Development and validation of knowledge, attitude, and practice scale regarding antibiotic use for Chinese medical students.

AIMS AND OBJECTIVES: This study aimed to develop and validate a knowledge, attitude, and practice scale of antibiotic use for Chinese medical students. METHOD: A five-phased procedure was adopted: (a) A item pool was constructed after literature review; (b) Delphi method was used to refine the items; (c) A pilot study was conducted to clarify the item; (d) Item analysis and exploratory factor analysis were used to finalize the scale; (e) Content validity, construct validity and reliability of the scale were analysed. RESULTS: The scale of 32 items, respectively 15, 9, and 8 for knowledge, attitude, and practice, was finalized. The item-level content validity ranged from 0.80 to 1.00. The scale-level content validity of the scale was 0.90. Model fit indices of total scale and the three dimensions met the criteria. Cronbach's α and the split-half coefficient were respectively 0.81 and 0.65 for the total scale. For each dimension, Cronbach's α varied from 0.68 to 0.89 and the split-half coefficient varied from 0.64 to 0.83. CONCLUSION: The scale can be used as a whole or separately, serving as an effective tool to measure medical students' knowledge, attitude, or practice regarding antibiotic use.

Ultrafast Conversion of Water and Oxygen Molecules With Dissociation of Hydrogen Bonding Effect to Achieve Extra-High Energy Efficiency of Secondary Metal-Air Batteries.

Metal-air secondary batteries with ultrahigh specific energies have received vast attention and are considered new promising energy storage. The slow redox reactions between oxygen-water molecules lead to low energy efficiency (55-71%) and limited applications. Herein, it is proposed that the MIL-68(In)-derived porous carbon nanotube supports the CoNiFeP heteroconjugated alloy catalyst with an overboiling point electrolyte to achieve the ultrahigh oxidation rate of water molecules. Structural characterization and density functional theory calculations reveal that the new catalyst greatly reduces the free energy of the process, and the overboiling point further accelerates the dissociation of O─H and hydrogen bonds, and the release of O2 molecules, achieving an extra-low overpotential of 110 mV@10 mA cm-2 far lower than commercial Ir/C catalysts of 192 mV at 125 °C and state-of-the-art. Furthermore, the energy efficiency of assembled rechargeable zinc-air batteries begins to break through at 85 °C, jumps at 100 °C, and reaches ultrahigh energy efficiency of 88.1% at 125 °C with an ultralow decay rate of 0.0068% after 150 cycles far superior to those of reported metal-air batteries. This work provides a new catalyst and electrolyte joint-design strategy and reexamines the battery operating temperature to construct higher energy efficiency for secondary fuel cells.

Combined healthy lifestyle behaviours and incident dementia: A systematic review and dose-response meta-analysis of cohort studies.

BACKGROUND: The associations of combined healthy lifestyle behaviours and incident dementia have not been systematically reviewed and the dose-response relationship was uncertain. OBJECTIVES: To evaluate the associations of combined healthy lifestyle behaviours with incident dementia and other cognitive outcomes, assess the dose-response relationship between the number of lifestyle behaviours and incident dementia, and summarise the adherence to healthy lifestyle behaviours. DESIGN: Systematic review and meta-analysis. METHODS: PubMed, EMBASE, Web of Science and PsycINFO were searched from inception to 20 Jan 2024. Cohort studies reporting associations of combined healthy lifestyle behaviours with incident dementia or other cognitive outcomes were included. We used the random-effects meta-analysis to pool the risk estimates and the robust error meta-regression method to examine the dose-response relationship. The methodological quality was assessed using the Newcastle-Ottawa Scale. RESULTS: A total of 22 articles including 25 cohort studies mostly from high-income economics were included, with all assessed as high methodological quality. Adherence to a healthy lifestyle was associated with a decreased risk of incident dementia, either per healthy lifestyle behaviour increase (pooled hazard ratio 0.89, 95 % confidence interval 0.85-0.94) or the highest level versus the lowest level (pooled hazard ratio 0.61, 95 % confidence interval 0.49-0.76). An inverse, linear dose-response relationship (Pnon-linear = 0.845) between the number of healthy lifestyle behaviours and incident dementia was observed, with an 11 % risk reduction for each healthy behaviour increase. A relatively limited number of included studies indicated that adherence to a healthy lifestyle combination could yield benefits for cognitive decline, global cognition, memory and executive function. In addition, the adherence rates typically decreased as the number of healthy lifestyle behaviours increased. CONCLUSIONS: Adherence to a healthy lifestyle was associated with a lower risk of incident dementia and other cognitive outcomes. It is important to find a subtle balance between the benefits and adherence. Further large cohort studies for combined lifestyle behaviours with specific cognitive outcomes and dose-response relationships are required, especially based on middle- and low-income populations. REGISTRATION: The study was registered in PROSPERO (CRD42023418509). TWEETABLE ABSTRACT: Engaging in a greater number of healthy lifestyle behaviours yields increased benefits in preventing dementia, albeit with lower adherence rates as a trade-off. Finding a delicate balance between the benefits and adherence is crucial.

Interaction of physical activity and low-level air pollution on cardiovascular disease: a prospective cohort study in UK Biobank.

To investigate the associations of physical activity (PA), low-level air pollution, and interaction on cardiovascular diseases (CVD) incidence based on the UK Biobank. PA was measured by the International Physical Activity Questionnaire and five air pollutants were estimated using Land Use Regression. All association estimates were based on Cox regression. Dose-response relationship was explored by restricted cubic spline, while multiplicative and additive interaction were examined by Pinteraction and relative excess risk due to interaction (RERI). As deviating proportional hazards assumption, we analyzed data as follow-up < 4 years and ≥ 4 years, separately. PA with 1000-4000 Metabolic Equivalent Task (MET) min/week showed the strongest protective impact on CVD incidence, while only low-level nitrogen dioxides (NO2) showed negative impact among five air pollutants and was considered for further analysis. Multiplicative interaction between PA and NO2 was observed during ≥ 4 years follow-up (Pinteraction = 0.049) while not during < 4 years (Pinteraction = 0.290). Positive additive interactions were found for high PA and low NO2 (< 20 µg/m3) group (RERI: 0.07, 95% confidence intervals: 0.02-0.11) during < 4 years, and for moderate PA with NO2 at 40- µg/m3 (0.07, 0.02-0.13) and < 20 µg/m3 (0.07, 0.02-0.12), while high PA showed similar results with NO2 at 40-, 20- and < 20 µg/m3 during ≥ 4 years. PA about 1000-4000 METs min/week showed the lowest CVD risk. Possibility of interaction with PA and NO2 is more likely to present with the increase in follow-up duration. We call for the optimal thresholds of PA, and exploring interaction thoroughly by considering types of PA.

Trial characteristics and treatment effect estimates in randomized controlled trials of Chinese herbal medicine: A meta-epidemiological study.

BACKGROUND: Previously published meta-epidemiological studies focused on Western medicine have identified some trial characteristics that impact the treatment effect of randomized controlled trials (RCTs). Nevertheless, it remains unclear if similar associations exist in RCTs on Chinese herbal medicine (CHM). Further, Chinese medicine-related characteristics have not been explored yet. OBJECTIVE: To investigate trial characteristics related to treatment effect estimates on CHM RCTs. SEARCH STRATEGY: This meta-epidemiological study searched 5 databases for systematic reviews on CHM treatment published between January 2011 and July 2021. INCLUSION CRITERIA: An eligible systematic review should only include RCTs of CHM and conduct at least one meta-analysis. DATA EXTRACTION AND ANALYSIS: Two reviewers independently conducted data extraction on general characteristics of systematic reviews, meta-analyses and included RCTs. They also assessed the risk of bias of RCTs using the Cochrane risk of bias tool. A two-step approach was used for data analyses. The ratio of odds ratios (ROR) and difference in standardized mean differences (dSMD) with 95% confidence interval (CI) were applied to present the difference in effect estimates for binary and continuous outcomes, respectively. RESULTS: Ninety-one systematic reviews, comprising 1338 RCTs were identified. For binary outcomes, RCTs incorporated with syndrome differentiation (ROR: 1.23; 95 % CI: [1.07, 1.39]), adopting Chinese medicine formula (ROR: 1.19; 95% CI: [1.03, 1.34]), with low risk of bias on incomplete outcome data (ROR: 1.29; 95% CI: [1.06, 1.52]) and selective outcome reporting (ROR: 1.12; 95% CI: [1.01, 1.24]), as well as a trial size ≥ 100 (ROR: 1.23; 95% CI: [1.04, 1.42]) preferred to show larger effect estimates. As for continuous outcomes, RCTs with Chinese medicine diagnostic criteria (dSMD: 0.23; 95% CI: [0.06, 0.41]), judged as high/unclear risk of bias on allocation concealment (dSMD: -0.70; 95% CI: [-0.99, -0.42]), with low risk of bias on incomplete outcome data (dSMD: 0.30; 95% CI: [0.18, 0.43]), conducted at a single center (dSMD: -0.33; 95% CI: [-0.61, -0.05]), not using intention-to-treat analysis (dSMD: -0.75; 95% CI: [-1.43, -0.07]), and without funding support (dSMD: -0.22; 95% CI: [-0.41, -0.02]) tended to show larger effect estimates. CONCLUSION: This study provides empirical evidence for the development of a specific critical appraisal tool for risk of bias assessments on CHM RCTs. Please cite this article as: Wang BH, Lin YL, Gao YY, Song JL, Qin L, Li LQ, Liu WQ, Zhong CCW, Jiang MY, Mao C, Yang XB, Chung VCH, Wu IXY. Trial characteristics and treatment effect estimates in randomized controlled trials of Chinese herbal medicine: A meta-epidemiological study. J Integr Med. 2024; 22(3): 223-234.

Immunological parameters of maternal peripheral blood as predictors of future pregnancy outcomes in patients with unexplained recurrent pregnancy loss.

INTRODUCTION: Unexplained recurrent pregnancy loss (URPL), affecting approximately 1%-5% of women, exhibits a strong association with various maternal factors, particularly immune disorders. However, accurately predicting pregnancy outcomes based on the complex interactions and synergistic effects of various immune parameters without an automated algorithm remains challenging. MATERIAL AND METHODS: In this historical cohort study, we analyzed the medical records of URPL patients treated at Xiangya Hospital, Changsha, China, between January 2020 and October 2022. The primary outcomes included clinical pregnancy and miscarriage. Predictors included complement, autoantibodies, peripheral lymphocytes, immunoglobulins, thromboelastography findings, and serum lipids. Least absolute shrinkage and selection operator (LASSO) analysis and logistic regression analysis was performed for model development. The model's performance, discriminatory, and clinical applicability were assessed using area under the curve (AUC), calibration curve, and decision curve analysis, respectively. Additionally, models were visualized by constructing dynamic and static nomograms. RESULTS: In total, 502 patients with URPL were enrolled, of whom 291 (58%) achieved clinical pregnancy and 211 (42%) experienced miscarriage. Notable differences in complement, peripheral lymphocytes, and serum lipids were observed between the two outcome groups. Moreover, URPL patients with elevated peripheral NK cells (absolute counts and proportion), decreased complement levels, and dyslipidemia demonstrated a significantly increased risk of miscarriage. Four models were developed in this study, of which Model 2 demonstrated superior performance with only seven predictors, achieving an AUC of 0.96 (95% CI: 0.93-0.99) and an accuracy of 0.92. A web-based platform was established to visually present model 2 and to facilitate its utilization by clinicians in outpatient settings (available from: https://yingrongli.shinyapps.io/liyingrong/). CONCLUSIONS: Our findings suggest that the implementation of such prediction models could serve as valuable tools for providing comprehensive information and facilitating clinicians in their decision-making processes.

Development and Validation of Knowledge Assessment Scales for Dementia and Urinary Incontinence in Community Older People.

To develop and validate scales for reliably assessing dementia and urinary incontinence knowledge of older adults in the community. Items were generated through a literature review, refined through a Delphi study (n = 19), and then revised through a pilot study (n = 29). Item analysis and exploratory factor analysis were applied to finalize the scales (n = 244). Construct validity, reliability, and acceptability were evaluated (n = 243). The two knowledge assessment scales for dementia and urinary incontinence, respectively, comprised 12 items and 8 items. Model fit indicators of both met the criteria of confirmatory factor analysis. Cronbach's α were .82 and .70, respectively. Completion ratio and completion time of the two scales was 83.51% and 4.22 ± 1.90 minutes. The knowledge assessment scales for dementia and urinary incontinence with satisfactory validity, reliability, and acceptability, could be served as valid tools for disease prevention and management among older adults in the community.

Bimetallic-MOF Derived Carbon with Single Pt Anchored C4 Atomic Group Constructing Super Fuel Cell with Ultrahigh Power Density And Self-Change Ability.

Pursuing high power density with low platinum catalysts loading is a huge challenge for developing high-performance fuel cells (FCs). Herein, a new super fuel cell (SFC) is proposed with ultrahigh output power via specific electric double-layer capacitance (EDLC) + oxygen reduction reaction (ORR) parallel discharge, which is achieved using the newly prepared catalyst, single-atomic platinum on bimetallic metal-organic framework (MOF)-derived hollow porous carbon nanorods (PtSA /HPCNR). The PtSA-1.74 /HPCNR-based SFC has a 3.4-time higher transient specific power density and 13.3-time longer discharge time with unique in situ self-charge and energy storage ability than 20% Pt/C-based FCs. X-ray absorption fine structure, aberration-corrected high-angle annular dark-field scanning transmission electron microscope, and density functional theory calculations demonstrate that the synergistic effect of Pt single-atoms anchored on carbon defects significantly boosts its electron transfer, ORR catalytic activity, durability, and rate performance, realizing rapid " ORR+EDLC" parallel discharge mechanism to overcome the sluggish ORR process of traditional FCs. The promising SFC leads to a new pathway to boost the power density of FCs with extra-low Pt loading.

Precise Tuning of Hollow and Pore Size of Bimetallic MOFs Derivate to Construct High-Performance Nanoscale Materials for Supercapacitors and Sodium-Ion Batteries.

Precise control of pore volume and size of carbon nanoscale materials is crucial for achieving high capacity and rate performances of charge/discharge. In this paper, starting from the unique mechanism of the role of In, Zn combination, and carboxyl functional groups in the formation of the lumen and pore size, the composition of InZn-MIL-68 is regulated to precisely tune the diameter and wall pore size of the hollow carbon tubes. The hollow carbon nanotubes (CNT) with high-capacity storage and fast exchange of Na+ ions and charges are prepared. The CNT possess ultra-high specific capacitance and ultra-long cycle life and also offer several times higher Na+ ion storage capacity and rate performance than the existing CNTs. Density functional theory calculations and tests reveal that these superior characteristics are attributed to the spacious hollow structure, which provides sufficient space for Na+ storage and the tube wall's distinctive porosity of tube wall as well as open ends for facilitating Na+ rapid desorption. It is believed that precise control of sub-nanopore volume and pore size by tuning the composition of the carbon materials derived from bimetallic metal-organic frameworks (MOFs) will establish the basis for the future development of high-energy density and high-power density supercapacitors and batteries.

Development and validation of frailty and malnutrition knowledge assessment scale for community-dwelling older adults.

There is a lack of reliable tools to assess the knowledge of frailty and malnutrition in community-dwelling older adults. To develop and validate reliable frailty and malnutrition knowledge assessment scales for this population, two scales were developed and validated through five phases. Phase 1: the item pools were constructed through a literature review and research panel based on the symptom interpretation model. Phase 2: the expert consultation was performed to select the items. Phase 3: a pilot survey was conducted to assess the clarity of the items and further revise the scales. Phase 4: 242 older adults were surveyed to finalize the items. Phase 5: 241 older adults were surveyed to test the psychometric properties. The two scales each comprise 3 dimensions (symptoms, risk factors, and management strategies) and 11 items. They had good construct validity, with all indicators of correlation analysis and confirmatory factor analysis meeting their specific criteria. The reliability of the frailty and malnutrition knowledge assessment scales was good, with composite reliability coefficients all >0.60, Cronbach's alpha being 0.81 and 0.83, and the Spearman-Brown coefficient being 0.74 and 0.80, respectively. Their acceptability was good, with both having a completion rate of 92.18% and an average completion time of 3 min. The two scales are reliable tools to assess the knowledge of frailty and malnutrition among community-dwelling older adults, especially for large-scale surveys. They can help identify knowledge gaps in older adults and provide a basis for developing targeted educational interventions.

Development and validation of knowledge assessment scales on sarcopenia and fall for Chinese community-dwelling older adults.

AIM: This study aimed to develop and validate sarcopenia and fall knowledge assessment scales for community-dwelling older adults. METHODS: A five-phase, systematic and standardized process was used. Phase 1: item pools were constructed based on the Symptom Interpretation Model. Phase 2: the Delphi expert consultation was carried out for items selection and revision. Phase 3: a pilot survey was carried out to further select and revise the items. Phase 4: older adults were surveyed to finalize the items. Phase 5: older adults were surveyed to test the psychometric properties of the two developed scales, including construct validity, reliability and acceptability. RESULTS: Both scales comprise three dimensions (symptom, risk factor and management strategy), with 10 items for the sarcopenia knowledge assessment scale and 14 items for the fall knowledge assessment scale. They had acceptable construct validity, with all indicators meeting their specific criteria. Their reliability was acceptable, with the Cronbach's α coefficients being 0.82 for both scales, the value of spilt-half reliability being 0.86 for the sarcopenia knowledge assessment scale and 0.85 for the fall knowledge assessment scale. Their acceptability was good, with both scales having a completion rate of 94.35% and an average completion time of 5 min. DISCUSSION: Two Chinese knowledge assessment scales with acceptable validity, reliability and acceptability have been developed, which will facilitate the assessment of the knowledge on sarcopenia and fall among community-dwelling older adults, especially for large-scale surveys. Geriatr Gerontol Int 2023; 23: 430-436.

Intelligent Chip-Controlled Smart Oxygen Electrodes for Constructing Rechargeable Zinc-Air Batteries with Excellent Energy Efficiency and Durability.

High-performance rechargeable oxygen electrodes are key devices for realizing high-specific-energy batteries, including zinc-air and lithium-air batteries. However, these batteries have severe problems of premature decay in energy efficiency by serious corrosion, wide charge-discharge gap, and catalyst peeling off. Herein, we propose a "smart dual-oxygen electrode", which is composed of an intelligent switch control module + heterostructured Fe1Ni3-LDH/PNCNF OER catalysis electrode layer + ion conductive | electronic insulating membrane + Pt/C ORR catalysis electrode layer, where OER and ORR layers are automatically switched by the intelligent switch control module as required. This smart dual-oxygen electrode offers an ultralow energy efficiency decay rate of 0.0067% after 300 cycles during cycling, much lower than that of the commercial Pt/C electrode (1.82%). The assembled rechargeable zinc-air battery (RZAB) displays a super narrow voltage gap and achieves a high energy efficiency of 71.7%, far higher than that of the existing RZABs (about 50%). Therefore, this strategy provides a complete solution for designing various high-performance metal-air secondary batteries.

Lifestyle trajectories and ischaemic heart diseases: a prospective cohort study in UK Biobank.

AIMS: To evaluate the associations of baseline and long-term trajectories of lifestyle with incident ischaemic heart diseases (IHDs). METHODS AND RESULTS: 29 164 participants in the UK Biobank who had at least one follow-up assessment and were free of IHD at the last follow-up assessment were included. We constructed a weighted unhealthy lifestyle score though summing five lifestyle factors [smoking, physical activity, diet, body mass index, and sleep duration]. Lifestyle assessed at baseline (2006-09), the first follow-up assessment (2012-13), and the second follow-up assessment (since 2014) were used to derive the trajectories of each individual. The joint categories were created through cross-classifying the three baseline lifestyle categories (ideal, intermediate, and poor) by the three lifestyle trajectory categories (improve, maintain, and decline). During a median follow-up period of 4.2 years, 868 IHD events were recorded. The hazard ratio (HR) of incident IHD associated with per unit increase in unhealthy lifestyle trajectory was 1.08 [95% confidence interval (CI): 0.99-1.17]. Subgroup analyses indicated such association was stronger among individuals with hypertension (HR: 1.13, 95% CI: 1.03-1.24), diabetes (HR: 1.23, 95% CI: 0.96-1.58), or hyperlipidaemia (HR: 1.09, 95% CI: 0.97-1.22). Compared with participants consistently adhering to an ideal lifestyle (ideal-maintain), the HRs of incident IHD were 1.30 (1.07-1.58) for intermediate-maintain, 1.52 (1.23-1.88) for poor-maintain, 1.25 (0.93-1.68) for intermedia-improve, 1.48 (1.17-1.88) for poor-improve, 1.46 (1.08-1.99) for intermedia-decline, and 1.77 (1.21-2.59) for poor-decline. CONCLUSIONS: A declined lifestyle trajectory increased the risk of incident IHD, irrespective of baseline lifestyle levels. Individuals with hypertension, diabetes, or hyperlipidaemia were more predisposed to the influence of lifestyle change.

It is known that an unhealthy lifestyle at baseline was associated with an increased risk of cardiovascular diseases (CVDs), but the risk attributed to the lifestyle changes (or trajectories) over the long term has not been well quantified. Meanwhile, the effects of lifestyle, either in baseline level or trajectories, on different CVD subtypes such as ischaemic heart diseases (IHDs) and stroke varied. Thus, this study used the data from UK Biobank to construct a weighted unhealthy lifestyle score and to evaluate the prospective associations of baseline and long-term trajectories of the unhealthy lifestyle score with the risk of incident IHD. A total of 352 251 and 29 164 participants were included in the unhealthy lifestyle construction and lifestyle trajectory analysis, respectively. We found a poorer lifestyle at baseline was significantly associated with an increased risk of incident IHD in a linear dose­response fashion. Besides, a declined lifestyle trajectory was associated with an increased risk of incident IHD, irrespective of baseline lifestyle levels, and such an association was stronger among individuals with hypertension, diabetes, or hyperlipidaemia. Compared with the maintainers, risks of incident IHD attenuated when individuals improved their lifestyle and strengthened when declined their lifestyle.A declined lifestyle trajectory increased the risk of incident IHD, irrespective of baseline lifestyle levels. Such association was stronger among participants with hypertension, diabetes, or hyperlipidaemia.Compared with the maintainers of lifestyle, risks of incident IHD attenuated when individuals improved their lifestyle and strengthened when declined their lifestyle.

Predictive models for the incidence of Parkinson's disease: systematic review and critical appraisal.

Numerous predictive models for Parkinson's disease (PD) incidence have been published recently. However, the model performance and methodological quality of those available models are yet needed to be summarized and assessed systematically. In this systematic review, we systematically reviewed the published predictive models for PD incidence and assessed their risk of bias and applicability. Three international databases were searched. Cohort or nested case-control studies that aimed to develop or validate a predictive model for PD incidence were considered eligible. The Prediction model Risk Of Bias ASsessment Tool (PROBAST) was used for risk of bias and applicability assessment. Ten studies covering 10 predictive models were included. Among them, four studies focused on model development, covering eight models, while the remaining six studies focused on model external validation, covering two models. The discrimination of the eight new development models was generally poor, with only one model reported C index > 0.70. Four out of the six external validation studies showed excellent or outstanding discrimination. All included studies had high risk of bias. Three predictive models (the International Parkinson and Movement Disorder Society [MDS] prodromal PD criteria, the model developed by Karabayir et al. and models validated by Faust et al.) are recommended for clinical application by considering model performance and resource-demanding. In conclusion, the performance and methodological quality of most of the identified predictive models for PD incidence were unsatisfactory. The MDS prodromal PD criteria, model developed by Karabayir et al. and model validated by Faust et al. may be considered for clinical use.

Prediction Models for Osteoporotic Fractures Risk: A Systematic Review and Critical Appraisal.

Osteoporotic fractures (OF) are a global public health problem currently. Many risk prediction models for OF have been developed, but their performance and methodological quality are unclear. We conducted this systematic review to summarize and critically appraise the OF risk prediction models. Three databases were searched until April 2021. Studies developing or validating multivariable models for OF risk prediction were considered eligible. Used the prediction model risk of bias assessment tool to appraise the risk of bias and applicability of included models. All results were narratively summarized and described. A total of 68 studies describing 70 newly developed prediction models and 138 external validations were included. Most models were explicitly developed (n=31, 44%) and validated (n=76, 55%) only for female. Only 22 developed models (31%) were externally validated. The most validated tool was Fracture Risk Assessment Tool. Overall, only a few models showed outstanding (n=3, 1%) or excellent (n=32, 15%) prediction discrimination. Calibration of developed models (n=25, 36%) or external validation models (n=33, 24%) were rarely assessed. No model was rated as low risk of bias, mostly because of an insufficient number of cases and inappropriate assessment of calibration. There are a certain number of OF risk prediction models. However, few models have been thoroughly internally validated or externally validated (with calibration being unassessed for most of the models), and all models showed methodological shortcomings. Instead of developing completely new models, future research is suggested to validate, improve, and analyze the impact of existing models.

Trial-level characteristics associate with treatment effect estimates: a systematic review of meta-epidemiological studies.

BACKGROUND: To summarize the up-to-date empirical evidence on trial-level characteristics of randomized controlled trials associated with treatment effect estimates. METHODS: A systematic review searched three databases up to August 2020. Meta-epidemiological (ME) studies of randomized controlled trials on intervention effect were eligible. We assessed the methodological quality of ME studies using a self-developed criterion. Associations between treatment effect estimates and trial-level characteristics were presented using forest plots. RESULTS: Eighty ME studies were included, with 25/80 (31%) being published after 2015. Less than one-third ME studies critically appraised the included studies (26/80, 33%), published a protocol (23/80, 29%), and provided a list of excluded studies with justifications (12/80, 15%). Trials with high or unclear (versus low) risk of bias on sequence generation (3/14 for binary outcome and 1/6 for continuous outcome), allocation concealment (11/18 and 1/6), double blinding (5/15 and 2/4) and smaller sample size (4/5 and 2/2) significantly associated with larger treatment effect estimates. Associations between high or unclear risk of bias on allocation concealment (5/6 for binary outcome and 1/3 for continuous outcome), double blinding (4/5 and 1/3) and larger treatment effect estimates were more frequently observed for subjective outcomes. The associations between treatment effect estimates and non-blinding of outcome assessors were removed in trials using multiple observers to reach consensus for both binary and continuous outcomes. Some trial characteristics in the Cochrane risk-of-bias (RoB2) tool have not been covered by the included ME studies, including using validated method for outcome measures and selection of the reported results from multiple outcome measures or multiple analysis based on results (e.g., significance of the results). CONCLUSIONS: Consistently significant associations between larger treatment effect estimates and high or unclear risk of bias on sequence generation, allocation concealment, double blinding and smaller sample size were found. The impact of allocation concealment and double blinding were more consistent for subjective outcomes. The methodological and reporting quality of included ME studies were dissatisfactory. Future ME studies should follow the corresponding reporting guideline. Specific guidelines for conducting and critically appraising ME studies are needed.