Heidi Splete

An amoxicillin/clavulanate combination was significantly more effective than azithromycin in eliminating bacterial acute otitis media, including penicillin-resistant strains, reported Alejandro Hoberman, M.D., of the Children's Hospital of Pittsburgh, and his colleagues.

In a randomized, investigator-blinded study sponsored in part by GlaxoSmithKline, 730 children aged 6–30 months were randomized to receive either a 90-mg amoxicillin and a 6.4-mg clavulanate/kg combination daily in 2 divided doses for 10 days, or a 10-mg/kg dose of azithromycin once daily for 1 day, followed by 5 mg/kg once daily for 4 days.

The study was conducted at 34 centers worldwide, including ones in Bulgaria, Chile, the Dominican Republic, Guatemala, Israel, Peru, Romania, Latvia, Mexico, and the United States from April 2001 to November 2002.

The evolution of antimicrobial resistance among pathogens that cause acute otitis media (AOM) and the approval of a large-dose pediatric formulation of amoxicillin/clavulanate prompted the study.

At baseline, 494 (68%) of the children had at least one protocol-defined pathogen. Of those, 249 were in the amoxicillin/clavulanate group and 245 were in the azithromycin group.

Of these, 19 (8%) children in the amoxicillin/clavulanate group and 38 (16%) in the azithromycin group had more than one pathogen at baseline (Pediatr. Infect. Dis. J. 2005:24:525–32).

The children without discernible pathogens at baseline (118 in each group) were included in the safety analysis.

In addition, of the 229 total Streptococcus pneumoniae isolates (111 children in the amoxicillin/clavulanate group and 118 children in the azithromycin group), 49%, 11%, and 21% were not susceptible to penicillin, amoxicillin, and azithromycin, respectively.

Overall, clinical success rates among children with baseline AOM pathogens were significantly greater in the amoxicillin/clavulanate group (91%), compared with the azithromycin group (81%).

Clinical success was defined as the lessening or complete resolution of acute ear infection and inflammation, with or without middle-ear effusion, to the extent that no additional antibiotics were needed.

Clinical response at 12–14 days after the start of therapy served as the primary end point of the study.

Bacteriologic success was defined as the eradication of the initial AOM pathogen with or without a new pathogen, based on a lack of middle-ear fluid.

Bacteriologic success at an “on-therapy” visit 4–6 days after the start of treatment was associated with clinical success at the end of the therapy in 96 of 105 children (91%) in the group treated with the amoxicillin/clavulanate combo and in 80 of 89 (90%) children in the azithromycin group.

The distribution of pathogens was similar between the two groups.

H. influenzae was the more common. It was found in 49% of the group that was treated with amoxicillin/clavulanate and in 51% of the azithromycin group.

In the subset of 101 amoxicillin/clavulanate patients and 82 azithromycin patients who demonstrated bacteriologic responses after 4–6 days, amoxicillin/clavulanate was significantly more effective than azithromycin against penicillin-resistant S. pneumoniae, with eradication in 23 of 25 cases (92%) vs. 12 of 22 cases (55%), respectively.

Although significantly more children in the amoxicillin/clavulanate group withdrew from the study due to an adverse event, compared with the azithromycin group (21 vs. 7), the total number of adverse events was not significantly different between the two groups (139 vs. 128).

Fever was the most common adverse event reported, and it occurred in approximately 10% of the patients in each group.

Diarrhea occurred in 6% of patients taking amoxicillin/clavulanate and 4% of those taking azithromycin.

Overall, the compliance rates were high in both groups: 86% in the amoxicillin/clavulanate group and 91% in the azithromycin group.

An amoxicillin/clavulanate combination was significantly more effective than azithromycin in eliminating bacterial acute otitis media, including penicillin-resistant strains, reported Alejandro Hoberman, M.D., of the Children's Hospital of Pittsburgh, and his colleagues.

In a randomized, investigator-blinded study sponsored in part by GlaxoSmithKline, 730 children aged 6–30 months were randomized to receive either a 90-mg amoxicillin and a 6.4-mg clavulanate/kg combination daily in 2 divided doses for 10 days, or a 10-mg/kg dose of azithromycin once daily for 1 day, followed by 5 mg/kg once daily for 4 days.

The study was conducted at 34 centers worldwide, including ones in Bulgaria, Chile, the Dominican Republic, Guatemala, Israel, Peru, Romania, Latvia, Mexico, and the United States from April 2001 to November 2002.

The evolution of antimicrobial resistance among pathogens that cause acute otitis media (AOM) and the approval of a large-dose pediatric formulation of amoxicillin/clavulanate prompted the study.

At baseline, 494 (68%) of the children had at least one protocol-defined pathogen. Of those, 249 were in the amoxicillin/clavulanate group and 245 were in the azithromycin group.

Of these, 19 (8%) children in the amoxicillin/clavulanate group and 38 (16%) in the azithromycin group had more than one pathogen at baseline (Pediatr. Infect. Dis. J. 2005:24:525–32).

The children without discernible pathogens at baseline (118 in each group) were included in the safety analysis.

In addition, of the 229 total Streptococcus pneumoniae isolates (111 children in the amoxicillin/clavulanate group and 118 children in the azithromycin group), 49%, 11%, and 21% were not susceptible to penicillin, amoxicillin, and azithromycin, respectively.

Overall, clinical success rates among children with baseline AOM pathogens were significantly greater in the amoxicillin/clavulanate group (91%), compared with the azithromycin group (81%).

Clinical success was defined as the lessening or complete resolution of acute ear infection and inflammation, with or without middle-ear effusion, to the extent that no additional antibiotics were needed.

Clinical response at 12–14 days after the start of therapy served as the primary end point of the study.

Bacteriologic success was defined as the eradication of the initial AOM pathogen with or without a new pathogen, based on a lack of middle-ear fluid.

Bacteriologic success at an “on-therapy” visit 4–6 days after the start of treatment was associated with clinical success at the end of the therapy in 96 of 105 children (91%) in the group treated with the amoxicillin/clavulanate combo and in 80 of 89 (90%) children in the azithromycin group.

The distribution of pathogens was similar between the two groups.

H. influenzae was the more common. It was found in 49% of the group that was treated with amoxicillin/clavulanate and in 51% of the azithromycin group.

In the subset of 101 amoxicillin/clavulanate patients and 82 azithromycin patients who demonstrated bacteriologic responses after 4–6 days, amoxicillin/clavulanate was significantly more effective than azithromycin against penicillin-resistant S. pneumoniae, with eradication in 23 of 25 cases (92%) vs. 12 of 22 cases (55%), respectively.

Although significantly more children in the amoxicillin/clavulanate group withdrew from the study due to an adverse event, compared with the azithromycin group (21 vs. 7), the total number of adverse events was not significantly different between the two groups (139 vs. 128).

Fever was the most common adverse event reported, and it occurred in approximately 10% of the patients in each group.

Diarrhea occurred in 6% of patients taking amoxicillin/clavulanate and 4% of those taking azithromycin.

Overall, the compliance rates were high in both groups: 86% in the amoxicillin/clavulanate group and 91% in the azithromycin group.

An amoxicillin/clavulanate combination was significantly more effective than azithromycin in eliminating bacterial acute otitis media, including penicillin-resistant strains, reported Alejandro Hoberman, M.D., of the Children's Hospital of Pittsburgh, and his colleagues.

In a randomized, investigator-blinded study sponsored in part by GlaxoSmithKline, 730 children aged 6–30 months were randomized to receive either a 90-mg amoxicillin and a 6.4-mg clavulanate/kg combination daily in 2 divided doses for 10 days, or a 10-mg/kg dose of azithromycin once daily for 1 day, followed by 5 mg/kg once daily for 4 days.

The study was conducted at 34 centers worldwide, including ones in Bulgaria, Chile, the Dominican Republic, Guatemala, Israel, Peru, Romania, Latvia, Mexico, and the United States from April 2001 to November 2002.

The evolution of antimicrobial resistance among pathogens that cause acute otitis media (AOM) and the approval of a large-dose pediatric formulation of amoxicillin/clavulanate prompted the study.

At baseline, 494 (68%) of the children had at least one protocol-defined pathogen. Of those, 249 were in the amoxicillin/clavulanate group and 245 were in the azithromycin group.

Of these, 19 (8%) children in the amoxicillin/clavulanate group and 38 (16%) in the azithromycin group had more than one pathogen at baseline (Pediatr. Infect. Dis. J. 2005:24:525–32).

The children without discernible pathogens at baseline (118 in each group) were included in the safety analysis.

In addition, of the 229 total Streptococcus pneumoniae isolates (111 children in the amoxicillin/clavulanate group and 118 children in the azithromycin group), 49%, 11%, and 21% were not susceptible to penicillin, amoxicillin, and azithromycin, respectively.

Overall, clinical success rates among children with baseline AOM pathogens were significantly greater in the amoxicillin/clavulanate group (91%), compared with the azithromycin group (81%).

Clinical success was defined as the lessening or complete resolution of acute ear infection and inflammation, with or without middle-ear effusion, to the extent that no additional antibiotics were needed.

Clinical response at 12–14 days after the start of therapy served as the primary end point of the study.

Bacteriologic success was defined as the eradication of the initial AOM pathogen with or without a new pathogen, based on a lack of middle-ear fluid.

Bacteriologic success at an “on-therapy” visit 4–6 days after the start of treatment was associated with clinical success at the end of the therapy in 96 of 105 children (91%) in the group treated with the amoxicillin/clavulanate combo and in 80 of 89 (90%) children in the azithromycin group.

The distribution of pathogens was similar between the two groups.

H. influenzae was the more common. It was found in 49% of the group that was treated with amoxicillin/clavulanate and in 51% of the azithromycin group.

In the subset of 101 amoxicillin/clavulanate patients and 82 azithromycin patients who demonstrated bacteriologic responses after 4–6 days, amoxicillin/clavulanate was significantly more effective than azithromycin against penicillin-resistant S. pneumoniae, with eradication in 23 of 25 cases (92%) vs. 12 of 22 cases (55%), respectively.

Although significantly more children in the amoxicillin/clavulanate group withdrew from the study due to an adverse event, compared with the azithromycin group (21 vs. 7), the total number of adverse events was not significantly different between the two groups (139 vs. 128).

Fever was the most common adverse event reported, and it occurred in approximately 10% of the patients in each group.

Diarrhea occurred in 6% of patients taking amoxicillin/clavulanate and 4% of those taking azithromycin.

Overall, the compliance rates were high in both groups: 86% in the amoxicillin/clavulanate group and 91% in the azithromycin group.

ROCKVILLE, MD. — Should the United States face an influenza pandemic, the federal government should buy all the vaccine, members of the National Vaccine Advisory Committee agreed at a joint meeting with the Advisory Committee on Immunization Practices.

The committees met to review the work of the Pandemic Influenza Working Group and vote on several points in the Department of Health and Human Services' current draft Pandemic Influenza Preparedness Plan.

During deliberations of the National Vaccine Advisory Committee (NVAC), members preferred the government vaccine purchase option over three others, including the current standard purchase of vaccines by a mix of public and private groups. However, they emphasized that the universal government vaccine purchase applied only in the event of a pandemic.

The NVAC also voted to accept the recommendations of the working group's antiviral subgroup. These recommendations included creation of an antiviral drug stockpile sufficient to reduce the public health impact of a flu pandemic. At least 40 million courses of antiviral drugs are needed to provide critical response support in the event of a pandemic, said Andrew Pavia, M.D., of the University of Utah, Salt Lake City, who presented the recommendations.

The NVAC voted that oseltamivir should be the primary drug stockpiled for a flu pandemic, with zanamivir stockpiled as a backup. Although vaccination is the most formidable weapon against a flu pandemic, antiviral drugs are effective when used early in the disease if vaccines are not available, Dr. Pavia noted.

In addition, NVAC members voted to accept the recommendation of the antiviral subgroup on the approximate numbers of drug courses needed for priority target groups including hospitalized patients, health care workers with direct patient contact, pandemic health responders, public safety officials, and government decision makers. They also approved the subgroup's recommendations that additional research to support the use of antivirals in the event of a flu pandemic should include the safety of oseltamivir in infants less than 1 year of age, the sensitivity of rapid diagnostic tests for flu strains with pandemic potential, such as H5N1, the impact of antiviral treatment of a flu pandemic on hospital admissions, the testing of an optimal treatment dose and schedule in a ferret model with H5N1 and other flu strains, and the investigation of the potential for use of other antiviral agents.

The NVAC and the Advisory Committee on Immunization Practices (ACIP), both of which advise the Centers for Disease Control and Prevention, also met jointly and voted in favor of a “prioritization table” of people who would be the first to receive vaccines in the event of a flu pandemic.

The supply of vaccine will likely be limited, and identification of priority groups will help decrease the overall health impact of a pandemic while limiting economic disruption and reducing the overall societal impact, said Ben Schwartz, M.D., of the National Vaccine Program Office at the Department of Health and Human Services. The draft prioritization table, created by the Joint ACIP/NVAC Working Group on Pandemic Influenza Vaccine Prioritization, established four tiers.

Tier 1 is subdivided to include persons with direct patient contact and critical support staff, patients in the highest risk group based on the standard ACIP criteria, household contacts of children younger than 6 months, pregnant women, and critical government leaders and pandemic responders.

Tier 2 includes other high-risk patients, followed by those in critical community infrastructure, such as public health emergency responders, public safety, utility, and telecommunications workers.

Tier 3 includes other important government health care decision makers, and mortuary service personnel.

Tier 4 includes healthy people aged 2–64 years who are not in any other group.

“We in clinical care need to have very explicit guidelines as to which patients can be identified upfront [for vaccine priority] by the use of things like administrative databases, coding, and demographic information,” commented Jonathan Temte, M.D., the American Academy of Family Physicians' liaison to ACIP.

“We need to develop lists now that correspond to the priority groups, rather than trying to do that on the fly,” he said. Explicit definitions given to those in charge of clinics can avoid disruption with staff over situations such as, “you work in the file room, so you don't get a shot.”

The draft of the Pandemic Influenza Preparedness Response Plan has been sent to the Department of Health and Human Services for review, with additional revisions possible later this year.

U.S. Government Requests 22 Million Avian Flu Vaccine Doses

The U.S. government aims to buy millions of doses of avian influenza vaccine, which preliminary data have shown produces a robust immune response against the A (H5N1) virus in some doses.

“We have been asked to provide up to 20 million doses of the vaccine, in addition to the 2 million we have already agreed to supply,” Len Lavenda, spokesman for Sanofi-Pasteur, Swiftwater, Pa., told FAMILY PRACTICE NEWS. The contract would be contingent on the vaccine being approved after thorough testing in clinical trials. Currently, only preliminary information is available about immunogenicity in adults, and trials in children and the elderly have yet to start.

If the vaccine is approved, the 22 million doses will be added to the Strategic National Stockpile of drugs, and distributed only in the event of an H5N1 pandemic.

Although the first clinical trial of 452 healthy adults aged 18–64 years is ongoing, early data show immune response in the 113 subjects for whom serology is available, John Treanor, M.D., said in an interview. The trial is testing four doses of the vaccine (7.5 mcg, 15 mcg, 45 mcg, and 90 mcg). Subjects received an initial vaccination plus a booster of the same dose given about a month later.

All doses produced some response, but only two 90-mcg doses gave a response robust enough to inspire confidence about immunity, said Dr. Treanor, principal investigator of the trial conducted at the University of Rochester (N.Y.).

With the 90-mcg doses, “We're confident the immune response would be protective against the H5 virus,” he said. “There was definitely a dose-response reaction.”

But the large dose required to produce optimal response could put a strain on manufacturing, making it tough for the government to meet its preliminary quota of 22 million doses, said Anthony Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases.

“This will put an extra strain on the production issue—which has been an issue of concern even before this,” he told this newspaper. “We've been talking about the lack of ability to manufacture a global vaccine for a long time. This underscores the issue. It's a problem that will only be solved by getting more companies involved.”

Several factors affect vaccine production capacity, said Mr. Lavenda. The concentration of antigen in each dose is one factor.

However, he said, the company recently began construction of a new influenza vaccine facility, which will more than double its U.S. capacity. The facility will probably come online by 2008. An overhaul of the company's French facility, which will double its capacity, is in the works as well.

Researchers will be searching for ways to decrease the antigen load in each dose, Dr. Treanor said. “We'll be looking at reducing the dose but achieving the same response, maybe by adding adjuvants or going a different route of administration.”

The vaccine must also still be tested in children and the elderly, he noted. But the preliminary results in adults are raising hopes for similarly good responses in other age groups. The quick turnaround on the development of this vaccine also shows that vaccines against other emergent strains could be produced rapidly, Dr. Treanor said.

Work on the vaccine began in early 2004, when the initial viral sample was isolated in Southeast Asia. Proceeding from virus isolation to vaccine clinical trials in little more than 1 year is unprecedented, Dr. Treanor and Dr. Fauci said.

“The most important part of this study is that for the first time we have gone through the whole process of identifying the virus, making a genetically engineered seed virus, producing the vaccine, and then getting immune results 4 months from vaccination,” said Dr. Treanor.

Having such a process in place gives some assurance that researchers would be able to respond quickly to any antigenic drift the H5 virus might experience, Dr. Fauci said. “The virus might change so significantly that this vaccine would offer much less protection. This exercise that we have gone through is an important dry run in being able to produce a vaccine as quickly as possible.”

Michele G. Sullivan

ROCKVILLE, MD. — Should the United States face an influenza pandemic, the federal government should buy all the vaccine, members of the National Vaccine Advisory Committee agreed at a joint meeting with the Advisory Committee on Immunization Practices.

The committees met to review the work of the Pandemic Influenza Working Group and vote on several points in the Department of Health and Human Services' current draft Pandemic Influenza Preparedness Plan.

During deliberations of the National Vaccine Advisory Committee (NVAC), members preferred the government vaccine purchase option over three others, including the current standard purchase of vaccines by a mix of public and private groups. However, they emphasized that the universal government vaccine purchase applied only in the event of a pandemic.

The NVAC also voted to accept the recommendations of the working group's antiviral subgroup. These recommendations included creation of an antiviral drug stockpile sufficient to reduce the public health impact of a flu pandemic. At least 40 million courses of antiviral drugs are needed to provide critical response support in the event of a pandemic, said Andrew Pavia, M.D., of the University of Utah, Salt Lake City, who presented the recommendations.

The NVAC voted that oseltamivir should be the primary drug stockpiled for a flu pandemic, with zanamivir stockpiled as a backup. Although vaccination is the most formidable weapon against a flu pandemic, antiviral drugs are effective when used early in the disease if vaccines are not available, Dr. Pavia noted.

In addition, NVAC members voted to accept the recommendation of the antiviral subgroup on the approximate numbers of drug courses needed for priority target groups including hospitalized patients, health care workers with direct patient contact, pandemic health responders, public safety officials, and government decision makers. They also approved the subgroup's recommendations that additional research to support the use of antivirals in the event of a flu pandemic should include the safety of oseltamivir in infants less than 1 year of age, the sensitivity of rapid diagnostic tests for flu strains with pandemic potential, such as H5N1, the impact of antiviral treatment of a flu pandemic on hospital admissions, the testing of an optimal treatment dose and schedule in a ferret model with H5N1 and other flu strains, and the investigation of the potential for use of other antiviral agents.

The NVAC and the Advisory Committee on Immunization Practices (ACIP), both of which advise the Centers for Disease Control and Prevention, also met jointly and voted in favor of a “prioritization table” of people who would be the first to receive vaccines in the event of a flu pandemic.

The supply of vaccine will likely be limited, and identification of priority groups will help decrease the overall health impact of a pandemic while limiting economic disruption and reducing the overall societal impact, said Ben Schwartz, M.D., of the National Vaccine Program Office at the Department of Health and Human Services. The draft prioritization table, created by the Joint ACIP/NVAC Working Group on Pandemic Influenza Vaccine Prioritization, established four tiers.

Tier 1 is subdivided to include persons with direct patient contact and critical support staff, patients in the highest risk group based on the standard ACIP criteria, household contacts of children younger than 6 months, pregnant women, and critical government leaders and pandemic responders.

Tier 2 includes other high-risk patients, followed by those in critical community infrastructure, such as public health emergency responders, public safety, utility, and telecommunications workers.

Tier 3 includes other important government health care decision makers, and mortuary service personnel.

Tier 4 includes healthy people aged 2–64 years who are not in any other group.

“We in clinical care need to have very explicit guidelines as to which patients can be identified upfront [for vaccine priority] by the use of things like administrative databases, coding, and demographic information,” commented Jonathan Temte, M.D., the American Academy of Family Physicians' liaison to ACIP.

“We need to develop lists now that correspond to the priority groups, rather than trying to do that on the fly,” he said. Explicit definitions given to those in charge of clinics can avoid disruption with staff over situations such as, “you work in the file room, so you don't get a shot.”

The draft of the Pandemic Influenza Preparedness Response Plan has been sent to the Department of Health and Human Services for review, with additional revisions possible later this year.

U.S. Government Requests 22 Million Avian Flu Vaccine Doses

The U.S. government aims to buy millions of doses of avian influenza vaccine, which preliminary data have shown produces a robust immune response against the A (H5N1) virus in some doses.

“We have been asked to provide up to 20 million doses of the vaccine, in addition to the 2 million we have already agreed to supply,” Len Lavenda, spokesman for Sanofi-Pasteur, Swiftwater, Pa., told FAMILY PRACTICE NEWS. The contract would be contingent on the vaccine being approved after thorough testing in clinical trials. Currently, only preliminary information is available about immunogenicity in adults, and trials in children and the elderly have yet to start.

If the vaccine is approved, the 22 million doses will be added to the Strategic National Stockpile of drugs, and distributed only in the event of an H5N1 pandemic.

Although the first clinical trial of 452 healthy adults aged 18–64 years is ongoing, early data show immune response in the 113 subjects for whom serology is available, John Treanor, M.D., said in an interview. The trial is testing four doses of the vaccine (7.5 mcg, 15 mcg, 45 mcg, and 90 mcg). Subjects received an initial vaccination plus a booster of the same dose given about a month later.

All doses produced some response, but only two 90-mcg doses gave a response robust enough to inspire confidence about immunity, said Dr. Treanor, principal investigator of the trial conducted at the University of Rochester (N.Y.).

With the 90-mcg doses, “We're confident the immune response would be protective against the H5 virus,” he said. “There was definitely a dose-response reaction.”

But the large dose required to produce optimal response could put a strain on manufacturing, making it tough for the government to meet its preliminary quota of 22 million doses, said Anthony Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases.

“This will put an extra strain on the production issue—which has been an issue of concern even before this,” he told this newspaper. “We've been talking about the lack of ability to manufacture a global vaccine for a long time. This underscores the issue. It's a problem that will only be solved by getting more companies involved.”

Several factors affect vaccine production capacity, said Mr. Lavenda. The concentration of antigen in each dose is one factor.

However, he said, the company recently began construction of a new influenza vaccine facility, which will more than double its U.S. capacity. The facility will probably come online by 2008. An overhaul of the company's French facility, which will double its capacity, is in the works as well.

Researchers will be searching for ways to decrease the antigen load in each dose, Dr. Treanor said. “We'll be looking at reducing the dose but achieving the same response, maybe by adding adjuvants or going a different route of administration.”

The vaccine must also still be tested in children and the elderly, he noted. But the preliminary results in adults are raising hopes for similarly good responses in other age groups. The quick turnaround on the development of this vaccine also shows that vaccines against other emergent strains could be produced rapidly, Dr. Treanor said.

Work on the vaccine began in early 2004, when the initial viral sample was isolated in Southeast Asia. Proceeding from virus isolation to vaccine clinical trials in little more than 1 year is unprecedented, Dr. Treanor and Dr. Fauci said.

“The most important part of this study is that for the first time we have gone through the whole process of identifying the virus, making a genetically engineered seed virus, producing the vaccine, and then getting immune results 4 months from vaccination,” said Dr. Treanor.

Having such a process in place gives some assurance that researchers would be able to respond quickly to any antigenic drift the H5 virus might experience, Dr. Fauci said. “The virus might change so significantly that this vaccine would offer much less protection. This exercise that we have gone through is an important dry run in being able to produce a vaccine as quickly as possible.”

Michele G. Sullivan

ROCKVILLE, MD. — Should the United States face an influenza pandemic, the federal government should buy all the vaccine, members of the National Vaccine Advisory Committee agreed at a joint meeting with the Advisory Committee on Immunization Practices.

The committees met to review the work of the Pandemic Influenza Working Group and vote on several points in the Department of Health and Human Services' current draft Pandemic Influenza Preparedness Plan.

During deliberations of the National Vaccine Advisory Committee (NVAC), members preferred the government vaccine purchase option over three others, including the current standard purchase of vaccines by a mix of public and private groups. However, they emphasized that the universal government vaccine purchase applied only in the event of a pandemic.

The NVAC also voted to accept the recommendations of the working group's antiviral subgroup. These recommendations included creation of an antiviral drug stockpile sufficient to reduce the public health impact of a flu pandemic. At least 40 million courses of antiviral drugs are needed to provide critical response support in the event of a pandemic, said Andrew Pavia, M.D., of the University of Utah, Salt Lake City, who presented the recommendations.

The NVAC voted that oseltamivir should be the primary drug stockpiled for a flu pandemic, with zanamivir stockpiled as a backup. Although vaccination is the most formidable weapon against a flu pandemic, antiviral drugs are effective when used early in the disease if vaccines are not available, Dr. Pavia noted.

In addition, NVAC members voted to accept the recommendation of the antiviral subgroup on the approximate numbers of drug courses needed for priority target groups including hospitalized patients, health care workers with direct patient contact, pandemic health responders, public safety officials, and government decision makers. They also approved the subgroup's recommendations that additional research to support the use of antivirals in the event of a flu pandemic should include the safety of oseltamivir in infants less than 1 year of age, the sensitivity of rapid diagnostic tests for flu strains with pandemic potential, such as H5N1, the impact of antiviral treatment of a flu pandemic on hospital admissions, the testing of an optimal treatment dose and schedule in a ferret model with H5N1 and other flu strains, and the investigation of the potential for use of other antiviral agents.

The NVAC and the Advisory Committee on Immunization Practices (ACIP), both of which advise the Centers for Disease Control and Prevention, also met jointly and voted in favor of a “prioritization table” of people who would be the first to receive vaccines in the event of a flu pandemic.

The supply of vaccine will likely be limited, and identification of priority groups will help decrease the overall health impact of a pandemic while limiting economic disruption and reducing the overall societal impact, said Ben Schwartz, M.D., of the National Vaccine Program Office at the Department of Health and Human Services. The draft prioritization table, created by the Joint ACIP/NVAC Working Group on Pandemic Influenza Vaccine Prioritization, established four tiers.

Tier 1 is subdivided to include persons with direct patient contact and critical support staff, patients in the highest risk group based on the standard ACIP criteria, household contacts of children younger than 6 months, pregnant women, and critical government leaders and pandemic responders.

Tier 2 includes other high-risk patients, followed by those in critical community infrastructure, such as public health emergency responders, public safety, utility, and telecommunications workers.

Tier 3 includes other important government health care decision makers, and mortuary service personnel.

Tier 4 includes healthy people aged 2–64 years who are not in any other group.

“We in clinical care need to have very explicit guidelines as to which patients can be identified upfront [for vaccine priority] by the use of things like administrative databases, coding, and demographic information,” commented Jonathan Temte, M.D., the American Academy of Family Physicians' liaison to ACIP.

“We need to develop lists now that correspond to the priority groups, rather than trying to do that on the fly,” he said. Explicit definitions given to those in charge of clinics can avoid disruption with staff over situations such as, “you work in the file room, so you don't get a shot.”

The draft of the Pandemic Influenza Preparedness Response Plan has been sent to the Department of Health and Human Services for review, with additional revisions possible later this year.

U.S. Government Requests 22 Million Avian Flu Vaccine Doses

The U.S. government aims to buy millions of doses of avian influenza vaccine, which preliminary data have shown produces a robust immune response against the A (H5N1) virus in some doses.

“We have been asked to provide up to 20 million doses of the vaccine, in addition to the 2 million we have already agreed to supply,” Len Lavenda, spokesman for Sanofi-Pasteur, Swiftwater, Pa., told FAMILY PRACTICE NEWS. The contract would be contingent on the vaccine being approved after thorough testing in clinical trials. Currently, only preliminary information is available about immunogenicity in adults, and trials in children and the elderly have yet to start.

If the vaccine is approved, the 22 million doses will be added to the Strategic National Stockpile of drugs, and distributed only in the event of an H5N1 pandemic.

Although the first clinical trial of 452 healthy adults aged 18–64 years is ongoing, early data show immune response in the 113 subjects for whom serology is available, John Treanor, M.D., said in an interview. The trial is testing four doses of the vaccine (7.5 mcg, 15 mcg, 45 mcg, and 90 mcg). Subjects received an initial vaccination plus a booster of the same dose given about a month later.

All doses produced some response, but only two 90-mcg doses gave a response robust enough to inspire confidence about immunity, said Dr. Treanor, principal investigator of the trial conducted at the University of Rochester (N.Y.).

With the 90-mcg doses, “We're confident the immune response would be protective against the H5 virus,” he said. “There was definitely a dose-response reaction.”

But the large dose required to produce optimal response could put a strain on manufacturing, making it tough for the government to meet its preliminary quota of 22 million doses, said Anthony Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases.

“This will put an extra strain on the production issue—which has been an issue of concern even before this,” he told this newspaper. “We've been talking about the lack of ability to manufacture a global vaccine for a long time. This underscores the issue. It's a problem that will only be solved by getting more companies involved.”

Several factors affect vaccine production capacity, said Mr. Lavenda. The concentration of antigen in each dose is one factor.

However, he said, the company recently began construction of a new influenza vaccine facility, which will more than double its U.S. capacity. The facility will probably come online by 2008. An overhaul of the company's French facility, which will double its capacity, is in the works as well.

Researchers will be searching for ways to decrease the antigen load in each dose, Dr. Treanor said. “We'll be looking at reducing the dose but achieving the same response, maybe by adding adjuvants or going a different route of administration.”

The vaccine must also still be tested in children and the elderly, he noted. But the preliminary results in adults are raising hopes for similarly good responses in other age groups. The quick turnaround on the development of this vaccine also shows that vaccines against other emergent strains could be produced rapidly, Dr. Treanor said.

Work on the vaccine began in early 2004, when the initial viral sample was isolated in Southeast Asia. Proceeding from virus isolation to vaccine clinical trials in little more than 1 year is unprecedented, Dr. Treanor and Dr. Fauci said.

“The most important part of this study is that for the first time we have gone through the whole process of identifying the virus, making a genetically engineered seed virus, producing the vaccine, and then getting immune results 4 months from vaccination,” said Dr. Treanor.

Having such a process in place gives some assurance that researchers would be able to respond quickly to any antigenic drift the H5 virus might experience, Dr. Fauci said. “The virus might change so significantly that this vaccine would offer much less protection. This exercise that we have gone through is an important dry run in being able to produce a vaccine as quickly as possible.”

Michele G. Sullivan

BETHESDA, MD. — Community-acquired methicillin-resistant Staphylococcus aureus was three times more prevalent than nosocomial MRSA in a small, nonteaching community hospital, reported Ananthakrishnan Ramini, M.D., at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

MRSA was once limited to tertiary care centers and large hospitals but is rapidly becoming a dominant community pathogen, said Dr. Ramini, a physician at Columbia Memorial Hospital, a 192-bed facility in Hudson, N.Y.

Dr. Ramini and his colleagues conducted a prospective study of all MRSA infections in the hospital from January to December 2004. The investigators identified 78 cases of MRSA, of which 58 (74%) were community-acquired. The definition of community-acquired infection was an infection that surfaced within 48 hours of hospital admission.

Among the 51 patients older than 70 years, 47 had MRSA resistant to both clindamycin and erythromycin, which suggests more comorbidities in older patients, Dr. Ramini said. None of the organisms was resistant to oxacillin. In addition, more of the MRSA cases (both community-acquired and nosocomial) occurred outside than inside the ICU (56 vs. 22).

“There was a very high mortality among these patients,” Dr. Ramini noted.

Of the infected patients, 21 died, 39 were discharged to a nursing home, 15 went home, and 3 entered a tertiary care facility.

“What was surprising was that community MRSA was so much more prevalent than nosocomial MRSA,” Dr. Ramini said. “We need to be aware that treatment with a b-lactam alone is no longer a reliable empiric therapy,” he added. He had no conflicts of interest to report.

BETHESDA, MD. — Community-acquired methicillin-resistant Staphylococcus aureus was three times more prevalent than nosocomial MRSA in a small, nonteaching community hospital, reported Ananthakrishnan Ramini, M.D., at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

MRSA was once limited to tertiary care centers and large hospitals but is rapidly becoming a dominant community pathogen, said Dr. Ramini, a physician at Columbia Memorial Hospital, a 192-bed facility in Hudson, N.Y.

Dr. Ramini and his colleagues conducted a prospective study of all MRSA infections in the hospital from January to December 2004. The investigators identified 78 cases of MRSA, of which 58 (74%) were community-acquired. The definition of community-acquired infection was an infection that surfaced within 48 hours of hospital admission.

Among the 51 patients older than 70 years, 47 had MRSA resistant to both clindamycin and erythromycin, which suggests more comorbidities in older patients, Dr. Ramini said. None of the organisms was resistant to oxacillin. In addition, more of the MRSA cases (both community-acquired and nosocomial) occurred outside than inside the ICU (56 vs. 22).

“There was a very high mortality among these patients,” Dr. Ramini noted.

Of the infected patients, 21 died, 39 were discharged to a nursing home, 15 went home, and 3 entered a tertiary care facility.

“What was surprising was that community MRSA was so much more prevalent than nosocomial MRSA,” Dr. Ramini said. “We need to be aware that treatment with a b-lactam alone is no longer a reliable empiric therapy,” he added. He had no conflicts of interest to report.

BETHESDA, MD. — Community-acquired methicillin-resistant Staphylococcus aureus was three times more prevalent than nosocomial MRSA in a small, nonteaching community hospital, reported Ananthakrishnan Ramini, M.D., at the annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

MRSA was once limited to tertiary care centers and large hospitals but is rapidly becoming a dominant community pathogen, said Dr. Ramini, a physician at Columbia Memorial Hospital, a 192-bed facility in Hudson, N.Y.

Dr. Ramini and his colleagues conducted a prospective study of all MRSA infections in the hospital from January to December 2004. The investigators identified 78 cases of MRSA, of which 58 (74%) were community-acquired. The definition of community-acquired infection was an infection that surfaced within 48 hours of hospital admission.

Among the 51 patients older than 70 years, 47 had MRSA resistant to both clindamycin and erythromycin, which suggests more comorbidities in older patients, Dr. Ramini said. None of the organisms was resistant to oxacillin. In addition, more of the MRSA cases (both community-acquired and nosocomial) occurred outside than inside the ICU (56 vs. 22).

“There was a very high mortality among these patients,” Dr. Ramini noted.

Of the infected patients, 21 died, 39 were discharged to a nursing home, 15 went home, and 3 entered a tertiary care facility.

“What was surprising was that community MRSA was so much more prevalent than nosocomial MRSA,” Dr. Ramini said. “We need to be aware that treatment with a b-lactam alone is no longer a reliable empiric therapy,” he added. He had no conflicts of interest to report.

New benzodiazepine receptor agonists for chronic insomnia–zaleplon, zolpidem, and eszopiclone–have shown fewer adverse effects compared with other medications, but additional studies are needed to assess these drugs' long-term effectiveness, concluded members of an independent panel convened by the National Institutes of Health in Bethesda, Md.

Only eszopiclone (Lunesta) has been approved for the long-term treatment of insomnia; the other drugs are approved for up to 35 days of use.

Five benzodiazepines–estazolam, flurazepam, quazepam, temazepam, and triazolam–also are approved by the Food and Drug Administration to treat insomnia, but adverse events including dependence, daytime sleepiness, and lack of motor coordination are more likely with these drugs than with the new receptor agonists.

Although commonly used, all of these medications require more research.

“The real problem with these kinds of compounds is that there are very few data on their efficacy in the treatment of chronic insomnia, yet we know from other research that they produce substantial side effects,” panel member Robert J. DeRubeis, Ph.D., said in an interview.

After reviewing information on the latest research and the available treatments, the panel members concluded that limited guidance and resources exist for clinicians about the treatment of chronic insomnia. They emphasized that more research is needed on the available treatment methods, which include hypnotic medications, behavioral therapy, and alternative medicine, as well as antidepressants, antihistamines, and antipsychotics.

Given the availability of treatments with demonstrated efficacy and fewer side effects in the short term, the panel could not recommend off-label use of nonapproved substances, said Dr. DeRubeis, chair of the department of psychology at the University of Pennsylvania in Philadelphia.

Antidepressants, particularly trazodone, are often prescribed off label for insomnia, but there are no data on the effects of long-term use of such agents, the panelists noted.

“Trazodone is not without danger,” panel member James N. Kvale, M.D., a professor in the department of family and community medicine at the University of Texas, San Antonio, said in an interview. “It loses effectiveness as a sleep aid after 7 days, and its real value for the chronically ill person is to be questioned.”

Chronic sleep loss is a public health problem associated with impaired psychomotor and cognitive function, and may contribute to the risk of falls in older adults, the panelists wrote in a draft consensus statement.

In addition, millions of Americans attempt to treat their sleep problems for prolonged periods of time with untested or off-label products including alcohol and antihistamines, despite a lack of evidence for their effectiveness.

Doctors can start by advising sleepless patients to consider environmental factors, including temperature, light, and sound in the bedroom. If problems persist, doctors should consider referring patients for cognitive-behavioral therapy before prescribing medications, Dr. Kvale said. Given the lack of evidence to support even the approved drug treatments for long-term use, it's important to explore nonpharmaceutical ways to manage sleep problems, he explained.

Cognitive-behavioral therapy (CBT) has proved successful for managing insomnia in randomized, controlled trials. Use of CBT involves training in relaxation, controlling external stimuli, and targeting anxiety-inducing beliefs about sleep and sleep loss. But few clinicians are experts in treating chronic insomnia with CBT, and these techniques are not widely used, the panelists noted.

Although CBT and benzodiazepine receptor agonists have shown benefits in patients with chronic insomnia, additional research is needed to compare the various treatments with each other, and to determine the effectiveness of the treatments across different populations.

The hormone melatonin and the herb valerian have been used for insomnia, but neither of these substances is regulated by the FDA, and the variation in content among preparations makes scientific comparison difficult.

Other alternative treatments for insomnia include light therapy, acupuncture, yoga, and tai chi, but none of these have been sufficiently evaluated, the panel said in the draft statement.

To close the gaps in knowledge, the panel recommended that future studies be randomized, controlled trials comparing at least two effective or promising treatments, including drugs, CBT, and combination therapies.

Understudied features of chronic insomnia include its effects on daytime functioning that prevent people from engaging in a productive and enjoyable work and social life, Dr. DeRubeis added.

Little is known about the incidence of chronic insomnia because it can be difficult to identify as a distinct problem, as opposed to a side effect of other conditions or medications. For example, a middle-aged woman with arthritis may have trouble sleeping, but she talks to her doctor about her arthritis without mentioning insomnia. Population-based studies suggest that about 30% of the general population complain of sleep problems, the panelists noted.

New benzodiazepine receptor agonists for chronic insomnia–zaleplon, zolpidem, and eszopiclone–have shown fewer adverse effects compared with other medications, but additional studies are needed to assess these drugs' long-term effectiveness, concluded members of an independent panel convened by the National Institutes of Health in Bethesda, Md.

Only eszopiclone (Lunesta) has been approved for the long-term treatment of insomnia; the other drugs are approved for up to 35 days of use.

Five benzodiazepines–estazolam, flurazepam, quazepam, temazepam, and triazolam–also are approved by the Food and Drug Administration to treat insomnia, but adverse events including dependence, daytime sleepiness, and lack of motor coordination are more likely with these drugs than with the new receptor agonists.

Although commonly used, all of these medications require more research.

“The real problem with these kinds of compounds is that there are very few data on their efficacy in the treatment of chronic insomnia, yet we know from other research that they produce substantial side effects,” panel member Robert J. DeRubeis, Ph.D., said in an interview.

After reviewing information on the latest research and the available treatments, the panel members concluded that limited guidance and resources exist for clinicians about the treatment of chronic insomnia. They emphasized that more research is needed on the available treatment methods, which include hypnotic medications, behavioral therapy, and alternative medicine, as well as antidepressants, antihistamines, and antipsychotics.

Given the availability of treatments with demonstrated efficacy and fewer side effects in the short term, the panel could not recommend off-label use of nonapproved substances, said Dr. DeRubeis, chair of the department of psychology at the University of Pennsylvania in Philadelphia.

Antidepressants, particularly trazodone, are often prescribed off label for insomnia, but there are no data on the effects of long-term use of such agents, the panelists noted.

“Trazodone is not without danger,” panel member James N. Kvale, M.D., a professor in the department of family and community medicine at the University of Texas, San Antonio, said in an interview. “It loses effectiveness as a sleep aid after 7 days, and its real value for the chronically ill person is to be questioned.”

Chronic sleep loss is a public health problem associated with impaired psychomotor and cognitive function, and may contribute to the risk of falls in older adults, the panelists wrote in a draft consensus statement.

In addition, millions of Americans attempt to treat their sleep problems for prolonged periods of time with untested or off-label products including alcohol and antihistamines, despite a lack of evidence for their effectiveness.

Doctors can start by advising sleepless patients to consider environmental factors, including temperature, light, and sound in the bedroom. If problems persist, doctors should consider referring patients for cognitive-behavioral therapy before prescribing medications, Dr. Kvale said. Given the lack of evidence to support even the approved drug treatments for long-term use, it's important to explore nonpharmaceutical ways to manage sleep problems, he explained.

Cognitive-behavioral therapy (CBT) has proved successful for managing insomnia in randomized, controlled trials. Use of CBT involves training in relaxation, controlling external stimuli, and targeting anxiety-inducing beliefs about sleep and sleep loss. But few clinicians are experts in treating chronic insomnia with CBT, and these techniques are not widely used, the panelists noted.

Although CBT and benzodiazepine receptor agonists have shown benefits in patients with chronic insomnia, additional research is needed to compare the various treatments with each other, and to determine the effectiveness of the treatments across different populations.

The hormone melatonin and the herb valerian have been used for insomnia, but neither of these substances is regulated by the FDA, and the variation in content among preparations makes scientific comparison difficult.

Other alternative treatments for insomnia include light therapy, acupuncture, yoga, and tai chi, but none of these have been sufficiently evaluated, the panel said in the draft statement.

To close the gaps in knowledge, the panel recommended that future studies be randomized, controlled trials comparing at least two effective or promising treatments, including drugs, CBT, and combination therapies.

Understudied features of chronic insomnia include its effects on daytime functioning that prevent people from engaging in a productive and enjoyable work and social life, Dr. DeRubeis added.

Little is known about the incidence of chronic insomnia because it can be difficult to identify as a distinct problem, as opposed to a side effect of other conditions or medications. For example, a middle-aged woman with arthritis may have trouble sleeping, but she talks to her doctor about her arthritis without mentioning insomnia. Population-based studies suggest that about 30% of the general population complain of sleep problems, the panelists noted.

New benzodiazepine receptor agonists for chronic insomnia–zaleplon, zolpidem, and eszopiclone–have shown fewer adverse effects compared with other medications, but additional studies are needed to assess these drugs' long-term effectiveness, concluded members of an independent panel convened by the National Institutes of Health in Bethesda, Md.

Only eszopiclone (Lunesta) has been approved for the long-term treatment of insomnia; the other drugs are approved for up to 35 days of use.

Five benzodiazepines–estazolam, flurazepam, quazepam, temazepam, and triazolam–also are approved by the Food and Drug Administration to treat insomnia, but adverse events including dependence, daytime sleepiness, and lack of motor coordination are more likely with these drugs than with the new receptor agonists.

Although commonly used, all of these medications require more research.

“The real problem with these kinds of compounds is that there are very few data on their efficacy in the treatment of chronic insomnia, yet we know from other research that they produce substantial side effects,” panel member Robert J. DeRubeis, Ph.D., said in an interview.

After reviewing information on the latest research and the available treatments, the panel members concluded that limited guidance and resources exist for clinicians about the treatment of chronic insomnia. They emphasized that more research is needed on the available treatment methods, which include hypnotic medications, behavioral therapy, and alternative medicine, as well as antidepressants, antihistamines, and antipsychotics.

Given the availability of treatments with demonstrated efficacy and fewer side effects in the short term, the panel could not recommend off-label use of nonapproved substances, said Dr. DeRubeis, chair of the department of psychology at the University of Pennsylvania in Philadelphia.

Antidepressants, particularly trazodone, are often prescribed off label for insomnia, but there are no data on the effects of long-term use of such agents, the panelists noted.

“Trazodone is not without danger,” panel member James N. Kvale, M.D., a professor in the department of family and community medicine at the University of Texas, San Antonio, said in an interview. “It loses effectiveness as a sleep aid after 7 days, and its real value for the chronically ill person is to be questioned.”

Chronic sleep loss is a public health problem associated with impaired psychomotor and cognitive function, and may contribute to the risk of falls in older adults, the panelists wrote in a draft consensus statement.

In addition, millions of Americans attempt to treat their sleep problems for prolonged periods of time with untested or off-label products including alcohol and antihistamines, despite a lack of evidence for their effectiveness.

Doctors can start by advising sleepless patients to consider environmental factors, including temperature, light, and sound in the bedroom. If problems persist, doctors should consider referring patients for cognitive-behavioral therapy before prescribing medications, Dr. Kvale said. Given the lack of evidence to support even the approved drug treatments for long-term use, it's important to explore nonpharmaceutical ways to manage sleep problems, he explained.

Cognitive-behavioral therapy (CBT) has proved successful for managing insomnia in randomized, controlled trials. Use of CBT involves training in relaxation, controlling external stimuli, and targeting anxiety-inducing beliefs about sleep and sleep loss. But few clinicians are experts in treating chronic insomnia with CBT, and these techniques are not widely used, the panelists noted.

Although CBT and benzodiazepine receptor agonists have shown benefits in patients with chronic insomnia, additional research is needed to compare the various treatments with each other, and to determine the effectiveness of the treatments across different populations.

The hormone melatonin and the herb valerian have been used for insomnia, but neither of these substances is regulated by the FDA, and the variation in content among preparations makes scientific comparison difficult.

Other alternative treatments for insomnia include light therapy, acupuncture, yoga, and tai chi, but none of these have been sufficiently evaluated, the panel said in the draft statement.

To close the gaps in knowledge, the panel recommended that future studies be randomized, controlled trials comparing at least two effective or promising treatments, including drugs, CBT, and combination therapies.

Understudied features of chronic insomnia include its effects on daytime functioning that prevent people from engaging in a productive and enjoyable work and social life, Dr. DeRubeis added.

Little is known about the incidence of chronic insomnia because it can be difficult to identify as a distinct problem, as opposed to a side effect of other conditions or medications. For example, a middle-aged woman with arthritis may have trouble sleeping, but she talks to her doctor about her arthritis without mentioning insomnia. Population-based studies suggest that about 30% of the general population complain of sleep problems, the panelists noted.

Female Victimization and Violence

Girls who reported being the victims of violence were 2.2 times more likely to engage in violent behavior themselves, wrote Beth E. Molnar, Sc.D., and her colleagues at Harvard University (Arch. Pediatr. Adolesc. Med. 2005;159:731–9).

In a longitudinal study, a population-based sample of 637 girls aged 9–15 years at baseline participated in three home interviews between November 1995 and January 2002. Overall, 38% of the girls reported engaging in at least one violent act during the previous 12 months at baseline; 28% reported violent behavior during the past 12 months at the first follow-up interview; and 14% reported violent behavior at the second follow-up interview.

The investigators said their results point to the key role of violent victimization in the development of aggression by girls.

Family Teasing Hits Home

When family members teased middle school girls about their appearance, the teasing had a significant impact on the girls' dissatisfaction with their bodies, said Helene Keery, Ph.D., of the Eating Disorders Institute at Methodist Hospital, St. Louis Park, Minn., and her colleagues.

The study included self-reported data from 372 girls, mean age 12.6 years (J. Adolesc. Health 2005;37:120–7). Overall, 23% of the girls reported that a parent teased them about their appearance, and 12% reported parental teasing about being overweight. Fathers were more likely than mothers to tease about appearance (19% vs. 13%) and about being overweight (10% vs. 6%). Paternal teasing was a significant predictor of body dissatisfaction, eating restriction, bulimic behavior, low self-esteem, and depression; maternal teasing was a significant predictor of depression.

Quest for Muscles and Steroid Use

Both boys and girls who reported a desire to look like celebrities in magazines were significantly more likely to use products to enhance their physiques, reported Alison E. Field, Sc.D., of Harvard University, and her colleagues.

In a cross-sectional study of 6,212 girls and 4,237 boys aged 12–18 years, 8% of girls and 12% of boys reported using products to enhance appearance or strength. Overall, about 30% of both boys and girls reported that they frequently thought about wanting more muscle tone and definition (Pediatrics 2005;116:214–20).

After adjustment for confounding variables, boys who read men's magazines were significantly more likely to use products such as protein powder or creatine at least weekly, compared with their peers who did not read such magazines. Girls who were trying to look like female celebrities were significantly more likely to use appearance-enhancing products than their peers who were not trying to look like celebrities, independent of efforts to gain or lose weight.

Early Warning Signs in Boys?

Conduct disorder symptoms in 8-year-old boys were independent predictors of substance abuse, antisocial personality, and psychotic disorders in adulthood, said Andre Sourander, M.D., of Turku (Finland) University Hospital, and his associates.

The 10- to 15-year follow-up study included data on 2,712 males who had completed the Children's Depression Inventory when they were 8 years old (J. Am Acad. Child Adolesc. Psychiatry 2005;44:756–67). Their teachers and parents also completed questionnaires.

Overall, 283 (10.4%) of the men had a psychiatric disorder based on follow-up data in early adulthood. Given these findings, mental health care professionals would do well to increase efforts to improve prevention, early identification, and treatment efficacy, the investigators said.

ADHD and Moderate Mental Retardation

Risperidone was associated with a greater reduction of attention-deficit hyperactivity disorder symptoms compared with methylphenidate in children with moderate mental retardation, said Alceu Gomes Correia Filho, M.D., of the Federal University of Rio Grande do Sul, Brazil, and colleagues.

By the end point of the 4-week, single-blind study, sponsored in part by Novartis and Janssen-Cilag, 24 children and adolescents aged 6–16 years had received a mean final dose of 25 mg/day of methylphenidate and 21 had received a mean final dose of 2.9 mg/day of risperidone (Risperdal).

Efficacy in both groups improved as dosage increased during the course of the study, but risperidone was associated with greater efficacy on the overall SNAP-IV Total scores. A significant weight gain of 1.01 kg was seen in the risperidone group; a mean weight loss of 0.53 kg was seen in the methylphenidate group.

Side effects profiles in both groups were similar to those found in children and adolescents with IQ levels in the normal range who were taking these medications for attention-deficit hyperactivity disorder.

Female Victimization and Violence

Girls who reported being the victims of violence were 2.2 times more likely to engage in violent behavior themselves, wrote Beth E. Molnar, Sc.D., and her colleagues at Harvard University (Arch. Pediatr. Adolesc. Med. 2005;159:731–9).

In a longitudinal study, a population-based sample of 637 girls aged 9–15 years at baseline participated in three home interviews between November 1995 and January 2002. Overall, 38% of the girls reported engaging in at least one violent act during the previous 12 months at baseline; 28% reported violent behavior during the past 12 months at the first follow-up interview; and 14% reported violent behavior at the second follow-up interview.

The investigators said their results point to the key role of violent victimization in the development of aggression by girls.

Family Teasing Hits Home

When family members teased middle school girls about their appearance, the teasing had a significant impact on the girls' dissatisfaction with their bodies, said Helene Keery, Ph.D., of the Eating Disorders Institute at Methodist Hospital, St. Louis Park, Minn., and her colleagues.

The study included self-reported data from 372 girls, mean age 12.6 years (J. Adolesc. Health 2005;37:120–7). Overall, 23% of the girls reported that a parent teased them about their appearance, and 12% reported parental teasing about being overweight. Fathers were more likely than mothers to tease about appearance (19% vs. 13%) and about being overweight (10% vs. 6%). Paternal teasing was a significant predictor of body dissatisfaction, eating restriction, bulimic behavior, low self-esteem, and depression; maternal teasing was a significant predictor of depression.

Quest for Muscles and Steroid Use

Both boys and girls who reported a desire to look like celebrities in magazines were significantly more likely to use products to enhance their physiques, reported Alison E. Field, Sc.D., of Harvard University, and her colleagues.

In a cross-sectional study of 6,212 girls and 4,237 boys aged 12–18 years, 8% of girls and 12% of boys reported using products to enhance appearance or strength. Overall, about 30% of both boys and girls reported that they frequently thought about wanting more muscle tone and definition (Pediatrics 2005;116:214–20).

After adjustment for confounding variables, boys who read men's magazines were significantly more likely to use products such as protein powder or creatine at least weekly, compared with their peers who did not read such magazines. Girls who were trying to look like female celebrities were significantly more likely to use appearance-enhancing products than their peers who were not trying to look like celebrities, independent of efforts to gain or lose weight.

Early Warning Signs in Boys?

Conduct disorder symptoms in 8-year-old boys were independent predictors of substance abuse, antisocial personality, and psychotic disorders in adulthood, said Andre Sourander, M.D., of Turku (Finland) University Hospital, and his associates.

The 10- to 15-year follow-up study included data on 2,712 males who had completed the Children's Depression Inventory when they were 8 years old (J. Am Acad. Child Adolesc. Psychiatry 2005;44:756–67). Their teachers and parents also completed questionnaires.

Overall, 283 (10.4%) of the men had a psychiatric disorder based on follow-up data in early adulthood. Given these findings, mental health care professionals would do well to increase efforts to improve prevention, early identification, and treatment efficacy, the investigators said.

ADHD and Moderate Mental Retardation

Risperidone was associated with a greater reduction of attention-deficit hyperactivity disorder symptoms compared with methylphenidate in children with moderate mental retardation, said Alceu Gomes Correia Filho, M.D., of the Federal University of Rio Grande do Sul, Brazil, and colleagues.

By the end point of the 4-week, single-blind study, sponsored in part by Novartis and Janssen-Cilag, 24 children and adolescents aged 6–16 years had received a mean final dose of 25 mg/day of methylphenidate and 21 had received a mean final dose of 2.9 mg/day of risperidone (Risperdal).

Efficacy in both groups improved as dosage increased during the course of the study, but risperidone was associated with greater efficacy on the overall SNAP-IV Total scores. A significant weight gain of 1.01 kg was seen in the risperidone group; a mean weight loss of 0.53 kg was seen in the methylphenidate group.

Side effects profiles in both groups were similar to those found in children and adolescents with IQ levels in the normal range who were taking these medications for attention-deficit hyperactivity disorder.

Female Victimization and Violence

Girls who reported being the victims of violence were 2.2 times more likely to engage in violent behavior themselves, wrote Beth E. Molnar, Sc.D., and her colleagues at Harvard University (Arch. Pediatr. Adolesc. Med. 2005;159:731–9).

In a longitudinal study, a population-based sample of 637 girls aged 9–15 years at baseline participated in three home interviews between November 1995 and January 2002. Overall, 38% of the girls reported engaging in at least one violent act during the previous 12 months at baseline; 28% reported violent behavior during the past 12 months at the first follow-up interview; and 14% reported violent behavior at the second follow-up interview.

The investigators said their results point to the key role of violent victimization in the development of aggression by girls.

Family Teasing Hits Home

When family members teased middle school girls about their appearance, the teasing had a significant impact on the girls' dissatisfaction with their bodies, said Helene Keery, Ph.D., of the Eating Disorders Institute at Methodist Hospital, St. Louis Park, Minn., and her colleagues.

The study included self-reported data from 372 girls, mean age 12.6 years (J. Adolesc. Health 2005;37:120–7). Overall, 23% of the girls reported that a parent teased them about their appearance, and 12% reported parental teasing about being overweight. Fathers were more likely than mothers to tease about appearance (19% vs. 13%) and about being overweight (10% vs. 6%). Paternal teasing was a significant predictor of body dissatisfaction, eating restriction, bulimic behavior, low self-esteem, and depression; maternal teasing was a significant predictor of depression.

Quest for Muscles and Steroid Use

Both boys and girls who reported a desire to look like celebrities in magazines were significantly more likely to use products to enhance their physiques, reported Alison E. Field, Sc.D., of Harvard University, and her colleagues.

In a cross-sectional study of 6,212 girls and 4,237 boys aged 12–18 years, 8% of girls and 12% of boys reported using products to enhance appearance or strength. Overall, about 30% of both boys and girls reported that they frequently thought about wanting more muscle tone and definition (Pediatrics 2005;116:214–20).

After adjustment for confounding variables, boys who read men's magazines were significantly more likely to use products such as protein powder or creatine at least weekly, compared with their peers who did not read such magazines. Girls who were trying to look like female celebrities were significantly more likely to use appearance-enhancing products than their peers who were not trying to look like celebrities, independent of efforts to gain or lose weight.

Early Warning Signs in Boys?

Conduct disorder symptoms in 8-year-old boys were independent predictors of substance abuse, antisocial personality, and psychotic disorders in adulthood, said Andre Sourander, M.D., of Turku (Finland) University Hospital, and his associates.

The 10- to 15-year follow-up study included data on 2,712 males who had completed the Children's Depression Inventory when they were 8 years old (J. Am Acad. Child Adolesc. Psychiatry 2005;44:756–67). Their teachers and parents also completed questionnaires.

Overall, 283 (10.4%) of the men had a psychiatric disorder based on follow-up data in early adulthood. Given these findings, mental health care professionals would do well to increase efforts to improve prevention, early identification, and treatment efficacy, the investigators said.

ADHD and Moderate Mental Retardation

Risperidone was associated with a greater reduction of attention-deficit hyperactivity disorder symptoms compared with methylphenidate in children with moderate mental retardation, said Alceu Gomes Correia Filho, M.D., of the Federal University of Rio Grande do Sul, Brazil, and colleagues.

By the end point of the 4-week, single-blind study, sponsored in part by Novartis and Janssen-Cilag, 24 children and adolescents aged 6–16 years had received a mean final dose of 25 mg/day of methylphenidate and 21 had received a mean final dose of 2.9 mg/day of risperidone (Risperdal).

Efficacy in both groups improved as dosage increased during the course of the study, but risperidone was associated with greater efficacy on the overall SNAP-IV Total scores. A significant weight gain of 1.01 kg was seen in the risperidone group; a mean weight loss of 0.53 kg was seen in the methylphenidate group.

Side effects profiles in both groups were similar to those found in children and adolescents with IQ levels in the normal range who were taking these medications for attention-deficit hyperactivity disorder.

WASHINGTON — “The art and science of behavior change asks physicians to accept delayed gratification,” David Katz, M.D., said at the annual meeting of the American College of Preventive Medicine.

Promoting behavior change in a clinical setting is a multidisciplinary task. Time constraints are a major concern, and overworked physicians spend most of their time on problems with immediate solutions, such as treating the infection or managing an acute injury, said Dr. Katz, a nutrition and preventive medicine specialist at Yale University, New Haven.

That said, physicians can experiment with office-based strategies including exam room posters, preappointment questionnaires, and the use of a dedicated staff member to provide in-depth counseling on prevention, according to several physicians and behavioral experts who spoke at a workshop at the meeting.

Although primary care physicians can initiate conversations about preventive medicine, it isn't reasonable for them to be completely up to date on what communities offer as support programs for increasing physical activity, losing weight, or quitting smoking, said Karen Eden, Ph.D., of Oregon Health and Science University, Portland.

But a nurse or other staff member can be trained to keep track of local resources, and to provide information and encouragement to a patient who expresses interest in finding out about a local Weight Watchers or a walking club.

Alternatively, a patient may be referred to someone in the community or in the medical facility, who serves as a contact person for all the patients in a medical practice. For example, Dr. Eden mentioned a health system in Portland, Ore., that uses a dedicated health educator.

Larry Dickey, M.D., of the California Department of Health Services, shared the Staying Healthy Assessment, a 20-item questionnaire developed by his department that is now standard for Medicaid patients in California. (See box.) The questionnaire is either mailed to the patient prior to the visit or given in the waiting room.

Pilot studies with the questionnaires show that they were well received by patients. Use of the questionnaires triggered doctors to provide brief preventive medicine counseling, but formal evaluations are pending. To view the questionnaires for all age groups in PDF form, visit www.dhs.ca.gov/ps/ocpm/html/staying%20healthy.htm

Dr. Scott Gee, a pediatrician who serves as director of prevention and health information at Northern California Kaiser Permanente, reported success with exam room posters and computer-generated office visit reminders.

His exam room posters, designed by Kaiser Permanente, include such topics as “How ready are you to eat more vegetables?” on a scale of 1–10; how much TV children watch and where; and what types of activities equal moderate exercise.

“I was initially skeptical of the exam room posters,” he said. “But the patients actually look at them, and they are arguing about it when you come into the exam room, especially about getting the TV out of the bedroom.”

In addition, Dr. Gee's Kaiser facility, the Pleasanton Pediatrics Group in Livermore, Calif., uses computer-generated office visit reminders that include “preventive health prompts” for tests that are due, such as blood pressure checks and childhood immunizations.

When a Kaiser patient comes in, he or she receives a printout that shows what services, if any, they need at that time, Dr. Gee explained. The printout is risk adjusted, with the immediate items at the top of the list, and upcoming tests or immunizations listed further down. “This has had a huge impact on compliance,” he said. Mothers have reaped the greatest benefits, since they have to manage their children's care as well as their own, he noted.

In the end, preventive medicine must still battle for time in an office visit, despite the best laid plans of primary care physicians, Dr. Gee acknowledged. “We want physicians to focus on behavior, but we don't want them to forget about the other things.”

Play 20 Questions About Health

The following questions are excerpted from a questionnaire given to all Medicaid patients in California, with answer choices of “yes,” “no,” or “skip.”

Do you receive health care from anyone besides a medical doctor, such as an acupuncturist, herbalist, curandero, or other healer?

Do you see the dentist at least once a year?

Do you drink milk or eat yogurt or cheese at least three times each day?

Do you eat at least five servings of fruits or vegetables each day?

Do you try to limit the amount of fried or fast foods that you eat?

Do you exercise or do moderate physical activity such as walking or gardening 5 days a week?

Do you think you need to lose or gain weight?

Do you often feel sad, down, or hopeless?

Do you have friends or family members who smoke in your house?

Do you often spend time outdoors without sunscreen or other protection such as a hat or shirt?

Do you smoke cigarettes or cigars or use any other kinds of tobacco?

Do you use any drugs or medicines to go to sleep, relax, calm down, feel better, or lose weight?

Do you often have more than two drinks containing alcohol in 1 day?

Do you think you or your partner could be pregnant?

Do you think you or your partner could have a sexually transmitted disease?

Have you or your partner(s) had sex without using birth control in the last year?

Have you or your partner(s) had sex with other people in the past year?

Have you or your partner(s) had sex without a condom in the past year?

Have you ever been forced or pressured to have sex?

Have you ever been hit, slapped, kicked, or physically hurt by someone?

Do you have other questions or concerns about your health? (Please identify.)

Source: State of California Office of Clinical Preventive Medicine

WASHINGTON — “The art and science of behavior change asks physicians to accept delayed gratification,” David Katz, M.D., said at the annual meeting of the American College of Preventive Medicine.

Promoting behavior change in a clinical setting is a multidisciplinary task. Time constraints are a major concern, and overworked physicians spend most of their time on problems with immediate solutions, such as treating the infection or managing an acute injury, said Dr. Katz, a nutrition and preventive medicine specialist at Yale University, New Haven.

That said, physicians can experiment with office-based strategies including exam room posters, preappointment questionnaires, and the use of a dedicated staff member to provide in-depth counseling on prevention, according to several physicians and behavioral experts who spoke at a workshop at the meeting.

Although primary care physicians can initiate conversations about preventive medicine, it isn't reasonable for them to be completely up to date on what communities offer as support programs for increasing physical activity, losing weight, or quitting smoking, said Karen Eden, Ph.D., of Oregon Health and Science University, Portland.

But a nurse or other staff member can be trained to keep track of local resources, and to provide information and encouragement to a patient who expresses interest in finding out about a local Weight Watchers or a walking club.

Alternatively, a patient may be referred to someone in the community or in the medical facility, who serves as a contact person for all the patients in a medical practice. For example, Dr. Eden mentioned a health system in Portland, Ore., that uses a dedicated health educator.

Larry Dickey, M.D., of the California Department of Health Services, shared the Staying Healthy Assessment, a 20-item questionnaire developed by his department that is now standard for Medicaid patients in California. (See box.) The questionnaire is either mailed to the patient prior to the visit or given in the waiting room.

Pilot studies with the questionnaires show that they were well received by patients. Use of the questionnaires triggered doctors to provide brief preventive medicine counseling, but formal evaluations are pending. To view the questionnaires for all age groups in PDF form, visit www.dhs.ca.gov/ps/ocpm/html/staying%20healthy.htm

Dr. Scott Gee, a pediatrician who serves as director of prevention and health information at Northern California Kaiser Permanente, reported success with exam room posters and computer-generated office visit reminders.

His exam room posters, designed by Kaiser Permanente, include such topics as “How ready are you to eat more vegetables?” on a scale of 1–10; how much TV children watch and where; and what types of activities equal moderate exercise.

“I was initially skeptical of the exam room posters,” he said. “But the patients actually look at them, and they are arguing about it when you come into the exam room, especially about getting the TV out of the bedroom.”

In addition, Dr. Gee's Kaiser facility, the Pleasanton Pediatrics Group in Livermore, Calif., uses computer-generated office visit reminders that include “preventive health prompts” for tests that are due, such as blood pressure checks and childhood immunizations.

When a Kaiser patient comes in, he or she receives a printout that shows what services, if any, they need at that time, Dr. Gee explained. The printout is risk adjusted, with the immediate items at the top of the list, and upcoming tests or immunizations listed further down. “This has had a huge impact on compliance,” he said. Mothers have reaped the greatest benefits, since they have to manage their children's care as well as their own, he noted.

In the end, preventive medicine must still battle for time in an office visit, despite the best laid plans of primary care physicians, Dr. Gee acknowledged. “We want physicians to focus on behavior, but we don't want them to forget about the other things.”

Play 20 Questions About Health

The following questions are excerpted from a questionnaire given to all Medicaid patients in California, with answer choices of “yes,” “no,” or “skip.”

Do you receive health care from anyone besides a medical doctor, such as an acupuncturist, herbalist, curandero, or other healer?

Do you see the dentist at least once a year?

Do you drink milk or eat yogurt or cheese at least three times each day?

Do you eat at least five servings of fruits or vegetables each day?

Do you try to limit the amount of fried or fast foods that you eat?

Do you exercise or do moderate physical activity such as walking or gardening 5 days a week?

Do you think you need to lose or gain weight?

Do you often feel sad, down, or hopeless?

Do you have friends or family members who smoke in your house?

Do you often spend time outdoors without sunscreen or other protection such as a hat or shirt?

Do you smoke cigarettes or cigars or use any other kinds of tobacco?

Do you use any drugs or medicines to go to sleep, relax, calm down, feel better, or lose weight?

Do you often have more than two drinks containing alcohol in 1 day?

Do you think you or your partner could be pregnant?

Do you think you or your partner could have a sexually transmitted disease?

Have you or your partner(s) had sex without using birth control in the last year?

Have you or your partner(s) had sex with other people in the past year?

Have you or your partner(s) had sex without a condom in the past year?

Have you ever been forced or pressured to have sex?

Have you ever been hit, slapped, kicked, or physically hurt by someone?

Do you have other questions or concerns about your health? (Please identify.)

Source: State of California Office of Clinical Preventive Medicine

WASHINGTON — “The art and science of behavior change asks physicians to accept delayed gratification,” David Katz, M.D., said at the annual meeting of the American College of Preventive Medicine.

Promoting behavior change in a clinical setting is a multidisciplinary task. Time constraints are a major concern, and overworked physicians spend most of their time on problems with immediate solutions, such as treating the infection or managing an acute injury, said Dr. Katz, a nutrition and preventive medicine specialist at Yale University, New Haven.

That said, physicians can experiment with office-based strategies including exam room posters, preappointment questionnaires, and the use of a dedicated staff member to provide in-depth counseling on prevention, according to several physicians and behavioral experts who spoke at a workshop at the meeting.

Although primary care physicians can initiate conversations about preventive medicine, it isn't reasonable for them to be completely up to date on what communities offer as support programs for increasing physical activity, losing weight, or quitting smoking, said Karen Eden, Ph.D., of Oregon Health and Science University, Portland.

But a nurse or other staff member can be trained to keep track of local resources, and to provide information and encouragement to a patient who expresses interest in finding out about a local Weight Watchers or a walking club.

Alternatively, a patient may be referred to someone in the community or in the medical facility, who serves as a contact person for all the patients in a medical practice. For example, Dr. Eden mentioned a health system in Portland, Ore., that uses a dedicated health educator.

Larry Dickey, M.D., of the California Department of Health Services, shared the Staying Healthy Assessment, a 20-item questionnaire developed by his department that is now standard for Medicaid patients in California. (See box.) The questionnaire is either mailed to the patient prior to the visit or given in the waiting room.

Pilot studies with the questionnaires show that they were well received by patients. Use of the questionnaires triggered doctors to provide brief preventive medicine counseling, but formal evaluations are pending. To view the questionnaires for all age groups in PDF form, visit www.dhs.ca.gov/ps/ocpm/html/staying%20healthy.htm

Dr. Scott Gee, a pediatrician who serves as director of prevention and health information at Northern California Kaiser Permanente, reported success with exam room posters and computer-generated office visit reminders.

His exam room posters, designed by Kaiser Permanente, include such topics as “How ready are you to eat more vegetables?” on a scale of 1–10; how much TV children watch and where; and what types of activities equal moderate exercise.

“I was initially skeptical of the exam room posters,” he said. “But the patients actually look at them, and they are arguing about it when you come into the exam room, especially about getting the TV out of the bedroom.”

In addition, Dr. Gee's Kaiser facility, the Pleasanton Pediatrics Group in Livermore, Calif., uses computer-generated office visit reminders that include “preventive health prompts” for tests that are due, such as blood pressure checks and childhood immunizations.

When a Kaiser patient comes in, he or she receives a printout that shows what services, if any, they need at that time, Dr. Gee explained. The printout is risk adjusted, with the immediate items at the top of the list, and upcoming tests or immunizations listed further down. “This has had a huge impact on compliance,” he said. Mothers have reaped the greatest benefits, since they have to manage their children's care as well as their own, he noted.

In the end, preventive medicine must still battle for time in an office visit, despite the best laid plans of primary care physicians, Dr. Gee acknowledged. “We want physicians to focus on behavior, but we don't want them to forget about the other things.”

Play 20 Questions About Health

The following questions are excerpted from a questionnaire given to all Medicaid patients in California, with answer choices of “yes,” “no,” or “skip.”

Do you receive health care from anyone besides a medical doctor, such as an acupuncturist, herbalist, curandero, or other healer?

Do you see the dentist at least once a year?

Do you drink milk or eat yogurt or cheese at least three times each day?

Do you eat at least five servings of fruits or vegetables each day?

Do you try to limit the amount of fried or fast foods that you eat?

Do you exercise or do moderate physical activity such as walking or gardening 5 days a week?

Do you think you need to lose or gain weight?

Do you often feel sad, down, or hopeless?

Do you have friends or family members who smoke in your house?

Do you often spend time outdoors without sunscreen or other protection such as a hat or shirt?

Do you smoke cigarettes or cigars or use any other kinds of tobacco?

Do you use any drugs or medicines to go to sleep, relax, calm down, feel better, or lose weight?

Do you often have more than two drinks containing alcohol in 1 day?

Do you think you or your partner could be pregnant?

Do you think you or your partner could have a sexually transmitted disease?

Have you or your partner(s) had sex without using birth control in the last year?

Have you or your partner(s) had sex with other people in the past year?

Have you or your partner(s) had sex without a condom in the past year?

Have you ever been forced or pressured to have sex?

Have you ever been hit, slapped, kicked, or physically hurt by someone?

Do you have other questions or concerns about your health? (Please identify.)

Source: State of California Office of Clinical Preventive Medicine

BETHESDA, MD. — Evidence suggests that multidrug-resistant gram-negative organisms contribute to worse patient outcomes if patients are not severely ill, Arjun Srinivasan, M.D., said at an annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

“When you factor severity of illness, extremely severe illness overrides the impact of multidrug resistance on mortality,” Dr. Srinivasan said in an interview.

In some studies of patients with gram-negative infections, multidrug resistance was not associated with significantly higher all-cause mortality. But many outcome studies in this research area have not differentiated between colonized vs. infected patients, or controlled for severity of illness, noted Dr. Srinivasan, a medical epidemiologist in the division of health care quality promotion at the Centers for Disease Control and Prevention in Atlanta.

Dr. Srinivasan and his colleagues conducted an outcome study of 96 patients with multidrug-resistant Acinetobacter in 2004. The researchers used validated definitions to separate colonized and infected patients and used Acute Physiology and Chronic Health Evaluation (APACHE) III scores and the Charleston comorbidity index to assess severity of illness. They compared the infected patients with two different control groups, one group of 90 patients with susceptible Acinetobacter infections and one group of 89 patients without Acinetobacter infections.

The resulting patient characteristics were “exactly what we had expected from the beginning,” Dr. Srinivasan said.

Patients who were infected with multidrug-resistant Acinetobacter were significantly sicker than were patients in the two control groups. They also had higher APACHE III scores, which indicated that they were more severely ill, and more comorbidities compared with both control groups.

In a univariate analysis, the patients with multidrug-resistant Acinetobacter had a significantly higher rate of mortality (27.1%) compared with both the susceptible Acinetobacter group (16.7%) and the no Acinetobacter group (12.4%). In addition, the mean length of hospital stay was significantly higher in the multidrug resistant group (27 days) compared with the other two groups (20 days and 19 days, respectively).

To assess the independent impact of resistance, the researchers used a multivariate analysis to control for the effect of severity of illness. Patients with multidrug-resistant Acinetobacter were twice as likely as were the controls to have a longer-than-average hospital stay and were 2–3 times more likely to have a longer-than-average ICU stay.

But the multivariate model showed no significant difference in mortality among the groups. The findings emphasize that drug resistance cannot overcome the impact of severity on mortality, although resistance was associated with a longer hospital stay.

Assessment of the role of illness severity continues to challenge researchers in outcome studies of drug resistance, Dr. Srinivasan said.

“The nature of the epidemiology of resistant gram-negative pathogens is a dynamic one. It's not steady, and it is going to continue to evolve,” Dr. Srinivasan commented. “The resistant pathogens are becoming a bigger and bigger problem, and our therapeutic options simply are not keeping pace.”

Five risk factors for infection or colonization with gram-negative organisms have surfaced frequently in studies: severity of illness, prolonged mechanical ventilation, prior antimicrobial exposures, prolonged hospital or ICU stay, and exposure to invasive medical devices.

Klebsiella pneumoniae carbapenemases, or KPCs, are perhaps the next big thing in gram-negative resistance. They cleave carbapenems, effectively conferring moderate to high levels of drug resistance to all drugs in the carbapenem class.

BETHESDA, MD. — Evidence suggests that multidrug-resistant gram-negative organisms contribute to worse patient outcomes if patients are not severely ill, Arjun Srinivasan, M.D., said at an annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

“When you factor severity of illness, extremely severe illness overrides the impact of multidrug resistance on mortality,” Dr. Srinivasan said in an interview.

In some studies of patients with gram-negative infections, multidrug resistance was not associated with significantly higher all-cause mortality. But many outcome studies in this research area have not differentiated between colonized vs. infected patients, or controlled for severity of illness, noted Dr. Srinivasan, a medical epidemiologist in the division of health care quality promotion at the Centers for Disease Control and Prevention in Atlanta.

Dr. Srinivasan and his colleagues conducted an outcome study of 96 patients with multidrug-resistant Acinetobacter in 2004. The researchers used validated definitions to separate colonized and infected patients and used Acute Physiology and Chronic Health Evaluation (APACHE) III scores and the Charleston comorbidity index to assess severity of illness. They compared the infected patients with two different control groups, one group of 90 patients with susceptible Acinetobacter infections and one group of 89 patients without Acinetobacter infections.

The resulting patient characteristics were “exactly what we had expected from the beginning,” Dr. Srinivasan said.

Patients who were infected with multidrug-resistant Acinetobacter were significantly sicker than were patients in the two control groups. They also had higher APACHE III scores, which indicated that they were more severely ill, and more comorbidities compared with both control groups.

In a univariate analysis, the patients with multidrug-resistant Acinetobacter had a significantly higher rate of mortality (27.1%) compared with both the susceptible Acinetobacter group (16.7%) and the no Acinetobacter group (12.4%). In addition, the mean length of hospital stay was significantly higher in the multidrug resistant group (27 days) compared with the other two groups (20 days and 19 days, respectively).

To assess the independent impact of resistance, the researchers used a multivariate analysis to control for the effect of severity of illness. Patients with multidrug-resistant Acinetobacter were twice as likely as were the controls to have a longer-than-average hospital stay and were 2–3 times more likely to have a longer-than-average ICU stay.

But the multivariate model showed no significant difference in mortality among the groups. The findings emphasize that drug resistance cannot overcome the impact of severity on mortality, although resistance was associated with a longer hospital stay.

Assessment of the role of illness severity continues to challenge researchers in outcome studies of drug resistance, Dr. Srinivasan said.

“The nature of the epidemiology of resistant gram-negative pathogens is a dynamic one. It's not steady, and it is going to continue to evolve,” Dr. Srinivasan commented. “The resistant pathogens are becoming a bigger and bigger problem, and our therapeutic options simply are not keeping pace.”

Five risk factors for infection or colonization with gram-negative organisms have surfaced frequently in studies: severity of illness, prolonged mechanical ventilation, prior antimicrobial exposures, prolonged hospital or ICU stay, and exposure to invasive medical devices.

Klebsiella pneumoniae carbapenemases, or KPCs, are perhaps the next big thing in gram-negative resistance. They cleave carbapenems, effectively conferring moderate to high levels of drug resistance to all drugs in the carbapenem class.

BETHESDA, MD. — Evidence suggests that multidrug-resistant gram-negative organisms contribute to worse patient outcomes if patients are not severely ill, Arjun Srinivasan, M.D., said at an annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

“When you factor severity of illness, extremely severe illness overrides the impact of multidrug resistance on mortality,” Dr. Srinivasan said in an interview.

In some studies of patients with gram-negative infections, multidrug resistance was not associated with significantly higher all-cause mortality. But many outcome studies in this research area have not differentiated between colonized vs. infected patients, or controlled for severity of illness, noted Dr. Srinivasan, a medical epidemiologist in the division of health care quality promotion at the Centers for Disease Control and Prevention in Atlanta.

Dr. Srinivasan and his colleagues conducted an outcome study of 96 patients with multidrug-resistant Acinetobacter in 2004. The researchers used validated definitions to separate colonized and infected patients and used Acute Physiology and Chronic Health Evaluation (APACHE) III scores and the Charleston comorbidity index to assess severity of illness. They compared the infected patients with two different control groups, one group of 90 patients with susceptible Acinetobacter infections and one group of 89 patients without Acinetobacter infections.

The resulting patient characteristics were “exactly what we had expected from the beginning,” Dr. Srinivasan said.

Patients who were infected with multidrug-resistant Acinetobacter were significantly sicker than were patients in the two control groups. They also had higher APACHE III scores, which indicated that they were more severely ill, and more comorbidities compared with both control groups.

In a univariate analysis, the patients with multidrug-resistant Acinetobacter had a significantly higher rate of mortality (27.1%) compared with both the susceptible Acinetobacter group (16.7%) and the no Acinetobacter group (12.4%). In addition, the mean length of hospital stay was significantly higher in the multidrug resistant group (27 days) compared with the other two groups (20 days and 19 days, respectively).

To assess the independent impact of resistance, the researchers used a multivariate analysis to control for the effect of severity of illness. Patients with multidrug-resistant Acinetobacter were twice as likely as were the controls to have a longer-than-average hospital stay and were 2–3 times more likely to have a longer-than-average ICU stay.

But the multivariate model showed no significant difference in mortality among the groups. The findings emphasize that drug resistance cannot overcome the impact of severity on mortality, although resistance was associated with a longer hospital stay.

Assessment of the role of illness severity continues to challenge researchers in outcome studies of drug resistance, Dr. Srinivasan said.

“The nature of the epidemiology of resistant gram-negative pathogens is a dynamic one. It's not steady, and it is going to continue to evolve,” Dr. Srinivasan commented. “The resistant pathogens are becoming a bigger and bigger problem, and our therapeutic options simply are not keeping pace.”

Five risk factors for infection or colonization with gram-negative organisms have surfaced frequently in studies: severity of illness, prolonged mechanical ventilation, prior antimicrobial exposures, prolonged hospital or ICU stay, and exposure to invasive medical devices.

Klebsiella pneumoniae carbapenemases, or KPCs, are perhaps the next big thing in gram-negative resistance. They cleave carbapenems, effectively conferring moderate to high levels of drug resistance to all drugs in the carbapenem class.

WASHINGTON — The severity of vertebral fractures increases significantly in patients whose trabecular bone volume falls below the critical value of 15%, Harry K. Genant, M.D., said in his oral presentation of a poster at an international symposium sponsored by the National Osteoporosis Foundation.

Dr. Genant, a member of the Osteoporosis and Arthritis Research Group at the University of California, San Francisco, and his colleagues assessed the bone quality of 190 postmenopausal women, mean age 69 years, using radiographic data from 2D histomorphometry and 3D microCT.

The women were categorized into four groups based on varying severity of vertebral fractures, with 0 meaning “no fracture,” and 1, 2, and 3, corresponding to mild, moderate, and severe levels of fracture, respectively.

Based on the radiographic data, patients in the moderate and severe fracture groups had significantly reduced 2-dimensional trabecular bone volumes (0.15 and 0.13, respectively), compared with patients who had no fractures (0.20). On further analysis of the radiographs, the researchers found that as the severity of vertebral fractures grew worse, patients had progressively worse bone quality based on measurements including trabecular separation, trabecular number, and 3-dimensional trabecular bone volume.

These latest results are consistent with earlier findings that patients are at significantly increased risk of fracture when the trabecular bone volume falls below approximately 15%. Dr. Genant said that he has received grants and research support, as well as an honorarium, from Eli Lilly & Co.

WASHINGTON — The severity of vertebral fractures increases significantly in patients whose trabecular bone volume falls below the critical value of 15%, Harry K. Genant, M.D., said in his oral presentation of a poster at an international symposium sponsored by the National Osteoporosis Foundation.

Dr. Genant, a member of the Osteoporosis and Arthritis Research Group at the University of California, San Francisco, and his colleagues assessed the bone quality of 190 postmenopausal women, mean age 69 years, using radiographic data from 2D histomorphometry and 3D microCT.

The women were categorized into four groups based on varying severity of vertebral fractures, with 0 meaning “no fracture,” and 1, 2, and 3, corresponding to mild, moderate, and severe levels of fracture, respectively.

Based on the radiographic data, patients in the moderate and severe fracture groups had significantly reduced 2-dimensional trabecular bone volumes (0.15 and 0.13, respectively), compared with patients who had no fractures (0.20). On further analysis of the radiographs, the researchers found that as the severity of vertebral fractures grew worse, patients had progressively worse bone quality based on measurements including trabecular separation, trabecular number, and 3-dimensional trabecular bone volume.

These latest results are consistent with earlier findings that patients are at significantly increased risk of fracture when the trabecular bone volume falls below approximately 15%. Dr. Genant said that he has received grants and research support, as well as an honorarium, from Eli Lilly & Co.

WASHINGTON — The severity of vertebral fractures increases significantly in patients whose trabecular bone volume falls below the critical value of 15%, Harry K. Genant, M.D., said in his oral presentation of a poster at an international symposium sponsored by the National Osteoporosis Foundation.

Dr. Genant, a member of the Osteoporosis and Arthritis Research Group at the University of California, San Francisco, and his colleagues assessed the bone quality of 190 postmenopausal women, mean age 69 years, using radiographic data from 2D histomorphometry and 3D microCT.

The women were categorized into four groups based on varying severity of vertebral fractures, with 0 meaning “no fracture,” and 1, 2, and 3, corresponding to mild, moderate, and severe levels of fracture, respectively.

Based on the radiographic data, patients in the moderate and severe fracture groups had significantly reduced 2-dimensional trabecular bone volumes (0.15 and 0.13, respectively), compared with patients who had no fractures (0.20). On further analysis of the radiographs, the researchers found that as the severity of vertebral fractures grew worse, patients had progressively worse bone quality based on measurements including trabecular separation, trabecular number, and 3-dimensional trabecular bone volume.

These latest results are consistent with earlier findings that patients are at significantly increased risk of fracture when the trabecular bone volume falls below approximately 15%. Dr. Genant said that he has received grants and research support, as well as an honorarium, from Eli Lilly & Co.

WASHINGTON — Postmenopausal women with osteoporosis who can't tolerate oral ibandronate may welcome an intravenous option, Michael Bolognese, M.D., reported at an international symposium sponsored by the National Osteoporosis Foundation.

One-year results from the Dosing Intravenous Administration (DIVA) study, an ongoing randomized, double-blind, phase III trial, showed that rapid injections of ibandronate (Boniva) in amounts of 2 mg every 2 months or 3 mg every 3 months were more effective than the standard oral daily dose of 2.5 mg at increasing bone mineral density (BMD), Dr. Bolognese of Bethesda (Md.) Health Research and his colleagues wrote in a poster presentation of their findings.

The increases in the BMD at the lumbar spine were significantly greater for women on both the 2-mg/2-mo (5.1%) and 3-mg/3-mo (4.8%) regimens compared with the 2.5-mg daily oral dosage (3.8%). In addition, significantly more patients demonstrated increased BMD from baseline in both the lumbar spine and total hip in the 2-mg/2-mo and 3-mg/3-mo groups compared with the daily oral 2.5-mg group.

The study included 1,395 women aged 55–80 years with postmenopausal osteoporosis. In addition to their ibandronate regimens, women in all treatment groups received 500 mg of calcium and 400 IU of vitamin D daily.

The incidence of renal adverse events such as urinary incontinence, renal impairment, or nephrolithiasis, was 3% or less across all treatment arms, and there were no significant changes in serum creatinine levels in any of the patients compared with baseline. The incidence of flu-like illness was low as well—3.3%, 3.2%, and 0.6% in the 2-mg/2-mo, 3-mg/3-mo, and 2.5-mg oral groups, respectively.

In addition, the overall incidence of clinical fractures, including vertebral fractures, was 3.1%, and did not differ significantly among the three groups, although it was slightly higher in the oral group (3.7%) compared with the 2-mg/2-mo group (2.9%) and the 3-mg/3-mo group (2.8%).

Dr. Bolognese is a consultant for Eli Lilly & Co. and Procter & Gamble Co., and has received grants or research support from Aventis Pharmaceuticals Inc., Pfizer Inc., Lilly, and Wyeth.

WASHINGTON — Postmenopausal women with osteoporosis who can't tolerate oral ibandronate may welcome an intravenous option, Michael Bolognese, M.D., reported at an international symposium sponsored by the National Osteoporosis Foundation.

One-year results from the Dosing Intravenous Administration (DIVA) study, an ongoing randomized, double-blind, phase III trial, showed that rapid injections of ibandronate (Boniva) in amounts of 2 mg every 2 months or 3 mg every 3 months were more effective than the standard oral daily dose of 2.5 mg at increasing bone mineral density (BMD), Dr. Bolognese of Bethesda (Md.) Health Research and his colleagues wrote in a poster presentation of their findings.

The increases in the BMD at the lumbar spine were significantly greater for women on both the 2-mg/2-mo (5.1%) and 3-mg/3-mo (4.8%) regimens compared with the 2.5-mg daily oral dosage (3.8%). In addition, significantly more patients demonstrated increased BMD from baseline in both the lumbar spine and total hip in the 2-mg/2-mo and 3-mg/3-mo groups compared with the daily oral 2.5-mg group.

The study included 1,395 women aged 55–80 years with postmenopausal osteoporosis. In addition to their ibandronate regimens, women in all treatment groups received 500 mg of calcium and 400 IU of vitamin D daily.

The incidence of renal adverse events such as urinary incontinence, renal impairment, or nephrolithiasis, was 3% or less across all treatment arms, and there were no significant changes in serum creatinine levels in any of the patients compared with baseline. The incidence of flu-like illness was low as well—3.3%, 3.2%, and 0.6% in the 2-mg/2-mo, 3-mg/3-mo, and 2.5-mg oral groups, respectively.

In addition, the overall incidence of clinical fractures, including vertebral fractures, was 3.1%, and did not differ significantly among the three groups, although it was slightly higher in the oral group (3.7%) compared with the 2-mg/2-mo group (2.9%) and the 3-mg/3-mo group (2.8%).

Dr. Bolognese is a consultant for Eli Lilly & Co. and Procter & Gamble Co., and has received grants or research support from Aventis Pharmaceuticals Inc., Pfizer Inc., Lilly, and Wyeth.

WASHINGTON — Postmenopausal women with osteoporosis who can't tolerate oral ibandronate may welcome an intravenous option, Michael Bolognese, M.D., reported at an international symposium sponsored by the National Osteoporosis Foundation.

One-year results from the Dosing Intravenous Administration (DIVA) study, an ongoing randomized, double-blind, phase III trial, showed that rapid injections of ibandronate (Boniva) in amounts of 2 mg every 2 months or 3 mg every 3 months were more effective than the standard oral daily dose of 2.5 mg at increasing bone mineral density (BMD), Dr. Bolognese of Bethesda (Md.) Health Research and his colleagues wrote in a poster presentation of their findings.

The increases in the BMD at the lumbar spine were significantly greater for women on both the 2-mg/2-mo (5.1%) and 3-mg/3-mo (4.8%) regimens compared with the 2.5-mg daily oral dosage (3.8%). In addition, significantly more patients demonstrated increased BMD from baseline in both the lumbar spine and total hip in the 2-mg/2-mo and 3-mg/3-mo groups compared with the daily oral 2.5-mg group.

The study included 1,395 women aged 55–80 years with postmenopausal osteoporosis. In addition to their ibandronate regimens, women in all treatment groups received 500 mg of calcium and 400 IU of vitamin D daily.

The incidence of renal adverse events such as urinary incontinence, renal impairment, or nephrolithiasis, was 3% or less across all treatment arms, and there were no significant changes in serum creatinine levels in any of the patients compared with baseline. The incidence of flu-like illness was low as well—3.3%, 3.2%, and 0.6% in the 2-mg/2-mo, 3-mg/3-mo, and 2.5-mg oral groups, respectively.

In addition, the overall incidence of clinical fractures, including vertebral fractures, was 3.1%, and did not differ significantly among the three groups, although it was slightly higher in the oral group (3.7%) compared with the 2-mg/2-mo group (2.9%) and the 3-mg/3-mo group (2.8%).

Dr. Bolognese is a consultant for Eli Lilly & Co. and Procter & Gamble Co., and has received grants or research support from Aventis Pharmaceuticals Inc., Pfizer Inc., Lilly, and Wyeth.

WASHINGTON — With elderly patients taking more medications than ever, convenient bisphosphonate regimen options may help reduce the overall medication burden and improve compliance with the osteoporosis therapy, suggest findings from a recent study of prescription trends.

In an investigation of prescription data for 250,286 postmenopausal women, about 65% of those prescribed daily or weekly bisphosphonates were also prescribed one to three concomitant medications, Deborah T. Gold, Ph.D., reported in a poster presented at an international symposium sponsored by the National Osteoporosis Foundation.

What's more, 12% of the study population received four concomitant medications, 7% received five, and 17% received six or more.

On average, the women were taking more than three concomitant medications, a burden shown to increase the risk of noncompliance in elderly patients (Arthritis Rheum. 2004;15[Suppl.]:S513).

Compliance is a significant problem with bisphosphonate therapy, in part because the strict fasting and administration requirements of the osteoporosis drugs can conflict with those of other medications.

Dr. Gold of Duke University, Durham, North Carolina, and colleagues analyzed information from a HIPAA-compliant, longitudinal patient database to determine the degree of concomitant medication use among women prescribed alendronate doses of 5, 10, 35, or 70 mg, or risedronate doses of 5 or 35 mg. The women were aged 50 years and older.

Overall, the mean number of concomitant medications among women who received daily bisphosphonates increased from 3.1 in November 1999 to 4.2 in June 2004.

Among women who received weekly bisphosphonates, the burden of concomitant medications increased from 3.7 drugs in November 2000 to 3.8 in June 2004.

The number of prescribed concomitant medications increased with patient age, from 2.7 to 3.2 among women aged 50–64 years, compared with 3.2 to 4.0 among women aged 75 years and older.

The most common medications prescribed in conjunction with bisphosphonates in this study population were levothyroxine, atorvastatin, atenolol, furosemide, amlodipine, potassium chloride, hydrochlorothiazide, lisinopril, celecoxib, and simvastatin.

The investigators concluded that with greater concomitant medication burden, the convenience of bisphosphonate regimens may have a instrumental effect on adherence.

WASHINGTON — With elderly patients taking more medications than ever, convenient bisphosphonate regimen options may help reduce the overall medication burden and improve compliance with the osteoporosis therapy, suggest findings from a recent study of prescription trends.

In an investigation of prescription data for 250,286 postmenopausal women, about 65% of those prescribed daily or weekly bisphosphonates were also prescribed one to three concomitant medications, Deborah T. Gold, Ph.D., reported in a poster presented at an international symposium sponsored by the National Osteoporosis Foundation.

What's more, 12% of the study population received four concomitant medications, 7% received five, and 17% received six or more.

On average, the women were taking more than three concomitant medications, a burden shown to increase the risk of noncompliance in elderly patients (Arthritis Rheum. 2004;15[Suppl.]:S513).

Compliance is a significant problem with bisphosphonate therapy, in part because the strict fasting and administration requirements of the osteoporosis drugs can conflict with those of other medications.

Dr. Gold of Duke University, Durham, North Carolina, and colleagues analyzed information from a HIPAA-compliant, longitudinal patient database to determine the degree of concomitant medication use among women prescribed alendronate doses of 5, 10, 35, or 70 mg, or risedronate doses of 5 or 35 mg. The women were aged 50 years and older.

Overall, the mean number of concomitant medications among women who received daily bisphosphonates increased from 3.1 in November 1999 to 4.2 in June 2004.

Among women who received weekly bisphosphonates, the burden of concomitant medications increased from 3.7 drugs in November 2000 to 3.8 in June 2004.

The number of prescribed concomitant medications increased with patient age, from 2.7 to 3.2 among women aged 50–64 years, compared with 3.2 to 4.0 among women aged 75 years and older.

The most common medications prescribed in conjunction with bisphosphonates in this study population were levothyroxine, atorvastatin, atenolol, furosemide, amlodipine, potassium chloride, hydrochlorothiazide, lisinopril, celecoxib, and simvastatin.

The investigators concluded that with greater concomitant medication burden, the convenience of bisphosphonate regimens may have a instrumental effect on adherence.

WASHINGTON — With elderly patients taking more medications than ever, convenient bisphosphonate regimen options may help reduce the overall medication burden and improve compliance with the osteoporosis therapy, suggest findings from a recent study of prescription trends.

In an investigation of prescription data for 250,286 postmenopausal women, about 65% of those prescribed daily or weekly bisphosphonates were also prescribed one to three concomitant medications, Deborah T. Gold, Ph.D., reported in a poster presented at an international symposium sponsored by the National Osteoporosis Foundation.

What's more, 12% of the study population received four concomitant medications, 7% received five, and 17% received six or more.

On average, the women were taking more than three concomitant medications, a burden shown to increase the risk of noncompliance in elderly patients (Arthritis Rheum. 2004;15[Suppl.]:S513).

Compliance is a significant problem with bisphosphonate therapy, in part because the strict fasting and administration requirements of the osteoporosis drugs can conflict with those of other medications.

Dr. Gold of Duke University, Durham, North Carolina, and colleagues analyzed information from a HIPAA-compliant, longitudinal patient database to determine the degree of concomitant medication use among women prescribed alendronate doses of 5, 10, 35, or 70 mg, or risedronate doses of 5 or 35 mg. The women were aged 50 years and older.

Overall, the mean number of concomitant medications among women who received daily bisphosphonates increased from 3.1 in November 1999 to 4.2 in June 2004.

Among women who received weekly bisphosphonates, the burden of concomitant medications increased from 3.7 drugs in November 2000 to 3.8 in June 2004.

The number of prescribed concomitant medications increased with patient age, from 2.7 to 3.2 among women aged 50–64 years, compared with 3.2 to 4.0 among women aged 75 years and older.

The most common medications prescribed in conjunction with bisphosphonates in this study population were levothyroxine, atorvastatin, atenolol, furosemide, amlodipine, potassium chloride, hydrochlorothiazide, lisinopril, celecoxib, and simvastatin.

The investigators concluded that with greater concomitant medication burden, the convenience of bisphosphonate regimens may have a instrumental effect on adherence.