A YEAR after deadly H5N1 bird flu first arrived in Europe, the UK is dealing with its first outbreak on a farm. Yet European efforts to track the virus, let alone defend its poultry, are still in disarray.

Later this month, scientists will meet to hammer out a Europe-wide surveillance scheme that will try to work out exactly where the virus is lurking and prevent further outbreaks.

The British outbreak, on a large turkey farm in eastern England, follows repeated insistence by British officials that the nation’s wild birds do not have the virus, even though an infected dead swan turned up in Scotland last April. But there is a chance that surveillance is missing the virus.

This year’s emergence of H5N1 in western Europe seems to be following a similar pattern to last year. The highly pathogenic virus evolved in poultry in East Asia and crossed Eurasia during 2005. It was then carried to western Europe that autumn by wild birds (see Map) — possibly dabbling ducks, which unlike many birds stay healthy while carrying H5N1. However, there were no visible outbreaks in western Europe until February 2006. Now the same thing is happening this year, with outbreaks of H5N1 in Hungary on 24 January and the UK on 3 February. This suggests H5N1 arrived in the ducks’ wintering grounds in autumn but didn’t immediately strike a visible target.

Yet there was no warning of impending flu outbreaks, partly because Europe has no coordinated surveillance for flu in wild birds that would enable researchers to work more closely and share data.

For example, between August 2006 and January 2007 the UK Veterinary Laboratories Agency (VLA) tested 4054 wild British birds, nearly half of them dabbling ducks, but only 15 (0.8 per cent) of the ducks tested positive for any strain of bird flu. In contrast, last autumn BjГ¶rn Olsen of the University of Kalmar in Sweden, who runs one of Europe’s largest flu surveillance programmes, found ordinary flu in 20 to 40 per cent of ducks using the same migration path as British ducks. Similar findings last year led researchers to query whether the VLA’s sampling technique had let virus degrade through samples drying out (New Scientist, 12 April 2006, p 12). “I would say 0.8 per cent is too low,” says Olsen. “But it is important to harmonise our sampling techniques, or we can’t compare data.”

Later this month, European scientists will meet in Rotterdam, the Netherlands, to launch the NEW-FLUBIRD programme to standardise sampling methodology and determine exactly which birds carry the virus.

No sampling so far has detected a healthy bird carrying H5N1. “I’m most concerned that we may be sampling the wrong end of the bird,” says Osterhaus, who now believes H5N1 may be more likely to turn up on a throat swab than in a faecal sample.

NEW SCIENTIST
Reed Business Information Limited
151 Wardour St
London
W1F 8WE
newscientist

Administering a new form of immunotherapy to children with neuroblastoma, a nervous system cancer, increased the percentage of those who were alive and free of disease progression after two years, according to researchers at the University of California, San Diego School of Medicine and fellow institutions. The percentage rose from 46 percent for children receiving a standard therapy to 66 percent for children receiving immunotherapy plus standard therapy, according to the study published in the Sept. 30, 2010 issue of the New England Journal of Medicine.

“This is the first clinical trial to document that a combination of anti-cancer monoclonal antibody (mAb) with cytokines is an effective anti-cancer therapy,” said Alice L. Yu, MD, PhD, study chair and Professor of Pediatric Hematology Oncology at Moores UCSD Cancer Center. “This is also the first time a mAb targeting a glycolipid is shown to be effective for cancer immunotherapy since all therapeutic anti-cancer mAbs previously approved by FDA are directed against protein antigen. Overall, these findings present a clear paradigm shift and establish immunotherapy as a cornerstone to high-risk neuroblastoma treatment. This immunotherapy regimen will now be standard of care for children in first remission.”

Neuroblastoma is a cancer of the peripheral nervous system (found outside of the brain and spinal cord), and is responsible for 12 percent of all deaths due to cancer in children under 15 years of age. It is the most common non-brain solid tumor in children. Nearly 50 percent of patients with neuroblastoma have a high-risk form of the disease and have poor long-term survival despite very intensive treatment.

The previously established standard treatment for neuroblastoma uses high doses of chemotherapy to destroy as many cancer cells as possible. But this form of chemotherapy (myleoablative therapy) also destroys some normal blood-forming cells, so it is followed by giving back previously collected blood-forming cells to restore immune system function and blood cell formation. Patients who respond to this therapy are then given a derivative of vitamin A to further treat any remaining cancer cells. More than half of the patients with high-risk neuroblastoma treated in this manner succumb to the disease.

A newer approach to cancer treatment is immunotherapy, which in this instance uses an antibody called ch14.18 to target a substance on the surface of tumor cells called GD2. The GD2 is expressed by cancers such as neuroblastoma but is also present on some normal nerve cells. Early-phase studies demonstrated the safety and activity of ch14.18 when it was given with other drugs that boost the immune system. Those drugs include a factor which stimulates white blood cell growth and a hormone that increases the number and activity of certain types of immune cells.

In this study, 226 children with high-risk neuroblastoma who had responded to myeloablative therapy were randomly assigned to receive standard therapy (isotretinoin), or isotretinoin, ch14.18, and the immune system boosting drugs. The median time these patients were followed in the study was approximately two years. Although the original plan had been to compare outcomes after three years, the study stopped early because of the strongly positive results, allowing those on standard therapy to switch to ch14.18 immunotherapy if they wished.

Toxicities, including pain, low blood pressure, capillary leak and hypersensitivity reactions, were encountered with the immunotherapy treatment at a significantly greater rate than compared to those who just received the standard therapy. However, side effects in the immunotherapy group were temporary and primarily resolved when treatment was stopped.

The randomized phase III clinical trial was coordinated by the Children’s Oncology Group (COG), a national consortium of researchers supported by the National Cancer Institute (NCI), part of the NIH.

Because there was no pharmaceutical company to make ch14.18 when the phase III trial started, NCI manufactured the agent and provided it to COG for the clinical trial. NCI continues to manufacture ch14.18 and to make it available to children with high-risk neuroblastoma through ongoing Children’s Oncology Group clinical trials. NCI has identified a pharmaceutical partner, United Therapeutics Corp., Silver Spring, Md., that will eventually take over responsibility for manufacturing ch14.18 and which will be responsible for obtaining U.S. Food and Drug Administration approval of ch14.18 for the treatment of high-risk neuroblastoma.

Fellow researchers included Andrew L. Gilman, MD, M. Fevzi Ozkaynak, MD, Wendy B. London, PhD, Susan G. Kreissman, MD, Helen X. Chen, MD, Malcolm Smith, MD, PhD, Barry Anderson, MD, Judith G. Villablanca, MD, Katherine K. Matthay, MD, Hiro Shimada, MD, Stephan A. Grupp, MD, PhD, Robert Seeger, MD, C. Patrick Reynolds, MD, PhD, Allen Buxton, MS, Ralph A. Reisfeld, PhD, Steven D. Gillies, PhD, Susan L. Cohn, MD, John M. Maris, MD, and Paul M. Sondel, MD, PhD, for the Children’s Oncology Group.

Source:

University of California, San Diego Health Sciences

The fight against the MRSA bug will take a step forward this week when a new-style hospital gown goes on trial at a London hospital.

The patient gown combines a new and innovative design with an anti-microbial finish that controls the growth of bacteria.

The gown’s unique design aims to reduce the spread of infection by minimising patient handling. It facilitates access to the patient’s body for examination and makes it easier to change than regular gowns. Less patient handling means less contact with nurse’s uniforms which reduces the chance of cross-contamination.

The gown was designed by DCS Designs, a graduate start-up company emerging from the University of Portsmouth. Fatima BA-Alawi invented the design while she was still a student and working in a hospital as a health care assistant where she noticed improvements could be made to the conventional patient gown.

She has teamed up with Carrington Career & Workwear Ltd whose product, Permagard, provides the bug-busting ingredient.

“I’m thrilled that my design is being used for the trial. I designed the gown to promote patient dignity, comfort and safety but I’m delighted that it might help prevent the spread of diseases like MRSA,” Fatima said.

Recently, due to overuse of antibiotics, strains of MRSA have evolved to become resistant to certain drugs but Permagard destroys bacteria by physical rather than chemical means so bacteria cannot adapt and become resistant to it. Permagard works on all bacteria, not just the MRSA bug.

The trial will take place at University College London Hospital (UCLH) in a ward, in the intensive care unit and in an operating theatre. Approximately 30 patients will wear the gowns and the trial is expected to take eight weeks.

Afterwards both patients and staff will be surveyed to assess the gown’s benefits and laboratory tests will analyse how successful they have been in cutting the number of bugs.

Mike Rollins, Projects Manager, Environmental Hygiene Research at UCLH is supervising the trial in conjunction the Infection Control Nurses team. He said: “I’m delighted that Fatima identified the need and applied her prior experience as a health care worker to create a practical, effective solution to one of the worries facing healthcare professionals every day. Her innovative design concept increases the
efficiency of providing patient care, improves patient safety and comfort and may well contribute to a reduction in hospital infections.”

Fatima said: “Having the support of the University to start my business has made all the difference. The Centre for Enterprise didn’t just given me the start up funds, it gave me the confidence and support I needed to take my idea off the ground and make it happen.”

PORTSMOUTH UNIVERSITY
University House
Winston Churchill Avenue
Portsmouth
Hampshire PO1 2UP
port.ac

View drug information on Carrington patch.

It is possible to improve the antioxidant action of tomatoes by a directed change in the production of flavonoids by means of genetic modification. This has been shown in research by Elio Schijlen at Plant Research Internationa, part of Wageningen University and Research Centre in the Netherlands. Schijlen demonstrated that this approach enables tomatoes to produce larger amounts of specific flavonoids and to let tomatoes produce flavonoids they cannot produce by nature. On the basis of the research Schijlen obtained HIS his PhD-degree on Thursday 8 February at the University of Amsterdam.

The results of this research show that genetic modification is a possible approach to further increase the health promoting value of vegetables and fruit. Flavonoids are frequently occurring and important metabolites in plants. About 6000 different flavonoids are known to be involved in various natural processes. The colour of flowers and ripe fruits, e.g., are often caused by flavonoids. But flavonoids also play an important role in other plant processes such as pollen production, disease resistance, and protection against UV radiation.

Because flavonoids are so frequently occurring in plants, they are a permanent component of our food. Part of the health promoting effects of vegetables and fruit is attributed to flavonoids. It may therefore be attractive to increase the amount of flavonoids and/or change their composition.

This was why Schijlen, working at Plant Research International of Wageningen UR, studied the possibilities of steering the production of flavonoids by a directed change of the biosynthesis route via genetic modification. He followed various approaches to achieve this. One approach was to investigate the possibility of increasing the amount of flavonoids in tomato by means of so-called transcription factors, proteins involved in regulating gene activity.

Schijlen also investigated the possibility to produce new flavonoids in tomatoes which might increase the health promoting properties of tomatoes. For this purpose he used genes form other crops such as grape and alfalfa, genes that are involved in certain steps in the biosynthesis of flavonoids in these crops.

Both approaches were found to be successful. Through genetic modification Schijlen succeeded in developing tomatoes not only with more flavonoids but also with new flavonoids.

Via biochemical analysis Schijlen demonstrated an increased antioxidant action of tomatoes with flavones and more flavonoles, two specific groups of flavonoids. In cooperation with scientists of BASF Plant Science and TNO, the potential health promoting effects of these tomatoes were tested in feeding studies with mice. Blood analyses showed that that the tomatoes with increased flavonoids had a stronger positive effect on blood properties that are characteristic of a reduced risk of cardiovascular disorders.

With his results, Schijlen has shown that genetic modification can further increase the health promoting effects of vegetables and fruit.

About WAGENINGEN UNIVERSITY AND RESEARCH CENTRE

Wageningen University and Research Centre is an internationally leading knowledge institution, making essential contributions to the quality of life with pioneering research and innovative teaching programmes in the areas of nutrition and health, sustainable agrosystems, a viable environment and processes of social change.

WAGENINGEN UNIVERSITY AND RESEARCH CENTRE
Postbus 9101 6700 HB Wageningen
wageningen-ur.nl

Bayer CropScience presented its Green World project to a wide-ranging trade audience at Fruit Logistica in Berlin. “Since the summer of 2006, Bayer CropScience has been supporting small-holders in Kenya, helping them reach demanding quality and food-safety standards,” said Hans-Joachim Wegfahrt, Managing Director of Bayer East Africa Ltd. and Country Head of Bayer CropScience in Kenya, describing the company’s philosophy. “We believe that projects like Green World are exceptionally important because they safeguard the population’s food supply and, in the longer term, enable farmers to establish a successful export business.”

The project is based on the concept of providing local traders with intensive training by experts from Bayer CropScience. They learn about sustainable agriculture, integrated farming methods, modern crop protection, and the safe, environmentally compatible use of Bayer CropScience products and then pass on this knowledge directly to their customers, the small-holders. The initial results are promising. The farmers produce more vegetables and corn than they need for their families and so can then sell the surplus at local markets and, increasingly, for export. The company has also involved seed producers, exporters and the Kenyan Ministry of Agriculture in the Green World project under the umbrella of the “food chain partnership”. All the players are working to produce high-quality, safe food. Some of the traders are visiting this year’s Fruit Logistica at Bayer CropScience’s invitation. They reported on their experience to an international trade audience with the aim of encouraging new partnerships and new projects.

Resounding response to Bayer’s training programs

Incorrect use of crop protection products and the prevalence of products for which regulatory approval has not been obtained continue to be problematic in Kenya. In addition, counterfeit active ingredients and low-quality generics are increasingly reaching the Kenyan market. With projects like Green World, Bayer CropScience is contributing to greater protection for users, the environment and consumers alike. The training programs include information on innovative products from Bayer CropScience, assistance with drawing up spraying schedules, and topics such as “good agricultural practice” and environmentally compatible production. Wegfahrt explained: “We particularly want to help the smallest-scale farmers in Kenya.” At the conclusion of the intensive training program, Bayer CropScience invited small-holders to attend field days at which the Green World traders were able to pass on their new-found knowledge. These events each attracted up to 3,000 visitors. “The traders who took part in our training program were enthusiastic about passing on their knowledge,” Wegfahrt commented. This enthusiasm is also evident among the small-holders.”

Maintaining village structures and preventing migration

With a surface area of 582,000 square kilometers, Kenya is about the size of France. Five million of the more than 30 million inhabitants are small-holders, making agriculture the most important sector of the economy ahead of even tourism. In addition to well-known products such as coffee, tea and flowers, Kenya has been exporting increasing volumes of fruit and vegetables to Europe in recent years.

In addition to boosting the country’s export business, Green World is also aiming to improve the lives of people in Kenya. Bayer CropScience is collaborating with the German Society for Technical Cooperation, which launched an environmental project focusing on Kenyan small-holders at the same time, to maintain the country’s village structures. The villages are the backbone of Kenyan society and if these structures can be maintained, migration of the population to big cities such as Nairobi and Mombasa can be prevented. This in turn will stop the proliferation of slums in the cities.

Bayer CropScience AG, a subsidiary of Bayer AG with annual sales of about EUR 5.9 billion (2005), is one of the world’s leading innovative crop science companies in the areas of crop protection, non-agricultural pest control, seeds and plant biotechnology. The company offers an outstanding range of products and extensive service backup for modern, sustainable agriculture and for non-agricultural applications. Bayer CropScience has a global workforce of about 19,000 and is represented in more than 120 countries.

Forward-looking statements

This news release contains forward-looking statements based on current assumptions and forecasts made by Bayer CropScience AG management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future consolidated results, financial situation, development or performance of our parent company, Bayer AG, and the estimates given here. These factors include those discussed in public reports filed by Bayer AG with the Frankfurt Stock Exchange and with the U.S. Securities and Exchange Commission (including Form 20-F). Neither Bayer AG nor Bayer CropScience AG assumes any liability whatsoever to update these forward-looking statements or to confirm them to future events or developments.

Bayer
bayer/en/Homepage.aspx

What does confirming H5N1 in a poultry farm mean for animal health?

Defra have put in place a 3km Protection Zone and 10 km Surveillance Zone around the infected premises, requiring certain biosecurity measures, the housing of birds, and movement restrictions. A wider Restricted Zone has been put in place which covers east Suffolk and South East Norfolk bounded to the west and the north broadly covered by the A140 and A47 respectively, and is approximately 2090km2. It requires the isolation of poultry from wild birds and permits movements only under licence. All bird keepers, throughout the UK should continue their efforts to maintain high levels of biosecurity (please see the Defra website for further biosecurity advice), and develop their plans to bring their birds indoors should it become necessary.

What are the zones and what do they mean?

Protection Zone (PZ) 3km

Measures:

– Housing or isolation of poultry and other captive birds;

– Movement restrictions on poultry, other captive birds, mammals, eggs, poultry meat, carcasses and poultry waste except where licensed;

– Biosecurity measures for people, premises and vehicles;

– A ban on bird gatherings;

– A ban on the release of game birds.

Duration: At least 21 days after the preliminary cleansing and disinfection of the infected premises and then becomes part of the surveillance zone. The duration of the PZ will take account of surveillance in the area to identify whether or not disease is present.

Surveillance Zone (SZ) 10km

Slightly less restrictive.

– Movements of poultry, other captive birds and eggs restricted except under licence.

– Housing or Isolation of birds

– Biosecurity measures for premises, people and vehicles;

– A ban on the hunting of wild birds, the release of game birds and bird gatherings.

Duration: At least 30 days after the preliminary cleansing and disinfection of the infected premises. The duration of the SZ will take account of surveillance in the area to identify whether or not disease is present.

Restricted Zone (RZ) 2090km2

– Housing or isolation of poultry from wild birds

– Movements under license

To note:

– The duration of the PZ and SZ will take account of surveillance in the area showing that there is no disease present.

– National restrictions — All bird gatherings, including fairs, markets, shows, exhibitions and pigeon races, are banned in England, Scotland and Wales. All such gatherings planned over the next few weeks must be cancelled.

What are the next steps?

– Culling was completed at approximately 18:45 on 5 February.

– All carcasses were removed from the site on 5 February.

– Rendering is estimated to be completed by end 8 February.

– The material that is left as a product of the rendering is being stored safely on site at the rendering plant. This material no longer carries infection. It will be incinerated or co-incinerated at an approved plant. No timetable for this has been confirmed.

– Preliminary Cleansing & Disinfection (C&D) began on Monday 5 February. We are not able to be definite about when this will be finished, but current estimates are Thursday 8 February. Preliminary C&D is undertaken by the SVS or a contractor under the supervision of the SVS. It involves the spraying of all material, equipment and housing with approved disinfectants.

– Secondary C&D is the responsibility of the keeper so we cannot be definite about when this will start. Secondary C&D is the responsibility of the poultry keeper, but will also be done under the supervision of the SVS. It involves the removal of all organic matter, followed by washing and de-greasing, followed by further spraying if disinfectants

– Re-populating of the site cannot occur until at least 21 days after the secondary C&D has been completed.

– Legislation states that the PZ must remain for a minimum of 21 days after preliminary C&D has been completed. At this point, after a veterinary check on all poultry/ bird premises in the PZ, the zone becomes part of the SZ and all the SZ measure apply.

– Legislation states that the SZ must remain in place for a minimum of 30 days after preliminary C&D has been completed.

– The length of time that the RZ stays in place will be based on veterinary risk assessment.

– According to the OIE, the international health organisation, highly pathogenic notifiable avian influenza free status can be regained 3 months after a stamping-out policy, including disinfection of all affected establishments; and provided that surveillance is carried out during that three-month period.

How is the farm cleaned to ensure no infection is on site?

Preliminary Cleansing and Disinfection (C&D) is undertaken by the SVS or a contractor under the supervision of the SVS. This involves the spraying of all material, equipment and housing with approved disinfectants.

Secondary C&D is the responsibility of the poultry keeper, but will also be done under the supervision of the SVS. This involves the removal of all organic matter, followed by washing and de-greasing, followed by the spraying of all equipment and housing with approved disinfectants

What exactly is involved in this investigation?

Essentially investigations to determine when infection was introduced and all possible sources of infection. This involves possible movements of birds and animals and their products, people, vehicles, equipment, feedstuffs, bedding material, etc. In this case there has been specific involvement of expert ornithologists to assist with investigating a possible wild bird source. Patrolling the previously identified reserves containing large populations of the species of interest to obtain dead birds have been increased to at least twice per week and additional reserves in the area have been included in this active surveillance. Investigations are naturally concerned with the possible transmission of infection to other poultry premises.

The results of molecular genetical analyses are also important in the epidemiological investigations.

Did H5N1 spread to the other sheds?

As part of our epidemiological investigation samples were taken from all the other 21 sheds on the infected premises when the birds were culled. The turkeys were clinically healthy, but initial test results have indicated that some of the birds in 3 additional sheds were infected with avian influenza. All tests are not yet completed and we will make the results available when they are confirmed.

What information did Defra know and when about poultry imports from Hungary?

We were aware of regular consignments from Hungary in compliance with EU intra-community trade legislation. Our understanding was that they came from uninfected parts of the country. Test results have revealed that the strain of the virus found in the turkeys may be identical to the strain found in Hungary. In addition yesterday (Thursday) new information from the laboratories came to light which revealed that the transmission for the virus is poultry to poultry. This makes transmission direct from Hungary more likely, rather than a pathway via wild birds, hence the announcement today of our investigation yesterday.

If you think that wild birds are unlikely why not lift housing and shooting restrictions in the area?

Our epidemiological investigation is on-going, we have not yet ruled out infection in the wild bird population in the area, or any role that they may possibly play in its mechanical transfer. Until our investigations are complete restrictions therefore need to remain in place. Whatever the means by which infection reached the area now that it is present we need to ensure that it does not spread further via wild birds or other movements, the restriction zone achieves that.

defra

The following highlights health issues in recently released state budget proposals.
Florida: Gov. Charles Crist (R) has proposed a budget that includes $20 million for stem cell research, with a restriction that funding cannot go toward research that uses embryonic stem cells, the Miami Herald reports. Crist also proposed spending $36.7 million to establish a state stockpile of flu vaccine and $1.3 million to create a Governor’s Commission on Physical Fitness. In addition, Crist’s budget includes $79 million to house convicted criminals who have been ruled “mentally incompetent” and to provide community services to people with mental illnesses, according to the Herald (Miami Herald, 2/3).

Pennsylvania: Gov. Ed Rendell (D) on Tuesday proposed a $27.3 billion fiscal year 2007-2008 budget that includes a 1% increase on the state sales tax, which will be used in part to fund health care programs, the Philadelphia Inquirer reports. Under the proposal, the state sales tax would increase from 6% to 7%. Half of the revenue generated by the tax increase, $420 million, would be used to fill gaps in the general fund caused by reductions in federal health care funding, Rendell said (Worden, Philadelphia Inquirer, 2/7). Rendell also proposed increasing the state cigarette tax by 10 cents per pack and placing taxes on smokeless tobacco, pipe tobacco and cigars (Barnes, Pittsburgh Post-Gazette, 2/7). The tobacco tax increase would be used to fund the governor’s Prescription for Pennsylvania health care proposal that aims to extend access to government-subsidized coverage for the 767,000 uninsured state residents. Rendell said the plan would cost $255 million in the first year, and his administration estimates abut 153,600 people would enroll in the program during the first year. The program also would be funded through federal matching funds, a 3% tax on total payrolls of companies that do not offer health insurance to workers and existing funds, Rendell said (Goldstein, Philadelphia Inquirer, 2/7).

New York: Gov. Eliot Spitzer (D) last week released a state budget proposal that would freeze Medicaid reimbursements at hospitals statewide, the Long Island Newsday reports (Ochs, Long Island Newsday, 2/6). Spitzer proposed reducing health care spending by $1.2 billion (PГ©rez-PeГ±a, New York Times, 2/6). About $1 million in cuts would be from Medicaid (Long Island Newsday, 2/6). More than $350 million of the cuts would come from reducing payments to hospitals. The cuts will reduce hospitals’ revenue by 1% on average. Fifteen hospitals that treat higher numbers of Medicaid beneficiaries would absorb more than half of the cuts for all of the state’s 200 hospitals, according to the New York Times (New York Times, 2/6). Hospital officials and legislators are concerned that the freeze in reimbursements might lead to layoffs or decrease the quality of care because “many hospitals already are operating in the red or close to it,” Newsday reports (Long Island Newsday, 2/6).

Rhode Island: Gov. Donald Carcieri (R) proposed a FY 2008 budget that would impose a new tax on health insurers to generate $15.1 million, the Providence Journal reports. The proposal would place the tax on insurers that use more than 12% of their revenue on nonmedical expenses. Under the proposal, not-for-profit Blue Cross and Blue Shield of Rhode Island would be assessed up to 1% of gross premiums and for-profit UnitedHealthcare of New England would be taxed at a rate of up to 2% if the insurers do not meet spending requirements. According to a state insurance department spokesperson, the two insurers are exempt from the current premium tax. Carcieri also proposed a new tax on outpatient surgical, diagnostic and imaging centers to generate $4 million. Under the proposal, such facilities would be required to pay the state 2% of their gross patient revenue. In addition, the governor proposed a 10% reduction in reimbursements for outpatient care to save $1.4 million; mandating that the state pay hospitals a flat rate for emergency department care to save $1.3 million; and speeding the process by which the state and hospitals settle their accounts to save $14.1 million (Freyer, Providence Journal, 2/6).

Virginia: State lawmakers on Sunday announced “competing” plans to amend a two-year budget proposal offered by Gov. Timothy Kaine (D), the Washington Post reports. The state House Appropriations Committee proposed higher Medicaid reimbursements to doctors and hospitals. The state Senate Finance Committee announced “similar expansions of health care programs, including better Medicaid coverage for pregnant women,” the Post reports. Both proposals include funding for HPV vaccines to help prevent cervical cancer (Shear/Gardner, Washington Post, 2/5).

“Reprinted with permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation . © 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved.

By not including funds to offset a pending cut in Medicare payments to physicians, the president’s FY 2008 budget will accelerate the collapse of primary care, create access problems, and manufacture obstacles to fundamental reform of physician payment policies, the American College of Physicians (ACP) said. The organization of 120,000 internists and medical students noted that the budget assumes at least an 8 percent cut in Medicare payments to doctors — which is not sustainable — and is certain to have a multitude of adverse effects.

“This Medicare payment cut will cause severe access problems and will stand in the way of achieving long-standing and fundamental reforms in physician payment policy to support quality improvement and patient-centered primary and principal care,” ACP President Lynne M. Kirk, MD, FACP emphasized. “It is essential that lawmakers agree on a longer-term fix that will provide positive and stable updates, create sustained incentives for quality improvement, and support patient-centered care coordinated by a personal physician.”

The administration’s budget seeks to squeeze some $101.5 billion of savings from Medicare and Medicaid over the next five years. The two plans cover more than one in four Americans.

The FY 2008 budget proposes changes in the State Children’s Health Insurance Program (S-CHIP) to focus more on low-income families. The changes would reduce S-CHIP spending by $223 million, or 4 percent, from this year’s level.

ACP instead proposes that Congress provide increased funding to sustain and expand the S-CHIP program to more low-income children and their parents. The College also recommends that Congress take steps to expand Medicaid to all individuals with incomes below the federal poverty level.

ACP applauds the almost $11 million increase proposed in the budget for the Agency for Healthcare Research and Quality (AHRQ). The nation’s leading Federal agency for research on health care quality, costs, outcomes, and patient safety provides critical information for the improvement of health care.

The College expresses concern, however, that the Department of Veterans Affairs’ medical budget request has been reduced from $27.5 billion a year ago to $27.2 billion for FY 2008.

In addition, ACP urges Congress to provide at least $300 million for Title VII health professions programs in the FY 2008 budget. Elimination or serious under-funding of these programs will undermine the nation’s ability to educate and train primary care physicians. The program is essential to address impending shortages of primary care physicians and to deliver care to the nation’s most vulnerable communities.

“Congress should review the President’s budget requests and assure adequate funding for programs that are critical to the health care of low-income children and adults, the elderly and veterans,” continued Dr. Kirk. “Congress should also move forward on comprehensive reforms to expand health insurance to the nearly 47 million Americans who now lack coverage.”

###

The American College of Physicians is the largest medical specialty organization and the second-largest physician group in the United States. ACP members include 120,000 internal medicine physicians (internists), related subspecialists, and medical students. Internists specialize in the prevention, detection and treatment of illness in adults.

Contact: David Kinsman

American College of Physicians

Sanofi-aventis today announced
that the U.S. Food and Drug Administration (FDA) has approved revisions to
the US Prescribing Information for Ketek(R) (telithromycin).

These revisions follow discussions with the FDA and are based on
recommendations of a FDA Joint Advisory Committee meeting of the Drug
Safety and Risk Management Advisory Committee and Anti-infective Drug
Advisory Committee held in December 2006. The revisions include:

- A boxed warning to alert physicians and patients that the use of the
drug is contraindicated in patients with myasthenia gravis (a rare
autoimmune disease),

– Updated warnings about possible visual disturbances and loss of
consciousness (syncope).

– Deletion of the indications for acute exacerbation of chronic bronchitis
(AECB) and acute bacterial sinusitis (ABS).

Ketek(R) remains indicated in patients with mild to moderate community-
acquired pneumonia (CAP) caused by susceptible pathogens, including
multidrug- resistant Streptococcus pneumoniae (MDRSP).

Ketek(R), when used as directed in its approved indication continues to
be an important option in the anti-infective armamentarium and helps to
satisfy a medical need.

Ketek(R) is currently approved and marketed in over 50 countries. Since
its launch, it is estimated that 28 million patients have been treated with
Ketek(R) worldwide.

MORE INFORMATION

In consultation with the FDA, sanofi-aventis has prepared a Medication
Guide to be distributed to patients along with every prescription of Ketek.
The Medication Guide communicates the rare but potentially serious adverse
events associated with the use of Ketek.

In the U.S., sanofi-aventis will inform healthcare professionals about
the revisions to the U.S. prescribing information through a “Dear
Healthcare Professional” letter, sales force educational communications to
healthcare professionals and the posting of the updated prescribing
information and Medication Guide on the company and product Web sites
(sanofi- aventis.us and Ketek).

Sanofi-aventis will also be contacting several patient organizations
concerned with myasthenia gravis to ensure these parties have the most
updated information regarding the label change of Ketek.

Additional information regarding the Medication Guide and update to the
Ketek prescribing information can be found on the FDA Web site.

About Ketek

Ketek is contraindicated in patients with myasthenia gravis. There have
been reports of fatal and life-threatening respiratory failure in patients
with myasthenia gravis associated with the use of Ketek.

KETEK tablets are indicated for the treatment of community-acquired
pneumonia (of mild to moderate severity) due to Streptococcus pneumoniae,
(including multi-drug resistant isolates [MDRSP*]), Haemophilus influenzae,
Moraxella catarrhalis, Chlamydophila pneumoniae, or Mycoplasma pneumoniae,
for patients 18 years old and above.

MDRSP, Multi-drug resistant Streptococcus pneumoniae includes
isolates known as PRSP (penicillin-resistant Streptococcus pneumoniae), and
are isolates resistant to two or more of the following antibiotics:
penicillin, 2nd generation cephalosporins, e.g., cefuroxime, macrolides,
tetracyclines and trimethoprim/sulfamethoxazole.

KETEK is contraindicated in patients with myasthenia gravis.
Exacerbations of myasthenia gravis have been reported in patients and
sometimes occurred within a few hours of the first dose of telithromycin.
Reports have included fatal and life-threatening acute respiratory failure
with a rapid onset and progression.

KETEK is contraindicated in patients with previous history of hepatitis
and/or jaundice associated with the use of KETEK tablets, or any macrolide
antibiotic.

KETEK is contraindicated in patients with a history of hypersensitivity
to telithromycin and/or any components of KETEK tablets, or any macrolide
antibiotic.

Concomitant administration of KETEK with cisapride or pimozide is
contraindicated.

Acute hepatic failure and severe liver injury, in some cases fatal,
have been reported in patients treated with KETEK. These hepatic reactions
included fulminant hepatitis and hepatic necrosis leading to liver
transplant, and were observed during or immediately after treatment. In
some of these cases, liver injury progressed rapidly and occurred after
administration of a few doses of KETEK.

Physicians and patients should monitor for the appearance of signs or
symptoms of hepatitis, such as fatigue, malaise, anorexia, nausea,
jaundice, bilirubinuria, acholic stools, liver tenderness or hepatomegaly.
Patients with signs or symptoms of hepatitis must be advised to discontinue
KETEK and immediately seek medical evaluation, which should include liver
function tests. If clinical hepatitis or transaminase elevations combined
with other systemic symptoms occur, KETEK should be permanently
discontinued.

Ketek must not be re-administered to patients with a previous history
of hepatitis and/or jaundice associated with the use of KETEK tablets, or
any macrolide antibiotic.

In addition, less severe hepatic dysfunction associated with increased
liver enzymes, hepatitis and in some cases jaundice was reported with the
use of KETEK. These events associated with less severe forms of liver
toxicity were reversible.

Telithromycin has the potential to prolong the QTc interval of the
electrocardiogram in some patients. QTc prolongation may lead to an
increased risk for ventricular arrhythmias, including torsades de pointes.
Thus, telithromycin should be avoided in patients with congenital
prolongation of the QTc interval, and in patients with ongoing
proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia,
clinically significant bradycardia, and in patients receiving Class IA
(e.g., quinidine and procainamide) or Class III (e.g., dofetilide)
antiarrhythmic agents.

Cases of torsades de pointes have been reported post-marketing with
KETEK. In clinical trials, no cardiovascular morbidity or mortality
attributable to QTc prolongation occurred with telithromycin treatment in
4780 patients in clinical trials, including 204 patients having a prolonged
QTc at baseline.

KETEK may cause visual disturbances particularly in slowing the ability
to accommodate and the ability to release accommodation. Visual
disturbances included blurred vision, difficulty focusing, and diplopia.
Most events were mild to moderate; however, severe cases have been
reported.

There have been post-marketing adverse event reports of transient loss
of consciousness including some cases associated with vagal syndrome.

Because of potential visual difficulties or loss of consciousness,
patients should attempt to minimize activities such as driving a motor
vehicle, operating heavy machinery or engaging in other hazardous
activities during treatment with KETEK. If patients experience visual
disorders or loss of consciousness while taking KETEK, patients should not
drive a motor vehicle, operate heavy machinery or engage in other hazardous
activities.

Clostridium difficile associated diarrhea (CDAD) has been reported with
use of nearly all antibacterial agents, including KETEK, and may range in
severity from mild diarrhea to fatal colitis. Treatment with antibacterial
agents alters the normal flora of the colon leading to overgrowth of C.
difficile.

C. difficile produces toxins A and B which contribute to the
development of CDAD. Hypertoxin producing strains of C. difficile cause
increased morbidity and mortality, as these infections can be refractory to
antimicrobial therapy and may require colectomy. CDAD must be considered in
all patients who present with diarrhea following antibiotic use. Careful
medical history is necessary since CDAD has been reported to occur over two
months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed
against C. difficile may need to be discontinued. Appropriate fluid and
electrolyte management, protein supplementation, antibiotic treatment of C
difficile, and surgical evaluation should be instituted as clinically
indicated.

Therapy with simvastatin, lovastatin, or atorvastatin should be
suspended during the course of KETEK treatment. Concomitant treatment of
KETEK with rifampin, a CYP 3A4 inducer, should be avoided.

Most adverse events were mild to moderate and included diarrhea,
nausea, headache, dizziness, and vomiting.

About sanofi-aventis

Sanofi-aventis is one of the world’s leading pharmaceutical companies.
Backed by a world-class R&D organization, sanofi-aventis is developing
leading positions in seven major therapeutic areas: cardiovascular,
thrombosis, oncology, metabolic diseases, central nervous system, internal
medicine and vaccines. Sanofi-aventis is listed in Paris (EURONEXT: SAN)
and in New York (NYSE: SNY).

Forward Looking Statements

This press release contains forward-looking statements as defined in
the Private Securities Litigation Reform Act of 1995. Forward-looking
statements are statements that are not historical facts. These statements
include financial projections and estimates and their underlying
assumptions, statements regarding plans, objectives and expectations with
respect to future events, operations, products and services, and statements
regarding future performance. Forward-looking statements are generally
identified by the words “expect,” “anticipates,” “believes,” “intends,”
“estimates,” “plans” and similar expressions. Although sanofi-aventis’
management believes that the expectations reflected in such forward-looking
statements are reasonable, investors are cautioned that forward-looking
information and statements are subject to various risks and uncertainties,
many of which are difficult to predict and generally beyond the control of
sanofi-aventis, that could cause actual results and developments to differ
materially from those expressed in, or implied or projected by, the
forward-looking information and statements. These risks and uncertainties
include those discussed or identified in the public filings with the SEC
and the AMF made by sanofi-aventis, including those listed under “Risk
Factors” and “Cautionary Statement Regarding Forward- Looking Statements”
in sanofi-aventis’ annual report on Form 20-F for the year ended December
31, 2005. Other than as required by applicable law, sanofi- aventis does
not undertake any obligation to update or revise any forward- looking
information or statements.

sanofi-aventis
sanofi-aventis.us

View drug information on Ketek.

The International
Association for Organ Donation and Wayne State University School of
Medicine will be hosting the 4th World Summit on Organ Donation at the Ritz
Carlton in Dearborn, MI on April 19-20, 2007. The International Association
for Organ Donation is a non-profit organization specializing in educating
minorities as well as the general public about organ donation and related
issues to help dispel misnomers about transplantation and help increase
organ donation registration. The organization is located in Detroit, MI and
is headed by Fouad Beydoun, PhD, President, IAOD, Vice Chairman, Board of
Trustees Harper University Hospital/Hutzel Hospital, Detroit Medical
Center. This global symposium will bring together professionals from around
the world to share best practices, explore new technologies, present new
ideas and information in the field of organ donation and cancer. The
keynote speaker for the World Summit will be Robert M. Mentzer, Jr., M.D.,
Dean, Wayne State University School of Medicine and senior advisor to the
president for medical affairs.

Claire Vajdic, PhD will be presenting recent findings on Cancer
Incidence Before and After Kidney Transplantation. An article published in
JAMA, December 20, 2006 concludes that: Kidney transplantation is
associated with a marked increase in cancer risk at a wide variety of
sites. Immune suppression may be responsible for the increased risk.

There will be a unique opportunity to hear from representatives from
Canada; Kimberly Young, Executive Director, Canadian Council for Donation
and Transplantation, Austria; Marcia Coleman, Chairman, Australian Donate
and the United States; Jade Perdue, Public Health Analyst, Division of
Transplantation, who will be discussing the international approach and the
growing statistical support for change in practices.

Hear about the controversial accusations from the recently published
Kilgour-Matas report regarding illegal organ harvesting in China, along
with other astounding revelations about the black market and unethical
practices in Pakistan, Brazil, and South Africa. There will also be many
more cutting edge presentations from doctors in the United States,
including increasing the use of ECD and DCD.

Join us, the evening of April 20th, for the 8th Annual “Celebrating
Life After Transplant” Gala which will follow the last day of the Summit at
the Ritz Carlton with keynote speaker Tom LaSorda, President and CEO for
the Chrysler Group. This event will be different from all others as it will
be a true celebration recognizing DaimlerChrysler and Former Secretary of
Health and Human Services Tommy Thompson for their tremendous work to
educate the public about the facts regarding organ donation and
transplantation, as well as recipients and individuals on the transplant
wait list. Randy Scott and his band will be providing the entertainment for
the entire celebration with dinner and dancing.

Event Sponsors: DaimlerChrysler, Ford, GM, UAW, Wayne State University
School of Medicine, Oakwood Hospital, Epoch Restaurant, Inc., Astellas,
Pfizer, Roche, BCBSM, Henry Ford Health System, Compuware and the many
individuals who share our mission to save lives each year will be present
for the celebration.

International Association for Organ Donation
iaod/