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Abstract Background Prescribing trends suggest that pharmacologic alternatives to antipsychotics are gaining in popularity, but randomized trial (RCT) data of their comparative safety is scarce. Our objective was to describe the comparative safety of pharmacologic interventions for treating neuropsychiatric symptoms in dementia. Methods We searched MEDLINE, EMBASE, CENTRAL, CINAHL, and PsycINFO, from inception to May 28, 2019, for studies of pharmacologic interventions used to treat neuropsychiatric symptoms in dementia. Dementia care partners selected fracture risk as our primary outcome. Pairs of reviewers, working independently, conducted all study screening, data abstraction, and risk of bias appraisal. We conducted Bayesian random-effects network meta-analyses (NMAs) using data from RCTs to derive odds ratios (ORs). In secondary analyses, we conducted frequentist random-effects NMAs using data from RCTs and Bayesian three-level hierarchical random-effects NMAs incorporating data from RCTs and non-randomized studies. Results Our systematic review included 209 randomized and non-randomized studies (889,378 persons with dementia). In NMAs of data from randomized trials, there were no increased odds of fracture associated with any intervention in primary analyses; however, data were sparse. We found increased odds of cerebrovascular events associated with antipsychotics (odds ratio [OR] 2.12, 95% credible interval [CrI] 1.29 to 3.62; number needed to harm [NNH] = 99) and increased odds of falls associated with dextromethorphan-quinidine (OR 4.16, 95% CrI 1.47 to 14.22; NNH = 55) compared to placebo in persons with dementia. In a subgroup of persons with Alzheimer disease, antipsychotics were associated with increased odds of fracture compared to anticonvulsants (OR 54.1, 95% CrI 1.15 to 38,300; NNH = 18). In older persons (mean age ≥ 80 years) with dementia, anticonvulsants were associated with increased odds of death compared to placebo (OR 8.36, 95% CrI 1.17 to 203.4; NNH = 35) and antipsychotics were associated with increased odds of death compared to antidepressants (OR 5.28, 95% CrI 1.06 to 3.51; NNH = 47). Conclusion Although antipsychotics were associated with greater harm than antidepressants and anticonvulsants in subgroups of persons with dementia, medications used in lieu of antipsychotics for treating neuropsychiatric symptoms in dementia, such as anticonvulsants and dextromethorphan-quinidine, were also associated with harm. Decision-making concerning treatments prescribed in lieu of antipsychotics should include potential harms. PROSPERO registration CRD42017050130.

Abstract Background Positive impacts of quality improvement initiatives on health care and services have not been substantial. Knowledge translation (KT) strategies (tools, products and interventions) strive to facilitate the uptake of knowledge thereby the potential to improve care, but there is little guidance on how to develop them. Existing KT guidance or planning tools fall short in operationalizing all aspects of KT practice activities conducted by knowledge users (researchers, clinicians, patients, decision-makers), and most do not consider their variable needs or to deliver recommendations that are most relevant and useful for them. Methods We conducted a 3-phase study. In phase 1, we used several sources to develop a conceptual framework for creating optimized Knowledge-activated Tools (KaT) (consultation with our integrated KT team, the use of existing KT models and frameworks, findings of a systematic review of multimorbidity interventions and a literature review and document analysis on existing KT guidance tools). In phase 2, we invited KT experts to participate in a Delphi study to refine and evaluate the conceptual KaT framework. In phase 3, we administered an online survey to knowledge users (researchers, clinicians, decision-makers, trainees) to evaluate the potential usefulness of an online mock-up version of the KaT framework. Results We developed the conceptual KaT framework, and iteratively refined it with 35 KT experts in a 3-round Delphi study. The final framework represents the blueprint for what is needed to create KT strategies. Feedback from 201 researcher, clinician, decision-maker and trainee knowledge users on the potential need and usefulness of an online, interactive version of KaT indicated that they liked the idea of it (mean score 4.36 on a 5-point Likert scale) and its proposed features (mean score range 4.30–4.79). Conclusions Our findings suggest that mostly Canadian KT experts and knowledge users perceived the KaT framework and the future development of an online, interactive version to be important and needed. We anticipate that the KaT framework will provide clarity for knowledge users about how to identify their KT needs and what activities can address these needs, and to help streamline the process of these activities to facilitate efficient uptake of knowledge.