Key Message

Recent, large, high-quality trials have demonstrated some benefits of dapagliflozin for the treatment of chronic kidney disease (most often in patients with type 2 diabetes) as compared to placebo.

Data describing the clinical effectiveness of dapagliflozin have identified both relative benefits and no differences compared to placebo in various measures of renal and cardiovascular health and function, as well as health care utilization, mortality, and adverse events.

A large proportion of the available data has been generated from the same randomized controlled trial that has recently been reported in multiple publications describing various patient subgroups and outcomes.

No evidence was identified describing the cost-effectiveness of dapagliflozin for the treatment of patients with chronic kidney disease.

Key Message

There is some evidence of benefit of melatonin compared with placebo for the short-term treatment of insomnia in children and adolescents with neurodisabilities.

The short-term safety profile of melatonin suggested that it was well-tolerated, although some severe adverse events may occur. There was a lack of long-term safety data.

The American Academy of Neurology guideline recommends high-grade melatonin should be prescribed for treatment of sleep disturbance in children and adolescents with autism spectrum disorder if first-line treatment with behavioural strategies is not helpful.

Evidence comparing the clinical effectiveness of melatonin with prescription sedatives for the treatment of insomnia in children and adolescents was not identified.

No evidence was found regarding the cost-effectiveness of melatonin compared with placebo or prescription sedatives for the treatment of insomnia in children and adolescents.

Key Message

Evidence was summarized to determine the effect of alteplase in adult stroke patients. There is substantial uncertainty concerning the evidence due to the risk of bias in the available studies and imprecision in how the magnitude of the treatment effects were estimated.

The identified research suggests that alteplase administered within 3 hours of a stroke might result in:

• fewer deaths after 18 months and little-to-no difference in death after 7 days, 3 months, 6 months, or 3 years
• increased brain bleeds after 7 days but no difference after 36 hours or after 3 months
• improvements in functioning and independence after 7 days and after 6 months; at 3 months, some studies showed no difference in independence and another study showed higher functioning.

The identified research suggests that alteplase administered between 3 hours and 4.5 hours after a stroke might result in:

• little-to-no difference in deaths after 3 months; at 7 days, some evidence showed little-to-no difference in death while other evidence suggested more deaths
• little-to-no differences in brain bleeds after 36 hours; at 7 days, some evidence showed no effect on brain bleeds, while other evidence showed more brain bleeds
• no differences in functioning and independence after 6 months; at 3 months, some evidence showed no effect on functioning, while other evidence reported improved functioning.

Key Message

Three evidence-based guidelines were identified about the use of clozapine for patients with psychotic disorders.

The included guidelines provide recommendations for testing and assessment of key health parameters for patients who are prescribed clozapine via various means such as laboratory tests and electrocardiogram.

The guidelines provide recommendations of co-prescription for patients who have not responded adequately to an optimized dose of clozapine alone.

Two guidelines offer specific recommendations on clozapine dosing.

The guidelines were generally well developed, clearly reported, and consistent in their recommendations. However, several of the recommendations were derived from sources of evidence that may not be considered of the highest quality, with the strength of recommendation not reported and unclear.

The diagnostic accuracy of high-sensitivity troponin I testing versus troponin T testing for detecting myocarditis or cardiomyopathy in patients receiving clozapine for psychotic disorders is unknown as no relevant evidence was identified.

Given the limited availability and varying quality of evidence, the diagnostic accuracy of high-sensitivity troponin I testing and how best to monitor for clozapine-induced myocarditis and cardiomyopathy in patients with psychotic disorders remains uncertain.

Key Message

Three guidelines included in this report recommend rituximab, thrombopoietic agents (drugs that promote platelet growth), and thrombopoietin receptor agonists (e.g., romiplostim, eltrombopag) over splenectomy as second-line treatment in children with immune thrombocytopenia who do not respond to first-line treatment.

Three guidelines included in this report recommend for children with persistent or chronic immune thrombocytopenia who have no response to 1 thrombopoietin receptor agonist or who lose an initial response that treatment can be switched to another thrombopoietin receptor agonist and/or combined with mycophenolate mofetil or another immunosuppressant. For individuals who do not respond to thrombopoietin receptor agonists, the recommendation is to consider rituximab and dexamethasone, especially for adolescent females.

No relevant evidence-based recommendation was identified regarding the use of dapsone for the treatment of children with immune thrombocytopenia.