancer Center.
"This is the most important work that we've done out of the kidney cancer program at UCLA," Belldegrun said. "We outline the foundation for personalized kidney cancer therapy. We have shown that not all kidney cancer patients are the same, not all localized kidney cancers are the same and not all metastatic kidney cancers are the same."
The study appears in the Nov. 1, 2008 issue of Cancer, the peer-reviewed journal of the American Cancer Society.
The study found that patients with localized kidney cancer, cancer that has not spread to other organs, could have either low, intermediate or high risk cancers based on the chance for recurrence. Patients with cancers that have already spread also fell into similarly different subsets. Some have better outcomes while others may have very aggressive cancers that may not warrant treatment.
"We showed for the first time, using an integrated staging system developed at UCLA, that we can identify which patients with localized disease fall into the low, intermediate and high risk subsets and which patients with metastasized cancers are either low, intermediate or high risk patients," Belldegrun said. "Now we can make treatment decisions based on that."
If a patient with localized cancer is identified as low risk, his five-year survival rate is expected to be 97 percent, while his 10-year survival rate is 92 percent. An intermediate risk patient with localized disease would have a five-year survival rate of 81 percent and a 10-year survival rate of 61 percent. A high risk patient has a five-year survival rate of 62 percent, with a 10-year survival of 41 percent.
"All of these patients with cancers that have not spread present to their doctors with presumably localized disease and in the past they may have been treated the same way," Belldegrun said. "They need to be treated individually according to their risk levels."
The study showed that a patient with low-risk, localized kidney cancer could be treated only with surgery and expect an excellent outcome. Such a move would spare the patient from having to undergo radiation or immunotherapy, which result in harsh side effects. However, for a patient with high-risk, localized kidney cancer, surgery would not be enough. Additional therapy such as targeted treatments or immunotherapy should be considered in order to give the patient the best possible outcome.
In metastatic patients, someone with low-risk cancer should get very aggressive treatment, Belldegrun said, because there's a good chance the therapy will help the patient. Those with high-risk, metastatic disease won't get much, if any, benefit from treatment and may want to forego surgery and the toxic therapies.
"Our paper identifies, very precisely, which patients should get which therapies," Belldegrun said.
The study represents 15 years of experience in UCLA's leading-edge kidney cancer program, an interdisciplinary approach to treating cancer that brings together medical oncologists, urologists, surgeons, clinical trials experts and scientists under one roof, a concept that was first conceptualized at UCLA. The study analyzed the first 1,492 patients treated in the program and "demonstrated that outstanding results can be achieved using this approach," Belldegrun said.
About 25 percent of the patients with metastatic kidney cancer achieved long-term responses – five to 15 year survivals – from their therapy, Belldegrun said. Less than 5 percent of metastatic kidney cancer patient typically achieve long term survivals or a cure when treated with conventional treatments.
"This is by far the best survival data in such a difficult group of patients," Belldegrun said. "This can be achieved today only in kidney cancer centers of excellence like we are operating at UCLA, where we have all the expertise at hand, the best scientists, clinicians and surgeons working together."
The results of the study come as new targeted therapies are being introduced specifically for kidney cancer. The U.S. Food & Drug Administration has recently approved three such drugs. Belldegrun said the survival rates detailed in their paper should be used as a benchmark to which these new therapies should be compared.
"While the field of kidney cancer is undergoing dramatic changes it is as yet still unclear how these changes are affecting patient outcome," the study states. "A critical assessment of the potential improvement in the new treatment era necessitates a comparison to a known benchmark. We present long-term, single institution data to provide a thorough understanding of the results that have been achieved until now using a consistent, aggressive approach for localized and metastatic disease. For future patient care, it will be important to select patients that will do best using existing therapies, and those who should be treated using the newly approved treatments."
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Other lead investigators on the study include Dr. Fairooz Kabbinavar, medical director of the kidney cancer program at UCLA and a professor of hematology/oncology, and Dr. Allan Pantuck, director for translational research and an associate professor of urology. Both are scientists with the Jonsson Cancer Center.
UCLA's Jonsson Comprehensive Cancer Center comprises about 235 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2008, the Jonsson Cancer Center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for nine consecutive years. For more information on the Jonsson Cancer Center, visit our website at http://www.cancer.ucla.edu.

ICAAC-IDSA: Pneumonia Linked to Acute Coronary Syndrome

WASHINGTON, 02 nov 2008-- Patients hospitalized with bacterial pneumonia have about eight times the risk of acute coronary syndrome as those admitted for other causes, a researcher said here.
The risk is highest within 15 days of admission, said Vicente Corrales-Medina, M.D., of Baylor College of Medicine in Houston.
The association -- found in a retrospective case-control analysis -- is "so striking" it suggested a causal relationship, Dr. Corrales-Medina said at the Interscience Conference on Antimicrobial Agents and Chemotherapy, held jointly with the Infectious Diseases Society of America meeting.
"There is evidence that suggests that acute infections -- not just pneumonia -- can cause acute changes in atherosclerotic plaques," Dr. Corrals-Medina said.
Such changes, combined with effects of pneumonia such as respiratory stress, might lead to acute coronary syndromes, including unstable angina or myocardial infarction, he said.
Dr. Corrales-Medina and colleagues analyzed the records of 206 patients admitted to the Michael E. DeBakey VA Medical Center in Houston with a clinical, radiological, and bacteriological diagnosis of pneumonia from January 2000 through December 2006.
Of those cases, 144 were caused by Streptococcus pneumoniae and 62 by Haemophilus influenzae, Dr. Corrales-Medina said.
For a control group, the researchers identified 395 patients admitted with a diagnosis that was neither pneumonia nor acute coronary syndrome, who were matched by date and time of admission.
When the two groups were compared, 22 of the pneumonia patients (10.7%) had acute coronary syndrome within 15 days of admission, compared with six (1.5%) of the controls, Dr. Corrales-Medina said.
In a univariate analysis, he said, the odds ratio was 7.8, with a 95% confidence interval from 3.1 to 19.4, which was significant at P<0.001.>

COPD Exacerbations Linked to Depression and Anxiety

By Crystal Phend
MONTREAL, 02 nov 2008-- Depression may cause exacerbations of chronic obstructive pulmonary disease, and anxiety prolongs them, researchers said. COPD patients with symptoms of depression were at a 51% to 56% increased risk of exacerbations and a 72% increased risk of hospitalization, reported Jean Bourbeau, M.D., of McGill University here, and colleagues in the Nov. 1 issue of the American Journal of Respiratory and Critical Care Medicine. The prospective, longitudinal study also showed that exacerbations lasted almost twice as long for patients with pre-existing anxiety symptoms. A comprehensive evaluation of confounding suggested that the associations were likely causal, although Dr. Bourbeau emphasized the need for caution in talking about causal relationships.
Since better detection and treatment of depression in COPD patients could improve clinical outcomes, the findings provide a further argument for treating depression in these patients, he said.
Like other chronic diseases, COPD is frequently seen with comorbid depression and anxiety, the researchers said.
For chronic conditions like diabetes and hypertension, increasing evidence suggests that depression and anxiety directly impact health rather than merely being consequences or markers of disease severity, they noted.
To see whether the same was true for COPD, the researchers conducted a prospective cohort study of 491 adults with stable COPD seen at the respiratory departments of 10 general hospitals in Beijing.
All participants completed questionnaires on baseline anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and were followed monthly by telephone over a 12-month period for subsequent exacerbations and other clinical events.
Depression was probable for 9% of patients based on HADS depression scores above 11 at baseline. Anxiety was also probable for the 5.1% of patients with HADS anxiety scores greater than 11.
After adjustment for known confounders and COPD severity, depression showed a significant dose-response association with clinical events.
Compared with nondepressed patients who had HADS depression scores below seven, probable depression was associated with an increased risk of the following:
Exacerbations with worsening of dyspnea or sputum amount, color or purulence (incidence rate ratio 1.51, 95% confidence interval 1.01 to 2.24).
Exacerbations with worsening symptoms and a change in antibiotics, corticosteroid, or bronchodilator medication (IRR 1.56, 95% CI 1.02 to 2.40).
Hospitalization (IRR 1.72, 95% CI 1.04 to 2.85).
These associations remained significant after adjustment for lung function measured by FEV1% and grade of dyspnea, although not consistently so after controlling for baseline six-minute-walk distance.
Although anxiety was not linked to exacerbation incidence or hospitalization, it was associated with a 1.92 times longer duration of exacerbation than was seen among those with no anxiety as indicated by scores below seven (95% CI 1.04 to 3.54).
Hospitalizations also tended to be longer -- 2.45 times longer with probable depression (95% CI 0.76 to 7.87) and 1.99 times longer with probable anxiety (95% CI 0.59 to 6.72) -- but the associations were not significant.
Possible mechanisms to explain the effect of depression on COPD exacerbation suggested by Dr. Bourbeau's group included:
Immune effects of depression that may impact susceptibility to environmental triggers of COPD exacerbation, such as viral or bacterial infection and air pollutants.
Reduced ability to adapt to having a chronic illness and increased awareness of and focus on physical symptoms.
Lower self-confidence and a feeling of hopelessness leading to poor self-care and adherence to medications that may make them more vulnerable when exposed to a trigger of COPD exacerbation.
Limitations of the study included an 8% dropout rate, which was higher among patients with more severe COPD, and other possible unmeasured confounders.
Further study is needed to confirm the findings and determine whether intervention to treat depression and anxiety may reduce exacerbations and improve health resource utilization, the researchers said.
The study was supported by the Canadian Institute of Health Research through the Global Health Research Initiative.
The researchers reported no conflicts of interest.
Primary source: American Journal of Respiratory and Critical Care MedicineSource reference:Xu W, et al "Independent Effect of Depression and Anxiety on Chronic Obstructive Pulmonary Disease Exacerbations and Hospitalizations" Am J Respir Crit Care Med 2008; 178: 913-920.

Compound in Veggies May Increase Effectiveness of Cancer Treatment

By John Gever
RIVERSIDE, Calif., 02 nov 2008A flavonoid compound found in many fruits and vegetables may make cancers more sensitive to standard DNA-damaging treatments, researchers here said.
Cultured neuroblastoma cells were more likely to die after dosing with etoposide if they were pretreated with the flavonoid, called apigenin, reported Xuan Liu, Ph.D., and Xin Cai, Ph.D., of the University of California Riverside, online in the Proceedings of the National Academy of Sciences.
The researchers said apigenin appears to work by restoring the p53 tumor-suppressor protein's normal function in cancer cells where the protein has been rendered inactive.
When fully functioning, p53 forces cells with DNA damage that cannot be repaired to undergo apoptosis. Its deactivation allows cancer cells to survive DNA-damaging treatments such as certain chemotherapies and radiation.
Dr. Liu said the study supported inclusion of more vegetables and fruits in the diet to prevent cancer, although it did not address whether the apigenin in foods exerts the same effect in vivo.
The researchers also suggested that other compounds using the same p53-targeted mechanism could be developed that have stronger treatment-sensitizing effects.
The specific action of apigenin is that it inhibits phosphorylation of p53 by another protein called Thr-55, the researchers said.
When this phosphorylation takes place, p53 is ejected from the cell nucleus and destroyed.
Treatment with apigenin, Drs. Liu and Cai found, restores p53's nuclear localization and allows it to trigger apoptosis in response to DNA damage.
But apigenin was not wholly effective in the etoposide-treated neuroblastoma cells.
Pretreatment with apigenin raised the rate of apoptosis to 53%, compared with 20% in cells dosed only with etoposide.
Previous research had found that apigenin inhibits growth of tumor cell lines in vitro, but its mechanism was unknown, Drs. Liu and Cai said.
Earlier studies had also indicated apigenin does not affect normal human cells, "suggesting that perhaps this dietary flavonoid is not toxic to non-transformed cells and thus could be used to specifically sensitize cancers caused by abnormal cytoplasm localization of wild-type p53," they added.
The study was funded by the National Cancer Institute.
No potential conflicts of interest were reported.
Primary source: Proceedings of the National Academy of SciencesSource reference:Cai X, et al "Inhibition of Thr55 phosphorylation restores p53 nuclear localization and sensitizes cancer cells to DNA damage" PNAS 2008; DOI: 10.1073/pnas.0804608105.

Wisdom of Preoperative Beta-Blockers Questioned

By Charles Bankhead
WEST ROXBURY, Mass., 02 nov 2008-- In noncardiac surgery, preoperative beta-blockers may increase cardiovascular risks despite achieving adequate heart-rate control, especially in patients who are not at high risk, investigators here concluded.
Patients treated with beta-blockers had a higher rate of myocardial infarction at 30 days and 30-day mortality, compared with a control group, Kamal M. F. Itani, M.D., of the Boston VA, and colleagues reported in the October issue of Archives of Surgery.
In the beta-blocker group, patients who died had a significantly higher baseline heart rate, but none of the deaths involved patients considered to be at high cardiac risk.
"Our study adds to the controversy regarding the optimal use of perioperative beta-blockers in patient populations at various levels of cardiac risk," the authors said. "Overall, our data found worse perioperative cardiovascular outcome and worse overall mortality associated with the use of beta-blockers."
"Further investigations in this field with standardizing of beta-blockade regimen and with monitoring of heart rate in populations at various levels of cardiac risk should be pursued," they added.
Evidence linking perioperative ischemic events to a rise in heart rate sparked interest in use of beta-blockers to improve surgical outcomes. However, multiple studies failed to demonstrate a clear benefit, and some studies suggested that perioperative beta-blockers increased surgical risk.
In a 2006 guideline update, the American College of Cardiology and American Heart Association recommended limiting perioperative beta-blockers to two groups of patients undergoing noncardiac surgery: 1. Those already on beta-blockers, and 2. High-risk patients undergoing vascular surgery.
The ACC-AHA guideline recommends a resting heart rate of 50 to 60 bpm and maintenance of a heart rate less than 80 bpm through the intraoperative and perioperative periods.
Previous studies had not evaluated perioperative beta-blockers in patients at low or intermediate risk, the authors said. Additionally, few studies evaluated the optimal drug, dose, regimen, or duration of therapy.
"No definitive consensus has been reached regarding the population at intermediate cardiac risk and the target heart rate needed for effect," they said. In an effort to bring some clarity to the discussion, investigators retrospectively reviewed data on 1,238 patients who received perioperative beta-blockers in conjunction with noncardiac surgery. The patients were stratified by baseline cardiac risk from high to negligible. They were matched with a similar number of patients who had surgery without beta-blockers.
The primary outcome was 30-day stroke, cardiac arrest, myocardial infarction, and mortality, as well as one-year mortality.
Across all levels of baseline risk, patients who received beta-blockers had a significantly lower preoperative heart rate compared with the control group (70 versus 74 bpm, P<0.001).
The beta-blocker group had a 30-day mortality of 2.52% versus 0.25% in the control group (P=0.007) and a 30-day nonfatal MI incidence of 2.94% compared with 0.74% (P=0.03). The 30-day incidence of cerebrovascular accident (0% versus 0.49%) and cardiac arrest (0% versus 0.25%) did not differ between groups, nor did one-year mortality (4.31% versus 2.70%).
Total cardiac morbidity was significantly higher in the beta-blocker group (5.04% versus 1.47%, P=0.003).
Noting that deaths in the beta-blocker group involved patients at low and intermediate risk, the authors said their findings raise questions about the safety of beta-blockers in those patients.
"In addition, the patients who died within 30 days had a clinically and statistically higher preoperative heart rate than did their counterparts [86 versus 70 bpm, P=0.03)]," the authors said. "As subtle as it may be, this finding suggests that a low target preoperative rather than intraoperative heart rate is essential for the protective effect of beta-blockers."
The authors noted several limitations of the study including the fact that it is a retrospective study, and some additional confounding variables might exist.
In addition, they acknowledged, the study population was a predominantly male veteran population and the results might not be applicable to the general population. They also noted that there was no uniform regimen for β-blockade, and data regarding the concomitant use of statins, β-blockers, or antiplatelet therapy were unavailable.
In an invited critique, Todd E. Rasmussen, M.D., of Wilford Hall Air Force Medical Center in San Antonio, wondered whether "use of preoperative beta-blockers" had already categorized patients as high risk.
"It is conceivable, if not likely, that patients in the beta-blocker group were indeed at higher risk, having been identified as candidates for preoperative beta-blocker therapy," said Dr. Rasmussen. "Such patients may not have displayed overt clinical risk . . . to change their risk category but were perceived as having 'enough of a risk' to trigger starting the well-publicized cardioprotective therapy of oral beta-blockade."
The authors and Dr. Rasmussen reported no conflicts of interest.
Primary source: Archives of SurgerySource reference:Kaafarani HMA, et al "Beta-blockade in noncardiac surgery. Outcome at all levels of cardiac risk" Arch Surg 2008; 143: 940-944. Additional source: Archives of SurgerySource reference: Rasmussen TE "Invited critique" Arch Surg 2008; 143: 944.

Heart Failure Linked to Higher Hip Fracture Risk

By Todd Neale
EDMONTON, Alberta, 02 nov 2008 -- Older heart failure patients have an increased risk of fracture, particularly of the hip, researchers found.
Patients ages 65 and older who presented to an emergency room for heart failure were four times more likely to suffer a fracture over the next year than patients with other cardiovascular diseases (OR 4.0, 95% CI 3.0 to 5.2), Justin Ezekowitz, M.B.B.Ch., of the University of Alberta here, and colleagues reported online in Circulation: Journal of the American Heart Association.
The risk of hip fracture specifically was increased 6.3-fold (95% CI 3.4 to 11.8).
The elevated risks remained significant even after excluding patients who were using bisphosphonates.
The results suggest that "increased attention needs to be paid to the screening for and treatment of osteoporosis to reduce fracture risk in those with heart failure," the researchers said.
The reasons behind the association between heart failure and fracture remain unclear, the researchers said.
Although heart failure and fracture share some risk factors, it hadn't been known whether heart failure patients had an increased risk of fracture, according to the researchers.
So they evaluated data from 2,041 patients with a first diagnosis of heart failure and 14,253 patients with other cardiovascular disease treated at emergency rooms throughout the province of Alberta over a three-year period.
Heart failure patients were significantly older (median 78 versus 73) and more likely to have hypertension, diabetes, atrial fibrillation, prior cerebrovascular disease, peripheral vascular disease, renal disease, and chronic obstructive pulmonary disease (P≤0.001 for all).
They were also more likely to be taking ACE inhibitors or angiotensin receptor blockers, diuretics, spironolactone, vitamin K antagonists, and thyroid replacement hormones (P≤0.01 for all).
The use of bisphosphonates (P=0.04) and other osteoporosis medications (P<0.0001) was more common in the control group.
Within a year after the emergency room visit, 4.6% of the heart failure patients and 1% of the control patients sustained a fracture (P<0.001).
Hip fractures occurred in 1.3% of heart failure patients and 0.1% of the controls (P<0.001).
Aside from heart failure, other significant predictors of fracture were increasing age (OR 1.26), bisphosphonate use (OR 2.55), and female sex (OR 2.17).
Although the reasons behind the association between heart failure and fracture are unclear, the mechanism may involve elevated levels of parathyroid hormone, angiotensin II, or aldosterone and lower levels of vitamin D, the researchers said.
In addition, they said, certain cardiovascular medications -- such as beta-blockers, thiazide diuretics, and loop diuretics -- may influence the risk of osteoporosis and fracture.
"Further elucidation of the potential mechanism for increased orthopedic fracture risk in heart failure patients requires further pathophysiological studies," they said.
Regardless of the mechanism, the researchers said that the low numbers of patients receiving treatment for osteoporosis indicated that efforts needed to be undertaken to increase screening for bone loss in patients ages 65 and older.
"Although our data do not allow us to determine whether other comorbidities that coexist with or are part of the underlying pathophysiology of heart failure (e.g., anemia and malnutrition) are the cause of fracture," they said, "patients with heart failure are readily identifiable and need to have better attention paid to bone mass and amelioration of fracture risk."
They acknowledged some limitations of the study, including the use of administrative data, the possibility that patients with preexisting heart failure were placed in the control group, the inability to detect fractures treated in an outpatient setting, the fact that fall risk increases with age, the inability to track over-the-counter use of calcium and vitamin D, and potential residual bias and confounding.
Dr. Ezekowitz is supported by the Randomized Controlled Trials program of the Canadian Institutes of Health Research (CIHR). His co-authors are supported by the Alberta Heritage Foundation for Medical Research, the CIHR, and the Merck Frosst-Aventis Chair in Patient Health Management. The study was supported by an operating grant from the CIHR.
The authors made no financial disclosures.
Primary source: Circulation: Journal of the American Heart AssociationSource reference:Van Diepen, et al "Heart failure is a risk factor for orthopedic fracture: a population-based analysis of 16,294 patients" Circulation 2008; DOI: 10.1161/CIRCULATIONAHA.108.784009.

While prevalent, sexual problems in women not always associated with distress

01 nov 2008--The largest such study ever published finds that, while about 40 percent of women surveyed report having sexual problems, only 12 percent indicate that those issues are a source of significant personal distress. The report led by a Massachusetts General Hospital (MGH) physician appears in the November issue of Obstetrics & Gynecology.
"Sexual problems are common in women, but problems associated with personal distress, those which are truly bothersome and affect a woman's quality of life, are much less frequent." says Jan Shifren, MD, of the MGH Obstetrics and Gynecology Service, who led the study. "For a sexual concern to be considered a medical problem, it must be associated with distress, so it's important to assess this in both research studies and patient care."
Several studies and surveys of sexual problems in women have found problems with low desire, diminished arousal or difficulties with orgasm in approximately 40 percent of women, but few of those have asked about levels of distress associated with those problems. The current study surveyed 32,000 women aged 18 to over 100 from across the U.S. using a well-established survey of sexual function supplemented by a validated measure of a woman's distress related to her sex life – including feelings of anger, guilt, frustration, and worry.
Some level of sexual problem was reported in 43 percent of respondents – with 39 percent reporting low levels of desire, 26 percent problems with arousal and 21 percent difficulties with orgasm. But distress related to any of these problems was reported by only 12 percent of study participants. Although the prevalence of sexual problems was highest in women over 65, that group reported the lowest levels of distress, while distress was reported most frequently in women aged 45 to 64. The youngest group – those from 18 to 44 – had lower levels of both problems and distress. Women with depression were more than twice as likely to report distress over any type of sexual problem as those not suffering from depression.
"Although sexual problems were very common in women over age 65, these problems often weren't associated with distress," Shifren says. "Several factors could be behind the lower levels of distress in the oldest group. If their partners also have low desire, it may not be looked on as a problem, or additional health issues could be of greater concern.
"While distressing sexual problems are much less common in women than sexual problems overall, they still affect approximately one in eight adult women," she adds. "As part of a thorough health assessment, it's important that health care providers ask their female patients if they have sexual concerns and if those problems are associated with distress. Although this study did not examine treatments for sexual problems, effective options are available – including relationship counseling, treatment of associated medical conditions and sex therapy." Shifren is an associate professor of Obstetrics, Gynecology and Reproductive Biology at Harvard Medical School.
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Co-authors of the study, which was funded by Boehringer Ingelheim International, are Brigitta Monz, MD, Boehringer Ingelheim; Patricia Russo, PhD, PRC Health Service Research Management and Consulting; Anthony Segreti, PhD, ASG, Inc., and Catherine Johannes, PhD, RTI Health Solutions.

Vigorous Exercise Can Cut Breast Cancer Risk

01 nov 2008-- Vigorous activity can reduce the risk of breast cancer by about 30 percent in normal-weight women, according to an 11-year U.S. study of 32,269 postmenopausal women.
For the study, vigorous activity was defined as heavy housework (scrubbing floors, washing windows, demanding yard work, digging, chopping wood) and strenuous sports or exercise, such as running, fast jogging, competitive tennis, aerobics, bicycling on hills, and fast dancing.
While vigorous activity reduced breast cancer risk in normal-weight women, it had no effect in women who were overweight or obese, according to study leader Michael F. Leitzmann and colleagues.
They also found that non-vigorous activity, such as light housework (vacuuming, doing laundry, painting, general gardening) and light sports or exercise (walking, hiking, light jogging, recreational tennis, bowling) offered no protection against breast cancer.
The findings were published in the journal Breast Cancer Research.
"Possible mechanisms through which physical activity may protect against breast cancer that are independent of body mass include reduced exposure to growth factors, enhanced immune function, and decreased chronic inflammation, variables that are related both to greater physical activity and to lower breast cancer risk," the study authors wrote.
"An alternative explanation for the stronger apparent effect of vigorous activity among lean over heavy women is that heavier women may misreport non-vigorous activities as vigorous activities," the researchers added.

Obesity blamed for doubling rate of diabetes cases

By MIKE STOBBE
ATLANTA, 01 nov 2008- The nation's obesity epidemic is exacting a heavy toll: The rate of new diabetes cases nearly doubled in the United States in the past 10 years, the government said Thursday. The highest rates were in the South, according to the first state-by-state review of new diagnoses. The worst was in West Virginia, where about 13 in 1,000 adults were diagnosed with the disease in 2005-07. The lowest was in Minnesota, where the rate was 5 in 1,000.
Nationally, the rate of new cases climbed from about 5 per 1,000 in the mid-1990s to 9 per 1,000 in the middle of this decade.
Roughly 90 percent of cases are Type 2 diabetes, the form linked to obesity.
The findings dovetail with trends seen in obesity and lack of exercise — two health measures where Southern states also rank at the bottom.
"It isn't surprising the problem is heaviest in the South — no pun intended," agreed Matt Petersen, who oversees data and statistics for the American Diabetes Association.
The study, led by Karen Kirtland of the Centers for Disease Control and Prevention, provides an up-to-date picture of where the disease is exploding. The information should be a big help as the government and health insurance companies decide where to focus prevention campaigns, Petersen said.
Diabetes was the nation's seventh-leading cause of death in 2006, according to the CDC. More than 23 million Americans have diabetes, and the number is rapidly growing. About 1.6 million new cases were diagnosed among adults last year.
In Type 2 diabetes, cells do not properly use insulin, a hormone needed to convert sugar into energy, and the pancreas gradually loses its ability to produce it. The illness can cause sugar to build up in the body, leading to complications such as heart disease, blindness, kidney failure and poor circulation that leads to foot amputations.
The study involved a random-digit-dialed survey of more than 260,000 adults. Participants were asked if they had ever been told by a doctor that they have diabetes, and when the diagnosis was made. The comparisons between 1995-97 and 2005-07 covered only the 33 states for which the CDC had complete data for both time periods.
The researchers had data for 40 states for the years 2005-07.
West Virginia, South Carolina, Alabama, Georgia, Texas and Tennessee had the highest rates, all at 11 cases per 1,000 or higher. Puerto Rico was about as high as West Virginia. Minnesota, Hawaii and Wyoming had the lowest rates.
It is not entirely clear why some states were worse than others. Older people, blacks and Hispanics tend to have higher rates of Type 2 diabetes, and the South has large concentrations of all three groups. However, West Virginia is overwhelmingly white.
The report asked about diagnosed diabetes only. Because an estimated one in four diabetics have not been diagnosed, the findings probably underestimate the problem, said Angela Liese, a diabetes researcher at the University of South Carolina.
The underestimates may be particularly bad in the rural South and other areas where patients have trouble getting health care, she noted.

Scientists Develop New Strategy to Fight Obesity

01 nov 2008-- An antibody that breaks down and suppresses an appetite stimulant produced by the human body has been discovered.
Scientists with The Scripps Research Institute say the antibody catalyst, GHR-11E11, increased the metabolic rate in fasting mice and curbed their eating even after the rodents went 24 hours without food.
The antibody counteracts ghrelin, a gastric hormone that promotes weight gain and fat storage through metabolic actions that decrease the breakdown of stored fat for energy as well as energy expenditure itself. The body releases the substance to encourage eating during periods of calorie restriction. The findings were published in this week's online issue of the Proceedings of the National Academy of Sciences.
"Our study showed that this novel catalytic ghrelin antibody could specifically seek out and degrade ghrelin," co-lead investigator Kim Janda, a professor of chemistry, said in a news release from the institute. "While this antibody lacks a high level of catalytic efficiency, our study clearly demonstrates that even a basal level of catalysis can effectively modulate feeding behavior. These findings not only validate antibody-based therapeutics, but strongly suggest that catalytic anti-ghrelin antibodies might help patients reach and maintain their weight-loss goals."
Because obesity has a complex nature, any antibody-based treatment would likely be combined with other weight-loss strategies, including medicinal, nutritional, exercise, educational and psychosocial components, Janda said. However, he added, more research is needed to better understand the effect of the antibodies over the long-term and other issues.
According to recent reports from the World Health Organization, about 1 billion people worldwide are overweight or obese, with most of these in the developed world.

Can your doctor correctly read a critical heart test?

University of Maryland School of Medicine physicians lead drive to improve accuracy of electrocardiogram interpretation

01 nov 2008--You have a burning chest pain and a doctor looks at a squiggly-lined graph to determine the cause. That graph, an electrocardiogram (ECG or EKG), can help the doctor decide whether you're having a heart attack or an acid attack from last night's spaghetti. Correct interpretation may prompt life-saving, emergency measures; incorrect interpretation may delay care with life-threatening consequences. Currently, there is no uniform way to teach doctors in training how to interpret an ECG or assess their competence in the interpretation.
To address the lack of uniformity, a team of physicians from the University of Maryland School of Medicine and the American College of Cardiology has developed the first Web-based training and examination program for reading ECGs. It is an interactive computer program to teach and assess the competence of doctors in training. Details of the new tool will be revealed on October 31, 2008, during the annual meeting of the Association of Program Directors in Internal Medicine, in Orlando.
"We hope this tool helps increase expertise among general practitioners in the interpretation of a very commonly used screening test that's part of nearly every adult examination," says team leader R. Michael Benitez, M.D., associate professor of medicine at the University of Maryland School of Medicine in Baltimore and director of the Cardiovascular Fellowship Training Program. "There is no mechanism now for establishing competency among internists or family physicians or for an interim analysis of how a trainee is performing," says Dr. Benitez, who is also a cardiologist at the University of Maryland Medical Center.
Two major medical accrediting bodies, the Accreditation Council for Graduate Medical Education's Residency Review Committee for Internal Medicine and the American College of Physicians, recognize the importance of establishing competent ECG interpretation during Internal Medicine residency. But there is no consensus on how competence should be achieved, documented or even defined.
A physician who wants to specialize in cardiology must pass electrocardiographic interpretation as part of the initial certifying process; failure of the ECG section means failure of the entire exam. However, physicians who will practice general internal medicine do not have to pass an ECG interpretation section in order to pass their board examination, according to Dr. Benitez.
General practitioners are often the first to detect a person with an underlying cardiac disease during a general screening evaluation. "They need to correctly identify and diagnose problems that can significantly and imminently affect the health of their patients," says Dr. Benitez.
The New ECG Training Program
The Web-based computer module, called ACCIS (American College of Cardiology In-Service), includes both an assessment section and a "Teaching Materials" section. The test-taker is presented with 50 electrocardiograms that focus on 12 key categories of ECG interpretation. Test-takers and training program directors receive the test results. In the case of an incorrect diagnosis, the test-taker is referred to more than 100 case studies with additional teaching materials for self-directed learning. The results will be followed over time to determine if the training program actually improves ECG knowledge and will be used to set benchmarks of competency in ECG interpretation.
ECG Background
An electrocardiogram shows the heart's electrical activity. An ECG can indicate heartbeat irregularities and pinpoint heart muscle abnormalities. There are 120 codes used to define events detected through 12 leads attached to the chest. Doctors in internal medicine are expected to learn how to read the ECG to identify a potential heart problem; cardiologists are expected to be experts at ECG readings, pinpointing specific or rare problems.
"A lot of memorization is necessary to learn how to read an ECG," says Dr. Benitez. "The rules include such things as: what is the voltage in a particular lead or a combination of leads or what is the axis of the vector of this electrical signal?" Pattern recognition is also part of the learning process.
While the basic ECG technology was developed more than a hundred years ago, the field of ECG interpretation has become part of the high-tech revolution. Computers can make a preliminary interpretation of the ECG readout. But more often than not, says Dr. Benitez, the computer gets certain things wrong, such as the interpretation of rhythm abnormalities. "It does not usually under-call things like acute heart attack, but it does over-call them," he says. "Somehow our brains are better than computers in terms of the amalgamation of all the data that's required to read ECGs."
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"A Novel Method for Assessment of Resident Competency of Electrocardiographic Interpretation with Linked Guide to Self-Improvement." Benitez RM, Southall N, Wolfsthal SD, Galiatsatos L, Raimist D, Lewis RP. Poster, Association of Program Directors in Medicine, 10/31/2008.