Hospice care increasing for nursing home patients with dementia

A new study of nursing home records shows more residents with dementia are seeking a hospice benefit and using it longer. The study also estimates that 40 percent of nursing home residents die with some degree of dementia. Researchers hope the new data will help policymakers preserve the hospice benefit even as they seek to control Medicare costs.

16 dec 2010--In newly published research analyzing data on more than 3.8 million deceased nursing home residents, researchers at Brown University and Hebrew SeniorLife/Deaconess Medical Center in Boston found the proportion of residents with dementia who benefited from Medicare hospice care nearly tripled — and the duration of care more than doubled — between 1999 and 2006.

Because hospice care provides important medical benefits to patients with dementia, including more attentive assistance with feeding and medication, the increased use of the benefit is good news, said Brown University gerontologist Susan Miller, the study's lead author. But the data need to be considered carefully by policymakers, hospice administrators, physicians and families in the context of efforts to control Medicare costs, she said.

"Families and caregivers don't always recognize it as a terminal illness, but people die of dementia," said Miller, research associate professor of community health in the Warren Alpert Medical School of Brown University. "Ideally the higher the proportion of people with dementia who are in hospice care the better because many studies have shown a benefit. But the issue is the cost and the length of stay."

The paper, published in the December issue of the American Journal of Alzheimer's Disease and Other Dementias, is the first to estimate the proportion of people who die in nursing homes with mild to moderately severe or an advanced degree of dementia, an important indicator of the prevalence of the condition in nursing homes. It puts the figure at 40.6 percent nationwide in 2006, although that varies widely by state.

Length of stay

Miller also found wide state-by-state variations in the length of stay in hospice care. That is a key finding because Medicare requires patients to have a terminal prognosis of six months or less before they can be enrolled for the hospice benefit. Because the prognosis of someone with dementia is hard to determine so precisely, some patients with dementia have remained in hospice care for much longer than six months, Miller said, and that concerns Medicare officials who must manage costs.

While the national average length of stay for nursing home patients with advanced dementia increased from 46 days in 1999 to 118 days in 2006 — still within the six-month time frame — in eight states more than a quarter of such patients retained hospice care for more than six months. Oklahoma had the largest proportion of long-staying patients with 46.6 percent, followed by Alabama, New Mexico, Wyoming, South Carolina, Mississippi, Arizona, and North Dakota.

The variations revealed in the state-by-state data suggest that very long stays are not just a product of a general uncertainty about prognosis but also of very different practices in different parts of the country.

As Medicare officials consider the cost of the rising use of the hospice benefit, especially with regard to patients with dementia, Miller said she hopes they will not create "perverse financial incentives" that make it harder for patients to get care they really need. For example, physicians should not be discouraged from referring dementia patients for hospice care even though determining an exact prognosis is difficult. They should retain the latitude to act in good faith, Miller said. Meanwhile, reimbursement should be configured in such a way that it does not unduly favor short hospice stays.

"Initiatives focusing on reducing long hospice stays could disproportionately and adversely affect the timing of hospice referral for persons with dementia," she wrote in the paper along with co-authors Julie Lima of Brown and Susan Mitchell of Hebrew SeniorLife and Deaconess. "It is critical that the creation of any new policy explicitly consider the challenges inherent in the timing of hospice referral for nursing home residents dying with dementia."

Provided by Brown University

It's time for a new approach to Alzheimer's disease

Karl Herrup thinks that the national research effort to understand Alzheimer’s disease has gone about as far as it can go with its current theories. And that’s not far enough.

15 dec 2010--Alzheimer's disease is an incurable, degenerative, eventually fatal disease that attacks cognitive function. It affects more than 26 million people around the world and is the most common form of dementia among people over the age of 65. Over the last three decades, most Alzheimer’s research has been governed by the “amyloid cascade hypothesis.” The theory – which holds that the beta-amyloid peptide is the key to the initiation and progression of the disease – has had significant appeal as the peptide is the main ingredient of the disease-related plaques that are common in the brains of those affected.

Indeed, this persistent correlation has led researchers to spend many years and many millions of dollars looking for ways to prevent plaques as a way of treating, curing or preventing Alzheimer’s. In recent years, however, dozens of human clinical trials based on this theory have failed.

Herrup, the chair of the Department of Cell Biology and Neuroscience at Rutgers University, suggests an alternative perspective, which he has set forth in a paper published today in the Journal of Neuroscience. Pointing out that age is the most important risk factor in the disease, he suggests a new hypothesis with age as the starting point.

Age slows the brain's agility and blunts its responses to change; on their own, however, age-related changes lead only to a slow ‘natural’ decline in cognitive function, Herrup says. He posits that while these changes might increase one’s risk of the Alzheimer’s, they do not cause the disease.

Herrup believes three three key steps that are needed for an individual to progress from this natural path to the full spectrum of Alzheimer’s clinical symptoms: an initiating injury that is probably vascular in nature; an inflammatory response that is both chronic and unique to Alzheimer’s; and a cellular change of state, a one-way cell biological door that permanently alters the physiology of neurons and several other cell types in the Alzheimer’s disease brain.

"The initiating injury might trigger a protective response in the brain cells," Herrup said. "But the real problem is that in the elderly the response doesn't know when to quit. It continues even after the injury itself subsides. In the end, the real damage is done by the persistence of the response and not by the injury, itself."

Herrup hopes his new theory will stimulate discussion and open the way to new experimental and diagnostic advances. “This new hypothesis, for example, emphasizes the value of anti-inflammatory approaches to the prevention of Alzheimer’s disease,” Herrup says.

He concedes that the individual components of the model aren’t entirely new, but points out that by rearranging their order and shifting their priority, his view has enormous implications for modern Alzheimer’s research.

“My hypothesis implies that beta-amyloid aggregation is not a central part of the biology of Alzheimer’s disease,” Herrup says. “It predicts that one can have plaques without having Alzheimer’s and that one can have Alzheimer’s without having plaques.

“Researchers should be cautious about following up these predictions, but since we’ve gone about as far as we can with our current hypothesis, we may have reached a point where too much caution is ill-advised. It’s time to re-imagine Alzheimer’s disease, so we can think creatively about treating it.”

Provided by Rutgers University

We spend more time sick now than a decade ago

Increased life expectancy in the United States has not been accompanied by more years of perfect health, reveals new research published in the December issue of the Journal of Gerontology.

14 dec 2010--Indeed, a 20-year-old today can expect to live one less healthy year over his or her lifespan than a 20-year-old a decade ago, even though life expectancy has grown.

From 1970 to 2005, the probability of a 65-year-old surviving to age 85 doubled, from about a 20 percent chance to a 40 percent chance. Many researchers presumed that the same forces allowing people to live longer, including better health behaviors and medical advances, would also delay the onset of disease and allow people to spend fewer years of their lives with debilitating illness.

But new research from Eileen Crimmins, AARP Chair in Gerontology at the University of Southern California, and Hiram Beltrán-Sánchez, a postdoctoral fellow at the Andrus Gerontology Center at USC, shows that average "morbidity," or, the period of life spend with serious disease or loss of functional mobility, has actually increased in the last few decades.

"We have always assumed that each generation will be healthier and longer lived than the prior one," Crimmins explained. "However, the compression of morbidity may be as illusory as immortality."

While people might be expected to live more years with disease simply as a function of living longer in general, the researchers show that the average number of healthy years has decreased since 1998. We spend fewer years of our lives without disease, even though we live longer.

A male 20-year-old in 1998 could expect to live another 45 years without at least one of the leading causes of death: cardiovascular disease, cancer or diabetes. That number fell to 43.8 years in 2006, the loss of more than a year. For young women, expected years of life without serious disease fell from 49.2 years to 48 years over the last decade.

At the same time, the number of people who report lack of mobility has grown, starting with young adults. Functional mobility was defined as the ability to walk up ten steps, walk a quarter mile, stand or sit for 2 hours, and stand, bend or kneel without using special equipment.

A male 20-year-old today can expect to spend 5.8 years over the rest of his life without basic mobility, compared to 3.8 years a decade ago — an additional two years unable to walk up ten steps or sit for two hours. A female 20-year-old can expect 9.8 years without mobility, compared to 7.3 years a decade ago.

"There is substantial evidence that we have done little to date to eliminate or delay disease while we have prevented death from diseases," Crimmins explained. "At the same time, there have been substantial increases in the incidences of certain chronic diseases, specifically, diabetes."

From 1998 to 2006, the prevalence of cardiovascular disease increased among older men, the researchers found. Both older men and women showed an increased prevalence of cancer. Diabetes increased significantly among all adult age groups over age 30.

The proportion of the population with multiple diseases also increased.

"The increasing prevalence of disease may to some extent reflect better diagnostics, but what it most clearly reflects is increasing survival of people with disease," Crimmins said. "The cost of maintaining and providing care for people with chronic conditions is an important part of determining the economic well-being of countries with established social security and government-provided health services."

Crimmins and Beltrán-Sánchez note that only delaying the onset of disease through preventive care will clearly lead to longer disease-free lives.

"The growing problem of lifelong obesity and increases in hypertension and high cholesterol are a sign that health may not be improving with each generation," Crimmins said. "We do not appear to be moving to a world where we die without experiencing significant periods of disease, functioning loss, and disability."

More information: Crimmins and Beltrán-Sánchez. "Mortality and Morbidity Trends: Is There Compression of Morbidity?" Journal of Gerontology: 2010.

Provided by University of Southern California

Personalized diets for elderly after hospitalization decreases mortality rates

Intense, individually tailored dietary treatment for acutely hospitalized elderly has a significant impact on mortality, according to a new study by researchers at Ben-Gurion University of the Negev.

13 dec 2010--The intervention study just published in the prestigious Journal of the American Geriatric Society showed higher death rates six months after discharge (11.6 percent) of the control group compared to the intervention group's death rate of 3.8 percent, which received intensive nutritional treatment designed and implemented by a registered dietician.

The study recruited 259 hospitalized adults aged 65 and older who were nutritionally at risk. After six months, the rise in the mini-nutritional assessment score (an indicator of nutritional status) was significantly higher in the intervention group than in the control group.

According to BGU researcher Dr. Danit R. Shahar, "This is the first study that used an individually tailored dietary treatment for acutely hospitalized elderly people. The results indicate that intense dietary treatment reduces mortality and can help reduce the need for re-hospitalization."

In the study, a dietician met each patient upon admission to the hospital. The dietitian then followed the patient in his home, visiting three times after discharge.

The study dieticians (case managers) were the decision-makers regarding appropriate treatment and set up treatment goals. The basic approach was to develop a dietary menu based on inexpensive food sources and recipes. Patients had monthly contact by telephone to improve cooperation and prevent dropout from the study. The dieticians performed follow up assessment three to six months after discharges for all patients.

While the overall dropout rate was 25.8 percent, a standard range for elderly studies, after six months the rise in the mini-nutritional assessment score (an indicator of nutritional status) was significantly higher in the intervention group than in the control group.

Provided by American Associates, Ben-Gurion University of the Negev

Older survivors of mechanical ventilation can expect significant disability

Patients aged 65 and older who survive an episode of mechanical ventilation during a hospitalization are more likely to suffer from long-term disabilities after leaving the hospital than those who survive hospitalization without mechanical ventilation, according to researchers at the University of Pittsburgh. These results were borne out even though the levels of functional disability prior to hospitalization were similar in both groups.

The study was published online ahead of the print edition of the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

12 dec 2010--"Our findings offer the first nationally-representative estimates of functional status outcomes for elderly patients who have survived mechanical ventilation, using a prospective population-based sample," said Amber Barnato, MD, associate professor of medicine, University of Pittsburgh. "Unfortunately, 70 percent of elders who receive mechanical ventilation will not survive the year. And the 30 percent who are strong enough to survive will be very disabled."

Previous studies of the effects of mechanical ventilation on elderly patients have offered conflicting results, and were limited by their local patient sampling and lack of first-person information about physical function before the illness.

"This study puts to rest the controversy: doctors can confidently tell their elderly patients that if they survive an episode of mechanical ventilation they will be much more disabled than before, and may require nursing home care," noted Dr. Barnato.

To complete their study, the researchers used data collected over a seven-year period in the Medicare Current Beneficiary Survey (MCBS), a continuous survey of a nationally representative sample of aged, disabled and institutionalized Medicare beneficiaries sponsored by the Centers for Medicare and Medicaid Services. MCBS conducts in-person interviews with each sampled beneficiary four times per year for four years, after which they rotate off the panel and new beneficiaries are invited to join. Questions related to health and functional status are asked every autumn.

For this study, the researchers linked beneficiaries' survey responses from the autumn survey with their responses one year later. Beneficiaries who were hospitalized during the 12-month period and who survived until their next autumn interview were included and divided into two groups: those who had received mechanical ventilation during hospitalization and those who had not. The researchers reviewed more than 130,000 person-years of data, from which about 12,000 person-years of data qualified for inclusion in the study.

"We restricted the study to include Medicare beneficiaries aged 65 and older who were living in the community at the time of the initial interview, and who were not enrolled in a group health plan, since these plans do not report claims data to Medicare," said Dr. Barnato. "Each beneficiary could contribute up to three years of observation during their four years of participation in the MCBS."

Researchers rated patients' pre- and post-hospitalization disability levels with regard to mobility and activities of daily living (ADL), rating patients in both areas using scores ranging from 0 (not disabled) to 100 (completely disabled).

Comparing the two groups, the researchers found those who survived mechanical ventilation experienced 30 percent greater ADL disability (14.9 vs. 11.5) and 14 percent greater mobility difficulty (25.4 vs. 22.3) than non-ventilated counterparts.

"This is especially important because the pre-hospitalization scores of the patients who were and weren't mechanically ventilated were similar," Dr. Barnato said. "Being sick enough to require mechanical ventilation, and perhaps even the experience of mechanical ventilation itself, really takes the vim and vigor out of people."

Although mechanical ventilation may be lifesaving, the possibility of prolonged disability could influence health-care decision-making, she noted.

"The greater risk of significant disability for those who survive mechanical ventilation has implications for patients' treatment goals, since Dr. Terri Fried, at Yale, has shown that many elders might not elect to receive a high-burden intervention if they knew it would result in survival with substantial disability," Dr. Barnato said.

"Clinicians should discuss outcomes that are important to patients, such as disability, as well as mortality, when working with patients and their families to make decisions about the use of mechanical ventilation," she added.

Provided by American Thoracic Society

Psychotic-like symptoms associated with poor outcomes in patients with depression

Among patients with depression, the presence of many aspects of illness which may be associated with bipolar disorder does not appear to be associated with treatment resistance—evidence against the common hypothesis that some cases of difficult-to-treat depression are actually unrecognized bipolar disorder, according to a report posted online today that will appear in the April 2011 print issue of Archives of General Psychiatry. However, many patients with depression also report psychotic-like symptoms, such as hearing voices or believing they are being spied on or plotted against, and those who do are less likely to respond to treatment.

11 dec 2011--"The distinction between major depressive disorder and bipolar disorder remains a challenging clinical problem when individuals present with a major depressive episode," the authors write as background information in the article. "The identification of individuals at risk for bipolar disorder is of more than academic importance, as treatment may be markedly different; in particular, antidepressants have been suggested to exacerbate the illness course of at least a subset of bipolar individuals."

To assess the association between features of bipolar disorder and the outcomes of treatment for depression, Roy H. Perlis, M.D., M.Sc., of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues studied 4,041 adults with a diagnosis of depression. Patients were treated with the antidepressant citalopram, followed by up to three next-step treatments as needed depending on their response.

At the beginning of the study, patients were asked about psychotic symptoms—including beliefs about being controlled, having special powers or being plotted against. Almost one-third (1,198, or 30 percent) of the patients reported having at least one such symptom in the previous six months. Those who did were significantly less likely to go into remission over all the treatment periods

Participants were also asked about other features characteristic of bipolar disorder; 1,524 patients (38.1 percent) with depression described at least one manic-like symptom. One of these, irritability, was also associated with poor treatment outcomes. "On the other hand, several indicators consistently associated with bipolar disposition in the literature, including history of manic symptoms and family history of bipolar disorder, were not associated with outcome of treatment with antidepressants in the STAR*D study," the authors write. "Briefer episode duration, suggested to represent a risk marker for bipolarity, was associated with greater likelihood of remission."

"Considered as a whole, our results cast doubt on the frequent assertion that unrecognized bipolar disorder is widespread in clinical practice and particularly in treatment-resistant major depressive disorder," they conclude. "Screening for bipolar disorder among psychiatric patients remains important, as does considering individual risk factors such as family history or age at onset. Still, our findings indicate that, in most individuals presenting with a major depressive episode without a prior manic or hypomanic episode, unrecognized bipolarity does not appear to be a major determinant of treatment resistance."

More information: Arch Gen Psychiatry. Published online December 6, 2010. doi:10.1001/archgenpsychiatry.2010.179

Provided by JAMA and Archives Journals

Maintaining mobility in older age

A study by the New Dynamics of Ageing Programme, a joint initiative by Research Council's UK, examines the relationship between successful aging and mobility patterns. While maintaining mobility plays a significant part in healthy aging, a new study highlights a high degree of inactivity even among an "elite" sample of fit and healthy older people aged between 72 and 92 years.

10 dec 2010--"Mobility is hugely important in terms of older people being able to remain independent," explains Dr Lynn McInnes. "Reduced mobility can restrict a person's social life as well as limiting their access to shops, leisure and other activities. People fear not being able to look after themselves and being a burden on others. Often a cause of this dependence is a decline in mobility."

The study used innovative methods, such as location awareness technologies for mapping the mobility of the oldest-old members (75 years and over) of an existing 25-year longitudinal study of ageing.

The daily mobility activities of a fairly active group of people showed that 70 per cent of the day is spent sitting or lying, 22 per cent of the day standing and seven per cent of the day walking. The furthest distance travelled from their home is on average four miles, or approximately 23 miles in a single week, spread over five journeys per week. As much as 78 per cent of the day is spent indoors and 14 per cent of the day is spent on outdoor activities.

Evidence suggests that sitting most of the time is an important factor to take into account when looking at patterns of behaviour. The daily life of a person includes a combination of active, non-active or brief activities. These patterns suggest that changes occur as people age and starting an activity may be harder later in the day.

Lead researcher Dr McInnes points out: "New methods are needed to examine how much activity an individual does throughout a day. Monitoring activity levels by using tracking devices will help to assess the mobility ability of older people. Additionally, monitoring health and well-being can help identify individuals who may be at risk."

In addition these findings highlight the importance of providing effective transport networks and a good range of local services to meet older people's needs," Dr McInnes explains. "Being able to stay mobile is crucial to older people's wellbeing, as loss of mobility means the loss of so many other things from their lives such as the ability to go shopping, meet friends and pursue hobbies and interests."

This project has helped to establish a reliable mobility profile of the oldest-old members of society by determining where individuals go and how active they are in the process and shows there is a clear relationship between mobility, health and well-being. It is encouraging to know that old age is not necessarily a time of ill health, a decline in thought processes or becoming a burden. Participants in this study exemplified 'successful ageing'.

Provided by Economic & Social Research Council

Low and high vitamin D levels in older women associated with increased likelihood of frailty

A recent study accepted for publication in The Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM) found that lower and higher vitamin D levels were associated with an increased likelihood of frailty in older women. Women with vitamin D levels between 20.0 and 29.9 ng/ml were at the lowest risk of frailty.

09 dec 2010--Vitamin D deficiency and frailty are common with aging. Dimensions of frailty, including weakness and slowness are potential outcomes of vitamin D deficiency and many experts have recommended measuring vitamin D levels in older adults and prescribing vitamin D supplementation if levels are less than 30 ng/ml to prevent adverse health outcomes. This new study however found a U-shaped relationship between vitamin D levels and frailty; older women with vitamin D levels higher than 30 ng/ml and those with levels lower than 20 ng/ml were more likely to be frail.

"Vitamin D supplementation has grown in popularity, yet the association between vitamin D status and risk of adverse health outcomes in older adults is uncertain," said Kristine Ensrud, MD, professor of medicine and epidemiology, Minneapolis VA Medical Center and the University of Minnesota and lead author of the study. "Our study did not find that higher vitamin D status was associated with lower subsequent risks of frailty or death. In fact, higher levels of vitamin D were associated with increased likelihood of frailty."

In this study, researchers measured vitamin D levels and assessed frailty status in a cohort of 6,307 women aged 69 and older. To determine whether lower vitamin D levels were associated with an increased risk of greater frailty status at a later date, 4,551 women classified as non-frail at baseline had frailty status reassessed an average of 4.5 years later. They found that older women with vitamin D levels less than 20 ng/ml and more than 30 ng/ml had higher odds of frailty at baseline. Lower vitamin D levels among non-frail women at baseline were associated with an increased risk of frailty or death at follow-up.

"Evidence is lacking to support use of vitamin D supplementation for prevention of frailty and other outcomes including cancer or all-cause mortality," said Ensrud. "Our results indicate that well-designed large randomized trials of sufficient duration are needed to accurately quantify health effects of vitamin D supplementation, including whether or not supplementation reduces the incidence or progression of frailty in older adults."

More information: The article, "Circulating 25-hydroxyvitamin D Levels and Frailty Status in Older Women," appears in the December 2010 issue of JCEM.

Provided by The Endocrine Society

Low-dose aspirin reduces death rates from range of cancers by between 20 and 30 percent

The London School of Hygiene & Tropical Medicine (LSHTM) has contributed to a study showing that a low dose of aspirin reduces the occurrence of several common cancers. The study is published in today's Lancet.

08 dec 2010--The work was started and carried out by Professor Peter Rothwell in Oxford, and is based on an overview of several randomised trials of aspirin. These have been primarily concerned with reducing heart attacks, but have also gathered information on deaths from cancer.

The trial contributing most information to the overview has been the Thrombosis Prevention Trial (funded jointly by the Medical Research Council and the British Heart Foundation) which was carried out by Tom Meade when he was with the Medical Research Council. Professor Meade is now Emeritus Professor of Epidemiology in LSHTM's Department of Non-Communicable Disease Epidemiology.

As well as confirming that low dose aspirin reduces large bowel cancer cases reported in another recent study also led by Professor Rothwell and to which Professor Meade contributed, it also reduces total deaths due to cancer because it affects several common individual cancers, such as those of the oesophagus (gullet), lung, stomach, pancreas and possibly the brain. Reductions in deaths are around 20-30%.

Benefit is unrelated to aspirin dose from 75mg upwards, gender or smoking habit but increases with age. Aspirin may need to be taken for at least five years before it confers benefit, probably longer for some cancers, but benefit is generally greater the longer aspirin has been taken.

Hitherto, advice about aspirin has been mainly concerned with reducing heart attacks and strokes in those who have already had them. Caution should be exercised by those who are so far free of these conditions because, unless a person's risk of them is very high, the benefit may be outweighed by the risk of serious bleeding.

Professor Meade says: 'These are very exciting and potentially important findings. They are likely to alter clinical and public health advice about low dose aspirin because the balance between benefit and bleeding has probably been altered towards using it', although Professor Meade adds that this does not mean everyone should automatically take aspirin. Health professionals and others will now have to consider the practical implications.

Provided by London School of Hygiene & Tropical Medicine

Exposure to death and dying can have a positive impact

Exposure to death and dying does not negatively affect palliative and hospice care professionals and can actually have positive benefits, states an article in CMAJ (Canadian Medical Association Journal).

07 dec 2010--A study of palliative and hospice care professionals in five centres across Canada over was conducted to explore how death affects their personal lives and practices. Since these professionals are constantly around death and dying, it was thought that their insight could benefit others. Participants reported that being around dying people has allowed them to have a better understanding of the meaning of life, has helped them become more spiritual and has helped them come to terms with their own mortality.

"Participants reported that their work provided a unique opportunity for them to discover meaning in life through the lessons of their patients, and an opportunity to incorporate these teachings in their own lives," writes Shane Sinclair, Spiritual Care Services, Tom Baker Cancer Centre, Calgary, Alberta, and CIHR Postdoctoral Fellowship with the Manitoba Palliative Care Research Unit, University of Manitoba. "Although Western society has been described as a death-denying culture, the participants felt that their frequent exposure to death and dying was largely positive, fostering meaning in the present and curiosity about the continuity of life."

"Participants attested to the weighty nature of their vocation, but this was far outweighed by the many affirming life lessons that participants incorporated into their own lives and practices," concludes Sinclair. "Although the end of life is arguably the most challenging phase of life, it may also be the most meaningful, providing hope to those who are living with an incurable illness as well as individuals who will inevitably face their mortality in the future."

In a related commentary Dr. Pamela McGrath, International Program of Psycho-Social Health Research, Central Queensland University, Brisbane, Australia writes that the important message to learn from Dr. Sinclair's research is that "with support and the opportunity to incorporate the experiences into personal and professional lives, doctors can find caring for the dying meaningful and professionally satisfying. This message challenges widely held misconceptions about the inherently morbid and negative nature of the health professionals' experience of caring for the dying."

Provided by Canadian Medical Association Journal

Gene duplication detected in depression

A large genetic study of people with major depression has found that a duplicated region of DNA on chromosome 5 predisposes people to the disorder. The gene involved plays an important role in the development of nerve cells, adding to evidence that disruptions in neurotransmission networks form a biological basis for depression.

06 dec 2010--"The copy number variations we discovered were exclusive to people with depression, and were located in a gene region important in signaling among brain cells," said study leader Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia. "This finding extends work by other researchers suggesting that disruptions in neurotransmitter networks in the brain are an underlying cause of major depressive disorders."

The study appears online today in Public Library of Science One (PLoS One).

The current research is the first large-scale genome-wide study of copy number variation (CNV) in major depressive disorder (MDD), a major psychiatric and behavioral disorder affecting an estimated 16 percent of the U.S. population. CNVs are deletions or duplications of segments of DNA. While a specific CNV is relatively rare in a population, it often exerts a strong effect on an individual who harbors the CNV in their genes.

Hakonarson's group conducted a whole-genome scan of DNA from 1,693 patients with MDD, mainly from a European database, and from 4,506 control subjects.

The researchers identified 12 CNVs exclusive to MDD cases. Their most notable finding was a large duplication of DNA segments on chromosome 5q35.1, a CNV shared by five unrelated patients and not observed in healthy controls. Residing at that location is the gene SLIT3, which is involved in axon development. The axon is the portion of a neuron that carries nerve impulses away from the cell body.

Hakonarson added that he plans follow-up studies with more refined sequencing technology, in which he expects to identify many more CNVs and possibly other types of mutations in the SLIT3 gene, as well as in other functionally related genes that may predispose to depression. Further studies may also reveal how strongly CNVs at SLIT3 and other related genes contribute to the risk of depression.

"Clinical applications for our discoveries are still in the future, but it may be possible at some point to incorporate these findings into personalized medicine," Hakonarson said. "Identifying causative genes may suggest future targets for drug development, and may also help us predict a person's future risk of developing depression," he added.

More information: "Duplication of the SLIT3 Locus on 5q35.1 Predisposes to Major Depressive Disorder," PLoS One, published online Dec. 1, 2010.

Provided by Children's Hospital of Philadelphia

Omega-3s in fish, seafood may protect seniors' eyes; a new test may catch glaucoma early

Seniors interested in lifestyle choices that help protect vision will be encouraged by a Johns Hopkins School of Medicine study, and people concerned about glaucoma can take heart from work on early detection by the University of Miami Miller School of Medicine. Both studies are published in the December issue of Ophthalmology, the journal of the American Academy of Ophthalmology.

New Evidence for Eye-Protective Effects of Omega-3-Rich Fish, Shellfish

05 dec 2010--Researchers at Wilmer Eye Institute, Johns Hopkins School of Medicine, wanted to know how the risk of age-related macular degeneration (AMD) would be affected in a population of older people who regularly ate fish and seafood, since some varieties are good sources of omega-3 fatty acids. A diet rich in omega-3s probably protects against advanced AMD, the leading cause of blindness in whites in the United States, according to the Age-Related Eye Disease Study (AREDS) and other recent studies. High concentrations of omega-3s have been found in the eye's retina, and evidence is mounting that the nutrient may be essential to eye health. The new research, led by Sheila K. West, PhD, was part of the Salisbury Eye Evaluation (SEE) study.

Food intake information with details on fish and shellfish consumed was collected over one year using a validated questionnaire for 2,391 participants aged 65 to 84 years who lived along Maryland's Eastern Shore. After dietary assessment was complete, participants were evaluated for AMD. Those with no AMD were classified as controls (1,942 persons), 227 had early AMD, 153 had intermediate-stage disease, and 68 had advanced AMD. In the advanced AMD group, the macular area of the retina exhibited either neovascularization (abnormal blood vessel growth and bleeding) or a condition called geographic atrophy. Both conditions can result in blindness or severe vision loss.

"Our study corroborates earlier findings that eating omega-3-rich fish and shellfish may protect against advanced AMD." Dr. West said. "While participants in all groups, including controls, averaged at least one serving of fish or shellfish per week, those who had advanced AMD were significantly less likely to consume high omega-3 fish and seafood," she said.

The study also looked at whether dietary zinc from crab and oyster consumption impacted advanced AMD risk, but no significant relationship was found. Zinc is also considered protective against AMD and is included in an AMD-vitamin/nutrient supplement developed from the AREDS study. Dr. West speculated that her study found no effect because the levels of zinc obtained from seafood/fish were low compared to supplement levels.

A side note: fish and shellfish were part of the normal diet of the study population, rather than added with the intention of improving health. The links between fish consumption, omega-3s and healthy lifestyles were not widely known in the early 1990s when the dietary survey was conducted. In fact, some of the study participants who consumed the most seafood were also smokers and/or overweight, two factors usually associated with AMD and other health risks.

Retinal Nerve Function May be Key to Early Glaucoma Detection

Catching glaucoma as early as possible–before it destroys the optic nerve–is vital to preventing vision loss. Now a research team at Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, has shown that a test that measures the functionality of the eye's retinal nerve cells may be a key to early detection. Eventually, the test may also help evaluate how well glaucoma treatments are working.

The research, led by Mitra Sehi, PhD, and David Greenfield, MD, was based on the knowledge that retinal ganglion cells (RGCs) become dysfunctional as glaucoma progresses and that such changes can be measured using the pattern electroretinogram optimized for glaucoma screening (PERGLA). PERGLA measures the electrical activity of a patient's retina as he or she views an alternating pattern of black and white lines. (The retinal area in the back of the eye receives images and transmits them to the optic nerve.) Other studies had shown that abnormal changes in RGCs begin early in the glaucoma process, so PERGLA is potentially valuable as a non-invasive detection tool.

The Bascom Palmer study included 47 patients (47 eyes) in whom intraocular pressure (IOP) could not be controlled with medication and who therefore had surgery to prevent optic nerve damage. All patients had two PERGLA evaluations (as well as complete ocular exams, optic nerve assessment, and blood pressure measurement), one before surgery and one at three months post surgery. IOP and PERGLA measurements of the patients' fellow, non-glaucomatous, non-treated eyes were stable before and after surgeries. The surgeries improved fluid drainage in the eyes to reduce IOP; 34 eyes had trabeculectomy and 13 had glaucoma drainage implants.

PERGLA results showed that RGC dysfunction was reversed and IOP was reduced in all patients following surgery. The patients' central visual field tests improved, as well. Dr. Sehi says these results should be interpreted cautiously until confirmed by larger studies. She calls for longitudinal studies to clarify the relationship between reduced IOP and increased RGC response and to further investigate PERGLA assessment of RGC dysfunction as a biomarker for glaucoma.

Provided by American Academy of Ophthalmology

Tricyclic anti-depressants linked to increased risk of heart disease

Research that followed nearly 15,000 people in Scotland has shown that a class of older generation anti-depressant is linked to an increased risk of cardiovascular disease (CVD). The study showed that tricyclic anti-depressants were associated with a 35% increased risk of CVD, but that there was no increased risk with the newer anti-depressants such as the selective serotonin reuptake inhibitors (SSRIs). The study is published online today (Wednesday 1 December) in the European Heart Journal and was led by researchers from University College London (UCL).

04 dec 2010--The prospective study, which followed 14,784 men and women without a known history of CVD, is the first to look at the risks associated with the use of anti-depressants in a large, representative sample of the general population. Until now, there have been uncertain and conflicting findings from earlier studies that have looked at the link between anti-depressant use and the risk of CVD.

Dr Mark Hamer, Senior Research Fellow in the Department of Epidemiology and Public Health at UCL (London, UK), said: "Our study is the first to contain a representative sample of the whole community, including elderly and unemployed participants, men and women, etc. Therefore, our results can be generalised better to the wider community. The majority of previous work in this area has focused on clinical cardiac patients, so studies in healthy participants are very important. Given that anti-depressants, such as SSRIs, are now prescribed not only for depression, but for a wide range of conditions such as back pain, headache, anxiety and sleeping problems, the risks associated with anti-depressants have increasing relevance to the general population."

Dr Hamer and his colleagues used data from the Scottish Health Survey, which collects information from the general population every three to five years. They combined data from separate surveys in 1995, 1998 and 2003 in adults aged over 35 and linked them with records on hospital admissions and deaths, with follow-up until 2007. Anyone with a history of clinically confirmed CVD was excluded.

During the surveys, interviewers visited eligible households and asked participants a range of questions on demographics and lifestyle, such as smoking, alcohol intake and physical activity, and measured their height and weight. They assessed psychological distress using a questionnaire (the General Health Questionnaire) that enquires about symptoms of anxiety and depression in the last four weeks. In a separate visit, nurses collected information on medical history, including psychiatric hospital admissions, and medication, and took blood pressure readings.

During an average of eight years follow-up there were 1,434 events related to CVD, of which 26.2% were fatal. Of the study participants, 2.2%, 2% and 0.7% reported taking tricyclic anti-depressants, SSRIs or other antidepressants respectively. After adjusting for various confounding factors, including indicators of mental illness, the researchers found there was a 35% increased risk of CVD associated with tricyclic anti-depressants. The use of SSRIs was not associated with any increased risk of CVD, nor did the researchers find any significant associations between anti-depressant use and deaths from any cause.

Dr Hamer said: "Our findings suggest that there is an association between the use of tricyclic anti-depressants and an increased risk of CVD that is not explained by existing mental illness. This suggests that there may be some characteristic of tricyclics that is raising the risk. Tricyclics are known to have a number of side effects; they are linked to increased blood pressure, weight gain and diabetes and these are all risk factors for CVD."

He continued: "It is important that patients who are already taking anti-depressants should not cease taking their medication suddenly, but should consult their GPs [primary care physicians] if they are worried. There are two important points to be made. First, tricyclics are the older generation of anti-depressant medicines and we found no excess risk with the newer drugs (SSRIs). Secondly, people taking the anti-depressants are also more likely to smoke, be overweight, and do little or no physical activity – by giving up smoking, losing weight, and becoming more active a person can reduce their risk of CVD by two to three-fold, which largely out-weighs the risks of taking the medications in the first place. In addition, physical exercise and weight loss can improve symptoms of depression and anxiety.

"Our findings suggest that clinicians should be cautious about prescribing anti-depressants and should also consider lifestyle advice, such as smoking cessation, exercise and sensible alcohol intake."

More information: "Anti-depressant medication use and future risk of cardiovascular disease: the Scottish Health Survey". European Heart Journal. doi:10.1093/eurheartj/ehq438

Provided by European Society of Cardiology

New study identifies ideal body mass index

A study looking at deaths from any cause found that a body mass index (BMI) between 20.0 and 24.9 is associated with the lowest risk of death in healthy non-smoking adults. Investigators also provided precise estimates of the increased risk of death among people who are overweight and obese. Previous studies that examined the risks from being overweight were inconclusive, with some reporting only modestly increased risks of death and others showing a reduced risk. Also, the precise risks for different levels of obesity were uncertain.

03 dec 2010--The research team included investigators from the National Cancer Institute (NCI), part of the National Institutes of Health, and collaborators from a dozen other major research institutions worldwide. The results appear in the Dec. 2, 2010, issue of the New England Journal of Medicine.

BMI, the most commonly used measure for body fat, is calculated by dividing a person's weight in kilograms by the square of his/her height in meters (kg/m2). Current guidelines from the U.S. Centers for Disease Control and Prevention, and the World Health Organization define a normal BMI range as 18.5 to 24.9. Overweight is defined as a BMI of 25.0 to 29.9; obesity is defined as a BMI over 30.0; and severe obesity is defined as BMI 35 or higher. For a BMI calculator, go to http://www.nhlbisupport.com/bmi/bmicalc.htm.

Obesity has emerged as a leading public health concern in the United States. It has been well-established that people who are obese face increased risks of death from heart disease, stroke, and certain cancers. Currently, two-thirds of U.S. adults are overweight or obese. Even more worrisome, 17 percent of women and 11 percent of men are severely obese.

In this large analysis, investigators pooled data from 19 long-term studies designed to follow participants over time, from 5 to 28 years, depending on the study.

They found that healthy women who had never smoked and who were overweight were 13 percent more likely to die during the study follow-up period than those with a BMI between 22.5 and 24.9. Women categorized as obese or severely obese had a dramatically higher risk of death. As compared with a BMI of 22.5 to 24.9, the researchers report a 44 percent increase in risk of death for participants with a BMI of 30.0 to 34.9; an 88 percent increase in risk for those with a BMI of 35.0 to 39.9; and a 2.5 times (250 percent) higher risk of death for participants whose BMI was 40.0 to 49.9. Results were broadly similar for men. Overall for men and women combined, for every five unit increase in BMI, the researchers observed a 31 percent increase in risk of death.

"By combining data on nearly 1.5 million participants from 19 studies we were able to evaluate a wide range of BMI levels and other characteristics that may influence the relationship between excess weight and risk of death," said NCI's Amy Berrington de Gonzalez, D.Phil., lead author of the study. "Smoking and pre-existing illness or disease are strongly associated with the risk of death and with obesity. A paramount aspect of the study was our ability to minimize the impact of these factors by excluding those participants from the analysis."

The investigators observed similar patterns of risk even after accounting for differences in alcohol consumption, physical activity, and education level. The increased risk of death for a BMI of 25 or greater was also seen in all age groups, although it was more prominent for those who were overweight or obese before age 50.

The investigators gathered information about BMI and other characteristics from questionnaires participants completed at the beginning of each study. Causes of death were obtained from death certificates or medical records. This analysis was restricted to non-Hispanic whites aged 19 to 84. The investigators noted the relationship between BMI and mortality may differ across racial and ethnic groups. Other efforts are underway to study the effect of BMI on mortality in other racial and ethnic groups.

More information: Reference: Berrington de Gonzalez B, Hartge P, Cerhan JR, Flint AJ, Hannan L, MacInnis RJ, Moore SC, Tobias GS, Anton-Culver H, Beane Freeman L, W. Beeson L, Clipp SL, English DR, Folsom AR, Freedman DM, Giles G, Hakansson N, Henderson KD, Hoffman-Bolton J, Hoppin JA, Koenig KL, Lee IM, Linet MS, Park Y, Pocobelli G, Schatzkin A, Sesso HD, Weiderpass E, Willcox BJ, Wolk A, Zeleniuch-Jacquotte A, Willett WC, Thun MJ. Body-Mass Index and Mortality-- Prospective Analysis of 1.46 Million White Adults. Dec. 2, 2010, NEJM, Vol. 362, No. 23.

Provided by National Institutes of Health

Fatigue and excessive daytime sleepiness should be assessed separately in Parkinson's

Nearly three-quarters of patients with Parkinson's disease experience fatigue or excessive daytime sleepiness (EDS), but clinicians should assess both problems separately in order to improve the profession's understanding of their distinct, but overlapping, physiology. That is the key finding of a study published in the December issue of the European Journal of Neurology.

02 dec 2010--Researchers from the University Hospital of Zurich, Switzerland, studied 88 outpatients with Parkinson's. They found that 72% suffered from fatigue or EDS, with just under half of them suffering from both.

"Sleep-wake disturbances such as fatigue and EDS are important non-motor features of Parkinson's" says co-author Dr Christian Baumann. "Their causes remain elusive, but it is possible that multiple factors such as neurodegeneration and medication contribute to them.

"It is important that physicians assess these symptoms, because they have a marked impact on patients' motor functions, everyday activities and quality of life.

"EDS tends to affect up to 50% to 75% of Parkinson's disease patients. This is higher than in other brain disorders such as multiple sclerosis, ischaemic stroke and traumatic brain injury. Fatigue is estimated to affect 40% to 60% of patients with Parkinson's disease, but is often not diagnosed.

"The aim of our study was to systematically assess EDS and fatigue in Parkinson's disease, to determine the overlap between the two symptoms and associate them with other motor and non-motor symptoms and dopaminergic medication."

Eighty-eight consecutive patients aged 38 to 84 attending a movement disorders clinic over a ten-month period were included in the study. Their average age was 67.5 years and 69% were male. Disease duration ranged from two to 28 years, with an average of just under ten years.

Key findings included:

• 72% of patients suffered from fatigue, EDS or a combination of both. 59% reported fatigue, 24% on its own and 35% with EDS. 48% reported EDS, 13% on its own and 35% with fatigue.
  
• Fatigued patients were almost twice as likely to suffer from EDS than non-fatigued patients (60% versus 31%).
  
• EDS was more common and severe with longer disease duration, but the same pattern was not observed when it came to fatigue.
  
• Fatigued patients with Parkinson's disease had more severe motor symptoms than patients without fatigue. They were also more likely to suffer from Parkinson's-related insomnia than patients without fatigue (77% versus 53%), autonomic disturbances (46% versus 19%) and depression (52% versus 28%).
  
• Insomnia was more prevalent in patients with EDS than without (79% versus 57%) but the researchers found no differences when it came to severity of motor symptoms, hallucinations, autonomic disturbances or depression.
  
• Increased sleep duration (hypersomnia) was associated with fatigue but not EDS. The 17% of patients who reported increased sleep duration were more likely to be severely affected by motor symptoms than patients with average sleep duration, but did not show an increase in other symptoms.
  
• Most of the patients (50%) were receiving a combination of levodopa and a dopamine agonist, 38% were just receiving levodopa and 10% were just receiving a dopamine agonist. No patients were on rasagiline or selegiline.
  
• Dopaminergic treatment exerted a stronger influence on EDS than on fatigue. When dopamine agonists were combined with levodopa, this made EDS even worse.

"Our findings suggest that although fatigue and EDS often co-exist in patients with Parkinson's they are differently associated with severity of motor symptoms, disease duration, depression and dopaminergic treatment" concludes Dr Baumann. "For this reason, we feel that fatigue and EDS should be separately assessed in patients with Parkinson's in order to improve our understanding of their distinct but overlapping physiology."

More information: Fatigue and excessive daytime sleepiness in idiopathic Parkinson's disease differently correlate with motor symptoms, depression and dopaminergic treatment. Valko et al. European Journal of Neurology. 17, pp1428-1436. (December 2010). DOI: 10.1111/j.1468-1331.2010.03063.x

Report: A bit more vitamin D is good, not too much

Got milk? You may need a couple cups more than today's food labels say to get enough vitamin D for strong bones. But don't go overboard: Long-awaited new dietary guidelines say there's no proof that megadoses prevent cancer or other ailments - sure to frustrate backers of the so-called sunshine vitamin.

01 dec 2010--The decision by the prestigious Institute of Medicine, the health arm of the National Academy of Sciences, could put some brakes on the nation's vitamin D craze, warning that super-high levels could be risky.

"More is not necessarily better," cautioned Dr. Joann Manson of Harvard Medical School, who co-authored the Institute of Medicine's report being released Tuesday.

Most people in the U.S. and Canada - from age 1 to age 70 - need to consume no more than 600 international units of vitamin D a day to maintain health, the report found. People in their 70s and older need as much as 800 IUs. The report set those levels as the "recommended dietary allowance" for vitamin D.

That's a bit higher than the target of 400 IUs set by today's government-mandated food labels, and higher than 1997 recommendations by the Institute of Medicine that ranged from 200 to 600 IUs, depending on age.

But it's far below the 2,000 IUs a day that some scientists recommend, pointing to studies that suggest people with low levels of vitamin D are at increased risk of certain cancers or heart disease.

"This is a stunning disappointment," said Dr. Cedric Garland of the University of California, San Diego, who wasn't part of the institute's study and says the risk of colon cancer in particular could be slashed if people consumed enough vitamin D.

"Have they gone far enough? In my opinion probably not, but it's a step in the right direction," added prominent vitamin D researcher Dr. Michael Holick of Boston University Medical Center, who said the new levels draw needed attention to the vitamin D debate and encourage more food fortification.

Vitamin D and calcium go hand in hand, and you need a lifetime of both to build and maintain strong bones. But the two-year study by the Institute of Medicine's panel of experts concluded research into vitamin's D possible roles in other diseases is conflicting. Some studies show no effect, or even signs of harm.

A National Cancer Institute study last summer was the latest to report no cancer protection from vitamin D and the possibility of an increased risk of pancreatic cancer in people with the very highest D levels. Super-high doses - above 10,000 IUs a day - are known to cause kidney damage, and Tuesday's report sets 4,000 IUs as an upper daily limit - but not the amount people should strive for.

And Manson pointed to history's cautionary tales: A list of other supplements - vitamins C and E and beta carotene - plus menopause hormone pills that once were believed to prevent cancer or heart disease didn't pan out, and sometimes caused harm, when put to rigorous testing.

Stay tuned: To help settle the issue, Manson is heading a government-funded study that's recruiting 20,000 healthy older Americans to test whether taking 2,000 IUs of vitamin D really will lower their risk for heart disease, a stroke or certain cancers.

In the meantime, it's hard to consume 600 IUs of vitamin D from food alone. A cup of D-fortified milk or orange juice has about 100 IUs. The best sources may be fatty fish - some servings of salmon can provide about a day's supply. Other good sources are D-fortified cereals.

But here's the report's big surprise: While some people truly are seriously deficient in vitamin D, the average American in fact already has enough circulating in his or her blood - because we also make vitamin D from sun exposure, and because many people already take multivitamins or other D-containing dietary supplements.

Wait a minute: Headlines in recent years have insisted the opposite, that a majority of people don't get enough vitamin D, especially during the winter. What explains the contradiction?

Most testing laboratories are using a too-high cutoff for those blood levels, said report co-author Dr. Clifford Rosen of the Maine Medical Center. The report says at least 20 nanograms is adequate for bone health, while many labs instead list people as low if their blood levels are below 30 ng. Serious vitamin D deficiencies are diagnosed when levels dip well below 20, something that hasn't changed.

Rosen called the state of vitamin D testing "the wild, wild West," and said he hoped that "with this report, we can at least temper people's enthusiasm for just taking tons of supplements."

As for calcium, the report recommended already accepted levels to go along with your daily D - about 1,000 milligrams of calcium a day for most adults, 700 to 1,000 mg for young children, and 1,300 mg for teenagers and menopausal women. Too much can cause kidney stones; the report said that risk increases once people pass 2,000 mg a day.

It's true that most studies link poor health to vitamin D levels that are below 20 ng, said preventive cardiologist Dr. Erin Michos, a Johns Hopkins University School of Medicine professor who wasn't part of the study.

But, "I'm not sure I'm going to dramatically change my practice," said Michos, who pushes her patients to boost their levels until they're between 30 and 50 ng.

First blood test to determine cognitive impairment in Parkinson's disease developed

Researchers at the University of Pennsylvania School of Medicine’s Udall Center for Parkinson's Research have developed the first blood-based biomarker test to predict cognitive decline in Parkinson’s disease (PD). If results can be replicated and standardized in other Parkinson patients, by other investigators, the test could be a useful tool to use in selecting patients for the development of new drugs that can slow or prevent this complication of the disease.

30 nov 2010--After searching through a hundred different proteins found in blood plasma, researchers found that epidermal growth factor (EGF), a protein involved in regulating cell growth, proliferation, and differentiation, provided a strong biomarker signal for cognitive impairment in PD. The study determined that PD patients with low EGF levels and normal cognition were more likely to subsequently develop serious cognitive impairments during the 21-month median follow-up period. The study is published in the current issue of the Annals of Neurology.

“As a PD doctor, I hear all the time that my patients want to know whether their disease will progress rapidly, and if they’ll have the type of Parkinson’s where they get dementia,” said Alice Chen-Plotkin, MD, assistant professor of Neurology at the University of Pennsylvania and the study’s lead author. “If other studies verify these results, measuring EGF levels may be useful both as a clinical diagnostic tool and in the design of trials aimed at preserving cognition in Parkinson’s disease.”

As many as 83 percent of PD patients become demented over the long course of the illness. Although duration of the disease and advanced age have been identified as risk factors, some patients experience cognitive impairment relatively soon after the disease strikes, while others won’t experience dementia until the very end of their disease. And nearly 20 percent of patients never have dementia.

In the study, PD patients with EGF levels in the lowest range were eight times more likely to develop dementia, half of this group had dementia after 14 months. Cognitive follow-up data from the second set of patients, the replication group, will be available in 2012, to see if this pattern continues.

The most efficient and cost-effective way to test a drug that could preserve cognition in PD is to identify the most at-risk population for a clinical trial and evaluate the effect of the drug in a short timeframe. The EGF assay was designed to be broadly useful in clinical practice, and if validated, it could be used to select Parkinson patients for clinical trials.

“A test for cognitive impairment in PD could not only help patients in planning their futures, but by selecting patients at the greatest risk, we could significantly reduce the amount of time it would take to determine whether new drugs work,” said senior author John Q. Trojanowski, MD, PhD, director of the Penn Udall Center and co-director at Penn’s Center for Neurodegenerative Disease Research.

The EGF study was supported by the Penn-Pfizer Alliance – a peer-reviewed grant process sponsored by Pfizer and administered by Penn – and funding from the National Institutes of Health and the Marian S. Ware Alzheimer Program. Dr. Chen-Plotkin is also supported by a Burroughs Wellcome Fund Career Award for Medical Scientists and the Benaroya Fund.

More information: The EGF blood test is not currently available, except in select research studies aimed at replicating and potentially verifying these findings. For patients interested in participating in the Biofluid Collection Research Program at the Penn Udall Center – which involves cognitive, motor and biofluid (i.e. blood, spinal fluid, DNA) tests – please contact Jacqueline Rick at 215-829-7778 or Jacqui.Rick(at)uphs.upenn.edu.

Provided by University of Pennsylvania School of Medicine

Gene therapy prevents memory problems in mice with Alzheimer's disease

Scientists at the Gladstone Institute of Neurological Disease (GIND) in San Francisco have discovered a new strategy to prevent memory deficits in a mouse model of Alzheimer's disease (AD). Humans with AD and mice genetically engineered to simulate the disease have abnormally low levels of an enzyme called EphB2 in memory centers of the brain. Improving EphB2 levels in such mice by gene therapy completely fixed their memory problems. The findings will be published in the November 28 issue of the journal Nature.

29 nov 2010--In both humans and mice, learning and memory requires effective communication between brain cells called neurons. This communication involves the release of chemicals from neurons that stimulate cell surface receptors on other neurons. This important process, called neurotransmission, is impaired by amyloid proteins, which build up to abnormally high levels in brains of AD patients and are widely thought to cause the disease. But how exactly these poisonous proteins disrupt neurotransmission is unknown.

"EphB2 is a really cool molecule that acts as both a receptor and an enzyme," said Moustapha Cisse, PhD, lead author of the study. "We thought it might be involved in memory problems of AD because it is a master regulator of neurotransmission and its brain levels are decreased in the disease."

To determine if low EphB2 levels actually contribute to the development of memory problems, the investigators used gene therapy to experimentally alter EphB2 levels in memory centers of mice.
Reducing EphB2 levels in normal healthy mice disrupted neurotransmission and gave them memory problems similar to those seen in AD. This finding suggests that the reduced EphB2 levels in AD brains contribute to the memory problems that characterize this condition.

"What we were most curious about, of course, was whether normalizing EphB2 levels could fix memory problems caused by amyloid proteins," said Lennart Mucke, MD, director of the GIND and senior author of the study. "We were absolutely thrilled to discover that it did."

Increasing EphB2 levels in neurons of mice engineered to produce high levels of human amyloid proteins in the brain prevented their neurotransmission deficits, memory problems and behavioral abnormalities. The scientists also discovered that amyloid proteins directly bind to EphB2 and cause its degradation, which helps explain why EphB2 levels are reduced in AD and related mouse models.

"Based on our results, we think that blocking amyloid proteins from binding to EphB2 and enhancing EphB2 levels or functions with drugs might be of benefit in AD." said Mucke. "We are excited about these possibilities and look forward to pursuing them in future studies."

Provided by Gladstone Institutes

New device may reduce swallowing health risk in patients with Parkinson's disease

Speech pathologist Christine Sapienza (right) helps patient Lou DeLaney use an Expiratory Muscle Strength Training device at the UF Speech and Hearing Center on Sept. 29, 2010. New UF research shows that EMST therapy can improve swallowing function in patients with Parkinson’s disease.

28 nov 2010-- A hand-held device that strengthens the muscles involved in swallowing can address a serious symptom of Parkinson's disease, according to a new University of Florida study.

In what researchers believe is the largest randomized trial of a behavioral swallowing treatment in patients with Parkinson’s disease, scientists found that about one-third of the volunteers who used the device improved their ability to swallow. The findings appear in the Nov. 23 issue of the journal Neurology, the medical journal of the American Academy of Neurology.

Nearly 1 million Americans have Parkinson’s disease, according to the Parkinson’s Disease Foundation. Finding solutions to their swallowing problems is important because their most common cause of death is pneumonia caused by inhaling foreign material, such as food, during swallowing.

“The many muscles involved in swallowing progressively weaken in patients with Parkinson’s disease and become uncoordinated in the same way that patients lose coordination and strength in their arms and legs,” said Michelle Troche, the study’s lead investigator and a clinical lecturer and speech pathologist in the UF College of Public Health and Health Professions’ department of speech, language and hearing sciences.

It also becomes more difficult for patients to sense material in their airways and cough hard enough to expel it, she said.

For the study, researchers trained participants with Parkinson’s disease to exhale into an Expiratory Muscle Strength Training, or EMST, device. In previous studies, EMST has improved swallowing and cough function in patients with multiple sclerosis and in elderly, sedentary adults.

“EMST uses the basic exercise theory behind any strength training program,” said co-investigator Christine Sapienza, a professor and chairwoman of the department of speech, language and hearing sciences. “This small device capitalizes on that concept of overload with a calibrated pressure release valve that won’t open until you generate a great enough lung pressure. The patient or clinician can vary how much pressure is needed to open the valve on the device. The greater the pressure you need, the stronger the muscles have to be. It acts much like a pin on a weight machine and uses the same concept to strengthen the muscles involved in swallowing and breathing.”

Sapienza developed the device along with UF researchers Paul Davenport, a professor and interim chairman of the department of physiological sciences in the College of Veterinary Medicine, and A. Daniel Martin, a professor in the department of physical therapy.

“Their efforts are pioneering and it is likely that this study will stand the test of time as a landmark in Parkinson’s disease swallowing research,” said research collaborator Dr. Michael Okun, a co-director of UF’s Movement Disorders Center and an associate professor of neurology with the College of Medicine and UF’s McKnight Brain Institute.

Participants in the Parkinson’s disease study were divided into two groups of 30. In one group participants used the EMST device with proper calibration. The other participants used a device that looked exactly the same but did not work to strengthen the muscles. Neither the participants nor the study therapists knew who had the real device and who had the sham device. Participants used the devices in their homes for 20 minutes a day, five days a week for four weeks. Therapists visited once a week to make sure participants used the device correctly. Following the study period, participants in the sham group received the EMST treatment.

The researchers measured participants’ swallowing function before and after treatment with a standardized swallow safety scale, the Penetration-Aspiration scale, developed in part by UF faculty member John Rosenbek, also with the department of speech, language and hearing sciences. Researchers used videofluoroscopy to obtain motion X-ray images of the participants’ swallowing muscles as they swallowed liquid.

One-third of participants who used the device with calibration had significantly improved swallow safety scores compared to 14 percent of the participants in the sham group. The researchers also found that for patients in the treatment group, there was greater movement in the muscles that lift the voice box out of the way during swallowing. Quality-of-life measures related to swallowing improved in both the treatment and sham groups.

“The fact that EMST is a home-based treatment is of particular importance as many individuals with Parkinson’s disease cannot travel the long distance to attend clinic or hospital therapy sessions,” said Stephanie Daniels, a visiting associate professor at the University of Houston and an assistant professor at Baylor College of Medicine, who was not involved in the study. “Very few swallowing treatment studies have incorporated the rigorous research design used in this study. We need more studies such as this to support the different treatment approaches used in swallowing rehabilitation.”

Sapienza has a potential financial interest in Aspire Products LLC, the manufacturer of EMST. Portions of the study were funded by the Veterans Affairs Rehabilitation Research and Development, the Michael J. Fox Foundation and the National Institutes of Health. The UF Movement Disorders Center receives support from the National Parkinson Foundation Center of Excellence.

Provided by University of Florida

Half of Americans will be diabetic or pre-diabetic by 2020

26 nov 2010-- A recent study by US health insurance giant UnitedHealth Group Inc. predicts that by 2020 over half of Americans will have either pre-diabetic conditions or type 2 diabetes if current trends continue, and the annual cost will be around $500 billion a year by the end of the decade, or one tenth of all health care spending. The estimate for 2010 is $194 billion.

The cost of healthcare in the US for non-diabetics was $4,400 per person in 2009, and $11,700 for diabetics. For those with complications arising from the disease the cost is around $20,700 per year. If the predicted rise in the incidence of diabetes eventuates, the total cumulative cost to the US health care system may be as high as $3.35 trillion, with over 60 percent paid for by the government. However, the report offers a number of suggestions, which if adopted could save as much as $250 billion over the next decade.

The United Health Group report said around 27 million Americans are estimated to have diabetes and as many as another 67 million may have undiagnosed pre-diabetic conditions. These figures differ from those issued in October by the US government’s Centers for Disease Control and Prevention, which estimated at least 32 million American adults have diabetes and the number of cases will more than double by 2050.

Complications of diabetes can include circulatory problems (sometimes leading to limb amputations), nerve damage, kidney disease, blindness, and it is a major contributor to heart disease and strokes. Pre-diabetes symptoms include high blood sugar levels, high blood pressure and high cholesterol levels, but the symptoms may not be obvious.

The report was titled: “The United States of Diabetes: Challenges and Opportunities in the Decade Ahead” and was produced for the National Diabetes Awareness month in November. It emphasizes the predicted rise in incidence of diabetes and related costs is not inevitable if measures are taken urgently to address the problem.

Diabetes is a progressive disease with people developing pre-diabetes many years before diabetes. This means there are many intervention possibilities that can prevent pre-diabetic people from developing the disease.

Type 2 diabetes is strongly associated with being seriously overweight or obese, and in the US the report estimates 68.3 percent of Americans were overweight or obese in 2008, with this figure rising each year. For people with pre-diabetes the odds of developing diabetes are considerably reduced if they reduce their weight by five percent or more and increase their levels of physical activity.

Simon Stevens, who is chairman of the UnitedHealth Center for Health Reform & Modernization and executive vice president of UnitedHealth Group, said what is needed now is “concerted, national, multi-stakeholder action.” He said some of the most promising preventive care models should be scaled up, and health plans should be developed to “engage customers in new ways.” The benefits to the US, both in economic and human terms, will be substantial if the steep rise can be averted.

More information: http://www.unitedh … 9dfdc97cedc5

Retirement reduces tiredness and depression

Retirement leads to a substantial reduction in mental and physical fatigue and depressive symptoms, finds a study published in the British Medical Journal today. However, the research also concludes that retirement does not change the risk of major chronic illnesses such as respiratory disease, diabetes and heart disease.

25 nov 2010--The authors, led by Dr Hugo Westerlund from Stockholm University, say their research findings have important implications given that people will be working for longer and retiring later in life.

Retirement is a major life transition, says the study. But the results of various studies investigating the health effects of retirement have been inconsistent with some suggesting a beneficial effect and others concluding the reverse.

This large scale population based study is ground-breaking as it observes participants for a long period of time (15 years) and for 7 years prior to retirement and 7 years post retirement. The research is based on almost 190,000 observation years.

The participants were drawn from a large French cohort study and included 11,246 men and 2,858 women who were surveyed annually from 1989 to 2007. The researchers argue that "a major strength of this study is that it is based on repeated yearly measurements over an extended time period."

Most participants were married (89%) and belonged to higher or middle employment grades. They all retired on a statutory basis - 72% between the ages of 53 and 57 inclusive - and all participants had retired by the age of 64. In the year before retirement, one in four (25%) participants had suffered from depressive symptoms and 728 (7%) were diagnosed with one or more of the following: respiratory disease, diabetes, heart disease or stroke.

Unmarried respondents and those in low employment grades had higher odds of physical (but not mental) fatigue.

The results show that retirement is linked with a substantial decrease in both mental and physical fatigue, with a smaller but significant decrease in depressive symptoms. However, the research also shows there is no association between retirement and chronic disease. As expected, say the authors, these diseases gradually increased with age.

The authors believe there are a number of explanations for the findings: "if work is tiring for many older workers, the decrease in fatigue could simply reflect removal of the source of the problem ... furthermore, retirement may allow people more time to engage in stimulating and restorative activities, such as physical exercise," they write.

They conclude that their research results "indicate that fatigue may be an underlying reason for early exit from the labour market and decreased productivity, and redesign of work, healthcare interventions or both may be necessary to enable a larger proportion of older people to work in full health."

In an accompanying editorial, Alex Burdorf, a professor in the determinants of public health in the Netherlands, says the study "is unique in that annual health measurements were carried out several years before and after retirement."

Burdorf believes further research is needed to corroborate the findings as they contradict other studies and says "it is too early to make definite claims about positive and negative benefits from retirement at a particular age." The author agrees, however, that efforts are needed to improve and adapt working conditions "to help elderly workers maintain good health."

Provided by British Medical Journal

3 big developments make AIDS outlook more hopeful

24 nov 2010-- In the nearly 30 years the AIDS epidemic has raged, there has never been a more hopeful day than this. Three striking developments took place Tuesday: U.N. officials said new HIV cases are dropping dramatically worldwide. A study showed that a daily pill already on pharmacy shelves could help prevent new infections in gay men. And the pope opened the way for the use of condoms to prevent AIDS.

"I don't know of a day where so many pieces are beginning to align for HIV prevention and treatment, and frankly with a view to ending the epidemic," said Mitchell Warren, head of the AIDS Vaccine Advocacy Coalition, a nonprofit group that works on HIV prevention research. "This is an incredibly opportune moment and we have to be sure we seize it."

President Barack Obama said the groundbreaking research on the AIDS drug "could mark the beginning of a new era in HIV prevention."

The U.N. report said that new cases dropped nearly 20 percent over the last decade and that 33.3 million people are living with HIV now.

"We can say with confidence and conviction that we have broken the trajectory of the AIDS pandemic," said UNAIDS Executive Director Michel Sidibe in Geneva.

Health officials credit part of the decline to wider condom use, and on Tuesday, in a historic shift in church teachings, the Vatican said that using a condom is a lesser evil than infecting a sexual partner with HIV.

Condoms remain the best weapon against AIDS, and the new prevention pill is not the chemical equivalent. But scientists called it a true breakthrough. The pill, Gilead Science's Truvada, is already used to treat people with HIV. A three-year global study found that daily doses cut the risk of infection in healthy gay and bisexual men when given with condoms, counseling and other prevention services.

The drug lowered the chances of infection by 44 percent, and by 73 percent or more among men who took their pills most faithfully. Researchers had feared the pills might give a false sense of security and make men less likely to use condoms or to limit their partners, but the opposite happened - risky sex declined.

The results are "a major advance" that can help curb the epidemic in gay men, said Dr. Kevin Fenton, AIDS prevention chief at the U.S. Centers for Disease Control and Prevention. But he warned they may not apply to people exposed to HIV through male-female sex, drug use or other ways. Studies in those groups are under way.

Because Truvada is already on the market, the CDC is rushing to develop guidelines for doctors who want to use it to prevent HIV, and urged people to wait until those are ready.

As a practical matter, price could limit use. The pills cost $5,000 to $14,000 a year in the United States, but roughly $140 a year in some poor countries where they are sold in generic form.

Whether insurers or government health programs should pay for them is one of the tough issues to be sorted out, said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases.

"This is an exciting finding," but it "is only one study in one specific study population," so its impact on others is unknown, Fauci said.

His institute sponsored the study with the Bill & Melinda Gates Foundation. The findings were published online by the New England Journal of Medicine.

It is the third AIDS prevention victory in about a year. In September 2009, scientists announced that a vaccine they are now trying to improve protected 1 in 3 people from getting HIV in a study in Thailand. In July, research in South Africa showed that a vaginal gel spiked with an AIDS drug could cut nearly in half a woman's chances of getting HIV from an infected partner.

Gay and bisexual men account for nearly half of the more than 1 million Americans living with HIV. Worldwide, more than 7,000 new infections occur each day. Only 5 to 10 percent of global cases involve sex between men.

"The condom is still the first line of defense," because it also prevents other sexually spread diseases and unwanted pregnancies, said the study leader, Dr. Robert M. Grant of the Gladstone Institutes, a private foundation affiliated with the University of California, San Francisco. But many men don't or won't use condoms all the time, so researchers have been testing other prevention tools.

AIDS drugs already are used to prevent infection in health care workers accidentally exposed to HIV, and in babies born to infected mothers. Taking these drugs before exposure to the virus may keep it from taking hold, just as taking malaria pills in advance can prevent that disease when someone is bitten by an infected mosquito.

The strategy showed great promise in monkey studies using tenofovir (brand name Viread) and emtricitabine, or FTC (Emtriva), sold in combination as Truvada by California-based Gilead Sciences Inc.

The company donated Truvada for the study, which involved about 2,500 men at high risk of HIV infection in Peru, Ecuador, Brazil, South Africa, Thailand and the United States (San Francisco and Boston). The foreign sites were chosen because of high rates of HIV infection and diverse populations.

More than 40 percent of participants had taken money for sex at least once. At the start of the study, they had 18 partners on average; that dropped to around six by the end.

The men were given either Truvada or dummy pills. All had monthly visits to get HIV testing, more pills and counseling. Every six months, they were tested for other sexually spread diseases and treated as needed.

After a median follow-up of just over a year, there were 64 HIV infections among the 1,248 men on dummy pills, and only 36 among the 1,251 on Truvada.

Among men who took their pills at least half the time, the risk of infection fell by 50 percent. For those who took pills on 90 percent or more days, risk fell 73 percent. Tests of drug levels in the blood confirmed that more consistent pill-taking gave better protection, and in one subgroup, the reduction in risk was 92 percent.

The treatment was safe. Side effects were similar in both groups except for nausea in the Truvada patients. Weight loss also was more common in the drug group, but it occurred in very few. Further study is needed on possible long-term risks.

All participants will get a chance to take Truvada in an 18-month extension of the study to see if men will take the pill more consistently if they know it helps, and whether that provides better protection. About 20,000 people are enrolled in other studies testing Truvada or its component drugs around the world.

The government will review all ongoing prevention studies, such as those of vaccines or anti-AIDS gels, and consider whether people getting dummy medicines should now get Truvada since it has been shown effective in gay men.

Gilead may seek approval to market Truvada for prevention, said Dr. Howard Jaffe, president of the company's philanthropic arm. Doctors can prescribe it for this purpose now if patients are willing to pay for it, and some already do.

Some people have speculated that could expose Gilead to new liability concerns, if someone took the pill and then sued if it did not prevent infection.

"The potential for having an intervention like this that has never been broadly available before raises new questions. It is something we would have to discuss internally and externally," Jaffe said.

Until the CDC's detailed advice on Truvada is available, the agency said gay and bisexual men should use condoms consistently and correctly, get tested and treated for HIV and other sexually transmitted diseases, get counseling and reduce their number of sexual partners.

More information:
CDC advice: http://www.cdc.gov … stp/newsroom

AIDS information: http://www.aidsinfo.nih.gov

and http://www3.niaid. … ics/HIVAIDS/

Pill study: http://www.iprexnews.com

Journal: http://www.nejm.org

UNAIDS: http://tinyurl.com/krq7kr

Prevention efforts: http://www.avac.org

The not-so-sweet truth about sugar : a risk choice?

More and more people have become aware of the dangers of excessive fructose in diet. A new review on fructose in an upcoming issue of the Journal of the American Society of Nephrology (JASN) indicates just how dangerous this simple sugar may be.

23 nov 2010--Richard J. Johnson, MD and Takahiko Nakagawa, MD (Division of Renal Diseases and Hypertension, University of Colorado) provide a concise overview of recent clinical and experimental studies to understand how excessive amounts of fructose, present in added sugars, may play a role in high blood pressure, diabetes, obesity, and chronic kidney disease (CKD).

Dietary fructose is present primarily in added dietary sugars, honey, and fruit. Americans most frequently ingest fructose from sucrose, a disaccharide containing 50% fructose and 50% glucose bonded together, and high fructose corn syrup (HFCS), a mixture of free fructose and free glucose, usually in a 55/45 proportion. With the introduction of HFCS in the 1970s, an increased intake of fructose has occurred and obesity rates have risen simultaneously.

The link between excessive intake of fructose and metabolic syndrome is becoming increasingly established. However, in this review of the literature, the authors conclude that there is also increasing evidence that fructose may play a role in hypertension and renal disease. "Science shows us there is a potentially negative impact of excessive amounts of sugar and high fructose corn syrup on cardiovascular and kidney health," explains Dr. Johnson. He continues that "excessive fructose intake could be viewed as an increasingly risky food and beverage additive."

Concerned that physicians may be overlooking this health problem when advising CKD patients to follow a low protein diet, Dr. Johnson and Dr. Nakagawa recommend that low protein diets include an attempt to restrict added sugars containing fructose.

More information: The article, entitled "The Effect of Fructose on Renal Biology and Disease," will appear online on November 29, 2010

Provided by American Society of Nephrology