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.

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.

New light on ω-3 polyunsaturated fatty acids and diabetes debate: a population pharmacokinetic-pharmacodynamic modelling and intake threshold study.

OBJECTIVE: ω-3 polyunsaturated fatty acids (PUFA) are a key modifiable factor in the intervention of type 2 diabetes, yet recommendations for dietary consumption of ω-3 PUFA in type 2 diabetes remain ambiguous and controversial. Here, we revisit the subject in the light of population pharmacokinetic-pharmacodynamic (PPK-PD) modeling and propose a threshold for intake. RESEARCH DESIGN AND METHODS: Plasma levels of ω-3 PUFA and glycosylated hemoglobin (HbA1c) were measured as pharmacokinetic and pharmacodynamic indicator, respectively. The nonlinear mixed effect analysis was used to construct a PPK-PD model for ω-3 PUFA and to quantify the effects of FADS gene polymorphism, age, liver and kidney function, and other covariables. RESULTS: Data from 161 patients with type 2 diabetes in the community were modeled in a two-compartment model with primary elimination, and HDL was a statistically significant covariate. The simulation results showed that HbA1c showed a dose-dependent decrease of ω-3 PUFA plasma level. A daily intake of ω-3 PUFA at 0.4 g was sufficient to achieve an HbA1c level of 7% in more than 95% of patients. CONCLUSIONS: PPK/PD modeling was proposed as a multilevel analytical framework to quantitatively investigate finer aspects of the complex relationship between ω-3 PUFA and type 2 diabetes on genetic and non-genetic influence factors. The results support a beneficial role for ω-3 PUFA in type 2 diabetes and suggested the intake threshold. This new approach may provide insights into the interaction of the two and an understanding of the context in which changes occur.

The relationship between psychological distress and weight maintenance in weight cycling: mediating role of eating behavior.

BACKGROUND: Obesity is a global public health concern. The goal of this study was to see if eating habits could mediate the relationship between psychological distress and weight maintenance in a population with a history of weight cycling. METHODS: A 3-month outpatient intervention consisting of a diet and exercise program was provided to 153 participants. Psychological distress, appetite, and behavior were assessed at the beginning and end of the study. Anthropometric measurements were taken at baseline and six months. RESULTS: After the structural equation model was developed, it was discovered that the psychological status of people with obesity and weight cycling histories correlated with the weight loss outcome effect (three and six months). This effect was mediated by factors related to eating behavior. Associative psychological factors had a direct effect on eating behavior (three months: ß = 0.181, 95% CI: 0.055-0.310; six months: ß = 0.182, 95% CI: 0.039-0.332) and appetite had a direct effect on eating behavior (three months: ß = 0.600, 95% CI: 0.514-0.717; six months: ß = 0.581, 95% CI: 0.457-0.713), both of which were significant (p < 0.01). At three months, psychological distress has a more substantial positive impact on weight change, with eating behavior acting as a partial mediator. At six months, there was no support for appetite's moderating role in eating behavior. CONCLUSIONS: The findings suggest that psychological interventions should be strengthened to improve weight loss effectiveness, particularly in participants with a history of weight cycling, making weight loss more complicated and prone to rebound. CLINICAL TRIAL REGISTRATION: The study has been registered in Clinical Trials (NCT05311462).

Identification of novel serum metabolic signatures to predict chronic kidney disease among Chinese elders using UPLC-Orbitrap-MS.

BACKGROUND: Chronic kidney disease (CKD) is a major public health concern. However, validated and broadly applicable biomarkers for early CKD diagnosis are currently not available. We aimed to identify serum metabolic signatures at an early stage of CKD to provide a reference for future investigations into the early diagnostic biomarkers. METHODS: Serum metabolites were extracted from 65 renal dysfunction (RD) patients and 121 healthy controls (discovery cohort: 12 RD patients and 55 health participants; validation cohort: 53 RD patients and 66 health participants). Metabolite extracts were analyzed by ultraperformance liquid chromatography coupled with quadrupole-electrostatic field orbital trap mass spectrometry (UPLC-QE-Orbitrap MS) for untargeted metabolomics. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was performed to detect different compounds between groups. Receiver operating characteristic (ROC) curve analysis was carried out to determine the diagnostic value of the validated differential metabolites between groups. We referred to the Kyoto Encyclopedia of Gene and Genomes (KEGG) to elucidate the metabolic pathways of the validated differential metabolites. RESULTS: A total of 22 and 23 metabolites had significantly different abundances in the discovery and validation cohort, respectively. Six of them (creatinine, L-proline, citrulline, butyrylcarnitine, 1-methylhistidine, and valerylcarnitine) in the RD group was more abundant than that of the health group in both cohorts. The combination of the six validated differential metabolites were able to accurately detect RD (AUC 0.86). Three of the six metabolites are involved in the metabolism of arginine and proline. CONCLUSIONS: The present study highlights that creatinine, L-proline, citrulline, butyrylcarnitine, 1-methylhistidine, and valerylcarnitine are metabolite indicators with potential predictive value for CKD.

Chimeric antigen receptor T cell and regulatory T cell therapy in non-oncology diseases: A narrative review of studies from 2017 to 2023.

Recently, the remarkable success of chimeric antigen receptor T cell (CAR-T) therapy in treating certain tumors has led to numerous studies exploring its potential application to treat non-oncology diseases. This review discusses the progress and evolution of CAR-T cell therapies for treating non-oncology diseases over the past 5 years. Additionally, we summarize the advantages and disadvantages of CAR-T cell therapy in treating non-oncological diseases and identify any difficulties that should be overcome. After conducting an in-depth analysis of the most recent studies on CAR-T technology, we discuss the key elements of CAR-T therapy, such as developing an effective CAR design for non-oncological diseases, controlling the rate and duration of response, and implementing safety measures to reduce toxicity. These studies provide new insights into different delivery strategies, the discovery of new target molecules, and improvements in the safety of CAR-T therapy for non-oncological diseases.

Effect of Resveratrol on Endothelial Function in Patients with CKD and Diabetes: A Randomized Controlled Trial.

BACKGROUND: Patients with CKD and diabetes are at higher risk of developing cardiovascular disease, in part, because of impaired endothelial function. Cardioprotective compounds such as resveratrol could improve endothelial function and attenuate the cardiovascular burden in patients with CKD and diabetes. We hypothesized that resveratrol supplementation would improve endothelial function in patients with CKD and diabetes. METHODS: Twenty-eight adults aged 68±7 years (84% men) with stage 3 CKD and diabetes were enrolled in a randomized, double-blind, placebo-controlled, crossover study to investigate the effects of 6-week resveratrol supplementation (400 mg/d) on endothelial function. Endothelial function was determined through brachial artery flow-mediated dilation. RESULTS: The mean values for eGFR and hemoglobin A 1c were 40±9 ml/min per 1.73 m 2 and 7.36%±0.72%, respectively. Compared with placebo, resveratrol supplementation increased flow-mediated dilation (ratio of geometric mean changes and 95% confidence interval for between-group comparisons, 1.43 (1.15 to 1.77); P value = 0.001). eGFR, hemoglobin A 1c , BP, and nitroglycerin-mediated dilation were unchanged with resveratrol or placebo ( P = 0.15), suggesting the observed change in flow-mediated dilation was likely independent of changes in traditional cardiovascular risk factors. CONCLUSIONS: Resveratrol supplementation improved endothelial function in patients with CKD and diabetes. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Resveratrol and Vascular Function in CKD, NCT03597568 .

Orthogeriatric co-managements lower early mortality in long-lived elderly hip fracture: a post-hoc analysis of a prospective study.

OBJECTIVE: To evaluate the clinical effectiveness of orthogeriatric co-management care in long-lived elderly hip fracture patients (age ≥ 90). METHODS: Secondary analysis was conducted in long-lived hip fracture patients between 2018 to 2019 in 6 hospitals in Beijing, China. Patients were divided into the orthogeriatric co-management group (CM group) and traditional consultation mode group (TC group) depending on the management mode. With 30-day mortality as the primary outcome, multivariate regression analyses were performed after adjusting for potential covariates. 30-day mobility and quality of life were compared between groups. RESULTS: A total of 233 patients were included, 223 of whom completed follow-up (125 in CM group, 98 in TC group). The average age was 92.4 ± 2.5 years old (range 90-102). The 30-day mortality in CM group was significantly lower than that in TC group after adjustments for (2.4% vs. 10.2%; OR = 0.231; 95% CI 0.059 ~ 0.896; P = 0.034). The proportion of patients undergoing surgery and surgery performed within 48 h also favored the CM group (97.6% vs. 85.7%, P = 0.002; 74.4% vs. 24.5%, P < 0.001; respectively). In addition, much more patients in CM group could walk with or without aids in postoperative 30 days than in the TC group (87.7% vs. 60.2%, P < 0.05), although differences were not found after 1-year follow-up. And there was no significant difference in total cost between the two groups (P > 0.05). CONCLUSIONS: For long-lived elderly hip fracture patients, orthogeriatric co-management care lowered early mortality, improved early mobility and compared with the traditional consultation mode.

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.

Characteristics of falls among older hip fracture patients from six Chinese hospitals: a post-hoc descriptive analysis.

BACKGROUND: There is well-established evidence to understand the characteristics of falls among the older patients with hip fracture in many countries, but very little knowledge existed in China. This study described the characteristics of falls in older patients with hip fractures from six Chinese hospitals. METHODS: This cross-sectional study is a post-hoc descriptive analysis of a recently completed trial. Eligible patients were aged 65 years and older, with confirmed hip fractures due to falls, and were admitted to the hospital within 21 days of the fracture. All patients were consecutively enrolled and screened within one year (November 15, 2018, to November 14, 2019). The collected data included patient demographics and fall-related information. RESULTS: A total of 1,892 patients' fall-related information were described. Most patients with hip fractures caused by falls were in the oldest old age group (60.4% in age group ≥ 80), with an overall average age of 80.7 (7.6) years. There were more females (n = 1,325, 70.0%) than males (n = 567, 30.0%). The majority lived in urban (n = 1,409, 74.5%). Most falls (n = 1,237, 67.3%) occurred during the daytime (6:01-18:00). There were 1,451 patients had their falls occurring at home (76.7%). Lost balance (n = 1,031, 54.5%) was reported as the primary reason to cause falls. The most common activity during a fall was walking (n = 1,079, 57.0%). CONCLUSIONS: Although the incidence of fall-related hip fractures in China is unclear, preventing falls and fall-related hip fractures in older people remains an urgent health concern as the ageing society increases. Studies with larger sample size and diverse population are needed to robustly understand this growing epidemic.

Prognostic value of apparent diffusion coefficient in neuroendocrine carcinomas of the uterine cervix.

Objectives: This research was designed to examine the associations between the apparent diffusion coefficient (ADC) values and clinicopathological parameters, and to explore the prognostic value of ADC values in predicting the International Federation of Gynecology and Obstetrics (FIGO) stage and outcome of patients suffering from neuroendocrine carcinomas of the uterine cervix (NECCs). Methods: This retrospective study included 83 patients with NECCs, who had undergone pre-treatment magnetic resonance imaging (MRI) between November 2002 and June 2019. The median follow-up period was 50.7 months. Regions of interest (ROIs) were drawn manually by two radiologists. ADC values in the lesions were calculated using the Functool software. These values were compared between different clinicopathological parameters groups. The Kaplan-Meier approach was adopted to forecast survival rates. Prognostic factors were decided by the Cox regression method. Results: In the cohort of 83 patients, nine, 42, 23, and nine patients were in stage I, II, III, and IV, respectively. ADCmean, ADCmax, and ADCmin were greatly lower in stage IIB-IVB than in stage I-IIA tumours, as well as in tumours measuring ≥ 4 cm than in those < 4 cm. ADCmean, FIGO stage, and age at dianosis were independent prognostic variables for the 5-year overall survival (OS). ADCmin, FIGO stage, age at diagnosis and para-aortic lymph node metastasis were independent prognostic variables for the 5-year progression-free survival (PFS) in multivariate analysis. For surgically treated patients (n = 45), ADCmax was an independent prognostic parameter for both 5-year OS and 5-year PFS. Conclusions: ADCmean, ADCmin, and ADCmax are independent prognostic factors for NECCs. ADC analysis could be useful in predicting the survival outcomes in patients with NECCs.

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. TRIAL REGISTRATION: PROSPERO Registration: CRD42023387377 .

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.

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.

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.

Risk of abnormal pregnancy outcomes after using ondansetron during pregnancy: A systematic review and meta-analysis.

Background: Hyperemesis gravidarum is a serious pregnancy complication that affects approximately 1% of pregnancies worldwide. Objective: To determine whether the use of ondansetron during pregnancy is associated with abnormal pregnancy outcomes. Search strategy: PubMed, Cochrane Library, CINAHL, Embase, CNKI, CBM, WANFANG, and ClinicalTrials.gov were searched for citations published in any language from inception to 15 December 2021. Selection criteria: Eligible studies included any observational study. Data collection and analysis: Odds ratio (OR) and 95% confidence interval (CI) were used as indicators to examine the association between ondansetron and abnormal pregnancy outcomes. Main results: Twenty articles from 1,558 citations were included. Our preliminary analysis showed that compared with the unexposed group, the use of ondansetron during pregnancy may be associated with an increased incidence of cardiac defects (OR = 1.06, 95% CI: 1.01-1.10), neural tube defects (OR = 1.12, 95% CI: 1.05-1.18), and chest cleft (OR = 1.21, 95% CI: 1.07-1.37). Further sensitivity analysis showed no significant association between ondansetron and cardiac defects (OR = 1.15,95% CI: 0.94-1.40) or neural tube defects (OR = 0.87,95% CI: 0.46-1.66). When controversial studies were eliminated, the results for the chest defects disappeared. Simultaneously, we found that the use of ondansetron was associated with a reduced incidence of miscarriage (OR = 0.53, 95% CI: 0.31-0.89). Ondansetron was not associated with orofacial clefts (OR = 1.09,95% CI: 0.95-1.25), spinal limb defects (OR = 1.14,95% CI: 0.89-1.46), urinary tract deformities (OR = 1.06,95% CI: 0.97-1.15), any congenital malformations (OR = 1.03,95% CI: 0.98-1.09), stillbirth (OR = 0.97,95% CI: 0.83-1.15), preterm birth (OR = 1.22,95% CI: 0.80-1.85), neonatal asphyxia (OR = 1.05,95% CI: 0.72-1.54), or neonatal development (OR = 1.18,95% CI: 0.96-1.44) in our primary analysis. Conclusion: In our analysis, using ondansetron during pregnancy was not associated with abnormal pregnancy outcomes. Although our study did not find sufficient evidence of ondansetron and adverse pregnancy outcomes, future studies including the exposure period and dose of ondansetron, as well as controlling for disease status, may be useful to truly elucidate the potential risks and benefits of ondansetron.

An umbrella review of meta-analyses on diagnostic accuracy of C-reactive protein.

BACKGROUND: Multiple studies and meta-analyses have reported the diagnostic value of C-reactive protein (CRP) in several diseases. However, the precision, and influence of potential bias regarding the diagnostic values of existing evidence may have implications for clinical practice. METHODS: We performed an umbrella review of diagnostic test accuracy studies of CRP for diseases by searching PubMed, Embase, China National Knowledge Infrastructure, and WanFang databases up to March 7, 2021. Five independent reviewers evaluated eligibility, extracted data, and assessed methodological quality. We descriptively analyzed the diagnostic accuracy of CRP for multiple diseases, heterogeneity between studies, and publication bias. RESULTS: Seventy-four meta-analyses were included, with 13 diseases classified according to the International Classification of Diseases-11 (ICD-11). The methodological quality of the included meta-analyses was mostly low, with only 16 meta-analyses rated as moderate or high, including seven diseases classified by ICD-11. CRP had a relatively greater diagnostic accuracy for two of these diseases. For postoperative infectious complications after bariatric surgery, sensitivity and specificity were 0.81 (0.34-1) and 0.91 (0.73-1), respectively. For anastomotic leakage after colorectal surgery, sensitivity and specificity were 0.95 (0.75-0.99) and 0.95 (0.75-0.99), respectively. CONCLUSIONS: The diagnostic accuracy of CRP for multiple diseases has been extensively studied; however, most studies have low methodological quality. Evidence indicates that CRP has a relatively greater diagnostic accuracy for inflammation and infection diseases, especially for postoperative infectious complications after bariatric surgery and anastomotic leakage after colorectal surgery.