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BackgroundDepressive disorders are common in young people and are associated with significant negative impacts. Selective serotonin reuptake inhibitors (SSRIs) are often used, however, evidence of their effectiveness in children and adolescents is not clear. Furthermore, there have been warnings against their use in this population due to concerns about increased risk of suicidal ideation and behaviour.ObjectivesTo determine the efficacy and adverse outcomes, including definitive suicidal behaviour and suicidal ideation, of SSRIs compared to placebo in the treatment of depressive disorders in children and adolescents.Search strategyWe searched the CCDAN Trials Register, MEDLINE, PSYCHINFO and CENTRAL. Reference lists were checked, letters were sent to key researchers and internet databases searched.Selection criteriaWe included published and unpublished randomised controlled trials.Data collection and analysisTwo or three review authors selected the trials, assessed the quality and extracted trial and outcome data. We used a fixed‐effect meta‐analysis. The relative risk was used to summarise dichotomous outcomes and the mean difference to summarise continuous measures.Main resultsTwelve trials were eligible for inclusion, with ten providing usable data. At 8‐12 weeks, there was evidence that children and adolescents 'responded' to treatment with SSRIs (RR 1.28, 95% CI 1.17 to 1.41). There was also evidence of an increased risk of suicidal ideation and behaviour for those prescribed SSRIs (RR 1.80, 95% CI 1.19 to 2.72). Fluoxetine was the only SSRI where there was consistent evidence from three trials that it was effective in reducing depression symptoms in both children and adolescents (CDRS‐R treatment effect ‐5.63, 95% CI ‐7.38 to ‐3.88), and 'response' to treatment (RR 1.86, 95% CI 1.49 to 2.32). Where rates of adverse events were reported, this was higher for those prescribed SSRIs.Authors' conclusionsCaution is required to interpret the results. First, there were methodological issues, including high attrition, issues regarding measurement instruments and clinical usefulness of outcomes, often variously defined across trials. Second, patients seen in clinical practice are likely to be more unwell, and at greater risk of suicide, compared to those in the trials, and it is unclear how this group would respond to SSRIs. This needs to be considered, along with the evidence of an increased risk of suicide related outcomes in those treated with SSRIs. It is unclear what the effect of SSRIs is on suicide completion. While untreated depression is associated with the risk of completed suicide and impacts on functioning, it is unclear whether SSRIs would modify this risk in a clinically meaningful way.Plain language summarySelective serotonin reuptake inhibitors (new generation antidepressants) for depressive disorders in children and adolescentsDepressive disorders are common in young people and have significant negative impacts. Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for the treatment of depressive disorder in children and adolescents. The review of 12 trials highlighted limitations with the data, making it difficult to answer questions about the effectiveness and safety of SSRIs in clinical practice. Overall, there was evidence of greater reduction in depressive symptoms to a predetermined level deemed a "response" on SSRI compared to placebo. However, response was variously defined across trials making interpretation of this outcome difficult. Fluoxetine was the only SSRI where there was consistent evidence from three trials showing that it was effective in reducing symptoms of depressive disorder in both children and adolescents. Those receiving fluoxetine had a greater improvement, scoring on average 5.63 lower on the Children's Depression Rating Scale‐Revised (CDRS‐R) scale (range 17‐113) than those on placebo. It is unclear whether this small difference is a meaningful outcome for children and adolescents with depressive disorders. Nor is it apparent how children and adolescents with co‐morbid conditions and at risk of suicide would respond to SSRIs, given this group were largely excluded from the trials.There is evidence that those prescribed SSRIs are at an increased risk of suicidal ideation and attempts (RR 1.80, 95% CI 1.19 to 2.72) consistent with a number of similar reviews in the area. Additionally, there was an increased risk of other adverse events. It is unclear how this relates to the risk of suicide completion. The trials were not designed to measure any of the suicide related outcomes adequately. At the same time, untreated depression is associated with the risk of completed suicide and impacts on academic and social functioning, however, it is not clear whether treatment with an SSRI will modify this risk in a clinically meaningful way for children and young people.Clinicians need to provide accurate information to children and adolescents and their families about the uncertainties regarding the benefits and risks of SSRI medication for depressive disorders.

Background: Hyponatraemia is associated with increased morbidity, increased mortality and is frequently hospital-acquired due to inappropriate administration of hypotonic fluids. Despite several attempts to minimise the risk, knowledge is lacking as to whether inappropriate prescribing practice continues to be a concern. Methods: A cross-sectional survey was performed in Danish emergency department physicians in spring 2019. Prescribing practices were assessed by means of four clinical scenarios commonly encountered in the emergency department. Thirteen multiple-choice questions were used to measure knowledge. Results: 201 physicians responded corresponding to 55.4% of the total population of physicians working at emergency departments in Denmark. About a quarter reported that they would use hypotonic fluids in patients with increased intracranial pressure and 29.4% would use hypotonic maintenance fluids in children, both of which are against guideline recommendations. Also, 29.4% selected the correct fluid, a 3% hypertonic saline solution, for a patient with hyponatraemia and severe neurological symptoms, which is a medical emergency. Most physicians were unaware of the impact of hypotonic fluids on plasma sodium in acutely ill patients. Conclusion: Inappropriate prescribing practices and limited knowledge of a large number of physicians calls for further interventions to minimise the risk of hospital-acquired hyponatraemia.

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Hypotonic intravenous (IV) fluids are associated with an increased risk of hospital-acquired hyponatraemia, eventually leading to brain injury and death. We evaluated the effectiveness of a treatment guide to improve prescribing practices of IV fluids. We conducted a before-and-after cross-sectional survey among physicians working at Danish emergency departments. The primary outcome was prescribing practices of IV fluids. Participants were asked which IV fluid they would select in four clinical scenarios. We applied multivariate logistic regression models to estimate the odds ratio of selecting hypotonic fluids. Secondary outcomes included knowledge about IV fluids and hyponatraemia, and the receipt, reading, and usefulness of the treatment guide. After the intervention, about a third (47/154) reported that they would use hypotonic fluids in patients with increased intracranial pressure, and a quarter (39/154) would use hypotonic maintenance fluids in children, both of which are against guideline recommendations. A total of 46% selected the correct fluid, a 3% hypertonic saline solution for a patient with hyponatraemia and severe neurological symptoms. None of the knowledge questions met the predefined criteria of success of 80% correct answers. Of the respondents, 22% had received the treatment guide. Since the implementation failed, we recommend improving distribution by applying methods from implementation science.

This study aimed to evaluate the impact of the risk minimisation measures issued by the European Medicines Agency in 2014 to restrict the combined use of reninangiotensin system (RAS) blocking agents in Denmark. Data from the Danish National Prescription Registry covering all medications dispensed during January 2008-December 2018 was used. The outcome was monthly prevalence of patients codispensed RAS blockers. Autoregressive integrated moving average interrupted time series regression was used to evaluate dispensing trends. The prevalence of patients codispensed RAS blockers decreased from 0.01 to 0.0003%. Preintervention trend was declining and further decreased with an additional À0.45 (95% confidence interval À0.66, À0.25) codispensing per million population after the intervention. Overall, the intervention had minimal impact on the combined use of RAS blockers. However, as the combined use of RAS blockers is low, further interventions to restrict the combined use of RAS blockers may not be required in Denmark at this point.