Key Message

The results of 1 systematic review suggest that supplementation with vitamin D may provide some benefit for cancer-related mortality in older adults. It is unclear whether there is a benefit of vitamin D supplementation for all-cause mortality; however, no benefit was found for cardiovascular disease mortality, cardiovascular disease events, or cancer incidence.

There is limited and mixed evidence on the effectiveness of vitamin D supplementation for dementia and mild cognitive impairment in older adults.

The results of 1 systematic review suggest that vitamin D supplementation may provide protection against acute respiratory infections in the overall population; however, this result was not significant in the subgroup of patients older than 65 years.

No evidence-based guidelines were identified regarding vitamin D supplementation for the prevention and/or treatment of cardiovascular disease, cancer, and other conditions in elderly patients residing in long-term care facilities.

Key Message

The relevant publications identified comprised 1 overview of systematic reviews and 2 systematic reviews. There is a suggestion that for seniors living in long-term care facilities, compared to control, vitamin D supplementation, with or without calcium, may reduce the rate of falls and fractures; however, the reductions were not always statistically significant.There were no statistically significant differences in the number of seniors who fell with vitamin D supplementation, with or without calcium, compared with control groups. Findings need to be interpreted with caution, considering the limitations such as primary studies of variable quality (critically low to moderate) and lack of clarity with respect to the type of long-term care setting.No cost-effectiveness studies regarding vitamin D supplementation for the prevention of falls and fractures in elderly patients residing in long-term care facilities were identified. No evidence-based guidelines regarding vitamin D supplementation for the prevention of falls and fractures in elderly patients residing in long-term care facilities were identified.

Key Message

This report identified high to moderate quality evidence from clinical studies and economic evaluations, as well as high-quality guidelines regarding the use of palonosetron in the prevention of chemotherapy-induced nausea and vomiting in adult and pediatric patients receiving different emetogenic chemotherapies. Interpretations of the findings should be taken with caution because of the presence of some identified limitations in both clinical and economic evidence.

In adult patients receiving high emetogenic chemotherapy, a fixed antiemetic combination of netupitant and palonosetron (NEPA) plus dexamethasone demonstrated noninferiority relative to a triple regimen of granisetron-aprepitant-dexamethasone. Similarly, palonosetron had similar efficacy compared to granisetron with the co-administration of neurokinin 1 receptor antagonist (e.g., aprepitant or fosaprepitant) and dexamethasone. However, in the absence of aprepitant, a 2-drug combination of palonosetron-dexamethasone appeared to be significantly more effective than granisetron-dexamethasone for the prevention of both acute and delayed emesis.

In adult patients receiving moderate emetogenic chemotherapy, palonosetron plus dexamethasone was found to be noninferior compared with ondansetron plus dexamethasone. Similar efficacy was also observed between palonosetron plus dexamethasone and transdermal granisetron plus dexamethasone.

In a mixed population of adult patients receiving high or moderate emetogenic chemotherapy, a palonosetron regimen appeared to have greater efficacy than ondansetron for delayed emesis. The efficacy of triple regimen of palonosetron-aprepitant-dexamethasone and granisetron-aprepitant-dexamethasone was comparable at all phases.

In pediatric patients receiving high emetogenic chemotherapy, palonosetron plus dexamethasone had similar efficacy compared with ondansetron plus dexamethasone in the acute phase, but was more effective in delayed and overall phases of chemotherapy-induced nausea and vomiting.

In a mixed population of pediatric patients receiving high or moderate emetogenic chemotherapy, palonosetron plus dexamethasone was noninferior to ondansetron plus dexamethasone.

There were no significant differences between palonosetron and ondansetron or between palonosetron and granisetron treatment regimens in adverse events or quality of life.

A cost-utility analysis revealed that NEPA plus dexamethasone was dominant (i.e., cost less, more effective) relative to granisetron-aprepitant-dexamethasone and ondansetron-aprepitant or fosaprepitant-dexamethasone in adult patients receiving high emetogenic chemotherapy. In contrast, double or triple regimens of palonosetron was not cost-effective compared to granisetron regimens, mainly due to large difference in price and small quality-adjusted life-years gained. These economic evaluations may not be applicable to the Canadian context.

The identified high-quality guidelines have recommendations on the use of specific antiemetic regimens for adult and pediatric patients receiving high emetogenic chemotherapy or moderate emetogenic chemotherapy and suggest that palonosetron may be offered as an alternative to other 5-hydroxytryptamine-3 receptor antagonists and that 1 5-hydroxytryptamine-3 receptor antagonist is not preferred over another based on the available evidence.

Key Message

• There has been an increase in investment, funding, and interest in the use of artificial intelligence (AI) in the mental health area, especially over the past five years. The types of AI in use for mental health problems and illnesses include neural networks, support vector machines, logistic regression, linear discriminant analysis, and random forests.
• Currently, the use of AI for mental health is limited in a clinical environment. Consultations revealed that the majority of AI applications are in research and development and have not been expanded to clinical or patient use. The applications of AI in mental health include conversational agents, computerized adaptive testing, diagnosis of mental health conditions, prediction of behaviour, and prediction of prognostic outcomes in treatment.
• The professions currently using and researching AI are primarily researchers in the fields of psychology and computer science. There are limited AI applications available commercially, but some AI applications, such as chatbots, are available for the general public through mobile application stores such as Apple and Google Play.
• Four key domains of research and development in the use of AI for mental health are diagnosis, prognosis, public health, and clinical administration; most of the identified research is in the area of diagnosis.
• Research and development initiatives for mental health diagnosis using AI include the use of biomarkers, neuroimaging, genetics, metabolomic data and proteomic data to diagnose or detect mental illness, and new data collection methods such as smartphone-based data collection or wearable sensors paired with AI applications. Research initiatives for treatment include improvements in currently available chatbots, the creation of new AI chatbots, and research on whether individuals will respond to particular treatments based on their specific characteristics. Prognosis initiatives include predictions of mental health trajectories and potential future costs of illness.
• Trends in the development of AI for mental health include chatbots for mental health treatment, increased explainability of models, and an increase in wearable devices and smartphone-based sensors for data collection.
• In regard to specific life stages, there are some identified AI algorithms used in children and youth, including Kids’ Help Phone’s crisis text service, Bark’s AI parental control application, and AI algorithms for the diagnosis of internalizing disorders and bipolar disorder. In older adults, there are several AI applications to combat loneliness in seniors using companion robots, and some AI specific to seniors for diagnosing depression.
• Policy and program initiatives in mental health–based AI include the translation of lab-based research initiatives into clinical applications. This translation may require careful planning to ensure that ethical standards are met, that assessments are carried out to determine the suitability of the AI for each aspect of mental health diagnosis and treatment, and that generalizable and culturally sensitive algorithms are created

This environmental scan was commissioned by The Mental Health Commission of Canada to address the role of AI in mental health services. This report is a companion to a Rapid Response review on clinical effectiveness and guidelines for AI in mental health [Artificial Intelligence and Machine Learning in Mental Health Services: A Literature Review. Ottawa: Canadian Agency for Drugs and Technology in Health (CADTH), Mental Health Commission of Canada (MHCC); 2021 June.]

Key Message

Thirty-four studies were identified that were relevant for this report. Eight studies were systematic reviews (SRs), three were randomized controlled trials (RCTs), and 23 were non-randomized studies. No relevant evidence-based guidelines were identified. The studies included a variety of populations, including individuals with bipolar disorder, schizophrenia, MDD, postpartum depression, post-traumatic stress disorder, and individuals who have suicidal ideation or have attempted suicide. No specific information on subgroups (such as immigrant, refugee, ethnocultural, or racialized individuals; or First Nations, Métis, Inuit; or lesbian, gay, bisexual, transgender, queer or questioning, and two-spirited [LGBTQ2+]) were found. Two studies focused on young children (ages three to seven), and one study used the National Health and Nutrition Examination Survey (NHANES), which includes children and adults. No effectiveness or accuracy information was found on adolescents or older adults with mental health conditions, as the majority of studies focused on adults over the age of 18 and under the age of 65. Intended users of these AI technologies were primarily clinicians (for diagnosis), but three studies examined models that were intended for use by patients. The primary purpose of the AI or ML models was to differentiate patients who have or do not have mental health conditions or to assist in treatment. Diagnostic accuracy of AI or ML models was generally moderate to high when compared with physician assessment, and AI-based applications for the treatment of patients significantly reduced depression symptoms and increased the use of crisis resources in studies that compared various versions of electronic applications for mental health.

This literature review was commissioned by The Mental Health Commission of Canada to address the role of AI in mental health services. This report is a companion to an Environmental Scan, which provides more information on the types and trends of AI either emerging or currently in use for the prevention, diagnosis, or treatment of mental health problems and illnesses, research and development initiatives, and the professional groups and organizations involved in the development or use of these technologies in Canada and internationally [Artificial Intelligence and Machine Learning in Mental Health Services: An Environmental Scan. Ottawa: Canadian Agency for Drugs and Technology in Health (CADTH), Mental Health Commission of Canada (MHCC); 2021 June.]

Key Message

Nine evidence-based guidelines were identified that recommend the use of conventional synthetic disease-modifying antirheumatic drugs as a first-line therapy for patients with rheumatoid arthritis prior to using biologic disease-modifying antirheumatic drugs or Janus kinase inhibitors. Methotrexate monotherapy was the most commonly recommended conventional synthetic disease-modifying antirheumatic drug recommended as first-line therapy by the included guidelines. Eight of the included guidelines recommend combination therapy using multiple conventional synthetic disease-modifying antirheumatic drugs if monotherapy is ineffective and 4 included guidelines recommend the use of glucocorticoids in combination with conventional synthetic disease-modifying antirheumatic drugs.

Key Message

• People generally describe wanting access to carrier screening because knowing about the risk of passing along a genetic condition is considered important and supportive of their desires to be prepared. In the context of expanded carrier screening programs, this could mean that an increased number of people would want to access these programs. • Supporting people who are considering carrier screening can be challenging and is likely to be more involved than simply sharing high-level descriptive information about testing details and potential outcomes. Descriptive information is important to help people understand the screening process and the types of results that could emerge from testing; however, programs might be more supportive of informed decision-making if the providers take a proactive role and are open to facilitating speculative conversations about potential ramifications in people’s actual lives. This is challenging given the expressed desire by health care providers, clinical geneticists in particular, to provide “neutral information” that patients would not experience as prescriptive. • Given the challenge of supporting people making decisions about whether or not to pursue carrier screening, and the likely increase in people who would consider carrier screening if targeted programs were expanded to population-level screening, it is important to ensure that health care providers are both aware of jurisdictional carrier screening programs and competent in what carrier screening can offer their patients in terms of clinical actionability. Although this is particularly true for general practitioners who are often the primary point of contact with the health care system for their patients, it is also important for people who work in family planning clinics and women’s health clinics. • Having the option to engage with carrier screening at the preconception stage was universally preferred by participants across the included studies. Compared with prenatal carrier screening, preconception carrier screening was seen as providing prospective parents with more reproductive options. Health care providers were concerned that offering carrier screening during pregnancy might lead pregnant people and their partners to confuse it with other prenatal testing which would limit people’s ability to be truly informed before deciding whether or not to pursue screening. However, if offered as a prenatal option, most people consider it important to do so as early as possible because it could be paired with other prenatal tests. Although not referred to specifically by any of the included studies, we note that offering carrier screening prenatally rather than at preconception, could place the responsibility to make the decision on cisgender women and non-binary or transgender people with uteruses. • Sequentially designed carrier screening programs were the most common across the included studies; however, people moving through programs with this design found the interim period between receiving their positive carrier results and receiving their partners’ results difficult. This was particularly true for people who were already pregnant because this interim period forced them to reimagine both their relationship with the fetus and the future they had imagined with that child. Of course, this reimagining might be necessary if both partners’ screening results came back positive for the condition in question, but to stagger the return of the results could put undue anxiety on potential parents. • Carrier screening will not affect everyone in the same way, and reproductive decision-making will still be complex and difficult. As such, the opportunity to engage with genetic counsellors on reproductive options following positive carrier status result is considered valuable.

Key Message

Opioid agonist and methadone maintenance therapies are essential medical interventions for effectively managing opioid use disorder. However, side effects, including constipation and erectile dysfunction can compromise treatment adherence and increase the risk of relapse. No studies or guidelines describing the clinical effectiveness or recommendations for the use of laxatives or erectile dysfunction medications in the treatment of constipation or erectile dysfunction in patients undergoing OAT or MMT were identified. Research is needed to understand the clinical effectiveness and inform guidance concerning the treatment of constipation with laxatives and the use of medications indicated for erectile dysfunction.

Key Message

​• Two systematic reviews, 3 randomized controlled trials, and 2 single-arm safety trials were identified that evaluated several combinations of psychedelic-assisted psychotherapy. Psilocybin was the psychedelic most tested. Other psychedelics identified in the systematic reviews and primary studies were 3,4-methylenedioxymethamphetamine (or MDMA), lysergic acid diethylamide (or LSD), ayahuasca (also named N,N-dimethyltryptamine [or DMT]), ibogaine, ketamine, and nitrous oxide. • Manualized therapy (not defined) and non-directive support (not defined) were the psychotherapies most studied in the relevant primary studies in the 2 systematic reviews. Other psychotherapies identified included integrative psychotherapy, cognitive behavioural therapy (CBT), CBT and motivational enhancement therapy, psychosocial interventions, non-directive support, group talk therapy, and guided support. • Clinical effectiveness lasting weeks to months was observed in 1 systematic review that reviewed primary studies examining various combinations of psychedelics and psychotherapy in patients with various mental health conditions. Significant improvement in symptom scores related to mental illnesses and no serious and long-term adverse events were reported in the other systematic review. • Various combinations of psychedelics and psychotherapies were evaluated in 3 randomized controlled trials (RCTs) and 2 safety studies. Ketamine-assisted psychotherapies were associated with improvements in the symptoms related to substance use disorder in 2 RCTs. Psilocybin-assisted psychotherapy was reported to be efficacious in treating MDD in 1 RCT. No serious adverse effects were reported in the RCTs or in 2 safety trials using MDMA-assisted psychotherapy. • There were several limitations to the included studies, including small sample sizes (less than 20 in the majority of primary studies), relatively short follow-ups (1 week to 3 years; less than or equal to 1 year in 27 out of 31 relevant publications), differences in psychotherapy classification between systematic reviews, considerable heterogeneity between studies, and unclear generalizability and availability of the interventions in Canadian contexts. Therefore, findings should be interpreted with caution. No relevant guidelines were identified.