Sunday, May 10, 2009

Swine flu vacine

10 may 2009--The World Health Organization says that work on a vaccine for swine flu began as soon as the first human case of the virus became known. It estimates that the first doses of the vaccine will be available five to six months from now.

People who have had swine flu seem to be recovering. Why do we need a vaccine for it?

Although most people who have had swine flu seem to be recovering well, some people have died. Seasonal flu vaccines are important for the elderly and people with weakened immune systems, as they are particularly susceptible to complications like pneumonia.

The vaccine is also needed in case swine flu continues to spread, especially in case it becomes more of a problem over winter, which is peak flu season.

Will existing vaccines work for swine flu?

The WHO says that current evidence (while incomplete) suggests that seasonal influenza vaccines will offer little or no protection against swine flu.

Each year a new batch of flu vaccine is made to match the strains that the WHO decides will be most likely to circulate that winter, which is the peak flu season.

The influenza virus comes in many different strains that all have slightly different proteins on their surfaces. The body’s defences can only attack and destroy a virus if they recognise these proteins and, therefore, antibodies that recognise one strain may not recognise other strains.

If the proteins on the surface of the swine flu strain are highly similar to those of the strains used to create previous vaccines, then previous vaccines may provide some protection against swine flu. The NIBSC says that it is looking at the swine flu virus (an H1N1 strain of influenza A) and past H1N1 seasonal vaccines to determine if this is the case.

When will a vaccine be ready for swine flu?

Vaccines are prepared after a virus emerges, as the virus itself is the starting material for vaccine production. Therefore, there is always a time lag while a vaccine is prepared.

Vaccine preparation involves multiple steps. Therefore, it can take several months for a vaccine to be ready.

The WHO estimates that the virus for making the vaccine will be available to vaccine manufacturers by mid-May, and the first doses of a new vaccine could be available five to six months after this, but may take longer if the virus strain used to make the vaccine grows slowly in the laboratory.

Will the vaccine work for all cases of swine flu?

Vaccination is very effective in preventing and reducing the impact of serious illness. However, vaccines are not 100% effective and could become less effective if the virus mutates. Current flu vaccines last for about a year and give about 70-80% protection against infection with strains of influenza virus that are very similar to those used to make the vaccine.

The WHO says that it is too early to predict how the influenza A(H1N1) virus might change. The WHO is closely monitoring the virus for changes, and this will help countries to make a quick response if the virus undergoes important changes.

What is the difference between vaccines and antivirals?

Vaccines prepare the body to fight against certain diseases, in case it comes into contact with them in the future.

Antiviral drugs tend to be used in people who have already been exposed to a virus or are already known to be infected with a virus. Different antiviral drugs work in different ways, but generally they stop the virus from making new viruses and from spreading from cell to cell in the body.

Vaccines can be given long before exposure to an infectious agent and give people long-lasting protection against that agent. Antivirals are only effective if given within a specific time before or after exposure to the virus and only give protection while they are being used.

What is a vaccine?

A vaccine prepares the body to fight against certain infectious diseases in case we come into contact with them in the future. It does this by prompting the immune system to produce antibodies against them. Antibodies are proteins produced by the immune system to help identify and destroy disease-causing organisms such as viruses and bacteria.

Vaccines are usually made from tiny amounts of the disease-causing organism that have been killed or weakened. By introducing them to the body, the immune system can be trained to recognise these organisms in future and rapidly produce antibodies to fight them off.

How is a vaccine made?

To make a vaccine, a large amount of the virus or bacteria is needed. In the case of swine flu, the US Centers for Disease Control and Prevention (CDC) began isolating and preparing strains of the swine flu virus as soon as the first human case became known. These strains were sent to its counterparts in other countries including the National Institute for Biological Standards and Control (NIBSC) in the UK. These organisations prepare the virus strains to be used in making the vaccine.

Viruses can be grown in hens’ eggs, but often the infectious influenza virus strains do not grow well in eggs. To get around this, the infectious virus is injected into the eggs with another influenza virus that thrives in eggs. The two viruses swap pieces of their genetic material and produce hybrids, some of which both grow well in hens’ eggs and also have the elements of the disease-causing virus needed for a vaccine. These hybrids are isolated and the best candidate for making a vaccine is selected. This chosen hybrid strain is then grown and distributed to vaccine manufacturers.

The vaccine manufacturers use dead or weakened virus to create the vaccine. Other constituents can also be added to the vaccine, such as a suspending fluid to carry the virus into the body, preservatives and stabilisers that allow the vaccine to be stored safely, and chemicals to help the vaccine to promote an immune response.

Who usually gets vaccinated for flu?

People who are most likely to suffer from complications usually get vaccinated for seasonal flu. This includes:

people aged 65 years and over,
people with certain long-term medical conditions, such as chronic respiratory, heart, renal, or neurological disease, diabetes mellitus or immunosuppression,
health and social care professionals, and
poultry workers (to reduce the risk of being infected with both human and avian flu at the same time).

The recommended groups for vaccination with any new swine flu vaccine may be different.

Where did the story come from?

This research was conducted by Dr Ji-Song Guan, Professor Li-Huei Tsai and colleagues mostly from the Massachusetts Institute of Technology in the US. Funding was provided by a number of societies and foundations including the National Institute of Neurological Disorders and Stroke in the US. It was published in the peer-reviewed science journal Nature.

What kind of scientific study was this?

This was an animal study conducted in mice, looking at how histone deacetylase (HDAC) inhibitor drugs affected their brains, behaviour and learning. HDAC inhibitors are a class of compounds that interfere with histone deacetylase, an enzyme that is thought to play a role in regulating the expression of genes by changing how they form coils.

Drugs that inhibit HDACs are in experimental stages and the researchers say that, to date, HDAC inhibitors have not been used to treat Alzheimer's disease or dementia. They have been tested in early studies to treat Huntington's disease, and some HDAC inhibitors are already on the market to treat certain forms of cancer.

The researchers were interested in seeing the effect these drugs had on mice, so they genetically engineered two strains of “transgenic” mice that produced larger amounts of HDAC1 or HDAC2 proteins in their brains than normal mice.

The researchers then conducted learning and memory tasks using these transgenic mice. For example, they used a water maze to test if the mice could remember the correct swimming path to escape onto a platform. These tests were recorded by a video camera and analysed. They then injected the mice with HDAC inhibitors into the abdominal cavity and retested them.

The researchers then looked at a number of different aspects within the mouse brains including immunochemistry and gene expression. They were interested in synapse formation, memory formation and “synaptic plasticity”. Synaptic plasticity describes the strength of a connection, or synapse, between two neurons. Changes in strength can be due to changes in the levels of neurotransmitters released into the synapse or to changes in how effectively cells respond to those neurotransmitters.

Synaptic plasticity is important because memories are thought to be represented by the large interconnected networks of synapses in the brain, and, therefore, it is an important neurochemical foundation for learning and memory.

What were the results of the study?

The large quantities of HDAC1 and 2 the mice produced did not affect their brain anatomy, but HDAC2 did affect the memory, learning and behaviours of the mice. Synapses in the brains of HDAC2 mice were affected too, and these mice had impaired synaptic plasticity.

After taking HDAC inhibitors the mice regained their long-term memory and ability to learn new tasks. When mice were genetically engineered to produce no HDAC2 at all they exhibited enhanced memory formation.

What interpretations did the researchers draw from these results?

The researchers say that their research has shown that “inhibiting HDAC2 has the potential to boost synaptic plasticity, synapse formation and memory formation”. They say the next step is to “develop new HDAC2-selective inhibitors and test their function for human diseases".

The researchers say that the fact that long-term memories can be recovered supports the idea that apparent memory loss is really a reflection of memories becoming inaccessible. They say that their findings are in line with a phenomenon known as fluctuating memories, in which demented patients experience temporary periods of apparent clarity.

This study will be of interest to those researching new treatments and approaches to Alzheimer’s disease. The fact that reduced neuronal levels of HDAC2 but not HDAC1 increase synaptic plasticity, memory formation and changes in the neurons that are associated with memory raises the possibility that drugs specifically targeted at HDAC2 might be of value in the treatment of human diseases associated with memory loss.

Further research will clarify how close we are to any potential use of these drugs in humans with Alzheimer’s. Professor Li-Huei Tsai, one author of the study, said to the BBC that: "This is exciting because more potent and safe drugs can be developed to treat Alzheimer's by targeting this HDAC. However, treatment for humans is still a decade or more away.”

Links to the headlines

Trial drugs 'reverse' Alzheimer's. BBC news, May 07 2009

Drugs could aid memory. Daily Mirror, May 07 2009

Links to the science

Guan JS, Haggarty SJ, Giacometti E et al. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 459, 55-60 (7 May 2009)

Saturday, May 09, 2009

Up to 1 in 6 older people living at home face malnutrition risk

Overall risk is higher for women and depression increases risk for men

09 may 2009--As many as one in six people who took part in a study of older people who live at home were under-nourished and at risk of malnutrition, according to the May issue of the Journal of Clinical Nursing.

Researchers at Linkoping University, Sweden, found an overall malnutrition risk of 14.5 per cent when they studied 579 older people aged 75 and 80 as part of an ongoing study. Fifty-two per cent of the people who took part in the study were male.

They found that women faced a higher overall risk and that men were more likely to be at risk if they were depressed.

At the first yearly follow-up ten per cent of the 436 people still in the study were under-nourished and faced a malnutrition risk. By the second yearly follow-up the number studied had fallen to 371 but the malnutrition risk had risen to just over 16 per cent.

The researchers continued studying the 75 year-olds for another two years, reporting malnutrition risk rates of 11 per cent (out of 157 people) at the third annual follow-up and eight per cent (out of 145 people) at the fourth.

"We carried out a wide range of physical and biochemical tests on the people who took part in the study and asked them lots of questions, including how they perceived their health and their health-related quality of life" explains Yvonne Johansson from the Department of Medical and Health Sciences at the University.

"Our aim was to discover how prevalent the problem was and identify key factors that can predict an increased risk of malnutrition among older people living at home.

"We discovered that people were most likely to be at risk of malnutrition if they felt their health was poor. The second factor was symptoms of depression – especially in men – and higher age."

Key findings of the study, which was carried out between 2001 and 2006 in southern Sweden, include:

Women were more likely to be at risk than men – for example,19 per cent versus 10.5 per cent at baseline, 11 per cent versus nine per cent at the first follow-up and 17 per cent versus 15.5 per cent at the second follow-up.
Three-quarters of women in the at-risk group (75 per cent) described themselves as unhealthy compared with 44 per cent of the women who were not at risk. The figures for the men were 63 per cent and 38 per cent. Men and women in the at-risk groups were more likely to be registered with a doctor.
Women in the at risk group were more likely to live alone than women in the no risk group (63.5 per cent versus 50 per cent) but the difference in the men's group was less marked (19 per cent versus 17 per cent).
Women in the at-risk group were more likely to be unsatisfied with contact with others (42 per cent) than women in the no risk group (16 per cent). The difference between the two male groups was less marked (25 per cent and 28 per cent).
Men and women in the at-risk groups had lower handgrip strength than people in the no risk group.
The risk of malnutrition was also higher in people who showed symptoms of depression. This was particularly apparent among men.

"We hope that the findings of our study will be of use to health professionals working with older people" concludes Yvonne Johansson. "They clearly show that people who feel their health is poor and show symptoms of depression face a higher risk of developing malnutrition and that the risk gets higher as people get older.

"Our population is ageing and it is vital to ensure that health professionals are looking after their nutritional health as well as caring for any medical conditions they may have. This study provides evidence of some of the key warning signs to look out for."

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Notes to editors

Malnutrition in a home-living older population: prevalence, incidence and risk factors. A prospective study. Johansson et al. Journal of Clinical Nursing. 18,1354-1364 (May 2009).

Top flu expert warns of a swine flu-bird flu mix

MEXICO CITY, 09 may 2009 – Bird flu kills more than 60 percent of its human victims, but doesn't easily pass from person to person. Swine flu can be spread with a sneeze or handshake, but kills only a small fraction of the people it infects.

So what happens if they mix?

This is the scenario that has some scientists worried: The two viruses meet — possibly in Asia, where bird flu is endemic — and combine into a new bug that is both highly contagious and lethal and can spread around the world.

Scientists are unsure how likely this possibility is, but note that the new swine flu strain — a never-before-seen mixture of pig, human and bird viruses — has shown itself to be especially adept at snatching evolutionarily advantageous genetic material from other flu viruses.

"This particular virus seems to have this unique ability to pick up other genes," said leading virologist Dr. Robert Webster, whose team discovered an ancestor of the current flu virus at a North Carolina pig farm in 1998.

The current swine flu strain — known as H1N1 — has sickened more than 2,300 people in 24 countries. While people can catch bird flu from birds, the bird flu virus — H5N1 — does not easily jump from person to person. It has killed at least 258 people worldwide since it began to ravage poultry stocks in Asia in late 2003.

The World Health Organization reported two new human cases of bird flu on Wednesday. One patient is recovering in Egypt, while another died in Vietnam — a reminder that the H5N1 virus is far from gone.

"Do not drop the ball in monitoring H5N1," WHO Director-General Margaret Chan told a meeting of Asia's top health officials in Bangkok on Friday by video link. "We have no idea how H5N1 will behave under the pressure of a pandemic."

Experts have long feared that bird flu could mutate into a form that spreads easily among people. The past three flu pandemics — the 1918 Spanish flu, the 1957-58 Asian flu and the Hong Kong flu of 1968-69 — were all linked to birds, though some scientists believe pigs also played a role in 1918.

Webster, who works at St. Jude's Children's Research Hospital in Memphis, Tenn., said bird flu should be a worry now. Bird flu is endemic in parts of Asia and Africa, and cases of swine flu have already been confirmed in South Korea and Hong Kong.

"My great worry is that when this H1N1 virus gets into the epicenters for H5N1 in Indonesia, Egypt and China, we may have real problems," he told The Associated Press. "We have to watch what's going on very diligently now."

The U.S. Centers for Disease Control and Prevention are extraordinarily busy trying to understand the swine flu virus itself, and haven't had time to break off staff to look at the possibility of a swine flu-bird flu mix, spokesman Dave Daigle said.

Malik Peiris, a flu expert at Hong Kong University, said the more immediate worry is that swine flu will mix with regular flu viruses, as flu season begins in the Southern Hemisphere. It is unclear what such a combination would produce.

But he said there are indications that scenario is possible. Peiris noted that the swine flu virus jumped from a farmworker in Canada and infected about 220 pigs. The worker and the pigs recovered, but the incident showed how easily the virus can leap to a different species.

"It will get passed back to pigs and then probably go from pigs to humans," Peiris said. "So there would be opportunities for further reassortments to occur with viruses in pigs."

He said so far bird flu hasn't established itself in pigs — but that could change.

"H5N1 itself has not got established in pigs," he said. "If that were to happen and then these two viruses were both established in pigs in Asia, that would be quite a worrying scenario."

Michael Osterholm, an infectious disease specialist at the University of Minnesota who has advised the U.S. government on flu preparations, said while flu experts are discussing the scenario, he has yet to see specific evidence causing him to think it will happen.

"Everything with influenza is a huge guessing game because Mother Nature holds all the rules, and we don't even know what they are, so anything's possible," he said. "We don't have any evidence that this particular reassortment is that much more likely to pick up H5N1 than any other reassortment out there."

"We don't have to put these things together," he added. "This is not chocolate and peanut butter running into each other in the dark hallway."

But there is in fact discussion of putting them together — in a high-security laboratory — to see what a combination would look like, according to Webster. Similar tests have been done at the CDC mixing bird flu and seasonal human flu, resulting in a weak product, he said.

Daigle, the CDC spokesman, said the agency wants to look at the question in the future.

Webster has done groundbreaking work on both swine and bird flus in his 40-year career, and has followed the evolution of the current swine flu strain from a virus that sickened a handful of people who worked with North Carolina hogs into a bug that has spread from person to person around the world.

He is closely involved in the global effort to analyze what the virus might do next. It has killed 42 people in Mexico and two in Texas, but so far has not proven very deadly elsewhere, leading to some criticism that the World Health Organization's warnings of a potential pandemic have been overblown.

Webster said underestimating the swine flu virus would be a huge mistake.

"This H1N1 hasn't been overblown. It's a puppy, it's an infant, and it's growing," he said. "This virus has got the whole human population in the world to breed in — it's just happened. What we have to do is to watch it, and it may become a wimp and disappear, or it may become nasty."

Death Rate After Ablation of Atrial Fibrillation 1 in 1,000

Most patients with atrial tachycardia recover left ventricular function after ablation

09 may 2009-- While most patients with focal atrial tachycardia recover left ventricular function after catheter ablation, 1 in 1,000 patients with atrial fibrillation die, according to two studies in the May 12 issue of the Journal of the American College of Cardiology.

In the first study, Caroline Medi, from the University of Melbourne in Australia, and colleagues examined the characteristics and outcomes of 345 patients with focal atrial tachycardia, where 30 had tachycardia-mediated cardiomyopathy. They found that the frequency of incessant or very frequent paroxysmal tachycardia was much higher in patients with cardiomyopathy (100 versus 20 percent). Left ventricle function was restored in nearly all patients (97 percent) at a mean of three months after successful catheter ablation of the tachycardia focus.

In the second study, Riccardo Cappato, M.D., from Policlinico San Donato in Milan, Italy, and colleagues examined the incidence and causes of death in 32,569 patients who had undergone catheter ablation of atrial fibrillation. They found that 32 patients died (0.98 per 1,000 patients). The most common causes were tamponade, stroke, atrioesophageal fistula, and massive pneumonia.

"The data reported by Cappato et al. are of great clinical interest, and the authors should be congratulated for a contribution that will certainly raise awareness in the electrophysiologic community of the state of contemporary atrial fibrillation ablation," Bernard Belhassen, M.D., from Tel Aviv University in Israel writes in an accompanying editorial.

Several authors disclosed financial and consulting relationships with makers of ablation equipment and catheters, including Ablation Frontiers and Biosense Webster.

Abstract - Medi
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Abstract - Cappato
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Editorial (subscription or payment may be required)

Acupuncture eases a side effect of radiation

NEW YORK, 09 may 2009- When people with head or neck cancer are treated with radiation, a common side effect is dry mouth, and now researchers have shown that the problem can be relieved by acupuncture.

Excessive dryness of the mouth is technically termed xerostomia. Dr. Mark Chambers and colleagues from The University of Texas M. D. Anderson Cancer Center, Houston, conducted a pilot study to see if radiation-induced xerostomia resulting from radiation therapy for cancer in the head and neck region can be reversed using acupuncture.

Among 19 patients treated twice weekly for 4 weeks, scores on a standard xerostomia assessment scale improved significantly at the end of acupuncture treatment, as well as at 8 weeks after the start of treatment, the researchers report in the medical journal Head and Neck.

However, significant increases in average saliva volume or saliva output were not apparent, they note.

Nonetheless, at week 5 and week 8, there were significant improvements in total quality-of-life scores, as well as improvements in physical well-being at week 8.

"This pilot study demonstrates that acupuncture can improve the subjective symptoms of dry mouth in patients with radiation-induced xerostomia as early as two weeks after starting treatment, and the benefits can remain at least one month after treatment ends," the authors conclude.

"These results are very promising," Chambers told Reuters Health. "However, further research is needed." The team is planning formal clinical trials in China and in the US.

SOURCE: Head and Neck, April 17, of 2009.

Botox injections may ease diabetic foot pain

NEW YORK , 09 may 2009 - People with diabetes often suffer from chronic foot pain because of nerve damage, but relief may be at hand. Taiwanese doctors have shown that the pain can be reduced substantially by injections of botulinum toxin type A -- better known as Botox -- into the skin on top of the foot.

Dr. Chaur-Jong Hu, at Taipei Medical University, and associates tested the treatment in 18 patients with type 2 diabetes who had nerve-related pain in both feet.

The participants were randomly assigned to get injections of Botox or saline, then 12 weeks later crossed over to receive the opposite treatment.

A local anesthetic gel was applied first, and then the injections were administered into the skin (rather than into muscles) at 12 sites across the top of the foot, the team explains in the medical journal Neurology.

At the start of the study, the average pain score on a scale of 0-10 points was 6.36. There were significant differences in the decrease in pain scores between the Botox and saline injections during each 12-week period.

Specifically, at 12 weeks, the score was reduced by 2.53 points with Botox injections compared with 0.53 points with the saline injections.

Moreover, 44 percent of the subjects had a reduction of at least 3 points in their pain score within 12 weeks after the Botox injections.

An added benefit was that patients are able to sleep much better after the treatment.

Hu's team concludes that intradermal Botox injections "are an effective and safe method of relieving diabetic neuropathic pain in the feet." However, "the detailed underlying mechanisms, optimal dosage, and precise course of therapy require further evaluation."

SOURCE: Neurology, April 28, 2009.

Friday, May 08, 2009

Dementia: Early detection is key

08 may 2009--The leader of dementia research in CSIRO's Preventative Health National Research Flagship, Dr Cassandra Szoeke, says the report highlights the challenge the nation faces with the number dementia sufferers predicted to double to 465,000 by 2030.

"About 80 per cent of dementia in Australia is caused by Alzheimer's disease," Dr Szoeke, says. "Early diagnosis is crucial if we are to begin managing this crisis more effectively."

"By the time sufferers show symptoms of memory loss, severe irreversible brain cell death may have already occurred."

"In Australia every week another 1000 people are being diagnosed with dementia. It is only by early diagnosis that treatment can be effective, preserving memory and brain."

"With the initiation of the AIBL (Australian Imaging, Biomarker and Lifestyle) cluster study the combined institutions have potentially brought forward the detection of Alzheimer's disease by 18 months," Dr Szoeke says.

"Early detection can not only aid with future treatment options but it can also help with the planning and delivery of dementia care services in Australia."

Released earlier this week, the Access Economics report also found that investment in dementia research is a key strategy for addressing the epidemic.

"There is no question that research is the key to reducing the burden of the disease on the community for the future and CSIRO and its partners will continue to seek effective, new approaches to prevention, diagnosis and treatment of these diseases," Dr Szoeke says.

* The Australian Imaging, Biomarker and Lifestyle (AIBL) Flagship Study of Ageing is a collaboration initiated by the CSIRO Preventative Health National Research Flagship. AIBL is a joint activity between the Flagship, the University of Melbourne, Edith Cowan University - Western Australia, Neurosciences Australia, the Mental Health Research Institute of Victoria and the National Ageing Research Institute.

National Research Flagships

CSIRO initiated the National Research Flagships to provide science-based solutions in response to Australia's major research challenges and opportunities. The nine Flagships form multidisciplinary teams with industry and the research community to deliver impact and benefits for Australia.

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Image available at: http://www.scienceimage.csiro.au/mediarelease/mr09-78.html

Visceral Fat-Depression Link Explored in Women

Visceral adiposity may be key to higher cardiovascular disease, diabetes risk in depressed women

08 may 2009 -- Middle-aged women with depression tend to have more visceral fat than their nondepressed counterparts, which could explain why they are at higher risk for diabetes and cardiovascular disease, according to a study published online April 27 in Psychosomatic Medicine.

Susan A. Everson-Rose, Ph.D., of the University of Minnesota in Minneapolis, and colleagues conducted a study of 409 middle-aged women with a mean age of 50.4 years, of whom 44.7 percent were black and 55.3 percent were white. They looked at the women's levels of visceral and subcutaneous fat, as well as their scores on the Center for Epidemiological Studies Depression Scale (CES-D).

The investigators found that women diagnosed as depressed due to a CES-D score of 16 or above had 24.5 percent more visceral fat than their counterparts whose CES-D scores were lower. The results stood even after accounting for race and level of physical activity, and obese and overweight women showed the strongest association, the researchers discovered.

"Depressive symptoms were independently related to visceral adipose tissue but not subcutaneous fat or waist circumference, suggesting depressive symptoms may contribute to excess risk of diabetes and cardiovascular disease via increased visceral adiposity," the authors write. "Research is needed to examine mechanisms underlying this association and to determine whether depressive symptoms lead to greater accumulation of visceral adiposity over time."

Abstract
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Osteoarthritis: A review of treatment options

08 may 2009--Osteoarthritis (OA), also known as degenerative joint disease (DJD), is the most common form of arthritis in the United States.¹ Although OA can occur in any synovial joint in the body, it most commonly affects the knees, hips, and hands. OA is the leading cause of disability in elderly persons and affects approximately 14% of all adults aged ≥25 years; >12 million of those affected are aged ≥65 years. Women are more commonly affected than men.² OA is associated with remarkable personal, health, and economic costs, including 400,000 hospitalizations and an estimated $8 billion for knee and hip replacements annually.¹ The prevalence of OA is expected to increase in the coming years as risk factors, such as an aging population and obesity, become more prevalent.

ETIOLOGY

The development of OA involves multiple factors that contribute to excessive joint loading, repetitive motion or injury, and inflammation. The most common risk factors in the etiology of OA include advanced age, obesity, past occupation, participation in certain sports, joint trauma, and family history.^1–3

Genetic factors are also thought to play a role in the development of OA, and different genes may be implicated in different types of arthritis.³ Heberden nodes, bony enlargements of the distal interphalangeal joints of the hand, are 10-fold more prevalent in women than in men, and they occur twice as often in women whose mothers developed these nodes. Genetic factors have been linked to generalized OA, as well as OA of the first metatarsophalangeal joint. This genetic link has been substantiated in twin studies, which have demonstrated a 60% correlation in hip OA and a 70% correlation in spine OA between twins.⁴

To date, many intracellular regulators have been identified as potential markers for the expression of OA pathologies. These identified markers include interleukin-1 (IL-1), interleukin-4 (IL-4), and genes that code for asporin, an extracellular matrix protein, and calmodulin, an intracellular regulator.⁵

PATHOPHYSIOLOGY

OA has previously been considered a disease resulting from wear and tear of the joints; however, it can be more accurately described as a condition that is a result of various biochemical, biomechanical, inflammatory, and immunologic factors.⁵ These factors can cause structural and functional failure of synovial joints with erosion and loss of articular cartilage, meniscal degeneration, and osteophytes.⁶ OA can be categorized into 2 major etiologic classes: primary (idiopathic) or secondary. Primary OA is the most common type and can be further classified as localized (involving only 1 or 2 sites) or generalized (affecting ≥3 sites).^3,5 Secondary OA is associated with a known cause such as rheumatoid or other arthritis, trauma, metabolic or endocrine disorders, or congenital factors.

Signs and symptoms of OA may be present for months or years before medical attention is sought; deep, aching, generalized pain is typically what causes patients to initially seek medical attention. Pain is most commonly associated with movement in the beginning stages of disease but also occurs at rest in advanced OA. Other symptoms include joint stiffness that is most pronounced in the morning or after a period of inactivity ("gelling"), lasts <30>

NONPHARMACOLOGIC TREATMENT OPTIONS

The goal of OA treatment is to control symptoms, prevent disease progression, minimize disability, and improve quality of life. Management of OA includes varied techniques and principles, both nonpharmacologic and pharmacologic in nature.

Prevention of OA is the best treatment option. Limiting modifiable risk factors such as obesity, smoking, joint damage, and lack of adequate exercise can have a significant effect on decreasing the risk of OA development. Joint damage can be avoided by limiting exposure to vocational and recreational activities that involve prolonged high-impact and repetitive motion, kneeling, squatting, or heavy lifting. Repetitive recreational activities such as running have not demonstrated the same association with increased development of OA.⁴ Once a patient has been diagnosed with OA, appropriate nonpharmacologic methods should be employed as first-line treatments in mild disease or concurrently with pharmacologic management in progressive disease. These techniques include patient education, weight loss, exercise, physical and occupational therapy, assistive devices, acupuncture, ultrasound, and surgery.

Education. Patient education should always be the first step and a continued, integral part of OA treatment. Education should address the disease process, prognosis, and appropriate treatment options, as well as proper resources that the patient can consult for accurate self-management information and programs. The Arthritis Foundation offers such patient-oriented support.⁷

Diet and exercise. Obesity remains the most important and modifiable risk factor for the development of OA. In a study of 2,623 patients, Niu et al⁸ observed a significant relative risk for developing knee OA in obese (2.4) and very obese (3.2) patients versus those patients with normal body mass index (BMI) (P<.001). The results, however, did not demonstrate an overall correlation between obesity and the progression of existing OA. A 4-year cohort trial conducted by Wang et al⁹ in 39,023 volunteers determined that there was a 3- to 4-fold increased risk of primary joint replacement associated with increased body weight, BMI, fat mass, and percentage fat. Increased waist circumference and waist-to-hip ratio were also associated with an increased risk, suggesting that both biomechanical and metabolic mechanisms associated with adiposity contribute to the risk of joint replacement.⁹ Therefore, weight reduction and exercise in combination should be encouraged in all patients with OA, especially in those with OA of the knee and hip. Although each alone is beneficial in disease treatment and prognosis, one 18-month program of a combined regimen of caloric restriction and exercise resulted in a 24% improvement in physical function and a 30.3% reduction in knee pain, a significant improvement compared with the participants who followed only diet restrictions or exercise alone.¹⁰

Physical and occupational therapy. Formal physical and occupational therapy is useful in those patients who are not benefiting from home exercise programs or in those who need further instruction in range of motion, joint protection, or muscle-strengthening principles. In a randomized, controlled trial of 83 patients, Deyle et al¹¹ determined that improvements in walking distance, function, pain, and stiffness in the group receiving manual therapy of the knee (n=42) were clinically and statistically superior (P<.05) to the improvements in a control group receiving subtherapeutic ultrasound therapy after 8 weeks and 1 year of treatment. At 1 year, 20% of the control group versus 5% of the treatment group had undergone arthroplasty. Recommendations for exercise regimens should be patient-specific and should include both strengthening and low-impact aerobic exercise such as walking, swimming, or bicycling. Strength training that focuses on the quadriceps, adductor, and abductor muscles has been demonstrated to improve both knee and hip stabilization. All exercise regimens should be initiated by a trained exercise practitioner and continued at home, with intensity and duration increasing slowly as tolerated.^12,13

Assistive devices. Patients with OA may consider using canes and orthotics to assist with stability. The American College of Rheumatology (ACR) recommends using a cane contralaterally to the affected knee joint to manage OA symptoms.^14,15 Reaction forces in an osteoarthritic hip may be reduced by 50% when a patient uses a cane in the contralateral hand. A randomized, controlled trial assessed the use of orthotics and demonstrated no short-term symptomatic relief within a 6-week period, whereas 2 additional randomized, controlled trials determined that knee braces and therapeutic taping of the knee were effective interventions for the management of OA.^16–18 A 6-month, prospective, parallel-group, randomized clinical trial in 119 patients concluded that the use of knee braces (neoprene sleeves and unloader braces) in the management of OA of the knee results in a significant improvement in quality of life (P=.001) and function (P≤.001) specific to OA.¹⁷ Unloader braces appear more effective than neoprene sleeves in relieving symptoms.¹⁷ A 3-week trial of therapeutic knee taping demonstrated a significant reduction in knee pain (21 of 29 patients) when compared with both a control-tape group (14/29) and a no-tape group (3/29); this reduction in pain was maintained for 3 weeks after treatment cessation.¹⁸

Alternative. Acupuncture may provide some pain relief when administered alone or in combination with diclofenac.¹⁹ Acupuncture alone has been associated with improved function; however, it cannot be determined to what extent this improvement is caused by a placebo effect.²⁰ In randomized, placebo-controlled studies, therapeutic ultrasound has not been demonstrated to be more effective than placebo after 3 months, whether continuous therapeutic ultrasound, galvanic current, or shortwave diathermy was used.²¹

Surgery. Surgery should be reserved as a last-resort effort to manage OA symptoms in patients whose disease is refractory to less-invasive management methods. Surgical interventions include total joint arthroplasty and joint lavage and debridement. There is no evidence demonstrating that lavage or debridement is more effective in relieving pain or improving function than nonsurgical treatment.²² Arthroplasty has significantly reduced knee and hip pain and increased functionality in patients who were severely incapacitated before surgery.¹⁴ Studies comparing surgical and nonsurgical management techniques are lacking.¹⁴ If surgery is determined to be the treatment of choice, joint replacement should not be delayed to preserve optimal restorative function.²³ Prosthesis rejection and infection are among the complications that can occur.

PHARMACOLOGIC TREATMENT OPTIONS

Pharmacologic treatment options are listed in the table on p 146-47.^24,25

Acetaminophen and NSAIDs. Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are effective for mild-to-moderate pain associated with OA.²⁶ Data suggest that NSAIDs are more effective than acetaminophen; however, based on the side- effect profile of NSAIDs, acetaminophen is preferred as first-line therapy.

A systematic review involving 5,986 patients confirmed that acetaminophen is effective for the treatment of OA.²⁶ This study demonstrated that the number needed to treat (NNT) ranges from 4 (for pain response) to 16 (for overall pain reduction). Acetaminophen was more effective than placebo in 5 of 7 trials; the meta-analysis of these data confirmed that acetaminophen is significantly more effective than placebo for reduction of overall pain and pain on motion. This systematic review also confirmed that NSAIDs were superior to acetaminophen for OA in 10 trials. Acetaminophen should be avoided in patients with hepatic impairment.

NSAIDs have consistently demonstrated efficacy for pain relief in OA; however, a meta-analysis of 23 trials that included 10,845 patients demonstrated that NSAIDs are only slightly more effective than placebo for short-term pain relief in OA of the knee.^27–29 All NSAIDs, including cyclooxygenase-2 (COX-2) selective agents, are equally effective for pain relief in OA; choice of agent should be based on patient comorbidities, cost, and side-effect profile.^29,30 Gastrointestinal (GI) and cardiovascular (CV) risks limit routine use of NSAIDs in many patients (see table); a large meta-analysis recommended limiting use of NSAIDs because of the potential for serious adverse effects.²⁹ Caution is recommended when NSAIDs are administered to patients with CV risk factors; COX-2 selective agents are known to cause CV events, but nonselective agents (such as diclofenac and indomethacin) have also been implicated in increasing the risk of CV complications.³¹ Nonacetylated salicylates may be considered for patients with mild renal insufficiency.

COX-2 selective NSAIDs may be beneficial in patients at high risk for peptic ulcer disease or GI bleeding; however, the GI protective benefits of COX-2 selective agents may be negated if the patient is also taking aspirin (even in low doses).³² Patients who do not respond to selective COX-2 NSAIDs, are on concomitant aspirin therapy, or are at increased CV risk may be candidates for treatment with a nonselective NSAID plus a proton-pump inhibitor (PPI) or misoprostol for added GI protection.^33,34 Misoprostol protects against gastric and duodenal NSAID-induced ulcers. Misoprostol is contraindicated in pregnant woman because of its abortive effects and should be used with caution in women in their child-bearing years who are not using an effective contraceptive. Misoprostol is available alone or in combination with diclofenac. Adverse effects such as abdominal cramps and diarrhea may limit its use.³⁴ Prophylaxis therapy with a PPI in combination with an NSAID has been demonstrated to be superior to histamine (H₂) receptor antagonists combined with an NSAID in preventing GI ulcers and erosions, although the combination of PPI and NSAID is not FDA approved.³³ The decision of which therapy a patient is prescribed should take into consideration the cost, compliance issues, and past response to other therapies.

Topical analgesics. Topical NSAIDs and capsaicin may offer alternatives for patients unable to tolerate systemic agents and may also offer adjunctive therapy for those exhibiting partial response to conventional therapy. The long-term efficacy of topical NSAIDs has been debated; however, a meta-analysis of 4 trials that examined the efficacy of topical NSAIDs in trials lasting >4 weeks demonstrated that diclofenac and eltenac are effective for long-term pain relief in knee OA.^35,36 Topical capsaicin works by depleting the neuropeptide substance P and must be used for at least 3 to 4 weeks to achieve maximal benefit; a meta-analysis of 3 trials confirmed that topical capsaicin is more effective than placebo for pain relief in OA.³⁷ Capsaicin is commonly associated with a transient local burning sensation. Despite this effect, 1 study reported dropout rates as low as 2%.³⁸ Given its unique mechanism of action, topical capsaicin may also be useful as an adjunct to an oral analgesic.

Although not formally indicated for OA, lidocaine 5% patches may also offer a topical alternative for some patients.³⁹ One trial suggests that these patches may be as effective as COX-2 selective NSAIDs; however, these data are limited as the trial ended early because of safety concerns with COX-2 agents.⁴⁰

Glucosamine and chondroitin. The efficacy of glucosamine and chondroitin remains controversial. Glucosamine, which is naturally produced in the body, is an aminomonosaccharide that acts as a substrate for glycosaminoglycans, proteoglycans, and hyaluronic acid to form articular cartilage. Chondroitin also serves as a building block for joint cartilage.⁴¹ The large-scale Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT; N=1,583) failed to demonstrate a significant reduction in overall pain after 24 weeks in patients treated with glucosamine only, chondroitin only, or the combination of glucosamine plus chondroitin; however, a subgroup of patients with moderate-to-severe pain did experience significant pain reduction with the combination of glucosamine and chondroitin.⁴² An ancillary study of GAIT lasting 2 years evaluated joint space width in 572 patients; the combination of glucosamine and chondroitin failed to demonstrate a reduction in joint width loss.⁴³ A systematic review of 20 studies involving 2,570 patients demonstrated conflicting results based on glucosamine formulation.⁴⁴ Another meta-analysis of 15 trials concluded that there is likely evidence of some degree of efficacy for these agents.⁴⁵ Based on the benign side-effect profile of both agents and their potential for efficacy, a trial of glucosamine and chondroitin might be warranted in patients with mild-to-moderate knee OA.

Narcotic analgesics. According to the American Academy of Rheumatology, opioid analgesics such as codeine and oxycodone are not considered a first-line treatment option and should be considered only if traditional methods of pain management (eg, acetaminophen, NSAIDs, or tramadol) have been ineffective for OA or are intolerable; even then, only low-dose opioids should be used, especially in elderly patients.^46,47 The use of strong opioids for long-term pain relief in patients without cancer is a controversial topic; the risks of dependence, addiction, and hyperalgesia are the primary concerns.^46,47 Investigators conducted a meta-analysis of 18 placebo-controlled trials in 4,856 patients treated with weak or strong opioids.⁴⁸ Opioids significantly reduced the intensity of pain but had only moderate effects on physical function. Efficacy was assessed by measuring changes in pain intensity or an increase in physical function. The pooled effect size of all opioids for pain intensity was –0.79 (95% CI, –0.98 to –0.59). The pooled effect size of all opioids for physical function was –0.31 (95% CI, –0.39 to –0.24). Safety was measured by the number of treatments that had to be discontinued because of adverse effects. The most common adverse effects were nausea, constipation, dizziness, somnolence, and vomiting. The average rate of discontinuance was higher among patients treated with strong opioids (31%) than among those treated with weak opioids (19%). The number needed to harm among patients treated with strong or weak opioids versus those treated with placebo was 4 and 9, respectively. The high incidence of adverse effects should be considered before opioids are used as a treatment option in patients with OA.

The fentanyl patch provides continuous medication for 24 hours, but this agent should not be used in opioid-naïve patients. According to Langford et al,⁴⁹ patients with hip or knee OA experienced a reduction in pain and improved functionality with the fentanyl patch compared with placebo during a 6-week trial.⁴⁹ Although adverse effects with this agent are similar to those observed with other opioids, with fewer reports of constipation, the patch is thought to be more tolerable. For optimal results, opioids should be used in conjunction with nonpharmacologic therapies and considered for short-term use only.

Tramadol. Tramadol is an atypical opioid with a dual mechanism of action; it acts centrally on the mu-opioid receptors and inhibits the reuptake of norepinephrine and serotonin.⁵⁰ Unlike NSAIDs, tramadol has not been associated with GI bleeds. Eleven trials have compared tramadol or tramadol/acetaminophen with placebo or active controls for the treatment of OA.⁵¹ Patients taking tramadol or tramadol/acetaminophen experienced less pain and increased functionality but reported twice as many adverse effects (see table). The effectiveness of tramadol is still questionable; lack of anti-inflammatory properties and the development of tolerance to tramadol may limit this agent's effectiveness.⁵¹ Tramadol is contraindicated in patients with opioid hypersensitivity and in patients with acute alcohol intoxication.

Intra-articular glucocorticoids. For patients experiencing an acute local inflammation with a buildup of fluid in the joint (effusions), intra-articular glucocorticoid injections (triamcinolone acetonide, triamcinolone hexacetonide, betamethasone, and microcrystalline methylprednisolone) are a safe and effective nonsurgical option.^52,53 The efficacy of corticosteroid injections in areas other than the knee is questionable. Studies evaluating the efficacy of corticosteroid injections in OA of the hip have not been conducted, and the procedure is technically difficult to perform, as it requires fluoroscopic guidance.⁵⁴ The ACR recommends that, to reduce the risk of infection, these injections be performed by an experienced physician. A cell count, Gram stain, and culture should be performed if infection is suspected; leukocytosis, fever, or rapid onset of an effusion may be indicative of an infection in the joint.⁵² The dose of injection depends on the size of the joint being treated; these agents create a rapid response to pain, but long-term pain relief has not been established.⁵⁵

Hyaluronate injections. Intra-articular hyaluron (hyaluronic acid) is a polysaccharide found in the extracellular connective tissue that can act as a joint lubricant. When compared with placebo and NSAIDs, hyaluronic acid injections provided only a slight benefit in pain relief.⁵⁶ These agents are approved only for OA of the knee, not of the hip. Although the onset of action is slower than that observed with corticosteroids, these injections have the benefit of a longer duration, but they are also more costly.⁵⁵ Hyaluronate injections are administered as weekly injections for 3 to 5 weeks; hylan G-F 20 is administered as a single injection.

Disease-modulating agents. Disease-modulating agents are being investigated as alternative agents for OA. These agents are not intended for the treatment of painful symptoms but for the prevention of further damage to the joints or for the slowing of disease progression in joints already affected. Tetracyclines have certain anti-inflammatory properties and are inhibitors of collagenase and gelatinase; in OA, collagenase, gelatinase, and stromelysin levels are increased.⁵⁷ Doxycycline may slow the progression of OA. A 30-month trial comparing doxycycline 100 mg twice daily with placebo in 431 obese women demonstrated radiologic evidence of slowed progression of joint space narrowing (by 33%) in doxycycline-treated patients versus placebo-treated patients.⁵⁸ Withdrawals were more frequent in the doxycycline group because of adverse effects such as nausea, heartburn, and photosensitivity (23 vs 9).

Diacerein is currently not available in the United States. This agent has anti-inflammatory and analgesic properties when 50 mg is administered orally twice daily. Studies have demonstrated that diacerein is modestly effective compared with placebo and as effective as NSAIDs for pain relief of hip or knee OA.⁵⁹ The most common adverse effect is diarrhea, which is typically observed during the first 2 weeks of treatment.⁶⁰

FUTURE DIRECTIONS

Progress is being made in identifying and understanding the possible genetic contributions to the development of OA. This identification of the common alleles responsible for coding regulatory proteins involved in cartilage function may lead to the potential for new drugs that affect these regulatory proteins and thus potentially prevent, treat, or eradicate OA. The investigation into the role of inflammatory markers in OA such as IL-1, prostaglandin E2, tumor necrosis factor (TNF)-alpha, and nitric oxide also may lead to further treatment options for disease eradication.⁵

CONCLUSIONS/ RECOMMENDATIONS

Nonpharmacologic therapy such as patient education, weight loss, and exercise are the cornerstone of OA treatment. Other nonpharmacologic options such as physical and occupational therapy, assistive devices, acupuncture, and ultrasound may be considered for some patients. Because of the chronic nature of OA, long-term pharmacotherapy is often necessary; the safest pharmacologic option for long-term use is acetaminophen. If acetaminophen is not successful or is contraindicated, a short-term trial of the lowest effective dose of a short-acting NSAID such as ibuprofen or naproxen is recommended (see figure).⁶¹ Topical agents such as capsaicin and topical NSAIDs may offer an alternative in patients unable to tolerate systemic agents and may also be used as additive therapy. Though effective, opioids should be reserved for resistant cases and should be considered for short-term use only. The efficacy of intra-articular glucocorticoids, tramadol, and glucosamine with or without chondroitin is questionable; these agents may be tried when other options fail.

Dr Seed is assistant professor, Pharmacy Practice, Massachusetts College of Pharmacy and Health Science, Worcester. Dr Dunican is assistant professor, Pharmacy Practice, Massachusetts College of Pharmacy and Health Science. Dr Lynch is associate professor, Pharmacy Practice, Massachusetts College of Pharmacy and Health Science.

Disclosure Information: The authors report no financial disclosures as related to products discussed in this article.

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SCAI: Proton Pump Inhibitors Linked to Major Heart Risks

Heartburn drugs may reduce activity of clopidogrel in patients with coronary stents

08 may 2009-- In patients prescribed clopidogrel after coronary stenting, the use of proton pump inhibitors may significantly increase the risk of major adverse cardiovascular events, suggesting that the heartburn drugs interfere with clopidogrel's antiplatelet activity, according to research presented at the annual meeting of the Society for Cardiovascular Angiography and Interventions, held from May 6 to 9 in Las Vegas.

Eric J. Stanek, of Medco Health Solutions in Franklin Lakes, N.J., and colleagues compared one-year outcomes in 16,690 patients, including 41 percent who took a proton pump inhibitor for more than nine months of the year.

Compared to patients who didn't take proton pump inhibitors, the researchers found that proton pump inhibitor users had a 51 percent increased risk of major adverse cardiovascular events. They also found that the increased risk ranged from 39 percent in omeprazole and lansoprazole users to 57 percent in esomeprazole users and 61 percent in pantoprazole users.

"Given the large number of patients who undergo coronary stent procedures each year, and the recommended and wide use of clopidogrel following this procedure, our findings have implications for many thousands of patients across the United States," Stanek said in a statement. "Clopidogrel should continue to be taken as prescribed, and the need for proton pump inhibitor therapy should be carefully evaluated to ensure that it is prescribed only when clearly indicated."

This study was supported by Medco Health Solutions Inc.

More Information

Correct Diagnosis of Syncope Important for Treatment

Diagnosis often difficult due to multiple causes of loss of consciousness

08 may 2009-- Although difficult, correctly diagnosing the cause of syncope, a transient lack of consciousness followed by a quick recovery, is important in initiating effective treatment, according to a review in the May 12 issue of the Journal of the American College of Cardiology.

David G. Benditt, M.D., and John T. Nguyen, M.D., from the University of Minnesota Medical School in Minneapolis note that syncope is a transient loss of consciousness due to insufficient cerebral nutrient supply, with complete and prompt recovery. Even though syncope is rarely fatal, they note that it can increase the risk of physical injury and reduce quality of life.

The researchers write that since syncope is not the only cause of transient loss of consciousness, and symptoms are fleeting and often unwitnessed by medical professionals, diagnosis can be challenging. Nevertheless, identifying the cause of syncope, such as structural heart disease, is important and is best done by initial risk stratification to obtain the correct diagnosis and initiate effective treatment.

"Despite the difficulties, a thorough evaluation of the cause of syncope is warranted in all patients -- not just in those deemed to be at high mortality risk," Benditt and Nguyen conclude. "The goal in every case should be to determine the cause with sufficient confidence to provide a reliable assessment of prognosis and treatment options."

Benditt is a consultant to three companies that manufacture instruments that evaluate and treat syncope.

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Thursday, May 07, 2009

WHO casts wary eye on meat, blood of H1N1-infected pigs

* Flu viruses can survive freezing, be present on thawed meat

* Blood of H1N1 infected pigs may contain virus

* Meat from sick pigs or pigs found dead must not be consumed

* WHO drawing up guidelines to protect workers handling pigs

HONG KONG, 07 may 2009- Meat from pigs infected with the new H1N1 virus shouldn't be used for human consumption, the World Health Organization cautioned on Wednesday, adding it was drawing up guidelines to protect workers handling pigs.

The WHO comments appear more cautious than those from the Food and Agriculture Organization (FAO) and World Organization for Animal Health (OIE), which said import bans are not required to safeguard public health because the disease is not food-borne and has not been identified in dead animal tissue.

The WHO however said it was possible for flu viruses to survive the freezing process and be present in thawed meat, as well as in blood.

"Meat from sick pigs or pigs found dead should not be processed or used for human consumption under any circumstances," Jorgen Schlundt, director of WHO's Department of Food Safety, Zoonoses and Foodborne Diseases.

"While it is possible for influenza viruses to survive the freezing process and be present on thawed meat, there are no data available on the survival of Influenza A/H1N1 on meat nor any data on the infectious dose for people," he wrote in an email reply to questions from Reuters concerning the safety of pork, respiratory secretions and blood of H1N1-infected pigs.

Schlundt warned people to be cautious with blood and meat-juices from H1N1-infected pigs.

"The likelihood of influenza viruses to be in the blood of an infected animal depends on the specific virus. Blood (and meat-juice) from influenza H1N1-infected pigs may potentially contain virus, but at present, this has not been established," Schlundt said.

"Nonetheless, in general, we recommend that persons involved in activities where they could come in contact with large amounts of blood and secretions, such as those slaughtering/eviscerating pigs, wear appropriate protective equipment," he said.

The new H1N1 swine flu virus is being transmitted from person to person, not from pigs to people.

Its global spread has prompted many countries to limit pork imports, however. As many as 20 governments have imposed import bans on live pigs and meat from affected countries to prevent exposure to the virus. Such fears increased after Canadian authorities said on Saturday a herd of swine was infected by a farmer who had returned from Mexico.

The WHO said 22 countries have officially reported 1,534 cases of the flu virus.

While health officials say the outbreak appears to be slowing down in Mexico, authorities everywhere are asking how far the virus would spread and how serious it would be.

U.S. officials confirmed that a Texas woman with the H1N1 swine flu virus died earlier this week, the second death outside Mexico. Last week, a Mexican toddler visiting Texas died. Mexican officials have reported 29 confirmed deaths.

While the new virus is mainly spread from person to person through coughing and sneezing, experts do not know for sure how this virus came to be, which animal passed it to the first human patient and when that occurred.

But the case of the farmer infecting the pigs in Canada fueled fears of the virus yet again jumping the species barrier -- this time from pig to human -- and possibly becoming more virulent in the process.

Joseph Domenech, FAO chief veterinary officer, said on Tuesday: "This new strain of influenza virus does not contaminate humans easily and has a very low pathogenicity for both humans and pigs, unlike the avian flu which killed millions of poultry."

On Tuesday, Alex Thiermann, senior adviser to the OIE's director-general, said there was no difference between raw and cooked meat in terms of H1N1 transmission risks.

"The OIE is very concerned that differences are being made between cooked and not cooked meat. All pork products are safe for consumption," Thiermann said.

Does new swine flu virus kill by causing a 'cytokine storm'?

New Rochelle, NY, 07 may 2009—The swine flu outbreak that began in Mexico and continues to spread around the globe may be particularly dangerous for young, otherwise healthy adults because it contains genetic components of the H5N1 avian influenza virus, which can induce a "cytokine storm," in which a patient's hyper-activated immune system causes potentially fatal damage to the lungs. Research studies and review articles exploring the regulation of cytokine responses in the lung and how infection-related dysregulation can cause a cytokine storm have been published in Viral Immunology, a peer-reviewed journal published by Mary Ann Liebert, Inc. (www.liebertpub.com/vim).

A cytokine storm occurs when the body's immune system over-reacts to an intruder, such as a virus, by producing high levels of cytokines, which are signaling chemicals that help mobilize immune cells capable of removing infectious agents from the body. When too many cytokines are produced, they can stimulate an inflammatory response in which the accumulation of immune cells and fluid at the site of infection may prevent affected tissues and organs such as the lungs from functioning properly and may even cause death.

H5N1 avian influenza virus—parts of which are present in the Mexican H1N1 swine flu virus causing the current outbreak—tend to cause an unusually high proportion of deaths among healthy young adults with well-functioning immune systems who become infected, most likely due to this cytokine storm phenomenon. The Spanish influenza pandemic of 1918, for example, was particularly deadly for young healthy adults.

David L. Woodland, PhD, Editor-in Chief of Viral Immunology, and President and Director of the Trudeau Institute, Inc. (Saranac Lake, NY), emphasizes that much is still not known about the current influenza outbreak and the human/avian combination virus causing it. "We do not know how long ago this virus emerged, how deadly it is, whether it has pandemic potential, how the severity of infection relates to patient age, and why some infected patients die—whether a cytokine storm is responsible for these deaths," says Woodland.

What we do know, he adds, is that some H1N1 viruses have pandemic potential and that historical evidence supports the possibility that young healthy adults may be especially susceptible to more severe infection and poor outcomes due to the ability of a strong immune system to initiate a cytokine storm.

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Viral Immunology is an authoritative peer-reviewed journal published bimonthly in print and online that presents the growing body of research in viral immunology. Topics cover both human and animal viral immunology, exploring viral-based immunological diseases, pathogenic mechanisms, and virus-associated tumor and cancer immunology. The Journal includes original research articles, review articles, and commentaries covering the spectrum of laboratory and clinical research and exploring developments in vaccines and diagnostics targeting viral infections. Tables of contents and a free sample issue may be viewed online at www.liebertpub.com/vim

Study shows benefits of anti-clotting medications reduced by common heartburn drugs

Proton pump inhibitors interfere with anti-clotting protection of clopidogrel

LAS VEGAS, 07 may 2009— The anti-clotting action of the medication clopidogrel (Plavix) can be compromised by common drugs for the treatment of heartburn and ulcers resulting in a roughly 50% increase in the combined risk of hospitalization for heart attack, stroke and other serious cardiovascular illnesses, according to a new study presented today at the Society for Cardiovascular Angiography and Interventions (SCAI) 32nd Annual Scientific Sessions. The study specifically focused on the effects of proton pump inhibitors (PPI) omeprazole (Prilosec), esomeprazole (Nexium), pantoprazole (Protonix), and lansoprazole (Prevacid), which together accounted for about 96% of PPI use in the study.

Patients who receive a drug-eluting stent benefit from taking anti-clotting medications, including thienopyradines (such as clopidogrel or ticlopidine) and aspirin, for at least one year following the procedure. Doctors often also prescribe PPIs to patients taking clopidogrel because of pre-existing stomach disease or to reduce the risk of common side effects such as nausea and gastroesophageal reflux (heartburn). Before clopidogrel can exert its anti-clotting effects, it must be converted from its inactive, pro-drug form to an active drug by enzymes in the liver. PPIs—the sixth most commonly prescribed drug class in the U.S.—can interfere with those liver enzymes, according to the study.

"Given the large number of patients who undergo coronary stent procedures each year, and the recommended and wide use of clopidogrel following this procedure, our findings have implications for many thousands of patients across the United States," said Eric J. Stanek, PharmD, senior director of research, personalized medicine research and development, Medco Health Solutions, Franklin Lakes, NJ, and the study's principal investigator. "Clopidogrel should continue to be taken as prescribed, and the need for PPI therapy should be carefully evaluated to ensure that it is prescribed only when clearly indicated."

For the study, researchers analyzed integrated data on pharmacy and medical claims from more than 10 million patients, including 16,690 patients taking clopidogrel for a full year following coronary stenting. Of these, 41% also took a PPI, on average, for more than nine months of the year. Over that 12-month period when patients took clopidogrel, investigators evaluated the risk of hospitalization for major adverse cardiovascular events (MACE), which they defined as a combination of heart attack, unstable angina, stroke or temporary stroke-like symptoms, repeat coronary procedures, or cardiovascular death.

The overall MACE risk was 51% higher among patients taking any PPI. The findings were equally concerning when the effects of individual PPIs were analyzed. Omeprazole correlated with a 39% increased risk of MACE, esomeprazole to a 57% increased risk, pantoprazole to a 61% increased risk and lansoprazole to a 39% increased risk. All of the associations were highly statistically significant. Overall, the incidence of hospitalization for upper gastrointestinal bleeding was only 1.1% among patients taking a PPI and 0.07% among those not taking a PPI.

Additional research is needed to determine whether newer, less widely used PPIs such as rabeprazole (Aciphex) and dexlansoprazole (Kapidex) are also associated with increased cardiovascular risk in patients taking clopidogrel. Researchers are also interested in examining how genetic variations in the liver enzymes that activate clopidogrel might alter the impact of PPIs on clopidogrel effectiveness, the potential influence of the timing of PPI administration, the effect of alternate dosing of clopidogrel, and the comparative effectiveness of other anti-clotting medications.

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This study was supported independently by Medco Health Solutions, Inc, and conducted in collaboration with investigators from the Indiana University School of Medicine.

Mealtime interaction encourages hospitalized seniors to eat more

Universite de Montreal study highlights importance of socializing over food

07 may 2009--Sharing a meal in good company can stimulate the appetite – particularly among hospitalized seniors – according to a new Université de Montréalstudy published in The Gerontologist.

"The more social interaction occurs at mealtimes in hospital geriatric re-adaptation units the better food intake will be," says Danielle St-Arnaud McKenzie.

A graduate of the Université de Montréal Department of Nutrition, St-Arnaud McKenzie conducted the study with Professor Marie-Jeanne Kergoat of the Faculty of Medicine, Professor Guylaine Ferland of the Department of Nutrition, as well as Laurette Dubé of McGill University.

Research has shown that a majority of patients suffer from nutritional deterioration during hospitalization. "Approximately 35 percent of elderly people suffer from malnutrition," says Marie-Jeanne Kergoat. "That's a scary estimate when we consider that nutrition tends to deteriorate during hospitalization."

St-Arnaud McKenzie observed some 30 patients during mealtimes at the re-adaptation unit of the Institut universitaire de gériatrie de Montréal (IUGM), which is affiliated to the Université de Montréal. Using an evaluation grid, she measured their verbal and non-verbal behaviors. By observing these patients at mealtimes she calculated the level of conviviality. She then measured food intake by looking at the quantity of food leftover after the meal.

Results were clear – there was a correlation between food intake and social interaction. What's more, patients ate more when social interactions were friendly and lively. The research team also found that nutritional deficiencies mostly occur when patients eat alone in their rooms.

As the population ages, the number of seniors will rise and researchers must find solutions to elderly malnutrition. "By eating poorly, elderly patients risk developing other age-related health problems," says St-Arnaud McKenzie.

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On the Web:

About the Université de Montréal: www.umontreal.ca/english/index.htm

Study finds link between hot flashes and lower bone density in women

07 may 2009 : UCLA researchers and colleagues analyzed data for 2,213 women between the ages of 42 and 52 who participated in the bone sub-study of the Study of Women's Health Across the Nation to determine whether women with vasomotor symptoms (VMS) — which include hot flashes and night sweats — had lower bone mineral density.

The researchers found that postmenopausal women with VMS had lower lumbar and total hip bone mineral density than those without VMS. Premenopausal women and early perimenopausal women who had VMS were found to have lower femoral neck bone mineral density than those without VMS.

AUTHORS: UCLA study co-authors Dr. Carolyn J. Crandall, associate clinical professor of general internal medicine and health services research; Gail A. Greendale, professor of medicine in geriatrics; and Yan Zheng, of the division of general internal medicine and health services research, are available for interviews.

JOURNAL: The research appeared in the March/April 2009 issue of the journal Menopause.

FUNDING: The National Institute on Aging, the U.S. Department of Health and Human Services' National Institutes of Health, the National Institute of Nursing Research, and the NIH Office of Research on Women's Health supported this study.

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