Bhupendrasinh F Chauhan

Diagnosis, management, and prognosis of preschool wheeze

Preschool children (ie, those aged 5 years or younger) with wheeze consume a disproportionately high amount of health-care resources compared with older children and adults with wheeze or asthma, representing a diagnostic challenge. Although several phenotype classifications have been described, none have been validated to identify individuals responding to specific therapeutic approaches. Several risk factors related to genetic, prenatal, and postnatal environment are associated with preschool wheezing. Findings from several cohort studies have shown that preschool children with wheeze have deficits in lung function at 6 years of age that persisted until early and middle adulthood, suggesting increased susceptibility in the first years of life that might lead to persistent sequelae. Daily inhaled corticosteroids seem to be the most effective therapy for recurrent wheezing in trials of children with interim symptoms or atopy; intermittent high-dose inhaled corticosteroids are effective in moderate-to-severe viral-induced wheezing without interim symptoms. The role of leukotriene receptor antagonist is less clear. Interventions to modify the short-term and long-term outcomes of preschool wheeze should be a research priority.

Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies.

BACKGROUND Nonnutritive sweeteners, such as aspartame, sucralose and stevioside, are widely consumed, yet their long-term health impact is uncertain. We synthesized evidence from prospective studies to determine whether routine consumption of non-nutritive sweeteners was associated with long-term adverse cardiometabolic effects. METHODS We searched MEDLINE, Embase and Cochrane Library (inception to January 2016) for randomized controlled trials (RCTs) that evaluated interventions for nonnutritive sweeteners and prospective cohort studies that reported on consumption of non-nutritive sweeteners among adults and adolescents. The primary outcome was body mass index (BMI). Secondary outcomes included weight, obesity and other cardiometabolic end points. RESULTS From 11 774 citations, we included 7 trials (1003 participants; median follow-up 6 mo) and 30 cohort studies (405 907 participants; median follow-up 10 yr). In the included RCTs, nonnutritive sweeteners had no significant effect on BMI (mean difference −0.37 kg/m2; 95% confidence interval [CI] −1.10 to 0.36; I2 9%; 242 participants). In the included cohort studies, consumption of nonnutritive sweeteners was associated with a modest increase in BMI (mean correlation 0.05, 95% CI 0.03 to 0.06; I2 0%; 21 256 participants). Data from RCTs showed no consistent effects of nonnutritive sweeteners on other measures of body composition and reported no further secondary outcomes. In the cohort studies, consumption of nonnutritive sweeteners was associated with increases in weight and waist circumference, and higher incidence of obesity, hypertension, metabolic syndrome, type 2 diabetes and cardiovascular events. Publication bias was indicated for studies with diabetes as an outcome. INTERPRETATION Evidence from RCTs does not clearly support the intended benefits of nonnutritive sweeteners for weight management, and observational data suggest that routine intake of nonnutritive sweeteners may be associated with increased BMI and cardiometabolic risk. Further research is needed to fully characterize the long-term risks and benefits of nonnutritive sweeteners. Protocol registration: PROSPERO-CRD42015019749

Early Exposure to Nonnutritive Sweeteners and Long-term Metabolic Health: A Systematic Review.

CONTEXT: Nonnutritive sweetener (NNS) consumption is increasing among children, yet its long-term health impact is unclear, particularly when exposure occurs during early life. OBJECTIVE: To synthesize evidence from prospective studies evaluating the association of early-life NNS exposure and long-term metabolic health. DATA SOURCES: Medline, Embase, and Cochrane Library (inception to July 2015). STUDY SELECTION: We aimed to include randomized controlled trials (RCTs) evaluating NNS-based interventions and prospective cohort studies reporting NNS exposure among pregnant women, infants, or children (<12 years of age), with a minimum study duration of 6 months. DATA EXTRACTION: The primary outcome was BMI; secondary outcomes included growth velocity, overweight/obesity, adiposity, and adverse metabolic effects. Study quality and risk of bias were evaluated using validated assessment tools. RESULTS: We identified 6 eligible cohort studies and 2 RCTs (n = 15 641 children). Half of the cohorts reported increasing weight gain or fat mass accumulation with increasing NNS intake, and pooled data from 2 cohorts showed a significant correlation with BMI gain (weighted mean correlation 0.023, 95% confidence interval 0.006 to 0.041). RCTs reported contradictory effects on weight change in children receiving NNSs. No eligible studies evaluated prenatal or infant NNS exposure. LIMITATIONS: Meta-analysis was limited because of the small number of eligible studies and heterogeneity of populations and outcomes. CONCLUSIONS: There is limited and inconsistent evidence of the long-term metabolic effects of NNS exposure during gestation, infancy, and childhood. Further research is needed to inform recommendations for the use of NNSs in this sensitive population.

Behavior change interventions and policies influencing primary healthcare professionals’ practice—an overview of reviews

BackgroundThere is a plethora of interventions and policies aimed at changing practice habits of primary healthcare professionals, but it is unclear which are the most appropriate, sustainable, and effective. We aimed to evaluate the evidence on behavior change interventions and policies directed at healthcare professionals working in primary healthcare centers.MethodsStudy design: overview of reviews.Data source: MEDLINE (Ovid), Embase (Ovid), The Cochrane Library (Wiley), CINAHL (EbscoHost), and grey literature (January 2005 to July 2015).Study selection: two reviewers independently, and in duplicate, identified systematic reviews, overviews of reviews, scoping reviews, rapid reviews, and relevant health technology reports published in full-text in the English language.Data extraction and synthesis: two reviewers extracted data pertaining to the types of reviews, study designs, number of studies, demographics of the professionals enrolled, interventions, outcomes, and authors’ conclusions for the included studies. We evaluated the methodological quality of the included studies using the AMSTAR scale. For the comparative evaluation, we classified interventions according to the behavior change wheel (Michie et al.).ResultsOf 2771 citations retrieved, we included 138 reviews representing 3502 individual studies. The majority of systematic reviews (91%) investigated behavior and practice changes among family physicians. Interactive and multifaceted continuous medical education programs, training with audit and feedback, and clinical decision support systems were found to be beneficial in improving knowledge, optimizing screening rate and prescriptions, enhancing patient outcomes, and reducing adverse events. Collaborative team-based policies involving primarily family physicians, nurses, and pharmacists were found to be most effective. Available evidence on environmental restructuring and modeling was found to be effective in improving collaboration and adherence to treatment guidelines. Limited evidence on nurse-led care approaches were found to be as effective as general practitioners in patient satisfaction in settings like asthma, cardiovascular, and diabetes clinics, although this needs further evaluation. Evidence does not support the use of financial incentives to family physicians, especially for long-term behavior change.ConclusionsBehavior change interventions including education, training, and enablement in the context of collaborative team-based approaches are effective to change practice of primary healthcare professionals. Environmental restructuring approaches including nurse-led care and modeling need further evaluation. Financial incentives to family physicians do not influence long-term practice change.

Factors associated with failure of emergency department management in children with acute moderate or severe asthma: a prospective, multicentre, cohort study

BACKGROUND The management of paediatric asthma exacerbations is based on trials in children of all ages. Recent studies from 2009 raised the possibility that preschoolers (younger than 6 years) with viral-induced wheezing and children exposed to tobacco smoke might be at an increased risk of treatment failure. The study objective was to identify factors associated with management failure in children presenting to the emergency department with moderate or severe asthma exacerbations. METHODS We undertook a prospective, multicentre cohort study of children aged 1-17 years presenting to five emergency departments with moderate or severe asthma (defined as a Pediatric Respiratory Assessment Measure [PRAM] of 4 to 12). Children received oral corticosteroids and severity-specific inhaled bronchodilator therapy. The primary outcome was emergency department management failure (hospital admission, prolonged emergency department therapy [≥8 h], or relapse within 72 h of discharge from the emergency department with admission to hospital or prolonged emergency department stay). Viral cause was ascertained by PCR on nasopharyngeal specimens and environmental tobacco smoke exposure by salivary cotinine concentration. This study is registered at ClinicalTrials.gov (NCT02013076). FINDINGS Between Feb 14, 2011, and Dec 20, 2013, we screened 1893 children and enrolled 1012 eligible children. Of those eligible children, 973 participants were included in the analysis. 165 (17%) of 965 children experienced management failure in the emergency department, which was significantly associated with viral detection (110 [19%] of 579 participants with virus detection vs 46 [13%] of 354 participants without viral detection, odds ratio [OR] 1·57; 95% CI 1·04-2·37), fever (24% vs 15%, 1·96; 1·32-2·92), baseline PRAM (OR 1·38 per 1-point increase; 1·22-1·56), oxygen saturation of less than 92% (50% vs 12%, 3·94; 1·97-7·89), and presence of symptoms between exacerbations (21% vs 16%, 1·73; 1·13-2·64). Age, salivary cotinine concentration, and oral corticosteroids dose were not significantly associated with management failure. Viral detection (67% vs 46%, p<0·0001) and fever (31% vs 16%, p<0·0001) occurred more frequently in preschoolers than in older children. Viral detection was also associated with reduced speed of recovery over the 10 days after discharge. INTERPRETATION In children presenting with moderate or severe asthma, viral detection, but not age, was associated with failure of symptom management, independently from exacerbation severity (ie, baseline PRAM and oxygen saturation), fever, and symptom chronicity (viral detection). Although it did not reach statistical significance, the association between treatment management failure and exposure to tobacco smoke warrants further investigation. FUNDING Canadian Institutes of Health Research.

Inhaled corticosteroids in children with persistent asthma: is there a dose response impact on growth? - an overview of Cochrane reviews

Aniela I. Pruteanu , Bhupendrasinh F. Chauhan , Linjie Zhang , Silvio O.M. Prietsch , Francine M. Ducharme * Department of Paediatrics, University of Montreal, Montreal, Canada Clinical Research Unit on Childhood Asthma, Research Centre, CHU Sainte-Justine, Montreal, Canada 3 Faculty of Medicine, Federal University of Rio Grande, Rio Grande, Brazil Research Centre, CHU Sainte-Justine, Montreal, Canada

Cochrane in context: Inhaled corticosteroids in children with persistent asthma: effects on growth and dose–response effects on growth

Cochrane Review: Inhaled corticosteroids in children with persistent asthma: effects on growth Zhang L, Prietsch SOM, Ducharme FM. Inhaled corticosteroids in children with persistent asthma: effects on growth. Cochrane Database of Systematic Reviews 2014, Issue 7. Art. No.: CD009471. DOI: 10.1002/14651858.CD009471.pub2 Cochrane Review: Inhaled corticosteroids in children with persistent asthma: dose-response effects on growth Pruteanu AI, Chauhan BF, Zhang L, Prietsch SOM, Ducharme FM. Inhaled corticosteroids in children with persistent asthma: dose–response effects on growth. Cochrane Database of Systematic Reviews 2014, Issue 7. Art. No.: CD009878. DOI: 10.1002/14651858.CD009878.pub2 This companion piece to the reviews, “Inhaled corticosteroids in children with persistent asthma: effects on growth” and “Inhaled corticosteroids in children with persistent asthma: dose–response effects on growth,” contains the following pieces: The abstract of each review A commentary from one or more of the review authors, explaining why the review team felt both reviews were important to produce A review of clinical practice guidelines Some other recently published references on this topic

Should we Substitute Intermittent for Maintenance Inhaled Corticosteroids in Patients with Persistent Asthma? A Systematic Review and Meta-Analysis

Background: Although guidelines recommend maintenance inhaled corticosteroids (ICS) in mild persistent asthma, most patients use, and many physicians prescribe, intermittent ICS. Objective: To compare the efficacy and safety of maintenance versus intermittent ICS in children and adults with persistent asthma and to explore potential effect modifiers attributable to either strategy. Methods: We searched the literature using: the Cochrane airways group specialized register of trials and ClinicalTrials.gov website until October 2012. All randomized controlled trials, at least of four-week duration, comparing maintenance and intermittent ICS initiated at the onset of exacerbations. The primary efficacy and safety outcomes were the risk of patients with exacerbations requiring rescue oral corticosteroids and serious adverse events, respectively. Secondary outcomes included exacerbations, asthma control, lung function, airway inflammation, withdrawals, and adverse events. Results: Six (4 pediatric; 2 adult) trials involving 1211 patients with mild persistent asthma met the eligibility criteria; they lasted 12-52 weeks. There was no statistically significant group difference in the risk of patients with exacerbations requiring rescue oral corticosteroids (RR 1.07; 95% CI 0.87, 1.32). The response magnitude was not influenced by age, asthma severity, step-up protocol, and intervention duration. Maintenance ICS was superior to intermittent ICS in several indicators of symptoms, s2-agonist use, lung function, and airway inflammation. There was no group difference in the risk of patients with serious adverse events (RR=0.82; 95% CI 0.33, 2.03). In children, maintenance ICS was associated with less linear growth (MD=0.41 95% CI 0.13, 0.69) over 44-52 weeks. Conclusions: In children and adults with persistent asthma, maintenance and intermittent ICS strategies did not significantly differ in the risk of patients experiencing exacerbations requiring rescue oral corticosteroids and severe adverse events; however the wide confidence interval precludes equivalence. Maintenance ICS was superior to intermittent ICS in several indicators of lung function, airway inflammation, asthma control and reliever use. The paucity of trials prevents firm conclusions.

Efficacy and safety of pulmonary application of corticosteroids in preterm infants with respiratory distress syndrome: a systematic review and meta-analysis

Background Systemic corticosteroids as the frontline treatment of respiratory distress syndrome (RDS) in preterm infants are associated with adverse effects on growth and neurodevelopmental outcome, but the pulmonary administration of steroids may help prevent the development of bronchopulmonary dysplasia (BPD) without these side effects. Objectives To evaluate the efficacy and safety of pulmonary application of corticosteroids in preterm infants with RDS. Methods MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, the WHO’s International Clinical Trials Registry and grey literature were searched with no restriction on date and language of publication from inception to May 2016. Using a random-effect model, we pooled data from randomised controlled trials (RCTs) comparing inhaled or endotracheal corticosteroids with the standard of care, placebo or no other intervention in preterm infants with RDS. Results We identified 873 potential citations and included 12 unique RCTs. Pulmonary corticosteroid therapy was associated with a significant reduction in the composite outcome of BPD or death (relative risk (RR) 0.85, 95% CI 0.76 to 0.96). Pulmonary application of corticosteroids significantly reduced the incidence of patent ductus arteriosus (PDA) (RR 0.82, 95% CI 0.74 to 0.92) and pneumonia (RR 0.57, 95% CI 0.35 to 0.92). There was no evidence of a significant difference regarding the risk of neurodevelopmental impairment or other side effects. Conclusions Pulmonary administration of corticosteroids reduces the incidence of BPD or death, pneumonia, PDA without causing any major side effects in preterm infants with RDS.