Key Message

​Seven systematic reviews (three of which contained relevant primary studies) were identified regarding the clinical effectiveness of pilocarpine in the treatment of Sjögren’s syndrome-induced dry mouth and/or dry eyes. In addition, two evidence-based guidelines were identified regarding pilocarpine for the treatment of dry mouth and dry eyes in Sjögren’s syndrome. No evidence on the cost-effectiveness of pilocarpine for patients with Sjögren’s syndrome experiencing either dry mouth or dry eyes was identified.

Three systematic reviews of critically low quality contained three relevant primary studies which provided a limited quantity of evidence applicable to this report. The three primary studies provided heterogenous evidence as they had different patient populations, comparators and outcomes. Overall, pilocarpine was effective in the treatment of Sjögren’s syndrome-induced dry mouth and dry eyes but may not be as tolerable as cevimeline. 

Both guidelines recommend the use of pilocarpine for the treatment of dry mouth. One guideline also recommends pilocarpine for the treatment of dry eyes whilst the second guideline states it may be considered for the treatment of dry eyes.

Overall, the findings of this report come with a degree of uncertainty as the identified evidence was of critically low quality and quantity. 

Key Message

This review included one systematic review, five primary studies, one economic study and two guidelines regarding the use of lurasidone hydrochloride for the treatment of adults with bipolar disorder. 

Based on findings from a network meta-analysis, lurasidone monotherapy of acute bipolar depression (mostly type I) was more efficacious than aripiprazole and ziprasidone monotherapy. Lurasidone was associated with less weight gain than olanzapine and quetiapine, and lower somnolence incidence than quetiapine and ziprasidone. 

Common adverse events of lurasidone therapy included nausea, somnolence, headache, dizziness, akathisia, fatigue, insomnia, tremor, Parkinsonism, nasopharyngitis, anxiety, depression, and extrapyramidal symptoms. Discontinuation of treatment due to adverse events was 9% or less. Metabolic related changes in weight, glucose and lipids were not clinically meaningful. 

Based on the US third-party payer perspective, lurasidone monotherapy resulted in an incremental cost-effectiveness ratio of $3,474 per remission gained when compared with quetiapine extended release for the treatment of adults with bipolar I depression.

Both good quality guidelines recommend lurasidone (monotherapy or adjunctive to lithium or valproate) as first-line treatment for acute bipolar depression. For maintenance therapy, lurasidone adjunctive may be appropriate as second line in patients who responded to lurasidone during a depressive episode.

Well-designed trials are needed that directly compare lurasidone monotherapy or lurasidone adjunctive therapy with other interventions. Cost-effectiveness studies of lurasidone that are conducted with respect to the Canadian health care perspective are also warranted. Current findings may not be generalizable to the Canadian context, and they should be interpreted with caution given their limitations. ​

Key Message

Six relevant publications (four randomized controlled trials and two non-randomized studies) were identified regarding the clinical effectiveness of prenatal and postnatal home visiting programs for mothers, newborns, and babies. One systematic review was identified regarding the cost-effectiveness of prenatal and postnatal home visiting programs for mothers, newborns, and babies up to two years of age. No relevant evidence-based guidelines were identified regarding the provision of home visiting programs for parents, newborns, or babies. 

Overall, there was evidence that care delivered in the prenatal and postnatal periods had both short- and long-term health outcomes. 

Regarding postnatal maternal health outcomes, one randomized controlled trial of limited quality demonstrated no statistically significant difference in incidence of completed postpartum visits by eight weeks postpartum or postpartum depression between postnatal home visit and standard office visit groups. There was evidence regarding postnatal child health outcomes from four randomized controlled trials and two quasi-experimental studies. Compared to those who received usual care, newborns and babies who received the Family Connects postnatal nurse home visiting program group were found to have statistically significantly reduced incidence of emergency medical care utilization or inpatient hospital overnight stay. Compared to standard care, infants who received a home-based early preventative care postnatal home visit program within their first year of life had a statistically significantly reduced likelihood of having a mathematics impairment and no statistically significant difference in serious adverse events, most developmental outcomes measured at age eight. Compared to no home visit, first-time mothers who received the Kentucky Health Access Nurturing Development Services prenatal and postnatal home visit program had a significantly reduced incidence of preterm birth, delivering low birth weight infants, and child maltreatment. Compared to no home visit, high-risk pregnancy women who received the public health nurse prenatal home visit program in Japan statistically significantly reduced the incidence of preterm birth. No statistically significant difference was found in the proportion of infants born small for gestational age between the group of high-risk pregnant women that received home visits from public health nurses and the group that did not receive home visits. No statistically significant difference was found between first-time teenage mothers who received the Family Nurse Partnership prenatal and postnatal home-visit program and those who received usual care in rates of emergency department attendances or hospital admissions. No statistically significant difference was found between pregnant women who received a postnatal newborn well-child home visits program and those who received standard office visits in the number of health checks, sick visits, or usage of urgent care. 

There was low-to-moderate quality evidence from seven studies in the systematic review of economic evaluations that home visiting programs were cost-effective in comparison to no home visits, depending on the willingness-to-pay threshold and the perspective of the payers.

Key Message

Evidence from three randomized controlled trials in pediatric patients with mild to moderate dehydration secondary to gastroenteritis, suggests that ondansetron is effective for decreasing risk of requiring intravenous rehydration and reducing vomiting as compared to placebo, both in combination with oral rehydration solution. In another RCT in which level of dehydration was not described, ondansetron was not superior to placebo for reduction of vomiting. Evidence from a randomized controlled trial in which children were at risk of but with no dehydration did not find ondansetron to be effective as compared to placebo, both in combination with oral rehydration solution.

Evidence from a non-randomized study among children with mild to moderate dehydration secondary to gastroenteritis who were discharged from the emergency department indicated no difference in returns and readmissions to the emergency department within 72 hours, for patients receiving ondansetron compared to those who did not.

Key Message

No relevant literature was identified regarding the comparative clinical effectiveness of universal versus high-risk palivizumab or seasonal versus year-round palivizumab prophylaxis in Inuit children up to 4 years of age. Additionally, no relevant literature was identified regarding the comparative cost effectiveness of universal versus high-risk palivizumab or seasonal versus year-round palivizumab prophylaxis in Inuit children up to 4 years of age.

Key Message

One relevant non-randomized study was identified regarding the comparative clinical effectiveness of intraosseous contrast media injection versus intravenous contrast media injection for patients undergoing computed tomography scan. No relevant evidence-based guidelines were identified.

Although the study found no difference in objective and subjective computed tomography image quality between intraosseous and intravenous contrast media delivery, it remains uncertain whether the findings are reliable given that the study was likely not adequately powered nor reflective of the larger clinical population.

The limitations of the included study, such as lack of blinding to treatment, inadequate comprehensiveness of post-interventional complications reporting, small sample size, and disproportionate gender balance, should be considered when interpreting the results.

Key Message

No evidence was identified regarding the clinical effectiveness of combined ivabradine and sacubitril/valsartan for the treatment for heart failure and no evidence-based guidelines regarding the combination of ivabradine and sacubitril/valsartan for the treatment of heart failure were identified.

Key Message

This review included four systematic reviews, one randomized controlled trial, and six economic studies. Two evidence-based guidelines on the use of quetiapine for treatment of patients with major depressive disorder were identified. 
Based on findings from a network meta-analysis, quetiapine monotherapy in older adults with major depressive disorder was found to be more efficacious compared to several antidepressants; however, However there remain uncertainty regarding the robustness of these findings, given the lack of available comparative data.

The efficacy of quetiapine add-on therapy in patients with treatment-resistant depression, characterized by response rate, remission rate, or depressive symptoms was not significantly different compared to competing interventions including other atypical antipsychotics, antidepressants, and lithium. Quetiapine add-on therapy and quetiapine monotherapy were associated with higher withdrawals due to adverse events compared to placebo, thyroid hormone and lithium. Common adverse events of quetiapine add-on therapy and quetiapine monotherapy included somnolence, fatigue, dry mouth, sedation, headache, dizziness and weight gain.

Quetiapine add-on therapy was associated with significantly higher in total medical costs, and outpatient services costs, but lower in pharmacy costs compared with brexpiprazole. Compared with aripiprazole, quetiapine and olanzapine were associated with higher all-cause hospitalization, all-cause emergency department visits, and total medical costs. In cost-effective analyses, quetiapine add-on therapy was found to be less cost-effective than aripiprazole.

Both guidelines recommend quetiapine as add-on therapy in patients who were insufficiently treated with antidepressants. Evidence on quetiapine misuse and abuse by patients with major depressive disorder were not identified.

Well-designed trials are needed that directly compare quetiapine add-on therapy or quetiapine monotherapy with competing interventions. Cost-effectiveness studies of quetiapine that are conducted with respect to the Canadian health care perspective are also warranted. Current findings may not be generalizable to the Canadian context, and they should be interpreted with caution given their limitations.

Key Message

A total of 13 relevant publications were included in this report: five systematic reviews (including four meta-analysis and one network meta-analysis), seven randomized controlled trials, and one cost-effectiveness study. No evidence-based guidelines were identified from the literature within the last five years regarding the use of bimatoprost in lowering intraocular pressure.

The overall findings from the systematic reviews and clinical trials are seemingly contradictory. Results from the systematic reviews showed bimatoprost be clinically superior over other prostaglandin analogues (including latanoprost, travoprost, and tafluprost) with respect to intraocular pressure; whereas with the exception of a crossover trial, none of the randomized trials with a parallel group design demonstrated the clinical superiority of bimatoprost. Most studies concluded that the clinical profile of the four prostaglandin analogues is similar; with all four prostamides effective in reducing intraocular pressure in patients with open angle glaucoma or ocular hypertension, irrespective of prior treatment status or other risk factors. In terms of adverse events, bimatoprost was found to be relatively less tolerated compared to the others and may result in hyperemia and growth of eyelashes. However, these findings are not consistently reported in all trials, and the safety profile of the four prostamides may be similar. A single cost-effectiveness study from the United States showed bimatoprost to be the most cost-effective prostamide, using robust methodology and different perspectives (societal, third party insurance, and ophthalmic), although its applicability is debatable in the Canadian health care context.

The mixed and inconclusive findings across the studies may be a result of a number of factors: inclusion of studies that are heterogeneous in nature with respect to patient population, intervention (including dosage), assessment of study outcomes, and overall study design; as well as methodological limitations arising from small sample size, and inadequate reporting of data. Overall, bimatoprost appears to be at least as effective as latanoprost, travoprost, and tafluprost, either as monotherapy, or in combination with timolol. However, bimatoprost showed to be the most cost-effective prostamide, which may support its use over other alternatives.