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).

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.

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.

Objective: To describe and record the evolution of EBM in China. Study Design and Setting: We conducted the study following the general methodology of oral history. The interviews were done at Lanzhou University, between 18th and 22 nd April 2019 using pre-defined questions. All interviews were videorecorded. Two investigators extracted and analyzed the information from the interviews independently. Results: One international expert and ten Chinese experts participated in the interviews. After the introduction of EBM in China in the mid-1990s, more than 20 EBM centres have been established. According to the interviewees, Gordon Guyatt, David Sackett and lain Chalmers are the international experts who played the most important role in the development of EBM in China. China has contributed to EBM on the international level by conducting systematic reviews, developing reporting checklists, and introducing the principles of EBM into Traditional Medicine. The Chinese Cochrane Centre and the EBM Centre of Lanzhou University were ranked the top two EBM Centres in China by the interviewees. Conclusion: EBM has been developing in China for nearly a quarter of a century. Many achievements have been reached, however, EBM is still facing many challenges in China, including shortages of funding support and personnel, as well as limited local high-quality evidence. (C) 2021 Elsevier Inc. All rights reserved.