ADHD Drug Dosage Cut by Behavioral Therapy : The low level of side effects produced by lower doses could put behavior modification in the spotlight.

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WASHINGTON – Behavior modification can reduce the level of medication needed in school-aged children with attention-deficit hyperactivity disorder, William E. Pelham Jr., Ph.D., said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

Few studies have addressed the issue of how behavioral and pharmacologic therapies should be sequenced in children, said Dr. Pelham, a professor of pediatrics and psychiatry at the State University of New York, Buffalo.

Dr. Pelham and his colleagues have completed two studies funded by the National Institutes of Health that examined dosing and sequencing of behavior modification and medication. “We measured impairment–not core symptoms–because impairment is what you want to focus on; that is what causes the most problems for kids,” said Dr. Pelham, who is also a professor of psychology at the university.

The first study included 154 children aged 5–12 years (130 boys and 24 girls) who participated in a summer day camp program. They were divided for 3 weeks into three behavior modification groups–no behavior modification, low-intensity behavior modification, and high-intensity behavior modification. In addition, the children were divided into four dosage groups for methylphenidate (placebo, 0.15 mg/kg, 0.3 mg/kg, and 0.6 mg/kg, three times daily).

Medication was randomized each day, and the program counselors recorded the children's behavior in areas such as failing to comply with staff requests, following activity rules, and exhibiting conduct problems.

When the data were reviewed at summer's end, the lowest dose of medication–0.15 mg/kg three times daily–had a surprising and substantial effect on reducing ADHD impairment. In fact, the maximum incremental value of medication to behavior modification occurred at this low dose.

“There was no incremental value for most children beyond the 0.15-mg/kg dose in combination with behavior modification, but the highest dose–0.6 mg/kg–produced the largest effects in the absence of behavior modification,” Dr. Pelham said. This dosage normalized the largest number of children when combined with behavior modification. The effects of behavior modification alone and medication alone were comparable.

“Medication alone does not normalize the children's performance,” he explained. “Even at the highest dose of 0.6 mg/kg three times daily, many children were not normalized; the effect of behavior modification is as strong as the effect of medication.” Lower doses produce a substantially lower level of side effects–a benefit of using behavior modification as the first-line intervention.

Parents also evaluated the treatment conditions; they ranked a high level of behavior modification therapy, either alone or in combination with medication, as their first choice for managing ADHD, compared with medication alone or with a lower level of behavior modification alone.

The investigators conducted a follow-up study to assess the effectiveness of sequencing medication and behavior modification in a school setting. The primary outcome measure was the maintenance of acceptable behavior without medication after summer exposure to both medication and behavioral therapy.

The study included 128 of the children from the summer program who were randomly assigned to one of three groups. A total of 44 children received high behavior modification treatment, 43 received low behavior modification treatment, and 41 received no behavior modification treatment.

Overall, nearly twice the number of children who received some level of behavior modification remained off medication at school during the fall semester, compared with children who received no behavior modification (60% vs. 30%).

In addition, about 80% of children who had received behavior modification remained off medication at home. A caveat, however, was that almost all the children (75%) had been taking medication before enrollment in the summer study, which influenced their ability to remain unmedicated, Dr. Pelham noted.

Children who received no behavior modification started taking medication during the school day after 13 weeks, compared with 19 weeks for the low-intensity behavioral therapy group and 20 weeks for the high-intensity behavioral therapy group. Similarly, children who received no behavior modification therapy started taking medication at home after 27 weeks, compared with 38 weeks for the low behavior modification group and 32 weeks for the high behavior modification group.

Future research will include younger, medication-naive children, recruited at age 5–6 years, he said. “If we could use a low level of behavior modification therapy in this group, we may be able to keep them off medication,” Dr. Pelham said.

Dr. Pelham has been a consultant, scientific adviser, speaker, and grant recipient for the following companies: McNeil Consumer Healthcare/ALZA (developers and marketers of the methylphenidate product known as Concerta), Abbott, Shire, Noven, Eli Lilly, and Cephalon.

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WASHINGTON – Behavior modification can reduce the level of medication needed in school-aged children with attention-deficit hyperactivity disorder, William E. Pelham Jr., Ph.D., said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

Few studies have addressed the issue of how behavioral and pharmacologic therapies should be sequenced in children, said Dr. Pelham, a professor of pediatrics and psychiatry at the State University of New York, Buffalo.

Dr. Pelham and his colleagues have completed two studies funded by the National Institutes of Health that examined dosing and sequencing of behavior modification and medication. “We measured impairment–not core symptoms–because impairment is what you want to focus on; that is what causes the most problems for kids,” said Dr. Pelham, who is also a professor of psychology at the university.

The first study included 154 children aged 5–12 years (130 boys and 24 girls) who participated in a summer day camp program. They were divided for 3 weeks into three behavior modification groups–no behavior modification, low-intensity behavior modification, and high-intensity behavior modification. In addition, the children were divided into four dosage groups for methylphenidate (placebo, 0.15 mg/kg, 0.3 mg/kg, and 0.6 mg/kg, three times daily).

Medication was randomized each day, and the program counselors recorded the children's behavior in areas such as failing to comply with staff requests, following activity rules, and exhibiting conduct problems.

When the data were reviewed at summer's end, the lowest dose of medication–0.15 mg/kg three times daily–had a surprising and substantial effect on reducing ADHD impairment. In fact, the maximum incremental value of medication to behavior modification occurred at this low dose.

“There was no incremental value for most children beyond the 0.15-mg/kg dose in combination with behavior modification, but the highest dose–0.6 mg/kg–produced the largest effects in the absence of behavior modification,” Dr. Pelham said. This dosage normalized the largest number of children when combined with behavior modification. The effects of behavior modification alone and medication alone were comparable.

“Medication alone does not normalize the children's performance,” he explained. “Even at the highest dose of 0.6 mg/kg three times daily, many children were not normalized; the effect of behavior modification is as strong as the effect of medication.” Lower doses produce a substantially lower level of side effects–a benefit of using behavior modification as the first-line intervention.

Parents also evaluated the treatment conditions; they ranked a high level of behavior modification therapy, either alone or in combination with medication, as their first choice for managing ADHD, compared with medication alone or with a lower level of behavior modification alone.

The investigators conducted a follow-up study to assess the effectiveness of sequencing medication and behavior modification in a school setting. The primary outcome measure was the maintenance of acceptable behavior without medication after summer exposure to both medication and behavioral therapy.

The study included 128 of the children from the summer program who were randomly assigned to one of three groups. A total of 44 children received high behavior modification treatment, 43 received low behavior modification treatment, and 41 received no behavior modification treatment.

Overall, nearly twice the number of children who received some level of behavior modification remained off medication at school during the fall semester, compared with children who received no behavior modification (60% vs. 30%).

In addition, about 80% of children who had received behavior modification remained off medication at home. A caveat, however, was that almost all the children (75%) had been taking medication before enrollment in the summer study, which influenced their ability to remain unmedicated, Dr. Pelham noted.

Children who received no behavior modification started taking medication during the school day after 13 weeks, compared with 19 weeks for the low-intensity behavioral therapy group and 20 weeks for the high-intensity behavioral therapy group. Similarly, children who received no behavior modification therapy started taking medication at home after 27 weeks, compared with 38 weeks for the low behavior modification group and 32 weeks for the high behavior modification group.

Future research will include younger, medication-naive children, recruited at age 5–6 years, he said. “If we could use a low level of behavior modification therapy in this group, we may be able to keep them off medication,” Dr. Pelham said.

Dr. Pelham has been a consultant, scientific adviser, speaker, and grant recipient for the following companies: McNeil Consumer Healthcare/ALZA (developers and marketers of the methylphenidate product known as Concerta), Abbott, Shire, Noven, Eli Lilly, and Cephalon.

WASHINGTON – Behavior modification can reduce the level of medication needed in school-aged children with attention-deficit hyperactivity disorder, William E. Pelham Jr., Ph.D., said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

Few studies have addressed the issue of how behavioral and pharmacologic therapies should be sequenced in children, said Dr. Pelham, a professor of pediatrics and psychiatry at the State University of New York, Buffalo.

Dr. Pelham and his colleagues have completed two studies funded by the National Institutes of Health that examined dosing and sequencing of behavior modification and medication. “We measured impairment–not core symptoms–because impairment is what you want to focus on; that is what causes the most problems for kids,” said Dr. Pelham, who is also a professor of psychology at the university.

The first study included 154 children aged 5–12 years (130 boys and 24 girls) who participated in a summer day camp program. They were divided for 3 weeks into three behavior modification groups–no behavior modification, low-intensity behavior modification, and high-intensity behavior modification. In addition, the children were divided into four dosage groups for methylphenidate (placebo, 0.15 mg/kg, 0.3 mg/kg, and 0.6 mg/kg, three times daily).

Medication was randomized each day, and the program counselors recorded the children's behavior in areas such as failing to comply with staff requests, following activity rules, and exhibiting conduct problems.

When the data were reviewed at summer's end, the lowest dose of medication–0.15 mg/kg three times daily–had a surprising and substantial effect on reducing ADHD impairment. In fact, the maximum incremental value of medication to behavior modification occurred at this low dose.

“There was no incremental value for most children beyond the 0.15-mg/kg dose in combination with behavior modification, but the highest dose–0.6 mg/kg–produced the largest effects in the absence of behavior modification,” Dr. Pelham said. This dosage normalized the largest number of children when combined with behavior modification. The effects of behavior modification alone and medication alone were comparable.

“Medication alone does not normalize the children's performance,” he explained. “Even at the highest dose of 0.6 mg/kg three times daily, many children were not normalized; the effect of behavior modification is as strong as the effect of medication.” Lower doses produce a substantially lower level of side effects–a benefit of using behavior modification as the first-line intervention.

Parents also evaluated the treatment conditions; they ranked a high level of behavior modification therapy, either alone or in combination with medication, as their first choice for managing ADHD, compared with medication alone or with a lower level of behavior modification alone.

The investigators conducted a follow-up study to assess the effectiveness of sequencing medication and behavior modification in a school setting. The primary outcome measure was the maintenance of acceptable behavior without medication after summer exposure to both medication and behavioral therapy.

The study included 128 of the children from the summer program who were randomly assigned to one of three groups. A total of 44 children received high behavior modification treatment, 43 received low behavior modification treatment, and 41 received no behavior modification treatment.

Overall, nearly twice the number of children who received some level of behavior modification remained off medication at school during the fall semester, compared with children who received no behavior modification (60% vs. 30%).

In addition, about 80% of children who had received behavior modification remained off medication at home. A caveat, however, was that almost all the children (75%) had been taking medication before enrollment in the summer study, which influenced their ability to remain unmedicated, Dr. Pelham noted.

Children who received no behavior modification started taking medication during the school day after 13 weeks, compared with 19 weeks for the low-intensity behavioral therapy group and 20 weeks for the high-intensity behavioral therapy group. Similarly, children who received no behavior modification therapy started taking medication at home after 27 weeks, compared with 38 weeks for the low behavior modification group and 32 weeks for the high behavior modification group.

Future research will include younger, medication-naive children, recruited at age 5–6 years, he said. “If we could use a low level of behavior modification therapy in this group, we may be able to keep them off medication,” Dr. Pelham said.

Dr. Pelham has been a consultant, scientific adviser, speaker, and grant recipient for the following companies: McNeil Consumer Healthcare/ALZA (developers and marketers of the methylphenidate product known as Concerta), Abbott, Shire, Noven, Eli Lilly, and Cephalon.

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Antibiotic Resistance Doesn't Raise UTI Risk in Long-Term Care Patients

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WASHINGTON — Antibiotic resistance did not increase the number of nosocomial urinary tract infections among elderly patients in a long-term care facility, Dr. Walter Zingg reported in a poster presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Dr. Zingg, of the University Children's Hospital, and his colleagues at University Hospital, Zürich, tested urine samples for Escherichia coli to determine the impact of resistant E. coli on the development and outcome of UTIs in long-term care facility residents.

Prevalence studies were conducted from June 2002 to May 2004. The 80 patients with E. coli (mean age 86 years) and 91 controls (mean age 85 years) were observed for an average of 278 days and 365 days, respectively. Overall, 96% of the E. coli cases showed reduced susceptibility against combination amoxicillin/clavulanic acid, 55% showed reduced susceptibility against trimethoprim/sulfamethoxazole, 41% showed reduced susceptibility against norfloxacin, and 10% showed reduced susceptibility against ciprofloxacin.

Surprisingly, the level of resistance did not result in more frequent nosocomial infections, the investigators found. The incidence density (the estimated rate of occurrence of infection) was 3.3 per 1,000 days among patients with E. coli, compared with 3.2 per 1,000 days among controls.

The meeting was sponsored by the American Society for Microbiology.

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WASHINGTON — Antibiotic resistance did not increase the number of nosocomial urinary tract infections among elderly patients in a long-term care facility, Dr. Walter Zingg reported in a poster presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Dr. Zingg, of the University Children's Hospital, and his colleagues at University Hospital, Zürich, tested urine samples for Escherichia coli to determine the impact of resistant E. coli on the development and outcome of UTIs in long-term care facility residents.

Prevalence studies were conducted from June 2002 to May 2004. The 80 patients with E. coli (mean age 86 years) and 91 controls (mean age 85 years) were observed for an average of 278 days and 365 days, respectively. Overall, 96% of the E. coli cases showed reduced susceptibility against combination amoxicillin/clavulanic acid, 55% showed reduced susceptibility against trimethoprim/sulfamethoxazole, 41% showed reduced susceptibility against norfloxacin, and 10% showed reduced susceptibility against ciprofloxacin.

Surprisingly, the level of resistance did not result in more frequent nosocomial infections, the investigators found. The incidence density (the estimated rate of occurrence of infection) was 3.3 per 1,000 days among patients with E. coli, compared with 3.2 per 1,000 days among controls.

The meeting was sponsored by the American Society for Microbiology.

WASHINGTON — Antibiotic resistance did not increase the number of nosocomial urinary tract infections among elderly patients in a long-term care facility, Dr. Walter Zingg reported in a poster presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

Dr. Zingg, of the University Children's Hospital, and his colleagues at University Hospital, Zürich, tested urine samples for Escherichia coli to determine the impact of resistant E. coli on the development and outcome of UTIs in long-term care facility residents.

Prevalence studies were conducted from June 2002 to May 2004. The 80 patients with E. coli (mean age 86 years) and 91 controls (mean age 85 years) were observed for an average of 278 days and 365 days, respectively. Overall, 96% of the E. coli cases showed reduced susceptibility against combination amoxicillin/clavulanic acid, 55% showed reduced susceptibility against trimethoprim/sulfamethoxazole, 41% showed reduced susceptibility against norfloxacin, and 10% showed reduced susceptibility against ciprofloxacin.

Surprisingly, the level of resistance did not result in more frequent nosocomial infections, the investigators found. The incidence density (the estimated rate of occurrence of infection) was 3.3 per 1,000 days among patients with E. coli, compared with 3.2 per 1,000 days among controls.

The meeting was sponsored by the American Society for Microbiology.

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Regulatory Diligence Today May Keep OSHA Inspectors Away

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SAN DIEGO — The best way to avoid safety and quality violations is to stay abreast of guidelines prescribed by the Occupational Safety and Health Administration and by the Clinical Laboratory Improvement Amendments, Dr. Richard Hoang said at a meeting sponsored by the American Society for Mohs Surgery.

The lack of an up-to-date plan for control of blood-borne-pathogen exposure was among the most common violations for which Mohs surgeons were cited by OSHA during the period from January to August 2003, said Dr. Hoang, a dermatologist and dermatologic surgeon in private practice in San Diego.

"There are always unusually high fines for blood-borne-pathogen-exposure control-plan citations, so make sure yours is updated annually," Dr. Hoang said.

OSHA inspections are typically prompted by complaints or accidents. If an OSHA citation is given, there is always an opportunity to contest the violation, he noted.

In addition to the need for a blood-borne-pathogen-exposure control plan, OSHA guidelines that are particularly relevant to Mohs surgery practices include those on the identification of hazardous materials in the office. OSHA requires a safety data sheet for each chemical. Also, surgeons who work with hazardous materials must label all chemical containers and, when transferring chemicals to other containers, make sure all transfer containers reflect the original information about the chemical, Dr. Hoang said.

The Clinical Laboratory Improvement Amendments (CLIA), first published in 1992, were prompted by the poor quality of Pap smear results produced by large laboratories. CLIA classifies laboratory tests based on levels of complexity, and ranks Mohs histopathology tests as highly complex, Dr. Hoang said. Because of that ranking, Mohs practices must apply for a certificate, pay the required fees, and participate in proficiency testing.

The manual includes directions for performing tests. "All you have to do is make any revisions to the basic manual that are specific to your lab, and update it annually," Dr. Hoang explained.

In the section on specimen collection and handling, for example, Mohs surgeons should note that the surgeon will correlate the tissue with the Mohs map. Any tests performed should be documented with a test requisition in the patient's chart. In addition to this required documentation, Dr. Hoang recommends keeping a special Mohs log with the patient's name, the site worked on, and the number of slides to help the surgeon create an operative report.

Quality control in a Mohs practice—defined as the monitoring of testing procedures to achieve accurate, consistent results—also falls under CLIA requirements. To achieve accurate, consistent results, confirm the quality and sterility of reagents and record the expiration dates and lot numbers. Document the cleaning and maintenance of microscopes and report the daily temperature of the cryostat. The cryostat should be cleaned regularly.

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SAN DIEGO — The best way to avoid safety and quality violations is to stay abreast of guidelines prescribed by the Occupational Safety and Health Administration and by the Clinical Laboratory Improvement Amendments, Dr. Richard Hoang said at a meeting sponsored by the American Society for Mohs Surgery.

The lack of an up-to-date plan for control of blood-borne-pathogen exposure was among the most common violations for which Mohs surgeons were cited by OSHA during the period from January to August 2003, said Dr. Hoang, a dermatologist and dermatologic surgeon in private practice in San Diego.

"There are always unusually high fines for blood-borne-pathogen-exposure control-plan citations, so make sure yours is updated annually," Dr. Hoang said.

OSHA inspections are typically prompted by complaints or accidents. If an OSHA citation is given, there is always an opportunity to contest the violation, he noted.

In addition to the need for a blood-borne-pathogen-exposure control plan, OSHA guidelines that are particularly relevant to Mohs surgery practices include those on the identification of hazardous materials in the office. OSHA requires a safety data sheet for each chemical. Also, surgeons who work with hazardous materials must label all chemical containers and, when transferring chemicals to other containers, make sure all transfer containers reflect the original information about the chemical, Dr. Hoang said.

The Clinical Laboratory Improvement Amendments (CLIA), first published in 1992, were prompted by the poor quality of Pap smear results produced by large laboratories. CLIA classifies laboratory tests based on levels of complexity, and ranks Mohs histopathology tests as highly complex, Dr. Hoang said. Because of that ranking, Mohs practices must apply for a certificate, pay the required fees, and participate in proficiency testing.

The manual includes directions for performing tests. "All you have to do is make any revisions to the basic manual that are specific to your lab, and update it annually," Dr. Hoang explained.

In the section on specimen collection and handling, for example, Mohs surgeons should note that the surgeon will correlate the tissue with the Mohs map. Any tests performed should be documented with a test requisition in the patient's chart. In addition to this required documentation, Dr. Hoang recommends keeping a special Mohs log with the patient's name, the site worked on, and the number of slides to help the surgeon create an operative report.

Quality control in a Mohs practice—defined as the monitoring of testing procedures to achieve accurate, consistent results—also falls under CLIA requirements. To achieve accurate, consistent results, confirm the quality and sterility of reagents and record the expiration dates and lot numbers. Document the cleaning and maintenance of microscopes and report the daily temperature of the cryostat. The cryostat should be cleaned regularly.

SAN DIEGO — The best way to avoid safety and quality violations is to stay abreast of guidelines prescribed by the Occupational Safety and Health Administration and by the Clinical Laboratory Improvement Amendments, Dr. Richard Hoang said at a meeting sponsored by the American Society for Mohs Surgery.

The lack of an up-to-date plan for control of blood-borne-pathogen exposure was among the most common violations for which Mohs surgeons were cited by OSHA during the period from January to August 2003, said Dr. Hoang, a dermatologist and dermatologic surgeon in private practice in San Diego.

"There are always unusually high fines for blood-borne-pathogen-exposure control-plan citations, so make sure yours is updated annually," Dr. Hoang said.

OSHA inspections are typically prompted by complaints or accidents. If an OSHA citation is given, there is always an opportunity to contest the violation, he noted.

In addition to the need for a blood-borne-pathogen-exposure control plan, OSHA guidelines that are particularly relevant to Mohs surgery practices include those on the identification of hazardous materials in the office. OSHA requires a safety data sheet for each chemical. Also, surgeons who work with hazardous materials must label all chemical containers and, when transferring chemicals to other containers, make sure all transfer containers reflect the original information about the chemical, Dr. Hoang said.

The Clinical Laboratory Improvement Amendments (CLIA), first published in 1992, were prompted by the poor quality of Pap smear results produced by large laboratories. CLIA classifies laboratory tests based on levels of complexity, and ranks Mohs histopathology tests as highly complex, Dr. Hoang said. Because of that ranking, Mohs practices must apply for a certificate, pay the required fees, and participate in proficiency testing.

The manual includes directions for performing tests. "All you have to do is make any revisions to the basic manual that are specific to your lab, and update it annually," Dr. Hoang explained.

In the section on specimen collection and handling, for example, Mohs surgeons should note that the surgeon will correlate the tissue with the Mohs map. Any tests performed should be documented with a test requisition in the patient's chart. In addition to this required documentation, Dr. Hoang recommends keeping a special Mohs log with the patient's name, the site worked on, and the number of slides to help the surgeon create an operative report.

Quality control in a Mohs practice—defined as the monitoring of testing procedures to achieve accurate, consistent results—also falls under CLIA requirements. To achieve accurate, consistent results, confirm the quality and sterility of reagents and record the expiration dates and lot numbers. Document the cleaning and maintenance of microscopes and report the daily temperature of the cryostat. The cryostat should be cleaned regularly.

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Creative Customization Makes Offices Mohs Ready

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SAN DIEGO — Most Mohs surgeons don't have the luxury of designing an ideal office from scratch—they must work with their preexisting office space, said Dr. James Del Rosso at a meeting sponsored by the American Society for Mohs Surgery.

Think of the acronym SPACE: Skills, Personnel, Area, Coordination, and Equipment, said Dr. Del Rosso of the University of Nevada, Las Vegas.

Skills. To succeed as a Mohs surgeon, build on your basic surgical skills, and remember to start slow, small, and safe, Dr. Del Rosso said. Mohs involves a change in surgical technique with regard to removing skin cancer; the difference is in the conceptualization of lesion removal. Mohs surgeons consider tangential margin control, which calls for a different approach than a standard surgical excision. A dermatology residency, attendance at Mohs surgery courses, and observation of Mohs colleagues during procedures will help refine your skills.

Personnel. Educate the office staff about Mohs surgery, what it involves, and why you have decided to offer it. Consider cross-training staff members so that they know how to cut tissue sections if the regular technician calls in sick, for example. Division of responsibility is crucial. You will also need to hire laboratory staff. Designate individuals for certain paperwork responsibilities, including logs on patient care and on instrument maintenance, and designate backup staff for all duties. In addition, educate staff about anatomical landmarks. "Make sure that everyone who is documenting procedures uses the same terminology," Dr. Del Rosso said. Also, train patients to be observers, and notice other problems.

Define office procedures, and document them in office manuals. "I recommend having someone in the office put together a short 'Cliff's Notes' version of one or two pages with highlights of the basic office procedures," he said.

Area. Ideally, a Mohs surgeon can design an office space to specifications, but most surgeons work with the space they have. However, a standard surgical room that will be used for Mohs surgery should have eyewash stations, appropriately sized adjustable chairs for both the doctor and patient, and step stools for nurses or other staff who need a higher view of the procedures. If you have a step stool, make this rule: The person who uses it moves it out of the way when he or she is done. Kick buckets—buckets on wheels that can be moved with the feet while the surgeon is gloved during a procedure—are extremely helpful in a Mohs surgical suite.

Coordination. Think about how the patients, the staff, and the specimens will flow through the office. A separate waiting room is ideal, but a separate section of the waiting room is the next best thing. Be sure that staff members know which patients are waiting between surgical sections, and that these patients are monitored and kept comfortable. "These patients will be waiting with bandages between layers, they may bleed and contaminate other patients, or they could faint, or become vasovagal," Dr. Del Rosso said.

Equipment. The equipment for Mohs is expensive, and equipment maintenance goes without saying. "It is penny wise and pound foolish not to buy good surgical tools," Dr. Del Rosso said. "The way to save money is to make sure that equipment is properly cared for in the future." Establishing a Mohs laboratory—with its unique processing of specimens and methods of record keeping—is one of the biggest challenges for beginning Mohs surgeons, as is interpreting the sections.

"I would plan for two cryostats, even if you don't have two in the beginning," he said. "You will also need to allow for an inking station." Use color-coded glass slides for different stages to help keep samples organized.

Keep a prepared tray with the entire collection of surgical equipment ready, including small cups with saline and peroxide to soak the instruments between sections. Make sure the trays are organized so that the instruments are easy to locate, and discourage staff from tossing gauze on the trays and obscuring the instruments. "Hemostats should be on every tray, whether it is a repair tray or a Mohs tray," Dr. Del Rosso noted.

His favorite instruments include tenotomy scissors, Bishop-Harmon forceps, and blunt-edged dedicated undermining scissors. Some surgeons use sharp scissors for undermining.

Although many surgeons use disposable blades, Dr. Del Rosso recommends purchasing good quality blades and either sharpening them on-site or sending them out for regular sharpening. "If your knives aren't kept sharp, you will have problems with the quality of your sections," he explained. Reusable blades are more cost effective and allow the surgeon greater control over the blade quality.

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SAN DIEGO — Most Mohs surgeons don't have the luxury of designing an ideal office from scratch—they must work with their preexisting office space, said Dr. James Del Rosso at a meeting sponsored by the American Society for Mohs Surgery.

Think of the acronym SPACE: Skills, Personnel, Area, Coordination, and Equipment, said Dr. Del Rosso of the University of Nevada, Las Vegas.

Skills. To succeed as a Mohs surgeon, build on your basic surgical skills, and remember to start slow, small, and safe, Dr. Del Rosso said. Mohs involves a change in surgical technique with regard to removing skin cancer; the difference is in the conceptualization of lesion removal. Mohs surgeons consider tangential margin control, which calls for a different approach than a standard surgical excision. A dermatology residency, attendance at Mohs surgery courses, and observation of Mohs colleagues during procedures will help refine your skills.

Personnel. Educate the office staff about Mohs surgery, what it involves, and why you have decided to offer it. Consider cross-training staff members so that they know how to cut tissue sections if the regular technician calls in sick, for example. Division of responsibility is crucial. You will also need to hire laboratory staff. Designate individuals for certain paperwork responsibilities, including logs on patient care and on instrument maintenance, and designate backup staff for all duties. In addition, educate staff about anatomical landmarks. "Make sure that everyone who is documenting procedures uses the same terminology," Dr. Del Rosso said. Also, train patients to be observers, and notice other problems.

Define office procedures, and document them in office manuals. "I recommend having someone in the office put together a short 'Cliff's Notes' version of one or two pages with highlights of the basic office procedures," he said.

Area. Ideally, a Mohs surgeon can design an office space to specifications, but most surgeons work with the space they have. However, a standard surgical room that will be used for Mohs surgery should have eyewash stations, appropriately sized adjustable chairs for both the doctor and patient, and step stools for nurses or other staff who need a higher view of the procedures. If you have a step stool, make this rule: The person who uses it moves it out of the way when he or she is done. Kick buckets—buckets on wheels that can be moved with the feet while the surgeon is gloved during a procedure—are extremely helpful in a Mohs surgical suite.

Coordination. Think about how the patients, the staff, and the specimens will flow through the office. A separate waiting room is ideal, but a separate section of the waiting room is the next best thing. Be sure that staff members know which patients are waiting between surgical sections, and that these patients are monitored and kept comfortable. "These patients will be waiting with bandages between layers, they may bleed and contaminate other patients, or they could faint, or become vasovagal," Dr. Del Rosso said.

Equipment. The equipment for Mohs is expensive, and equipment maintenance goes without saying. "It is penny wise and pound foolish not to buy good surgical tools," Dr. Del Rosso said. "The way to save money is to make sure that equipment is properly cared for in the future." Establishing a Mohs laboratory—with its unique processing of specimens and methods of record keeping—is one of the biggest challenges for beginning Mohs surgeons, as is interpreting the sections.

"I would plan for two cryostats, even if you don't have two in the beginning," he said. "You will also need to allow for an inking station." Use color-coded glass slides for different stages to help keep samples organized.

Keep a prepared tray with the entire collection of surgical equipment ready, including small cups with saline and peroxide to soak the instruments between sections. Make sure the trays are organized so that the instruments are easy to locate, and discourage staff from tossing gauze on the trays and obscuring the instruments. "Hemostats should be on every tray, whether it is a repair tray or a Mohs tray," Dr. Del Rosso noted.

His favorite instruments include tenotomy scissors, Bishop-Harmon forceps, and blunt-edged dedicated undermining scissors. Some surgeons use sharp scissors for undermining.

Although many surgeons use disposable blades, Dr. Del Rosso recommends purchasing good quality blades and either sharpening them on-site or sending them out for regular sharpening. "If your knives aren't kept sharp, you will have problems with the quality of your sections," he explained. Reusable blades are more cost effective and allow the surgeon greater control over the blade quality.

SAN DIEGO — Most Mohs surgeons don't have the luxury of designing an ideal office from scratch—they must work with their preexisting office space, said Dr. James Del Rosso at a meeting sponsored by the American Society for Mohs Surgery.

Think of the acronym SPACE: Skills, Personnel, Area, Coordination, and Equipment, said Dr. Del Rosso of the University of Nevada, Las Vegas.

Skills. To succeed as a Mohs surgeon, build on your basic surgical skills, and remember to start slow, small, and safe, Dr. Del Rosso said. Mohs involves a change in surgical technique with regard to removing skin cancer; the difference is in the conceptualization of lesion removal. Mohs surgeons consider tangential margin control, which calls for a different approach than a standard surgical excision. A dermatology residency, attendance at Mohs surgery courses, and observation of Mohs colleagues during procedures will help refine your skills.

Personnel. Educate the office staff about Mohs surgery, what it involves, and why you have decided to offer it. Consider cross-training staff members so that they know how to cut tissue sections if the regular technician calls in sick, for example. Division of responsibility is crucial. You will also need to hire laboratory staff. Designate individuals for certain paperwork responsibilities, including logs on patient care and on instrument maintenance, and designate backup staff for all duties. In addition, educate staff about anatomical landmarks. "Make sure that everyone who is documenting procedures uses the same terminology," Dr. Del Rosso said. Also, train patients to be observers, and notice other problems.

Define office procedures, and document them in office manuals. "I recommend having someone in the office put together a short 'Cliff's Notes' version of one or two pages with highlights of the basic office procedures," he said.

Area. Ideally, a Mohs surgeon can design an office space to specifications, but most surgeons work with the space they have. However, a standard surgical room that will be used for Mohs surgery should have eyewash stations, appropriately sized adjustable chairs for both the doctor and patient, and step stools for nurses or other staff who need a higher view of the procedures. If you have a step stool, make this rule: The person who uses it moves it out of the way when he or she is done. Kick buckets—buckets on wheels that can be moved with the feet while the surgeon is gloved during a procedure—are extremely helpful in a Mohs surgical suite.

Coordination. Think about how the patients, the staff, and the specimens will flow through the office. A separate waiting room is ideal, but a separate section of the waiting room is the next best thing. Be sure that staff members know which patients are waiting between surgical sections, and that these patients are monitored and kept comfortable. "These patients will be waiting with bandages between layers, they may bleed and contaminate other patients, or they could faint, or become vasovagal," Dr. Del Rosso said.

Equipment. The equipment for Mohs is expensive, and equipment maintenance goes without saying. "It is penny wise and pound foolish not to buy good surgical tools," Dr. Del Rosso said. "The way to save money is to make sure that equipment is properly cared for in the future." Establishing a Mohs laboratory—with its unique processing of specimens and methods of record keeping—is one of the biggest challenges for beginning Mohs surgeons, as is interpreting the sections.

"I would plan for two cryostats, even if you don't have two in the beginning," he said. "You will also need to allow for an inking station." Use color-coded glass slides for different stages to help keep samples organized.

Keep a prepared tray with the entire collection of surgical equipment ready, including small cups with saline and peroxide to soak the instruments between sections. Make sure the trays are organized so that the instruments are easy to locate, and discourage staff from tossing gauze on the trays and obscuring the instruments. "Hemostats should be on every tray, whether it is a repair tray or a Mohs tray," Dr. Del Rosso noted.

His favorite instruments include tenotomy scissors, Bishop-Harmon forceps, and blunt-edged dedicated undermining scissors. Some surgeons use sharp scissors for undermining.

Although many surgeons use disposable blades, Dr. Del Rosso recommends purchasing good quality blades and either sharpening them on-site or sending them out for regular sharpening. "If your knives aren't kept sharp, you will have problems with the quality of your sections," he explained. Reusable blades are more cost effective and allow the surgeon greater control over the blade quality.

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Parental Mood Disorder Packs a One-Two Punch for Children

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WASHINGTON — The role of parental depression is not a consistent, equivalent risk factor for youth depression, Benjamin L. Hankin, Ph.D., said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

Parental depression affects children in two main ways, Dr. Hankin noted. First, children can be exposed to such high levels of stress due to parental depression that the children's normal coping skills cannot handle the initial stress and hence they develop depressive symptoms when confronted with additional outside stressors.

Second, depressed parents model poor skills for coping with stress, which leaves the child susceptible to depressive symptoms in the face of additional stress.

The extent to which parental depression is a risk factor for youth depression depends on the contextual domain of the stressor, said Dr. Hankin, of the University of South Carolina, Columbia.

Dr. Hankin and associates conducted a longitudinal study of 421 8th- and 10th-grade students from 18 suburban Chicago high schools. About 55% were female, and 87% were white. The youth were evaluated at baseline, 6 months, and 12 months.

The results were based on reports from both the parents and the youths. The data included self-report questionnaires and a 7-day reporting of events at each of the three measurement times using a daily diary in which the youth recorded the worst events of each day. Entries ranged from dropping books in the hallway and receiving poor test grades to fighting with a girlfriend or being kicked out of school.

The researchers analyzed the responses and divided the events into categories of interpersonal stressors, such as family, romantic, peer, and athletic. Parental depressive symptoms interacted with youth stressors to increase the odds of depression in the youth when the interpersonal stressors fell into the family or romantic categories, Dr. Hankin said.

Parental depressive symptoms also contributed to poor coping skills among youth. These poor coping skills, when combined with stressors in the family or romantic categories, left the youth more vulnerable to depressive symptoms, Dr. Hankin said.

The results were consistent with the limited studies on depressive symptoms in youths whose parents are depressed.

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WASHINGTON — The role of parental depression is not a consistent, equivalent risk factor for youth depression, Benjamin L. Hankin, Ph.D., said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

Parental depression affects children in two main ways, Dr. Hankin noted. First, children can be exposed to such high levels of stress due to parental depression that the children's normal coping skills cannot handle the initial stress and hence they develop depressive symptoms when confronted with additional outside stressors.

Second, depressed parents model poor skills for coping with stress, which leaves the child susceptible to depressive symptoms in the face of additional stress.

The extent to which parental depression is a risk factor for youth depression depends on the contextual domain of the stressor, said Dr. Hankin, of the University of South Carolina, Columbia.

Dr. Hankin and associates conducted a longitudinal study of 421 8th- and 10th-grade students from 18 suburban Chicago high schools. About 55% were female, and 87% were white. The youth were evaluated at baseline, 6 months, and 12 months.

The results were based on reports from both the parents and the youths. The data included self-report questionnaires and a 7-day reporting of events at each of the three measurement times using a daily diary in which the youth recorded the worst events of each day. Entries ranged from dropping books in the hallway and receiving poor test grades to fighting with a girlfriend or being kicked out of school.

The researchers analyzed the responses and divided the events into categories of interpersonal stressors, such as family, romantic, peer, and athletic. Parental depressive symptoms interacted with youth stressors to increase the odds of depression in the youth when the interpersonal stressors fell into the family or romantic categories, Dr. Hankin said.

Parental depressive symptoms also contributed to poor coping skills among youth. These poor coping skills, when combined with stressors in the family or romantic categories, left the youth more vulnerable to depressive symptoms, Dr. Hankin said.

The results were consistent with the limited studies on depressive symptoms in youths whose parents are depressed.

WASHINGTON — The role of parental depression is not a consistent, equivalent risk factor for youth depression, Benjamin L. Hankin, Ph.D., said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

Parental depression affects children in two main ways, Dr. Hankin noted. First, children can be exposed to such high levels of stress due to parental depression that the children's normal coping skills cannot handle the initial stress and hence they develop depressive symptoms when confronted with additional outside stressors.

Second, depressed parents model poor skills for coping with stress, which leaves the child susceptible to depressive symptoms in the face of additional stress.

The extent to which parental depression is a risk factor for youth depression depends on the contextual domain of the stressor, said Dr. Hankin, of the University of South Carolina, Columbia.

Dr. Hankin and associates conducted a longitudinal study of 421 8th- and 10th-grade students from 18 suburban Chicago high schools. About 55% were female, and 87% were white. The youth were evaluated at baseline, 6 months, and 12 months.

The results were based on reports from both the parents and the youths. The data included self-report questionnaires and a 7-day reporting of events at each of the three measurement times using a daily diary in which the youth recorded the worst events of each day. Entries ranged from dropping books in the hallway and receiving poor test grades to fighting with a girlfriend or being kicked out of school.

The researchers analyzed the responses and divided the events into categories of interpersonal stressors, such as family, romantic, peer, and athletic. Parental depressive symptoms interacted with youth stressors to increase the odds of depression in the youth when the interpersonal stressors fell into the family or romantic categories, Dr. Hankin said.

Parental depressive symptoms also contributed to poor coping skills among youth. These poor coping skills, when combined with stressors in the family or romantic categories, left the youth more vulnerable to depressive symptoms, Dr. Hankin said.

The results were consistent with the limited studies on depressive symptoms in youths whose parents are depressed.

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For Teens Who Are 'Best Pals,' Depression Can Be Catching

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WASHINGTON — Depression in a best friend was significantly associated with the development of depressive symptoms in adolescents under conditions of social anxiety, Mitchell Prinstein, Ph.D., said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

Peer relationships during adolescence are characterized by high levels of emotional disclosure and intimacy. Adolescents often use feedback from peers, and their perceived standing among peers is a primary source of their own identity, said Dr. Prinstein of the University of North Carolina, Chapel Hill.

Previous research has shown that adolescents and their friends have remarkably similar characteristics, both concurrently and longitudinally.

Adolescents are likely to choose friends with similar social and psychological characteristics, attitudes, and behavior preferences, and previous research has shown that exposure to these friends extends these similar attitudes and behaviors longitudinally.

Dr. Prinstein and his colleagues studied 100 community-dwelling adolescents, each of whom chose a friend who was also in the data set. No friend was allowed to be selected more than once. The mean age was 16 years at baseline, and 60% were female.

Among girls, a best friend's depression as reported by that friend was associated with depression in the primary adolescent under conditions of social anxiety. Among boys, a lesser level of friendship intimacy was associated with a greater level of association between a best friend's depression and the development of depressive symptoms in the primary adolescent. Among both girls and boys, the higher the level of the best friend's popularity, as rated by peers, the stronger the association between depression in that best friend and the development of depressive symptoms in the primary adolescent.

The results support previous studies of the relevance of peer contagion as a potential contributor to depression in adolescents. “Interventions should not seek to detach teens from relationships, but [should] work to influence adolescent resilience by moderating factors such as anxiety,” Dr. Prinstein said. “Getting adolescents to change who their friends are is generally unsuccessful.”

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WASHINGTON — Depression in a best friend was significantly associated with the development of depressive symptoms in adolescents under conditions of social anxiety, Mitchell Prinstein, Ph.D., said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

Peer relationships during adolescence are characterized by high levels of emotional disclosure and intimacy. Adolescents often use feedback from peers, and their perceived standing among peers is a primary source of their own identity, said Dr. Prinstein of the University of North Carolina, Chapel Hill.

Previous research has shown that adolescents and their friends have remarkably similar characteristics, both concurrently and longitudinally.

Adolescents are likely to choose friends with similar social and psychological characteristics, attitudes, and behavior preferences, and previous research has shown that exposure to these friends extends these similar attitudes and behaviors longitudinally.

Dr. Prinstein and his colleagues studied 100 community-dwelling adolescents, each of whom chose a friend who was also in the data set. No friend was allowed to be selected more than once. The mean age was 16 years at baseline, and 60% were female.

Among girls, a best friend's depression as reported by that friend was associated with depression in the primary adolescent under conditions of social anxiety. Among boys, a lesser level of friendship intimacy was associated with a greater level of association between a best friend's depression and the development of depressive symptoms in the primary adolescent. Among both girls and boys, the higher the level of the best friend's popularity, as rated by peers, the stronger the association between depression in that best friend and the development of depressive symptoms in the primary adolescent.

The results support previous studies of the relevance of peer contagion as a potential contributor to depression in adolescents. “Interventions should not seek to detach teens from relationships, but [should] work to influence adolescent resilience by moderating factors such as anxiety,” Dr. Prinstein said. “Getting adolescents to change who their friends are is generally unsuccessful.”

WASHINGTON — Depression in a best friend was significantly associated with the development of depressive symptoms in adolescents under conditions of social anxiety, Mitchell Prinstein, Ph.D., said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

Peer relationships during adolescence are characterized by high levels of emotional disclosure and intimacy. Adolescents often use feedback from peers, and their perceived standing among peers is a primary source of their own identity, said Dr. Prinstein of the University of North Carolina, Chapel Hill.

Previous research has shown that adolescents and their friends have remarkably similar characteristics, both concurrently and longitudinally.

Adolescents are likely to choose friends with similar social and psychological characteristics, attitudes, and behavior preferences, and previous research has shown that exposure to these friends extends these similar attitudes and behaviors longitudinally.

Dr. Prinstein and his colleagues studied 100 community-dwelling adolescents, each of whom chose a friend who was also in the data set. No friend was allowed to be selected more than once. The mean age was 16 years at baseline, and 60% were female.

Among girls, a best friend's depression as reported by that friend was associated with depression in the primary adolescent under conditions of social anxiety. Among boys, a lesser level of friendship intimacy was associated with a greater level of association between a best friend's depression and the development of depressive symptoms in the primary adolescent. Among both girls and boys, the higher the level of the best friend's popularity, as rated by peers, the stronger the association between depression in that best friend and the development of depressive symptoms in the primary adolescent.

The results support previous studies of the relevance of peer contagion as a potential contributor to depression in adolescents. “Interventions should not seek to detach teens from relationships, but [should] work to influence adolescent resilience by moderating factors such as anxiety,” Dr. Prinstein said. “Getting adolescents to change who their friends are is generally unsuccessful.”

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Vaccine for Human Papillomavirus Prevents Genital Warts, Cervical Ca

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WASHINGTON — A human papillomavirus vaccine developed by Merck & Co. is 100% effective in preventing genital warts in women in addition to preventing cervical cancer, Dr. John T. Schiller reported at the annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy.

The vaccine, known as Gardasil, includes HPV types 6, 11, 16, and 18. Types 16 and 18 account for about 70% of cervical cancer, and types 6 and 11 account for about 90% of genital warts, said Dr. Schiller, head of the neoplastic disease section of the National Cancer Institute, Bethesda, Md.

At 2 years of follow-up, Gardasil achieved 100% efficacy against genital warts, vulvar neoplasia, and vaginal neoplasia, in addition to the previously reported 100% efficacy against cervical intraepithelial neoplasia (CIN). The phase II Females United to Unilaterally Reduce Endo-Ectocervical Disease study (FUTURE I) included 2,717 women randomized to a vaccine group and 2,725 randomized to a placebo group. Overall, there were no cases of genital warts in the vaccine group, compared with 40 cases in the placebo group.

Dr. Schiller also shared the latest findings from the FUTURE II study, a randomized, double-blind, phase III clinical trial that included about 12,000 women aged 18–25 years. The intent-to-treat numbers in the FUTURE II study showed extremely strong protection at 2 years of follow-up—only two cases of CIN grade 2 or 3—and the vaccine was generally well tolerated. One case of CIN was associated with HPV type 16, and the other was associated with a combination of types 16 and 18. The phase III studies are ongoing, and the data remain under review, but findings similar to those from the phase II study are expected with regard to genital warts and vulvar and vaginal neoplasia.

Merck filed its Gardasil data with the Food and Drug Administration on Dec. 1, 2005, and a vaccine could be available in the United States by late summer in 2006, Dr. Schiller said. GlaxoSmithKline Inc. has stated that it will seek regulatory approval in 2006 for its vaccine, Cervarix, which immunizes against HPV 16 and 18, but that it might seek initial approval in Europe.

Once the vaccine becomes available, the top candidates for immunization will be 10- to 13-year-old girls. “They are the ideal first targets because presumably, they have not yet been exposed to sexually transmitted viruses,” Dr. Schiller said at the meeting, sponsored by the American Society for Microbiology.

But before the vaccine becomes standard for young girls, it may be used in young women because of the high demand in that population, he noted. Some adult women may not have been exposed to the oncogenic strains of HPV, and vaccination may reduce transmission to their partners as well. An HPV vaccine has yet to be tested in men, but only 10% of HPV cancers occur in men, and high vaccination coverage of women may result in sufficient herd immunity, Dr. Schiller noted.

The HPV vaccines are based on purified viruslike particles (VLPs) that consist of single proteins. They are noninfectious and nononcogenic, but they can induce high titres of neutralizing antibodies, Dr. Schiller said.

Despite the promising results, several questions about HPV vaccination remain unresolved, including effects on current cancer screening programs, public acceptance, price, and distribution to underserved populations.

“Women might think that they are protected from cervical cancer because they have the vaccine, and abandon their screening programs, which would be a disaster,” Dr. Schiller said. Vaccination would not replace the need for a pap test, he emphasized, although it might reduce the incidence of repeat pap tests resulting from unclear results.

Vaccine acceptance is another issue, but preliminary surveys of parents suggest that as many as 75% would agree to vaccination of their adolescent daughters. But the logistics of delivering three intramuscular doses of vaccine to early adolescent girls over a 6-month period may prove challenging, Dr. Schiller added.

The price of the vaccine is critical to how many women and girls receive it. It is likely to be expensive at first, “perhaps as much as $100 per dose,” Dr. Schiller said.

Price is a huge barrier to providing the HPV vaccine to the underserved women who need it most. “Cervical cancer is a disease of poverty—80% of cases occur in developing countries where women don't have access to good quality pap screening,” Dr. Schiller noted. “This vaccine will not have the impact it should if the only women who are vaccinated are those who already get good cervical cancer screening.”

Regional production might be the best way to build up the amount of the vaccine and reduce the cost. In addition, researchers continue to investigate a second-generation vaccine that could be administered orally.

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WASHINGTON — A human papillomavirus vaccine developed by Merck & Co. is 100% effective in preventing genital warts in women in addition to preventing cervical cancer, Dr. John T. Schiller reported at the annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy.

The vaccine, known as Gardasil, includes HPV types 6, 11, 16, and 18. Types 16 and 18 account for about 70% of cervical cancer, and types 6 and 11 account for about 90% of genital warts, said Dr. Schiller, head of the neoplastic disease section of the National Cancer Institute, Bethesda, Md.

At 2 years of follow-up, Gardasil achieved 100% efficacy against genital warts, vulvar neoplasia, and vaginal neoplasia, in addition to the previously reported 100% efficacy against cervical intraepithelial neoplasia (CIN). The phase II Females United to Unilaterally Reduce Endo-Ectocervical Disease study (FUTURE I) included 2,717 women randomized to a vaccine group and 2,725 randomized to a placebo group. Overall, there were no cases of genital warts in the vaccine group, compared with 40 cases in the placebo group.

Dr. Schiller also shared the latest findings from the FUTURE II study, a randomized, double-blind, phase III clinical trial that included about 12,000 women aged 18–25 years. The intent-to-treat numbers in the FUTURE II study showed extremely strong protection at 2 years of follow-up—only two cases of CIN grade 2 or 3—and the vaccine was generally well tolerated. One case of CIN was associated with HPV type 16, and the other was associated with a combination of types 16 and 18. The phase III studies are ongoing, and the data remain under review, but findings similar to those from the phase II study are expected with regard to genital warts and vulvar and vaginal neoplasia.

Merck filed its Gardasil data with the Food and Drug Administration on Dec. 1, 2005, and a vaccine could be available in the United States by late summer in 2006, Dr. Schiller said. GlaxoSmithKline Inc. has stated that it will seek regulatory approval in 2006 for its vaccine, Cervarix, which immunizes against HPV 16 and 18, but that it might seek initial approval in Europe.

Once the vaccine becomes available, the top candidates for immunization will be 10- to 13-year-old girls. “They are the ideal first targets because presumably, they have not yet been exposed to sexually transmitted viruses,” Dr. Schiller said at the meeting, sponsored by the American Society for Microbiology.

But before the vaccine becomes standard for young girls, it may be used in young women because of the high demand in that population, he noted. Some adult women may not have been exposed to the oncogenic strains of HPV, and vaccination may reduce transmission to their partners as well. An HPV vaccine has yet to be tested in men, but only 10% of HPV cancers occur in men, and high vaccination coverage of women may result in sufficient herd immunity, Dr. Schiller noted.

The HPV vaccines are based on purified viruslike particles (VLPs) that consist of single proteins. They are noninfectious and nononcogenic, but they can induce high titres of neutralizing antibodies, Dr. Schiller said.

Despite the promising results, several questions about HPV vaccination remain unresolved, including effects on current cancer screening programs, public acceptance, price, and distribution to underserved populations.

“Women might think that they are protected from cervical cancer because they have the vaccine, and abandon their screening programs, which would be a disaster,” Dr. Schiller said. Vaccination would not replace the need for a pap test, he emphasized, although it might reduce the incidence of repeat pap tests resulting from unclear results.

Vaccine acceptance is another issue, but preliminary surveys of parents suggest that as many as 75% would agree to vaccination of their adolescent daughters. But the logistics of delivering three intramuscular doses of vaccine to early adolescent girls over a 6-month period may prove challenging, Dr. Schiller added.

The price of the vaccine is critical to how many women and girls receive it. It is likely to be expensive at first, “perhaps as much as $100 per dose,” Dr. Schiller said.

Price is a huge barrier to providing the HPV vaccine to the underserved women who need it most. “Cervical cancer is a disease of poverty—80% of cases occur in developing countries where women don't have access to good quality pap screening,” Dr. Schiller noted. “This vaccine will not have the impact it should if the only women who are vaccinated are those who already get good cervical cancer screening.”

Regional production might be the best way to build up the amount of the vaccine and reduce the cost. In addition, researchers continue to investigate a second-generation vaccine that could be administered orally.

WASHINGTON — A human papillomavirus vaccine developed by Merck & Co. is 100% effective in preventing genital warts in women in addition to preventing cervical cancer, Dr. John T. Schiller reported at the annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy.

The vaccine, known as Gardasil, includes HPV types 6, 11, 16, and 18. Types 16 and 18 account for about 70% of cervical cancer, and types 6 and 11 account for about 90% of genital warts, said Dr. Schiller, head of the neoplastic disease section of the National Cancer Institute, Bethesda, Md.

At 2 years of follow-up, Gardasil achieved 100% efficacy against genital warts, vulvar neoplasia, and vaginal neoplasia, in addition to the previously reported 100% efficacy against cervical intraepithelial neoplasia (CIN). The phase II Females United to Unilaterally Reduce Endo-Ectocervical Disease study (FUTURE I) included 2,717 women randomized to a vaccine group and 2,725 randomized to a placebo group. Overall, there were no cases of genital warts in the vaccine group, compared with 40 cases in the placebo group.

Dr. Schiller also shared the latest findings from the FUTURE II study, a randomized, double-blind, phase III clinical trial that included about 12,000 women aged 18–25 years. The intent-to-treat numbers in the FUTURE II study showed extremely strong protection at 2 years of follow-up—only two cases of CIN grade 2 or 3—and the vaccine was generally well tolerated. One case of CIN was associated with HPV type 16, and the other was associated with a combination of types 16 and 18. The phase III studies are ongoing, and the data remain under review, but findings similar to those from the phase II study are expected with regard to genital warts and vulvar and vaginal neoplasia.

Merck filed its Gardasil data with the Food and Drug Administration on Dec. 1, 2005, and a vaccine could be available in the United States by late summer in 2006, Dr. Schiller said. GlaxoSmithKline Inc. has stated that it will seek regulatory approval in 2006 for its vaccine, Cervarix, which immunizes against HPV 16 and 18, but that it might seek initial approval in Europe.

Once the vaccine becomes available, the top candidates for immunization will be 10- to 13-year-old girls. “They are the ideal first targets because presumably, they have not yet been exposed to sexually transmitted viruses,” Dr. Schiller said at the meeting, sponsored by the American Society for Microbiology.

But before the vaccine becomes standard for young girls, it may be used in young women because of the high demand in that population, he noted. Some adult women may not have been exposed to the oncogenic strains of HPV, and vaccination may reduce transmission to their partners as well. An HPV vaccine has yet to be tested in men, but only 10% of HPV cancers occur in men, and high vaccination coverage of women may result in sufficient herd immunity, Dr. Schiller noted.

The HPV vaccines are based on purified viruslike particles (VLPs) that consist of single proteins. They are noninfectious and nononcogenic, but they can induce high titres of neutralizing antibodies, Dr. Schiller said.

Despite the promising results, several questions about HPV vaccination remain unresolved, including effects on current cancer screening programs, public acceptance, price, and distribution to underserved populations.

“Women might think that they are protected from cervical cancer because they have the vaccine, and abandon their screening programs, which would be a disaster,” Dr. Schiller said. Vaccination would not replace the need for a pap test, he emphasized, although it might reduce the incidence of repeat pap tests resulting from unclear results.

Vaccine acceptance is another issue, but preliminary surveys of parents suggest that as many as 75% would agree to vaccination of their adolescent daughters. But the logistics of delivering three intramuscular doses of vaccine to early adolescent girls over a 6-month period may prove challenging, Dr. Schiller added.

The price of the vaccine is critical to how many women and girls receive it. It is likely to be expensive at first, “perhaps as much as $100 per dose,” Dr. Schiller said.

Price is a huge barrier to providing the HPV vaccine to the underserved women who need it most. “Cervical cancer is a disease of poverty—80% of cases occur in developing countries where women don't have access to good quality pap screening,” Dr. Schiller noted. “This vaccine will not have the impact it should if the only women who are vaccinated are those who already get good cervical cancer screening.”

Regional production might be the best way to build up the amount of the vaccine and reduce the cost. In addition, researchers continue to investigate a second-generation vaccine that could be administered orally.

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Shunts, Chills, MRSA History Can Flag Bacteremic Patients

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WASHINGTON — Three clinical characteristics—arteriovenous shunts or grafts, history of methicillin-resistant Staphylococcus aureus, and the presence of chills—were significantly associated with S. aureus bacteremia in a study of 1,015 patients, Dr. Zeina A. Kanafani reported in a poster presented at the annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy.

The findings may facilitate earlier detection of infection and encourage the timely initiation of antibiotics in bacteremic patients, noted Dr. Kanafani and her colleagues at Duke University Medical Center in Durham, N.C.

Data were collected from hospitalized patients aged 18 years and older with fevers of at least 38° C who underwent blood cultures between December 2003 and December 2004. A total of 235 patients (23%) had positive blood cultures; 76 were excluded from the study due to possible culture contamination.

Of the remaining 159 patients (7.7% of the original patient population), 78 had S. aureus bacteremia; the other 81 patients grew organisms including Candida species, Enterococcus species, and Bacteroides species.

Overall, 15 (19%) of patients with S. aureus bacteremia had histories of S. aureus infection, compared with 42 (5%) of the 780 patients whose blood cultures were negative for bacteremia. In addition, 25 (32%) of bacteremia patients had an arteriovenous shunt or graft, compared with 74 (10%) of culture-negative patients, and 34 (44%) of bacteremia patients suffered from chills, compared with 126 (16%) of the culture-negative patients.

In a subgroup of 829 nonhemodialysis patients, 45 (5%) had S. aureus bacteremia, and these patients were significantly more likely to have a tunneled-cuff catheter and a history of methicillin-resistant S. aureus.

The meeting was sponsored by the American Society for Microbiology.

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WASHINGTON — Three clinical characteristics—arteriovenous shunts or grafts, history of methicillin-resistant Staphylococcus aureus, and the presence of chills—were significantly associated with S. aureus bacteremia in a study of 1,015 patients, Dr. Zeina A. Kanafani reported in a poster presented at the annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy.

The findings may facilitate earlier detection of infection and encourage the timely initiation of antibiotics in bacteremic patients, noted Dr. Kanafani and her colleagues at Duke University Medical Center in Durham, N.C.

Data were collected from hospitalized patients aged 18 years and older with fevers of at least 38° C who underwent blood cultures between December 2003 and December 2004. A total of 235 patients (23%) had positive blood cultures; 76 were excluded from the study due to possible culture contamination.

Of the remaining 159 patients (7.7% of the original patient population), 78 had S. aureus bacteremia; the other 81 patients grew organisms including Candida species, Enterococcus species, and Bacteroides species.

Overall, 15 (19%) of patients with S. aureus bacteremia had histories of S. aureus infection, compared with 42 (5%) of the 780 patients whose blood cultures were negative for bacteremia. In addition, 25 (32%) of bacteremia patients had an arteriovenous shunt or graft, compared with 74 (10%) of culture-negative patients, and 34 (44%) of bacteremia patients suffered from chills, compared with 126 (16%) of the culture-negative patients.

In a subgroup of 829 nonhemodialysis patients, 45 (5%) had S. aureus bacteremia, and these patients were significantly more likely to have a tunneled-cuff catheter and a history of methicillin-resistant S. aureus.

The meeting was sponsored by the American Society for Microbiology.

WASHINGTON — Three clinical characteristics—arteriovenous shunts or grafts, history of methicillin-resistant Staphylococcus aureus, and the presence of chills—were significantly associated with S. aureus bacteremia in a study of 1,015 patients, Dr. Zeina A. Kanafani reported in a poster presented at the annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy.

The findings may facilitate earlier detection of infection and encourage the timely initiation of antibiotics in bacteremic patients, noted Dr. Kanafani and her colleagues at Duke University Medical Center in Durham, N.C.

Data were collected from hospitalized patients aged 18 years and older with fevers of at least 38° C who underwent blood cultures between December 2003 and December 2004. A total of 235 patients (23%) had positive blood cultures; 76 were excluded from the study due to possible culture contamination.

Of the remaining 159 patients (7.7% of the original patient population), 78 had S. aureus bacteremia; the other 81 patients grew organisms including Candida species, Enterococcus species, and Bacteroides species.

Overall, 15 (19%) of patients with S. aureus bacteremia had histories of S. aureus infection, compared with 42 (5%) of the 780 patients whose blood cultures were negative for bacteremia. In addition, 25 (32%) of bacteremia patients had an arteriovenous shunt or graft, compared with 74 (10%) of culture-negative patients, and 34 (44%) of bacteremia patients suffered from chills, compared with 126 (16%) of the culture-negative patients.

In a subgroup of 829 nonhemodialysis patients, 45 (5%) had S. aureus bacteremia, and these patients were significantly more likely to have a tunneled-cuff catheter and a history of methicillin-resistant S. aureus.

The meeting was sponsored by the American Society for Microbiology.

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Resistant Staph Often Present In Long-Term Care Centers

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WASHINGTON — The percentage of Staphylococcus aureus isolates resistant to methicillin was about 68% in a survey of more than 100 long-term care facilities, Susan Beekmann, R.N., M.P.H., reported in a poster presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

This “extraordinarily high” rate was higher than the documented MRSA rates from surveys of acute care hospitals nationwide, noted Ms. Beekmann and her colleagues at the University of Iowa, Iowa City.

The multicenter, longitudinal surveillance study included 1,060 S. aureus and 1,979 Enterococcus isolates collected from long-term care facilities across the United States during three 1-year periods from 1999 to 2004, Dr. Beekmann reported. The S. aureus isolates included 325 skin or soft tissue specimens, 489 urine specimens, and 246 other specimens. The Enterococcus isolates included 81 skin or soft tissue specimens, 1,835 urine specimens, and 63 other specimens.

The MRSA rate remained fairly stable (66%–71%) throughout the study period. By contrast, the overall infection rate of vancomycin-resistant enterococcus was relatively low (5%), and ranged from 4% in 1999 to 7% in 2003. No evidence of VRE was found in any of the skin or soft tissue isolates, the investigators noted.

Only five MRSA isolates showed no coresistances to other antibiotics. An additional 22 were resistant to ciprofloxacin only; these 22 were also susceptible to clindamycin. Only two of the Enterococcus isolates were linezolid resistant, and eight were intermediate resistant to linezolid, whereas none of the S. aureus isolates was resistant to linezolid.

The meeting was sponsored by the American Society for Microbiology.

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WASHINGTON — The percentage of Staphylococcus aureus isolates resistant to methicillin was about 68% in a survey of more than 100 long-term care facilities, Susan Beekmann, R.N., M.P.H., reported in a poster presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

This “extraordinarily high” rate was higher than the documented MRSA rates from surveys of acute care hospitals nationwide, noted Ms. Beekmann and her colleagues at the University of Iowa, Iowa City.

The multicenter, longitudinal surveillance study included 1,060 S. aureus and 1,979 Enterococcus isolates collected from long-term care facilities across the United States during three 1-year periods from 1999 to 2004, Dr. Beekmann reported. The S. aureus isolates included 325 skin or soft tissue specimens, 489 urine specimens, and 246 other specimens. The Enterococcus isolates included 81 skin or soft tissue specimens, 1,835 urine specimens, and 63 other specimens.

The MRSA rate remained fairly stable (66%–71%) throughout the study period. By contrast, the overall infection rate of vancomycin-resistant enterococcus was relatively low (5%), and ranged from 4% in 1999 to 7% in 2003. No evidence of VRE was found in any of the skin or soft tissue isolates, the investigators noted.

Only five MRSA isolates showed no coresistances to other antibiotics. An additional 22 were resistant to ciprofloxacin only; these 22 were also susceptible to clindamycin. Only two of the Enterococcus isolates were linezolid resistant, and eight were intermediate resistant to linezolid, whereas none of the S. aureus isolates was resistant to linezolid.

The meeting was sponsored by the American Society for Microbiology.

WASHINGTON — The percentage of Staphylococcus aureus isolates resistant to methicillin was about 68% in a survey of more than 100 long-term care facilities, Susan Beekmann, R.N., M.P.H., reported in a poster presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

This “extraordinarily high” rate was higher than the documented MRSA rates from surveys of acute care hospitals nationwide, noted Ms. Beekmann and her colleagues at the University of Iowa, Iowa City.

The multicenter, longitudinal surveillance study included 1,060 S. aureus and 1,979 Enterococcus isolates collected from long-term care facilities across the United States during three 1-year periods from 1999 to 2004, Dr. Beekmann reported. The S. aureus isolates included 325 skin or soft tissue specimens, 489 urine specimens, and 246 other specimens. The Enterococcus isolates included 81 skin or soft tissue specimens, 1,835 urine specimens, and 63 other specimens.

The MRSA rate remained fairly stable (66%–71%) throughout the study period. By contrast, the overall infection rate of vancomycin-resistant enterococcus was relatively low (5%), and ranged from 4% in 1999 to 7% in 2003. No evidence of VRE was found in any of the skin or soft tissue isolates, the investigators noted.

Only five MRSA isolates showed no coresistances to other antibiotics. An additional 22 were resistant to ciprofloxacin only; these 22 were also susceptible to clindamycin. Only two of the Enterococcus isolates were linezolid resistant, and eight were intermediate resistant to linezolid, whereas none of the S. aureus isolates was resistant to linezolid.

The meeting was sponsored by the American Society for Microbiology.

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Vaccine Effective Against hMPV

Lower respiratory tract infections associated with human metapneumovirus were reduced by 45%, and clinical pneumonia was reduced by 55% among non-HIV-infected children who had received at least three doses of 9-valent conjugate pneumococcal vaccine, Dr. Shabir A. Madhi reported in a poster presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The randomized, placebo-controlled study enrolled nearly 40,000 children in South Africa between March 1998 and October 2000. The children received the first dose of vaccine at approximately 6 weeks of age and two additional doses at approximately 11 and 16 weeks of age.

In addition, lower respiratory tract infections due to hMPV and clinical pneumonia were reduced by 53% and 65%, respectively, among HIV-infected children who had been fully vaccinated, wrote Dr. Madhi of the University of the Witwatersrand, Soweto, South Africa, and associates.

Overall, 1,533 vaccinated children were hospitalized with a lower respiratory tract infection, compared with 1,643 placebo patients between January 1, 2000 and December 31, 2002. Of these, 1,306 vaccinated patients and 1,409 placebo patients were successfully tested for hMPV, which was identified in 76 (5.8%) and 126 (8.9%) cases, respectively.

Of the 189 hMPV-associated lower respiratory tract infections in which blood was cultured, only four HIV-infected children experienced episodes of Staphylococcus aureus bacteremia. One of the children had been vaccinated, and the other three were in the placebo group. The results suggest that bacterial coinfection with pneumococcus plays a role in hMPV-associated lower respiratory tract infections, and that use of the pneumococcal conjugate vaccine may prevent a significant number of these infections, the investigators said at the meeting, also sponsored by the American Society for Microbiology.

hMPV Contributes to URIs

Human metapneumovirus appeared in 5% of 2,384 nasal wash specimens from infants and children with upper respiratory tract infections, reported Dr. John V. Williams of Vanderbilt University, Nashville, Tenn., and his colleagues.

The Vanderbilt Vaccine Clinic conducted the study to evaluate the clinical characteristics of human metapneumovirus (hMPV) in otherwise healthy children over a period of 20 years (J. Infect. Dis. 2006;193:387–95). Most of the illnesses (78%) occurred between December and May of each year from January 1982 through December 2001, with 38% occurring in March and April. During the study period, 1,532 children, mean age 20 months, were followed for an average of 2.4 years.

Fifty percent of the children with upper respiratory infections (URIs) were prescribed antibiotics for acute otitis media.

Children who presented with URIs caused by hMPV were significantly less likely to be febrile, compared with children with influenza (54% vs. 85%). The mean duration of symptoms in the sick children prior to medical attention was 2.7 days for hMPV infection, compared with 3.2 days for influenza, 4.3 days for respiratory syncytial virus, and 3.8 days for parainfluenza virus. Children with URIs caused by hMPV also presented with standard symptoms including cough and rhinorrhea. However, these symptoms were not useful in diagnosis because of the overlap among the pathogens, and rapid tests are needed to distinguish hMPV from the influenza virus, respiratory syncytial virus, and parainfluenza virus.

Predictive Model of Lyme Meningitis

Three conditions—the presence of cranial neuritis, a long-lasting headache, and a predominance of cerebral spinal fluid mononuclear cells—can predict Lyme meningitis in children aged 2–13 years, said Dr. Robert A. Avery of the Alfred I. duPont Hospital for Children in Wilmington, Del., and his colleagues.

Data from a study of 27 children with Lyme meningitis (LM) and 148 children with aseptic meningitis (AM) provide the first model to distinguish between the two conditions in areas where Lyme disease is endemic (Pediatrics 2006;117:1–7).

Overall, 16 of the 27 (59%) patients with LM experienced headaches longer than 3 days' duration, compared with 37 of 148 (25%) patients with AM. The average duration of headache was 7.5 days among LM patients vs. 2.8 days among AM patients.

In addition, 15 (56%) of the LM patients had cranial neuritis, compared with 5 (3%) of the AM patients.

Finally, the average percentage of mononuclear cells in samples of cerebrospinal fluid was 87% in LM patients vs. 58% in AM patients, and 19 (70%) of the LM patients had CSF mononuclear cell levels greater than 86% compared with 42 (28%) of the AM patients.

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Vaccine Effective Against hMPV

Lower respiratory tract infections associated with human metapneumovirus were reduced by 45%, and clinical pneumonia was reduced by 55% among non-HIV-infected children who had received at least three doses of 9-valent conjugate pneumococcal vaccine, Dr. Shabir A. Madhi reported in a poster presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The randomized, placebo-controlled study enrolled nearly 40,000 children in South Africa between March 1998 and October 2000. The children received the first dose of vaccine at approximately 6 weeks of age and two additional doses at approximately 11 and 16 weeks of age.

In addition, lower respiratory tract infections due to hMPV and clinical pneumonia were reduced by 53% and 65%, respectively, among HIV-infected children who had been fully vaccinated, wrote Dr. Madhi of the University of the Witwatersrand, Soweto, South Africa, and associates.

Overall, 1,533 vaccinated children were hospitalized with a lower respiratory tract infection, compared with 1,643 placebo patients between January 1, 2000 and December 31, 2002. Of these, 1,306 vaccinated patients and 1,409 placebo patients were successfully tested for hMPV, which was identified in 76 (5.8%) and 126 (8.9%) cases, respectively.

Of the 189 hMPV-associated lower respiratory tract infections in which blood was cultured, only four HIV-infected children experienced episodes of Staphylococcus aureus bacteremia. One of the children had been vaccinated, and the other three were in the placebo group. The results suggest that bacterial coinfection with pneumococcus plays a role in hMPV-associated lower respiratory tract infections, and that use of the pneumococcal conjugate vaccine may prevent a significant number of these infections, the investigators said at the meeting, also sponsored by the American Society for Microbiology.

hMPV Contributes to URIs

Human metapneumovirus appeared in 5% of 2,384 nasal wash specimens from infants and children with upper respiratory tract infections, reported Dr. John V. Williams of Vanderbilt University, Nashville, Tenn., and his colleagues.

The Vanderbilt Vaccine Clinic conducted the study to evaluate the clinical characteristics of human metapneumovirus (hMPV) in otherwise healthy children over a period of 20 years (J. Infect. Dis. 2006;193:387–95). Most of the illnesses (78%) occurred between December and May of each year from January 1982 through December 2001, with 38% occurring in March and April. During the study period, 1,532 children, mean age 20 months, were followed for an average of 2.4 years.

Fifty percent of the children with upper respiratory infections (URIs) were prescribed antibiotics for acute otitis media.

Children who presented with URIs caused by hMPV were significantly less likely to be febrile, compared with children with influenza (54% vs. 85%). The mean duration of symptoms in the sick children prior to medical attention was 2.7 days for hMPV infection, compared with 3.2 days for influenza, 4.3 days for respiratory syncytial virus, and 3.8 days for parainfluenza virus. Children with URIs caused by hMPV also presented with standard symptoms including cough and rhinorrhea. However, these symptoms were not useful in diagnosis because of the overlap among the pathogens, and rapid tests are needed to distinguish hMPV from the influenza virus, respiratory syncytial virus, and parainfluenza virus.

Predictive Model of Lyme Meningitis

Three conditions—the presence of cranial neuritis, a long-lasting headache, and a predominance of cerebral spinal fluid mononuclear cells—can predict Lyme meningitis in children aged 2–13 years, said Dr. Robert A. Avery of the Alfred I. duPont Hospital for Children in Wilmington, Del., and his colleagues.

Data from a study of 27 children with Lyme meningitis (LM) and 148 children with aseptic meningitis (AM) provide the first model to distinguish between the two conditions in areas where Lyme disease is endemic (Pediatrics 2006;117:1–7).

Overall, 16 of the 27 (59%) patients with LM experienced headaches longer than 3 days' duration, compared with 37 of 148 (25%) patients with AM. The average duration of headache was 7.5 days among LM patients vs. 2.8 days among AM patients.

In addition, 15 (56%) of the LM patients had cranial neuritis, compared with 5 (3%) of the AM patients.

Finally, the average percentage of mononuclear cells in samples of cerebrospinal fluid was 87% in LM patients vs. 58% in AM patients, and 19 (70%) of the LM patients had CSF mononuclear cell levels greater than 86% compared with 42 (28%) of the AM patients.

Vaccine Effective Against hMPV

Lower respiratory tract infections associated with human metapneumovirus were reduced by 45%, and clinical pneumonia was reduced by 55% among non-HIV-infected children who had received at least three doses of 9-valent conjugate pneumococcal vaccine, Dr. Shabir A. Madhi reported in a poster presented at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.

The randomized, placebo-controlled study enrolled nearly 40,000 children in South Africa between March 1998 and October 2000. The children received the first dose of vaccine at approximately 6 weeks of age and two additional doses at approximately 11 and 16 weeks of age.

In addition, lower respiratory tract infections due to hMPV and clinical pneumonia were reduced by 53% and 65%, respectively, among HIV-infected children who had been fully vaccinated, wrote Dr. Madhi of the University of the Witwatersrand, Soweto, South Africa, and associates.

Overall, 1,533 vaccinated children were hospitalized with a lower respiratory tract infection, compared with 1,643 placebo patients between January 1, 2000 and December 31, 2002. Of these, 1,306 vaccinated patients and 1,409 placebo patients were successfully tested for hMPV, which was identified in 76 (5.8%) and 126 (8.9%) cases, respectively.

Of the 189 hMPV-associated lower respiratory tract infections in which blood was cultured, only four HIV-infected children experienced episodes of Staphylococcus aureus bacteremia. One of the children had been vaccinated, and the other three were in the placebo group. The results suggest that bacterial coinfection with pneumococcus plays a role in hMPV-associated lower respiratory tract infections, and that use of the pneumococcal conjugate vaccine may prevent a significant number of these infections, the investigators said at the meeting, also sponsored by the American Society for Microbiology.

hMPV Contributes to URIs

Human metapneumovirus appeared in 5% of 2,384 nasal wash specimens from infants and children with upper respiratory tract infections, reported Dr. John V. Williams of Vanderbilt University, Nashville, Tenn., and his colleagues.

The Vanderbilt Vaccine Clinic conducted the study to evaluate the clinical characteristics of human metapneumovirus (hMPV) in otherwise healthy children over a period of 20 years (J. Infect. Dis. 2006;193:387–95). Most of the illnesses (78%) occurred between December and May of each year from January 1982 through December 2001, with 38% occurring in March and April. During the study period, 1,532 children, mean age 20 months, were followed for an average of 2.4 years.

Fifty percent of the children with upper respiratory infections (URIs) were prescribed antibiotics for acute otitis media.

Children who presented with URIs caused by hMPV were significantly less likely to be febrile, compared with children with influenza (54% vs. 85%). The mean duration of symptoms in the sick children prior to medical attention was 2.7 days for hMPV infection, compared with 3.2 days for influenza, 4.3 days for respiratory syncytial virus, and 3.8 days for parainfluenza virus. Children with URIs caused by hMPV also presented with standard symptoms including cough and rhinorrhea. However, these symptoms were not useful in diagnosis because of the overlap among the pathogens, and rapid tests are needed to distinguish hMPV from the influenza virus, respiratory syncytial virus, and parainfluenza virus.

Predictive Model of Lyme Meningitis

Three conditions—the presence of cranial neuritis, a long-lasting headache, and a predominance of cerebral spinal fluid mononuclear cells—can predict Lyme meningitis in children aged 2–13 years, said Dr. Robert A. Avery of the Alfred I. duPont Hospital for Children in Wilmington, Del., and his colleagues.

Data from a study of 27 children with Lyme meningitis (LM) and 148 children with aseptic meningitis (AM) provide the first model to distinguish between the two conditions in areas where Lyme disease is endemic (Pediatrics 2006;117:1–7).

Overall, 16 of the 27 (59%) patients with LM experienced headaches longer than 3 days' duration, compared with 37 of 148 (25%) patients with AM. The average duration of headache was 7.5 days among LM patients vs. 2.8 days among AM patients.

In addition, 15 (56%) of the LM patients had cranial neuritis, compared with 5 (3%) of the AM patients.

Finally, the average percentage of mononuclear cells in samples of cerebrospinal fluid was 87% in LM patients vs. 58% in AM patients, and 19 (70%) of the LM patients had CSF mononuclear cell levels greater than 86% compared with 42 (28%) of the AM patients.

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