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Abstract Background Network meta-analysis (NMA) has rapidly grown in use during the past decade for the comparison of healthcare interventions. While its general use in the comparison of conventional medicines has been studied previously, to our awareness, its use to assess complementary and alternative medicines (CAM) has not been studied. A scoping review of the literature was performed to identify systematic reviews incorporating NMAs involving one or more CAM interventions. Methods An information specialist executed a multi-database search (e.g., MEDLINE, Embase, Cochrane), and two reviewers performed study selection and data collection. Information on publication characteristics, diseases studied, interventions compared, reporting transparency, outcomes assessed, and other parameters were extracted from each review. Results A total of 89 SR/NMAs were included. The largest number of NMAs was conducted in China (39.3%), followed by the United Kingdom (12.4%) and the United States (9.0%). Reviews were published between 2010 and 2018, with the majority published between 2015 and 2018. More than 90 different CAM therapies appeared at least once, and the median number per NMA was 2 (IQR 1–4); 20.2% of reviews consisted of only CAM therapies. Dietary supplements (51.1%) and vitamins and minerals (42.2%) were the most commonly studied therapies, followed by electrical stimulation (31.1%), herbal medicines (24.4%), and acupuncture and related treatments (22.2%). A diverse set of conditions was identified, the most common being various forms of cancer (11.1%), osteoarthritis of the hip/knee (7.8%), and depression (5.9%). Most reviews adequately addressed a majority of the PRISMA NMA extension items; however, there were limitations in indication of an existing review protocol, exploration of network geometry, and exploration of risk of bias across studies, such as publication bias. Conclusion The use of NMA to assess the effectiveness of CAM interventions is growing rapidly. Efforts to identify priority topics for future CAM-related NMAs and to enhance methods for CAM comparisons with conventional medicine are needed. Systematic review registration https://ruor.uottawa.ca/handle/10393/35658

Abstract Background Self-care refers to a range of activities and approaches undertaken by an individual to maintain health and manage ill-health which may include various complementary or alternative approaches. The purpose of this study was to identify the self-care approaches used by the general public for depression and anxiety, assess the usefulness of Cochrane reviews for informing decisions on self-care and highlight any gaps in the evidence. Methods Searches were carried out for surveys of self-care for anxiety and/or depression and for Cochrane reviews and protocols of interventions with potential for use in self-care. Data was extracted from each review and Plain Language Summaries assessed for content, consistency and readability. Interventions reported in surveys and in Cochrane reviews were compared and effectiveness of each assessed. Results Surveys from 10 countries reported a variety of self-care interventions, 17 of which appeared in 2 or more surveys and which included dietary supplements, herbal medicines, mind-body therapies and various forms of exercise. Twenty-two reviews and 5 protocols on potential self-care interventions were identified, the majority in depression. Twelve interventions were judged effective or promising, most with small effect sizes. Readability of summaries was highly variable: half were written at college/university level. Several commonly used approaches were not covered by Cochrane reviews. Conclusions This study has revealed the interventions currently used by the general public which are judged effective or promising based on Cochrane reviews. Some disparity is highlighted between interventions used in practice and the availability of reliable evidence, and in the presentation of effectiveness and safety. Being able to direct patients to reliable, accessible information is a positive step in ensuring effective patient-centered, evidence-informed care. Addressing gaps, ensuring consistency and increasing usability of evidence intended for the general public will support this goal.

Abstract Background Prediabetes describes a state of hyperglycemia outside of normal limits that does not meet the criteria for diabetes diagnosis, is generally symptomless, and affects an estimated 38% of adults in the United States. Prediabetes typically precedes the diagnosis of type 2 diabetes, which accounts for increased morbidity and mortality. Although the use of dietary and herbal supplements is popular worldwide, and a variety of single herbal medicines have been examined for glycemic management, the potential of increasingly common polyherbal formulations to return glycemic parameters to normal ranges among adults with prediabetes remains largely unexplored. The purpose of this study is to evaluate the efficacy of a commercially available, polyherbal dietary supplement on glycemic and lipid parameters in prediabetic individuals. Methods In this multi-site, double-blinded, randomized controlled clinical trial, 40 participants with prediabetes will be randomized to either a daily oral polyherbal dietary supplement (GlucoSupreme™ Herbal; Designs for Health®, Suffield, CT, USA; containing cinnamon bark (Cinnamomum cassia), banaba leaf (Lagerstroemia speciosa standardized to 1% corosolic acid), kudzu root (Pueraria lobata standardized to 40% isoflavones), fenugreek seed (Trigonella foenum-graceum standardized to 60% saponins), gymnema leaf (Gymnema sylvestre standardized to 25% gymnemic acid), American ginseng root (Panax quinquefolius standardized to 5% ginsenosides), and berberine HCl derived from bark (Berberis aristata)) or placebo for 12 weeks. Short-, medium-, and comparatively long-term markers of glycemic control (blood glucose and fasting insulin, fructosamine, and glycated hemoglobin/A1c, respectively), and other glycemic parameters (GlycoMark, β-cell function, and insulin sensitivity/resistance) will be obtained. Lipid profile (total cholesterol, LDL, HDL, and triglycerides), inflammation (hs-CRP), progression to type 2 diabetes mellitus, as well as safety indices (ALT, AST) will be obtained. An intention-to-treat analysis will be used to assess changes in study outcomes. Discussion Treatment options for adults with prediabetes are currently limited. This study aims to evaluate the safety and efficacy of a commercially available dietary supplement in the popular, but as yet insufficiently studied, category of polyherbal formulas for the management of glycemic parameters and other biomarkers associated with prediabetes. Trial registration ClinicalTrials.gov, ID: NCT03388762. Retrospectively registered on 4 January 2018.

Abstract Background Determining which therapies fall under the umbrella of complementary, alternative, and/or integrative medicine (CAIM) is difficult for several reasons. An operational definition is dynamic, and changes depending on both historical time period and geographical location, with many countries integrating or considering their traditional system(s) of medicine as conventional care. We have previously reported the first operational definition of CAIM informed by a systematic search. In the present study, we have developed a comprehensive search string informed by an operational definition of CAIM for systematic bibliographic database search strategies. Methods We developed a single search string for the most common bibliographic databases, including those searchable on the OVID platform (e.g., MEDLINE, EMBASE, PsycINFO, AMED), the EBSCO platform (e.g., ERIC, CINAHL), Scopus, and Web of Science, using the finalised operational definition of CAIM’s 604 therapies. We searched the Therapeutic Research Center’s “Natural Medicines” database for all 604 therapies, and each item’s scientific name and/or synonym was included as a keyword or phrase in the search string. Results This developed search string provides a standardised list of CAIM terms (i.e., keywords and phrases) that may be searched on bibliographic databases including those found on the OVID platform (e.g., MEDLINE, EMBASE, PsycINFO, AMED), the EBSCO platform (e.g., ERIC, CINAHL), Scopus, and Web of Science. Conclusion Researchers can select relevant terms for their CAIM study and insert the keywords/phrases into these databases to receive all accessible data. This search technique can simply be copied and pasted into the search bar of each database to identify research by keywords, which is the most inclusive, or by words in the article title, which is more selective. Given its versatility across multiple commonly used academic platforms/databases, it is expected that this search string will be of great value to those conducting research on CAIM topics involving systematic search strategies.

Abstract Background Identifying what therapies constitute complementary, alternative, and/or integrative medicine (CAIM) is complex for a multitude of reasons. An operational definition is dynamic, and changes based on both historical time period and geographical location whereby many jurisdictions may integrate or consider their traditional system(s) of medicine as conventional care. To date, only one operational definition of “complementary and alternative medicine” has been proposed, by Cochrane researchers in 2011. This definition is not only over a decade old but also did not use systematic methods to compile the therapies. Furthermore, it did not capture the concept “integrative medicine”, which is an increasingly popular aspect of the use of complementary therapies in practice. An updated operational definition reflective of CAIM is warranted given the rapidly increasing body of CAIM research literature published each year. Methods Four peer-reviewed or otherwise quality-assessed information resource types were used to inform the development of the operational definition: peer-reviewed articles resulting from searches across seven academic databases (MEDLINE, EMBASE, AMED, PsycINFO, CINAHL, Scopus and Web of Science); the “aims and scope” webpages of peer-reviewed CAIM journals; CAIM entries found in online encyclopedias, and highly-ranked websites identified through searches of CAIM-related terms on HONcode. Screening of eligible resources, and data extraction of CAIM therapies across them, were each conducted independently and in duplicate. CAIM therapies across eligible sources were deduplicated. Results A total of 101 eligible resources were identified: peer-reviewed articles (n = 19), journal “aims and scope” webpages (n = 22), encyclopedia entries (n = 11), and HONcode-searched websites (n = 49). Six hundred four unique CAIM terms were included in this operational definition. Conclusions This updated operational definition is the first to be informed by systematic methods, and could support the harmonization of CAIM-related research through the provision of a standard of classification, as well as support improved collaboration between different research groups.

Abstract Background Elderberry has traditionally been used to prevent and treat respiratory problems. During the COVID-19 pandemic, there has been interest in elderberry supplements to treat or prevent illness, but also concern that elderberry might overstimulate the immune system and increase the risk of ‘cytokine storm’. We aimed to determine benefits and harms of elderberry for the prevention and treatment of viral respiratory infections, and to assess the relationship between elderberry supplements and negative health impacts associated with overproduction of pro-inflammatory cytokines. Methods We conducted a systematic review and searched six databases, four research registers, and two preprint sites for studies. Two reviewers independently assessed studies for inclusion, extracted data from studies, assessed risk of bias using Cochrane tools, and evaluated certainty of estimates using GRADE. Outcomes included new illnesses and the severity and duration of illness. Results We screened 1187 records and included five randomized trials on elderberry for the treatment or prevention of viral respiratory illness. We did not find any studies linking elderberry to clinical inflammatory outcomes. However, we found three studies measuring production of cytokines ex vivo after ingestion of elderberry. Elderberry may not reduce the risk of developing the common cold; it may reduce the duration and severity of colds, but the evidence is uncertain. Elderberry may reduce the duration of influenza but the evidence is uncertain. Compared to oseltamivir, an elderberry-containing product may be associated with a lower risk of influenza complications and adverse events. We did not find evidence on elderberry and clinical outcomes related to inflammation. However, we found evidence that elderberry has some effect on inflammatory markers, although this effect may decline with ongoing supplementation. One small study compared elderberry to diclofenac (a nonsteroidal anti-inflammatory drug) and provided some evidence that elderberry is as effective or less effective than diclofenac in cytokine reduction over time. Conclusions Elderberry may be a safe option for treating viral respiratory illness, and there is no evidence that it overstimulates the immune system. However, the evidence on both benefits and harms is uncertain and information from recent and ongoing studies is necessary to make firm conclusions.

Abstract Background There has been increased interest in the role of cannabis for treating medical conditions. The availability of different cannabis-based products can make the side effects of exposure unpredictable. We sought to conduct a scoping review of systematic reviews assessing benefits and harms of cannabis-based medicines for any condition. Methods A protocol was followed throughout the conduct of this scoping review. A protocol-guided scoping review conduct. Searches of bibliographic databases (e.g., MEDLINE®, Embase, PsycINFO, the Cochrane Library) and gray literature were performed. Two people selected and charted data from systematic reviews. Categorizations emerged during data synthesis. The reporting of results from systematic reviews was performed at a high level appropriate for a scoping review. Results After screening 1975 citations, 72 systematic reviews were included. The reviews covered many conditions, the most common being pain management. Several reviews focused on management of pain as a symptom of conditions such as multiple sclerosis (MS), injury, and cancer. After pain, the most common symptoms treated were spasticity in MS, movement disturbances, nausea/vomiting, and mental health symptoms. An assessment of review findings lends to the understanding that, although in a small number of reviews results showed a benefit for reducing pain, the analysis approach and reporting in other reviews was sub-optimal, making it difficult to know how consistent findings are when considering pain in general. Adverse effects were reported in most reviews comparing cannabis with placebo (49/59, 83%) and in 20/24 (83%) of the reviews comparing cannabis to active drugs. Minor adverse effects (e.g., drowsiness, dizziness) were common and reported in over half of the reviews. Serious harms were not as common, but were reported in 21/59 (36%) reviews that reported on adverse effects. Overall, safety data was generally reported study-by-study, with few reviews synthesizing data. Only one review was rated as high quality, while the remaining were rated of moderate (n = 36) or low/critically low (n = 35) quality. Conclusions Results from the included reviews were mixed, with most reporting an inability to draw conclusions due to inconsistent findings and a lack of rigorous evidence. Mild harms were frequently reported, and it is possible the harms of cannabis-based medicines may outweigh benefits. Systematic review registration The protocol for this scoping review was posted in the Open Access (https://ruor.uottawa.ca/handle/10393/37247).