li guowei

ObjectivesRandomized controlled trials (RCTs) with repeatedly measured continuous variables as primary outcomes are common. Although statistical methodologies for calculating sample sizes in such trials have been extensively investigated, their practical application remains unclear. This study aims to provide an overview of sample size calculation methods for different research questions (e.g., key time point treatment effect, treatment effect change over time) and evaluate the adequacy of current practices in trial design.Study Design and SettingWe conducted a comprehensive search of PubMed to identify RCTs published in core journals in 2019 that utilized repeatedly measured continuous variables as their primary outcomes. Data were extracted using a predefined questionnaire including general study characteristics, primary outcomes, detailed sample size calculation methods, and methods for analyzing …

Background Stevioside (SV) with minimal calories is widely used as a natural sweetener in beverages due to its high sweetness and safety. However, the effects of SV on glucose uptake and the pyruvate dehydrogenase kinase isoenzyme (PDK4) as an important protein in the regulation of glucose metabolism, remain largely unexplored. In this study, we used C2C12 skeletal muscle cells that was induced by palmitic acid (PA) to assess the effects and mechanisms of SV on glucose uptake and PDK4. Methods The glucose uptake of C2C12 cells was determined by 2‐NBDG; expression of the Pdk4 gene was measured by quantitative real‐time PCR; and expression of the proteins PDK4, p‐AMPK, TBC1D1 and GLUT4 was assessed by Western blotting. Results In PA‐induced C2C12 myotubes, SV could significantly promote cellular glucose uptake by decreasing PDK4 levels and increasing p‐AMPK and …

Background and ObjectivesAmong observational studies of routinely collected health data (RCD) for exploring treatment effects, algorithms are used to identify study variables. However, the extent to which algorithms are reliable and impact the credibility of effect estimates is far from clear. This study aimed to investigate the validation of algorithms for identifying study variables from RCD, and examine the impact of alternative algorithms on treatment effects.MethodsWe searched PubMed for observational studies published in 2018 that used RCD to explore drug treatment effects. Information regarding the reporting, validation, and interpretation of algorithms was extracted. We summarized the reporting and methodological characteristics of algorithms and validation. We also assessed the divergence in effect estimates given alternative algorithms by calculating the ratio of estimates of the primary vs. alternative …

Aim Heart failure (HF) is a major cause of morbidity and mortality in older adults. Randomized controlled trials (RCTs) inform HF policy and practice, but the accurate interpretation of results is contingent on clear and transparent reporting. The CONsolidated Standards Of Reporting Trials (CONSORT) statement serves as a guide to RCT reporting. We evaluated the quality of reporting in HF RCTs in high‐impact journals by assessing their adherence to CONSORT. Methods and results We searched MEDLINE, EMBASE and CINAHL for HF RCTs published in high‐impact journals 2000–2020. We assessed the proportion of CONSORT criteria that individual HF RCTs adhered to, and used the Jonckheere–Terpstra test to examine temporal trends in adherence. Multivariable linear regression explored the association between trial characteristics and adherence to CONSORT. Primary analysis assessed adherence to …

Background Chronic kidney disease (CKD) poses a significant global public health challenge. While lipoprotein(a) (Lp[a]) has been established as a significant factor in cardiovascular disease, its connection to CKD risk remains a topic of debate. Existing evidence indicates diverse risks of kidney disease among individuals with various renal function indicators, even when within the normal range. Objective This study aims to investigate the joint associations between different renal function indicators and Lp(a) regarding the risks of incident CKD in the general population. Methods The analysis involved a cohort of 329,415 participants without prior CKD who were enrolled in the UK Biobank between 2006 and 2010. The participants, with an average age of 56 (SD 8.1) years, included 154,298/329,415 (46.84%) males. At baseline, Lp(a) levels were measured using an immunoturbidimetric assay and classified into 2 groups: low (<75 nmol/L) and high (≥75 nmol/L). To assess participants’ baseline renal function, we used the baseline urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). The relationship between Lp(a), renal function indicators, and the risk of CKD was evaluated using multivariable Cox regression models. These models were adjusted for various factors, including sociodemographic variables, lifestyle factors, comorbidities, and laboratory measures. Results A total of 6003 incident CKD events were documented over a median follow-up period of 12.5 years. The association between elevated Lp(a) levels and CKD risk did …

Objective Time‐varying treatments are common in observational studies. However, when assessing treatment effects, the methodological framework has not been systematically established for handling time‐varying treatments. This study aimed to examine the current methods for dealing with time‐varying treatments in observational studies and developed practical recommendations. Methods We searched PubMed from 2000 to 2021 for methodological articles about time‐varying treatments, and qualitatively summarized the current methods for handling time‐varying treatments. Subsequently, we developed practical recommendations through interactive internal group discussions and consensus by a panel of external experts. Results Of the 36 eligible reports (22 methodological reviews, 10 original studies, 2 tutorials and 2 commentaries), most examined statistical methods for time‐varying treatments, and …

ObjectiveWe aimed to investigate the independent and joint associations between metabolic status, PA (physical activity) and risk of CVD (cardiovascular disease) in participants with obesity.MethodsWe included 109,301 adults with obesity free of baseline CVD enrolled from 2006 to 2010 in the UK Biobank cohort (aged 56 ± 7.9 years). Based on metabolic status, obesity was grouped into metabolically healthy obesity (MHO; free of hypertension, hypercholesterolemia and diabetes; n = 26,989; BMI 33 ± 3.3 kg/m2) and metabolically unhealthy obesity (MUO; n = 82,312; BMI 34 ± 4.0 kg/m2). PA was categorized into four groups according to moderate-to-vigorous PA (MVPA): none, low, medium, and high. Multivariable Cox regression models were used for the main analyses adjusting for sociodemographic factors, lifestyles and comorbidities.ResultsThere were 8,059 CVD events during a median follow …

MethodsWe searched Medline (via PubMed) for RCTs that enrolled newborns or their birthing parents, reported outcomes in the children, and were published between January 1, 2020, and December 31, 2022. The search was limited to selected high-impact general medical journals (Lancet, New England Journal of Medicine, Journal of the American Medical Association, British Medical Journal), and pediatric specialty journals (JAMA Pediatrics, Pediatrics, Lancet Child and Adolescent Health). We did not intend to perform a systematic review of imputation practices in all recently published perinatal and neonatal trials. Instead, we examined a small sample of target journals for perinatal and neonatal RCTs with high impact factors to examine best-case scenarios of current imputation practices.

Steviol glycosides (SGs) are recognized as safe natural sweeteners; however, evidence from randomized controlled trials (RCTs) showed an inconclusive effect of SGs on glucose metabolism in adult participants. We aimed to conduct a systematic review and meta-analysis of RCTs to assess the effect of SGs on glucose metabolism. We systematically searched PubMed, Web of Science and EMBASE to include eligible RCTs. Our primary outcomes were differences between SGs and the control group with respect to changes in blood glucose from the baseline to the end of intervention (including fasting blood glucose [FBG], and HbA1c measurements). A random-effects meta-analysis was conducted for data synthesis to calculate the pooled mean difference (MD). There were twelve RCTs included for analyses with a total of 871 participants (48% females). A significant effect of SGs on FBG (MD = −4.10 mg dl−1, 95 …

Uncontrolled pathogenic genome mutations in germline cells might impair adult fertility, lead to birth defects or even affect the adaptability of a species. Understanding the sources of DNA damage, as well as the features of damage response in germline cells are the overarching tasks to reduce the mutations in germline cells. With the accumulation of human genome data and genetic reports, genome variants formed in germline cells are being extensively explored. However, the sources of DNA damage, the damage repair mechanisms, and the effects of DNA damage or mutations on the development of germline cells are still unclear. Besides exogenous triggers of DNA damage such as irradiation and genotoxic chemicals, endogenous exposure to inflammation may also contribute to the genome instability of germline cells. In this review, we summarized the features of de novo mutations and the specific DNA …

The association between dietary iron intake and the risk of type 2 diabetes mellitus (T2DM) remains inconsistent. In this study, we aimed to investigate the relationship between trajectories of dietary iron intake and risk of T2DM. This study comprised a total of 61,115 participants without a prior T2DM from the UK Biobank database. We used the group-based trajectory model (GBTM) to identify different dietary iron intake trajectories. Cox proportional hazards models were used to evaluate the relationship between trajectories of dietary iron intake and risk of T2DM. During a mean follow-up of 4.8 years, a total of 677 T2DM events were observed. Four trajectory groups of dietary iron intake were characterized by the GBTM: trajectory group 1 (with a mean dietary iron intake of 10.9 mg/day), 2 (12.3 mg/day), 3 (14.1 mg/day) and 4 (17.6 mg/day). Trajectory group 3 was significantly associated with a 38% decreased risk of …

Aims To explore the relationship between remnant cholesterol (RC) and the risk of premature mortality as well as life expectancy in the general population. Methods We included a total of 428 804 participants from the UK Biobank for analyses. Equivalent population percentiles approach based on the low-density lipoprotein cholesterol cut-off points was performed to categorize participants into three RC groups: low (with a mean RC of 0.34 mmol/L), moderate (0.53 mmol/L), and high (1.02 mmol/L). We used multivariable Cox proportional hazards models to evaluate the relationship between RC groups and the risk of premature mortality (defined as death before age 75 years). Life table methods were used to estimate life expectancy by RC groups. Results During a median follow-up of 12.1 years (Q1–Q3 11.0–13.0), there were 23 693 all-cause premature …

Type 2 diabetes mellitus prevalence increases with age and the disease predisposes to increased risk of fractures and skeletal complications. One possible contributor to skeletal weakening in diabetes is a decline in blood supply. We hypothesised that bone blood flow is impaired in diabetic mice and that chronic administration of glucagon-like peptide-1 receptor agonists (GLP-1RA) can increase blood flow to bone, thereby stimulating bone formation and improving bone architecture.Nine weeks old male diabetic (db/db) and control mice were daily injected subcutaneously for 28 days with saline or the GLP-1RA Exenatide (Ex-4)(10 μg/kg per day)(n= 10/group). The effect of Ex-4 on hind limb perfusion was measured by laser Doppler imaging. Tibial bone architecture was imaged by micro-CT ex-vivo.

Objectives To explore trends in risk factor control (hypertension, diabetes mellitus, hyperlipidaemia) in patients with gout and medication use among those whose risk factor control targets were not achieved. Methods We used the data from National Health and Nutrition Examination Survey (NHANES) between 2007–2008 and 2017–2018 for analyses. The study samples were weighted so that they could be representative of the non-institutionalized US population. We conducted a cross-sectional analysis to assess trends in risk factor control and medication use, and employed logistic regression analyses to explore patient characteristics associated with risk factor control. Results The prevalence of participants in whom blood pressure control target was achieved decreased from 64.6% in 2007–2008 to 55.3% in 2017–2018 (P-value for trend = 0.03). The …

Background Time‐varying drug treatments are common in studies using routinely collected health data (RCD) for assessing treatment effects. This study aimed to examine how these studies reported, handled, and interpreted time‐varying drug treatments. Methods A systematic search was conducted on PubMed from 2018 to 2020. Eligible studies were those used RCD to explore drug treatment effects. We summarized the reporting characteristics and methods employed for handling time‐varying treatments. Logistic regressions were performed to investigate the association between study characteristics and the reporting of time‐varying treatments. Results Two hundred and fifty‐six studies were included, and 225 (87.9%) studies involved time‐varying treatments. Of these, 24 (10.7%) reported the proportion of time‐varying treatments and 105 (46.7%) reported methods used to handle time‐varying treatments …

BackgroundRoutinely collected health data (RCD) are important resource for exploring drug treatment effects. Adequate reporting of data source profiles may increase the credibility of evidence generated from these data. This study conducted a systematic literature review to evaluate the reporting characteristics of databases used by RCD studies to explore the effects of drug treatment.MethodsObservational studies published in 2018 that used RCD to explore the effects of drug treatment were identified by searching PubMed. We categorized eligible reports into two groups by journal impact factor (IF), including the top 5 general medical journals (NEJM, Lancet, JAMA, BMJ and JAMA Internal Medicine) and the other journals. The reporting characteristics of the databases used were described and compared between the two groups and between studies citing and not citing database references.ResultsA total of 222 …

Introduction Limited evidence indicates an association between sleep factors and the risk of Parkinson’s disease (PD). However, large prospective cohort studies including both sexes are needed to verify the association between daytime sleepiness, sleep duration, and PD risk. Furthermore, other sleep factors like chronotype and snoring and their impact on increased PD risk should be explored by simultaneously considering daytime sleepiness and snoring. Methods This study included 409,923 participants from the UK Biobank. Data on five sleep factors (chronotype, sleep duration, sleeplessness/insomnia, snoring, and daytime sleepiness) were collected using a standard self-administered questionnaire. PD occurrence was identified using linkages with primary care, hospital admission, death register, or self-report. Cox proportional hazard models were used to investigate the association between sleep factors …

Background Evidence about the associations between obesity severity, metabolic status and risk of incident cardiovascular disease (CVD) in adults with obesity remains limited. Methods The study included 109,301 adults with obesity free of prior CVD based on the UK Biobank cohort. Metabolic status was categorized into metabolically healthy obesity (MHO; free of hypertension, hypercholesterolemia and diabetes) and metabolically unhealthy obesity (MUO). Obesity severity was classified into three levels: class I (body mass index of 30.0–34.9 kg/m2), II (35.0–39.9) and III (≥40.0). Cox proportional hazards models were used for analyses. Results There were 8059 incident CVD events during a median follow‐up of 8.1 years. MUO was significantly associated with a 74% increased CVD risk compared with MHO (HR = 1.74, 95% CI: 1.62–1.83). There was a significant interaction between obesity severity and …

The Authors Reply: We appreciate the comments on our paper. 1 Previous studies showed that patients with diabetes mellitus (DM) had more than two-fold higher risk of developing heart failure (HF) than patients without DM. 2, 3 Moreover, there was evidence displaying that the occurrence of HF in participants with DM increased their mortality risk by 10-fold, with the 5-year survival rate being only 12.5%. 4 Thus, our study targeted patients with DM to evaluate the relationship between remnant cholesterol (RC) and risk of HF. However, we agreed with their comments on participants with acute coronary syndrome and future endeavors to specify diabetes patients with and without coronary heart disease would be worthwhile.Regarding the concern about competing events of mortality, we indeed performed a sensitivity analysis by using a competing risk model and taking all-cause deaths as the competing events of HF …

Introduction Although interest in including non-randomised studies of interventions (NRSIs) in meta-analysis of randomised controlled trials (RCTs) is growing, estimates of effectiveness obtained from NRSIs are vulnerable to greater bias than RCTs. The objectives of this study are to:(1) explore how NRSIs can be integrated into a meta-analysis of RCTs;(2) assess concordance of the evidence from non-randomised and randomised trials and explore factors associated with agreement; and (3) investigate the impact on estimates of pooled bodies of evidence when NRSIs are included. Methods and analysis We will conduct a systematic survey of 210 systematic reviews that include both RCTs and NRSIs, published from 2017 to 2022. We will randomly select reviews, stratified in a 1: 1 ratio by Core vs non-Core clinical journals, as defined by the National Library of Medicine. Teams of paired reviewers will …