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      Systematic Review of the Toxicity of Long-Course Oral Corticosteroids in Children

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          Long courses of oral corticosteroids are commonly used in children in the management of chronic conditions. Various adverse drug reactions (ADRs) are known to occur with their use. This systematic review aimed to identify the most common and serious ADRs and to determine their relative risk levels.


          A literature search of Embase, Medline, International Pharmaceutical Abstracts, CINAHL, Cochrane Library and PubMed was performed with no language restrictions in order to identify studies where oral corticosteroids were administered to patients aged 28 days to 18 years of age for at least 15 days of treatment. Each database was searched from their earliest dates to January 2016. All studies providing clear information on ADRs were included.


          One hundred and one studies including 33 prospective cohort studies; 21 randomised controlled trials; 21 case series and 26 case reports met the inclusion criteria. These involved 6817 children and reported 4321 ADRs. The three ADRs experienced by the highest number of patients were weight gain, growth retardation and Cushingoid features with respective incidence rates of 21.1%, 18.1% and 19.4% of patients assessed for these ADRs. 21.5% of patients measured showed decreased bone density and 0.8% of patients showed osteoporosis. Biochemical HPA axis suppression was detected in 269 of 487 patients where it was measured. Infection was the most serious ADR, with twenty one deaths. Varicella zoster was the most frequent infection (9 deaths).


          Weight gain, growth retardation and Cushingoid features were the most frequent ADRs seen when long-course oral corticosteroids were given to children. Increased susceptibility to infection was the most serious ADR.

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          Most cited references 117

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          Population-based assessment of adverse events associated with long-term glucocorticoid use.

          The frequency of many adverse events (AEs) associated with low-dose glucocorticoid use is unclear. We sought to determine the prevalence of glucocorticoid-associated AEs in a large US managed care population. Using linked administrative and pharmacy claims, adults receiving >or=60 days of glucocorticoids were identified. These individuals were surveyed about glucocorticoid use and symptoms of 8 AEs commonly attributed to glucocorticoid use. Of the 6,517 eligible glucocorticoid users identified, 2,446 (38%) returned the mailed survey. Respondents were 29% men with a mean +/- SD age of 53 +/- 14 years; 79% were white and 13% were African American. Respondents had a mean +/- SD of 7 +/- 3 comorbid conditions and were prescribed a mean +/- SD prednisone-equivalent dosage of 16 +/- 14 mg/day. More than 90% of individuals reported at least 1 AE associated with glucocorticoid use; 55% reported that at least 1 AE was very bothersome. Weight gain was the most common self-reported AE (70% of the individuals), cataracts (15%) and fractures (12%) were among the most serious. After multivariable adjustment, all AEs demonstrated a strong dose-dependent association with cumulative glucocorticoid use. Among users of low-dose therapy (
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            Systematic reviews of adverse effects: framework for a structured approach

            Background As every healthcare intervention carries some risk of harm, clinical decision making needs to be supported by a systematic assessment of the balance of benefit to harm. A systematic review that considers only the favourable outcomes of an intervention, without also assessing the adverse effects, can mislead by introducing a bias favouring the intervention. Much of the current guidance on systematic reviews is directed towards the evaluation of effectiveness; but this differs in important ways from the methods used in assessing the safety and tolerability of an intervention. A detailed discussion of why, how and when to include adverse effects in a systematic review, is required. Methods This discussion paper, which presupposes a basic knowledge of systematic review methodology, was developed by consensus among experienced reviewers, members of the Adverse Effects Subgroup of The Cochrane Collaboration, and supplemented by a consultation of content experts in reviews methodology, as well as those working in drug safety. Results A logical framework for making decisions in reviews that incorporate adverse effects is provided. We explore situations where a comprehensive investigation of adverse effects is warranted and suggest strategies to identify practicable and clinically useful outcomes. The advantages and disadvantages of including observational and experimental study designs are reviewed. The consequences of including separate studies for intended and unintended effects are explained. Detailed advice is given on designing electronic searches for studies with adverse effects data. Reviewers of adverse effects are given general guidance on the assessment of study bias, data collection, analysis, presentation and the interpretation of harms in a systematic review. Conclusion Readers need to be able to recognize how strategic choices made in the review process determine what harms are found, and how the findings may affect clinical decisions. Researchers undertaking a systematic review that incorporates adverse effect data should understand the rationale for the suggested methods and be able to implement them in their review.
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              Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children.

              Although eosinophilic esophagitis is recognized increasingly, outcome data guiding therapy are limited. We conducted a prospective randomized trial comparing oral prednisone (P) and swallowed fluticasone (F) for histologic and clinical response. Patients were randomized to receive P or F for 4 weeks, followed by an 8-week weaning protocol. Esophageal histology was evaluated at baseline and after 4 weeks of therapy. Clinical assessments were performed at weeks 0, 4, 12, 18, and 24. Eighty patients with eosinophilic esophagitis were enrolled: 40 in the P arm and 40 in the F arm. Histologic improvement was seen in 30 of 32 P and 34 of 36 F patients, with a greater degree of histologic improvement in the P group. All P and 35 of 36 F patients were free of presenting symptom(s) at week 4. Symptom relapse was seen in 45% of patients by week 24. Kaplan-Meier analysis showed no difference between P and F with regard to relapse rate (P = .7399). No significant difference in time to relapse was found between groups (P = .2529). Systemic adverse effects were noted in 40% of the P arm, whereas esophageal candidal overgrowth was seen in 15% of the F arm. Systemic and topical corticosteroids were effective in achieving initial histologic and clinical improvement. P resulted in a greater degree of histologic improvement, without evidence of an associated clinical advantage over F in terms of symptom resolution, relapse rates, or time to relapse. Symptom relapse was common to both groups upon therapy discontinuation, highlighting the need for maintenance treatment protocols.

                Author and article information

                Role: Editor
                PLoS One
                PLoS ONE
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                26 January 2017
                : 12
                : 1
                Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, Royal Derby Hospital Centre, Derby, United Kingdom
                York University, UNITED KINGDOM
                Author notes

                Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Imti Choonara is an Academic Editor of the journal.

                • Conceptualization: IC SC.

                • Data curation: FA.

                • Formal analysis: FA.

                • Investigation: FA.

                • Methodology: IC SC FA.

                • Project administration: IC SC FA.

                • Resources: IC SC.

                • Supervision: IC SC.

                • Validation: IC SC FA.

                • Visualization: IC SC FA.

                • Writing – original draft: IC SC FA.

                • Writing – review & editing: IC SC FA.

                © 2017 Aljebab et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 5, Tables: 5, Pages: 18
                The authors received no specific funding for this work. Fahad Aljebab is a postgraduate student and would like to acknowledge his sponsor the Saudi Arabian government (Prince Mohammed Medical City). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Research Article
                Research and Analysis Methods
                Research Design
                Cohort Studies
                Medicine and Health Sciences
                Child Development
                Child Growth
                Growth Restriction
                Research and Analysis Methods
                Research Design
                Clinical Research Design
                Case Series
                Biology and Life Sciences
                Physiological Parameters
                Body Weight
                Weight Gain
                Medicine and Health Sciences
                Physiological Parameters
                Body Weight
                Weight Gain
                Medicine and Health Sciences
                Adverse Reactions
                Research and Analysis Methods
                Database and Informatics Methods
                Database Searching
                Research and Analysis Methods
                Research Assessment
                Systematic Reviews
                Medicine and Health Sciences
                Drug Therapy
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.



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