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Systematic reviews are necessary to synthesize available evidence and inform clinical practice and health policy decisions. There has been an explosion of evidence available in many fields; this makes it challenging to keep evidence syntheses up to date and useful. Comparative effectiveness systematic reviews are informative; however, producing these often-large reviews bring intense time and resource demands. This commentary describes the implementation of a systematic review using a collaborative model of evidence synthesis. We are implementing the collaborative review model to update a large Cochrane review investigating the efficacy and comparative effectiveness of the design, delivery, and type of exercise treatment for people with chronic low-back pain. Three key benefits of the collaborative review model for evidence synthesis are (1) team coordination and collaboration, (2) quality control measures, and (3) advanced comparative and other analyses. This new collaborative review model is developed and implemented to produce and share high-quality, comparative evidence more efficiently while building capacity and community within a research field.

Radiotherapy and chemotherapy are used to improve survival in colorectal cancer but adverse effects can be a problem. Severe adverse effects may result in dose reduction or cessation of treatment, which have an impact on survival. Coriolus versicolor (Trametes versicolor or 'Turkey Tail') mushroom and its extracts have been used by cancer patients to help with adverse effects.To assess the effects of adjunctive Coriolus versicolor (Trametes versicolor) and its extracts on adverse effects and on survival during colorectal cancer treatment (chemotherapy and radiotherapy) compared with no adjunctive treatment.We searched databases including CENTRAL, MEDLINE, Embase, AMED and CINAHL, Chinese and Japanese databases, and trials registers to 12th April 2022 without restriction of language or publication status. We screened reference lists and attempted to contact researchers in the field to identify additional studies.We included randomised controlled trials (RCTs) investigating the efficacy and safety of Coriolus versicolor and its extracts in adult participants with a confirmed diagnosis of colorectal cancer, in addition to conventional treatment. Interventions included any preparation of Coriolus versicolor (raw, decoction, capsule, tablet, tincture, extract, injection), any part of the fungus (cap, stem, mycelium or whole), in any dose or regimen. Outcomes included adverse events rates, survival, disease progression and recurrence, response rates and quality of life.Two review authors independently screened and selected studies, extracted outcome data, and assessed risk of bias. We evaluated the overall certainty of evidence using the GRADE approach.We included seven parallel RCTs (1569 participants). Six studies (1516 participants) were conducted in Japan and one study (53 participants) in China. Studies included both male and female participants with colorectal cancer (five studies), colon cancer (one study) or rectal cancer (one study). Participants were diagnosed with cancer ranging from stage II to stage IV. Coriolus was used in the form of an extract in all seven studies and was generally used after curative resection, although in one study it was used preoperatively. Duration of treatment with the extract varied between four weeks and three years. Chemotherapeutic regimens in six studies consisted of an oral fluoropyrimidine which was preceded by weekly intravenous 5-Fluorouracil (5-FU) in one study, by mitomycin C in two studies, and which was combined with folinic acid (Leucovorin) in two studies and with radiotherapy preoperatively in one study. XELOX (oxaliplatin intravenous infusion and capecitabine) was used in the remaining study. We found very low-certainty evidence of little to no effect of adjunctive treatment with Coriolus (in the form of an extract, polysaccharide-Krestin, PSK) on withdrawal from treatment due to adverse events (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.45 to 2.34; 703 participants; 3 studies;). We are uncertain whether adjunctive Coriolus versicolor and its extracts compared to usual care alone resulted in a difference in adverse events including neutropenia (RR 0.41, 95% CI 0.24 to 0.71; 133 participants; 3 studies; very low certainty), oral cavity disorders such as oral dryness and mucositis (RR 0.37, 95% CI 0.13 to 1.03; 1022 participants; 5 studies; very low certainty), nausea (RR 0.73, 95% CI 0.44 to 1.22; 969 participants; 4 studies; very low certainty), diarrhoea (RR 0.77, 95% CI 0.32 to 1.86; 1022 participants; 5 studies; very low certainty), and fatigue (RR 0.76; 95% CI 0.33 to 1.78; 133 participants; 3 studies; very low certainty). We found low-certainty evidence of a small effect of adjunctive Coriolus on improved survival at five years compared with no adjunctive care (RR 1.08, 95% CI 1.01 to 1.15; 1094 participants; 3 studies; number needed to benefit (NNTB) = 16 (95% Cl 9 to 70). The effect at earlier time points was unclear.Due to the very low certainty of evidence, we were uncertain about the effect of adjunctive Coriolus (in the form of an extract PSK) on adverse events resulting from conventional chemotherapy for colorectal cancer. This includes effects on withdrawal of treatment due to adverse events and on specific adverse outcomes such as neutropenia and nausea. The uncertainty in the evidence also means that it was unclear whether any adverse events were due to the chemotherapy or to the extract itself. While there was low-certainty evidence of a small effect on overall survival at five years, the influence of reduced adverse effects on this could not be determined. In addition, chemotherapy regimens used in assessing this outcome do not reflect current preferred practice.

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.

BackgroundElderberry 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.MethodsWe 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.ResultsWe 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.ConclusionsElderberry 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.

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.

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

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 bibliographic database keyword search strategy for CAIM based on this operational definition, in order to standardize research involving systematic searches such as systematic reviews and bibliometric analyses. Methods Using the finalised operational definition of CAIM's 604 therapies, a single keyword search strategy was developed 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. The Therapeutic Research Center's “Natural Medicines” database was searched for all 604 therapies, and each item's scientific name and/or synonym was included as a phrase to the search strategy. Results This developed bibliographic database search strategy provides a standardised list of CAIM terms 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 or 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 strategy will be of great value to those conducting research on CAIM topics involving systematic searches.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of yoga for osteoarthritis of the hip or knee, compared to other interventions or no intervention.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effectiveness and safety of zinc for the prevention and treatment of the common cold.

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.

BackgroundThere 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.MethodsA 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.ResultsAfter 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.ConclusionsResults 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 registrationThe protocol for this scoping review was posted in the Open Access (https://ruor.uottawa.ca/handle/10393/37247).

Cochrane is an international non-profit organization established in 1993 to produce and disseminate high quality and unbiased systematic reviews of evidence on health care interventions. At the forefront of systematic review methodology, Cochrane is generally accepted to be among the most carefully prepared and rigorous sources of systematic review evidence. There are numerous Cochrane reviews on nonpharmacologic interventions for pain and multiple Cochrane reviews evaluating acupuncture therapy in pain conditions. But how complete and up to date are those reviews relative to other rigorous systematic reviews with meta-analyses of acupuncture therapy for pain published in the literature? In this ‘snapshot’ overview, we found 22 relevant Cochrane reviews, some concluding that acupuncture therapy is probably useful for treating specific pain conditions. However, many of the conditions for which acupuncture is most commonly used are either not represented in Cochrane reviews or the existing Cochrane reviews are seriously outdated and do not reflect current evidence. This creates confusion with the risks of adverse effects and addiction liability associated with pain medications, the prevalence of chronic pain, the ongoing opioid epidemic and the need for evidence-based options for pain as part of comprehensive pain care. Clinicians and patients want clarification on safe and effective options to treat pain. Issues involving reviewed trials’ inadequate use of sham comparators, of acupuncture as a complex intervention with interactive components and a shift in research focus from efficacy trials to real-world pragmatic trials are discussed in relation to updating Cochrane reviews of acupuncture therapy for pain.

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. Electronic supplementary material The online version of this article (10.1186/s13063-018-3032-6) contains supplementary material, which is available to authorized users.

BACKGROUND: The role of vitamin D supplementation as a treatment for COVID‐19 has been a subject of considerable discussion. A thorough understanding of the current evidence regarding the effectiveness and safety of vitamin D supplementation for COVID‐19 based on randomised controlled trials is required. OBJECTIVES: To assess whether vitamin D supplementation is effective and safe for the treatment of COVID‐19 in comparison to an active comparator, placebo, or standard of care alone, and to maintain the currency of the evidence, using a living systematic review approach. SEARCH METHODS: We searched the Cochrane COVID‐19 Study Register, Web of Science and the WHO COVID‐19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions to 11 March 2021. SELECTION CRITERIA: We followed standard Cochrane methodology. We included randomised controlled trials (RCTs) evaluating vitamin D supplementation for people with COVID‐19, irrespective of disease severity, age, gender or ethnicity. We excluded studies investigating preventive effects, or studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)). DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane risk of bias tool (ROB 2) for RCTs. We rated the certainty of evidence using the GRADE approach for the following prioritised outcome categories: individuals with moderate or severe COVID‐19: all‐cause mortality, clinical status, quality of life, adverse events, serious adverse events, and for individuals with asymptomatic or mild disease: all‐cause mortality, development of severe clinical COVID‐19 symptoms, quality of life, adverse events, serious adverse events. MAIN RESULTS: We identified three RCTs with 356 participants, of whom 183 received vitamin D. In accordance with the World Health Organization (WHO) clinical progression scale, two studies investigated participants with moderate or severe disease, and one study individuals with mild or asymptomatic disease. The control groups consisted of placebo treatment or standard of care alone. Effectiveness of vitamin D supplementation for people with COVID‐19 and moderate to severe disease We included two studies with 313 participants. Due to substantial clinical and methodological diversity of both studies, we were not able to pool data. Vitamin D status was unknown in one study, whereas the other study reported data for vitamin D deficient participants. One study administered multiple doses of oral calcifediol at days 1, 3 and 7, whereas the other study gave a single high dose of oral cholecalciferol at baseline. We assessed one study with low risk of bias for effectiveness outcomes, and the other with some concerns about randomisation and selective reporting. All‐cause mortality at hospital discharge (313 participants) We found two studies reporting data for this outcome. One study reported no deaths when treated with vitamin D out of 50 participants, compared to two deaths out of 26 participants in the control group (Risk ratio (RR) 0.11, 95% confidence interval (CI) 0.01 to 2.13). The other study reported nine deaths out of 119 individuals in the vitamin D group, whereas six participants out of 118 died in the placebo group (RR 1.49, 95% CI 0.55 to 4.04]. We are very uncertain whether vitamin D has an effect on all‐cause mortality at hospital discharge (very low‐certainty evidence). Clinical status assessed by the need for invasive mechanical ventilation (237 participants) We found one study reporting data for this outcome. Nine out of 119 participants needed invasive mechanical ventilation when treated with vitamin D, compared to 17 out of 118 participants in the placebo group (RR 0.52, 95% CI 0.24 to 1.13). Vitamin D supplementation may decrease need for invasive mechanical ventilation, but the evidence is uncertain (low‐certainty evidence). Quality of life We did not find data for quality of life. Safety of vitamin D supplementation for people with COVID‐19 and moderate to severe disease We did not include data from one study, because assessment of serious adverse events was not described and we are concerned that data might have been inconsistently measured. This study reported vomiting in one out of 119 participants immediately after vitamin D intake (RR 2.98, 95% CI 0.12 to 72.30). We are very uncertain whether vitamin D supplementation is associated with higher risk for adverse events (very low‐certainty). Effectiveness and safety of vitamin D supplementation for people with COVID‐19 and asymptomatic or mild disease We found one study including 40 individuals, which did not report our prioritised outcomes, but instead data for viral clearance, inflammatory markers, and vitamin D serum levels. The authors reported no events of hypercalcaemia, but recording and assessment of further adverse events remains unclear. Authors administered oral cholecalciferol in daily doses for at least 14 days, and continued with weekly doses if vitamin D blood levels were > 50 ng/mL. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to determine the benefits and harms of vitamin D supplementation as a treatment of COVID‐19. The evidence for the effectiveness of vitamin D supplementation for the treatment of COVID‐19 is very uncertain. Moreover, we found only limited safety information, and were concerned about consistency in measurement and recording of these outcomes. There was substantial clinical and methodological heterogeneity of included studies, mainly because of different supplementation strategies, formulations, vitamin D status of participants, and reported outcomes. There is an urgent need for well‐designed and adequately powered randomised controlled trials (RCTs) with an appropriate randomisation procedure, comparability of study arms and preferably double‐blinding. We identified 21 ongoing and three completed studies without published results, which indicates that these needs will be addressed and that our findings are subject to change in the future. Due to the living approach of this work, we will update the review periodically.

Systematic reviews on traditional Chinese medicine (TCM) are constantly increasing. However, if these reviews are to be of practical value, the evidence needs to be relevant, valid, and adequately reported. Cochrane Systematic Reviews (CSRs) are considered as high-quality systematic reviews that can inform health care decision making. Our aim was to provide an overview of the scope, findings, quality and impact of CSRs on the benefits and harms associated with TCM interventions for the treatment and prevention of disease to provide new information for clinical practice and future research.The Cochrane Database of Systematic Reviews was searched up to May 2021, and descriptive characteristics were extracted. The correspondence between the questions asked in the CSRs and the available evidence, conclusions and certainty of findings (according to GRADE assessment), methodological quality (AMSTAR 2), and impact (Altmetric Attention Score [AAS], total citations by guideline, and total citations in Web of Science [WoS]) of CSRs were extracted. Tabular and graphical summaries of these descriptive characteristics were constructed.Of 104 CSRs on TCM identified, 70 diseases belonged to 16 disease systems and contained 1642 primary studies with 157,943 participants. Interventions included Chinese herbal medicine (n = 70), acupuncture (n = 28), TCM exercises (n = 4), and moxibustion (n = 2). Among 1642 primary studies, 662 studies included an intervention group treated with at least one TCM therapy and 980 studies included a combination of therapies. Promising outcomes from the 104 CSRs were divided into endpoint outcomes (34 diseases), doctor- or patient-reported outcomes (27 diseases), and surrogate outcomes (37 diseases). Despite the presence of promising outcomes, only 5/104 CSRs drew overall positive conclusions, 42 CSRs concluded the evidence was insufficient, and 54 failed to draw firm conclusions. GRADE assessments were reported in 41.3% of the CSRs, and the ratings were mostly low or very low. Comparing the questions asked and results obtained, there was frequently a lack of information about specific outcomes. Only 16 CSRs obtained results for all outcomes listed in the methods section. According to AMSTAR 2, 51 CSRs (49.0%) were of low quality. The total number of citations in the WoS was 2135 (mean ± SD: 20.8 ± 21.2), and 38.5% of the CSRs had been cited in guidelines 95 times.Although TCM is commonly used, evidence of its effectiveness remains largely inconclusive. Rigorous high-quality trials are needed to support the performance of high-quality reviews and to increase the evidence base. It is critical to emphasize quality over quantity in future TCM research.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the efficacy and safety of Ginkgo for the treatment of people with diagnoses of cognitive impairment or dementia.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects of smartphone‐based m‐health interventions for overweight or obese adolescents and adults.

BACKGROUND: Viral epidemics or pandemics of acute respiratory infections (ARIs) pose a global threat. Examples are influenza (H1N1) caused by the H1N1pdm09 virus in 2009, severe acute respiratory syndrome (SARS) in 2003, and coronavirus disease 2019 (COVID‐19) caused by SARS‐CoV‐2 in 2019. Antiviral drugs and vaccines may be insufficient to prevent their spread. This is an update of a Cochrane Review published in 2007, 2009, 2010, and 2011. The evidence summarised in this review does not include results from studies from the current COVID‐19 pandemic. OBJECTIVES: To assess the effectiveness of physical interventions to interrupt or reduce the spread of acute respiratory viruses. SEARCH METHODS: We searched CENTRAL, PubMed, Embase, CINAHL on 1 April 2020. We searched ClinicalTrials.gov, and the WHO ICTRP on 16 March 2020. We conducted a backwards and forwards citation analysis on the newly included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and cluster‐RCTs of trials investigating physical interventions (screening at entry ports, isolation, quarantine, physical distancing, personal protection, hand hygiene, face masks, and gargling) to prevent respiratory virus transmission. In previous versions of this review we also included observational studies. However, for this update, there were sufficient RCTs to address our study aims. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence. Three pairs of review authors independently extracted data using a standard template applied in previous versions of this review, but which was revised to reflect our focus on RCTs and cluster‐RCTs for this update. We did not contact trialists for missing data due to the urgency in completing the review. We extracted data on adverse events (harms) associated with the interventions. MAIN RESULTS: We included 44 new RCTs and cluster‐RCTs in this update, bringing the total number of randomised trials to 67. There were no included studies conducted during the COVID‐19 pandemic. Six ongoing studies were identified, of which three evaluating masks are being conducted concurrent with the COVID pandemic, and one is completed. Many studies were conducted during non‐epidemic influenza periods, but several studies were conducted during the global H1N1 influenza pandemic in 2009, and others in epidemic influenza seasons up to 2016. Thus, studies were conducted in the context of lower respiratory viral circulation and transmission compared to COVID‐19. The included studies were conducted in heterogeneous settings, ranging from suburban schools to hospital wards in high‐income countries; crowded inner city settings in low‐income countries; and an immigrant neighbourhood in a high‐income country. Compliance with interventions was low in many studies. The risk of bias for the RCTs and cluster‐RCTs was mostly high or unclear. Medical/surgical masks compared to no masks We included nine trials (of which eight were cluster‐RCTs) comparing medical/surgical masks versus no masks to prevent the spread of viral respiratory illness (two trials with healthcare workers and seven in the community). There is low certainty evidence from nine trials (3507 participants) that wearing a mask may make little or no difference to the outcome of influenza‐like illness (ILI) compared to not wearing a mask (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.82 to 1.18. There is moderate certainty evidence that wearing a mask probably makes little or no difference to the outcome of laboratory‐confirmed influenza compared to not wearing a mask (RR 0.91, 95% CI 0.66 to 1.26; 6 trials; 3005 participants). Harms were rarely measured and poorly reported. Two studies during COVID‐19 plan to recruit a total of 72,000 people. One evaluates medical/surgical masks (N = 6000) (published Annals of Internal Medicine, 18 Nov 2020), and one evaluates cloth masks (N = 66,000). N95/P2 respirators compared to medical/surgical masks We pooled trials comparing N95/P2 respirators with medical/surgical masks (four in healthcare settings and one in a household setting). There is uncertainty over the effects of N95/P2 respirators when compared with medical/surgical masks on the outcomes of clinical respiratory illness (RR 0.70, 95% CI 0.45 to 1.10; very low‐certainty evidence; 3 trials; 7779 participants) and ILI (RR 0.82, 95% CI 0.66 to 1.03; low‐certainty evidence; 5 trials; 8407 participants). The evidence is limited by imprecision and heterogeneity for these subjective outcomes. The use of a N95/P2 respirator compared to a medical/surgical mask probably makes little or no difference for the objective and more precise outcome of laboratory‐confirmed influenza infection (RR 1.10, 95% CI 0.90 to 1.34; moderate‐certainty evidence; 5 trials; 8407 participants). Restricting the pooling to healthcare workers made no difference to the overall findings. Harms were poorly measured and reported, but discomfort wearing medical/surgical masks or N95/P2 respirators was mentioned in several studies. One ongoing study recruiting 576 people compares N95/P2 respirators with medical surgical masks for healthcare workers during COVID‐19. Hand hygiene compared to control Settings included schools, childcare centres, homes, and offices. In a comparison of hand hygiene interventions with control (no intervention), there was a 16% relative reduction in the number of people with ARIs in the hand hygiene group (RR 0.84, 95% CI 0.82 to 0.86; 7 trials; 44,129 participants; moderate‐certainty evidence), suggesting a probable benefit. When considering the more strictly defined outcomes of ILI and laboratory‐confirmed influenza, the estimates of effect for ILI (RR 0.98, 95% CI 0.85 to 1.13; 10 trials; 32,641 participants; low‐certainty evidence) and laboratory‐confirmed influenza (RR 0.91, 95% CI 0.63 to 1.30; 8 trials; 8332 participants; low‐certainty evidence) suggest the intervention made little or no difference. We pooled all 16 trials (61,372 participants) for the composite outcome of ARI or ILI or influenza, with each study only contributing once and the most comprehensive outcome reported. The pooled data showed that hand hygiene may offer a benefit with an 11% relative reduction of respiratory illness (RR 0.89, 95% CI 0.84 to 0.95; low‐certainty evidence), but with high heterogeneity. Few trials measured and reported harms. There are two ongoing studies of handwashing interventions in 395 children outside of COVID‐19. We identified one RCT on quarantine/physical distancing. Company employees in Japan were asked to stay at home if household members had ILI symptoms. Overall fewer people in the intervention group contracted influenza compared with workers in the control group (2.75% versus 3.18%; hazard ratio 0.80, 95% CI 0.66 to 0.97). However, those who stayed at home with their infected family members were 2.17 times more likely to be infected. We found no RCTs on eye protection, gowns and gloves, or screening at entry ports. AUTHORS' CONCLUSIONS: The high risk of bias in the trials, variation in outcome measurement, and relatively low compliance with the interventions during the studies hamper drawing firm conclusions and generalising the findings to the current COVID‐19 pandemic. There is uncertainty about the effects of face masks. The low‐moderate certainty of the evidence means our confidence in the effect estimate is limited, and that the true effect may be different from the observed estimate of the effect. The pooled results of randomised trials did not show a clear reduction in respiratory viral infection with the use of medical/surgical masks during seasonal influenza. There were no clear differences between the use of medical/surgical masks compared with N95/P2 respirators in healthcare workers when used in routine care to reduce respiratory viral infection. Hand hygiene is likely to modestly reduce the burden of respiratory illness. Harms associated with physical interventions were under‐investigated. There is a need for large, well‐designed RCTs addressing the effectiveness of many of these interventions in multiple settings and populations, especially in those most at risk of ARIs.