Background: The objective of the current study was to evaluate whether the use of traditional Chinese medicine, Fuzheng Yiqing granule (FZYQG), was associated with a reduced infection risk of COVID-19 in close contacts.

Research design and methods: This was a prospective cohort study across 203 quarantine centres for close contacts and secondary contacts of COVID-19 patients in Yangzhou city. FZYQG group was defined as quarantined individuals who voluntarily took FZYQG; control group did not take FZYQG. The primary outcome was the coronavirus test positive rate during quarantine period. Logistic regression with propensity score inverse probability weighting was used for adjusted analysis to evaluate independent association between FZYQG and test positive rate.

Results: From July 13, 2021 to September 30, 2021, 3438 quarantined individuals took FZYQG and 2248 refused to take the granule. Test positive rate was significantly lower among quarantined individuals who took FZYQG (0.29% vs. 1.73%, risk ratio 0.17, 95% confidence interval (CI): 0.08–0.34, p < 0.001). On logistic regression, odds for test positive were decreased in FZYQG group (odds ratio: 0.16, 95% CI: 0.08–0.32, p < 0.001).

Conclusions: Close and secondary contacts of COVID-19 patients who received FZYQG had a lower test positive rate than control individuals in real-world experience.

Trial registration: This study has been registered on Chinese Clinical Trial Registry (ChiCTR2100049590) on August 5, 2021.

Objective: This study aimed to quantify the association between step count and multiple health outcomes in a healthy population.

Methods: PubMed, Embase, Web of Science, and The Cochrane Library were systematically searched for systematic reviews and meta-analyses from inception to April 1, 2022. Literature screening, data extraction, and data analysis were performed in this umbrella review. The intervention factor was daily step counts measured based on devices. Multiple health outcomes included metabolic diseases, cardiovascular diseases, all-cause mortality, and other outcomes in the healthy population.

Results: Twenty studies with 94 outcomes were identified in this umbrella review. The increase in daily step count contributed to a range of human health outcomes. Furthermore, the special population, different age groups, countries, and cohorts should be carefully considered. Negative correlation between step counts and the following outcomes: metabolic outcomes, cardiovascular diseases, all-cause mortality, postural balance, cognitive function, and mental health. However, there was no association between participation in the outdoor walking group and the improvement of systolic blood pressure and diastolic blood pressure. Analysis of the dose–response association between increasing daily step count and the risk of cardiovascular disease events and all-cause mortality showed a substantially linear relationship.

Conclusion: A wide range of health outcomes can benefit from the right number of steps.

Objective: Thiazides are the first-line treatment for hypertension, however, they have been associated with hospitalizations for thiazide-associated hyponatremia (TAH). The aim of this study was to evaluate the risk of TAH and other drug-associated hyponatremia in a Korean population.

Methods: The study used big data from the National Health Insurance Sharing Service of 1,943,345 adults treated for hypertension from January 2014 to December 2016. The participants were divided into two groups based on the use of thiazides. Cox proportional hazard models were used to identify independent risk factors for the occurrence of hyponatremia.

Results: The study found that hyponatremia-related hospitalizations were significantly higher in the thiazide group than the control group (2.19% vs. 1.45%). The risk increased further with concurrent use of other diuretics or desmopressin, and thiazide+spironolactone+desmopressin and hospitalization risk further increased (4.0 and 6.9 times). Multivariate analysis showed that hyponatremia occurrence increased with age, diabetes mellitus, depression, and thiazide use (hazard ratio = 1.436, p < 0.001). The thiazide group had better 6-year overall survival than the control group but had more fractures and hyponatremia.

Conclusions: Thiazide use is associated with an increased risk of hyponatremia and related complications. However, the mortality rate decreased in those who received thiazides, suggesting that thiazide use itself is not harmful and may help decrease complications and improve prognosis with proper, cautious use in high-risk patients.

Aim: It is essential for health researchers to have a systematic understanding of third-party variables that influence both the exposure and outcome under investigation, as shown by a directed acyclic graph (DAG). The traditional construction of DAGs through literature review and expert knowledge often needs to be more systematic and consistent, leading to potential biases. We try to introduce an automatic approach to building network linking variables of interest.

Methods: Large-scale text mining from medical literature was utilized to construct a conceptual network based on the Semantic MEDLINE Database (SemMedDB). SemMedDB is a PubMed-scale repository of the “concept-relation-concept” triple format. Relations between concepts are categorized as Excitatory, Inhibitory, or General.

Results: To facilitate the use of large-scale triple sets in SemMedDB, we have developed a computable biomedical knowledge (CBK) system (https://cbk.bjmu.edu.cn/), a website that enables direct retrieval of related publications and their corresponding triples without the necessity of writing SQL statements. Three case studies were elaborated to demonstrate the applications of the CBK system.

Conclusions: The CBK system is openly available and user-friendly for rapidly capturing a set of influencing factors for a phenotype and building candidate DAGs between exposure-outcome variables. It could be a valuable tool to reduce the exploration time in considering relationships between variables, and constructing a DAG. A reliable and standardized DAG could significantly improve the design and interpretation of observational health research.

Aim: To determine the comparative effectiveness of fluid schemes for children with diabetic ketoacidosis (DKA).

Methods: We conducted a systematic review with an attempt to conduct network meta-analysis (NMA). We searched MEDLINE, EMBASE, CENTRAL, Epistemonikos, Virtual Health Library, and gray literature from inception to July 31, 2022. We included randomized controlled trials (RCTs) in children with DKA evaluating any intravenous fluid schemes. We planned to conduct NMA to compare all fluid schemes if heterogeneity was deemed acceptable.

Results: Twelve RCTs were included. Studies were heterogeneous in the population (patients and DKA episodes), interventions with different fluids (saline, Ringer's lactate (RL), and polyelectrolyte solution-PlasmaLyte^®), tonicity, volume, and administration systems. We identified 47 outcomes that measured clinical manifestations and metabolic control, including single and composite outcomes and substantial heterogeneity preventing statistical combination. No evidence was found of differences in neurological deterioration (main outcome), but differences were found among interventions in some comparisons to normalize acid-base status (∼2 h less with low vs. high volume); time to receive subcutaneous insulin (∼1 h less with low vs. high fluid rate); length of stay (∼6 h less with RL vs. saline); and resolution of the DKA (∼3 h less with two-bag vs. one-bag scheme). However, available evidence is scarce and poor.

Conclusions: There is not enough evidence to determine the best fluid therapy in terms of fluid type, tonicity, volume, or administration time for DKA treatment. There is an urgent need for more RCTs, and the development of a core outcome set on DKA in children.

Objective: The efficacy and prognostic value of circulating tumor cells (CTCs) in nonsmall cell lung cancer (NSCLC) are controversial based on the existing research. This systematic review and meta-analysis evaluated the significance of CTCs in NSCLC therapy monitoring and prognosis prediction, supporting their potential as clinical biomarkers.

Methods: We conducted a comprehensive search of PubMed, Embase, Web of Science, The Cochrane Library, WanFang Data, CNKI, and VIP through September 20, 2023. Inclusion criteria were cohort studies involving NSCLC patients, focusing on peripheral blood CTCs, and assessing outcomes such as pre- and posttreatment CTC rates or levels, progression-free survival (PFS), and overall survival (OS). Two reviewers independently extracted the data and assessed risk of bias using the Newcastle-Ottawa Scale. We utilized Review Manager 5.4.1 for meta-analysis, calculating pooled odds ratios (ORs) for dichotomous outcomes, mean differences for continuous variables and hazard ratios (HRs) for survival data, applying fixed- or random-effects models based on heterogeneity assessed by the I2 statistic. This study was registered in PROSPERO (No. CRD42023450035).

Results: Twenty-two eligible studies with a total of 1674 NSCLC patients were included. Meta-analysis results showed that the CTCs-positive rate (OR = 0.59, 95% CI 0.45 to 0.77, p = 0.0001) and CTCs count (mean difference = –3.10, 95% CI –5.52 to –0.69, p = 0.01) were significantly decreased after antitumor treatment. Compared with the CTCs nonreduced group, the CTC-reduced group showed better PFS (HR = 1.71, 95% CI 1.35 to 2.17, p < 0.00001) and OS (HR = 1.50, 95% CI 1.21 to 1.86, p = 0.0003) after treatment. PFS and OS in CTC-positive groups were lower than those in the CTCs-negative group pretreatment (HR = 2.49, 95% CI 1.78 to 3.47, p < 0.00001; HR = 1.80, 95% CI 1.29 to 2.52, p = 0.0006) and posttreatment (HR = 3.36, 95% CI 2.12 to 5.33, p < 0.00001; HR = 3.31, 95% CI 1.75 to 6.27, p = 0.0002).

Conclusions: CTCs can be used as a biomarker to monitor NSCLC efficacy, predict prognosis and guide follow-up treatment.

Objective: This meta-analysis aimed to comprehensively explore the risk factors for inadequate bowel preparation (IBP).

Methods: We searched the Embase, PubMed, Web of Science, and The Cochrane Library databases up to August 24, 2023, to identify observational studies and randomized controlled trials (RCTs) that examined risk factors for IBP. A random effects model was used to pool the adjusted odds ratios and 95% confidence intervals.

Results: A total of 125 studies (91 observational studies, 34 RCTs) were included. Meta-analyses of observational studies revealed that three preparation-related factors, namely, characteristics of last stool (solid or brown liquid), incomplete preparation intake, and incorrect diet restriction, were strong predictors of IBP. The other factors were moderately correlated with IBP incidence, including demographic variables (age, body mass index, male sex, Medicaid insurance, and current smoking), comorbidities (diabetes, liver cirrhosis, psychiatric disease, Parkinson's disease, previous IBP, poor mobility, inpatient, and Bristol stool form 1/2), medications (tricyclic antidepressants, opioids, antidepressants, narcotics, antipsychotics, and calcium channel blockers), and preparation-related factors (preparation-to-colonoscopy interval not within 3 to 5/6 h, nonsplit preparation, and preparation instructions not followed). No colonoscopy indications were found to be related to IBP. Meta-analyses of RCTs showed that education, constipation, stroke/dementia, and discomfort during preparation were also moderately associated with IBP. Most of the other findings were consistent with the pooled results of observational studies. However, primarily due to imprecision and inconsistency, the certainty of evidence for most factors was very low to moderate.

Conclusions: We summarized five categories of risk factors for IBP. Compared to demographic variables, comorbidities, medications, and colonoscopy indications, preparation-related elements were more strongly associated with IBP. These findings may help clinicians identify high-risk individuals and provide guidance for IBP prevention.

Background: The number of published journal articles has grown exponentially during the last 30 years, which may have led to some wasteful research. However, the terminology associated with research waste remains unclear. To address this, we aimed to identify, define, and categorize the aspects of research waste in published biomedical reports.

Methods: In this scoping review, we systematically searched for biomedical literature reports from 1993 to 2023 in two databases, focusing on those addressing and defining research waste. Through data charting, we analyzed and categorized the aspects of research waste.

Results: Based on 4285 initial records in the searches, a total of 832 reports were included in the analysis. The included reports were primarily narrative reviews (26%) and original reports (21%). We categorized research waste into five aspects: methodological, invisible, negligible, underreported, and structural (MINUS) research waste. More than half of the reports (56%) covered methodological research waste concerning flaws in study design, study conduct, or analysis. Invisible research waste covered nonpublication, discontinuation, and lack of data-sharing. Negligible research waste primarily concerned unnecessary repetition, for example, stemming from the absence of preceding a trial with a systematic review of the literature. Underreported research waste mainly included poor reporting, resulting in a lack of transparency. Structural research waste comprised inadequate management, collaboration, prioritization, implementation, and dissemination.

Conclusion: MINUS encapsulates the five main aspects of research waste. Recognizing these aspects of research waste is important for addressing and preventing further research waste and thereby ensuring efficient resource allocation and scientific integrity.

Objective: Existing evidence of the relationship between induced abortion and ectopic pregnancy has not been assessed rigorously. This systematic review provides a comprehensive evaluation to examine whether induced abortion (IA) can increase the rate of ectopic pregnancy (EP).

Methods: We searched PubMed, EMBASE, Web of Science, Cochrane, CNKI, WanFang, and Sinomed databases since their inception until February 2023. Eligibility criteria included case-control studies and cohort studies that analyzed induced abortion associated with ectopic pregnancy. Data analyses were conducted by using R-studio Version 1.1.383 software.

Results: A total of 33 case-control studies and 7 cohort studies involving 132,926 participants were included. In case-control studies, there was a significant association between induced abortion and ectopic pregnancy by using single-factor analysis data (OR = 2.32, 95% CI = 1.81–2.98). Subgroup analysis by region suggested no statistical significance in the Americas (OR = 1.15, 95% CI = 0.92–1.43) and Eastern Mediterranean (OR = 3.64, 95% CI = 0.88–15.18). The relationship was significant by using multiple regression analysis data (OR = 1.97, 95% CI = 1.38–2.80). In cohort studies, statistical significance was found (OR = 1.42, 95% CI = 1.001–2.018) after omitting one study in sensitivity analysis. The combined results of the two types of studies suggested that induced abortion would increase the risk of ectopic pregnancy to some degree, but the conclusion needs to be considered with caution.

Conclusion: This study indicated that IA could increase the risk of EP to some degree and the times of IA had a negative impact on the risk. Safe abortion and avoiding repeat abortion due to unintended pregnancy could protect women's fertility.

Objective: This study aimed to evaluate the safety and efficacy of the fixed-ratio combination (FRC) and free combination of basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1RA) in patients with type 2 diabetes mellitus (T2DM).

Methods: PubMed, Web of Science, Embase, The Cochrane Library, and four Chinese databases were searched for relevant studies from inception to April 13, 2023. Phase III clinical trials involving FRC or free combination in patients with uncontrolled T2DM were included. A network meta-analysis (NMA) was used to evaluate the effects of FRC and free combination. The Cochrane Collaboration's tool was used to evaluate the risk-of-bias. The primary outcomes were changes in hemoglobin A1c (HbA1c), body weight, and incident hypoglycemia. Secondary outcomes included changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP). This study was registered with PROSPERO (CRD42023409585).

Results: Forty-two trials with 23,619 patients were included in the NMA, and treatments were categorized as FRC, free combination and NOINSGLP (neither FRC nor free combination). The forest plots revealed comparable HbA1c control (mean difference (MD) = 0.07%, 95% confidence interval (CI): –0.17 to –0.30) between free combination and FRC. However, there were significant differences in the body weight (MD = –2.06 kg; 95% CI: –3.34 to –0.77), SBP (MD = –1.22 mmHg; 95% CI: –2.41 to –0.04), and DBP (MD = –1.09 mmHg; 95% CI: –1.94 to –0.24) between the two groups.

Conclusions: In patients with uncontrolled T2DM, the safety and efficacy of FRC and free combination therapy were comparable. The use of FRC is justifiable in patients requiring free combination.

Objective: The effect of hormone replacement therapy (HRT) on colorectal cancer (CRC) mortality and all-cause mortality remains unclear. We conducted a systematic review and dose–response meta-analysis to determine the effects of HRT on CRC mortality and all-cause mortality.

Methods: We searched the electronic databases of PubMed, Embase, and The Cochrane Library for all relevant studies published until January 2024 to investigate the effects of HRT exposure on survival rates for patients with CRC. Two reviewers independently extracted individual study data and evaluated the risk of bias between the studies using the Newcastle‒Ottawa Scale. We performed a two-stage random-effects dose–response meta-analysis to examine a possible nonlinear relationship between the year of HRT use and CRC mortality.

Results: Ten cohort studies with 480,628 individuals were included. HRT was inversely associated with the risk of CRC mortality (hazard ratios (HR) = 0.77, 95% CI (0.68, 0.87), I² = 69.5%, p < 0.05). The pooled results of seven cohort studies revealed a significant association between HRT and the risk of all-cause mortality (HR = 0.71, 95% CI (0.54, 0.92), I² = 89.6%, p < 0.05). A linear dose–response analysis (p for nonlinearity = 0.34) showed a 3% decrease in the risk of CRC for each additional year of HRT use; this decrease was significant (HR = 0.97, 95% CI (0.94, 0.99), p < 0.05). An additional linear (p for nonlinearity = 0.88) dose–response analysis showed a nonsignificant decrease in the risk of all-cause mortality for each additional year of HRT use.

Conclusions: This study suggests that the use of HRT is inversely associated with all-cause and colorectal cancer mortality, thus causing a significant decrease in mortality rates over time. More studies are warranted to confirm this association.

Objective: Narrowband ultraviolet B (NB-UVB) has been recommended as first-line therapy for early-stage mycosis fungoides (MF) in international guidelines. NB-UVB can be used as monotherapy or part of a multimodality treatment regimen. There is limited evidence on the effectiveness and optimal patients of NB-UVB in combination with systemic therapies in MF. We aimed to assess the effectiveness of the combination versus NB-UVB monotherapy in early-stage MF and if plaque lesion status was related to these effects.

Methods: This observational cohort study included 247 early-stage MF patients who had received NB-UVB combined with systemic therapies vs. NB-UVB monotherapy from 2009 to 2021. The primary outcome was partial or complete response. Overall response rate and median time to response were calculated. Hazard ratios (HRs) were estimated using the Cox model.

Results: In 139 plaque-stage patients, the response rate for combination therapy group was higher than that of monotherapy group (79.0% vs. 54.3%, p = 0.006). The adjusted HR for combination therapy compared with NB-UVB monotherapy was 3.11 (95% CI 1.72–5.63). The combination therapy group also showed shorter time to response (4 vs. 6 months, p = 0.002). In 108 patch-stage patients, the response rate and time to response in two treatment groups showed no significant difference. There was therefore an observed interaction with patients’ plaque lesion status for the effect size of NB-UVB combination therapy. No serious adverse events were observed.

Conclusions: Adding systemic treatments to NB-UVB did not improve the treatment outcome of patch-stage patients, but it surpassed NB-UVB monotherapy for early-stage patients with plaques.

Objective: As a large and populous country, China releases a high number of diagnostic criteria. However, the published diagnostic criteria have not yet been systematically analyzed. Therefore, the aim of this study is to investigate the characteristics, development methods, reporting quality, and evidence basis of diagnostic criteria published in China.

Methods: We searched five databases for diagnostic criteria from their inception until July 31, 2023. All diagnostic criteria were screened through abstract and full-text reading, and included if satisfying the prespecified criteria. Two researchers independently extracted data on the characteristics, development methods, reporting quality, and evidence basis of diagnostic criteria.

Results: A total of 143 diagnostic criteria were included. In terms of development methods, the proportions of diagnostic criteria that involved a systematic literature search (n = 2; 1.4%; 95% confidence interval (CI), 0.4% to 5.0%), adoption of formal consensus methods (n = 4; 2.8%; 95% CI, 1.1% to 7.0%), and criteria validation (n = 9; 6.3%; 95% CI, 3.3% to 11.5%) were relatively low. Regarding reporting quality, the average compliance with the ACCORD checklist was 5.1%; none of the diagnostic criteria reported on registration, expert inclusion criteria, expert recruitment process, or consensus results. A majority (58.7%; 95% CI, 50.6% to 66.5%) of criteria did not cite any research, and only one (0.7%; 95% CI, 0.1% to 3.9%) criterion was derived from a systematic review. Moreover, only 16.1% (95% CI, 11.0% to 23.0%) of diagnostic criteria used evidence from the Chinese population.

Conclusion: The diagnostic criteria developed in China exhibit serious flaws, particularly in evidence retrieval, formation of expert panels, consensus methods, and validation. Additionally, only few diagnostic criteria used a systematic synthesis of the evidence or evidence from the China. There is an urgent need to enhance the methodology for developing diagnostic criteria.

Inflammatory bowel disease (IBD) is a chronic and relapsing immune-mediated disease of the gastrointestinal tract with a gradually increasing global incidence and prevalence. A prolonged course of IBD leads to a decline in patient quality of life and the creation of a substantial economic burden on society. Owing to the lack of specific diagnostic markers, the diagnosis of IBD still needs a gold standard based on a combination of clinical manifestations, imaging, laboratory, and endoscopic results. Accordingly, the current goals of IBD treatment are to alleviate clinical symptoms and reduce recurrence rates. Therefore, it is imperative to develop a standard set of procedures to diagnose and treat IBD. In this review, we summarize prominent and emerging studies, outline classical and contemporary approaches to diagnosing and managing IBD, and integrate multiple guidelines. Furthermore, we propose the possibility of establishing an early and comprehensive diagnostic workflow and personalized management strategy in the future. We aim to enhance the quality and standardization of diagnostic and treatment procedures for IBD.

Rapid review (RR) could accelerate the traditional systematic review (SR) process by simplifying or omitting steps using various shortcuts. With the increasing popularity of RR, numerous shortcuts had emerged, but there was no consensus on how to choose the most appropriate ones. This study conducted a literature search in PubMed from inception to December 21, 2023, using terms such as “rapid review” “rapid assessment” “rapid systematic review” and “rapid evaluation”. We also scanned the reference lists and performed citation tracking of included impact studies to obtain more included studies. We conducted a narrative synthesis of all RR approaches, shortcuts and studies assessing their effectiveness at each stage of RRs. Based on the current evidence, we provided recommendations on utilizing certain shortcuts in RRs. Ultimately, we identified 185 studies focusing on summarizing RR approaches and shortcuts, or evaluating their impact. There was relatively sufficient evidence to support the use of the following shortcuts in RRs: limiting studies to those published in English-language; conducting abbreviated database searches (e.g., only searching PubMed/MEDLINE, Embase, and CENTRAL); omitting retrieval of grey literature; restricting the search timeframe to the recent 20 years for medical intervention and the recent 15 years for reviewing diagnostic test accuracy; conducting a single screening by an experienced screener. To some extent, the above shortcuts were also applicable to SRs. This study provided a reference for future RR researchers in selecting shortcuts, and it also presented a potential research topic for methodologists.

Aim: Both excessive intake of sodium and inadequate intake of potassium are associated with blood pressure elevation and subsequent increase in the risk of cardiovascular disease, which accounts for the largest number of deaths in China and worldwide. Low sodium salt, a mixture of mainly sodium chloride and potassium chloride, has shown its great potential as a promising population strategy for sodium intake reduction through multiple large-scale, multicenter, randomized controlled trials among populations including patients with cardiovascular disease, individuals with and without hypertension, older and younger adults, and men and women in China and other countries. This Guidelines aims to provide expert recommendations for promotion and use of low sodium salt in China, based on the current available scientific evidence regarding the effectiveness, safety, cost-effectiveness, and acceptability of low sodium salts in various population groups and different application scenarios. The suggestions to key stakeholders are also made.

Methods: A working group, an expert review committee and an advisory committee were established to be responsible for formulating the guidelines’ scope and key questions to be addressed, for searching, synthesizing, and evaluating research evidence, proposing and reviewing the recommendations. The consensus on the final recommendations was reached using the GRADE grid method.

Results: The working group summarized current available evidence of salt substitution regarding its effectiveness, safety, cost-effectiveness, acceptability, availability, suitability, etc. The Guidelines provided six recommendations advising different populations how to use low sodium salt, four recommendations on the application of low sodium salts in different scenarios, and five suggestions for key stakeholders to promote salt substitution.

Conclusion: The first evidence-based guidelines on promotion and use of low sodium salts covers all key questions in relevance and would play a critical role in prevention and control of hypertension and cardiovascular disease in China and worldwide.