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Outcomes of allergy to insect stings in children, with and without venom immunotherapy
in familial hypercholesterolemia: treatment with simvastatin. Arch Intern Med 2003;163:1837-41. 5. Smilde TJ, van Wissen S, Wollersheim H, Trip MD, Kastelein JJ, Stalenhoef AF. Effect of aggressive versus conventional lipid lowering on atherosclerosis progression in familial hypercholesterolaemia (ASAP): a prospective, randomised, double-blind trial. Lancet 2001;357:577-81. 6. Chambless LE, Heiss G, Folsom AR, Rosamond W, Szklo M, Sharrett AR, Clegg LX. Association of CAD incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) study, 1987-1993. Am J Epidemiol 1997;146: 483-94. 7. Tonstad S. Treatment of children with familial hypercholesterolemia. Exp Rev Cardiovasc Ther 2003;1:135-41.
Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial Treatment for Adolescents With Depression Study (TADS) Team. JAMA 2004;292:807-20. Context Initial treatment of major depressive disorder in adolescents may include cognitive-behavioral therapy (CBT) or a selective serotonin reuptake inhibitor. However, little is known about their relative or combined effectiveness. Objective To evaluate the effectiveness of 4 treatments among adolescents with major depressive disorder. Design Randomized controlled trial. Setting The trial was conducted at 13 US academic and community clinics between spring 2000 and summer 2003. Participants Volunteer sample of 439 patients, ages 12 to 17 years, with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of major depressive disorder. Interventions Twelve weeks of (1) fluoxetine alone (10 to 40 mg/d), (2) CBT alone, (3) CBT with fluoxetine (10 to 40 mg/d), or (4) placebo (equivalent to 10 to 40 mg/d). Placebo and fluoxetine alone were administered in a double-blinded fashion; CBT alone and CBT with fluoxetine were administered in unblinded fashion. Main outcome measures Children’s Depression Rating Scale-Revised total score and, for responder analysis, a (dichotomized) Clinical Global Impressions improvement score. Results Compared with placebo, the combination of fluoxetine with CBT was statistically significant (P = .001) on the Children’s Depression Rating Scale-Revised. Compared with fluoxetine alone (P = .02) and CBT alone (P = .01), treatment of fluoxetine with CBT was superior. Fluoxetine alone was a superior treatment to CBT alone (P = .01). Rates of response for fluoxetine with CBT were 71.0% (95% CI, 62% to 80%); fluoxetine alone, 60.6% (95% CI, 51% to 70%); CBT alone, 43.2% (95% CI, 34% to 52%); and placebo, 34.8% (95% CI, 26% to 44%). On the Clinical Global Impressions improvement
Clinical Research Abstracts For Pediatricians
responder analysis, the 2 fluoxetine-containing conditions were statistically superior to CBT and to placebo. Clinically significant suicidal thinking, which was present in 29% of the sample at baseline, improved significantly in all 4 treatment groups. Fluoxetine with CBT showed the greatest reduction (P = .02). Seven (1.6%) of 439 patients attempted suicide; there were no completed suicides. Conclusions The combination of fluoxetine with CBT offered the most favorable tradeoff between benefit and risk for adolescents with major depressive disorder. Comment Treatment of adolescents with major depression, and particularly the possibility of an increased risk of suicidal behavior associated with antidepressant drug treatment, have become issues of major controversy in recent months. Adolescent patients, their parents, and their physicians face heightened concerns in weighing the potential benefits and risks in making choices about treating major depression, a disorder marked by considerable suffering, functional impairment, and risk of death from suicide. This report of the 12-week primary results of the Treatment for Adolescents with Depression Study (TADS) provides important empiric data bearing on this clinical issue. This trial was the first to evaluate the efficacy in adolescents of combined treatment with a serotonin-selective antidepressant (fluoxetine) and CBT compared with fluoxetine alone, CBT alone, and placebo. Combined treatment was superior on most measures of response. Fluoxetine was administered in an unblinded fashion in the combined treatment group—a design limitation that might have advantaged the combined treatment group due to positive expectational effects. Suicidal thinking decreased with all 4 treatments, even placebo, reflecting the importance and clinical relevance of the careful monitoring and attention offered to all of the patients and parents in this multicenter, randomized, controlled trial. The results agree with previous trials in adult patients indicating that combined treatment with an evidence-based psychotherapy and antidepressant medication is optimal for most patients with major depression.
Richard M. Glass, MD University of Chicago Chicago, IL 60637
Outcomes of allergy to insect stings in children, with and without venom immunotherapy Golden DBK, Kagey-Sobotka A, Norman PS, Hamilton RG, Lichtenstein LM. N Engl J Med 2004;351:668-74. Context Children are thought to ‘‘outgrow’’ the allergy to insect stings, but there are no reports documenting the natural history of this reaction. Objectives To study the outcome of allergic reactions to insect stings in childhood 10 to 20 years afterward in patients who had not received venom immunotherapy and in those who had been treated.
145
Design Observational study.
sting systemic reactions even years after therapy has been stopped.
Setting Allergy clinic at a major urban health center in the United States. Participants Children (n = 1033) in whom allergic reaction to insect stings were diagnosed between 1978 and 1985, of whom 356 received venom immunotherapy. Interventions Telephone and mail survey between January 1997 and January 2000. Main outcome measures stings.
Type and severity of reactions to
Results Of the 1033 patients, 512 patients (50%) responded, with a mean follow-up period of 18 years, a mean duration of venom immunotherapy of 3.5 years in treated patients, and an incidence of stings of 43%. Systemic reactions occurred less frequently in patients who had received venom immunotherapy (2 of 64 patients, or 3%) than in untreated patients (19 of 111 patients, 17%; P = 0.007). Patients with a history of moderate-to-severe reactions had a higher rate of reaction if they had not been treated (7 of 22 patients, or 32%) than if they had received venom immunotherapy (2 of 43 patients, or 5%; P = .007). In patients who had been treated and who had a history of mild (cutaneous) systemic reaction (ie, one with only cutaneous manifestations), none of the 21 subjects who received stings had a systemic reaction. Conclusions A clinically important number of children do not outgrow allergic reactions to insect stings. Venom immunotherapy in children leads to a significantly lower risk of systemic reaction to stings even 10 to 20 years after treatment is stopped, and this prolonged benefit is greater than the benefit seen in adults. Comment This study is a retrospective analysis comparing outcomes in children after insect sting reactions, some of whom received venom immunotherapy and others who did not. Results demonstrate that systemic reactions occur less frequently in children for whom venom immunotherapy is indicated and who receive venom immunotherapy versus those who do not receive such therapy. In patients with a history of moderate-to-severe reactions, those who receive venom immunotherapy have a lower rate of reaction on resting than those who do not receive immunotherapy. Among treated patients with mild cutaneous reactions, none had a systemic reaction on subsequent stings. This was not significantly different than those who had not been given venom immunotherapy (P = .12). This study reveals that most children, regardless of whether or not they are treated, lose their insect sensitivity by adulthood. However, those with a history of moderate-to-severe reactions, who are at risk for a systemic reaction on subsequent stings, do statistically better with treatment even 10 to 20 years after immunotherapy is stopped. Thus, a course of venom immunotherapy for moderate-to-severe anaphylaxis is warranted to prevent re-
146
Clinical Research Abstracts For Pediatricians
Patrick J. DeMarco, MD Richard F. Lockey, MD Division of Allergy and Immunology University of South Florida College of Medicine and James A. Haley VA Hospital Tampa, FL 33612
Effect of dextromethorphan, diphenhydramine, and placebo on nocturnal cough and sleep quality for coughing children and their parents Paul IM, Yoder KE, Crowell KR, Shaffer ML, McMillan HS, Carlson LC, Dilworth DA, Berlin CM. Pediatrics 2004;114: e85-90. Context Although dextromethorphan and diphenhydramine are not recommended by the American Academy of Pediatrics for treatment of coughs, they are frequently used. Objectives To determine whether dextromethorphan and diphenhydramine are superior to placebo for the treatment of nocturnal cough and sleep difficulty associated with upper respiratory infections and to determine whether parents have improved sleep quality when their children receive the medications when compared with placebo. Design Randomized, double-blinded study. Setting Two university-affiliated practices in Hershey, Pennsylvania. Participants infections.
Parents of 100 children with upper respiratory
Interventions After stratification by age, patients were randomly assigned to receive either dextromethorphan (dosed based on age), diphenhydramine (dose based on weight), or placebo. Main outcome measures Frequency, severity, and bothersome nature of the nocturnal cough recorded on 2 consecutive days, initially on the day of presentation, when no medication had been given the previous evening, and then again on the subsequent day, after the intervention. Sleep quality for both the child and the parent were also assessed for both nights. Results For the entire cohort, all outcomes were significantly improved on the second night of the study when either medication or placebo was given. However, neither diphenhydramine nor dextromethorphan produced a superior benefit when compared with placebo for any of the outcomes studied. Insomnia was reported more frequently in those who were given dextromethorphan, and drowsiness was reported more commonly in those who were given diphenhydramine. Conclusions Diphenhydramine and dextromethorphan are not superior to placebo in providing nocturnal symptom relief for children with cough and sleep difficulty as a result of an upper respiratory infection. Furthermore, the medications
The Journal of Pediatrics January 2005
Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial Treatment for Adolescents With Depression Study (TADS) Team. JAMA 2004;292:807-20. Context Initial treatment of major depressive disorder in adolescents may include cognitive-behavioral therapy (CBT) or a selective serotonin reuptake inhibitor. However, little is known about their relative or combined effectiveness. Objective To evaluate the effectiveness of 4 treatments among adolescents with major depressive disorder. Design Randomized controlled trial. Setting The trial was conducted at 13 US academic and community clinics between spring 2000 and summer 2003. Participants Volunteer sample of 439 patients, ages 12 to 17 years, with a primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of major depressive disorder. Interventions Twelve weeks of (1) fluoxetine alone (10 to 40 mg/d), (2) CBT alone, (3) CBT with fluoxetine (10 to 40 mg/d), or (4) placebo (equivalent to 10 to 40 mg/d). Placebo and fluoxetine alone were administered in a double-blinded fashion; CBT alone and CBT with fluoxetine were administered in unblinded fashion. Main outcome measures Children’s Depression Rating Scale-Revised total score and, for responder analysis, a (dichotomized) Clinical Global Impressions improvement score. Results Compared with placebo, the combination of fluoxetine with CBT was statistically significant (P = .001) on the Children’s Depression Rating Scale-Revised. Compared with fluoxetine alone (P = .02) and CBT alone (P = .01), treatment of fluoxetine with CBT was superior. Fluoxetine alone was a superior treatment to CBT alone (P = .01). Rates of response for fluoxetine with CBT were 71.0% (95% CI, 62% to 80%); fluoxetine alone, 60.6% (95% CI, 51% to 70%); CBT alone, 43.2% (95% CI, 34% to 52%); and placebo, 34.8% (95% CI, 26% to 44%). On the Clinical Global Impressions improvement
Clinical Research Abstracts For Pediatricians
responder analysis, the 2 fluoxetine-containing conditions were statistically superior to CBT and to placebo. Clinically significant suicidal thinking, which was present in 29% of the sample at baseline, improved significantly in all 4 treatment groups. Fluoxetine with CBT showed the greatest reduction (P = .02). Seven (1.6%) of 439 patients attempted suicide; there were no completed suicides. Conclusions The combination of fluoxetine with CBT offered the most favorable tradeoff between benefit and risk for adolescents with major depressive disorder. Comment Treatment of adolescents with major depression, and particularly the possibility of an increased risk of suicidal behavior associated with antidepressant drug treatment, have become issues of major controversy in recent months. Adolescent patients, their parents, and their physicians face heightened concerns in weighing the potential benefits and risks in making choices about treating major depression, a disorder marked by considerable suffering, functional impairment, and risk of death from suicide. This report of the 12-week primary results of the Treatment for Adolescents with Depression Study (TADS) provides important empiric data bearing on this clinical issue. This trial was the first to evaluate the efficacy in adolescents of combined treatment with a serotonin-selective antidepressant (fluoxetine) and CBT compared with fluoxetine alone, CBT alone, and placebo. Combined treatment was superior on most measures of response. Fluoxetine was administered in an unblinded fashion in the combined treatment group—a design limitation that might have advantaged the combined treatment group due to positive expectational effects. Suicidal thinking decreased with all 4 treatments, even placebo, reflecting the importance and clinical relevance of the careful monitoring and attention offered to all of the patients and parents in this multicenter, randomized, controlled trial. The results agree with previous trials in adult patients indicating that combined treatment with an evidence-based psychotherapy and antidepressant medication is optimal for most patients with major depression.
Richard M. Glass, MD University of Chicago Chicago, IL 60637
Outcomes of allergy to insect stings in children, with and without venom immunotherapy Golden DBK, Kagey-Sobotka A, Norman PS, Hamilton RG, Lichtenstein LM. N Engl J Med 2004;351:668-74. Context Children are thought to ‘‘outgrow’’ the allergy to insect stings, but there are no reports documenting the natural history of this reaction. Objectives To study the outcome of allergic reactions to insect stings in childhood 10 to 20 years afterward in patients who had not received venom immunotherapy and in those who had been treated.
145
Design Observational study.
sting systemic reactions even years after therapy has been stopped.
Setting Allergy clinic at a major urban health center in the United States. Participants Children (n = 1033) in whom allergic reaction to insect stings were diagnosed between 1978 and 1985, of whom 356 received venom immunotherapy. Interventions Telephone and mail survey between January 1997 and January 2000. Main outcome measures stings.
Type and severity of reactions to
Results Of the 1033 patients, 512 patients (50%) responded, with a mean follow-up period of 18 years, a mean duration of venom immunotherapy of 3.5 years in treated patients, and an incidence of stings of 43%. Systemic reactions occurred less frequently in patients who had received venom immunotherapy (2 of 64 patients, or 3%) than in untreated patients (19 of 111 patients, 17%; P = 0.007). Patients with a history of moderate-to-severe reactions had a higher rate of reaction if they had not been treated (7 of 22 patients, or 32%) than if they had received venom immunotherapy (2 of 43 patients, or 5%; P = .007). In patients who had been treated and who had a history of mild (cutaneous) systemic reaction (ie, one with only cutaneous manifestations), none of the 21 subjects who received stings had a systemic reaction. Conclusions A clinically important number of children do not outgrow allergic reactions to insect stings. Venom immunotherapy in children leads to a significantly lower risk of systemic reaction to stings even 10 to 20 years after treatment is stopped, and this prolonged benefit is greater than the benefit seen in adults. Comment This study is a retrospective analysis comparing outcomes in children after insect sting reactions, some of whom received venom immunotherapy and others who did not. Results demonstrate that systemic reactions occur less frequently in children for whom venom immunotherapy is indicated and who receive venom immunotherapy versus those who do not receive such therapy. In patients with a history of moderate-to-severe reactions, those who receive venom immunotherapy have a lower rate of reaction on resting than those who do not receive immunotherapy. Among treated patients with mild cutaneous reactions, none had a systemic reaction on subsequent stings. This was not significantly different than those who had not been given venom immunotherapy (P = .12). This study reveals that most children, regardless of whether or not they are treated, lose their insect sensitivity by adulthood. However, those with a history of moderate-to-severe reactions, who are at risk for a systemic reaction on subsequent stings, do statistically better with treatment even 10 to 20 years after immunotherapy is stopped. Thus, a course of venom immunotherapy for moderate-to-severe anaphylaxis is warranted to prevent re-
146
Clinical Research Abstracts For Pediatricians
Patrick J. DeMarco, MD Richard F. Lockey, MD Division of Allergy and Immunology University of South Florida College of Medicine and James A. Haley VA Hospital Tampa, FL 33612
Effect of dextromethorphan, diphenhydramine, and placebo on nocturnal cough and sleep quality for coughing children and their parents Paul IM, Yoder KE, Crowell KR, Shaffer ML, McMillan HS, Carlson LC, Dilworth DA, Berlin CM. Pediatrics 2004;114: e85-90. Context Although dextromethorphan and diphenhydramine are not recommended by the American Academy of Pediatrics for treatment of coughs, they are frequently used. Objectives To determine whether dextromethorphan and diphenhydramine are superior to placebo for the treatment of nocturnal cough and sleep difficulty associated with upper respiratory infections and to determine whether parents have improved sleep quality when their children receive the medications when compared with placebo. Design Randomized, double-blinded study. Setting Two university-affiliated practices in Hershey, Pennsylvania. Participants infections.
Parents of 100 children with upper respiratory
Interventions After stratification by age, patients were randomly assigned to receive either dextromethorphan (dosed based on age), diphenhydramine (dose based on weight), or placebo. Main outcome measures Frequency, severity, and bothersome nature of the nocturnal cough recorded on 2 consecutive days, initially on the day of presentation, when no medication had been given the previous evening, and then again on the subsequent day, after the intervention. Sleep quality for both the child and the parent were also assessed for both nights. Results For the entire cohort, all outcomes were significantly improved on the second night of the study when either medication or placebo was given. However, neither diphenhydramine nor dextromethorphan produced a superior benefit when compared with placebo for any of the outcomes studied. Insomnia was reported more frequently in those who were given dextromethorphan, and drowsiness was reported more commonly in those who were given diphenhydramine. Conclusions Diphenhydramine and dextromethorphan are not superior to placebo in providing nocturnal symptom relief for children with cough and sleep difficulty as a result of an upper respiratory infection. Furthermore, the medications
The Journal of Pediatrics January 2005