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The Comparative Effectiveness and Safety of Insomnia Drugs: A Systematic Review and Network Meta-Analysis of 153 Randomized Trials
BackgroundPharmacological treatment is common in practice and widely used for the management of insomnia. However, evidence comparing the relative effectiveness, safety, and certainty of evidence among drug classes and individual drugs for insomnia are still lacking. This study aimed to determine the relative effectiveness, safety, and tolerability of drugs for insomnia.MethodsIn this systematic review and network meta-analysis we systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and ClinicalTrials.gov, from inception to January 10, 2022 to identify randomized controlled trials that compared insomnia drugs with placebo or an active comparator in adults with insomnia. We conducted random-effects frequentist network meta-analyses to summarize the evidence, and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty, categorize interventionsand present the findings.ResultsA total of 148 articles met our eligibility criteria; these included 153 trials which enrolled 46,412 participants and assessed 36 individual drugs from eight drug classes. Compared with placebo, both subjectively and objectively measured total sleep time were significantly improved with non-benzodiazepine (subjective: mean difference [MD] 25.07, 95% confidence interval [CI] 15.49-34.64, low certainty; objective: MD 22.34, 95% CI 7.64-37.05, high certainty), antidepressants (subjective: MD 54.40, 95% CI 34.96-75.83, low certainty; objective: MD 35.64, 95% CI 13.05-58.24, high certainty), and orexin receptor antagonists (subjective: MD 21.62, 95% CI 0.84-42.40, high certainty; objective: MD 31.81, 95% CI 2.66-60.95, high certainty); of which doxepin, almorexant, suvorexant, and lemborexant were among the relatively effective drugs with relatively good tolerability and lower risks of any adverse events (AEs). Both subjectively and objectively measured sleep onset latency were significantly shortened with non-benzodiazepines (subjective: MD - 10.12, 95% CI - 13.84 to - 6.40, moderate certainty; objective: MD - 12.11, 95% CI - 19.31 to - 4.90, moderate certainty) and melatonin receptor agonists (subjective: MD - 7.73, 95% CI - 15.21 to - 0.26, high certainty; objective: MD - 7.04, 95% CI - 12.12 to - 1.95, moderate certainty); in particular, zopiclone was among the most effective drugs with a lower risk of any AEs but worse tolerability. Non-benzodiazepines could significantly decrease both subjective and objective measured wake time after sleep onset (subjective: MD - 16.67, 95% CI - 21.79 to - 11.56, moderate certainty; objective: MD - 13.92, 95% CI - 22.71 to - 5.14, moderate certainty).ConclusionsNon-benzodiazepines probably improve total sleep time, sleep onset latency, and wake time after sleep onset. Other insomnia drug classes and individual drugs also showed potential benefits in improving insomnia symptoms. However, the choice of insomnia drugs should be based on the phenotype of insomnia presented, as well as each drug's safety and tolerability.Protocol registration PROSPERO (CRD42019138790).
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Saturated fat and human health: a protocol for a methodologically innovative systematic review and meta-analysis to inform public health nutrition guidelines
Background The health effects of dietary fats are a controversial issue on which experts and authoritative organizations have often disagreed. Care providers, guideline developers, policy-makers, and researchers use systematic reviews to advise patients and members of the public on optimal dietary habits, and to formulate public health recommendations and policies. Existing reviews, however, have serious limitations that impede optimal dietary fat recommendations, such as a lack of focus on outcomes important to people, substantial risk of bias (RoB) issues, ignoring absolute estimates of effects together with comprehensive assessments of the certainty of the estimates for all outcomes.Objective We therefore propose a methodologically innovative systematic review using direct and indirect evidence on diet and food-based fats (i.e., reduction or replacement of saturated fat with monounsaturated or polyunsaturated fat, or carbohydrates or protein) and the risk of important health outcomes.Methods We will collaborate with an experienced research librarian to search MEDLINE, EMBASE, CINAHL, and the Cochrane Database of Systematic Reviews (CDSR) for randomized clinical trials (RCTs) addressing saturated fat and our health outcomes of interest. In duplicate, we will screen, extract results from primary studies, assess their RoB, conduct de novo meta-analyses and/or network meta-analysis, assess the impact of missing outcome data on meta-analyses, present absolute effect estimates, and assess the certainty of evidence for each outcome using the GRADE contextualized approach. Our work will inform recommendations on saturated fat based on international standards for reporting systematic reviews and guidelines.Conclusion Our systematic review and meta-analysis will provide the most comprehensive and rigorous summary of the evidence addressing the relationship between saturated fat modification for people-important health outcomes. The evidence from this review will be used to inform public health nutrition guidelines.
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A critical appraisal of clinical practice guidelines on insomnia using the RIGHT statement and AGREE II instrument
Objective: Clinical Practice Guidelines (CPGs) have an indispensable role in guiding the selection of various treatments for insomnia, however, little is known about the quality of released insomnia CPGs. This study aims to critically appraise the quality of existing insomnia CPGs and identify quality limitations. Methods: PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang, China Biology Medicine disc, and 6 databases of international guideline developing institutions were systematically searched. CPGs on the diagnosis or treatment of insomnia were included. Reviewers independently extracted basic information and development methods, and assessed methodological quality and reporting quality using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool and Reporting Items for practice Guidelines in Healthcare (RIGHT) checklist respectively. Intraclass correlation coefficients (ICCs) were used to measure the agreement among reviewers and assess inter-rater reliability. Results: Twenty-six CPGs were identified that focused on adults, children, or children with autistic spectrum disorder, patients in the intensive care unit, patients with cancer and pregnant, lactating or menopausal women. Twenty-two CPGs used nine grading systems to rate the level of evidence and strength of recommendation. 53.85% CPGs were classified as "recommended with modification" according to the AGREE II scores (ICC from 0.64 to 0.90), and 2 CPGs were "recommended". The "clarity of presentation" domain achieved the highest mean score (67.9% +/- 11.04%) but the "applicability" domain (37.1% +/- 12.67%) achieved the lowest. The average reporting rate of RIGHT items in all guidelines was 67.87%. Conclusions: The quality of guidelines varied substantially. Guideline developers should realize the importance of guideline applicability, patients' preferences and values. (c) 2022 Elsevier B.V. All rights reserved.
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Efficacy and safety of chinese herbal medicine for treating mild or moderate COVID-19: A systematic review and meta-analysis of randomized controlled trials and observational studies
Background: The coronavirus disease 2019 (COVID-19) is still a pandemic globally, about 80% of patients infected with COVID-19 were mild and moderate. Chinese herbal medicine (CHM) has played a positive role in the treatment of COVID-19, with a certain number of primary studies focused on CHM in managing COVID-19 published. This study aims to systematically review the currently published randomized controlled trials (RCTs) and observational studies (OBs), and summarize the effectiveness and safety of CHM in the treatment of mild/moderate COVID-19 patients. Methods: We searched 9 databases up to 19 March 2022. Pairs of reviewers independently screened literature, extracted data and assessed risk of bias. For overall effect, we calculated the absolute risk difference (ARD) of weighted averages of different estimates, and certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. Results: We included 35 RCTs and 24 OBs enrolling 16,580 mild/moderate patients. The certainty of evidence was very low to low. Compared with usual supportive treatments, most effect estimates of CHM treatments were consistent in direction. CHMs presented significant benefits in reducing rate of conversion to severe cases (ARD = 99 less per 1000 patients in RCTs and 131 less per 1000 patients in OBs, baseline risk: 16.52%) and mortality (ARD = 3 less per 1000 patients in RCTs and OBs, baseline risk: 0.40%); shortening time to symptom resolution (3.35 days in RCTs and 2.94 days in OBs), length of hospital stay (2.36 days in RCTs and 2.12 days in OBs) and time to viral clearance (2.64 days in RCTs and 4.46 days in OBs); increasing rate of nucleic acid conversion (ARD = 73 more per 1000 patients in OBs, baseline risk: 16.30%). No serious adverse reactions were found and the differences between CHM and usual supportive care were insignificant. Conclusion: Encouraging evidence showed that CHMs were beneficial in treating mild or moderate patients. CHMs have been proved to possess a safety profile that is comparable to that of usual supportive treatment alone. More rigorously designed clinical trials and mechanism studies are still warranted to further confirm the present findings.
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White rice consumption and risk of cardiometabolic and cancer outcomes: A systematic review and dose-response meta-analysis of prospective cohort studies
White rice is the food more than half of the world's population depends on. White rice intake can significantly increase the glycemic load of consumers and bring some adverse health effects. However, the quality of evidence implicating white rice in adverse health outcomes remains unclear. To evaluate the association between white rice consumption and the risk of cardiometabolic and cancer outcomes, a systematic review and dose-response meta-analysis of the relevant publications were performed. Twenty-three articles including 28 unique prospective cohorts with 1,527,198 participants proved eligible after a comprehensive search in four databases. For the risk of type 2 diabetes mellitus (T2DM), the pooled RR was 1.18 (16 more per 1000 persons) for comparing the highest with the lowest category of white rice intake, with moderate certainty evidence. Females presented a higher risk (23 more per 1000 persons) in subgroup analysis. And every additional 150 grams of white rice intake per day was associated with a 6% greater risk of T2DM (5 more per 1000 persons) with a linear positive trend. We found no significant associations between white rice intake and risk of cardiovascular diseases (CVD), CVD mortality, cancer, and metabolic syndrome. In conclusion, moderate certainty evidence demonstrated that white rice intake was associated with T2DM risk, with a linear positive trend. However, low to very low certainty of evidence suggested that no substantial associations were found between white rice intake and other cardiometabolic and cancer outcomes. More cohorts are needed to strength the evidence body.
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Role of Traditional Chinese Medicine in Treating Severe or Critical COVID-19: A Systematic Review of Randomized Controlled Trials and Observational Studies
Background: The coronavirus disease 2019 (COVID-19) continues to spread globally. Due to the higher risk of mortality, the treatment of severe or critical patients is a top priority. Traditional Chinese medicine (TCM) treatment has played an extremely important role in the fight against COVID-19 in China; a timely evidence summary on TCM in managing COVID-19 is crucial to update the knowledge of healthcare for better clinical management of COVID-19. This study aimed to assess the effects and safety of TCM treatments for severe/critical COVID-19 patients by systematically collecting and synthesizing evidence from randomized controlled trials (RCTs) and observational studies (e.g., cohort). Methods: We searched nine databases up to 19th March 2022 and the reference lists of relevant publications. Pairs of reviewers independently screened studies, extracted data of interest, and assessed risk of bias. We performed qualitative systematic analysis with visual presentation of results and compared the direction and distribution of effect estimates for each patient's important outcome. We performed sensitivity analyses to observe the robustness of results by restricting analysis to studies with low risk of bias. Results: The search yielded 217,761 records, and 21 studies (6 RCTs and 15 observational studies) proved eligible. A total of 21 studies enrolled 12,981 severe/critical COVID-19 patients with a mean age of 57.21 years and a mean proportion of men of 47.91%. Compared with usual supportive treatments, the effect estimates of TCM treatments were consistent in direction, illustrating that TCM treatments could reduce the risk of mortality, rate of conversion to critical cases, and mechanical ventilation, and showed significant advantages in shortening the length of hospital stay, time to viral clearance, and symptom resolution. The results were similar when we restricted analyses to low-risk-bias studies. No serious adverse events were reported with TCM treatments, and no significant differences were observed between groups. Conclusion: Encouraging evidence suggests that TCM presents substantial advantages in treating severe/critical COVID-19 patients. TCM has a safety profile that is comparable to that of conventional treatment alone. TCMs have played an important role in China's prevention and treatment of COVID-19, which sets an example of using traditional medicine in preventing and treating COVID-19 worldwide.
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Comparative effectiveness of multiple acupuncture therapies for primary insomnia: a systematic review and network meta-analysis of randomized trial
Background: Acupuncture has been widely practiced for primary insomnia (PI). However, the relative benefit and harm among acupuncture therapies remain uncertain.Objectives: To compare and evaluate the effect differences of multiple acupuncture therapies for patients with PI.Methods: Systematic literature search for randomized controlled trials (RCTs). Pairs of reviewers independently conducted literature screening, data extraction, and risk of bias assessment. Meta-analysis was conducted using R and Stata software. The Grading of Recommendations Assessment, Development, and Evaluation system (GRADE) was used to assess certainty of evidence and interpret results.Results: Fifty-seven RCTs with 4678 patients were included. Compared with usual treatment, multiple acupuncture therapies showed a better effect for Pittsburgh sleep quality index score. And acupoints catgut embedding (ACE) was proved to be the most effective with a moderate certainty of evidence; auricular acupressure or auricular acupuncture plus manual acupuncture (AP + MA), electroacupuncture plus acupoint application (EA + APA), and intradermal needle (IN) might be also the most effective with low certainty of evidence. ACE, ACE + MA, AP + MA, EA, EA + APA, HPN, MA and PBN + MA showed significantly improvement in effective rate when compared with usual treatment. Insufficient evidence reported on Epworth Sleepiness Scale, Athens Insomnia Scale, and recurrence rate. The most common slight adverse events mainly included hematoma, pain, headache, and bleeding.Conclusions: With moderate to low certainty of evidence, multiple acupuncture therapies showed impressive insomnia improvement, especially ACE, AP + MA, and EA + APA. Differences between therapies were small or insignificant and based-on low or very low certainty of evidence.(c) 2022 Elsevier B.V. All rights reserved.
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Efficacy and Safety of Qingfei Paidu Decoction for Treating COVID-19: A Systematic Review and Meta-Analysis
Background: Qingfei Paidu decoction (QFPD) has been widely used in treating COVID-19 in China. However, there is still a lack of comprehensive and systematic evidence to demonstrate the effectiveness and safety of QFPD. This study aims to evaluate the efficacy and safety of QFPD in patients with COVID-19. Methods: We searched seven databases up to 5 March 2021. Two reviewers independently screened studies, extracted data of interest, and assessed risk of bias. The Cochrane risk of bias tool was used to assess the risk of bias of randomized controlled trials. The Newcastle-Ottawa scale was used to assess the risk of bias of cohort and non-randomized trials. The "Quality Assessment Tool for Before-After (Pre-Post) Studies With No Control Group" was adopted for controlled pre-post studies. We used the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) to assess the certainty of evidence. We carried out a random effect meta-analysis using RevMan 5.3. For outcomes that could not be meta-analyzed, we performed a descriptive analysis. Results: We identified 16 studies with 11,237 patients, including one RCT, six non-randomized trials, two cohort studies, and seven pre-post studies. The certainty of evidence was low to very low because of the observational study design. QFPD combined with conventional treatment might decrease the time for nucleic acid conversion (MD = -4.78 days, 95% CI: -5.79 to -3.77), shorten the length of hospital stay (MD = -7.95 days, 95% CI: -14.66 to -1.24), shorten the duration of symptoms recovery of fever (MD = -1.51 days, 95% CI: -1.92 to -1.09), cough (MD = -1.64 days, 95% CI: -1.91 to -1.36) and chest CT (MD = -2.23 days, 95% CI: -2.46 to -2.00), improve the overall traditional Chinese medicine symptom scores (MD = 41.58 scores, 95% CI: 32.67 to 50.49), and change the laboratory indexes, such as WBC, AST, and CRP. Conclusion: QFPD combined with conventional treatment might be effective for patients with COVID-19. No serious adverse reactions related to QFPD were observed. Further high-quality studies are still needed in the future.
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