Objective: A systematic review/meta-analysis was conducted to investigate the effect of cannabinoid type-1 receptor (CB1R) regulation on the sleep-wake cycle of rats and to provide new ideas and evidence-based basis for clinical research on the treatment of sleep disorders.
Methods: We searched Cochrane Library, PubMed, Web of Science, Embase, Chinese Biomedicine Literature Database (CBM), China National Knowledge Infrastructure, WanFang, and VIP databases for relevant papers, about the effects of CB1R agonists/antagonists on sleep-wake cycle in rats, from inception to November 2023. Two reviewers performed study screening, data extraction, and risk of bias assessment using the SYRCLE’s risk of bias tool. Meta-analysis was performed using RevMan 5.3 software. Heterogeneity test was performed on the included studies (Test standard α = 0.1). I2 value was used to evaluate the heterogeneity. Forest plot was drawn, and p ≤ 0.05 indicates statistically significant difference.
Results: A total of 16 trials involving 484 experimental rats were included. The methodological quality evaluation results showed that the overall quality of the included studies was low. The results of the meta-analysis showed that single administration of CB1R agonists could shorten the wakefulness (W) time in the first 6 h (h) (standardized mean difference (SMD) = –2.52, 95% confidence interval (CI) (–3.83, –1.22), p = 0.0002) and 24 h (SMD = –0.84, 95% CI (–1.31, –0.36), p = 0.0005) after administration, prolong nonrapid eye movement sleep (NREM) time (SMD = 1.75, 95% CI (0.54, 2.95), p = 0.005) and rapid eye movement sleep (REM) time (SMD = 1.76, 95% CI (0.26, 3.26), p = 0.02), and increase REM frequency after administration (SMD = 1.67, 95% CI (0.98, 2.35), p < 0.00001), these results were all statistically different. There were no significant differences in sleep latency and average duration of REM. Single administration of CB1R antagonists prolonged the first 6 h W time after administration (SMD = 1.36, 95%CI (0.29, 2.43), p = 0.01), shortened the first 6 h NREM time (SMD = –1.73, 95% CI (–2.88, –0.57), p = 0.003) and REM time (SMD = –2.07, 95% CI (–3.17, –0.96), p = 0.0003) after administration, and increased the frequency of W after administration (SMD = 3.57, 95% CI (1.42, 5.72), p = 0.001). There was no statistical difference in the average duration of W. REM time and REM frequency increased after continuous CB1R agonist withdrawal.
Conclusions: According to the existing evidence, CB1R played a pivotal role in regulating the sleep-wake cycle in rats. CB1R agonists tended to reduce W time, increase NREM and REM sleep times, boost REM frequency, and promote sleep. Conversely, CB1R antagonists could increase the duration and frequency of W, shorten NREM and REM sleep times, and promote W.
Objective: To summarize the evidence on the efficacy and safety of vancomycin compared with those of alternative treatments in adult patients with methicillin-resistant Staphylococcus aureus (MRSA) infection.
Methods: PubMed, Embase, and Web of Science were searched up to December 15, 2023, for systematic reviews and meta-analyses comparing vancomycin with alternative MRSA treatments. Primary outcomes included clinical cure and microbiological eradication rates. Organ-specific safety outcomes were assessed. Summary estimates were recalculated using a random-effects model. Evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. This study was registered in PROSPERO (CRD42022340359).
Results: This umbrella review included 19 studies and 71 meta-analyses (46 efficacy and 25 safety) comparing vancomycin with 10 alternative treatments across different MRSA infection types and populations. GRADE assessment showed that 29.58% of the meta-analyses were of high quality. Linezolid and daptomycin showed higher efficacy in MRSA-induced skin and soft tissue infections and pneumonia (moderate evidence quality) and bacteremia (very low evidence quality), respectively, compared with that of vancomycin. Cephalosporins had a higher risk of nausea, whereas linezolid had a higher risk of nausea, diarrhea, and thrombocytopenia than that of vancomycin. Vancomycin posed a higher risk of rash, pruritus, red man syndrome, and nephrotoxicity than that of alternatives.
Conclusions: The quality of evidence supporting the higher efficacy of alternative treatment over vancomycin for MRSA infection was not high. Given varying safety profiles and advancements in therapeutic monitoring, careful consideration of patient-specific factors and pharmacokinetics is crucial when selecting treatment alternatives to vancomycin.
Objective: This study aimed to evaluate the acceptability and effects of internet-based cognitive behavioral therapy (iCBT) or CBT-oriented interventions compared with control groups on depressive symptoms, remission of depression, and quality of life (QOL) in adolescents.
Methods: We searched English and Chinese databases for randomized controlled trials up to October 10, 2024 that investigated the effects of iCBT compared with controls in adolescents exhibiting elevated depressive symptoms or diagnosed with depression. Standardized mean differences (SMDs), relative risks (RRs), and 95% confidence intervals were applied to evaluate the pooled effects of outcomes.
Results: A total of 19 RCTs involving 3574 cases were included in this study. We found small effects on depressive symptoms severity at different time points (posttest: SMD = –0.49 [–0.66, –0.33]; 3-month follow-up [FU3]: SMD = –0.21 [–0.30, –0.11]; FU6: SMD = –0.18 [–0.35, –0.02]; FU12: SMD = –0.38 [–0.56, –0.20]). We also found a significant effect in depression remission rate at the posttest (RR = 1.74 [1.36, 2.21]) and a significant effect in QOL at the posttest (SMD = 0.30 [0.07, 0.54]). However, the result regarding acceptability was nonsignificant (RR = 1.22 [0.76, 1.97]). No significant publication bias was found in these results.
Conclusion: iCBT or internet-based CBT-oriented interventions can effectively reduce depressive symptom severity and improve depression remission rate and QOL in depressed adolescents. These results are preliminary and require further validation through future systematic reviews.
Purpose: To develop and validate the patient-reported outcome scale for idiopathic pulmonary fibrosis (IPF-PRO) to provide a reliable and scientific measure for clinical trials on idiopathic pulmonary fibrosis (IPF).
Methods: We analyzed the relevant literature and medical records and conducted interviews and panel discussions to develop the conceptual framework and generate the item pool. We subjected the collected items to removal, mergence, or modification to form the initial scale through a qualitative review by experts and patients. Subsequently, we conducted two field surveys to select items for the final scale based on the classical test theory and item response theory (IRT). Finally, we conducted a formal survey to assess the measurement properties of the IPF-PRO.
Results: The IPF-PRO included 18 items across four domains, namely physiology, psychology, environment, and satisfaction. The Cronbach’s α coefficient and generalized coefficient of the IPF-PRO were 0.917 and 0.931, respectively. The content validity, structural validity, criterion validity, and discriminant validity all met relevant standards. The results of the item analysis based on IRT were considered acceptable. The ordinal logistic regression analysis findings showed that all items’ p values were greater than 0.01 when the domain scores matched variables. The IPF-PRO response and completion rates were both 100%. The median completion time was 7 min [IRQ = 3.7 min (Q3 = 9.0 min, Q1 = 5.3 min)].
Conclusion: The 18-item IPF-PRO developed in this study has demonstrated good reliability and validity, indicating that it is a reliable and scientific measure for IPF clinical trials.
Objective: The objective of this study was to determine whether insulin resistance (IR) could be used as a predictor of poor prognosis at 3 months after subarachnoid hemorrhage (SAH).
Methods: The study included patients aged 18 years or older with a confirmed diagnosis of SAH due to ruptured aneurysm from January 2021 to March 2024. Patients with confirmed diabetes mellitus and taking glucose-lowering drugs, or taking lipid-lowering drugs, or SAH not due to ruptured aneurysm, or comorbid systemic diseases were excluded. Patients were classified into good prognosis (modified Rankin scale [MRS] 0–2) and poor prognosis (MRS 3–6). Receiver operating characteristic curve (ROC), least absolute shrinkage and selection operator (LASSO) analysis, and multivariate logistic regression analysis were used to determine the potential of triglyceride-glucose (TyG) index and the triglyceride to high-density lipoprotein cholesterol (TG/HDL) ratio as predictors of poor prognosis. Finally, a prognostic prediction model based on IR was constructed.
Results: A total of 358 patients were included in this study. Poor prognosis patients had higher age, BMI, hypertension percentage, glucose, triglycerides, TyG index and TG/HDL ratio, and lower HDL. ROC, LASSO, and multivariate logistic regression analysis revealed that age, glucose, TyG index, and TG/HDL ratio had significant potential to predict the prognosis of SAH patients. The prognostic prediction model constructed by combining age, glucose, TyG index, and TG/HDL ratio had high discriminatory power (area under the curve [AUC] = 0.80), satisfactory calibration curves, and good clinical utility.
Conclusion: IR is strongly associated with the prognosis of SAH patients, and the combination of age, glucose, TyG index, and TG/HDL ratio can provide a new direction for future treatment.
Objectives: Pregnant women had a large demand for diagnosis and treatment, but the clinical research was not sufficient, and there were many barriers for pregnant women to participate in clinical research. This study aimed to systematically identify these barriers and facilitators, map them with Theoretical Domains Framework (TDF) and Behavior Change Techniques (BCTs) to inform the development of interventions promoting pregnant women’s involvement in clinical research.
Methods: This was a mixed-methods systematic review. PubMed, Embase, Cochrane Library, APA PsycInfo, CINAHL, China National Knowledge Infrastructure, WanFang, VIP Database for Chinese Technical Periodicals, Chinese Biomedical Literature Database, and related references were searched. Qualitative, quantitative, and mixed-methods studies exploring barriers and facilitators to pregnant women’s participation in clinical trials were included. The barriers and facilitators were extracted, after transforming the quantitative data into qualitative data, all qualitative data were used to thematic synthesis. The identified barriers and facilitators were mapped into TDF and BCTs.
Results: A total of 103 studies (66 qualitative, 24 quantitative, and 13 mixed-methods) were included. Three main themes were formed: personal factors, environmental factors and research characteristics, with identified barriers and facilitators within each theme. “Knowledge, ” “Environmental Context and Resources, ” and “Beliefs about Consequences” were the main domains where barriers and facilitators identified by pregnant women and researchers were mapped in TDF. Additionally, the barriers and facilitators identified by pregnant women also mapped on “Social Influences” and “Goals.” “Instruction on how to perform a behavior, ” “restructuring the physical environment, ” “salience of consequences, ” “social support (unspecified), ” “goal setting (outcome)” were the main BCTs identified based on barriers and facilitators.
Conclusions: The barriers and facilitators to clinical research participation identified in this study involved three main themes of personal, environmental, and research characteristics, which mainly mapped to five TDF domains. Based on these barriers and facilitators, 23 BCTs were identified. Future research should focus on developing behavior change interventions, assessing their efficacy and implementability.
Objective: This study aims to investigate the occurrence of adverse events associated with topiramate by analyzing data from the FDA Adverse Event Reporting System. The goal is to provide a basis for the safe clinical use of topiramate.
Methods: Adverse event data from the FDA Adverse Event Reporting System, from its inception through the first quarter of 2024, were extracted. Signal detection was conducted using three methods: the reporting odds ratio, the medicines and healthcare products regulatory agency method, and the Bayesian confidence propagation neural network. Adverse events were statistically analyzed according to the preferred term and system organ class classifications from the Medical Dictionary for Regulatory Activities version 27.0. Positive signals were then compared against the drug label and the Important Medical Event list.
Results: A total of 12, 168 adverse event reports involving topiramate as the primary suspect were analyzed, resulting in the extraction of 244 positive signals across 15 system organ classes. Among these, 21 signals were identified as serious adverse reactions not included in the drug label, encompassing 5 system organ classes. Notable signals included hypospadias, spina bifida, abortion spontaneous, renal tubular dysfunction, uveitis, retinal detachment, and choroidal effusion. Additionally, signals such as osmotic demyelination syndrome and Arnold-Chiari malformation were identified as requiring further monitoring.
Conclusion: This study identified several unexpected and serious adverse reaction signals that align with previously reported cases. These findings underscore the need for ongoing study, focused attention, and vigilant monitoring during the clinical use of topiramate.
Background: Off-label drug use (OLDU) is a common practice in health care institutions, and numerous guidance documents have been developed to guide the management of OLDU in China. This scoping review aims to compare these documents and identify existing issues.
Methods: PubMed, EMbase, three Chinese databases, the National Public Service Platform for Standards Information and the official websites of pharmaceutical-related associations were searched to identify guidance documents relevant to the management of OLDU for Chinese health care institutions. We extracted and compared the recommended practices for various aspects of OLDU management, including management systems, organizational structure, prerequisites for OLDU, approval processes, evidence-based evaluation, informed consent, and other related aspects.
Results: A total of 16 guidance documents were included, comprising 12 expert consensuses, 2 practice guidelines, and 2 group standards. Only six documents provide specific requirements for the establishment of management systems. Management of OLDU requires involvement from multiple departments or committees, yet only a few documents explicitly delineate the supervisory authority, and the responsibilities of the parties involved. These documents also show significant disparities in their approval process, evidence-based evaluation, and informed consent recommendations. Furthermore, only a minority of the documents provide specific requirements for training and assessments focused on OLDU and improving adverse reaction monitoring.
Conclusion: These guidance documents differ significantly in their specific recommendations for the management of OLDU and lack sufficient emphasis on certain critical aspects. It may be beneficial for health administrative authorities to promote the development of unified national guidelines.
Objective: The optimal low-dose antiplatelet agents in patients with coronary heart disease (CHD) had not been determined. The objective of this study was to compare the impact of different low-dose antiplatelet agents on cardiovascular outcomes and bleeding risks in patients with CHD.
Methods: We searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, VIP, WanFang Data, and China Biology Medicine. Randomized controlled trials (RCTs) enrolling patients with CHD treated with different low-dose platelet aggregation inhibitors were included. The revised Cochrane Risk of Bias Tool for Randomized Trials Risk was used to assess risk of bias in RCTs. A Bayesian random network meta-analysis (NMA) was conducted, with odds ratios (OR) and 95% confidence intervals (CI) as effect estimates in R 4.2.2 software and Stata 15.0. The quality of evidence was assessed using the Confidence in NMA framework.
Results: Sixteen RCTs involving 6350 patients were included. All participants were treated with a recommended dose of aspirin plus a low or standard dose of P2Y12 receptor antagonist. Low-level evidence indicated the risk of major adverse cardiovascular events (MACE) was similar among low doses of prasugrel, ticagrelor, standard doses of prasugrel, ticagrelor, and clopidogrel. Low- to moderate-level evidence suggested there was no difference in bleeding risk among low dose of prasugrel, ticagrelor, clopidogrel compared to standard dose of prasugrel, ticagrelor, and clopidogrel. NMA showed that low dose of prasugrel had the highest probability of being the best intervention in terms of MACE, myocardial infarction, and bleeding events leading to discontinuation.
Conclusion: Based on low-level evidence, low dose of prasugrel combined with standard dose of aspirin can be recommended for patients with CHD, low dose of ticagrelor was similar in terms of MACE and bleeding compared with standard dose of P2Y12 receptor antagonist.
The systematic review was registered in PROSPERO with the registration number CRD42023438376.
Aim: The prognosis of masked hypertension is controversial. The aims of this meta-analysis were to determine the global prevalence of masked hypertension and to better understand its association with the risk of cardiorenal comorbidities and all-cause mortality.
Methods: We searched the PubMed, Embase (OVID), The Cochrane Library, WanFang Data, and CNKI databases for relevant studies published from inception until January 15, 2024. Cohort studies that reported an association of masked hypertension with the risk of cardiorenal comorbidities and all-cause mortality were eligible for meta-analysis.
Results: Twenty-six studies (with 129, 061 participants) were included. The median follow-up duration was 7.38 years. The pooled prevalence of masked hypertension was 18% (95% confidence interval [CI] 15%–21%). Compared with normotensive individuals, those with masked hypertension had an increased risk of all-cause mortality (relative risk [RR] 1.64, 95% CI 1.32–2.04) and incident cardiovascular disease (RR 1.57, 95% CI 1.45–1.69). The results were similar regardless of treatment status and in multiple subgroup analyses. Masked hypertension was also associated with increased risks of cardiovascular mortality (RR 1.69, 95% CI 1.02–2.78) and composite renal outcomes (RR 3.57, 95% CI 2.32–5.50).
Conclusion: Masked hypertension is prevalent in adults and associated with increased risks of all-cause mortality, cardiovascular disease, cardiovascular mortality, and composite renal events.
Background: Multiple and complicated hepatolithiasis can be associated with decompensated cirrhosis. Endoscopic retrograde cholangiopancreatography is unavailable for multiple and complicated hepatolithiasis, and the mainstay for decompensated cirrhosis is liver transplantation. However, due to the ethical factors and the complexity of operation, liver transplantation cannot be widely operated. This study aimed to evaluate percutaneous transhepatic cholangioscopy in the extraction of stones and the recompensation of cirrhosis in patients with hepatolithiasis associated with decompensated cirrhosis.
Methods: Between January 2021 and February 2024, we retrospectively reviewed the clinical data of 21 patients with multiple and complicated hepatolithiasis associated with decompensated cirrhosis. Before PTCS, the 21 patients were all assessed by the Model for End-stage Liver Disease as having indications for liver transplantation. One-step PTCS (n = 19) and two-step PTCS (n = 2) were used to remove the stones.
Results: The technical success rate was 100%, and most stones were cleared 90.48% (19/21). After 3 months of PTCS, MELD score of the patients had significantly decreased (10.81 ± 3.31 vs. 17.24 ± 3.40,p < 0.05), and it was lowest at 6 months after the operation (9.94 ± 4.31). After a median follow-up period of 18 months (up to 40 months), the stone recurrence rate was 28.57% (6/21), 13 patients survived without liver transplantation, three patients underwent liver transplantation and survived, and five patients died of liver failure or cancer (mortality rate 23.81%).
Conclusions: PTCS can significantly improve patients’ liver function in hepatolithiasis associated with decompensated cirrhosis.
Both hypertension and type 2 diabetes are attributable to premature death, cardiovascular and kidney diseases with largely overlapping population. Followed the GRADE approach, this expert consensus aimed to reduce the cardiovascular and kidney death and disability due to hypertension and minimize the treatment burden in adults with type 2 diabetes. Through online survey and discussion, a multidisciplinary team comprehensively prioritized seven key guideline questions. Informed by the evidence synthesis and online discussion, the team developed 12 recommendations under the GRADE Evidence-to-decision (EtD) framework. The recommendations covered the screening of hypertension in adults diagnosed with type 2 diabetes but not hypertension and the monitoring, lifestyle interventions, and medications in those diagnosed with type 2 diabetes and hypertension.
Developing a clinical practice guideline (CPG) for integrating traditional Chinese medicine (TCM) and Western medicine (WM) requires the accurate identification, collation, and integration of all available evidence on TCM and WM in a comprehensive, meaningful, and resource-efficient manner. This entails framing appropriate clinical questions, retrieving and synthesizing evidence from multiple resources, and providing concise and complete recommendations for specific diseases. However, some existing CPGs for integrating TCM and WM lack deep and organic integration. As the effective preparation of a CPG for integrating TCM and WM typically involves a complex set of principles, methodology, and steps, we believe that a cohesive, step-by-step guide on how to prepare a CPG for integrating TCM and WM is essential. To facilitate the design and development of a robust CPG, we present a clear and concise methodology, outlining relevant principles and procedures, supported by references for guidance. This technical specification aims to simplify the methodology for preparing a CPG for integrating TCM and WM; provide healthcare professionals and researchers with methodologically sound tools; and enhance the quality of CPGs for integrating TCM and WM. This technical specification may help elucidate this complex process, facilitate evaluation of the quality of published CPGs for integrating TCM and WM, and improve the understanding and application of recommendations for the combined and integrated use of TCM and WM in a new system.