New and Updated Cochrane Systematic Reviews

Background and aims Retinopathy of Prematurity (ROP) is an important cause of visual impairment and blindness in children.1 Aim Conduct a systematic review and meta-analysis to determine the association between blood transfusion and the development of ROP in preterm infants <32 weeks gestational age or birthweight <1500 grams. Data Sources: MEDLINE, EMBASE, Cochrane Register, CINAHL, LILACS, Web of Knowledge, clinicaltrial.gov and Open SIGLE. Study Selection Criteria: Cohort and case-control studies from 2000 onwards: Four reviewers independently assessed eligibility. Data Extraction and analysis: The outcome measure was 'all stages of ROP'. Quality assessment of studies was done using Newcastle-Ottawa scale. A random effects meta-analysis model was used and heterogeneity was assessed using I2 statistic. Results Nine studies met the final selection criteria. Total sample size was 2106 preterm infants with median gestational age 30 weeks and birth weight 1228 grams. Blood transfusion was associated with the development of ROP; unadjusted odds ratio (OR) = 3.05 (95% CI 2.16 to 4.32) with a significant heterogeneity (I2 = 54.8% p = 0.02). The unadjusted pooled OR in three of these studies was 2.59 (95% CI 1.35 to 4.98) and the adjusted pooled OR was 1.18 (95% CI 0.96 to 1.33), I2 = 8.8%. Conclusion Blood transfusion was associated with the development of ROP in preterm infants. However once other factors such as gestational age and birth weight were adjusted for, the association between blood transfusion and ROP development was considerably weaker. Publication type: Journal: Conference Abstract Source: EMBASE Full text: Available ARCHIVES OF DISEASE IN CHILDHOOD at Archives of disease in childhood Full text: Available ARCHIVES OF DISEASE IN CHILDHOOD at Salisbury District Hospital Healthcare Library 6.Title: Brain changes in early-onset bipolar and unipolar depressive disorders: a systematic review in children and adolescents. Citation: European Child & Adolescent Psychiatry, November 2014, vol./is. 23/11(1023-41), 1018-8827;1435-165X (2014 Nov) Author(s): Serafini G, Pompili M, Borgwardt S, Houenou J, Geoffroy PA, Jardri R, Girardi P, Amore M Language: English Abstract: Pediatric bipolar disorder (BD) and unipolar disorder (UD) share common symptomatic and functional impairments. Various brain imaging techniques have been used to investigate the integrity of brain white matter (WM) and gray matter (GM) in these disorders. Despite promising preliminary findings, it is still unclear whether these alterations may be considered as common trait markers or may be used to distinguish BD from UD. A systematic literature search of studies between 1980 and September 2013 which reported WM/GM changes in pediatric and adolescent BD/UD, as detected by diffusion tensor imaging and voxel-based analysis was conducted. Of the 34 articles judged as eligible, 17 fulfilled our inclusion criteria and were finally retained in this review. More abnormalities have been documented in the brains of children and adolescents with BD than UD. Reductions in the volume of basal ganglia and the hippocampus appeared more specific for pediatric UD, whereas reduced corpus callosum volume and increased rates of deep WM hyperintensities were more specific for pediatric BD. Seminal papers failed to address the possibility that the differences between unipolar and bipolar samples might be related to illness severity, medication status, comorbidity or diagnosis. UD and BD present both shared and distinctive impairments in the WM and GM compartments. More WM abnormalities have been reported in children and adolescents with bipolar disease than in those with unipolar disease, maybe as a result of a low number of DTI studies in pediatric UD. Future longitudinal studies should investigate whether neurodevelopmental changes are diagnosis-specific. Publication type: Journal Article Source: MEDLINE 7.Title: Clinical and social outcomes of adolescent self harm: Population based birth cohort study Citation: BMJ (Online), October 2014, vol./is. 349/, 0959-8146;1756-1833 (22 Oct 2014) Author(s): Mars B., Heron J., Crane C., Hawton K., Lewis G., Macleod J., Tilling K., Gunnell D. Language: English Abstract: Objectives: To investigate the mental health, substance use, educational, and occupational outcomes of adolescents who self harm in a general population sample, and to examine whether these outcomes differ according to self reported suicidal intent. Design: Population based birth cohort study. Setting: Avon Longitudinal Study of Parents and Children (ALSPAC), a UK birth cohort of children born in 1991-92. Participants: Data on lifetime history of self harm with and without suicidal intent were available for 4799 respondents who completed a detailed self harm questionnaire at age 16 years. Multiple imputation was used to account for missing data. Main outcome measures: Mental health problems (depression and anxiety disorder), assessed using the clinical interview schedule-revised at age 18 years, self reported substance use (alcohol, cannabis, cigarette smoking, and illicit drugs) at age 18 years, educational attainment at age 16 and 19 years, occupational outcomes at age 19 years, and self harm at age 21 years. Results: Participants who self harmed with and without suicidal intent at age 16 years were at increased risk of developing mental health problems, future self harm, and problem substance misuse, with stronger associations for suicidal self harm than for non-suicidal self harm. For example, in models adjusted for confounders the odds ratio for depression at age 18 years was 2.21 (95% confidence interval 1.55 to 3.15) in participants who had self harmed without suicidal intent at age 16 years and 3.94 (2.67 to 5.83) in those who had self harmed with suicidal intent. Suicidal self harm, but not self harm without suicidal intent, was also associated with poorer educational and employment outcomes. Conclusions: Adolescents who self harm seem to be vulnerable to a range of adverse outcomes in early adulthood. Risks were generally stronger in those who had self harmed with suicidal intent, but outcomes were also poor among those who had self harmed without suicidal intent. These findings emphasise the need for early identification and treatment of adolescents who self harm. Publication type: Journal: Article Source: EMBASE Full text: Available BMJ (Clinical research ed.) at The BMJ 8.Title: Current role of rufinamide in the treatment of childhood epilepsy: Literature review and treatment guidelines Citation: European Journal of Paediatric Neurology, November 2014, vol./is. 18/6(685-690), 1090-3798;1532-2130 (01 Nov 2014) Author(s): Coppola G., Besag F., Cusmai R., Dulac O., Kluger G., Moavero R., Nabbout R., Nikanorova M., Pisani F., Verrotti A., Von Stulpnagel C., Curatolo P. Language: English Abstract: Purpose The literature on the efficacy and safety of rufinamide in childhood-onset epilepsy syndromes currently includes approximately 600 paediatric patients. This paper summarizes the views of a panel of experienced European epileptologists with regard to the current role of rufinamide in the treatment of childhood epilepsies.Results Rufinamide is effective in decreasing the seizure frequency in the Lennox-Gastaut syndrome (LGS), especially tonic and atonic seizures. It might consequently be preferred to other drugs as a second-line treatment for LGS when drop-attacks are frequent. The mean responder rate in the published studies is 38% with seizure freedom achieved in 2.4% of patients. Rufinamide has shown some efficacy in epileptic encephalopathies other than LGS. It can be also effective as adjunctive therapy in children and adolescents with drug-resistant partial seizures. The available data suggest that rufinamide has an acceptable risk/benefit ratio with quite a low risk of aggravating seizures. Common adverse effects (somnolence, nausea and vomiting) are usually mild and self-limiting; they are more frequently observed during titration than in the maintenance phase, suggesting that low escalation rates might be associated with fewer adverse effects. Rufinamide appears to have a favourable cognitive profile compared with other antiepileptic drugs.Conclusion Rufinamide is only approved for adjunctive treatment of seizures associated with LGS in children 4 years of age and older. There are very few data on rufinamide treatment at the onset of LGS or early in the course of the disorder; whether early treatment will improve outcome has yet to be determined. Publication type: Journal: Review Source: EMBASE 9.Title: Dexamethasone may be a viable alternative to prednisone/prednisolone for the treatment of acute asthma exacerbation in the paediatric emergency department. Citation: Evidence Based Medicine, October 2014, vol./is. 19/5(175), 1356-5524;1473-6810 (2014 Oct) Author(s): Andrews AL, Simpson AN Language: English Publication type: Comment, Journal Article Source: MEDLINE Full text: Available Highwire Press at Evidence-Based Medicine 10.Title: Early intubate-surfactant-extubate (INSURE) versus non-invasive continuous positive airway pressure (ncpap) to prevent bronchopulmonary dysplasia: A systematic review and meta-analysis Citation: Archives of Disease in Childhood, October 2014, vol./is. 99/(A214-A215), 0003-9888 (October 2014) Author(s): Isayama T., Chai-Adisaksopha C., McDonald S. Language: English Abstract: Background and aims In preterm infants, early non-invasive continuous positive airway pressure (NCPAP) use decreases "bronchopulmonary dysplasia (BPD) or death" compared with early intubation. However, it was not yet clear whether early Intubation-for-SURfactant-followed-by-Extubation to NCPAP (INSURE) is more effective to prevent BPD or Death or "BPD or death" or either than keeping infants on NCPAP. This systematic review aimed to investigate this question. Methods This systematic review included randomised control trials comparing the INSURE and NCPAP for preterm infants with or at high risk of respiratory distress syndrome who had never been intubated before the study entry. Primary outcomes included BPD at 36 weeks postmenstrual age, Death, and "BPD or Death". A systematic literature search was conducted of MEDLINE, EMBASE, CENTRAL, and CINAHL as well as conference proceedings and trial registrations. Two reviewers independently selected studies and extracted data. Meta-analyses were conducted with a random-effect method using Review manager 5.2 (statistical significance with two-sided p-value of 0.05). Results Nine trials were included from 1622 non-duplicate records. The meta-analysis results were shown in a table with pooled risk ratios (RR) and 95% confidence interval (CI). (Table Presented). Publication type: Journal: Conference Abstract Source: EMBASE Full text: Available ARCHIVES OF DISEASE IN CHILDHOOD at Archives of disease in childhood Full text: Available ARCHIVES OF DISEASE IN CHILDHOOD at Salisbury District Hospital Healthcare Library 11. Title: Effect of a single inactivated poliovirus vaccine dose on intestinal immunity against poliovirus in children previously given oral vaccine: An open-label, randomised controlled trial Citation: The Lancet, October 2014, vol./is. 384/9953(1505-1512), 0140-6736;1474-547X (25 Oct 2014) Author(s): John J., Giri S., Karthikeyan A.S., Iturriza-Gomara M., Muliyil J., Abraham A., Grassly N.C., Kang G. Language: English Abstract: Summary Background Intestinal immunity induced by oral poliovirus vaccine (OPV) is imperfect and wanes with time, permitting transmission of infection by immunised children. Inactivated poliovirus vaccine (IPV) does not induce an intestinal mucosal immune response, but could boost protection in children who are mucosally primed through previous exposure to OPV. We aimed to assess the effect of IPV on intestinal immunity in children previously vaccinated with OPV.Methods We did an open-label, randomised controlled trial in children aged 1-4 years from Chinnallapuram, Vellore, India, who were healthy, had not received IPV before, and had had their last dose of OPV at least 6 months before enrolment. Children were randomly assigned (1:1) to receive 05 mL IPV intramuscularly (containing 40, 8, and 32 D antigen units for serotypes 1, 2, and 3) or no vaccine. The randomisation sequence was computer generated with a blocked randomisation procedure with block sizes of ten by an independent statistician. The laboratory staff did blinded assessments. The primary outcome was the proportion of children shedding poliovirus 7 days after a challenge dose of serotype 1 and 3 bivalent OPV (bOPV). A second dose of bOPV was given to children in the no vaccine group to assess intestinal immunity resulting from the first dose. A per-protocol analysis was planned for all children who provided a stool sample at 7 days after bOPV challenge. This trial is registered with Clinical Trials Registry of India, number CTRI/2012/09/003005.Findings Between Aug 19, 2013, and Sept 13, 2013, 450 children were enrolled and randomly assigned into study groups. 225 children received IPV and 225 no vaccine. 222 children in the no vaccine group and 224 children in the IPV group had stool samples available for primary analysis 7 days after bOPV challenge. In the IPV group, 27 (12%) children shed serotype 1 poliovirus and 17 (8%) shed serotype 3 poliovirus compared with 43 (19%) and 57 (26%) in the no vaccine group (risk ratio 062, 95% CI 040-097, p=00375; 030, 018-049, p<00001). No adverse events were related to the study interventions.Interpretation The substantial boost in intestinal immunity conferred by a supplementary dose of IPV given to children younger than 5 years who had previously received OPV shows a potential role for this vaccine in immunisation activities to accelerate eradication and prevent outbreaks of poliomyelitis.Funding Bill & Melinda Gates Foundation. Publication type: Journal: Article Source: EMBASE Full text: Available Lancet at Salisbury District Hospital Healthcare Library Full text: Available Lancet at Lancet, The 12. Title: Effects of methylphenidate on cognitive functions in children and adolescents with attentiondeficit/hyperactivity disorder: evidence from a systematic review and a meta-analysis. Citation: Biological Psychiatry, October 2014, vol./is. 76/8(603-15), 0006-3223;1873-2402 (2014 Oct 15) Author(s): Coghill DR, Seth S, Pedroso S, Usala T, Currie J, Gagliano A Language: English Abstract: BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with a broad range of neuropsychological impairments. The relationship between these neuropsychological deficits and the defining symptoms of ADHD seems more complex than originally thought. Methylphenidate (MPH) is an effective treatment for ADHD symptoms, but its impact on cognition is less clearly understood.METHODS: With a common systematic search strategy and a rigorous coding and data extraction strategy across domains, we searched electronic databases to identify published placebo controlled trials that compared MPH and placebo on executive and nonexecutive memory, reaction time, reaction time variability and response inhibition in children and adolescents (5-18 years) with a formal diagnosis of ADHD.RESULTS: Sixty studies were included in the review, of which 36 contained sufficient data for meta-analysis. Methylphenidate was superior to placebo in all five meta-analyses: executive memory, standardized mean difference (SMD) .26, 95% confidence interval (CI): -.39 to -.13; non-executive memory, SMD .60, 95% CI: -.79 to -.41; reaction time, SMD .24, 95% CI: -.33 to .15; reaction time variability, SMD .62, 95% CI: -.90 to -.34; response inhibition, SMD .41, 95% CI: -.55 to .27.CONCLUSIONS: These data support the potentially important effects of MPH on various aspects of cognition known to be associated with ADHD. Consideration should be given to adding cognitive outcomes to the assessment of treatment outcome in ADHD, considering the complexity of the relationship between ADHD symptoms and cognition. 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved. Publication type: Journal Article Source: MEDLINE 13. Title: Efficacy and safety of histamine-2 receptor antagonists Citation: JAMA Pediatrics, October 2014, vol./is. 168/10(947-954), 2168-6203 (01 Oct 2014) Author(s): Van Der Pol R., Langendam M., Benninga M., Van Wijk M., Tabbers M. Language: English Abstract: IMPORTANCE: Histamine-2 receptor antagonists (H2RAs) are frequently used in the treatment of gastroesophageal reflux disease (GERD) in children; however, their efficacy and safety is questionable.OBJECTIVE: To systematically review the literature to assess the efficacy and safety of H2RAs in pediatric GERD.EVIDENCE REVIEW: PubMed, EMBASE, and the Cochrane database were searched for randomized clinical trials investigating the efficacy and safety of H2RAs in pediatric GERD. Two reviewers independently extracted data from the included articles. The quality of the evidence was assessed using the Grades of Recommendations, Assessment, Development, and Evaluation approach. When possible, infants and children were analyzed separately.FINDINGS: Eight studies with a total of 276 children (0-15 years of age) were included. Compared with the placebo, H2RAs were more effective in the reduction of symptoms in terms of histologic healing and increasing gastric pH and had a larger overall treatment effect. In infants, H2RAs were only more effective in terms of histologic healing. Comparing H2RAs with antacids, H2RAs were more effective in symptom reduction in only 1 study. H2RAs compared with proton pump inhibitors were not significantly different in any of the outcome measures. For safety analysis, data were not reported in a quantitative manner and for all outcomes, the quality of evidence was very low.CONCLUSIONS AND RELEVANCE: Evidence to support the efficacy and safety of H2RAs in infants and children is limited and of poor quality.Well-designed placebo-controlled trials are needed before thorough conclusions can be drawn. Publication type: Journal: Review Source: EMBASE 14. Title: Environmental tobacco smoke exposure and risk of allergic sensitisation in children: a systematic review and meta-analysis. Citation: Archives of Disease in Childhood, November 2014, vol./is. 99/11(985-92), 0003-9888;1468-2044 (2014 Nov) Author(s): Feleszko W, Ruszczynski M, Jaworska J, Strzelak A, Zalewski BM, Kulus M Language: English Abstract: BACKGROUND: Environmental tobacco smoke (ETS) exposure in children is linked with the development of allergic asthma. However, its influence on allergic sensitisation in children has not been conclusively determined.OBJECTIVE: To systematically review existing evidence of ETS exposure's impact on markers of allergic sensitisation in children.METHODS: CENTRAL, MEDLINE and EMBASE databases were searched. Included studies assessed following markers of atopic sensitisation: total immunoglobulin E (tIgE) concentrations, at least one specific IgE (sIgE+), and positive skin-prick tests (SPTs+) in ETS-exposed and non-exposed children.RESULTS: 8 studies on the influence of ETS on tIgE concentration (2603 patients), 6 studies on ETS and sIgE+ (9230 participants) and 14 papers on ETS and SPT (14 150 patients) met our inclusion criteria. ETS was shown to raise tIgE concentrations by 27.7 IU/mL (95% CI 7.8 to 47.7; I(2)=58%; results based on 3 studies) and to increase the risk of atopic sensitisation, as assessed by sIgE+ (OR=1.12, 95%CI 1.00 to 1.25; I(2)=54%; results based on 4 studies) and SPT+ (OR=1.15; 95% CI 1.04 to 1.28; I(2)=0%; results based on 10 studies). In a subgroup analysis, this effect was most pronounced in children <7 years (preschoolers) by OR=1.20; (95% CI 1.05 to 1.38) and OR=1.30 (95% CI 1.05 to 1.61), (for sIgE+ and SPT+, respectively).CONCLUSIONS: Current analysis supports an association between ETS exposure in early childhood and the increased risk of allergic sensitisation. Subgroup meta-analyses demonstrate that younger children suffer the most from detrimental immunomodulating effects of ETS exposure. This study underscores ETS as an important but avoidable risk factor for the development of allergic disease in children. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. Publication type: Journal Article Source: MEDLINE Full text: Available ARCHIVES OF DISEASE IN CHILDHOOD at Archives of disease in childhood Full text: Available ARCHIVES OF DISEASE IN CHILDHOOD at Salisbury District Hospital Healthcare Library 15. Title: Epilepsy in children with menkes disease: a systematic review of literature. Citation: Journal of Child Neurology, December 2014, vol./is. 29/12(1757-64), 0883-0738;1708-8283 (2014 Dec) Author(s): Verrotti A, Carelli A, Coppola G Language: English Abstract: Menkes disease is a lethal multisystemic disorder of copper metabolism characterized by connective tissue abnormalities, progressive neurodegeneration and peculiar "kinky hair." Epilepsy is one of the main clinical features of this disease but it has been described in detail by only a few authors. Most patients develop seizures from 2 to 3 months of age, accompanied by a neurodevelopmental regression. The history of epilepsy is usually characterized by 3 stages: an early stage with focal clonic seizures and status epilepticus, an intermediate stage with infantile spasms, and a late stage with multifocal, myoclonic, and tonic seizures. At the onset, epilepsy can be controlled with anticonvulsant therapy, whereas with the progression of disease, it becomes extremely resistant to all antiepileptic drugs. In this article, we analyze clinical and electroencephalographic (EEG) characteristics of epilepsy in patients with this syndrome. The Author(s) 2014. Publication type: Journal Article Source: MEDLINE 16. Title: Family presence during resuscitation and invasive procedures in pediatric critical care: a systematic review. Citation: American Journal of Critical Care, November 2014, vol./is. 23/6(477-85), 1062-3264;1937-710X (2014 Nov) Author(s): McAlvin SS, Carew-Lyons A Language: English Abstract: BACKGROUND: In pediatric critical care, family-centered care is a central theme that ensures holistic care of the patient and the patient's family. Parents expect and are encouraged to be involved in the care of their child throughout all phases of the child's illness. Family presence is generally accepted when the child's condition is stable; however, there is less consensus about family presence when the child becomes critically ill and requires resuscitation and/or invasive procedures.METHODS: The PRISMA model guided this systematic literature search of CINAHL, MEDLINE, Ovid, and PubMed for articles published between 1995 and 2012. Specific search terms used included pediatric intensive care, parent presence, family presence, pediatrics, invasive procedures, and resuscitation.RESULTS: This literature search yielded 117 articles. Ninety-five abstracts were evaluated for relevance. Six articles met criteria and were included in this review. The findings indicate that parents want to be present during invasive procedures and resuscitation, would choose to be present again, recommend being present to others, and would not have changed anything about the presence experience. Parents who were present had better coping and better adjustment to the child's death. Parents who were not present reported more distress.CONCLUSIONS: These studies support the suggestion that family presence during resuscitation and invasive procedures increases parents' satisfaction and coping. However, the generalizability of these findings is limited by small sample sizes and inconsistent evaluation of confounding variables. Further research is needed to determine the benefits of family presence and prevent barriers to true implementation. 2014 American Association of Critical-Care Nurses. Publication type: Journal Article Source: MEDLINE Full text: Available American journal of critical care : an official publication, American Association of Critical-Care Nurses at American Journal of Critical Care 17. Title: Fine motor skills in children with prenatal alcohol exposure or fetal alcohol spectrum disorder. Citation: Journal of Developmental & Behavioral Pediatrics, November 2014, vol./is. 35/9(598-609), 0196-206X;1536-7312 (2014 Nov-Dec) Author(s): Doney R, Lucas BR, Jones T, Howat P, Sauer K, Elliott EJ Language: English Abstract: OBJECTIVE: Prenatal alcohol exposure (PAE) can cause fetal alcohol spectrum disorders (FASD) and associated neurodevelopmental impairments. It is uncertain which types of fine motor skills are most likely to be affected after PAE or which assessment tools are most appropriate to use in FASD diagnostic assessments. This systematic review examined which types of fine motor skills are impaired in children with PAE or FASD; which fine motor assessments are appropriate for FASD diagnosis; and whether fine motor impairments are evident at both "low" and "high" PAE levels.METHODS: A systematic review of relevant databases was undertaken using key terms. Relevant studies were extracted using a standardized form, and methodological quality was rated using a critical appraisal tool.RESULTS: Twenty-four studies met inclusion criteria. Complex fine motor skills, such as visual-motor integration, were more frequently impaired than basic fine motor skills, such as grip strength. Assessment tools that specifically assessed fine motor skills more consistently identified impairments than those which assessed fine motor skills as part of a generalized neurodevelopmental assessment. Fine motor impairments were associated with "moderate" to "high" PAE levels. Few studies reported fine motor skills of children with "low" PAE levels, so the effect of lower PAE levels on fine motor skills remains uncertain.CONCLUSIONS: Comprehensive assessment of a range of fine motor skills in children with PAE is important to ensure an accurate FASD diagnosis and develop appropriate therapeutic interventions for children with PAE-related fine motor impairments. Publication type: Journal Article Source: MEDLINE 18. Title: Global child health competencies for paediatricians Citation: The Lancet, October 2014, vol./is. 384/9952(1403-1405), 0140-6736;1474-547X (18 Oct 2014) Author(s): Williams B., Morrissey B., Goenka A., Magnus D., Allen S. Language: English Publication type: Journal: Note Source: EMBASE Full text: Available Lancet at Salisbury District Hospital Healthcare Library Full text: Available Lancet at Lancet, The 19. Title: Interventions for reducing medication errors in children in hospital: A systematic review Citation: Archives of Disease in Childhood, October 2014, vol./is. 99/(A156), 0003-9888 (October 2014) Author(s): Maaskant J., Vermeulen H., Apampa B., Fernando B., Ghaleb M., Neubert A., Thayyil S., Soe A. Language: English Abstract: Background and aims Children are considered to be at high risk of experiencing harm due to medication erros (MEs). Hospitals implement various interventions to reduce MEs, but their effectiveness is unclear. Therefore, we performed a systematic review to identify evidence-based interventions to reduce MEs in hospitalised children. Methods We searched the following databases: CINAHL, CENTRAL, Dissertations and Theses Database, EMBASE, EPOC Group Specialised Register, MEDLINE, Nursing and Allied Health, PsycINFO, Web of Science, Cochrane Database of Systematic Reviews and DARE. Furthermore, we searched the grey literature, trial registries and the reference lists of all included studies. We included randomised controlled trials, controlled before-after studies and interrupted time series. The outcome measures included MEs, (potential) patient harm, resource utilisation and unintended consequences of the interventions. Two reviewers independently selected studies and assessed the studies quality. Results Seven studies were included describing five different interventions: clinical pharmacist (two studies), computerised physician order entry (two studies), barcode medication administration, a structured prescribing form, and a check and control checklist in combination with feedback. Most studies resulted in a reduction in MEs, but the benefits for the patients in terms of less harm were not conclusive. Clinical and methodological heterogeneity between the studies precluded meta-analyses. Conclusion The current evidence on effective interventions to prevent MEs in a paediatric population in hospital is limited. There is a need for comparative studies with robust study designs that investigate interventions including components that focus on specific paediatric safety issues. Publication type: Journal: Conference Abstract Source: EMBASE Full text: Available ARCHIVES OF DISEASE IN CHILDHOOD at Archives of disease in childhood Full text: Available ARCHIVES OF DISEASE IN CHILDHOOD at Salisbury District Hospital Healthcare Library 20. Title: Introduction of gluten, HLA status, and the risk of celiac disease in children Citation: New England Journal of Medicine, October 2014, vol./is. 371/14(1295-1303), 0028-4793;1533-4406 (02 Oct 2014) Author(s): Lionetti E., Castellaneta S., Francavilla R., Pulvirenti A., Tonutti E., Arnarri S., Barbato M., Barbera C., Barera G., Bellantoni A., Castellano E., Guariso G., Limongelli M.G., Pellegrino S., Polloni C., Ughi C., Zuin G., Fasano A., Catassi C. Language: English Abstract: BACKGROUND The relationship between the risk of celiac disease and both the age at which gluten is introduced to a child's diet and a child's early dietary pattern is unclear. METHODS We randomly assigned 832 newborns who had a first-degree relative with celiac disease to the introduction of dietary gluten at 6 months (group A) or 12 months (group B). The HLA genotype was determined at 15 months of age, and serologic screening for celiac disease was evaluated at 15, 24, and 36 months and at 5, 8, and 10 years. Patients with positive serologic findings underwent intestinal biopsies. The primary outcome was the prevalence of celiac disease autoimmunity and of overt celiac disease among the children at 5 years of age. RESULTS Of the 707 participants who remained in the trial at 36 months, 553 had a standard-risk or high-risk HLA genotype and completed the study. At 2 years of age, significantly higher proportions of children in group A than in group B had celiac disease autoimmunity (16% vs. 7%, P = 0.002) and overt celiac disease (12% vs. 5%, P=0.01). At 5 years of age, the between-group differences were no longer significant for autoimmunity (21% in group A and 20% in group B, P = 0.59) or overt disease (16% and 16%, P=0.78 by the log-rank test). At 10 years, the risk of celiac disease autoimmunity was far higher among children with high-risk HLA than among those with standard-risk HLA (38% vs. 19%, P=0.001), as was the risk of overt celiac disease (26% vs. 16%, P=0.05). Other variables, including breast-feeding, were not associated with the development of celiac disease. CONCLUSIONS Neither the delayed introduction of gluten nor breast-feeding modified the risk of celiac disease among at-risk infants, although the later introduction of gluten was associated with a delayed onset of disease. A high-risk HLA genotype was an important predictor of disease. (Funded by the Fondazione Celiachia of the Italian Society for Celiac Disease; CELIPREV ClinicalTrials.gov number, NCT00639444.) Publication type: Journal: Review Source: EMBASE Full text: Available Massachusetts Medical Society at New England Journal of Medicine (NEJM) 21. Title: Micafungin in Premature and Non-premature Infants: A Systematic Review of 9 Clinical Trials. Citation: Pediatric Infectious Disease Journal, November 2014, vol./is. 33/11(e291-8), 0891-3668;1532-0987 (2014 Nov) Author(s): Manzoni P, Wu C, Tweddle L, Roilides E Language: English Abstract: BACKGROUND: Invasive fungal infections cause excessive morbidity and mortality in premature neonates and severely ill infants.METHODS: Safety and efficacy outcomes of micafungin were compared between prematurely and nonprematurely born infants <2 years of age. Data were obtained from all completed phase I-III clinical trials with micafungin that had enrolled infants (<2 years of age) that were listed in the Astellas Clinical Study Database. Demographics, adverse events, hepatic function tests and treatment success data were extracted and validated by the Astellas biostatistical group for all micafungin-treated patients, <2 years of age, using the unique patient identifier.RESULTS: One-hundred and sixteen patients included in 9 clinical trials, 48% premature [birth weight (BW) <2500 g and/or gestational age <37 weeks], 52% non-premature, received >1 dose of micafungin. Among premature patients, 14.5% were low BW (1500-2499 g), 36.4% very low BW (1000-1499 g) and 49.1% extremely low BW (<1000 g). Ninety patients (78%) completed the studies; 13 [11% (4 premature)] died. Significantly more non-premature than premature patients discontinued treatment (P = 0.003). Treatment-related adverse events were recorded in 23% of patients with no difference between groups. More extremely low BW (n = 4, 15%) and very low BW (n = 8, 40%) infants experienced treatment-related adverse events than low BW (n = 0) and there was no relation to micafungin dose or duration. For a subgroup of 30 patients with invasive candidiasis, treatment success was achieved in 73% in both premature and non-premature groups. Prophylaxis was successful in 4/5 non-premature hematopoietic stem cell transplant patients.CONCLUSION: Micafungin has a safe profile in premature and non-premature infants with substantial efficacy. Publication type: Journal Article Source: MEDLINE Full text: Available The Pediatric infectious disease journal at Pediatric Infectious Disease Journal 22. Title: Oral morphine versus ibuprofen for post-fracture pain management in children: A randomized controlled study Citation: Annals of Emergency Medicine, October 2014, vol./is. 64/4 SUPPL. 1(S60), 0196-0644 (October 2014) Author(s): Teefy J., Bhullar G., Lin K., Papini A., Nedadur R., Howard J., Bale M., Mainprize D., Seabrook J., Poonai N. Language: English Abstract: Study Objectives: In the emergency department (ED), fractures are a common painful condition where evidence suggests that analgesia is under-utilized. Codeine has been removed from many pediatric formularies due to safety concerns and the use of a theoretically more predictable drug: oral morphine has increased. However, it has not been studied in the pain management of pediatric fractures. This study was undertaken to determine if oral morphine is superior to ibuprofen in relieving post-fracture pain without an increase in adverse effects. Methods: Children aged 5-17 years who presented to the ED with a non-operative fracture were randomized to receive either oral morphine 0.5 mg/kg (max 10 mg) or ibuprofen 10 mg/kg (max 600 mg) every 6 hours as needed for pain for 24 hours following discharge. The primary outcome variable was the pre-post intervention difference in self-reported pain scores using the Faces Pain Scale Revised (FPS-R). Results: A total of 131 participants were included in the analysis with a mean age + SD of 10.7 + 3.2 years. In both arms, there was a reduction in pain scores following the intervention at each dose, with no significant differences in the change in pain for any of the four doses. However, there were significantly more adverse effects reported in the oral morphine group (55.6% versus 30.9%, P=.005). Conclusion: Both oral morphine and ibuprofen were effective at reducing pain in children with fractures. Although there was no significant difference in analgesic efficacy between the two agents, oral morphine was associated with significantly more adverse effects. Publication type: Journal: Conference Abstract Source: EMBASE 23. Title: Paediatric palliative care: A systematic review and recommendations for treatment of symptoms Citation: Pediatric Blood and Cancer, December 2014, vol./is. 61/(S394-S395), 1545-5009 (December 2014) Author(s): Knops R.R.G., Kremer L.C.M., Verhagen A.A.E. Language: English Abstract: Objectives: Children dying of a life threatening disease suffer a great deal at the end of life. Symptom control in children dying of cancer is often unsatisfactory at this stage of disease, partly because many caregivers are simply not familiar with paediatric palliative care. Symptom control and relieve of suffering are the cornerstones of paediatric palliative care, but evidence based recommendations in paediatric palliative care are not available. The aim of this study is to improve palliative care for children by making high quality care recommendations to recognize and relieve symptoms in paediatric palliative care. Methods: An extensive search was performed for guidelines and systematic reviews on paediatric palliative care. An expert panel combined the evidence that resulted from this search with consensus to form recommendations on the treatment of symptoms in paediatric palliative care. Results: We appraised 21 guidelines and identified 693 potentially eligible articles of which only four met our inclusion criteria. None gave recommendations on recognizing and treating symptoms in paediatric palliative care. Two textbooks and an adult palliative care website were eventually our main sources of evidence on recognizing and treating symptoms in paediatric palliative care. Conclusions: Hardly any evidence is available for the treatment of symptoms in paediatric palliative care. By combining evidence for adult palliative care and the sparse evidence for paediatric palliative care with paediatric expert opinion we were able to define a unique set of high quality care recommendations to relieve symptoms and lessen the suffering of children in palliative care. The results of this study are an important tool to educate caregivers on how to relieve symptoms in children with life threatening conditions and improve quality of paediatric palliative care. Publication type: Journal: Conference Abstract