Jane Salodof MacNeil

ASPEN, COLO. — Stool cultures cost millions of dollars annually, but rarely turn up meaningful information for physicians managing diarrhea in the United States, according to Ann-Christine Nyquist, M.D.

Cultures should be ordered only when the results would affect treatment or if they suspect an infectious disease outbreak, she advised at an annual conference on pediatric infectious diseases sponsored by Children's Hospital, Denver.

“Is it going to make a difference in what you are going to do with that patient—whether you treat or not? You are probably going to treat symptomatically,” said Dr. Nyquist, the hospital's medical director of infection.

She cited a review of 598 cultures done in pediatric hospital patients—only 18 (3%) were positive (Arch. Pediatr. Adolesc. Med. 1997;151:142–5). Extrapolating the $26,084 cost of these negative tests against 1990 census data for hospitalized children, ages 14 and under, Dr. Nyquist estimated that more than $45 million a year was being thrown away on negative stool tests for this population.

More useful information can be gotten from patient history, she said, urging physicians to be thorough in their questioning. “You really want to get to the nitty-gritty of what did the poop look like …” she said. “Eighty percent of the story can be gotten by looking at the history.”

Specific questions about stool characteristics should focus on such features as “watery, bloody, mucous, purulent, greasy, etc.,” she said. Be sure to ask about dysenteric symptoms (fever, tenesmus, blood and/or pus in the stool), symptoms of volume depletion, and associated symptoms, such as “nausea, vomiting, abdominal pain, cramps, headache, myalgia, altered sensorium.”

Review of clinical and epidemiologic features should include whether the illness had an abrupt or gradual onset, duration of symptoms, frequency of bowel movements, and relative quantity of stool produced, according to Dr. Nyquist, also of the University of Colorado.

Focusing on epidemiological risk factors in children, she suggested questions about travel outside the United States; day care attendance; exposure to pets, petting zoos, or unsafe foods; swimming in or drinking fresh untreated surface water; knowing other ill individuals; medication use; and underlying medical conditions. Ask about contact with reptiles as well, she advised.

Recent travel abroad is one of four criteria in an evidence- and consensus-based guideline cited by Dr. Nyquist for ordering a stool culture. The others are “history of blood with or without mucus in stool, [being] systematically unwell, severe or prolonged diarrhea, [and] a history suggestive of food poisoning” (Arch. Dis. Child. 2001;85:132).

Tests should be ordered selectively, starting with the most likely pathogens, she said. About 80% of traveller's diarrhea is caused by a bacterial agent, according to Dr. Nyquist. It can occur in the U.S. without travel to a developing country.

The parasitic agents Giardia lamblia and cryptosporidium also are common causes for which new tests are available. Among the viral causes of diarrhea, she identified rotavirus as the leader with 3.5 million episodes occurring annually each year in the United States. Not detectable by routine viral cultures, it requires more expensive tests.

Dr. Nyquist urged caution with empiric use of antimicrobial agents, and warned that most experts advise against using antibiotics in patients with bloody stool.

Antibiotics might induce disease-producing phage in some cases, she said; they may worsen the risk of postdiarrheal hemolytic uremic syndrome (HUS) in patients with shiga toxin Escherichia coli infections.

Treatment options discussed by Dr. Nyquist included rifaximin for simple traveler's diarrhea (but not in complex cases with bloody stool); tinidazole, a new agent for parasitic diseases; and Alinia (active ingredient nitazoxanide), which is approved for pediatric diarrhea caused by cryptosporidium or Giardia intestinalis.

Hand hygiene among heath care providers is also very important, according to Dr. Nyquist. Rotavirus can survive for days on hospital surfaces (which must be cleaned with a bleach solution), and hand-washing gels are not effective against Clostridium difficile.

In all cases, no matter what the cause, she added, “If your hands are visibly soiled, you need to use soap and water.”

ASPEN, COLO. — Stool cultures cost millions of dollars annually, but rarely turn up meaningful information for physicians managing diarrhea in the United States, according to Ann-Christine Nyquist, M.D.

Cultures should be ordered only when the results would affect treatment or if they suspect an infectious disease outbreak, she advised at an annual conference on pediatric infectious diseases sponsored by Children's Hospital, Denver.

“Is it going to make a difference in what you are going to do with that patient—whether you treat or not? You are probably going to treat symptomatically,” said Dr. Nyquist, the hospital's medical director of infection.

She cited a review of 598 cultures done in pediatric hospital patients—only 18 (3%) were positive (Arch. Pediatr. Adolesc. Med. 1997;151:142–5). Extrapolating the $26,084 cost of these negative tests against 1990 census data for hospitalized children, ages 14 and under, Dr. Nyquist estimated that more than $45 million a year was being thrown away on negative stool tests for this population.

More useful information can be gotten from patient history, she said, urging physicians to be thorough in their questioning. “You really want to get to the nitty-gritty of what did the poop look like …” she said. “Eighty percent of the story can be gotten by looking at the history.”

Specific questions about stool characteristics should focus on such features as “watery, bloody, mucous, purulent, greasy, etc.,” she said. Be sure to ask about dysenteric symptoms (fever, tenesmus, blood and/or pus in the stool), symptoms of volume depletion, and associated symptoms, such as “nausea, vomiting, abdominal pain, cramps, headache, myalgia, altered sensorium.”

Review of clinical and epidemiologic features should include whether the illness had an abrupt or gradual onset, duration of symptoms, frequency of bowel movements, and relative quantity of stool produced, according to Dr. Nyquist, also of the University of Colorado.

Focusing on epidemiological risk factors in children, she suggested questions about travel outside the United States; day care attendance; exposure to pets, petting zoos, or unsafe foods; swimming in or drinking fresh untreated surface water; knowing other ill individuals; medication use; and underlying medical conditions. Ask about contact with reptiles as well, she advised.

Recent travel abroad is one of four criteria in an evidence- and consensus-based guideline cited by Dr. Nyquist for ordering a stool culture. The others are “history of blood with or without mucus in stool, [being] systematically unwell, severe or prolonged diarrhea, [and] a history suggestive of food poisoning” (Arch. Dis. Child. 2001;85:132).

Tests should be ordered selectively, starting with the most likely pathogens, she said. About 80% of traveller's diarrhea is caused by a bacterial agent, according to Dr. Nyquist. It can occur in the U.S. without travel to a developing country.

The parasitic agents Giardia lamblia and cryptosporidium also are common causes for which new tests are available. Among the viral causes of diarrhea, she identified rotavirus as the leader with 3.5 million episodes occurring annually each year in the United States. Not detectable by routine viral cultures, it requires more expensive tests.

Dr. Nyquist urged caution with empiric use of antimicrobial agents, and warned that most experts advise against using antibiotics in patients with bloody stool.

Antibiotics might induce disease-producing phage in some cases, she said; they may worsen the risk of postdiarrheal hemolytic uremic syndrome (HUS) in patients with shiga toxin Escherichia coli infections.

Treatment options discussed by Dr. Nyquist included rifaximin for simple traveler's diarrhea (but not in complex cases with bloody stool); tinidazole, a new agent for parasitic diseases; and Alinia (active ingredient nitazoxanide), which is approved for pediatric diarrhea caused by cryptosporidium or Giardia intestinalis.

Hand hygiene among heath care providers is also very important, according to Dr. Nyquist. Rotavirus can survive for days on hospital surfaces (which must be cleaned with a bleach solution), and hand-washing gels are not effective against Clostridium difficile.

In all cases, no matter what the cause, she added, “If your hands are visibly soiled, you need to use soap and water.”

ASPEN, COLO. — Stool cultures cost millions of dollars annually, but rarely turn up meaningful information for physicians managing diarrhea in the United States, according to Ann-Christine Nyquist, M.D.

Cultures should be ordered only when the results would affect treatment or if they suspect an infectious disease outbreak, she advised at an annual conference on pediatric infectious diseases sponsored by Children's Hospital, Denver.

“Is it going to make a difference in what you are going to do with that patient—whether you treat or not? You are probably going to treat symptomatically,” said Dr. Nyquist, the hospital's medical director of infection.

She cited a review of 598 cultures done in pediatric hospital patients—only 18 (3%) were positive (Arch. Pediatr. Adolesc. Med. 1997;151:142–5). Extrapolating the $26,084 cost of these negative tests against 1990 census data for hospitalized children, ages 14 and under, Dr. Nyquist estimated that more than $45 million a year was being thrown away on negative stool tests for this population.

More useful information can be gotten from patient history, she said, urging physicians to be thorough in their questioning. “You really want to get to the nitty-gritty of what did the poop look like …” she said. “Eighty percent of the story can be gotten by looking at the history.”

Specific questions about stool characteristics should focus on such features as “watery, bloody, mucous, purulent, greasy, etc.,” she said. Be sure to ask about dysenteric symptoms (fever, tenesmus, blood and/or pus in the stool), symptoms of volume depletion, and associated symptoms, such as “nausea, vomiting, abdominal pain, cramps, headache, myalgia, altered sensorium.”

Review of clinical and epidemiologic features should include whether the illness had an abrupt or gradual onset, duration of symptoms, frequency of bowel movements, and relative quantity of stool produced, according to Dr. Nyquist, also of the University of Colorado.

Focusing on epidemiological risk factors in children, she suggested questions about travel outside the United States; day care attendance; exposure to pets, petting zoos, or unsafe foods; swimming in or drinking fresh untreated surface water; knowing other ill individuals; medication use; and underlying medical conditions. Ask about contact with reptiles as well, she advised.

Recent travel abroad is one of four criteria in an evidence- and consensus-based guideline cited by Dr. Nyquist for ordering a stool culture. The others are “history of blood with or without mucus in stool, [being] systematically unwell, severe or prolonged diarrhea, [and] a history suggestive of food poisoning” (Arch. Dis. Child. 2001;85:132).

Tests should be ordered selectively, starting with the most likely pathogens, she said. About 80% of traveller's diarrhea is caused by a bacterial agent, according to Dr. Nyquist. It can occur in the U.S. without travel to a developing country.

The parasitic agents Giardia lamblia and cryptosporidium also are common causes for which new tests are available. Among the viral causes of diarrhea, she identified rotavirus as the leader with 3.5 million episodes occurring annually each year in the United States. Not detectable by routine viral cultures, it requires more expensive tests.

Dr. Nyquist urged caution with empiric use of antimicrobial agents, and warned that most experts advise against using antibiotics in patients with bloody stool.

Antibiotics might induce disease-producing phage in some cases, she said; they may worsen the risk of postdiarrheal hemolytic uremic syndrome (HUS) in patients with shiga toxin Escherichia coli infections.

Treatment options discussed by Dr. Nyquist included rifaximin for simple traveler's diarrhea (but not in complex cases with bloody stool); tinidazole, a new agent for parasitic diseases; and Alinia (active ingredient nitazoxanide), which is approved for pediatric diarrhea caused by cryptosporidium or Giardia intestinalis.

Hand hygiene among heath care providers is also very important, according to Dr. Nyquist. Rotavirus can survive for days on hospital surfaces (which must be cleaned with a bleach solution), and hand-washing gels are not effective against Clostridium difficile.

In all cases, no matter what the cause, she added, “If your hands are visibly soiled, you need to use soap and water.”

ORLANDO – Single injections of methylnaltrexone relieved opioid-induced constipation in 4 hours for 60% of hospice and palliative care patients in a randomized, placebo-controlled phase III trial.

The earliest responses occurred within 5 minutes, and most patients responded within 2 hours, investigator Jay Thomas, M.D., reported at the annual meeting of the American Society of Clinical Oncology. The patients in the trial had not had a bowel movement for at least 48 hours prior to treatment, despite being on a stable laxative regimen for at least 3 days.

Dr. Thomas, clinical medical director of the San Diego Hospice and Palliative Care Center, reported that the single-dose trial enrolled 154 patients with advanced medical disease from 16 hospices. Of the 154 patients, 123 (80%) had cancer. The population also included patients with pulmonary disorders (12) AIDS (8), amyotrophic lateral sclerosis (3), cardiovascular conditions (2), and other disorders (6).

“These patients were very sick and near the end of life,” Dr. Thomas said. Since most patients lived at home, visiting nurses trained family members to give the injections in place of an enema or other rescue regimen. If the study drug did not provide relief within 4 hours, rescue was permitted.

The trial randomized patients into three groups: 52 patients were given a placebo, 57 received 0.15 mg/kg of methylnaltrexone, and 55 received 0.30 mg of methylnaltrexone/kg. Median time to laxation was 70 minutes for the 0.15-mg dose, 45 minutes at 0.30 mg, and more than 1,440 minutes (24 hours) with placebo.

Dr. Thomas, an internist, said the difference in efficacy between the two methylnaltrexone doses was negligible. “With the higher dose, you didn't get more bang for your buck,” he said. “If anything, you got more side effects.”

Side effects were minimal, however. The two most common adverse events, abdominal cramping and flatulence, were associated with successful laxation. The next most common side effects were nausea and dizziness.

The trial's sponsor, Progenics Pharmaceuticals Inc. of Tarrytown, N.Y., has already started a second phase III study at 30 centers to assess repetitive doses in patients with chronic constipation due to opioid painkillers. The company hopes to apply for U.S. Food and Drug Administration approval by the end of the year, Robert J. Israel, M.D., medical affairs vice president, told this newspaper.

The late Leon Goldberg, a pharmacologist at the University of Chicago, synthesized methylnaltrexone 25 years ago to help a dying friend who suffered from morphine-induced constipation. A μ receptor antagonist, it does not cross the blood-brain barrier, and therefore can act on opioid-induced constipation without blocking the pain-killing effects of opioids.

Dr. Israel said Progenics obtained the rights to develop methylnaltrexone after he read a report on a randomized trial in which the experimental drug relieved constipation in methadone patients (JAMA 2000;283:367–72).

“The market was small for end of life, so a lot of [drug companies] look at that as not attractive,” Dr. Israel said. “We are a small company. That was not an obstacle for us.”

Enthusiastic physicians surrounded Dr. Thomas and Dr. Israel after the presentation. “The sooner it gets to market, the better,” said Lee Schwartzberg, M.D., research director of the West Clinic in Memphis, as others in the crowd suggested strategies for convincing insurance companies to provide reimbursement.

In a podium discussion of the presentation, Kathleen M. Foley, M.D., called methylnaltrexone “the palliative and pain world's answer to a targeted therapy.” Dr. Foley of Memorial Sloan-Kettering Cancer Center in New York said the investigators need to refine the dose in short-term vs. long-term opioid users, and to explore intravenous and oral delivery systems. She also suggested that methylnaltrexone might have a role in treating postoperative ileus.

Dr. Thomas predicted that drug makers would eventually be able to offer pills combining methylnaltrexone with opioid painkillers. “When someone takes OxyContin they would have methylnaltrexone in the pill, so they would never have the opioid-induced side effect of nausea, urinary retention, and constipation,” he said.

ORLANDO – Single injections of methylnaltrexone relieved opioid-induced constipation in 4 hours for 60% of hospice and palliative care patients in a randomized, placebo-controlled phase III trial.

The earliest responses occurred within 5 minutes, and most patients responded within 2 hours, investigator Jay Thomas, M.D., reported at the annual meeting of the American Society of Clinical Oncology. The patients in the trial had not had a bowel movement for at least 48 hours prior to treatment, despite being on a stable laxative regimen for at least 3 days.

Dr. Thomas, clinical medical director of the San Diego Hospice and Palliative Care Center, reported that the single-dose trial enrolled 154 patients with advanced medical disease from 16 hospices. Of the 154 patients, 123 (80%) had cancer. The population also included patients with pulmonary disorders (12) AIDS (8), amyotrophic lateral sclerosis (3), cardiovascular conditions (2), and other disorders (6).

“These patients were very sick and near the end of life,” Dr. Thomas said. Since most patients lived at home, visiting nurses trained family members to give the injections in place of an enema or other rescue regimen. If the study drug did not provide relief within 4 hours, rescue was permitted.

The trial randomized patients into three groups: 52 patients were given a placebo, 57 received 0.15 mg/kg of methylnaltrexone, and 55 received 0.30 mg of methylnaltrexone/kg. Median time to laxation was 70 minutes for the 0.15-mg dose, 45 minutes at 0.30 mg, and more than 1,440 minutes (24 hours) with placebo.

Dr. Thomas, an internist, said the difference in efficacy between the two methylnaltrexone doses was negligible. “With the higher dose, you didn't get more bang for your buck,” he said. “If anything, you got more side effects.”

Side effects were minimal, however. The two most common adverse events, abdominal cramping and flatulence, were associated with successful laxation. The next most common side effects were nausea and dizziness.

The trial's sponsor, Progenics Pharmaceuticals Inc. of Tarrytown, N.Y., has already started a second phase III study at 30 centers to assess repetitive doses in patients with chronic constipation due to opioid painkillers. The company hopes to apply for U.S. Food and Drug Administration approval by the end of the year, Robert J. Israel, M.D., medical affairs vice president, told this newspaper.

The late Leon Goldberg, a pharmacologist at the University of Chicago, synthesized methylnaltrexone 25 years ago to help a dying friend who suffered from morphine-induced constipation. A μ receptor antagonist, it does not cross the blood-brain barrier, and therefore can act on opioid-induced constipation without blocking the pain-killing effects of opioids.

Dr. Israel said Progenics obtained the rights to develop methylnaltrexone after he read a report on a randomized trial in which the experimental drug relieved constipation in methadone patients (JAMA 2000;283:367–72).

“The market was small for end of life, so a lot of [drug companies] look at that as not attractive,” Dr. Israel said. “We are a small company. That was not an obstacle for us.”

Enthusiastic physicians surrounded Dr. Thomas and Dr. Israel after the presentation. “The sooner it gets to market, the better,” said Lee Schwartzberg, M.D., research director of the West Clinic in Memphis, as others in the crowd suggested strategies for convincing insurance companies to provide reimbursement.

In a podium discussion of the presentation, Kathleen M. Foley, M.D., called methylnaltrexone “the palliative and pain world's answer to a targeted therapy.” Dr. Foley of Memorial Sloan-Kettering Cancer Center in New York said the investigators need to refine the dose in short-term vs. long-term opioid users, and to explore intravenous and oral delivery systems. She also suggested that methylnaltrexone might have a role in treating postoperative ileus.

Dr. Thomas predicted that drug makers would eventually be able to offer pills combining methylnaltrexone with opioid painkillers. “When someone takes OxyContin they would have methylnaltrexone in the pill, so they would never have the opioid-induced side effect of nausea, urinary retention, and constipation,” he said.

ORLANDO – Single injections of methylnaltrexone relieved opioid-induced constipation in 4 hours for 60% of hospice and palliative care patients in a randomized, placebo-controlled phase III trial.

The earliest responses occurred within 5 minutes, and most patients responded within 2 hours, investigator Jay Thomas, M.D., reported at the annual meeting of the American Society of Clinical Oncology. The patients in the trial had not had a bowel movement for at least 48 hours prior to treatment, despite being on a stable laxative regimen for at least 3 days.

Dr. Thomas, clinical medical director of the San Diego Hospice and Palliative Care Center, reported that the single-dose trial enrolled 154 patients with advanced medical disease from 16 hospices. Of the 154 patients, 123 (80%) had cancer. The population also included patients with pulmonary disorders (12) AIDS (8), amyotrophic lateral sclerosis (3), cardiovascular conditions (2), and other disorders (6).

“These patients were very sick and near the end of life,” Dr. Thomas said. Since most patients lived at home, visiting nurses trained family members to give the injections in place of an enema or other rescue regimen. If the study drug did not provide relief within 4 hours, rescue was permitted.

The trial randomized patients into three groups: 52 patients were given a placebo, 57 received 0.15 mg/kg of methylnaltrexone, and 55 received 0.30 mg of methylnaltrexone/kg. Median time to laxation was 70 minutes for the 0.15-mg dose, 45 minutes at 0.30 mg, and more than 1,440 minutes (24 hours) with placebo.

Dr. Thomas, an internist, said the difference in efficacy between the two methylnaltrexone doses was negligible. “With the higher dose, you didn't get more bang for your buck,” he said. “If anything, you got more side effects.”

Side effects were minimal, however. The two most common adverse events, abdominal cramping and flatulence, were associated with successful laxation. The next most common side effects were nausea and dizziness.

The trial's sponsor, Progenics Pharmaceuticals Inc. of Tarrytown, N.Y., has already started a second phase III study at 30 centers to assess repetitive doses in patients with chronic constipation due to opioid painkillers. The company hopes to apply for U.S. Food and Drug Administration approval by the end of the year, Robert J. Israel, M.D., medical affairs vice president, told this newspaper.

The late Leon Goldberg, a pharmacologist at the University of Chicago, synthesized methylnaltrexone 25 years ago to help a dying friend who suffered from morphine-induced constipation. A μ receptor antagonist, it does not cross the blood-brain barrier, and therefore can act on opioid-induced constipation without blocking the pain-killing effects of opioids.

Dr. Israel said Progenics obtained the rights to develop methylnaltrexone after he read a report on a randomized trial in which the experimental drug relieved constipation in methadone patients (JAMA 2000;283:367–72).

“The market was small for end of life, so a lot of [drug companies] look at that as not attractive,” Dr. Israel said. “We are a small company. That was not an obstacle for us.”

Enthusiastic physicians surrounded Dr. Thomas and Dr. Israel after the presentation. “The sooner it gets to market, the better,” said Lee Schwartzberg, M.D., research director of the West Clinic in Memphis, as others in the crowd suggested strategies for convincing insurance companies to provide reimbursement.

In a podium discussion of the presentation, Kathleen M. Foley, M.D., called methylnaltrexone “the palliative and pain world's answer to a targeted therapy.” Dr. Foley of Memorial Sloan-Kettering Cancer Center in New York said the investigators need to refine the dose in short-term vs. long-term opioid users, and to explore intravenous and oral delivery systems. She also suggested that methylnaltrexone might have a role in treating postoperative ileus.

Dr. Thomas predicted that drug makers would eventually be able to offer pills combining methylnaltrexone with opioid painkillers. “When someone takes OxyContin they would have methylnaltrexone in the pill, so they would never have the opioid-induced side effect of nausea, urinary retention, and constipation,” he said.

SCOTTSDALE, ARIZ. – The next revision of 9-year-old guidelines for management of severe traumatic brain injury should endorse patient cooling, Donald Marion, M.D., chair of a committee evaluating the evidence on therapeutic hypothermia, said at the annual meeting of the Neurocritical Care Society.

Dr. Marion, a neurosurgeon and senior research fellow at the Brain Trauma Foundation, New York, said he intends to recommend that therapeutic hypothermia be a standard consideration in these cases and “that moderate hypothermia for 48 hours or less should be considered for patients with elevated ICP [intracranial pressure].”

His remarks were intended to give the society a “heads-up on a process that is really just starting.” Dr. Marion said he anticipates the revised guidelines will be completed in 2006 and encouraged physicians to send him comments at [email protected]

The guidelines, created in 1996, are a joint project of the Brain Trauma Foundation, the American Association of Neurological Surgeons, the Congress of Neurological Surgeons, and the AANS/CNS Joint Section on Neurotrauma and Critical Care. According to Dr. Marion, “Evidence-based conclusions would support the following statements:

▸ Hypothermia improves outcomes.

▸ Hypothermia reduces elevated ICP.

▸ If the patient is cooled to greater than or equal to 32° C for no more than 48 hours, there are no clinically significant risks of infection, of cardiac arrhythmia, or coagulopathy.”

He reported 10 of the 15 trials had at least 15 patients in each arm. Among these, he reviewed nine complete manuscripts (the exception being a study from China). That seven were single-center studies should not make them less highly regarded, according to Dr. Marion.

“In all seven there is a trend to improved outcomes, and most reach statistical significance. The only ones that don't show a trend to improved outcomes are the two multicenter trials,” he said, questioning whether randomized multicenter trials are realistic for a condition as complex as traumatic brain injury (TBI).

Dr. Marion said that his analysis of cumulative outcomes from all nine studies found 52% of patients treated with hypothermia were alive and functional at designated times ranging from 3 months to 2 years afterward. Only 39% of those treated at normal temperatures did as well, he said. This 13% difference became 24% when the two multicenter trials were excluded.

He also described a published metaanalysis of hypothermia trials as flawed (Arch. Neurol. 2002;59:1077–83). It only gave weight to four trials, one of which had twice as many patients as the other three trials combined, he said. A second negative study (Ann. Surg. 1997;226:439–47) included few TBI patients and did not consider functional outcomes as distinct from mortality, Dr. Marion said.

A second presenter on clinical use of hypothermia, Stefan Schwab, M.D., of the University of Heidelberg (Germany), reported that his institution has cooled about 200 stroke patients. He characterized hypothermia as a promising neuroprotective therapy with the potential to control fever but said the evidence does not support making it a standard of care for ischemic stroke.

Among the many open questions still to be resolved, Dr. Schwab listed optimal time to target temperature, duration of cooling, target temperature, ventilation mode, and methods of cooling and rewarming. He also cited safety, efficacy, and whether it should be used in patients with moderate, severe, or very severe stroke.

“For optimal treatment of severe stroke, decompressive surgery is still the standard,” Dr. Schwab concluded, speculating that hypothermia might be beneficial as an added therapy or in stroke cases that are severe but not very severe. “Obviously hypothermia is something that works, but we need to see how we can use it,” he said.

Michael A. DeGeorgia, M.D., of the Cleveland Clinic Foundation reviewed studies that led to the International Liaison Committee on Resuscitation (ILCOR) task force advisory statement endorsing use of therapeutic hypothermia after cardiac arrest (Circulation 2003;108:118–21).

“We're further ahead in head trauma and cardiac arrest. Maybe this is something we should be doing in selective patients,” Dr. DeGeorgia said.

SCOTTSDALE, ARIZ. – The next revision of 9-year-old guidelines for management of severe traumatic brain injury should endorse patient cooling, Donald Marion, M.D., chair of a committee evaluating the evidence on therapeutic hypothermia, said at the annual meeting of the Neurocritical Care Society.

Dr. Marion, a neurosurgeon and senior research fellow at the Brain Trauma Foundation, New York, said he intends to recommend that therapeutic hypothermia be a standard consideration in these cases and “that moderate hypothermia for 48 hours or less should be considered for patients with elevated ICP [intracranial pressure].”

His remarks were intended to give the society a “heads-up on a process that is really just starting.” Dr. Marion said he anticipates the revised guidelines will be completed in 2006 and encouraged physicians to send him comments at [email protected]

The guidelines, created in 1996, are a joint project of the Brain Trauma Foundation, the American Association of Neurological Surgeons, the Congress of Neurological Surgeons, and the AANS/CNS Joint Section on Neurotrauma and Critical Care. According to Dr. Marion, “Evidence-based conclusions would support the following statements:

▸ Hypothermia improves outcomes.

▸ Hypothermia reduces elevated ICP.

▸ If the patient is cooled to greater than or equal to 32° C for no more than 48 hours, there are no clinically significant risks of infection, of cardiac arrhythmia, or coagulopathy.”

He reported 10 of the 15 trials had at least 15 patients in each arm. Among these, he reviewed nine complete manuscripts (the exception being a study from China). That seven were single-center studies should not make them less highly regarded, according to Dr. Marion.

“In all seven there is a trend to improved outcomes, and most reach statistical significance. The only ones that don't show a trend to improved outcomes are the two multicenter trials,” he said, questioning whether randomized multicenter trials are realistic for a condition as complex as traumatic brain injury (TBI).

Dr. Marion said that his analysis of cumulative outcomes from all nine studies found 52% of patients treated with hypothermia were alive and functional at designated times ranging from 3 months to 2 years afterward. Only 39% of those treated at normal temperatures did as well, he said. This 13% difference became 24% when the two multicenter trials were excluded.

He also described a published metaanalysis of hypothermia trials as flawed (Arch. Neurol. 2002;59:1077–83). It only gave weight to four trials, one of which had twice as many patients as the other three trials combined, he said. A second negative study (Ann. Surg. 1997;226:439–47) included few TBI patients and did not consider functional outcomes as distinct from mortality, Dr. Marion said.

A second presenter on clinical use of hypothermia, Stefan Schwab, M.D., of the University of Heidelberg (Germany), reported that his institution has cooled about 200 stroke patients. He characterized hypothermia as a promising neuroprotective therapy with the potential to control fever but said the evidence does not support making it a standard of care for ischemic stroke.

Among the many open questions still to be resolved, Dr. Schwab listed optimal time to target temperature, duration of cooling, target temperature, ventilation mode, and methods of cooling and rewarming. He also cited safety, efficacy, and whether it should be used in patients with moderate, severe, or very severe stroke.

“For optimal treatment of severe stroke, decompressive surgery is still the standard,” Dr. Schwab concluded, speculating that hypothermia might be beneficial as an added therapy or in stroke cases that are severe but not very severe. “Obviously hypothermia is something that works, but we need to see how we can use it,” he said.

Michael A. DeGeorgia, M.D., of the Cleveland Clinic Foundation reviewed studies that led to the International Liaison Committee on Resuscitation (ILCOR) task force advisory statement endorsing use of therapeutic hypothermia after cardiac arrest (Circulation 2003;108:118–21).

“We're further ahead in head trauma and cardiac arrest. Maybe this is something we should be doing in selective patients,” Dr. DeGeorgia said.

SCOTTSDALE, ARIZ. – The next revision of 9-year-old guidelines for management of severe traumatic brain injury should endorse patient cooling, Donald Marion, M.D., chair of a committee evaluating the evidence on therapeutic hypothermia, said at the annual meeting of the Neurocritical Care Society.

Dr. Marion, a neurosurgeon and senior research fellow at the Brain Trauma Foundation, New York, said he intends to recommend that therapeutic hypothermia be a standard consideration in these cases and “that moderate hypothermia for 48 hours or less should be considered for patients with elevated ICP [intracranial pressure].”

His remarks were intended to give the society a “heads-up on a process that is really just starting.” Dr. Marion said he anticipates the revised guidelines will be completed in 2006 and encouraged physicians to send him comments at [email protected]

The guidelines, created in 1996, are a joint project of the Brain Trauma Foundation, the American Association of Neurological Surgeons, the Congress of Neurological Surgeons, and the AANS/CNS Joint Section on Neurotrauma and Critical Care. According to Dr. Marion, “Evidence-based conclusions would support the following statements:

▸ Hypothermia improves outcomes.

▸ Hypothermia reduces elevated ICP.

▸ If the patient is cooled to greater than or equal to 32° C for no more than 48 hours, there are no clinically significant risks of infection, of cardiac arrhythmia, or coagulopathy.”

He reported 10 of the 15 trials had at least 15 patients in each arm. Among these, he reviewed nine complete manuscripts (the exception being a study from China). That seven were single-center studies should not make them less highly regarded, according to Dr. Marion.

“In all seven there is a trend to improved outcomes, and most reach statistical significance. The only ones that don't show a trend to improved outcomes are the two multicenter trials,” he said, questioning whether randomized multicenter trials are realistic for a condition as complex as traumatic brain injury (TBI).

Dr. Marion said that his analysis of cumulative outcomes from all nine studies found 52% of patients treated with hypothermia were alive and functional at designated times ranging from 3 months to 2 years afterward. Only 39% of those treated at normal temperatures did as well, he said. This 13% difference became 24% when the two multicenter trials were excluded.

He also described a published metaanalysis of hypothermia trials as flawed (Arch. Neurol. 2002;59:1077–83). It only gave weight to four trials, one of which had twice as many patients as the other three trials combined, he said. A second negative study (Ann. Surg. 1997;226:439–47) included few TBI patients and did not consider functional outcomes as distinct from mortality, Dr. Marion said.

A second presenter on clinical use of hypothermia, Stefan Schwab, M.D., of the University of Heidelberg (Germany), reported that his institution has cooled about 200 stroke patients. He characterized hypothermia as a promising neuroprotective therapy with the potential to control fever but said the evidence does not support making it a standard of care for ischemic stroke.

Among the many open questions still to be resolved, Dr. Schwab listed optimal time to target temperature, duration of cooling, target temperature, ventilation mode, and methods of cooling and rewarming. He also cited safety, efficacy, and whether it should be used in patients with moderate, severe, or very severe stroke.

“For optimal treatment of severe stroke, decompressive surgery is still the standard,” Dr. Schwab concluded, speculating that hypothermia might be beneficial as an added therapy or in stroke cases that are severe but not very severe. “Obviously hypothermia is something that works, but we need to see how we can use it,” he said.

Michael A. DeGeorgia, M.D., of the Cleveland Clinic Foundation reviewed studies that led to the International Liaison Committee on Resuscitation (ILCOR) task force advisory statement endorsing use of therapeutic hypothermia after cardiac arrest (Circulation 2003;108:118–21).

“We're further ahead in head trauma and cardiac arrest. Maybe this is something we should be doing in selective patients,” Dr. DeGeorgia said.

ORLANDO — Two-thirds of gastric cancer patients still do not receive an adequate lymph node assessment for staging of their disease prior to surgery, Natalie G. Coburn, M.D., reported at the annual meeting of the American Society for Clinical Oncology. According to an analysis of 11,602 U.S. patients operated on from 1988 through 2001, only 27.6% had at least 15 nodes removed for examination, said Dr. Coburn of Princess Margaret Hospital and the University of Toronto.

The American Joint Commission on Cancer changed its guidelines in 1997 to make 15 nodes the standard for assessment. Though the Canadian investigators found some improvement subsequently, only 32.7% of cases from 1998 to 2001 were in compliance.

Dr. Coburn reported the median number of lymph nodes assessed was nine, with wide variation among the nine geographic regions included in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database.

Hawaii had the best results. A median of 15 lymph nodes were examined, and 52.5% of patients received care that met the standard for adequate assessment. That state also had the best median survival (26 months) and the best 5-year actuarial overall survival (33.4%).

In contrast, Utah had the worst record. The median number of lymph nodes examined was six, and only 17.5% of patients received an adequate assessment. Utah's median survival was the lowest (15 months), as was its 5-year actuarial overall survival (16.2%).

“Patients who had more adequate surgery and lymph node assessment had better outcomes,” Dr. Coburn said at a press briefing, noting that variations in the number of lymph nodes collected correlated with disparities in survival.

Dr. Coburn reported a variety of factors affected the chance of receiving an adequate lymph node assessment. Better odds ratios (ORs) were associated with the following:

▸ Year of diagnosis (1998–2001, OR 1.4).

▸ Female gender (OR 1.3).

▸ Asian (OR 1.4–1.8) or African American (OR 1.4) descent.

▸ Tumor stage more advanced than T1 (OR 1.3–1.7).

▸ Increase in grade from well differentiated to undifferentiated (OR 1.4–1.8).

Patients were more likely to have an adequate assessment if they had a major surgery such as total resection (OR 1.8) or en bloc resection (OR 1.9). Patients under the age of 74 also were more likely to have an adequate assessment.

Although only a small number of patients had neoadjuvant radiation, they had lower odds of an adequate lymph node assessment (OR 0.2). Other investigators have reported similar results, according to Dr. Coburn. “They feel it's due to radiation changes in the surgical bed,” she said.

Many hazard ratios (HRs) for death reflected the odds for adequate assessment. Older patients were more likely to die (HR 1.4). Japanese and other Asian Americans (HR 0.82) were less likely to die, as were women (HR 0.83). However, risk of death also increased with higher tumor stage (HR 1.4–3.4) and grade (HR 1.4), she said.

Patients with total resections had a better hazard ratio (0.88) than did those with distal resections, but the odds of dying were higher with gastrectomy (HR 1.2) and en bloc surgery (HR 1.12). Neoadjuvant radiation did not have an effect on hazard ratios, but adjuvant radiation reduced risk slightly (HR 0.9).

The investigators calculated that having an adequate number of lymph nodes removed for assessment reduced the risk of death by 14% (HR 0.86).

ORLANDO — Two-thirds of gastric cancer patients still do not receive an adequate lymph node assessment for staging of their disease prior to surgery, Natalie G. Coburn, M.D., reported at the annual meeting of the American Society for Clinical Oncology. According to an analysis of 11,602 U.S. patients operated on from 1988 through 2001, only 27.6% had at least 15 nodes removed for examination, said Dr. Coburn of Princess Margaret Hospital and the University of Toronto.

The American Joint Commission on Cancer changed its guidelines in 1997 to make 15 nodes the standard for assessment. Though the Canadian investigators found some improvement subsequently, only 32.7% of cases from 1998 to 2001 were in compliance.

Dr. Coburn reported the median number of lymph nodes assessed was nine, with wide variation among the nine geographic regions included in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database.

Hawaii had the best results. A median of 15 lymph nodes were examined, and 52.5% of patients received care that met the standard for adequate assessment. That state also had the best median survival (26 months) and the best 5-year actuarial overall survival (33.4%).

In contrast, Utah had the worst record. The median number of lymph nodes examined was six, and only 17.5% of patients received an adequate assessment. Utah's median survival was the lowest (15 months), as was its 5-year actuarial overall survival (16.2%).

“Patients who had more adequate surgery and lymph node assessment had better outcomes,” Dr. Coburn said at a press briefing, noting that variations in the number of lymph nodes collected correlated with disparities in survival.

Dr. Coburn reported a variety of factors affected the chance of receiving an adequate lymph node assessment. Better odds ratios (ORs) were associated with the following:

▸ Year of diagnosis (1998–2001, OR 1.4).

▸ Female gender (OR 1.3).

▸ Asian (OR 1.4–1.8) or African American (OR 1.4) descent.

▸ Tumor stage more advanced than T1 (OR 1.3–1.7).

▸ Increase in grade from well differentiated to undifferentiated (OR 1.4–1.8).

Patients were more likely to have an adequate assessment if they had a major surgery such as total resection (OR 1.8) or en bloc resection (OR 1.9). Patients under the age of 74 also were more likely to have an adequate assessment.

Although only a small number of patients had neoadjuvant radiation, they had lower odds of an adequate lymph node assessment (OR 0.2). Other investigators have reported similar results, according to Dr. Coburn. “They feel it's due to radiation changes in the surgical bed,” she said.

Many hazard ratios (HRs) for death reflected the odds for adequate assessment. Older patients were more likely to die (HR 1.4). Japanese and other Asian Americans (HR 0.82) were less likely to die, as were women (HR 0.83). However, risk of death also increased with higher tumor stage (HR 1.4–3.4) and grade (HR 1.4), she said.

Patients with total resections had a better hazard ratio (0.88) than did those with distal resections, but the odds of dying were higher with gastrectomy (HR 1.2) and en bloc surgery (HR 1.12). Neoadjuvant radiation did not have an effect on hazard ratios, but adjuvant radiation reduced risk slightly (HR 0.9).

The investigators calculated that having an adequate number of lymph nodes removed for assessment reduced the risk of death by 14% (HR 0.86).

ORLANDO — Two-thirds of gastric cancer patients still do not receive an adequate lymph node assessment for staging of their disease prior to surgery, Natalie G. Coburn, M.D., reported at the annual meeting of the American Society for Clinical Oncology. According to an analysis of 11,602 U.S. patients operated on from 1988 through 2001, only 27.6% had at least 15 nodes removed for examination, said Dr. Coburn of Princess Margaret Hospital and the University of Toronto.

The American Joint Commission on Cancer changed its guidelines in 1997 to make 15 nodes the standard for assessment. Though the Canadian investigators found some improvement subsequently, only 32.7% of cases from 1998 to 2001 were in compliance.

Dr. Coburn reported the median number of lymph nodes assessed was nine, with wide variation among the nine geographic regions included in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database.

Hawaii had the best results. A median of 15 lymph nodes were examined, and 52.5% of patients received care that met the standard for adequate assessment. That state also had the best median survival (26 months) and the best 5-year actuarial overall survival (33.4%).

In contrast, Utah had the worst record. The median number of lymph nodes examined was six, and only 17.5% of patients received an adequate assessment. Utah's median survival was the lowest (15 months), as was its 5-year actuarial overall survival (16.2%).

“Patients who had more adequate surgery and lymph node assessment had better outcomes,” Dr. Coburn said at a press briefing, noting that variations in the number of lymph nodes collected correlated with disparities in survival.

Dr. Coburn reported a variety of factors affected the chance of receiving an adequate lymph node assessment. Better odds ratios (ORs) were associated with the following:

▸ Year of diagnosis (1998–2001, OR 1.4).

▸ Female gender (OR 1.3).

▸ Asian (OR 1.4–1.8) or African American (OR 1.4) descent.

▸ Tumor stage more advanced than T1 (OR 1.3–1.7).

▸ Increase in grade from well differentiated to undifferentiated (OR 1.4–1.8).

Patients were more likely to have an adequate assessment if they had a major surgery such as total resection (OR 1.8) or en bloc resection (OR 1.9). Patients under the age of 74 also were more likely to have an adequate assessment.

Although only a small number of patients had neoadjuvant radiation, they had lower odds of an adequate lymph node assessment (OR 0.2). Other investigators have reported similar results, according to Dr. Coburn. “They feel it's due to radiation changes in the surgical bed,” she said.

Many hazard ratios (HRs) for death reflected the odds for adequate assessment. Older patients were more likely to die (HR 1.4). Japanese and other Asian Americans (HR 0.82) were less likely to die, as were women (HR 0.83). However, risk of death also increased with higher tumor stage (HR 1.4–3.4) and grade (HR 1.4), she said.

Patients with total resections had a better hazard ratio (0.88) than did those with distal resections, but the odds of dying were higher with gastrectomy (HR 1.2) and en bloc surgery (HR 1.12). Neoadjuvant radiation did not have an effect on hazard ratios, but adjuvant radiation reduced risk slightly (HR 0.9).

The investigators calculated that having an adequate number of lymph nodes removed for assessment reduced the risk of death by 14% (HR 0.86).

ORLANDO — Gastric cancer patients who received perioperative chemotherapy showed a 13% absolute improvement in 5-year survival in a large phase III trial sponsored by the United Kingdom's Medical Research Council.

Of the patients who received chemotherapy before and after surgery, 36% were alive 5 years after diagnosis, whereas only 23% of a control group randomized to surgery alone lived that long, investigator David Cunningham, M.D., reported at the annual meeting of the American Society of Clinical Oncology.

The chemotherapy regimen downstaged primary tumors and signif-icantly improved progression-free survival as well, said Dr. Cunningham of the Royal Marsden Hospital in Surrey, England. He reported recurrences in 62% of the control group but in only 42% of patients who received perioperative chemotherapy.

The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial enrolled 503 patients with operable cancer of the stomach and lower esophagus from July 1994 to April 2002. The trial randomized 253 patients to surgery alone and 250 to receive surgery plus three preoperative and three postoperative cycles of chemotherapy.

The chemotherapy regimen contained an intravenous bolus of 50 mg/m

Fewer patients in the chemotherapy arm proceeded to surgery: 219 patients (about 88%) vs. 240 patients (95%) in the control group. Yet more chemotherapy patients had operations that were deemed curative: 169 patients (about 79%) compared with 166 patients (about 70%) who had no chemotherapy.

Postoperative deaths (6%) and complications (46%) were the same for both groups, as was the median postoperative hospital stay (13 days).

Postsurgery pathology showed the chemotherapy patients had a smaller maximum tumor diameter (median 3 cm vs. 5 cm in the control group). The chemotherapy patients with gastric tumors were more likely to have less advanced disease: 52% were classified as T1 or T2 vs. 38% of the control group. They were also less likely to have more advanced nodal status: 16% were classified as N3 or N4 vs. 29% of the controls.

Median survival was calculated as 24 months with chemotherapy and 20 months with surgery alone. The unadjusted hazard ratio for death was 0.75 in the chemotherapy arm. Progression-free survival was also superior, with a hazard ratio of 0.66 favoring chemotherapy.

Survival results were based on an intent-to-treat analysis at a median follow-up greater than 3 years. In all, 90% of patients were followed 2 or more years or until death.

In response to an audience question, Dr. Cunningham declined to claim that the trial established perioperative chemotherapy as a new standard. Surgery alone has been standard in Europe, he said, whereas postoperative chemoradiation has been common in the United States since its benefits were reported in another standardized trial (N. Engl. J. Med. 2001;345:725–30).

“It is difficult to compare and contrast the two different strategies, but I think what the study does do is offer us the option of two different strategies for patients with this disease—either perioperative chemotherapy or surgery and then postoperative chemoradiation,” he said. “And maybe combining those strategies can improve outcomes.”

Dr. Cunningham rejected a suggestion that patients in the MAGIC trial's control arm had poorer survival than did patients in other adjunctive therapy trials. He said these groups could not be compared, because the MAGIC trial enrolled “all comers,” whereas adjunctive therapy trials enroll only patients who have had successful operations.

“There hasn't been much improvement in outcome [for gastric cancer patients until now], but with these multimodalities we are hoping there will be,” Dr. Cunningham told this newspaper. He described the current outlook for patients with non-colorectal gastrointestinal cancers as “pretty grim,” but predicted that current investigations would soon lead to “massive” improvement.

In a discussion of the MAGIC trial, Robert J. Mayer, M.D., said the results “are convincing, validating the concept of perioperative chemotherapy.” What remains unclear, said Dr. Mayer, director of the center for gastrointestinal oncology at the Dana-Farber Cancer Institute in Boston, is which chemotherapy regimen is the best combination, not only for perioperative chemotherapy but also for postoperative chemoradiation.

ORLANDO — Gastric cancer patients who received perioperative chemotherapy showed a 13% absolute improvement in 5-year survival in a large phase III trial sponsored by the United Kingdom's Medical Research Council.

Of the patients who received chemotherapy before and after surgery, 36% were alive 5 years after diagnosis, whereas only 23% of a control group randomized to surgery alone lived that long, investigator David Cunningham, M.D., reported at the annual meeting of the American Society of Clinical Oncology.

The chemotherapy regimen downstaged primary tumors and signif-icantly improved progression-free survival as well, said Dr. Cunningham of the Royal Marsden Hospital in Surrey, England. He reported recurrences in 62% of the control group but in only 42% of patients who received perioperative chemotherapy.

The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial enrolled 503 patients with operable cancer of the stomach and lower esophagus from July 1994 to April 2002. The trial randomized 253 patients to surgery alone and 250 to receive surgery plus three preoperative and three postoperative cycles of chemotherapy.

The chemotherapy regimen contained an intravenous bolus of 50 mg/m

Fewer patients in the chemotherapy arm proceeded to surgery: 219 patients (about 88%) vs. 240 patients (95%) in the control group. Yet more chemotherapy patients had operations that were deemed curative: 169 patients (about 79%) compared with 166 patients (about 70%) who had no chemotherapy.

Postoperative deaths (6%) and complications (46%) were the same for both groups, as was the median postoperative hospital stay (13 days).

Postsurgery pathology showed the chemotherapy patients had a smaller maximum tumor diameter (median 3 cm vs. 5 cm in the control group). The chemotherapy patients with gastric tumors were more likely to have less advanced disease: 52% were classified as T1 or T2 vs. 38% of the control group. They were also less likely to have more advanced nodal status: 16% were classified as N3 or N4 vs. 29% of the controls.

Median survival was calculated as 24 months with chemotherapy and 20 months with surgery alone. The unadjusted hazard ratio for death was 0.75 in the chemotherapy arm. Progression-free survival was also superior, with a hazard ratio of 0.66 favoring chemotherapy.

Survival results were based on an intent-to-treat analysis at a median follow-up greater than 3 years. In all, 90% of patients were followed 2 or more years or until death.

In response to an audience question, Dr. Cunningham declined to claim that the trial established perioperative chemotherapy as a new standard. Surgery alone has been standard in Europe, he said, whereas postoperative chemoradiation has been common in the United States since its benefits were reported in another standardized trial (N. Engl. J. Med. 2001;345:725–30).

“It is difficult to compare and contrast the two different strategies, but I think what the study does do is offer us the option of two different strategies for patients with this disease—either perioperative chemotherapy or surgery and then postoperative chemoradiation,” he said. “And maybe combining those strategies can improve outcomes.”

Dr. Cunningham rejected a suggestion that patients in the MAGIC trial's control arm had poorer survival than did patients in other adjunctive therapy trials. He said these groups could not be compared, because the MAGIC trial enrolled “all comers,” whereas adjunctive therapy trials enroll only patients who have had successful operations.

“There hasn't been much improvement in outcome [for gastric cancer patients until now], but with these multimodalities we are hoping there will be,” Dr. Cunningham told this newspaper. He described the current outlook for patients with non-colorectal gastrointestinal cancers as “pretty grim,” but predicted that current investigations would soon lead to “massive” improvement.

In a discussion of the MAGIC trial, Robert J. Mayer, M.D., said the results “are convincing, validating the concept of perioperative chemotherapy.” What remains unclear, said Dr. Mayer, director of the center for gastrointestinal oncology at the Dana-Farber Cancer Institute in Boston, is which chemotherapy regimen is the best combination, not only for perioperative chemotherapy but also for postoperative chemoradiation.

ORLANDO — Gastric cancer patients who received perioperative chemotherapy showed a 13% absolute improvement in 5-year survival in a large phase III trial sponsored by the United Kingdom's Medical Research Council.

Of the patients who received chemotherapy before and after surgery, 36% were alive 5 years after diagnosis, whereas only 23% of a control group randomized to surgery alone lived that long, investigator David Cunningham, M.D., reported at the annual meeting of the American Society of Clinical Oncology.

The chemotherapy regimen downstaged primary tumors and signif-icantly improved progression-free survival as well, said Dr. Cunningham of the Royal Marsden Hospital in Surrey, England. He reported recurrences in 62% of the control group but in only 42% of patients who received perioperative chemotherapy.

The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial enrolled 503 patients with operable cancer of the stomach and lower esophagus from July 1994 to April 2002. The trial randomized 253 patients to surgery alone and 250 to receive surgery plus three preoperative and three postoperative cycles of chemotherapy.

The chemotherapy regimen contained an intravenous bolus of 50 mg/m

Fewer patients in the chemotherapy arm proceeded to surgery: 219 patients (about 88%) vs. 240 patients (95%) in the control group. Yet more chemotherapy patients had operations that were deemed curative: 169 patients (about 79%) compared with 166 patients (about 70%) who had no chemotherapy.

Postoperative deaths (6%) and complications (46%) were the same for both groups, as was the median postoperative hospital stay (13 days).

Postsurgery pathology showed the chemotherapy patients had a smaller maximum tumor diameter (median 3 cm vs. 5 cm in the control group). The chemotherapy patients with gastric tumors were more likely to have less advanced disease: 52% were classified as T1 or T2 vs. 38% of the control group. They were also less likely to have more advanced nodal status: 16% were classified as N3 or N4 vs. 29% of the controls.

Median survival was calculated as 24 months with chemotherapy and 20 months with surgery alone. The unadjusted hazard ratio for death was 0.75 in the chemotherapy arm. Progression-free survival was also superior, with a hazard ratio of 0.66 favoring chemotherapy.

Survival results were based on an intent-to-treat analysis at a median follow-up greater than 3 years. In all, 90% of patients were followed 2 or more years or until death.

In response to an audience question, Dr. Cunningham declined to claim that the trial established perioperative chemotherapy as a new standard. Surgery alone has been standard in Europe, he said, whereas postoperative chemoradiation has been common in the United States since its benefits were reported in another standardized trial (N. Engl. J. Med. 2001;345:725–30).

“It is difficult to compare and contrast the two different strategies, but I think what the study does do is offer us the option of two different strategies for patients with this disease—either perioperative chemotherapy or surgery and then postoperative chemoradiation,” he said. “And maybe combining those strategies can improve outcomes.”

Dr. Cunningham rejected a suggestion that patients in the MAGIC trial's control arm had poorer survival than did patients in other adjunctive therapy trials. He said these groups could not be compared, because the MAGIC trial enrolled “all comers,” whereas adjunctive therapy trials enroll only patients who have had successful operations.

“There hasn't been much improvement in outcome [for gastric cancer patients until now], but with these multimodalities we are hoping there will be,” Dr. Cunningham told this newspaper. He described the current outlook for patients with non-colorectal gastrointestinal cancers as “pretty grim,” but predicted that current investigations would soon lead to “massive” improvement.

In a discussion of the MAGIC trial, Robert J. Mayer, M.D., said the results “are convincing, validating the concept of perioperative chemotherapy.” What remains unclear, said Dr. Mayer, director of the center for gastrointestinal oncology at the Dana-Farber Cancer Institute in Boston, is which chemotherapy regimen is the best combination, not only for perioperative chemotherapy but also for postoperative chemoradiation.

ASPEN, COLO. — Routine vaccinations can be accelerated to protect very young travelers against infectious diseases in developing countries, Sarah K. Parker, M.D., advised at a conference on pediatric infectious diseases sponsored by Children's Hospital, Denver.

“They can be really protected by about 13½ months of age,” said Dr. Parker of Children's Hospital and a faculty member in pediatric infectious diseases at the University of Colorado Health Sciences Center, Denver.

Dr. Parker also recommended that physicians do a pretravel assessment to identify additional vaccination requirements by endemic conditions in destination countries.

The assessment would include consideration of chemoprophylaxis and counseling parents on ways to prevent infectious disease while traveling abroad.

“Infection only causes about 1% of traveler deaths. However, it is a large fraction of what causes illness while traveling,” she said. About 50%–70% of travelers become ill. Diarrhea accounts for about 40% of illnesses. Plus, it can be more severe and prolonged in children.

Routine vaccinations can start at 6 weeks of age, she said, outlining an accelerated schedule. Babies can receive four doses of inactivated polio vaccine; three doses of DTaP vaccine, Haemophilus influenzae type b vaccine, and 7-valent pneumococcal polysaccharide vaccine; and two doses of hepatitis B virus vaccine by 14 weeks.

MMR can be given at 6 months, she said, but does not count. If given at 12 months, it can be followed by a booster at 13 months. The accelerated schedule also permits hepatitis A virus vaccine off label at 12 months.

A family traveling to Africa's “meningitis belt” should use the polysaccharide conjugate vaccine for children older than 11 years, the polysaccharide meningococcal vaccine for children 2–11 years, and consider its use off label in younger children at high risk, she said.

The polysaccharide vaccine has been studied at 3 months with a 12-month booster with a rise in titers against meningococcus A, the predominant strain in Africa. Varicella zoster virus (VZV) and influenza vaccines cannot be accelerated, however.

If one is protecting against hepatitis A with hepatitis A immunoglobulin, Dr. Parker noted that hepatitis A IgG interferes with MMR and VZV. Therefore, MMR and/or VZV vaccines should be given 2 weeks earlier, she said, adding that hepatitis A vaccine and IgG can be given together.

Hepatitis A IgG must be repeated every 5 months while the child is in an endemic area.

Dr. Parker urged primary care physicians to consider prevalence of disease in destination nations when reviewing itineraries. Influenza should not be overlooked, she said. It is endemic year around close to the equator and from March to October in the southern hemisphere. She suggested stockpiling flu vaccine released in October for use through June 30.

Meningococcal vaccine is required for pilgrims making the hajj, according to Dr. Parker. She said it also should be considered, even if off label, for children heading to Africa's “meningitis belt” and other potential risk areas.

Causing 22 million cases a year, Salmonella typhi is a concern throughout the developing world, she said. She advised vaccinating anyone older than 2 years of age who is heading to an endemic area.

Two vaccines are options if typhoid is a risk, Dr. Parker said. The injectable capsular polysaccharide vaccine is approved for children over 2 years and can be given 2 weeks prior to travel. Oral live, attenuated Ty21 a virus vaccine is approved for children older than 6 years but cannot be given if the child is immunodeficient.

Yellow fever vaccine is indicated for travel to endemic areas and required by some countries unless contraindicated. It should not be given to infants younger than 4 months old and is contraindicated in infants 5–9 months of age.

Because encephalitis can be a side effect, “you don't want to give it to someone who doesn't need it,” she advised.

Japanese encephalitis is a risk in parts of Asia. Mortality is high, however, with deaths in 5%–30% of those who develop symptoms, according to Dr. Parker.

If mosquito exposure is likely during an extended stay in an endemic area during the endemic season, she recommended vaccination with an inactivated virus. It is approved for persons over 1 year of age. Because severe allergic reactions can occur up to 10 days afterward, she said this vaccine should be given at least 2 weeks in advance of travel.

No drug can prevent malarial infection, Dr. Parker said, but some agents can prevent disease. For pediatric considerations in prophylaxis, she referred physicians to a journal article (Semin. Pediatr. Infect. Dis. 2004;15:137–49).

Whether or not prophylaxis is used, families should try to prevent mosquito bites by making careful use of N,N-diethyl-m-toluamide (DEET), wearing permethrin-treated clothing, and covering exposed skin.

Dogs and sweets pose special risks when traveling with young children who love both.

Along with the usual dietary precautions, Dr. Parker warned that frozen desserts may not be pasteurized. Parents should be told to seek care early if a child gets diarrhea.

Much of the world has dog rabies, Dr. Parler added, so teaching children not to pet animals is very important, albeit difficult. She recommended vaccinating children against rabies before travel to highly endemic areas, where good health care and rabies immunoglobulin are not readily available. But she warned that a vaccinated child would have to be revaccinated if bitten.

“Vaccination is not enough. It just buys time,” Dr. Parker said, noting that postexposure prophylaxis is not available in some countries.

Visits to Families Abroad Pose Risks

Foreign-born families taking young children to meet relatives in their home countries face significantly greater health risks, compared with other travelers, said Dr. Parker.

The youngsters are often very young; mothers may travel while pregnant; and, sometimes, family members are ill even before they leave on trips timed to family occasions, she said.

These families also stay longer, use less safe local transportation, and have difficulty refusing unsafe food or water in the homes of friends and relatives, Dr. Parker observed. As a result, visitors of friends and relatives are 10 times as likely to get malaria or typhoid as other travelers.

Yet, foreign-born parents often do not seek medical advice before these journeys, according to Dr. Parker. Even if they have concerns, many don't seek pretravel advice because of the expense.

Some do not believe their families have to worry about organisms in the communities where they grew up. These travelers often see themselves and their children as “already immune,” which in large part is a myth, especially for their children, said Dr. Parker.

Even if they see a physician, travelers going back home are less likely to follow medical advice than are ecotourists, adventurers, missionaries, or relief workers traveling to developing countries.

Selected Travel Health Web Sites

CDC Traveler's Health Web Site

www.cdc.gov/travel/destinat.htm

CDC Yellow Book

http://www.cdc.gov/travel/yb/index.htm

World Health Organization Vaccine Preventable Diseases Monitoring System

(Vaccine schedules listed by country)

www.who.int/immunization_monitoring/en/globalsummary/scheduleselect.cfm

WHO Global Health Atlas

(Communicable disease, including rabies)

www.who.int/globalatlas

Pan American Health Organization

www.paho.org

International Association for Medical Assistance to Travelers (IAMAT)

www.iamat.org

U.S. State Department

http://travel.state.gov/travel/travel_1744.html

Source: Dr. Parker

ASPEN, COLO. — Routine vaccinations can be accelerated to protect very young travelers against infectious diseases in developing countries, Sarah K. Parker, M.D., advised at a conference on pediatric infectious diseases sponsored by Children's Hospital, Denver.

“They can be really protected by about 13½ months of age,” said Dr. Parker of Children's Hospital and a faculty member in pediatric infectious diseases at the University of Colorado Health Sciences Center, Denver.

Dr. Parker also recommended that physicians do a pretravel assessment to identify additional vaccination requirements by endemic conditions in destination countries.

The assessment would include consideration of chemoprophylaxis and counseling parents on ways to prevent infectious disease while traveling abroad.

“Infection only causes about 1% of traveler deaths. However, it is a large fraction of what causes illness while traveling,” she said. About 50%–70% of travelers become ill. Diarrhea accounts for about 40% of illnesses. Plus, it can be more severe and prolonged in children.

Routine vaccinations can start at 6 weeks of age, she said, outlining an accelerated schedule. Babies can receive four doses of inactivated polio vaccine; three doses of DTaP vaccine, Haemophilus influenzae type b vaccine, and 7-valent pneumococcal polysaccharide vaccine; and two doses of hepatitis B virus vaccine by 14 weeks.

MMR can be given at 6 months, she said, but does not count. If given at 12 months, it can be followed by a booster at 13 months. The accelerated schedule also permits hepatitis A virus vaccine off label at 12 months.

A family traveling to Africa's “meningitis belt” should use the polysaccharide conjugate vaccine for children older than 11 years, the polysaccharide meningococcal vaccine for children 2–11 years, and consider its use off label in younger children at high risk, she said.

The polysaccharide vaccine has been studied at 3 months with a 12-month booster with a rise in titers against meningococcus A, the predominant strain in Africa. Varicella zoster virus (VZV) and influenza vaccines cannot be accelerated, however.

If one is protecting against hepatitis A with hepatitis A immunoglobulin, Dr. Parker noted that hepatitis A IgG interferes with MMR and VZV. Therefore, MMR and/or VZV vaccines should be given 2 weeks earlier, she said, adding that hepatitis A vaccine and IgG can be given together.

Hepatitis A IgG must be repeated every 5 months while the child is in an endemic area.

Dr. Parker urged primary care physicians to consider prevalence of disease in destination nations when reviewing itineraries. Influenza should not be overlooked, she said. It is endemic year around close to the equator and from March to October in the southern hemisphere. She suggested stockpiling flu vaccine released in October for use through June 30.

Meningococcal vaccine is required for pilgrims making the hajj, according to Dr. Parker. She said it also should be considered, even if off label, for children heading to Africa's “meningitis belt” and other potential risk areas.

Causing 22 million cases a year, Salmonella typhi is a concern throughout the developing world, she said. She advised vaccinating anyone older than 2 years of age who is heading to an endemic area.

Two vaccines are options if typhoid is a risk, Dr. Parker said. The injectable capsular polysaccharide vaccine is approved for children over 2 years and can be given 2 weeks prior to travel. Oral live, attenuated Ty21 a virus vaccine is approved for children older than 6 years but cannot be given if the child is immunodeficient.

Yellow fever vaccine is indicated for travel to endemic areas and required by some countries unless contraindicated. It should not be given to infants younger than 4 months old and is contraindicated in infants 5–9 months of age.

Because encephalitis can be a side effect, “you don't want to give it to someone who doesn't need it,” she advised.

Japanese encephalitis is a risk in parts of Asia. Mortality is high, however, with deaths in 5%–30% of those who develop symptoms, according to Dr. Parker.

If mosquito exposure is likely during an extended stay in an endemic area during the endemic season, she recommended vaccination with an inactivated virus. It is approved for persons over 1 year of age. Because severe allergic reactions can occur up to 10 days afterward, she said this vaccine should be given at least 2 weeks in advance of travel.

No drug can prevent malarial infection, Dr. Parker said, but some agents can prevent disease. For pediatric considerations in prophylaxis, she referred physicians to a journal article (Semin. Pediatr. Infect. Dis. 2004;15:137–49).

Whether or not prophylaxis is used, families should try to prevent mosquito bites by making careful use of N,N-diethyl-m-toluamide (DEET), wearing permethrin-treated clothing, and covering exposed skin.

Dogs and sweets pose special risks when traveling with young children who love both.

Along with the usual dietary precautions, Dr. Parker warned that frozen desserts may not be pasteurized. Parents should be told to seek care early if a child gets diarrhea.

Much of the world has dog rabies, Dr. Parler added, so teaching children not to pet animals is very important, albeit difficult. She recommended vaccinating children against rabies before travel to highly endemic areas, where good health care and rabies immunoglobulin are not readily available. But she warned that a vaccinated child would have to be revaccinated if bitten.

“Vaccination is not enough. It just buys time,” Dr. Parker said, noting that postexposure prophylaxis is not available in some countries.

Visits to Families Abroad Pose Risks

Foreign-born families taking young children to meet relatives in their home countries face significantly greater health risks, compared with other travelers, said Dr. Parker.

The youngsters are often very young; mothers may travel while pregnant; and, sometimes, family members are ill even before they leave on trips timed to family occasions, she said.

These families also stay longer, use less safe local transportation, and have difficulty refusing unsafe food or water in the homes of friends and relatives, Dr. Parker observed. As a result, visitors of friends and relatives are 10 times as likely to get malaria or typhoid as other travelers.

Yet, foreign-born parents often do not seek medical advice before these journeys, according to Dr. Parker. Even if they have concerns, many don't seek pretravel advice because of the expense.

Some do not believe their families have to worry about organisms in the communities where they grew up. These travelers often see themselves and their children as “already immune,” which in large part is a myth, especially for their children, said Dr. Parker.

Even if they see a physician, travelers going back home are less likely to follow medical advice than are ecotourists, adventurers, missionaries, or relief workers traveling to developing countries.

Selected Travel Health Web Sites

CDC Traveler's Health Web Site

www.cdc.gov/travel/destinat.htm

CDC Yellow Book

http://www.cdc.gov/travel/yb/index.htm

World Health Organization Vaccine Preventable Diseases Monitoring System

(Vaccine schedules listed by country)

www.who.int/immunization_monitoring/en/globalsummary/scheduleselect.cfm

WHO Global Health Atlas

(Communicable disease, including rabies)

www.who.int/globalatlas

Pan American Health Organization

www.paho.org

International Association for Medical Assistance to Travelers (IAMAT)

www.iamat.org

U.S. State Department

http://travel.state.gov/travel/travel_1744.html

Source: Dr. Parker

ASPEN, COLO. — Routine vaccinations can be accelerated to protect very young travelers against infectious diseases in developing countries, Sarah K. Parker, M.D., advised at a conference on pediatric infectious diseases sponsored by Children's Hospital, Denver.

“They can be really protected by about 13½ months of age,” said Dr. Parker of Children's Hospital and a faculty member in pediatric infectious diseases at the University of Colorado Health Sciences Center, Denver.

Dr. Parker also recommended that physicians do a pretravel assessment to identify additional vaccination requirements by endemic conditions in destination countries.

The assessment would include consideration of chemoprophylaxis and counseling parents on ways to prevent infectious disease while traveling abroad.

“Infection only causes about 1% of traveler deaths. However, it is a large fraction of what causes illness while traveling,” she said. About 50%–70% of travelers become ill. Diarrhea accounts for about 40% of illnesses. Plus, it can be more severe and prolonged in children.

Routine vaccinations can start at 6 weeks of age, she said, outlining an accelerated schedule. Babies can receive four doses of inactivated polio vaccine; three doses of DTaP vaccine, Haemophilus influenzae type b vaccine, and 7-valent pneumococcal polysaccharide vaccine; and two doses of hepatitis B virus vaccine by 14 weeks.

MMR can be given at 6 months, she said, but does not count. If given at 12 months, it can be followed by a booster at 13 months. The accelerated schedule also permits hepatitis A virus vaccine off label at 12 months.

A family traveling to Africa's “meningitis belt” should use the polysaccharide conjugate vaccine for children older than 11 years, the polysaccharide meningococcal vaccine for children 2–11 years, and consider its use off label in younger children at high risk, she said.

The polysaccharide vaccine has been studied at 3 months with a 12-month booster with a rise in titers against meningococcus A, the predominant strain in Africa. Varicella zoster virus (VZV) and influenza vaccines cannot be accelerated, however.

If one is protecting against hepatitis A with hepatitis A immunoglobulin, Dr. Parker noted that hepatitis A IgG interferes with MMR and VZV. Therefore, MMR and/or VZV vaccines should be given 2 weeks earlier, she said, adding that hepatitis A vaccine and IgG can be given together.

Hepatitis A IgG must be repeated every 5 months while the child is in an endemic area.

Dr. Parker urged primary care physicians to consider prevalence of disease in destination nations when reviewing itineraries. Influenza should not be overlooked, she said. It is endemic year around close to the equator and from March to October in the southern hemisphere. She suggested stockpiling flu vaccine released in October for use through June 30.

Meningococcal vaccine is required for pilgrims making the hajj, according to Dr. Parker. She said it also should be considered, even if off label, for children heading to Africa's “meningitis belt” and other potential risk areas.

Causing 22 million cases a year, Salmonella typhi is a concern throughout the developing world, she said. She advised vaccinating anyone older than 2 years of age who is heading to an endemic area.

Two vaccines are options if typhoid is a risk, Dr. Parker said. The injectable capsular polysaccharide vaccine is approved for children over 2 years and can be given 2 weeks prior to travel. Oral live, attenuated Ty21 a virus vaccine is approved for children older than 6 years but cannot be given if the child is immunodeficient.

Yellow fever vaccine is indicated for travel to endemic areas and required by some countries unless contraindicated. It should not be given to infants younger than 4 months old and is contraindicated in infants 5–9 months of age.

Because encephalitis can be a side effect, “you don't want to give it to someone who doesn't need it,” she advised.

Japanese encephalitis is a risk in parts of Asia. Mortality is high, however, with deaths in 5%–30% of those who develop symptoms, according to Dr. Parker.

If mosquito exposure is likely during an extended stay in an endemic area during the endemic season, she recommended vaccination with an inactivated virus. It is approved for persons over 1 year of age. Because severe allergic reactions can occur up to 10 days afterward, she said this vaccine should be given at least 2 weeks in advance of travel.

No drug can prevent malarial infection, Dr. Parker said, but some agents can prevent disease. For pediatric considerations in prophylaxis, she referred physicians to a journal article (Semin. Pediatr. Infect. Dis. 2004;15:137–49).

Whether or not prophylaxis is used, families should try to prevent mosquito bites by making careful use of N,N-diethyl-m-toluamide (DEET), wearing permethrin-treated clothing, and covering exposed skin.

Dogs and sweets pose special risks when traveling with young children who love both.

Along with the usual dietary precautions, Dr. Parker warned that frozen desserts may not be pasteurized. Parents should be told to seek care early if a child gets diarrhea.

Much of the world has dog rabies, Dr. Parler added, so teaching children not to pet animals is very important, albeit difficult. She recommended vaccinating children against rabies before travel to highly endemic areas, where good health care and rabies immunoglobulin are not readily available. But she warned that a vaccinated child would have to be revaccinated if bitten.

“Vaccination is not enough. It just buys time,” Dr. Parker said, noting that postexposure prophylaxis is not available in some countries.

Visits to Families Abroad Pose Risks

Foreign-born families taking young children to meet relatives in their home countries face significantly greater health risks, compared with other travelers, said Dr. Parker.

The youngsters are often very young; mothers may travel while pregnant; and, sometimes, family members are ill even before they leave on trips timed to family occasions, she said.

These families also stay longer, use less safe local transportation, and have difficulty refusing unsafe food or water in the homes of friends and relatives, Dr. Parker observed. As a result, visitors of friends and relatives are 10 times as likely to get malaria or typhoid as other travelers.

Yet, foreign-born parents often do not seek medical advice before these journeys, according to Dr. Parker. Even if they have concerns, many don't seek pretravel advice because of the expense.

Some do not believe their families have to worry about organisms in the communities where they grew up. These travelers often see themselves and their children as “already immune,” which in large part is a myth, especially for their children, said Dr. Parker.

Even if they see a physician, travelers going back home are less likely to follow medical advice than are ecotourists, adventurers, missionaries, or relief workers traveling to developing countries.

Selected Travel Health Web Sites

CDC Traveler's Health Web Site

www.cdc.gov/travel/destinat.htm

CDC Yellow Book

http://www.cdc.gov/travel/yb/index.htm

World Health Organization Vaccine Preventable Diseases Monitoring System

(Vaccine schedules listed by country)

www.who.int/immunization_monitoring/en/globalsummary/scheduleselect.cfm

WHO Global Health Atlas

(Communicable disease, including rabies)

www.who.int/globalatlas

Pan American Health Organization

www.paho.org

International Association for Medical Assistance to Travelers (IAMAT)

www.iamat.org

U.S. State Department

http://travel.state.gov/travel/travel_1744.html

Source: Dr. Parker

ASPEN, COLO. — Rapid antigen detection tests have a high false-negative rate, and cannot be relied upon to diagnosis strep throat without a confirmatory throat culture, according to S. Michael Marcy, M.D.

“Many people are using antigen detection tests alone. This is not what is recommended yet,” he said, urging caution in adopting the new tests. Dr. Marcy was speaking at a conference on pediatric infectious diseases sponsored by Children's Hospital, Denver.

Throat culture is still the preferred method, advised Dr. Marcy of the University of Southern California and the University of California, Los Angeles.

In nearly all cases, he said antibiotics should not be prescribed until group A streptococcal infection is confirmed.

One exception to that approach would be in the case of a very sick child presenting with doughnut-like papules that have white centers. “These are diagnostic,” Dr. Marcy explained.

The Centers for Disease Control and Prevention and the American Academy of Pediatrics say antibiotics may be prescribed without a culture if an antigen detection test is positive, according to Dr. Marcy. If it is negative, both recommend the results be confirmed by a throat culture.

“The problem with antigen detection tests, in my opinion, is unless you get the answer immediately, you don't have a huge advantage,” he said.

In pediatric practices where tests are processed in a batch, Dr. Marcy said the results typically arrive after the parent has taken the child home. Then the family has to be called back for the confirmatory culture or sent to the pharmacy.

In his own medical practice at Kaiser Foundation Hospital in Panorama City, Calif., Dr. Marcy said he does not bother giving the rapid test at all. Instead, he does a culture if strep is suspected and the clinical signs do not strongly suggest a viral etiology.

While waiting for the results from the throat culture, Dr. Marcy prescribes Tylenol to prevent fever and pain. “I tell parents about preventing rather than chasing the symptoms,” he said, calling Tylenol “as good as penicillin” during the wait.

He also posts a chart published in this newspaper in June 2002 that illustrates how long cold and flu symptoms, including sore throat, persist. The chart explains that these are viral illnesses for which antibiotics will not work.

“Parents look at it and say, 'I don't need to see you,'” Dr. Marcy recounted, calling the chart on cold and flu symptoms “very useful.”

Only about 20% of throat cultures are positive for strep, according to Dr. Marcy. He cited a Finnish study that found a viral infection in 42% of children with febrile exudative pharyngitis; no pathogen was detected in 37%. While 37% had bacterial infections, just 12% of pathogens were group A streptococci (Pediatrics 1987;80:6–12). Coinfections brought the total above 100%.

Current recommendations call for physicians to take throat cultures with two swabs, Dr. Marcy noted. He further explained that the samples must be taken from the patient's right and left tonsils. “If you only touch one side, you will get a false negative 30% of the time. Three separate papers show that. You must touch them both.”

If group A strep is confirmed, amoxicillin is the treatment of choice, Dr. Marcy said. He recommended prescribing 750 mg once a day for 5 days.

“Compliance is better” than it is with the twice-a-day option, he said, dismissing controversy over the efficacy of cephalosporin vs. penicillin as dated. “What needs to be done at this time is [a trial comparing] cephalosporin versus amoxicillin. This has to be done.”

ASPEN, COLO. — Rapid antigen detection tests have a high false-negative rate, and cannot be relied upon to diagnosis strep throat without a confirmatory throat culture, according to S. Michael Marcy, M.D.

“Many people are using antigen detection tests alone. This is not what is recommended yet,” he said, urging caution in adopting the new tests. Dr. Marcy was speaking at a conference on pediatric infectious diseases sponsored by Children's Hospital, Denver.

Throat culture is still the preferred method, advised Dr. Marcy of the University of Southern California and the University of California, Los Angeles.

In nearly all cases, he said antibiotics should not be prescribed until group A streptococcal infection is confirmed.

One exception to that approach would be in the case of a very sick child presenting with doughnut-like papules that have white centers. “These are diagnostic,” Dr. Marcy explained.

The Centers for Disease Control and Prevention and the American Academy of Pediatrics say antibiotics may be prescribed without a culture if an antigen detection test is positive, according to Dr. Marcy. If it is negative, both recommend the results be confirmed by a throat culture.

“The problem with antigen detection tests, in my opinion, is unless you get the answer immediately, you don't have a huge advantage,” he said.

In pediatric practices where tests are processed in a batch, Dr. Marcy said the results typically arrive after the parent has taken the child home. Then the family has to be called back for the confirmatory culture or sent to the pharmacy.

In his own medical practice at Kaiser Foundation Hospital in Panorama City, Calif., Dr. Marcy said he does not bother giving the rapid test at all. Instead, he does a culture if strep is suspected and the clinical signs do not strongly suggest a viral etiology.

While waiting for the results from the throat culture, Dr. Marcy prescribes Tylenol to prevent fever and pain. “I tell parents about preventing rather than chasing the symptoms,” he said, calling Tylenol “as good as penicillin” during the wait.

He also posts a chart published in this newspaper in June 2002 that illustrates how long cold and flu symptoms, including sore throat, persist. The chart explains that these are viral illnesses for which antibiotics will not work.

“Parents look at it and say, 'I don't need to see you,'” Dr. Marcy recounted, calling the chart on cold and flu symptoms “very useful.”

Only about 20% of throat cultures are positive for strep, according to Dr. Marcy. He cited a Finnish study that found a viral infection in 42% of children with febrile exudative pharyngitis; no pathogen was detected in 37%. While 37% had bacterial infections, just 12% of pathogens were group A streptococci (Pediatrics 1987;80:6–12). Coinfections brought the total above 100%.

Current recommendations call for physicians to take throat cultures with two swabs, Dr. Marcy noted. He further explained that the samples must be taken from the patient's right and left tonsils. “If you only touch one side, you will get a false negative 30% of the time. Three separate papers show that. You must touch them both.”

If group A strep is confirmed, amoxicillin is the treatment of choice, Dr. Marcy said. He recommended prescribing 750 mg once a day for 5 days.

“Compliance is better” than it is with the twice-a-day option, he said, dismissing controversy over the efficacy of cephalosporin vs. penicillin as dated. “What needs to be done at this time is [a trial comparing] cephalosporin versus amoxicillin. This has to be done.”

ASPEN, COLO. — Rapid antigen detection tests have a high false-negative rate, and cannot be relied upon to diagnosis strep throat without a confirmatory throat culture, according to S. Michael Marcy, M.D.

“Many people are using antigen detection tests alone. This is not what is recommended yet,” he said, urging caution in adopting the new tests. Dr. Marcy was speaking at a conference on pediatric infectious diseases sponsored by Children's Hospital, Denver.

Throat culture is still the preferred method, advised Dr. Marcy of the University of Southern California and the University of California, Los Angeles.

In nearly all cases, he said antibiotics should not be prescribed until group A streptococcal infection is confirmed.

One exception to that approach would be in the case of a very sick child presenting with doughnut-like papules that have white centers. “These are diagnostic,” Dr. Marcy explained.

The Centers for Disease Control and Prevention and the American Academy of Pediatrics say antibiotics may be prescribed without a culture if an antigen detection test is positive, according to Dr. Marcy. If it is negative, both recommend the results be confirmed by a throat culture.

“The problem with antigen detection tests, in my opinion, is unless you get the answer immediately, you don't have a huge advantage,” he said.

In pediatric practices where tests are processed in a batch, Dr. Marcy said the results typically arrive after the parent has taken the child home. Then the family has to be called back for the confirmatory culture or sent to the pharmacy.

In his own medical practice at Kaiser Foundation Hospital in Panorama City, Calif., Dr. Marcy said he does not bother giving the rapid test at all. Instead, he does a culture if strep is suspected and the clinical signs do not strongly suggest a viral etiology.

While waiting for the results from the throat culture, Dr. Marcy prescribes Tylenol to prevent fever and pain. “I tell parents about preventing rather than chasing the symptoms,” he said, calling Tylenol “as good as penicillin” during the wait.

He also posts a chart published in this newspaper in June 2002 that illustrates how long cold and flu symptoms, including sore throat, persist. The chart explains that these are viral illnesses for which antibiotics will not work.

“Parents look at it and say, 'I don't need to see you,'” Dr. Marcy recounted, calling the chart on cold and flu symptoms “very useful.”

Only about 20% of throat cultures are positive for strep, according to Dr. Marcy. He cited a Finnish study that found a viral infection in 42% of children with febrile exudative pharyngitis; no pathogen was detected in 37%. While 37% had bacterial infections, just 12% of pathogens were group A streptococci (Pediatrics 1987;80:6–12). Coinfections brought the total above 100%.

Current recommendations call for physicians to take throat cultures with two swabs, Dr. Marcy noted. He further explained that the samples must be taken from the patient's right and left tonsils. “If you only touch one side, you will get a false negative 30% of the time. Three separate papers show that. You must touch them both.”

If group A strep is confirmed, amoxicillin is the treatment of choice, Dr. Marcy said. He recommended prescribing 750 mg once a day for 5 days.

“Compliance is better” than it is with the twice-a-day option, he said, dismissing controversy over the efficacy of cephalosporin vs. penicillin as dated. “What needs to be done at this time is [a trial comparing] cephalosporin versus amoxicillin. This has to be done.”

ASPEN, COLO. — Two groups of immunocompromised children present special challenges in community-based practices, Elizabeth J. McFarland, M.D., said at a conference on pediatric infectious diseases, sponsored by Children's Hospital, Denver.

Weakened immune systems can make some vaccinations worrisome for youngsters taking high-dose steroids to control asthma and can make other vaccinations vital for children without a spleen, said Dr. McFarland, director of the hospital's immunodeficiency clinic.

Even more serious, she warned, is the risk of sepsis, with high mortality rates from postsplenectomy sepsis. Half of sepsis cases occur within 2 years of spleen removal, but 3% have been documented 20 years afterward (Br. J. Surg. 1991;78:1031–8).

Asthma and Steroid Issues

Dr. McFarland acknowledged that steroids are “important drugs” for controlling asthma.

The problem is that by interfering with cytokine production and lessening immune cell activity, steroids reduce the body's “ability to mount immune response or react to vaccine.”

According to Dr. McFarland, the American Academy of Pediatrics supports giving inactivated virus vaccines to children who are prescribed steroids, but she cautions that immunogenicity is uncertain. Live virus vaccines should be delayed until high-dose steroids are stopped.

If children take a high-dose steroid daily or on alternate days for more than 14 days, doctors should wait 1 month after stopping steroid use before giving vaccines, Dr. McFarland said. She also said that if the dosage period is less than 14 days, live virus vaccines can be given after stopping, but some experts recommend waiting 2 weeks.

The American Academy of Pediatrics recommends inactivated influenza vaccine for patients with asthma. Dr. McFarland said studies have shown similar antibody responses to the influenza vaccine in patients receiving inhaled steroids and short-course oral steroids, when compared with patients not receiving steroids at the time of immunization.

The live varicella zoster virus (VZV) vaccine is not recommended during high-dose steroid use, because vaccine safety is not established in this population. However, Dr. McFarland said a health maintenance organization study found that inhaled steroids given 3 months prior to VZV vaccination were not associated with increased risk of breakthrough disease (Pediatrics 2003;112:e98-e113), but the study did find increased breakthrough disease after VZV vaccination when oral steroids were given in the 3 months prior.

Postsplenectomy Issues

European studies have shown that about a quarter of physicians do not comply with guidelines for postsplenectomy care, Dr. McFarland said. She could not find any similar studies in the United States.

Although splenectomies in children may be necessary after trauma, she said the operation is being done less often owing to greater recognition of the spleen's importance to immune defense and to newer splenic salvage techniques. Dr. McFarland urged pneumococcal vaccination for postsplenectomy patients. About two-thirds of sepsis cases have been traced to Streptococcus pneumoniae in this population.

If the regular pneumococcal conjugate vaccine (PCV) series was not given before age 24 months, doctors should give two doses of PCV, she said. She recommended one dose of pneumococcal polysaccharide vaccine 6–8 weeks after PCV, and a second dose 3–5 years afterward.

Postsplenectomy children also should be vaccinated against meningococcus, according to Dr. McFarland. The new meningococcal conjugate vaccine (MCV4) is preferred for patients aged 11–55; only meningococcal polysaccharide vaccine (MPSV4) is approved for patients aged 2–11. Optimally, vaccinations for the encapsulated bacteria should be given prior to a planned splenectomy.

She suggested giving an extra dose of Haemophilus influenzae type b (Hib) vaccine prior to splenectomy, if possible.

Afterward, these children also should receive annual influenza shots, she said.

Daily antibiotic prophylaxis is recommended, especially in the first 2 years after splenectomy.

However, Dr. McFarland said the randomized studies supporting its use were performed in young sickle cell anemia patients with functional asplenia.

Determining when to discontinue daily prophylaxis is difficult, she said, as there are no direct data for children with splenectomies. Physicians should discuss the risks and benefits.

The recommended dosages are 125 mg of penicillin V twice daily in children under age 5 and 250 mg twice daily in children over age 5; some experts use amoxicillin (20 mg/kg daily).

Empiric therapy is another option, often used if daily prophylaxis is discontinued. At the first sign of a fever, the parents administer a dose of oral antibiotics and then bring in the child “pronto” for further evaluation.

Dr. McFarland recommended 50 mg/kg of amoxicillin/clavulanate potassium (Augmentin) divided into 2–3 dosages daily or an alternative, possibly a cephalosporin, if the child is allergic to penicillin.

Pneumococcal resistance to penicillin is a concern, she said, and she urged physicians to find out the rate in their community.

For sepsis cases, however, she recommended starting with vancomycin and a cephalosporin.

Indeed, family education is a priority when caring for a child who has lost a spleen.

“You need to give them something written, as you want them to understand the risk of infection,” she said. “And you want to do it more than once.”

Pet Safety: Teach Parents About Zoonoses

Many physicians—Dr. McFarland among them—do not have the heart to banish all pets from the home of an immunocompromised child.

“The better you can take care of your animal … the less likely your pet will get sick,” is the message she urged pediatricians to give to parents of immunocompromised patients. Keeping the animal healthy will help the child stay well.

Dr. McFarland said the U.S. Public Health Service has identified five zoonoses of particular concern that immunocompromised children can pick up from animals: salmonellosis, campylobacteriosis, bacillary angiomatosis (Bartonella henselae, or cat scratch disease), cryptosporidiosis, and toxoplasmosis.

Countering these risks, she summarized the benefits of pet ownership, including decreased loneliness and increased feeling of intimacy and constancy.

The first principle of pet safety, she said, is to buy or adopt a healthy animal, preferably an adult. Young animals are more vulnerable to pathogens. No animal with diarrhea should be handled by the child.

Second, keep the animal healthy by preventing exposure to pathogens. For example, don't let cats or dogs roam. Fleas and ticks are a concern, as well as exposure to other animals and their feces, and anything else the pet might eat off the street.

Keep the animal inside, and keep the toilet seat down so the pet does not use the fixture as a fountain. Feed the animal well, and make sure it does not get into the garbage.

Third, avoid all contact with feces.

Dr. McFarland offered additional recommendations for patients, including children, who undergo hematopoietic stem cell transplants (MMWR 2000;49[RR10]:1–128).

Parents should be advised of the risks, but children don't need to be forced to part with their pets.

Animals should be fed high-quality commercial pet food, according to Dr. McFarland. All dairy foods should be pasteurized, and any foods containing eggs, poultry, or meat should be well cooked.

Stem cell recipients should always wash their hands after handling an animal. Someone else should clean a cage, a litter box, or a fish tank while the patient is immunocompromised. Litter boxes should be cleaned daily and kept away from food preparation or eating areas.

At the first suspicion of a pet's illness, the animal should be taken to the vet, Dr. McFarland said.

Even with these precautions, some animals are prohibited as pets. She listed all reptiles (with a warning against reptile fomites), ducklings or chicks, and exotic pets, including nonhuman primates.

“Kissing frogs is not recommended,” she said; kissing dogs, cats, and other household pets also is discouraged.

For more information, including brochures to download, Dr. McFarland recommended referring parents to

www.cdc.gov/healthypets

ASPEN, COLO. — Two groups of immunocompromised children present special challenges in community-based practices, Elizabeth J. McFarland, M.D., said at a conference on pediatric infectious diseases, sponsored by Children's Hospital, Denver.

Weakened immune systems can make some vaccinations worrisome for youngsters taking high-dose steroids to control asthma and can make other vaccinations vital for children without a spleen, said Dr. McFarland, director of the hospital's immunodeficiency clinic.

Even more serious, she warned, is the risk of sepsis, with high mortality rates from postsplenectomy sepsis. Half of sepsis cases occur within 2 years of spleen removal, but 3% have been documented 20 years afterward (Br. J. Surg. 1991;78:1031–8).

Asthma and Steroid Issues

Dr. McFarland acknowledged that steroids are “important drugs” for controlling asthma.

The problem is that by interfering with cytokine production and lessening immune cell activity, steroids reduce the body's “ability to mount immune response or react to vaccine.”

According to Dr. McFarland, the American Academy of Pediatrics supports giving inactivated virus vaccines to children who are prescribed steroids, but she cautions that immunogenicity is uncertain. Live virus vaccines should be delayed until high-dose steroids are stopped.

If children take a high-dose steroid daily or on alternate days for more than 14 days, doctors should wait 1 month after stopping steroid use before giving vaccines, Dr. McFarland said. She also said that if the dosage period is less than 14 days, live virus vaccines can be given after stopping, but some experts recommend waiting 2 weeks.

The American Academy of Pediatrics recommends inactivated influenza vaccine for patients with asthma. Dr. McFarland said studies have shown similar antibody responses to the influenza vaccine in patients receiving inhaled steroids and short-course oral steroids, when compared with patients not receiving steroids at the time of immunization.

The live varicella zoster virus (VZV) vaccine is not recommended during high-dose steroid use, because vaccine safety is not established in this population. However, Dr. McFarland said a health maintenance organization study found that inhaled steroids given 3 months prior to VZV vaccination were not associated with increased risk of breakthrough disease (Pediatrics 2003;112:e98-e113), but the study did find increased breakthrough disease after VZV vaccination when oral steroids were given in the 3 months prior.

Postsplenectomy Issues

European studies have shown that about a quarter of physicians do not comply with guidelines for postsplenectomy care, Dr. McFarland said. She could not find any similar studies in the United States.

Although splenectomies in children may be necessary after trauma, she said the operation is being done less often owing to greater recognition of the spleen's importance to immune defense and to newer splenic salvage techniques. Dr. McFarland urged pneumococcal vaccination for postsplenectomy patients. About two-thirds of sepsis cases have been traced to Streptococcus pneumoniae in this population.

If the regular pneumococcal conjugate vaccine (PCV) series was not given before age 24 months, doctors should give two doses of PCV, she said. She recommended one dose of pneumococcal polysaccharide vaccine 6–8 weeks after PCV, and a second dose 3–5 years afterward.

Postsplenectomy children also should be vaccinated against meningococcus, according to Dr. McFarland. The new meningococcal conjugate vaccine (MCV4) is preferred for patients aged 11–55; only meningococcal polysaccharide vaccine (MPSV4) is approved for patients aged 2–11. Optimally, vaccinations for the encapsulated bacteria should be given prior to a planned splenectomy.

She suggested giving an extra dose of Haemophilus influenzae type b (Hib) vaccine prior to splenectomy, if possible.

Afterward, these children also should receive annual influenza shots, she said.

Daily antibiotic prophylaxis is recommended, especially in the first 2 years after splenectomy.

However, Dr. McFarland said the randomized studies supporting its use were performed in young sickle cell anemia patients with functional asplenia.

Determining when to discontinue daily prophylaxis is difficult, she said, as there are no direct data for children with splenectomies. Physicians should discuss the risks and benefits.

The recommended dosages are 125 mg of penicillin V twice daily in children under age 5 and 250 mg twice daily in children over age 5; some experts use amoxicillin (20 mg/kg daily).

Empiric therapy is another option, often used if daily prophylaxis is discontinued. At the first sign of a fever, the parents administer a dose of oral antibiotics and then bring in the child “pronto” for further evaluation.

Dr. McFarland recommended 50 mg/kg of amoxicillin/clavulanate potassium (Augmentin) divided into 2–3 dosages daily or an alternative, possibly a cephalosporin, if the child is allergic to penicillin.

Pneumococcal resistance to penicillin is a concern, she said, and she urged physicians to find out the rate in their community.

For sepsis cases, however, she recommended starting with vancomycin and a cephalosporin.

Indeed, family education is a priority when caring for a child who has lost a spleen.

“You need to give them something written, as you want them to understand the risk of infection,” she said. “And you want to do it more than once.”

Pet Safety: Teach Parents About Zoonoses

Many physicians—Dr. McFarland among them—do not have the heart to banish all pets from the home of an immunocompromised child.

“The better you can take care of your animal … the less likely your pet will get sick,” is the message she urged pediatricians to give to parents of immunocompromised patients. Keeping the animal healthy will help the child stay well.

Dr. McFarland said the U.S. Public Health Service has identified five zoonoses of particular concern that immunocompromised children can pick up from animals: salmonellosis, campylobacteriosis, bacillary angiomatosis (Bartonella henselae, or cat scratch disease), cryptosporidiosis, and toxoplasmosis.

Countering these risks, she summarized the benefits of pet ownership, including decreased loneliness and increased feeling of intimacy and constancy.

The first principle of pet safety, she said, is to buy or adopt a healthy animal, preferably an adult. Young animals are more vulnerable to pathogens. No animal with diarrhea should be handled by the child.

Second, keep the animal healthy by preventing exposure to pathogens. For example, don't let cats or dogs roam. Fleas and ticks are a concern, as well as exposure to other animals and their feces, and anything else the pet might eat off the street.

Keep the animal inside, and keep the toilet seat down so the pet does not use the fixture as a fountain. Feed the animal well, and make sure it does not get into the garbage.

Third, avoid all contact with feces.

Dr. McFarland offered additional recommendations for patients, including children, who undergo hematopoietic stem cell transplants (MMWR 2000;49[RR10]:1–128).

Parents should be advised of the risks, but children don't need to be forced to part with their pets.

Animals should be fed high-quality commercial pet food, according to Dr. McFarland. All dairy foods should be pasteurized, and any foods containing eggs, poultry, or meat should be well cooked.

Stem cell recipients should always wash their hands after handling an animal. Someone else should clean a cage, a litter box, or a fish tank while the patient is immunocompromised. Litter boxes should be cleaned daily and kept away from food preparation or eating areas.

At the first suspicion of a pet's illness, the animal should be taken to the vet, Dr. McFarland said.

Even with these precautions, some animals are prohibited as pets. She listed all reptiles (with a warning against reptile fomites), ducklings or chicks, and exotic pets, including nonhuman primates.

“Kissing frogs is not recommended,” she said; kissing dogs, cats, and other household pets also is discouraged.

For more information, including brochures to download, Dr. McFarland recommended referring parents to

www.cdc.gov/healthypets

ASPEN, COLO. — Two groups of immunocompromised children present special challenges in community-based practices, Elizabeth J. McFarland, M.D., said at a conference on pediatric infectious diseases, sponsored by Children's Hospital, Denver.

Weakened immune systems can make some vaccinations worrisome for youngsters taking high-dose steroids to control asthma and can make other vaccinations vital for children without a spleen, said Dr. McFarland, director of the hospital's immunodeficiency clinic.

Even more serious, she warned, is the risk of sepsis, with high mortality rates from postsplenectomy sepsis. Half of sepsis cases occur within 2 years of spleen removal, but 3% have been documented 20 years afterward (Br. J. Surg. 1991;78:1031–8).

Asthma and Steroid Issues

Dr. McFarland acknowledged that steroids are “important drugs” for controlling asthma.

The problem is that by interfering with cytokine production and lessening immune cell activity, steroids reduce the body's “ability to mount immune response or react to vaccine.”

According to Dr. McFarland, the American Academy of Pediatrics supports giving inactivated virus vaccines to children who are prescribed steroids, but she cautions that immunogenicity is uncertain. Live virus vaccines should be delayed until high-dose steroids are stopped.

If children take a high-dose steroid daily or on alternate days for more than 14 days, doctors should wait 1 month after stopping steroid use before giving vaccines, Dr. McFarland said. She also said that if the dosage period is less than 14 days, live virus vaccines can be given after stopping, but some experts recommend waiting 2 weeks.

The American Academy of Pediatrics recommends inactivated influenza vaccine for patients with asthma. Dr. McFarland said studies have shown similar antibody responses to the influenza vaccine in patients receiving inhaled steroids and short-course oral steroids, when compared with patients not receiving steroids at the time of immunization.

The live varicella zoster virus (VZV) vaccine is not recommended during high-dose steroid use, because vaccine safety is not established in this population. However, Dr. McFarland said a health maintenance organization study found that inhaled steroids given 3 months prior to VZV vaccination were not associated with increased risk of breakthrough disease (Pediatrics 2003;112:e98-e113), but the study did find increased breakthrough disease after VZV vaccination when oral steroids were given in the 3 months prior.

Postsplenectomy Issues

European studies have shown that about a quarter of physicians do not comply with guidelines for postsplenectomy care, Dr. McFarland said. She could not find any similar studies in the United States.

Although splenectomies in children may be necessary after trauma, she said the operation is being done less often owing to greater recognition of the spleen's importance to immune defense and to newer splenic salvage techniques. Dr. McFarland urged pneumococcal vaccination for postsplenectomy patients. About two-thirds of sepsis cases have been traced to Streptococcus pneumoniae in this population.

If the regular pneumococcal conjugate vaccine (PCV) series was not given before age 24 months, doctors should give two doses of PCV, she said. She recommended one dose of pneumococcal polysaccharide vaccine 6–8 weeks after PCV, and a second dose 3–5 years afterward.

Postsplenectomy children also should be vaccinated against meningococcus, according to Dr. McFarland. The new meningococcal conjugate vaccine (MCV4) is preferred for patients aged 11–55; only meningococcal polysaccharide vaccine (MPSV4) is approved for patients aged 2–11. Optimally, vaccinations for the encapsulated bacteria should be given prior to a planned splenectomy.

She suggested giving an extra dose of Haemophilus influenzae type b (Hib) vaccine prior to splenectomy, if possible.

Afterward, these children also should receive annual influenza shots, she said.

Daily antibiotic prophylaxis is recommended, especially in the first 2 years after splenectomy.

However, Dr. McFarland said the randomized studies supporting its use were performed in young sickle cell anemia patients with functional asplenia.

Determining when to discontinue daily prophylaxis is difficult, she said, as there are no direct data for children with splenectomies. Physicians should discuss the risks and benefits.

The recommended dosages are 125 mg of penicillin V twice daily in children under age 5 and 250 mg twice daily in children over age 5; some experts use amoxicillin (20 mg/kg daily).

Empiric therapy is another option, often used if daily prophylaxis is discontinued. At the first sign of a fever, the parents administer a dose of oral antibiotics and then bring in the child “pronto” for further evaluation.

Dr. McFarland recommended 50 mg/kg of amoxicillin/clavulanate potassium (Augmentin) divided into 2–3 dosages daily or an alternative, possibly a cephalosporin, if the child is allergic to penicillin.

Pneumococcal resistance to penicillin is a concern, she said, and she urged physicians to find out the rate in their community.

For sepsis cases, however, she recommended starting with vancomycin and a cephalosporin.

Indeed, family education is a priority when caring for a child who has lost a spleen.

“You need to give them something written, as you want them to understand the risk of infection,” she said. “And you want to do it more than once.”

Pet Safety: Teach Parents About Zoonoses

Many physicians—Dr. McFarland among them—do not have the heart to banish all pets from the home of an immunocompromised child.

“The better you can take care of your animal … the less likely your pet will get sick,” is the message she urged pediatricians to give to parents of immunocompromised patients. Keeping the animal healthy will help the child stay well.

Dr. McFarland said the U.S. Public Health Service has identified five zoonoses of particular concern that immunocompromised children can pick up from animals: salmonellosis, campylobacteriosis, bacillary angiomatosis (Bartonella henselae, or cat scratch disease), cryptosporidiosis, and toxoplasmosis.

Countering these risks, she summarized the benefits of pet ownership, including decreased loneliness and increased feeling of intimacy and constancy.

The first principle of pet safety, she said, is to buy or adopt a healthy animal, preferably an adult. Young animals are more vulnerable to pathogens. No animal with diarrhea should be handled by the child.

Second, keep the animal healthy by preventing exposure to pathogens. For example, don't let cats or dogs roam. Fleas and ticks are a concern, as well as exposure to other animals and their feces, and anything else the pet might eat off the street.

Keep the animal inside, and keep the toilet seat down so the pet does not use the fixture as a fountain. Feed the animal well, and make sure it does not get into the garbage.

Third, avoid all contact with feces.

Dr. McFarland offered additional recommendations for patients, including children, who undergo hematopoietic stem cell transplants (MMWR 2000;49[RR10]:1–128).

Parents should be advised of the risks, but children don't need to be forced to part with their pets.

Animals should be fed high-quality commercial pet food, according to Dr. McFarland. All dairy foods should be pasteurized, and any foods containing eggs, poultry, or meat should be well cooked.

Stem cell recipients should always wash their hands after handling an animal. Someone else should clean a cage, a litter box, or a fish tank while the patient is immunocompromised. Litter boxes should be cleaned daily and kept away from food preparation or eating areas.

At the first suspicion of a pet's illness, the animal should be taken to the vet, Dr. McFarland said.

Even with these precautions, some animals are prohibited as pets. She listed all reptiles (with a warning against reptile fomites), ducklings or chicks, and exotic pets, including nonhuman primates.

“Kissing frogs is not recommended,” she said; kissing dogs, cats, and other household pets also is discouraged.

For more information, including brochures to download, Dr. McFarland recommended referring parents to

www.cdc.gov/healthypets

LOS ANGELES — A small study adds to the growing body of evidence implicating periodontal disease in poor pregnancy outcomes.

Twelve percent of the women with periodontal disease had low-birth-weight babies in a 277-patient observational study.

In comparison, only 2% of women with healthy gums had small babies, a statistically significant difference.

The data were presented in poster form at the annual meeting of the Society for Gynecologic Investigation.

The women with periodontal disease also had a higher incidence of preterm births (7% vs. 3%) but Alexis L. Shub, M.D., an investigator in the study, said this difference was not statistically significant.

About 15% of women in the study had periodontal disease.

An updated analysis completed just before the meeting also found higher rates of tumor necrosis factor-α in the cord blood of women with periodontal disease, Dr. Shub, an obstetrician at the University of Western Australia in Perth, said in an interview.

These data were not included in the poster presentation, she noted, adding that the findings suggest an ongoing inflammatory process in these women and their fetuses.

John P. Newnham, M.D., the study's lead author and director of the Women and Infants Research Foundation at King Edward Memorial Hospital in Perth, said in an interview that he is also working on a large, randomized controlled trial to study this issue.

The investigators have begun to divide 1,000 pregnant women with periodontal disease into two cohorts: one given periodontal care during pregnancy and the other afterward.

The trial's primary outcomes will be preterm birth, fetal growth, and preeclampsia.

He said the investigators are concerned that heightened awareness of possible harm from periodontal disease could skew outcomes.

The investiagators suspect that screening patients for periodontal disease in the observational study led to better dental care.

The preterm birth rates were expected to be about 11%, according to Dr. Newnham, who also plans to monitor pregnancy outcomes and prenatal care in a region-wide medical database.

“The exciting thing is that it is possible that a simple community-based public health intervention could have a profound impact on the need for expensive high-tech hospital resources,” Dr. Newnham commented.

LOS ANGELES — A small study adds to the growing body of evidence implicating periodontal disease in poor pregnancy outcomes.

Twelve percent of the women with periodontal disease had low-birth-weight babies in a 277-patient observational study.

In comparison, only 2% of women with healthy gums had small babies, a statistically significant difference.

The data were presented in poster form at the annual meeting of the Society for Gynecologic Investigation.

The women with periodontal disease also had a higher incidence of preterm births (7% vs. 3%) but Alexis L. Shub, M.D., an investigator in the study, said this difference was not statistically significant.

About 15% of women in the study had periodontal disease.

An updated analysis completed just before the meeting also found higher rates of tumor necrosis factor-α in the cord blood of women with periodontal disease, Dr. Shub, an obstetrician at the University of Western Australia in Perth, said in an interview.

These data were not included in the poster presentation, she noted, adding that the findings suggest an ongoing inflammatory process in these women and their fetuses.

John P. Newnham, M.D., the study's lead author and director of the Women and Infants Research Foundation at King Edward Memorial Hospital in Perth, said in an interview that he is also working on a large, randomized controlled trial to study this issue.

The investigators have begun to divide 1,000 pregnant women with periodontal disease into two cohorts: one given periodontal care during pregnancy and the other afterward.

The trial's primary outcomes will be preterm birth, fetal growth, and preeclampsia.

He said the investigators are concerned that heightened awareness of possible harm from periodontal disease could skew outcomes.

The investiagators suspect that screening patients for periodontal disease in the observational study led to better dental care.

The preterm birth rates were expected to be about 11%, according to Dr. Newnham, who also plans to monitor pregnancy outcomes and prenatal care in a region-wide medical database.

“The exciting thing is that it is possible that a simple community-based public health intervention could have a profound impact on the need for expensive high-tech hospital resources,” Dr. Newnham commented.

LOS ANGELES — A small study adds to the growing body of evidence implicating periodontal disease in poor pregnancy outcomes.

Twelve percent of the women with periodontal disease had low-birth-weight babies in a 277-patient observational study.

In comparison, only 2% of women with healthy gums had small babies, a statistically significant difference.

The data were presented in poster form at the annual meeting of the Society for Gynecologic Investigation.

The women with periodontal disease also had a higher incidence of preterm births (7% vs. 3%) but Alexis L. Shub, M.D., an investigator in the study, said this difference was not statistically significant.

About 15% of women in the study had periodontal disease.

An updated analysis completed just before the meeting also found higher rates of tumor necrosis factor-α in the cord blood of women with periodontal disease, Dr. Shub, an obstetrician at the University of Western Australia in Perth, said in an interview.

These data were not included in the poster presentation, she noted, adding that the findings suggest an ongoing inflammatory process in these women and their fetuses.

John P. Newnham, M.D., the study's lead author and director of the Women and Infants Research Foundation at King Edward Memorial Hospital in Perth, said in an interview that he is also working on a large, randomized controlled trial to study this issue.

The investigators have begun to divide 1,000 pregnant women with periodontal disease into two cohorts: one given periodontal care during pregnancy and the other afterward.

The trial's primary outcomes will be preterm birth, fetal growth, and preeclampsia.

He said the investigators are concerned that heightened awareness of possible harm from periodontal disease could skew outcomes.

The investiagators suspect that screening patients for periodontal disease in the observational study led to better dental care.

The preterm birth rates were expected to be about 11%, according to Dr. Newnham, who also plans to monitor pregnancy outcomes and prenatal care in a region-wide medical database.

“The exciting thing is that it is possible that a simple community-based public health intervention could have a profound impact on the need for expensive high-tech hospital resources,” Dr. Newnham commented.

HOUSTON — Strict adherence to diagnostic criteria for Behçet's disease can lead physicians to misdiagnose patients who actually have complex aphthosis, Peter J. Lynch, M.D., warned at a conference on vulvovaginal diseases sponsored by Baylor College of Medicine.

Oral and genital ulcers characterize both conditions, but classic Behçet's disease typically leads to blindness and death, said Dr. Lynch, a professor emeritus at the University of California, Davis. Though recurring and troublesome, complex aphthosis is a far more benign disorder.

“In the United States and Western Europe, complex aphthosis is usually not associated with systemic symptoms and signs. That's important, because I don't want these women labeled with Behçet's disease that they don't really have,” Dr. Lynch said.

“If they tell their primary care doctors that they have Behçet's disease or if they go online and look up Behçet's disease,” he warned, “they're going to be overwhelmed with the fact that they are going to be dead in a couple of years, and they are going to have terrible brain disease, and they are going to go blind. This is very frightening.”

Dr. Lynch traced the overlap to diagnostic criteria developed in 1990 by the International Study Group for Behçet's Disease (Lancet 1990;335:1078–80). Although other criteria have since been written to avert confusion, he said, the original ISGBD guidelines are still widely used.

If patients with complex aphthosis are to be included in the Behçet's disease spectrum, he suggested the “Western” form of the disease be distinguished from the “Eastern” form, which he characterized as classic Behçet's disease. He contrasted the two forms as follows:

▸ The Eastern form occurs along the “Silk Road” from Asia to Eastern Europe; the Western form presents in Western Europe and North America.

▸ Men outnumber women among patients with the Eastern form; women are more likely to be affected in the West.

▸ Central nervous system involvement occurs only in the Eastern form.

▸ Posterior eye inflammation often leads to blindness with the Eastern form. Anterior eye disease sometimes occurs with the Western form, but is less severe and rarely, if ever, leads to vision loss.

▸ The HLA-B51 haplotype is almost always positive with the Eastern form. People with this haplotype are much more likely to develop Behçet's disease if they live along the Silk Road (relative risk about 6.0) than in Western countries (relative risk about 1.5).

▸ Prognosis is poor in the East, good in the West.

Complex aphthosis has a nonspecific histology and is usually diagnosed by ruling out other conditions, according to Dr. Lynch. These ulcers can appear simultaneously in oral and genital locations, but are often independent of each other. “Almost always you will get a history of oral ulcers in the past, but they don't come out exactly at the same time,” he said.

Comparing aphthosis major ulcers to ordinary canker sores, Dr. Lynch said the former are larger, longer lasting, and more painful. They also heal with scarring and are more likely to appear on mucosa in women and on skin in men.

“There are no good age data, but in my own practice over the years I am impressed with the number of very young women from age 13 to about 20 who develop this,” he said.

Most lesions respond within a few days to topical application of fluocinonide and clobetasol. Lidocaine or sucralfate are good for pain relief, and 5 mg/cc of triamcinolone acetonide for larger ulcers and ulcers that do not respond to topical steroids. For systemic therapy, he proposed 7–10 days of treatment with systemic steroids. Dapsone, colchicine, pentoxifylline, and thalidomide can be effective for episodic treatment and prophylaxis, he said, warning against thalidomide and other tumor necrosis factors in women of child-bearing age.

HOUSTON — Strict adherence to diagnostic criteria for Behçet's disease can lead physicians to misdiagnose patients who actually have complex aphthosis, Peter J. Lynch, M.D., warned at a conference on vulvovaginal diseases sponsored by Baylor College of Medicine.

Oral and genital ulcers characterize both conditions, but classic Behçet's disease typically leads to blindness and death, said Dr. Lynch, a professor emeritus at the University of California, Davis. Though recurring and troublesome, complex aphthosis is a far more benign disorder.

“In the United States and Western Europe, complex aphthosis is usually not associated with systemic symptoms and signs. That's important, because I don't want these women labeled with Behçet's disease that they don't really have,” Dr. Lynch said.

“If they tell their primary care doctors that they have Behçet's disease or if they go online and look up Behçet's disease,” he warned, “they're going to be overwhelmed with the fact that they are going to be dead in a couple of years, and they are going to have terrible brain disease, and they are going to go blind. This is very frightening.”

Dr. Lynch traced the overlap to diagnostic criteria developed in 1990 by the International Study Group for Behçet's Disease (Lancet 1990;335:1078–80). Although other criteria have since been written to avert confusion, he said, the original ISGBD guidelines are still widely used.

If patients with complex aphthosis are to be included in the Behçet's disease spectrum, he suggested the “Western” form of the disease be distinguished from the “Eastern” form, which he characterized as classic Behçet's disease. He contrasted the two forms as follows:

▸ The Eastern form occurs along the “Silk Road” from Asia to Eastern Europe; the Western form presents in Western Europe and North America.

▸ Men outnumber women among patients with the Eastern form; women are more likely to be affected in the West.

▸ Central nervous system involvement occurs only in the Eastern form.

▸ Posterior eye inflammation often leads to blindness with the Eastern form. Anterior eye disease sometimes occurs with the Western form, but is less severe and rarely, if ever, leads to vision loss.

▸ The HLA-B51 haplotype is almost always positive with the Eastern form. People with this haplotype are much more likely to develop Behçet's disease if they live along the Silk Road (relative risk about 6.0) than in Western countries (relative risk about 1.5).

▸ Prognosis is poor in the East, good in the West.

Complex aphthosis has a nonspecific histology and is usually diagnosed by ruling out other conditions, according to Dr. Lynch. These ulcers can appear simultaneously in oral and genital locations, but are often independent of each other. “Almost always you will get a history of oral ulcers in the past, but they don't come out exactly at the same time,” he said.

Comparing aphthosis major ulcers to ordinary canker sores, Dr. Lynch said the former are larger, longer lasting, and more painful. They also heal with scarring and are more likely to appear on mucosa in women and on skin in men.

“There are no good age data, but in my own practice over the years I am impressed with the number of very young women from age 13 to about 20 who develop this,” he said.

Most lesions respond within a few days to topical application of fluocinonide and clobetasol. Lidocaine or sucralfate are good for pain relief, and 5 mg/cc of triamcinolone acetonide for larger ulcers and ulcers that do not respond to topical steroids. For systemic therapy, he proposed 7–10 days of treatment with systemic steroids. Dapsone, colchicine, pentoxifylline, and thalidomide can be effective for episodic treatment and prophylaxis, he said, warning against thalidomide and other tumor necrosis factors in women of child-bearing age.

HOUSTON — Strict adherence to diagnostic criteria for Behçet's disease can lead physicians to misdiagnose patients who actually have complex aphthosis, Peter J. Lynch, M.D., warned at a conference on vulvovaginal diseases sponsored by Baylor College of Medicine.

Oral and genital ulcers characterize both conditions, but classic Behçet's disease typically leads to blindness and death, said Dr. Lynch, a professor emeritus at the University of California, Davis. Though recurring and troublesome, complex aphthosis is a far more benign disorder.

“In the United States and Western Europe, complex aphthosis is usually not associated with systemic symptoms and signs. That's important, because I don't want these women labeled with Behçet's disease that they don't really have,” Dr. Lynch said.

“If they tell their primary care doctors that they have Behçet's disease or if they go online and look up Behçet's disease,” he warned, “they're going to be overwhelmed with the fact that they are going to be dead in a couple of years, and they are going to have terrible brain disease, and they are going to go blind. This is very frightening.”

Dr. Lynch traced the overlap to diagnostic criteria developed in 1990 by the International Study Group for Behçet's Disease (Lancet 1990;335:1078–80). Although other criteria have since been written to avert confusion, he said, the original ISGBD guidelines are still widely used.

If patients with complex aphthosis are to be included in the Behçet's disease spectrum, he suggested the “Western” form of the disease be distinguished from the “Eastern” form, which he characterized as classic Behçet's disease. He contrasted the two forms as follows:

▸ The Eastern form occurs along the “Silk Road” from Asia to Eastern Europe; the Western form presents in Western Europe and North America.

▸ Men outnumber women among patients with the Eastern form; women are more likely to be affected in the West.

▸ Central nervous system involvement occurs only in the Eastern form.

▸ Posterior eye inflammation often leads to blindness with the Eastern form. Anterior eye disease sometimes occurs with the Western form, but is less severe and rarely, if ever, leads to vision loss.

▸ The HLA-B51 haplotype is almost always positive with the Eastern form. People with this haplotype are much more likely to develop Behçet's disease if they live along the Silk Road (relative risk about 6.0) than in Western countries (relative risk about 1.5).

▸ Prognosis is poor in the East, good in the West.

Complex aphthosis has a nonspecific histology and is usually diagnosed by ruling out other conditions, according to Dr. Lynch. These ulcers can appear simultaneously in oral and genital locations, but are often independent of each other. “Almost always you will get a history of oral ulcers in the past, but they don't come out exactly at the same time,” he said.

Comparing aphthosis major ulcers to ordinary canker sores, Dr. Lynch said the former are larger, longer lasting, and more painful. They also heal with scarring and are more likely to appear on mucosa in women and on skin in men.

“There are no good age data, but in my own practice over the years I am impressed with the number of very young women from age 13 to about 20 who develop this,” he said.

Most lesions respond within a few days to topical application of fluocinonide and clobetasol. Lidocaine or sucralfate are good for pain relief, and 5 mg/cc of triamcinolone acetonide for larger ulcers and ulcers that do not respond to topical steroids. For systemic therapy, he proposed 7–10 days of treatment with systemic steroids. Dapsone, colchicine, pentoxifylline, and thalidomide can be effective for episodic treatment and prophylaxis, he said, warning against thalidomide and other tumor necrosis factors in women of child-bearing age.