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Objective:To estimate the proportion of healthcare interventions tested within Cochrane Reviews that are effective according to high-quality evidence. Methods:We selected a random sample of 2,428 (35%) of all Cochrane Reviews published between 1 January 2008 and 5 March 2021. We extracted data about interventions within these reviews that were compared with placebo, or no treatment, and whose outcome quality was rated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. We calculated the proportion of interventions whose benefits were based on high-quality evidence (defined as having high quality GRADE rating for at least one primary outcome, statistically significant positive results, and being judged by review authors as effective. We also calculated the proportion of interventions that suggested harm. Results:Of 1,567 eligible interventions, 87 (5.6%) had high-quality evidence supporting their benefits. Harms were measured for 577 (36.8%) interventions. There was statistically significant evidence for harm in 127 (8.1%) of these. Our dependence on the reliability of Cochrane author assessments (including their GRADE assessments) was the main potential limitation of our study. Conclusion:More than 9 in 10 healthcare interventions studied within recent Cochrane Reviews are not supported by high-quality evidence, and harms are under-reported.

Objectives: Homeopathy (HOM) is a therapeutic method, which is widely used by patients and medical professionals. The medical conditions as well as the homeopathic medical products investigated vary strongly. There is an extensive amount of research, and this necessitates a bibliography that comprehensively presents the entire body of clinical evidence grouped according to medical conditions. Design: Thirty-seven online sources as well as print libraries were searched for HOM and related terms in eight languages (1980 to March 2021). We included studies that compared a homeopathic medicine or intervention with a control regarding the therapeutic or preventive outcome of a disease (classified according to International Classification of Diseases-10). The data were extracted independently by two reviewers and analyzed descriptively. Results: A total of 636 investigations met the inclusion criteria, of which 541 had a therapeutic and 95 a preventive purpose. Seventy-three percent were randomized controlled trials (n = 463), whereas the rest were non-randomized studies (n = 173). The leading comparator was placebo (n = 400). The type of homeopathic intervention was classified as multi-constituent or complex (n = 272), classical or individualized (n = 176), routine or clinical (n = 161) and isopathic (n = 19), or various (n = 8). The potencies ranged from 1X (dilution of -10,000) to 10 M (100-10.000). The included studies explored the effect of HOM in 223 medical indications. We present the evidence in an online database. Conclusions: This bibliography maps the status quo of clinical research in HOM. The data will serve for future targeted reviews, which may focus on the most studied conditions and/or homeopathic medicines, clinical impact, and the risk of bias of the included studies.

Purpose Cancer-related fatigue remains one of the most prevalent and distressing symptoms experienced by cancer patients. Effective treatments for cancer-related fatigue are needed. The objective of this meta-analysis is to determine the impact of mistletoe extracts as a pharmacological treatment for the management of cancer-related fatigue. Methods We included randomized clinical trials (RCTs) and non-randomized studies of interventions (NRSIs) in cancer patients. Inclusion criteria were cancer-related fatigue severity or prevalence as an outcome and testing of mistletoe extracts compared to control groups. We searched Medline (EuropePMC), Embase, the Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and opengrey.org through October 2020. We assessed the risk of bias using the Cochrane risk of bias tools for RCTs and NRSIs and conducted a meta-analysis. Results We performed one meta-analysis with 12 RCTs, including 1494 participants, and one meta-analysis with seven retrospective NRSIs, including 2668 participants. Heterogeneity between the studies was high in both meta-analyses. Most studies had a high risk of bias. A random-effects model showed for RCTs a standardized mean difference of –0.48 (95% confidence interval –0.82 to –0.14; p = 0.006) and for NRSIs an odds ratio of 0.36 (95% confidence interval 0.20 to 0.66; p = 0.0008). Conclusion Treatment with mistletoe extracts shows a moderate effect on cancer-related fatigue of similar size to physical activity. These results need to be confirmed by more placebo-controlled trials. Future trials should investigate different treatment durations and their effect on cancer-related fatigue in post-treatment cancer survivors. Trial registration. This meta-analysis has been registered under the PROSPERO registration number CRD42020191967 on October 7, 2020.

ZusammenfassungDer Fokus der Demenzforschung liegt nach wie vor auf der Untersuchung der molekularen, pathophysiologischen Mechanismen. Wir umreißen in diesem Beitrag einige unserer Befunde, die aus systematischen Überblicksarbeiten der Literatur herrühren. Daraus kann man ableiten, dass Demenz sehr wohl einige Zusammenhänge mit Verhalten, vor allem mit dem Lebensstil und der Ernährung aufweist und daher auch durch entsprechende Lebensstiländerungen präventiv und aktiv angegangen werden kann. Die Empfehlungen, die wir daraus für unser lebensstilbasiertes Präventionsprogramm abgeleitet haben, sind ähnlich denen, die relativ generisch auch für andere chronische Krankheiten gelten, mit einigen demenzspezifischen Besonderheiten. Wichtig ist dabei neben der Vermeidung und allenfalls sachgerechten Ausleitung von Schwermetallen in der Ernährung eine gute Balance von Omega-3- und Omega-6-Fettsäuren, Vorsicht mit Zucker und mit rasch in Zucker metabolisierbaren Kohlehydraten und daher eher eine ketogene bzw. dieser ähnliche Ernährungsform mit viel Antioxidantien, ein normaler Body-Mass-Index sowie ausreichende Bewegung, gute Sozialkontakte und am besten eine regelmäßige Form der Bewusstseinskultur, etwa Meditation oder Achtsamkeit. Wir haben eine Lebensstildiagnostik zusammengestellt, die allgemein verfügbar ist.

Objectives The objective of the study was to determine the change in quality of evidence in updates of Cochrane reviews that were initially published between January 1, 2013 and June 30, 2014. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system to document evidence quality. Study Design and Setting We searched the Cochrane Database of Systematic Reviews on March 20, 2020 to identify which of the reviews from the initial (2013/14) sample had been updated. Using the same methods to determine the quality of evidence in the previous analysis, we assessed the quality of evidence for the first-listed primary outcomes in the updated reviews. Results Of the 608 reviews in the original sample, 154 had been updated with and 151 contained available data for both original and updated systematic reviews (24.8%). The updated reviews included: 15 (9.9%) with high-quality evidence, 56 (37.1%) with moderate-quality evidence, 47 (31.1%) with low-quality evidence, and 33 (21.9%) with very low-quality evidence. No change in the GRADE quality of evidence was found for most (103, 68.2%) of the updated reviews. The quality of evidence rating was downgraded in 28 reviews (58.3%) and upgraded in 20 (41.7%), although only six reviews were promoted to high quality. Conclusion Updated systematic reviews continued to suggest that only a minority of outcomes for health care interventions are supported by high-quality evidence. The quality of the evidence did not consistently improve or worsen in updated reviews.

Background Mistletoe extracts are used as an adjunct therapy for cancer patients, but there is dissent as to whether this therapy has a positive impact on quality of life (QoL). Methods We conducted a systematic review searching in several databases (Medline, Embase, CENTRAL, CINAHL, PsycInfo, Science Citation Index, clinicaltrials.gov, opengrey.org) by combining terms that cover the fields of “neoplasm”, “quality of life” and “mistletoe”. We included prospective controlled trials that compared mistletoe extracts with a control in cancer patients and reported QoL or related dimensions. The quality of the studies was assessed with the Cochrane Risk of Bias tool version 2. We conducted a quantitative meta-analysis. Results We included 26 publications with 30 data sets. The studies were heterogeneous. The pooled standardized mean difference (random effects model) for global QoL after treatment with mistletoe extracts vs. control was d = 0.61 (95% CI 0.41–0.81, p Conclusion Mistletoe extracts produce a significant, medium-sized effect on QoL in cancer. Risk of bias in the analyzed studies is likely due to the specific type of treatment, which is difficult to blind; yet this risk is unlikely to affect the outcome. PROSPERO registration CRD42019137704.

Background - Social prescribing is a process whereby primary care patients are linked or referred to nonmedical sources of support in the community and voluntary sector. It is a concept that has arisen in practice and implemented widely in the United Kingdom and has been evaluated by various organizations.Objective - The aim of our study was to characterize, collate, and analyze the evidence from evaluation of social prescribing for type 2 diabetes in the United Kingdom and Ireland, comparing information available on publicly available websites with the published literature.Methods - We used a broad, pragmatic definition of social prescribing and conducted Web-based searches for websites of organizations providing potentially relevant services. We also explored linked information. In parallel, we searched Medline, PubMed, Cochrane Library, Google Scholar, and reference lists for relevant studies published in peer-reviewed journals. We extracted the data systematically on the characteristics, any reported evaluation, outcomes measured and results, and terminology used to describe each service.Results - We identified 40 UK- or Ireland-based projects that referred people with type 2 diabetes and prediabetes to nonmedical interventions or services provided in the community. We located evaluations of 24 projects; 11 as published papers, 12 as Web-based reports, and 1 as both a paper and a Web-based report. The interventions and services identified included structured group educational programs, exercise referral schemes, and individualized advice and support with signposting of health-related activities in the community. Although specific interventions such as community-based group educational programs and exercise referral have been evaluated in randomized controlled trials, evaluation of individualized social prescribing services involving people with type 2 diabetes has, in most cases, used pre-post and mixed methods approaches. These evaluations report generic improvement in a broad range of outcomes and provide an insight into the criteria for the success of social prescribing services.Conclusions - Our study revealed the varied models of social prescribing and nonmedical, community-based services available to people with type 2 diabetes and the extent of evaluation of these, which would not have been achieved by searching databases alone. The findings of this scoping study do not prove that social prescribing is an effective measure for people with type 2 diabetes in the United Kingdom, but can be used to inform future evaluation and contribute to the development of the evidence base for social prescribing. Accessing Web-based information provides a potential method for investigating how specific innovative health concepts, such as social prescribing, have been translated, implemented, and evaluated in practice. Several challenges were encountered including defining the concept, focusing on process plus intervention, and searching diverse, evolving Web-based sources. Further exploration of this approach will inform future research on the application of innovative health care concepts into practice.

It has been suggested that the intake of certain fatty acids may influence the risk of dementia. However, current reviews have focused only on the therapeutic effects of omega-3 fatty acids, mostly as supplements. To date, the evidence for the relevance of the omega-6/omega-3 ratio has been neglected. Therefore, we searched the databases Alois, Medline, Biosis, Embase, Cochrane Central Register of Controlled Trials, and The Cochrane Database of Systematic Reviews for "essential fatty acids" and "dementia" and aimed to conduct a comprehensive review across study types. All studies that reported on the association between the n-6/n-3 ratio and dementia or cognitive decline were selected. In the 13 animal studies we examined, the dietary n-6/n-3 ratio was shown to affect brain composition, Alzheimer's disease pathology, and behavior. Our review of the 14 studies in humans that fulfilled the selection criteria (7 prospective studies, 3 cross-sectional studies, 1 controlled trial, 3 case-control studies) provided evidence, albeit limited, supporting an association between the n-6/n-3 ratio, cognitive decline, and incidence of dementia. This review supports growing evidence of a positive association between the dietary n-6/n-3 ratio and the risk of Alzheimer's disease.

Objective: Obesity is a risk factor of dementia. Current forecasts of dementia prevalence fail to take the rising obesity prevalence into account. Design and Methods: Embase and Medline were searched for observational studies on the association between overweight (BMI 25-30 kg/m2) or obesity (BMI > 30 kg/m2) and dementia and pooled the effect sizes by meta-analysis. The population attributable risk (PAR) was calculated for different time points and adjusted them for confounders. Based on current prevalence rates of dementia and demographic forecasts, patient numbers were calculated and adjusted by the growth rates of PAR. Results: Compared to normal weight, midlife obesity increases the risk of dementia later in life (BMI 25-30: RR = 1.34 [95% CI 1.08, 1.66], BMI > 30: RR = 1.91 [1.4, 2.62]). If obesity is included into forecast models, the prevalence of dementia is estimated to be 7.1 million (6.9, 7.3) and 11.3 million (10.9, 11.7) for the United States in 2030 and 2050, respectively. In China, the estimate is 13.1 million (12.8, 13.3) in 2030 and 26.2 million (25.1, 27.4) in 2050. These figures are 9% and 19% higher for the United States and China, respectively, than forecasts that rely solely on the demographic change. Conclusion: The past and ongoing increase in midlife obesity prevalence will contribute significantly to the future prevalence of dementia and public health measures to reduce midlife obesity are simultaneously primary prevention measures to reduce the risk of dementia.