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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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Risk of incident diabetes after COVID-19 infection: A systematic review and meta-analysis
Background: COVID-19 might be a risk factor for various chronic diseases. However, the association between COVID-19 and the risk of incident diabetes remains unclear. We aimed to meta-analyze evidence on the relative risk of incident diabetes in patients with COVID-19. Methods: In this systematic review and meta-analysis, the Embase, PubMed, CENTRAL, and Web of Science databases were searched from December 2019 to June 8, 2022. We included cohort studies that provided data on the number, proportion, or relative risk of diabetes after confirming the COVID-19 diagnosis. Two reviewers independently screened studies for eligibility, extracted data, and assessed risk of bias. We used a random-effects meta-analysis to pool the relative risk with corresponding 95 % confidence intervals. Prespecified subgroup and meta-regression analyses were conducted to explore the potential influencing factors. We converted the relative risk to the absolute risk difference to present the evidence. This study was registered in advance (PROSPERO CRD42022337841). Main findings: Ten articles involving 11 retrospective cohorts with a total of 47.1 million participants proved eligible. We found a 64 % greater risk (RR = 1.64, 95%CI: 1.51 to 1.79) of diabetes in patients with COVID-19 compared with non-COVID-19 controls, which could increase the number of diabetes events by 701 (558 more to 865 more) per 10,000 persons. We detected significant subgroup effects for type of diabetes and sex. Type 2 diabetes has a higher relative risk than type 1. Moreover, men may be at a higher risk of overall diabetes than women. Sensitivity analysis confirmed the robustness of the results. No evidence was found for publication bias. Conclusions: COVID-19 is strongly associated with the risk of incident diabetes, including both type 1 and type 2 diabetes. We should be aware of the risk of developing diabetes after COVID-19 and prepare for the associated health problems, given the large and growing number of people infected with COVID-19. However, the body of evidence still needs to be strengthened.
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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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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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Acupuncture for cancer pain: an evidence-based clinical practice guideline
Background:This study aims to develop an evidence-based clinical practice guideline of acupuncture in the treatment of patients with moderate and severe cancer pain. Methods:The development of this guideline was triggered by a systematic review published in JAMA Oncology in 2020. We searched databases and websites for evidence on patient preferences and values, and other resources of using acupuncture for treatment of cancer pain. Recommendations were developed through a Delphi consensus of an international multidisciplinary panel including 13 western medicine oncologists, Chinese medicine/acupuncture clinical practitioners, and two patient representatives. The certainty of evidence, patient preferences and values, resources, and other factors were fully considered in formulating the recommendations. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was employed to rate the certainty of evidence and the strength of recommendations. Results:The guideline proposed three recommendations: (1) a strong recommendation for the treatment of acupuncture rather than no treatment to relieve pain in patients with moderate to severe cancer pain; (2) a weak recommendation for the combination treatments with acupuncture/acupressure to reduce pain intensity, decrease the opioid dose, and alleviate opioid-related side effects in moderate to severe cancer pain patients who are using analgesics; and (3) a strong recommendation for acupuncture in breast cancer patients to relieve their aromatase inhibitor-induced arthralgia. Conclusion:This proposed guideline provides recommendations for the management of patients with cancer pain. The small sample sizes of evidence limit the strength of the recommendations and highlights the need for additional research.
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Association between shift work and risk of type 2 diabetes mellitus: a systematic review and dose-response meta-analysis of observational studies
To evaluate the association between shift work and risk of type 2 diabetes mellitus, we searched PubMed, EMBASE and Web of Science from their inception to June 8, 2019. Observational studies examining the relationship between shift work and type 2 diabetes were included. Subgroup analyses were conducted to explore whether specific characteristics would affect the relationship. A dose-response relationship was estimated by using generalized least squares trend regression. Finally, twelve cohort studies and nine cross-sectional studies were included (inter-rater agreement, k = 0.96). The result of meta-analysis indicated that shift work was associated with an increased risk of type 2 diabetes (relative risk = 1.10, 95% confidence interval = 1.05-1.14). Subgroup analyses demonstrated that female shift workers have increased risk of type 2 diabetes while male not observed, health care workers showed the highest risk compared with civil servants and manual workers, and night shift and rotating shift were associated with an increased risk of type 2 diabetes. Dose-response meta-analysis based on three cohorts among female workers indicated that there might be a positive association between duration of shift work and the risk of type 2 diabetes. In conclusion, shift work is positively associated with an increased risk of type 2 diabetes. Among female workers, with the years of exposure to shift work prolonged, the risk of type 2 diabetes might increase accordingly. In the future, more studies are needed to confirm the results of dose-response analysis.
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The Effectiveness of Music Therapy for Terminally Ill Patients: A Meta-Analysis and Systematic Review
Context: The quality of death has increasingly raised concern because of the physical and psychological suffering of patients with advanced disease. Music therapy has been widely used in palliative care; however, its physical and mental effectiveness remains unclear. Objective: To assess the effectiveness of music therapy during palliative care in improving physiology and psychology outcomes. Methods: Randomized controlled trials evaluating music therapy for terminally ill patients were searched and included from inception up to April 25, 2018. The quality of the studies was assessed using the risk of bias tool recommended by the Cochrane Handbook V.5.1.0. Results: In this study, 11 randomized controlled trials (inter-rater agreement, κ = 0.86) involving 969 participants were included. The quality of the included studies ranged from moderate to high. Compared with general palliative care, music therapy can reduce pain (standardized mean difference: -0.44, 95% confidence interval: -0.60 to -0.27, P < 0.00001) and improve the quality of life (standardized mean difference: 0.61, 95% confidence interval: 0.41 to 0.82, P < 0.00001) in terminally ill patients. In addition, anxiety, depression, and emotional function are improved as well. However, no significant differences were found in the patient's physical status, fatigue, and social function. Conclusion: This meta-analysis study demonstrated that music therapy served as an effective intervention to alleviate pain and psychological symptoms of terminally ill patients. However, considering the limitation of the quantity of the studies included, these results would need to be further confirmed.
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