Jane Salodof MacNeil

PARIS – Selective serotonin reuptake inhibitors have not been shown to increase suicide risk in children and adolescents with obsessive-compulsive disorder and should not be withheld from these patients, Dr. Martine F. Flament advised at the annual congress of the European College of Neuropsychopharmacology.

Individual studies and pooled analyses have shown SSRIs to be comparable with clomipramine in pediatric cases of obsessive-compulsive disorder (OCD), said Dr. Flament, a professor of psychiatry and research director of the youth program at the University of Ottawa Institute of Mental Health Research.

Both clomipramine and SSRIs have produced 20%–45% improvement in clinical trials conducted since 1985, according to Dr. Flament. Clomipramine at 141–150 mg per day has been shown to be superior to placebo and to desipramine.

Fluoxetine at 20–64 mg per day, sertraline at 160–167 mg per day, and fluvoxamine at 50–200 mg per day also were superior to placebo in randomized trials.

She also cited a meta-analysis that found a statistically significant but modest benefit for SSRIs in the treatment of pediatric OCD (Am. J. Psychiatry 2003;160:1919–28). “So there is evidence that medication works. It brings some improvement, but not complete remission,” she said.

Despite growing concern that SSRIs increase suicide risk in children and adolescents being treated for depression, Dr. Flament said no individual study has shown SSRIs are associated with more suicidal ideation or behavior than placebo in children being treated for OCD. Most recent studies have not identified any treatment-emergent suicidal behaviors, she added.

Pooled analyses of controlled studies in OCD and other anxiety disorders have shown other behavioral side effects, she said, listing activation, akathisia, disinhibition, impulsivity, and hyperactivity. Again, she said, no analysis has shown a significant risk for increased suicidal thoughts or behaviors.

“Rigorous clinical monitoring for suicidal ideation and behavior is advised in youth, as in older patients,” she said, adding that “in pediatric OCD, SSRI treatment is generally thought to show a favorable risk-to-benefit ratio.”

To optimize treatment response, Dr. Flament recommended assessing how a child with OCD responds to the first medication prescribed. If the patient does not respond in 10–12 weeks to one SSRI, she suggested trying another SSRI.

If, however, the child has a partial response, Dr. Flament offered two options. Combining medication with behavioral therapy has been shown to improve outcomes and decrease the relapse rate when medication is discontinued, she said.

The other option is augmentation either to enhance serotonin neurotransmission or to antagonize dopamine neurotransmission in children with comorbid tic disorders.

Augmentation has been shown to improve outcomes, Dr. Flament said, with the caveat that very few studies have been conducted and with very small numbers of children.

Clomipramine and SSRIs have produced 20%–45% improvement in clinical trials since 1985. DR. FLAMENT

PARIS – Selective serotonin reuptake inhibitors have not been shown to increase suicide risk in children and adolescents with obsessive-compulsive disorder and should not be withheld from these patients, Dr. Martine F. Flament advised at the annual congress of the European College of Neuropsychopharmacology.

Individual studies and pooled analyses have shown SSRIs to be comparable with clomipramine in pediatric cases of obsessive-compulsive disorder (OCD), said Dr. Flament, a professor of psychiatry and research director of the youth program at the University of Ottawa Institute of Mental Health Research.

Both clomipramine and SSRIs have produced 20%–45% improvement in clinical trials conducted since 1985, according to Dr. Flament. Clomipramine at 141–150 mg per day has been shown to be superior to placebo and to desipramine.

Fluoxetine at 20–64 mg per day, sertraline at 160–167 mg per day, and fluvoxamine at 50–200 mg per day also were superior to placebo in randomized trials.

She also cited a meta-analysis that found a statistically significant but modest benefit for SSRIs in the treatment of pediatric OCD (Am. J. Psychiatry 2003;160:1919–28). “So there is evidence that medication works. It brings some improvement, but not complete remission,” she said.

Despite growing concern that SSRIs increase suicide risk in children and adolescents being treated for depression, Dr. Flament said no individual study has shown SSRIs are associated with more suicidal ideation or behavior than placebo in children being treated for OCD. Most recent studies have not identified any treatment-emergent suicidal behaviors, she added.

Pooled analyses of controlled studies in OCD and other anxiety disorders have shown other behavioral side effects, she said, listing activation, akathisia, disinhibition, impulsivity, and hyperactivity. Again, she said, no analysis has shown a significant risk for increased suicidal thoughts or behaviors.

“Rigorous clinical monitoring for suicidal ideation and behavior is advised in youth, as in older patients,” she said, adding that “in pediatric OCD, SSRI treatment is generally thought to show a favorable risk-to-benefit ratio.”

To optimize treatment response, Dr. Flament recommended assessing how a child with OCD responds to the first medication prescribed. If the patient does not respond in 10–12 weeks to one SSRI, she suggested trying another SSRI.

If, however, the child has a partial response, Dr. Flament offered two options. Combining medication with behavioral therapy has been shown to improve outcomes and decrease the relapse rate when medication is discontinued, she said.

The other option is augmentation either to enhance serotonin neurotransmission or to antagonize dopamine neurotransmission in children with comorbid tic disorders.

Augmentation has been shown to improve outcomes, Dr. Flament said, with the caveat that very few studies have been conducted and with very small numbers of children.

Clomipramine and SSRIs have produced 20%–45% improvement in clinical trials since 1985. DR. FLAMENT

PARIS – Selective serotonin reuptake inhibitors have not been shown to increase suicide risk in children and adolescents with obsessive-compulsive disorder and should not be withheld from these patients, Dr. Martine F. Flament advised at the annual congress of the European College of Neuropsychopharmacology.

Individual studies and pooled analyses have shown SSRIs to be comparable with clomipramine in pediatric cases of obsessive-compulsive disorder (OCD), said Dr. Flament, a professor of psychiatry and research director of the youth program at the University of Ottawa Institute of Mental Health Research.

Both clomipramine and SSRIs have produced 20%–45% improvement in clinical trials conducted since 1985, according to Dr. Flament. Clomipramine at 141–150 mg per day has been shown to be superior to placebo and to desipramine.

Fluoxetine at 20–64 mg per day, sertraline at 160–167 mg per day, and fluvoxamine at 50–200 mg per day also were superior to placebo in randomized trials.

She also cited a meta-analysis that found a statistically significant but modest benefit for SSRIs in the treatment of pediatric OCD (Am. J. Psychiatry 2003;160:1919–28). “So there is evidence that medication works. It brings some improvement, but not complete remission,” she said.

Despite growing concern that SSRIs increase suicide risk in children and adolescents being treated for depression, Dr. Flament said no individual study has shown SSRIs are associated with more suicidal ideation or behavior than placebo in children being treated for OCD. Most recent studies have not identified any treatment-emergent suicidal behaviors, she added.

Pooled analyses of controlled studies in OCD and other anxiety disorders have shown other behavioral side effects, she said, listing activation, akathisia, disinhibition, impulsivity, and hyperactivity. Again, she said, no analysis has shown a significant risk for increased suicidal thoughts or behaviors.

“Rigorous clinical monitoring for suicidal ideation and behavior is advised in youth, as in older patients,” she said, adding that “in pediatric OCD, SSRI treatment is generally thought to show a favorable risk-to-benefit ratio.”

To optimize treatment response, Dr. Flament recommended assessing how a child with OCD responds to the first medication prescribed. If the patient does not respond in 10–12 weeks to one SSRI, she suggested trying another SSRI.

If, however, the child has a partial response, Dr. Flament offered two options. Combining medication with behavioral therapy has been shown to improve outcomes and decrease the relapse rate when medication is discontinued, she said.

The other option is augmentation either to enhance serotonin neurotransmission or to antagonize dopamine neurotransmission in children with comorbid tic disorders.

Augmentation has been shown to improve outcomes, Dr. Flament said, with the caveat that very few studies have been conducted and with very small numbers of children.

Clomipramine and SSRIs have produced 20%–45% improvement in clinical trials since 1985. DR. FLAMENT

PARIS – A series of studies in children and adolescents suggests that they may be more vulnerable than adults to some side effects of antipsychotics, Dr. Celso Arango warned at the annual congress of the European College of Neuropsychopharmacology.

Dr. Arango, head of the adolescent unit at Hospital Gregorio Marañón in Madrid, cited dyskinesia, hyperprolactinemia, sleepiness and sedation, and weight gain among the side effects identified by the investigations at his hospital.

Despite a sixfold increase from 1993 to 2002 in the prescribing of antipsychotics to youths in the United States, he said, little is known about these drugs' safety and tolerability in children and adolescents. Long-term effects on sexual development, age-specific requirements in dosing, and impact on cognition have not been adequately studied in young patients, Dr. Arango said.

“Children and adolescents may not only be more vulnerable to some side effects but also some side effects may specifically interfere with functioning and induce lack of adherence in this population,” he said.

Singling out the potential impact on learning, he cautioned, “Some of these side effects may mean that our patients do not gain what they should be gaining [from school] because they cannot pay attention in class or they are too sleepy.”

The first study described by Dr. Arango followed 110 patients for 1 year. Their average age was 14.5 years, and 60% were males. Only about one-third were being treated for psychotic disorders. Affective disorders and eating disorders accounted for about 14% of the population. Other diagnoses included pervasive development disorders, tic disorders, attention-deficit hyperactivity disorder, and mental retardation.

Many patients were prescribed more than one antipsychotic during the course of the year: 45% were given a first-generation antipsychotic, 84% a second-generation agent, and 9% both combined. Other psychotropic drugs also were prescribed.

Preliminary analysis of extrapyramidal symptoms showed a significant increase in dyskinesia, rising from 30.9% of 110 patients to 47.8% of 86 patients between the first and second visits. By the third visit, it fell back to 33.3% of 54 patients. Twenty percent of patients had never before taken an antipsychotic, Dr. Arango added; 11.8% of them experienced dyskinesia.

He also reported that hyperprolactinemia was found in 81% of serum samples taken at baseline and that youths treated with first-generation antipsychotics had significantly higher scores on a Parkinsonism subscale. Risperidone (Risperdal) was associated with a significantly higher number of dystonic episodes, he said, and with increases in prolactin and body mass index (BMI).

Treatment with olanzapine (Zyprexa) also led to a significant increase in BMI.

The second study compared 60 patients on antipsychotics for less than 1 month with 66 patients treated for more than 1 year. The average age was 15.6 years.

Dr. Arango reported finding mild dys- kinetic movements in 21.7% of short-term patients and 37.9% of long-term patients. Tic-like eye movements, jerky finger and wrist movements, jerky arm movements, and rigid masked facial expression were significantly more common in the young people on antipsychotics for more than a year.

The third study, also reported in a poster at the meeting, was the only one to show no ill effects of antipsychotic use. Dr. Arango's group performed electrocardiograms on 111 consecutive adolescents (mean age 14.9 years) who were treated with antipsychotics for more than 2 weeks after admission to an inpatient unit. None had a pathologically prolonged QTc interval, and no relevant cardiovascular side effects were detected.

The fourth study, also reported in a poster, randomized 24 first-episode adolescent psychosis patients to quetiapine and 26 to olanzapine.

The two groups, stratified by age (mean age 15.9 years) and gender, included patients diagnosed with schizophrenia, bipolar disorder, and other psychotic disorders. Sixteen patients in each arm completed the 6-month study.

None of the dropouts was attributed to adverse events.

Dr. Arango reported that whereas significantly more patients on olanzapine experienced rigidity, diminished sexual desire was significantly more common with quetiapine. Both groups gained weight during 6 months of treatment, but the patients on olanzapine gained significantly more: 16.5 kg on average vs. 5.4 kg.

In addition, a review of subjective side effects showed about 70% of patients in both groups complaining of sleepiness and sedation. More olanzapine patients reported concentration difficulties and failing memory. Constipation and palpitations/tachycardia were cited more often by those on quetiapine (Seroquel).

The fifth study followed 67 patients in the first-episode clinic at Dr. Arango's unit for 6 months. The population comprised 22 patients on risperidone, 20 on olanzapine, and 25 on quetiapine. Their mean age was 15.7 years, about two-thirds were males, and none had previously taken an antipsychotic. About half had schizophrenia.

The male patients gained more weight, the patients' HbA_1c was related to changes in BMI, and those on olanzapine had significantly increased systolic blood pressure.

In conclusion, he recommended that clinicians assess risk/benefit ratios carefully when prescribing antipsychotics to children and adolescents, especially if the patient has a nonpsychotic disorder. He also urged frequent reconsideration of whether these medications need to be continued in patients who are not psychotic and said that all young patients should be monitored for adverse metabolic and endocrine effects.

'Some side effects may specifically interfere with functioning' in children and adolescents. DR. ARANGO

PARIS – A series of studies in children and adolescents suggests that they may be more vulnerable than adults to some side effects of antipsychotics, Dr. Celso Arango warned at the annual congress of the European College of Neuropsychopharmacology.

Dr. Arango, head of the adolescent unit at Hospital Gregorio Marañón in Madrid, cited dyskinesia, hyperprolactinemia, sleepiness and sedation, and weight gain among the side effects identified by the investigations at his hospital.

Despite a sixfold increase from 1993 to 2002 in the prescribing of antipsychotics to youths in the United States, he said, little is known about these drugs' safety and tolerability in children and adolescents. Long-term effects on sexual development, age-specific requirements in dosing, and impact on cognition have not been adequately studied in young patients, Dr. Arango said.

“Children and adolescents may not only be more vulnerable to some side effects but also some side effects may specifically interfere with functioning and induce lack of adherence in this population,” he said.

Singling out the potential impact on learning, he cautioned, “Some of these side effects may mean that our patients do not gain what they should be gaining [from school] because they cannot pay attention in class or they are too sleepy.”

The first study described by Dr. Arango followed 110 patients for 1 year. Their average age was 14.5 years, and 60% were males. Only about one-third were being treated for psychotic disorders. Affective disorders and eating disorders accounted for about 14% of the population. Other diagnoses included pervasive development disorders, tic disorders, attention-deficit hyperactivity disorder, and mental retardation.

Many patients were prescribed more than one antipsychotic during the course of the year: 45% were given a first-generation antipsychotic, 84% a second-generation agent, and 9% both combined. Other psychotropic drugs also were prescribed.

Preliminary analysis of extrapyramidal symptoms showed a significant increase in dyskinesia, rising from 30.9% of 110 patients to 47.8% of 86 patients between the first and second visits. By the third visit, it fell back to 33.3% of 54 patients. Twenty percent of patients had never before taken an antipsychotic, Dr. Arango added; 11.8% of them experienced dyskinesia.

He also reported that hyperprolactinemia was found in 81% of serum samples taken at baseline and that youths treated with first-generation antipsychotics had significantly higher scores on a Parkinsonism subscale. Risperidone (Risperdal) was associated with a significantly higher number of dystonic episodes, he said, and with increases in prolactin and body mass index (BMI).

Treatment with olanzapine (Zyprexa) also led to a significant increase in BMI.

The second study compared 60 patients on antipsychotics for less than 1 month with 66 patients treated for more than 1 year. The average age was 15.6 years.

Dr. Arango reported finding mild dys- kinetic movements in 21.7% of short-term patients and 37.9% of long-term patients. Tic-like eye movements, jerky finger and wrist movements, jerky arm movements, and rigid masked facial expression were significantly more common in the young people on antipsychotics for more than a year.

The third study, also reported in a poster at the meeting, was the only one to show no ill effects of antipsychotic use. Dr. Arango's group performed electrocardiograms on 111 consecutive adolescents (mean age 14.9 years) who were treated with antipsychotics for more than 2 weeks after admission to an inpatient unit. None had a pathologically prolonged QTc interval, and no relevant cardiovascular side effects were detected.

The fourth study, also reported in a poster, randomized 24 first-episode adolescent psychosis patients to quetiapine and 26 to olanzapine.

The two groups, stratified by age (mean age 15.9 years) and gender, included patients diagnosed with schizophrenia, bipolar disorder, and other psychotic disorders. Sixteen patients in each arm completed the 6-month study.

None of the dropouts was attributed to adverse events.

Dr. Arango reported that whereas significantly more patients on olanzapine experienced rigidity, diminished sexual desire was significantly more common with quetiapine. Both groups gained weight during 6 months of treatment, but the patients on olanzapine gained significantly more: 16.5 kg on average vs. 5.4 kg.

In addition, a review of subjective side effects showed about 70% of patients in both groups complaining of sleepiness and sedation. More olanzapine patients reported concentration difficulties and failing memory. Constipation and palpitations/tachycardia were cited more often by those on quetiapine (Seroquel).

The fifth study followed 67 patients in the first-episode clinic at Dr. Arango's unit for 6 months. The population comprised 22 patients on risperidone, 20 on olanzapine, and 25 on quetiapine. Their mean age was 15.7 years, about two-thirds were males, and none had previously taken an antipsychotic. About half had schizophrenia.

The male patients gained more weight, the patients' HbA_1c was related to changes in BMI, and those on olanzapine had significantly increased systolic blood pressure.

In conclusion, he recommended that clinicians assess risk/benefit ratios carefully when prescribing antipsychotics to children and adolescents, especially if the patient has a nonpsychotic disorder. He also urged frequent reconsideration of whether these medications need to be continued in patients who are not psychotic and said that all young patients should be monitored for adverse metabolic and endocrine effects.

'Some side effects may specifically interfere with functioning' in children and adolescents. DR. ARANGO

PARIS – A series of studies in children and adolescents suggests that they may be more vulnerable than adults to some side effects of antipsychotics, Dr. Celso Arango warned at the annual congress of the European College of Neuropsychopharmacology.

Dr. Arango, head of the adolescent unit at Hospital Gregorio Marañón in Madrid, cited dyskinesia, hyperprolactinemia, sleepiness and sedation, and weight gain among the side effects identified by the investigations at his hospital.

Despite a sixfold increase from 1993 to 2002 in the prescribing of antipsychotics to youths in the United States, he said, little is known about these drugs' safety and tolerability in children and adolescents. Long-term effects on sexual development, age-specific requirements in dosing, and impact on cognition have not been adequately studied in young patients, Dr. Arango said.

“Children and adolescents may not only be more vulnerable to some side effects but also some side effects may specifically interfere with functioning and induce lack of adherence in this population,” he said.

Singling out the potential impact on learning, he cautioned, “Some of these side effects may mean that our patients do not gain what they should be gaining [from school] because they cannot pay attention in class or they are too sleepy.”

The first study described by Dr. Arango followed 110 patients for 1 year. Their average age was 14.5 years, and 60% were males. Only about one-third were being treated for psychotic disorders. Affective disorders and eating disorders accounted for about 14% of the population. Other diagnoses included pervasive development disorders, tic disorders, attention-deficit hyperactivity disorder, and mental retardation.

Many patients were prescribed more than one antipsychotic during the course of the year: 45% were given a first-generation antipsychotic, 84% a second-generation agent, and 9% both combined. Other psychotropic drugs also were prescribed.

Preliminary analysis of extrapyramidal symptoms showed a significant increase in dyskinesia, rising from 30.9% of 110 patients to 47.8% of 86 patients between the first and second visits. By the third visit, it fell back to 33.3% of 54 patients. Twenty percent of patients had never before taken an antipsychotic, Dr. Arango added; 11.8% of them experienced dyskinesia.

He also reported that hyperprolactinemia was found in 81% of serum samples taken at baseline and that youths treated with first-generation antipsychotics had significantly higher scores on a Parkinsonism subscale. Risperidone (Risperdal) was associated with a significantly higher number of dystonic episodes, he said, and with increases in prolactin and body mass index (BMI).

Treatment with olanzapine (Zyprexa) also led to a significant increase in BMI.

The second study compared 60 patients on antipsychotics for less than 1 month with 66 patients treated for more than 1 year. The average age was 15.6 years.

Dr. Arango reported finding mild dys- kinetic movements in 21.7% of short-term patients and 37.9% of long-term patients. Tic-like eye movements, jerky finger and wrist movements, jerky arm movements, and rigid masked facial expression were significantly more common in the young people on antipsychotics for more than a year.

The third study, also reported in a poster at the meeting, was the only one to show no ill effects of antipsychotic use. Dr. Arango's group performed electrocardiograms on 111 consecutive adolescents (mean age 14.9 years) who were treated with antipsychotics for more than 2 weeks after admission to an inpatient unit. None had a pathologically prolonged QTc interval, and no relevant cardiovascular side effects were detected.

The fourth study, also reported in a poster, randomized 24 first-episode adolescent psychosis patients to quetiapine and 26 to olanzapine.

The two groups, stratified by age (mean age 15.9 years) and gender, included patients diagnosed with schizophrenia, bipolar disorder, and other psychotic disorders. Sixteen patients in each arm completed the 6-month study.

None of the dropouts was attributed to adverse events.

Dr. Arango reported that whereas significantly more patients on olanzapine experienced rigidity, diminished sexual desire was significantly more common with quetiapine. Both groups gained weight during 6 months of treatment, but the patients on olanzapine gained significantly more: 16.5 kg on average vs. 5.4 kg.

In addition, a review of subjective side effects showed about 70% of patients in both groups complaining of sleepiness and sedation. More olanzapine patients reported concentration difficulties and failing memory. Constipation and palpitations/tachycardia were cited more often by those on quetiapine (Seroquel).

The fifth study followed 67 patients in the first-episode clinic at Dr. Arango's unit for 6 months. The population comprised 22 patients on risperidone, 20 on olanzapine, and 25 on quetiapine. Their mean age was 15.7 years, about two-thirds were males, and none had previously taken an antipsychotic. About half had schizophrenia.

The male patients gained more weight, the patients' HbA_1c was related to changes in BMI, and those on olanzapine had significantly increased systolic blood pressure.

In conclusion, he recommended that clinicians assess risk/benefit ratios carefully when prescribing antipsychotics to children and adolescents, especially if the patient has a nonpsychotic disorder. He also urged frequent reconsideration of whether these medications need to be continued in patients who are not psychotic and said that all young patients should be monitored for adverse metabolic and endocrine effects.

'Some side effects may specifically interfere with functioning' in children and adolescents. DR. ARANGO

SAN FRANCISCO — Preteenagers and adolescents with asthma who were also depressed or anxious suffered from asthma symptoms on significantly more days and were more prone to individual symptoms, according to a study presented at the annual meeting of the Pediatric Academic Societies.

Investigators urged physicians to screen for anxiety and depressive disorders when young people have asthma symptoms that do not respond to medication.

“We conclude that youth with asthma and depressive disorders do have a higher symptom burden, and providers should consider screening for depression in youth with high symptom burden if they are not responding to medication or treatment as expected,” Dr. Laura Richardson said in a poster presentation.

The researchers surveyed by telephone 767 young people, 11–17 years of age, who had asthma and were enrolled in a staff-model health maintenance organization. They used the Children's Health Survey for Asthma-Teen Version (CHSA-T) questionnaire to assess the number of days of asthma symptoms each participant had experienced in the 2 weeks prior to a call and the incidence of individual symptoms.

Determination of anxiety and depressive disorders was based on the Diagnostic Interview Schedule for Children. In addition, the investigators mined automated medical record data for information on asthma treatment intensity, severity, number of emergency department visits, and hospital admissions.

A total of 125 respondents (16%) were found to have anxiety or depressive disorders, while 642 did not (84%). Nearly two-thirds of the depressed youth but fewer than half of the other respondents were female. Both groups were 14 years old on average, reported Dr. Richardson, a pediatrician specializing in adolescent medicine at the University of Washington in Seattle.

Similar proportions of both groups met Health Plan Employer Data Information Set (HEDIS) asthma severity criteria: 69% of the depressed group and 70% of those who were not depressed. The depressed patients had higher Chronic Disease Scores, however (794.8 vs. 580.5).

“After controlling for asthma severity and other covariates, [we found that] youth with anxiety or depressive disorders had an average of 5.4 symptom days in the prior 2 weeks, compared to 3.5 days in those without anxiety or depressive disorders,” Dr. Richardson said.

Respondents with anxiety or depressive disorders also were significantly more likely than the other to report each of six asthma-specific symptoms (wheezing with a cold, cold that would not go away, cough, wheezing without a cold, tightness in chest, and shortness of breath) and five less-specific symptoms (difficulty sleeping, stuffy nose/congestion, itchy eyes, skin rash, and headache).

In addition, the investigators charted a linear relationship between the number of symptoms of anxiety and depression and the number of asthma symptoms that the patients reported. “The more anxiety and depression you have, the more asthma you have,” Dr. Richardson said in an interview at the meeting, which was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — Preteenagers and adolescents with asthma who were also depressed or anxious suffered from asthma symptoms on significantly more days and were more prone to individual symptoms, according to a study presented at the annual meeting of the Pediatric Academic Societies.

Investigators urged physicians to screen for anxiety and depressive disorders when young people have asthma symptoms that do not respond to medication.

“We conclude that youth with asthma and depressive disorders do have a higher symptom burden, and providers should consider screening for depression in youth with high symptom burden if they are not responding to medication or treatment as expected,” Dr. Laura Richardson said in a poster presentation.

The researchers surveyed by telephone 767 young people, 11–17 years of age, who had asthma and were enrolled in a staff-model health maintenance organization. They used the Children's Health Survey for Asthma-Teen Version (CHSA-T) questionnaire to assess the number of days of asthma symptoms each participant had experienced in the 2 weeks prior to a call and the incidence of individual symptoms.

Determination of anxiety and depressive disorders was based on the Diagnostic Interview Schedule for Children. In addition, the investigators mined automated medical record data for information on asthma treatment intensity, severity, number of emergency department visits, and hospital admissions.

A total of 125 respondents (16%) were found to have anxiety or depressive disorders, while 642 did not (84%). Nearly two-thirds of the depressed youth but fewer than half of the other respondents were female. Both groups were 14 years old on average, reported Dr. Richardson, a pediatrician specializing in adolescent medicine at the University of Washington in Seattle.

Similar proportions of both groups met Health Plan Employer Data Information Set (HEDIS) asthma severity criteria: 69% of the depressed group and 70% of those who were not depressed. The depressed patients had higher Chronic Disease Scores, however (794.8 vs. 580.5).

“After controlling for asthma severity and other covariates, [we found that] youth with anxiety or depressive disorders had an average of 5.4 symptom days in the prior 2 weeks, compared to 3.5 days in those without anxiety or depressive disorders,” Dr. Richardson said.

Respondents with anxiety or depressive disorders also were significantly more likely than the other to report each of six asthma-specific symptoms (wheezing with a cold, cold that would not go away, cough, wheezing without a cold, tightness in chest, and shortness of breath) and five less-specific symptoms (difficulty sleeping, stuffy nose/congestion, itchy eyes, skin rash, and headache).

In addition, the investigators charted a linear relationship between the number of symptoms of anxiety and depression and the number of asthma symptoms that the patients reported. “The more anxiety and depression you have, the more asthma you have,” Dr. Richardson said in an interview at the meeting, which was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — Preteenagers and adolescents with asthma who were also depressed or anxious suffered from asthma symptoms on significantly more days and were more prone to individual symptoms, according to a study presented at the annual meeting of the Pediatric Academic Societies.

Investigators urged physicians to screen for anxiety and depressive disorders when young people have asthma symptoms that do not respond to medication.

“We conclude that youth with asthma and depressive disorders do have a higher symptom burden, and providers should consider screening for depression in youth with high symptom burden if they are not responding to medication or treatment as expected,” Dr. Laura Richardson said in a poster presentation.

The researchers surveyed by telephone 767 young people, 11–17 years of age, who had asthma and were enrolled in a staff-model health maintenance organization. They used the Children's Health Survey for Asthma-Teen Version (CHSA-T) questionnaire to assess the number of days of asthma symptoms each participant had experienced in the 2 weeks prior to a call and the incidence of individual symptoms.

Determination of anxiety and depressive disorders was based on the Diagnostic Interview Schedule for Children. In addition, the investigators mined automated medical record data for information on asthma treatment intensity, severity, number of emergency department visits, and hospital admissions.

A total of 125 respondents (16%) were found to have anxiety or depressive disorders, while 642 did not (84%). Nearly two-thirds of the depressed youth but fewer than half of the other respondents were female. Both groups were 14 years old on average, reported Dr. Richardson, a pediatrician specializing in adolescent medicine at the University of Washington in Seattle.

Similar proportions of both groups met Health Plan Employer Data Information Set (HEDIS) asthma severity criteria: 69% of the depressed group and 70% of those who were not depressed. The depressed patients had higher Chronic Disease Scores, however (794.8 vs. 580.5).

“After controlling for asthma severity and other covariates, [we found that] youth with anxiety or depressive disorders had an average of 5.4 symptom days in the prior 2 weeks, compared to 3.5 days in those without anxiety or depressive disorders,” Dr. Richardson said.

Respondents with anxiety or depressive disorders also were significantly more likely than the other to report each of six asthma-specific symptoms (wheezing with a cold, cold that would not go away, cough, wheezing without a cold, tightness in chest, and shortness of breath) and five less-specific symptoms (difficulty sleeping, stuffy nose/congestion, itchy eyes, skin rash, and headache).

In addition, the investigators charted a linear relationship between the number of symptoms of anxiety and depression and the number of asthma symptoms that the patients reported. “The more anxiety and depression you have, the more asthma you have,” Dr. Richardson said in an interview at the meeting, which was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — Nearly a third of infants and toddlers with upper respiratory infections also will develop acute otitis media, Dr. Krystal F.Z. Revai reported at the annual meeting of the Pediatric Academic Societies.

Dr. Revai and her colleagues at the University of Texas Medical Branch in Galveston followed 112 children, starting at ages 6–35 months, for 1 year. During the subsequent study period, the children had 630 upper respiratory infections, 205 cases of acute otitis media (AOM), and 52 sinusitis episodes. Most of the ear infections, 188 cases, occurred within 3 weeks of an upper respiratory infection. The rate of AOM after upper respiratory infections was 30% in children 6–47 months of age.

Infants enrolled at 6–11 months of age were the most vulnerable, according to the investigators. The highest rate of AOM, 36%, occurred in children under 1 year of age. The rate was 29% in children enrolled at 12–23 months, and fell to 15% in the cohort aged 24–35 months. “That 6- to 12-month-old window is critical,” Dr. Revai said in a poster-side interview at the meeting, sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics. One implication of the study is that keeping children less than 1 year of age out of day care could protect them from AOM if they have fewer upper respiratory infections as a result.

“By avoiding day care or choosing small-group day care, you will decrease their burden of AOM significantly,” she said.

About 30% of children in the study were in day care, and 29% were exposed to smoke, another risk factor. While nearly two-thirds were fully immunized with the pneumococcal conjugate (PCV7) vaccine, the investigators found no difference in the rates of AOM or sinusitis after upper respiratory infection when they compared children who were fully immunized with those who were not.

Overall, 8% of upper respiratory infections were complicated by sinusitis. The sinusitis rate peaked at 10% in the middle group of children aged 12–23 months. The rate was 7% when the children were older or younger. Dr. Revai also reported that adenovirus, respiratory syncytial virus, and parainfluenza virus were most often associated with AOM. Adenovirus was found in 65% of cases, and each of the other two viruses in 50%.

'By avoiding day care or choosing small-group day care, you will decrease [a child's] burden of AOM significantly.' DR. REVAI

SAN FRANCISCO — Nearly a third of infants and toddlers with upper respiratory infections also will develop acute otitis media, Dr. Krystal F.Z. Revai reported at the annual meeting of the Pediatric Academic Societies.

Dr. Revai and her colleagues at the University of Texas Medical Branch in Galveston followed 112 children, starting at ages 6–35 months, for 1 year. During the subsequent study period, the children had 630 upper respiratory infections, 205 cases of acute otitis media (AOM), and 52 sinusitis episodes. Most of the ear infections, 188 cases, occurred within 3 weeks of an upper respiratory infection. The rate of AOM after upper respiratory infections was 30% in children 6–47 months of age.

Infants enrolled at 6–11 months of age were the most vulnerable, according to the investigators. The highest rate of AOM, 36%, occurred in children under 1 year of age. The rate was 29% in children enrolled at 12–23 months, and fell to 15% in the cohort aged 24–35 months. “That 6- to 12-month-old window is critical,” Dr. Revai said in a poster-side interview at the meeting, sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics. One implication of the study is that keeping children less than 1 year of age out of day care could protect them from AOM if they have fewer upper respiratory infections as a result.

“By avoiding day care or choosing small-group day care, you will decrease their burden of AOM significantly,” she said.

About 30% of children in the study were in day care, and 29% were exposed to smoke, another risk factor. While nearly two-thirds were fully immunized with the pneumococcal conjugate (PCV7) vaccine, the investigators found no difference in the rates of AOM or sinusitis after upper respiratory infection when they compared children who were fully immunized with those who were not.

Overall, 8% of upper respiratory infections were complicated by sinusitis. The sinusitis rate peaked at 10% in the middle group of children aged 12–23 months. The rate was 7% when the children were older or younger. Dr. Revai also reported that adenovirus, respiratory syncytial virus, and parainfluenza virus were most often associated with AOM. Adenovirus was found in 65% of cases, and each of the other two viruses in 50%.

'By avoiding day care or choosing small-group day care, you will decrease [a child's] burden of AOM significantly.' DR. REVAI

SAN FRANCISCO — Nearly a third of infants and toddlers with upper respiratory infections also will develop acute otitis media, Dr. Krystal F.Z. Revai reported at the annual meeting of the Pediatric Academic Societies.

Dr. Revai and her colleagues at the University of Texas Medical Branch in Galveston followed 112 children, starting at ages 6–35 months, for 1 year. During the subsequent study period, the children had 630 upper respiratory infections, 205 cases of acute otitis media (AOM), and 52 sinusitis episodes. Most of the ear infections, 188 cases, occurred within 3 weeks of an upper respiratory infection. The rate of AOM after upper respiratory infections was 30% in children 6–47 months of age.

Infants enrolled at 6–11 months of age were the most vulnerable, according to the investigators. The highest rate of AOM, 36%, occurred in children under 1 year of age. The rate was 29% in children enrolled at 12–23 months, and fell to 15% in the cohort aged 24–35 months. “That 6- to 12-month-old window is critical,” Dr. Revai said in a poster-side interview at the meeting, sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics. One implication of the study is that keeping children less than 1 year of age out of day care could protect them from AOM if they have fewer upper respiratory infections as a result.

“By avoiding day care or choosing small-group day care, you will decrease their burden of AOM significantly,” she said.

About 30% of children in the study were in day care, and 29% were exposed to smoke, another risk factor. While nearly two-thirds were fully immunized with the pneumococcal conjugate (PCV7) vaccine, the investigators found no difference in the rates of AOM or sinusitis after upper respiratory infection when they compared children who were fully immunized with those who were not.

Overall, 8% of upper respiratory infections were complicated by sinusitis. The sinusitis rate peaked at 10% in the middle group of children aged 12–23 months. The rate was 7% when the children were older or younger. Dr. Revai also reported that adenovirus, respiratory syncytial virus, and parainfluenza virus were most often associated with AOM. Adenovirus was found in 65% of cases, and each of the other two viruses in 50%.

'By avoiding day care or choosing small-group day care, you will decrease [a child's] burden of AOM significantly.' DR. REVAI

ATLANTA — Anastrozole decreased bone mineral density by an average of 6.1% in the lumbar spine and 7.2% in the hip over the 5 years that postmenopausal breast cancer patients were enrolled in a study presented by Dr. Robert E. Coleman at the annual meeting of the American Society of Clinical Oncology.

Osteoporosis risk appeared limited to women who were osteopenic before starting treatment with anastrozole (Arimidex), an aromatase inhibitor. Less clear was the likelihood of progression to osteopenia in women who started out with normal bone mineral density (BMD).

All the women who became osteoporotic—four treated with anastrozole and one who was treated with tamoxifen—were osteopenic before they began adjuvant hormonal therapy in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial.

“No patient with normal bone at baseline became osteoporotic after 5 years of treatment,” Dr. Coleman, a professor of medical oncology at Weston Park Hospital in Sheffield, England, said in his report on a subset of 167 women who were tracked for bone loss.

Among 81 patients tracked in the anastrozole arm of the trial, just 13 had normal BMD after 5 years. All but one had been classified as having normal bone before the study started.

The group of patients identified as osteopenic after 5 years was more mixed, comprising 14 women who entered the study with normal BMD and 21 who were osteopenic at the outset. Dr. Coleman calculated that 17% of patients on anastrozole progressed from normal BMD to osteopenia during the study.

About a third of the anastrozole patients had not reached 5 years of follow-up, however. They were categorized as “not recorded” in Dr. Coleman's analysis.

In a discussion of the trial, Dr. Julie Gralow, of the University of Washington, Seattle, excluded the 27 unrecorded patients, 6 of whom started out with normal BMD, from a recalculation of the data. When she looked only at patients for whom 5-year data were available, she found that 53% of the women who started with normal BMD became osteopenic on anastrozole.

That anastrozole caused bone loss was no surprise to Dr. Coleman and his coinvestigators. The 9,366-patient ATAC trial reported that the aromatase inhibitor was more effective than tamoxifen at preventing breast cancer recurrences and had fewer side effects overall. Fractures were an exception, however, occurring in 11% of women on anastrozole but in only 7.7% of those on tamoxifen (Lancet 2005;365:60-2).

“Anastrozole suppresses postmenopausal estradiol levels by about 97%, so one would anticipate it would have an effect on bone health,” Dr. Coleman said, noting that the bone-loss study was planned when the trial was designed.

Tamoxifen increases estradiol levels and was associated with significantly less bone loss for 86 women in the other arm of the study. Their average BMD loss was just 2.8% in the lumbar spine and 0.7% in the hip.

Despite greater bone loss with anastrozole, he said its “superior efficacy and better overall tolerability, compared with tamoxifen” would continue to give anastrozole the advantage in a risk-benefit analysis.

AstraZeneca provided research funds and honoraria.

ATLANTA — Anastrozole decreased bone mineral density by an average of 6.1% in the lumbar spine and 7.2% in the hip over the 5 years that postmenopausal breast cancer patients were enrolled in a study presented by Dr. Robert E. Coleman at the annual meeting of the American Society of Clinical Oncology.

Osteoporosis risk appeared limited to women who were osteopenic before starting treatment with anastrozole (Arimidex), an aromatase inhibitor. Less clear was the likelihood of progression to osteopenia in women who started out with normal bone mineral density (BMD).

All the women who became osteoporotic—four treated with anastrozole and one who was treated with tamoxifen—were osteopenic before they began adjuvant hormonal therapy in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial.

“No patient with normal bone at baseline became osteoporotic after 5 years of treatment,” Dr. Coleman, a professor of medical oncology at Weston Park Hospital in Sheffield, England, said in his report on a subset of 167 women who were tracked for bone loss.

Among 81 patients tracked in the anastrozole arm of the trial, just 13 had normal BMD after 5 years. All but one had been classified as having normal bone before the study started.

The group of patients identified as osteopenic after 5 years was more mixed, comprising 14 women who entered the study with normal BMD and 21 who were osteopenic at the outset. Dr. Coleman calculated that 17% of patients on anastrozole progressed from normal BMD to osteopenia during the study.

About a third of the anastrozole patients had not reached 5 years of follow-up, however. They were categorized as “not recorded” in Dr. Coleman's analysis.

In a discussion of the trial, Dr. Julie Gralow, of the University of Washington, Seattle, excluded the 27 unrecorded patients, 6 of whom started out with normal BMD, from a recalculation of the data. When she looked only at patients for whom 5-year data were available, she found that 53% of the women who started with normal BMD became osteopenic on anastrozole.

That anastrozole caused bone loss was no surprise to Dr. Coleman and his coinvestigators. The 9,366-patient ATAC trial reported that the aromatase inhibitor was more effective than tamoxifen at preventing breast cancer recurrences and had fewer side effects overall. Fractures were an exception, however, occurring in 11% of women on anastrozole but in only 7.7% of those on tamoxifen (Lancet 2005;365:60-2).

“Anastrozole suppresses postmenopausal estradiol levels by about 97%, so one would anticipate it would have an effect on bone health,” Dr. Coleman said, noting that the bone-loss study was planned when the trial was designed.

Tamoxifen increases estradiol levels and was associated with significantly less bone loss for 86 women in the other arm of the study. Their average BMD loss was just 2.8% in the lumbar spine and 0.7% in the hip.

Despite greater bone loss with anastrozole, he said its “superior efficacy and better overall tolerability, compared with tamoxifen” would continue to give anastrozole the advantage in a risk-benefit analysis.

AstraZeneca provided research funds and honoraria.

ATLANTA — Anastrozole decreased bone mineral density by an average of 6.1% in the lumbar spine and 7.2% in the hip over the 5 years that postmenopausal breast cancer patients were enrolled in a study presented by Dr. Robert E. Coleman at the annual meeting of the American Society of Clinical Oncology.

Osteoporosis risk appeared limited to women who were osteopenic before starting treatment with anastrozole (Arimidex), an aromatase inhibitor. Less clear was the likelihood of progression to osteopenia in women who started out with normal bone mineral density (BMD).

All the women who became osteoporotic—four treated with anastrozole and one who was treated with tamoxifen—were osteopenic before they began adjuvant hormonal therapy in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial.

“No patient with normal bone at baseline became osteoporotic after 5 years of treatment,” Dr. Coleman, a professor of medical oncology at Weston Park Hospital in Sheffield, England, said in his report on a subset of 167 women who were tracked for bone loss.

Among 81 patients tracked in the anastrozole arm of the trial, just 13 had normal BMD after 5 years. All but one had been classified as having normal bone before the study started.

The group of patients identified as osteopenic after 5 years was more mixed, comprising 14 women who entered the study with normal BMD and 21 who were osteopenic at the outset. Dr. Coleman calculated that 17% of patients on anastrozole progressed from normal BMD to osteopenia during the study.

About a third of the anastrozole patients had not reached 5 years of follow-up, however. They were categorized as “not recorded” in Dr. Coleman's analysis.

In a discussion of the trial, Dr. Julie Gralow, of the University of Washington, Seattle, excluded the 27 unrecorded patients, 6 of whom started out with normal BMD, from a recalculation of the data. When she looked only at patients for whom 5-year data were available, she found that 53% of the women who started with normal BMD became osteopenic on anastrozole.

That anastrozole caused bone loss was no surprise to Dr. Coleman and his coinvestigators. The 9,366-patient ATAC trial reported that the aromatase inhibitor was more effective than tamoxifen at preventing breast cancer recurrences and had fewer side effects overall. Fractures were an exception, however, occurring in 11% of women on anastrozole but in only 7.7% of those on tamoxifen (Lancet 2005;365:60-2).

“Anastrozole suppresses postmenopausal estradiol levels by about 97%, so one would anticipate it would have an effect on bone health,” Dr. Coleman said, noting that the bone-loss study was planned when the trial was designed.

Tamoxifen increases estradiol levels and was associated with significantly less bone loss for 86 women in the other arm of the study. Their average BMD loss was just 2.8% in the lumbar spine and 0.7% in the hip.

Despite greater bone loss with anastrozole, he said its “superior efficacy and better overall tolerability, compared with tamoxifen” would continue to give anastrozole the advantage in a risk-benefit analysis.

AstraZeneca provided research funds and honoraria.

SAN FRANCISCO — Fluconazole prophylaxis reduced fungal infections and mortality in very low-birth-weight infants at two neonatal intensive care units in retrospective studies that were presented during the annual meeting of the Pediatric Academic Societies.

Incidence of invasive candidiasis in very low-birth-weight (VLBW) infants went from 6.7% to zero at Cooper University Hospital in Camden, N.J., Dr. Zubair H. Aghai reported. However, the intensive regimen used in the neonatal intensive care unit (NICU) led to a significant increase, from 16% to 45%, in conjugated hyperbilirubinemia.

At Brookdale University Hospital and Medical Center in Brooklyn, N.Y., a regimen given only to neonates colonized with Candida reduced candidal sepsis from 12.1% to 8.2% in VLBW infants.

Although the data reported by Dr. M. Roger Kim and colleagues at Brookdale was not statistically significant, associated mortality also declined from 16% to 9%. Dr. Vaishali Jha, the lead author, said in an interview that the Brookdale neonatologists did not see an increase in jaundice or any other adverse effects with their regimen.

Investigators from both groups said they introduced fluconazole prophylaxis because of the increased risk and incidence of invasive fungal infections with the growing number of VLBW infants in NICUs.

Dr. Manjula Mudduluru, the lead author of the poster on the Cooper hospital experience, cited a candidal sepsis rate of 5.5%–10% in neonates who weigh 1,000 g or less at birth. Fungal sepsis is associated with a mortality of 31.8% in premature neonates, according to Dr. Mudduluru, Dr. Aghai, and their colleagues from the hospital.

The Cooper hospital group compared 140 VLBW infants born from March 2002 to September 2005 with 137 historical controls born between January 1998 and February 2002, which was prior to the introduction of the fluconazole regimen. The only significant differences at baseline were that more infants on prophylaxis also received surfactant and prenatal steroids. The regimen delivered 3 mg/kg of fluconazole intravenously every 72 hours for 2 weeks, every 48 hours for 2 weeks, and daily for 3 weeks.

Nine infants developed invasive candidiasis and six of them died during the 2 years prior to introduction of the prophylaxis. Overall mortality fell from 39.4% to 25.7% after the prophylaxis was introduced and invasive candidiasis eliminated.

The investigators estimated that treating 15 VLBW infants with the prophylaxis would prevent one invasive candidiasis infection in their NICU—and that they would need to treat 69 neonates to prevent one death.

Dr. Mudduluru said the clinicians are experimenting with a less frequent dosing schedule to see whether they can reduce the rate of conjugated hyperbilirubinemia.

The investigators at Brookdale hospital considered infants who weighed up to 1,500 g at birth in their review. They compared 141 neonates born from January 2002 to May 2004 with 85 neonates born from July 2004 through June 2005.

During the latter period, weekly surveillance cultures were performed for neonates weighing less than 1,500 g. Infants colonized by Candida species received 3 mg/kg of fluconazole every 48 hours for 6 weeks or until their weight reached 1,500 g. The number of cases of invasive candidiasis per 1,000 patient-days fell from 2.1 to 1.6 during this period.

Dr. Jha said the investigators believe the improved outcomes would reach statistical significance with a larger patient sample. They are planning a randomized, multicenter trial, she said at the meeting, which was sponsored by the American Pediatric Society, the Society for Pediatric Research, the Ambulatory Pediatric Association, and the American Academy of Pediatrics.

Fungal sepsis is associated with a mortality of 31.8% in premature neonates. DR. MUDDULURU

SAN FRANCISCO — Fluconazole prophylaxis reduced fungal infections and mortality in very low-birth-weight infants at two neonatal intensive care units in retrospective studies that were presented during the annual meeting of the Pediatric Academic Societies.

Incidence of invasive candidiasis in very low-birth-weight (VLBW) infants went from 6.7% to zero at Cooper University Hospital in Camden, N.J., Dr. Zubair H. Aghai reported. However, the intensive regimen used in the neonatal intensive care unit (NICU) led to a significant increase, from 16% to 45%, in conjugated hyperbilirubinemia.

At Brookdale University Hospital and Medical Center in Brooklyn, N.Y., a regimen given only to neonates colonized with Candida reduced candidal sepsis from 12.1% to 8.2% in VLBW infants.

Although the data reported by Dr. M. Roger Kim and colleagues at Brookdale was not statistically significant, associated mortality also declined from 16% to 9%. Dr. Vaishali Jha, the lead author, said in an interview that the Brookdale neonatologists did not see an increase in jaundice or any other adverse effects with their regimen.

Investigators from both groups said they introduced fluconazole prophylaxis because of the increased risk and incidence of invasive fungal infections with the growing number of VLBW infants in NICUs.

Dr. Manjula Mudduluru, the lead author of the poster on the Cooper hospital experience, cited a candidal sepsis rate of 5.5%–10% in neonates who weigh 1,000 g or less at birth. Fungal sepsis is associated with a mortality of 31.8% in premature neonates, according to Dr. Mudduluru, Dr. Aghai, and their colleagues from the hospital.

The Cooper hospital group compared 140 VLBW infants born from March 2002 to September 2005 with 137 historical controls born between January 1998 and February 2002, which was prior to the introduction of the fluconazole regimen. The only significant differences at baseline were that more infants on prophylaxis also received surfactant and prenatal steroids. The regimen delivered 3 mg/kg of fluconazole intravenously every 72 hours for 2 weeks, every 48 hours for 2 weeks, and daily for 3 weeks.

Nine infants developed invasive candidiasis and six of them died during the 2 years prior to introduction of the prophylaxis. Overall mortality fell from 39.4% to 25.7% after the prophylaxis was introduced and invasive candidiasis eliminated.

The investigators estimated that treating 15 VLBW infants with the prophylaxis would prevent one invasive candidiasis infection in their NICU—and that they would need to treat 69 neonates to prevent one death.

Dr. Mudduluru said the clinicians are experimenting with a less frequent dosing schedule to see whether they can reduce the rate of conjugated hyperbilirubinemia.

The investigators at Brookdale hospital considered infants who weighed up to 1,500 g at birth in their review. They compared 141 neonates born from January 2002 to May 2004 with 85 neonates born from July 2004 through June 2005.

During the latter period, weekly surveillance cultures were performed for neonates weighing less than 1,500 g. Infants colonized by Candida species received 3 mg/kg of fluconazole every 48 hours for 6 weeks or until their weight reached 1,500 g. The number of cases of invasive candidiasis per 1,000 patient-days fell from 2.1 to 1.6 during this period.

Dr. Jha said the investigators believe the improved outcomes would reach statistical significance with a larger patient sample. They are planning a randomized, multicenter trial, she said at the meeting, which was sponsored by the American Pediatric Society, the Society for Pediatric Research, the Ambulatory Pediatric Association, and the American Academy of Pediatrics.

Fungal sepsis is associated with a mortality of 31.8% in premature neonates. DR. MUDDULURU

SAN FRANCISCO — Fluconazole prophylaxis reduced fungal infections and mortality in very low-birth-weight infants at two neonatal intensive care units in retrospective studies that were presented during the annual meeting of the Pediatric Academic Societies.

Incidence of invasive candidiasis in very low-birth-weight (VLBW) infants went from 6.7% to zero at Cooper University Hospital in Camden, N.J., Dr. Zubair H. Aghai reported. However, the intensive regimen used in the neonatal intensive care unit (NICU) led to a significant increase, from 16% to 45%, in conjugated hyperbilirubinemia.

At Brookdale University Hospital and Medical Center in Brooklyn, N.Y., a regimen given only to neonates colonized with Candida reduced candidal sepsis from 12.1% to 8.2% in VLBW infants.

Although the data reported by Dr. M. Roger Kim and colleagues at Brookdale was not statistically significant, associated mortality also declined from 16% to 9%. Dr. Vaishali Jha, the lead author, said in an interview that the Brookdale neonatologists did not see an increase in jaundice or any other adverse effects with their regimen.

Investigators from both groups said they introduced fluconazole prophylaxis because of the increased risk and incidence of invasive fungal infections with the growing number of VLBW infants in NICUs.

Dr. Manjula Mudduluru, the lead author of the poster on the Cooper hospital experience, cited a candidal sepsis rate of 5.5%–10% in neonates who weigh 1,000 g or less at birth. Fungal sepsis is associated with a mortality of 31.8% in premature neonates, according to Dr. Mudduluru, Dr. Aghai, and their colleagues from the hospital.

The Cooper hospital group compared 140 VLBW infants born from March 2002 to September 2005 with 137 historical controls born between January 1998 and February 2002, which was prior to the introduction of the fluconazole regimen. The only significant differences at baseline were that more infants on prophylaxis also received surfactant and prenatal steroids. The regimen delivered 3 mg/kg of fluconazole intravenously every 72 hours for 2 weeks, every 48 hours for 2 weeks, and daily for 3 weeks.

Nine infants developed invasive candidiasis and six of them died during the 2 years prior to introduction of the prophylaxis. Overall mortality fell from 39.4% to 25.7% after the prophylaxis was introduced and invasive candidiasis eliminated.

The investigators estimated that treating 15 VLBW infants with the prophylaxis would prevent one invasive candidiasis infection in their NICU—and that they would need to treat 69 neonates to prevent one death.

Dr. Mudduluru said the clinicians are experimenting with a less frequent dosing schedule to see whether they can reduce the rate of conjugated hyperbilirubinemia.

The investigators at Brookdale hospital considered infants who weighed up to 1,500 g at birth in their review. They compared 141 neonates born from January 2002 to May 2004 with 85 neonates born from July 2004 through June 2005.

During the latter period, weekly surveillance cultures were performed for neonates weighing less than 1,500 g. Infants colonized by Candida species received 3 mg/kg of fluconazole every 48 hours for 6 weeks or until their weight reached 1,500 g. The number of cases of invasive candidiasis per 1,000 patient-days fell from 2.1 to 1.6 during this period.

Dr. Jha said the investigators believe the improved outcomes would reach statistical significance with a larger patient sample. They are planning a randomized, multicenter trial, she said at the meeting, which was sponsored by the American Pediatric Society, the Society for Pediatric Research, the Ambulatory Pediatric Association, and the American Academy of Pediatrics.

Fungal sepsis is associated with a mortality of 31.8% in premature neonates. DR. MUDDULURU

SAN DIEGO — Advanced age by itself should not be a barrier to switching a patient with community-acquired pneumonia from intravenous to oral antimicrobial therapy soon after the patient shows clinical improvement, Dr. Paulo Rossi said in a poster presentation at the International Conference of the American Thoracic Society.

An observational study of 2,648 adult patients at 40 hospitals in 13 countries showed that, regardless of age, about two-thirds were discharged within 24 hours of meeting the criteria for “switch therapy.” Of 372 patients aged 85 years or older, 65% were discharged in this early time frame, as were 68% of 1,161 patients aged 65–84 years and 72% of 1,115 patients aged 18–64 years. No deaths occurred in the youngest group after switch therapy, and mortality was low in the older groups: 9 deaths (1.6%) of the 554 switch-therapy patients in the 65–84 age group and 2 deaths (1.2%) of the 164 patients in the oldest cohort.

The study shows that frail elderly patients with community-acquired pneumonia (CAP) can handle switch therapy, said Dr. Rossi of S. Maria della Misericordia Hospital in Udine, Italy.

He and his coinvestigators reviewed records of CAP patients who were entered into the Community-Acquired Pneumonia Organization database from June 2001 to May 2005. The database includes hospitals in the United States, and the study coordinator was based at the University of Louisville (Ky.).

The study relied on American Thoracic Society guidelines for time to switch therapy. Patients had to meet four criteria to be considered candidates for a switch: improvement in cough and shortness of breath; at least 8 hours without a fever; leukocytosis reduced by at least 10% from the previous day; and “tolerating oral intake with adequate gastrointestinal absorption.”

The investigators considered patients to be candidates for hospital discharge after they met the above criteria for oral therapy, a diagnostic work-up was completed, any comorbidity was treated, and social needs were met. Any discharge within 24 hours of the patient's meeting the criteria for switch therapy was considered an early discharge.

Of the oldest patients, 90% were classified as being at high risk—a much larger proportion than in any other age group. Nonetheless, 51.6% met the criteria for switch therapy on or before the 6th day of hospitalization. In the middle group of patients, aged 65–84 years, 54.2% passed this goal by the 5th day. In the youngest group, 57.1% were ready to switch on or before the 4th day.

The proportions of patients who met the criteria for switch therapy declined with age, going from 71% of the youngest group to 63% of the middle group to 56% of the oldest group. However, the proportion of patients who were switched was similar across groups: 80% of the under-65 patients, 76% of the middle group, and 78% of those aged 85 and up.

After therapy was switched, the oldest patients were the least likely to require reestablishment of intravenous antibiotics. Just 2 (1.2%) of the 164 patients in the oldest group had to be switched back, compared with 20 (3.6%) of the 554 patients in the middle group and 46 (7.4%) of the 621 patients in the youngest group.

ELSEVIER GLOBAL MEDICAL NEWS

SAN DIEGO — Advanced age by itself should not be a barrier to switching a patient with community-acquired pneumonia from intravenous to oral antimicrobial therapy soon after the patient shows clinical improvement, Dr. Paulo Rossi said in a poster presentation at the International Conference of the American Thoracic Society.

An observational study of 2,648 adult patients at 40 hospitals in 13 countries showed that, regardless of age, about two-thirds were discharged within 24 hours of meeting the criteria for “switch therapy.” Of 372 patients aged 85 years or older, 65% were discharged in this early time frame, as were 68% of 1,161 patients aged 65–84 years and 72% of 1,115 patients aged 18–64 years. No deaths occurred in the youngest group after switch therapy, and mortality was low in the older groups: 9 deaths (1.6%) of the 554 switch-therapy patients in the 65–84 age group and 2 deaths (1.2%) of the 164 patients in the oldest cohort.

The study shows that frail elderly patients with community-acquired pneumonia (CAP) can handle switch therapy, said Dr. Rossi of S. Maria della Misericordia Hospital in Udine, Italy.

He and his coinvestigators reviewed records of CAP patients who were entered into the Community-Acquired Pneumonia Organization database from June 2001 to May 2005. The database includes hospitals in the United States, and the study coordinator was based at the University of Louisville (Ky.).

The study relied on American Thoracic Society guidelines for time to switch therapy. Patients had to meet four criteria to be considered candidates for a switch: improvement in cough and shortness of breath; at least 8 hours without a fever; leukocytosis reduced by at least 10% from the previous day; and “tolerating oral intake with adequate gastrointestinal absorption.”

The investigators considered patients to be candidates for hospital discharge after they met the above criteria for oral therapy, a diagnostic work-up was completed, any comorbidity was treated, and social needs were met. Any discharge within 24 hours of the patient's meeting the criteria for switch therapy was considered an early discharge.

Of the oldest patients, 90% were classified as being at high risk—a much larger proportion than in any other age group. Nonetheless, 51.6% met the criteria for switch therapy on or before the 6th day of hospitalization. In the middle group of patients, aged 65–84 years, 54.2% passed this goal by the 5th day. In the youngest group, 57.1% were ready to switch on or before the 4th day.

The proportions of patients who met the criteria for switch therapy declined with age, going from 71% of the youngest group to 63% of the middle group to 56% of the oldest group. However, the proportion of patients who were switched was similar across groups: 80% of the under-65 patients, 76% of the middle group, and 78% of those aged 85 and up.

After therapy was switched, the oldest patients were the least likely to require reestablishment of intravenous antibiotics. Just 2 (1.2%) of the 164 patients in the oldest group had to be switched back, compared with 20 (3.6%) of the 554 patients in the middle group and 46 (7.4%) of the 621 patients in the youngest group.

ELSEVIER GLOBAL MEDICAL NEWS

SAN DIEGO — Advanced age by itself should not be a barrier to switching a patient with community-acquired pneumonia from intravenous to oral antimicrobial therapy soon after the patient shows clinical improvement, Dr. Paulo Rossi said in a poster presentation at the International Conference of the American Thoracic Society.

An observational study of 2,648 adult patients at 40 hospitals in 13 countries showed that, regardless of age, about two-thirds were discharged within 24 hours of meeting the criteria for “switch therapy.” Of 372 patients aged 85 years or older, 65% were discharged in this early time frame, as were 68% of 1,161 patients aged 65–84 years and 72% of 1,115 patients aged 18–64 years. No deaths occurred in the youngest group after switch therapy, and mortality was low in the older groups: 9 deaths (1.6%) of the 554 switch-therapy patients in the 65–84 age group and 2 deaths (1.2%) of the 164 patients in the oldest cohort.

The study shows that frail elderly patients with community-acquired pneumonia (CAP) can handle switch therapy, said Dr. Rossi of S. Maria della Misericordia Hospital in Udine, Italy.

He and his coinvestigators reviewed records of CAP patients who were entered into the Community-Acquired Pneumonia Organization database from June 2001 to May 2005. The database includes hospitals in the United States, and the study coordinator was based at the University of Louisville (Ky.).

The study relied on American Thoracic Society guidelines for time to switch therapy. Patients had to meet four criteria to be considered candidates for a switch: improvement in cough and shortness of breath; at least 8 hours without a fever; leukocytosis reduced by at least 10% from the previous day; and “tolerating oral intake with adequate gastrointestinal absorption.”

The investigators considered patients to be candidates for hospital discharge after they met the above criteria for oral therapy, a diagnostic work-up was completed, any comorbidity was treated, and social needs were met. Any discharge within 24 hours of the patient's meeting the criteria for switch therapy was considered an early discharge.

Of the oldest patients, 90% were classified as being at high risk—a much larger proportion than in any other age group. Nonetheless, 51.6% met the criteria for switch therapy on or before the 6th day of hospitalization. In the middle group of patients, aged 65–84 years, 54.2% passed this goal by the 5th day. In the youngest group, 57.1% were ready to switch on or before the 4th day.

The proportions of patients who met the criteria for switch therapy declined with age, going from 71% of the youngest group to 63% of the middle group to 56% of the oldest group. However, the proportion of patients who were switched was similar across groups: 80% of the under-65 patients, 76% of the middle group, and 78% of those aged 85 and up.

After therapy was switched, the oldest patients were the least likely to require reestablishment of intravenous antibiotics. Just 2 (1.2%) of the 164 patients in the oldest group had to be switched back, compared with 20 (3.6%) of the 554 patients in the middle group and 46 (7.4%) of the 621 patients in the youngest group.

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — An investigational formulation of lansoprazole can safely treat gastroesophageal reflux disease in neonates and infants as old as 1 year of age, according to the results of a pair of phase I trials presented in a poster at the annual meeting of the Pediatric Academic Societies.

Dr. Margaret Ann Springer reported that the new formulation of lansoprazole (Prevacid), a proton pump inhibitor, relieved symptoms for most babies in the two studies. At the end of 5 days, the investigators saw improvement in 79% of 24 neonates and in 88% of 24 older infants.

Gastroesophageal reflux disease (GERD) did not worsen in any of the babies. Although four neonates and one older infant had adverse events related to the treatment, no baby had to be withdrawn from the trial because of side effects.

All the babies met judicious criteria for clinically evident GERD before being enrolled, said Dr. Springer, of Louisiana State University in Shreveport, in an interview at the meeting. These included feeding intolerance and refusing to eat; vomiting after feeding; irritability and/or crying while being fed; an arching back; impaired growth; and respiratory symptoms. “Babies can die of these pneumonias. Babies can slow their heart down enough to stop breathing. Babies don't gain weight and grow because every time they eat it hurts.”

Lansoprazole is approved for short-term treatment of GERD in children aged 1–17 years. Dr. Springer said the Food and Drug Administration agreed to test it in infants and newborns because GERD is highly symptomatic in this population. She estimated a third to half of babies present with some GERD symptoms, and about 10% have serious cases requiring special care.

TAP Pharmaceutical Products Inc. of Lake Forest, Ill., maker of lansoprazole, sponsored the two open-label trials, which enrolled babies in the United States and Poland. The phase I neonate trial enrolled 24 term or postterm newborns. The average age was 3.7 weeks; mean weight, 3,015 g. The second phase I trial enrolled 24 infants aged 4 weeks to 1 year. Their average age was 24.1 weeks; mean weight, 6,379 g.

Clinicians reconstituted a prepackaged granular powder of lansoprazole in sterile water. For the neonates, they used a concentration of 1 mg/mL, which was delivered once daily in a 0.5-mg/kg or 1.0- mg/kg dose. The older infants were given a 2-mg/mL concentration in a daily 1.0- mg/kg or 2.0-mg/kg dose.

Lansoprazole could be administered by syringe, intraorally, or via a gastronomy tube. An analysis of pharmacokinetics found infants 10 weeks or younger had “substantially higher exposures” to lansoprazole compared with the older infants.

Each trial included 24-hour pH profiles of six babies to determine changes in intragastric levels. Investigators used a pH level of 4 or greater as a goal to demonstrate the drug was indeed reducing stomach acid. The average percentage of time that pH levels were greater than 4 increased from 77% on day 1 to 97% by day 5 for neonates on 0.5 mg/kg per day of drug, and from 59% to 99% for those on the 1.0-mg/kg daily dose.

The older infants substantially increased the percentage of time their pH profiles reached the target, but the result was not as great. Their proportions went from 50% to 85% on the 1.0-mg/kg daily dose and from 52% to 84% on 2.0 mg/kg per day.

The treatment-related adverse events included two cases of flushing, one of anemia, and one increase in transaminase in the neonates plus one increase in hepatic enzyme in an older infant. Two serious adverse events, respiratory distress syndrome and viral pneumonia, occurred after the last day on lansoprazole, but neither was deemed study related.

Dr. Springer said the pharmaceutical company has initiated a longer safety and efficacy trial based on the results. The meeting was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

'Babies can die of these pneumonias. … [They] don't gain weight and grow because every time they eat it hurts.' DR. SPRINGER

SAN FRANCISCO — An investigational formulation of lansoprazole can safely treat gastroesophageal reflux disease in neonates and infants as old as 1 year of age, according to the results of a pair of phase I trials presented in a poster at the annual meeting of the Pediatric Academic Societies.

Dr. Margaret Ann Springer reported that the new formulation of lansoprazole (Prevacid), a proton pump inhibitor, relieved symptoms for most babies in the two studies. At the end of 5 days, the investigators saw improvement in 79% of 24 neonates and in 88% of 24 older infants.

Gastroesophageal reflux disease (GERD) did not worsen in any of the babies. Although four neonates and one older infant had adverse events related to the treatment, no baby had to be withdrawn from the trial because of side effects.

All the babies met judicious criteria for clinically evident GERD before being enrolled, said Dr. Springer, of Louisiana State University in Shreveport, in an interview at the meeting. These included feeding intolerance and refusing to eat; vomiting after feeding; irritability and/or crying while being fed; an arching back; impaired growth; and respiratory symptoms. “Babies can die of these pneumonias. Babies can slow their heart down enough to stop breathing. Babies don't gain weight and grow because every time they eat it hurts.”

Lansoprazole is approved for short-term treatment of GERD in children aged 1–17 years. Dr. Springer said the Food and Drug Administration agreed to test it in infants and newborns because GERD is highly symptomatic in this population. She estimated a third to half of babies present with some GERD symptoms, and about 10% have serious cases requiring special care.

TAP Pharmaceutical Products Inc. of Lake Forest, Ill., maker of lansoprazole, sponsored the two open-label trials, which enrolled babies in the United States and Poland. The phase I neonate trial enrolled 24 term or postterm newborns. The average age was 3.7 weeks; mean weight, 3,015 g. The second phase I trial enrolled 24 infants aged 4 weeks to 1 year. Their average age was 24.1 weeks; mean weight, 6,379 g.

Clinicians reconstituted a prepackaged granular powder of lansoprazole in sterile water. For the neonates, they used a concentration of 1 mg/mL, which was delivered once daily in a 0.5-mg/kg or 1.0- mg/kg dose. The older infants were given a 2-mg/mL concentration in a daily 1.0- mg/kg or 2.0-mg/kg dose.

Lansoprazole could be administered by syringe, intraorally, or via a gastronomy tube. An analysis of pharmacokinetics found infants 10 weeks or younger had “substantially higher exposures” to lansoprazole compared with the older infants.

Each trial included 24-hour pH profiles of six babies to determine changes in intragastric levels. Investigators used a pH level of 4 or greater as a goal to demonstrate the drug was indeed reducing stomach acid. The average percentage of time that pH levels were greater than 4 increased from 77% on day 1 to 97% by day 5 for neonates on 0.5 mg/kg per day of drug, and from 59% to 99% for those on the 1.0-mg/kg daily dose.

The older infants substantially increased the percentage of time their pH profiles reached the target, but the result was not as great. Their proportions went from 50% to 85% on the 1.0-mg/kg daily dose and from 52% to 84% on 2.0 mg/kg per day.

The treatment-related adverse events included two cases of flushing, one of anemia, and one increase in transaminase in the neonates plus one increase in hepatic enzyme in an older infant. Two serious adverse events, respiratory distress syndrome and viral pneumonia, occurred after the last day on lansoprazole, but neither was deemed study related.

Dr. Springer said the pharmaceutical company has initiated a longer safety and efficacy trial based on the results. The meeting was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

'Babies can die of these pneumonias. … [They] don't gain weight and grow because every time they eat it hurts.' DR. SPRINGER

SAN FRANCISCO — An investigational formulation of lansoprazole can safely treat gastroesophageal reflux disease in neonates and infants as old as 1 year of age, according to the results of a pair of phase I trials presented in a poster at the annual meeting of the Pediatric Academic Societies.

Dr. Margaret Ann Springer reported that the new formulation of lansoprazole (Prevacid), a proton pump inhibitor, relieved symptoms for most babies in the two studies. At the end of 5 days, the investigators saw improvement in 79% of 24 neonates and in 88% of 24 older infants.

Gastroesophageal reflux disease (GERD) did not worsen in any of the babies. Although four neonates and one older infant had adverse events related to the treatment, no baby had to be withdrawn from the trial because of side effects.

All the babies met judicious criteria for clinically evident GERD before being enrolled, said Dr. Springer, of Louisiana State University in Shreveport, in an interview at the meeting. These included feeding intolerance and refusing to eat; vomiting after feeding; irritability and/or crying while being fed; an arching back; impaired growth; and respiratory symptoms. “Babies can die of these pneumonias. Babies can slow their heart down enough to stop breathing. Babies don't gain weight and grow because every time they eat it hurts.”

Lansoprazole is approved for short-term treatment of GERD in children aged 1–17 years. Dr. Springer said the Food and Drug Administration agreed to test it in infants and newborns because GERD is highly symptomatic in this population. She estimated a third to half of babies present with some GERD symptoms, and about 10% have serious cases requiring special care.

TAP Pharmaceutical Products Inc. of Lake Forest, Ill., maker of lansoprazole, sponsored the two open-label trials, which enrolled babies in the United States and Poland. The phase I neonate trial enrolled 24 term or postterm newborns. The average age was 3.7 weeks; mean weight, 3,015 g. The second phase I trial enrolled 24 infants aged 4 weeks to 1 year. Their average age was 24.1 weeks; mean weight, 6,379 g.

Clinicians reconstituted a prepackaged granular powder of lansoprazole in sterile water. For the neonates, they used a concentration of 1 mg/mL, which was delivered once daily in a 0.5-mg/kg or 1.0- mg/kg dose. The older infants were given a 2-mg/mL concentration in a daily 1.0- mg/kg or 2.0-mg/kg dose.

Lansoprazole could be administered by syringe, intraorally, or via a gastronomy tube. An analysis of pharmacokinetics found infants 10 weeks or younger had “substantially higher exposures” to lansoprazole compared with the older infants.

Each trial included 24-hour pH profiles of six babies to determine changes in intragastric levels. Investigators used a pH level of 4 or greater as a goal to demonstrate the drug was indeed reducing stomach acid. The average percentage of time that pH levels were greater than 4 increased from 77% on day 1 to 97% by day 5 for neonates on 0.5 mg/kg per day of drug, and from 59% to 99% for those on the 1.0-mg/kg daily dose.

The older infants substantially increased the percentage of time their pH profiles reached the target, but the result was not as great. Their proportions went from 50% to 85% on the 1.0-mg/kg daily dose and from 52% to 84% on 2.0 mg/kg per day.

The treatment-related adverse events included two cases of flushing, one of anemia, and one increase in transaminase in the neonates plus one increase in hepatic enzyme in an older infant. Two serious adverse events, respiratory distress syndrome and viral pneumonia, occurred after the last day on lansoprazole, but neither was deemed study related.

Dr. Springer said the pharmaceutical company has initiated a longer safety and efficacy trial based on the results. The meeting was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

'Babies can die of these pneumonias. … [They] don't gain weight and grow because every time they eat it hurts.' DR. SPRINGER

SAN FRANCISCO — Ceftriaxone by itself is not sufficient for acute or chronic pediatric mastoiditis, according to a group of emergency physicians who compared cases treated before and after adoption of the pneumococcal conjugate vaccine.

The proportion of Streptococcus pneumoniae isolates that were resistant to ceftriaxone increased from 7% in the pre-PCV era to 30% afterward, Dr. Dewesh Agrawal reported in a poster at the annual meeting of the Pediatric Academic Societies.

Although S. pneumoniae remained the most frequent cause of acute mastoiditis, Pseudomonas aeruginosa was found in five of seven chronic cases in which children had ear disease for more than 3 weeks before coming to the emergency department. In addition, P. aeruginosa was the second most common cause of acute mastoiditis.

“That's a really bad bug, and ceftriaxone isn't good enough for that,” Dr. Agrawal, of the Children's National Medical Center in Washington, said in an interview with this newspaper.

The study compared 68 cases seen from January 1995 through December 2000 with 54 cases seen from January 2005 through April 2005. Patients ranged in age from 30 days to 18 years with a median age of 5 years. Over half (54%) were female.

All told, 93 patients (76%) had acute mastoiditis, and 29 patients (24%) had chronic mastoiditis.

In all, 75 children (61%) went on to have surgery; among these, myringotomy tubes were placed in ears (57 children) and/or mastoidectomy was performed (56 children).

The investigators were able to determine the etiologic agents causing mastoiditis in 60 children (49%). The other pathogens that they identified in the study were Staphylococcus aureus, Staphylococcus pyogenes, and Haemophilus influenzae (acute only).

Dr. Agrawal said the investigators were surprised to find that the proportion of mastoiditis cases caused by S. pneumoniae did not decrease in the PCV era. S. pneumoniae accounted for 21% (14 of 68) of the early cases and 19% (10 of 54) of the later cases.

He speculated that the study may have been done “too soon” in that many of the older children in the post-PCV-era cohort turned out not to have been given the vaccine.

The investigators found that physicians were much more likely to choose empirical parenteral combination therapy with ceftriaxone when treating acute mastoiditis: It was used in 49% of acute cases vs. 10% of chronic cases.

Empirical parenteral combination therapy with ceftriaxone was used more often in the post-PCV era as well (57% of the later cases vs. 24% in the earlier cohort). Clindamycin use, either alone or in combination, also increased from 12% of the early cases to 22% of later cases.

Even so, Dr. Agrawal and his colleagues reported that, based on the etiologic findings and antibiotic sensitivities, only 43% of the first-choice antibiotics were appropriate in the vaccine era.

“In the post-PCV era, or in chronic mastoiditis, empirical antimicrobial therapy with ceftriaxone alone is not appropriate,” they concluded.

“With acute ear disease, you've got to add on other antibiotics,” Dr. Agrawal said at the meeting, which was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — Ceftriaxone by itself is not sufficient for acute or chronic pediatric mastoiditis, according to a group of emergency physicians who compared cases treated before and after adoption of the pneumococcal conjugate vaccine.

The proportion of Streptococcus pneumoniae isolates that were resistant to ceftriaxone increased from 7% in the pre-PCV era to 30% afterward, Dr. Dewesh Agrawal reported in a poster at the annual meeting of the Pediatric Academic Societies.

Although S. pneumoniae remained the most frequent cause of acute mastoiditis, Pseudomonas aeruginosa was found in five of seven chronic cases in which children had ear disease for more than 3 weeks before coming to the emergency department. In addition, P. aeruginosa was the second most common cause of acute mastoiditis.

“That's a really bad bug, and ceftriaxone isn't good enough for that,” Dr. Agrawal, of the Children's National Medical Center in Washington, said in an interview with this newspaper.

The study compared 68 cases seen from January 1995 through December 2000 with 54 cases seen from January 2005 through April 2005. Patients ranged in age from 30 days to 18 years with a median age of 5 years. Over half (54%) were female.

All told, 93 patients (76%) had acute mastoiditis, and 29 patients (24%) had chronic mastoiditis.

In all, 75 children (61%) went on to have surgery; among these, myringotomy tubes were placed in ears (57 children) and/or mastoidectomy was performed (56 children).

The investigators were able to determine the etiologic agents causing mastoiditis in 60 children (49%). The other pathogens that they identified in the study were Staphylococcus aureus, Staphylococcus pyogenes, and Haemophilus influenzae (acute only).

Dr. Agrawal said the investigators were surprised to find that the proportion of mastoiditis cases caused by S. pneumoniae did not decrease in the PCV era. S. pneumoniae accounted for 21% (14 of 68) of the early cases and 19% (10 of 54) of the later cases.

He speculated that the study may have been done “too soon” in that many of the older children in the post-PCV-era cohort turned out not to have been given the vaccine.

The investigators found that physicians were much more likely to choose empirical parenteral combination therapy with ceftriaxone when treating acute mastoiditis: It was used in 49% of acute cases vs. 10% of chronic cases.

Empirical parenteral combination therapy with ceftriaxone was used more often in the post-PCV era as well (57% of the later cases vs. 24% in the earlier cohort). Clindamycin use, either alone or in combination, also increased from 12% of the early cases to 22% of later cases.

Even so, Dr. Agrawal and his colleagues reported that, based on the etiologic findings and antibiotic sensitivities, only 43% of the first-choice antibiotics were appropriate in the vaccine era.

“In the post-PCV era, or in chronic mastoiditis, empirical antimicrobial therapy with ceftriaxone alone is not appropriate,” they concluded.

“With acute ear disease, you've got to add on other antibiotics,” Dr. Agrawal said at the meeting, which was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

ELSEVIER GLOBAL MEDICAL NEWS

SAN FRANCISCO — Ceftriaxone by itself is not sufficient for acute or chronic pediatric mastoiditis, according to a group of emergency physicians who compared cases treated before and after adoption of the pneumococcal conjugate vaccine.

The proportion of Streptococcus pneumoniae isolates that were resistant to ceftriaxone increased from 7% in the pre-PCV era to 30% afterward, Dr. Dewesh Agrawal reported in a poster at the annual meeting of the Pediatric Academic Societies.

Although S. pneumoniae remained the most frequent cause of acute mastoiditis, Pseudomonas aeruginosa was found in five of seven chronic cases in which children had ear disease for more than 3 weeks before coming to the emergency department. In addition, P. aeruginosa was the second most common cause of acute mastoiditis.

“That's a really bad bug, and ceftriaxone isn't good enough for that,” Dr. Agrawal, of the Children's National Medical Center in Washington, said in an interview with this newspaper.

The study compared 68 cases seen from January 1995 through December 2000 with 54 cases seen from January 2005 through April 2005. Patients ranged in age from 30 days to 18 years with a median age of 5 years. Over half (54%) were female.

All told, 93 patients (76%) had acute mastoiditis, and 29 patients (24%) had chronic mastoiditis.

In all, 75 children (61%) went on to have surgery; among these, myringotomy tubes were placed in ears (57 children) and/or mastoidectomy was performed (56 children).

The investigators were able to determine the etiologic agents causing mastoiditis in 60 children (49%). The other pathogens that they identified in the study were Staphylococcus aureus, Staphylococcus pyogenes, and Haemophilus influenzae (acute only).

Dr. Agrawal said the investigators were surprised to find that the proportion of mastoiditis cases caused by S. pneumoniae did not decrease in the PCV era. S. pneumoniae accounted for 21% (14 of 68) of the early cases and 19% (10 of 54) of the later cases.

He speculated that the study may have been done “too soon” in that many of the older children in the post-PCV-era cohort turned out not to have been given the vaccine.

The investigators found that physicians were much more likely to choose empirical parenteral combination therapy with ceftriaxone when treating acute mastoiditis: It was used in 49% of acute cases vs. 10% of chronic cases.

Empirical parenteral combination therapy with ceftriaxone was used more often in the post-PCV era as well (57% of the later cases vs. 24% in the earlier cohort). Clindamycin use, either alone or in combination, also increased from 12% of the early cases to 22% of later cases.

Even so, Dr. Agrawal and his colleagues reported that, based on the etiologic findings and antibiotic sensitivities, only 43% of the first-choice antibiotics were appropriate in the vaccine era.

“In the post-PCV era, or in chronic mastoiditis, empirical antimicrobial therapy with ceftriaxone alone is not appropriate,” they concluded.

“With acute ear disease, you've got to add on other antibiotics,” Dr. Agrawal said at the meeting, which was sponsored by the American Pediatric Society, Society for Pediatric Research, Ambulatory Pediatric Association, and American Academy of Pediatrics.

ELSEVIER GLOBAL MEDICAL NEWS

SAN DIEGO — Pharmacologic prophylaxis can sharply reduce the risk of deep venous thrombosis when cancer patients undergo surgery, Dr. Michael J. Leonardi reported at a symposium sponsored by the Society of Surgical Oncology.

The deep venous thrombosis (DVT) rate falls from 35% without prophylaxis to 12% when surgical oncology patients are given heparin, according to Dr. Leonardi of the University of California, Los Angeles. A combination of mechanical prophylaxis with heparin further reduces the DVT rate to just 5%.

“Cancer patients need some form of prophylaxis,” Dr. Leonardi said in an interview after his review of data from dozens of randomized, controlled trials. “If bleeding risk is not a concern,” he added, “pharmacological prophylaxis is better than mechanical prophylaxis, and combination therapy has been shown to be even more effective.”

Dr. Leonardi and his colleagues in the UCLA surgery department undertook their study to help institutions develop guidelines for DVT. They searched the Medline database for English-language trials and found 55 randomized, controlled trials published from 1966 to 2005 on DVT prophylaxis in general surgery. Among these, 26 trials reported outcomes for 7,639 cancer patients, Dr. Leonardi said.

Colorectal and major abdominal surgical procedures accounted for 39% and 38% of cases, respectively. Upper gastrointestinal and small bowel operations were the next most common at 11%, followed by gynecologic surgery at 3%.

After a review of the wide variety of patients and surgeons in these trials, he said the best prophylaxis for individual cancers is still not known. For example, not even one randomized controlled trial was found that evaluated DVT prophylaxis in breast cancer patients. The incidence of DVT in breast cancer “is probably not as high as in some other cancers, but because breast cancer is so common, a lot of DVTs are associated with it,” he said.

Among the findings from the analysis, Dr. Leonardi reported that:

▸ DVT rates vary with the detection method used. Venography was the most sensitive method, and ultrasound the least.

▸ Higher heparin doses are more effective than lower doses. DVT rates were 8% for higher doses and 14% for lower doses of the forms of heparin in 17 trials with a total of 4,005 patients.

▸ Low-molecular-weight heparin and low-weight unfractionated heparin are equally effective. Both cut DVT rates to 8% at high doses in the 17 trials just cited. At low doses, the rate was 14% for LMW heparin and 13% for unfractionated heparin.

▸ Heparin reduces the rate of proximal DVTs. The rate went from 41% to 13% in nine trials reporting on 284 patients with DVTs. Location was unaffected by the use of LMW vs. unfractionated heparin.

▸ Major complications occur in only 1% of cases with pharmacologic prophylaxis. Based on seven trials, minor complications occurred in 10% of patients and major complications in 1%, he reported. There was no difference between LMW and unfractionated heparin. In four trials, 3% of patients discontinued prophylaxis.

'If bleeding risk is not a concern, pharmacological prophylaxis is better than mechanical prophylaxis.' DR. LEONARDI

SAN DIEGO — Pharmacologic prophylaxis can sharply reduce the risk of deep venous thrombosis when cancer patients undergo surgery, Dr. Michael J. Leonardi reported at a symposium sponsored by the Society of Surgical Oncology.

The deep venous thrombosis (DVT) rate falls from 35% without prophylaxis to 12% when surgical oncology patients are given heparin, according to Dr. Leonardi of the University of California, Los Angeles. A combination of mechanical prophylaxis with heparin further reduces the DVT rate to just 5%.

“Cancer patients need some form of prophylaxis,” Dr. Leonardi said in an interview after his review of data from dozens of randomized, controlled trials. “If bleeding risk is not a concern,” he added, “pharmacological prophylaxis is better than mechanical prophylaxis, and combination therapy has been shown to be even more effective.”

Dr. Leonardi and his colleagues in the UCLA surgery department undertook their study to help institutions develop guidelines for DVT. They searched the Medline database for English-language trials and found 55 randomized, controlled trials published from 1966 to 2005 on DVT prophylaxis in general surgery. Among these, 26 trials reported outcomes for 7,639 cancer patients, Dr. Leonardi said.

Colorectal and major abdominal surgical procedures accounted for 39% and 38% of cases, respectively. Upper gastrointestinal and small bowel operations were the next most common at 11%, followed by gynecologic surgery at 3%.

After a review of the wide variety of patients and surgeons in these trials, he said the best prophylaxis for individual cancers is still not known. For example, not even one randomized controlled trial was found that evaluated DVT prophylaxis in breast cancer patients. The incidence of DVT in breast cancer “is probably not as high as in some other cancers, but because breast cancer is so common, a lot of DVTs are associated with it,” he said.

Among the findings from the analysis, Dr. Leonardi reported that:

▸ DVT rates vary with the detection method used. Venography was the most sensitive method, and ultrasound the least.

▸ Higher heparin doses are more effective than lower doses. DVT rates were 8% for higher doses and 14% for lower doses of the forms of heparin in 17 trials with a total of 4,005 patients.

▸ Low-molecular-weight heparin and low-weight unfractionated heparin are equally effective. Both cut DVT rates to 8% at high doses in the 17 trials just cited. At low doses, the rate was 14% for LMW heparin and 13% for unfractionated heparin.

▸ Heparin reduces the rate of proximal DVTs. The rate went from 41% to 13% in nine trials reporting on 284 patients with DVTs. Location was unaffected by the use of LMW vs. unfractionated heparin.

▸ Major complications occur in only 1% of cases with pharmacologic prophylaxis. Based on seven trials, minor complications occurred in 10% of patients and major complications in 1%, he reported. There was no difference between LMW and unfractionated heparin. In four trials, 3% of patients discontinued prophylaxis.

'If bleeding risk is not a concern, pharmacological prophylaxis is better than mechanical prophylaxis.' DR. LEONARDI

SAN DIEGO — Pharmacologic prophylaxis can sharply reduce the risk of deep venous thrombosis when cancer patients undergo surgery, Dr. Michael J. Leonardi reported at a symposium sponsored by the Society of Surgical Oncology.

The deep venous thrombosis (DVT) rate falls from 35% without prophylaxis to 12% when surgical oncology patients are given heparin, according to Dr. Leonardi of the University of California, Los Angeles. A combination of mechanical prophylaxis with heparin further reduces the DVT rate to just 5%.

“Cancer patients need some form of prophylaxis,” Dr. Leonardi said in an interview after his review of data from dozens of randomized, controlled trials. “If bleeding risk is not a concern,” he added, “pharmacological prophylaxis is better than mechanical prophylaxis, and combination therapy has been shown to be even more effective.”

Dr. Leonardi and his colleagues in the UCLA surgery department undertook their study to help institutions develop guidelines for DVT. They searched the Medline database for English-language trials and found 55 randomized, controlled trials published from 1966 to 2005 on DVT prophylaxis in general surgery. Among these, 26 trials reported outcomes for 7,639 cancer patients, Dr. Leonardi said.

Colorectal and major abdominal surgical procedures accounted for 39% and 38% of cases, respectively. Upper gastrointestinal and small bowel operations were the next most common at 11%, followed by gynecologic surgery at 3%.

After a review of the wide variety of patients and surgeons in these trials, he said the best prophylaxis for individual cancers is still not known. For example, not even one randomized controlled trial was found that evaluated DVT prophylaxis in breast cancer patients. The incidence of DVT in breast cancer “is probably not as high as in some other cancers, but because breast cancer is so common, a lot of DVTs are associated with it,” he said.

Among the findings from the analysis, Dr. Leonardi reported that:

▸ DVT rates vary with the detection method used. Venography was the most sensitive method, and ultrasound the least.

▸ Higher heparin doses are more effective than lower doses. DVT rates were 8% for higher doses and 14% for lower doses of the forms of heparin in 17 trials with a total of 4,005 patients.

▸ Low-molecular-weight heparin and low-weight unfractionated heparin are equally effective. Both cut DVT rates to 8% at high doses in the 17 trials just cited. At low doses, the rate was 14% for LMW heparin and 13% for unfractionated heparin.

▸ Heparin reduces the rate of proximal DVTs. The rate went from 41% to 13% in nine trials reporting on 284 patients with DVTs. Location was unaffected by the use of LMW vs. unfractionated heparin.

▸ Major complications occur in only 1% of cases with pharmacologic prophylaxis. Based on seven trials, minor complications occurred in 10% of patients and major complications in 1%, he reported. There was no difference between LMW and unfractionated heparin. In four trials, 3% of patients discontinued prophylaxis.

'If bleeding risk is not a concern, pharmacological prophylaxis is better than mechanical prophylaxis.' DR. LEONARDI