Suppression In Children Research Articles

Adrenocortical Suppression in Children with Nephrotic Syndrome Treated with Low-Dose Alternate Day Corticosteroids.

Corticosteroids form the mainstay of therapy for all forms of nephrotic syndrome. The long-term use of this medication is associated with serious side effects including adrenocortical suppression. The primary objective of this study was to identify adrenocortical suppression (assessed by single morning serum cortisol levels) in children with nephrotic syndrome on treatment with low-dose alternate day steroids. This cross-sectional study was conducted in the Department of Pediatrics in a tertiary care hospital from January 2014 to January 2015. Seventy children (1–18 years) with nephrotic syndrome (steroid sensitive and resistant) who were in remission and on low-dose alternate day steroids for at least 8 weeks or had received steroids of 2 mg/kg/d for at least 2 weeks in the last 1 year (infrequent relapsers) were enrolled. Relevant history was taken, clinical examination was done and blood samples were drawn for serum cortisol, lipid profile, kidney function tests, fasting blood sugar, glycated hemoglobin (HbA1c), and serum albumin. Forty percent (28/70) children had adrenocortical suppression as assessed by low morning serum cortisol levels. The mean serum cortisol levels were 188 nmol/L and were significantly lower in frequently relapsing individuals (85.9 nmol/L) as compared to other types of nephrotic syndrome (P = 0.05). The prevalence of adrenocortical suppression was higher in steroid-resistant patients (57%) as compared to 28% in frequently relapsing and 11% in steroid-dependent patients. Fifty-seven percent of patients with adrenocortical suppression had short stature while 50% had obesity. All individuals had normal serum HbA1c levels. The cumulative steroid doses and total duration of corticosteroid therapy were significantly higher in patients with adrenocortical suppression. Children with nephrotic syndrome treated with low-dose alternate day steroids have a high prevalence of adrenocortical suppression on screening with single morning cortisol sample. Those with frequently relapsing or steroid-resistant diseases are at a higher risk of suppression.

A systematic review of the safety and efficacy of systemic corticosteroids in atopic dermatitis

Systemic corticosteroids are often used to treat atopic dermatitis (AD). However, few studies have assessed the safety and efficacy of systemic corticosteroids in AD. To systematically review the literature on efficacy and safety of systemic corticosteroid use (oral, intramuscular, and intravenous) in AD. PubMed, Embase, Medline, Scopus, Web of Science, and Cochrane Library were searched. We included systematic reviews, guidelines, and treatment reviews of systemic corticosteroid use among patients of all ages with a diagnosis of AD (52 reviews and 12 studies). There was general consensus in the literature to limit the use of systemic steroids to short courses as a bridge to steroid-sparing therapies. Systemic side effects include growth suppression in children, osteoporosis, osteonecrosis, adrenal insufficiency, Cushing syndrome, hypertension, glucose intolerance, diabetes, gastritis, gastroesophageal reflux, peptic ulcer disease, weight gain, emotional lability, behavioral changes, opportunistic infections, cataracts, glaucoma, myopathy, myalgia, dysaesthesia, pseudotumor cerebri, hyperlipidemia, malignancy, thrombosis, skin atrophy, sleep disturbance, and rebound flaring. Baseline clinical severity, corticosteroid delivery and dose, and treatment response were reported incompletely and heterogeneously across studies. Evidence is not strong enough to determine optimal delivery or duration of systemic corticosteroids in AD.

The effect of community-based support for caregivers on the risk of virological failure in children and adolescents with HIV in Harare, Zimbabwe (ZENITH): an open-label, randomised controlled trial

SummaryBackgroundChildren and adolescents have poorer HIV treatment outcomes than adults. We aimed to assess the effect of community-based support for caregivers of HIV-infected children and adolescents, who are key mediators to children engaging with care, on treatment outcomes.MethodsIn this open-label, randomised contolled trial, we recruited children aged 6–15 years with newly-diagnosed HIV attending primary health-care clinics in Harare, Zimbabwe. Children were randomly assigned to receive decentralised primary health-care clinic-based HIV care (control group), according to national guidelines for 18 months, or decentralised care plus structured support visits by trained community health workers (intervention group) according to national guidelines for 18 months. Primary outcomes were the proportion of participants who died or had an HIV viral load of 400 copies per mL or higher at 12 months after antiretroviral therapy (ART) initiation (among those who started ART within 6 months of enrolment); and the proportion who missed two or more scheduled clinic visits by 18 months post-enrolment (among all participants). Analyses were complete-case, modified-intention-to-treat. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201212000442288.FindingsBetween January, 2013, and January, 2015, 470 participants tested HIV-positive at seven study primary health-care clinics and were screened for eligibility. Of the 334 eligible children and adolescents, 166 were randomly assigned to the intervention group and 168 to the control group. The median age of participants was 11 years (IQR 8–13) and 178 (53%) were girls. Among the 238 participants who started ART within 6 months of enrolment, the proportion who died or had a viral load of 400 copies/mL or higher at 12 months post-ART initiation was significantly lower in the intervention group than in the control group (31 [33%] of 94 participants vs 42 [49%] of 86 participants, respectively, adjusted odds ratio [aOR] 0·46, 95% CI 0·23–0·89; p=0·02). The proportion of children missing two or more scheduled visits was similar in the intervention group and control group (27 [17%] of 155 vs 30 [18%] of 165, aOR 0·92, 95% CI 0·49–1·74; p=0·79). One participant withdrew from the trial 240 days after enrolment and 12 died during follow-up (five in the intervention group; seven in the control group).InterpretationCommunity-based support for caregivers has high potential for scalability and could have a substantial effect on HIV virological suppression in children and adolescents, a group with disproportionately poor treatment outcomes.FundingWellcome Trust.

Ictal Symmetric Tonic Extension Posturing and Postictal Generalized EEG Suppression Arising From Sleep in Children With Epilepsy

BackgroundThe identification of a biomarker for sudden unexpected death in epilepsy (SUDEP) has the potential to save lives. Generalized convulsive seizures and postictal generalized suppression on electroencephalography (EEG) most often precede sudden unexpected death in epilepsy (SUDEP) and are potential biomarkers. We identify the EEG and seizure characteristics associated with postictal generalized EEG suppression in children with epilepsy. MethodsVideo EEGs were reviewed for seizure type, duration and semiology, and electrographic features. To identify predictors of postictal generalized EEG suppression, we identified 40 children with generalized convulsive seizures from a group of 399 patients who experienced an electroclinical seizure during video-EEG. Seventy-seven generalized convulsive seizures with and without postictal generalized EEG suppression were anayzed. ResultsAge of seizure onset was older in 19 children with postictal generalized EEG suppression (mean 6.8 years old, 95% CI [4.7-8.9]) than in 21 without postictal generalized EEG suppression (3.0 years old, [1.1-4.1], P = 0.041). Postictal generalized EEG suppression occurred significantly more often from sleep than awake (point of estimate 16.67; 95% CI [0.97-32.36], P < 0.038). Shorter duration of the clonic phase (−0.76; [−1.338, −0.133], P = 0.018) was significantly associated with postictal generalized EEG suppression. Ictal symmetric tonic extension posturing significantly increased the odds of postictal generalized EEG suppression (42.94; [18.77, 67.12], P = 0.001). All 15 generalized convulsive seizures with a terminal burst-suppression pattern were followed by postictal generalized EEG suppression in contrast to 19 of 62 generalized convulsive seizures without burst-suppression (15.32, P < 0.001). ConclusionsIctal decerebrate-like symmetric tonic extension posturing with shorter clonic phase and a terminal burst-suppression pattern identify malignant generalized convulsive seizures, associated with postictal generalized EEG suppression and a potentially increased risk of sudden unexpected death in epilepsy.

Binocular Therapy for Childhood Amblyopia Improves Vision Without Breaking Interocular Suppression.

Amblyopia is a common developmental visual impairment characterized by a substantial difference in acuity between the two eyes. Current monocular treatments, which promote use of the affected eye by occluding or blurring the fellow eye, improve acuity, but are hindered by poor compliance. Recently developed binocular treatments can produce rapid gains in visual function, thought to be as a result of reduced interocular suppression. We set out to develop an effective home-based binocular treatment system for amblyopia that would engage high levels of compliance but that would also allow us to assess the role of suppression in children's response to binocular treatment. Balanced binocular viewing therapy (BBV) involves daily viewing of dichoptic movies (with "visibility" matched across the two eyes) and gameplay (to monitor compliance and suppression). Twenty-two children (3-11 years) with anisometropic (n = 7; group 1) and strabismic or combined mechanism amblyopia (group 2; n = 6 and 9, respectively) completed the study. Groups 1 and 2 were treated for a maximum of 8 or 24 weeks, respectively. The treatment elicited high levels of compliance (on average, 89.4% ± 24.2% of daily dose in 68.23% ± 12.2% of days on treatment) and led to a mean improvement in acuity of 0.27 logMAR (SD 0.22) for the amblyopic eye. Importantly, acuity gains were not correlated with a reduction in suppression. BBV is a binocular treatment for amblyopia that can be self-administered at home (with remote monitoring), producing rapid and substantial benefits that cannot be solely mediated by a reduction in interocular suppression.

Knemometry Assessment of Short-term Growth in Children With Asthma Receiving Fluticasone Furoate for 2 Weeks: A Randomized, Placebo-controlled, Crossover Trial

PurposeA dry powder inhaler formulation of the inhaled corticosteroid fluticasone furoate (FF) is being evaluated for use in children. An important potential risk associated with the use of inhaled corticosteroids in children is growth suppression. Therefore, the aim of this study was to assess the short-term lower leg growth in children with asthma treated for 2 weeks with inhaled FF versus placebo from the ELLIPTA inhaler. MethodsPrepubertal children with persistent asthma (n = 60; aged 5 to <12 years) were recruited into a randomized, double-blind, placebo-controlled, 2-way crossover, noninferiority study. The study consisted of four 2-week periods: run-in, 2 treatment periods, 1 washout period, and a 1-week follow-up period. Interventions were FF 50 µg and placebo once daily in the evening. Lower leg length was measured by using knemometry. FindingsThe randomized ITT population comprised 36 boys and 24 girls with a mean age of 8.7 (standard deviation, 1.5; range, 5–11) years; 58% had a duration of asthma ≥5 years. Fifty-eight subjects completed both treatment periods. The least squares mean growth rate was 0.31 mm/week during treatment with FF and 0.36 mm/week during the placebo period. The difference in adjusted least squares mean growth rates between FF and placebo was –0.052 mm/week with a 95% CI of –0.122 to 0.018. This finding was greater than the prespecified noninferiority margin of –0.20 mm/week. The overall incidence of adverse events was 35% with placebo and 22% with FF. ImplicationsInhaled FF 50 µg provided once daily for 2 weeks was noninferior to placebo in terms of effects on short-term lower leg growth in children with asthma. To further quantify the risk of growth suppression in children, intermediate-term growth studies should be conducted. Inhaled FF 50 µg was well tolerated in this study population. ClinicalTrials.gov identifier: NCT02502734.

Interocular suppression in children with deprivation amblyopia

In patients with anisometropic or strabismic amblyopia, interocular suppression can be minimized by presenting high contrast stimulus elements to the amblyopic eye and lower contrast elements to the fellow eye. This suggests a structurally intact binocular visual system that is functionally suppressed. We investigated whether suppression can also be overcome by contrast balancing in children with deprivation amblyopia due to childhood cataracts. To quantify interocular contrast balance, contrast interference thresholds were measured using an established dichoptic global motion technique for 21 children with deprivation amblyopia, 14 with anisometropic or mixed strabismic/anisometropic amblyopia and 10 visually normal children (mean age mean=9.9years, range 5–16years). We found that interocular suppression could be overcome by contrast balancing in most children with deprivation amblyopia, at least intermittently, and all children with anisometropic or mixed anisometropic/strabismic amblyopia. However, children with deprivation amblyopia due to early unilateral or bilateral cataracts could tolerate only very low contrast levels to the stronger eye indicating strong suppression. Our results suggest that treatment options reliant on contrast balanced dichoptic presentation could be attempted in a subset of children with deprivation amblyopia.

Virological suppression in children and adolescents is not influenced by genotyping, but depends on optimal adherence to antiretroviral therapy

ObjectiveTo evaluate the virological outcomes in children and adolescents infected with HIV-1 in Salvador, Bahia according to genotyping results. MethodsWe retrospectively evaluated the rates of virological suppression of children and adolescents submitted to HIV-1 genotyping test from January/2008 to December/2012. The participants were followed in the two referral centers for pediatric AIDS care, in Salvador, Brazil. Resistance mutations, drug sensitivity profiles, and viral subtypes were analyzed using the Stanford HIV-1 Drug Resistance Database. Adherence was estimated by drugs withdrawal at pharmacies of the two sites. Results101 subjects were included: 35 (34.6%) were drug-naïve, and the remaining 66 were failing ART. In drug-naïve group, 3 (8.6%), presented with NNRTIs resistance mutations, along with polymorphic mutations to PIs in most (82.8%) of them. Among the failing therapy group, we detected a high frequency (89.4%) of resistance mutations to PIs, NRTI (84.8%), and NNRTI (59.1%). Virological suppression after introduction/modification of genotyping-guided ART was achieved only for patients (53.1%) with drug withdrawal over 95%. Main detected HIV-1 subtypes were B (67.3%), F (7.9), C (1.9%), and recombinant forms (22.9%). ConclusionsDespite the use of genotyping tests in guidance of a more effective antiretroviral regimen, poor adherence to ART seems to be the main determinant of low virological suppression rate for children and adolescents, in Salvador, Brazil.

Adrenal suppression in children treated with swallowed fluticasone and oral viscous budesonide for eosinophilic esophagitis.

BackgroundAdrenal suppression (AS), a glucocorticoid (GC) side effect associated with significant morbidity, is well described related to inhaled corticosteroid therapy for asthma. Swallowed topical glucocorticoid therapy is the main pharmacotherapy treatment for eosinophilic esophagitis (EoE) and therefore children with EoE are potentially at increased risk of AS.MethodsIn this prospective cohort study, we included children and youth <18 years diagnosed with EoE and treated with swallowed fluticasone or oral viscous budesonide for more than 1 month. First morning cortisol and low dose adrenocorticotropic hormone stimulation test (LDST) were performed 2 weeks following GC discontinuation. AS was defined as an abnormal LDST result (cortisol peak <500 nmol/L). We determined the prevalence and duration of AS related to swallowed topical GC therapy in EoE by LDST, as well as the diagnostic accuracy of first morning cortisol compared to LDST.ResultsOf 29 participants enrolled, 26 (89.7 %) received oral viscous budesonide and 3 (10.3 %) received swallowed fluticasone. Nineteen (65.5 %) participants had AS. Median duration of AS was 43 weeks. Five (17.2 %) participants had persistent AS at 12 months. There were no identifiable risk factors for the development of AS. First morning cortisol was highly specific but had poor sensitivity for detection of AS.ConclusionsThe majority of children with EoE had AS after discontinuation of swallowed topical GC therapy. Stress steroids should be considered in children treated with swallowed topical GC therapy for EoE, even after GC discontinuation, to prevent possible adrenal crisis.Electronic supplementary materialThe online version of this article (doi:10.1186/s13223-016-0154-9) contains supplementary material, which is available to authorized users.

Measuring cognitive reappraisal and expressive suppression in children: A parent-rating version of the emotion regulation questionnaire

The frequency of using cognitive reappraisal and expressive suppression strategies to regulate emotions has been associated with social-emotional adjustment. The aim of the present study was to evaluate the Parent-Rating Emotion Regulation Questionnaire (P-ERQ), a parent-rating version of the Emotion Regulation Questionnaire (ERQ) in children aged five to six years. Children from Germany (N = 112) and the U.S. (N = 59) participated. Confirmatory factor analyses of P-ERQ data from Germany indicated a two-factor structure that closely reflected the factor structure of the adult ERQ with adequate scale reliabilities. Correlations with a measure of coping strategies supported the convergent validity of the P-ERQ. Cross-country measurement invariance analyses between samples from Germany and the U.S. suggested partial scalar invariance for the cognitive reappraisal subscale and metric invariance for the expressive suppression subscale. Findings provide preliminary evidence that the P-ERQ can be recommended for use in developmental research.

Weekends-off efavirenz-based antiretroviral therapy in HIV-infected children, adolescents, and young adults (BREATHER): a randomised, open-label, non-inferiority, phase 2/3 trial

SummaryBackgroundFor HIV-1-infected young people facing lifelong antiretroviral therapy (ART), short cycle therapy with long-acting drugs offers potential for drug-free weekends, less toxicity, and better quality-of-life. We aimed to compare short cycle therapy (5 days on, 2 days off ART) versus continuous therapy (continuous ART).MethodsIn this open-label, non-inferiority trial (BREATHER), eligible participants were aged 8–24 years, were stable on first-line efavirenz with two nucleoside reverse transcriptase inhibitors, and had HIV-1 RNA viral load less than 50 copies per mL for 12 months or longer. Patients were randomly assigned (1:1) to remain on continuous therapy or change to short cycle therapy according to a computer-generated randomisation list, with permuted blocks of varying size, stratified by age and African versus non-African sites; the list was prepared by the trial statistician and randomisation was done via a web service accessed by site clinician or one of the three coordinating trials units. The primary outcome was the proportion of participants with confirmed viral load 50 copies per mL or higher at any time up to the 48 week assessment, estimated with the Kaplan-Meier method. The trial was powered to exclude a non-inferiority margin of 12%. Analyses were intention to treat. The trial was registered with EudraCT, number 2009-012947-40, ISRCTN, number 97755073, and CTA, number 27505/0005/001-0001.FindingsBetween April 1, 2011, and June 28, 2013, 199 participants from 11 countries worldwide were randomly assigned, 99 to the short cycle therapy and 100 to continuous therapy, and were followed up until the last patient reached 48 weeks. 105 (53%) were men, median age was 14 years (IQR 12–18), and median CD4 cell count was 735 cells per μL (IQR 576–968). Six (6%) patients assigned to the short cycle therapy versus seven (7%) assigned to continuous therapy had confirmed viral load 50 copies per mL or higher (difference −1·2%, 90% CI −7·3 to 4·9, non-inferiority shown). 13 grade 3 or 4 events occurred in the short cycle therapy group and 14 in the continuous therapy group (p=0·89). Two ART-related adverse events (one gynaecomastia and one spontaneous abortion) occurred in the short cycle therapy group compared with 14 (p=0·02) in the continuous therapy group (five lipodystrophy, two gynaecomastia, one suicidal ideation, one dizziness, one headache and syncope, one spontaneous abortion, one neutropenia, and two raised transaminases).InterpretationNon-inferiority of maintaining virological suppression in children, adolescents, and young adults was shown for short cycle therapy versus continous therapy at 48 weeks, with similar resistance and a better safety profile. This short cycle therapy strategy is a viable option for adherent HIV-infected young people who are stable on efavirenz-based ART.FundingUK National Institute for Health Research Health Technology Assessment; UK Medical Research Council; European Commission; PENTA Foundation; INSERM SC10-US19, France.

Attentional Selection and Suppression in Children With Attention-Deficit/Hyperactivity Disorder

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with prominent impairments in directing and sustaining attention. The aim of this study was to identify the neurophysiologic bases of attention deficits in ADHD, focusing on electroencephalography markers of attentional selection (posterior contralateral N2 [N2pc]) and suppression (distractor positivity [PD]). MethodsThe electroencephalography data were collected from 135 children 9–15 years old with and without ADHD while they searched for a shape target in either the absence (experiment 1) or the presence (experiment 2) of a salient but irrelevant color distractor. ResultsIn experiment 1, the shape target elicited a smaller N2pc in children with ADHD (n = 38) compared with typically developing children (n = 36). The smaller N2pc amplitude predicted higher levels of inattentive symptoms in children with ADHD. Moreover, the target-elicited N2pc was followed by a positivity in typically developing children but not in children with ADHD. In experiment 2, the salient but irrelevant color distractor elicited a smaller PD component in children with ADHD (n = 32) compared with typically developing children (n = 29). The smaller PD predicted higher inattentive symptom severity as well as lower behavioral accuracy in children with ADHD. ConclusionsThe correlation between N2pc/PD amplitudes and ADHD symptom severity suggests that these signals of attentional selection and suppression may serve as potential candidates for neurophysiologic markers of ADHD. Our findings provide a neurophysiologic basis for the subjective reports of attention deficits in children with ADHD and highlight the importance of spatial attention impairments in ADHD.

Adrenal Suppression in Pediatric Patients during Treatment for Acute Lymphoblastic Leukemia

Background: Hypothalamic-pituitary-adrenal (HPA) axis suppression is a form of adrenal insufficiency that can be found following the use of corticosteroids. Individuals with adrenal insufficiency may have non-specific symptoms or even no regular symptoms, however if presented with a physiologic stress such as infection, injury, or surgery, they are at risk of adrenal crisis. Adrenal crisis typically manifests with hypoglycemia, hypotension and critical illness; this condition is associated with significant morbidity and even mortality. Children being treated for leukemia are at increased risk of infection and may require surgical procedures, thus putting them at risk of adrenal crisis in the context of adrenal suppression.It is known that adrenal suppression exists in the short term after the induction phase of treatment in patients with acute lymphoblastic leukemia (ALL), but the prevalence and duration of suppression is still not fully understood. In addition, adrenal suppression has not been specifically evaluated during the maintenance phase of therapy. During maintenance there may be ongoing adrenal suppression from steroid use in induction, or new suppression from steroid use for maintenance therapy itself. There does not yet exist an accepted protocol to monitor for adrenal insufficiency in ALL. Knowing the prevalence and duration of adrenal suppression in maintenance will enable care teams to better recognize and manage the condition, potentially preventing significant morbidity and mortality.Methods: All cases of ALL treated at the Children's Hospital of Eastern Ontario from 2000 to 2014 were retrospectively reviewed for adrenal suppression. Patient characteristics, clinical features, laboratory data, treatment protocol utilized, adverse events and outcomes were examined.Results: 176 patients were diagnosed with new ALL at The Children's Hospital of Eastern Ontario between 2000 and 2014. Prompted by clinical suspicion, 24 had testing done to investigate for adrenal suppression during this time period. 9 of those patients had cortisol levels indicative of adrenal suppression and required further management for the same. Adrenal suppression was identified in early phases of treatment for ALL. Adrenal suppression was also identified in patients during the maintenance phase of treatment. Many more patients had symptoms that could be attributed to adrenal suppression, but never had cortisol levels tested.Conclusion: Adrenal suppression is found in children being treated for ALL, including during the maintenance phase of therapy. Adrenal suppression may have been present in greater numbers of children, but no routine testing protocol exists to identify these patients. Identifying and reviewing cases of adrenal suppression in children during treatment for ALL, including the maintenance phase, gives a better understanding of the risk of HPA axis suppression in this population. This study also provides background data for the development of a prospective study to further look at adrenal suppression in the maintenance phase of ALL. These studies will guide development of a testing protocol to better identify and manage adrenal suppression, thereby reducing its morbidity and mortality, in children being treated for ALL. DisclosuresNo relevant conflicts of interest to declare.

Adrenal Suppression in Children Treated With Oral Viscous Budesonide for Eosinophilic Esophagitis.

We sought to determine the prevalence of adrenal suppression (AS) in children with eosinophilic esophagitis treated with oral viscous budesonide (OVB). This was a retrospective review of a quality assurance initiative, whereby all children in our center treated with OVB for ≥3 months were referred over an 18-month time frame for endocrine assessment including 1 μg adrenocorticotropic hormone stimulation test. Fourteen of 19 children complied with the referral; of these 14 children, 6 (43%) had suboptimal stimulated cortisol (range 343-497 nmol/L, mean [±SD] 424.7 nmol/L [±52.4], normal ≥500 nmol/L). There was no significant association to treatment duration, dose, or concomitant use of inhaled/nasal corticosteroids. This study suggests that children treated with OVB may be at risk for AS.

Adrenal Suppression in EoE Treated With Budesonide?

See “Adrenal Suppression in Children Treated With Oral Viscous Budesonide for Eosinophilic Esophagitis” by Panagiotopoulos et al on page 190. In this issue of the Journal of Pediatric Gastroenterology and Nutrition, Panagiotopoulos et al (1) report on the results of a quality assurance (QA) project conducted in children with eosinophilic esophagitis (EoE) treated with budesonide. They disclose evidence that adrenal suppression may result from administering therapeutic doses of budesonide for relatively short (<3 months and longer) time periods. During the last decade, the number of children being diagnosed as having EoE has greatly increased. A full understanding of the implications of the diagnosis is lacking. Therefore, an appreciation of the risks and benefits of any 1 therapy, such as glucocorticoids (GCs), is also unclear. That the study was undertaken as a QA project raises issues both of its scientific value and its place in a scientific peer-reviewed journal. Readers should take note that this is not a rigorously designed prospective study of the type all editors like to publish. It does however have a place as a “hypothesis generating” or (as described) a “pilot” study. The authors have felt appropriately compelled to bring to our attention the potential risks inherent in a treatment regarded as relatively benign. Budesonide treats the symptoms of EoE effectively. It is a GC, but because it is rapidly metabolized in the liver, it is considered less likely to result in adverse effects associated with the systemic use of other GCs. It has never been suggested that budesonide is completely safe, but it is possible that clinicians have become too comfortable with its safety profile. The introduction of GC as therapy for various clinical conditions started in the 1950s (2). Currently, they are used as physiologic replacement in adrenal insufficiency and pharmacologic treatment in a variety of conditions including rheumatologic diseases, nephrotic syndrome, asthma, inflammatory bowel diseases, and EoE. As a general rule, treatment with GC requires close monitoring for both undertreatment and overtreatment. Undertreatment can result in adrenal insufficiency, and overtreatment may lead to growth suppression, iatrogenic Cushing syndrome, and hypothalamic-pituitary-adrenal (HPA) axis suppression/secondary adrenal insufficiency. HPA axis suppression can occur with the use of GC therapy of >2 weeks duration, which exceeds physiological doses (the normal endogenous cortisol secretory rate is 6–8 mg · m−2 · day−1 in children and adults (3,4)). HPA axis suppression has been reported in prolonged systemic, topical, and intralesional GC therapy (2,5). The low-dose 1-μg adrenocorticotropic hormone test used by the authors is more sensitive than the standard-dose (250 μg) test (2,6–8); thus, if the findings reported are confirmed, then the screening and testing for secondary adrenal insufficiency in patients being treated with budesonide for an extended time period is warranted. Also, stringent guidelines for the use of budesonide might be considered. The authors did not find significant association with the treatment duration, dose, or concomitant use of inhaled/nasal corticosteroids. This should be interpreted with caution because of the small sample size and study design (or perhaps lack of design.) Other risk factors for adrenal suppression may include efficiency of gastrointestinal absorption related to diet, gastric acidity, bowel transit time, and interindividual sensitivity to GC related to genetic factors (9). A prospective study measuring adrenal suppression in EoE patients matched for disease extent and randomized to receive either budesonide or a nonsteroid treatment is warranted to determine the significance of the findings disclosed. The early symptoms of secondary adrenal insufficiency can be too subtle to note, but until the true incidence and extent of adrenal suppression is known, it is worthy of consideration to provide hydrocortisone supplementation in times of stress (such as major surgery) to any patient who has been treated with budesonide for 3 months in the last year.

International agricultural research to reduce food risks: case studies on aflatoxins

Despite massive expansion of human and livestock populations, fuelled by agricultural innovations, nearly one billion people are hungry and 2 billion are sickened each year from the food they eat. Agricultural and food systems are intimately connected to health outcomes, but health policy and programs often stop at the clinic door. A consensus is growing that the disconnection between agriculture, health and nutrition is at least partly responsible for the disease burden associated with food and farming. Mycotoxins produced by fungi are one of the most serious food safety problems affecting staple crops (especially maize and groundnuts). Aflatoxins, the best studied of these mycotoxins, cause around 90,000 cases of liver cancer each year and are strongly associated with stunting and immune suppression in children. Mycotoxins also cause major economic disruptions through their impacts on trade and livestock production. In this paper we use the case of fungal toxins to explore how agricultural research can produce innovations, understand incentives and enable institutions to improve, simultaneously, food safety, food accessibility for poor consumers and access to markets for smallholder farmers, thus making the case for research investors to support research into agricultural approaches for enhancing food safety in value chains. We first discuss the evolution of food safety research within the CGIAR. Then we show how taking an epidemiological and economic perspective on aflatoxin research connects health and nutrition outcomes. Finally, we present three case studies illustrating the traditional strengths of CGIAR research: breeding better varieties and developing new technologies.

The Effect of Viola odorata Flower Syrup on the Cough of Children With Asthma

This study aimed to investigate the effect of violet syrup on cough alleviation in children with intermittent asthma. In a parallel, double-blind, randomized controlled trial, 182 children aged 2 to 12 years with intermittent asthma were randomly assigned 1:1 to receive violet syrup or placebo along with the common standard treatments in both groups (short-acting β-agonist). Both groups were evaluated in terms of the duration until cough suppression was achieved. No significant difference was observed in basic characteristics. The duration lasting to yield more than 50% cough reduction and 100% cough suppression was significantly less in the violet syrup group compared to placebo (P = .001, P < .001, respectively). There was no significant difference in therapeutic effects between boys and girls. There was a significant inverse correlation between the age of children and rate of cough alleviation and suppression by violet syrup. This study showed that the adjuvant use of violet syrup with short-acting β-agonist can enhance the cough suppression in children with intermittent asthma.

Signal pathway defects of Toll-like receptors 2-p38 mitogen activated protein kinase signal pathway defects and immune suppression in children with measles

Objective To investigate the expression of Toll-like receptors 2(TLR2)mRNA, p38 mitogen activated protein kinase(p38 MAPK)mRNA and cytokine in peripheral blood of children with measles and to study the effect and possible mechanism for TLR2-p38 MAPK signal pathway defects on immune suppression in the children with measles during acute phase. Methods Thirty children with measles hospitalized in the department of infectious diseases from June 2012 to July 2013 were enrolled into the measles group, and 30 healthy children were chosen as the healthy control group.The mRNA expressions of TLR and p38 MAPK in peripheral blood mononuclear cells (PBMC)were detected by reverse transcription-polymerase chain reaction (RT-PCR). The protein levels of interferon-γ(IFN-γ), tumor necrosis factor-β(TNF-β), interleukin(IL)-12, IL-6 and IL-10 in plasma were measured by using enzyme linked immunosorbent assay (ELISA), and flow cytometry (FCM)was applied to detect the percentage of lymphocyte subpopulation.The serum IgG, IgA and IgM levels were detected by velocity scatter turbidimetry. Results (1)The expressions of TLR2 mRNA and p38 MAPK mRNA in the measles group were both significantly lower than those in the healthy control group (all P 0.05). Conclusions The mRNA expressions of TLR2 and p38 MAPK are low in PBMC in the measles children during acute phase.There are different degrees of suppression of cell immunity, humoral immune and cytokines disorder in children with measles.Defects of TLR2-p38 MAPK signal pathway may cause the formation of measles immune suppression. Key words: Measles; Toll-like receptors 2; p38 mitogen activated protein kinase; Immune suppression; Child

High incidence of adrenal suppression in children with Kawasaki disease treated with intravenous immunoglobulin plus prednisolone

Combination treatment with intravenous immunoglobulin (IVIG) plus prednisolone, newly designed for children with severe Kawasaki disease (KD), reduces coronary artery abnormalities significantly. As prednisolone is administered for approximately 20 days in this regimen, we examined whether adrenal function of the treated patients is suppressed. A prospective study was performed at one medical institution in 21 children with KD (age range 0.3-10.4 years, median 3.1 years) who were treated with the regimen between February and June, 2012. We assessed cortisol and ACTH values before the initiation and after the cessation of prednisolone administration as well as peak cortisol and ACTH values at corticotropin-releasing hormone (CRH) stimulation tests, which were repeated 0, 2, and 6 months after the treatment. Morning cortisol and ACTH values after the cessation of prednisolone treatment were suppressed. Peak cortisol values at the first CRH stimulation test ranged from 5.1 to 25.4 μg/dL and were less than 20 μg/dL in 17 of 21 patients, but were restored to more than 14.6 μg/dL in all patients by 6 months after the prednisolone treatment. A significant positive correlation was observed between cortisol values at 09:00 h after the prednisolone treatment and peak cortisol values at the following CRH stimulation test (r = 0.727, p < 0.001). We conclude that adrenal suppression can occur in a high proportion of children with KD treated with IVIG plus prednisolone, despite rather short duration and relatively small amounts of administered glucocorticoids.

CSACI position statement: systemic effect of inhaled corticosteroids on adrenal suppression in the management of pediatric asthma.

Asthma is a chronic inflammatory disease of the airways that affects a growing number of children and adolescents. Inhaled corticosteroids (ICS) are the mainstay of treatment in persistent asthma, with a stepwise approach to increasing doses of ICS depending on asthma severity and control. ICS have known local and systemic side effects, of which adrenal suppression is still under-recognized. The latter is associated with chronic exposure and higher doses, although it has rarely been reported in children receiving low doses for a short period of time. The Canadian Society of Allergy and Clinical Immunology (CSACI) therefore recommends that physicians screen for adrenal suppression in children receiving high doses for more than 6 months and to consider screening those on medium dose if the risk is deemed higher by factors that increase an individual’s systemic corticosteroid exposure. Morning serum cortisol level can be used as a screening tool and abnormal results or normal results with a high index of suspicion should be confirmed with low-dose ACTH stimulation tests.