Altered hippocampal function with preserved cognitive performance in treatment-naive major depressive disorder.

The hippocampus is implicated in the pathophysiology of major depressive disorder (MDD), with evidence that morphological changes occur with disease progression. It was hypothesized that treatment-naive patients with depression would show performance deficits in hippocampus-dependent memory trials, with concurrent hippocampal activation deficits on functional magnetic resonance imaging, compared with control participants. Thirteen treatment-naive patients with MDD and 13 control participants completed a hippocampus-dependent memory functional magnetic resonance imaging process-dissociation task. On behavioural measures of habit memory and guessing, there were no significant differences between groups. Functional magnetic resonance imaging analysis indicated that compared with the control group, the MDD group showed increased activation in the parahippocampal gyrus and hippocampus on habit memory and nonitem trials. These alterations in hippocampal functioning with preserved cognitive performance on a test of hippocampus-dependent memory in MDD may be indicative of a compensatory mechanism.

Correction: Gastroenteritis Therapies in Developed Countries: Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.1371/journal.pone.0128754.].

A Systematic Review of Social Media Use to Discuss and View Deliberate Self-Harm Acts.

OBJECTIVE: To conduct a systematic review of studies of social media platforms used by young people to discuss and view deliberate self-harm. STUDY DESIGN: 11 electronic databases were searched from January 2000 to January 2012 for primary research; in June 2014 an updated search of Medline was conducted. Grey literature sources were also searched. Search results were screened by two reviewers. Data were extracted by one reviewer and verified by another. Methodological quality was assessed using the Mixed Methods Appraisal Tool. RESULTS: Due to heterogeneity in study objectives and outcomes, results were not pooled; a narrative analysis is presented. 26 studies were included. Most were conducted in Canada or the UK (30.8% each), used qualitative designs (42.3%), and evaluated discussion forums (73.1%). Participants were most often aged 19-21 years (69.2%), female (mean 68.6%), and 19.2% had a documented history of depression. The social media platforms evaluated were commonly supportive and provided a sense of community among users. Support included suggestions for formal treatment, advice on stopping self-harming behavior, and encouragement. Harms included normalizing and accepting self-harming behavior; discussion of motivation or triggers, concealment, suicidal ideation or plans; and live depictions of self-harm acts. CONCLUSIONS: Although this evidence is limited by its descriptive nature, studies identify beneficial and detrimental effects for young people using social media to discuss and view deliberate self-harm. The connections users make online may be valuable to explore for therapeutic benefit. Prospective, longitudinal investigations are needed to identify short- and long-term potential harms associated with use.

What Works and What's Safe in Pediatric Emergency Procedural Sedation: An Overview of Reviews.

BACKGROUND: Sedation is increasingly used to facilitate procedures on children in emergency departments (EDs). This overview of systematic reviews (SRs) examines the safety and efficacy of sedative agents commonly used for procedural sedation in children in the ED or similar settings. METHODS: We followed standard SR methods: comprehensive search; dual study selection, quality assessment, data extraction. We included SRs of children (1 month to 18 years) where the indication for sedation was procedure-related and performed in the ED. RESULTS: Fourteen SRs were included (210 primary studies). The most data were available for propofol (six reviews/50,472 sedations) followed by ketamine (7/8,238), nitrous oxide (5/8,220), and midazolam (4/4,978). Inconsistent conclusions for propofol were reported across six reviews. Half concluded that propofol was sufficiently safe; three reviews noted a higher occurrence of adverse events, particularly respiratory depression (upper estimate 1.1%; 5.4% for hypotension requiring intervention). Efficacy of propofol was considered in four reviews and found adequate in three. Five reviews found ketamine to be efficacious and seven reviews showed it to be safe. All five reviews of nitrous oxide concluded it is safe (0.1% incidence of respiratory events); most found it effective in cooperative children. Four reviews of midazolam made varying recommendations. To be effective, midazolam should be combined with another agent that increases the risk of adverse events (upper estimate 9.1% for desaturation, 0.1% for hypotension requiring intervention). CONCLUSIONS: This comprehensive examination of an extensive body of literature shows consistent safety and efficacy for nitrous oxide and ketamine, with very rare significant adverse events for propofol. There was considerable heterogeneity in outcomes and reporting across studies and previous reviews. Standardized outcome sets and reporting should be encouraged to facilitate evidence-based recommendations for care.

Prevalence and Effect of Cyberbullying on Children and Young People: A Scoping Review of Social Media Studies.

IMPORTANCE: Social media has had a profound effect on how children and adolescents interact. While there are many benefits to the use of social media, cyberbullying has emerged as a potential harm, raising questions regarding its influence on mental health. OBJECTIVE: To review existing publications that examine the health-related effects of cyberbullying via social media among children and adolescents. EVIDENCE REVIEW: We searched 11 electronic databases from January 1, 2000, through January 17, 2012 (updated June 24, 2014). Studies were screened by 2 independent reviewers and were included if they reported primary research, described or evaluated the use of a social media tool in the context of cyberbullying, and were conducted with children or adolescents. Data were extracted by 1 reviewer and verified by a second. All studies were assessed by 2 reviewers for methodological quality using the Mixed Methods Appraisal Tool. Results were not pooled owing to heterogeneity in study objectives and outcomes; a narrative analysis is presented. FINDINGS: Thirty-six studies in 34 publications were included. Most were conducted in the United States (21 [58.3%]), sampled middle and high school populations (24 [66.7%]), and included adolescents who were 12 to 18 years of age (35 [97.2%]). The median reported prevalence of cyberbullying was 23.0% (interquartile range, 11.0%-42.6%). Five studies reported inconsistent and/or weak correlations between cyberbullying and anxiety. Ten studies found a statistically significant association between cyberbullying and report of depression. Five studies investigated self-harm or suicidality, with conflicting results. Results indicate that the most common reason for cyberbullying is relationship issues, with girls most often being the recipients. Responses to cyberbullying are most often passive, with a pervasive lack of awareness or confidence that anything can be done. CONCLUSIONS AND RELEVANCE: There is a consistent relationship across studies between cyberbullying and depression among children and adolescents; however, the evidence of the effect of cyberbullying on other mental health conditions is inconsistent. This review provides important information that characterizes cyberbullying within the context of social media, including attributes of the recipients and perpetrators, reasons for and the nature of bullying behaviors, and how recipients react to and manage bullying behaviors. This information is critical to the development of effective prevention and management strategies.

Gastroenteritis Therapies in Developed Countries: Systematic Review and Meta-Analysis.

CONTEXT: Gastroenteritis remains a leading cause of childhood morbidity. OBJECTIVE: Because prior reviews have focused on isolated symptoms and studies conducted in developing countries, this study focused on interventions commonly considered for use in developed countries. Intervention specific, patient-centered outcomes were selected. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, trial registries, grey literature, and scientific meetings. STUDY SELECTION: Randomized controlled trials, conducted in developed countries, of children aged <18 years, with gastroenteritis, performed in emergency department or outpatient settings which evaluated oral rehydration therapy (ORT), antiemetics, probiotics or intravenous fluid administration rate. DATA EXTRACTION: The study was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA guidelines. Data were independently extracted by multiple investigators. Analyses employed random effects models. RESULTS: 31 trials (4,444 patients) were included. ORT: Compared with intravenous rehydration, hospitalization (RR 0.80, 95%CI 0.24, 2.71) and emergency department return visits (RR 0.86, 95%CI 0.39, 1.89) were similar. Antiemetics: Fewer children administered an antiemetic required intravenous rehydration (RR 0.40, 95%CI 0.26, 0.60) While the data could not be meta-analyzed, three studies reported that ondansetron administration does increase the frequency of diarrhea. Probiotics: No studies reported on the primary outcome, three studies evaluated hospitalization within 7 days (RR 0.87, 95%CI 0.25, 2.98). Rehydration: No difference in length of stay was identified for rapid vs. standard intravenous or nasogastric rehydration. A single study found that 5% dextrose in normal saline reduced hospitalizations compared with normal saline alone (RR 0.70, 95% CI 0.53, 0.92). CONCLUSIONS: There is a paucity of patient-centered outcome evidence to support many interventions. Since ORT is a low-cost, non-invasive intervention, it should continue to be used. Routine probiotic use cannot be endorsed at this time in outpatient children with gastroenteritis. Despite some evidence that ondansetron administration increases diarrhea frequency, emergency department use leads to reductions in intravenous rehydration and hospitalization. No benefits were associated with ondansetron use following emergency department discharge.

Design and Implementation of an fMRI Study Examining Thought Suppression in Young Women with, and At-risk, for Depression.

Ruminative brooding is associated with increased vulnerability to major depression. Individuals who regularly ruminate will often try to reduce the frequency of their negative thoughts by actively suppressing them. We aim to identify the neural correlates underlying thought suppression in at-risk and depressed individuals. Three groups of women were studied; a major depressive disorder group, an at-risk group (having a first degree relative with depression) and controls. Participants performed a mixed block-event fMRI paradigm involving thought suppression, free thought and motor control periods. Participants identified the re-emergence of "to-be-suppressed" thoughts ("popping" back into conscious awareness) with a button press. During thought suppression the control group showed the greatest activation of the dorsolateral prefrontal cortex, followed by the at-risk, then depressed group. During the re-emergence of intrusive thoughts compared to successful re-suppression of those thoughts, the control group showed the greatest activation of the anterior cingulate cortices, followed by the at-risk, then depressed group. At-risk participants displayed anomalies in the neural regulation of thought suppression resembling the dysregulation found in depressed individuals. The predictive value of these changes in the onset of depression remains to be determined.

Diagnosing clinically significant dehydration in children with acute gastroenteritis using noninvasive methods: a meta-analysis.

OBJECTIVE: To determine the most accurate, noninvasive method of assessing dehydration. STUDY DESIGN: The following data sources were searched: electronic databases, gray literature, scientific meetings, reference lists, and authors of unpublished studies. Eligible studies were comparative outpatient evaluations that used an accepted reference standard and were conducted in developed countries in children aged <18 years with gastroenteritis. Data extraction was completed independently by multiple reviewers before a consensus was made. RESULTS: Nine studies that included 1039 participants were identified. The 4-item Clinical Dehydration Scale (CDS), the "Gorelick" score, and unstructured physician assessment were evaluated in 3, 2, and 5 studies, respectively. Bedside ultrasound, capillary digital videography, and urinary measurements were each evaluated in one study. The CDS had a positive likelihood ratio (LR) range of 1.87-11.79 and a negative LR range of 0.30-0.71 to predict 6% dehydration. When combined with the 4-item Gorelick Score, the positive LR was 1.93 (95% CI 1.07-3.49) and negative LR was of 0.40 (95% CI 0.24-0.68). Unstructured dehydration assessment had a pooled positive LR of 2.13 (95% CI 1.33-3.44) and negative LR of 0.48 (95% CI 0.28-0.82) to detect ≥ 5% dehydration. CONCLUSIONS: Overall, the clinical scales evaluated provide some improved diagnostic accuracy. However, test characteristics indicate that their ability to identify children both with and without dehydration is suboptimal. Current evidence does not support the routine use of ultrasound or urinalysis to determine dehydration severity.

A systematic review of the use and effectiveness of social media in child health.

BACKGROUND: Social media use is highly prevalent among children, youth, and their caregivers, and its use in healthcare is being explored. The objective of this study was to conduct a systematic review to determine: 1) for what purposes social media is being used in child health and its effectiveness; and 2) the attributes of social media tools that may explain how they are or are not effective. METHODS: We searched Medline, CENTRAL, ERIC, PubMed, CINAHL, Academic Search Complete, Alt Health Watch, Health Source, Communication and Mass Media Complete, Web of Knowledge, and Proquest Dissertation and Theses Database from 2000-2013. We included primary research that evaluated the use of a social media tool, and targeted children, youth, or their families or caregivers. Quality assessment was conducted on all included analytic studies using tools specific to different quantitative designs. RESULTS: We identified 25 studies relevant to child health. The majority targeted adolescents (64%), evaluated social media for health promotion (52%), and used discussion forums (68%). Most often, social media was included as a component of a complex intervention (64%). Due to heterogeneity in conditions, tools, and outcomes, results were not pooled across studies. Attributes of social media perceived to be effective included its use as a distraction in younger children, and its ability to facilitate communication between peers among adolescents. While most authors presented positive conclusions about the social media tool being studied (80%), there is little high quality evidence of improved outcomes to support this claim. CONCLUSIONS: This comprehensive review demonstrates that social media is being used for a variety of conditions and purposes in child health. The findings provide a foundation from which clinicians and researchers can build in the future by identifying tools that have been developed, describing how they have been used, and isolating components that have been effective.

An fMRI study of reward circuitry in patients with minimal or extensive history of major depression.

Functional abnormalities in regions associated with reward processing are apparent in people with depression, but the extent to which disease burden impacts on the processing of reward is unknown. This research examined the neural correlates of reward processing in patients with major depressive disorder and varying degrees of past illness burden. Twenty-nine depressed patients and twenty-five healthy subjects with no lifetime history of psychiatric illness completed the study. Subsets of fourteen patients were presenting for first lifetime treatment of a depressive episode, and fifteen patients had at least three treated episodes of depression. We used functional magnetic resonance imaging to study blood oxygen level-dependent signals during the performance of a contingency reversal reward paradigm. The results identified group differences in the response to punishers bilaterally in the orbitofrontal and medial prefrontal regions. In addition, areas such as the nucleus accumbens, anterior cingulate and ventral prefrontal cortices were activated greatest by controls during reward processing, less by patients early in the course of illness and least by patients with highly recurrent illness-suggesting that these areas are sensitive to the impact of disease burden and repeated episodes of depression. Reward processing in people with depression may be associated with diminished signaling of incentive salience, a reduction in the formation of reward-related associations and heightened sensitivities for negatively valenced stimuli, all of which could contribute to symptoms of depression.

A systematic review of interventions to support siblings of children with chronic illness or disability.

AIM: Chronic illness or disability in children can have a deleterious effect on the psychosocial health of well siblings. This systematic review synthesised evidence from studies evaluating sibling-oriented care aimed at improving behavioural and emotional outcomes in well siblings of children with chronic illness or disability. METHODS: Twenty electronic databases were searched. Study selection, data extraction and assessment of methodological quality were performed by two independent reviewers. RESULTS: Five controlled and nine uncontrolled studies were included. In higher-quality controlled trials, benefits of sibling-oriented care included reduced anxiety, improved mood and behavioural adjustment; however, these findings were not consistently demonstrated across studies. Study differences made it difficult to determine which sibling care features were most salient. CONCLUSIONS: Study findings highlight the potential for enhancing emotional and behavioural outcomes in well siblings. Future evaluations need to clearly identify the intended purpose of the care (what improvements are intended) and which types of siblings are most likely to benefit. This approach may yield more consistent and clinically important results.

Neural systems underlying thought suppression in young women with, and at-risk, for depression.

OBJECTIVE: Ruminative brooding is associated with increased vulnerability to major depression. Individuals who regularly ruminate will often try to reduce the frequency of their negative thoughts by actively suppressing them. We aimed to identify the neural correlates underlying thought suppression in at-risk and depressed individuals. METHODS: Three groups of women were studied; a major depressive disorder group, an at-risk group (having a first degree relative with depression) and controls. Participants performed a mixed block-event fMRI paradigm involving thought suppression, free thought and motor control periods. Participants identified the re-emergence of "to-be-suppressed" thoughts with a button press. RESULTS: During thought suppression the control group showed the greatest activation of the dorsolateral prefrontal cortex, followed by the at-risk, then depressed group. During the re-emergence of intrusive thoughts compared to successful re-suppression of those thoughts, the control group showed the greatest activation of the anterior cingulate cortices, followed by the at-risk, then depressed group. CONCLUSIONS: At-risk participants displayed anomalies in the neural regulation of thought suppression resembling the dysregulation found in depressed individuals. The predictive value of these changes in the onset of depression remains to be determined.

Social media use by health care professionals and trainees: a scoping review.

PURPOSE: To conduct a scoping review of the literature on social media use by health care professionals and trainees. METHOD: The authors searched MEDLINE, CENTRAL, ERIC, PubMed, CINAHL Plus Full Text, Academic Search Complete, Alt Health Watch, Health Source, Communication and Mass Media Complete, Web of Knowledge, and ProQuest for studies published between 2000 and 2012. They included those reporting primary research on social media use by health care professionals or trainees. Two reviewers screened studies for eligibility; one reviewer extracted data and a second verified a 10% sample. They analyzed data descriptively to determine which social media tools were used, by whom, for what purposes, and how they were evaluated. RESULTS: The authors included 96 studies in their review. Discussion forums were the most commonly studied tools (43/96; 44.8%). Researchers more often studied social media in educational than practice settings. Of common specialties, administration, critical appraisal, and research appeared most often (11/96; 11.5%), followed by public health (9/96; 9.4%). The objective of most tools was to facilitate communication (59/96; 61.5%) or improve knowledge (41/96; 42.7%). Thirteen studies evaluated effectiveness (13.5%), and 41 (42.7%) used a cross-sectional design. CONCLUSIONS: These findings provide a map of the current literature on social media use in health care, identify gaps in that literature, and provide direction for future research. Social media use is widespread, particularly in education settings. The versatility of these tools suggests their suitability for use in a wide range of professional activities. Studies of their effectiveness could inform future practice.

Social media use among patients and caregivers: a scoping review.

OBJECTIVE: To map the state of the existing literature evaluating the use of social media in patient and caregiver populations. DESIGN: Scoping review. DATA SOURCES: Medline, CENTRAL, ERIC, PubMed, CINAHL Plus Full Text, Academic Search Complete, Alt Health Watch, Health Source, Communication and Mass Media Complete, Web of Knowledge and ProQuest (2000-2012). STUDY SELECTION: Studies reporting primary research on the use of social media (collaborative projects, blogs/microblogs, content communities, social networking sites, virtual worlds) by patients or caregivers. DATA EXTRACTION: Two reviewers screened studies for eligibility; one reviewer extracted data from relevant studies and a second performed verification for accuracy and completeness on a 10% sample. Data were analysed to describe which social media tools are being used, by whom, for what purpose and how they are being evaluated. RESULTS: Two hundred eighty-four studies were included. Discussion forums were highly prevalent and constitute 66.6% of the sample. Social networking sites (14.8%) and blogs/microblogs (14.1%) were the next most commonly used tools. The intended purpose of the tool was to facilitate self-care in 77.1% of studies. While there were clusters of studies that focused on similar conditions (eg, lifestyle/weight loss (12.7%), cancer (11.3%)), there were no patterns in the objectives or tools used. A large proportion of the studies were descriptive (42.3%); however, there were also 48 (16.9%) randomised controlled trials (RCTs). Among the RCTs, 35.4% reported statistically significant results favouring the social media intervention being evaluated; however, 72.9% presented positive conclusions regarding the use of social media. CONCLUSIONS: There is an extensive body of literature examining the use of social media in patient and caregiver populations. Much of this work is descriptive; however, with such widespread use, evaluations of effectiveness are required. In studies that have examined effectiveness, positive conclusions are often reported, despite non-significant findings.

Testing the Newcastle Ottawa Scale showed low reliability between individual reviewers.

OBJECTIVES: To assess inter-rater reliability and validity of the Newcastle Ottawa Scale (NOS) used for methodological quality assessment of cohort studies included in systematic reviews. STUDY DESIGN AND SETTING: Two reviewers independently applied the NOS to 131 cohort studies included in eight meta-analyses. Inter-rater reliability was calculated using kappa (κ) statistics. To assess validity, within each meta-analysis, we generated a ratio of pooled estimates for each quality domain. Using a random-effects model, the ratios of odds ratios for each meta-analysis were combined to give an overall estimate of differences in effect estimates. RESULTS: Inter-rater reliability varied from substantial for length of follow-up (κ = 0.68, 95% confidence interval [CI] = 0.47, 0.89) to poor for selection of the nonexposed cohort and demonstration that the outcome was not present at the outset of the study (κ = -0.03, 95% CI = -0.06, 0.00; κ = -0.06, 95% CI = -0.20, 0.07). Reliability for overall score was fair (κ = 0.29, 95% CI = 0.10, 0.47). In general, reviewers found the tool difficult to use and the decision rules vague even with additional information provided as part of this study. We found no association between individual items or overall score and effect estimates. CONCLUSION: Variable agreement and lack of evidence that the NOS can identify studies with biased results underscore the need for revisions and more detailed guidance for systematic reviewers using the NOS.

Testing the risk of bias tool showed low reliability between individual reviewers and across consensus assessments of reviewer pairs.

OBJECTIVES: To assess the reliability of the Cochrane Risk of Bias (ROB) tool between individual raters and across consensus agreements of pairs of reviewers and examine the impact of study-level factors on reliability. STUDY DESIGN AND SETTING: Two reviewers assessed risk of bias for 154 randomized controlled trials (RCTs). For 30 RCTs, two reviewers from each of four centers assessed risk of bias and reached consensus. We assessed interrater agreement using kappas and the impact of study-level factors through subgroup analyses. RESULTS: Reliability between two reviewers was fair for most domains (κ=0.24-0.37), except sequence generation (κ=0.79, substantial). Reliability results across reviewer pairs: sequence generation, moderate (κ=0.60); allocation concealment and "other sources of bias," fair (κ=0.37-0.27); and other domains, slight (κ=0.05-0.09). Reliability was influenced by the nature of the outcome, nature of the intervention, study design, trial hypothesis, and funding source. Variability resulted from different interpretation of the tool rather than different information identified in the study reports. CONCLUSION: Low agreement has implications for interpreting systematic reviews. These findings suggest the need for detailed guidance in assessing the risk of bias.

Abnormal hippocampal activation in patients with extensive history of major depression: an fMRI study.

BACKGROUND: Impairment of recollection memory is consistently reported in patients with major depressive disorder (MDD) and may reflect underlying functional hippocampal changes, particularly in those with extensive histories of illness. We hypothesized that relative to controls, patients with a protracted course of illness would show diminished hippocampal activation on functional magnetic resonance imaging (fMRI) during a recollection memory task. METHODS: Patients who experienced 3 or more previously treated depressive episodes were compared with age- and sex-matched controls. We acquired fMRI data while participants performed a recollection memory process dissociation task. RESULTS: Using bilateral regions of interest (ROIs) prescribed for the right and left hippocampal/parahippocampal complex, we observed increased activation of the right hippocampal and left parahippocampal gyrus in controls compared with patients with MDD during recollection memory trials. Within-group comparisons revealed heightened engagement of the hippocampal head (R/L) for controls during recollection trials, and greater activation of the hippocampal body/tail (R/L) during the learn-list encoding period in both the MDD and control groups. Recollection memory performance was significantly correlated with changes in blood oxygen level-dependent signal during recollection trials in the ROIs of the right hippocampus and right hippocampal head. LIMITATIONS: This study was limited by the inclusion of patients taking antidepressant medication, raising the possibility that the reported findings were treatment effects. CONCLUSION: The findings of decreased recruitment of the right hippocampal and left parahippocampalgyrus in patients with MDD suggest that these regions may be sensitive to the impact of disease burden and repeated episodes of MDD. This attenuated activation may represent stable changes in hippocampal function that occur over the course of illness in patients with MDD. The findings from within-group comparisons show that the group differences in the activation of the right hippocampal head were driven by greater engagement of this region among controls during recollection memory performance. These results also associate recollection performance impairments in patients with MDD with diminished hippocampal engagement.

Steroids and bronchodilators for acute bronchiolitis in the first two years of life: systematic review and meta-analysis.

OBJECTIVE: To evaluate and compare the efficacy and safety of bronchodilators and steroids, alone or combined, for the acute management of bronchiolitis in children aged less than 2 years. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Central, Scopus, PubMed, LILACS, IranMedEx, conference proceedings, and trial registers. Inclusion criteria Randomised controlled trials of children aged 24 months or less with a first episode of bronchiolitis with wheezing comparing any bronchodilator or steroid, alone or combined, with placebo or another intervention (other bronchodilator, other steroid, standard care). REVIEW METHODS: Two reviewers assessed studies for inclusion and risk of bias and extracted data. Primary outcomes were selected by clinicians a priori based on clinical relevance: rate of admission for outpatients (day 1 and up to day 7) and length of stay for inpatients. Direct meta-analyses were carried out using random effects models. A mixed treatment comparison using a Bayesian network model was used to compare all interventions simultaneously. RESULTS: 48 trials (4897 patients, 13 comparisons) were included. Risk of bias was low in 17% (n = 8), unclear in 52% (n = 25), and high in 31% (n = 15). Only adrenaline (epinephrine) reduced admissions on day 1 (compared with placebo: pooled risk ratio 0.67, 95% confidence interval 0.50 to 0.89; number needed to treat 15, 95% confidence interval 10 to 45 for a baseline risk of 20%; 920 patients). Unadjusted results from a single large trial with low risk of bias showed that combined dexamethasone and adrenaline reduced admissions on day 7 (risk ratio 0.65, 0.44 to 0.95; number needed to treat 11, 7 to 76 for a baseline risk of 26%; 400 patients). A mixed treatment comparison supported adrenaline alone or combined with steroids as the preferred treatments for outpatients (probability of being the best treatment based on admissions at day 1 were 45% and 39%, respectively). The incidence of reported harms did not differ. None of the interventions examined showed clear efficacy for length of stay among inpatients. CONCLUSIONS: Evidence shows the effectiveness and superiority of adrenaline for outcomes of most clinical relevance among outpatients with acute bronchiolitis, and evidence from a single precise trial for combined adrenaline and dexamethasone.

A descriptive analysis of a representative sample of pediatric randomized controlled trials published in 2007.

BACKGROUND: Randomized controlled trials (RCTs) are the gold standard for trials assessing the effects of therapeutic interventions; therefore it is important to understand how they are conducted. Our objectives were to provide an overview of a representative sample of pediatric RCTs published in 2007 and assess the validity of their results. METHODS: We searched Cochrane Central Register of Controlled Trials using a pediatric filter and randomly selected 300 RCTs published in 2007. We extracted data on trial characteristics; outcomes; methodological quality; reporting; and registration and protocol characteristics. Trial registration and protocol availability were determined for each study based on the publication, an Internet search and an author survey. RESULTS: Most studies (83%) were efficacy trials, 40% evaluated drugs, and 30% were placebo-controlled. Primary outcomes were specified in 41%; 43% reported on adverse events. At least one statistically significant outcome was reported in 77% of trials; 63% favored the treatment group. Trial registration was declared in 12% of publications and 23% were found through an Internet search. Risk of bias (ROB) was high in 59% of trials, unclear in 33%, and low in 8%. Registered trials were more likely to have low ROB than non-registered trials (16% vs. 5%; p = 0.008). Effect sizes tended to be larger for trials at high vs. low ROB (0.28, 95% CI 0.21,0.35 vs. 0.16, 95% CI 0.07,0.25). Among survey respondents (50% response rate), the most common reason for trial registration was a publication requirement and for non-registration, a lack of familiarity with the process. CONCLUSIONS: More than half of this random sample of pediatric RCTs published in 2007 was at high ROB and three quarters of trials were not registered. There is an urgent need to improve the design, conduct, and reporting of child health research.

Increased choline-containing compounds in the orbitofrontal cortex and hippocampus in euthymic patients with bipolar disorder: a proton magnetic resonance spectroscopy study.

The neuronal mechanisms underlying the pathophysiology of bipolar disorder (BD) have not been fully characterized. The aim of this study was to compare metabolite levels in the hippocampus and the orbitofrontal cortex in a homogenous population of 12 euthymic patients with well-established BD and 12 age- and sex-matched healthy comparison subjects. Using a GE Signa, 3-Tesla scanner, we performed proton magnetic resonance spectroscopy (H-MRS) to examine levels of N-acetyl aspartate, glutamate and choline-containing compounds. Choline-containing compounds were significantly increased in the hippocampus and the orbitofrontal cortex in BD patients relative to control subjects. Significant elevations of glycerophosphocholine+phosphocholine (GPC+PCh) were measured in the hippocampus and the orbitofrontal cortex of patients. As choline is a marker of membrane phospholipid metabolism, the elevated choline in patients may indicate increased membrane breakdown in the brain regions examined. Abnormal neuronal loss within the hippocampus and orbitofrontal cortex further supports previous work suggesting that these regions are involved in the pathophysiology of BD.