Diana Mahoney

BOSTON — Nebulizers are better than nonnebulized devices for delivering inhaled corticosteroids to children with asthma, results of a study have shown.

Although nebulizers are not necessarily more effective than nonnebulized devices such as a metered-dose inhaler and holding chamber, “the improved outcomes may be a function of better compliance and a higher likelihood of correct use,” Carlos A. Camargo, M.D., reported at the annual meeting of the American College of Allergy, Asthma, and Immunology.

Dr. Camargo, assistant professor of medicine at Harvard Medical School in Boston, and his colleagues used a managed care organization database to compare the health outcomes achieved by children with asthma who received inhaled corticosteroids by nebulizer with those of children who received the treatment via a nonnebulized device.

The investigators identified 1,552 children aged 8 years and younger with an asthma diagnosis and an asthma-related hospitalization or emergency department visit between July 2000 and June 2002. All of the patients had prescription claims for an inhaled corticosteroid within 30 days of discharge.

The primary outcome measure was the relative risk of rehospitalization or recurrent emergency department visits between days 31 and 180 after the baseline visit. The patient population was divided in two age groups: 0–4 years and 5–8 years. Regression analyses controlled for sex, age, current and prior asthma medications, prior oral corticosteroid and short-acting β2 adrenergic agonist use, and the initial type of index event.

Of the 1,552 patients with claims for inhaled corticosteroids, 729 were in the nebulizer group, of whom 480 were younger than 4 years. Among the 823 patients in the nonnebulized group, 292 were younger than 4 years.

The overall postindex rehospitalization/emergency visit rate was 12.4%. “After model risk adjustment, patients using nebulized steroids had a 53% risk reduction for hospitalization or emergency department recurrence compared with those not using nebulized therapy,” said Dr. Camargo.

The comparative risk reductions by age group were 62% in the 0–4 years nebulizer group and 52% in the 5–8 year range.

The differences held relatively steady after adjustment for age differences between the groups. With respect to asthma severity at baseline for this study, “if anything, the nebulized group was sicker to start with than the nonnebulized group,” Dr. Camargo commented.

Improved compliance with nebulizers compared with other devices in the real-world setting is one possible explanation for the results, said Dr. Camargo, noting that the adherence issue might not be apparent in clinical trials. “In the real world, it could be that kids treated with nebulizers are more likely to actually get their medications than kids treated with metered-dose inhalers—possibly because of the mask used with the nebulizer or because of greater parent involvement,” he commented.

Previous studies investigating the proper use of inhalation devices and techniques also suggest another explanation. These studies have shown that nebulizers are used correctly more often than metered-dose inhalers, and young age is highly associated with improper use using a metered-dose inhaler and holding chamber, which could explain the higher risk reduction in the 0–4 years group with the nebulizer delivery, said Dr. Camargo.

The findings of this study suggest that prescribing inhaled corticosteroids with nebulizer delivery for children who present to emergency departments with asthma exacerbation might reduce the high number of children requiring emergency asthma care annually, Dr. Camargo concluded.

BOSTON — Nebulizers are better than nonnebulized devices for delivering inhaled corticosteroids to children with asthma, results of a study have shown.

Although nebulizers are not necessarily more effective than nonnebulized devices such as a metered-dose inhaler and holding chamber, “the improved outcomes may be a function of better compliance and a higher likelihood of correct use,” Carlos A. Camargo, M.D., reported at the annual meeting of the American College of Allergy, Asthma, and Immunology.

Dr. Camargo, assistant professor of medicine at Harvard Medical School in Boston, and his colleagues used a managed care organization database to compare the health outcomes achieved by children with asthma who received inhaled corticosteroids by nebulizer with those of children who received the treatment via a nonnebulized device.

The investigators identified 1,552 children aged 8 years and younger with an asthma diagnosis and an asthma-related hospitalization or emergency department visit between July 2000 and June 2002. All of the patients had prescription claims for an inhaled corticosteroid within 30 days of discharge.

The primary outcome measure was the relative risk of rehospitalization or recurrent emergency department visits between days 31 and 180 after the baseline visit. The patient population was divided in two age groups: 0–4 years and 5–8 years. Regression analyses controlled for sex, age, current and prior asthma medications, prior oral corticosteroid and short-acting β2 adrenergic agonist use, and the initial type of index event.

Of the 1,552 patients with claims for inhaled corticosteroids, 729 were in the nebulizer group, of whom 480 were younger than 4 years. Among the 823 patients in the nonnebulized group, 292 were younger than 4 years.

The overall postindex rehospitalization/emergency visit rate was 12.4%. “After model risk adjustment, patients using nebulized steroids had a 53% risk reduction for hospitalization or emergency department recurrence compared with those not using nebulized therapy,” said Dr. Camargo.

The comparative risk reductions by age group were 62% in the 0–4 years nebulizer group and 52% in the 5–8 year range.

The differences held relatively steady after adjustment for age differences between the groups. With respect to asthma severity at baseline for this study, “if anything, the nebulized group was sicker to start with than the nonnebulized group,” Dr. Camargo commented.

Improved compliance with nebulizers compared with other devices in the real-world setting is one possible explanation for the results, said Dr. Camargo, noting that the adherence issue might not be apparent in clinical trials. “In the real world, it could be that kids treated with nebulizers are more likely to actually get their medications than kids treated with metered-dose inhalers—possibly because of the mask used with the nebulizer or because of greater parent involvement,” he commented.

Previous studies investigating the proper use of inhalation devices and techniques also suggest another explanation. These studies have shown that nebulizers are used correctly more often than metered-dose inhalers, and young age is highly associated with improper use using a metered-dose inhaler and holding chamber, which could explain the higher risk reduction in the 0–4 years group with the nebulizer delivery, said Dr. Camargo.

The findings of this study suggest that prescribing inhaled corticosteroids with nebulizer delivery for children who present to emergency departments with asthma exacerbation might reduce the high number of children requiring emergency asthma care annually, Dr. Camargo concluded.

BOSTON — Nebulizers are better than nonnebulized devices for delivering inhaled corticosteroids to children with asthma, results of a study have shown.

Although nebulizers are not necessarily more effective than nonnebulized devices such as a metered-dose inhaler and holding chamber, “the improved outcomes may be a function of better compliance and a higher likelihood of correct use,” Carlos A. Camargo, M.D., reported at the annual meeting of the American College of Allergy, Asthma, and Immunology.

Dr. Camargo, assistant professor of medicine at Harvard Medical School in Boston, and his colleagues used a managed care organization database to compare the health outcomes achieved by children with asthma who received inhaled corticosteroids by nebulizer with those of children who received the treatment via a nonnebulized device.

The investigators identified 1,552 children aged 8 years and younger with an asthma diagnosis and an asthma-related hospitalization or emergency department visit between July 2000 and June 2002. All of the patients had prescription claims for an inhaled corticosteroid within 30 days of discharge.

The primary outcome measure was the relative risk of rehospitalization or recurrent emergency department visits between days 31 and 180 after the baseline visit. The patient population was divided in two age groups: 0–4 years and 5–8 years. Regression analyses controlled for sex, age, current and prior asthma medications, prior oral corticosteroid and short-acting β2 adrenergic agonist use, and the initial type of index event.

Of the 1,552 patients with claims for inhaled corticosteroids, 729 were in the nebulizer group, of whom 480 were younger than 4 years. Among the 823 patients in the nonnebulized group, 292 were younger than 4 years.

The overall postindex rehospitalization/emergency visit rate was 12.4%. “After model risk adjustment, patients using nebulized steroids had a 53% risk reduction for hospitalization or emergency department recurrence compared with those not using nebulized therapy,” said Dr. Camargo.

The comparative risk reductions by age group were 62% in the 0–4 years nebulizer group and 52% in the 5–8 year range.

The differences held relatively steady after adjustment for age differences between the groups. With respect to asthma severity at baseline for this study, “if anything, the nebulized group was sicker to start with than the nonnebulized group,” Dr. Camargo commented.

Improved compliance with nebulizers compared with other devices in the real-world setting is one possible explanation for the results, said Dr. Camargo, noting that the adherence issue might not be apparent in clinical trials. “In the real world, it could be that kids treated with nebulizers are more likely to actually get their medications than kids treated with metered-dose inhalers—possibly because of the mask used with the nebulizer or because of greater parent involvement,” he commented.

Previous studies investigating the proper use of inhalation devices and techniques also suggest another explanation. These studies have shown that nebulizers are used correctly more often than metered-dose inhalers, and young age is highly associated with improper use using a metered-dose inhaler and holding chamber, which could explain the higher risk reduction in the 0–4 years group with the nebulizer delivery, said Dr. Camargo.

The findings of this study suggest that prescribing inhaled corticosteroids with nebulizer delivery for children who present to emergency departments with asthma exacerbation might reduce the high number of children requiring emergency asthma care annually, Dr. Camargo concluded.

BOSTON — A new immunotherapy protocol can substantially and safely reduce the amount of time it takes for children with allergies to experience relief from their symptoms, compared with conventional allergen vaccination, reported William Smits, M.D.

In addition to saving time and money, the compressed vaccination schedule appears to improve patient compliance, Dr. Smits said in a presentation at the annual meeting of the American College of Allergy, Asthma, and Immunology.

A type of “rush” regimen, this is a novel protocol that jump-starts allergy immunotherapy with a series of in-office vaccinations given over a 2.5-hour period. Unlike other rapid desensitization efforts—many of which have been shown to evoke serious systemic reactions in a large proportion of patients—this protocol includes 3 days of premedication with corticosteroids and H1 antagonists to minimize the potential for adverse reactions.

“Previous studies [of rapid vaccination regimens] have shown reaction rates of anywhere from 30% to 40%, which is the major concern with rush protocols,” said. Dr. Smits of Indiana University, Fort Wayne. “With our approach, we've found a rate close to that of conventional immunotherapy.”

Dr. Smits and his colleagues tested the rapid vaccination protocol in 148 children aged 1–18 years diagnosed with mild to severe asthma (118), allergic rhinitis (143), and/or chronic sinusitis (23). All of the children were pretreated for 3 days with prednisone or prednisolone and second-generation antihistamines, including cetirizine (Zyrtec), loratadine (Claritin), and fexofenadine (Allegra). On the vaccination day, the children received eight injections given at 15-minute intervals. The doses increased from an initial 1:1,000,000 dilution to a final 1:1,000 dilution.

In addition to premedication, a key to the success of this treatment is lowering the target end point dosage, said Dr. Smits. The harmful reactions reported in earlier studies generally occurred at the end of the rapid treatment phase, when the patient received a final high dose to be maintained for the duration of the therapy. “We stopped just before that time and gave the patients the last injections over a 2-month period.”

The investigators monitored the children for systemic reactions. Of the full cohort, eight patients—seven of whom were asthma patients on inhaled corticosteroids—experienced a systemic reaction following the vaccination. None of the eight patients experienced true anaphylaxis. The patients who had reactions were treated with one or a combination of the following: nebulized breathing treatment with albuterol, two sprays in each nostril of azelastine (Astelin), and diphenhydramine (Benadryl), either orally or intramuscularly. None of the patients requiring treatment needed subcutaneous epinephrine or further treatment for recurrent symptoms. Also, none needed hospitalization.

Following the rapid protocol, all of the patients in the study continued with a conventional allergen immunotherapy regimen to reach their maintenance dose.

“Overall, the patients reached efficacious dosages almost immediately,” said Dr. Smits, who estimated the average amount of build-up time saved by the new protocol to be about 6 months. “And adherence rates were better than what we typically see with conventional immunotherapy,” he said. Patient adherence rates were 95.3%, 90.5%, and 79.7% at 3, 6, and 12 months, respectively, compared with approximately 50% adherence associated with conventional immunotherapy.

“Contrary to what everyone thinks, there is a way to do this safely,” said Dr. Smits, who uses the rapid protocol in approximately 75% of the adults and children he treats.

The bottom line, he concluded, is that the rapid protocol “costs less, incidents of illness are reduced, and people see results more quickly.”

BOSTON — A new immunotherapy protocol can substantially and safely reduce the amount of time it takes for children with allergies to experience relief from their symptoms, compared with conventional allergen vaccination, reported William Smits, M.D.

In addition to saving time and money, the compressed vaccination schedule appears to improve patient compliance, Dr. Smits said in a presentation at the annual meeting of the American College of Allergy, Asthma, and Immunology.

A type of “rush” regimen, this is a novel protocol that jump-starts allergy immunotherapy with a series of in-office vaccinations given over a 2.5-hour period. Unlike other rapid desensitization efforts—many of which have been shown to evoke serious systemic reactions in a large proportion of patients—this protocol includes 3 days of premedication with corticosteroids and H1 antagonists to minimize the potential for adverse reactions.

“Previous studies [of rapid vaccination regimens] have shown reaction rates of anywhere from 30% to 40%, which is the major concern with rush protocols,” said. Dr. Smits of Indiana University, Fort Wayne. “With our approach, we've found a rate close to that of conventional immunotherapy.”

Dr. Smits and his colleagues tested the rapid vaccination protocol in 148 children aged 1–18 years diagnosed with mild to severe asthma (118), allergic rhinitis (143), and/or chronic sinusitis (23). All of the children were pretreated for 3 days with prednisone or prednisolone and second-generation antihistamines, including cetirizine (Zyrtec), loratadine (Claritin), and fexofenadine (Allegra). On the vaccination day, the children received eight injections given at 15-minute intervals. The doses increased from an initial 1:1,000,000 dilution to a final 1:1,000 dilution.

In addition to premedication, a key to the success of this treatment is lowering the target end point dosage, said Dr. Smits. The harmful reactions reported in earlier studies generally occurred at the end of the rapid treatment phase, when the patient received a final high dose to be maintained for the duration of the therapy. “We stopped just before that time and gave the patients the last injections over a 2-month period.”

The investigators monitored the children for systemic reactions. Of the full cohort, eight patients—seven of whom were asthma patients on inhaled corticosteroids—experienced a systemic reaction following the vaccination. None of the eight patients experienced true anaphylaxis. The patients who had reactions were treated with one or a combination of the following: nebulized breathing treatment with albuterol, two sprays in each nostril of azelastine (Astelin), and diphenhydramine (Benadryl), either orally or intramuscularly. None of the patients requiring treatment needed subcutaneous epinephrine or further treatment for recurrent symptoms. Also, none needed hospitalization.

Following the rapid protocol, all of the patients in the study continued with a conventional allergen immunotherapy regimen to reach their maintenance dose.

“Overall, the patients reached efficacious dosages almost immediately,” said Dr. Smits, who estimated the average amount of build-up time saved by the new protocol to be about 6 months. “And adherence rates were better than what we typically see with conventional immunotherapy,” he said. Patient adherence rates were 95.3%, 90.5%, and 79.7% at 3, 6, and 12 months, respectively, compared with approximately 50% adherence associated with conventional immunotherapy.

“Contrary to what everyone thinks, there is a way to do this safely,” said Dr. Smits, who uses the rapid protocol in approximately 75% of the adults and children he treats.

The bottom line, he concluded, is that the rapid protocol “costs less, incidents of illness are reduced, and people see results more quickly.”

BOSTON — A new immunotherapy protocol can substantially and safely reduce the amount of time it takes for children with allergies to experience relief from their symptoms, compared with conventional allergen vaccination, reported William Smits, M.D.

In addition to saving time and money, the compressed vaccination schedule appears to improve patient compliance, Dr. Smits said in a presentation at the annual meeting of the American College of Allergy, Asthma, and Immunology.

A type of “rush” regimen, this is a novel protocol that jump-starts allergy immunotherapy with a series of in-office vaccinations given over a 2.5-hour period. Unlike other rapid desensitization efforts—many of which have been shown to evoke serious systemic reactions in a large proportion of patients—this protocol includes 3 days of premedication with corticosteroids and H1 antagonists to minimize the potential for adverse reactions.

“Previous studies [of rapid vaccination regimens] have shown reaction rates of anywhere from 30% to 40%, which is the major concern with rush protocols,” said. Dr. Smits of Indiana University, Fort Wayne. “With our approach, we've found a rate close to that of conventional immunotherapy.”

Dr. Smits and his colleagues tested the rapid vaccination protocol in 148 children aged 1–18 years diagnosed with mild to severe asthma (118), allergic rhinitis (143), and/or chronic sinusitis (23). All of the children were pretreated for 3 days with prednisone or prednisolone and second-generation antihistamines, including cetirizine (Zyrtec), loratadine (Claritin), and fexofenadine (Allegra). On the vaccination day, the children received eight injections given at 15-minute intervals. The doses increased from an initial 1:1,000,000 dilution to a final 1:1,000 dilution.

In addition to premedication, a key to the success of this treatment is lowering the target end point dosage, said Dr. Smits. The harmful reactions reported in earlier studies generally occurred at the end of the rapid treatment phase, when the patient received a final high dose to be maintained for the duration of the therapy. “We stopped just before that time and gave the patients the last injections over a 2-month period.”

The investigators monitored the children for systemic reactions. Of the full cohort, eight patients—seven of whom were asthma patients on inhaled corticosteroids—experienced a systemic reaction following the vaccination. None of the eight patients experienced true anaphylaxis. The patients who had reactions were treated with one or a combination of the following: nebulized breathing treatment with albuterol, two sprays in each nostril of azelastine (Astelin), and diphenhydramine (Benadryl), either orally or intramuscularly. None of the patients requiring treatment needed subcutaneous epinephrine or further treatment for recurrent symptoms. Also, none needed hospitalization.

Following the rapid protocol, all of the patients in the study continued with a conventional allergen immunotherapy regimen to reach their maintenance dose.

“Overall, the patients reached efficacious dosages almost immediately,” said Dr. Smits, who estimated the average amount of build-up time saved by the new protocol to be about 6 months. “And adherence rates were better than what we typically see with conventional immunotherapy,” he said. Patient adherence rates were 95.3%, 90.5%, and 79.7% at 3, 6, and 12 months, respectively, compared with approximately 50% adherence associated with conventional immunotherapy.

“Contrary to what everyone thinks, there is a way to do this safely,” said Dr. Smits, who uses the rapid protocol in approximately 75% of the adults and children he treats.

The bottom line, he concluded, is that the rapid protocol “costs less, incidents of illness are reduced, and people see results more quickly.”

BOSTON — Pimecrolimus cream for atopic dermatitis leads to itch-free kids and happier parents, a study has shown.

In a randomized, double-blind trial enrolling 275 children from 3 months to 11 years old with moderate to severe atopic dermatitis, the parents of those children treated with a 1% strength of the topical immunomodulator pimecrolimus (Elidel) reported substantially improved quality of life, compared with parents of children treated with topical corticosteroids, Jennifer Sung, M.D., said at the annual meeting of the American College of Allergy, Asthma, and Immunology.

All of the parents whose children were enrolled in the multicenter vehicle-controlled investigation completed a patient gender-specific version of the Parent's Index of Quality of Life in Atopic Dermatitis (PIQoL-AD) at baseline, week 12, and at the end of the study at week 24.

The questionnaire, which is the only survey specifically designed for parents of children aged 3 months to 12 years, contains 28 true/not true items and has been shown to have good psychometric properties, said Dr. Sung, a clinical investigator at Novartis Pharmaceuticals, East Hanover, N.J., the manufacturer of Elidel.

The questionnaire includes items addressing parents' concerns about their children's appearance, the effort required to prevent itching and provide appropriate care, and the stress of worrying about the condition and the effect of treatments.

Responses are numbered and summed. Scores range from 0 to 28, with higher scores indicating a poorer quality of life. The investigators used an analysis of covariance model to compare changes in scores from baseline to the end of the study, controlling for treatment, center, and baseline score.

At baseline, all mean demographic and clinical characteristics between the 183 children who received the pimecrolimus-based therapy and the 92 who received corticosteroid-based treatment were the same.

In both groups, atopic dermatitis affected at least 5% of each subject's total body surface area.

All of the children in the study received emollients for dry skin and either pimecrolimus cream 1% or corticosteroid twice daily at any sign of active atopic dermatitis.

Corticosteroid subjects who experienced severe flares were given a midpotency topical corticosteroid for evening use until complete resolution, for a maximum of 3 weeks.

The baseline PIQoL-AD score for parents of children in the pimecrolimus and corticosteroid groups, respectively, was 8.4 and 9.3.

At 24 weeks, the respective scores were 4.9 and 6.3, representing an improvement from baseline of 37.6% for the pimecrolimus group and 26.8% for the corticosteroid group, Dr. Sung reported.

“A number of studies have already shown [pimecrolimus] to be a safe, effective, nonsteroidal option for these kids. This study tells us that there's a beneficial effect on their parents' quality of life also,” Dr. Sung said. “Parents are especially relieved not to have to worry about corticosteroid-related side effects.”

BOSTON — Pimecrolimus cream for atopic dermatitis leads to itch-free kids and happier parents, a study has shown.

In a randomized, double-blind trial enrolling 275 children from 3 months to 11 years old with moderate to severe atopic dermatitis, the parents of those children treated with a 1% strength of the topical immunomodulator pimecrolimus (Elidel) reported substantially improved quality of life, compared with parents of children treated with topical corticosteroids, Jennifer Sung, M.D., said at the annual meeting of the American College of Allergy, Asthma, and Immunology.

All of the parents whose children were enrolled in the multicenter vehicle-controlled investigation completed a patient gender-specific version of the Parent's Index of Quality of Life in Atopic Dermatitis (PIQoL-AD) at baseline, week 12, and at the end of the study at week 24.

The questionnaire, which is the only survey specifically designed for parents of children aged 3 months to 12 years, contains 28 true/not true items and has been shown to have good psychometric properties, said Dr. Sung, a clinical investigator at Novartis Pharmaceuticals, East Hanover, N.J., the manufacturer of Elidel.

The questionnaire includes items addressing parents' concerns about their children's appearance, the effort required to prevent itching and provide appropriate care, and the stress of worrying about the condition and the effect of treatments.

Responses are numbered and summed. Scores range from 0 to 28, with higher scores indicating a poorer quality of life. The investigators used an analysis of covariance model to compare changes in scores from baseline to the end of the study, controlling for treatment, center, and baseline score.

At baseline, all mean demographic and clinical characteristics between the 183 children who received the pimecrolimus-based therapy and the 92 who received corticosteroid-based treatment were the same.

In both groups, atopic dermatitis affected at least 5% of each subject's total body surface area.

All of the children in the study received emollients for dry skin and either pimecrolimus cream 1% or corticosteroid twice daily at any sign of active atopic dermatitis.

Corticosteroid subjects who experienced severe flares were given a midpotency topical corticosteroid for evening use until complete resolution, for a maximum of 3 weeks.

The baseline PIQoL-AD score for parents of children in the pimecrolimus and corticosteroid groups, respectively, was 8.4 and 9.3.

At 24 weeks, the respective scores were 4.9 and 6.3, representing an improvement from baseline of 37.6% for the pimecrolimus group and 26.8% for the corticosteroid group, Dr. Sung reported.

“A number of studies have already shown [pimecrolimus] to be a safe, effective, nonsteroidal option for these kids. This study tells us that there's a beneficial effect on their parents' quality of life also,” Dr. Sung said. “Parents are especially relieved not to have to worry about corticosteroid-related side effects.”

BOSTON — Pimecrolimus cream for atopic dermatitis leads to itch-free kids and happier parents, a study has shown.

In a randomized, double-blind trial enrolling 275 children from 3 months to 11 years old with moderate to severe atopic dermatitis, the parents of those children treated with a 1% strength of the topical immunomodulator pimecrolimus (Elidel) reported substantially improved quality of life, compared with parents of children treated with topical corticosteroids, Jennifer Sung, M.D., said at the annual meeting of the American College of Allergy, Asthma, and Immunology.

All of the parents whose children were enrolled in the multicenter vehicle-controlled investigation completed a patient gender-specific version of the Parent's Index of Quality of Life in Atopic Dermatitis (PIQoL-AD) at baseline, week 12, and at the end of the study at week 24.

The questionnaire, which is the only survey specifically designed for parents of children aged 3 months to 12 years, contains 28 true/not true items and has been shown to have good psychometric properties, said Dr. Sung, a clinical investigator at Novartis Pharmaceuticals, East Hanover, N.J., the manufacturer of Elidel.

The questionnaire includes items addressing parents' concerns about their children's appearance, the effort required to prevent itching and provide appropriate care, and the stress of worrying about the condition and the effect of treatments.

Responses are numbered and summed. Scores range from 0 to 28, with higher scores indicating a poorer quality of life. The investigators used an analysis of covariance model to compare changes in scores from baseline to the end of the study, controlling for treatment, center, and baseline score.

At baseline, all mean demographic and clinical characteristics between the 183 children who received the pimecrolimus-based therapy and the 92 who received corticosteroid-based treatment were the same.

In both groups, atopic dermatitis affected at least 5% of each subject's total body surface area.

All of the children in the study received emollients for dry skin and either pimecrolimus cream 1% or corticosteroid twice daily at any sign of active atopic dermatitis.

Corticosteroid subjects who experienced severe flares were given a midpotency topical corticosteroid for evening use until complete resolution, for a maximum of 3 weeks.

The baseline PIQoL-AD score for parents of children in the pimecrolimus and corticosteroid groups, respectively, was 8.4 and 9.3.

At 24 weeks, the respective scores were 4.9 and 6.3, representing an improvement from baseline of 37.6% for the pimecrolimus group and 26.8% for the corticosteroid group, Dr. Sung reported.

“A number of studies have already shown [pimecrolimus] to be a safe, effective, nonsteroidal option for these kids. This study tells us that there's a beneficial effect on their parents' quality of life also,” Dr. Sung said. “Parents are especially relieved not to have to worry about corticosteroid-related side effects.”

BOSTON — Daptomycin may be an effective option for difficult-to-treat gram-positive bloodstream infections, John Segreti, M.D., reported at the annual meeting of the Infectious Diseases Society of America.

In a retrospective study, 31 patients were treated with daptomycin (Cubicin) for bacteremia and/or infective endocarditis at two medical centers. Of these, 24 achieved clinical resolution of the life-threatening conditions, including all 11 patients with methicillin-resistant Staphylococcus aureus (MRSA) infection, 6 of 7 patients with methicillin-susceptible Staphylococcus aureus (MSSA) infection, and 5 of 11 patients with vancomycin-resistant enterococci (VRE).

These findings are particularly important in light of the increasing prevalence of serious infections involving gram-positive cocci and the increasing concern about antimicrobial resistance, especially in hospital intensive care units, said Dr. Segreti of Rush Medical College in Chicago. “Unfortunately, the gold standard for many serious gram-positive infections—vancomycin—is threatened. Its increased use for S. aureus infections leads to an increased risk for recurrent bacteremia and mortality.

“This may be a consequence of inadequate bactericidal activity of vancomycin, especially when treating some strains of S. aureus.” Daptomycin is a more rapidly bactericidal agent than vancomycin, “which is critical when treating bloodstream infections, especially in eradicating the vegetative mass associated with infective endocarditis,” he explained.

Between November 2003 and July 2004, 31 patients at Rush University Medical Center in Chicago and Fountain Valley (Calif.) Regional Hospital received 6 mg/kg daptomycin daily or every other day for bloodstream infections. Overall, 22 of the patients had been diagnosed with bacteremia only, 8 had culture-positive infective endocarditis, and 1 had culture-negative endocarditis. In 24 cases, the patients had received prior antibiotic therapy for their infections, including vancomycin in 18 patients and linezolid in 4, but they required a change because of limited success of the initial therapy or intolerable adverse effects.

The pathogens identified in the study population included MRSA in 11 patients, VRE in 11, MSSA in 7, and coagulase-negative staphylococcus in 1; 1 other patient had an infection of unknown etiology. An analysis of the patient records showed that daptomycin was effective for 18 of the 22 bacteremic patients without endocarditis and for 6 of the 9 patients with infective endocarditis. The seven patients for whom treatment was not successful died during hospitalization.

In general, daptomycin was safe and well tolerated, even for extended durations of therapy, Dr. Segreti said.

Currently, daptomycin is approved for the treatment of complicated skin and skin structure infections. A clinical trial is underway to assess the efficacy of higher dosages of the drug as well as the optimal dosage and duration of treatment and the long-term efficacy for these infections, he said.

The results of this study suggest that daptomycin “may provide an additional option for the treatment of bloodstream infections, not only for patients who fail prior antimicrobial therapy but also as initial therapy for patients at risk for drug-resistant gram-positive infections,” he concluded.

Dr. Segreti and his colleagues in this investigation reported no financial interest in the manufacturer of daptomycin, Cubist Pharmaceuticals Inc.

BOSTON — Daptomycin may be an effective option for difficult-to-treat gram-positive bloodstream infections, John Segreti, M.D., reported at the annual meeting of the Infectious Diseases Society of America.

In a retrospective study, 31 patients were treated with daptomycin (Cubicin) for bacteremia and/or infective endocarditis at two medical centers. Of these, 24 achieved clinical resolution of the life-threatening conditions, including all 11 patients with methicillin-resistant Staphylococcus aureus (MRSA) infection, 6 of 7 patients with methicillin-susceptible Staphylococcus aureus (MSSA) infection, and 5 of 11 patients with vancomycin-resistant enterococci (VRE).

These findings are particularly important in light of the increasing prevalence of serious infections involving gram-positive cocci and the increasing concern about antimicrobial resistance, especially in hospital intensive care units, said Dr. Segreti of Rush Medical College in Chicago. “Unfortunately, the gold standard for many serious gram-positive infections—vancomycin—is threatened. Its increased use for S. aureus infections leads to an increased risk for recurrent bacteremia and mortality.

“This may be a consequence of inadequate bactericidal activity of vancomycin, especially when treating some strains of S. aureus.” Daptomycin is a more rapidly bactericidal agent than vancomycin, “which is critical when treating bloodstream infections, especially in eradicating the vegetative mass associated with infective endocarditis,” he explained.

Between November 2003 and July 2004, 31 patients at Rush University Medical Center in Chicago and Fountain Valley (Calif.) Regional Hospital received 6 mg/kg daptomycin daily or every other day for bloodstream infections. Overall, 22 of the patients had been diagnosed with bacteremia only, 8 had culture-positive infective endocarditis, and 1 had culture-negative endocarditis. In 24 cases, the patients had received prior antibiotic therapy for their infections, including vancomycin in 18 patients and linezolid in 4, but they required a change because of limited success of the initial therapy or intolerable adverse effects.

The pathogens identified in the study population included MRSA in 11 patients, VRE in 11, MSSA in 7, and coagulase-negative staphylococcus in 1; 1 other patient had an infection of unknown etiology. An analysis of the patient records showed that daptomycin was effective for 18 of the 22 bacteremic patients without endocarditis and for 6 of the 9 patients with infective endocarditis. The seven patients for whom treatment was not successful died during hospitalization.

In general, daptomycin was safe and well tolerated, even for extended durations of therapy, Dr. Segreti said.

Currently, daptomycin is approved for the treatment of complicated skin and skin structure infections. A clinical trial is underway to assess the efficacy of higher dosages of the drug as well as the optimal dosage and duration of treatment and the long-term efficacy for these infections, he said.

The results of this study suggest that daptomycin “may provide an additional option for the treatment of bloodstream infections, not only for patients who fail prior antimicrobial therapy but also as initial therapy for patients at risk for drug-resistant gram-positive infections,” he concluded.

Dr. Segreti and his colleagues in this investigation reported no financial interest in the manufacturer of daptomycin, Cubist Pharmaceuticals Inc.

BOSTON — Daptomycin may be an effective option for difficult-to-treat gram-positive bloodstream infections, John Segreti, M.D., reported at the annual meeting of the Infectious Diseases Society of America.

In a retrospective study, 31 patients were treated with daptomycin (Cubicin) for bacteremia and/or infective endocarditis at two medical centers. Of these, 24 achieved clinical resolution of the life-threatening conditions, including all 11 patients with methicillin-resistant Staphylococcus aureus (MRSA) infection, 6 of 7 patients with methicillin-susceptible Staphylococcus aureus (MSSA) infection, and 5 of 11 patients with vancomycin-resistant enterococci (VRE).

These findings are particularly important in light of the increasing prevalence of serious infections involving gram-positive cocci and the increasing concern about antimicrobial resistance, especially in hospital intensive care units, said Dr. Segreti of Rush Medical College in Chicago. “Unfortunately, the gold standard for many serious gram-positive infections—vancomycin—is threatened. Its increased use for S. aureus infections leads to an increased risk for recurrent bacteremia and mortality.

“This may be a consequence of inadequate bactericidal activity of vancomycin, especially when treating some strains of S. aureus.” Daptomycin is a more rapidly bactericidal agent than vancomycin, “which is critical when treating bloodstream infections, especially in eradicating the vegetative mass associated with infective endocarditis,” he explained.

Between November 2003 and July 2004, 31 patients at Rush University Medical Center in Chicago and Fountain Valley (Calif.) Regional Hospital received 6 mg/kg daptomycin daily or every other day for bloodstream infections. Overall, 22 of the patients had been diagnosed with bacteremia only, 8 had culture-positive infective endocarditis, and 1 had culture-negative endocarditis. In 24 cases, the patients had received prior antibiotic therapy for their infections, including vancomycin in 18 patients and linezolid in 4, but they required a change because of limited success of the initial therapy or intolerable adverse effects.

The pathogens identified in the study population included MRSA in 11 patients, VRE in 11, MSSA in 7, and coagulase-negative staphylococcus in 1; 1 other patient had an infection of unknown etiology. An analysis of the patient records showed that daptomycin was effective for 18 of the 22 bacteremic patients without endocarditis and for 6 of the 9 patients with infective endocarditis. The seven patients for whom treatment was not successful died during hospitalization.

In general, daptomycin was safe and well tolerated, even for extended durations of therapy, Dr. Segreti said.

Currently, daptomycin is approved for the treatment of complicated skin and skin structure infections. A clinical trial is underway to assess the efficacy of higher dosages of the drug as well as the optimal dosage and duration of treatment and the long-term efficacy for these infections, he said.

The results of this study suggest that daptomycin “may provide an additional option for the treatment of bloodstream infections, not only for patients who fail prior antimicrobial therapy but also as initial therapy for patients at risk for drug-resistant gram-positive infections,” he concluded.

Dr. Segreti and his colleagues in this investigation reported no financial interest in the manufacturer of daptomycin, Cubist Pharmaceuticals Inc.

BOSTON — Daptomycin may effectively treat gram-positive bone and joint infections and may be less likely than standard antimicrobials to cause drug resistance as a consequence of long-term therapy, Michael S. Finney, M.D., said at the annual meeting of the Infectious Diseases Society of America.

In a retrospective medical record study, daptomycin (Cubicin) successfully eradicated infections in 9 of 10 patients diagnosed with gram-positive osteomyelitis, septic joint infection, septic arthritis infection, and/or bacteremia. The patients were treated at two medical centers between November 2003 and April 2004, Dr. Finney said.

“Eight of the patients were infected with methicillin-resistant Staphylococcus aureus [MRSA], and enterococcus and streptococcus were isolated from two patients,” said Dr. Finney of Fountain Valley (Calif.) Regional Hospital, where six of the patients were treated. The remaining four patients were treated at Rush University Medical Center in Chicago.

Daptomycin was effective in treating seven of eight MRSA-infected patients and both of the non-MRSA patients. Of the 10 patients, 4 had a diagnosis of osteomyelitis only and 6 had some combination of osteomyelitis, septic joint infection, septic arthritis infection, and/or bacteremia.

Nine had undergone prior unsuccessful treatment with one or more antibiotics: Eight received vancomycin, three received linezolid, and three received quinupristin/dalfopristin. Among the patients successfully treated with daptomycin were seven who had failed or could not tolerate vancomycin, which is often a first-line treatment for osteomyelitis.

The daptomycin treatment duration averaged 30 days, ranging from 21 to 42 days. “In general, the therapy was well tolerated, even for the longer treatment durations,” Dr. Finney said. No patients had severe adverse effects; one stopped therapy at 3 weeks because of nausea, and another had a mild elevation in CPK levels but not enough to warrant discontinuing therapy.

The one patient in the case series whose infection was not resolved had a relapse during daptomycin therapy, “possibly as a result of underdosing,” Dr. Finney said. Because of renal insufficiency, the septic arthritis patient was started on alternate-day vs. daily dosing and was not adjusted to daily dosing once renal function improved. During the course of therapy, the patient developed an epidural abscess from MRSA with reduced susceptibility to daptomycin.

Bone and joint infections are notoriously difficult to resolve, require prolonged treatment, and are associated with a high risk of recurrence. “Effective treatment requires the antibiotic to penetrate the site of infection at an adequate concentration to effectively kill the causative pathogen,” Dr. Finney noted. Because gram-positive organisms, particularly S. aureus, are the predominant cause of these infections, the possibility of drug resistance further complicates treatment.

Vancomycin is a standard treatment for bone and joint infections, but it is not highly active against some gram-positive organisms, including S. aureus. In fact, Dr. Finney said, “studies have shown an increased risk of recurrence with vancomycin treatment for S. aureus osteomyelitis.” It is possible that bacteriostatic antimicrobials such as vancomycin, which merely inhibit the growth of bacteria, have a higher risk of causing drug resistance during therapy than do bactericidal agents such as daptomycin, he said.

Currently, daptomycin is approved for the treatment of complicated skin and skin structure infections. The findings from this case series suggest that further studies are warranted to determine the agent's role in treating gram-positive bone and joint infections as well as to determine optimal dosing, “to improve clinical outcomes and to reduce the risk of resistance,” Dr. Finney said.

He and his colleagues in this investigation reported that they have no financial interest in the manufacturer of daptomycin, Cubist Pharmaceuticals Inc.

BOSTON — Daptomycin may effectively treat gram-positive bone and joint infections and may be less likely than standard antimicrobials to cause drug resistance as a consequence of long-term therapy, Michael S. Finney, M.D., said at the annual meeting of the Infectious Diseases Society of America.

In a retrospective medical record study, daptomycin (Cubicin) successfully eradicated infections in 9 of 10 patients diagnosed with gram-positive osteomyelitis, septic joint infection, septic arthritis infection, and/or bacteremia. The patients were treated at two medical centers between November 2003 and April 2004, Dr. Finney said.

“Eight of the patients were infected with methicillin-resistant Staphylococcus aureus [MRSA], and enterococcus and streptococcus were isolated from two patients,” said Dr. Finney of Fountain Valley (Calif.) Regional Hospital, where six of the patients were treated. The remaining four patients were treated at Rush University Medical Center in Chicago.

Daptomycin was effective in treating seven of eight MRSA-infected patients and both of the non-MRSA patients. Of the 10 patients, 4 had a diagnosis of osteomyelitis only and 6 had some combination of osteomyelitis, septic joint infection, septic arthritis infection, and/or bacteremia.

Nine had undergone prior unsuccessful treatment with one or more antibiotics: Eight received vancomycin, three received linezolid, and three received quinupristin/dalfopristin. Among the patients successfully treated with daptomycin were seven who had failed or could not tolerate vancomycin, which is often a first-line treatment for osteomyelitis.

The daptomycin treatment duration averaged 30 days, ranging from 21 to 42 days. “In general, the therapy was well tolerated, even for the longer treatment durations,” Dr. Finney said. No patients had severe adverse effects; one stopped therapy at 3 weeks because of nausea, and another had a mild elevation in CPK levels but not enough to warrant discontinuing therapy.

The one patient in the case series whose infection was not resolved had a relapse during daptomycin therapy, “possibly as a result of underdosing,” Dr. Finney said. Because of renal insufficiency, the septic arthritis patient was started on alternate-day vs. daily dosing and was not adjusted to daily dosing once renal function improved. During the course of therapy, the patient developed an epidural abscess from MRSA with reduced susceptibility to daptomycin.

Bone and joint infections are notoriously difficult to resolve, require prolonged treatment, and are associated with a high risk of recurrence. “Effective treatment requires the antibiotic to penetrate the site of infection at an adequate concentration to effectively kill the causative pathogen,” Dr. Finney noted. Because gram-positive organisms, particularly S. aureus, are the predominant cause of these infections, the possibility of drug resistance further complicates treatment.

Vancomycin is a standard treatment for bone and joint infections, but it is not highly active against some gram-positive organisms, including S. aureus. In fact, Dr. Finney said, “studies have shown an increased risk of recurrence with vancomycin treatment for S. aureus osteomyelitis.” It is possible that bacteriostatic antimicrobials such as vancomycin, which merely inhibit the growth of bacteria, have a higher risk of causing drug resistance during therapy than do bactericidal agents such as daptomycin, he said.

Currently, daptomycin is approved for the treatment of complicated skin and skin structure infections. The findings from this case series suggest that further studies are warranted to determine the agent's role in treating gram-positive bone and joint infections as well as to determine optimal dosing, “to improve clinical outcomes and to reduce the risk of resistance,” Dr. Finney said.

He and his colleagues in this investigation reported that they have no financial interest in the manufacturer of daptomycin, Cubist Pharmaceuticals Inc.

BOSTON — Daptomycin may effectively treat gram-positive bone and joint infections and may be less likely than standard antimicrobials to cause drug resistance as a consequence of long-term therapy, Michael S. Finney, M.D., said at the annual meeting of the Infectious Diseases Society of America.

In a retrospective medical record study, daptomycin (Cubicin) successfully eradicated infections in 9 of 10 patients diagnosed with gram-positive osteomyelitis, septic joint infection, septic arthritis infection, and/or bacteremia. The patients were treated at two medical centers between November 2003 and April 2004, Dr. Finney said.

“Eight of the patients were infected with methicillin-resistant Staphylococcus aureus [MRSA], and enterococcus and streptococcus were isolated from two patients,” said Dr. Finney of Fountain Valley (Calif.) Regional Hospital, where six of the patients were treated. The remaining four patients were treated at Rush University Medical Center in Chicago.

Daptomycin was effective in treating seven of eight MRSA-infected patients and both of the non-MRSA patients. Of the 10 patients, 4 had a diagnosis of osteomyelitis only and 6 had some combination of osteomyelitis, septic joint infection, septic arthritis infection, and/or bacteremia.

Nine had undergone prior unsuccessful treatment with one or more antibiotics: Eight received vancomycin, three received linezolid, and three received quinupristin/dalfopristin. Among the patients successfully treated with daptomycin were seven who had failed or could not tolerate vancomycin, which is often a first-line treatment for osteomyelitis.

The daptomycin treatment duration averaged 30 days, ranging from 21 to 42 days. “In general, the therapy was well tolerated, even for the longer treatment durations,” Dr. Finney said. No patients had severe adverse effects; one stopped therapy at 3 weeks because of nausea, and another had a mild elevation in CPK levels but not enough to warrant discontinuing therapy.

The one patient in the case series whose infection was not resolved had a relapse during daptomycin therapy, “possibly as a result of underdosing,” Dr. Finney said. Because of renal insufficiency, the septic arthritis patient was started on alternate-day vs. daily dosing and was not adjusted to daily dosing once renal function improved. During the course of therapy, the patient developed an epidural abscess from MRSA with reduced susceptibility to daptomycin.

Bone and joint infections are notoriously difficult to resolve, require prolonged treatment, and are associated with a high risk of recurrence. “Effective treatment requires the antibiotic to penetrate the site of infection at an adequate concentration to effectively kill the causative pathogen,” Dr. Finney noted. Because gram-positive organisms, particularly S. aureus, are the predominant cause of these infections, the possibility of drug resistance further complicates treatment.

Vancomycin is a standard treatment for bone and joint infections, but it is not highly active against some gram-positive organisms, including S. aureus. In fact, Dr. Finney said, “studies have shown an increased risk of recurrence with vancomycin treatment for S. aureus osteomyelitis.” It is possible that bacteriostatic antimicrobials such as vancomycin, which merely inhibit the growth of bacteria, have a higher risk of causing drug resistance during therapy than do bactericidal agents such as daptomycin, he said.

Currently, daptomycin is approved for the treatment of complicated skin and skin structure infections. The findings from this case series suggest that further studies are warranted to determine the agent's role in treating gram-positive bone and joint infections as well as to determine optimal dosing, “to improve clinical outcomes and to reduce the risk of resistance,” Dr. Finney said.

He and his colleagues in this investigation reported that they have no financial interest in the manufacturer of daptomycin, Cubist Pharmaceuticals Inc.

ORLANDO, FLA.–Red-tinted contact lenses provided rapid, safe, nonpharmacologic relief to most patients with acute migraine pain in a recent study.

The red lenses filter specific wavelengths of light that may overstimulate retinal receptors in some migraine sufferers, resulting in the characteristic headache pain that is exacerbated by light exposure, Richard L. Garrison, M.D., reported in a poster presentation at the annual meeting of the North American Primary Care Research Group.

Dr. Garrison and colleague Kathleen Saathoff of San Jacinto Methodist Hospital in Baytown, Texas, presented the results of a case series of 33 patients with a history of photophobic headache who were offered bilateral insertion of special-order red-tinted contact lenses during acute pain attacks. The light-filtering lenses brought immediate pain relief to 31 of the patients.

“With the exception of two subjects–who, in addition to migraine, had diagnoses of photophobic muscle contraction headache and pseudotumor cerebri, respectively–all of the other patients [in the study] had relief within minutes of inserting the lenses, and pain relief was maximal within 90 minutes,” Dr. Garrison reported.

All but 5 of the 31 migraine-only patients had total pain relief, and the 5 who did not get full relief had significantly reduced final pain scores of 0.5–1.5 on a 10-point visual analog scale, he said.

To control for a possible placebo effect in future randomized placebo-controlled trials, patients will be treated with contact lenses designed to filter varying wavelengths of light. The lenses them will be colors other than red.

Benefits From Light Filtering

Tinted glasses, goggles, and, more recently, contact lenses have been used to relieve pain and decrease photophobia in patients with various ophthalmologic conditions.

Because photophobia is so prominent in migraine, Dr. Garrison and Ms. Saathoff, who began investigating tinted contact lenses with patients with cone-rod dystrophy a decade ago in her work with low-vision patients, hypothesized that the light-filtering treatment might benefit migraine sufferers as well.

The inherited progressive disorder cone rod dystrophy causes deterioration of the photoreceptor cells and often results in blindness.

Ideal Tinting Uncertain

Tinted contact lenses were chosen over ordinary glasses with tinted lenses because the latter allow too much glare to reach the retina, both from the side and above, for sufficient filtering. In contrast, therapeutic contact lenses applied directly on the eye provide optimal filtration, Dr. Garrison said.

In the San Jacinto study, the 30 female and 3 male patients recruited for participation had physician diagnoses of migraine. All patients were instructed to present themselves for contact lens insertion during episodes of acute pain.

The special-order contact lenses were dark red and filtered 80% of the light.

“The sample color was the result of trial and error from previous patients, predominantly with cone-rod dystrophy, who were extremely photophobic and may have experienced blepharospasms,” a dystonia that results in uncontrollable contraction of the muscle that causes the eye to blink, Dr. Garrison noted.

No assurance exists, he continued, “that the tint chosen for this series is optimal. The choice of tint was derived solely from experience treating a different disease. Other tints that filter different wavelengths of light may prove to be as or more effective.”

Rapid Onset of Relief

Of the 26 patients reporting total relief of all migraine pain, 5 reported complete relief within 10 seconds of the insertion of the second lens. For most patients, pain relief began within 5 minutes, and approximately 50% relief was obtained within 20 minutes, Dr. Garrison said.

It is unlikely that the migraine relief observed was a consequence of a decreased intensity of light in general. If it were, any darkening strategy would work just as well, and that's not true, he explained. “People with migraines do seek darkness for partial relief from headache. But even total darkness only diminishes, does not ablate, headache.”

In fact, it may be that by blocking certain light wavelengths and admitting others is the key. “Whereas certain tinted filters block stimulation of migraine pain, the admission to the retina of filtered light may actually inhibit migraine,” Dr. Garrison hypothesized.

Of Retinas and Wavelengths

The human retina uses three cone types, with three different absorption spectra, to resolve the wavelength composition of light. These three types of cones, L-, M-, and S-cones, represent classes of photoreceptors that are primarily sensitive to long-wavelength light (L), medium wavelength light (M), and short wavelength light (S) within the visible spectrum.

The lenses used in this case series effectively blocked 90% of wavelengths of 600 nm or less and admitted 90% of wavelengths of 700 nm or more, effectively excluding stimulation of M- and S-cones and allowing selective stimulation of L-cones only, “which may account in some way for the mechanism of action,” he said.

These questions as well as others related to the comparative efficacy of other colors of lenses and other ways of selectively exposing the retina to certain wavelengths will be explored in further randomized controlled trials, Dr. Garrison stated.

ORLANDO, FLA.–Red-tinted contact lenses provided rapid, safe, nonpharmacologic relief to most patients with acute migraine pain in a recent study.

The red lenses filter specific wavelengths of light that may overstimulate retinal receptors in some migraine sufferers, resulting in the characteristic headache pain that is exacerbated by light exposure, Richard L. Garrison, M.D., reported in a poster presentation at the annual meeting of the North American Primary Care Research Group.

Dr. Garrison and colleague Kathleen Saathoff of San Jacinto Methodist Hospital in Baytown, Texas, presented the results of a case series of 33 patients with a history of photophobic headache who were offered bilateral insertion of special-order red-tinted contact lenses during acute pain attacks. The light-filtering lenses brought immediate pain relief to 31 of the patients.

“With the exception of two subjects–who, in addition to migraine, had diagnoses of photophobic muscle contraction headache and pseudotumor cerebri, respectively–all of the other patients [in the study] had relief within minutes of inserting the lenses, and pain relief was maximal within 90 minutes,” Dr. Garrison reported.

All but 5 of the 31 migraine-only patients had total pain relief, and the 5 who did not get full relief had significantly reduced final pain scores of 0.5–1.5 on a 10-point visual analog scale, he said.

To control for a possible placebo effect in future randomized placebo-controlled trials, patients will be treated with contact lenses designed to filter varying wavelengths of light. The lenses them will be colors other than red.

Benefits From Light Filtering

Tinted glasses, goggles, and, more recently, contact lenses have been used to relieve pain and decrease photophobia in patients with various ophthalmologic conditions.

Because photophobia is so prominent in migraine, Dr. Garrison and Ms. Saathoff, who began investigating tinted contact lenses with patients with cone-rod dystrophy a decade ago in her work with low-vision patients, hypothesized that the light-filtering treatment might benefit migraine sufferers as well.

The inherited progressive disorder cone rod dystrophy causes deterioration of the photoreceptor cells and often results in blindness.

Ideal Tinting Uncertain

Tinted contact lenses were chosen over ordinary glasses with tinted lenses because the latter allow too much glare to reach the retina, both from the side and above, for sufficient filtering. In contrast, therapeutic contact lenses applied directly on the eye provide optimal filtration, Dr. Garrison said.

In the San Jacinto study, the 30 female and 3 male patients recruited for participation had physician diagnoses of migraine. All patients were instructed to present themselves for contact lens insertion during episodes of acute pain.

The special-order contact lenses were dark red and filtered 80% of the light.

“The sample color was the result of trial and error from previous patients, predominantly with cone-rod dystrophy, who were extremely photophobic and may have experienced blepharospasms,” a dystonia that results in uncontrollable contraction of the muscle that causes the eye to blink, Dr. Garrison noted.

No assurance exists, he continued, “that the tint chosen for this series is optimal. The choice of tint was derived solely from experience treating a different disease. Other tints that filter different wavelengths of light may prove to be as or more effective.”

Rapid Onset of Relief

Of the 26 patients reporting total relief of all migraine pain, 5 reported complete relief within 10 seconds of the insertion of the second lens. For most patients, pain relief began within 5 minutes, and approximately 50% relief was obtained within 20 minutes, Dr. Garrison said.

It is unlikely that the migraine relief observed was a consequence of a decreased intensity of light in general. If it were, any darkening strategy would work just as well, and that's not true, he explained. “People with migraines do seek darkness for partial relief from headache. But even total darkness only diminishes, does not ablate, headache.”

In fact, it may be that by blocking certain light wavelengths and admitting others is the key. “Whereas certain tinted filters block stimulation of migraine pain, the admission to the retina of filtered light may actually inhibit migraine,” Dr. Garrison hypothesized.

Of Retinas and Wavelengths

The human retina uses three cone types, with three different absorption spectra, to resolve the wavelength composition of light. These three types of cones, L-, M-, and S-cones, represent classes of photoreceptors that are primarily sensitive to long-wavelength light (L), medium wavelength light (M), and short wavelength light (S) within the visible spectrum.

The lenses used in this case series effectively blocked 90% of wavelengths of 600 nm or less and admitted 90% of wavelengths of 700 nm or more, effectively excluding stimulation of M- and S-cones and allowing selective stimulation of L-cones only, “which may account in some way for the mechanism of action,” he said.

These questions as well as others related to the comparative efficacy of other colors of lenses and other ways of selectively exposing the retina to certain wavelengths will be explored in further randomized controlled trials, Dr. Garrison stated.

ORLANDO, FLA.–Red-tinted contact lenses provided rapid, safe, nonpharmacologic relief to most patients with acute migraine pain in a recent study.

The red lenses filter specific wavelengths of light that may overstimulate retinal receptors in some migraine sufferers, resulting in the characteristic headache pain that is exacerbated by light exposure, Richard L. Garrison, M.D., reported in a poster presentation at the annual meeting of the North American Primary Care Research Group.

Dr. Garrison and colleague Kathleen Saathoff of San Jacinto Methodist Hospital in Baytown, Texas, presented the results of a case series of 33 patients with a history of photophobic headache who were offered bilateral insertion of special-order red-tinted contact lenses during acute pain attacks. The light-filtering lenses brought immediate pain relief to 31 of the patients.

“With the exception of two subjects–who, in addition to migraine, had diagnoses of photophobic muscle contraction headache and pseudotumor cerebri, respectively–all of the other patients [in the study] had relief within minutes of inserting the lenses, and pain relief was maximal within 90 minutes,” Dr. Garrison reported.

All but 5 of the 31 migraine-only patients had total pain relief, and the 5 who did not get full relief had significantly reduced final pain scores of 0.5–1.5 on a 10-point visual analog scale, he said.

To control for a possible placebo effect in future randomized placebo-controlled trials, patients will be treated with contact lenses designed to filter varying wavelengths of light. The lenses them will be colors other than red.

Benefits From Light Filtering

Tinted glasses, goggles, and, more recently, contact lenses have been used to relieve pain and decrease photophobia in patients with various ophthalmologic conditions.

Because photophobia is so prominent in migraine, Dr. Garrison and Ms. Saathoff, who began investigating tinted contact lenses with patients with cone-rod dystrophy a decade ago in her work with low-vision patients, hypothesized that the light-filtering treatment might benefit migraine sufferers as well.

The inherited progressive disorder cone rod dystrophy causes deterioration of the photoreceptor cells and often results in blindness.

Ideal Tinting Uncertain

Tinted contact lenses were chosen over ordinary glasses with tinted lenses because the latter allow too much glare to reach the retina, both from the side and above, for sufficient filtering. In contrast, therapeutic contact lenses applied directly on the eye provide optimal filtration, Dr. Garrison said.

In the San Jacinto study, the 30 female and 3 male patients recruited for participation had physician diagnoses of migraine. All patients were instructed to present themselves for contact lens insertion during episodes of acute pain.

The special-order contact lenses were dark red and filtered 80% of the light.

“The sample color was the result of trial and error from previous patients, predominantly with cone-rod dystrophy, who were extremely photophobic and may have experienced blepharospasms,” a dystonia that results in uncontrollable contraction of the muscle that causes the eye to blink, Dr. Garrison noted.

No assurance exists, he continued, “that the tint chosen for this series is optimal. The choice of tint was derived solely from experience treating a different disease. Other tints that filter different wavelengths of light may prove to be as or more effective.”

Rapid Onset of Relief

Of the 26 patients reporting total relief of all migraine pain, 5 reported complete relief within 10 seconds of the insertion of the second lens. For most patients, pain relief began within 5 minutes, and approximately 50% relief was obtained within 20 minutes, Dr. Garrison said.

It is unlikely that the migraine relief observed was a consequence of a decreased intensity of light in general. If it were, any darkening strategy would work just as well, and that's not true, he explained. “People with migraines do seek darkness for partial relief from headache. But even total darkness only diminishes, does not ablate, headache.”

In fact, it may be that by blocking certain light wavelengths and admitting others is the key. “Whereas certain tinted filters block stimulation of migraine pain, the admission to the retina of filtered light may actually inhibit migraine,” Dr. Garrison hypothesized.

Of Retinas and Wavelengths

The human retina uses three cone types, with three different absorption spectra, to resolve the wavelength composition of light. These three types of cones, L-, M-, and S-cones, represent classes of photoreceptors that are primarily sensitive to long-wavelength light (L), medium wavelength light (M), and short wavelength light (S) within the visible spectrum.

The lenses used in this case series effectively blocked 90% of wavelengths of 600 nm or less and admitted 90% of wavelengths of 700 nm or more, effectively excluding stimulation of M- and S-cones and allowing selective stimulation of L-cones only, “which may account in some way for the mechanism of action,” he said.

These questions as well as others related to the comparative efficacy of other colors of lenses and other ways of selectively exposing the retina to certain wavelengths will be explored in further randomized controlled trials, Dr. Garrison stated.

BERLIN – School-based preventive interventions can positively affect children's antisocial behavior at the time of transition to middle school, and the gains can be maintained for at least a year after the intervention ends.

Elementary school children identified by their peers and teachers as aggressive have been shown to be at risk for later delinquency and substance use, according to John Lochman, Ph.D., professor and Saxon Chair of Clinical Psychology at the University of Alabama, Tuscaloosa.

Exposing these moderate- to high-risk preadolescents to specific social-cognitive coping techniques in the classroom–while also engaging parents in the preventive intervention–can mitigate the potential for their developing conduct disorders during adolescence, Dr. Lochman reported at the 16th World Congress of the International Association for Child and Adolescent Psychiatry and Allied Professions.

Dr. Lochman and his colleagues evaluated the effects of a school-based aggression-intervention program on two samples of teacher-rated aggressive preadolescent children at the time of transition from elementary to middle school. The Coping Power program is based on an empirical model of risk factors for substance use. It addresses high-risk children's deficits in social competence, self-regulation, school bonding, and positive parental involvement.

The first sample included 183 fourth- and fifth-grade boys from 11 elementary schools, and the second sample comprised 245 fifth-grade boys and girls from 17 elementary schools. The children in both samples were randomly assigned to one of three groups: the Coping Power child component, the full Coping Power program with a combined parent and child component, or a control group.

In the second sample, some classrooms were also randomly assigned to a universal intervention through which the teachers received special training to help foster Coping Power skills in all students within the class.

The child component of the Coping Power program included 33 1-hour group sessions (4–6 boys per group) in an after-school setting over a 15-month period.

The sessions, which were led by a family-school program specialist and a school guidance counselor, focused on behavioral and personal goal setting; awareness of feelings and their associated physiologic arousal; the use of coping self-statements, distraction techniques, and relaxation methods; the development of organizational and study skills, perspective-taking strategies, and social problem-solving skills; attribution retraining; and dealing with peer pressure and neighborhood-based problems.

During the same 15-month period, the parental component of the program included 16 group sessions, with four to six parents/couples per group. The program content was derived from social learning theory-based training programs and included skills for identifying both prosocial and disruptive behavioral targets in their children, rewarding appropriate child behaviors, giving effective instructions, establishing age-appropriate rules and expectations, applying effective consequences to negative child behavior, and establishing ongoing communication through weekly family meetings. Parents also learned to be supportive of the Coping Power skills their children were attaining, and they were introduced to stress management techniques to help them remain calm during difficult interactions with their children.

One year after the end of the intervention period, children in both samples who participated in the Coping Power program had lower rates of self-reported delinquent behavior. Children in the first group had lower parent-rated substance use, and children in the second group had lower self-reported substance use. Both intervention conditions (child-only and combined child and parent) produced positive effects on the children's social competence and self-regulation and the parents' parenting skills, Dr. Lochman reported. “The intervention effects were most apparent for the full Coping Power, with parent and child components,” he said.

The intervention was also associated with teacher-rated behavioral improvements in school during the follow-up year–effects that appeared to be primarily influenced by the child component of the program, Dr. Lochman said. The follow-up measures also indicated that the universal intervention directly affected child substance use ratings and enhanced the Coping Power effects on delinquency. This finding suggests that providing teachers with the appropriate cognitive-behavioral techniques can have an effect on student aggression and antisocial behaviors.

The current study is the first to show that the effects of the intervention are maintained 1 year after the end of the program, and that an intervention that includes a combined parent and child component produces a greater improvement than does the Coping Power child component alone, Dr. Lochman noted.

BERLIN – School-based preventive interventions can positively affect children's antisocial behavior at the time of transition to middle school, and the gains can be maintained for at least a year after the intervention ends.

Elementary school children identified by their peers and teachers as aggressive have been shown to be at risk for later delinquency and substance use, according to John Lochman, Ph.D., professor and Saxon Chair of Clinical Psychology at the University of Alabama, Tuscaloosa.

Exposing these moderate- to high-risk preadolescents to specific social-cognitive coping techniques in the classroom–while also engaging parents in the preventive intervention–can mitigate the potential for their developing conduct disorders during adolescence, Dr. Lochman reported at the 16th World Congress of the International Association for Child and Adolescent Psychiatry and Allied Professions.

Dr. Lochman and his colleagues evaluated the effects of a school-based aggression-intervention program on two samples of teacher-rated aggressive preadolescent children at the time of transition from elementary to middle school. The Coping Power program is based on an empirical model of risk factors for substance use. It addresses high-risk children's deficits in social competence, self-regulation, school bonding, and positive parental involvement.

The first sample included 183 fourth- and fifth-grade boys from 11 elementary schools, and the second sample comprised 245 fifth-grade boys and girls from 17 elementary schools. The children in both samples were randomly assigned to one of three groups: the Coping Power child component, the full Coping Power program with a combined parent and child component, or a control group.

In the second sample, some classrooms were also randomly assigned to a universal intervention through which the teachers received special training to help foster Coping Power skills in all students within the class.

The child component of the Coping Power program included 33 1-hour group sessions (4–6 boys per group) in an after-school setting over a 15-month period.

The sessions, which were led by a family-school program specialist and a school guidance counselor, focused on behavioral and personal goal setting; awareness of feelings and their associated physiologic arousal; the use of coping self-statements, distraction techniques, and relaxation methods; the development of organizational and study skills, perspective-taking strategies, and social problem-solving skills; attribution retraining; and dealing with peer pressure and neighborhood-based problems.

During the same 15-month period, the parental component of the program included 16 group sessions, with four to six parents/couples per group. The program content was derived from social learning theory-based training programs and included skills for identifying both prosocial and disruptive behavioral targets in their children, rewarding appropriate child behaviors, giving effective instructions, establishing age-appropriate rules and expectations, applying effective consequences to negative child behavior, and establishing ongoing communication through weekly family meetings. Parents also learned to be supportive of the Coping Power skills their children were attaining, and they were introduced to stress management techniques to help them remain calm during difficult interactions with their children.

One year after the end of the intervention period, children in both samples who participated in the Coping Power program had lower rates of self-reported delinquent behavior. Children in the first group had lower parent-rated substance use, and children in the second group had lower self-reported substance use. Both intervention conditions (child-only and combined child and parent) produced positive effects on the children's social competence and self-regulation and the parents' parenting skills, Dr. Lochman reported. “The intervention effects were most apparent for the full Coping Power, with parent and child components,” he said.

The intervention was also associated with teacher-rated behavioral improvements in school during the follow-up year–effects that appeared to be primarily influenced by the child component of the program, Dr. Lochman said. The follow-up measures also indicated that the universal intervention directly affected child substance use ratings and enhanced the Coping Power effects on delinquency. This finding suggests that providing teachers with the appropriate cognitive-behavioral techniques can have an effect on student aggression and antisocial behaviors.

The current study is the first to show that the effects of the intervention are maintained 1 year after the end of the program, and that an intervention that includes a combined parent and child component produces a greater improvement than does the Coping Power child component alone, Dr. Lochman noted.

BERLIN – School-based preventive interventions can positively affect children's antisocial behavior at the time of transition to middle school, and the gains can be maintained for at least a year after the intervention ends.

Elementary school children identified by their peers and teachers as aggressive have been shown to be at risk for later delinquency and substance use, according to John Lochman, Ph.D., professor and Saxon Chair of Clinical Psychology at the University of Alabama, Tuscaloosa.

Exposing these moderate- to high-risk preadolescents to specific social-cognitive coping techniques in the classroom–while also engaging parents in the preventive intervention–can mitigate the potential for their developing conduct disorders during adolescence, Dr. Lochman reported at the 16th World Congress of the International Association for Child and Adolescent Psychiatry and Allied Professions.

Dr. Lochman and his colleagues evaluated the effects of a school-based aggression-intervention program on two samples of teacher-rated aggressive preadolescent children at the time of transition from elementary to middle school. The Coping Power program is based on an empirical model of risk factors for substance use. It addresses high-risk children's deficits in social competence, self-regulation, school bonding, and positive parental involvement.

The first sample included 183 fourth- and fifth-grade boys from 11 elementary schools, and the second sample comprised 245 fifth-grade boys and girls from 17 elementary schools. The children in both samples were randomly assigned to one of three groups: the Coping Power child component, the full Coping Power program with a combined parent and child component, or a control group.

In the second sample, some classrooms were also randomly assigned to a universal intervention through which the teachers received special training to help foster Coping Power skills in all students within the class.

The child component of the Coping Power program included 33 1-hour group sessions (4–6 boys per group) in an after-school setting over a 15-month period.

The sessions, which were led by a family-school program specialist and a school guidance counselor, focused on behavioral and personal goal setting; awareness of feelings and their associated physiologic arousal; the use of coping self-statements, distraction techniques, and relaxation methods; the development of organizational and study skills, perspective-taking strategies, and social problem-solving skills; attribution retraining; and dealing with peer pressure and neighborhood-based problems.

During the same 15-month period, the parental component of the program included 16 group sessions, with four to six parents/couples per group. The program content was derived from social learning theory-based training programs and included skills for identifying both prosocial and disruptive behavioral targets in their children, rewarding appropriate child behaviors, giving effective instructions, establishing age-appropriate rules and expectations, applying effective consequences to negative child behavior, and establishing ongoing communication through weekly family meetings. Parents also learned to be supportive of the Coping Power skills their children were attaining, and they were introduced to stress management techniques to help them remain calm during difficult interactions with their children.

One year after the end of the intervention period, children in both samples who participated in the Coping Power program had lower rates of self-reported delinquent behavior. Children in the first group had lower parent-rated substance use, and children in the second group had lower self-reported substance use. Both intervention conditions (child-only and combined child and parent) produced positive effects on the children's social competence and self-regulation and the parents' parenting skills, Dr. Lochman reported. “The intervention effects were most apparent for the full Coping Power, with parent and child components,” he said.

The intervention was also associated with teacher-rated behavioral improvements in school during the follow-up year–effects that appeared to be primarily influenced by the child component of the program, Dr. Lochman said. The follow-up measures also indicated that the universal intervention directly affected child substance use ratings and enhanced the Coping Power effects on delinquency. This finding suggests that providing teachers with the appropriate cognitive-behavioral techniques can have an effect on student aggression and antisocial behaviors.

The current study is the first to show that the effects of the intervention are maintained 1 year after the end of the program, and that an intervention that includes a combined parent and child component produces a greater improvement than does the Coping Power child component alone, Dr. Lochman noted.

BERLIN – When prescribing atypical antipsychotic drugs to children with major psychiatric disorders, physicians “can't be guided by scientific data alone because there are just not enough from properly conducted trials,” Stanley Kutcher, M.D., advised.

Clinicians need to proceed with caution and “consider the symptoms, adverse effects, function, and evidence associated with each of the drugs relative to the symptoms they're being used to treat,” he said at the 16th World Congress of the International Association for Child and Adolescent Psychiatry and Allied Professions.

The literature on atypical antipsychotics in pediatric patients is limited. With the exception of a small number of controlled studies, “most of the published data come from anecdotal case reports and small open-label trials,” said Dr. Kutcher of Dalhousie University, Halifax, N.S.

“You can't determine the efficacy and tolerability of any medication from open-label studies or case series, regardless of the number of participants, and while there have been some acute, controlled studies, data from these cannot be extrapolated to the long term. There can be a loss of efficacy over time, and there can be problems with side effects that don't show up in the first few months of treatment, but emerge later,” he explained.

What little evidence does exist–mostly from adult studies–suggests that the atypical, or second-generation, antipsychotics are at least as effective as first-generation compounds and have a lower incidence of extrapyramidal symptoms such as dystonia, parkinsonism, and akathisia. Anecdotally, the atypical drugs have been linked to favorable outcomes in children with psychotic disorders, which in turn has evoked interest in their use for other psychiatric conditions, including bipolar disorder, autism-spectrum disorders, aggression and disruptive behavior disorders, and tic disorders, Dr. Kutcher noted.

A review of the literature on the use of atypical antipsychotics showed 2 double-blind randomized control trials, 22 open-label studies, 10 retrospective investigations, and 14 published reviews. “Basically, it looks like there are more people reviewing what's out there than writing anything new,” Dr. Kutcher joked. And even the two randomized control trials looked only at short-term results (6 and 8 weeks) and examined the effects of very different dosages, making it impossible to extract definitive guidelines, he said.

The dearth of scientifically based treatment guidelines has many pediatric and adolescent psychiatrists walking a tightrope without a net. “The incentive to use the newer antipsychotics is there because of their efficacy in reducing acute psychiatric symptoms, but caution must be exercised, particularly in the face of the false security brought on by a quick, dramatic response,” he said.

Physicians must be aware that the drugs described as atypical antipsychotics–clozapine (Clozaril), risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), and aripiprazole (Abilify)–are not interchangeable. Each has a unique pharmacologic profile and may be associated with a range of different adverse events that can drive treatment decisions. “For example, some drugs may be more likely than others to induce akathisia. To those not aware of this, the effect can be misinterpreted as an increase in psychosis, leading clinicians to increase the medication dose when it should be decreased,” Dr. Kutcher noted.

Careful consideration of the drugs' actions and side effects can help mitigate potential problems, Dr. Kutcher said.

Dosing Recommendations for Atypicals

Dosage determination is critical when prescribing atypical antipsychotics to children. Current dosage recommendations have been extrapolated from adult studies, typically relying on body weight and proportionately reducing an adult dosage. This approach is problematic, though, because the different pharmacokinetics in children and adolescents could make the resulting plasma concentration either subtherapeutic or toxic, Dr. Kutcher said.

To minimize the risk of adverse events and maximize the potential for therapeutic effect, children and adolescents should always be started on the lowest possible dose with any of the antipsychotic agents. Gradual increases should be guided by clinical response. Because there are also insufficient data to support hard and fast recommendations for medication duration, these decisions must be guided by clinical instinct as well.

Toward that end, Dr. Kutcher made the following recommendations:

▸ When a minimal therapeutic dose is established, maintain the pediatric patient on this dose for 1 year, carefully monitoring the patient for changes and potential adverse events.

▸ After 1 year of stable treatment, partner with the patient and parents to discuss medication withdrawal.

▸ Choose the correct time to make a change. Any changes should not be implemented during a critical or stressful period in the child's life.

▸ Devise a slow discontinuation schedule, monitoring the child carefully for symptoms.

▸ If symptoms recur, return to the therapeutic dose of the medication.

BERLIN – When prescribing atypical antipsychotic drugs to children with major psychiatric disorders, physicians “can't be guided by scientific data alone because there are just not enough from properly conducted trials,” Stanley Kutcher, M.D., advised.

Clinicians need to proceed with caution and “consider the symptoms, adverse effects, function, and evidence associated with each of the drugs relative to the symptoms they're being used to treat,” he said at the 16th World Congress of the International Association for Child and Adolescent Psychiatry and Allied Professions.

The literature on atypical antipsychotics in pediatric patients is limited. With the exception of a small number of controlled studies, “most of the published data come from anecdotal case reports and small open-label trials,” said Dr. Kutcher of Dalhousie University, Halifax, N.S.

“You can't determine the efficacy and tolerability of any medication from open-label studies or case series, regardless of the number of participants, and while there have been some acute, controlled studies, data from these cannot be extrapolated to the long term. There can be a loss of efficacy over time, and there can be problems with side effects that don't show up in the first few months of treatment, but emerge later,” he explained.

What little evidence does exist–mostly from adult studies–suggests that the atypical, or second-generation, antipsychotics are at least as effective as first-generation compounds and have a lower incidence of extrapyramidal symptoms such as dystonia, parkinsonism, and akathisia. Anecdotally, the atypical drugs have been linked to favorable outcomes in children with psychotic disorders, which in turn has evoked interest in their use for other psychiatric conditions, including bipolar disorder, autism-spectrum disorders, aggression and disruptive behavior disorders, and tic disorders, Dr. Kutcher noted.

A review of the literature on the use of atypical antipsychotics showed 2 double-blind randomized control trials, 22 open-label studies, 10 retrospective investigations, and 14 published reviews. “Basically, it looks like there are more people reviewing what's out there than writing anything new,” Dr. Kutcher joked. And even the two randomized control trials looked only at short-term results (6 and 8 weeks) and examined the effects of very different dosages, making it impossible to extract definitive guidelines, he said.

The dearth of scientifically based treatment guidelines has many pediatric and adolescent psychiatrists walking a tightrope without a net. “The incentive to use the newer antipsychotics is there because of their efficacy in reducing acute psychiatric symptoms, but caution must be exercised, particularly in the face of the false security brought on by a quick, dramatic response,” he said.

Physicians must be aware that the drugs described as atypical antipsychotics–clozapine (Clozaril), risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), and aripiprazole (Abilify)–are not interchangeable. Each has a unique pharmacologic profile and may be associated with a range of different adverse events that can drive treatment decisions. “For example, some drugs may be more likely than others to induce akathisia. To those not aware of this, the effect can be misinterpreted as an increase in psychosis, leading clinicians to increase the medication dose when it should be decreased,” Dr. Kutcher noted.

Careful consideration of the drugs' actions and side effects can help mitigate potential problems, Dr. Kutcher said.

Dosing Recommendations for Atypicals

Dosage determination is critical when prescribing atypical antipsychotics to children. Current dosage recommendations have been extrapolated from adult studies, typically relying on body weight and proportionately reducing an adult dosage. This approach is problematic, though, because the different pharmacokinetics in children and adolescents could make the resulting plasma concentration either subtherapeutic or toxic, Dr. Kutcher said.

To minimize the risk of adverse events and maximize the potential for therapeutic effect, children and adolescents should always be started on the lowest possible dose with any of the antipsychotic agents. Gradual increases should be guided by clinical response. Because there are also insufficient data to support hard and fast recommendations for medication duration, these decisions must be guided by clinical instinct as well.

Toward that end, Dr. Kutcher made the following recommendations:

▸ When a minimal therapeutic dose is established, maintain the pediatric patient on this dose for 1 year, carefully monitoring the patient for changes and potential adverse events.

▸ After 1 year of stable treatment, partner with the patient and parents to discuss medication withdrawal.

▸ Choose the correct time to make a change. Any changes should not be implemented during a critical or stressful period in the child's life.

▸ Devise a slow discontinuation schedule, monitoring the child carefully for symptoms.

▸ If symptoms recur, return to the therapeutic dose of the medication.

BERLIN – When prescribing atypical antipsychotic drugs to children with major psychiatric disorders, physicians “can't be guided by scientific data alone because there are just not enough from properly conducted trials,” Stanley Kutcher, M.D., advised.

Clinicians need to proceed with caution and “consider the symptoms, adverse effects, function, and evidence associated with each of the drugs relative to the symptoms they're being used to treat,” he said at the 16th World Congress of the International Association for Child and Adolescent Psychiatry and Allied Professions.

The literature on atypical antipsychotics in pediatric patients is limited. With the exception of a small number of controlled studies, “most of the published data come from anecdotal case reports and small open-label trials,” said Dr. Kutcher of Dalhousie University, Halifax, N.S.

“You can't determine the efficacy and tolerability of any medication from open-label studies or case series, regardless of the number of participants, and while there have been some acute, controlled studies, data from these cannot be extrapolated to the long term. There can be a loss of efficacy over time, and there can be problems with side effects that don't show up in the first few months of treatment, but emerge later,” he explained.

What little evidence does exist–mostly from adult studies–suggests that the atypical, or second-generation, antipsychotics are at least as effective as first-generation compounds and have a lower incidence of extrapyramidal symptoms such as dystonia, parkinsonism, and akathisia. Anecdotally, the atypical drugs have been linked to favorable outcomes in children with psychotic disorders, which in turn has evoked interest in their use for other psychiatric conditions, including bipolar disorder, autism-spectrum disorders, aggression and disruptive behavior disorders, and tic disorders, Dr. Kutcher noted.

A review of the literature on the use of atypical antipsychotics showed 2 double-blind randomized control trials, 22 open-label studies, 10 retrospective investigations, and 14 published reviews. “Basically, it looks like there are more people reviewing what's out there than writing anything new,” Dr. Kutcher joked. And even the two randomized control trials looked only at short-term results (6 and 8 weeks) and examined the effects of very different dosages, making it impossible to extract definitive guidelines, he said.

The dearth of scientifically based treatment guidelines has many pediatric and adolescent psychiatrists walking a tightrope without a net. “The incentive to use the newer antipsychotics is there because of their efficacy in reducing acute psychiatric symptoms, but caution must be exercised, particularly in the face of the false security brought on by a quick, dramatic response,” he said.

Physicians must be aware that the drugs described as atypical antipsychotics–clozapine (Clozaril), risperidone (Risperdal), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), and aripiprazole (Abilify)–are not interchangeable. Each has a unique pharmacologic profile and may be associated with a range of different adverse events that can drive treatment decisions. “For example, some drugs may be more likely than others to induce akathisia. To those not aware of this, the effect can be misinterpreted as an increase in psychosis, leading clinicians to increase the medication dose when it should be decreased,” Dr. Kutcher noted.

Careful consideration of the drugs' actions and side effects can help mitigate potential problems, Dr. Kutcher said.

Dosing Recommendations for Atypicals

Dosage determination is critical when prescribing atypical antipsychotics to children. Current dosage recommendations have been extrapolated from adult studies, typically relying on body weight and proportionately reducing an adult dosage. This approach is problematic, though, because the different pharmacokinetics in children and adolescents could make the resulting plasma concentration either subtherapeutic or toxic, Dr. Kutcher said.

To minimize the risk of adverse events and maximize the potential for therapeutic effect, children and adolescents should always be started on the lowest possible dose with any of the antipsychotic agents. Gradual increases should be guided by clinical response. Because there are also insufficient data to support hard and fast recommendations for medication duration, these decisions must be guided by clinical instinct as well.

Toward that end, Dr. Kutcher made the following recommendations:

▸ When a minimal therapeutic dose is established, maintain the pediatric patient on this dose for 1 year, carefully monitoring the patient for changes and potential adverse events.

▸ After 1 year of stable treatment, partner with the patient and parents to discuss medication withdrawal.

▸ Choose the correct time to make a change. Any changes should not be implemented during a critical or stressful period in the child's life.

▸ Devise a slow discontinuation schedule, monitoring the child carefully for symptoms.

▸ If symptoms recur, return to the therapeutic dose of the medication.

BERLIN – A short-term video feedback intervention in early childhood can enhance parent-child relationships in adoptive families and minimize later child psychopathology associated with attachment problems, Femmie Juffer, Ph.D., said at the 16th World Congress of the International Association for Child and Adolescent Psychiatry and Allied Professions.

Previous studies have found that adopted children present more behavior problems and are overrepresented in clinical and mental health services, possibly as a consequence of disorganized infant attachment, Dr. Juffer noted.

To assess the effect that family interventions based on attachment theory can have on adopted child mental health, Dr. Juffer and her colleagues at Leiden (the Netherlands) University tested two intervention programs on 130 families with 6-month-old infants adopted from Sri Lanka, South Korea, and Colombia.

Two samples of families participated in the prospective longitudinal study: 90 families with a first-adopted child only and 40 families with birth children and a first-adopted child. All families were randomly assigned to one of three conditions. In the first condition, 30 families were given a personal book that included suggestions and advice on how to parent a child in a sensitive way. In the second condition, 50 families received the same book combined with three home-based sessions offering video feedback. The remaining 50 families were assigned to the control condition and received no intervention.

Both intervention programs “aimed at enhancing parental sensitive responsiveness, with the ultimate goal of promoting secure infant-parent attachment relationships and infant competence,” Dr. Juffer said.

Post-test assessments conducted 3 months after the end of the intervention period showed that the video feedback/personal book intervention resulted in statistically significant enhanced maternal sensitive responsiveness.

Additionally, the children of mothers who received this intervention were less likely to be classified as having disorganized attachment at the age of 12 months, compared with infants in the control group, while the book-only intervention had no effect on the number of infants with disorganized attachment classifications, Dr. Juffer reported.

A long-term follow-up study when the children were 7 years old showed positive effects of the video-feedback intervention among the children who were adopted into families with birth children. “Adopted children in 'mixed' adoptive families presented fewer internalizing behavior problems,” Dr. Juffer said.

Also, adopted girls who were in the video-intervention group scored higher on ego resiliency and social competence, compared with controls at age 7, according to Dr. Juffer.

In the total sample, “early parent-child relationship and parental sensitivity predicted adopted children's socioemotional and cognitive development and rate of behavior problems in middle childhood,” Dr. Juffer stated.

In a separate metaanalysis of adoptive family interventions, Dr. Juffer and her colleagues concluded that effective interventions focused on sensitivity, began at or after 6 months, and were implemented by intervention professionals. The most effective interventions used a moderate number of sessions and a clear-cut behavioral focus. “The video-feedback intervention matches this description well,” she said.

Interventions that were more effective in enhancing parental sensitivity were also more effective in enhancing attachment security, “which supports the notion of a causal role of sensitivity in shaping attachment,” Dr. Juffer said.

“The effectiveness of the [video] intervention in the sample of adoptive parents and their genetically unrelated children documents the importance of parenting in the developing of infant attachment disorganization,” she concluded.

BERLIN – A short-term video feedback intervention in early childhood can enhance parent-child relationships in adoptive families and minimize later child psychopathology associated with attachment problems, Femmie Juffer, Ph.D., said at the 16th World Congress of the International Association for Child and Adolescent Psychiatry and Allied Professions.

Previous studies have found that adopted children present more behavior problems and are overrepresented in clinical and mental health services, possibly as a consequence of disorganized infant attachment, Dr. Juffer noted.

To assess the effect that family interventions based on attachment theory can have on adopted child mental health, Dr. Juffer and her colleagues at Leiden (the Netherlands) University tested two intervention programs on 130 families with 6-month-old infants adopted from Sri Lanka, South Korea, and Colombia.

Two samples of families participated in the prospective longitudinal study: 90 families with a first-adopted child only and 40 families with birth children and a first-adopted child. All families were randomly assigned to one of three conditions. In the first condition, 30 families were given a personal book that included suggestions and advice on how to parent a child in a sensitive way. In the second condition, 50 families received the same book combined with three home-based sessions offering video feedback. The remaining 50 families were assigned to the control condition and received no intervention.

Both intervention programs “aimed at enhancing parental sensitive responsiveness, with the ultimate goal of promoting secure infant-parent attachment relationships and infant competence,” Dr. Juffer said.

Post-test assessments conducted 3 months after the end of the intervention period showed that the video feedback/personal book intervention resulted in statistically significant enhanced maternal sensitive responsiveness.

Additionally, the children of mothers who received this intervention were less likely to be classified as having disorganized attachment at the age of 12 months, compared with infants in the control group, while the book-only intervention had no effect on the number of infants with disorganized attachment classifications, Dr. Juffer reported.

A long-term follow-up study when the children were 7 years old showed positive effects of the video-feedback intervention among the children who were adopted into families with birth children. “Adopted children in 'mixed' adoptive families presented fewer internalizing behavior problems,” Dr. Juffer said.

Also, adopted girls who were in the video-intervention group scored higher on ego resiliency and social competence, compared with controls at age 7, according to Dr. Juffer.

In the total sample, “early parent-child relationship and parental sensitivity predicted adopted children's socioemotional and cognitive development and rate of behavior problems in middle childhood,” Dr. Juffer stated.

In a separate metaanalysis of adoptive family interventions, Dr. Juffer and her colleagues concluded that effective interventions focused on sensitivity, began at or after 6 months, and were implemented by intervention professionals. The most effective interventions used a moderate number of sessions and a clear-cut behavioral focus. “The video-feedback intervention matches this description well,” she said.

Interventions that were more effective in enhancing parental sensitivity were also more effective in enhancing attachment security, “which supports the notion of a causal role of sensitivity in shaping attachment,” Dr. Juffer said.

“The effectiveness of the [video] intervention in the sample of adoptive parents and their genetically unrelated children documents the importance of parenting in the developing of infant attachment disorganization,” she concluded.

BERLIN – A short-term video feedback intervention in early childhood can enhance parent-child relationships in adoptive families and minimize later child psychopathology associated with attachment problems, Femmie Juffer, Ph.D., said at the 16th World Congress of the International Association for Child and Adolescent Psychiatry and Allied Professions.

Previous studies have found that adopted children present more behavior problems and are overrepresented in clinical and mental health services, possibly as a consequence of disorganized infant attachment, Dr. Juffer noted.

To assess the effect that family interventions based on attachment theory can have on adopted child mental health, Dr. Juffer and her colleagues at Leiden (the Netherlands) University tested two intervention programs on 130 families with 6-month-old infants adopted from Sri Lanka, South Korea, and Colombia.

Two samples of families participated in the prospective longitudinal study: 90 families with a first-adopted child only and 40 families with birth children and a first-adopted child. All families were randomly assigned to one of three conditions. In the first condition, 30 families were given a personal book that included suggestions and advice on how to parent a child in a sensitive way. In the second condition, 50 families received the same book combined with three home-based sessions offering video feedback. The remaining 50 families were assigned to the control condition and received no intervention.

Both intervention programs “aimed at enhancing parental sensitive responsiveness, with the ultimate goal of promoting secure infant-parent attachment relationships and infant competence,” Dr. Juffer said.

Post-test assessments conducted 3 months after the end of the intervention period showed that the video feedback/personal book intervention resulted in statistically significant enhanced maternal sensitive responsiveness.

Additionally, the children of mothers who received this intervention were less likely to be classified as having disorganized attachment at the age of 12 months, compared with infants in the control group, while the book-only intervention had no effect on the number of infants with disorganized attachment classifications, Dr. Juffer reported.

A long-term follow-up study when the children were 7 years old showed positive effects of the video-feedback intervention among the children who were adopted into families with birth children. “Adopted children in 'mixed' adoptive families presented fewer internalizing behavior problems,” Dr. Juffer said.

Also, adopted girls who were in the video-intervention group scored higher on ego resiliency and social competence, compared with controls at age 7, according to Dr. Juffer.

In the total sample, “early parent-child relationship and parental sensitivity predicted adopted children's socioemotional and cognitive development and rate of behavior problems in middle childhood,” Dr. Juffer stated.

In a separate metaanalysis of adoptive family interventions, Dr. Juffer and her colleagues concluded that effective interventions focused on sensitivity, began at or after 6 months, and were implemented by intervention professionals. The most effective interventions used a moderate number of sessions and a clear-cut behavioral focus. “The video-feedback intervention matches this description well,” she said.

Interventions that were more effective in enhancing parental sensitivity were also more effective in enhancing attachment security, “which supports the notion of a causal role of sensitivity in shaping attachment,” Dr. Juffer said.

“The effectiveness of the [video] intervention in the sample of adoptive parents and their genetically unrelated children documents the importance of parenting in the developing of infant attachment disorganization,” she concluded.

HARROGATE, ENGLAND — Calcium and vitamin D supplementation do not reduce the risk of clinical fracture among women identified as having one or more risk factors for hip fracture, a randomized controlled trial has shown.

Investigators at the University of York (England), in collaboration with community primary care providers, recruited 3,322 women aged 70 years and older, who had at least one of the following risk factors for hip fracture: previous fracture, low body weight, maternal history of hip fracture, a fall in the previous 12 months, or older age (per year increase).

About half of the women were randomized to receive daily oral supplementation of 1,000 mg of calcium and 800 IU vitamin D, along with a patient information leaflet on dietary calcium intake and fall prevention.

The remaining patients were randomized to a control group and received only the patient information leaflet, reported York University research fellow Jill Porthouse in a presentation at the annual conference of the National Osteoporosis Society.

After a median follow-up of 25 months, there were no significant differences between the two groups in the rates of all clinical fractures or hip fractures. The odds ratio for all fractures in the supplement group compared with the control group was 1.03. For hip fractures specifically, the odds ratio was 0.82.

The findings are disappointing, Ms. Porthouse noted.

“Fall-related low-trauma fractures represent a significant burden of illness in older people. Calcium and vitamin D supplementation is a relatively inexpensive intervention, but it does not appear to reduce fracture rates in women at risk,” she said.

HARROGATE, ENGLAND — Calcium and vitamin D supplementation do not reduce the risk of clinical fracture among women identified as having one or more risk factors for hip fracture, a randomized controlled trial has shown.

Investigators at the University of York (England), in collaboration with community primary care providers, recruited 3,322 women aged 70 years and older, who had at least one of the following risk factors for hip fracture: previous fracture, low body weight, maternal history of hip fracture, a fall in the previous 12 months, or older age (per year increase).

About half of the women were randomized to receive daily oral supplementation of 1,000 mg of calcium and 800 IU vitamin D, along with a patient information leaflet on dietary calcium intake and fall prevention.

The remaining patients were randomized to a control group and received only the patient information leaflet, reported York University research fellow Jill Porthouse in a presentation at the annual conference of the National Osteoporosis Society.

After a median follow-up of 25 months, there were no significant differences between the two groups in the rates of all clinical fractures or hip fractures. The odds ratio for all fractures in the supplement group compared with the control group was 1.03. For hip fractures specifically, the odds ratio was 0.82.

The findings are disappointing, Ms. Porthouse noted.

“Fall-related low-trauma fractures represent a significant burden of illness in older people. Calcium and vitamin D supplementation is a relatively inexpensive intervention, but it does not appear to reduce fracture rates in women at risk,” she said.

HARROGATE, ENGLAND — Calcium and vitamin D supplementation do not reduce the risk of clinical fracture among women identified as having one or more risk factors for hip fracture, a randomized controlled trial has shown.

Investigators at the University of York (England), in collaboration with community primary care providers, recruited 3,322 women aged 70 years and older, who had at least one of the following risk factors for hip fracture: previous fracture, low body weight, maternal history of hip fracture, a fall in the previous 12 months, or older age (per year increase).

About half of the women were randomized to receive daily oral supplementation of 1,000 mg of calcium and 800 IU vitamin D, along with a patient information leaflet on dietary calcium intake and fall prevention.

The remaining patients were randomized to a control group and received only the patient information leaflet, reported York University research fellow Jill Porthouse in a presentation at the annual conference of the National Osteoporosis Society.

After a median follow-up of 25 months, there were no significant differences between the two groups in the rates of all clinical fractures or hip fractures. The odds ratio for all fractures in the supplement group compared with the control group was 1.03. For hip fractures specifically, the odds ratio was 0.82.

The findings are disappointing, Ms. Porthouse noted.

“Fall-related low-trauma fractures represent a significant burden of illness in older people. Calcium and vitamin D supplementation is a relatively inexpensive intervention, but it does not appear to reduce fracture rates in women at risk,” she said.