It's a pain to take care of pain

While many studies have looked at the treatment of chronic pain from the patient's perspective, there has been little research on those who provide care for chronic pain.

23 dec 2010--In a study in the November 2010 issue of the journal Pain Medicine, researchers from the Regenstrief Institute, the Indiana University School of Medicine, the IU School of Liberal Arts and the Roudebush VA Medical Center report that chronic pain takes a toll on primary care providers as well as their patients. They conclude that providers' needs should not be ignored if pain care is to be improved.

Most chronic pain is treated by primary care providers and necessitates frequent interactions with the patient. In this study the researchers surveyed 20 primary care providers (15 physicians, four nurse practitioners and one pharmacist) with varying clinical experience in the Roudebush VA Medical Center in Indianapolis. All 10 men and 10 women were asked open-ended questions designed to elicit their experiences with chronic pain management.

"Many providers criticized themselves because they felt unable to treat chronic pain effectively. Many internalized their lack of success with pain treatment, felt stress, and had guilty feelings. These negative feelings were compounded by hostile interactions with some patients, suspicions and distrust of some patients, especially those they suspected might be seeking pain medications for uses other than pain control, or to sell," said study first author Marianne Matthias, Ph.D., a Regenstrief Institute investigator, adjunct assistant professor of communication studies in the IU School of Liberal Arts and a research scientist at the Roudebush VA Medical Center.

Unlike other symptoms, such as elevated blood pressure or cholesterol readings, pain is subjective without any objective tests to confirm. One individual might rate pain a four on a one to 10 pain scale; another might label the same degree of pain a six or a seven. While high blood pressure and cholesterol often can be lowered with medication; successful treatment of chronic pain -- especially pain for which there is no known cause -- can be elusive, which is frustrating to both patients and care providers and can put a strain on their relationship, which can ultimately impact both patients' and providers' well-being.

"The providers often described dread when seeing a patient's name on their clinic schedule, knowing the interaction was going to be unsuccessful at best, difficult or hostile at worst. They described feeling ineffective and unsuccessful in their ability to treat many of their patients with pain. Interestingly, reports of frustration and negative experiences were present throughout the sample. Even those who were generally positive about their relationships with their patients reported difficulties, distrust and other relational issues at times," said Dr. Matthias, who is a health services researcher.

One provider interviewed said, "I beat myself up with it…You want to be liked by your patients. You want to be respected by your peers. You don't want to personally feel like you are being Cruella Deville by denying taking them out of pain. Of course, you want to relieve their pain, so I beat myself up. I feel guilty when these people end up yelling at me, and they do."

The study authors conclude that strategies to ease frustrations and defuse potential hostility in clinical interactions will ultimately improve pain management from the perspectives of both patients and providers. However they also note that potential solutions to difficulties in chronic pain care extend beyond the individual provider. The culture of the organizations -- for example if there is pressure to prescribe or not to prescribe opioids for chronic pain -- in which providers practice play an important role in providers' experiences, potentially making a difference in relationships with chronic pain patients.

"As an internist who frequently treats patients with chronic pain, I know how debilitating and disheartening chronic pain can be for patients. Clinicians need to work with their patients to give them hope that effective treatment of pain is possible," said the paper's senior author, Matthew Bair, M.D., a Regenstrief Institute investigator, assistant professor of medicine at the IU School of Medicine and a research scientist at the Roudebush VA Medical Center.

Provided by Indiana University School of Medicine

Exercise and vitamin D help to prevent falls in seniors

22 dec 2010-- A systematic review of over 50 clinical trials finds that exercise and Vitamin D supplements are the best ways to reduce the risk of falling in people aged 65 and over. The review is published in the December 21 issue of Annals of Internal Medicine and was commissioned by the US Preventive Services Task Force. A researcher at the Drexel University School of Public Health worked with colleagues at the Kaiser Permanente Center for Health Research, which is part of the Oregon Evidenced-based Practice Center, to conduct the study.

“Our evidence review shows that exercise and Vitamin D supplementation are the most effective primary care interventions to prevent falls,” said Yvonne L. Michael, ScD, MS, an associate professor at the Drexel University School of Public Health and lead review author of the report. “This is important news because falls are extremely common in this population and they are the leading cause of death and injury for the elderly. We need to help primary care clinicians find better ways to prevent falls, and this review will help to do that.”

Michael and her colleagues evaluated 18 clinical trials of exercise and physical therapy involving nearly 4,000 people who were aged 65 or older. Some of the trials involved group exercise or Thai Chi classes; others involved individualized exercise instruction at home. There were a variety of exercises included but most were aimed at improving gait, balance, strength and flexibility needed to do everyday activities. The interventions ranged from six weeks to 12 months or longer and the evaluation periods lasted up to 18 months after the programs ended. When taken individually most of these trials showed no statistical difference, but when the results were pooled together the exercisers had a 13 percent lower risk of falling compared to those who did not exercise.

For the review of Vitamin D supplementation researchers evaluated nine clinical trials involving nearly 6,000 participants who received daily oral doses of Vitamin D with or without calcium. The dosage ranged from 10 to 1,000 IU’s per day, in one trial participants received a larger single intramuscular injection of 600,000 IU’s of Vitamin D. The trials lasted from eight weeks to three years. Follow up periods ranged from six to 36 months. Participants who received Vitamin D had a 17 percent reduced risk of falling, compared to participants who did not receive Vitamin D.

Other interventions that addressed single risk factors including vision correction, medication assessment, home hazard modification, and education and behavioral counseling did not significantly reduce the risk of falling in the elderly. Interventions that provided comprehensive risk assessment and management did reduce the risk of falling by 11 percent. In these trials—called multifactorial assessment and management interventions—healthcare providers evaluated and managed multiple risk factors including medication use, visual problems, home environment and gait and balance issues. In many of the successful trials, home health nurses or case managers developed an individual tailored approach specifically for that participant. For example, the nurse might conduct a home visit to remove obstacles, help the patient enroll in an exercise class to improve balance, and help the patient get in to see an ophthalmologist to address a vision problem.

Michael received her ScD in epidemiology and health and social behavior from the Harvard School of Public Health, master of science degree in health and social behavior from the Harvard School of Public Health and bachelor of arts degree in government from the College of William and Mary. Her research areas include the impact of social characteristics of communities and individuals on population health, particularly as it relates to active aging, women’s health and health disparities.

Provided by Drexel University

PSA test better predicts cancer in men taking prostate-shrinking drug

The PSA screening test for prostate cancer is not perfect. It can indicate cancer when none is present and miss life-threatening tumors. But a new study suggests the test is more reliable in men taking dutasteride , a drug widely prescribed to shrink an enlarged prostate gland.

21 dec 2010--Dutasteride lowers PSA levels by about half within six months. But the researchers found that even a slight rise in PSA levels among men taking the drug was a stronger indicator of prostate cancer, particularly aggressive tumors that require early diagnosis and treatment, than rising PSA levels in men who took a placebo.

"Dutasteride stabilizes the amount of PSA that comes from enlarged prostates and low-grade cancers," says lead author Gerald Andriole, MD, the Robert Killian Royce, MD, Distinguished Professor and chief of urologic surgery at Washington University School of Medicine in St. Louis. "This enhances a rising PSA's ability to detect high-grade cancers that require early diagnosis and treatment, while reducing the discovery of tumors that are unlikely to cause harm if left untreated."

The study is now available online and will be published in January in the Journal of Urology.

The PSA test measures the amount of prostate-specific antigen in the blood. The larger a man's prostate, the more PSA he produces. Elevated levels can point to cancer. But PSA often rises naturally as men age, mainly due to benign prostatic hyperplasia (BPH), a progressive enlargement of the prostate. This leads to many false positive PSA tests for cancer. Indeed, biopsies only find cancer in about one in four men with an elevated PSA.

In the new study, the researchers looked more closely at data from a four-year trial that evaluated whether dutasteride could reduce the risk of detecting prostate cancer in men with an increased risk of the disease. The study involved 8,231 men ages 50-75 who were randomly assigned to receive a placebo or a daily 0.5 mg dose of dutasteride. The men had elevated PSA levels (2.5 ng/ml-10 ng/ml) but no evidence of cancer on biopsies performed within six months of enrolling in the trial.

Results published earlier this year in the New England Journal of Medicine showed that dutasteride reduced the risk of a prostate cancer diagnosis by 23 percent. Dutasteride appears to keep tumors small or shrink them to the point that they are less likely to be detected by a biopsy, says Andriole, who led the steering committee that oversaw the earlier trial.

In the current analysis, the researchers looked at the performance of PSA as a marker for prostate cancer, particularly for aggressive cancer. Among men taking dutasteride, the investigators found that any subsequent rise in PSA levels over the course of the study was more likely to be linked to aggressive, high-grade tumors (Gleason score 7-10), compared to rising PSA levels in men on a placebo.

The Gleason scoring system measures tumor aggressiveness based on biopsy results and can range from 2-10, with 10 being the most aggressive.

"If a man is taking dutastride and his PSA level starts to rise, he has a higher chance of having an aggressive cancer," Andriole says. "This makes PSA a more effective screening tool for prostate cancer but even more importantly for aggressive cancer."

Over four years, PSA levels increased in 72 percent of men taking a placebo and only 29 percent of men taking dutasteride, the data show. However, there was no significant difference in high-grade tumors between the two groups.

Men taking dutasteride were almost twice as likely to have aggressive prostate cancer if their PSA levels rose, compared to men whose PSA levels went up while taking a placebo. In men with any increase in PSA, aggressive, high-grade tumors were diagnosed in 13.2 percent of those on dutasteride and 7.7 percent of those taking a placebo.

Even a slight rise in PSA levels was a more accurate predictor of aggressive tumors. Among men whose PSA levels increased one point or less, 10.3 percent of those taking dutasteride had aggressive cancer, compared with 5.4 percent taking a placebo.

That trend also held for larger increases in PSA levels. Among men whose PSA levels rose two points or more, nearly 20.9 percent of those taking dutasteride had aggressive cancer, compared with 9.8 percent taking a placebo.

In contrast, PSA levels tended to decrease or remain stable in men taking dutasteride who either had low-grade tumors or no cancer at all.

The study's authors do not suggest that men take dutasteride just to get a more accurate readout of PSA levels attributable to cancer. "However, men who are taking dutasteride can be confident that the drug does not weaken the ability of PSA to find cancer if it develops," Andriole says. "Rather, the drug enhances the ability to find cancer if PSA levels are rising."

More information: Andriole GL, Bostwick D, Brawley OW, Gomella L, Marberger M, Montorsi F, Pettaway, Tammela TLJ, Teloken C, Tindall D, Freedland SJ, Somerville MC, Wilson TH, Fowler I, Castro R, Rittmaster RS. The effect of dutastride on the usefulness of prostate specific antigen for the diagnosis of high grade and clinical relevant prostate cancer in men with a previous negative biopsy: Results from the REDUCE study. Journal of Urology, January 2011.

Provided by Washington University School of Medicine

High levels of 'good' cholesterol may be associated with lower risk of Alzheimer's disease

High levels of high-density lipoprotein (HDL), also known as "good" cholesterol, appear to be associated with a reduced risk for Alzheimer's disease in older adults, according to a report in the December issue of Archives of Neurology.

20 dec 2010--"Dyslipidemia [high total cholesterol and triglycerides] and late-onset Alzheimer's disease are highly frequent in western societies," the authors write as background information in the article. "More than 50 percent of the U.S. adult population has high cholesterol. About 1 percent of people age 65 to 69 years develop Alzheimer's disease, and the prevalence increases to more than 60 percent for people older than 95 years."

Christiane Reitz, M.D., Ph.D., and colleagues at Columbia University's Taub Institute, New York, studied 1,130 older adults to examine the association of blood lipid (fat) levels with Alzheimer's disease. The study included a random sampling of Medicare recipients 65 or older residing in northern Manhattan, with no history of dementia or cognitive impairment. The researchers defined higher levels of HDL cholesterol as 55 milligrams per deciliter or more.

To determine this association, data were collected from medical, neurological and neuropsychological evaluations. Additionally, the authors assigned a diagnosis of "probable" Alzheimer's disease when onset of dementia could not be explained by any other disorder. A diagnosis of "possible" Alzheimer's disease was made when the most likely cause of dementia was Alzheimer's disease but there were other disorders that could contribute to the dementia, such as stroke or Parkinson disease.

During the course of follow-up, there were 101 new cases of Alzheimer's disease, of which 89 were probable and 12 were possible. The mean (average) age of individuals at the onset of probable and possible Alzheimer's disease was 83 years, and compared with people who were not diagnosed with incident Alzheimer's disease, those who did develop dementia were more often Hispanic and had a higher prevalence of diabetes at the start of the study. Higher plasma levels of HDL cholesterol were associated with a decreased risk of both probable and possible Alzheimer's disease, even after adjusting for vascular risk factors and lipid-lowering treatments. Although higher plasma total cholesterol, non-HDL cholesterol and LDL cholesterol levels also were associated with decreased risks of probable and possible Alzheimer's disease, these associations became non-significant after adjusting for vascular risk factors and lipid-lowering treatments.

"In this study, higher levels of HDL cholesterol were associated with a decreased risk of both probable and possible Alzheimer's disease," the authors conclude. "An important consideration in the interpretation of the results is that it was conducted in an urban multiethnic elderly community with a high prevalence of risk factors for mortality and dementia. Thus, our results may not be generalizeable to cohorts with younger individuals or to cohorts with participants with a lower morbidity [disease] burden."

More information: Arch Neurol. 2010;67[12]:1491-1497

Provided by JAMA and Archives Journals

Opioid use associated with increased risk of adverse events among older adults

Opioids appear to be associated with more adverse events among older adults with arthritis than other commonly used analgesics, including coxibs and non-steroidal anti-inflammatories, according to a report in the December 13/27 issue of Archives of Internal Medicine. In a second report assessing only opioid use, different types of drugs within the class were associated with different safety events among older patients with non-malignant pain.

19 dec 2010--"In the United States, one in five adults received a prescription for an analgesic in 2006, accounting for 230 million prescription purchases; however, the comparative safety of these drugs is unclear," the authors write as background information in one of the articles. "Although the cardiovascular safety of nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) and selective cyclooxygenase-2 inhibitors (coxibs) has been called into question, there is little comparable information about the third major analgesic group, opioids."

In the first report, Daniel H. Solomon, M.D., M.P.H., and colleagues at Brigham and Women's Hospital, Boston, examined the comparative safety of nsNSAIDs, coxibs and opioids among 12,840 Medicare beneficiaries who received at least one of these analgesics between 1999 and 2005. Using data from a large health care utilization (claims) database, the authors evaluated the occurrence of cardiovascular events (heart attacks, stroke and heart failure, among others), gastrointestinal events (GI tract bleeding and bowel obstruction), acute kidney injuries, toxic effects on the liver, as well as falls and fractures.

Opioid users experienced higher rates for most types of serious adverse events than patients taking coxibs or nsNSAIDs, and nsNSAID users experienced the lowest risks. For example, fractures occurred among 101 per 1,000 opioid users per year, compared with 19 per 1,000 per year among coxib users.

Coxibs and opioids appear to be associated with greater cardiac risks than nsNSAIDs, but use of opioids and not coxibs was associated with a greater risk of hospitalization or death than use of nsNSAIDs. Conversely, the risk of gastrointestinal tract bleeding was reduced among those taking coxibs (12 per 1,000 per year, compared with 21 per 1,000 per year among those taking nsNSAIDs).

"Analgesics are used daily by millions of people; however, current data do not allow patients or physicians to determine which type of agent is safest. We compared nsNSAIDs, coxibs and opioids across a wide range of specific safety events and several composite safety events," the authors write. "Although nsNSAIDs pose certain risks, these analyses support the safety of these agents compared with other analgesics. The recent concerns raised about opioid use in non-malignant pain syndromes appear warranted on the basis of these data."

In a second article, Dr. Solomon and colleagues at Brigham and Women's Hospital studied only those Medicare beneficiaries who received opioids for non-malignant pain between 1996 and 2005. They compared the rates of adverse events after 30 and 180 days among 6,275 patients each taking one of five types of opioids: codeine, hydrocodone, oxycodone, propoxyphene and tramadol.

The risk of gastrointestinal adverse events remained similar for all the medications studied, and thirty days after beginning opioid therapy, the risk of cardiovascular events was also similar across all types. However, after 180 days, the risk of cardiovascular events was increased among those taking codeine. With hydrocodone as the reference point, risk of fracture was 79 percent lower among those taking tramadol and 46 percent lower among those taking propoxyphene. Compared with those taking hydrocodone, death from any cause was 2.4 times as likely among those taking oxycodone and twice as likely among those taking codeine.

"This study's findings do not agree with a commonly held belief that all opioids are associated with similar risk," the authors write. "The risks were not explained by the dosage being prescribed and did not vary across a range of sensitivity analyses. The risks were substantial and translated into numbers needed to treat that would be considered clinically significant. Our findings regarding cardiovascular risk were surprising and require validation in other data sets."

Proving a cause-and-effect relationship between types of opioids and adverse events requires an experimental rather than observation study design, they note, "but these results should prompt caution and further study."

In addition, a research letter, published in the same issue, found double the risk of cardiovascular events among patients followed for a median (midpoint) of 189 days after they stopped taking the analgesic drug rofecoxib during off-drug follow-up of a clinical trial. Joseph S. Ross, M.D., M.H.S., of Yale University School of Medicine, and colleagues analyzed data from a clinical trial that became available through litigation. Twenty-two cardiovascular events and 23 deaths occurred among patients who had taken rofecoxib in the trial, compared with six cardiovascular events and nine deaths among participants who took placebo.

More information: Arch Intern Med. 2010;170[22]:1968-1978, 1979-1986, 2035-2036.

Provided by JAMA and Archives Journals

Vitamin D and parathyroid hormone levels may not affect cardiovascular mortality

There is burgeoning public interest in possible wide-ranging health benefits from vitamin D, including cardiovascular health. In a study published in the December 2010 issue of The American Journal of Medicine, investigators found that there was no independent association between serum levels of vitamin D or parathyroid hormone and cardiovascular mortality in this prospective study, the first in a population of older community-dwelling adults with a low prevalence of vitamin D deficiency and a broad range of kidney function.

18 dec 2010--Researchers collected data from the Rancho Bernardo study, which was established in 1972. Between 1997 and 1999, 1091 participants attended a follow-up visit where blood samples were collected, along with detailed surveys of medical history, medications, cigarette smoking, alcohol consumption, and exercise; serum levels of 25-hydroxyvitamin D (25[OH]D) (mean 42 ng/mL), 1,25-dihydroxyvitamin D (1,25[OH]2D) (median 29 pg/mL), and intact parathyroid hormone (median 46 pg/mL) were measured; mean estimated glomerular filtration rate (eGFR) was 74 mL/min/1.73 m2. Using data from 1073 participants who qualified for this study, these people were followed for a median of 6.8 years (maximum 10.7 years). During this period, there were 266 deaths, including 111 cardiovascular deaths. Of those 111, 71 had normal kidney function (eGFR > 60 mL/min/1.73 m2) and 40 had reduced kidney function (eGFR <>

In populations with chronic kidney disease, low levels of 25(OH)D and 1,25[OH]2D, and high levels of intact parathyroid hormone have been suggested to explain the association between chronic kidney disease and cardiovascular mortality. Even in people with intact kidney function, there are multiple mechanisms that could link Vitamin D and cardiovascular disease.

"To our knowledge, this is the first prospective study to investigate the role of serum 25[OH]D, 1,25[OH]2D, and intact parathyroid hormone in the prediction of cardiovascular mortality in a population of older community-dwelling adults with a low prevalence of vitamin D deficiency and a broad range of kidney function," commented Lead investigator Simerjot K. Jassal, MD, Division of General Internal Medicine and Geriatrics, Department of Medicine, University of California, San Diego, and VA San Diego Healthcare System, La Jolla.

Dr. Jassal continued, "After adjusting for age alone, there was no independent association between serum levels of 25(OH)D, 1,25(OH)2D, or intact parathyroid hormone and cardiovascular mortality. Prior published literature in community-dwelling adults suggests an increased risk of cardiovascular mortality only in individuals with vitamin D levels lower than levels observed here. Our null results may mean that only larger disruptions in levels of 25(OH)D and 1,25(OH)2D contribute to cardiovascular mortality. These null findings are also compatible with results from randomized clinical trials in which vitamin D supplementation has failed to prevent cardiovascular outcomes, although the doses of vitamin D in these trials may have been too low."

More information: The article is "Vitamin D, Parathyroid Hormone, and Cardiovascular Mortality in Older Adults: The Rancho Bernardo Study" by Simerjot K. Jassal, MD, Michel Chonchol, MD, Denise von Mühlen, MD, PhD, Gerard Smits, PhD, and Elizabeth Barrett-Connor, MD. It appears in The American Journal of Medicine, Volume 123, Issue 12 (December 2010)

Provided by Elsevier

Better spaces for older people

Urban planning needs to consider how older people use walking routes as well as public areas, concludes a Research Council UK-funded research project from the New Dynamics of Ageing Programme. Planning should include a smooth transition between walking, driving and using public transport and should take account of how older people navigate between these.

17 dec 2010--The research project 'Older People's Use of Unfamiliar Space' (OPUS) examined the strategies used by older people to find their way in unfamiliar spaces as pedestrians and users of public transport. As part of the research, older people were shown town scenes and pedestrian routes and gave feedback on signposting, ease of navigation and general impressions. Their heart rates were measured to monitor stress levels. Participants were also taken to a town centre to walk through the same routes in person.

Initial findings show:

• Signs are of limited use even in unfamiliar new areas – they were often positioned incorrectly or too high, and without indicating the distance to the destination;
  
• Designing outdoor spaces that are more easily navigable and walkable are important in making the environment less stressful and anxiety-inducing;
  
• Buildings and landmarks are particularly important as navigational aids, especially churches.

The research project also conducted interviews with spatial planners to examine how older people were included in the planning process. The responses indicated that older people are being increasingly engaged, not least through the Equality Impact Assessment where older people are represented as an important group. Planners considered that older people today have greater political awareness and power and were able to collaborate with the process. Efforts are currently made to make public spaces 'older person-friendly' as part of lifetime places guidelines – for instance the location and number of bus shelters, seating and public toilets. Older people's needs are also considered in relation to housing issues, such as location, neighbourhood considerations and land use requirements for special housing, and mechanisms to encourage older people to downsize.

However, the diversity of older people and their different needs are not fully recognised. Planning focus has tended to be on combating particular issues such as youth crime and problem drinking, or the mobility needs of elderly people. There is still a need to understand older people's various requirements in their use of space, reflecting their diversity and different backgrounds. While some are experienced travellers who are used to finding their way in unfamiliar spaces, others may suffer cognitive impairment which makes previously familiar areas unrecognisable and means they need different cues in their environment. Treating 'age' as a single category can therefore be unhelpful for planners in designing urban spaces, concludes the research.

"Older people are increasingly experiencing unfamiliar places through travel. Creating spaces that make the urban environment more friendly and pleasant will be ever more important to enable older people to remain independent," comments lead researcher Professor Judith Phillips. "The OPUS findings have significance for planners in redesigning town centres, allowing them to develop inclusive environments that have meaning for older people."

Provided by Economic & Social Research Council

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.