Toenail and blood selenium mediated regulation of thyroid dysfunction through immune cells: a mediation Mendelian randomization analysis.

Purpose: Specific nutrients found in food, such as minerals, antioxidants, and macronutrients, have a significant impact on immune function and human health. However, there is currently limited research exploring the relationship between specific nutrients, immune system function, and thyroid dysfunction commonly observed in autoimmune thyroid diseases, which manifest predominantly as hyperthyroidism or hypothyroidism. Therefore, the objective of this study was to investigate the connections between dietary traits and thyroid dysfunction, as well as the potential mediating role of immune cells, using Mendelian randomization (MR) analysis. Methods: The two-step MR analysis used single-nucleotide polymorphisms as instruments, with a threshold of p < 5e-08 for nutrients and thyroid dysfunction, and p < 5e-06 for immune cells. Data from different GWAS databases and UK Biobank were combined to analyze 8 antioxidants and 7 minerals, while the data for 4 macronutrients came from a cohort of 235,000 individuals of European. The outcome data (hypothyroidism, N = 3340; hyperthyroidism, N = 1840; free thyroxin [FT4], N = 49,269; thyroid-stimulating hormone [TSH], N = 54,288) were source from the ThyroidOmics consortium. Immune trait data, including 731 immune phenotypes, were collected from the GWAS catalog. Results: The results revealed that nutrient changes, such as lycopene, toenail and blood selenium, and α-tocopherol, impacted the immune system. Immune cells also affected thyroid function, with cDC cells promoting hypothyroidism and median fluorescence intensity (MFI) phenotypes correlating strongly with FT4 levels. Toenail and blood selenium reduce the relative cell counts (RCC) phenotypes of immune cells (CD62L- plasmacytoid DC %DC and transitional B cells %Lymphocyte), thereby diminishing its promoting effect on hypothyroidis. Furthermore, toenail and blood selenium mainly impacted phenotypes in three types of T cells (CD25 + ⁣ + CD8br, CD3 on CD45RA- CD4+, and CD45RA on Terminally Differentiated CD8br), reinforcing the negative regulation of FT4 levels. Conclusion: The role of immune cells as mediators in the relationship between nutrients and thyroid dysfunction highlights their potential as diagnostic or therapeutic markers. Toenail and blood selenium levels can indirectly impact hypothyroidism by influencing the RCC levels of two types of immune cells, and can indirectly affect FT4 levels by influencing three types of T cells.

The suboptimal clinical applicability of prognostic prediction models for severe postpartum hemorrhage: a meta-epidemiological study.

OBJECTIVE: To systematically investigate clinical applicability of the current prognostic prediction models for severe postpartum hemorrhage (SPPH). STUDY DESIGN AND SETTING: A meta-epidemiological study of prognostic prediction models was conducted for SPPH. A pre-designed structured questionnaire was adopted to extract the study characteristics, predictors and the outcome, modelling methods, predictive performance, classification ability for high-risk individuals, and clinical use scenarios. The risk of bias among studies were assessed by the Prediction model Risk Of Bias ASsessment Tool. RESULTS: Twenty-two studies containing 27 prediction models were included. The number of predictors in the final models varied from 3 to 53. However, one-third of the models (11) did not clearly specify the timing of predictor measurement. Calibration was found to be lacking in 10 (37.0%) models. Among 20 models had an incidence rate of predicted outcome below 15.0%, none of the models estimated the area under the precision-recall curve, and all reported positive predictive values were below 40.0%. Only two (7.4%) models specified the target clinical setting, while seven (25.9%) models clarified the intended timing of model use. Lastly, all 22 studies were deemed to be at high risk of bias. CONCLUSION: Current SPPH prediction models have limited clinical applicability due to methodological flaws, including unclear predictor measurement, inadequate calibration assessment, and insufficient evaluation of classification ability. Additionally, there is a lack of clarity regarding the timing for model use, target users, and clinical settings. These limitations raise concerns about the reliability and usefulness of these models in real-world clinical practice.

Hepatitis B virus infection during pregnancy and the risk of postpartum hemorrhage: a protocol for systematic review and meta-analysis.

Background: Hepatitis B virus (HBV) infection is a significant public health issue worldwide, with a hepatitis B surface antigen (HBsAg) seroprevalence of 3.5%. Maternal HBV infection during pregnancy, a common comorbidity, is associated with an increase in the risk of adverse obstetric and perinatal outcomes. However, the relationship between maternal HBV infection and postpartum hemorrhage (PPH), a leading contributor to maternal morbidity and mortality, is currently uncertain. The aim of this study is to comprehensively clarify the potential impact of maternal HBV on PPH risk. Methods and Analysis: The authors initially searched five English databases and three Chinese databases from their inception to 26th June 2023. Two reviewers will independently conduct study selection, data extraction, and quality assessment. Cohort and case-control studies investigating the effect of maternal HBV infection on PPH will be included, with study quality assessed using the Newcastle-Ottawa Scale (NOS). Meta-analyses will be performed using a fixed-effects model for I 2≤50% or a random-effects model otherwise. Several categories of subgroup analyses (e.g. sample size more than 1000 vs. less than 1000) and sensitivity analyses (e.g. omit NOS scores less than 7) will be conducted, and publication bias will be assessed through funnel plots, Begg's and Egger's tests using STATA 18.0. Ethics and Dissemination: This systematic review and meta-analysis do not require ethics approval and the results will be published in peer-reviewed journals. The findings of this systematic review will provide evidence on the impact of maternal HBV infection on PPH, which will contribute to better prevention and management of PPH in clinical practice and a better understanding of the disease burden of HBV infection. PROSPERO registration number: CRD42023442626.

Comparison of stimulation protocols for dose determination of gonadotropins: A systematic review and Bayesian network meta-analysis based on randomized controlled trials.

BACKGROUND: To date, evidence regarding the effectiveness and safety of individualized controlled ovarian stimulation (COS) compared with standard dose COS has been inadequate. OBJECTIVES: To evaluate the updated evidence from published randomized controlled trials (RCTs) about the efficacy and safety of individualized COS with different ovarian reserve test biomarkers or clinical experience versus standard dose COS. SEARCH STRATEGY: Terms and descriptors related to COS, individualized or standard, and RCT were combined to search, and only English language studies were included. Conference abstracts and comments were excluded. SELECTION CRITERIA: RCTs with comparison between different individualized COS strategies and standard starting dose strategy were included. DATA COLLECTION AND ANALYSIS: Two reviews independently assessed the eligibility of retrieved citations in a predefined standardized manner. Relative risk (RRs) and the weighted mean difference (WMD) with 95% confidence intervals (CIs) were pooled using a random-effects model on R software version 4.2.2. MAIN RESULTS: Compared with the standard dose COS strategy in pairwise meta-analysis, the individualized COS strategy was associated with a notable lower risk of ovarian hyperstimulation syndrome (OHSS; 174/2384 [7.30%] vs 114/2412 [4.73%], RR 0.66, 95% CI: 0.47-0.93, I2 = 46%), a significantly lower risk of hyperresponse to stimulation (hyperresponse; 476/2402 [19.82%] vs 331/2437 [13.58%], RR 0.71, 95% CI: 0.57-0.90, I2 = 61%), and a slightly longer ovarian stimulation days (duration of stimulation; WMD 0.20, 95% CI: 0.01-0.40, I2 = 66%). Bayesian network meta-analysis also found that biomarker-tailored strategy had a significantly lower risk of OHSS than standard dose strategy (OHSS; RR 0.63, 95% CI: 0.41-0.97, I2 = 47.5%). CONCLUSION: Compared with standard dose COS strategy, individualized COS strategy could significantly reduce the risks of OHSS and hyperresponse to stimulation, but the duration of stimulation was slightly longer. TRIAL REGISTRATION: PROSPERO: CRD42023358439.

A population-based cohort of drug exposures and adverse pregnancy outcomes in China (DEEP): rationale, design, and baseline characteristics.

The DEEP cohort is the first population-based cohort of pregnant population in China that longitudinally documented drug uses throughout the pregnancy life course and adverse pregnancy outcomes. The main goal of the study aims to monitor and evaluate the safety of drug use through the pregnancy life course in the Chinese setting. The DEEP cohort is developed primarily based on the population-based data platforms in Xiamen, a municipal city of 5 million population in southeast China. Based on these data platforms, we developed a pregnancy database that documented health care services and outcomes in the maternal and other departments. For identifying drug uses, we developed a drug prescription database using electronic healthcare records documented in the platforms across the primary, secondary and tertiary hospitals. By linking these two databases, we developed the DEEP cohort. All the pregnant women and their offspring in Xiamen are provided with health care and followed up according to standard protocols, and the primary adverse outcomes - congenital malformations - are collected using a standardized Case Report Form. From January 2013 to December 2021, the DEEP cohort included 564,740 pregnancies among 470,137 mothers, and documented 526,276 live births, 14,090 miscarriages and 6,058 fetal deaths/stillbirths and 25,723 continuing pregnancies. In total, 13,284,982 prescriptions were documented, in which 2,096 chemicals drugs, 163 biological products, 847 Chinese patent medicines and 655 herbal medicines were prescribed. The overall incidence rate of congenital malformations was 2.0% (10,444/526,276), while there were 25,526 (4.9%) preterm births and 25,605 (4.9%) live births with low birth weight.

Optimization of Diagnosis-Related Groups for 14,246 Patients with Uterine Leiomyoma in a Single Center in Western China Using a Machine Learning Model.

Background: Uterine leiomyoma (UL) is one of the most common benign tumors in women, and its incidence is gradually increasing in China. The clinical complications of UL have a negative impact on women's health, and the cost of treatment poses a significant burden on patients. Diagnosis-related groups (DRG) are internationally recognized as advanced healthcare payment management methods that can effectively reduce costs. However, there are variations in the design and grouping rules of DRG policies across different regions. Therefore, this study aims to analyze the factors influencing the hospitalization costs of patients with UL and optimize the design of DRG grouping schemes to provide insights for the development of localized DRG grouping policies. Methods: The Mann-Whitney U-test or the Kruskal-Wallis H-test was employed for univariate analysis, and multiple stepwise linear regression analysis was utilized to identify the primary influencing factors of hospitalization costs for UL. Case combination classification was conducted using the exhaustive chi-square automatic interactive detection (E-CHAID) algorithm within a decision tree framework. Results: Age, occupation, number of hospitalizations, type of medical insurance, Transfer to other departments, length of stay (LOS), type of UL, admission condition, comorbidities and complications, type of primary procedure, other types of surgical procedures, and discharge method had a significant impact on hospitalization costs (P<0.05). Among them, the type of primary procedure, other types of surgical procedures, and LOS were the main factors influencing hospitalization costs. By incorporating the type of primary procedure, other types of surgical procedures, and LOS into the decision tree model, patients were divided into 11 DRG combinations. Conclusion: Hospitalization costs for UL are mainly related to the type of primary procedure, other types of surgical procedures, and LOS. The DRG case combinations of UL based on E-CHAID algorithm are scientific and reasonable.

Investigation of statistical methods used in prognostic prediction models for obstetric care: A 10 year-span cross-sectional study.

INTRODUCTION: Obstetric care is a highly active area in the development and application of prognostic prediction models. The development and validation of these models often require the utilization of advanced statistical techniques. However, failure to adhere to rigorous methodological standards could greatly undermine the reliability and trustworthiness of the resultant models. Consequently, the aim of our study was to examine the current statistical practices employed in obstetric care and offer recommendations to enhance the utilization of statistical methods in the development of prognostic prediction models. MATERIAL AND METHODS: We conducted a cross-sectional survey using a sample of studies developing or validating prognostic prediction models for obstetric care published in a 10-year span (2011-2020). A structured questionnaire was developed to investigate the statistical issues in five domains, including model derivation (predictor selection and algorithm development), model validation (internal and external), model performance, model presentation, and risk threshold setting. On the ground of survey results and existing guidelines, a list of recommendations for statistical methods in prognostic models was developed. RESULTS: A total of 112 eligible studies were included, with 107 reporting model development and five exclusively reporting external validation. During model development, 58.9% of the studies did not include any form of validation. Of these, 46.4% used stepwise regression in a crude manner for predictor selection, while two-thirds made decisions on retaining or dropping candidate predictors solely based on p-values. Additionally, 26.2% transformed continuous predictors into categorical variables, and 80.4% did not consider nonlinear relationships between predictors and outcomes. Surprisingly, 94.4% of the studies did not examine the correlation between predictors. Moreover, 47.1% of the studies did not compare population characteristics between the development and external validation datasets, and only one-fifth evaluated both discrimination and calibration. Furthermore, 53.6% of the studies did not clearly present the model, and less than half established a risk threshold to define risk categories. In light of these findings, 10 recommendations were formulated to promote the appropriate use of statistical methods. CONCLUSIONS: The use of statistical methods is not yet optimal. Ten recommendations were offered to assist the statistical methods of prognostic prediction models in obstetric care.

Estimates of the global burden of non-Hodgkin lymphoma attributable to HIV: a population attributable modeling study.

Background: Human immunodeficiency virus (HIV) significantly increases the risk of non-Hodgkin lymphoma (NHL) development, yet the population-level impact on NHL burden is unquantified. We aim to quantify this association and estimate the global burden of HIV-associated NHL. Methods: In this meta-analysis, we searched five databases (PubMed, EMBASE, Cochrane Library, Web of Science, Scopus) from database inception up to September 13, 2023, identifying cohort, case-control, or cross-sectional studies with an effective control group to assess NHL risk among individuals with HIV infection, with two authors extracting summary data from reports. Global and regional HIV-associated population attributable fraction (PAF) and NHL disease burden were calculated based on the pooled risk ratio (RR). HIV prevalence and NHL incidence were obtained from the Joint United Nations Programme on HIV/AIDS (UNAIDS) and Global Burden of Diseases, Injuries, and Risk Factors Study 2019. Trends in NHL incidence due to HIV were assessed using age-standardised incidence rate (ASIR) and estimated annual percentage change (EAPC). This study was registered with PROSPERO (CRD42023404150). Findings: Out of 14,929 literature sources, 39 articles met our inclusion criteria. The risk of NHL was significantly increased in the population living with HIV (pooled RR 23.51, 95% CI 17.62-31.37; I2 = 100%, p < 0.0001), without publication bias. Globally, 6.92% (95% CI 2.18%-11.57%) of NHL new cases in 2019 were attributable to HIV infection (30,503, 95% CI 9585-52,209), which marked a more than three-fold increase from 1990 (8340, 95% CI 3346-13,799). The UNAIDS region of Eastern and Southern Africa was the highest affected region, with 44.46% (95% CI 19.62%-58.57%) of NHL new cases attributed to HIV infection. The Eastern Europe and Central Asia region experienced the highest increase in ASIR of NHL due to HIV in the past thirty years, wherein the EAPC was 8.74% (95% CI 7.66%-9.84%), from 2010 to 2019. Interpretation: People with HIV infection face a significantly increased risk of NHL. Targeted prevention and control policies are especially crucial for countries in Eastern and Southern Africa, Eastern Europe and Central Asia, to achieve the UNAIDS's '90-90-90' Fast-Track targets. Limited studies across diverse regions and heterogeneity between research have hindered precise estimations for specific periods and regions. Funding: Sichuan Provincial People's Hospital, Chengdu, China; Health Care for Cadres of Sichuan Province, Chengdu, China; Science and Technology Department of Sichuan Province, Chengdu, China.

Impact of maternal hepatitis B carrier status on congenital abnormalities: a systematic review and meta-analysis.

OBJECTIVES: This study aims to explore whether maternal hepatitis B carrier status is associated with an increased risk of congenital abnormalities. DESIGN: A systematic review and meta-analysis of observational studies. DATA SOURCES: PubMed, Embase (Ovid), Scopus, the China National Knowledge Infrastructure (CNKI) and the Wanfang databases. STUDY SELECTION: Five databases were searched systematically from inception to 7 September 2021. Cohort and case-control studies that investigated the association between maternal hepatitis B virus (HBV) infection and congenital abnormalities were included. This study was conducted according to MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently collected data, as well as assessed risk of bias by using Newcastle-Ottawa Scale. We pooled crude relative risk (cRR) and adjusted OR (aOR) by DerSimonian-Laird random-effects model. Heterogeneity was explored by I 2 statistics, Cochran's Q test. Several subgroup analyses and sensitivity analyses were performed. RESULTS: In total, 14 studies involving 16 205 pregnant women exposed to HBV were included. The pooled cRR of 1.15 (95% CI: 0.92 to 1.45; 14 studies included) showed a marginal but not significant association between maternal HBV-carrier status and congenital abnormalities. However, the pooled aOR of 1.40 (95% CI: 1.01 to 1.93; 8 studies included) indicated that pregnant women with HBV infection might be associated with a higher risk of congenital abnormalities. Subgroup analyses of adjusted data showed a higher pooling cRR or aOR on high prevalence HBV infection populations, as well as studies from Asia and Oceania. CONCLUSIONS: Maternal hepatitis B carrier status might be at potential risk for congenital abnormalities. The existing evidence was not sufficient to draw a firm conclusion. Additional studies may be warranted to confirm the association. PROSPERO REGISTRATION NUMBER: CRD42020205459.

The use of Chinese herbal medicines throughout the pregnancy life course and their safety profiles: a population-based cohort study.

BACKGROUND: Chinese herbal medicines have been long used among pregnant populations in China. However, despite the high susceptibility of this population to drug exposure, it continued to remain unclear about how often they were used, to what extent they were used at different pregnancy stages, and whether their use was based on sound safety profiles, particularly when used in combination with pharmaceutical drugs. OBJECTIVE: This descriptive cohort study aimed to systematically investigate the use of Chinese herbal medicines throughout pregnancy and their safety profiles. STUDY DESIGN: A large medication use cohort was developed by linking a population-based pregnancy registry and a population-based pharmacy database, which documented all prescriptions at both outpatients and inpatients from conception to 7 days after delivery, including pharmaceutical drugs and processed Chinese herbal medicine formulas that were approved by the regulatory authority and prepared under the guidance of national quality standards. The prevalence of the use of Chinese herbal medicine formulas, prescription pattern, and combination use of pharmaceutical drugs throughout pregnancy were investigated. Multivariable log-binomial regression was performed to assess temporal trends and further explore the potential characteristics associated with the use of Chinese herbal medicines. Of note, 2 authors independently conducted a qualitative systematic review of patient package inserts of the top 100 Chinese herbal medicine formulas used to identify their safety profiles. RESULTS: This study included 199,710 pregnancies; of those pregnancies, 131,235 (65.71%) used Chinese herbal medicine formulas, including 26.13% during pregnancy (corresponding to 14.00%, 8.91%, and 8.26% in the first, second, and third trimesters of pregnancy) and 55.63% after delivery. The peak uses of Chinese herbal medicines occurred between 5 and 10 weeks of gestation. The use of Chinese herbal medicines significantly increased over the years (from 63.28% in 2014 to 69.59% in 2018; adjusted relative risk, 1.11; 95% confidence interval, 1.10-1.13), which was particularly great during pregnancy (from 18.47% in 2014 to 32.46% in 2018; adjusted relative risk, 1.84; 95% confidence interval, 1.77-1.90). Our study observed 291,836 prescriptions involving 469 Chinese herbal medicine formulas, and the top 100 most used Chinese herbal medicines accounted for 98.28% of the total prescriptions. Of those, a third (33.39%) were dispensed at outpatient visits; 6.79% were external use, and 0.29% were administered intravenously. However, Chinese herbal medicines were very often prescribed in combination with pharmaceutical drugs (94.96% overall), involving 1175 pharmaceutical drugs with 1,667,459 prescriptions. The median of pharmaceutical drugs prescribed in combination with Chinese herbal medicines per pregnancy was 10 (interquartile range, 5-18). The systematic review of drug patient package inserts found that the 100 most frequently prescribed Chinese herbal medicines contained a total of 240 herb constituents (median, 4.5); 7.00% were explicitly indicated for pregnancy or postpartum conditions; 43.00% were reported with efficacy or safety data from randomized controlled trials. Information was lacking about whether the medications had any reproductive toxicity, were excreted in human milk, or crossed the placenta. CONCLUSION: The use of Chinese herbal medicines was prevalent throughout pregnancy and increased over the years. The use of Chinese herbal medicines peaked in the first trimester of pregnancy and was very often used in combination with pharmaceutical drugs. However, their safety profiles were mostly unclear or incomplete, suggesting a strong need for postapproval surveillance for the use of Chinese herbal medicines during pregnancy.

The reporting of prognostic prediction models for obstetric care was poor: a cross-sectional survey of 10-year publications.

BACKGROUND: To investigate the reporting of prognostic prediction model studies in obstetric care through a cross-sectional survey design. METHODS: PubMed was searched to identify prognostic prediction model studies in obstetric care published from January 2011 to December 2020. The quality of reporting was assessed by the TRIPOD checklist. The overall adherence by study and the adherence by item were calculated separately, and linear regression analysis was conducted to explore the association between overall adherence and prespecified study characteristics. RESULTS: A total of 121 studies were included, while no study completely adhered to the TRIPOD. The results showed that the overall adherence was poor (median 46.4%), and no significant improvement was observed after the release of the TRIPOD (43.9 to 46.7%). Studies including both model development and external validation had higher reporting quality versus those including model development only (68.1% vs. 44.8%). Among the 37 items required by the TRIPOD, 10 items were reported adequately with an adherence rate over of 80%, and the remaining 27 items had an adherence rate ranging from 2.5 to 79.3%. In addition, 11 items had a report rate lower than 25.0% and even covered key methodological aspects, including blinding assessment of predictors (2.5%), methods for model-building procedures (4.5%) and predictor handling (13.5%), how to use the model (13.5%), and presentation of model performance (14.4%). CONCLUSIONS: In a 10-year span, prognostic prediction studies in obstetric care continued to be poorly reported and did not improve even after the release of the TRIPOD checklist. Substantial efforts are warranted to improve the reporting of obstetric prognostic prediction models, particularly those that adhere to the TRIPOD checklist are highly desirable.

Effectiveness and Safety of Two Consecutive Cycles of Single Embryo Transfer Compared With One Cycle of Double Embryo Transfer: A Systematic Review and Meta-Analysis.

Objective: To date, evidence regarding the effectiveness and safety of two consecutive cycles of single embryo transfer (2SETs) compared with one cycle of double embryo transfer (DET) has been inadequate, particularly considering infertile women with different prognostic factors. This study aimed to comprehensively summarize the evidence by comparing 2SETs with DET. Methods: PubMed, Embase, Cochrane Library databases, ClinicalTrails.gov, and the WHO International Clinical Trials Registry Platform were searched up to March 22, 2022. Peer-reviewed, English-language randomized controlled trials (RCTs) and observational studies (OS) comparing the outcomes of 2SETs with DET in infertile women with their own oocytes and embryos were included. Two authors independently conducted study selection, data extraction, and bias assessment. The Mantel-Haenszel random-effects model was used for pooling RCTs, and a Bayesian design-adjusted model was conducted to synthesize the results from both RCTs and OS. Main Results: Twelve studies were finally included. Compared with the DET, 2SETs were associated with a similar cumulative live birth rate (LBR; 48.24% vs. 48.91%; OR, 0.97; 95% credible interval (CrI), 0.89-1.13, τ2 = 0.1796; four RCTs and six observational studies; 197,968 women) and a notable lower cumulative multiple birth rate (MBR; 0.87% vs. 17.72%; OR, 0.05; 95% CrI, 0.02-0.10, τ2 = 0.1036; four RCTs and five observational studies; 197,804 women). Subgroup analyses revealed a significant increase in cumulative LBR (OR, 1.33; 95% CrI, 1.29-1.38, τ2 = 0) after two consecutive cycles of single blastocyst transfer compared with one cycle of double blastocyst transfer. Moreover, a lower risk of cesarean section, antepartum hemorrhage, preterm birth, low birth weight, and neonatal intensive care unit admission but a higher gestational age at birth and birth weight were found in the 2SETs group. Conclusion: Compared to the DET strategy, 2SETs result in a similar LBR while simultaneously reducing the MBR and improving maternal and neonatal adverse outcomes. The 2SETs strategy appears to be especially beneficial for women aged ≤35 years and for blastocyst transfers.

Dose-response association between maternal pre-pregnancy bodyweight and gestational diabetes mellitus following ART treatment: a population-based cohort study.

BACKGROUND: The impact of maternal pre-pregnancy bodyweight on gestational diabetes mellitus (GDM) following assisted reproductive technology (ART) treatment has been insufficiently investigated. The aim of this study was to investigate the association between maternal pre-pregnancy bodyweight and GDM following ART. METHODS: From January 2014 to March 2019, this population-based retrospective cohort study included pregnancies achieved by ART treatment in a pregnancy registration database in China. Multivariate regression analysis and restricted cubic splines were used to explore the association between bodyweight and GDM. RESULTS: A total of 6,598 pregnancies were included. The incidence of GDM was 26.0% (1715/6598). A total of 868 (13.2%) pregnant women were underweight, 665 (10.8%) were overweight, and 145 (2.20%) were obesity. We found a linear dose-response relation between maternal body mass index and GDM by restricted cubic splines, where one unit body mass index increase was associated with the 15% elevated risk of GDM (adjusted odds ratio [OR] 1.15, 95% CI 1.08-1.22). Compared to the normal weight group, maternal underweight was associated with lower risk of GDM (adjusted OR 0.68, 95% CI 0.57-0.82), while increased risk was found for overweight (adjusted OR 1.54 95% CI 1.29-1.84) and obesity (adjusted OR 1.74, 95% CI 1.23-2.47). CONCLUSIONS: Our study found a linear dose-effect relationship between pre-pregnancy bodyweight and GDM following ART treatment. The findings in this study support the clinical recommendation of advising women with overweight or obesity to lose weight prior to ART treatment.

The impact of biparental hepatitis B virus infection on pregnancy outcomes in patients undergoing assisted reproductive technology treatment: a systematic review and meta-analysis.

PURPOSE: To evaluate the association between biparental hepatitis B virus (HBV) infection (hepatitis B surface antigen [HBsAg] seropositivity) and pregnancy outcomes in patients undergoing assisted reproductive technology (ART) treatment, including clinical pregnancy rate (CPR) and live birth rate (LBR). METHODS: We searched various literature databases from the earliest date available until May 20, 2021, including PubMed, Embase, Medline, Web of Science, Scopus, CNKI, and Wangfang. Four patterns of biparental HBV infection for pregnancy outcomes following ART were synthesized separately by using random-effects model. We also performed subgroup analyses (matched or unmatched) and two forms of sensitivity analysis. RESULTS: A total of 25 retrospective cohort studies, involving more than 19,269 couples, were included. Maternal and paternal HBV co-infection (crude relative risk [cRR]: 0.58, 95% confidence interval: 0.28-1.23), either maternal or paternal infection (cRR: 1.05, 0.88-1.24), maternal HBV infection alone (cRR: 0.96, 0.79-1.16), or paternal HBV infection alone (cRR: 1.02, 0.91-1.13) were not associated with significant reductions in CPR at per woman level. These patterns of infection were also not significantly associated with decreased LBR at per woman level. However, paternal HBV infection alone reduced CPR (adjusted odds ratio: 0.54, 0.33-0.86) and LBR (cRR: 0.52, 0.28-0.99) at per cycle level. Subgroup analyses and sensitivity analyses were mostly consistent with the primary results. CONCLUSIONS: Paternal HBV infection alone probably decrease CPR after ART at per cycle level. However, maternal HBV infection was not associated with reductions in CPR and LBR in women undergoing ART at per woman level.

Effects of Motherwort Injection Versus Intramuscular Oxytocin for Preventing Postpartum Hemorrhage Among Women Who Underwent Cesarean Section.

Objectives: Subject to ethical constraints, real-world data are an important resource for evaluating treatment effects of medication use during pregnancy and the postpartum period. This study investigated whether motherwort injection, a traditional Chinese medicine preparation, was more effective than intramuscular (IM) oxytocin for preventing postpartum hemorrhage (PPH) in a real-world setting when intravenous (IV) oxytocin is administered. Methods: We conducted an active-controlled, propensity-score matched cohort study using an established pregnancy registry database. Women who underwent cesarean section and received IV oxytocin at the third stage of labor were included. We used an active-comparator design to minimize indication bias, in which we compared IM motherwort injection in the uterus versus IM oxytocin, both on top of IV oxytocin use. We applied 1:1 propensity-score matching (PSM) to balance patient baseline characteristics and used a logistic regression model to estimate treatment effect (i.e., risk difference (RD) and odds ratio (OR)) by using the counterfactual framework. The outcomes of interest were blood loss over 500 ml within 2 h after delivery (PPH, primary) and blood loss over 1,000 ml (severe PPH, secondary). We conducted four sensitivity analyses to examine the robustness of the results. Results: A total of 22,519 pregnant women underwent cesarean sections, among which 4,081 (18.12%) PPH and 480 (2.13%) severe PPH occurred. Among included women, 586 (2.60%) were administrated with IM motherwort injection, and 21,933 (97.40%) used IM oxytocin. After PSM, patient baseline characteristics were well balanced. Compared with IM oxytocin, the use of IM motherwort injection was associated with significantly lower risk of PPH (RD -25.26%, 95% CI -30.04% to -20.47%, p < 0.001; OR 0.25, 95% CI 0.18 to 0.32, p < 0.001) and severe PPH (RD -3.58%, 95% CI -5.87% to -1.30%, p < 0.001; OR 0.39, 95% CI 0.20 to 0.71, p < 0.002). Sensitivity analyses showed that the results were similar. Conclusion: With the use of data from a real-world setting, the findings consistently showed that among women undergoing cesarean section who had received IV oxytocin, the additional use of IM motherwort injection could achieve a lower risk of PPH as compared to the additional use of IM oxytocin. Our study suggested a paradigm for investigating the treatment effect of Chinese herbal medicine in the real-world practice setting.

A methodological framework for tackling confounding by indication when assessing the treatment effects of Chinese herbal injections in the real world.

AIM: In the context of integrative medicine, whether Chinese herbal injections are effective in routine practice has become a question of broad interest. However, confounding by indication (i.e., indication bias) is a prevalent and highly challenging methodological issue when using routinely collected health care data to assess the real-world effectiveness of Chinese herbal injections. METHODS AND RESULTS: We proposed a methodological approach to tackling confounding by indication in assessing the real-world effectiveness of Chinese herbal injections, incorporating empirical experiences, a literature review and interactive discussions, and a panel of external experts to finally achieve a consensus. This approach consisted of three cohesive steps, including a full understanding of treatment patterns, construction of fair comparisons by identifying appropriate combination treatments and comparators, and using statistical methods to further control for confounding. In the investigation of treatment patterns, we proposed five domains to identify treatment patterns with Chinese herbal injections, and we offered five patterns of combination treatments to characterize how Chinese herbal injections are used in conjunction with other treatments. In constructing fair comparisons, we suggested the use of both nonuse and active comparators; given the diverse combination treatments, we developed six scenarios that may form fair comparisons. In the statistical analysis, we discussed five statistical models for controlling confounding by indication, including their pros and cons. We also included a practical example to illustrate the usefulness of the methodological approach. CONCLUSION: The proposed approach may serve as an effective tool to guide researchers to reliably assess the effectiveness of Chinese herbal injections in the context of integrative medicine.

Prevalence and risk factors of senile pruritus: a systematic review and meta-analysis.

OBJECTIVES: To systematically assess the prevalence and risk factors for senile pruritus (SP) in the elderly (≥60 years of age). DESIGN: A meta-analysis was used to pool the prevalence and risk factors for SP estimated from individual studies. Four subgroup analyses were conducted to explore the prevalence for SP in different age, sex, research sites and region. SETTING, PARTICIPANTS AND MEASURES: SP reduces quality of life in the elderly, yet the worldwide prevalence is unclear. Moreover, the risk factors for SP are controversial. Data from cross-sectional studies, case-control studies, longitudinal studies and cohort studies that reported the prevalence or the risk factors for SP were collected by searching nine electronic databases up to October 2020, including Web of Science, PubMed, Embase, Cochrane Library, CINAHL, CBM, CNKI, Wanfang and VIP. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and assessed methodological quality. Data analysis was performed using Stata V.15.1 software. RESULTS: Seventeen studies involving 28 666 participants were included. The overall pooled prevalence of SP was 21.04% (95% CI 11.37% to 32.72%). In addition, the results showed that smoking, excessive drinking and monophagism were possible risk factors for SP, with pooled ORs of 1.26 (95% CI 1.14 to 1.40), 25.03 (95% CI 18.28 to 34.25) and 1.22 (95% CI 1.12 to 1.33), respectively. CONCLUSIONS: The overall prevalence of SP was high. Smoking, excessive drinking and monophagism were possible risk factors for SP. PROSPERO REGISTRATION NUMBER: CRD42019143295.

Association between Klebsiella pneumoniae and ankylosing spondylitis: A systematic review and meta-analysis.

AIM: The aim of this study is to evaluate the association between Klebsiella pneumoniae infection and ankylosing spondylitis (AS). METHOD: Five electronic databases, PubMed, Embase, Medline, Web of Science, and Scopes, were searched until September 29, 2021. Cohort and case-control studies that assessed the association between K. pneumoniae infection and AS were included. Pooled odds ratio (OR) was selected to show the effect size. Subgroup analysis (active or inactive AS) and 2 forms of sensitivity analysis were conducted. All statistical analyses were conducted by using STATA 12.0. RESULTS: There were 25 case-control studies finally included, including 8 studies concerning presence of K. pneumoniae in feces, and 17 studies concerning serum antibody (immunoglobulin [Ig]G, IgM, IgA) against K. pneumoniae. The results suggested that when compared with healthy people, presence of K. pneumoniae in feces was associated with AS (OR: 5.65; 95% CI: 1.68-19.00). Similarly, when compared with healthy people, higher positive rates of IgA (OR: 6.28; 95% CI: 3.32-11.91) and IgG (OR: 5.22; 95% CI: 1.36-19.99) were observed. Subgroup analyses suggested that association between K. pneumoniae and AS appears stronger in active AS. CONCLUSION: When compared with healthy people, a significantly higher positive rate of K. pneumoniae in feces, serum IgA and IgG were observed in patients with AS, suggesting that K. pneumoniae probably plays a crucial role in the occurrence of AS. The findings in this study need further prospective investigations for confirmation.

Comparisons of benefits and risks of single embryo transfer versus double embryo transfer: a systematic review and meta-analysis.

BACKGROUND: Evidence referring to the trade-offs between the benefits and risks of single embryo transfer (SET) versus double embryo transfer (DET) following assisted reproduction technology are insufficient, especially for those women with a defined embryo quality or advanced age. METHODS: A systematic review and meta-analysis was conducted according to PRISMA guidelines. PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov were searched based on established search strategy from inception through February 2021. Pre-specified primary outcomes were live birth rate (LBR) and multiple pregnancy rate (MPR). Odds ratio (OR) with 95% confidence interval (CI) were pooled by a random-effects model using R version 4.1.0. RESULTS: Eighty-five studies (14 randomized controlled trials and 71 observational studies) were eligible. Compared with DET, SET decreased the probability of a live birth (OR = 0.78, 95% CI: 0.71-0.85, P < 0.001, n = 62), and lowered the rate of multiple pregnancy (0.05, 0.04-0.06, P < 0.001, n = 45). In the sub-analyses of age stratification, both the differences of LBR (0.87, 0.54-1.40, P = 0.565, n = 4) and MPR (0.34, 0.06-2.03, P = 0.236, n = 3) between SET and DET groups became insignificant in patients aged ≥40 years. No significant difference in LBR for single GQE versus two embryos of mixed quality [GQE + PQE (non-good quality embryo)] (0.99, 0.77-1.27, P = 0.915, n = 8), nor any difference of MPR in single PQE versus two PQEs (0.23, 0.04-1.49, P = 0.123, n = 6). Moreover, women who conceived through SET were associated with lower risks of poor outcomes, including cesarean section (0.64, 0.43-0.94), antepartum haemorrhage (0.35, 0.15-0.82), preterm birth (0.25, 0.21-0.30), low birth weight (0.20, 0.16-0.25), Apgar1 < 7 rate (0.12, 0.02-0.93) or neonatal intensive care unit admission (0.30, 0.14-0.66) than those following DET. CONCLUSIONS: In women aged < 40 years or if any GQE is available, SET should be incorporated into clinical practice. While in the absence of GQEs, DET may be preferable. However, for elderly women aged ≥40 years, current evidence is not enough to recommend an appropriate number of embryo transfer. The findings need to be further confirmed.