Jing Tan

Ensuring safe and effective anti‐infective use during pregnancy is a global priority, yet evidence remains fragmented across heterogeneous clinical contexts and study designs. We thus comprehensively assessed the safety of prenatal anti‐infective exposure and strengthen the evidence base for safer medication. Six databases were searched to include meta‐analyses evaluating prenatal exposure to anti‐infective agents in humans and reporting neonatal outcomes or long‐term offspring outcomes. Overlapping primary studies were quantified using citation matrices, prioritizing the most recent and comprehensive analyses. A total of 138 evidence syntheses comprising 1298 non‐overlapping meta‐analyses were included, covering 127 drug exposures and 109 offspring outcomes. Harmful associations were identified in 160 meta‐analyses, including 51 classified as increased risk and 109 as suspected increased risk. Increased risks supported by at least low‐certainty evidence were identified for several commonly used agents, including macrolides, metronidazole, tetracyclines, sulfonamides, fluconazole, protease inhibitor‐based and zidovudine‐containing antiretroviral regimens, quinine, and chloroquine. Notably, 43% of implicated exposures involved FDA pregnancy category B agent. This panoramic assessment clarifies where existing evidence is relatively robust versus uncertain and identifies drug classes warranting heightened scrutiny. Future research should prioritize indication‐specific, rigorously controlled studies to better disentangle medication‐related risks from those associated with underlying maternal infections.

Anti-infective agents are widely used during pregnancy to prevent, treat, and mitigate the transmission of infections, and their utilisation has significantly increased over the past decade. However, concerns persist regarding their potential embryotoxicity, compounded by inconsistencies in safety data that complicate medication decision-making. This protocol details an umbrella review that aims to provide a comprehensive and methodologically sound synthesis of evidence from systematic reviews (SRs) on the adverse effects of prenatal anti-infective exposure on offspring. The review will incorporate a standardised, three-stage data extraction strategy and an R-based algorithm to efficiently identify and manage overlapping evidence. We will conduct a comprehensive search across six databases (PubMed, Embase, Scopus, Web of Science, Cochrane Library, and Epistemonikos) from inception to June 22, 2024. The search will cover three key concepts-pregnant women, anti-infective agents, and systematic reviews-without restrictions on controls or outcomes. We will include SRs, with or without meta-analyses, that evaluate the adverse effects of prenatal anti-infective exposure and report either neonatal outcomes (e.g. birth defects) or long-term offspring outcomes (e.g. neurodevelopmental disorders). To address overlapping evidence, a structured three-stage data extraction process, supported by an R-based algorithm, will be implemented, sequentially handling PICO definition extraction, overlapping evidence management, and quantitative data extraction. At least two independent reviewers will screen studies, extract data, and assess methodological quality and evidence strength using AMSTAR-2 and GRADE, respectively. Evidence synthesis will be conducted narratively, drawing on meta-analytic associations from direct comparative analyses and organising findings by anti-infective agents, indications, outcomes, effect estimates, certainty of evidence, and methodological quality. Anti-infectives with safety concerns will be summarised in tables and evidence maps. By adopting a standardised process that incorporates an automated algorithm for managing overlapping evidence, the planned umbrella review will provide a comprehensive synthesis of existing evidence on the adverse effects of anti-infective use during pregnancy. The findings are expected to inform clinical practice, guide policy decisions, and support infection management in pregnant patients. Furthermore, the review will identify key knowledge gaps, help prioritise future research, and ultimately contribute to improving maternal and offspring health outcomes. PROSPERO CRD42024577013.

Psoriasis is a chronic inflammatory skin disease mediated by T cells, characterized by distinct sex differences and variations across different reproductive stages, suggesting that sex hormones may play a significant role in its pathogenesis. In recent years, research has increasingly focused on the bidirectional effects of sex hormones in psoriasis: on one hand, changes in hormone levels can affect the onset and progression of psoriasis; on the other hand, the systemic inflammation of psoriasis can interfere with the homeostasis of the sex hormone axis. This review systematically integrates clinical epidemiological evidence of sex hormone abnormalities in cutaneous psoriasis patients, outlines the molecular mechanisms of estrogen, androgen, and progesterone in immune-inflammatory regulation of psoriasis, and further explores how psoriasis-related inflammation, through cytokines, stress responses, and metabolic abnormalities, can in turn disrupt sex hormone balance. The focus is primarily on immunopathological mechanisms, with a secondary consideration of the impact of metabolic and stress-related factors, which modulate immune responses and may indirectly influence disease progression. We highlight the complex immune-endocrine network interaction between sex hormones and cutaneous psoriasis, emphasizing the need for future sex-stratified studies, dynamic hormone monitoring, and mechanistic validation models to clarify their causal pathways. This will aid in understanding the sex-specific clinical manifestations of psoriasis and provide a theoretical basis for developing hormone-targeted intervention strategies.

Importance: Target trial emulation (TTE) is increasingly used to estimate causal effects with observational data, yet its clinical applications and methodologic quality remain unclear. Objective: To characterize the clinical scenarios where TTE has been applied, assess methodologic limitations in design and implementation, and provide structured recommendations for strengthening future practice. Design, Setting, and Participants: This cross-sectional study searched PubMed for TTE studies published from January 1, 2017, to December 15, 2023, in clinical journals in the top Journal Impact Factor quartile, supplemented by studies from 3 prior scoping reviews. Eligible studies explicitly aimed to emulate a target trial using observational data. Data were extracted using a standardized, consensus-based tool. Main Outcomes and Measures: Study characteristics, application scenarios, specification of target trials, and adherence to 7 methodologic domains of TTE were evaluated. Recommendations were developed to address observed gaps. Results: Among 237 included studies, over half (128 [54.0%]) evaluated drug interventions, commonly in infectious diseases, cardiology, and oncology. TTE was applied in 8 recurring clinical scenarios, including randomized clinical trial replication and extending evidence to underrepresented populations or rare outcomes. TTE was most frequently applied to assess treatment effectiveness (165 studies [69.6%]), long-term outcomes (39 [16.5%]), emergency-use medications (42 [17.7%]), and active-treatment comparisons (49 [20.7%]). Major methodologic gaps were evident: only 134 studies (56.5%) developed a prespecified protocol, 127 (53.6%) did not review existing randomized clinical trials, and most that emulated existing trials (20 of 31 [64.5%]) or hypothetical trials (147 of 153 [96.1%]) did not justify the choice of trial to emulate. During implementation, 103 studies (43.5%) did not report all 7 methodologic components, 36 (15.2%) used postbaseline information inappropriately for eligibility, only 40 (16.9%) provided follow-up diagrams to define time zero, and only 73 (30.8%) addressed unmeasured confounding. A 5-step framework for target trial design and practical considerations for implementing methodologic principles was developed. Conclusions and Relevance: This cross-sectional study of TTE identified 8 common clinical scenarios for TTE application and substantial methodologic heterogeneity that threatened the credibility of resulting evidence. The study highlighted common pitfalls and proposed actionable recommendations to complement reporting standards such as the Transparent Reporting of Observational Studies Emulating a Target Trial guideline, which may support the generation of more robust observational evidence for clinical and policy decision-making.

Aim: Hepatitis B virus (HBV) infection during pregnancy is one of the most common comorbidities, which may increase the risk of adverse obstetric and perinatal outcomes. However, the association between maternal HBV infection and postpartum hemorrhage (PPH) remains uncertain. The aim of this study is to evaluate whether maternal HBV infection will increase the risk of PPH. Methods: Five English and three Chinese databases were searched from inception to 30 June 2024, with the aim to include recently published eligible studies. Cohort and case–control studies that evaluated the association between maternal HBV infection and PPH were included. The Newcastle–Ottawa scale was used to evaluate the risk of bias for the included studies. We pooled crude relative risk (cRR) and adjusted odds ratio (aOR) as effect sizes. Three subgroup analyses and seven sensitivity analyses were performed. Results: A total of 21 cohort studies involving 379,782 participants were included. The pooled results of the unadjusted data revealed that maternal HBV infection was associated with an increased risk of PPH [cRR = 1.18, 95% confidence interval (CI): 1.06–1.31]. Furthermore, the pooled results of adjusted data showed a similar risk of PPH (aOR = 1.50, 95% CI: 1.29–1.73). The effect was similar in three subgroup analyses (i.e., sample size, study region, and prevalence of HBV infection). Sensitivity analyses confirmed that the primary results were robust. Conclusions: Maternal HBV infection is associated with an increased risk of PPH. Further studies are warranted to evaluate the impact of maternal HBeAg serostatus and HBV DNA levels on PPH. Systematic Review Registration: identifier CRD42023442626.

Aim: Infertility is a growing global health issue affecting millions worldwide. While endometriosis, polycystic ovarian syndrome (PCOS) and unexplained infertility are recognized as the major contributors, their specific burden and impact on infertility among women of childbearing age (WCBA) remain inadequately quantified. This study aimed to evaluate the global burden of three diseases and infertility attributable to them. Methods: Using data from Global Burden of Disease Study 2021, we assessed the temporal trends of three diseases by average annual percentage change (AAPC) in age‐standardized prevalence rate (ASPR) and DALYs rate (ASDR), and evaluated their correlation with socio‐demographic index (SDI). We also calculated the age‐standardized prevalence and years lived with disability (YLDs) rates of infertility attributable to three diseases. Results: In 2021, the global ASPRs of endometriosis, PCOS, and unexplained infertility were 1070.7 (AAPC: –1.02%, declining), 3364.5 (AAPC: 0.74%, increasing), and 5586.2 (AAPC: 0.70%, increasing), and infertility attributable to three diseases were 60.6, 638.2, and 5586.2 per 100,000 population, respectively. Regionally, Oceania had the highest ASPR for endometriosis, East Asia for unexplained infertility, and high‐income Asia Pacific for PCOS. Infertility attributable to PCOS exhibited higher age‐standardized prevalence and YLDs rates compared to endometriosis in most regions. Notably, ASPRs and ASDRs for endometriosis and unexplained infertility decreased with SDI, while PCOS rates increased with SDI. Conclusions: The increasing global burden of endometriosis, PCOS, and unexplained infertility among WCBA has significantly contributed to rising infertility rates, with distinct regional and demographic disparities. Targeted public health strategies are needed to address these trends.

Objectives: Electronic health records (EHRs) offer valuable real-world data (RWD) for Chinese medicine research. However, significant methodological challenges remain in developing integrative Chinese-Western medicine (ICWM) databases. This study aims to establish a best-practice methodological framework, referred to as BRIDGE, to guide the construction of ICWM databases using EHRs. Methods: We developed the methodological framework through a comprehensive process, including systematic literature review, synthesis of empirical experiences, thematic expert discussions, and consultation with an external panel to reach consensus. Results: The BRIDGE framework outlines 6 core components for ICWM-EHR database development: Overall design, database architecture, data extraction and linkage, data governance, data verification, and data quality evaluation. Key data elements include variables related to study population, treatment or exposure, outcomes, and confounders. These databases support various research applications, particularly in evaluating the effectiveness and safety of integrative therapies. To demonstrate its practical value, we developed an ICWM-EHR database on women’s reproductive lifespan, encompassing 2,064,482 patients. This database captures women’s health conditions across the life course, from reproductive age to older adulthood. Conclusions: The BRIDGE methodological framework provides a standardized approach to building high-quality ICWM-EHR databases. It offers a unique opportunity to strengthen the methodological rigor and real-world relevance of Chinese medicine research in integrated healthcare settings.