NIH News

U.S. Department of Health and Human Services
Eunice Kennedy Shriver National Institute of Child Health and Human Development
For Immediate Release: Tuesday, January 13, 2009

The National Institutes of Health announced today that the National Children’s Study will begin recruiting volunteers to take part in its comprehensive study of how genes and the environment interact to affect children’s health. The study will track the health and development of more than 100,000 children from before birth through to their 21st birthday.

At a briefing, NIH officials announced that the first phase of recruitment for the study will begin in Duplin County, N.C., and the New York City borough of Queens.

“The principal benefit of a large scale, long-term study like the National Children’s Study is that it will uncover important health information at virtually every phase of life,” said Duane Alexander, M.D., Director of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), one of a consortium of federal agencies implementing the study. “Initially, it will provide major insights into disorders of birth and infancy, such as preterm birth and its health consequences. Ultimately it will lead to a greater understanding of adult disorders, many of which are thought to be heavily influenced by early life exposures and events. ”

Dr. Alexander added that the large size of the study should yield information that smaller and more limited studies cannot. For example, because of the large number of individuals enrolled, the study has the capability to assess uncommon disorders, as well as how exposures to different environmental conditions and genetic factors may interact.

In addition to the NICHD, other members of the consortium carrying out the study are the NIH’s National Institute of Environmental Health Sciences, the Centers for Disease Control and Prevention, and the U.S. Environmental Protection Agency. The National Children’s Study was authorized by Congress in the Children’s Health Act of 2000.

When it is fully operational, the National Children’s Study is expected to have roughly 40 study centers recruiting volunteers from 105 designated study locations throughout the United States. The study locations are counties and clusters of counties chosen by National Children’s Study researchers to be representative of children in the United States.

Of seven initial, or Vanguard, study centers, two will be the first to recruit. This week, the University of North Carolina at Chapel Hill will begin recruiting study volunteers from Duplin County, N.C.. The Mount Sinai School of Medicine in New York City will recruit volunteers from the Borough of Queens.

The centers will hold presentations and other community awareness activities in their respective locations to inform prospective volunteers. Some families in those areas will receive letters introducing the study, explained Peter Scheidt, M.D., M.P.H., director, National Children’s Study. Prenatal care providers and clinics in the study locations will also inform women about the study.

In April of 2009, the remaining five Vanguard centers will also begin recruiting and enrolling women to participate in the study. At the end of 18 months, each center is expected to have recruited a total of approximately 375 volunteers.

A listing of the seven Vanguard center locations is available on the National Children’s Study Web site at

Dr. Scheidt added that during this initial recruitment phase, referred to as the Vanguard cohort phase, study researchers will evaluate their recruitment and sampling methods.

“We’ll look at what we’ve accomplished, see if our recruitment efforts were sufficient, see if our sampling methods were successful, and if we’ve otherwise asked the right questions to get the information we need,” Dr. Scheidt said. “Along the way, we’ll undertake any fine tuning that we need to in preparation for further enrollment after the Vanguard cohort phase.”

The information collected during this Vanguard phase can be pooled with the data collected during later phases of the study to provide the basis for later scientific analysis.

Although the study can be expected to provide information throughout its duration, information on disorders and conditions of early life is expected within the next few years. Because the study will enroll pregnant women and, in some cases, women who are not yet pregnant, study scientists hope to identify a range of early life factors that influence later development.

“It is very exciting to reach the point at which we’re beginning enrollment and data collection,” Dr. Scheidt said. “Findings from the study will ultimately benefit all Americans by providing researchers, health care providers, and public health officials with information from which to develop prevention strategies, health and safety guidelines, and possibly new treatments and perhaps even cures for disease.”

The two Vanguard Cohort Centers will reflect the study’s representative design in their recruitment, said Dr. Barbara Entwisle, the principal investigator of the National Children’s Study Center at the University of North Carolina at Chapel Hill.

“From city streets to far-flung small towns, the two Vanguard centers will capture a broad sample that’s reflective of America’s diversity,” she said.

Dr. Entwisle explained that, unlike Queens, which is a densely populated urban area, Duplin County is a sparsely populated rural county spread out over a large area-819 square miles. Many large hog and turkey farms are located in Duplin County, as well as the factories that process them. There are about 800 births per year in Duplin County, a small fraction of the more than 30,000 births that occur in Queens each year, she added.

“The children in the Duplin sample will be representative of other rural areas of the U.S.,” Dr. Entwisle said.

The study location in Queens has a population of 2.23 million and is home to thousands of immigrants from more than 100 nations, said Dr. Philip Landrigan, principal investigator, Mount Sinai School of Medicine.

Like many urban counties in the United States, Dr. Landrigan added, Queens is disproportionately affected by many conditions for which the National Children’s Study will help find environmental predecessors and information on the causes. For example, he said, in some parts of New York City, 1 in 4 children have asthma. In addition, one fifth of the city’s children entering kindergarten are overweight.


The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute’s Web site at .

The National Institutes of Health (NIH) – The Nation’s Medical Research Agency – includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases.

For more information about NIH and its programs, visit .

This NIH News Release is available online at:


For Immediate Release: January 9, 2009

On December 19, 2008, CDC issued interim guidance for health care professionals on the use of influenza antiviral medications this flu season. The guidance was issued in response to early data from a limited number of states indicating that a high proportion of influenza A (H1N1) viruses are resistant to the influenza antiviral medication oseltamivir (Tamiflu®). Worldwide, the proportion of H1N1 viruses that are resistant to oseltamivir has been increasing so this development is not surprising.

Recent media reports may have led some to believe that these developments mean physicians are without influenza treatment options for the 2008-2009 flu season.

At this time, it’s not possible to predict how common H1N1 viruses will be during the rest of this flu season, as there are many different flu viruses and every influenza season is different. The current samples studied come from a handful of states, and may not be indicative of how the rest of the season will progress or what viruses will circulate in other states. However the circulation of oseltamivir-resistant viruses does have treatment implications for health care professionals. CDC is continuing to monitor this situation very closely, but has issued interim guidance for health care professionals to guide their treatment decisions in the current situation.

In fact, the interim CDC guidance provides advice for clinicians on how to treat patients with influenza antiviral medications this season. Clinicians can use influenza test results and information, if available, about which viruses are circulating, to help decide which antiviral(s) should be used. If H1N1 viruses are circulating in the community, or it’s not clear which viruses are circulating, health care providers are recommended to use an alternative antiviral, zanamivir (Relenza®), or to use combination therapy of oseltamivir and rimantadine. Use of zanamivir or dual therapy with oseltamivir and rimantadine would provide effective treatment against all circulating influenza viruses. In some instances, oseltamivir alone can still be used, such as when influenza B is diagnosed, or H1N1 viruses are not circulating.

It is important to remember that CDC recommends annual influenza vaccination as the first and best step in preventing the flu. It is not too late to get vaccinated and this year′s influenza vaccine is expected to be effective against currently circulating oseltamivir-resistant influenza A (H1N1) viruses.

Helpful Links

· Summary of December 19, 2008 Guidance

· Full Text of Guidance:

· Podcast on Influenza Antiviral Resistance and Interim Guidance:

· Flu activity and surveillance:

· Downloadable high-resolution flu image:

· Flu references and resources:




This is an official

Distributed via Health Alert Network
Friday, December 19, 2008, 11:50 EST (11:50 AM EST)

CDC Issues Interim Recommendations for the Use of Influenza Antiviral Medications in the Setting of Oseltamivir Resistance among Circulating Influenza A (H1N1) Viruses,
2008-09 Influenza Season

Although influenza activity is low in the United States to date, preliminary data from a limited number of states indicate that the prevalence of influenza A (H1N1) virus strains resistant to the antiviral medication oseltamivir is high. Therefore, CDC is issuing interim recommendations for antiviral treatment and chemoprophylaxis of influenza during the 2008-09 influenza season. When influenza A (H1N1) virus infection or exposure is suspected, zanamivir or a combination of oseltamivir and rimantadine are more appropriate options than oseltamivir alone. Local influenza surveillance data and laboratory testing can help with physician decision-making regarding the choice of antiviral agents for their patients. The 2008-09 influenza vaccine is expected to be effective in preventing or reducing the severity of illness with currently circulating influenza viruses, including oseltamivir-resistant influenza A (H1N1) virus strains. Since influenza activity remains low and is expected to increase in the weeks and months to come, CDC recommends that influenza vaccination efforts continue.


Influenza A viruses, including two subtypes (H1N1) and (H3N2), and influenza B viruses, currently circulate worldwide, but the prevalence of each can vary among communities and within a single community over the course of an influenza season. In the United States, four prescription antiviral medications (oseltamivir, zanamivir, amantadine and rimantadine) are approved for treatment and chemoprophylaxis of influenza. Since January 2006, the neuraminidase inhibitors (oseltamivir, zanamivir) have been the only recommended influenza antiviral drugs because of widespread resistance to the adamantanes (amantadine, rimantadine) among influenza A (H3N2) virus strains. The neuraminidase inhibitors have activity against influenza A and B viruses while the adamantanes have activity only against influenza A viruses. In 2007-08, a significant increase in the prevalence of oseltamivir resistance was reported among influenza A (H1N1) viruses worldwide. During the 2007-08 influenza season, 10.9% of H1N1 viruses tested in the U.S. were resistant to oseltamivir.

Influenza activity has been low thus far this season in the United States. As of December 19, 2008, a limited number of influenza viruses isolated in the U.S. since October 1 have been available for antiviral resistance testing at CDC. Of the 50 H1N1 viruses tested to date from 12 states, 98% were resistant to oseltamivir, and all were susceptible to zanamivir, amantadine and rimantadine. Preliminary data indicate that oseltamivir-resistant influenza A (H1N1) viruses do not cause different or more severe symptoms compared to oseltamivir sensitive influenza A (H1N1) viruses. Influenza A (H3N2) and B viruses remain susceptible to oseltamivir. The proportion of influenza A (H1N1) viruses among all influenza A and B viruses that will circulate during the 2008-09 season cannot be predicted, and will likely vary over the course of the season and among communities. Oseltamivir-resistant influenza A (H1N1) viruses are antigenically similar to the influenza A (H1N1) virus strain represented in 2008-09 influenza vaccine, and CDC recommends that influenza vaccination efforts continue as the primary method to prevent influenza.

Oseltamivir resistance among circulating influenza A (H1N1) virus strains presents challenges for the selection of antiviral medications for treatment and chemoprophylaxis of influenza, and provides additional reasons for clinicians to test patients for influenza virus infection and to consult surveillance data when evaluating persons with acute respiratory illnesses during influenza season. These interim guidelines provide options for treatment or chemoprophylaxis of influenza in the United States if oseltamivir-resistant H1N1 viruses are circulating widely in a community or if the prevalence of oseltamivir resistant H1N1 viruses is uncertain.

Interim Recommendations

Persons providing medical care for patients with suspected influenza or persons who are candidates for chemoprophylaxis against influenza should consider the following guidance for assessing and treating patients during the 2008-09 influenza season (see Table below). Guidance Table):

1) Review local or state influenza virus surveillance data weekly during influenza season, to determine which types (A or B) and subtypes of influenza A virus (H3N2 or H1N1) are currently circulating in the area. For some communities, surveillance data might not be available or timely enough to provide information useful to clinicians.

2) Consider use of influenza tests that can distinguish influenza A from influenza B.

a. Patients testing positive for influenza B may be given either oseltamivir or zanamivir (no preference) if treatment is indicated.

b. At this time, if a patient tests positive for influenza A, use of zanamivir should be considered if treatment is indicated. Oseltamivir should be used alone only if recent local surveillance data indicate that circulating viruses are likely to be influenza A (H3N2) or influenza B viruses. Combination treatment with oseltamivir and rimantadine is an acceptable alternative, and might be necessary for patients that cannot receive zanamivir, (e.g., patient is <7 years old, has chronic underlying airways disease, or cannot use the zanamivir inhalation device), or zanamivir is unavailable. Amantadine can be substituted for rimantadine if rimantadine is unavailable.

c. If a patient tests negative for influenza, consider treatment options based on local influenza activity and clinical impression of the likelihood of influenza. Because rapid antigen tests may have low sensitivity, treatment should still be considered during periods of high influenza activity for persons with respiratory symptoms consistent with influenza who test negative and have no alternative diagnosis. Use of zanamivir should be considered if treatment is indicated. Combination treatment with oseltamivir and rimantadine (substitute amantadine if rimantadine unavailable) is an acceptable alternative. Oseltamivir should be used alone only if recent local surveillance data indicates that circulating viruses are likely to be influenza A(H3N2) or influenza B viruses.

d. If available, confirmatory testing with a diagnostic test capable of distinguishing influenza caused by influenza A (H1N1) virus from influenza caused by influenza A (H3N2) or influenza B virus can also be used to guide treatment. When treatment is indicated, influenza A (H3N2) and influenza B virus infections should be treated with oseltamivir or zanamivir (no preference). Influenza A (H1N1) virus infections should be treated with zanamivir or combination treatment with oseltamivir and rimantadine is an acceptable alternative.

3) Persons who are candidates for chemoprophylaxis (e.g., residents in an assisted living facility during an influenza outbreak, or persons who are at higher risk for influenza-related complications and have had recent household or other close contact with a person with laboratory confirmed influenza) should be provided with medications most likely to be effective against the influenza virus that is the cause of the outbreak, if known. Respiratory specimens from ill persons during institutional outbreaks should be obtained and sent for testing to determine the type and subtype of influenza A viruses associated with the outbreak and to guide antiviral therapy decisions. Persons whose need for chemoprophylaxis is due to potential exposure to a person with laboratory-confirmed influenza A (H3N2) or influenza B should receive oseltamivir or zanamivir (no preference). Zanamivir should be used when persons require chemoprophylaxis due to exposure to influenza A ( H1N1) virus. Rimantadine can be used if zanamivir use is contraindicated.

Enhanced surveillance for influenza antiviral resistance is ongoing at CDC in collaboration with local and state health departments. Clinicians should remain alert for additional changes in recommendations that might occur as the 2008–09 influenza season progresses. Oseltamivir resistant influenza A (H1N1) viruses are antigenically similar to the influenza A(H1N1) viruses represented in the vaccine, and vaccination should continue to be considered the primary prevention strategy regardless of oseltamivir sensitivity. Information on antiviral resistance will be updated in weekly surveillance reports (available at

For more information on antiviral medications and additional considerations related to antiviral use during the 2008-09 influenza season, visit


Interim recommendations for the selection of antiviral treatment using laboratory test results and viral surveillance data, United States, 2008-09 season‡

Rapid antigen or other laboratory test

Predominant virus(es) in community

Preferred medication(s)

Alternative (combination antiviral treatment)

Not done or negative, but clinical suspicion for influenza

H1N1 or unknown


Oseltamivir + Rimantadine*

Not done or negative, but clinical suspicion for influenza

H3N2 or B

Oseltamivir or Zanamivir


Positive A

H1N1 or unknown


Oseltamivir + Rimantadine*

Positive A

H3N2 or B

Oseltamivir or Zanamivir


Positive B


Oseltamivir or Zanamivir


Positive A+B**

H1N1 or unknown


Oseltamivir + Rimantadine*

Positive A+B**

H3N2 or B

Oseltamivir or Zanamivir


*Amantadine can be substituted for rimantadine but has increased risk of adverse events. Human data are lacking to support the benefits of combination antiviral treatment of influenza; however, these interim recommendations are intended to assist clinicians treating patients who might be infected with oseltamivir-resistant influenza A (H1N1) virus.

**Positive A+B indicates a rapid antigen test that cannot distinguish between influenza and influenza B viruses

‡ Influenza antiviral medications used for treatment are most beneficial when initiated within the first two days of illness. Clinicians should consult the package insert of each antiviral medication for specific dosing information, approved indications and ages, contraindications/warnings/precautions, and adverse effects.

##This Message was distributed to State and Local Health Officers, Public Information Officers, Epidemiologists, State Laboratory Directors, PHEP/BT Coordinators and HAN Coordinators, as well as Public Health Associations and Clinician organizations##

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2008-2009 Influenza Season Week 53 ending January 3, 2009

(All data are preliminary and may change as more reports are received.)


During week 53 (December 28, 2008 – January 3, 2009), influenza activity in the United States remained at approximately the same level as in the previous week.

· Seventy-nine (3.2%) specimens tested by U.S. World Health Organization (WHO) and National Respiratory and Enteric Virus Surveillance System (NREVSS) collaborating laboratories and reported to CDC/Influenza Division were positive for influenza.

· The proportion of deaths attributed to pneumonia and influenza (P&I) was below the epidemic threshold.

· The proportion of outpatient visits for influenza-like illness (ILI) was below national and region-specific baseline levels.

· Four states reported regional activity; 11 states reported local influenza activity; the District of Columbia and 30 states reported sporadic influenza activity; and five states reported no influenza activity.

Picture 2.png

* Elevated means the % of visits for ILI is at or above the national or region-specific baseline
† National data is for current week; regional data is for the most recent three weeks.
‡ Includes all 50 states and the District of Columbia

U.S. Virologic Surveillance:

WHO and NREVSS collaborating laboratories located in all 50 states and Washington D.C. report to CDC the number of respiratory specimens tested for influenza each week. The results of tests performed during the current week and cumulative totals for the season are summarized in the table below.

Picture 3.png
The District of Columbia and 42 states from all nine surveillance regions have reported laboratory-confirmed influenza this season. Three states account for 794 (67.7%) of the 1,173 reported influenza viruses.


Antigenic Characterization:

CDC has antigenically characterized 110 influenza viruses [68 influenza A (H1), 13 influenza A (H3) and 29 influenza B viruses] collected by U.S. laboratories since October 1, 2008.

All 68 influenza A (H1) viruses are related to the influenza A (H1N1) component of the 2008-09 influenza vaccine (A/Brisbane/59/2007). All 13 influenza A (H3N2) viruses are related to the A (H3N2) vaccine component (A/Brisbane/10/2007).

Influenza B viruses currently circulating can be divided into two distinct lineages represented by the B/Yamagata/16/88 and B/Victoria/02/87 viruses. Nine influenza B viruses tested belong to the B/Yamagata lineage and are related to the vaccine strain (B/Florida/04/2006). The remaining 20 viruses belong to the B/Victoria lineage and are not related to the vaccine strain. Seventeen of the 20 viruses belonging to the B/Victoria lineage were from two states.

Data on antigenic characterization should be interpreted with caution given that:

1. Few U.S. isolates are available for testing because of limited influenza activity thus far.

2. The majority of viruses antigenically characterized to date come from only three states and may not be nationally representative.

3. Antigenic characterization data is based on hemagglutination inhibition (HI) testing using a panel of reference ferret antisera and results may not correlate with clinical protection against circulating viruses provided by influenza vaccination.

Annual influenza vaccination is expected to provide the best protection against those virus strains that are related to the vaccine strains, but limited to no protection may be expected when the vaccine and circulating virus strains are so different as to be from different lineages, as is seen with the two lineages of influenza B viruses.

Antiviral Resistance:

Since October 1, 2008, 88 influenza A (H1N1), 14 influenza A (H3N2), and 40 influenza B viruses from 25 states have been tested for resistance to the neuraminidase inhibitors (oseltamivir and zanamivir). Eighty-eight influenza A (H1N1) and 14 influenza A (H3N2) viruses from 23 states have been tested for resistance to the adamantanes (amantadine and rimantadine). The results of antiviral resistance testing performed on these viruses are summarized in the table below.

IPicture 4.png
*The adamantanes (amantadine and rimantadine) are not effective against influenza B viruses.

With low levels of influenza activity thus far in the 2008-09 season in the United States, overall numbers of virus specimens and the number of states that have submitted specimens for testing is limited. The limited number and geographic diversity of specimens tested for antiviral resistance, as well as the uncertainty regarding which influenza virus types or subtypes will predominate during the season, make it too early to make an accurate determination of the prevalence of influenza viruses resistant to oseltamivir nationally or regionally at this time. CDC has solicited a representative sample of viruses from WHO collaborating laboratories in the United States, and more specimens are expected as influenza activity increases.

Pneumonia and Influenza (P&I) Mortality Surveillance

During week 53, 7.0% of all deaths reported through the 122-Cities Mortality Reporting System were due to P&I. This percentage is below the epidemic threshold of 7.6% for week 53.


Influenza-Associated Pediatric Mortality

No influenza-associated pediatric deaths were reported during week 53. A total of one influenza-associated pediatric death occurring during the 2008-09 season has been reported.


Influenza-Associated Hospitalizations

Laboratory-confirmed influenza-associated hospitalizations are monitored in two population-based surveillance networks: the Emerging Infections Program (EIP) and the New Vaccine Surveillance Network (NVSN).

No influenza-associated hospitalizations have been reported from the New Vaccine Surveillance Network this season.

During October 1, 2008 – January 3, 2009, preliminary laboratory-confirmed influenza-associated hospitalization rates reported by the EIP for children aged 0-4 years and 5-17 years were 0.3 per 10,000 and 0.01 per 10,000, respectively. For adults aged 18-49 years, 50-64 years, and = 65 years, the rates were 0.03 per 10,000, 0.05 per 10,000, and 0.2 per 10,000, respectively.


Outpatient Illness Surveillance:

During week 53, 1.8% of patient visits reported through the U.S. Outpatient Influenza-like Illness Surveillance Network (ILINet) were due to influenza-like illness (ILI). This percentage is less than the national baseline of 2.4%. On a regional level, the percentage of visits for ILI ranged from 0.2% to 4.6%. All nine surveillance regions reported percentages of visits for ILI below their respective region-specific baselines.



Got the flu? CDC says Tamiflu may not be much help

By MIKE STOBBE – Dec 19, 2008

ATLANTA (AP) — The medical arsenal against the flu just got weaker. Government health officials said Friday that a leading flu medicine, Tamiflu, might not work against all cases of the flu this year. The most common flu bug right now is overwhelmingly resistant to Tamiflu, they said. The alert is “an early heads-up” for doctors. If current trends continue, they may need to change how they treat patients this flu season, said Dr. Julie Gerberding, director of the U.S. Centers for Disease Control and Prevention.

Health officials say they aren’t too worried, for several reasons. First, it’s early in the flu season, and it’s not clear this strain will dominate through the next several months. Second, not many people take antiviral medications for the flu.

Third, the flu vaccine — the primary weapon against flu — seems well matched against the circulating bugs.

But doctors need to take it seriously, said William Schaffner, a Vanderbilt University infectious diseases expert.

“Each influenza seasons provides a bit of a surprise and we got our (surprise) a little early this year,” he added.

The flu causes 200,000 hospitalizations and 36,000 deaths annually, according to official estimates. The elderly, young children and people with chronic illnesses are considered at greatest risk.

For the public, the best course of action is vaccination, health officials said. Only about 30 percent of U.S. adults had gotten a flu vaccination this flu season, according to an online survey conducted by the RAND Corporation in November. A flu shot is recommended for those 50 and older, children from 6 months to 18 years, pregnant women, nursing home patients and those with certain medical conditions or who care for people with those conditions.

For people who get the flu, the two most commonly used antivirals are Tamiflu, a pill also known as oseltamivir, and Relenza, an inhaled drug also called zanamivir. The drugs are most effective if taken within two days of getting sick but most people don’t see a doctor that quickly.

Early tests indicate that 49 of 50 samples of the main flu virus circulating this year — H1N1 — were resistant to Tamiflu. The samples came mainly from Hawaii, Texas and ten other states. Widespread flu has not yet been reported in most of the country.

“It could fizzle out,” or H1N1 could become the dominant strain, Gerberding said.

A spokesman for Tamiflu’s manufacturer — Roche, a Swiss company — said it’s too early to draw strong conclusions about the drug’s usefulness this flu season. The basis of the CDC’s alert “is a small sample in a limited number of states, and Tamiflu is showing good activity against other circulating viruses,” said spokesman Terry Hurley.

For those sick with the flu, doctors cannot simply choose Relenza instead of Tamiflu. That treatment is not approved for children younger than 7 or people who have asthma or certain other breathing problems. GlaxoSmithKline PLC, which makes Relenza, said Friday it has enough to meet the demands of the current flu season.

An option for some patients, Gerberding said, may be a combination of Tamiflu and rimantadine, another antiviral medication that works against H1N1 but lost effectiveness against another kind of flu virus.

However, it’s not clear how well that combination will work, Schaffner said.

“This is a ‘best advice with our back against the wall’ kind of thing,” he said.

On the Net:

· The CDC flu report:

ScienceDaily, January 9, 2009 — Patients with advanced Parkinson disease (PD) who received deep brain stimulation treatment had more improvement in movement skills and quality of life after six months than patients who received other medical therapy, but also had a higher risk of a serious adverse events, according to a new study.

Deep brain stimulation is a surgical treatment involving the implantation of electrodes that send electrical stimulation to specific parts of the brain to reduce involuntary movements and tremors. It is the surgical intervention of choice when PD motor (movement) complications are inadequately managed with medications, according to background information in the article. “However, recent reports highlighting unexpected behavioral effects of stimulation suggest that deep brain stimulation, while improving motor function, may have other less desirable consequences,” the authors write. They add that there are few randomized trials comparing treatments, and most studies exclude older patients.

Frances M. Weaver, Ph.D., of Hines VA Hospital, Hines, Ill., and colleagues conducted a randomized trial to compare the benefits and risks of deep brain stimulation with those of best medical therapy for patients, of a wide age range, with PD. A total of 255 patients with PD were enrolled; 25 percent were age 70 years or older. The participants were randomized to receive bilateral deep brain stimulation with leads of the stimulation device implanted in the following locations of the brain: subthalamic nucleus (n = 60) or globus pallidus (n = 61); or received best medical therapy (n = 134), which included management by movement disorder neurologists, who monitored medication use and nonpharmacological therapy (e.g., physical, occupational, and speech therapy).

The researchers found that at 6 months, deep brain stimulation patients gained an average of 4.6 hours per day of on time (the time of good symptom control or unimpeded motor function) without troubling dyskinesia (involuntary movements), while the average change for the best medical therapy group was 0 hours. Motor function improved significantly with deep brain stimulation compared with best medical therapy, with 71 percent of deep brain stimulation patients vs. 32 percent of best medical therapy patients experiencing clinically meaningful motor function improvements at 6 months, while 3 percent of deep brain stimulation patients and 21 percent of best medical therapy patients had clinically worsening scores.

Compared with patients in the best medical therapy group, patients in the deep brain stimulation group experienced significant improvements in the summary measure of quality of life and on 7 of 8 PD quality-of-life scores. Neurocognitive testing revealed small decrements in some areas of information processing for patients receiving deep brain stimulation vs. best medical therapy.

The overall risk of experiencing a serious adverse event was 3.8 times higher in deep brain stimulation patients than in best medical therapy patients. Forty-nine deep brain stimulation patients (40 percent) experienced 82 serious adverse events. Fifteen best medical therapy patients (11 percent) experienced 19 serious adverse events. The most common serious adverse event was surgical site infection, with other serious adverse events including nervous system disorders, psychiatric disorders, device-related complications and cardiac disorders.

“The clinical significance of the adverse events and minor neurocognitive changes observed in patients in the deep brain stimulation group and, more importantly, whether patients who undergo deep brain stimulation view improvement in motor function and quality of life as outweighing adverse events, remain to be explored. More detailed analyses of adverse events and neurocognitive functioning following the conclusion of phase 2 of this study will shed light on these issues. Caution should be exercised, however, against overstating or understating the risks of deep brain stimulation for patients with PD. Physicians must continue to weigh the potential short-term and long-term risks with the benefits of deep brain stimulation in each patient,” the authors conclude.

Editorial: Neurostimulation for Parkinson Disease

In an accompanying editorial, Günther Deuschl, M.D., Ph.D., of the Universitätsklinikum Schleswig-Holstein, Kiel, Germany, comments on the findings of Weaver and colleagues.

“Although deep brain stimulation is the most important innovation for treatment of advanced PD since the discovery of levodopa [drug used to treat PD], many questions are still unanswered. For instance, the optimal timing for the implantation is unknown. The majority of patients undergo deep brain stimulation surgery more than 10 years after disease onset when the patients are already incapable of working and when the disease-related psychosocial decline has already begun. As quality of life is improved with this treatment it may improve psychosocial functioning in general for these advanced stages. With the aging of the general population, PD will become even more common and patients with PD will get older. Therefore, the present results showing similar efficacy and tolerability of deep brain stimulation in younger and older patients must be replicated because it is at variance with some other reports demonstrating lower rates of operative and postoperative complications in younger patients.”

“Overall the results of this important study by Weaver et al have convincingly confirmed the 6-month efficacy of deep brain stimulation for advanced PD in the largest patient group studied thus far. However, this study, along with previous research on this therapy, shows that such progress cannot be made without costs in terms of adverse effects.”, January 10, 2009 — Researchers at Oregon Health & Science University’s School of Dentistry have discovered that the nerve cells controlling heart rate and blood pressure synthesize a molecule known to be critically important for proper nervous system growth.

The finding could someday play a significant role in the prevention of Sudden Infant Death Syndrome (SIDS) and high blood pressure. According to the National Institutes of Health, SIDS is the leading cause of death in children between 1 month and 1 year of age. About one in three adults in the United States has high blood pressure.

The new discovery was published in a January issue of the Journal of Neurochemistry (vol. 108, pp. 450-464) and released online December 1, 2008.

“Our discovery sheds light on how the nerve supply to the cardiovascular system is established during development,” said Agnieszka Balkowiec, M.D., Ph.D., principal investigator, OHSU School of Dentistry assistant professor of integrative biosciences and OHSU School of Medicine adjunct assistant professor of physiology and pharmacology. “Someday we hope to better understand cardiorespiratory developmental disorders such as SIDS.”

Changes in blood pressure are signaled to the brain by nerve cells called baroreceptors. The OHSU study shows that baroreceptors make a molecule called Brain-Derived Neurotrophic Factor (BDNF), which belongs to the family of neurotrophins that play a critical role in the development and plasticity of other nerve cells. (Studies suggest that developmental abnormalities in nerve pathways that control the cardiovascular and respiratory system may result in SIDS).

Balkowiec and her team found that the stimulation of baroreceptors, as experienced during an increase in blood pressure, leads to the release of BDNF. The study also discovered that BDNF is present at the central end of baroreceptors in the brainstem.

“In fact, BDNF is likely to play the most important role at the central end of baroreceptors, where they connect to second-order neurons in the blood-pressure control pathway,” said Balkowiec. “BDNF has previously been shown to play an important role in establishing neuronal connections in other parts of the nervous system, but this is the first time it has been considered a factor in the blood pressure control system.”

Studies under way, in collaboration with Virginia Brooks, Ph.D., OHSU School of Medicine professor of physiology and pharmacology, indicate that levels of BDNF in cardiorespiratory nerve cells increase dramatically when blood pressure rises. This suggests a direct role of BDNF in regulation of blood pressure, said Balkowiec.

Additional study authors include neuroscience graduate student Jessica Martin, B.S., and two OHSU research assistants, Victoria Jenkins, B.A., and Hui-ya Hsieh, B.S.

The study was supported by grants from the American Heart Association and the National Institute’s of Health’s National Heart, Lung, and Blood Institute.