Heidi Splete

A quadrivalent measles, mumps, rubella, and varicella vaccine was well-tolerated and effective in children aged 12–23 months, according to data from a pair of studies conducted by Henry Shinefield, M.D., of the University of San Francisco, California, and his colleagues.

The studies, which were sponsored in part by Merck & Co., indicated that either a one- or two-dose vaccine containing antibodies to all four diseases was similar in safety and efficacy to a combination of the previous measles, mumps, and rubella vaccine (MMR II) and a separate dose of the varicella virus vaccine (Varivax).

In a randomized, multicenter study, 480 healthy children received either MMR II plus Varivax (VV) or the quadrivalent vaccine (MMRV) plus a placebo. Children in the MMRV group had significantly higher rates of elevated temperature from 5–12 days after vaccination, compared with the MMR-plus-VV group (28% vs. 19%), but the fevers were generally mild and averaged less than 2 days' duration. Adverse events were not significantly different between the two groups at 42 days after vaccination (Pediatr. Infect. Dis. J. 2005;24:665–9).

A measles-like rash was the most common adverse event in both groups; the rashes averaged 6 days' duration and were mild to moderate. The incidence of pain and redness at the injection sites and the proportion of children with at least one adverse event were similar between the groups.

In a separate study of 1,559 healthy children, antibody responses from the MMRV were equal to those from a combination of MMR plus VV (Pediatr. Infect. Dis. J. 2005;24:670–5).

The children were randomized to one of four treatment groups and received a quadrivalent vaccine with a low, middle, or high varicella-zoster virus (VZV) potency or a dose of MMR plus VV. Those in the quadrivalent groups received a second MMRV injection 90 days after the first injection.

The antibody rates in all three MMRV groups after the second injection were at least as high as the MMR-plus-VV group, and most of the children who had not responded to the VZV in the first injection did so after the second injection.

After the second injection, the observed response rates for measles in the low, middle, and high potency groups were 99.4%, 99.7%, and 100%, respectively, compared with 99.7%, in the MMR-plus-VV group. The observed response rates for varicella in the low, middle, and high potency groups were 99.7%, 100%, and 99%, respectively, compared with 93.1% in the MMR-plus-VV group. Similar response rates to those of measles and varicella were seen in the low, middle and high potency groups for mumps and rubella.

The incidence of measles-like rashes was similar in all groups, and the incidence of both varicella-like and measles-like rashes was lower in the MMRV group after the second MMRV injection, compared with the MMR-plus-VV group.

Approximately 70% of the children in any of the MMRV groups as well as the combination group reported at least one systemic adverse event, including fever, irritability, and upper respiratory tract infection. A febrile seizure suffered by a child in the middle potency group was the only severe adverse event thought to be vaccine related.

Febrile seizures might indeed be a cause for concern when using the quadrivalent vaccine, said Margaret Rennels, M.D., the American Academy of Pediatrics' coliaison to the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

But on the whole, the quadrivalent vaccine is a public health achievement, she said in an interview.

“Many of us believe that we should be giving a second dose of varicella and this [quadrivalent vaccine] would make that very easy,” said Dr. Rennels, clinical chief of infectious diseases at the University of Maryland, Baltimore.

A quadrivalent measles, mumps, rubella, and varicella vaccine was well-tolerated and effective in children aged 12–23 months, according to data from a pair of studies conducted by Henry Shinefield, M.D., of the University of San Francisco, California, and his colleagues.

The studies, which were sponsored in part by Merck & Co., indicated that either a one- or two-dose vaccine containing antibodies to all four diseases was similar in safety and efficacy to a combination of the previous measles, mumps, and rubella vaccine (MMR II) and a separate dose of the varicella virus vaccine (Varivax).

In a randomized, multicenter study, 480 healthy children received either MMR II plus Varivax (VV) or the quadrivalent vaccine (MMRV) plus a placebo. Children in the MMRV group had significantly higher rates of elevated temperature from 5–12 days after vaccination, compared with the MMR-plus-VV group (28% vs. 19%), but the fevers were generally mild and averaged less than 2 days' duration. Adverse events were not significantly different between the two groups at 42 days after vaccination (Pediatr. Infect. Dis. J. 2005;24:665–9).

A measles-like rash was the most common adverse event in both groups; the rashes averaged 6 days' duration and were mild to moderate. The incidence of pain and redness at the injection sites and the proportion of children with at least one adverse event were similar between the groups.

In a separate study of 1,559 healthy children, antibody responses from the MMRV were equal to those from a combination of MMR plus VV (Pediatr. Infect. Dis. J. 2005;24:670–5).

The children were randomized to one of four treatment groups and received a quadrivalent vaccine with a low, middle, or high varicella-zoster virus (VZV) potency or a dose of MMR plus VV. Those in the quadrivalent groups received a second MMRV injection 90 days after the first injection.

The antibody rates in all three MMRV groups after the second injection were at least as high as the MMR-plus-VV group, and most of the children who had not responded to the VZV in the first injection did so after the second injection.

After the second injection, the observed response rates for measles in the low, middle, and high potency groups were 99.4%, 99.7%, and 100%, respectively, compared with 99.7%, in the MMR-plus-VV group. The observed response rates for varicella in the low, middle, and high potency groups were 99.7%, 100%, and 99%, respectively, compared with 93.1% in the MMR-plus-VV group. Similar response rates to those of measles and varicella were seen in the low, middle and high potency groups for mumps and rubella.

The incidence of measles-like rashes was similar in all groups, and the incidence of both varicella-like and measles-like rashes was lower in the MMRV group after the second MMRV injection, compared with the MMR-plus-VV group.

Approximately 70% of the children in any of the MMRV groups as well as the combination group reported at least one systemic adverse event, including fever, irritability, and upper respiratory tract infection. A febrile seizure suffered by a child in the middle potency group was the only severe adverse event thought to be vaccine related.

Febrile seizures might indeed be a cause for concern when using the quadrivalent vaccine, said Margaret Rennels, M.D., the American Academy of Pediatrics' coliaison to the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

But on the whole, the quadrivalent vaccine is a public health achievement, she said in an interview.

“Many of us believe that we should be giving a second dose of varicella and this [quadrivalent vaccine] would make that very easy,” said Dr. Rennels, clinical chief of infectious diseases at the University of Maryland, Baltimore.

A quadrivalent measles, mumps, rubella, and varicella vaccine was well-tolerated and effective in children aged 12–23 months, according to data from a pair of studies conducted by Henry Shinefield, M.D., of the University of San Francisco, California, and his colleagues.

The studies, which were sponsored in part by Merck & Co., indicated that either a one- or two-dose vaccine containing antibodies to all four diseases was similar in safety and efficacy to a combination of the previous measles, mumps, and rubella vaccine (MMR II) and a separate dose of the varicella virus vaccine (Varivax).

In a randomized, multicenter study, 480 healthy children received either MMR II plus Varivax (VV) or the quadrivalent vaccine (MMRV) plus a placebo. Children in the MMRV group had significantly higher rates of elevated temperature from 5–12 days after vaccination, compared with the MMR-plus-VV group (28% vs. 19%), but the fevers were generally mild and averaged less than 2 days' duration. Adverse events were not significantly different between the two groups at 42 days after vaccination (Pediatr. Infect. Dis. J. 2005;24:665–9).

A measles-like rash was the most common adverse event in both groups; the rashes averaged 6 days' duration and were mild to moderate. The incidence of pain and redness at the injection sites and the proportion of children with at least one adverse event were similar between the groups.

In a separate study of 1,559 healthy children, antibody responses from the MMRV were equal to those from a combination of MMR plus VV (Pediatr. Infect. Dis. J. 2005;24:670–5).

The children were randomized to one of four treatment groups and received a quadrivalent vaccine with a low, middle, or high varicella-zoster virus (VZV) potency or a dose of MMR plus VV. Those in the quadrivalent groups received a second MMRV injection 90 days after the first injection.

The antibody rates in all three MMRV groups after the second injection were at least as high as the MMR-plus-VV group, and most of the children who had not responded to the VZV in the first injection did so after the second injection.

After the second injection, the observed response rates for measles in the low, middle, and high potency groups were 99.4%, 99.7%, and 100%, respectively, compared with 99.7%, in the MMR-plus-VV group. The observed response rates for varicella in the low, middle, and high potency groups were 99.7%, 100%, and 99%, respectively, compared with 93.1% in the MMR-plus-VV group. Similar response rates to those of measles and varicella were seen in the low, middle and high potency groups for mumps and rubella.

The incidence of measles-like rashes was similar in all groups, and the incidence of both varicella-like and measles-like rashes was lower in the MMRV group after the second MMRV injection, compared with the MMR-plus-VV group.

Approximately 70% of the children in any of the MMRV groups as well as the combination group reported at least one systemic adverse event, including fever, irritability, and upper respiratory tract infection. A febrile seizure suffered by a child in the middle potency group was the only severe adverse event thought to be vaccine related.

Febrile seizures might indeed be a cause for concern when using the quadrivalent vaccine, said Margaret Rennels, M.D., the American Academy of Pediatrics' coliaison to the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices.

But on the whole, the quadrivalent vaccine is a public health achievement, she said in an interview.

“Many of us believe that we should be giving a second dose of varicella and this [quadrivalent vaccine] would make that very easy,” said Dr. Rennels, clinical chief of infectious diseases at the University of Maryland, Baltimore.

BETHESDA, MD. — The supply of weapons against multidrug-resistant gram-negative pathogens is running low, Henry M. Blumberg, M.D., said at an annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

“We are struggling to treat these infections,” said Dr. Blumberg, professor of medicine at Emory University, Atlanta. “There's not a lot of information in the literature about controlling gram-negative pathogens. Most studies are about VRE [vancomycin-resistant enterococci] and MRSA [methicillin-resistant Staphylococcus aureus],” he explained.

Physicians at Grady Hospital in Atlanta, where Dr. Blumberg is an epidemiologist, have been unable to completely eradicate some forms of persistent multidrug-resistant (MDR) gram-negative bacteria, but they have developed strategies to reduce the risk of infections.

Here are seven strategies to help in the battle:

▸ Improve hand hygiene. Physicians are often the worst offenders and the ICU staff often has the poorest hand hygiene, Dr. Blumberg noted. Also, artificial fingernails have been associated with nosocomial infections and should not be worn by health care workers.

▸ Prevent nosocomial infections, especially pneumonia. Gram-negative pathogens are often the source of ICU infections.

▸ Use selective digestive tract decontamination. Use of intravenous prophylaxis for digestive tract decontamination has been shown to reduce the risk of bacterial infections during the early postoperative period. However, there have been reports of increased MRSA and VRE with this method.

▸ Reduce bloodstream infections. Techniques that have proved helpful include the use of maximum sterile barrier techniques; use of chlorhexidine on the skin prior to central line insertion also has been shown to reduce infection.

▸ Enhance environmental cleaning. A clean environment is important for the reduction and control of pathogens such as Acinetobacter baumannii, for which the environment might play a significant role in transmission.

▸ Improve nurse-to-patient staffing ratios. Data from previous studies have shown a relationship between increased resistance and fewer nursing hours per patient-day, but resistance decreased as staffing consistency improved.

▸ Improve antibiotic utilization. Potential methods to reduce inappropriate use of antibiotics include the application of practice guidelines, formulary restriction, and antibiotic cycling.

The staff at Grady Hospital conducted a self-study in which two groups of care teams were randomized either to an intervention designed to control for antibiotic resistance or to standard-of-care guidelines that had been developed by the hospital. In the intervention group, an antibiotic utilization team recommended an optimal therapy if the prescription was inappropriate based on hospital guidelines. The control group prescribed antibiotics without review by a utilization team.

Overall, the intervention group was deemed to have used antibiotics appropriately in 82% of cases, compared with 67% for the controls, Dr. Blumberg said.

“We can't eradicate these organisms, especially in surgery, but we are working to control them,” he said. “We need more studies to help us determine the best ways.”

Another management strategy, the “search-and-destroy” method of MDR infection management, involves active surveillance via frequent screening of patient cultures and contact isolation for anyone infected or colonized with MDR gram-negative bacteria. However, “what you screen for is based on what you are finding in your hospital,” he noted.

Although the search-and-destroy method may eradicate pathogens in some situations, it is almost impossible to do so in a surgical setting, he said.

Dr. Blumberg had no conflicts of interest to disclose.

BETHESDA, MD. — The supply of weapons against multidrug-resistant gram-negative pathogens is running low, Henry M. Blumberg, M.D., said at an annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

“We are struggling to treat these infections,” said Dr. Blumberg, professor of medicine at Emory University, Atlanta. “There's not a lot of information in the literature about controlling gram-negative pathogens. Most studies are about VRE [vancomycin-resistant enterococci] and MRSA [methicillin-resistant Staphylococcus aureus],” he explained.

Physicians at Grady Hospital in Atlanta, where Dr. Blumberg is an epidemiologist, have been unable to completely eradicate some forms of persistent multidrug-resistant (MDR) gram-negative bacteria, but they have developed strategies to reduce the risk of infections.

Here are seven strategies to help in the battle:

▸ Improve hand hygiene. Physicians are often the worst offenders and the ICU staff often has the poorest hand hygiene, Dr. Blumberg noted. Also, artificial fingernails have been associated with nosocomial infections and should not be worn by health care workers.

▸ Prevent nosocomial infections, especially pneumonia. Gram-negative pathogens are often the source of ICU infections.

▸ Use selective digestive tract decontamination. Use of intravenous prophylaxis for digestive tract decontamination has been shown to reduce the risk of bacterial infections during the early postoperative period. However, there have been reports of increased MRSA and VRE with this method.

▸ Reduce bloodstream infections. Techniques that have proved helpful include the use of maximum sterile barrier techniques; use of chlorhexidine on the skin prior to central line insertion also has been shown to reduce infection.

▸ Enhance environmental cleaning. A clean environment is important for the reduction and control of pathogens such as Acinetobacter baumannii, for which the environment might play a significant role in transmission.

▸ Improve nurse-to-patient staffing ratios. Data from previous studies have shown a relationship between increased resistance and fewer nursing hours per patient-day, but resistance decreased as staffing consistency improved.

▸ Improve antibiotic utilization. Potential methods to reduce inappropriate use of antibiotics include the application of practice guidelines, formulary restriction, and antibiotic cycling.

The staff at Grady Hospital conducted a self-study in which two groups of care teams were randomized either to an intervention designed to control for antibiotic resistance or to standard-of-care guidelines that had been developed by the hospital. In the intervention group, an antibiotic utilization team recommended an optimal therapy if the prescription was inappropriate based on hospital guidelines. The control group prescribed antibiotics without review by a utilization team.

Overall, the intervention group was deemed to have used antibiotics appropriately in 82% of cases, compared with 67% for the controls, Dr. Blumberg said.

“We can't eradicate these organisms, especially in surgery, but we are working to control them,” he said. “We need more studies to help us determine the best ways.”

Another management strategy, the “search-and-destroy” method of MDR infection management, involves active surveillance via frequent screening of patient cultures and contact isolation for anyone infected or colonized with MDR gram-negative bacteria. However, “what you screen for is based on what you are finding in your hospital,” he noted.

Although the search-and-destroy method may eradicate pathogens in some situations, it is almost impossible to do so in a surgical setting, he said.

Dr. Blumberg had no conflicts of interest to disclose.

BETHESDA, MD. — The supply of weapons against multidrug-resistant gram-negative pathogens is running low, Henry M. Blumberg, M.D., said at an annual conference on antimicrobial resistance sponsored by the National Foundation for Infectious Diseases.

“We are struggling to treat these infections,” said Dr. Blumberg, professor of medicine at Emory University, Atlanta. “There's not a lot of information in the literature about controlling gram-negative pathogens. Most studies are about VRE [vancomycin-resistant enterococci] and MRSA [methicillin-resistant Staphylococcus aureus],” he explained.

Physicians at Grady Hospital in Atlanta, where Dr. Blumberg is an epidemiologist, have been unable to completely eradicate some forms of persistent multidrug-resistant (MDR) gram-negative bacteria, but they have developed strategies to reduce the risk of infections.

Here are seven strategies to help in the battle:

▸ Improve hand hygiene. Physicians are often the worst offenders and the ICU staff often has the poorest hand hygiene, Dr. Blumberg noted. Also, artificial fingernails have been associated with nosocomial infections and should not be worn by health care workers.

▸ Prevent nosocomial infections, especially pneumonia. Gram-negative pathogens are often the source of ICU infections.

▸ Use selective digestive tract decontamination. Use of intravenous prophylaxis for digestive tract decontamination has been shown to reduce the risk of bacterial infections during the early postoperative period. However, there have been reports of increased MRSA and VRE with this method.

▸ Reduce bloodstream infections. Techniques that have proved helpful include the use of maximum sterile barrier techniques; use of chlorhexidine on the skin prior to central line insertion also has been shown to reduce infection.

▸ Enhance environmental cleaning. A clean environment is important for the reduction and control of pathogens such as Acinetobacter baumannii, for which the environment might play a significant role in transmission.

▸ Improve nurse-to-patient staffing ratios. Data from previous studies have shown a relationship between increased resistance and fewer nursing hours per patient-day, but resistance decreased as staffing consistency improved.

▸ Improve antibiotic utilization. Potential methods to reduce inappropriate use of antibiotics include the application of practice guidelines, formulary restriction, and antibiotic cycling.

The staff at Grady Hospital conducted a self-study in which two groups of care teams were randomized either to an intervention designed to control for antibiotic resistance or to standard-of-care guidelines that had been developed by the hospital. In the intervention group, an antibiotic utilization team recommended an optimal therapy if the prescription was inappropriate based on hospital guidelines. The control group prescribed antibiotics without review by a utilization team.

Overall, the intervention group was deemed to have used antibiotics appropriately in 82% of cases, compared with 67% for the controls, Dr. Blumberg said.

“We can't eradicate these organisms, especially in surgery, but we are working to control them,” he said. “We need more studies to help us determine the best ways.”

Another management strategy, the “search-and-destroy” method of MDR infection management, involves active surveillance via frequent screening of patient cultures and contact isolation for anyone infected or colonized with MDR gram-negative bacteria. However, “what you screen for is based on what you are finding in your hospital,” he noted.

Although the search-and-destroy method may eradicate pathogens in some situations, it is almost impossible to do so in a surgical setting, he said.

Dr. Blumberg had no conflicts of interest to disclose.

ORLANDO – When prescribing stimulants for children, play it safe and screen for heart conditions, said Howard Schubiner, M.D., at a meeting sponsored by the American Academy of Pediatrics.

Although population-based studies fail to show a significant increased risk for sudden cardiac death associated with stimulant use, concerns remain, and physicians should quickly evaluate any cardiac symptoms that arise while children are taking stimulant medications, said Dr. Schubiner of Providence Hospital in Southfield, Mich.

The controlled-release amphetamine Adderall XR was removed from Canadian markets earlier this year because of concerns raised by sudden cardiac death in 12 children and 8 adults in the United States who were taking the medication. As of press time, the U.S. Food and Drug Administration had not taken any action to remove the product from U.S. markets, although the product now carries a black box warning about the increased risk for cardiac events. The FDA's decision stems from an analysis of data suggesting that the risk of sudden death does not differ significantly between children treated with stimulants and untreated children.

The 12 cases of death linked to Adderall occurred between 1999 and 2003, and the children (all males, mean age 12 years) had been taking daily doses of 10 mg–50 mg for durations of 1 day to 8 years.

Overall, the rate of sudden cardiac death in children in the United States is approximately 600 per year, excluding sudden infant death syndrome, Dr. Schubiner noted. Sudden, nontraumatic death accounts for 2%–20% of all deaths among children aged 1–20 years. Boys are three times more likely to die than girls. He cited a 1996 study in which 40 of 50 (80%) sudden deaths in children were due to underlying cardiac abnormalities (Am. J. Cardiol. 1996;77:992–5).

The most common cause of sudden cardiac death in children is hypertrophic cardiomyopathy, an autosomal dominant disorder seen in approximately 1 of every 500 people. Left ventricular hypertrophy occurs in approximately 75%–95% of these patients, but most do not have a discernible heart murmur.

Other cardiac problems that could increase the risk for sudden death in the presence of a stimulant include coronary artery syndrome, arrhythmogenic right ventricle dysplasia, long QT syndrome, and Brugada syndrome, the odds of which are several thousand to one, Dr. Schubiner said.

Adderall is most often used to treat attention-deficit hyperactivity disorder (ADHD), and is still warranted for use in children and adolescents with ADHD, as are other stimulants, Dr. Schubiner noted.

However, it is important and prudent to inquire into a personal history of any chest discomfort, shortness of breath (particularly with exercise), syncopal episodes, palpitations, dizziness, or fatigue.

It is also critical to ask about any family history of sudden cardiac deaths, myocardial infarctions prior to the age of 50 in men and 60 in women, cardiomyopathy, or congenital heart disorders.

ORLANDO – When prescribing stimulants for children, play it safe and screen for heart conditions, said Howard Schubiner, M.D., at a meeting sponsored by the American Academy of Pediatrics.

Although population-based studies fail to show a significant increased risk for sudden cardiac death associated with stimulant use, concerns remain, and physicians should quickly evaluate any cardiac symptoms that arise while children are taking stimulant medications, said Dr. Schubiner of Providence Hospital in Southfield, Mich.

The controlled-release amphetamine Adderall XR was removed from Canadian markets earlier this year because of concerns raised by sudden cardiac death in 12 children and 8 adults in the United States who were taking the medication. As of press time, the U.S. Food and Drug Administration had not taken any action to remove the product from U.S. markets, although the product now carries a black box warning about the increased risk for cardiac events. The FDA's decision stems from an analysis of data suggesting that the risk of sudden death does not differ significantly between children treated with stimulants and untreated children.

The 12 cases of death linked to Adderall occurred between 1999 and 2003, and the children (all males, mean age 12 years) had been taking daily doses of 10 mg–50 mg for durations of 1 day to 8 years.

Overall, the rate of sudden cardiac death in children in the United States is approximately 600 per year, excluding sudden infant death syndrome, Dr. Schubiner noted. Sudden, nontraumatic death accounts for 2%–20% of all deaths among children aged 1–20 years. Boys are three times more likely to die than girls. He cited a 1996 study in which 40 of 50 (80%) sudden deaths in children were due to underlying cardiac abnormalities (Am. J. Cardiol. 1996;77:992–5).

The most common cause of sudden cardiac death in children is hypertrophic cardiomyopathy, an autosomal dominant disorder seen in approximately 1 of every 500 people. Left ventricular hypertrophy occurs in approximately 75%–95% of these patients, but most do not have a discernible heart murmur.

Other cardiac problems that could increase the risk for sudden death in the presence of a stimulant include coronary artery syndrome, arrhythmogenic right ventricle dysplasia, long QT syndrome, and Brugada syndrome, the odds of which are several thousand to one, Dr. Schubiner said.

Adderall is most often used to treat attention-deficit hyperactivity disorder (ADHD), and is still warranted for use in children and adolescents with ADHD, as are other stimulants, Dr. Schubiner noted.

However, it is important and prudent to inquire into a personal history of any chest discomfort, shortness of breath (particularly with exercise), syncopal episodes, palpitations, dizziness, or fatigue.

It is also critical to ask about any family history of sudden cardiac deaths, myocardial infarctions prior to the age of 50 in men and 60 in women, cardiomyopathy, or congenital heart disorders.

ORLANDO – When prescribing stimulants for children, play it safe and screen for heart conditions, said Howard Schubiner, M.D., at a meeting sponsored by the American Academy of Pediatrics.

Although population-based studies fail to show a significant increased risk for sudden cardiac death associated with stimulant use, concerns remain, and physicians should quickly evaluate any cardiac symptoms that arise while children are taking stimulant medications, said Dr. Schubiner of Providence Hospital in Southfield, Mich.

The controlled-release amphetamine Adderall XR was removed from Canadian markets earlier this year because of concerns raised by sudden cardiac death in 12 children and 8 adults in the United States who were taking the medication. As of press time, the U.S. Food and Drug Administration had not taken any action to remove the product from U.S. markets, although the product now carries a black box warning about the increased risk for cardiac events. The FDA's decision stems from an analysis of data suggesting that the risk of sudden death does not differ significantly between children treated with stimulants and untreated children.

The 12 cases of death linked to Adderall occurred between 1999 and 2003, and the children (all males, mean age 12 years) had been taking daily doses of 10 mg–50 mg for durations of 1 day to 8 years.

Overall, the rate of sudden cardiac death in children in the United States is approximately 600 per year, excluding sudden infant death syndrome, Dr. Schubiner noted. Sudden, nontraumatic death accounts for 2%–20% of all deaths among children aged 1–20 years. Boys are three times more likely to die than girls. He cited a 1996 study in which 40 of 50 (80%) sudden deaths in children were due to underlying cardiac abnormalities (Am. J. Cardiol. 1996;77:992–5).

The most common cause of sudden cardiac death in children is hypertrophic cardiomyopathy, an autosomal dominant disorder seen in approximately 1 of every 500 people. Left ventricular hypertrophy occurs in approximately 75%–95% of these patients, but most do not have a discernible heart murmur.

Other cardiac problems that could increase the risk for sudden death in the presence of a stimulant include coronary artery syndrome, arrhythmogenic right ventricle dysplasia, long QT syndrome, and Brugada syndrome, the odds of which are several thousand to one, Dr. Schubiner said.

Adderall is most often used to treat attention-deficit hyperactivity disorder (ADHD), and is still warranted for use in children and adolescents with ADHD, as are other stimulants, Dr. Schubiner noted.

However, it is important and prudent to inquire into a personal history of any chest discomfort, shortness of breath (particularly with exercise), syncopal episodes, palpitations, dizziness, or fatigue.

It is also critical to ask about any family history of sudden cardiac deaths, myocardial infarctions prior to the age of 50 in men and 60 in women, cardiomyopathy, or congenital heart disorders.

Brain Abnormalities and Schizophrenia

Structural abnormalities in the white matter of the brain might be associated with the development of early-onset schizophrenia, said Sanjiv Kumra, M.D., of the Zucker Hillside Hospital, Glen Oaks, New York, and associates.

The researchers used diffusion tensor imaging, an MRI technique that estimates the orientation of fiber bundles in the brain's white matter based on the diffusion of water, to examine the brains of 26 schizophrenia patients (mean age 15 years) and 34 age-matched healthy controls (J. Am. Acad. Child Adolesc. Psychiatry 2005;44:934–41).

The patients showed significantly lower levels of fractional anistropy (FA), a measure of how much the diffusion of water follows one direction, compared with the controls. Decreases in the FA of white matter have been associated with brain tissue structure disorders such as multiple sclerosis.

The median age at onset of symptoms was 12 years, and the median duration of illness was 2 years at the time of the study. Medication use had no apparent effects on the findings.

Multiple Substance Use and Sex

Virgins who used three or more substances, including alcohol, tobacco, and marijuana, were three times more likely to become sexually active during the next 9 months, compared with virgins who did not use any substances, reported Jiantong Guo of Wayne State University, Detroit, and colleagues (J. Adolesc. Health 2005;37:252–5).

In a longitudinal study, 310 boys and 436 girls aged 12–16 years living in rural West Virginia were recruited through schools or community centers. The students completed questionnaires at baseline and after 3, 6, and 9 months. Of the 53 teens who used three or more substances, 36% initiated sex within the next 9 months, compared with 29% of the 130 using two substances, 22% of the 174 using one substance, and 8% of the 389 using no substances. The use of three or more substances as a screen for sexual initiation in the near future was 90%, although sensitivity was only 50%. Patterns of use were similar between boys and girls.

Overall, 49% of the young people reported alcohol use, 34% reported tobacco use, 9% reported marijuana use, and 7% reported using all three substances.

CBT, Fluoxetine, and Depression

Depressed adolescents who received a combination of five to nine sessions of cognitive-behavioral therapy (CBT) plus fluoxetine showed no significant overall improvement, compared with those who received fluoxetine alone, wrote Gregory Clarke, Ph.D., of the Kaiser Permanente Center for Health Research in Portland, Ore.

The randomized study included 152 adolescents aged 12–18 years with major depressive disorder (J. Am. Acad. Child Adolesc. Psychiatry 2005;44:888–98). Those in the combination group had fewer medical outpatient visits and used 20% less medication, compared with the treatment-as-usual group. However, after 1 year, 11% of the teens in the combined group and 6% of those in the fluoxetine-only group were suffering from a depressive episode.

Impact of Adversity on Schizophrenia

Children with four measures of social adversity were 2.7 times more likely to develop schizophrenia than children with no measurable social adversity, reported Susanne Wicks, B.Sc., of the Stockholm Centre for Public Health, Sweden, and her associates.

In a population-based study of about 2.1 million children born in Sweden between 1963 and 1983, the incidence of schizophrenia was 18.7 per 10,000 among children from households receiving welfare benefits, compared with 8.3 per 10,000 children in households not receiving welfare (Am. J. Psychiatry 2005;162:1652–7).

After adjusting for confounding variables, parental inpatient care for psychosis carried the highest associated risk for schizophrenia (hazard ratio 8.4).

Genetic Traits, Eating Disorders Linked

Six genetic traits–obsessionality, age at menarche, anxiety, lifetime minimum body mass index, concern over mistakes, and food-related obsessions–appear to be linked to genes associated with anorexia nervosa and bulimia nervosa, according to Cynthia M. Bulik, Ph.D., of the University of North Carolina, Chapel Hill, and her colleagues.

In a genetic analysis of 154 families with affected siblings with anorexia and 244 families with affected siblings with bulimia, these traits were especially prominent compared with controls. No single measure captures “eating disorderedness,” but the analysis provides a map for selecting traits that can be used in future research, the investigators said (Am. J. Med. Genet. B Neuropsychiatr. Genet. [online] 2005;

www3.interscience.wiley.com/cgi-bin/abstract/111090304/ABSTRACT

Brain Abnormalities and Schizophrenia

Structural abnormalities in the white matter of the brain might be associated with the development of early-onset schizophrenia, said Sanjiv Kumra, M.D., of the Zucker Hillside Hospital, Glen Oaks, New York, and associates.

The researchers used diffusion tensor imaging, an MRI technique that estimates the orientation of fiber bundles in the brain's white matter based on the diffusion of water, to examine the brains of 26 schizophrenia patients (mean age 15 years) and 34 age-matched healthy controls (J. Am. Acad. Child Adolesc. Psychiatry 2005;44:934–41).

The patients showed significantly lower levels of fractional anistropy (FA), a measure of how much the diffusion of water follows one direction, compared with the controls. Decreases in the FA of white matter have been associated with brain tissue structure disorders such as multiple sclerosis.

The median age at onset of symptoms was 12 years, and the median duration of illness was 2 years at the time of the study. Medication use had no apparent effects on the findings.

Multiple Substance Use and Sex

Virgins who used three or more substances, including alcohol, tobacco, and marijuana, were three times more likely to become sexually active during the next 9 months, compared with virgins who did not use any substances, reported Jiantong Guo of Wayne State University, Detroit, and colleagues (J. Adolesc. Health 2005;37:252–5).

In a longitudinal study, 310 boys and 436 girls aged 12–16 years living in rural West Virginia were recruited through schools or community centers. The students completed questionnaires at baseline and after 3, 6, and 9 months. Of the 53 teens who used three or more substances, 36% initiated sex within the next 9 months, compared with 29% of the 130 using two substances, 22% of the 174 using one substance, and 8% of the 389 using no substances. The use of three or more substances as a screen for sexual initiation in the near future was 90%, although sensitivity was only 50%. Patterns of use were similar between boys and girls.

Overall, 49% of the young people reported alcohol use, 34% reported tobacco use, 9% reported marijuana use, and 7% reported using all three substances.

CBT, Fluoxetine, and Depression

Depressed adolescents who received a combination of five to nine sessions of cognitive-behavioral therapy (CBT) plus fluoxetine showed no significant overall improvement, compared with those who received fluoxetine alone, wrote Gregory Clarke, Ph.D., of the Kaiser Permanente Center for Health Research in Portland, Ore.

The randomized study included 152 adolescents aged 12–18 years with major depressive disorder (J. Am. Acad. Child Adolesc. Psychiatry 2005;44:888–98). Those in the combination group had fewer medical outpatient visits and used 20% less medication, compared with the treatment-as-usual group. However, after 1 year, 11% of the teens in the combined group and 6% of those in the fluoxetine-only group were suffering from a depressive episode.

Impact of Adversity on Schizophrenia

Children with four measures of social adversity were 2.7 times more likely to develop schizophrenia than children with no measurable social adversity, reported Susanne Wicks, B.Sc., of the Stockholm Centre for Public Health, Sweden, and her associates.

In a population-based study of about 2.1 million children born in Sweden between 1963 and 1983, the incidence of schizophrenia was 18.7 per 10,000 among children from households receiving welfare benefits, compared with 8.3 per 10,000 children in households not receiving welfare (Am. J. Psychiatry 2005;162:1652–7).

After adjusting for confounding variables, parental inpatient care for psychosis carried the highest associated risk for schizophrenia (hazard ratio 8.4).

Genetic Traits, Eating Disorders Linked

Six genetic traits–obsessionality, age at menarche, anxiety, lifetime minimum body mass index, concern over mistakes, and food-related obsessions–appear to be linked to genes associated with anorexia nervosa and bulimia nervosa, according to Cynthia M. Bulik, Ph.D., of the University of North Carolina, Chapel Hill, and her colleagues.

In a genetic analysis of 154 families with affected siblings with anorexia and 244 families with affected siblings with bulimia, these traits were especially prominent compared with controls. No single measure captures “eating disorderedness,” but the analysis provides a map for selecting traits that can be used in future research, the investigators said (Am. J. Med. Genet. B Neuropsychiatr. Genet. [online] 2005;

www3.interscience.wiley.com/cgi-bin/abstract/111090304/ABSTRACT

Brain Abnormalities and Schizophrenia

Structural abnormalities in the white matter of the brain might be associated with the development of early-onset schizophrenia, said Sanjiv Kumra, M.D., of the Zucker Hillside Hospital, Glen Oaks, New York, and associates.

The researchers used diffusion tensor imaging, an MRI technique that estimates the orientation of fiber bundles in the brain's white matter based on the diffusion of water, to examine the brains of 26 schizophrenia patients (mean age 15 years) and 34 age-matched healthy controls (J. Am. Acad. Child Adolesc. Psychiatry 2005;44:934–41).

The patients showed significantly lower levels of fractional anistropy (FA), a measure of how much the diffusion of water follows one direction, compared with the controls. Decreases in the FA of white matter have been associated with brain tissue structure disorders such as multiple sclerosis.

The median age at onset of symptoms was 12 years, and the median duration of illness was 2 years at the time of the study. Medication use had no apparent effects on the findings.

Multiple Substance Use and Sex

Virgins who used three or more substances, including alcohol, tobacco, and marijuana, were three times more likely to become sexually active during the next 9 months, compared with virgins who did not use any substances, reported Jiantong Guo of Wayne State University, Detroit, and colleagues (J. Adolesc. Health 2005;37:252–5).

In a longitudinal study, 310 boys and 436 girls aged 12–16 years living in rural West Virginia were recruited through schools or community centers. The students completed questionnaires at baseline and after 3, 6, and 9 months. Of the 53 teens who used three or more substances, 36% initiated sex within the next 9 months, compared with 29% of the 130 using two substances, 22% of the 174 using one substance, and 8% of the 389 using no substances. The use of three or more substances as a screen for sexual initiation in the near future was 90%, although sensitivity was only 50%. Patterns of use were similar between boys and girls.

Overall, 49% of the young people reported alcohol use, 34% reported tobacco use, 9% reported marijuana use, and 7% reported using all three substances.

CBT, Fluoxetine, and Depression

Depressed adolescents who received a combination of five to nine sessions of cognitive-behavioral therapy (CBT) plus fluoxetine showed no significant overall improvement, compared with those who received fluoxetine alone, wrote Gregory Clarke, Ph.D., of the Kaiser Permanente Center for Health Research in Portland, Ore.

The randomized study included 152 adolescents aged 12–18 years with major depressive disorder (J. Am. Acad. Child Adolesc. Psychiatry 2005;44:888–98). Those in the combination group had fewer medical outpatient visits and used 20% less medication, compared with the treatment-as-usual group. However, after 1 year, 11% of the teens in the combined group and 6% of those in the fluoxetine-only group were suffering from a depressive episode.

Impact of Adversity on Schizophrenia

Children with four measures of social adversity were 2.7 times more likely to develop schizophrenia than children with no measurable social adversity, reported Susanne Wicks, B.Sc., of the Stockholm Centre for Public Health, Sweden, and her associates.

In a population-based study of about 2.1 million children born in Sweden between 1963 and 1983, the incidence of schizophrenia was 18.7 per 10,000 among children from households receiving welfare benefits, compared with 8.3 per 10,000 children in households not receiving welfare (Am. J. Psychiatry 2005;162:1652–7).

After adjusting for confounding variables, parental inpatient care for psychosis carried the highest associated risk for schizophrenia (hazard ratio 8.4).

Genetic Traits, Eating Disorders Linked

Six genetic traits–obsessionality, age at menarche, anxiety, lifetime minimum body mass index, concern over mistakes, and food-related obsessions–appear to be linked to genes associated with anorexia nervosa and bulimia nervosa, according to Cynthia M. Bulik, Ph.D., of the University of North Carolina, Chapel Hill, and her colleagues.

In a genetic analysis of 154 families with affected siblings with anorexia and 244 families with affected siblings with bulimia, these traits were especially prominent compared with controls. No single measure captures “eating disorderedness,” but the analysis provides a map for selecting traits that can be used in future research, the investigators said (Am. J. Med. Genet. B Neuropsychiatr. Genet. [online] 2005;

www3.interscience.wiley.com/cgi-bin/abstract/111090304/ABSTRACT

MIAMI —The incidence of surgical site infections after colorectal surgery could be reduced through greater awareness of risk factors, Harry van Goor, M.D., said at the joint annual meeting of the Surgical Infection Society and the Surgical Infection Society-Europe.

In a prospective, randomized, multicenter study of adults who elected colorectal resection for benign disease, 163 of the 1,701 patients (9.6%) had at least one surgical site infection (SSI), reported Dr. van Goor, a surgeon at the University Medical Center Nijmegen (the Netherlands). Of these SSIs, 66 (3.8%) were incisional infections, and 111 (6.5%) were organ/space infections. Approximately 50% of the infections in a group of 1,701 colorectal surgery patients occurred within 9 days after surgery, and 97% occurred within 24 days after surgery.

Significant independent risk factors for incisional infections included high body mass index (odds ratio of 2.6), bowel preparation with antibiotics (OR 0.5), preoperative hospitalization (OR 1.8), and wound classification (OR 2.8).

Significant independent risk factors for organ/space infections included age (OR 0.4), preexisting abscess or fistula (OR 19.1), diabetes (OR 2.4), perioperative steroid use (OR 2.1), preoperative hospitalization (OR 1.4), multiple procedures (OR 2.5), and wrapping of the antiadhesion barrier around an anastomosis (OR 3.1).

“Hospital stay increases by an average of 7 days if a surgical site infection occurs,” said Dr. van Goor. Furthermore, patients with SSIs are more likely to be admitted to the ICU than patients without infections.

MIAMI —The incidence of surgical site infections after colorectal surgery could be reduced through greater awareness of risk factors, Harry van Goor, M.D., said at the joint annual meeting of the Surgical Infection Society and the Surgical Infection Society-Europe.

In a prospective, randomized, multicenter study of adults who elected colorectal resection for benign disease, 163 of the 1,701 patients (9.6%) had at least one surgical site infection (SSI), reported Dr. van Goor, a surgeon at the University Medical Center Nijmegen (the Netherlands). Of these SSIs, 66 (3.8%) were incisional infections, and 111 (6.5%) were organ/space infections. Approximately 50% of the infections in a group of 1,701 colorectal surgery patients occurred within 9 days after surgery, and 97% occurred within 24 days after surgery.

Significant independent risk factors for incisional infections included high body mass index (odds ratio of 2.6), bowel preparation with antibiotics (OR 0.5), preoperative hospitalization (OR 1.8), and wound classification (OR 2.8).

Significant independent risk factors for organ/space infections included age (OR 0.4), preexisting abscess or fistula (OR 19.1), diabetes (OR 2.4), perioperative steroid use (OR 2.1), preoperative hospitalization (OR 1.4), multiple procedures (OR 2.5), and wrapping of the antiadhesion barrier around an anastomosis (OR 3.1).

“Hospital stay increases by an average of 7 days if a surgical site infection occurs,” said Dr. van Goor. Furthermore, patients with SSIs are more likely to be admitted to the ICU than patients without infections.

MIAMI —The incidence of surgical site infections after colorectal surgery could be reduced through greater awareness of risk factors, Harry van Goor, M.D., said at the joint annual meeting of the Surgical Infection Society and the Surgical Infection Society-Europe.

In a prospective, randomized, multicenter study of adults who elected colorectal resection for benign disease, 163 of the 1,701 patients (9.6%) had at least one surgical site infection (SSI), reported Dr. van Goor, a surgeon at the University Medical Center Nijmegen (the Netherlands). Of these SSIs, 66 (3.8%) were incisional infections, and 111 (6.5%) were organ/space infections. Approximately 50% of the infections in a group of 1,701 colorectal surgery patients occurred within 9 days after surgery, and 97% occurred within 24 days after surgery.

Significant independent risk factors for incisional infections included high body mass index (odds ratio of 2.6), bowel preparation with antibiotics (OR 0.5), preoperative hospitalization (OR 1.8), and wound classification (OR 2.8).

Significant independent risk factors for organ/space infections included age (OR 0.4), preexisting abscess or fistula (OR 19.1), diabetes (OR 2.4), perioperative steroid use (OR 2.1), preoperative hospitalization (OR 1.4), multiple procedures (OR 2.5), and wrapping of the antiadhesion barrier around an anastomosis (OR 3.1).

“Hospital stay increases by an average of 7 days if a surgical site infection occurs,” said Dr. van Goor. Furthermore, patients with SSIs are more likely to be admitted to the ICU than patients without infections.

MIAMI — Blood product transfusion was an independent risk factor for ventilator-associated pneumonia in a study of 766 adult trauma patients, said Grant Bochicchio, M.D., at the joint annual meeting of the Surgical Infection Society and Surgical Infection Society-Europe.

In a prospective, observational cohort study, 26 patients developed ventilator-associated pneumonia, and 22 of the 26 (85%) received blood transfusions prior to their VAP diagnoses, noted Dr. Bochicchio, of the R. Adams Cowley Shock Trauma Center in Baltimore.

The patients, who did not have pneumonia on admission to the ICU, were on ventilators for at least 48 hours. Transfusions of any blood product—red blood cells, plasma, and platelets—were independent risk factors for VAP after controlling for gender, injury severity, number of days on the ventilator, and number of days in the ICU prior to developing VAP.

The odds ratio for VAP due to blood transfusion was significantly higher for trauma patients compared with other ICU patients. In trauma patients, the odds ratio for developing VAP was 3.34 for fresh frozen plasma transfusion, 4.19 for platelet transfusion, and 4.41 for red blood cell transfusion, compared with a 1.8 odds ratio for VAP among nontrauma patients in the ICU, Dr. Bochicchio noted.

Patients with VAP spent significantly more days on ventilators compared with non-VAP patients (35 vs. 11) and significantly more days in the ICU (31 vs. 12). There were no significant differences between VAP and non-VAP patients in terms of age or race, and most patients in each group were male.

MIAMI — Blood product transfusion was an independent risk factor for ventilator-associated pneumonia in a study of 766 adult trauma patients, said Grant Bochicchio, M.D., at the joint annual meeting of the Surgical Infection Society and Surgical Infection Society-Europe.

In a prospective, observational cohort study, 26 patients developed ventilator-associated pneumonia, and 22 of the 26 (85%) received blood transfusions prior to their VAP diagnoses, noted Dr. Bochicchio, of the R. Adams Cowley Shock Trauma Center in Baltimore.

The patients, who did not have pneumonia on admission to the ICU, were on ventilators for at least 48 hours. Transfusions of any blood product—red blood cells, plasma, and platelets—were independent risk factors for VAP after controlling for gender, injury severity, number of days on the ventilator, and number of days in the ICU prior to developing VAP.

The odds ratio for VAP due to blood transfusion was significantly higher for trauma patients compared with other ICU patients. In trauma patients, the odds ratio for developing VAP was 3.34 for fresh frozen plasma transfusion, 4.19 for platelet transfusion, and 4.41 for red blood cell transfusion, compared with a 1.8 odds ratio for VAP among nontrauma patients in the ICU, Dr. Bochicchio noted.

Patients with VAP spent significantly more days on ventilators compared with non-VAP patients (35 vs. 11) and significantly more days in the ICU (31 vs. 12). There were no significant differences between VAP and non-VAP patients in terms of age or race, and most patients in each group were male.

MIAMI — Blood product transfusion was an independent risk factor for ventilator-associated pneumonia in a study of 766 adult trauma patients, said Grant Bochicchio, M.D., at the joint annual meeting of the Surgical Infection Society and Surgical Infection Society-Europe.

In a prospective, observational cohort study, 26 patients developed ventilator-associated pneumonia, and 22 of the 26 (85%) received blood transfusions prior to their VAP diagnoses, noted Dr. Bochicchio, of the R. Adams Cowley Shock Trauma Center in Baltimore.

The patients, who did not have pneumonia on admission to the ICU, were on ventilators for at least 48 hours. Transfusions of any blood product—red blood cells, plasma, and platelets—were independent risk factors for VAP after controlling for gender, injury severity, number of days on the ventilator, and number of days in the ICU prior to developing VAP.

The odds ratio for VAP due to blood transfusion was significantly higher for trauma patients compared with other ICU patients. In trauma patients, the odds ratio for developing VAP was 3.34 for fresh frozen plasma transfusion, 4.19 for platelet transfusion, and 4.41 for red blood cell transfusion, compared with a 1.8 odds ratio for VAP among nontrauma patients in the ICU, Dr. Bochicchio noted.

Patients with VAP spent significantly more days on ventilators compared with non-VAP patients (35 vs. 11) and significantly more days in the ICU (31 vs. 12). There were no significant differences between VAP and non-VAP patients in terms of age or race, and most patients in each group were male.

WASHINGTON — The risk of vertebral fragility fractures is threefold higher among postmenopausal women with at least one prevalent radiographic fracture, compared with those without such a history, Ethel S. Siris, M.D., said at an international symposium sponsored by the National Osteoporosis Foundation.

Awareness of previous vertebral fractures can help physicians evaluate vertebral fragility and target osteoporosis therapy appropriately, Dr. Siris, a professor of clinical medicine at Columbia University, New York, and her colleagues, said in a poster presented at the meeting.

Their review of data on 2,651 postmenopausal women, mean age 67 years, included 1,181 women with prevalent vertebral fractures and assessed risk independent of lumbar spine bone mineral density.

Overall, the greater the number of prevalent vertebral fractures, the greater the risk of sustaining subsequent fractures.

Patients with three or more fractures had as much as an eightfold increased risk. Greater severity scores on the semi-quantitative deformity scale were associated with as much as an 11-fold increase in risk.

Dr. Siris is a consultant for and has received honoraria from Eli Lilly & Co., Merck & Co., Sanofi-Aventis, Procter & Gamble Pharmaceuticals, and Novartis.

WASHINGTON — The risk of vertebral fragility fractures is threefold higher among postmenopausal women with at least one prevalent radiographic fracture, compared with those without such a history, Ethel S. Siris, M.D., said at an international symposium sponsored by the National Osteoporosis Foundation.

Awareness of previous vertebral fractures can help physicians evaluate vertebral fragility and target osteoporosis therapy appropriately, Dr. Siris, a professor of clinical medicine at Columbia University, New York, and her colleagues, said in a poster presented at the meeting.

Their review of data on 2,651 postmenopausal women, mean age 67 years, included 1,181 women with prevalent vertebral fractures and assessed risk independent of lumbar spine bone mineral density.

Overall, the greater the number of prevalent vertebral fractures, the greater the risk of sustaining subsequent fractures.

Patients with three or more fractures had as much as an eightfold increased risk. Greater severity scores on the semi-quantitative deformity scale were associated with as much as an 11-fold increase in risk.

Dr. Siris is a consultant for and has received honoraria from Eli Lilly & Co., Merck & Co., Sanofi-Aventis, Procter & Gamble Pharmaceuticals, and Novartis.

WASHINGTON — The risk of vertebral fragility fractures is threefold higher among postmenopausal women with at least one prevalent radiographic fracture, compared with those without such a history, Ethel S. Siris, M.D., said at an international symposium sponsored by the National Osteoporosis Foundation.

Awareness of previous vertebral fractures can help physicians evaluate vertebral fragility and target osteoporosis therapy appropriately, Dr. Siris, a professor of clinical medicine at Columbia University, New York, and her colleagues, said in a poster presented at the meeting.

Their review of data on 2,651 postmenopausal women, mean age 67 years, included 1,181 women with prevalent vertebral fractures and assessed risk independent of lumbar spine bone mineral density.

Overall, the greater the number of prevalent vertebral fractures, the greater the risk of sustaining subsequent fractures.

Patients with three or more fractures had as much as an eightfold increased risk. Greater severity scores on the semi-quantitative deformity scale were associated with as much as an 11-fold increase in risk.

Dr. Siris is a consultant for and has received honoraria from Eli Lilly & Co., Merck & Co., Sanofi-Aventis, Procter & Gamble Pharmaceuticals, and Novartis.

ORLANDO — Pediatric skin conditions often pose diagnostic challenges because many cutaneous disorders have similar clinical features.

Annular lesions of granuloma annulare may be mistaken for tinea corporis; follicular papules of keratosis pilaris may be confused with follicular eczema; and nail psoriasis may be misdiagnosed as onychomycosis.

At a meeting sponsored by the American Academy of Pediatrics, Albert C. Yan, M.D., director of pediatric dermatology at the Children's Hospital of Philadelphia, provided some helpful diagnostic tips for distinguishing some of these potentially puzzling skin problems.

The Hair Collar Sign

A boy is born with an area of localized, circular alopecia covered by a glossy membrane. The area is surrounded by a collection of dark, terminal hairs. Palpation reveals that a lump is present.

Occasionally mistaken for fetal scalp monitor trauma, neonatal herpes simplex infection, or a nevus sebaceus of Jadassohn, this characteristic pattern—a collar of coarse hair surrounding an area of membranous aplasia cutis congenita—can be a marker for cranial dysraphism, a developmental defect of the skull potentially associated with structural neurologic defects. The scalp defect may represent only the tip of the iceberg, Dr. Yan noted, since underlying bony defects or ectopic brain tissue may be present.

In such cases, magnetic resonance imaging is essential to rule out underlying abnormalities, including atretic encephaloceles or heterotopic brain tissue.

Pilomatricoma

A 15-month-old girl presented with a bump on her cheek—a firm, bluish, cystic papule that moved back and forth under pressure. When one end of the lesion was palpated, the other end would pop up, a phenomenon also known as a “teeter-totter sign.”

Although these lesions may resemble dermoid cysts or epidermal inclusion cysts, the diagnosis in this case was pilomatricoma, distinguished by its bluish color and the presence of the teeter-totter sign. The lesions most often occur on the head or neck, although other areas occasionally are affected. Pilomatricomas generally are solitary, benign, frequently calcified, and arise from hair follicles. In some cases, the lesions resolve spontaneously, but more often, they persist and grow, and surgical intervention is recommended. Pilomatricomas may rupture, which can cause inflammation and scarring. Although pilomatricomas generally are isolated findings, they may be associated with systemic disorders such as Gardner's syndrome, myotonic dystrophy, and sarcoidosis.

Annular Urticaria/Urticaria Multiforme

A 3-year-old girl presented with red, swollen, annular plaques on her skin, and had swollen hands and feet. She had been otherwise healthy and was taking no medications. The condition arose suddenly; the parents noticed the rings and swelling one morning when picking up the child from her bed. On closer inspection, the rings were red and blanchable, with clear white centers. Some were imperfect circles.

The diagnosis is annular urticaria. “These types of cases are frequently referred for suspected erythema multiforme,” Dr. Yan noted. “Lesions of annular urticaria are evanescent; the lesions fade and move, and the lesions can form imperfect circles with clear centers. The lesions may disappear within 24 hours, only to show up elsewhere,” he said. By contrast, erythema multiforme appears as fixed target, or “bull's-eye,” lesions with dusky centers and is associated with mucous membrane ulcers.

The two conditions are treated quite differently, Dr. Yan emphasized. Annular urticaria responds to combinations of antihistamines or occasionally steroids; erythema multiforme requires a detailed history to determine underlying causes, removal or treatment of those causes, and consideration of steroid therapy if indicated. Dr. Yan often refers to annular urticaria as “urticaria multiforme” because these cases are so regularly mistaken.

ORLANDO — Pediatric skin conditions often pose diagnostic challenges because many cutaneous disorders have similar clinical features.

Annular lesions of granuloma annulare may be mistaken for tinea corporis; follicular papules of keratosis pilaris may be confused with follicular eczema; and nail psoriasis may be misdiagnosed as onychomycosis.

At a meeting sponsored by the American Academy of Pediatrics, Albert C. Yan, M.D., director of pediatric dermatology at the Children's Hospital of Philadelphia, provided some helpful diagnostic tips for distinguishing some of these potentially puzzling skin problems.

The Hair Collar Sign

A boy is born with an area of localized, circular alopecia covered by a glossy membrane. The area is surrounded by a collection of dark, terminal hairs. Palpation reveals that a lump is present.

Occasionally mistaken for fetal scalp monitor trauma, neonatal herpes simplex infection, or a nevus sebaceus of Jadassohn, this characteristic pattern—a collar of coarse hair surrounding an area of membranous aplasia cutis congenita—can be a marker for cranial dysraphism, a developmental defect of the skull potentially associated with structural neurologic defects. The scalp defect may represent only the tip of the iceberg, Dr. Yan noted, since underlying bony defects or ectopic brain tissue may be present.

In such cases, magnetic resonance imaging is essential to rule out underlying abnormalities, including atretic encephaloceles or heterotopic brain tissue.

Pilomatricoma

A 15-month-old girl presented with a bump on her cheek—a firm, bluish, cystic papule that moved back and forth under pressure. When one end of the lesion was palpated, the other end would pop up, a phenomenon also known as a “teeter-totter sign.”

Although these lesions may resemble dermoid cysts or epidermal inclusion cysts, the diagnosis in this case was pilomatricoma, distinguished by its bluish color and the presence of the teeter-totter sign. The lesions most often occur on the head or neck, although other areas occasionally are affected. Pilomatricomas generally are solitary, benign, frequently calcified, and arise from hair follicles. In some cases, the lesions resolve spontaneously, but more often, they persist and grow, and surgical intervention is recommended. Pilomatricomas may rupture, which can cause inflammation and scarring. Although pilomatricomas generally are isolated findings, they may be associated with systemic disorders such as Gardner's syndrome, myotonic dystrophy, and sarcoidosis.

Annular Urticaria/Urticaria Multiforme

A 3-year-old girl presented with red, swollen, annular plaques on her skin, and had swollen hands and feet. She had been otherwise healthy and was taking no medications. The condition arose suddenly; the parents noticed the rings and swelling one morning when picking up the child from her bed. On closer inspection, the rings were red and blanchable, with clear white centers. Some were imperfect circles.

The diagnosis is annular urticaria. “These types of cases are frequently referred for suspected erythema multiforme,” Dr. Yan noted. “Lesions of annular urticaria are evanescent; the lesions fade and move, and the lesions can form imperfect circles with clear centers. The lesions may disappear within 24 hours, only to show up elsewhere,” he said. By contrast, erythema multiforme appears as fixed target, or “bull's-eye,” lesions with dusky centers and is associated with mucous membrane ulcers.

The two conditions are treated quite differently, Dr. Yan emphasized. Annular urticaria responds to combinations of antihistamines or occasionally steroids; erythema multiforme requires a detailed history to determine underlying causes, removal or treatment of those causes, and consideration of steroid therapy if indicated. Dr. Yan often refers to annular urticaria as “urticaria multiforme” because these cases are so regularly mistaken.

ORLANDO — Pediatric skin conditions often pose diagnostic challenges because many cutaneous disorders have similar clinical features.

Annular lesions of granuloma annulare may be mistaken for tinea corporis; follicular papules of keratosis pilaris may be confused with follicular eczema; and nail psoriasis may be misdiagnosed as onychomycosis.

At a meeting sponsored by the American Academy of Pediatrics, Albert C. Yan, M.D., director of pediatric dermatology at the Children's Hospital of Philadelphia, provided some helpful diagnostic tips for distinguishing some of these potentially puzzling skin problems.

The Hair Collar Sign

A boy is born with an area of localized, circular alopecia covered by a glossy membrane. The area is surrounded by a collection of dark, terminal hairs. Palpation reveals that a lump is present.

Occasionally mistaken for fetal scalp monitor trauma, neonatal herpes simplex infection, or a nevus sebaceus of Jadassohn, this characteristic pattern—a collar of coarse hair surrounding an area of membranous aplasia cutis congenita—can be a marker for cranial dysraphism, a developmental defect of the skull potentially associated with structural neurologic defects. The scalp defect may represent only the tip of the iceberg, Dr. Yan noted, since underlying bony defects or ectopic brain tissue may be present.

In such cases, magnetic resonance imaging is essential to rule out underlying abnormalities, including atretic encephaloceles or heterotopic brain tissue.

Pilomatricoma

A 15-month-old girl presented with a bump on her cheek—a firm, bluish, cystic papule that moved back and forth under pressure. When one end of the lesion was palpated, the other end would pop up, a phenomenon also known as a “teeter-totter sign.”

Although these lesions may resemble dermoid cysts or epidermal inclusion cysts, the diagnosis in this case was pilomatricoma, distinguished by its bluish color and the presence of the teeter-totter sign. The lesions most often occur on the head or neck, although other areas occasionally are affected. Pilomatricomas generally are solitary, benign, frequently calcified, and arise from hair follicles. In some cases, the lesions resolve spontaneously, but more often, they persist and grow, and surgical intervention is recommended. Pilomatricomas may rupture, which can cause inflammation and scarring. Although pilomatricomas generally are isolated findings, they may be associated with systemic disorders such as Gardner's syndrome, myotonic dystrophy, and sarcoidosis.

Annular Urticaria/Urticaria Multiforme

A 3-year-old girl presented with red, swollen, annular plaques on her skin, and had swollen hands and feet. She had been otherwise healthy and was taking no medications. The condition arose suddenly; the parents noticed the rings and swelling one morning when picking up the child from her bed. On closer inspection, the rings were red and blanchable, with clear white centers. Some were imperfect circles.

The diagnosis is annular urticaria. “These types of cases are frequently referred for suspected erythema multiforme,” Dr. Yan noted. “Lesions of annular urticaria are evanescent; the lesions fade and move, and the lesions can form imperfect circles with clear centers. The lesions may disappear within 24 hours, only to show up elsewhere,” he said. By contrast, erythema multiforme appears as fixed target, or “bull's-eye,” lesions with dusky centers and is associated with mucous membrane ulcers.

The two conditions are treated quite differently, Dr. Yan emphasized. Annular urticaria responds to combinations of antihistamines or occasionally steroids; erythema multiforme requires a detailed history to determine underlying causes, removal or treatment of those causes, and consideration of steroid therapy if indicated. Dr. Yan often refers to annular urticaria as “urticaria multiforme” because these cases are so regularly mistaken.

WASHINGTON — “Burning mouth syndrome,” a constellation of symptoms involving burning sensations of the tongue, palate, lips, and buccal mucosa, responds to transcranial magnetic stimulation and drugs that increase levels of γ-aminobutyric acid, Robert I. Henkin, M.D., said at the Clinical Research 2005 meeting.

The neurologic condition, which occurs late in adulthood, is most common among postmenopausal women. The specific exact etiology remains unknown.

Many primary care physicians are unfamiliar with the phenomenon of burning mouth syndrome, and tell patients that they are imagining things, or that they are simply anxious, said Dr. Henkin, director of the Taste and Smell Clinic, in Washington.

The study included 53 patients with burning mouth syndrome, 42 women and 11 men, aged 20–84 years. Dr. Henkin and radiologist Lucien Levy, M.D., of the George Washington University Medical Center, used magnetic resonance spectroscopy (MRS), specifically, a standard 2-dimensional J-point resolved excitation in the steady state (J-PRESS) sequence, to measure levels of γ-aminobutyric acid (GABA), glutamic acid, N-acetylaspartate, choline, and creatine in various regions of patients' brains.

Prior to treatment, patients with burning mouth syndrome had significantly lower levels of GABA compared with healthy volunteer controls who were age- and sex-matched to the patients, Dr. Henkin said at the meeting, which was sponsored by the American Federation for Medical Research.

Treatment with transcranial magnetic stimulation (TCMS) increased the GABA concentrations in the brain and relieved the burning sensations in 31 (68%) of the 46 treated patients. Their response suggests that the etiology of burning mouth syndrome lies in changes in a specific inhibitory neurotransmitter in the central nervous system.

For the TCMS treatment, the patients, acting as their own controls, received TCMS on each shoulder and the neck at levels of 0.2–0.4 Tesla (T), the unit used to measure magnetic field intensity prior to the application of TCMS to the head at the level of 1.1 T. The patients reported no changes in their burning mouth sensations at 0.2–0.4 T, but 31 of the 46 patients who received magnetic stimulation to the head at a level of 1.1 T reported improvement in the burning sensations.

The magnetic treatment had no apparent side effects, no associated pain, and relieved the burning feeling in a matter of hours or days, Dr. Henkin said in an interview. The main drawback is that some patients required more than one or two additional magnetic stimulation treatments to completely alleviate their burning symptoms.

The results of the study provide measurable evidence that brain GABA levels mirror patients' pain levels, going up or down with brain GABA levels as shown in the images of MR spectroscopy of brain neurotransmitters, which show a 2-dimensional spectrum of the inhibitory neurotransmitter GABA.

Pharmacologic treatment with GABA-ergic drugs may be helpful to patients who don't respond to magnetic stimulation. The dose and length of treatment with GABA-ergic drugs to lessen the pain of burning mouth vary widely among patients, said Dr. Henkin, reporting on his experience.

The results may be complicated by side effects. For a drug such as haloperidol, for example, doses may vary from 0.5 to 1.5 mg daily and patients may need to take them for 4–10 weeks to obtain an effect. In addition, patients often need a maintenance dose, which might range from 0.25 to 0.5 mg. By contrast, most patients treated with TCMS find long-term relief after a few sessions and approximately 20% experience relief within a week of a single treatment, Dr. Henkin said.

The patients in the poster study who did not respond to TCMS have been treated with GABA-ergic drugs, but this treatment is ongoing and the results have yet to be analyzed, Dr. Henkin said.

Drug therapy for burning mouth syndrome requires careful supervision and time, compared with the simple, rapid, and direct improvements associated with TCMS, he noted.

Dentists or primary care physicians are often at a loss as to how to treat patients' “dragon breath,” and burning sensations in the oral cavity, since there is no anatomic change in the tissue. When a patient presents with such complaints, consider a neurologic referral and an evaluation for GABA-related treatments.

For more information about the diagnosis and treatment of burning mouth syndrome and other taste and smell disorders, visit www.tasteandsmell.com

Dr. Robert I. Henkin and associates used MR spectroscopy to measure levels of the inhibitory neurotransmitter GABA. This image shows an example of pure GABA in a solution. Courtesy Dr. Lucien Levy

WASHINGTON — “Burning mouth syndrome,” a constellation of symptoms involving burning sensations of the tongue, palate, lips, and buccal mucosa, responds to transcranial magnetic stimulation and drugs that increase levels of γ-aminobutyric acid, Robert I. Henkin, M.D., said at the Clinical Research 2005 meeting.

The neurologic condition, which occurs late in adulthood, is most common among postmenopausal women. The specific exact etiology remains unknown.

Many primary care physicians are unfamiliar with the phenomenon of burning mouth syndrome, and tell patients that they are imagining things, or that they are simply anxious, said Dr. Henkin, director of the Taste and Smell Clinic, in Washington.

The study included 53 patients with burning mouth syndrome, 42 women and 11 men, aged 20–84 years. Dr. Henkin and radiologist Lucien Levy, M.D., of the George Washington University Medical Center, used magnetic resonance spectroscopy (MRS), specifically, a standard 2-dimensional J-point resolved excitation in the steady state (J-PRESS) sequence, to measure levels of γ-aminobutyric acid (GABA), glutamic acid, N-acetylaspartate, choline, and creatine in various regions of patients' brains.

Prior to treatment, patients with burning mouth syndrome had significantly lower levels of GABA compared with healthy volunteer controls who were age- and sex-matched to the patients, Dr. Henkin said at the meeting, which was sponsored by the American Federation for Medical Research.

Treatment with transcranial magnetic stimulation (TCMS) increased the GABA concentrations in the brain and relieved the burning sensations in 31 (68%) of the 46 treated patients. Their response suggests that the etiology of burning mouth syndrome lies in changes in a specific inhibitory neurotransmitter in the central nervous system.

For the TCMS treatment, the patients, acting as their own controls, received TCMS on each shoulder and the neck at levels of 0.2–0.4 Tesla (T), the unit used to measure magnetic field intensity prior to the application of TCMS to the head at the level of 1.1 T. The patients reported no changes in their burning mouth sensations at 0.2–0.4 T, but 31 of the 46 patients who received magnetic stimulation to the head at a level of 1.1 T reported improvement in the burning sensations.

The magnetic treatment had no apparent side effects, no associated pain, and relieved the burning feeling in a matter of hours or days, Dr. Henkin said in an interview. The main drawback is that some patients required more than one or two additional magnetic stimulation treatments to completely alleviate their burning symptoms.

The results of the study provide measurable evidence that brain GABA levels mirror patients' pain levels, going up or down with brain GABA levels as shown in the images of MR spectroscopy of brain neurotransmitters, which show a 2-dimensional spectrum of the inhibitory neurotransmitter GABA.

Pharmacologic treatment with GABA-ergic drugs may be helpful to patients who don't respond to magnetic stimulation. The dose and length of treatment with GABA-ergic drugs to lessen the pain of burning mouth vary widely among patients, said Dr. Henkin, reporting on his experience.

The results may be complicated by side effects. For a drug such as haloperidol, for example, doses may vary from 0.5 to 1.5 mg daily and patients may need to take them for 4–10 weeks to obtain an effect. In addition, patients often need a maintenance dose, which might range from 0.25 to 0.5 mg. By contrast, most patients treated with TCMS find long-term relief after a few sessions and approximately 20% experience relief within a week of a single treatment, Dr. Henkin said.

The patients in the poster study who did not respond to TCMS have been treated with GABA-ergic drugs, but this treatment is ongoing and the results have yet to be analyzed, Dr. Henkin said.

Drug therapy for burning mouth syndrome requires careful supervision and time, compared with the simple, rapid, and direct improvements associated with TCMS, he noted.

Dentists or primary care physicians are often at a loss as to how to treat patients' “dragon breath,” and burning sensations in the oral cavity, since there is no anatomic change in the tissue. When a patient presents with such complaints, consider a neurologic referral and an evaluation for GABA-related treatments.

For more information about the diagnosis and treatment of burning mouth syndrome and other taste and smell disorders, visit www.tasteandsmell.com

Dr. Robert I. Henkin and associates used MR spectroscopy to measure levels of the inhibitory neurotransmitter GABA. This image shows an example of pure GABA in a solution. Courtesy Dr. Lucien Levy

WASHINGTON — “Burning mouth syndrome,” a constellation of symptoms involving burning sensations of the tongue, palate, lips, and buccal mucosa, responds to transcranial magnetic stimulation and drugs that increase levels of γ-aminobutyric acid, Robert I. Henkin, M.D., said at the Clinical Research 2005 meeting.

The neurologic condition, which occurs late in adulthood, is most common among postmenopausal women. The specific exact etiology remains unknown.

Many primary care physicians are unfamiliar with the phenomenon of burning mouth syndrome, and tell patients that they are imagining things, or that they are simply anxious, said Dr. Henkin, director of the Taste and Smell Clinic, in Washington.

The study included 53 patients with burning mouth syndrome, 42 women and 11 men, aged 20–84 years. Dr. Henkin and radiologist Lucien Levy, M.D., of the George Washington University Medical Center, used magnetic resonance spectroscopy (MRS), specifically, a standard 2-dimensional J-point resolved excitation in the steady state (J-PRESS) sequence, to measure levels of γ-aminobutyric acid (GABA), glutamic acid, N-acetylaspartate, choline, and creatine in various regions of patients' brains.

Prior to treatment, patients with burning mouth syndrome had significantly lower levels of GABA compared with healthy volunteer controls who were age- and sex-matched to the patients, Dr. Henkin said at the meeting, which was sponsored by the American Federation for Medical Research.

Treatment with transcranial magnetic stimulation (TCMS) increased the GABA concentrations in the brain and relieved the burning sensations in 31 (68%) of the 46 treated patients. Their response suggests that the etiology of burning mouth syndrome lies in changes in a specific inhibitory neurotransmitter in the central nervous system.

For the TCMS treatment, the patients, acting as their own controls, received TCMS on each shoulder and the neck at levels of 0.2–0.4 Tesla (T), the unit used to measure magnetic field intensity prior to the application of TCMS to the head at the level of 1.1 T. The patients reported no changes in their burning mouth sensations at 0.2–0.4 T, but 31 of the 46 patients who received magnetic stimulation to the head at a level of 1.1 T reported improvement in the burning sensations.

The magnetic treatment had no apparent side effects, no associated pain, and relieved the burning feeling in a matter of hours or days, Dr. Henkin said in an interview. The main drawback is that some patients required more than one or two additional magnetic stimulation treatments to completely alleviate their burning symptoms.

The results of the study provide measurable evidence that brain GABA levels mirror patients' pain levels, going up or down with brain GABA levels as shown in the images of MR spectroscopy of brain neurotransmitters, which show a 2-dimensional spectrum of the inhibitory neurotransmitter GABA.

Pharmacologic treatment with GABA-ergic drugs may be helpful to patients who don't respond to magnetic stimulation. The dose and length of treatment with GABA-ergic drugs to lessen the pain of burning mouth vary widely among patients, said Dr. Henkin, reporting on his experience.

The results may be complicated by side effects. For a drug such as haloperidol, for example, doses may vary from 0.5 to 1.5 mg daily and patients may need to take them for 4–10 weeks to obtain an effect. In addition, patients often need a maintenance dose, which might range from 0.25 to 0.5 mg. By contrast, most patients treated with TCMS find long-term relief after a few sessions and approximately 20% experience relief within a week of a single treatment, Dr. Henkin said.

The patients in the poster study who did not respond to TCMS have been treated with GABA-ergic drugs, but this treatment is ongoing and the results have yet to be analyzed, Dr. Henkin said.

Drug therapy for burning mouth syndrome requires careful supervision and time, compared with the simple, rapid, and direct improvements associated with TCMS, he noted.

Dentists or primary care physicians are often at a loss as to how to treat patients' “dragon breath,” and burning sensations in the oral cavity, since there is no anatomic change in the tissue. When a patient presents with such complaints, consider a neurologic referral and an evaluation for GABA-related treatments.

For more information about the diagnosis and treatment of burning mouth syndrome and other taste and smell disorders, visit www.tasteandsmell.com

Dr. Robert I. Henkin and associates used MR spectroscopy to measure levels of the inhibitory neurotransmitter GABA. This image shows an example of pure GABA in a solution. Courtesy Dr. Lucien Levy

No significant relationship was found between routine childhood vaccines and hospitalizations for nontargeted infections in a population-based study of 805,206 children under 5 years old, said Anders Hviid, M.Sc., and colleagues at the Statens Serum Institut in Copenhagen.

The complex nature of current routine vaccinations has prompted concern that children might suffer immune dysfunction and become vulnerable to diseases not targeted by the vaccines (JAMA 2005; 294:699–705).

The population-based study examined six vaccines and seven infectious disease categories for a total of 42 possible associations. There was one adverse association during 2,900,463 person-years of follow-up that occurred between the Haemophilus influenzae type b vaccine and acute upper respiratory tract infections, with an incident rate ratio of 1.05.

There was one adverse association of the incident rate ratios for vaccinated children within the 14-day lag period relative to unvaccinated children that occurred between the MMR vaccine and acute upper respiratory tract infections, with a nonsignificant incident rate ratio of 1.10. None of the incident rate ratios increased by more than 10% between vaccinated and unvaccinated children. The increase in the incident rate of hospitalizations per dose of vaccine was calculated, and yielded an incident rate ratio of 0.94 for viral pneumonia, 0.96 for bacterial pneumonia, 0.98 for septicemia, 0.99 for viral CNS infections, 0.99 for diarrhea, 0.99 for acute upper respiratory tract infections, and 1.00 for bacterial meningitis.

Other vaccines studied were diphtheria-tetanus-inactivated poliovirus, diphtheria-tetanus-acellular pertussis-inactivated poliovirus, whole-cell pertussis, and oral poliovirus.

No significant relationship was found between routine childhood vaccines and hospitalizations for nontargeted infections in a population-based study of 805,206 children under 5 years old, said Anders Hviid, M.Sc., and colleagues at the Statens Serum Institut in Copenhagen.

The complex nature of current routine vaccinations has prompted concern that children might suffer immune dysfunction and become vulnerable to diseases not targeted by the vaccines (JAMA 2005; 294:699–705).

The population-based study examined six vaccines and seven infectious disease categories for a total of 42 possible associations. There was one adverse association during 2,900,463 person-years of follow-up that occurred between the Haemophilus influenzae type b vaccine and acute upper respiratory tract infections, with an incident rate ratio of 1.05.

There was one adverse association of the incident rate ratios for vaccinated children within the 14-day lag period relative to unvaccinated children that occurred between the MMR vaccine and acute upper respiratory tract infections, with a nonsignificant incident rate ratio of 1.10. None of the incident rate ratios increased by more than 10% between vaccinated and unvaccinated children. The increase in the incident rate of hospitalizations per dose of vaccine was calculated, and yielded an incident rate ratio of 0.94 for viral pneumonia, 0.96 for bacterial pneumonia, 0.98 for septicemia, 0.99 for viral CNS infections, 0.99 for diarrhea, 0.99 for acute upper respiratory tract infections, and 1.00 for bacterial meningitis.

Other vaccines studied were diphtheria-tetanus-inactivated poliovirus, diphtheria-tetanus-acellular pertussis-inactivated poliovirus, whole-cell pertussis, and oral poliovirus.

No significant relationship was found between routine childhood vaccines and hospitalizations for nontargeted infections in a population-based study of 805,206 children under 5 years old, said Anders Hviid, M.Sc., and colleagues at the Statens Serum Institut in Copenhagen.

The complex nature of current routine vaccinations has prompted concern that children might suffer immune dysfunction and become vulnerable to diseases not targeted by the vaccines (JAMA 2005; 294:699–705).

The population-based study examined six vaccines and seven infectious disease categories for a total of 42 possible associations. There was one adverse association during 2,900,463 person-years of follow-up that occurred between the Haemophilus influenzae type b vaccine and acute upper respiratory tract infections, with an incident rate ratio of 1.05.

There was one adverse association of the incident rate ratios for vaccinated children within the 14-day lag period relative to unvaccinated children that occurred between the MMR vaccine and acute upper respiratory tract infections, with a nonsignificant incident rate ratio of 1.10. None of the incident rate ratios increased by more than 10% between vaccinated and unvaccinated children. The increase in the incident rate of hospitalizations per dose of vaccine was calculated, and yielded an incident rate ratio of 0.94 for viral pneumonia, 0.96 for bacterial pneumonia, 0.98 for septicemia, 0.99 for viral CNS infections, 0.99 for diarrhea, 0.99 for acute upper respiratory tract infections, and 1.00 for bacterial meningitis.

Other vaccines studied were diphtheria-tetanus-inactivated poliovirus, diphtheria-tetanus-acellular pertussis-inactivated poliovirus, whole-cell pertussis, and oral poliovirus.