Sharon Worcester

New data linking paroxetine use during the first trimester of pregnancy with increased risk of major congenital malformations has prompted changes to the drug's label.

Preliminary results of a retrospective epidemiologic study sponsored by GlaxoSmithKline Inc., the drug's maker, show paroxetine (marketed as Paxil), was associated with more congenital malformations (adjusted odds ratio 2.20) and more cardiovascular malformations (adjusted odds ratio 2.08) than other antidepressants in almost 3,600 pregnant women.

The prevalence of congenital malformations in the study was 4%, compared with about 3% in the general population.

The prevalence of cardiovascular malformations was 2%, compared with about 1% in the general population, according to a “Dear Healthcare Professional” letter issued by the company and the Food and Drug Administration.

Ventricular septal defects were the most common cardiovascular malformation in the study.

The GSK findings, along with those from two other recently published abstracts, warrant the voluntary label change, according to the company.

In one of the abstracts, Pia Wogelius, Ph.D., of the epidemiology department at Aarhus University Hospital, Denmark, and colleagues reported a link between SSRIs and major congenital malformations, including cardiac malformations. The risk of malformation was increased among women who had prescriptions for SSRIs filled in the 30 days before conception through the end of the first trimester, compared with those who had no SSRI prescriptions filled during the same period. These data did not specifically look at Paxil use.

The other abstract described a preliminary analysis of data obtained from the National Birth Defects Prevention Study suggesting an association between SSRI use between 1 month before and 3 months after conception and a significantly increased risk of omphalocele. The risk was greatest among paroxetine users, Sura Alwan, a Ph.D. student at the University of British Columbia, Vancouver, reported at the annual meeting of the Teratology Society.

SSRI use in that study also was linked with an increased risk of tetralogy of Fallot, she told FAMILY PRACTICE NEWS.

The Paxil labeling changes will be in the pregnancy subsection of the “precautions” section of the labels for Paxil and Paxil CR. The new language cites the GSK data but also notes that these data conflict with those from previous studies, including those from the Swedish Medical Birth Registry, which showed no increased risk of major malformations in infants born to 708 women exposed to SSRIs—including paroxetine—during pregnancy.

The conflicting data make it difficult to establish a causal relationship between SSRI use and major congenital malformations. Due to the lack of adequate and well-controlled studies, Paxil maintains its Pregnancy Category C status, according to GSK.

“As with all Pregnancy Category C drugs, health care providers are advised to carefully weigh the potential risks and benefits of using paroxetine therapy in women during pregnancy,” the company said in the letter.

Results of the GSK study are posted at the company's Clinical Trial Register at http://ctr.gsk.co.uk/welcome.asp

New data linking paroxetine use during the first trimester of pregnancy with increased risk of major congenital malformations has prompted changes to the drug's label.

Preliminary results of a retrospective epidemiologic study sponsored by GlaxoSmithKline Inc., the drug's maker, show paroxetine (marketed as Paxil), was associated with more congenital malformations (adjusted odds ratio 2.20) and more cardiovascular malformations (adjusted odds ratio 2.08) than other antidepressants in almost 3,600 pregnant women.

The prevalence of congenital malformations in the study was 4%, compared with about 3% in the general population.

The prevalence of cardiovascular malformations was 2%, compared with about 1% in the general population, according to a “Dear Healthcare Professional” letter issued by the company and the Food and Drug Administration.

Ventricular septal defects were the most common cardiovascular malformation in the study.

The GSK findings, along with those from two other recently published abstracts, warrant the voluntary label change, according to the company.

In one of the abstracts, Pia Wogelius, Ph.D., of the epidemiology department at Aarhus University Hospital, Denmark, and colleagues reported a link between SSRIs and major congenital malformations, including cardiac malformations. The risk of malformation was increased among women who had prescriptions for SSRIs filled in the 30 days before conception through the end of the first trimester, compared with those who had no SSRI prescriptions filled during the same period. These data did not specifically look at Paxil use.

The other abstract described a preliminary analysis of data obtained from the National Birth Defects Prevention Study suggesting an association between SSRI use between 1 month before and 3 months after conception and a significantly increased risk of omphalocele. The risk was greatest among paroxetine users, Sura Alwan, a Ph.D. student at the University of British Columbia, Vancouver, reported at the annual meeting of the Teratology Society.

SSRI use in that study also was linked with an increased risk of tetralogy of Fallot, she told FAMILY PRACTICE NEWS.

The Paxil labeling changes will be in the pregnancy subsection of the “precautions” section of the labels for Paxil and Paxil CR. The new language cites the GSK data but also notes that these data conflict with those from previous studies, including those from the Swedish Medical Birth Registry, which showed no increased risk of major malformations in infants born to 708 women exposed to SSRIs—including paroxetine—during pregnancy.

The conflicting data make it difficult to establish a causal relationship between SSRI use and major congenital malformations. Due to the lack of adequate and well-controlled studies, Paxil maintains its Pregnancy Category C status, according to GSK.

“As with all Pregnancy Category C drugs, health care providers are advised to carefully weigh the potential risks and benefits of using paroxetine therapy in women during pregnancy,” the company said in the letter.

Results of the GSK study are posted at the company's Clinical Trial Register at http://ctr.gsk.co.uk/welcome.asp

New data linking paroxetine use during the first trimester of pregnancy with increased risk of major congenital malformations has prompted changes to the drug's label.

Preliminary results of a retrospective epidemiologic study sponsored by GlaxoSmithKline Inc., the drug's maker, show paroxetine (marketed as Paxil), was associated with more congenital malformations (adjusted odds ratio 2.20) and more cardiovascular malformations (adjusted odds ratio 2.08) than other antidepressants in almost 3,600 pregnant women.

The prevalence of congenital malformations in the study was 4%, compared with about 3% in the general population.

The prevalence of cardiovascular malformations was 2%, compared with about 1% in the general population, according to a “Dear Healthcare Professional” letter issued by the company and the Food and Drug Administration.

Ventricular septal defects were the most common cardiovascular malformation in the study.

The GSK findings, along with those from two other recently published abstracts, warrant the voluntary label change, according to the company.

In one of the abstracts, Pia Wogelius, Ph.D., of the epidemiology department at Aarhus University Hospital, Denmark, and colleagues reported a link between SSRIs and major congenital malformations, including cardiac malformations. The risk of malformation was increased among women who had prescriptions for SSRIs filled in the 30 days before conception through the end of the first trimester, compared with those who had no SSRI prescriptions filled during the same period. These data did not specifically look at Paxil use.

The other abstract described a preliminary analysis of data obtained from the National Birth Defects Prevention Study suggesting an association between SSRI use between 1 month before and 3 months after conception and a significantly increased risk of omphalocele. The risk was greatest among paroxetine users, Sura Alwan, a Ph.D. student at the University of British Columbia, Vancouver, reported at the annual meeting of the Teratology Society.

SSRI use in that study also was linked with an increased risk of tetralogy of Fallot, she told FAMILY PRACTICE NEWS.

The Paxil labeling changes will be in the pregnancy subsection of the “precautions” section of the labels for Paxil and Paxil CR. The new language cites the GSK data but also notes that these data conflict with those from previous studies, including those from the Swedish Medical Birth Registry, which showed no increased risk of major malformations in infants born to 708 women exposed to SSRIs—including paroxetine—during pregnancy.

The conflicting data make it difficult to establish a causal relationship between SSRI use and major congenital malformations. Due to the lack of adequate and well-controlled studies, Paxil maintains its Pregnancy Category C status, according to GSK.

“As with all Pregnancy Category C drugs, health care providers are advised to carefully weigh the potential risks and benefits of using paroxetine therapy in women during pregnancy,” the company said in the letter.

Results of the GSK study are posted at the company's Clinical Trial Register at http://ctr.gsk.co.uk/welcome.asp

CHARLESTON, S.C. — Oral valacyclovir was the most economically favorable treatment choice for the prevention of intrapartum herpes transmission in a recent analysis.

The clinical outcomes and costs of the three strategies, including oral valacyclovir, oral acyclovir, and no prophylaxis, were compared using a decision analysis model in a hypothetical cohort of 1 million women with recurrent herpes infection.

All strategies included cesarean section for patients with active lesions during labor, Monique G. Lin, M.D., of the University of Alabama, Birmingham, and her colleagues reported in a poster at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

The valacyclovir model included 500 mg given twice daily beginning at 36 weeks' gestation.

The oral acyclovir model included 200 mg given four times daily beginning at 36 weeks' gestation.

The investigators used the literature and “local sources” to determine baseline costs.

Dr. Lin and her associates based their analysis on current treatment strategies that employ polymerase chain reaction, viral culture, and high-dose intravenous acyclovir for treatment of affected neonates.

Using this model, the researchers showed that the total costs in the hypothetical cohort were $9.94 billion for valacyclovir, $9.93 billion for acyclovir, and $13.7 billion for no prophylaxis.

The number of cases of neonatal death or moderate to severe neonatal morbidity associated with each treatment in this model was 1,911 with valacyclovir, 2,111 with acyclovir, and 8,240 with no prophylaxis.

The number of cases prevented by using valacyclovir prophylaxis was 6,239, and the number prevented by using acyclovir prophylaxis was 6,129.

The cost per case prevented was $1.57 million for valacyclovir prophylaxis and $1.62 million for acyclovir prophylaxis, Dr. Lin and her investigators found in their analysis.

CHARLESTON, S.C. — Oral valacyclovir was the most economically favorable treatment choice for the prevention of intrapartum herpes transmission in a recent analysis.

The clinical outcomes and costs of the three strategies, including oral valacyclovir, oral acyclovir, and no prophylaxis, were compared using a decision analysis model in a hypothetical cohort of 1 million women with recurrent herpes infection.

All strategies included cesarean section for patients with active lesions during labor, Monique G. Lin, M.D., of the University of Alabama, Birmingham, and her colleagues reported in a poster at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

The valacyclovir model included 500 mg given twice daily beginning at 36 weeks' gestation.

The oral acyclovir model included 200 mg given four times daily beginning at 36 weeks' gestation.

The investigators used the literature and “local sources” to determine baseline costs.

Dr. Lin and her associates based their analysis on current treatment strategies that employ polymerase chain reaction, viral culture, and high-dose intravenous acyclovir for treatment of affected neonates.

Using this model, the researchers showed that the total costs in the hypothetical cohort were $9.94 billion for valacyclovir, $9.93 billion for acyclovir, and $13.7 billion for no prophylaxis.

The number of cases of neonatal death or moderate to severe neonatal morbidity associated with each treatment in this model was 1,911 with valacyclovir, 2,111 with acyclovir, and 8,240 with no prophylaxis.

The number of cases prevented by using valacyclovir prophylaxis was 6,239, and the number prevented by using acyclovir prophylaxis was 6,129.

The cost per case prevented was $1.57 million for valacyclovir prophylaxis and $1.62 million for acyclovir prophylaxis, Dr. Lin and her investigators found in their analysis.

CHARLESTON, S.C. — Oral valacyclovir was the most economically favorable treatment choice for the prevention of intrapartum herpes transmission in a recent analysis.

The clinical outcomes and costs of the three strategies, including oral valacyclovir, oral acyclovir, and no prophylaxis, were compared using a decision analysis model in a hypothetical cohort of 1 million women with recurrent herpes infection.

All strategies included cesarean section for patients with active lesions during labor, Monique G. Lin, M.D., of the University of Alabama, Birmingham, and her colleagues reported in a poster at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

The valacyclovir model included 500 mg given twice daily beginning at 36 weeks' gestation.

The oral acyclovir model included 200 mg given four times daily beginning at 36 weeks' gestation.

The investigators used the literature and “local sources” to determine baseline costs.

Dr. Lin and her associates based their analysis on current treatment strategies that employ polymerase chain reaction, viral culture, and high-dose intravenous acyclovir for treatment of affected neonates.

Using this model, the researchers showed that the total costs in the hypothetical cohort were $9.94 billion for valacyclovir, $9.93 billion for acyclovir, and $13.7 billion for no prophylaxis.

The number of cases of neonatal death or moderate to severe neonatal morbidity associated with each treatment in this model was 1,911 with valacyclovir, 2,111 with acyclovir, and 8,240 with no prophylaxis.

The number of cases prevented by using valacyclovir prophylaxis was 6,239, and the number prevented by using acyclovir prophylaxis was 6,129.

The cost per case prevented was $1.57 million for valacyclovir prophylaxis and $1.62 million for acyclovir prophylaxis, Dr. Lin and her investigators found in their analysis.

CHARLESTON, S.C. — Once-daily treatment with valacyclovir for the suppression of genital herpes caused by herpes simplex virus type-2 was well-tolerated for up to 20 months in a recent study.

Previously, data were available only for up to 12 months of daily valacyclovir use, Zane A. Brown, M.D., of the University of Washington, Seattle, and his colleagues reported in a poster at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

For the current study, which was supported by GlaxoSmithKline Inc., 1,484 serodiscordant, heterosexual, monogamous couples were enrolled, and the seropositive partner was randomized to receive either placebo or 500 mg/day of valacyclovir for 8 months.

The results of this double-blind phase, which were previously reported by the investigators, showed that the treatment significantly reduced the risk of genital herpes transmission.

Following the double-blind phase, 1,018 of the 1,484 participants treated in the double-blind phase entered an open-label suppression phase of the study, which provided 12 months of suppressive therapy with 500 mg/day of valacyclovir. Patients in this phase were evaluated every three months for laboratory values and adverse events.

More than 85% of participants who completed the entire 20 months of treatment were at least 80% compliant with the study medication.

During the double-blind and open-label phases, the nature and incidence of adverse events were similar in the 519 participants originally assigned to receive valacyclovir (treatment group) and the 499 originally assigned to receive placebo.

Common adverse events included headache, nasopharyngitis, and upper respiratory tract infection.

Serious adverse events were reported infrequently and were similar in frequency in the treatment group (5% incidence rate) and the placebo group (3% incidence rate).

Only one serious adverse event (gastritis in one patient) during the entire 20-month study was considered by the investigators to be possibly attributable to valacyclovir, and it occurred during the open-label portion of the study.

Adverse events leading to treatment discontinuation occurred in fewer than 1% of those in the treatment group, and in 1% of those in the placebo group; clinically significant laboratory abnormalities occurred in 6% of patients in both groups.

No deaths occurred during the study periods.

Despite a prior lack of data on the safety of valacyclovir for the suppression of genital herpes caused by HSV-2 when used for longer than 12 months, some physicians prescribe such therapy for longer periods, the investigators noted.

These findings suggest that treatment with valacyclovir is as safe for up to 20 months as it is with 8–12 months of suppressive therapy, they concluded.

CHARLESTON, S.C. — Once-daily treatment with valacyclovir for the suppression of genital herpes caused by herpes simplex virus type-2 was well-tolerated for up to 20 months in a recent study.

Previously, data were available only for up to 12 months of daily valacyclovir use, Zane A. Brown, M.D., of the University of Washington, Seattle, and his colleagues reported in a poster at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

For the current study, which was supported by GlaxoSmithKline Inc., 1,484 serodiscordant, heterosexual, monogamous couples were enrolled, and the seropositive partner was randomized to receive either placebo or 500 mg/day of valacyclovir for 8 months.

The results of this double-blind phase, which were previously reported by the investigators, showed that the treatment significantly reduced the risk of genital herpes transmission.

Following the double-blind phase, 1,018 of the 1,484 participants treated in the double-blind phase entered an open-label suppression phase of the study, which provided 12 months of suppressive therapy with 500 mg/day of valacyclovir. Patients in this phase were evaluated every three months for laboratory values and adverse events.

More than 85% of participants who completed the entire 20 months of treatment were at least 80% compliant with the study medication.

During the double-blind and open-label phases, the nature and incidence of adverse events were similar in the 519 participants originally assigned to receive valacyclovir (treatment group) and the 499 originally assigned to receive placebo.

Common adverse events included headache, nasopharyngitis, and upper respiratory tract infection.

Serious adverse events were reported infrequently and were similar in frequency in the treatment group (5% incidence rate) and the placebo group (3% incidence rate).

Only one serious adverse event (gastritis in one patient) during the entire 20-month study was considered by the investigators to be possibly attributable to valacyclovir, and it occurred during the open-label portion of the study.

Adverse events leading to treatment discontinuation occurred in fewer than 1% of those in the treatment group, and in 1% of those in the placebo group; clinically significant laboratory abnormalities occurred in 6% of patients in both groups.

No deaths occurred during the study periods.

Despite a prior lack of data on the safety of valacyclovir for the suppression of genital herpes caused by HSV-2 when used for longer than 12 months, some physicians prescribe such therapy for longer periods, the investigators noted.

These findings suggest that treatment with valacyclovir is as safe for up to 20 months as it is with 8–12 months of suppressive therapy, they concluded.

CHARLESTON, S.C. — Once-daily treatment with valacyclovir for the suppression of genital herpes caused by herpes simplex virus type-2 was well-tolerated for up to 20 months in a recent study.

Previously, data were available only for up to 12 months of daily valacyclovir use, Zane A. Brown, M.D., of the University of Washington, Seattle, and his colleagues reported in a poster at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

For the current study, which was supported by GlaxoSmithKline Inc., 1,484 serodiscordant, heterosexual, monogamous couples were enrolled, and the seropositive partner was randomized to receive either placebo or 500 mg/day of valacyclovir for 8 months.

The results of this double-blind phase, which were previously reported by the investigators, showed that the treatment significantly reduced the risk of genital herpes transmission.

Following the double-blind phase, 1,018 of the 1,484 participants treated in the double-blind phase entered an open-label suppression phase of the study, which provided 12 months of suppressive therapy with 500 mg/day of valacyclovir. Patients in this phase were evaluated every three months for laboratory values and adverse events.

More than 85% of participants who completed the entire 20 months of treatment were at least 80% compliant with the study medication.

During the double-blind and open-label phases, the nature and incidence of adverse events were similar in the 519 participants originally assigned to receive valacyclovir (treatment group) and the 499 originally assigned to receive placebo.

Common adverse events included headache, nasopharyngitis, and upper respiratory tract infection.

Serious adverse events were reported infrequently and were similar in frequency in the treatment group (5% incidence rate) and the placebo group (3% incidence rate).

Only one serious adverse event (gastritis in one patient) during the entire 20-month study was considered by the investigators to be possibly attributable to valacyclovir, and it occurred during the open-label portion of the study.

Adverse events leading to treatment discontinuation occurred in fewer than 1% of those in the treatment group, and in 1% of those in the placebo group; clinically significant laboratory abnormalities occurred in 6% of patients in both groups.

No deaths occurred during the study periods.

Despite a prior lack of data on the safety of valacyclovir for the suppression of genital herpes caused by HSV-2 when used for longer than 12 months, some physicians prescribe such therapy for longer periods, the investigators noted.

These findings suggest that treatment with valacyclovir is as safe for up to 20 months as it is with 8–12 months of suppressive therapy, they concluded.

Warnings of a potential avian influenza pandemic have the nation and medical community on alert—but those who would be on the front lines appear to be taking the threat in stride.

“Everyone I know is fatalistic about it. Everyone knows it's coming, but it's difficult to prepare for,” Doug Campos-Outcalt, M.D., said in an interview with FAMILY PRACTICE NEWS.

Beyond promoting preventive hygiene measures, such as hand washing and covering one's mouth when coughing or sneezing—important for preventing transmission of any influenza virus—most preparations for a pandemic are “out of the hands of ordinary physicians,” said Dr. Campos-Outcalt, chair of the department of family and community medicine at the University of Arizona, Phoenix, and former chair of the American Academy of Family Physicians' commission on clinical policy.

The watch-and-wait mode is an appropriate place for individual physicians to be right now, said Bill Hall, a spokesperson for the Department of Health and Human Services.

The federal government, primarily through the HHS department, is maintaining open lines of communication with public health departments, and through those departments is working to keep physicians informed of world events related to the spread of avian influenza—particularly the H5N1 strain that is rampant in Asia, has spread to numerous other areas, continues to mutate, and has jumped from birds to multiple other species.

While there is a sense of urgency, there is, at this point, no influenza strain that is causing a pandemic, thus there is no alert to physicians with regard to a pandemic, Mr. Hall said in an interview.

In fact, the only panic—as in people running through the streets with arms flailing—is occurring among the media, he said.

Donald M. Poretz, M.D., vice president of the Infectious Diseases Society of America, agreed there doesn't appear to be—and there shouldn't be—major fear or panic in the United States regarding a pandemic at this point.

“We need to look at the information objectively, and not emotionally. I don't believe anyone can make a statement as to whether or not there will be a pandemic, but the likelihood is that there will be at some point, so one has to be prepared,” said Dr. Poretz, professor of medicine at Georgetown University in Washington.

As for recent press coverage of a leaked draft of the federal government's pandemic preparedness plan, which indicates the country is alarmingly unprepared for such a pandemic, Mr. Hall said only that the report has undergone and will continue to undergo revisions as the situation evolves.

The final report is anticipated, but its release won't be hastened in response to the flurry of media reports about the draft copy.

“What drives us is not the media, but global health, and being as prepared as possible for a pandemic,” he said.

According to information from the World Health Organization, IDSA, and various research projects, the H5N1 avian influenza strain does appear to have the potential for developing efficient person-to-person transmission capability, which it currently lacks, and which could be the bridge between the current situation and a future pandemic.

Should the virus obtain this capability, H5N1 could circle the globe within weeks or months, and could kill as many as 150 million people, according to a WHO estimate.

This scenario is the source of the sense of urgency that Mr. Hall mentioned.

At press time, WHO had confirmed 117 cases of human infection with H5N1 influenza, with cases in Vietnam, Thailand, Cambodia, and Indonesia. Human-to-human transmission has been documented in only two of those cases—both from a single household in Vietnam. The fatality rate among these cases is over 50%.

Infection in animals has been more widespread. The virus' ability to mutate and infect additional species, including cats, leopards, tigers, and pigs, is another source of that urgency, as are the findings of a recent study of the 1918 influenza pandemic, which killed an estimated 50 million people.

Researchers completed the virus coding sequence for the responsible virus and discovered that like H5N1, the 1918 strain was a bird flu that infected humans (Science 2005;310:77–80).

The findings of the study, coupled with the apparent staying power of the H5N1 strain (it has been circulating since 1997) and the fact that many experts say an influenza pandemic is overdue (historically such outbreaks occur about every 30 years, and the last one occurred 37 years ago) contribute to the urgency in preparing for a pandemic.

That urgency is apparent in the flurry of government activity in response to the pandemic threat.

The U.S. State Department recently hosted a meeting of senior health officials from nearly 70 countries to address the need for improved communications and efforts to prevent a pandemic. That meeting was not open to members of the press.

And President Bush has met with vaccine makers to urge increases in flu vaccine production.

Further, the Bush administration and Congress are considering spending billions to stockpile the antiviral drug Tamiflu (oseltamivir); legislation has been introduced that would further ramp up vaccine production and pandemic preparedness; and the National Institute of Allergy and Infectious Diseases has teamed with MedImmune Inc. to develop and manufacture new influenza vaccines, including vaccines against high-priority strains such as H5N1.

But some experts have suggested H5N1 does not confer a pandemic threat, saying that if it was going to develop the ability to efficiently transmit between people, it would have done so by now, and that because the current avian influenza strain is distantly related to earlier flu viruses, much of the population already has some level of immunity.

Whether or not H5N1 becomes pandemic, preparing for a potential pandemic is warranted and worthwhile, experts agree.

“Even if it does not materialize, the planning and development of effective interventions will provide the necessary preparations in the event that another avian strain jumps the species barrier or a known human pathogen like H2N2, to which large segments of the population lack immunity, reemerges,” John G. Bartlett, M.D., of Johns Hopkins University, Baltimore, and Frederick G. Hayden, M.D., University of Virginia Health Sciences Center, Charlottesville, Va., wrote in a recent editorial (Ann. Intern. Med. 2005;143:460–2).

Preparations would also enhance the nation's ability to cope with annual epidemics and their substantial toll.

Widespread vaccination and use of antiviral drugs could provide the foundation for responding to the next pandemic, thus warranting the stockpiling of antiviral agents, they wrote.

Physician groups are taking heed.

Emergency medicine in general has been planning for years for events such as an influenza pandemic. Severe acute respiratory syndrome (SARS), bioterrorism threats, and pandemic influenza have been on the radar screen for a while.

Planning at the national and local levels has been focused on how emergency departments should and will respond to such a crisis, Richard Rothman, M.D., Ph.D., of Johns Hopkins University and a member of the public health committeee for the American College of Emergency Physicians, said in an interview with FAMILY PRACTICE NEWS.

“It's there, people are aware of it, and they're trying to plan as best as possible,” Dr. Rothman, noting that both ACEP and the Society for Academic Emergency Medicine are actively addressing matters such as policy, clinical issues, and risk of hospital overcrowding.

Likewise, the American Academy of Family Physicians is participating in discussions regarding national and state preparedness, and the AAFP is encouraging and facilitating communications among local chapters.

The academy will be conducting educational activities to help physicians understand what their role will be in the event of a pandemic, Dr. Campos-Outcalt said.

What Can YOU Do?

The most effective thing individual physicians can do is in preparation for a potential avian influenza pandemic is to vaccinate patients against the currently circulating influenza strains, Dr. Poretz said.

Such vaccination will address the immediate concern of influenza outbreaks in the United States, and, according to WHO guidelines, could be useful for preventing co-infection with H5N1 and a human influenza strain.

According to the WHO, doing so will decrease the opportunity for genetic reassortment of the avian H5N1 strain with genes from a human (H1 or H3) strain and thereby reduce the likelihood that a novel pandemic strain will emerge from the current situation in Asia.

If an avian influenza pandemic does occur, diagnosis could prove quite difficult, because the symptoms of H5N1 are similar to those of “regular flu,” Dr. Campos-Outcalt said.

Communication and surveillance will be the cornerstones of effective management, he added. This is where education for and by physicians becomes important.

Physicians need to stay up to date, because so much is unknown about how patients would present in the event of a pandemic. And physicians need to educate patients about the preventive measures that will become imperative should available vaccines and antivirals prove ineffective for the pandemic strain.

When it comes to potential patient requests for antiviral medications such as oseltamivir, “I would encourage physicians to prescribe as recommended by the CDC and the manufacturer,” said Dr. Campos-Outcalt.

The CDC's influenza page is located at

www.cdc.gov/flu/

Warnings of a potential avian influenza pandemic have the nation and medical community on alert—but those who would be on the front lines appear to be taking the threat in stride.

“Everyone I know is fatalistic about it. Everyone knows it's coming, but it's difficult to prepare for,” Doug Campos-Outcalt, M.D., said in an interview with FAMILY PRACTICE NEWS.

Beyond promoting preventive hygiene measures, such as hand washing and covering one's mouth when coughing or sneezing—important for preventing transmission of any influenza virus—most preparations for a pandemic are “out of the hands of ordinary physicians,” said Dr. Campos-Outcalt, chair of the department of family and community medicine at the University of Arizona, Phoenix, and former chair of the American Academy of Family Physicians' commission on clinical policy.

The watch-and-wait mode is an appropriate place for individual physicians to be right now, said Bill Hall, a spokesperson for the Department of Health and Human Services.

The federal government, primarily through the HHS department, is maintaining open lines of communication with public health departments, and through those departments is working to keep physicians informed of world events related to the spread of avian influenza—particularly the H5N1 strain that is rampant in Asia, has spread to numerous other areas, continues to mutate, and has jumped from birds to multiple other species.

While there is a sense of urgency, there is, at this point, no influenza strain that is causing a pandemic, thus there is no alert to physicians with regard to a pandemic, Mr. Hall said in an interview.

In fact, the only panic—as in people running through the streets with arms flailing—is occurring among the media, he said.

Donald M. Poretz, M.D., vice president of the Infectious Diseases Society of America, agreed there doesn't appear to be—and there shouldn't be—major fear or panic in the United States regarding a pandemic at this point.

“We need to look at the information objectively, and not emotionally. I don't believe anyone can make a statement as to whether or not there will be a pandemic, but the likelihood is that there will be at some point, so one has to be prepared,” said Dr. Poretz, professor of medicine at Georgetown University in Washington.

As for recent press coverage of a leaked draft of the federal government's pandemic preparedness plan, which indicates the country is alarmingly unprepared for such a pandemic, Mr. Hall said only that the report has undergone and will continue to undergo revisions as the situation evolves.

The final report is anticipated, but its release won't be hastened in response to the flurry of media reports about the draft copy.

“What drives us is not the media, but global health, and being as prepared as possible for a pandemic,” he said.

According to information from the World Health Organization, IDSA, and various research projects, the H5N1 avian influenza strain does appear to have the potential for developing efficient person-to-person transmission capability, which it currently lacks, and which could be the bridge between the current situation and a future pandemic.

Should the virus obtain this capability, H5N1 could circle the globe within weeks or months, and could kill as many as 150 million people, according to a WHO estimate.

This scenario is the source of the sense of urgency that Mr. Hall mentioned.

At press time, WHO had confirmed 117 cases of human infection with H5N1 influenza, with cases in Vietnam, Thailand, Cambodia, and Indonesia. Human-to-human transmission has been documented in only two of those cases—both from a single household in Vietnam. The fatality rate among these cases is over 50%.

Infection in animals has been more widespread. The virus' ability to mutate and infect additional species, including cats, leopards, tigers, and pigs, is another source of that urgency, as are the findings of a recent study of the 1918 influenza pandemic, which killed an estimated 50 million people.

Researchers completed the virus coding sequence for the responsible virus and discovered that like H5N1, the 1918 strain was a bird flu that infected humans (Science 2005;310:77–80).

The findings of the study, coupled with the apparent staying power of the H5N1 strain (it has been circulating since 1997) and the fact that many experts say an influenza pandemic is overdue (historically such outbreaks occur about every 30 years, and the last one occurred 37 years ago) contribute to the urgency in preparing for a pandemic.

That urgency is apparent in the flurry of government activity in response to the pandemic threat.

The U.S. State Department recently hosted a meeting of senior health officials from nearly 70 countries to address the need for improved communications and efforts to prevent a pandemic. That meeting was not open to members of the press.

And President Bush has met with vaccine makers to urge increases in flu vaccine production.

Further, the Bush administration and Congress are considering spending billions to stockpile the antiviral drug Tamiflu (oseltamivir); legislation has been introduced that would further ramp up vaccine production and pandemic preparedness; and the National Institute of Allergy and Infectious Diseases has teamed with MedImmune Inc. to develop and manufacture new influenza vaccines, including vaccines against high-priority strains such as H5N1.

But some experts have suggested H5N1 does not confer a pandemic threat, saying that if it was going to develop the ability to efficiently transmit between people, it would have done so by now, and that because the current avian influenza strain is distantly related to earlier flu viruses, much of the population already has some level of immunity.

Whether or not H5N1 becomes pandemic, preparing for a potential pandemic is warranted and worthwhile, experts agree.

“Even if it does not materialize, the planning and development of effective interventions will provide the necessary preparations in the event that another avian strain jumps the species barrier or a known human pathogen like H2N2, to which large segments of the population lack immunity, reemerges,” John G. Bartlett, M.D., of Johns Hopkins University, Baltimore, and Frederick G. Hayden, M.D., University of Virginia Health Sciences Center, Charlottesville, Va., wrote in a recent editorial (Ann. Intern. Med. 2005;143:460–2).

Preparations would also enhance the nation's ability to cope with annual epidemics and their substantial toll.

Widespread vaccination and use of antiviral drugs could provide the foundation for responding to the next pandemic, thus warranting the stockpiling of antiviral agents, they wrote.

Physician groups are taking heed.

Emergency medicine in general has been planning for years for events such as an influenza pandemic. Severe acute respiratory syndrome (SARS), bioterrorism threats, and pandemic influenza have been on the radar screen for a while.

Planning at the national and local levels has been focused on how emergency departments should and will respond to such a crisis, Richard Rothman, M.D., Ph.D., of Johns Hopkins University and a member of the public health committeee for the American College of Emergency Physicians, said in an interview with FAMILY PRACTICE NEWS.

“It's there, people are aware of it, and they're trying to plan as best as possible,” Dr. Rothman, noting that both ACEP and the Society for Academic Emergency Medicine are actively addressing matters such as policy, clinical issues, and risk of hospital overcrowding.

Likewise, the American Academy of Family Physicians is participating in discussions regarding national and state preparedness, and the AAFP is encouraging and facilitating communications among local chapters.

The academy will be conducting educational activities to help physicians understand what their role will be in the event of a pandemic, Dr. Campos-Outcalt said.

What Can YOU Do?

The most effective thing individual physicians can do is in preparation for a potential avian influenza pandemic is to vaccinate patients against the currently circulating influenza strains, Dr. Poretz said.

Such vaccination will address the immediate concern of influenza outbreaks in the United States, and, according to WHO guidelines, could be useful for preventing co-infection with H5N1 and a human influenza strain.

According to the WHO, doing so will decrease the opportunity for genetic reassortment of the avian H5N1 strain with genes from a human (H1 or H3) strain and thereby reduce the likelihood that a novel pandemic strain will emerge from the current situation in Asia.

If an avian influenza pandemic does occur, diagnosis could prove quite difficult, because the symptoms of H5N1 are similar to those of “regular flu,” Dr. Campos-Outcalt said.

Communication and surveillance will be the cornerstones of effective management, he added. This is where education for and by physicians becomes important.

Physicians need to stay up to date, because so much is unknown about how patients would present in the event of a pandemic. And physicians need to educate patients about the preventive measures that will become imperative should available vaccines and antivirals prove ineffective for the pandemic strain.

When it comes to potential patient requests for antiviral medications such as oseltamivir, “I would encourage physicians to prescribe as recommended by the CDC and the manufacturer,” said Dr. Campos-Outcalt.

The CDC's influenza page is located at

www.cdc.gov/flu/

Warnings of a potential avian influenza pandemic have the nation and medical community on alert—but those who would be on the front lines appear to be taking the threat in stride.

“Everyone I know is fatalistic about it. Everyone knows it's coming, but it's difficult to prepare for,” Doug Campos-Outcalt, M.D., said in an interview with FAMILY PRACTICE NEWS.

Beyond promoting preventive hygiene measures, such as hand washing and covering one's mouth when coughing or sneezing—important for preventing transmission of any influenza virus—most preparations for a pandemic are “out of the hands of ordinary physicians,” said Dr. Campos-Outcalt, chair of the department of family and community medicine at the University of Arizona, Phoenix, and former chair of the American Academy of Family Physicians' commission on clinical policy.

The watch-and-wait mode is an appropriate place for individual physicians to be right now, said Bill Hall, a spokesperson for the Department of Health and Human Services.

The federal government, primarily through the HHS department, is maintaining open lines of communication with public health departments, and through those departments is working to keep physicians informed of world events related to the spread of avian influenza—particularly the H5N1 strain that is rampant in Asia, has spread to numerous other areas, continues to mutate, and has jumped from birds to multiple other species.

While there is a sense of urgency, there is, at this point, no influenza strain that is causing a pandemic, thus there is no alert to physicians with regard to a pandemic, Mr. Hall said in an interview.

In fact, the only panic—as in people running through the streets with arms flailing—is occurring among the media, he said.

Donald M. Poretz, M.D., vice president of the Infectious Diseases Society of America, agreed there doesn't appear to be—and there shouldn't be—major fear or panic in the United States regarding a pandemic at this point.

“We need to look at the information objectively, and not emotionally. I don't believe anyone can make a statement as to whether or not there will be a pandemic, but the likelihood is that there will be at some point, so one has to be prepared,” said Dr. Poretz, professor of medicine at Georgetown University in Washington.

As for recent press coverage of a leaked draft of the federal government's pandemic preparedness plan, which indicates the country is alarmingly unprepared for such a pandemic, Mr. Hall said only that the report has undergone and will continue to undergo revisions as the situation evolves.

The final report is anticipated, but its release won't be hastened in response to the flurry of media reports about the draft copy.

“What drives us is not the media, but global health, and being as prepared as possible for a pandemic,” he said.

According to information from the World Health Organization, IDSA, and various research projects, the H5N1 avian influenza strain does appear to have the potential for developing efficient person-to-person transmission capability, which it currently lacks, and which could be the bridge between the current situation and a future pandemic.

Should the virus obtain this capability, H5N1 could circle the globe within weeks or months, and could kill as many as 150 million people, according to a WHO estimate.

This scenario is the source of the sense of urgency that Mr. Hall mentioned.

At press time, WHO had confirmed 117 cases of human infection with H5N1 influenza, with cases in Vietnam, Thailand, Cambodia, and Indonesia. Human-to-human transmission has been documented in only two of those cases—both from a single household in Vietnam. The fatality rate among these cases is over 50%.

Infection in animals has been more widespread. The virus' ability to mutate and infect additional species, including cats, leopards, tigers, and pigs, is another source of that urgency, as are the findings of a recent study of the 1918 influenza pandemic, which killed an estimated 50 million people.

Researchers completed the virus coding sequence for the responsible virus and discovered that like H5N1, the 1918 strain was a bird flu that infected humans (Science 2005;310:77–80).

The findings of the study, coupled with the apparent staying power of the H5N1 strain (it has been circulating since 1997) and the fact that many experts say an influenza pandemic is overdue (historically such outbreaks occur about every 30 years, and the last one occurred 37 years ago) contribute to the urgency in preparing for a pandemic.

That urgency is apparent in the flurry of government activity in response to the pandemic threat.

The U.S. State Department recently hosted a meeting of senior health officials from nearly 70 countries to address the need for improved communications and efforts to prevent a pandemic. That meeting was not open to members of the press.

And President Bush has met with vaccine makers to urge increases in flu vaccine production.

Further, the Bush administration and Congress are considering spending billions to stockpile the antiviral drug Tamiflu (oseltamivir); legislation has been introduced that would further ramp up vaccine production and pandemic preparedness; and the National Institute of Allergy and Infectious Diseases has teamed with MedImmune Inc. to develop and manufacture new influenza vaccines, including vaccines against high-priority strains such as H5N1.

But some experts have suggested H5N1 does not confer a pandemic threat, saying that if it was going to develop the ability to efficiently transmit between people, it would have done so by now, and that because the current avian influenza strain is distantly related to earlier flu viruses, much of the population already has some level of immunity.

Whether or not H5N1 becomes pandemic, preparing for a potential pandemic is warranted and worthwhile, experts agree.

“Even if it does not materialize, the planning and development of effective interventions will provide the necessary preparations in the event that another avian strain jumps the species barrier or a known human pathogen like H2N2, to which large segments of the population lack immunity, reemerges,” John G. Bartlett, M.D., of Johns Hopkins University, Baltimore, and Frederick G. Hayden, M.D., University of Virginia Health Sciences Center, Charlottesville, Va., wrote in a recent editorial (Ann. Intern. Med. 2005;143:460–2).

Preparations would also enhance the nation's ability to cope with annual epidemics and their substantial toll.

Widespread vaccination and use of antiviral drugs could provide the foundation for responding to the next pandemic, thus warranting the stockpiling of antiviral agents, they wrote.

Physician groups are taking heed.

Emergency medicine in general has been planning for years for events such as an influenza pandemic. Severe acute respiratory syndrome (SARS), bioterrorism threats, and pandemic influenza have been on the radar screen for a while.

Planning at the national and local levels has been focused on how emergency departments should and will respond to such a crisis, Richard Rothman, M.D., Ph.D., of Johns Hopkins University and a member of the public health committeee for the American College of Emergency Physicians, said in an interview with FAMILY PRACTICE NEWS.

“It's there, people are aware of it, and they're trying to plan as best as possible,” Dr. Rothman, noting that both ACEP and the Society for Academic Emergency Medicine are actively addressing matters such as policy, clinical issues, and risk of hospital overcrowding.

Likewise, the American Academy of Family Physicians is participating in discussions regarding national and state preparedness, and the AAFP is encouraging and facilitating communications among local chapters.

The academy will be conducting educational activities to help physicians understand what their role will be in the event of a pandemic, Dr. Campos-Outcalt said.

What Can YOU Do?

The most effective thing individual physicians can do is in preparation for a potential avian influenza pandemic is to vaccinate patients against the currently circulating influenza strains, Dr. Poretz said.

Such vaccination will address the immediate concern of influenza outbreaks in the United States, and, according to WHO guidelines, could be useful for preventing co-infection with H5N1 and a human influenza strain.

According to the WHO, doing so will decrease the opportunity for genetic reassortment of the avian H5N1 strain with genes from a human (H1 or H3) strain and thereby reduce the likelihood that a novel pandemic strain will emerge from the current situation in Asia.

If an avian influenza pandemic does occur, diagnosis could prove quite difficult, because the symptoms of H5N1 are similar to those of “regular flu,” Dr. Campos-Outcalt said.

Communication and surveillance will be the cornerstones of effective management, he added. This is where education for and by physicians becomes important.

Physicians need to stay up to date, because so much is unknown about how patients would present in the event of a pandemic. And physicians need to educate patients about the preventive measures that will become imperative should available vaccines and antivirals prove ineffective for the pandemic strain.

When it comes to potential patient requests for antiviral medications such as oseltamivir, “I would encourage physicians to prescribe as recommended by the CDC and the manufacturer,” said Dr. Campos-Outcalt.

The CDC's influenza page is located at

www.cdc.gov/flu/

Warnings of a potential avian influenza pandemic have the nation and medical community on alert—but those who would be on the front lines appear to be taking the threat in stride.

One of the few concrete steps physicians can take at this time is to ensure that patients are vaccinated against conventional influenza strains, said Donald M. Poretz, M.D., vice president of the Infectious Diseases Society of America. (See box below.)

There doesn't appear to be—and there shouldn't be—major fear or panic in the United States regarding a pandemic at this point, he told this newspaper.

“We need to look at the information objectively, and not emotionally. I don't believe anyone can make a statement as to whether or not there will be a pandemic, but the likelihood is that there will be at some point, so one has to be prepared,” said Dr. Poretz, professor of medicine at Georgetown University in Washington.

Doug Campos-Outcalt, M.D., said that “everyone I know is fatalistic about it. Everyone knows it's coming, but it's difficult to prepare for.”

Beyond promoting preventive hygiene measures, such as hand washing and covering one's mouth when coughing or sneezing—important for preventing transmission of any influenza virus—most preparations for a pandemic are “out of the hands of ordinary physicians,” said Dr. Campos-Outcalt, chair of the department of family and community medicine at the University of Arizona, Phoenix, and former chair of the American Academy of Family Physicians' commission on clinical policy.

The watch-and-wait mode is an appropriate place for individual physicians to be right now, said Bill Hall, a spokesperson for the Department of Health and Human Services.

HHS is maintaining open lines of communication with public health departments, and through those departments is working to keep physicians informed of world events related to the spread of avian influenza—particularly the H5N1 strain that is rampant in Asia, has spread to numerous other areas, continues to mutate, and has jumped from birds to multiple other species. While there is a sense of urgency, there is, at this point, no influenza strain that is causing a pandemic, thus there is no alert to physicians in regard to a pandemic, Mr. Hall said in an interview.

In fact, the only panic—as in people running through the streets with arms flailing—is occurring in the media, he said.

As for recent press coverage of a leaked draft of the federal government's pandemic preparedness plan, which indicates the country is alarmingly unprepared for such a pandemic, Mr. Hall said only that the report has undergone and will continue to undergo revisions as the situation evolves.

The final report is anticipated, but its release won't be hastened in response to the flurry of media reports about the draft copy. “What drives us is not the media, but global health, and being as prepared as possible for a pandemic,” he said.

According to information from the World Health Organization, IDSA, and various research projects, the H5N1 avian influenza strain does appear to have the potential for developing efficient person-to-person transmission capability, which it currently lacks, and which could be the bridge between the current situation and a future pandemic. Should the virus obtain this capability, H5N1 could circle the globe within weeks or months, and could kill as many as 150 million people, according to a WHO estimate.

This scenario is the source of the sense of urgency that Mr. Hall mentioned.

At press time, WHO had confirmed 117 cases of human infection with H5N1 influenza, with cases in Vietnam, Thailand, Cambodia, and Indonesia. Human-to-human transmission has been documented in only two of those cases—both from a single household in Vietnam. The fatality rate among these cases is over 50%.

Infection in animals has been more widespread. The virus' ability to mutate and infect additional species, including cats, leopards, tigers, and pigs, is another source of that urgency, as are the findings of a recent study of the 1918 influenza pandemic, which killed an estimated 50 million people.

Researchers completed the virus coding sequence for the responsible virus and discovered that like H5N1, the 1918 strain was a bird flu that infected humans (Science 2005;310:77–80).

The findings of the study, coupled with the apparent staying power of the H5N1 strain (it has been circulating since 1997) and the fact that many experts say an influenza pandemic is overdue (historically such outbreaks occur about every 30 years, and the last one occurred 37 years ago) contribute to the urgency in preparing for a pandemic.

That urgency is apparent in the flurry of government activity in response to the pandemic threat.

The U.S. State Department recently hosted a meeting of senior health officials from nearly 70 countries to address the need for improved communications and efforts to prevent a pandemic. And President Bush has met with vaccine makers to urge increases in flu vaccine production.

Further, the Bush administration and Congress are considering spending billions to stockpile the antiviral drug Tamiflu, legislation has been introduced that would further ramp up vaccine production and pandemic preparedness, and the National Institute of Allergy and Infectious Diseases has teamed with MedImmune Inc. to develop and manufacture new influenza vaccines, including vaccines against high-priority strains such as H5N1.

But some experts have suggested H5N1 does not confer a pandemic threat, saying that if it was going to develop the ability to efficiently transmit between people, it would have done so by now, and that because the bird flu is distantly related to earlier flu viruses, much of the population already has some level of immunity.

Whether or not H5N1 becomes pandemic, preparing for a potential pandemic is warranted and worthwhile, experts agree.

“Even if it does not materialize, the planning and development of effective interventions will provide the necessary preparations in the event that another avian strain jumps the species barrier or a known human pathogen like H2N2, to which large segments of the population lack immunity, reemerges,” John G. Bartlett, M.D., of Johns Hopkins University, Baltimore, and Dr. Frederick G. Hayden, University of Virginia Health Sciences Center, Charlottesville, Va, stated in a recent editorial (Ann. Intern. Med. 2005;143:460–2).

Preparations would also enhance the nation's ability to cope with annual epidemics and their substantial toll. Widespread vaccination and use of antiviral drugs could provide the foundation for responding to the next pandemic, thus warranting the stockpiling of antiviral agents, they wrote.

Physician groups are taking heed. Emergency medicine in general has been planning for years for events such as an influenza pandemic. Severe acute respiratory syndrome (SARS), bioterrorism threats, and pandemic influenza have been on the radar screen for a while. Planning at the national and local levels has been focused on how emergency departments should and will respond to such a crisis, Richard Rothman, M.D., Ph.D., of Johns Hopkins University and a member of the American College of Emergency Physicians Public Health Committee, said in an interview.

“It's there, people are aware of it, and they're trying to plan as best as possible,” said Dr. Rothman, noting that both ACEP and the Society for Academic Emergency Medicine are actively addressing matters such as policy, clinical issues, and risk of hospital overcrowding.

Likewise, the American Academy of Family Physicians is participating in discussions regarding national and state preparedness, and the AAFP is encouraging and facilitating communications among local chapters. The academy will be conducting educational activities to help physicians understand what their role will be in the event of a pandemic, Dr. Campos-Outcalt said.

Giving Regular Flu Vaccine May Help

The most effective thing individual physicians can do is vaccinate patients against the currently circulating influenza strains, Dr. Poretz said.

Such vaccination will address the immediate concern of influenza outbreaks in the United States, and, according to WHO guidelines, could be useful for preventing co-infection with H5N1 and a human influenza strain.

According to the WHO, doing so will decrease the opportunity for genetic reassortment of the avian H5N1 strain with genes from a human (H1 or H3) strain and thereby reduce the likelihood that a novel pandemic strain will emerge from the current situation in Asia.

If an avian influenza pandemic does occur, diagnosis could prove quite difficult, because the symptoms of H5N1 are similar to those of “regular flu,” Dr. Campos-Outcalt said.

Communication and surveillance will be the cornerstones of effective management, he added. This is where education for and by physicians becomes important.

Physicians need to stay up to date, because so much is unknown about how patients would present in the event of a pandemic. And physicians need to educate patients about the preventive measures that will become imperative should available vaccines and antivirals prove ineffective for the pandemic strain.

Warnings of a potential avian influenza pandemic have the nation and medical community on alert—but those who would be on the front lines appear to be taking the threat in stride.

One of the few concrete steps physicians can take at this time is to ensure that patients are vaccinated against conventional influenza strains, said Donald M. Poretz, M.D., vice president of the Infectious Diseases Society of America. (See box below.)

There doesn't appear to be—and there shouldn't be—major fear or panic in the United States regarding a pandemic at this point, he told this newspaper.

“We need to look at the information objectively, and not emotionally. I don't believe anyone can make a statement as to whether or not there will be a pandemic, but the likelihood is that there will be at some point, so one has to be prepared,” said Dr. Poretz, professor of medicine at Georgetown University in Washington.

Doug Campos-Outcalt, M.D., said that “everyone I know is fatalistic about it. Everyone knows it's coming, but it's difficult to prepare for.”

Beyond promoting preventive hygiene measures, such as hand washing and covering one's mouth when coughing or sneezing—important for preventing transmission of any influenza virus—most preparations for a pandemic are “out of the hands of ordinary physicians,” said Dr. Campos-Outcalt, chair of the department of family and community medicine at the University of Arizona, Phoenix, and former chair of the American Academy of Family Physicians' commission on clinical policy.

The watch-and-wait mode is an appropriate place for individual physicians to be right now, said Bill Hall, a spokesperson for the Department of Health and Human Services.

HHS is maintaining open lines of communication with public health departments, and through those departments is working to keep physicians informed of world events related to the spread of avian influenza—particularly the H5N1 strain that is rampant in Asia, has spread to numerous other areas, continues to mutate, and has jumped from birds to multiple other species. While there is a sense of urgency, there is, at this point, no influenza strain that is causing a pandemic, thus there is no alert to physicians in regard to a pandemic, Mr. Hall said in an interview.

In fact, the only panic—as in people running through the streets with arms flailing—is occurring in the media, he said.

As for recent press coverage of a leaked draft of the federal government's pandemic preparedness plan, which indicates the country is alarmingly unprepared for such a pandemic, Mr. Hall said only that the report has undergone and will continue to undergo revisions as the situation evolves.

The final report is anticipated, but its release won't be hastened in response to the flurry of media reports about the draft copy. “What drives us is not the media, but global health, and being as prepared as possible for a pandemic,” he said.

According to information from the World Health Organization, IDSA, and various research projects, the H5N1 avian influenza strain does appear to have the potential for developing efficient person-to-person transmission capability, which it currently lacks, and which could be the bridge between the current situation and a future pandemic. Should the virus obtain this capability, H5N1 could circle the globe within weeks or months, and could kill as many as 150 million people, according to a WHO estimate.

This scenario is the source of the sense of urgency that Mr. Hall mentioned.

At press time, WHO had confirmed 117 cases of human infection with H5N1 influenza, with cases in Vietnam, Thailand, Cambodia, and Indonesia. Human-to-human transmission has been documented in only two of those cases—both from a single household in Vietnam. The fatality rate among these cases is over 50%.

Infection in animals has been more widespread. The virus' ability to mutate and infect additional species, including cats, leopards, tigers, and pigs, is another source of that urgency, as are the findings of a recent study of the 1918 influenza pandemic, which killed an estimated 50 million people.

Researchers completed the virus coding sequence for the responsible virus and discovered that like H5N1, the 1918 strain was a bird flu that infected humans (Science 2005;310:77–80).

The findings of the study, coupled with the apparent staying power of the H5N1 strain (it has been circulating since 1997) and the fact that many experts say an influenza pandemic is overdue (historically such outbreaks occur about every 30 years, and the last one occurred 37 years ago) contribute to the urgency in preparing for a pandemic.

That urgency is apparent in the flurry of government activity in response to the pandemic threat.

The U.S. State Department recently hosted a meeting of senior health officials from nearly 70 countries to address the need for improved communications and efforts to prevent a pandemic. And President Bush has met with vaccine makers to urge increases in flu vaccine production.

Further, the Bush administration and Congress are considering spending billions to stockpile the antiviral drug Tamiflu, legislation has been introduced that would further ramp up vaccine production and pandemic preparedness, and the National Institute of Allergy and Infectious Diseases has teamed with MedImmune Inc. to develop and manufacture new influenza vaccines, including vaccines against high-priority strains such as H5N1.

But some experts have suggested H5N1 does not confer a pandemic threat, saying that if it was going to develop the ability to efficiently transmit between people, it would have done so by now, and that because the bird flu is distantly related to earlier flu viruses, much of the population already has some level of immunity.

Whether or not H5N1 becomes pandemic, preparing for a potential pandemic is warranted and worthwhile, experts agree.

“Even if it does not materialize, the planning and development of effective interventions will provide the necessary preparations in the event that another avian strain jumps the species barrier or a known human pathogen like H2N2, to which large segments of the population lack immunity, reemerges,” John G. Bartlett, M.D., of Johns Hopkins University, Baltimore, and Dr. Frederick G. Hayden, University of Virginia Health Sciences Center, Charlottesville, Va, stated in a recent editorial (Ann. Intern. Med. 2005;143:460–2).

Preparations would also enhance the nation's ability to cope with annual epidemics and their substantial toll. Widespread vaccination and use of antiviral drugs could provide the foundation for responding to the next pandemic, thus warranting the stockpiling of antiviral agents, they wrote.

Physician groups are taking heed. Emergency medicine in general has been planning for years for events such as an influenza pandemic. Severe acute respiratory syndrome (SARS), bioterrorism threats, and pandemic influenza have been on the radar screen for a while. Planning at the national and local levels has been focused on how emergency departments should and will respond to such a crisis, Richard Rothman, M.D., Ph.D., of Johns Hopkins University and a member of the American College of Emergency Physicians Public Health Committee, said in an interview.

“It's there, people are aware of it, and they're trying to plan as best as possible,” said Dr. Rothman, noting that both ACEP and the Society for Academic Emergency Medicine are actively addressing matters such as policy, clinical issues, and risk of hospital overcrowding.

Likewise, the American Academy of Family Physicians is participating in discussions regarding national and state preparedness, and the AAFP is encouraging and facilitating communications among local chapters. The academy will be conducting educational activities to help physicians understand what their role will be in the event of a pandemic, Dr. Campos-Outcalt said.

Giving Regular Flu Vaccine May Help

The most effective thing individual physicians can do is vaccinate patients against the currently circulating influenza strains, Dr. Poretz said.

Such vaccination will address the immediate concern of influenza outbreaks in the United States, and, according to WHO guidelines, could be useful for preventing co-infection with H5N1 and a human influenza strain.

According to the WHO, doing so will decrease the opportunity for genetic reassortment of the avian H5N1 strain with genes from a human (H1 or H3) strain and thereby reduce the likelihood that a novel pandemic strain will emerge from the current situation in Asia.

If an avian influenza pandemic does occur, diagnosis could prove quite difficult, because the symptoms of H5N1 are similar to those of “regular flu,” Dr. Campos-Outcalt said.

Communication and surveillance will be the cornerstones of effective management, he added. This is where education for and by physicians becomes important.

Physicians need to stay up to date, because so much is unknown about how patients would present in the event of a pandemic. And physicians need to educate patients about the preventive measures that will become imperative should available vaccines and antivirals prove ineffective for the pandemic strain.

Warnings of a potential avian influenza pandemic have the nation and medical community on alert—but those who would be on the front lines appear to be taking the threat in stride.

One of the few concrete steps physicians can take at this time is to ensure that patients are vaccinated against conventional influenza strains, said Donald M. Poretz, M.D., vice president of the Infectious Diseases Society of America. (See box below.)

There doesn't appear to be—and there shouldn't be—major fear or panic in the United States regarding a pandemic at this point, he told this newspaper.

“We need to look at the information objectively, and not emotionally. I don't believe anyone can make a statement as to whether or not there will be a pandemic, but the likelihood is that there will be at some point, so one has to be prepared,” said Dr. Poretz, professor of medicine at Georgetown University in Washington.

Doug Campos-Outcalt, M.D., said that “everyone I know is fatalistic about it. Everyone knows it's coming, but it's difficult to prepare for.”

Beyond promoting preventive hygiene measures, such as hand washing and covering one's mouth when coughing or sneezing—important for preventing transmission of any influenza virus—most preparations for a pandemic are “out of the hands of ordinary physicians,” said Dr. Campos-Outcalt, chair of the department of family and community medicine at the University of Arizona, Phoenix, and former chair of the American Academy of Family Physicians' commission on clinical policy.

The watch-and-wait mode is an appropriate place for individual physicians to be right now, said Bill Hall, a spokesperson for the Department of Health and Human Services.

HHS is maintaining open lines of communication with public health departments, and through those departments is working to keep physicians informed of world events related to the spread of avian influenza—particularly the H5N1 strain that is rampant in Asia, has spread to numerous other areas, continues to mutate, and has jumped from birds to multiple other species. While there is a sense of urgency, there is, at this point, no influenza strain that is causing a pandemic, thus there is no alert to physicians in regard to a pandemic, Mr. Hall said in an interview.

In fact, the only panic—as in people running through the streets with arms flailing—is occurring in the media, he said.

As for recent press coverage of a leaked draft of the federal government's pandemic preparedness plan, which indicates the country is alarmingly unprepared for such a pandemic, Mr. Hall said only that the report has undergone and will continue to undergo revisions as the situation evolves.

The final report is anticipated, but its release won't be hastened in response to the flurry of media reports about the draft copy. “What drives us is not the media, but global health, and being as prepared as possible for a pandemic,” he said.

According to information from the World Health Organization, IDSA, and various research projects, the H5N1 avian influenza strain does appear to have the potential for developing efficient person-to-person transmission capability, which it currently lacks, and which could be the bridge between the current situation and a future pandemic. Should the virus obtain this capability, H5N1 could circle the globe within weeks or months, and could kill as many as 150 million people, according to a WHO estimate.

This scenario is the source of the sense of urgency that Mr. Hall mentioned.

At press time, WHO had confirmed 117 cases of human infection with H5N1 influenza, with cases in Vietnam, Thailand, Cambodia, and Indonesia. Human-to-human transmission has been documented in only two of those cases—both from a single household in Vietnam. The fatality rate among these cases is over 50%.

Infection in animals has been more widespread. The virus' ability to mutate and infect additional species, including cats, leopards, tigers, and pigs, is another source of that urgency, as are the findings of a recent study of the 1918 influenza pandemic, which killed an estimated 50 million people.

Researchers completed the virus coding sequence for the responsible virus and discovered that like H5N1, the 1918 strain was a bird flu that infected humans (Science 2005;310:77–80).

The findings of the study, coupled with the apparent staying power of the H5N1 strain (it has been circulating since 1997) and the fact that many experts say an influenza pandemic is overdue (historically such outbreaks occur about every 30 years, and the last one occurred 37 years ago) contribute to the urgency in preparing for a pandemic.

That urgency is apparent in the flurry of government activity in response to the pandemic threat.

The U.S. State Department recently hosted a meeting of senior health officials from nearly 70 countries to address the need for improved communications and efforts to prevent a pandemic. And President Bush has met with vaccine makers to urge increases in flu vaccine production.

Further, the Bush administration and Congress are considering spending billions to stockpile the antiviral drug Tamiflu, legislation has been introduced that would further ramp up vaccine production and pandemic preparedness, and the National Institute of Allergy and Infectious Diseases has teamed with MedImmune Inc. to develop and manufacture new influenza vaccines, including vaccines against high-priority strains such as H5N1.

But some experts have suggested H5N1 does not confer a pandemic threat, saying that if it was going to develop the ability to efficiently transmit between people, it would have done so by now, and that because the bird flu is distantly related to earlier flu viruses, much of the population already has some level of immunity.

Whether or not H5N1 becomes pandemic, preparing for a potential pandemic is warranted and worthwhile, experts agree.

“Even if it does not materialize, the planning and development of effective interventions will provide the necessary preparations in the event that another avian strain jumps the species barrier or a known human pathogen like H2N2, to which large segments of the population lack immunity, reemerges,” John G. Bartlett, M.D., of Johns Hopkins University, Baltimore, and Dr. Frederick G. Hayden, University of Virginia Health Sciences Center, Charlottesville, Va, stated in a recent editorial (Ann. Intern. Med. 2005;143:460–2).

Preparations would also enhance the nation's ability to cope with annual epidemics and their substantial toll. Widespread vaccination and use of antiviral drugs could provide the foundation for responding to the next pandemic, thus warranting the stockpiling of antiviral agents, they wrote.

Physician groups are taking heed. Emergency medicine in general has been planning for years for events such as an influenza pandemic. Severe acute respiratory syndrome (SARS), bioterrorism threats, and pandemic influenza have been on the radar screen for a while. Planning at the national and local levels has been focused on how emergency departments should and will respond to such a crisis, Richard Rothman, M.D., Ph.D., of Johns Hopkins University and a member of the American College of Emergency Physicians Public Health Committee, said in an interview.

“It's there, people are aware of it, and they're trying to plan as best as possible,” said Dr. Rothman, noting that both ACEP and the Society for Academic Emergency Medicine are actively addressing matters such as policy, clinical issues, and risk of hospital overcrowding.

Likewise, the American Academy of Family Physicians is participating in discussions regarding national and state preparedness, and the AAFP is encouraging and facilitating communications among local chapters. The academy will be conducting educational activities to help physicians understand what their role will be in the event of a pandemic, Dr. Campos-Outcalt said.

Giving Regular Flu Vaccine May Help

The most effective thing individual physicians can do is vaccinate patients against the currently circulating influenza strains, Dr. Poretz said.

Such vaccination will address the immediate concern of influenza outbreaks in the United States, and, according to WHO guidelines, could be useful for preventing co-infection with H5N1 and a human influenza strain.

According to the WHO, doing so will decrease the opportunity for genetic reassortment of the avian H5N1 strain with genes from a human (H1 or H3) strain and thereby reduce the likelihood that a novel pandemic strain will emerge from the current situation in Asia.

If an avian influenza pandemic does occur, diagnosis could prove quite difficult, because the symptoms of H5N1 are similar to those of “regular flu,” Dr. Campos-Outcalt said.

Communication and surveillance will be the cornerstones of effective management, he added. This is where education for and by physicians becomes important.

Physicians need to stay up to date, because so much is unknown about how patients would present in the event of a pandemic. And physicians need to educate patients about the preventive measures that will become imperative should available vaccines and antivirals prove ineffective for the pandemic strain.

New data linking paroxetine use in the first trimester of pregnancy with increased risk of major congenital malformations has prompted changes to the drug's label.

Preliminary results of a retrospective epidemiologic study sponsored by GlaxoSmithKline Inc., the drug's maker, show paroxetine (marketed as Paxil) was associated with more congenital malformations (adjusted odds ratio 2.20) and more cardiovascular malformations (adjusted odds ratio 2.08) than other antidepressants in almost 3,600 pregnant women.

The prevalence of congenital malformations in the study was 4%, compared with about 3% in the general population. The prevalence of cardiovascular malformations was 2%, compared with about 1% in the general population, according to a “Dear Healthcare Professional” letter issued by the company and the Food and Drug Administration. Ventricular septal defects were the most common cardiovascular malformation in the study.

The findings, along with those of two other recent abstracts, warrant the voluntary label change, the company indicated.

In one of the abstracts, Pia Wogelius, Ph.D., of the epidemiology department at Aarhus University Hospital, Denmark, and colleagues reported a link between SSRIs and major congenital malformations, including cardiac malformations. The risk of malformation was increased among women who had prescriptions for SSRIs filled in the 30 days before conception through the end of the first trimester, compared with those who had no SSRI prescriptions filled in the same period. These data did not specifically look at Paxil use.

The other abstract described a preliminary analysis of data obtained from the National Birth Defects Prevention Study suggesting an association between SSRI use between 1 month before and 3 months after conception and a significantly increased risk of omphalocele. The risk was greatest among paroxetine users, Sura Alwan, a Ph.D. student at the University of British Columbia, Vancouver, reported at the annual meeting of the Teratology Society.

SSRIs' use in that study also was linked with an increased risk of tetralogy of Fallot, she told this newspaper.

The Paxil labeling changes will be in the pregnancy subsection of the “precautions” section of the labels for Paxil and Paxil CR. The new language cites the GSK data but also notes these data conflict with those from previous studies, including those from the Swedish Medical Birth Registry, which showed no increased risk of major malformations in infants born to 708 women exposed to SSRIs—including paroxetine—during pregnancy.

The conflicting data make it difficult to establish a causal relationship between SSRI use and major congenital malformations. Due to the lack of adequate and well-controlled studies in humans, Paxil maintains its Pregnancy Category C status, according to GSK. However, the company said physicians should discuss the findings with their patients. Results of the GSK study are posted at the company's Clinical Trial Register at http://ctr.gsk.co.uk/welcome.asp

New data linking paroxetine use in the first trimester of pregnancy with increased risk of major congenital malformations has prompted changes to the drug's label.

Preliminary results of a retrospective epidemiologic study sponsored by GlaxoSmithKline Inc., the drug's maker, show paroxetine (marketed as Paxil) was associated with more congenital malformations (adjusted odds ratio 2.20) and more cardiovascular malformations (adjusted odds ratio 2.08) than other antidepressants in almost 3,600 pregnant women.

The prevalence of congenital malformations in the study was 4%, compared with about 3% in the general population. The prevalence of cardiovascular malformations was 2%, compared with about 1% in the general population, according to a “Dear Healthcare Professional” letter issued by the company and the Food and Drug Administration. Ventricular septal defects were the most common cardiovascular malformation in the study.

The findings, along with those of two other recent abstracts, warrant the voluntary label change, the company indicated.

In one of the abstracts, Pia Wogelius, Ph.D., of the epidemiology department at Aarhus University Hospital, Denmark, and colleagues reported a link between SSRIs and major congenital malformations, including cardiac malformations. The risk of malformation was increased among women who had prescriptions for SSRIs filled in the 30 days before conception through the end of the first trimester, compared with those who had no SSRI prescriptions filled in the same period. These data did not specifically look at Paxil use.

The other abstract described a preliminary analysis of data obtained from the National Birth Defects Prevention Study suggesting an association between SSRI use between 1 month before and 3 months after conception and a significantly increased risk of omphalocele. The risk was greatest among paroxetine users, Sura Alwan, a Ph.D. student at the University of British Columbia, Vancouver, reported at the annual meeting of the Teratology Society.

SSRIs' use in that study also was linked with an increased risk of tetralogy of Fallot, she told this newspaper.

The Paxil labeling changes will be in the pregnancy subsection of the “precautions” section of the labels for Paxil and Paxil CR. The new language cites the GSK data but also notes these data conflict with those from previous studies, including those from the Swedish Medical Birth Registry, which showed no increased risk of major malformations in infants born to 708 women exposed to SSRIs—including paroxetine—during pregnancy.

The conflicting data make it difficult to establish a causal relationship between SSRI use and major congenital malformations. Due to the lack of adequate and well-controlled studies in humans, Paxil maintains its Pregnancy Category C status, according to GSK. However, the company said physicians should discuss the findings with their patients. Results of the GSK study are posted at the company's Clinical Trial Register at http://ctr.gsk.co.uk/welcome.asp

New data linking paroxetine use in the first trimester of pregnancy with increased risk of major congenital malformations has prompted changes to the drug's label.

Preliminary results of a retrospective epidemiologic study sponsored by GlaxoSmithKline Inc., the drug's maker, show paroxetine (marketed as Paxil) was associated with more congenital malformations (adjusted odds ratio 2.20) and more cardiovascular malformations (adjusted odds ratio 2.08) than other antidepressants in almost 3,600 pregnant women.

The prevalence of congenital malformations in the study was 4%, compared with about 3% in the general population. The prevalence of cardiovascular malformations was 2%, compared with about 1% in the general population, according to a “Dear Healthcare Professional” letter issued by the company and the Food and Drug Administration. Ventricular septal defects were the most common cardiovascular malformation in the study.

The findings, along with those of two other recent abstracts, warrant the voluntary label change, the company indicated.

In one of the abstracts, Pia Wogelius, Ph.D., of the epidemiology department at Aarhus University Hospital, Denmark, and colleagues reported a link between SSRIs and major congenital malformations, including cardiac malformations. The risk of malformation was increased among women who had prescriptions for SSRIs filled in the 30 days before conception through the end of the first trimester, compared with those who had no SSRI prescriptions filled in the same period. These data did not specifically look at Paxil use.

The other abstract described a preliminary analysis of data obtained from the National Birth Defects Prevention Study suggesting an association between SSRI use between 1 month before and 3 months after conception and a significantly increased risk of omphalocele. The risk was greatest among paroxetine users, Sura Alwan, a Ph.D. student at the University of British Columbia, Vancouver, reported at the annual meeting of the Teratology Society.

SSRIs' use in that study also was linked with an increased risk of tetralogy of Fallot, she told this newspaper.

The Paxil labeling changes will be in the pregnancy subsection of the “precautions” section of the labels for Paxil and Paxil CR. The new language cites the GSK data but also notes these data conflict with those from previous studies, including those from the Swedish Medical Birth Registry, which showed no increased risk of major malformations in infants born to 708 women exposed to SSRIs—including paroxetine—during pregnancy.

The conflicting data make it difficult to establish a causal relationship between SSRI use and major congenital malformations. Due to the lack of adequate and well-controlled studies in humans, Paxil maintains its Pregnancy Category C status, according to GSK. However, the company said physicians should discuss the findings with their patients. Results of the GSK study are posted at the company's Clinical Trial Register at http://ctr.gsk.co.uk/welcome.asp

ATLANTA — Occlusion with plastic wrap may improve the delivery of topical estrogen to the vaginal area in postmenopausal women with vaginal atrophy who are being prepared for pelvic reconstructive or obliterative surgery, Peter L. Rosenblatt, M.D., said at the annual meeting of the American Urogynecologic Society.

It is generally accepted that local estrogen therapy improves vaginal thickness and integrity of the vagina in this population, and most surgeons typically recommend several months of treatment before pelvic reconstructive surgery, explained Dr. Rosenblatt of Harvard Medical School, Boston. But patients with advanced prolapse, who can have particularly poor tissue quality, are likely to have problems with the cream rubbing off on pads or undergarments. Pessaries can help, but some patients can't retain them due to poor perineal support, and in some cases they can cause or worsen erosions.

To keep the estrogen cream in place, Dr. Rosenblatt borrowed the plastic wrap occlusion technique from dermatologists, who often use plastic wrap with the application of EMLA cream before laser hair removal, skin biopsies, and other procedures.

Have the patient apply a thick layer of estrogen cream and cover it with plastic wrap or any other occlusive dressing, he advised.

“We have the patient use this every other night for several hours. … It's not pretty, but it gets the job done,” he said at the meeting.

In his “informal experience” with eight patients who were candidates for pelvic surgery, subjective improvement in tissue quality, including resolution of erosions in one patient, was noted in all except two patients. Those patients both had a prolapse that would recede when they weren't bearing down, which would displace the plastic wrap.

A prospective trial comparing the effects of standard estrogen cream application and estrogen cream application plus plastic wrap is planned, Dr. Rosenblatt said.

ATLANTA — Occlusion with plastic wrap may improve the delivery of topical estrogen to the vaginal area in postmenopausal women with vaginal atrophy who are being prepared for pelvic reconstructive or obliterative surgery, Peter L. Rosenblatt, M.D., said at the annual meeting of the American Urogynecologic Society.

It is generally accepted that local estrogen therapy improves vaginal thickness and integrity of the vagina in this population, and most surgeons typically recommend several months of treatment before pelvic reconstructive surgery, explained Dr. Rosenblatt of Harvard Medical School, Boston. But patients with advanced prolapse, who can have particularly poor tissue quality, are likely to have problems with the cream rubbing off on pads or undergarments. Pessaries can help, but some patients can't retain them due to poor perineal support, and in some cases they can cause or worsen erosions.

To keep the estrogen cream in place, Dr. Rosenblatt borrowed the plastic wrap occlusion technique from dermatologists, who often use plastic wrap with the application of EMLA cream before laser hair removal, skin biopsies, and other procedures.

Have the patient apply a thick layer of estrogen cream and cover it with plastic wrap or any other occlusive dressing, he advised.

“We have the patient use this every other night for several hours. … It's not pretty, but it gets the job done,” he said at the meeting.

In his “informal experience” with eight patients who were candidates for pelvic surgery, subjective improvement in tissue quality, including resolution of erosions in one patient, was noted in all except two patients. Those patients both had a prolapse that would recede when they weren't bearing down, which would displace the plastic wrap.

A prospective trial comparing the effects of standard estrogen cream application and estrogen cream application plus plastic wrap is planned, Dr. Rosenblatt said.

ATLANTA — Occlusion with plastic wrap may improve the delivery of topical estrogen to the vaginal area in postmenopausal women with vaginal atrophy who are being prepared for pelvic reconstructive or obliterative surgery, Peter L. Rosenblatt, M.D., said at the annual meeting of the American Urogynecologic Society.

It is generally accepted that local estrogen therapy improves vaginal thickness and integrity of the vagina in this population, and most surgeons typically recommend several months of treatment before pelvic reconstructive surgery, explained Dr. Rosenblatt of Harvard Medical School, Boston. But patients with advanced prolapse, who can have particularly poor tissue quality, are likely to have problems with the cream rubbing off on pads or undergarments. Pessaries can help, but some patients can't retain them due to poor perineal support, and in some cases they can cause or worsen erosions.

To keep the estrogen cream in place, Dr. Rosenblatt borrowed the plastic wrap occlusion technique from dermatologists, who often use plastic wrap with the application of EMLA cream before laser hair removal, skin biopsies, and other procedures.

Have the patient apply a thick layer of estrogen cream and cover it with plastic wrap or any other occlusive dressing, he advised.

“We have the patient use this every other night for several hours. … It's not pretty, but it gets the job done,” he said at the meeting.

In his “informal experience” with eight patients who were candidates for pelvic surgery, subjective improvement in tissue quality, including resolution of erosions in one patient, was noted in all except two patients. Those patients both had a prolapse that would recede when they weren't bearing down, which would displace the plastic wrap.

A prospective trial comparing the effects of standard estrogen cream application and estrogen cream application plus plastic wrap is planned, Dr. Rosenblatt said.

CHARLESTON, S.C. — Desquamative inflammatory vaginitis has been diagnosed as often as bacterial vaginosis in an ongoing study of women presenting with chronic vaginal symptoms, Paul Nyirjesy, M.D., reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

In 200 women referred to a tertiary care vaginitis center and enrolled in the study thus far, 251 diagnoses were made; many patients had more than one diagnosis.

Contact dermatitis was the most common diagnosis, occurring in 17% of patients, followed by recurrent vulvovaginal candidiasis (16% of patients), atrophic vaginitis (12% of patients), vulvar vestibulitis syndrome (10% of patients), physiologic leukorrhea (7% of patients), desquamative inflammatory vaginitis (DIV) (6% of patients), and recurrent bacterial vaginosis (5% of patients). The remaining patients were diagnosed with a number of other conditions, said Dr. Nyirjesy of Drexel University, Philadelphia.

The patients were grouped into diagnostic categories that best described the primary cause of their symptoms. A number of differences in demographics, symptoms, and effect on quality of life were observed among these diagnostic groups.

For example, those in the vulvar vestibulitis group were younger and were the least likely to have completed college. That group also had the least number of patients who were pregnant or who had children, Dr. Nyirjesy said.

The DIV group had the highest proportion with an annual income of more than $60,000 and were the least likely to still be menstruating.

In terms of symptoms, patients in the leukorrhea group were most likely to complain about odor and discharge (the DIV patients had the second highest number of complaints about discharge, with 75% reporting this symptom), and those in the candidiasis group complained the most about itching and burning symptoms.

More than 60% of the patients in the study had experienced symptoms for more than a year, Dr. Nyirjesy noted.

Patients in all groups said their condition had affected their social and work lives. The DIV group was the least affected in this regard, but in all groups, 50% or more said they had no or low sexual desire.

Pain scores were highest in the candidiasis and “other” groups, but the vulvar vestibulitis group had the highest score for pain during sexual intercourse (77 on a scale of 100).

Also, a substantial number in some diagnostic groups reported a pain syndrome, such as fibromyalgia, interstitial cystitis, or migraine headaches. Except for the leukorrhea group, which had the fewest patients with a pain syndrome, and the DIV group, which had a 25% rate of pain syndromes, the rates were in the 45%–50% range, which is twice as high as the rate of these syndromes in the general population, he said.

“Women with chronic vaginitis have a variety of diagnoses … and DIV, which is a condition that most gynecologists have never heard of, is about as common as bacterial vaginosis,” Dr. Nyirjesy said, noting that all of the diagnoses have a substantial impact on quality of life.

As the study database grows and more longitudinal data are obtained, more will be learned about chronic vaginitis, comorbidities, and treatment, he added.

CHARLESTON, S.C. — Desquamative inflammatory vaginitis has been diagnosed as often as bacterial vaginosis in an ongoing study of women presenting with chronic vaginal symptoms, Paul Nyirjesy, M.D., reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

In 200 women referred to a tertiary care vaginitis center and enrolled in the study thus far, 251 diagnoses were made; many patients had more than one diagnosis.

Contact dermatitis was the most common diagnosis, occurring in 17% of patients, followed by recurrent vulvovaginal candidiasis (16% of patients), atrophic vaginitis (12% of patients), vulvar vestibulitis syndrome (10% of patients), physiologic leukorrhea (7% of patients), desquamative inflammatory vaginitis (DIV) (6% of patients), and recurrent bacterial vaginosis (5% of patients). The remaining patients were diagnosed with a number of other conditions, said Dr. Nyirjesy of Drexel University, Philadelphia.

The patients were grouped into diagnostic categories that best described the primary cause of their symptoms. A number of differences in demographics, symptoms, and effect on quality of life were observed among these diagnostic groups.

For example, those in the vulvar vestibulitis group were younger and were the least likely to have completed college. That group also had the least number of patients who were pregnant or who had children, Dr. Nyirjesy said.

The DIV group had the highest proportion with an annual income of more than $60,000 and were the least likely to still be menstruating.

In terms of symptoms, patients in the leukorrhea group were most likely to complain about odor and discharge (the DIV patients had the second highest number of complaints about discharge, with 75% reporting this symptom), and those in the candidiasis group complained the most about itching and burning symptoms.

More than 60% of the patients in the study had experienced symptoms for more than a year, Dr. Nyirjesy noted.

Patients in all groups said their condition had affected their social and work lives. The DIV group was the least affected in this regard, but in all groups, 50% or more said they had no or low sexual desire.

Pain scores were highest in the candidiasis and “other” groups, but the vulvar vestibulitis group had the highest score for pain during sexual intercourse (77 on a scale of 100).

Also, a substantial number in some diagnostic groups reported a pain syndrome, such as fibromyalgia, interstitial cystitis, or migraine headaches. Except for the leukorrhea group, which had the fewest patients with a pain syndrome, and the DIV group, which had a 25% rate of pain syndromes, the rates were in the 45%–50% range, which is twice as high as the rate of these syndromes in the general population, he said.

“Women with chronic vaginitis have a variety of diagnoses … and DIV, which is a condition that most gynecologists have never heard of, is about as common as bacterial vaginosis,” Dr. Nyirjesy said, noting that all of the diagnoses have a substantial impact on quality of life.

As the study database grows and more longitudinal data are obtained, more will be learned about chronic vaginitis, comorbidities, and treatment, he added.

CHARLESTON, S.C. — Desquamative inflammatory vaginitis has been diagnosed as often as bacterial vaginosis in an ongoing study of women presenting with chronic vaginal symptoms, Paul Nyirjesy, M.D., reported at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.

In 200 women referred to a tertiary care vaginitis center and enrolled in the study thus far, 251 diagnoses were made; many patients had more than one diagnosis.

Contact dermatitis was the most common diagnosis, occurring in 17% of patients, followed by recurrent vulvovaginal candidiasis (16% of patients), atrophic vaginitis (12% of patients), vulvar vestibulitis syndrome (10% of patients), physiologic leukorrhea (7% of patients), desquamative inflammatory vaginitis (DIV) (6% of patients), and recurrent bacterial vaginosis (5% of patients). The remaining patients were diagnosed with a number of other conditions, said Dr. Nyirjesy of Drexel University, Philadelphia.

The patients were grouped into diagnostic categories that best described the primary cause of their symptoms. A number of differences in demographics, symptoms, and effect on quality of life were observed among these diagnostic groups.

For example, those in the vulvar vestibulitis group were younger and were the least likely to have completed college. That group also had the least number of patients who were pregnant or who had children, Dr. Nyirjesy said.

The DIV group had the highest proportion with an annual income of more than $60,000 and were the least likely to still be menstruating.

In terms of symptoms, patients in the leukorrhea group were most likely to complain about odor and discharge (the DIV patients had the second highest number of complaints about discharge, with 75% reporting this symptom), and those in the candidiasis group complained the most about itching and burning symptoms.

More than 60% of the patients in the study had experienced symptoms for more than a year, Dr. Nyirjesy noted.

Patients in all groups said their condition had affected their social and work lives. The DIV group was the least affected in this regard, but in all groups, 50% or more said they had no or low sexual desire.

Pain scores were highest in the candidiasis and “other” groups, but the vulvar vestibulitis group had the highest score for pain during sexual intercourse (77 on a scale of 100).

Also, a substantial number in some diagnostic groups reported a pain syndrome, such as fibromyalgia, interstitial cystitis, or migraine headaches. Except for the leukorrhea group, which had the fewest patients with a pain syndrome, and the DIV group, which had a 25% rate of pain syndromes, the rates were in the 45%–50% range, which is twice as high as the rate of these syndromes in the general population, he said.

“Women with chronic vaginitis have a variety of diagnoses … and DIV, which is a condition that most gynecologists have never heard of, is about as common as bacterial vaginosis,” Dr. Nyirjesy said, noting that all of the diagnoses have a substantial impact on quality of life.

As the study database grows and more longitudinal data are obtained, more will be learned about chronic vaginitis, comorbidities, and treatment, he added.

NEW ORLEANS — Decidual cast expulsion may occur in young patients using depot medroxyprogesterone acetate, Stephen M. Scott, M.D., said at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology.

Although decidual casts are typically associated with ectopic pregnancy and can be confused with spontaneous abortion, Dr. Scott described four cases that suggest decidual casts might be a rare but important side effect associated with use of the hormonal contraceptive—particularly among those exposed after a prolonged period of anovulatory endometrial proliferation.

The first case involved a postanorexic 16-year-old girl who was on depot medroxyprogesterone acetate (DMPA) for contraception and presented 1 month after her first injection. She had a large amount of white tissue protruding from the cervical os. The patient had experienced weight recovery and signs of estrogen stimulation at the time of the injection, but also had persistent amenor-rhea at the time of injection.

The second case involved a 20-year-old with cerebral palsy and mental retardation, who was using DMPA for the treatment of dysfunctional uterine bleeding. She presented with tissue passing from the vagina 3 weeks after her first injection.

The third case involved an 11-year-old with factor VIII deficiency, who was treated with DMPA to control hemorrhaging that occurred at her first menarche 8 months earlier. She presented with severe cramps and the sensation of a mass in the vagina. An examination revealed white tissue protruding from the cervical os.

The fourth case involved a 19-year-old who had a vaginal delivery 5 months earlier and who at 3 months post partum was breast-feeding and amenorrheic. She began using DMPA for contraception at that time, and 2 months later, she presented with bleeding and cramping. As with the first three cases, examination revealed a large amount of tissue at the cervical os.

The findings in each case were consistent with decidual cast expulsion, and all patients had a negative result on a pregnancy test. The removal of the protruding tissue resulted in symptom resolution, said Dr. Scott of the University of Colorado, Denver.

Because decidual casts are rare, “we don't really have a great idea of what elements are needed in order to form a decidual cast and pass it,” he said.

In theory, however, decidual cast formation can be expected when prolonged endometrial proliferation precedes progesterone exposure, leading to a thicker endometrial layer. When the progesterone levels falter, the likelihood of decidual cast formation may grow, he said.

Although these cases had varying scenarios, it is possible that similar hormonal events led to the decidual cast formation and passage, he explained.

The first three patients had an extended period of amenorrhea with estrogen-only stimulation of the endometrial lining, and thus endometrial proliferation. The fourth patient also may have had prolonged estrogen production with resumption of ovarian estrogen production late in breast-feeding.

DMPA treatment in these patients would then have resulted in a high level of progesterone exposure followed by a gradual decline in progesterone levels that might have led to the decidual casts, he said.

In most of these cases, the decidual casts were, understandably, very frightening for the patient and/or parent, he said.

For this reason, as well as to fully inform patients about the potential effects of DMPA and to promote treatment compliance, patient counseling should include discussion of decidual cast expulsion as a rare side effect associated with the drug.

Furthermore, because 1% of DMPA failures are ectopic pregnancies (although DMPA is not a known cause of ectopic pregnancies), and because decidual casts and ectopic pregnancies can be easily confused, patients using DMPA who experience tissue passage should be advised to bring the specimen in for evaluation and should undergo a pregnancy test.

NEW ORLEANS — Decidual cast expulsion may occur in young patients using depot medroxyprogesterone acetate, Stephen M. Scott, M.D., said at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology.

Although decidual casts are typically associated with ectopic pregnancy and can be confused with spontaneous abortion, Dr. Scott described four cases that suggest decidual casts might be a rare but important side effect associated with use of the hormonal contraceptive—particularly among those exposed after a prolonged period of anovulatory endometrial proliferation.

The first case involved a postanorexic 16-year-old girl who was on depot medroxyprogesterone acetate (DMPA) for contraception and presented 1 month after her first injection. She had a large amount of white tissue protruding from the cervical os. The patient had experienced weight recovery and signs of estrogen stimulation at the time of the injection, but also had persistent amenor-rhea at the time of injection.

The second case involved a 20-year-old with cerebral palsy and mental retardation, who was using DMPA for the treatment of dysfunctional uterine bleeding. She presented with tissue passing from the vagina 3 weeks after her first injection.

The third case involved an 11-year-old with factor VIII deficiency, who was treated with DMPA to control hemorrhaging that occurred at her first menarche 8 months earlier. She presented with severe cramps and the sensation of a mass in the vagina. An examination revealed white tissue protruding from the cervical os.

The fourth case involved a 19-year-old who had a vaginal delivery 5 months earlier and who at 3 months post partum was breast-feeding and amenorrheic. She began using DMPA for contraception at that time, and 2 months later, she presented with bleeding and cramping. As with the first three cases, examination revealed a large amount of tissue at the cervical os.

The findings in each case were consistent with decidual cast expulsion, and all patients had a negative result on a pregnancy test. The removal of the protruding tissue resulted in symptom resolution, said Dr. Scott of the University of Colorado, Denver.

Because decidual casts are rare, “we don't really have a great idea of what elements are needed in order to form a decidual cast and pass it,” he said.

In theory, however, decidual cast formation can be expected when prolonged endometrial proliferation precedes progesterone exposure, leading to a thicker endometrial layer. When the progesterone levels falter, the likelihood of decidual cast formation may grow, he said.

Although these cases had varying scenarios, it is possible that similar hormonal events led to the decidual cast formation and passage, he explained.

The first three patients had an extended period of amenorrhea with estrogen-only stimulation of the endometrial lining, and thus endometrial proliferation. The fourth patient also may have had prolonged estrogen production with resumption of ovarian estrogen production late in breast-feeding.

DMPA treatment in these patients would then have resulted in a high level of progesterone exposure followed by a gradual decline in progesterone levels that might have led to the decidual casts, he said.

In most of these cases, the decidual casts were, understandably, very frightening for the patient and/or parent, he said.

For this reason, as well as to fully inform patients about the potential effects of DMPA and to promote treatment compliance, patient counseling should include discussion of decidual cast expulsion as a rare side effect associated with the drug.

Furthermore, because 1% of DMPA failures are ectopic pregnancies (although DMPA is not a known cause of ectopic pregnancies), and because decidual casts and ectopic pregnancies can be easily confused, patients using DMPA who experience tissue passage should be advised to bring the specimen in for evaluation and should undergo a pregnancy test.

NEW ORLEANS — Decidual cast expulsion may occur in young patients using depot medroxyprogesterone acetate, Stephen M. Scott, M.D., said at the annual meeting of the North American Society for Pediatric and Adolescent Gynecology.

Although decidual casts are typically associated with ectopic pregnancy and can be confused with spontaneous abortion, Dr. Scott described four cases that suggest decidual casts might be a rare but important side effect associated with use of the hormonal contraceptive—particularly among those exposed after a prolonged period of anovulatory endometrial proliferation.

The first case involved a postanorexic 16-year-old girl who was on depot medroxyprogesterone acetate (DMPA) for contraception and presented 1 month after her first injection. She had a large amount of white tissue protruding from the cervical os. The patient had experienced weight recovery and signs of estrogen stimulation at the time of the injection, but also had persistent amenor-rhea at the time of injection.

The second case involved a 20-year-old with cerebral palsy and mental retardation, who was using DMPA for the treatment of dysfunctional uterine bleeding. She presented with tissue passing from the vagina 3 weeks after her first injection.

The third case involved an 11-year-old with factor VIII deficiency, who was treated with DMPA to control hemorrhaging that occurred at her first menarche 8 months earlier. She presented with severe cramps and the sensation of a mass in the vagina. An examination revealed white tissue protruding from the cervical os.

The fourth case involved a 19-year-old who had a vaginal delivery 5 months earlier and who at 3 months post partum was breast-feeding and amenorrheic. She began using DMPA for contraception at that time, and 2 months later, she presented with bleeding and cramping. As with the first three cases, examination revealed a large amount of tissue at the cervical os.

The findings in each case were consistent with decidual cast expulsion, and all patients had a negative result on a pregnancy test. The removal of the protruding tissue resulted in symptom resolution, said Dr. Scott of the University of Colorado, Denver.

Because decidual casts are rare, “we don't really have a great idea of what elements are needed in order to form a decidual cast and pass it,” he said.

In theory, however, decidual cast formation can be expected when prolonged endometrial proliferation precedes progesterone exposure, leading to a thicker endometrial layer. When the progesterone levels falter, the likelihood of decidual cast formation may grow, he said.

Although these cases had varying scenarios, it is possible that similar hormonal events led to the decidual cast formation and passage, he explained.

The first three patients had an extended period of amenorrhea with estrogen-only stimulation of the endometrial lining, and thus endometrial proliferation. The fourth patient also may have had prolonged estrogen production with resumption of ovarian estrogen production late in breast-feeding.

DMPA treatment in these patients would then have resulted in a high level of progesterone exposure followed by a gradual decline in progesterone levels that might have led to the decidual casts, he said.

In most of these cases, the decidual casts were, understandably, very frightening for the patient and/or parent, he said.

For this reason, as well as to fully inform patients about the potential effects of DMPA and to promote treatment compliance, patient counseling should include discussion of decidual cast expulsion as a rare side effect associated with the drug.

Furthermore, because 1% of DMPA failures are ectopic pregnancies (although DMPA is not a known cause of ectopic pregnancies), and because decidual casts and ectopic pregnancies can be easily confused, patients using DMPA who experience tissue passage should be advised to bring the specimen in for evaluation and should undergo a pregnancy test.

ST. PETE BEACH, FLA. — Periconceptional exposure to oral contraceptives was not associated with increased risk of adverse fetal outcomes in a recent prospective study.

None of the 45 women who were exposed to oral contraceptives during the periconceptional period and were followed until after delivery gave birth to an infant with congenital malformations, compared with 6 of 225 controls. The difference in the congenital malformation rate between the exposed and control groups was not significant, said H.K. Ahn, M.D., and colleagues of the Motherisk Program at Sungkyunkwan University, Seoul, South Korea, during a poster session at the annual meeting of the Teratology Society.

The groups were also similar in regard to mean gestational age at delivery (39 weeks in both groups) and birth weight (3,257 g in the exposed group, and 3,268 g in the controls), the investigators said.

Women in the exposed group took oral contraceptives containing either combined ethinyl estradiol and progesterone, or high-dose progesterone.

Although some earlier studies suggested a link between oral contraceptive use during pregnancy and increased risk of birth defects, later studies—including the current study—have failed to reproduce these findings.

“Exposure to oral contraceptives, including high doses of progesterone … did not increase adverse fetal outcomes,” the investigators said.

ST. PETE BEACH, FLA. — Periconceptional exposure to oral contraceptives was not associated with increased risk of adverse fetal outcomes in a recent prospective study.

None of the 45 women who were exposed to oral contraceptives during the periconceptional period and were followed until after delivery gave birth to an infant with congenital malformations, compared with 6 of 225 controls. The difference in the congenital malformation rate between the exposed and control groups was not significant, said H.K. Ahn, M.D., and colleagues of the Motherisk Program at Sungkyunkwan University, Seoul, South Korea, during a poster session at the annual meeting of the Teratology Society.

The groups were also similar in regard to mean gestational age at delivery (39 weeks in both groups) and birth weight (3,257 g in the exposed group, and 3,268 g in the controls), the investigators said.

Women in the exposed group took oral contraceptives containing either combined ethinyl estradiol and progesterone, or high-dose progesterone.

Although some earlier studies suggested a link between oral contraceptive use during pregnancy and increased risk of birth defects, later studies—including the current study—have failed to reproduce these findings.

“Exposure to oral contraceptives, including high doses of progesterone … did not increase adverse fetal outcomes,” the investigators said.

ST. PETE BEACH, FLA. — Periconceptional exposure to oral contraceptives was not associated with increased risk of adverse fetal outcomes in a recent prospective study.

None of the 45 women who were exposed to oral contraceptives during the periconceptional period and were followed until after delivery gave birth to an infant with congenital malformations, compared with 6 of 225 controls. The difference in the congenital malformation rate between the exposed and control groups was not significant, said H.K. Ahn, M.D., and colleagues of the Motherisk Program at Sungkyunkwan University, Seoul, South Korea, during a poster session at the annual meeting of the Teratology Society.

The groups were also similar in regard to mean gestational age at delivery (39 weeks in both groups) and birth weight (3,257 g in the exposed group, and 3,268 g in the controls), the investigators said.

Women in the exposed group took oral contraceptives containing either combined ethinyl estradiol and progesterone, or high-dose progesterone.

Although some earlier studies suggested a link between oral contraceptive use during pregnancy and increased risk of birth defects, later studies—including the current study—have failed to reproduce these findings.

“Exposure to oral contraceptives, including high doses of progesterone … did not increase adverse fetal outcomes,” the investigators said.