Healthcare News

The U.S. will spend an estimated $59 billion or more annually in 2033 to compensate disabled veterans, compared with $29 billion annually currently, according to internal Department of Veterans Affairs documents obtained by the Associated Press, the AP/Kansas City Star reports.

According to VA, while the number of total U.S. veterans is expected to decline from 24 million to 15 million in 2033, the annual cost — when factoring out inflation — of treating disabled veterans is expected to rise from $29 billion to $33 billion in today’s dollars, an increase of more than 10%. In addition, VA officials acknowledge the estimate could increase by 30%.

The decline in the total number of veterans is attributed to older veterans from World War II and Korea dying. However, the total number of disabled veterans has increased 25% since 2001 to 2.9 million, compared with a 4% increase during the six-year period before the wars in Iraq and Afghanistan began, according to data from the VA and U.S. Census Bureau. Advances in medical care are helping injured veterans from the Iraq and Afghanistan wars stay alive after “devastating injuries” that likely would have killed veterans from earlier wars, according to the AP/Star.

In addition, more veterans are aware of the benefits to which they are entitled, according to Steve Smithson, a deputy director at the American Legion. Smithson said, “It’s not like the WWII generation and Korean War generation, where they weren’t aware of what they could file for — and they were also reluctant to file if they didn’t think they needed it.” According to VA, of the 755,000 veterans of the Iraq and Afghanistan wars, more than 181,000 collect disability benefits.

Veterans are also living longer, and because payments increase as veterans age, individual veterans are costing VA more than they have in the past. According to VA, Vietnam War veterans constitute the largest group of veterans receiving disabilities payments, as many of their conditions worsen over the years, costing VA more money. According to the AP/Star, more than 947,000 Vietnam veterans were receiving disability payments at the end of 2007 (Kerr, AP/Kansas City Star, 5/11).

Suicide Rates

Rising suicide rates among veterans “is causing major concern among veterans’ groups and lawmakers,” the San Francisco Chronicle reports. An average of 18 U.S. veterans commit suicide daily, according to a recent CBS News report that has been confirmed by VA. According to the California Department of Public Health, in 2007, 21% of the 3,198 suicides in the state were veterans; however, veterans constituted 6% of California’s 37.1 million residents. Although causes for the rate increases are unknown, mental health professionals attribute them to post-traumatic stress disorder, which affects up to 30% of soldiers who served in Iraq and Afghanistan, according to the Chronicle.

According to VA spokesperson Kerri Childress, the department is increasing its prevention efforts by hiring more mental health care workers, creating a veteran suicide hotline and adding suicide prevention coordinators at all VA medical facilities (Koopman, San Francisco Chronicle, 5/12).

Healthcare News

There is an urgent need to improve end-of-life care for older people in the final stages of dementia, according to an international review published in the May issue of Journal of Clinical Nursing.

“We must act now to stop people with dementia from suffering from protracted, potentially uncomfortable and undignified deaths” says Jan Draper, Professor of Nursing for The Open University, UK.

“The management of dementia is becoming a major international public health concern because people are living longer which means that more people are likely to develop this disease.”

Professor Draper teamed up with Deborah Birch, a Clinical Nurse Specialist working with older people in Lincoln,UK, to review 10 years of published research. They carried out a detailed analysis of 29 studies, from the USA, UK, Canada, Israel, Switzerland, Ireland, the Netherlands, Sweden and Finland.

“Our review has reinforced the importance of providing appropriate palliative care to individuals suffering from end-stage dementia and clearly identified some of the barriers to extending such provision” says Professor Draper.

“These include concerns that such an expansion might lead to skills and funding shortages and, in turn, compromise the ability of existing palliative care teams to provide care to cancer patients, who tend to be the main recipients of this kind of care.

“We believe that clinicians and patient groups caring for patients with advanced dementia need to work together with specialist palliative care providers and health commissioners to develop, fund and evaluate appropriate cost-effective services that meet the needs of both patients and their families.

“If this is achieved, these improvements have the potential to increase people’s quality of life and reduce the amount of time they spend in acute hospitals.”

Birch and Draper say that the findings of their review indicate a number of ways that colleagues across healthcare disciplines can work together to enhance the quality of care they provide older people in the end stages of dementia. These include:

• Communicating the diagnosis of dementia in a sensitive way and indicating, as clearly as possible, how the disease is likely to progress.
• Acknowledging the potential influence that the individual beliefs and values of the healthcare team - such as difficult drug and treatment decisions - may have on the care provided.
• Improving and providing timely and accurate communication about key issues, including the role of advanced directives, such as living wills or do not resuscitate orders.
• Reconsidering aggressive medical treatments that have limited benefits and may cause further discomfort to dying patients.
• Encouraging professionals, carers and, where possible, patients to work together to plan appropriate care tailored to the needs of the individual.
• Reinforcing the need for multi-disciplinary ways of working.
• Reconsidering the most appropriate place to deliver end-of-life care.
• Acknowledging the right of all older people dying from end-stage dementia to have access to high-quality specialist palliative care services.

“Palliative care services are used to providing care for cancer patients, but high-quality care for people with end-stage dementia does not appear to be given the same priority” says Professor Draper.

“In the UK, for example, it has been a relatively neglected topic in relation to policy, planning, practice development and training.

“Population trends suggest that life expectancy is increasing and this will mean that more people are at risk of developing dementia, which affects one in 1,000 people under 65 but rises to one in five once people are over 85.

“Dementia is a progressive terminal illness for which there is currently no cure and patients dying from the disease have significant healthcare needs.

“Despite this, they are often denied the palliative care services that could improve their comfort and quality of life.”

http://www.blackwellpublishing.com/jcn

Disease/Infection News

A second outbreak of bird flu in Seoul, the capital of South Korea in less than a week has prompted the culling of all domestic fowl in the city.

The Ministry for Food, Agriculture, Forestry and Fisheries says a virulent strain of bird flu was confirmed in Songpa, southeastern Seoul and a suspected case was reported earlier in the day in Gyeongsan, North Gyeongsang Province.

The outbreak on a duck farm in Songpa is the second confirmed report of the H5N1 bird flu in the capital city following a case in the Gwangjin area last week.

The country has had a total of 67 bird flu reports since April 1st, with 40 having been confirmed as being caused by the virulent strain and 25 due to other diseases.

Since the beginning of April more than 7 million chickens and ducks have been slaughtered but even these stringent measures have not halted the spread of the deadly virus throughout South Korea faster than ever since the country’s first outbreak in 2003.

Officials say Seoul has slaughtered all the 15,000 chickens and ducks raised in the city as a pre-emptive measure following the outbreak at Songpa district which was confirmed on Monday and all birds raised on school premises have also been culled as a precautionary measure.

It was just last week that four birds raised in pens at a Seoul district government office in the eastern part of the city were found dead and tested positive for the avian flu virus and limited access to livestock markets and strict quarantine restrictions were then imposed.

The country’s first avian influenza outbreak between late 2003 and early 2004 meant the slaughter of 5.3 million birds and a second outbreak in 2007-2007 saw 2.8 million culled.

South Korea wants to increase it’s stockpile of vaccines such as Tamiflu and Relenza to sufficient levels to treat 2.5 million people, or 5 percent of the country’s population.

Disease/Infection News

The death toll in China from enterovirus 71 (EV71) has risen to 39 with the deaths of five more children; EV71 belongs to the same family as the polio virus and is a strain of hand, foot and mouth disease (HFMD).

While health officials claim the outbreak has been brought under control, children continue to be struck down with the deadly virus and as many as 27,500 cases of the disease have now been reported in China this year.

As health officials say more children are being discharged from hospital, a child died in eastern Anhui province on Thursday, another child died in southern Hainan province and three more have died in southern Guangdong.

According to the authorities new cases are declining in some of the worst affected areas such as Fuyang in the eastern Anhui province, where more than 5,000 cases and at least 23 deaths were reported; they say many who were critically ill have now recovered.

There is currently no vaccine for HFMD and while it is a common childhood illness, in the current outbreak it has been linked with enterovirus 71 (EV71), which can cause a severe form of the disease characterised by high fever, paralysis and meningitis.

HFMD causes symptoms including ulcers and blisters in the mouth, rashes on the hands and feet and fever and is spread mainly by EV71, but it can be caused by a number of other intestinal viruses.

As a rule most patients with HFMD, who are mainly infants and young children, recover within a week to 10 days.

The World Health Organization (WHO) says China’s efforts to curb the spread of infections is satisfactory .

Macao has had 99 reported cases of HFMD.

“You do not want to bring your children into the world where we go on with the number of children who are born with autism tripling every 20 years, and nobody knows why,” he said.

Even if the true prevalence of autism is increasing (which is highly debatable), it is not tripling every 20 years–nowhere near it. Again, the apparent increase in prevalence observed over the last two decades can be explained largely by increased awareness and diagnostic substitution. There is no autism epidemic.

The stupid, it burns.

Medical Studies/Trials

A St. Jude Children’s Research Hospital study shows that T cells, the body’s master immune regulators, do not use simple on/off switches to govern the cellular machinery that regulates their development and function. Rather, they possess sophisticated molecular controls that enable them to adjust their function with exquisite precision. Such subtle adjustment enables T cells to modulate their development and function, including avoiding autoimmunity.

In autoimmune disease, rather than attacking invading microbes, the immune system attacks the body’s own organs, tissues or cells. Some 80 autoimmune diseases are known, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis and lupus.

“Among the many mysteries surrounding autoimmune diseases is why they can sometimes take decades to manifest themselves,” said Dario Vignali, Ph.D., associate member in the St. Jude Department of Immunology. “Our findings hint that this delayed onset could be explained by subtle defects in the molecular controls on T cells.” Such T cells are white blood cells whose duties include shutting down the immune system when it has done its job and suppressing T cells that can attack the body.

Vignali is the senior author of a report on this work that appears in the advance online publication of the journal “Nature Immunology.”

The researchers explored the function of T cell receptors, proteins that span the cell membrane of T cells. These receptors receive outside signals that instruct T cells to develop, proliferate and transmit those signals into the cell. The St. Jude investigators sought to understand why T cell receptors need many copies of switch-like components called immunoreceptor tyrosine-based activation motifs (ITAMS). ITAMs are components of the CD3 adaptor proteins that attach to the T cell receptor and help transmit the control signals from the T cell receptor into the cell.

“The ITAMs we studied are little molecular tags inside the cell by which the T cell receptor communicates to the rest of the cell,” Vignali said. “The mystery we wanted to address was why the T cell receptor needs 10 ITAMs to do its job. Why not just have a simple on/off switch?”

To explore the role of multiple ITAMs, Jeff Holst, Ph.D., the paper’s first author and a St. Jude postdoctoral scientist, used a technique developed in the Vignali lab to produce mice whose T cells have variations in the number and type of functional ITAMs. The technique involved using a virus as a genetic cargo-carrier to transport genes for different combinations of normal and mutant non-functional ITAMs into the mouse cells.

The researchers found that reducing the number of normal ITAMs caused the mice to develop autoimmune disease. However, the investigators also found that some mice with fewer than normal functional ITAMs did not become sick with autoimmune disease. Vignali said this finding suggests that it is not just the number of ITAMs, but also their type that may influence T cell function.

“We theorized that there were two possibilities why the immune system needs so many ITAMs,” he said. “One is that the requirement was purely quantitative, and that the ITAMs were there for signal amplification. The second possibility is that different ITAMs do slightly different things-they do have slightly different structures, so maybe they bind to some signaling molecules better than others; and their positions in the T cell receptor are different. So, while our primary observation is that quantity is more important than ITAM type, we also found that type has some influence.”

The researchers’ analyses of the immune systems of the altered mice indicated that reducing the number of normal ITAMs crippled a process called “negative selection.” In this process, the immune system rids itself of immature T cells that might attack the body’s own cells, causing autoimmune disease. Vignali said that these findings might provide insight into how autoimmune diseases start.

“One implication of our findings is that a relatively small defect in the efficiency of signal transduction through the T cell receptor could give rise to a subtle failing in negative selection, which gives rise over a long period of time to a few overly active T cells that might initiate autoimmunity,” Vignali said. “Clearly from our studies there is the possibility that you don’t really need a very big reduction in T cell receptor signal strength to have a defect in negative selection.”

The study also showed that different T cell functions required different numbers of functional ITAMs. “We were surprised to find that many ITAMs were required to make T cells divide and expand, but only one or two was required to make T cells secrete cytokines,” Vignali said. Cytokines are soluble proteins used by cells of the immune system to communicate and send messages to one another. Vignali said these basic findings represent only the beginning of more detailed studies of the role of ITAMs in T cell function.

“We believe this idea that T cell signaling acts more like a rheostat than an on/off switch offers significant new insights into how T cell development and function is controlled,” Vignali said.

http://www.stjude.org/

Medical Studies/Trials

In both leukemia and solid tumors, there exists among the multitude of warrior cancer cells a small subgroup that work undercover, patiently lying in wait to launch their attacks. Known as either cancer initiating cells (CICs) or leukemia initiating cells (LICs), these stealth populations are impervious to conventional chemotherapy and undaunted by targeted cancer therapies. When a leukemia patient relapses following a period of remission, it is the LICs that bear responsibility for the disease’s reemergence.

The secret to the survival abilities of these cells has been unclear. But in a paradoxical discovery, a research team led by investigators at Beth Israel Deaconess Medical Center (BIDMC) has found that a tumor suppressor protein known as PML appears to be the factor that enables LICs to maintain their quiescence - the inert state that protects them from being destroyed by cancer therapies - and suggests that inhibition of PML is a promising target for new therapeutics.

Their findings, which appear in today’s advance on-line issue of the journal Nature, additionally demonstrate that PML can be degraded with an arsenic-based agent used in traditional Chinese medicine. Importantly, when combined with chemotherapy, the arsenic-based therapy — already proven safe and non-toxic in clinical trials — can successfully treat chronic myeloid leukemia.

“Leukemia initiating cells share many properties of normal hematopoetic stem cells,” explains senior author Pier Paolo Pandolfi, MD, PhD, Director of the Cancer Genetics Program in BIDMC’s Cancer Center and Professor of Medicine and of Pathology at Harvard Medical School. “They are pluripotent, they readily replicate and they can indefinitely remain in a dormant state of quiescence.”

Consequently, while the majority of leukemic cells are vulnerable to any cancer therapies - including chemotherapy and targeted cancer treatments - that destroy cells during active DNA replication, LICs, with their unique quiescent properties, resemble an automobile with an endless supply of fuel and a sturdy set of brakes: They sit quietly idling in place, waiting to reinitiate malignancy after a period of remission.

Pandolfi’s laboratory has been working to develop new therapeutic approaches to target LICs and thereby treat chronic myeloid leukemia (CML), one of the most extensively investigated of stem cell disorders. CML is typically treated with the targeted therapy imatinib (Gleevec), a tyrosine kinase inhibitor.

“Gleevec does dramatically improve prognosis of CML patients,” notes Pandolfi. “But, unfortunately, Gleevec is not curative in most cases. Because it targets only dividing cells, the pool of quiescent LICs are able to remain intact.” As a result, when Gleevec therapy is discontinued, the cancer almost inevitably relapses.

The investigators set out to analyze expression of PML, a tumor suppressor protein that controls fundamental processes such as apoptosis, cellular proliferation and senescence. PML is commonly associated with acute promyelocytic leukemia (APL), in which it leads to the formation of a fusion protein that blocks cell differentiation.

After ascertaining that PML was highly expressed in the LICs of a CML mouse model, Pandolfi’s team also determined that PML is highly expressed in blasts from CML patients and that low PML levels corresponded with patients’ increased response to therapy and overall survival rates.

“We then analyzed LIC function in the absence of PML and revealed that PML has an indispensable role in maintaining LIC quiescence,” he adds. “As a result, PML-deficient LICs grow exhausted over time, becoming incapable of generating CML in the transplanted animals.”

Lastly, the investigators examined the impact of As2O3, an arsenic-based therapy that targets PML for degradation and is currently used for the treatment of acute promyelocytic leukemia. As predicted, inhibition of PML by As2O3 successfully disrupted LICs, increasing the efficacy of the anti-cancer therapy by sensitizing the LICs to pro-apoptopic stimuli.

“It’s actually a very simple concept,” says Pandolfi. “Ninety percent of existing cancer treatments are antiproliferative agents - they target the pool of proliferative cells, leaving behind the dormant LICs.

“But in determining that PML serves to guard the LICs that have been left behind, we also discovered that if we knock out PML [through pharmacologic means], the LICs will lose their braking abilities and run out of gas, thereby commiting the fatal error of proliferation — and exposing themselves to the deadly effects of cancer therapies.”

Pandolfi’s laboratory is now trying to determine whether PML exerts a similar role in the stem cells of other tissues, as well as in the cancer initiating cells of solid tumors.

“If this turn out to be the case,” he adds, “the transient use of As2O3 may represent a more global strategy to target CICs in other forms of cancer.”

http://www.bidmc.harvard.edu/

Medical Studies/Trials

Losing a limb can be a traumatic experience and, in some cases, emotional and physical pain can linger for years. To better understand the phenomenon, dubbed “phantom limb syndrome,” Université de Montreal graduate student Emma Duerden is inviting amputees to come forward and share their experiences for a major study.

“Our main goal is to better understand why amputees retain the memory of pain after losing a limb,” explains Ms. Duerden, who is completing her doctorate in the laboratory of Dr. Gary Duncan at the Université de Montréal’s Department of Physiology and the Centre de recherche de l’Institut universitaire de gériatrie de Montréal (CRIUGM).

“People are born with a map of their body in their brain,” she continues. “After amputation, the representation of the body part still exists - as a type of sensory memory. The map of the body becomes distorted and previous research has shown that this ‘reorganization’ is linked to chronic pain. Our current goal is to study these organizational changes in the brain.”

Ms. Duerden and her team will use high-resolution imaging techniques to explore the organization of the sensory maps in the brains of amputees. They will utilize new brain imaging software called real-time fMRI, which allows subjects to view their own brain activity while undergoing a scan.

“We aim to develop techniques to help return amputees’ sensory map back to its original formation,” says Ms. Duerden. “We believe that patients can be trained to reorganize their internal map by focusing on their brain activity. This reorganization is believed to lead to a decrease in pain.”

http://www.umontreal.ca/

Medical Studies/Trials

Scientists at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the National Institutes of Health (NIH), demonstrate for the first time in a mouse model that skeletal muscle cells cultured in a low-calorie environment refrain from differentiating, an energy-demanding process by which cells mature and specialize.

They also describe for the first time the molecular pathway (the protein-signaling system by which cells read and react to their environment), involving the protein SIRT1 that becomes activated in mouse skeletal muscle cells when they receive fewer calories. The study appears in the May 13 issue of Developmental Cell.

The discovery of this molecular pathway in muscle is also of interest to diabetes researchers because calorie-restriction diets, as well as the drug metformin, are both treatments for type 2 diabetes and a related condition, metabolic syndrome. The treatments help the body better regulate the body’s uptake of sugar, a nutrient that people with these conditions have trouble regulating. But the exact mechanism of action of these treatments is unclear.

Vittorio Sartorelli, M.D., chief of the NIAMS’ Laboratory of Muscle Stem Cells and Gene Regulation and leader of the research team said, “We think this finding has given us a better molecular understanding of how lifestyle and drug interventions function in the treatment of type 2 diabetes and metabolic syndrome.” Skeletal muscle plays a critical role in type 2 diabetes and in a related condition, metabolic syndrome. It is responsible for more than 40 percent o’ the body?s uptake of sugar, a nutrient the body has trouble regulating in both conditions.

In their project, Sartorelli and his colleagues set out to investigate the relationship between skeletal muscle cells, calorie restriction, metformin and SIRT1 in mice. They cultured skeletal muscle cells from normal mice in a low-glucose environment to restrict calories and treated others with metformin. As expected, in each intervention the cells failed to mature and form myocytes, cells that are the building blocks of muscle fibers. What was new in their findings, however, was that metformin and calorie restriction both promoted the activation of two proteins, AMPK and Nampt, which in turn made SIRT1 more active and capable of suppressing cell differentiation.

When the scientists tried metformin and calorie restriction in the cells of mice engineered to have inactive SIRT1, the muscle cells ignored the suppressive effects of the interventions and remained able to produce mature myocytes. In addition, the usual changes in gene activity in response to calorie restriction in mice with inactive SIRT1 did not occur, another indication that SIRT1 is necessary to mediate the effects of calorie restriction.

Sartorelli said the team’s research shows that SIRT1 is a molecule that allows skeletal muscle to read a low amount of nutrients in the environment and suppress genes that promote cell differentiation, thereby conserving energy. He added that it also demonstrates that two interventions that can control diabetes - reduced caloric intake and metformin - both target SIRT1.

Collaborating institutions in this work included Weill Medical College of Cornell University in New York City, Children’s National Medical Center in Washington, D.C., and the Ottawa Health Research Center Institute in Canada.

For more information about diabetes prevention and treatment, visit the National Diabetes Information Clearinghouse of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), a part of the NIH, at http://diabetes.niddk.nih.gov/.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services’ National Institutes of Health (NIH), is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov.

http://www.nih.gov

Medical Research News

Scientists in the U.S. have confirmed a long held suspicion that traffic pollution can be deadly for some people.

The scientists from Harvard School of Public Health have found that breathing in air pollution from traffic fumes can raise the risk of potentially deadly blood clots forming in the body.

They say the tiny particulates found in exhaust fumes contain chemicals caused by burning fossil fuels which are known to increase the chances of heart disease and stroke but they also have an impact on the development of deep vein thrombosis (DVT) - blood clots in the legs.

The study examined over 2,000 people living in Lombardy, Italy, between 1995 and 2007, and found that the pollution made the blood more sticky and likely to clot and 870 of them developed DVT.

The risk of DVT is known to be increased by long periods of immobility, particularly in the case of passengers on long-haul flights.

But also vulnerable are people who spend long periods sitting at desks without exercising, or walking around - blood clots which form in the legs can travel to the lungs, where they can become lodged, triggering a potentially fatal pulmonary embolism.

By examining pollution readings from the areas where the study participants lived, the researchers found those exposed to higher levels of small particulates in the year before diagnosis were more likely to develop blood clots.

They found for every 10 microgrammes per square metre increase in small particulates, the risk of developing a DVT went up by 70%.

Guidelines regarding air quality guidelines usually advise that small particulate concentrations should not exceed 50 microgrammes.

Dr. Andrea Baccarelli who led the study says the findings introduce a new but common risk factor into the development of DVT and lend support to calls for tighter standards and continued efforts to reduce the impact of urban air pollutants on human health.

The researchers say the link between particle exposure and blood clots was stronger in men than in women, and disappeared among women taking oral contraceptives or hormone therapy.

They also say such hormone therapies are themselves risk factors for deep vein thrombosis, which was also confirmed in the study by the higher prevalence of oral contraceptive and hormone use in the DVT cases compared with the controls.