Methodological proposals for developing trustworthy recommendations of integrative Chinese-Western medicine.

Background: To refine the methods of developing clinical practice guidelines (CPGs) for integrative Chinese-Western medicine (ICWM), promoting the formation of trustworthy, implementable recommendations that integrate the strengths of Chinese and Western medicine. Methods: Using a nominal group technique (NGT) approach, a multidisciplinary expert panel was established. The panel identified key methodological issues in ICWM-CPG development through literature review and iterative discussions, and formulated methodological proposals to address these issues. The final set of proposals was achieved through consensus among the panel members. Results: The collaborative effort resulted in the identification of five pivotal methodological issues and the subsequent establishment of 22 specific recommendations. These encompass strict adherence to renowned standards, such as those proposed by the Institute of Medicine (IOM) and Guidelines International Network (G-I-N), the employment of methodologies like the GRADE approach and RIGHT statement, the strategic constitution of a balanced development group, the adept identification of ICWM-focused clinical inquiries, the nuanced integration of diverse evidence sources, and the detailed crafting of transparent, implementable recommendations. Conclusions: This study concentrates on the most crucial and prevalent methodological issues in ICWM-CPG development, proposing a series of recommendations. These suggestions result from a multidisciplinary expert consensus, aiming to provide methodological guidance for ICWM-CPG developers, building upon the current foundational methodologies.

Assessing the Risk of Bias in Randomized Clinical Trials With Large Language Models.

Importance: Large language models (LLMs) may facilitate the labor-intensive process of systematic reviews. However, the exact methods and reliability remain uncertain. Objective: To explore the feasibility and reliability of using LLMs to assess risk of bias (ROB) in randomized clinical trials (RCTs). Design, Setting, and Participants: A survey study was conducted between August 10, 2023, and October 30, 2023. Thirty RCTs were selected from published systematic reviews. Main Outcomes and Measures: A structured prompt was developed to guide ChatGPT (LLM 1) and Claude (LLM 2) in assessing the ROB in these RCTs using a modified version of the Cochrane ROB tool developed by the CLARITY group at McMaster University. Each RCT was assessed twice by both models, and the results were documented. The results were compared with an assessment by 3 experts, which was considered a criterion standard. Correct assessment rates, sensitivity, specificity, and F1 scores were calculated to reflect accuracy, both overall and for each domain of the Cochrane ROB tool; consistent assessment rates and Cohen κ were calculated to gauge consistency; and assessment time was calculated to measure efficiency. Performance between the 2 models was compared using risk differences. Results: Both models demonstrated high correct assessment rates. LLM 1 reached a mean correct assessment rate of 84.5% (95% CI, 81.5%-87.3%), and LLM 2 reached a significantly higher rate of 89.5% (95% CI, 87.0%-91.8%). The risk difference between the 2 models was 0.05 (95% CI, 0.01-0.09). In most domains, domain-specific correct rates were around 80% to 90%; however, sensitivity below 0.80 was observed in domains 1 (random sequence generation), 2 (allocation concealment), and 6 (other concerns). Domains 4 (missing outcome data), 5 (selective outcome reporting), and 6 had F1 scores below 0.50. The consistent rates between the 2 assessments were 84.0% for LLM 1 and 87.3% for LLM 2. LLM 1's κ exceeded 0.80 in 7 and LLM 2's in 8 domains. The mean (SD) time needed for assessment was 77 (16) seconds for LLM 1 and 53 (12) seconds for LLM 2. Conclusions: In this survey study of applying LLMs for ROB assessment, LLM 1 and LLM 2 demonstrated substantial accuracy and consistency in evaluating RCTs, suggesting their potential as supportive tools in systematic review processes.

An umbrella review of the diagnostic value of next-generation sequencing in infectious diseases.

BACKGROUND: An increasing number of systematic reviews (SRs) have evaluated the diagnostic values of next-generation sequencing (NGS) in infectious diseases (IDs). AIM: This umbrella analysis aimed to assess the potential risk of bias in existing SRs and to summarize the published diagnostic values of NGS in different IDs. METHOD: We searched PubMed, Embase, and the Cochrane Library until September 2023 for SRs assessing the diagnostic validity of NGS for IDs. Two investigators independently determined review eligibility, extracted data, and evaluated reporting quality, risk of bias, methodological quality, and evidence certainty in the included SRs. RESULTS: Eleven SRs were analyzed. Most SRs exhibited a moderate level of reporting quality, while a serious risk of bias was observed in all SRs. The diagnostic performance of NGS in detecting pneumocystis pneumonia and periprosthetic/prosthetic joint infection was notably robust, showing excellent sensitivity (pneumocystis pneumonia: 0.96, 95% CI 0.90-0.99, very low certainty; periprosthetic/prosthetic joint infection: 0.93, 95% CI 0.83-0.97, very low certainty) and specificity (pneumocystis pneumonia: 0.96, 95% CI 0.92-0.98, very low certainty; periprosthetic/prosthetic joint infection: 0.95, 95% CI 0.92-0.97, very low certainty). NGS exhibited high specificity for central nervous system infection, bacterial meningoencephalitis, and tuberculous meningitis. The sensitivity to these infectious diseases was moderate. NGS demonstrated moderate sensitivity and specificity for multiple infections and pulmonary infections. CONCLUSION: This umbrella analysis indicates that NGS is a promising technique for diagnosing pneumocystis pneumonia and periprosthetic/prosthetic joint infection with excellent sensitivity and specificity. More high-quality original research and SRs are needed to verify the current findings.

Association of previous stillbirth with subsequent perinatal outcomes: a systematic review and meta-analysis of cohort studies.

OBJECTIVE: We conducted a systematic review and meta-analysis to examine the relationship between stillbirth and various perinatal outcomes in subsequent pregnancy. DATA SOURCES: PubMed, the Cochrane Library, Embase, Web of Science, and CNKI databases were searched up to July 2023. STUDY ELIGIBILITY CRITERIA: Cohort studies that reported the association between stillbirth and perinatal outcomes in subsequent pregnancies were included. METHODS: We conducted this systematic review and meta-analysis in accordance with the PRISMA guidelines. Statistical analysis was performed using R and Stata software. We used random-effects models to pool each outcome of interest. We performed a meta-regression analysis to explore the potential heterogeneity. The certainty (quality) of evidence assessment was performed using the GRADE approach. RESULTS: Nineteen cohort studies were included, involving 4,855,153 participants. From these studies, we identified 28,322 individuals with previous stillbirths who met the eligibility criteria. After adjusting for confounders, evidence of low to moderate certainty indicated that compared with women with previous live births, women with previous stillbirths had higher risks of recurrent stillbirth (odds ratio, 2.68; 95% confidence interval, 2.01-3.56), preterm birth (odds ratio, 3.15; 95% confidence interval, 2.07-4.80), neonatal death (odds ratio, 4.24; 95% confidence interval, 2.65-6.79), small for gestational age/intrauterine growth restriction (odds ratio, 1.3; 95% confidence interval, 1.0-1.8), low birthweight (odds ratio, 3.32; 95% confidence interval, 1.46-7.52), placental abruption (odds ratio, 3.01; 95% confidence interval, 1.01-8.98), instrumental delivery (odds ratio, 2.29; 95% confidence interval, 1.68-3.11), labor induction (odds ratio, 4.09; 95% confidence interval, 1.88-8.88), cesarean delivery (odds ratio, 2.38; 95% confidence interval, 1.20-4.73), elective cesarean delivery (odds ratio, 2.42; 95% confidence interval, 1.82-3.23), and emergency cesarean delivery (odds ratio, 2.35; 95% confidence interval, 1.81-3.06) in subsequent pregnancies, but had a lower rate of spontaneous labor (odds ratio, 0.22; 95% confidence interval, 0.13-0.36). However, there was no association between previous stillbirth and preeclampsia (odds ratio, 1.72; 95% confidence interval, 0.63-4.70) in subsequent pregnancies. CONCLUSION: Our systematic review and meta-analysis provide a more comprehensive understanding of adverse pregnancy outcomes associated with previous stillbirth. These findings could be used to inform counseling for couples who are considering pregnancy after a previous stillbirth.

Risk of kidney and liver diseases after COVID-19 infection: A systematic review and meta-analysis.

COVID-19 is not only associated with substantial acute liver and kidney injuries, but also with an elevated risk of post-acute sequelae involving the kidney and liver system. We aimed to investigate whether COVID-19 exposure increases the long-term risk of kidney and liver disease, and what are the magnitudes of these associations. We searched PubMed, Embase, Web of Science, ClinicalTrials.gov, and the Living Overview of the Evidence COVID-19 Repository for cohort studies estimating the association between COVID-19 and kidney and liver outcomes. Random-effects meta-analyses were performed to combine the results of the included studies. We assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation approach. Fifteen cohort studies with more than 32 million participants were included in the systematic review COVID-19 was associated with a 35% greater risk of kidney diseases (10 more per 1000 persons; low certainty evidence) and 54% greater risk of liver disease (3 more per 1000 persons; low certainty evidence). The absolute increases due to COVID-19 for acute kidney injury, chronic kidney disease, and liver test abnormality were 3, 8, and 3 per 1000 persons, respectively. Subgroup analyses found no differences between different type of kidney and liver diseases. The findings provide further evidence for the association between COVID-19 and incident kidney and liver conditions. The absolute magnitude of the effect of COVID-19 on kidney and liver outcomes was, however, relatively small.

Efficacy and safety of Tanreqing injection for cough caused by acute trachea-bronchitis disease: A systematic review and meta-analysis of randomized controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Tanreqing injection (TRQI) is an intravenous herbal preparation derived from 5 types of traditional Chinese medicines including Scutellariae Radix, Lonicerae Japonicae Flos, Forsythiae Fructus, bear bile powder and goral horn, incorporating baicalin, chlorogenic acid, ursodeoxycholic acid, and goose deoxycholic acid and other compounds known for anti-inflammatory properties, is widely used in China to treat cough caused by acute trachea-bronchitis disease (ATB). AIM OF THE STUDY: To investigate the clinical efficacy and safety of Tanreqing injection (TRQI) with and without Western medicine (WM) for cough caused by acute trachea-bronchitis (ATB). MATERIALS AND METHODS: We systematically searched eight databases, including CENTRAL, Embase, PubMed, Science Direct, Wiley, China National Knowledge Infrastructure, Chinese Biomedical Literature Database and WanFang, from inception to August 2023 for randomized clinical trials (RCTs) on TRQI for cough caused by ATB. The critical outcomes of interest were time to symptom disappearance, including time for cough symptom to disappear and time to improve cough and sputum production. Important outcomes included symptom disappearance rate, adverse events (AEs) and lung function. We carried out random-effects meta-analysis using Review Manager 5.4 and assessed the certainty of evidence utilizing the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: A total of 2872 citations were identified by our search, of which 26 eligible RCTs enrolled 2731 participants. Low to moderate certainty evidence showed that when compared with WM, TRQI plus WM treatment was associated with a favorable effect on the time for cough symptom to disappear (MD -2.21 d, 95% CI -2.64 to -1.78), time to improve cough and sputum production (MD -0.68 d, 95% CI -0.83 to -0.53), symptom disappearance rate (RR 1.37, 95% CI 1.20 to 1.55), forced vital capacity, and forced expiratory volume in 1 s (MD 0.38 L, 95% CI 0.26 to 0.50; MD 2.92%, 95% CI 1.29 to 4.56, respectively). In terms of AEs, there was no association between TRQI plus WM and WM (RR 0.55, 95% CI 0.14 to 2.21; low-certainty evidence). Very low certainty evidence showed that TRQI alone was associated with reduced time to improve cough and sputum (MD -0.14 d, 95% CI -0.26 to -0.02) and increased symptom disappearance rate (RR 1.89, 95% CI 1.24 to 2.88; low certainty evidence) compared to WM. CONCLUSIONS: The overall efficacy of TRQI or WM for ATB cough is better than that of WM, and TRQI also effectively improve symptoms in patients with similar adverse events. However, due to the lack of methodological rigor of included studies, the present findings should be interpreted with caution. We advocate better high-quality and convincing clinical studies to be performed to prove the effectiveness and safety of TRQIs.

Traditional Chinese medicine for insomnia: Recommendation mapping of the global clinical guidelines.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) represents a rich repository of empirically-developed traditional medicines. The findings call for more rigorous study into the efficacy, safety, and mechanisms of action of TCM remedies to strengthen the evidence base. AIM OF THE STUDY: To systematically review the quality of insomnia clinical practice guidelines that involve TCM recommendations and to summarize the certainty of evidence supporting the recommendations, strength, and consistency of recommendations, providing valuable research references for the development of future insomnia guidelines. MATERIALS AND METHODS: We systematically searched PubMed, Web of Science, Embase, CNKI, Wanfang, Chinese Biomedical Literature Database, Chinese Medical Association, Chinese Sleep Research Society, Medsci, Medlive, British National Institute of Health and Clinical Excellence (NICE), and the International Guidelines Collaboration Network (GIN) for clinical practice guidelines on insomnia from inception to March 5, 2023. Four evaluators conducted independent assessments of the quality of the guidelines by employing the AGREE II tool. Subsequently, the guideline recommendations were consolidated and presented as evidence maps. RESULTS: Thirteen clinical practice guidelines addressing insomnia, encompassing 211 recommendations (consisting of 127 evidence-based and 84 expert consensus recommendations), were deemed eligible for inclusion in our analysis. The evaluation results revealed an overall suboptimal quality, with the "scope and purpose" domain achieving the highest score (58.1%), while the "applicability" domain garnered the lowest score (13.0%). Specifically, it was observed that 74.8% (n = 95) of the evidence-based recommendations were supported by evidence of either very low or low certainty, in contrast to the expert consensus recommendations, which accounted for 61.9% (n = 52). We subsequently synthesized 44 recommendations into four evidence maps, focusing on proprietary Chinese medicines, Chinese medicine prescriptions, acupuncture, and massage, respectively. Notably, Chinese herbal remedies and acupuncture exhibited robust support, substantiated by high-certainty evidence, exemplified by interventions such as Xuefu Zhuyu decoction, spleen decoction, body acupuncture, and ear acupuncture, resulting in solid recommendations. Conversely, proprietary Chinese medicines needed more high-certainty evidence, predominantly yielding weak recommendations. As for other therapies, the level of certainty was predominantly categorized as low or very low. Recommendations about magnetic therapy, bathing, and fumigation relied primarily on expert consensus, needing more substantive clinical research evidence, consequently forming weak recommendations. Hot ironing and acupoint injection recommendations were weakly endorsed, primarily based on observational studies. Furthermore, interventions like qigong, gua sha, and moxibustion displayed a relatively limited number of clinical studies, necessitating further exploration to ascertain their efficacy. CONCLUSIONS: Our analysis revealed a need for substantial improvement in the quality of all the included guidelines related to insomnia. Notably, recommendations for Traditional Chinese Medicine (TCM) treatments predominantly rely on low-certainty evidence. This study represents a pioneering effort in the utilization of recommendation mapping to both present and identify existing gaps in the evidence landscape within TCM therapies, thus setting the stage for future research initiatives. The evidence supporting TCM therapy recommendations must be fortified to achieve a more substantial level of recommendation and higher certainty. Consequently, there exists a critical and pressing demand for high-quality clinical investigations dedicated to TCM, with a specific focus on ascertaining its long-term efficacy, safety, and potential side effects in the context of insomnia treatment. These endeavors are poised to establish a robust scientific foundation to inform the development of TCM therapy recommendations within the insomnia guidelines.

Efficacy and safety of Shenqi Dihuang decoction for lupus nephritis: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Lupus Nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). However, the treatment of lupus nephritis using traditional Chinese medicine remains controversial. AIM OF THE STUDY: To assess the efficacy and safety of Shenqi Dihuang decoction in the treatment of LN and review the clinical guidelines. MATERIALS AND METHODS: Six databases (China National Knowledge Infrastructure, Wanfang, PubMed, China Biology Medicine, the Cochrane Library, and Embase) were searched from their inception to September 10, 2022, for randomized controlled trials on the treatment of lupus nephritis using Shenqi Dihuang decoction. We conducted a meta-analysis of random effects using Review Manager 5.4 and assessed the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: A total of 15,790 citations were identified, from which 14 eligible randomized controlled trials that enrolled 1002 participants were selected for this systematic review. Low-to-moderate certainty of evidence indicated that when compared with Western medicine, Shenqi Dihuang decoction combined with Western medicine was associated with favorable effects on clinical efficacy (risk ratio (RR) = 1.25, 95% confidence interval (CI): 1.15-1.37), vascular endothelial growth factor (mean difference (MD) = -30.90, 95% CI: -40.18 to -21.63), serum level (MD = -4.81 µmol L-1, 95% CI: -17.14 to 7.53), complement C3 (MD = -0.14 g L-1, 95% CI: -0.23 to -0.04), erythrocyte sedimentation rate (MD = -11.87 mm h-1, 95% CI: -22.01 to -1.73), and SLE disease activity score (MD = -3.38, 95% CI: -4.15 to -2.61), and exhibited a lower risk of infection (RR = 0.2, 95% CI: 0.05-0.90), gastrointestinal reaction (RR = 0.47, 95% CI: 0.17-1.28), and insomnia (RR = 0.29, 95% CI: 0.09-0.92). CONCLUSIONS: This systematic review provides a potential reference for understanding the efficacy and safety of Shenqi Dihuang decoction combined with Western medicine for treating patients with lupus nephritis. However, owing to the limited quality of the studies included in this review, lack of mycophenolate mofetil control, and high heterogeneity among the included studies, the current findings should be interpreted with caution. Therefore, the efficacy and safety of Shenqi Dihuang decoction in patients with PN still require further verification through future high-quality clinical studies.

Red blood cell distribution width improves the prediction of 28-day mortality for patients with sepsis-induced acute kidney injury: A retrospective analysis from MIMIC-IV database using propensity score matching.

Background: The predictive value of red blood cell distribution width (RDW) for mortality in patients with sepsis-induced acute kidney injury (SI-AKI) remains unclear. The present study aimed to investigate the potential association between RDW at admission and outcomes in patients with SI-AKI. Methods: The Medical Information Mart for Intensive Care (MIMIC)-IV (version 2.0) database, released in June of 2022, provides medical data of SI-AKI patients to conduct our related research. Based on propensity score matching (PSM) method, the main risk factors associated with mortality in SI-AKI were evaluated using Cox proportional hazards regression analysis to construct a predictive nomogram. The concordance index (C-index) and decision curve analysis were used to validate the predictive ability and clinical utility of this model. Patients with SI-AKI were classified into the high- and low-RDW groups according to the best cut-off value obtained by calculating the maximum value of the Youden index. Results: A total of 7574 patients with SI-AKI were identified according to the filter criteria. Compared with the low-RDW group, the high-RDW group had higher 28-day (9.49% vs. 31.40%, respectively, P <0.001) and 7-day (3.96% vs. 13.93%, respectively, P <0.001) mortality rates. Patients in the high-RDW group were more prone to AKI progression than those in the low-RDW group (20.80% vs. 13.60%, respectively, P <0.001). Based on matched patients, we developed a nomogram model that included age, white blood cells, RDW, combined hypertension and presence of a malignant tumor, treatment with vasopressor, dialysis, and invasive ventilation, sequential organ failure assessment, and AKI stages. The C-index for predicting the probability of 28-day survival was 0.799. Decision curve analysis revealed that the model with RDW offered greater net benefit than that without RDW. Conclusion: The present findings demonstrated the importance of RDW, which improved the predictive ability of the nomogram model for the probability of survival in patients with SI-AKI.

Molnupiravir for the treatment of non-severe COVID-19: a systematic review and meta-analysis of 14 randomized trials with 34 570 patients.

BACKGROUND: Molnupiravir has been considered a promising candidate for COVID-19. Its efficacy and safety in non-severe COVID-19 patients and the differences between patients with different risk factors need further evaluation. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials that allocated adult patients with non-severe COVID-19 to molnupiravir or a control. We used random-effects models, and conducted subgroup analyses and meta-regression for COVID-19 patients with high-risk factors. The GRADE approach was used to rate the certainty of evidence. RESULTS: Fourteen trials with 34 570 patients were included. Moderate- to low-certainty evidence showed that molnupiravir was associated with a reduction in the risk of hospitalization (relative risk [RR] = 0.63, 95% CI: 0.47-0.85), risk of mechanical ventilation (RR = 0.37, 95% CI: 0.19-0.72) and time to symptom resolution (mean differences [MD] = -2.91 days, 95% CI: -3.66 to -2.16). However, no significant differences were found in adverse events, all-cause mortality, rate of and time to viral clearance, or duration of hospitalization. For the rate of viral clearance, subgroup effects were found between trials with low and high risk of bias (P = 0.001) and between trials with male or female majority (P < 0.001). For admission to hospital, subgroup effects were also found between trials with ≥50% and <50% of the participants being female (P = 0.04). Meta-regression showed a significant association between higher trial mean age and elevated risk of hospitalization (P = 0.011), and female majority and elevated risk of hospitalization (P = 0.011). CONCLUSIONS: Molnupiravir was found to be effective in non-severe COVID-19, but the efficacy varied with age and sex.

Association of soft drinks and 100% fruit juice consumption with risk of cancer: a systematic review and dose-response meta-analysis of prospective cohort studies.

BACKGROUND: Studies of the associations between soft drinks and the risk of cancer showed inconsistent results. No previous published systematic reviews and meta-analysis has investigated a dose-response association between exposure dose and cancer risk or assessed the certainty of currently available evidence. Therefore, we aim to demonstrate the associations and assessed the certainty of the evidence to show our confidence in the associations. METHODS: We searched Embase, PubMed, Web of Science, and the Cochrane Library from inception to Jun 2022, to include relevant prospective cohort studies. We used a restricted cubic spline model to conduct a dose-response meta-analysis and calculated the absolute effect estimates to present the results. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of the evidence. RESULTS: Forty-two articles including on 37 cohorts enrolled 4,518,547 participants were included. With low certainty evidence, increased consumption of sugar-sweetened beverages (SSBs) per 250 mL/day was significantly associated with a 17% greater risk of breast cancer, a 10% greater risk of colorectal cancer, a 30% greater risk of biliary tract cancer, and a 10% greater risk of prostate cancer; increased consumption of artificially sweetened beverages (ASBs)re per 250 mL/day was significantly associated with a 16% greater risk of leukemia; increased consumption of 100% fruit juice per 250 mL/day was significantly associated with a 31% greater risk of overall cancer, 22% greater risk of melanoma, 2% greater risk of squamous cell carcinoma, and 29% greater risk of thyroid cancer. The associations with other specific cancer were no significant. We found linear dose-response associations between consumption of SSBs and the risk of breast and kidney cancer, and between consumption of ASBs and 100% fruit juices and the risk of pancreatic cancer. CONCLUSIONS: An increment in consumption of SSBs of 250 mL/day was positively associated with increased risk of breast, colorectal, and biliary tract cancer. Fruit juices consumption was also positively associated with the risk of overall cancer, thyroid cancer, and melanoma. The magnitude of absolute effects, however, was small and mainly based on low or very low certainty of evidence. The association of ASBs consumption with specific cancer risk was uncertain. TRIAL REGISTRATION: PROSPERO: CRD42020152223.

PROTOCOL: Assessment of publication time in Campbell systematic reviews: A cross-sectional survey.

This is the protocol for a Campbell systematic review. The objectives are as follows. This study has three main objectives: (1) To examine the time duration from title registration to publication of the protocol for a Campbell systematic review and publication of the completed Campbell systematic review; (2) To describe publication times in accordance with the characteristics of the reviews, which include year of publication, type of review, number of authors, number of collaborative institutions, the time gap between the date the search was conducted and review publication, and the length and complexity of the included review (including the number of pages, the number of tables and figures, the number of studies included in the review, the number and type of analyses undertaken, and the number of references); (3) To describe the differences in publication times between Campbell Review Groups.

The Comparative Effectiveness and Safety of Insomnia Drugs: A Systematic Review and Network Meta-Analysis of 153 Randomized Trials.

BACKGROUND: Pharmacological 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. METHODS: In 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. RESULTS: A 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). CONCLUSIONS: Non-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).

Bacteremia following different oral procedures: Systematic review and meta-analysis.

To evaluate the timing, duration and incidence of bacteremia following invasive dental procedures (IDPs) or activities of daily living (ADL). Eight databases were searched for randomized (RCTs) and nonrandomized controlled trials (nRCTs) evaluating bacteremia before and after IDPs or ADL in healthy individuals. The risk of bias was assessed by RoB 2.0 and ROBINS-I. For the meta-analysis, the primary outcomes were the timing and duration of bacteremia. The secondary outcome was the incidence of bacteremia, measuring the proportion of patients with bacteremia within 5 min after the end of the procedure compared with baseline. We included 64 nRCTs and 25 RCTs. Peak bacteremia occurred within 5 min after the procedure and then decreased over time. Dental extractions showed the highest incidence of bacteremia (62%-66%), followed by scaling and root planing (SRP) (44%-36%) and oral health procedures (OHP) (e.g., dental prophylaxis and dental probing without SRP) (27%-28%). Other ADL (flossing and chewing) (16%) and toothbrushing (8%-26%) resulted in bacteremia as well. The majority of studies had some concerns RCTs or moderate risk of bias nRCTs. Dental extractions, SRP and OHP, are associated with the highest frequency of bacteremia. Toothbrushing, flossing, and chewing also caused bacteremia in lower frequency.

Monoclonal Antibody for the Prevention of Respiratory Syncytial Virus in Infants and Children: A Systematic Review and Network Meta-analysis.

Importance: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection in children younger than 5 years; effective prevention strategies are urgently needed. Objective: To compare the efficacy and safety of monoclonal antibodies for the prevention of RSV infection in infants and children. Data Sources: In this systematic review and network meta-analysis, PubMed, Embase, CENTRAL, and ClinicalTrials.gov were searched from database inception to March 2022. Study Selection: Randomized clinical trials that enrolled infants at high risk of RSV infection to receive a monoclonal antibody or placebo were included. Keywords and extensive vocabulary related to monoclonal antibodies, RSV, and randomized clinical trials were searched. Data Extraction and Synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was used. Teams of 2 reviewers independently performed literature screening, data extraction, and risk of bias assessment. The Grading of Recommendations, Assessments, Developments, and Evaluation approach was used to rate the certainty of evidence. A random-effects model network meta-analysis was conducted using a consistency model under the frequentist framework. Main Outcomes and Measures: The main outcomes were all-cause mortality, RSV-related hospitalization, RSV-related infection, drug-related adverse events, intensive care unit admission, supplemental oxygen use, and mechanical ventilation use. Results: Fifteen randomized clinical trials involving 18 395 participants were eligible; 14 were synthesized, with 18 042 total participants (median age at study entry, 3.99 months [IQR, 3.25-6.58 months]; median proportion of males, 52.37% [IQR, 50.49%-53.85%]). Compared with placebo, with moderate- to high-certainty evidence, nirsevimab, palivizumab, and motavizumab were associated with significantly reduced RSV-related infections per 1000 participants (nirsevimab: -123 [95% CI, -138 to -100]; palivizumab: -108 [95% CI, -127 to -82]; motavizumab: -136 [95% CI, -146 to -125]) and RSV-related hospitalizations per 1000 participants (nirsevimab: -54 [95% CI, -64 to -38; palivizumab: -39 [95% CI, -48 to -28]; motavizumab: -48 [95% CI, -58 to -33]). With moderate-certainty evidence, both motavizumab and palivizumab were associated with significant reductions in intensive care unit admissions per 1000 participants (-8 [95% CI, -9 to -4] and -5 [95% CI, -7 to 0], respectively) and supplemental oxygen use per 1000 participants (-59 [95% CI, -63 to -54] and -55 [95% CI, -61 to -41], respectively), and nirsevimab was associated with significantly reduced supplemental oxygen use per 1000 participants (-59 [95% CI, -65 to -40]). No significant differences were found in all-cause mortality and drug-related adverse events. Suptavumab did not show any significant benefits for the outcomes of interest. Conclusions and Relevance: In this study, motavizumab, nirsevimab, and palivizumab were associated with substantial benefits in the prevention of RSV infection, without a significant increase in adverse events compared with placebo. However, more research is needed to confirm the present conclusions, especially for safety and cost-effectiveness.

Research trends on platelet-rich plasma in the treatment of wounds during 2002-2021: A 20-year bibliometric analysis.

Platelet-rich plasma (PRP) has attracted attention because of its potential to accelerate the wound healing process. However, resources for evaluating research trends in the treatment of wounds with PRP were limited. In this study, we aimed to make a bibliometric analysis of the literature related to PRP in the treatment of wounds and explore the research status, hotspots and frontiers in this field in recent 20 years. Studies about PRP treatment for wounds from 2002 to 2021 were retrieved from the Science Citation Index Expanded (SCI-E) of Web of Science (WOS) database. Visualisation softwares such as VOSviewer and SCImago Graphica, and CiteSpace were used to analyse the research trends and features. A total of 1748 studies were identified in the SCI-Expanded from 2002 to 2021. The number of publications on PRP in the treatment of wounds has shown an increasing trend, from 6 (in 2002) to 228 (in 2021). The papers published in the United States have led in times cited (14637) and H-index (63). Though Italy was slightly lower than China in the number of publications, the H-index and average cited (47, 28.45) were higher than that of China (38, 27.01). The strongest keyword was "fibrin" (strength = 13.07), and the longest burst duration keyword was "thrombin" (began in 2002 and ended in 2014). The largest 10 co-citation clusters are as follows: endothelial cell proliferation (#0), regenerative medicine-associated treatment (#1), diabetic wound healing (#2), autologous derived (#3), platelet-rich fibrin (#4), tissue engineering (#5), regenerative potential (#6), clinical randomised trial (#7), histologic observation (#8), and wound bacteria (#9). The United States has made the most outstanding contribution in this field. Chinese researchers need to enhance the quality of publications further. Wound Repair Regen. is the most noteworthy journal. The mechanism of growth factors of PRP, combination therapy, preparation of PRP, and related clinical trials may be topics that need attention.

An Increase in Admission RDW Value Is Associated with Excess Short-Term Mortality Rates in Patients with Severe Burns.

The predictive value of red blood cell distribution width (RDW) in severely burned patients remains unclear. This study aimed to investigate the potential association between admission RDW and outcomes in patients with severe burns. Data of severely burned patients in the burn center of Changhai Hospital were retrospectively evaluated. The relationship between admission RDW and mortality was analyzed and displayed using the receiver operating characteristic curve, Kaplan-Meier curve, Cox proportional hazards regression, and the nomogram method. A total of 342 patients were identified according to the filter criteria. The 30-day mortality was 12.9%, and the mortality rates in 7 days and 90 days were 2.9% and 16.7%, respectively. Patients with high admission RDW value were more likely to die than those with low RDW value. Multivariate analysis revealed that higher admission RDW, age, full-thickness burned area, and inhalation injury were independent risk factors with 30-day mortality. The nomogram based on these risk factors was established to predict survival probability in severe burn patients. The C-index of different follow-up times was computed between 0.867 and 0.904, and the nomogram model list fits the data well. Admission RDW played a valuable role in predicting short-term mortality in patients with severe burns. The nomogram containing admission RDW was established to predict mortality, which helps burn care providers identify the patients at higher risk of short-term mortality after severe burns. More attention should be paid to the application of these easy and inexpensive biochemical indicators in the early prediction of disease progression.

PFMT relevant strategies to prevent perineal trauma: a systematic review and network meta-analysis.

BACKGROUND: Most women suffer from perineal trauma during childbirth, whether it is natural tears or episiotomy. OBJECTIVES: To perform a systematic review and network meta-analysis investigating the effectiveness of different PFMT relevant strategies in the prevention of perineal trauma. SEARCH STRATEGY: PubMed, Embase, the Cochrane Library, CINAHL, CNKI, CBM, WANFANG DATABASE, and ClinicalTrials.gov were searched for citations published in any language from inception to 1 July 2021. SELECTION CRITERIA: Randomized controlled trials (RCTs) of PFMT relevant prevention strategies for preventing perineal trauma during childbirth. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two reviewers. Relative treatment effects were estimated using network meta-analysis (NMA). MAIN RESULTS: Of 12 632 citations searched, 21 RCTs were included. Comparing with usual care, "PFMT combine with perineal massage" and PFMT alone showed more superiority in intact perineum (RR = 5.37, 95% CI: 3.79 to 7.60, moderate certainty; RR = 2.58, 95% CI 1.34-4.97, moderate certainty, respectively), episiotomy (RR = 0.26, 95% CI 0.14-0.49, very low certainty; RR = 0.63, 95% CI 0.45-0.90, very low certainty, respectively), and OASIS (RR = 0.35, 95% CI 0.16-0.78, moderate certainty; RR = 0.49, 95% CI 0.28-0.85, high certainty, respectively). "PFMT combine with perineal massage" showed superiority in reducing perineal tear (RR = 0.41, 95% CI 0.20-0.85, moderate certainty). CONCLUSIONS: In view of the results, antenatal "PFMT combine with perineal massage" and PFMT were effective strategies for the prevention of perineal trauma.

Lubricant for reducing perineal trauma: A systematic review and meta-analysis of randomized controlled trials.

AIM: To assess the effect of lubricants on reducing perineal trauma during vaginal delivery. METHODS: PubMed, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, China Biology Medicine disc, WanFang databases, and ClinicalTrials.gov, were searched for literature up to 25 June 2021. Randomized controlled trials published in English or Chinese that compared the vaginal application of lubricant with standard care for women were included. Two reviewers independently performed study screening, data extraction, risk of bias assessment, and certainty of evidence assessment. Pooled effect sizes and corresponding 95% confidence intervals (CI) were calculated using meta-analysis. RESULTS: Nineteen trials enrolling 5445 pregnant women were included. Compared with standard care, women using lubricants had a lower incidence of perineal trauma (risk ratio [RR] 0.84, 95% CI 0.76-0.93; low certainty evidence), second-degree perineal laceration (RR 0.72, 95% CI 0.64-0.82; moderate certainty evidence) and episiotomy (RR 0.77, 95% CI 0.62-0.96; very low certainty evidence), and had a shorter duration of the second-stage labor (MD -13.72 min, 95% CI -22.68 to -4.77; very low certainty evidence). CONCLUSION: Lubricants might reduce the incidence of perineal trauma, especially second-degree perineal laceration, and shorten the duration of the second-stage labor. More well-designed studies will continue developing high-quality evidence in this field.