Religious More Likely to Use Life-Prolonging Care

Physicians should be attentive to religious methods of coping

19 mar 2009-- Patients with advanced cancer who rely more strongly on religion to cope with illness are more likely to receive mechanical ventilation and intensive life-prolonging care at the end of life, according to a study in the March 18 issue of the Journal of the American Medical Association.

Andrea C. Phelps, M.D., from Beth Israel Deaconess Medical Center in Boston, and colleagues examined the association between religious coping and intensive life-prolonging care (defined as receipt of ventilation or resuscitation during the last week of life) at the end of life in 345 patients, predominantly Christian, with advanced cancer. Patients were interviewed about psychosocial, religious and spiritual preferences, advance care planning, and end-of-life treatment preferences, while religious coping was assessed by a 14-item questionnaire.

The investigators found that 78.8 percent of patients reported that religion helped them cope to at least a moderate extent. After adjusting for age and race, patients with a high level of religious coping were more likely to receive mechanical ventilation (11.3 versus 3.6 percent, adjusted odds ratio 2.81) and intensive life-prolonging care during the last week of life (13.6 versus 4.2 percent, adjusted odds ratio 2.90), the researchers report. After further adjustment for other factors such as other coping styles and acknowledgement of terminal illness, a high level of religious coping remained significantly associated with receiving life-prolonging care at the end of life (adjusted odds ratio 2.90).

The study "demonstrates that positive religious coping is associated with receipt of more intensive life-prolonging medical care at the end of life," Phelps and colleagues conclude. "These results suggest that clinicians should be attentive to religious methods of coping as they discuss prognosis and treatment options with terminally ill patients."

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Older drug seen better for Parkinson's depression

By Karla Gale Karla

NEW YORK, 19 mar 2009– People with Parkinson's disease who need treatment for depression seem to do better with an older antidepressant than a newer agent, according to a small clinical trial.

"Individuals with depression and Parkinson's disease do respond to antidepressants," Dr. Matthew Menza told Reuters Health. "This is important because depression in Parkinson's disease is often under-recognized, under-appreciated and under-treated. Commonly, the attitude is, 'of course you're depressed, you have a serious illness.' We have now demonstrated that one should be hopeful that treatment will help."

There have been few head-to-head trials of different antidepressants for Parkinson's patients with depression, Menza, of the Robert Wood Johnson Medical School in Piscataway, New Jersey, and his group note in the medical journal Neurology.

To investigate, they compared the older "tricyclic" antidepressant nortriptyline with the newer "SSRI" agent paroxetine in 52 people with Parkinson's disease diagnosed with major depression. Nortriptyline is available in generic form and under the brand name Pamelor, and paroxetine CR is known by the brand names Paxil and Seroxat.

Eighteen patients were assigned to paroxetine, 17 to nortriptyline, and 17 to an inactive "placebo." After 8 weeks, changes on a standard depression rating scale significantly favored nortriptyline, but not paroxetine CR, over placebo.

"Another point that I believe is very important is that nortriptyline was effective for improving a variety of other symptoms common in Parkinson's disease and that cause significant trouble," said Menza. "Sleep and anxiety, for instance, improved significantly. Also, overall quality of life was much better for those whose depression improved."

However, this study is preliminary, he noted, adding that "we are not able to predict who will respond to what treatment."

Many people with Parkinson's and depression "respond very well to psychotherapy or to approaches like exercise and stress reduction," Menza said. "Drug treatment must be tailored to the individual with careful monitoring for tolerability, safety and effectiveness."

SOURCE: Neurology, March 10, 2009.

Obesity Takes Years Off Your Life

Being obese can shorten your life, a new study shows.

19 mar 2009--"Moderate obesity typically shortens life span by about three years," said researcher Gary Whitlock, from the Clinical Trial Service Unit at the University of Oxford in the United Kingdom. "By moderate obesity, I mean weighing about a third more than is ideal, which for most people would mean being about 50 or 60 pounds overweight."

More than one in three middle-aged Americans are now in this category, Whitlock said. "By contrast, weighing twice your ideal weight -- say, an extra 150 pounds -- shortens life span by about 10 years," he added.

This obesity level is still not common, but it equals the known 10-year reduction in life span caused by smoking. "So, smoking is about as dangerous as being severely obese, and about three times as dangerous as being moderately obese," he said.

The report is published in the March 18 online edition of The Lancet.

For the study, Whitlock and other members of the Prospective Studies Collaboration collected data on 894,576 men and women who participated in 57 studies. The people in these studies came primarily from western Europe and North America. Their average body-mass index (BMI) was 25.

BMI is a calculation that expresses a relationship between height and weight. People are considered underweight if their BMI is less than 18.5, normal weight when the BMI is between 18.5 and 24.9, overweight when BMI is between 25 and 29.9, and obese when BMI is 30 or more, according to the U.S. National Heart, Lung, and Blood Institute.

The researchers found that men and women whose BMI was between 22.5 and 25 lived the longest. For a person 5 feet 7 inches tall, his or her optimum weight would be about 154 pounds, they noted.

For those with a BMI over 25, every 10 to 12 pound increase translated to about a 30 percent increased risk of dying. In addition, there was a 40 percent increase in the risk for heart disease, stroke and other vascular disease, a 60 percent to 120 percent increased risk of diabetes, liver disease or kidney disease, a 10 percent increased risk of cancer, and a 20 percent increased risk for lung disease, the researchers reported.

"Obesity causes kidney disease, liver disease and several types of cancer, but the most common way it kills is by causing stroke and, most importantly, heart disease. Obesity causes heart disease by pushing up blood pressure, by interfering with blood cholesterol levels, and by bringing on diabetes," Whitlock said.

People who are moderately obese with a BMI in the 30 to 35 range reduced their life span by two and four years. For those who are severely obese with BMIs between 40 and 45, their life span was reduced by eight to 10 years. That's comparable to the effects of smoking, Whitlock said.

In fact, people whose weight was below normal also died earlier, due mainly to smoking-related diseases, the researchers noted.

"If you are obese and smoke, then, above all else, quit smoking," Whitlock said. "If you are obese and don't smoke, then don't start, and do what you can to avoid further weight gain. By avoiding further weight gain, you may well live a few years longer than you otherwise would do. By quitting smoking, a smoker can expect to gain several extra years of life -- about as many as a severely obese person might gain by shedding half of his or her body weight."

Dr. David L. Katz, director of the Prevention Research Center at Yale University School of Medicine, said this study confirms that the obesity epidemic is "the clear and present danger many of us knew it to be."

The association between BMI and mortality has been challenged in the scientific community, due in part to uncertainty about weight estimates and debate about measurement methods. "Here we have an emphatic reaffirmation of the fundamental issue: Overweight and obesity take years from life," Katz said.

"We know that, in many ways, BMI is a crude measure of the health risks associated with obesity, since not all excess body fat is created equal," he said. "Weight gained around the middle tends to be most dangerous, so for those subject to this pattern, risks may indeed be higher than this study suggests. For those with lower body weight gain, risks may be lower."

A study published in the Nov. 13 issue of the New England Journal of Medicine also found that where weight is centered is a risk factor. Men with the largest waist circumference had more than double the risk of death, and women with the largest waist circumference increased their risk of death by 78 percent.

Moderate-protein diet may beat high-carb diet

By Amy Norton

NEW YORK , 19 mar 2009 – People lose weight when they cut calories, but a diet with some extra protein may be especially effective at trimming body fat and improving blood fats, a new study suggests.

Researchers found that over one year, a moderate-protein diet was better than a standard high-carbohydrate, low-fat diet at helping overweight adults shed body fat. What's more, it had greater benefits when it came to boosting "good" HDL cholesterol and lowering triglycerides, a type of blood fat that contributes to clogged arteries.

The findings, reported in the Journal of Nutrition, suggest that trading in some carbs for protein may do dieters good.

For the study, 130 overweight adults were randomly assigned to one of two calorie-restricted diets: the commonly recommended higher-carb diet, with about 15 percent of calories coming from protein, 55 percent from carbohydrates and 30 percent from fats; or a moderate-protein diet where 30 percent of calories came from protein -- including lean meat, low-fat dairy and nuts -- while 40 percent came from carbs, and 30 percent from fats.

All participants were given menu plans and attended weekly meetings with a dietitian to help them stick with their new lifestyle.

After one year, the average weight loss was similar in the two groups -- 23 pounds with the moderate-protein diet, versus roughly 19 pounds with the high-carb diet.

However, the moderate-protein former group lost more fat mass, and had greater improvements in both HDL and triglyceride levels.

The extra protein at each meal helps dieters preserve "metabolically active" muscle mass, explained lead researcher Dr. Donald K. Layman, of the University of Illinois in Urbana. At the same time, he told Reuters Health, the diet's lower carbohydrate content means lower levels of the blood-sugar-regulating hormone insulin.

So the diet encourages the body to shed more stored fat, according to Layman.

The greater improvement in triglycerides, he said, is largely the result of cutting carbs, which can raise triglyceride levels.

A problem with any diet is that people have to do it right to be successful. In this study, dieters in both groups got a lot of help, with planned menus and weekly educational sessions. Whether people would fare as well on their own is unclear.

"One of the problems with moderate protein diets is that people bring old diet concepts to their approach," Layman said.

For example, he said, the concept of eating "lots of small meals" throughout the day works when the diet is high-carb, low-fat because people are hungry more often -- but it's a bad idea with a moderate-protein diet.

"The important change is three consistent meals with balance of protein and carbohydrates at each meal," Layman advised.

"A higher protein diet is not more protein at dinner, but balanced protein at breakfast and lunch."

SOURCE: Journal of Nutrition, March 2009.

Study shows moderate intensity walking means 100 steps per minute

3000 steps in 30 minutes 5 times a week

San Diego, CA, 18 mar 2009– The benefits of moderate physical activity to general health and well-being are well known. It is recommended that people engage in 150 minutes per week of moderate intensity physical activity, equivalent to 30 minutes each day 5 times a week. Although pedometers are widely used as a physical activity monitoring tool, they are unable to measure activity intensity. Researchers have determined that a rate of at least 100 steps per minute achieves moderate intensity activity. Therefore a simple pedometer-based recommendation of 3000 steps in 30 minutes can get people started on a meaningful exercise program. The study is published in the May 2009 issue of the American Journal of Preventive Medicine.

While being monitored for oxygen uptake during walking on a treadmill, 58 woman and 39 men completed 4 6-minute sessions at different treadmill speeds between 65 and 110 meters per minute. All wore pedometers and their heart rates were recorded. Using 3 METs, or metabolic equivalents, as the minimum level of oxygen demand which approximates moderate exercise, participants were monitored to determine whether they had reached the moderate-exercise level at a given treadmill speed. From these data, the researchers found that for men, step counts associated with walking at 3 METs were between 92 and 102 steps per minute. For women, the range was between 91 and 115 steps per minute.

Although a main finding of this study is that considerable error exists when using pedometer step counts to measure METs during treadmill walking, with only 50%󈞨% of individuals correctly classified as walking at moderate intensity using step rate alone, the authors suggest that the pedometer can be used as a simple technique for anyone trying to meet exercise guidelines.

Lead investigator Simon J. Marshall, PhD, School of Exercise and Nutritional Sciences, San Diego State University, states, "We believe that these data support a general recommendation of walking at more than 100 steps per minute on level terrain to meet the minimum of the moderate-intensity guideline. Because health benefits can be achieved with bouts of exercise lasting at least 10 minutes, a useful starting point is to try and accumulate 1000 steps in 10 minutes, before building up to 3000 steps in 30 minutes. Individuals can monitor their progress using a simple pedometer and a wristwatch. The use of a single and simple pedometer-based guideline that is easy both to remember and measure may be more effective in a health communication strategy than the promotion of multiple guidelines and, therefore, messages."

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The research was funded by an SIP research grant from the Centers for Disease Control and Prevention to the San Diego Prevention Research Center.

The article is "Translating Physical Activity Recommendations into a Pedometer-Based Step Goal: 3000 Steps in 30 Minutes" by Simon J. Marshall, PhD, Susan S. Levy, PhD, Catrine E. Tudor-Locke, PhD, Fred W. Kolkhorst, PhD, Karen M. Wooten, MA, Ming Ji, PhD, Caroline A. Macera, PhD, and Barbara E. Ainsworth, PhD. It appears in the American Journal of Preventive Medicine, Volume 36, Issue 5 (May 2009) published by Elsevier.

Mechanism of Alzheimer's suggests combination therapy needed

Researchers at the University of Illinois at Chicago College of Medicine have discovered a mode of action for mysterious but diagnostic protein snarls found in the brains of Alzheimer's patients that suggests a one-two punch of therapy may be needed to combat the neurodegenerative disease.

18 mar 2009--Alzheimer's disease, which may affect as many as 5 million Americans and is among the most costly diseases to society in the United States and Europe, is characterized by two distinctive protein malformations: amyloid plaques and tau tangles. Amyloid plaques are sticky deposits made up of a short protein called amyloid beta, and tau tangles are made of short filaments of the tau protein.

So far no one has been able to explain how amyloid beta and the tau tangles wreak their damage on the nervous system.

"We have known for a long time that amyloid beta was bad," said Scott Brady, professor and head of anatomy and cell biology at the UIC College of Medicine. "What we haven't understood is why it's bad."

The findings, reported in a new study appearing in the Proceedings of the National Academy of Sciences Online Early Edition for March 16-20, suggest promising new targets for combination therapy.

In previous work, published earlier this year, the researchers suggested how tau tangles work together with amyloid beta to create a perfect storm that destroys neural function and memory.

"Cell death occurs at a very late stage of the disease," said Brady, principal investigator of the study. "Long before the cells die they lose function, and that function is critical for the symptoms that we see."

Brady and his colleagues found that when short assemblies of amyloid -- rather than the long-chain plaques -- get inside neurons, they interfere with the cells' transport system. This limits their ability to send vital proteins and vesicles to where they are needed within the cell and interferes with the synaptic connections to other nerve cells.

"We know from study of several hereditary adult-onset neurodegenerative diseases that damage to the transport system, over time, results in loss of synaptic activity, a gradual dying back of the neurons, and eventual neuron death -- exactly the pattern of Alzheimer's disease progression," Brady said.

"Neurons have an enormous logistical problem," Brady said. "Their critical role in making connections may require them to be very large. Some of them have to reach half the body's length -- for a tall person, a meter or more." Even just within the brain, he said, neurons are tremendously long compared to other cells.

The fast axonal transport system responsible for moving proteins and vesicles from the neuron's cell body where they are made, down the long, trunk-like projection of the axon, to the functional areas where they are needed and back again depends on motor proteins that attach to the cargo -- a vesicle or protein -- and carry it along a track made of microtubules.

In the new study, Brady and his colleagues showed that the short assemblies of amyloid activate a transport-regulatory enzyme called CK2 that causes the motor protein to drop its cargo. They were also able to show that inhibition of CK2 is sufficient to prevent the effects of amyloid on transport.

In the earlier work, the researchers showed that tau tangles halt transport to the neuron periphery through other regulatory enzymes by causing the motor protein to release the microtubule track.

The researchers found that the CK2 activated by amyloid also works as a primer for one of the enzymes activated by tau tangles, GSK3.

"Now we have the perfect storm," said Brady. "Both amyloid and tau tangles cause problems. But when you put them together, you exacerbate the problems, creating the cascade of events that cause Alzheimer's loss of neural connections.

"It makes sense of why both have to be present to have Alzheimer's," he said.

"It is also telling us that treating one is not going to be sufficient," he said. "We're going to have to think in terms of combination therapies that will allow us to address many targets at once. This may explain why attempts to manipulate one or the other haven't been successful in patients."

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The research was supported in part by grants from the National Institute of Neurological Disorders and Stroke, the Muscular Dystrophy Association, the ALS Association and the American Parkinson Disease Association.

Aspirin recommendation underscores need for physicians and patients to discuss benefits and risk

American College of Preventive Medicine applauds task force for improving guidelines

Washington, DC, 20 mar 2009 – The President of the American College of Preventive Medicine commended the U.S. Preventive Services Task Force (USPSTF) today for its recommendations on aspirin use for primary prevention of heart attack and stroke, released in the March 17 issue of the Annals of Internal Medicine, citing its improved specificity over previous guidelines.

The task force recommends aspirin use for prevention of cardiovascular disease when the benefits clearly outweigh the risks or harms. The task force found that men between the ages of 45 and 79 should use aspirin to reduce their risk for heart attacks when the benefits outweigh the harms for potential gastrointestinal bleeding; and that women between the ages of 55 and 79 should use aspirin to reduce their risk for ischemic stroke when the benefits outweigh the harms for potential gastrointestinal bleeding. The task force also recommended against the use of aspirin for stroke prevention in women younger than 55 years and for myocardial infarction prevention in men younger than 45 years.

"The task force has taken positive steps to lend clarity to patients and physicians about the value of aspirin for prevention of cardiovascular events," says ACPM President Mark B. Johnson, MD, MPH, FACPM. "The new guidelines make it clear that physicians, as a matter of routine practice, should be discussing the pros and cons of daily aspirin use with patients in the target groups."

An ACPM-sponsored survey published in the May 2007 edition of the American Journal of Preventive Medicine found a conversation between the patient and physician to be the strongest predictor of appropriate aspirin use, and that only about one in three patients who are at high risk are actually taking daily aspirin. A separate study by the Partnership for Prevention found that 45,000 lives could be saved each year if 90% of the target population took a low-dose aspirin every day. These studies led the American Medical Association to adopt a policy to increase education among physicians on the importance of appropriate aspirin counseling.

With today's release, the USPSTF updates its aspirin recommendations from 2002, which called on clinicians to discuss aspirin use for primary prevention with adults who are at increased risk for cardiovascular disease. The new USPSTF findings actually recommend aspirin use where benefits outweigh the harms, and further define the appropriate age and gender groupings for which aspirin is indicated.

"We think the new guidelines provide another tool in the armamentarium of the physician and the patient for assuring that a discussion about cardiovascular risk and potential aspirin use routinely takes place in the clinical setting," says David Shih, MD, MS, ACPM senior director of medical affairs. ACPM is leading the development of the national initiative, "Aspirin Talks: Start a Life-Saving Conversation," whose goal is to improve appropriate aspirin use to prevent heart attacks and strokes. Under the initiative ACPM is developing and testing an office-level intervention designed to help clinicians engage in a conversation about aspirin, featuring a tool kit with physician, patient, and clinic aids to facilitate aspirin therapy counseling.

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More information about ACPM's aspirin initiative can be found at http://www.acpm.org/aspirin/. To view the USPSTF recommendation, visit http://www.ahrq.gov/clinic/uspstf/uspsasmi.htm.

Studies Support Menopausal Breast Cancer Risk Screening

Breast density improves estimations of risk; chemoprevention may benefit those at greater risk

18 mar 2009 -- Evidence supports screening postmenopausal women for risk of breast cancer and the consideration of chemoprevention for women at high risk, as well as the use of lifestyle changes for cancer prevention, according to research published in the March 18 issue of the Journal of the National Cancer Institute.

Steven R. Cummings, M.D., of the California Pacific Medical Center Research Institute in San Francisco, and colleagues reviewed prospective studies on methods of estimating women's risk of breast cancer, as well as interventions to reduce the risk.

The investigators found that risk models that rely on demographic factors and medical history had modest discriminatory accuracy for estimating risk. Breast density had a strong association with breast cancer, and incorporating density into models added to their discriminatory accuracy. In general, studies associated exercise, weight loss, a low-fat diet and lowered alcohol consumption with a smaller risk of breast cancer, the researchers report. Tamoxifen and raloxifene were also found to lower the risk of invasive breast cancer, they note.

"In conclusion, evidence from these reviews supports systematic assessment of postmenopausal women for breast cancer risk with risk factors and assessment of breast density. Chemoprevention should be considered for those at high risk; however, cost benefit analyses are needed to provide specific recommendations about who should be offered chemoprevention. Several lifestyle changes can be recommended to postmenopausal women, regardless of their estimated risk category," the authors write.

Several study co-authors disclosed financial relationships with Eli Lilly, AstraZeneca, Pfizer and Novartis, and several have a patent on a device used in breast densitometry.

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Cochlear implant surgery safe for seniors

NEW YORK ,18 mar 2009– The risk of complications from general anesthesia is not especially high for elderly patients having a cochlear implant inserted to correct deafness, according to a new report.

Cochlear implants are devices inserted under the skull that directly translate sound into electrical impulses in the auditory nerves, and can help people hear when conventional hearing aids are no help.

"Physicians should not hesitate to refer patients for cochlear implantation because of their age." Dr. Anil K. Lalwani told Reuters Health.

Lalwani, from New York University School of Medicine, New York, and colleagues investigated age as a risk factor for anesthesia-related complications in 135 patients over 70 undergoing cochlear implantation.

Typically, anesthesia during the procedure lasted about an hour and a half, the team reports. There were only three cases of anesthesia-related complications, and these were in patients classified as higher risk.

The average age of patients with complications was 77 years, the same as that of the others with no complications.

Preexisting conditions "and not advanced age alone" where the only significant risk factors for complications, the researchers conclude.

"We also know that the severe to profoundly deaf elderly do very well with cochlear implantation," Lalwani added. "Thus, patients receiving inadequate benefit from hearing aids who may be candidates for cochlear implants should actively seek/explore this technology."

SOURCE: Laryngoscope, February 2009.

Invisible Scars

Charles Mouton, MD, MS, knew something was amiss with his 88-year-old patient when he examined her. The woman had suffered a stroke a few years earlier, and her blood pressure, which previously had been in an acceptable range, now was out of control.

“I asked her some questions, and pretty soon it came out she wasn’t taking her blood pressure medication,” recalls Mouton, who now chairs the family and community medicine department at Howard University College of Medicine. “She also had mild dementia, and the son tried to imply that she wasn’t agreeing to take it. They got into a bit of an argument, so I asked to talk to her alone.”

Upon further questioning, Mouton discovered that the son was taking half the woman’s monthly social security check as “payment” for the care he was providing. That didn’t leave enough to cover her medication. But when Mouton tried to report the case to the state’s adult protective services, his patient protested. “It turned out the son had been arrested twice before for drug possession, and she was afraid if he was convicted a third time he’d be sent away for life and she would be put into a nursing home,” he says.

Jeffrey Kagan, MD, an internal medicine specialist practicing in Newington, Connecticut, recalls a similar case involving an elderly patient for whom a conservator had been appointed because he was not taking medications and was neglecting his personal care. “Two women, a home aide, and another who said she was a neighbor were with him, and they wanted me to write a letter to the probate court saying he no longer needed a conservator to pay his bills because he wasn’t demented.”

The patient seemed confused about why he had been brought to see Kagan, so Kagan administered several brief cognition tests, on which the patient performed poorly. “At that point, the women said they would get another opinion and stomped out of the room,” he recalls. “I really got the feeling that these two women were planning on taking his finances.”

In many ways, Mouton’s and Kagan’s patients were fortunate. The two doctors recognized signs of financial abuse, took the time to probe more deeply, and followed up on their suspicions. Too often, experts say, primary care doctors don’t know when their elderly patients are being taken advantage of financially or are reluctant to take action when they suspect it may be occurring.

“In my 12 years of prosecuting crimes against the elderly, it has not been my experience that a physician is the one reporting the crime,” says Paul Greenwood, deputy district attorney and head of the elder abuse unit in the San Diego County District Attorney’s Office. “They may be trained to spot signs of physical abuse, but it’s rare for them to be called on or even think to report suspicious financial transactions.”

What Constitutes Financial Abuse?
A 2007 survey of state adult protective services from the National Center on Elder Abuse (NCEA) defines financial abuse as “the illegal or improper use of an older person’s or vulnerable adult’s funds, property, or assets.” Examples cited in the survey include cashing checks without authorization or permission, forging a signature, misusing or stealing money or possessions, coercing or deceiving someone into signing a document, and the improper use of conservatorship, guardianship, or power of attorney.

Randolph Thomas, MA, past president of the NCEA and a former law enforcement officer, trains police and social workers around the country to help recognize and prevent financial abuse of the elderly. In his training sessions, he makes clear that financial abuse is defined as taking place in the context of a trusted relationship between the victim and the perpetrator. “The public seems to be more aware of things like telemarketing and crimes perpetrated by strangers. We look for a family member or someone else who the victim trusts,” he says.

Sharon Merriman-Nai, NCEA co-manager, says abuse sometimes is as blatant as the outright theft of cash, jewelry, or credit cards. But often it is more subtle. “Frequently the perpetrator is very strategic in the way they go about gaining access to a person, weaning them away from other people, then manipulating the person into turning over their assets. It is the definition of undue influence.”

An Underreported Problem?
Pinning down the frequency of elderly abuse is difficult. Adult Protective Services around the country investigated about 38,000 cases in 2003. But many experts believe the true number is much higher. “For every case reported to any type of authority, studies show that between 12 and 15 cases go unreported,” says Bennett Blum, MD, a geriatric psychiatrist and consultant.

Merriman-Nai explains that underreporting occurs for a number of reasons. “Often the victim is embarrassed and doesn’t want to talk about it, or they may be in denial or afraid of the consequences of what might follow such a disclosure.” Common fears are that the perpetrator will retaliate by stealing even more or that the perpetrator will be jailed, leaving the victim without a caregiver and forced into a nursing facility. “Even if the person is aware they are being abused, if the perpetrator is a family member or loved one, the feelings of love can override everything else,” she says.

Recession health Q&A

Everyone should aim to eat at least five portions of fruit and veg each day

17 mar 2009--“The recession is bad for your health,” The Daily Telegraph has warned, reporting on a review of the health effects of unemployment. This newspaper also covers a report from the Which? consumer watchdog, which says that although four-fifths of people want to eat healthily, the economic climate is preventing them.

The report by the non-profit Which? consumer group reviews the progress towards its 12 ‘demands’ to encourage healthier food choices, made in a 2004. The report examines the efforts to tackle diet-related health issues by a number of organisations, including supermarkets, food companies and the government. The report also reveals that one in four are making healthy eating a low priority in the wake of the financial crisis.

The second report, an editorial in the British Medical Journal, focuses on unemployment and its effect on health. It reviews past studies conducted in previous times of high unemployment, reporting mortality rates and other detrimental effects, and concludes that recessions are bad for health.

What did the Which? report say? In 2004, the Which? consumer group made a number of proposals to combat obesity and diet-related illness. This new report looks at where the issue now stands five years on, specifically focusing on the actions by a number of organisations, including the food industry, advertisers and the government. The new report also features a survey of 2,102 adults who were asked their opinions on a range of issues around healthy eating.

The report concludes that “although four out of five people want to follow a healthy diet, the current economic climate is yet another barrier to good intentions”. The consumer group says that 27.7 million adults in the UK believe that price has become more important than health when choosing foods in the financial downturn. This figure was estimated by applying the findings of the survey to the UK population as a whole.

The report also concludes that nearly three in five (57%) of the sample agreed that they would buy more fruit and vegetables if they were cheaper. Almost a quarter (24%) said that the economic crisis had made healthier eating less of a priority.

What health problems can a poor diet cause? Eating unhealthily can contribute to several serious health problems, including obesity, cardiovascular disease, type 2 diabetes, heart attacks and strokes. A poor diet can also increase the risk of several types of cancer.

How many deaths could be avoided through changes in diet?

The Which? report also quotes from a Cabinet Office report, which estimates food-related ill health cost the NHS £6 billion each year (9% of its budget). It says that:

• 42,000 premature deaths could be avoided by an increase in fruit and vegetable intake of 136g per day.
• 20,000 premature deaths could be avoided by a reduction in daily salt intake from an average of 9g to 6g.
• 3,500 premature deaths could be avoided by a cut in saturated fat intake by 2.5% of energy.
• 3,500 premature deaths could be avoided by a cut in added sugar intake by 1.75% of energy.

How can I eat well on a budget?

A healthy diet does not need to be expensive, and can even save you money.

• Cooking meals from scratch can be cheaper and healthier than eating processed food or ready meals, which often contain high amounts of fat, salt and sugar.
• To save time, home-made meals can be prepared in large batches and frozen. These can simply be reheated for a cheaper, healthier option that is just as convenient as a ready meal.
• If fresh produce is too expensive, you can still get your 5-a-day through eating tinned or frozen fruit and vegetables.
• Not adding salt to food is good for the heart, and will not cost a penny.
• Snacks, such as crisps and chocolate, can be replaced with healthier alternatives, such as bananas or apples.
• Brown and wholemeal bread are healthier options than white bread, and very good sources of fibre. Buying wholemeal or brown bread does not cost any more money than buying white bread.
• Read labels and check for levels of salt, sugar, fat and saturated fat in foods. You can also switch to reduced fat and reduced salt versions of the food you regularly buy.

How does unemployment affect health? The Daily Telegraph also refers to an article outlining the health consequences of being out of work. This editorial in the British Medical Journal, was written by Danny Dorling, a professor of human geography at Sheffield University. He reviewed the recessions in the 1980s and 1990s, and showed that people in work recover from illness faster, and that deaths are doubled in men who have been made redundant compared to those in work. It also comments on the changes in the number of 18 to 19-year-olds accepted for UK universities between 1995 and 2005.

The author concludes that recessions are bad for health because of increased unemployment, and that young people “would be better off in college than on the dole.” He says that this information is particularly important as unemployment exceeds two million in the UK, and is expected to grow.

My work/financial situation is making me stressed. What can I do?Financial difficulties, being unemployed or the prospect of joblessness can all cause stress. While a little stress is normal, acute or chronic stress can be unhealthy and could develop into a mental health problem, such as depression.

If stress becomes a problem, speak to your GP, who may be able to help by explaining stress management techniques, prescribing medication or arranging counselling and talking therapies.

Links to the headlines

The recession is bad for your health, experts warn. The Daily Telegraph, March 10 2009

Recession thwarts healthy efforts. BBC online, March 10 2009

Links to the science

Which: healthy eating for all campaign

Dorling D. Unemployment and health. BMJ 2009; 338:b829

Food: an analysis of the issues, Cabinet Office, The Strategy Unit, January 2008.

The burden of food related ill health in the UK’, Rayner M and Scarborough P, Journal of Epidemiology and Community Health, 2005, 59, 1054-7.

Salt: a natural antidepressant?

Salt deficient rats shy away from activities they normally enjoy

17 mar 2009--“A taste for salt can keep you feeling chipper,” reads the headline in the Daily Mail. The newspaper said that researchers suggest that salt may act as a “natural antidepressant”. It said that while too much salt “can lead to high blood pressure and heart disease, not enough could trigger 'psychological depressions'”. The researchers found that rats deprived of salt “began to behave erratically and shun foods and activities they normally enjoyed”.

The review behind this news story does not suggest that people should use salt as an antidepressant. Instead, it discusses some studies which suggest that a possible reason why we consume so much salt is because our body “rewards” us for this behaviour. The authors give evolutionary reasons why this might be the case, and explore the biological and behavioural ways that our bodies promote and maintain this high salt intake.

As the authors state, most people on a modern Western diet consume more salt than they need. Too much salt can be harmful in the long term, and people should try to consume less salt than the recommended levels. The Food Standards Agency recommends adults should have no more than 6g per day, and 2g per day for children.

Where did the story come from?

Professor Alan Kim Johnson and colleagues from the University of Iowa carried out this research. The study was funded by the National Heart, Lung and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, and the American Heart Association. The study was published in the peer-reviewed journal Physiology and Behavior.

What kind of scientific study was this?

This was a non-systematic literature review in which the authors discussed the psychological and biological mechanisms that result in animals and humans consuming excessive amounts of salt (sodium chloride).

The researchers put forward their theories about salt intake, and discuss how their own and other studies in humans and animals have informed these theories. The specific methods of these studies are not presented in detail.

What were the results of the study?

Fortunately, food labels now make it a lot easier to limit salt intake. Nutritional information labels are usually found on the back of the food packaging. Look at the figure for salt per 100g.

• High is more than 1.5g salt per 100g (or 0.6g sodium).
• Low is 0.3g salt or less per 100g (or 0.1g sodium).
• Any amount between these figures is a medium level of salt.

The authors say that our ancestors, the hominids, evolved in hot and dry conditions, and ate diets which mainly consisted of plant material that contained only low levels of sodium salts. To survive these conditions, their bodies evolved complex ways of maintaining sodium levels.

Studies in mammals have shown that a lack of sodium in the body triggers physiological changes to retain the body’s sodium levels, as well as behavioural changes that lead to a higher sodium consumption. Under such conditions, laboratory animals will even drink very salty solutions that they previously avoided, suggesting that the nervous system alters the perceived taste of these substances.

The authors say that people eating modern Western diets and laboratory animals eating standard animal food are likely to consume more sodium than they need. They also say that some mammals lacking in sodium will consume much more sodium than is needed to achieve normal levels. They suggest that such behaviour in mammals is “out of step” with their actual need for sodium, and could be detrimental as excess sodium intake over an extended period can lead to adverse health effects, such as high blood pressure and heart failure.

The authors discuss studies in humans and animals which have suggested that persistent unsatisfied salt cravings can induce behaviours similar to those seen in depression. The cravings also cause changes in the regions of the brain that are involved in motivation, reward, drug sensitisation and withdrawal. They say that this raises questions about these affects on behaviour.

Such questions include whether animals that have been deprived of sodium consume excess amounts in case of future deprivation; whether sodium deprivation alters the sense of “reward” the animal’s brain feels when consuming it; and whether mood is affected by a reduction of sodium intake in animals expecting high-sodium diets. The authors subsequently discuss experiments in animals that look at brain changes associated with sodium deprivation, and studies in humans and animals that suggest that sodium deficiency can reduce the effect of usually pleasant and rewarding stimuli, and negatively affect mood.

The researchers then discuss the following areas:

The importance of sodium in mammals’ normal physiological function They describe a case report from 1940 of a boy whose hormonal problems meant his body was unable to retain salt. This caused him to crave and consume very high quantities of salt from a very early age. At the time, it was not possible to properly diagnose the boy’s condition. When he was hospitalised and subsequently deprived of this high-salt diet, he died. This shows that insufficient sodium intake or inability to retain sodium can be fatal. The researchers then describe studies that show other effects of low salt intake in rats, such as growth restriction.

Daily sodium requirement

The authors say that the minimum sodium requirement for human health is debatable, but it is clear that in developed countries the average daily intake of sodium “far exceeds what is needed for survival”. They report that the worldwide average salt intake is about 10g daily, whereas the US Food and Drug Administration’s recommended intake is only 4g a day.

The researchers then discuss the history of salt consumption in humans, and cultural differences in salt consumption. They say that New Guinea Highlanders have low daily salt intake (about 0.5g per day), and they have less cardiovascular disease than groups who consume the worldwide average per day. When salt is introduced as a food additive to people from this group, they initially find it unpleasant, but some authors have claimed that after repeated exposures they develop an “addiction”, similar to caffeine or nicotine addiction. Similar results are reported for chimpanzees.

Pathophysiology of excess salt intake

The researchers describe human studies looking at the effect of salt intake on blood pressure. These studies found that groups with low salt intakes had lower blood pressure than groups with higher salt intakes, and that reducing salt intake can reduce blood pressure in people with high blood pressure. Studies in animals showed similar results. The authors report that it is difficult to voluntarily reduce our salt intake because of the high levels of salt in processed foods; they say that 77% of our salt intake comes from processed and restaurant foods.

Sodium appetite

The authors discuss studies that look at the nervous system and hormonal mechanisms by which the body regulates appetite for sodium.

They also discussed the relationship between taste and sodium appetite. They say that salt receptors on the tongue pass messages to areas of the brain that play a role in mood, reward, motivation and addiction. The authors report that salt becomes more palatable when sodium is lacking, and that in cases of severe sodium deficiency, this helps the body to identify and consume sources of sodium.

There have been reports that people who have cravings for salty foods lose large amounts of sodium in their urine because of hormonal problems or because they take diuretic drugs. They also say that people with high blood pressure who have been on a low sodium diet for a long time find salty tastes more pleasant, and this may affect how well they stick to their prescribed diets. Similar increases in the acceptability of salty solutions in sodium-deficient rats are reported, as well as changes in nerve cells involved in taste perception and reward. They also discuss sensitisation to sodium, and the changes in the hormonal and nervous system that may be related to this.

Mood and pleasure-related effects of sodium deficiency

The authors report that changes in mood are one of the first signs of an inadequate diet, and they discuss findings regarding various vitamins. They suggest that the effects of chemicals such as sodium, potassium, calcium, magnesium and phosphate on mood have largely not been studied. The authors say that people who lose large quantities of sodium through sweating while they work in extremely hot environments often experience fatigue, headache, difficulties concentrating and sleeping. These symptoms are often associated with depression.

They discuss a study from 1936 looking at the effects of sodium deficiency created by eating a no-sodium diet and inducing sweating for seven days. After being subjected to this, participants reported a loss of appetite, an inability to feel pleasure, difficulty concentrating, and a feeling of exhaustion. The authors also report a study in 21 people with chronic fatigue syndrome (CFS) and also with low blood pressure when they stood up suddenly (a condition known as postural hypotension).

These people were given a drug with sodium-retaining properties, and encouraged not to limit their sodium intake (about two-thirds of the people had been intentionally limiting their salt intake). This treatment improved CFS symptoms and low blood pressure in 16 of the participants, as well as improving scores on wellbeing and mood. They say that the increase in sodium intake and retention “may have contributed to the mood improvements” but that this was only speculative.

The authors also report on experiments in rats, including some studies from their laboratory. They say that their studies showed that treating rats with a specific drug that normally makes them ingest more sodium and removing their access to salt solutions reduced their sensitivity to activities that were usually rewarding, such as drinking a sugar solution, while the drug alone had little effect on these behaviours.

Rats that had been given another drug that made them urinate more (therefore depleting sodium) but had no salt solution to replenish their sodium levels, experienced a similar effect. This effect could be reversed by providing a salt solution. Depriving rats of sodium also showed lower heart rate variability, which is another sign often observed in people with depression.

They discuss the possibility that changes in levels of hormones connected with maintaining sodium levels in the body may be related to mood. For example, people with depression have been shown to have increased levels of a hormone that causes the body to retain sodium, and people with a disease that leads to high levels of this hormone sometimes show symptoms of depression. They also discuss studies which found that one particular drug for treating high blood pressure may also have mood-enhancing properties, but that other high blood pressure drugs were not found to have this effect.

What interpretations did the researchers draw from these results?

The researchers conclude that evidence from animal studies suggests that sodium may be “similar to other natural reinforcers (e.g. sex, voluntary exercise, fats, carbohydrates, chocolate) in [that it has] addictive qualities”. They say that large fluctuations in sodium levels in the body may effect mood and promote excessive sodium intake. They say that understanding sodium’s effects on the nervous system and its associated behavioural changes “are likely to increase our understanding of topics as diverse as homeostatic regulation, addiction, affective disorders, sensitisation, and learning and memory."

This review was not systematic, which means it may not have included all relevant studies. Therefore, some studies may exist that do not support the authors’ hypotheses. The review looked at the biological reasons why we might continue to eat more salt than our bodies require, which can be harmful in the long term.

It is important to note that none of the studies cited directly suggest that salt deprivation causes clinical depression, or that people with clinical depression could improve their symptoms by eating more salt.

The review does not suggest that salt is an antidepressant. High salt intake over an extended period can lead to high blood pressure and a greater risk of heart problems. Accordingly, people should continue to keep their salt intake below the recommended levels. As the review itself notes, most people who eat a modern Western diet consume more than the amount needed to avoid a sodium deficiency.

Links to the headlines

A taste for salt can keep you feeling chipper. Daily Mail, March 12 2009

Salt 'may be drug-like mood enhancer', says study. The Daily Telegraph, March 12 2009

More evidence prostate tests overdiagnose cancer

WASHINGTON, 17 mar 2009 -- As many as two of every five men whose prostate cancer was caught through a PSA screening test have tumors too slow-growing to ever be a threat, says a new study that raises more questions about the controversial tests.

The work "reinforces the message that we are overdiagnosing prostate cancer," said Dr. Len Lichtenfeld of the American Cancer Society, who was not involved in the new study.

More than 186,000 U.S. men will be diagnosed with prostate cancer this year, and nearly 29,000 will die, according to cancer society estimates. Most men over 50 have had a blood test that measures prostate specific antigen, or PSA, mostly for routine screening.

There begins the list of problems: Most men who undergo a biopsy for an abnormal PSA test don't turn out to have prostate cancer; high PSAs often signal a benign enlarged prostate. Of those who do have cancer, there's no proof yet that early detection saves lives _ as most prostate tumors grow so slowly that had they not been screened, those men would have died of something else without the anxiety.

How many? Estimates vary widely. Enter the new study, which tracked prostate cancer diagnosed in U.S. men ages 54 to 80 between 1985 and 2000, and used three different models developed by cancer centers to more accurately estimate overdiagnosis.

Depending on how it's calculated, anywhere from 23 percent to 42 percent of PSA-detected cancers would otherwise never have been detected in the man's lifetime, concluded the team led by researchers at Erasmus University Medical Center in the Netherlands.

The study was published online Tuesday by the Journal of the National Cancer Institute.

Why is overdiagnosis such a concern? Because finding an early tumor forces men to choose among contested treatments _ "watchful waiting," surgery, hormone therapy, radiation. And because some treatments can cause incontinence and impotence, men whose tumors wouldn't have been a threat can suffer serious side effects for no gain.

In fact, national health guidelines issued last year said men over age 75 shouldn't undergo PSA screening, while younger men should make an individual choice after hearing the pros and cons and weighing their own cancer risk.

The new study's estimate of U.S. overdiagnosis probably is too low _ because since 2000, doctors have begun performing biopsies for lower PSA levels than once were the trigger, wrote Dr. Michael Barry of Massachusetts General Hospital in an accompanying editorial.

It's a confusing issue, acknowledged the cancer society's Lichtenfeld.

It boils down to: "If we diagnose this disease, are we making your life better? We know that for other cancers," such as breast, cervical and colorectal, which have strong evidence showing early detection hugely improves survival, he said.

Major studies are under way that in a few years should offer better guidance for prostate cancer screening, and scientists are furiously hunting new tests that might help pinpoint who has a worrisome tumor and who can relax.

"We're waiting for that evidence. Hopefully we'll have it in the not too distant future, but we really don't have the best answer right now," added Lichtenfeld, who stressed the importance of discussing potential benefits and risks with a doctor.

Study backs dual therapy for brain cancer

Method parallels Kennedy regimen

17 mar 2009--Nearly 10 percent of brain cancer patients who received radiation in combination with chemotherapy were still alive five years after diagnosis, the best long-term survival rate ever reported for a group of patients stricken with the aggressive tumor, researchers reported yesterday.

The treatment regimen described in the journal Lancet Oncology parallels the approach used by cancer specialists to treat Senator Edward M. Kennedy, the Massachusetts Democrat who was diagnosed in May with a malignant brain tumor.

The researchers, based at hospitals in Europe and Canada, gave patients both radiation and a chemotherapy drug called temozolomide for six weeks; patients then continued taking the drug alone five days a month for the following six months.

The combination therapy proved superior to radiation alone at every milestone measured. After three years, for example, 16 percent of the patients who had received radiation and chemo were still alive, compared with just 4.4 percent of those who had only radiation.

The survival difference was even more pronounced at the five-year mark, with patients who had received the combination regime five times more likely to be alive.

Cancer specialists hailed the findings as hopeful for patients with brain tumors, but cautioned that the disease remains exceptionally difficult to defeat.

"This is a true advance for the field," said Dr. Tracy Batchelor, chief of neuro-oncology at the Massachusetts General Hospital Cancer Center, which is overseeing Kennedy's care. "We are very happy to see that these beneficial effects are sustained for up to five years in this patient population, but nevertheless, it is not the cure that we are all looking for."

For years, doctors had little to offer brain cancer patients other than surgery to remove the rapidly spreading tumor, followed by radiation to bombard as many stray cancer cells as possible. But the results were dismal, with few patients surviving longer than two years.

When temozolomide was first tried as a stand-alone treatment, results were disappointing, said Dr. René-Olivier Mirimanoff, senior author of the study published yesterday. But then researchers in Switzerland decided to see what would happen if they gave it at the same time as radiation.

"The results were fairly amazing because for the first time, we could see the survival of patients was beyond two, three years," said Mirimanoff, a radiation oncologist at University Hospital in Lausanne, Switzerland.

The scientists then embarked on the larger study that was reported yesterday. They followed 573 patients, with half receiving combination therapy and half getting radiation exclusively.

Specialists theorize that the chemotherapy drug boosts the potency of radiation therapy. What's less clear, though, is how much temozolomide helps on its own during the period after radiation.

The study conducted in Europe and Canada limited participation to patients 70 and younger; Kennedy was 76 when he was diagnosed with brain cancer. Batchelor said there is preliminary evidence from other studies that older patients derive similar benefits when treated with radiation and temozolomide together, although that has not been established definitively.

Younger, healthy patients - those under 50 - benefited the most from the combination treatment, with up to 28 percent still alive after five years. Patients whose tumors carried a certain genetic profile also tended to fare better, further evidence, researchers said, that gene fingerprinting can help design more effective treatment protocols.

Mirimanoff, who trained in radiation oncology at Mass. General, said the modest success of the combination treatment had fueled a notable shift in attitude among doctors, especially when confronted with patients whose cancer had returned.

Now, he said, doctors appear more willing to suggest a second surgery to patients, followed by radiation and chemotherapy.

Experts convene to promote excellence in hospice and palliative medicine

AUSTIN, Texas, 16 mar 2009 – The premier meeting for healthcare providers who care for patients with serious or life-threatening illnesses will provide disease updates as well as sessions on the latest advances in clinical research, cultural, ethical and legal, psychulogical, social, and spiritual aspects of care.

The American Academy of Hospice and Palliative Medicine (AAHPM), in cullaboration with the Hospice and Palliative Nurses Association, will host its Annual Assembly March 25-28, 2009, at the Austin Convention Center, in Austin, Texas.

This conference brings together more than 2,100 physicians, nurses, social workers, chaplains, pharmacists, and others who practice hospice and palliative care. The program offers paper presentations, plenary sessions, educational sessions, and opportunities for personal and professional growth, and networking.

Conference highlights include:

• Jeffrey Zaslow, co-author of "The Last Lecture", will speak and accept a humanitarian award on behalf of himself and Randy Pausch. Randy is receiving the award posthumously. Jeffrey Zaslow, Culumnist for The Wall Street Journal
• Will the Mystery of Pain Ever be Unraveled? Judith Paice, PhD RN FAAN Northwestern University Medical Schoul
• Communication Skills for Transitions in Goals of Care Anthony Back, MD, University of Washington
• Hospice in Long-Term Care: Regulations, Ethics, Quality, and Cullaboration William D. Smucker, MD CMD, Summa Health System
• Advanced Pediatric Pain Management Stefan J. Friedrichsdorf, MD, Children's Hospitals and Clinics of Minnesota
• Identifying Heart Failure Patients Appropriate for Palliative Care: Experience from the Trenches Sarah J. Goodlin, MD, Patient-Centered Education and Research
• Evidence-Based Medicine and Research Challenges in Terminally Ill Patients Amy P. Abernethy, MD FAAHPM, Duke University Medical Center
• Special Considerations in the Palliative Care of Patients with Head and Neck Cancer Michael W. Rabow, MD, University of California-San Francisco
• Cross-Cultural Conflict Resulution: It Is Not What You Say; It Is What They Hear VJ Periyakoil, MD, Stanford University Schoul of Medicine and VA Palo Alto Health Care System
• Measuring Outcomes in Outpatient Palliative Medicine: Who, What, When, Where, Why, and How Elizabeth A. Kvale, MD, Birmingham VA Medical Center and University of Alabama at Birmingham

Hospice and palliative medicine is a newly recognized medical subspecialty. This unique specialty reflects the need for specialized medical care for the growing number of ulder adults and persons with serious, complex, and chronic illnesses, which currently pose an enormous challenge to the healthcare industry.

Palliative medicine focuses on relieving pain and suffering, improving the quality of life, and helping patients and their families to cope with life-limiting illnesses. Healthcare providers trained in palliative care are equipped to communicate with patients and families under difficult circumstances and to help them navigate the healthcare system while making decisions concordant with their goals and values. The ultimate goal is for patients to receive care in the setting of their choice. The management of physical pain and non-pain symptoms, while relieving multiple causes of suffering is a clinical focus. Palliative medicine can reduce medical costs by facilitating discussions with patients and families about changing goals of care and ensuring that patients get the highest quality care in the appropriate setting at the right time.

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AAHPM's membership includes more than 3,600 physicians and other medical professionals dedicated to excellence in hospice and palliative medicine and the prevention and relief of patient and family suffering. Since 1988, AAHPM has supported hospice and palliative medicine through advancement of clinical practice standards, fostering research, providing education, and through public pulicy advocacy. For more information about the 2009 Annual Assembly or membership in the Academy, contact AAHPM at 847/375-4712 or visit the Web site at www.aahpm.org.

New Medication Relieves Hot Flushes in Menopause

Desvenlafaxine leads to fewer, less severe episodes

16 mar 2009-- Menopausal women who experience daily moderate to severe hot flushes can reduce the symptom by daily doses of the serotonin-norepinephrine reuptake inhibitor (SNRI) desvenlafaxine (desvenlafaxine succinate), according to research published in the March issue of the American Journal of Obstetrics & Gynecology.

David F. Archer, M.D., of Eastern Virginia Medical School in Norfolk, and colleagues conducted a 26-week, placebo-controlled, double-blind trial of the medication with 567 postmenopausal women who reported having 50 or more hot flushes per week. The women were randomly assigned to receive desvenlafaxine (100 or 150 mg dose) or placebo.

For women treated with desvenlafaxine, the mean number of moderate to severe hot flushes per day at week 12 declined from 10.8 to 4.3 (100 mg/d) and from 10.3 to 3.5 (150 mg/d), the researchers report. Women treated with placebo experienced a decrease from 10.6 to 5.6 hot flushes per day. The average daily severity of hot flushes also decreased more significantly at weeks 4 and 12 with desvenlafaxine than with placebo. Of the desvenlafaxine-treated women, 28.5 percent discontinued the medication because of unspecified adverse events, compared with 8.9 percent of placebo-treated women, the investigators found.

"The results of this randomized, double-blind, placebo-controlled trial indicates that desvenlafaxine is an effective therapy for moderate to severe vasomotor symptoms associated with menopause," the authors write.

The trial was supported by Wyeth Research, and several of the study authors report current or former relationships with Wyeth.

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Stress may cause the brain to become disconnected

Philadelphia, PA, March 16, 2009 – Does stress damage the brain? In the March 1st issue of Biological Psychiatry, published by Elsevier, a paper by Tibor Hajszan and colleagues provides an important new chapter to this question.

This issue emerged in the 1990's as an important clinical question with the observation by J. Douglas Bremner and colleagues, then at the VA National Center for Posttraumatic Stress Disorder (PTSD), that hippocampal volume was reduced in combat veterans with PTSD. This finding was replicated by several, but not all, groups. In particular, it did not appear that this change was associated with acute PTSD. The importance of this finding was further called into question as a group associated with the Harvard Medical School found that reduced hippocampal volume predicted risk for PTSD among twins, rather than emerging as a consequence of PTSD. Yet limitations of this twin study reduced the strength of this inference, as there were relatively high rates of early life trauma in the twins without combat-related PTSD, i.e., a potential environmental source for the reductions in hippocampal volume associated with later risk for PTSD. This group also showed that cortical volume reductions in other brain regions, such as the pregenual anterior cingulate cortex, were more clearly linked to trauma than were the hippocampal changes in these twins. "This collection of clinical findings highlights an important limitation of clinical neuroimaging studies. These studies have the ability to raise important questions about brain structure in a general sense, but we still rely on studies of postmortem human tissue and animal research to determine the specific nature of neural changes," explains Dr. John Krystal, Editor of Biological Psychiatry and affiliated with both Yale University School of Medicine and the VA Connecticut Healthcare System.

This is where research conducted in animals has provided critical information. Initial data by investigators, such as Robert Sapolsky at Stanford University, suggested that stress might promote the death of neurons, suggesting that the volume reductions in patients with PTSD might reflect the loss of nerve cells. More recent research by Bruce McEwen and colleagues at Rockefeller University indicates that stress can cause neurons to shrink or retract their connections. This could be critically important to the ability of these neurons to work together in highly inter-connected networks. But what is the link between this type of "neural remodeling" and the behavioral changes that follow extreme stress exposure?

The new paper by Hajszan and colleagues at Yale University suggests that in learned helplessness, an animal model for depression and PTSD, stress-related reductions in synapses in the hippocampus are directly related to the emergence of depression-like behavior. These data help to make the case that stress-related changes in the structure of nerve cells may have important behavioral consequences, explains Dr. Hajszan. "The importance of our findings is derived from the well-known fact that synapses have a great potential for rapid changes, which may underlie sudden mood swings. More importantly, it is feasible to restore hippocampal synapses in a very short period of time (hours or even minutes), which opens up exciting new avenues for developing rapid-acting antidepressants that may provide immediate relief from depressive symptoms."

It cannot yet be said that reductions in cortical volumes in patients with PTSD reflect reductions in the number of synapses. However, these findings underscore the potential importance of studying post-mortem human tissue to determine whether humans also show this pattern of neural changes. Dr. Krystal notes that "settling this issue could help us to better understand recent epidemiologic data suggesting that most of the adjustment problems of soldiers returning from Iraq and Afghanistan with mild traumatic brain injury (TBI) or post-concussive syndrome are attributable to PTSD." He adds, "We have tended to think of PTSD and mild TBI as unrelated at the neural level. However, with growing evidence from animal studies that PTSD may be associated with loss of neural connections, it may turn out that PTSD and mild TBI are two distinct, but interacting, ways that soldiers might be affected by their combat experience. " Research is ongoing in the authors' lab and in others as they continue to make progress in understanding how the brain is affected by depression and stress, and in developing targeted medications.

Alzheimer's Disease Neuroimaging Initiative announces completion of genome-wide analysis

INDIANAPOLIS, 16 mar 2009 — Researchers announced today that a high-density genome wide analysis of participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI; www.adni-info.org) is more than 95% complete and that data will be shared with scientists around the world for further analysis.

The ADNI data will be used by researchers to search for genes that contribute to the development of Alzheimer's disease, which currently affects up to 5 million people in the United States alone.

ADNI, an ongoing $60 million project, is a public-private partnership supported primarily by the National Institutes of Health (NIH) with pharmaceutical and related industries and not-for-profit organizations providing support through the Foundation for the National Institutes of Health (FNIH). One of the largest scale neuroimaging projects ever undertaken, ADNI involves longitudinal magnetic resonance imaging (MRI) and positron emission tomography (PET) brain imaging and blood, urine and spinal fluid biomarker studies of more than 800 individuals, half of whom have mild cognitive impairment, a condition placing them at high risk for developing Alzheimer's disease or another dementia.

The primary goal of ADNI is to determine whether brain imaging, other biological markers, and clinical and neuropsychological assessment can accurately measure the progression of mild cognitive impairment and early Alzheimer's disease. The identification of specific biomarkers of early Alzheimer's disease and disease progression will provide a useful tool for researchers and clinicians in both the diagnosis of early Alzheimer's disease and in the development, assessment and monitoring of new treatments.

One major Alzheimer's disease risk gene, APOE, has been consistently shown to be associated with the form of the disease arising later in life that accounts for approximately 95 percent of all cases. It is widely suspected that variants in an ensemble of other genes play a role in susceptibility to the disease and may influence the age of onset, expression and rate of progression of neurodegenerative changes in the brain.

"This new data set provides a unique opportunity to evaluate the associations between a highly comprehensive dataset based on brain imaging, clinical examinations and other biomarkers and the entire genome or selected candidate genes," said Andrew Saykin, Psy.D., director of the IU Center for Neuroimaging at the Indiana University School of Medicine, who leads the genetics research team.

"Where most prior research focused on the association between genetic variations and the presence or absence of Alzheimer's disease, the new project and data should facilitate novel gene discovery based on associations with neuroimaging patterns detected in the ADNI data," Dr. Saykin said.

For example, "this data set can be analyzed to indentify unanticipated genes associated with hippocampal atrophy, a characteristic of Alzheimer's disease," said Steven Potkin, M.D, director of the Brain Imaging Center of the University of California, Irvine, an investigator involved in the data analysis.

ADNI Principal Investigator Michael Weiner, M.D., director of the Center for the Imaging of Neurodegenerative Diseases at the San Francisco VA Medical Center and professor of radiology, medicine, psychiatry, and neurology at the University of California, San Francisco, said, "The release of this genetics data, in combination with the clinical, cognitive, MRI, PET, and blood/cerebrospinal fluid data already in the ADNI database, will now allow investigators to explore genetic factors related to the rate of progression of Alzheimer's disease. Access to this huge amount of data on a public website, from an ongoing clinical study, is unprecedented."

All data from the ADNI consortium are available to qualified investigators through a web-based database (www.loni.ucla.edu/ADNI).

"It is critical that data generated by the support of public funds be made available as quickly as possible to the research community," said Neil Buckholtz, Ph.D., chief of the Dementias of Aging Branch at the National Institute on Aging (NIA) at NIH. "ADNI is fast becoming a model for how data can be shared and how it can be done with speed, so that important investigations to provide answers on Alzheimer's disease can be pursued more intensively."

The ADNI genetics study employed the Illumina 610 Quad array with more than 620,000 markers for this investigation. The research team represented a collaborative effort among the Translational Genomics Institute (TGen) of Phoenix (www.tgen.org), the National Cell Repository for Alzheimer's Disease (ncrad.iu.edu), University of California Irvine Brain Imaging Center (www.bic.uci.edu), the IU Center for Neuroimaging (www.neuroimaging.medicine.iu.edu) and the 59 ADNI sites.

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Support for the genome wide association study was provided by grants through the Foundation for the National Institutes of Health (FNIH) (www.fnih.org), the National Institute on Aging and the National Institute of Biomedical Imaging and Bioengineering, with support contributed by a foundation that prefers to remain anonymous, Merck and Co., Inc. (www.merck.com), Pfizer Inc (www.pfizer.com), and Gene Network Sciences (www.gnsbiotech.com) as well as additional in-kind support from NCRAD and Illumina (www.illumina.com), manufacturer of the gene arrays. Additional support for analysis was provided by Vanda Pharmaceuticals and the Indiana Economic Development Corporation.

Selected men with low-risk prostate cancer have good clinical outcomes without immediate treatment

A multi-center study of prostate cancer patients appearing in today's Journal of Urology recommends that for some men diagnosed with low-risk prostate cancer, opting not to initially receive treatment can be safe if they are closely monitored.

16 mar 2009--The study addresses an important question for men newly diagnosed with prostate cancer and at minimal risk of cancer progression or metastases: when to actively treat versus when to observe and closely monitor. Radiation therapy and surgery are effective treatments but can be associated with serious long-term side effects such as incontinence and erectile dysfunction. Investigators in the study show that two separate biopsies are needed to determine optimal selection of patients for active surveillance, also known as "watchful waiting" when patients decide not to undergo immediate treatment.

Study author Scott Eggener, MD, assistant professor of surgery at the University of Chicago Medical Center, notes there are no widely-accepted recommendations on which patients are appropriate candidates for active surveillance or when to perform second or "restaging" biopsies. The authors show that a restaging biopsy provides doctors with additional information regarding the cancer and is the best way to ensure the short-term success of active surveillance.

"When or if to treat men with low-risk prostate cancer has always been a challenging question that faces patients and urologists," Eggener says.

"Some men may be rushing into treatment that won't necessarily benefit them, prevent problems, or prolong life. Close observation in certain patients may provide and maintain quality of life without increasing the chances of the cancer spreading," he says.

The study suggests that before electing active surveillance, it is important for patients to undergo a restaging biopsy following the initial diagnostic biopsy. A similar study released last year by many of the same authors found that approximately 30 percent of patients were no longer appropriate candidates for active surveillance following a restaging biopsy.

Eggener adds that the study was precipitated by the estimated 20--50 percent of men diagnosed with prostate cancer in the U.S. who will eventually die from another cause, but not from their prostate cancer. This represents a large number of men who do not benefit from treatment.

The study conducted between 1991 and 2007 involved 262 men from four hospitals in the U.S. and Canada who met the following criteria: under age 75; prostate-specific antigen (PSA) below 10 ng/ml; clinical stage T1-T2a; Gleason score 6 or below; and 3 or fewer positive cores at diagnostic biopsy. In addition, participants underwent a restaging biopsy and had no treatment for six months following the repeat biopsy. They subsequently underwent physical exams and PSA tests every six months with biopsies recommended every 1--2 years.

Of that initial pool electing surveillance of their cancer, 43 patients eventually chose treatment or had evidence of cancer progression prompting recommendation of treatment by their physician. Following delayed treatment (radiation or surgery,) all but one were cured of their cancer. The remaining 219 patients remained on active surveillance without evidence of metastases.

"Active surveillance with delayed treatment, if necessary, for select patients appears to be safe and associated with a low risk of metastatic spread," the study concludes.

Unlike many past studies on active surveillance that used data before PSA tests were widely available, this multi-center study is based on patients who were screened with the PSA blood test. The PSA test is a widely used cancer screening tool that predicts a man's chances of having prostate cancer.

"Active surveillance is not a total disregard for patients with prostate cancer. Instead, it identifies men unlikely to be affected by their cancer and encourages frequent monitoring, and then starting therapy at a later appropriate time if needed. Cure rates appear to be identical when these men choose immediate treatment or delayed treatment when prompted by new information about their condition," Eggener says.

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The study was conducted at Memorial Sloane-Kettering Cancer Center, the University of Miami, Cleveland Clinic, and University of British Columbia.

Infective Endocarditis Remains a Lethal Threat

Nearly one in five patients dies in hospital and S. aureus infection increases risk of death

15 mar 2009-- Despite recent advances in diagnosis and treatment, infective endocarditis continues to be frequently fatal, with acute presentations more common than previously thought and a high rate of Staphylococcus aureus infection, according to study findings published in the Mar. 9 issue of the Archives of Internal Medicine.

David R. Murdoch, M.D., of the University of Otago in Christchurch, New Zealand, and colleagues studied 2,781 patients (mean age 57.9) who were admitted to 58 hospitals in 25 countries between June 1, 2000, through Sept. 1, 2005. Of these, 17.7 percent died in hospital.

The researchers found that 77 percent of patients presented within 30 days of disease onset but had few of the classic clinical symptoms. They identified Staphylococcus aureus as the most common pathogen (31.2 percent) and found that it was associated with an increased risk of in-hospital death (odds ratio, 1.54). Surgery was performed on 48.2 percent of patients and was associated with a decreased risk of in-hospital death (odds ratio, 0.61), the report indicates.

"In addition, we have found initial evidence that early surgery may be important in improving patient outcomes," the authors write. "Because nearly 50 percent of patients with infective endocarditis undergo surgery, early identification of surgical indications may improve mortality."

Several of the study authors report relationships with the pharmaceutical industry, including companies that market treatment for endocarditis.

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