Projects listed as “in progress” are at various stages and points of completion. These products have different processes and timelines; therefore, the timing of posting of the final reports varies and expected completion dates may change. Find out more about Projects in Progress.
Projects listed as “in progress” are at various stages and points of completion. These products have different processes and timelines; therefore, the timing of posting of the final reports varies and expected completion dates may change. Find out more about Projects in Progress.
Gonorrhea is the second most common sexually transmitted infection in Canada. It is caused by the bacteria Neisseria gonorrhoeae and can be treated with antibiotics, but rising antimicrobial resistance makes implementing the current treatment guidance challenging.
We aimed to identify and summarize the literature since 2016 comparing the clinical effectiveness and safety of treatments for uncomplicated N. gonorrhoeae infections of the urethra, cervix, rectum, pharynx, and eye in adolescents and adults, including pregnant people. We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence.
This Rapid Review includes 4 randomized controlled trials and 1 companion report, all published since 2019. The studies evaluated the following treatments: gentamicin plus azithromycin compared to ceftriaxone plus azithromycin, gentamicin monotherapy compared to ceftriaxone monotherapy, and ceftriaxone monotherapy compared to ceftriaxone plus azithromycin.
There is a lack of comparative evidence evaluating the clinical effectiveness and safety of antibiotics for N. gonorrhoeae infections.
The included studies had mostly cisgender men as participants, so women and people with diverse gender identities were not well represented. Additionally, adolescents younger than 16 years of age and pregnant people were not included in any study.
All the studies were conducted in Europe, so their applicability to the Canadian clinical context is unclear.
Further randomized controlled trials with diverse participant populations are needed to evaluate the safety and efficacy of gentamicin, cefixime, and ciprofloxacin (monotherapy or in combination with azithromycin). Further research is required to evaluate the clinical effectiveness and safety of single-dose versus multidose cefixime.
There are several different formulations of drugs that target calcitonin gene–related peptide (CGRP) available in Canada for preventing migraine. This Rapid Review examines the evidence regarding the effectiveness of different CGRP inhibitors after failure on a first or second CGRP inhibitor due to lack of efficacy or tolerability.
The review includes 1 systematic review of 7 nonrandomized studies, 3 additional nonrandomized studies, and 2 clinical guidelines, all published since 2020. The included studies all examined changes in monthly migraine days after switching to a new CGRP inhibitor. No economic studies were identified.
The findings generally show that patients experience improvement with the second CGRP inhibitor based on reported migraine events. However, the guidelines found there was not enough evidence to consider this practice evidence-based.
All the studies, including the clinical guidelines, were conducted in other countries, so it is not clear how applicable they are to patients in Canada.
All studies had very significant methodological concerns and their results should not be considered conclusive. In particular, all the primary studies were uncontrolled, meaning that bias from regression to the mean could not be ruled out.
Overall, the included studies do not offer clear guidance on the effectiveness of prophylactic CGRP inhibitors in patients with migraine who have failed treatment on a different CGRP inhibitor.
Projects listed as “in progress” are at various stages and points of completion. These products have different processes and timelines; therefore, the timing of posting of the final reports varies and expected completion dates may change. Find out more about Projects in Progress.
What is the cost-effectiveness of the pneumococcal conjugate vaccination in adults aged 18 to 64 years who are at high risk for invasive pneumococcal disease?
Choline is an essential nutrient produced by humans and animals and is important during pregnancy, fetal growth, and the development of the brain and nervous system. Most people do not get enough choline from their diet.
Fetal alcohol spectrum disorders (FASD) are a set of conditions where fetuses have been exposed to alcohol and this affects memory, learning, and development from early childhood to later life.
Choline supplements are products used to complement choline-deficient diets. Given the role of choline in fetal development, choline supplements are a potential intervention to support pregnancy or to mitigate the developmental harms in children from prenatal exposure to alcohol if supported by evidence of their effectiveness for these purposes.
To inform decisions about the use and timing of choline supplementation to support health outcomes in infants and children, Canada's Drug Agency sought to identify and summarize the literature about the effectiveness and safety of choline supplementation given to any pregnant people or given to children with either prenatal alcohol exposure or FASD. We also attempted to identify evidence-based recommendations for using choline supplementation in these populations.
We searched key resources and conducted a focused internet search for relevant evidence published since 2014. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings.
We found few publications investigating this topic, and several studies had low statistical power and imprecise results. The clinical evidence was mixed depending on whether choline was given to the pregnant person or child, which interventional groups were compared, what the clinical exposures or diagnoses were in the study population, the time point and duration of choline supplementation, which outcomes were measured, and how old children were during follow-up.
For choline supplementation in healthy pregnant people, evidence was mixed for infant and child neurocognitive and neurodevelopmental outcomes or behavioural symptoms; there were little-to-no differences in safety outcomes.
For choline supplementation in pregnant people exposed to alcohol, evidence was mixed for infant and child neurocognitive and neurodevelopmental outcomes, body size, and brain region sizes; some minor side effects were reported overall.
For choline supplementation in children with FASD, most evidence showed little-to-no benefits for neurocognitive and neurodevelopmental outcomes, and brain structure; limited evidence showed higher fishy body odour and some other unspecified adverse symptoms for children given choline.
Guidelines based mostly on low-quality evidence or expert opinion recommend that all pregnant people, including those with gestational diabetes mellitus or on vegan or vegetarian diets, increase their choline intake through diet or supplements.
We did not find clinical effectiveness evidence for choline supplementation in infants with FASD, or guidelines regarding choline supplementation in either infants or children with FASD, that met inclusion criteria for our report.
Health care professionals and decision-makers can use this evidence to inform decisions around applicability of choline supplementation for pregnant people, or for infants and children with FASD, in their practice.
There may be a need to balance the knowledge that choline intake is low at the population level and important for fetal development with the identified clinical effectiveness evidence for choline supplementation, which was limited and mixed for all evaluated patient populations.
Careful consideration of the following may also be important to inform decisions about the appropriateness of choline supplementation: the care plan and other intensive and concurrent interventions for children with FASD; stigma and challenges faced by pregnant people and children in the context of prenatal alcohol exposure; cultural dietary practices; and accessibility, cost, and availability of supplements.
Multiple sclerosis is a chronic autoimmune disorder that causes damage to central nervous system cells. Relapsing-remitting multiple sclerosis is characterized by relapses (episodes of new or worsening symptoms) followed by periods of partial or complete recovery (remission). A clinically isolated syndrome is the first episode of clinical symptoms and objective findings suggestive of multiple sclerosis. It lasts at least 24 hours and occurs without fever or infection.
Disease-modifying therapies for multiple sclerosis include interferon beta-1a and interferon beta-1b, and glatiramer acetate.
Minocycline is an antibiotic that may have a potential role in treating multiple sclerosis. Understanding its possible benefits and harms in clinically isolated syndrome and relapsing-remitting multiple sclerosis is important to clarify its potential role in these patients.
The purpose of this report is to update 2 previous reports we conducted in 2019. We summarize the evidence regarding the clinical effectiveness of glatiramer acetate, interferon beta-1a, and interferon beta-1b for clinically isolated syndrome, as well as minocycline for clinically isolated syndrome and relapsing-remitting multiple sclerosis. Evidence-based guidelines were also summarized.
We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2019. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings.
We found 1 systematic review that evaluated the safety of interferon beta-1a and glatiramer acetate in patients with clinically isolated syndrome.
Serious adverse events and withdrawals due to adverse events were similar in patients with clinically isolated syndrome who received interferon beta-1a and placebo.
Serious adverse events were similar in patients with clinically isolated syndrome who received glatiramer acetate and placebo. Withdrawals due to adverse events were more common in patients with clinically isolated syndrome who received glatiramer acetate than placebo.
We did not identify any studies that evaluated the clinical effectiveness of interferon beta-1a, interferon beta-1b, glatiramer acetate, or minocycline in patients with clinically isolated syndrome, or minocycline in patients with relapsing-remitting multiple sclerosis published since our previous reports. We did not identify any evidence-based guidelines published since our earlier reports.
It is uncertain if interferon beta-1a, interferon beta-1b, glatiramer acetate, and minocycline are effective treatments for clinically isolated syndrome, or if minocycline is an effective treatment for relapsing-remitting multiple sclerosis due to the lack of evidence identified in this report.
Future studies are needed to understand the clinical effectiveness of interferon beta-1a, interferon beta-1b, glatiramer acetate, and minocycline in patients with clinically isolated syndrome, and minocycline in patients with relapsing-remitting multiple sclerosis.
Immune checkpoint inhibitor (ICI) therapy has become a treatment option for various types of advanced cancer, resulting in significant improvement in disease outcomes.
However, ICIs can overstimulate the immune system leading to various side effects known as immune-related adverse events (irAEs) that can occur in any organ system.
Administration of corticosteroids is the initial mainstay treatment of irAEs. However, there is little evidence of how to treat steroid-resistant irAEs. Treatment of steroid-resistant irAEs includes holding ICI and starting immunosuppressive therapy.
Decision-makers are interested in understanding the use of infliximab, a selective immunosuppressive drug, for the treatment of steroid-resistant irAEs affecting various organs.
We identified and summarized the literature regarding the efficacy and safety of infliximab for the treatment of steroid-resistant irAEs. Due to the limitation of evidence, we included studies of any design, including case reports and case series.
A research information specialist conducted a literature search of peer-reviewed and grey literature sources published between January 1, 2019 and April 8, 2024. One reviewer screened citations for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings.
The evidence presented in this report was based on 2 systematic reviews of case reports and case series, 1 retrospective cohort study, and 40 additional publications consisting of 29 case reports and 11 case series.
We identified 4 main irAEs, which were colitis, hepatitis, pneumonitis, and myocarditis.
Very low-quality evidence, which was mainly derived from case reports and case series, suggests that infliximab may be effective for the treatment of steroid-resistant immune-induced colitis, while there are concerns regarding its use for the treatment of hepatitis due to potential hepatotoxicity and infectious complications. There is mixed evidence regarding the use of infliximab for the treatment of immune-induced pneumonitis and myocarditis.
Recent consensus guidelines recommend the use of infliximab as first-line treatment for steroid-resistant immune-induced colitis, while its use for hepatitis is not recommended due to potential hepatotoxicity and infectious complications. The use of infliximab for the treatment of pneumonitis is an option, while its use for myocarditis remains to be determined.
The usual dose of infliximab was 5 mg/kg, administered by IV. A higher dose of 10 mg/kg was seen in some cases. The number of infusions, the period between infusions and the length of treatment varied depending on the responsiveness of infliximab and the type and severity of irAEs.
Treatment with infliximab as compared with vedolizumab resulted in comparable immune-induced colitis response rates, higher recurrent rate of colitis, and more hospitalizations despite a shorter time to clinical response.
What Does This Mean?
The very low-quality evidence identified suggests the potential benefits of infliximab in the management of immune-induced colitis due to its efficacy and fast response.
When using the clinical evidence and recommendations summarized in this report to inform decisions, decision-makers should consider that the evidence is of very low quality, mainly derived from case reports and case series.
Large prospective and comparative studies are needed to verify the findings and to determine the role of infliximab in the treatment of other irAEs.
Chronic pain is pain that lasts beyond 3 months. Chronic non-cancer pain conditions include osteoarthritis, low back pain, musculoskeletal pain, fibromyalgia, and neuropathic pain. Approximately 1 in 5 people in Canada live with chronic pain.
Nabilone (a cannabinoid) is indicated for the management of severe nausea and vomiting associated with cancer chemotherapy. Nabilone is also used in the management of chronic non-cancer pain. It is important to understand the potential benefits and harms of nabilone in people living with chronic non-cancer pain to support decision-making.
We sought to identify, summarize, and critically appraise literature comparing the clinical effectiveness of nabilone and placebo or alternative pharmacological options. We also searched for evidence-based guidelines that provide recommendations about the use of nabilone for the treatment of chronic non-cancer pain.
We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2015. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings.
We found 1 overview of reviews and 2 systematic reviews that assessed the clinical efficacy and safety of nabilone for the treatment of chronic non-cancer pain.
The evidence on the clinical efficacy of nabilone was mixed with some studies reporting an improvement in pain in those treated with nabilone versus placebo or active comparators and other studies reporting no difference between groups. Adverse events were more common in people living with chronic non-cancer pain who received nabilone than those who received placebo, ibuprofen, or amitriptyline. Adverse events were more common in those who received dihydrocodeine or gabapentin than nabilone.
It is uncertain if nabilone is an effective treatment for people living with chronic non-cancer pain due to the varied results and methodological limitations of the included studies.
We found 1 guideline that included a recommendation specific to nabilone and 2 guidelines that included recommendations on the use of cannabinoids in general. One guideline recommends against the use of nabilone for chronic pain, 1 guideline recommends offering a trial of non-inhaled cannabinoids (such as nabilone) for people living with chronic pain, and 1 guideline suggests cannabinoids be avoided in people with osteoarthritis and low back pain and discussed with people with neuropathic pain.
Due to the uncertainty of the clinical evidence, decision-makers may wish to consider other factors such as costs, equity, and patient values and preferences when making decisions on the use of nabilone for people living with chronic non-cancer pain.
Future high-quality, longer-term (e.g., RCT with follow-up studies) studies are needed to understand the efficacy and safety of nabilone for the treatment of people living with chronic non-cancer pain.