First-line Treatment For Children Research Articles

Recommendations Concerning the First-Line Treatment of Children with Tuberculosis.

This document describes the recommendations of a group of scientific societies concerning the first-line therapeutic approach to paediatric tuberculosis (TB). The treatment of pulmonary TB should be based on the existence of parenchymal involvement and the risk of antibiotic resistance. The treatment of extra-pulmonary TB is based on the regimens used for severe pulmonary TB. The administration of corticosteroids is recommended only in cases of miliary TB, tuberculous meningitis and tuberculous pericarditis. Vitamin B6 may be indicated in the case of isoniazid-treated TB in breastfeeding infants, severely malnourished subjects, or patients with other diseases at high risk of vitamin deficiency. Once having started treatment, children with TB should be carefully followed up in order to evaluate compliance, the response to treatment, the need for treatment changes, and the presence of drug-related adverse events. Primary care paediatricians can support reference centres in providing family healthcare education and encouraging treatment compliance.

Practical guide to treating children with juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatological disease of childhood. Symptom control is important in the initial management. Following definitive diagnosis methotrexate remains the first-line treatment for children with JIA. For those in whom methotrexate is ineffective, in whom it is not tolerated or in children whose disease affects the spine biologic agents play an important role. Biologics are a new group of treatments including monoclonal antibodies, soluble cytokine receptors or receptor antagonists that target key pathways of the immune system implicated in inflammation. These new drugs provide symptomatic relief, improvement in disease activity, prevention of damage, and promote normal growth and development for children with JIA. In order to optimize outcomes for children with JIA the British Society of Paediatric and Adolescent Rheumatology (BSPAR) recommends that whenever possible management and treatment initiation should be undertaken at a specialist centre within a clinical network.

Plasma-derived C1-INH for managing hereditary angioedema in pediatric patients: A systematic review.

Presently, medications approved for children with Hereditary Angioedema (HAE) are extremely limited. This is especially the case for children under 12 years of age. For this reason we reviewed and summarized the data on treatment of children with HAE. Available data indicate that plasma derived C1-inhibitor is a safe, effective treatment option for HAE in pediatric patients, including those below 12 years of age. Other therapies are also appear safe for the under 12 year of age, but less data are available. Importantly, home-based treatment of HAE in this age group appears to be safe and effective and can improve quality of life. These findings support current HAE consensus guidelines which strongly recommend the use of plasma derived C1-inhibitor as a first-line treatment in children and encourage home and self-treatment.

Syndrome de Wells de l’enfant et atopie : étude rétrospective de 11 cas et revue de la littérature

Well's syndrome, or eosinophilic cellulitis, is rare in childhood, with fewer than 40 pediatric cases being reported since 1979. The physiopathology is unknown. In February 2012, members of the research group of the Department of Pediatric Dermatology Society submitted their case of Wells' syndrome in children aged 0-15 years. Details of clinical, biological and histological features and of therapeutic strategies were collected by physicians using a standardized questionnaire. Pictures were reviewed by the authors. Eleven patients were included (average age: 6 years), with a strong prevalence of atopy (63%). Two types of clinical manifestation were noted: single or multiple cellulitis associated or not with vesiculobullous lesions and fixed urticaria. Eighty-two percent of patients had pruritus and 73% had eosinophilia. For all patients, histological examination of skin biopsies showed an eosinophilic infiltrate extending in the dermis with associated Sweet-like neutrophilic infiltrate being seen in 2 patients. The course of the disease was protracted (mean duration: 8 months) with flare-ups. Treatment varied depending on the doctors (topical or systemic steroids, tacrolimus and dapsone). Our study confirms some of the data in the literature concerning the clinical, histological features and course of Well's syndrome in children. The key information is the high prevalence of atopic children hitherto unreported. In a setting of insect bites, vaccination, infection or traumatism, this unusual background could explain the onset of inflammatory reaction with eosinophils. Oral or topical steroids appear to be the first-line treatment in children when necessary. Well's syndrome in children is rare and characterized by its polymorphism. We report for the first time in a series of patients a high prevalence of atopy, which raises new perspectives in understanding these rare diseases. We propose topical steroids as first-line therapy in children with superficial lesions, with oral steroids being given for cellulitic lesions or where topical therapy fails.

Psychopharmacological approach to the treatment of adolescents in the first psychotic episode

Introduction. The first psychotic episodes in adolescents represents a great challenge in the psychopharmacologic and diagnostic point of view. Atypical antipsychotics are the first line treatment of children and adolescents with psychotic disorders. Typical antipsychotics are used as second-line treatment. Objective. The aim of the study was to assess, analyze and present data on psychopharmacologic treatment of first psychotic episodes in adolescents who were hospitalized at the Clinic for Mental Disorders 'Dr Laza Lazarevic' in the Clinical department for older adolescents. Method. The research was conducted as a retrospective naturalistic study conducted in the period from 01.07.2012. to 08.30.2014. The sample consisted of 60 hospitalized patients with a first psychotic episode. The therapy administered at discharge was recorded. The survey instrument was a closed questionnaire composed for this article. Data analysis was performed by means of descriptive statistics. Results. Out of 60 patients incidence of those treated with typical antipsychotic was 40 %, atypical 33.33 %, while the in­cidence of combined therapy with typical and atypical was 26.67 %. The average length of treatment of patients on monotherapy typical antipsychotic was 28.79 days (X= 28.79), atypical 24.15 (X = 24.15) and a combination of typical and atypical 27.44 (X= 27.44). Hallucinations show a better response to typical antipsychotics, while delusions respond about the same in both drug groups. Conclusion. Successful treatment of initial psychotic episode, especially among adolescents, is crucial for minimizing the consequences for the personal and social functioning. In relation to the course of the disease, duration of treatment and side effects, atypical antipsychotics have the advantage over the first-generation drugs, as has been shown by the results of the study.

β-blockers in the treatment of periocular infantile capillary haemangioma.

Infantile capillary haemangioma (IH) is the most common congenital vascular tumor of childhood and infancy. Although the majority of these lesions regress spontaneously, many of children with IH particularly in the periocular or orbital region need treatment. Ocular indications for treatment include obstruction of the visual axis or high degrees of astigmatism causing amblyopia, exposure keratopathy secondary to proptosis or compressive optic neuropathy. Our purpose was to assess the effectiveness and tolerance of beta-blockers (BB),propranololand metoprolol, in the treatment of these lesions. We performed aretrospectivereview of 21 infant patients with periocular or/and orbital IH. The mode of treatment for 13 patients was with the non-selective βblocker propranolol (PR) and 8 patients were treated with the β1 selective blocker metoprolol (ME). We analysed the changes in IH lesion size, colour and thickness after the treatment with β-blockers, the onset and the period of their action, recurrence of IH and adverse effects of the treatment. The effectiveness of metoprolol to propranolol was compared as well as their use in combination with systemic steroids. In the first month of the treatment with beta-blockers, significant regression of the IH was observed in all patients. During the following months of treatment the regression was not rapid and after 6 to 12 months the lesions remained stationary. The final result of the treatment of 15 patients (71.4%) was deemed excellent while the treatment of 5 patients (23.8%) was deemed good. Asingle patient (4.7%) had only fair response to the therapy. During the whole series no serious life-threatening adverse effects were observed. The usage of beta-blockers, both propranolol and metoprolol, in the therapy of orbital and periocular capillary infantile haemangioma seems to be very effective in reduction of the tumor and had only rare, minimum adverse effects. These facts favour beta-blockers as the first line treatment of children with IH.

Lamivudine resistance in children with chronic hepatitis B.

Currently, although lamivudine (LAM) has a low genetic barrier, only interferon-alpha and LAM are available as a first-line treatment in children with chronic hepatitis B (CHB). LAM is a potent inhibitor of hepatitis B virus-deoxyribonucleic acid (HBV-DNA) polymerase replication by termination of the proviral HBV-DNA chain. LAM has a good safety and tolerability profile in CHB patients with hepatic decompensation. However, the main disadvantages of this HBV reverse transcriptase inhibitor are: (1) pre-existing covalently closed circular DNA cannot be eradicated by LAM, thus relapse after therapy withdrawal is frequent; and (2) although the longer LAM treatment induced the higher seroconversion rate, the risk of viral resistance increased through the selection of YMDD (tyrosine, methionine, aspartate, aspartate) motif. Insufficient suppression of viral replication leads to the emergence of resistant strains that could result in virological breakthrough which is usually followed by biochemical breakthrough. Mutant strains affects additional resistance and cross resistance, leading to drug resistance in a significant number of CHB patients. In this case, efficacy of more powerful anti-viral agents with higher genetic barrier against development of resistance is diminished. Furthermore, strains that are resistant to LAM could bring about vaccine escape mutants, decreasing the efficacy of HBV vaccine. A more potent drug with a high genetic barrier to resistance needs to be approved as the first-line treatment option for CHB in children.

Response to High Dose Imatinib and Long-Term Outcome in Children and Adolescents with Previously Untreated Chronic Myeloid Leukemia in Chronic Phase. the Italian Experience

Abstract Imatinib (IM) is an established first-line treatment for children with chronic myeloid leukemia (CML). However, the most effective dosage of IM and overall management of newly-diagnosed childhood CML in chronic phase (CP) are not well defined. This study was designed to evaluate (a) the response to IM at a dosage equivalent in terms of drug exposure to the 600 mg daily utilized in adults and (b) the long-term outcome in newly-diagnosed children and adolescents with CML. Patients aged <18 years with a diagnosis of CML in CP were treated with IM at a dosage of 340 mg/m2/day. Cytogenetic analyses were planned on bone marrow (BM) cells before and during IM therapy as well as quantitative RT-PCR on peripheral blood (PB) monthly and on BM every 3 months. Partial cytogenetic response (PCyR) was considered as the presence of Ph+ cells between 0 and 35%. Molecular response (MR) was considered as <0.01% BCR-ABL1 IS, while major MR (MMR) was defined as <0.1% BCR-ABL1 IS. This study was approved by the Istitutional Review Boards of each participating Institution. Between December 2002 and February 2014, 41 CML patients in CP (females: 13, males: 28; age <10 years: 13 patients) were recorded from 9 Italian pediatric centers. Twenty-seven patients (66%) have a follow-up >24 months. IM was started in all patients, including 16 with an HLA-matched sibling. The dosage of IM was modulated according to the occurrence of >2 WHO side-effects or response, mainly during the first 6 months of treatment. Forty patients are evaluable for treatment results. Median administered dosage of IM was 309 mg/m2/day, higher in males than in females (326 mg/m2vs 245 mg/m2, p .015) and in those younger than 10 years (314 mg/m2vs 262 mg/m2). Twenty-four patients (60%) experienced isolated or combined side effects: hematologic toxicity (medullary hypoplasia [n=1], neutropenia [n=7] and/or thrombocytopenia [n=6], anemia [n=1]) and/or extra-hematologic toxicity (arthralgia/myalgia [n=8], nausea [n=1], vomiting [n=1], diarrhea [n=1], abdominal pain [n=2], hepatitis [n=1], skin rash [n=2]. Persistent >3 WHO adverse events led to IM discontinuation in 6 patients (15%). At 3 months of IM treatment, hematologic response and PCyR rates were 91% and 54%, respectively; BCR-ABL1 transcript levels <10% were found in 69% and 75% of patients on BM and on PB cells, respectively. At 6 months, 77% of patients was in CCyR; 56% and 66% of patients showed BCR-ABL1 transcript levels <1% on BM and on PB cells, respectively. At 12 months, MMR was detected in 66.4% and 71.4% of patients on BM and on PB cells, respectively; BCR-ABL1 IS <0.0032% was found in 21% and 14% of patients on BM and on PB cells, respectively. All but 1 patient achieved a response. Overall, 94% obtained a CCyR at a median time of 6.4 months. Fourteen of 25 (56%) and 13/17 (76%) evaluable patients obtained a MR on BM and on PB cells at a median time of 13 and 15 months, respectively. Intermittent therapy (IM at the same daily dosage for 3 weeks a month) was started in 6 patients with a sustained MR; thereafter, 2 adolescents with <0.0032% BCR-ABL IS lasting >7years successfully discontinued IM and 2 patients resumed continuous IM because of an increased BCR-ABL transcript. IM was interrupted in 8/33 (24%) responder patients, 4 of them in BCR-ABL1 IS<0.1%, after a median time of 7 months because they underwent an allogeneic stem cell transplant (SCT). Treatment was also discontinued in 6 patients in continuous IM because of a disease recurrence (median response duration: 37 months; range, 21-115). Overall, 12 patients (30%) underwent a SCT after a median of 7.7 months: 8 from an identical sibling (BCR-ABL1 IS <0.1% in 3), 3 from a MUD and 1 from an umbilical cord blood. Three patients, transplanted from an identical sibling, had disease recurrence after 24, 36 and 83 months, respectively. Estimated probabilities of failure-free survival was 50% at 8 years for patients submitted to an SCT and 60% at 10 years for those still receiving IM. At the last follow-up, all patients are alive at a median of 44.6 months. In our experience, IM at a daily dose of 340 mg/m2 is effective in newly-diagnosed CML children with responses rates higher than those reported in children treated with IM at lower dosage. Considering the long-term follow-up, high-dose IM allowed to safely discontinue treatment in some patients with a deep MR; furthermore, it did not worsen the outcome both in patients submitted to a SCT and in those with disease progression or side-effects. Disclosures Saglio: BMS: Consultancy, Fees for occasional speeches Other; Novartis: Consultancy, Fees for occasional speeches, Fees for occasional speeches Other; Pfizer: Consultancy, Fees for occasional speeches, Fees for occasional speeches Other; ARIAD: Consultancy, Fees for occasional speeches, Fees for occasional speeches Other.

Inhaled corticosteroids in children with persistent asthma: dose-response effects on growth.

Background Inhaled corticosteroids (ICS) are the first-line treatment for children with persistent asthma. Their potential for growth suppression remains a matter of concern for parents and physicians. Objectives To assess whether increasing the dose of ICS is associated with slower linear growth, weight gain and skeletal maturation in children with asthma. Search methods We searched the Cochrane Airways Group Specialised Register of trials (CAGR) and the ClinicalTrials.gov website up to March 2014. Selection criteria Studies were eligible if they were parallel-group randomised trials evaluating the impact of different doses of the same ICS using the same device in both groups for a minimum of three months in children one to 17 years of age with persistent asthma. Data collection and analysis Two review authors ascertained methodological quality independently using the Cochrane Risk of bias tool. The primary outcome was linear growth velocity. Secondary outcomes included change over time in growth velocity, height, weight, body mass index and skeletal maturation. Main results Among 22 eligible trials, 17 pairs of groups comparisons were derived from 10 trials (3394 children with mild to moderate asthma), measured growth and contributed data to the meta-analysis. Trials used ICS (beclomethasone, budesonide, ciclesonide, fluticasone or mometasone) as monotherapy or as combination therapy with a long-acting beta2-agonist and generally compared low (50 to 100 μg) versus low to medium (200 μg) doses of hydrofluoroalkane (HFA)-beclomethasone equivalent over 12 to 52 weeks. In the four comparisons reporting linear growth over 12 months, a significant group difference was observed, clearly indicating lower growth velocity in the higher ICS dose group of 5.74 cm/y compared with 5.94 cm/y on lower-dose ICS (N = 728 school-aged children; mean difference (MD)0.20 cm/y, 95% confidence interval (CI) 0.02 to 0.39; high-quality evidence): No statistically significant heterogeneity was noted between trials contributing data. The ICS molecules (ciclesonide, fluticasone, mometasone) used in these four comparisons did not significantly influence the magnitude of effect (X2 = 2.19 (2 df), P value 0.33). Subgroup analyses on age, baseline severity of airway obstruction, ICS dose and concomitant use of non-steroidal antiasthmatic drugs were not performed because of similarity across trials or inadequate reporting. A statistically significant group difference was noted in unadjusted change in height from zero to three months (nine comparisons; N = 944 children; MD 0.15, 95% CI -0.28 to -0.02; moderate-quality evidence) in favour of a higher ICS dose. No statistically significant group differences in change in height were observed at other time points, nor were such differences in weight, body mass index and skeletal maturation reported with low quality of evidence due to imprecision. Authors' conclusions In prepubescent school-aged children with mild to moderate persistent asthma, a small but statistically significant group difference in growth velocity was observed between low doses of ICS and low to medium doses of HFA-beclomethasone equivalent, favouring the use of low-dose ICS. No apparent difference in the magnitude of effect was associated with three molecules reporting one-year growth velocity, namely, mometasone, ciclesonide and fluticasone. In view of prevailing parents’ and physicians’ concerns about the growth suppressive effect of ICS, lack of or incomplete reporting of growth velocity in more than 86% (19/22) of eligible paediatric trials, including those using beclomethasone and budesonide, is a matter of concern. All future paediatric trials comparing different doses of ICS with or without placebo should systematically document growth. Findings support use of the minimal effective ICS dose in children with asthma.

Inhaled corticosteroids in children with persistent asthma: dose-response effects on growth.

Inhaled corticosteroids (ICS) are the first-line treatment for children with persistent asthma. Their potential for growth suppression remains a matter of concern for parents and physicians. To assess whether increasing the dose of ICS is associated with slower linear growth, weight gain and skeletal maturation in children with asthma. We searched the Cochrane Airways Group Specialised Register of trials (CAGR) and the ClinicalTrials.gov website up to March 2014. Studies were eligible if they were parallel-group randomised trials evaluating the impact of different doses of the same ICS using the same device in both groups for a minimum of three months in children one to 17 years of age with persistent asthma. Two review authors ascertained methodological quality independently using the Cochrane Risk of bias tool. The primary outcome was linear growth velocity. Secondary outcomes included change over time in growth velocity, height, weight, body mass index and skeletal maturation. Among 22 eligible trials, 17 group comparisons were derived from 10 trials (3394 children with mild to moderate asthma), measured growth and contributed data to the meta-analysis. Trials used ICS (beclomethasone, budesonide, ciclesonide, fluticasone or mometasone) as monotherapy or as combination therapy with a long-acting beta2-agonist and generally compared low (50 to 100 μg) versus low to medium (200 μg) doses of hydrofluoroalkane (HFA)-beclomethasone equivalent over 12 to 52 weeks. In the four comparisons reporting linear growth over 12 months, a significant group difference was observed, clearly indicating lower growth velocity in the higher ICS dose group of 5.74 cm/y compared with 5.94 cm/y on lower-dose ICS (N = 728 school-aged children; mean difference (MD)0.20 cm/y, 95% confidence interval (CI) 0.02 to 0.39; high-quality evidence): No statistically significant heterogeneity was noted between trials contributing data. The ICS molecules (ciclesonide, fluticasone, mometasone) used in these four comparisons did not significantly influence the magnitude of effect (X(2) = 2.19 (2 df), P value 0.33). Subgroup analyses on age, baseline severity of airway obstruction, ICS dose and concomitant use of non-steroidal antiasthmatic drugs were not performed because of similarity across trials or inadequate reporting. A statistically significant group difference was noted in unadjusted change in height from zero to three months (nine comparisons; N = 944 children; MD 0.15, 95% CI -0.28 to -0.02; moderate-quality evidence) in favour of a higher ICS dose. No statistically significant group differences in change in height were observed at other time points, nor were such differences in weight, bone mass index and skeletal maturation reported with low quality of evidence due to imprecision. In prepubescent school-aged children with mild to moderate persistent asthma, a small but statistically significant group difference in growth velocity was observed between low doses of ICS and low to medium doses of HFA-beclomethasone equivalent, favouring the use of low-dose ICS. No apparent difference in the magnitude of effect was associated with three molecules reporting one-year growth velocity, namely, mometasone, ciclesonide and fluticasone. In view of prevailing parents' and physicians' concerns about the growth suppressive effect of ICS, lack of or incomplete reporting of growth velocity in more than 86% (19/22) of eligible paediatric trials, including those using beclomethasone and budesonide, is a matter of concern. All future paediatric trials comparing different doses of ICS with or without placebo should systematically document growth. Findings support use of the minimal effective ICS dose in children with asthma.

Early and frequent development of ocular hypertension in children with nephrotic syndrome.

Prednisolone, the first-line treatment for children with nephrotic syndrome, causes severe side effects. One of these side effects is ocular hypertension, which can result in severe and permanent visual disturbance. However, the exact prevalence, severity and timing of development of ocular hypertension have yet to be fully explored in this pediatric patient group. In this retrospective cohort study, children with nephrotic syndrome treated with prednisolone for their first episode were analyzed. Intraocular pressure was screened with an iCare® tonometer and confirmed with Goldmann applanation tonometry before the initiation of prednisolone treatment and at 1 and 4weeks thereafter. A total of 26 children with nephrotic syndrome were included in this study, of whom eight (30.8%) required treatment with eye drops for ocular hypertension. The median time interval between the diagnosis of ocular hypertension and start of treatment was 9 (range 5-31) days. At relapse of nephrotic syndrome, all children who had undergone treatment for ocular hypertension in their first episode again required treatment for ocular hypertension. Routine ophthalmologic examination should be conducted from the early phase after the start of prednisolone treatment. In addition, children with episodes of ocular hypertension may be at greater risk of its reappearance with relapse of the nephrotic syndrome.

Are salicylic formulations, liquid nitrogen or duct tape more effective than placebo for the treatment of warts in paediatric patients who present to ambulatory clinics?

Cutaneous warts are common in the general population. Salicylic acid (SA), cryotherapy and duct tape are commonly used to treat warts. Current, high-quality evidence suggests that topical SA is effective compared with placebo, and is the preferred first-line treatment in children due to ease of application and minimal side effects. The evidence does not suggest that cryotherapy is more effective than SA, and it is associated with more side effects. Duct tape has not been shown to be superior to placebo and side effects, including redness, itching, eczema and bleeding, are possible. Treatment of warts for a child should be aimed at reducing symptoms or improving appearance while minimizing side effects. Risks and benefits should be discussed with care providers. Because warts often resolve spontaneously within a period of months to years, it is acceptable to recommend no intervention.

Comparison of rabbit antithymocyte globulin and Jurkat cell-reactive anti-t lymphocyte globulin as a first-line treatment for children with aplastic anemia

The purpose of this study was to investigate the effects of rabbit antihuman thymocyte globulin (R-ATG) and Jurkat cell-reactive anti-T lymphocyte globulin (ATG-F) in the treatment of childhood aplastic anemia (AA) and compare their efficacy and side effects. A total of 53 children with AA were analyzed in the present study, including 32 cases of severe AA, 10 cases of very severe AA and 11 cases of transfusion-dependent nonsevere AA. While receiving immunosuppressive therapy (IST), 29 and 24 patients, all of whom received long-term oral supplement with cyclosporin A (CSA), androgen, and traditional Chinese medicines, were treated with R-ATG and ATG-F, respectively. If necessary, the patients were also given supportive care such as component transfusion and/or infection control. Absolute counts of peripheral blood lymphocyte at various time points were dynamically measured after ATG therapy. According to the International AA Treatment and Effect standards, we found that there were no statistically significant differences in the response rate (70.83% vs. 68.97%, p > 0.05) and the overall survive rate (83.33% vs. 82.76%, p > 0.05) between the ATG-F and R-ATG groups. In addition, no obvious differences were observed between these two groups in the response time, efficacy in severe AA and very severe AA, or the incidence rates of ATG-related adverse reactions. After ATG treatment, the extent of peripheral blood lymphocyte reduction and duration in peripheral blood were similar between the ATG-F and R-ATG groups. The results of this study showed that ATG-F and R-ATG had similar efficacy and adverse reactions in the first-line treatment of childhood AA, despite being derived from different immunogens.

Endoscopic management of vesicoureteral reflux in children in kosova.

Introduction:Vesicoureteral reflux (VUR) in children has been treated with subureteric deflux injection of Deflux (dextranomer hyaluronic acid copolymer) since 2009. The aim of this study was to analyze the results of endoscopic treatment of VUR in our clinic.Methods:Between March 2009 and December 2013, fifty-five children underwent endoscopic subureteral injection of Deflux in 78 ureters. Two months postoperatively voiding cystourethrogram (VCUG) was performed. This study examined the disappearance of VUR and urinary tract infection (UTI) as well as the quality of life during long-term follow-up.Results:The study included 55 patients (40 females and 15 males) with 78 refluxing ureters. There were 22 refluxed ureters altogether and 33 children had a unilateral reflux (two duplicated systems). All patients were treated, from the age 6 months up to 12 years old. The mean age of patients was 5.2 years. There has been no complications, but with few recurrences. In 6 patients (16.6%), endoscopic treatment with deflux was done twice, while in three patients (8.5%), the endoscopic treatment with deflux was performed three times, because of recurrence.Conclusion:We recommend the use of endoscopic Deflux injection as first line treatment for children with VUR. Endoscopic subureteral injection of Deflux is a minimally invasive method for VUR treatment in pediatric patients and is associated with low morbidity.

Cognitive Behavioral Therapy for Treatment of Pediatric Chronic Migraine

Headaches that occur more days than not are prevalent in youth, affecting asmanyas 1 in60childrenandadolescents.1,2 Chronic migraine is defined as frequently recurring episodes of severe pulsating headaches with features such as nausea, vomiting, and sensitivity to light and sound that occur along with daily or near-daily milder headaches.3 The majority of childrenwith this disorder experience substantial impairment in their ability to function at school and to participate in typical physical and social activities.1,4 Yet rarelydo childrenwithchronicmigraineseek treatment.1 If theydid,historically most clinicians had little treatment to offer because of insufficient training inheadachemanagement,5 lackof preventive medications approved by the US Food and Drug Administration for this condition, and limiteddata fromplacebocontrolled randomized trials to guide treatment.6 In this issueof JAMA, the reportbyPowersandcolleagues7 of their randomizedclinical trialofcognitivebehavioral therapy (CBT) for chronic migraine in children and adolescents enhances the evidence on which to base clinical treatment decisions for this population. The investigators randomly assigned 135 children and adolescents (aged 10-17 years; 79% female) having a diagnosis of chronic migraine (based on the criteria of the International Classification of Headache Disorders, 2nd Edition) and a Pediatric Migraine Disability AssessmentScore (PedMIDAS)ofgreater than20points to receiveCBT (n = 64) or headache education (control group; n = 71). Participants in both groups also received standardized dosing of amitriptyline for headache prevention. Of the enrolled patients, 129 completed the 20-week follow-up and 124 completed 12-month follow-up. At the 20week endpoint, therewere significantly greater reductions in days with headache per month in the CBT group (reduced by 11.5 days) compared with the control group (reduced by 6.8 days) and in the PedMIDAS (decreased by 52.7 points for the CBT group vs 38.6 points for the control group). Among children in theCBTgroup, 66%hada clinically significant (≥50%) reduction inheadachedays comparedwith 36%of children in thecontrolgroup.Theauthorsconcludethat their findingssupport the efficacy of CBT in the treatment of chronic migraine in children and adolescents. The study by Powers et al7 is unique in rigor among behavioral intervention trials forpediatric chronicheadache.The study is well described, sufficiently powered, conservatively controlledwitha crediblebehavioral “placebo”condition, and of sufficient duration with atypically excellent participant retention8 to validly judge theprimary findings. Although the contribution of the studymedication amitriptyline to the observed outcomes could not be determined due to the selected researchdesign, the trial quality lends confidence in asserting that superior outcomes inpain anddisability are likely to be observed with CBT (vs only extra headache education) whenused in conjunctionwith a prophylacticmedication for pediatric chronic migraine. Psychological therapies similar in content to the approach investigated in the study by Powers et al7 have a long history of demonstrated efficacy in the treatment of pediatric headache. Meta-analyses of interventions that CBT comprises, suchas instruction in relaxationstrategies (withorwithout biofeedback assistance) and cognitive pain coping skills, have reported an approximately 3-fold greater likelihood of clinically significant improvement inheadache relative to control conditions.9 As such, the suggestion by Powers et al7 that CBT along with medications be considered a first-line treatment for children with chronic migraine has scientific precedents. Firmempirical evidenceof interventionefficacy,however, is rarely sufficient for translation into clinical practice. Whereasprescribing amitriptyline as aprophylactic agent for pediatric chronic migraine is relatively straightforward to implement, a number of patient, clinician, and system variables may limit successful application of the findings of Powers et al7 into practice. First, youth seeking care for headaches are unlikely to follow advice to see a therapist no matter the evidence. Estimates suggest less than half of pediatric patientswithachronicpainconditionwill followthroughwith a physician’s recommendation to pursue CBT.10 Perhaps coincidentally, less than half of the patients assessed for eligibility agreed to participate in the trial by Powers et al,7 with common reasons including distance, time commitment, and preference formedicationmanagement. Adherence in implementing the skills learned in CBT also is necessary for optimal outcomes, yet may be subpar in children and teens11; no dataonpatient adherence inuseof the skills acquired through CBT were included in the results of the trial by Powers et al.7 Second, primary care clinicians may lack the time,12 training,5 or both, necessary to adequately explain the rationale for CBT for headache management to families and their childrenmeeting diagnostic criteria for chronicmigraine. Yet it is unlikely that familieswill pursue anevidence-based treatment without the recommendation by a trusted pediatrician or pediatric neurologist. Unless communicated carefully, suggesting a child see a therapist for headache treatment could inadvertently imply that the origin of chronicmigraine is psyRelated article page 2622 Opinion

Immunosuppressive therapy with horse anti-thymocyte globulin and cyclosporine as treatment for fulminant aplastic anemia in children

Patients with severe aplastic anemia (SAA) and an absolute neutrophil count (ANC) of 0 typically have fatal outcomes. We defined fulminant AA (FAA) as ANC = 0 for at least 2weeks prior to and after immunosuppressive therapy (IST). We analyzed the outcomes of 35 children with FAA among 288 children who enrolled in a prospective study for AA (AA-97 study). AA was classified as FAA (n = 35), very SAA (vSAA; n = 129), or SAA (n = 124). All of the children received the IST with horse anti-thymocyte globulin (ATG) and cyclosporine (CsA). A significantly lower response rate at 6months was seen in children with FAA when compared to those with vSAA or SAA (40.0, 63.6, and 63.7%, respectively; p = 0.027). Of 20 nonresponder patients in the FAA group, 11 were rescued by alternative donor transplantation, and 5 patients showed a late response after 6months. Consequently, no significant difference was noted in overall survival when comparing the FAA, vSAA, and SAA groups (88.5, 95.8, and 96.8%). These findings indicate that IST with ATG and CsA is justified as a first-line treatment for children with FAA who lack a human leukocyte antigen-matched sibling donor.

Infections in Children Admitted with Complicated Severe Acute Malnutrition in Niger

BackgroundAlthough malnutrition affects thousands of children throughout the Sahel each year and predisposes them to infections, there is little data on the etiology of infections in these populations. We present a clinical and biological characterization of infections in hospitalized children with complicated severe acute malnutrition (SAM) in Maradi, Niger.MethodsChildren with complicated SAM hospitalized in the intensive care unit of a therapeutic feeding center, with no antibiotics in the previous 7 days, were included. A clinical examination, blood, urine and stool cultures, and chest radiography were performed systematically on admission.ResultsAmong the 311 children included in the study, gastroenteritis was the most frequent clinical diagnosis on admission, followed by respiratory tract infections and malaria. Blood or urine culture was positive in 17% and 16% of cases, respectively, and 36% had abnormal chest radiography. Enterobacteria were sensitive to most antibiotics, except amoxicillin and cotrimoxazole. Twenty-nine (9%) children died, most frequently from sepsis. Clinical signs were poor indicators of infection and initial diagnoses correlated poorly with biologically or radiography-confirmed diagnoses.ConclusionsThese data confirm the high level of infections and poor correlation with clinical signs in children with complicated SAM, and provide antibiotic resistance profiles from an area with limited microbiological data. These results contribute unique data to the ongoing debate on the use and choice of broad-spectrum antibiotics as first-line treatment in children with complicated SAM and reinforce the call for an update of international guidelines on management of complicated SAM based on more recent data.

A Nine Case Series of Ultrasound-Guided Hydrostatic Reduction of Intussusception by Saline Enema

Non-surgical reduction of the intussusception is the first line treatment in children with intussusception. Among various radiological reduction techniques, barium enema reduction of the intussusception under fluoroscopy has been widely used in Thailand while pneumatic reduction under fluoroscopy has become popular in teaching hospitals. To our knowledge, ultrasound-guided hydrostatic reduction of the intussusception by saline enema (UGHSE) has never been used in Thailand. We reported 9 cases using UGHSE with 100% success rate without complication.

Asthma Therapy in Pediatric Patients: A Systematic Review of Treatment With Montelukast Versus Inhaled Corticosteroids

IntroductionInhaled corticosteroids (ICS) are a first-line treatment for mild persistent asthma, but montelukast (MON) monotherapy also has been beneficial. The aim of this review is to evaluate current evidence comparing MON versus ICS monotherapy in pediatric patients. MethodA systematic review was conducted of randomized controlled trials evaluating treatment of mild to moderate persistent asthma in which MON was compared with ICS monotherapy in children aged 2 to 18 years. PubMed, the Cumulative Index to Nursing and Allied Health Literature, and the Institute of Scientific Information's Web of Knowledge were searched using key words asthma, MON, and ICS. Studies that met inclusion criteria were appraised for quality. ResultsOf 214 identified studies, eight met inclusion criteria and seven were deemed high quality. Study sample sizes ranged from 62 to 994, 88% were multi-site, and the average length of follow-up was 8.2 months. Asthma symptoms improved with both therapies. Four studies reported superiority of ICS compared with MON; the remaining studies showed no differences between therapies. DiscussionThese results are consistent with the National Asthma Education and Prevention Program (2007) recommendation that ICS therapy should be first-line treatment in children with mild to moderate persistent asthma.

Polyarthritis Caused by Methimazole in Two Japanese Patients with Graves’ Disease

In many countries, methimazole (MMI) therapy is the first-line treatment in children with Graves’ disease (GD). The rate of side effects of antithyroid drugs (ATDs) in children has been reported to range between 6% and 35%. Of these side effects, polyarthritis is uncommon but serious, and can also develop as a part of the antineutrophil cytoplasmic antibody-associated vasculitis that is induced by ATDs. Here, we describe two GD girl patients aged 15 years and 11 years who developed polyarthritis. The onset of polyarthritis in these patients was 24 days and 28 days after the initiation of MMI therapy, respectively. MMI was suspected of causing the polyarthritis in the two patients and was withdrawn. The symptoms of polyarthritis disappeared rapidly following cessation of treatment. Subsequently, one patient was treated with 131I therapy and the other patient was subjected to thyroidectomy. Although it rarely occurs in pediatric GD patients, severe polyarthritis is a serious side effect of MMI and is an indication for prompt cessation of treatment. Conflict of interest:None declared.