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Introduction: Mental health problems, especially depressive symptoms, are becoming increasingly prominent, posing a significant risk to public health. Changes in the body mass index (BMI) may impact an individual's mental health, however, the relationship between BMI and depressive symptoms is unclear. The purpose of this study was to investigate the association between BMI and depressive symptoms. Methods: Using a multi-stage sampling method, 10,686 adults in Longgang District, Shenzhen City, Guangdong Province, China, were selected for participation in this study. Surveys were distributed in 2020 and 2021 to measure participant demographic data and health. Binary logistic regression, restricted cubic spline regression, and subgroup analyses were performed to explore the relationship between BMI and depressive symptoms. Results: The results showed a U-shaped relationship between BMI and depression. Both obesity and underweight increased the risk of depression among the participants, especially in subgroups of participants who were young, highly educated, single and employed. Conclusion: These findings suggest that adults should try to maintain a normal body weight as a way to prevent depression and maintain their physical and mental health. [ABSTRACT FROM AUTHOR]

Background: The current practice in guideline development is to use the control group event rate (CR) as a surrogate of baseline risk and to assume portability of the relative treatment effect across populations with low, moderate and high baseline risk. We sought to emulate this practice in a very large sample of meta-analyses. Methods: We retrieved data from all meta-analyses published in the Cochrane Database of Systematic Reviews (2003–2020) that evaluated a binary outcome, reported 2 × 2 data for each individual study and included at least 4 studies. We excluded studies with no events. We conducted meta-analyses with odds ratios and relative risks and performed subgroup analyses based on tertiles of CR. In sensitivity analyses, we evaluated the use of total event rate (TR) instead of CR and using quartiles instead of tertiles. Results: The analysis included 2,531 systematic reviews (27,692 meta-analyses, 226,975 studies, 25,669,783 patients).The percentages of meta-analyses with statistically significant interaction (P < 0.05) based on CR tertile or quartile ranged 12–18% across various sensitivity analyses. This percentage increased as the number of studies or range of CR per meta-analysis increased, reflecting increased power of the subgroup test. The percentages of meta-analyses with statistically significant interaction (P < 0.05) with TR quantiles were lower than those with CR but remained higher than expected by chance. Conclusion: This analysis suggests that when CR or TR are used as surrogates for baseline risk, relative treatment effects may not be portable across populations with varying baseline risks in many meta-analyses. Categroization of the continuous CR variable and not addressing measurement error limit inferences from such analyses and imply that CR is an undesirable source for baseline risk. Guideline developers and decision-makers should be provided with relative and absolute treatment effects that are conditioned on the baseline risk or derived from studies with similar baseline risk to their target populations. [ABSTRACT FROM AUTHOR]

Objectives: Differences in clinicopathological characteristics of extensive-stage small cell lung cancer (ES-SCLC) patients may influence the immune response. This study aims to evaluate the heterogeneity of response to first-line chemoimmunotherapy between subgroups in ES-SCLC to screen out suitable populations. Materials and methods: We searched the PubMed, EMBASE, and Cochrane Library databases from inception to December 3, 2022 for randomized controlled trials (RCTs) of ES-SCLC chemoimmunotherapy. We also reviewed main conferences from January 1, 2021 to October 1, 2023. A trial-specific hazard ratio (HR) ratio for each subgroup was calculated, and these ratios were then pooled using the deft approach. Results: A total of 9 RCTs with 4099 patients were finally included. The pooled ratios were 0.92 (95% CI = 0.77 to 1.09) for OS-HRs and 0.79 (95% CI = 0.55 to 1.13) for PFS-HRs in women versus men. The pooled ratios of OS-HRs and PFSHRs in patients with positive versus negative PD-L1 expression were 1.26 (95% CI = 0.91 to 1.73) and 1.08 (95% CI = 0.77 to 1.52), respectively. The pooled ratios of OS-HRs and PFS-HRs in patients without versus with brain metastasis were 0.77 (95% CI = 0.59 to 1.01) and 0.71 (95% CI = 0.44 to 1.12). No statistically significant differences were also found in terms of subgroups for age, liver metastasis, smoking status, ECOG PS, LDH level, type of platinum salt and race. Conclusion: Women or patients with negative PD-L1 expression or with LDH ≤ ULN or without brain metastasis tend to benefit more from first-line chemoimmunotherapy in ES-SCLC. More trials are needed to prospectively validate the therapeutic heterogeneity among clinicopathological characteristics. [ABSTRACT FROM AUTHOR]

Objective: With the accelerating urbanization process, the garden area is gradually expanding, and the production of green waste is also increasing. Composting green waste can not only reduce environmental pollution caused by incineration and landfill and improve the utilization efficiency of resources but also improve the soil and increase soil productivity. The study aims to investigate the comprehensive impact of green waste compost (GWC) application on soil nutrient conditions. Through comprehensive data analysis, the impact of compost application of green waste on soil properties was revealed as a reference for compost application and fertilizer reduction. Methods: Based on meta-analysis, we quantitatively investigated the response of soil properties to the application of green waste, collected published experimental data, and integrated 25 domestic and international literature to analyze the effects of different soil properties on soil nutrients. Literature was used to analyze the impact of different application rates of GWC on the physicochemical properties of soils with varying pH levels. The results were compared to control conditions with no GWC application. Results: The application of significantly improved soil quality by reducing soil bulk density and increasing the levels of soil organic matter, organic carbon, total nitrogen, available phosphorus, available potassium, and dehydrogenase activity. The increases in available potassium and soil organic carbon were consistently significant across all subgroups. However, the effects on available phosphorus and organic matter varied in significance depending on initial soil pH. Soil bulk density was influenced by the GWC content, while dehydrogenase activity showed significant effects only when initial soil pH was ≥8. Total nitrogen levels were significantly impacted by GWC application in soil with an initial pH of <8 and at GWC contents of ≥50%. Conclusion: The application of green waste compost demonstrates a positive effect on soil improvement. This study provides a comprehensive database that supports the use of GWC in enhancing soil quality and reducing the need for chemical fertilizers. [ABSTRACT FROM AUTHOR]

Background: Mental distress among retirees and older people is a severe public health challenge, and information on new risk groups is needed. This study aims to identify subgroups of old-age retirees with varying associations between low social support and mental distress by applying model-based recursive partitioning (MOB). Methods: We used the Helsinki Health Study follow-up survey data of old-age retired former municipal sector employees of the City of Helsinki, Finland. Phase 1 data were collected in 2000–2002, when all participants were employed, Phase 2 in 2007, Phase 3 in 2012, Phase 4 in 2017, and Phase 5 in 2022 (n = 4,466, 81% women). Social support and covariates were measured at each Phase 1–5 and the outcome, mental distress (Depression Anxiety Stress Scales [DASS-21]) was measured at a single occasion, during Phase 5. The three subscales and the common factor of general distress were analysed separately. An approach rooted in computational statistics was used to investigate risk factor heterogeneity in the association of low social support and mental distress. MOB combines decision trees with regression analysis to identify subgroups with the most significant heterogeneity among risk factors. Results: Median (IQR) general distress score from DASS-21 was 5.7 (3.0, 9.0), while Social Support Questionnaire number-score (SSQN) was 1.5 (1.15, 2.05). The primary effect modifier for the association between social support and general distress was education (p < 0.001). Those with high education had a different association of low social support and general distress than those with low or medium education. Additionally, the subgroup with low and medium education had a significant effect modification for age (p = 0.01). For the association between low social support and depressive symptoms, the moderating effect of education was dependent on gender, as men with medium–high education had the weakest association, while for women with medium–high education the association was strongest. Conclusions: Our results suggest that stratification by sociodemographic variables is justifiable when investigating risk factors of mental distress in old-age retirees. The incongruent association of low social support and depressive symptoms in men with medium–high education compared to women with medium–high education is a promising target for confirmatory research. [ABSTRACT FROM AUTHOR]

Background: The first-line treatment for advanced hepatocellular carcinoma has evolved significantly. This study aimed to identify the most beneficial regimen. Methods: A systematic search was conducted from July 2012 to August 2024 across the following four databases: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. This search focused on phase III prospective randomized controlled trials that compared first-line treatment for advanced hepatocellular carcinoma. Results: Seventeen studies involving 10322 patients were included in this network meta-analysis. Of the studies we included, twelve studies were global multicenter clinical studies, four were initiated in China, and one was initiated in Korea. The results of our statistical analysis suggest that Hepatic artery infusion chemotherapy with oxaliplatin plus fluorouracil (HAIC-FO) demonstrated significant overall survival (OS) benefits compared with most treatments, including various immune checkpoint inhibitors (ICIs) and anti-vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs). In terms of OS, HAIC had shown similar efficacy with sorafenib plus FOLFOX (HR, 0.88; 95% CI: 0.37-2.09) and transcatheter arterial chemoembolization (TACE) combined with lenvatinib (HR, 0.69; 95% CI: 0.30-1.56). Notably, immune-related treatments, such as ICIs combined with anti-VEGF therapies, also showed improved OS compared with anti-VEGF-TKIs alone. In terms of progression-free survival (PFS), HAIC-FO outperformed anti-VEGF-TKI monotherapy, ICI monotherapy, and several ICI combinations. However, it was not superior to lenvatinib plus TACE or lenvatinib plus pembrolizumab. Based on the Surface Under the Cumulative Ranking Curve (SUCRA) values, HAIC-FO was ranked the most effective in terms of OS (SUCRA = 0.961) and objective response rate (ORR) (SUCRA = 0.971). The results of the subgroup analysis suggested that HAIC-FO achieved the best OS benefit in the macrovascular invasion (MVI) and extrahepatic spread (EHS) subgroup (SUCRA = 0.99) and that tremelimumab combined with durvalumab achieved the best OS benefit in the Asian subgroup (SUCRA = 0.88). Conclusion: This systematic review and network meta-analysis suggest that HAIC-based therapies may become a potential first-line treatment option for advanced HCC, especially for patients in Mainland China with MVI and EHS. Additionally, immune-related treatments may be more suitable for Asian populations. [ABSTRACT FROM AUTHOR]

Aims: Serum calcium level is widely used for evaluating disease severity, but its impact on clinical outcomes in patients with congestive heart failure (CHF) remains poorly understood. The aim of this study is to investigate the relationship between serum calcium levels and in‐hospital mortality in CHF patients. Methods and results: We conducted a retrospective analysis utilizing clinical data from the Medical Information Mart for Intensive Care database, encompassing a cohort of 15 983 CHF patients. This cohort was stratified based on their serum calcium levels, with the primary objective being the determination of in‐hospital mortality. To assess the impact of admission serum calcium levels on in‐hospital mortality, we employed various statistical methodologies, including multivariable logistic regression models, a generalized additive model, a two‐piecewise linear regression model, and subgroup analysis. Comparative analysis of the reference group (Q3) revealed increased in‐hospital mortality in the first quintile (Q1, the group with the lowest blood calcium level) and the fifth quintile (Q5, the group with the highest blood calcium level), with fully adjusted odds ratios of 1.38 [95% confidence interval (CI): 1.13–1.68, P = 0.002] and 1.23 (95% CI: 1.01–1.5, P = 0.038), respectively. A U‐shaped relationship was observed between serum calcium levels and in‐hospital mortality, with the lowest risk occurring at a threshold of 8.35 mg/dL. The effect sizes and corresponding CIs below and above this threshold were 0.782 (95% CI: 0.667–0.915, P = 0.0023) and 1.147 (95% CI: 1.034–1.273, P = 0.0094), respectively. Stratified analyses confirmed the robustness of this correlation. Conclusions: Our study identifies a U‐shaped association between serum calcium levels and in‐hospital mortality in CHF patients, with a notable inflection point at 8.35 mg/dL. Further investigation through prospective, randomized, and controlled studies is warranted to validate the findings presented in this study. [ABSTRACT FROM AUTHOR]

Large-scale Randomised Controlled Trials (RCTs) are widely regarded as “the gold standard” for testing the causal effects of school-based interventions. RCTs typically present the statistical significance of the average treatment effect (ATE), which captures the effect an intervention has had on average for a given population. However, key decisions in child health and education are often about individuals who may be very different from those averages. One way to identify heterogeneous treatment effects across different individuals, not captured by the ATE, is to conduct subgroup analyses. For example, free school meal (FSM) pupils as required for projects funded by the Education Endowment Foundation (EEF) in England. These subgroup analyses, as we demonstrate in 48 EEF-funded RCTs involving over 200,000 students, are usually not standardised across studies and offer flexible degrees of freedom to researchers, potentially leading to mixed, if not misleading, results. Here, we develop and deploy an alternative to ATE and subgroup analysis, a machine-learning and regression-based framework to predict individualised treatment effects (ITEs). ITEs could show where an intervention worked, for which individuals, and to what extent. Our findings have implications for decision-makers in fields like education, healthcare, law, and clinical practices concerning children and adolescents. [ABSTRACT FROM AUTHOR]

Objective To explore the association between gallstones and CVD among ethnic minority populations in Guizhou Province, as well as the mediating effect of glomerular filtration rate (GFR) in this association, in order to provide reference suggestions for reducing the burden of CVD. Methods Based on the database of Cohort Study of Native Natural Population in Ethnic Minority Gathering Areas in Southwest China, stratified and multi-stage cluster sampling was used to conduct a baseline survey of ethnic minorities aged 30 - 79 years in Qiandongnan and Qiannan Prefectures of Guizhou Province from 2018 to 2019. Multivariate logistic regression was used to analyze the association between gallstones and CVD, and the mediating effect model was used to evaluate the mediating effect of glomerular filtration rate in the association. Results The detection rate of CVD in Guizhou minority population was 3.16%, among which the detection rates of Dong, Miao and Buyi were 3.27%, 3.07% and 3.12%, respectively. The total detection rate of gallstones was 9.03%. Logistic regression analysis showed that after adjusting for all the variables (model 3), the detection rates of CVD in the total population [OR(95%CI): 1.633(1.269-2.102)], the Dong [OR(95%CI): 1.567(1.077-2.280)], and Miao [OR(95%CI): 1.679(1.055-2.673)], gallstones were positively associated with CVD. No association between gallstones and CVD was found in the Buyi population. Subgroup analysis showed that Dong patients with gallstones < 60 years old were positively correlated with CVD [OR(95%CI): 1.825(1.022-3.258)], gallstone patients without hyperlipidemia [OR(95%CI): 2.151(1.352-3.422)], gallstone patients without hypertension [OR(95%CI): 1.612(1.013-2.565)] were positively correlated with CVD. Miao ≥ 60 years old [OR(95%CI): 1.878(1.038-3.397)], male [OR(95%CI): 1.546(1.212-5.586)], BMI ≥ 24 [OR(95%CI): 1.972(1.160-3.354)], gallstone patients with hypertension [OR(95%CI): 2.264(1.297 - 5.429)] were positively correlated with CVD. Mediation analysis revealed that the glomerular filtration rate accounted for 16.96%, 12.08%, 17.43%, and 14.52% of the mediating effect between gallstones and CVD in the total population, Dong, Miao, and Buyi people, respectively. Conclusion Gallstones are positively correlated with CVD in the Dong and Miao populations in Guizhou Province, especially in the overweight and hypertension population of the Miao nationality. There is no association between gallstones and CVD in the Buyi population. Glomerular filtration rate has a partial mediating effect between gallstones and CVD. [ABSTRACT FROM AUTHOR]

Background: This study investigated potential subgroups of children within the Kiel Obesity Prevention Study (KOPS) for differing treatment effects for the outcome measures of overweight or obesity at 4 years. The KOPS study delivered a multicomponent school intervention to cohorts of children in Kiel but found no overall effect on the weight status outcome. However, KOPS authors suggested there may be subgroup variations in treatment effect. Data were collected as part of the KOPS for samples of 6-year-olds between 1996 and 2001, with 4-year follow-up measurements between 2000 and 2004. Methods: The present study conducted a post hoc subgroup analysis of the odds of obesity or overweight at 4-year follow-up compared to normal weight (n = 1646). A generalized linear mixed-effects model, including a treatment–subgroup interaction term, was used to estimate subgroups as a moderator of the treatment effects on the outcomes of obesity or overweight at 4-year follow-up. Results: The findings indicated several subgroup–treatment interaction effects relating to physical activity indicators. TV or PC not being one of a child's top 3 activities at baseline was associated with a significantly decreased odds ratio of obesity at 4 years in the intervention group (OR, 0.04; 95% CI, 0.004 to 0.45) compared to the non-intervention group (OR, 0.96; 95% CI, 0.29 to 3.14), p = 0.02. Weekly activity in a sports club at baseline was associated with a decreased odds ratio of overweight at 4 years in the intervention group (OR, 0.38; 95% CI, 0.16 to 0.85) compared to the non-intervention group (OR, 0.91; 95% CI, 0.70 to 1.17). This was a significant difference (p = 0.04). Conclusions: These findings suggest that children's baseline physical activity may impact treatment effects on the outcomes of overweight and obesity, creating opportunities to increase the effectiveness of interventions on preventing obesity. [ABSTRACT FROM AUTHOR]

Background: Limited data are available regarding the association between serum transferrin saturation (TSAT) levels and heart failure (HF). Methods: We utilized data from National Health and Nutrition Examination Survey (NHANES) 2017-2020.03 for analysis. Data on TAST, HF and covariates were extracted and analyzed. Weighted logistic regression and subgroup analysis were used to explore the independent association between TSAT and HF. Furthermore, interaction tests were also carried out to evaluate the strata differences. We subsequently assessed whether there was a non-linear relationship between the 2 using Restricted cubic spline (RCS) and threshold effect models. Result: A total of 282 (3.87%) participants were identified to have HF. Among the total population, participants with HF had significantly lower TSAT levels compared to those without HF (24.63 vs. 27.95, P = 0.001). After fully adjusting for potential confounders, weighted multiple logistic regression models revealed a 2.6% reduced in the risk of HF when each unit of TSAT increased. There was also a negative association between elevated TSAT and developed risk of HF in the quartile groups (Q1 OR:1.00; Q2 OR: 0.924 [95%CI:0.593,1.440]; Q3 OR: 0.515 [95%CI:0.298,0.891]; Q4 OR:0.411 [95%CI:0.201,0.839]). The subgroup analysis results remained consistent across strata, with a strong negative correlation between TSAT and HF. Interaction tests showed no dependence on gender, age, Body Mass Index, race, diabetes, hypertension, hyperlipidemia, ratio of family income to poverty and education for this negative association between TSAT and HF (all p for interaction >0.05). The RCS and threshold effect models indicated a linear negative correlation between TSAT and HF, which was more pronounced when TSAT under 40%. Conclusion: Overall, these findings suggest a consistent and negative association between TSAT levels and the presence of HF among middle-aged and older adults in the United States. [ABSTRACT FROM AUTHOR]

Metabolic syndrome has become a significant public health concern. This study aims to investigate the impact of dietary patterns on metabolic syndrome in young adults and how physical activity modulates this effect. A cross-sectional study was conducted at a health management center in Tianjin, China, from September 2022 to March 2023. Participants aged 18–35 years were recruited using convenience sampling. Dietary intake was assessed using a validated food frequency questionnaire. Logistic regression models evaluated associations between these patterns and metabolic syndrome, adjusting for potential confounders. Among 442 participants, four dietary patterns were identified: Legume–Nut, Alcohol–Meat, Sugar–Processed, and Egg–Vegetable. The Legume–Nut dietary pattern was associated with a higher risk of metabolic syndrome (OR = 2.63, 95% CI: 1.08–6.37), while the Egg–Vegetable dietary pattern was associated with a lower risk (OR = 0.26, 95% CI: 0.10–0.70). No significant associations were found for the Sugar–Processed and Alcohol–Meat patterns. Subgroup analysis revealed that the Legume–Nut pattern increased the risk of metabolic syndrome among those with irregular physical activity, whereas the Egg–Vegetable pattern decreased the risk. These findings highlight the significant influence of dietary patterns on the risk of metabolic syndrome in young adults and the modifying effect of regular physical activity, underscoring the need for targeted dietary and lifestyle interventions to prevent metabolic syndrome in this population. [ABSTRACT FROM AUTHOR]

Abstract Background The current practice in guideline development is to use the control group event rate (CR) as a surrogate of baseline risk and to assume portability of the relative treatment effect across populations with low, moderate and high baseline risk. We sought to emulate this practice in a very large sample of meta-analyses. Methods We retrieved data from all meta-analyses published in the Cochrane Database of Systematic Reviews (2003–2020) that evaluated a binary outcome, reported 2 × 2 data for each individual study and included at least 4 studies. We excluded studies with no events. We conducted meta-analyses with odds ratios and relative risks and performed subgroup analyses based on tertiles of CR. In sensitivity analyses, we evaluated the use of total event rate (TR) instead of CR and using quartiles instead of tertiles. Results The analysis included 2,531 systematic reviews (27,692 meta-analyses, 226,975 studies, 25,669,783 patients).The percentages of meta-analyses with statistically significant interaction (P

Abstract Aims Serum calcium level is widely used for evaluating disease severity, but its impact on clinical outcomes in patients with congestive heart failure (CHF) remains poorly understood. The aim of this study is to investigate the relationship between serum calcium levels and in‐hospital mortality in CHF patients. Methods and results We conducted a retrospective analysis utilizing clinical data from the Medical Information Mart for Intensive Care database, encompassing a cohort of 15 983 CHF patients. This cohort was stratified based on their serum calcium levels, with the primary objective being the determination of in‐hospital mortality. To assess the impact of admission serum calcium levels on in‐hospital mortality, we employed various statistical methodologies, including multivariable logistic regression models, a generalized additive model, a two‐piecewise linear regression model, and subgroup analysis. Comparative analysis of the reference group (Q3) revealed increased in‐hospital mortality in the first quintile (Q1, the group with the lowest blood calcium level) and the fifth quintile (Q5, the group with the highest blood calcium level), with fully adjusted odds ratios of 1.38 [95% confidence interval (CI): 1.13–1.68, P = 0.002] and 1.23 (95% CI: 1.01–1.5, P = 0.038), respectively. A U‐shaped relationship was observed between serum calcium levels and in‐hospital mortality, with the lowest risk occurring at a threshold of 8.35 mg/dL. The effect sizes and corresponding CIs below and above this threshold were 0.782 (95% CI: 0.667–0.915, P = 0.0023) and 1.147 (95% CI: 1.034–1.273, P = 0.0094), respectively. Stratified analyses confirmed the robustness of this correlation. Conclusions Our study identifies a U‐shaped association between serum calcium levels and in‐hospital mortality in CHF patients, with a notable inflection point at 8.35 mg/dL. Further investigation through prospective, randomized, and controlled studies is warranted to validate the findings presented in this study.

Abstract Large-scale Randomised Controlled Trials (RCTs) are widely regarded as “the gold standard” for testing the causal effects of school-based interventions. RCTs typically present the statistical significance of the average treatment effect (ATE), which captures the effect an intervention has had on average for a given population. However, key decisions in child health and education are often about individuals who may be very different from those averages. One way to identify heterogeneous treatment effects across different individuals, not captured by the ATE, is to conduct subgroup analyses. For example, free school meal (FSM) pupils as required for projects funded by the Education Endowment Foundation (EEF) in England. These subgroup analyses, as we demonstrate in 48 EEF-funded RCTs involving over 200,000 students, are usually not standardised across studies and offer flexible degrees of freedom to researchers, potentially leading to mixed, if not misleading, results. Here, we develop and deploy an alternative to ATE and subgroup analysis, a machine-learning and regression-based framework to predict individualised treatment effects (ITEs). ITEs could show where an intervention worked, for which individuals, and to what extent. Our findings have implications for decision-makers in fields like education, healthcare, law, and clinical practices concerning children and adolescents.

In biomedical science, analyzing treatment effect heterogeneity plays an essential role in assisting personalized medicine. The main goals of analyzing treatment effect heterogeneity include estimating treatment effects in clinically relevant subgroups and predicting whether a patient subpopulation might benefit from a particular treatment. Conventional approaches often evaluate the subgroup treatment effects via parametric modeling and can thus be susceptible to model mis-specifications. In this paper, we take a model-free semiparametric perspective and aim to efficiently evaluate the heterogeneous treatment effects of multiple subgroups simultaneously under the one-step targeted maximum-likelihood estimation (TMLE) framework. When the number of subgroups is large, we further expand this path of research by looking at a variation of the one-step TMLE that is robust to the presence of small estimated propensity scores in finite samples. From our simulations, our method demonstrates substantial finite sample improvements compared to conventional methods. In a case study, our method unveils the potential treatment effect heterogeneity of rs12916-T allele (a proxy for statin usage) in decreasing Alzheimers disease risk.

Li Zuo,1,&ast; Wenhui Zhang,2,&ast; Ying Wang,3 Xin Qi1 1Department of Pulmonary and Critical Care Medicine, China Aerospace Science & Industry Corporation 731 Hospital, Beijing, 100074, People’s Republic of China; 2General Practice Clinic, Sijiqing Town Community Health Service Center of Haidian District, Beijing, 100097, People’s Republic of China; 3Department of Pharmacy, Wangtai Branch of Jincheng General Hospital, Jincheng, 048006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Qi, Department of pulmonary and critical care medicine, China Aerospace Science & Industry Corporation 731 Hospital, No. 3, Zhen Gang Nan Li, Feng Tai District, Beijing, 100074, People’s Republic of China, Email xinqixq015@163.comObjective: To explore serum KL-6 level and investigate its diagnostic value in interstitial lung diseases (ILDs).Methods: Serum KL-6 level was measured using the chemiluminescent enzyme immunoassay. Statistical analysis was performed for determining the KL-6 concentration of each group.Results: KL-6 level (U/mL) in the ILD group was 1388.321 ± 1943.116, which was higher than that in the control group, showing a significant statistical difference. ROC curve analysis based on the receiver operating characteristic curve showed the optimal cut-off value of 402.5U/mL, sensitivity of 77.4%, specificity of 93.4%, and accuracy of 89.4%; through Chi-square test with the two groups, the positive rate of KL-6 in patients with ILD was proved to be significantly higher than that in the control group. KL-6 level was 1063.00± 504.757 in the idiopathic pulmonary fibrosis (IPF) group, 1346.892 ± 1827.252 in the connective tissue disease-associated interstitial lung disease (CTD-ILD) group, 467.889± 288.859 in the organizing pneumonia (OP) group, 8252.333± 6050.625 in the pulmonary alveolar proteinosis (PAP) group, and 359.200± 392.707 in the sarcoidosis group. The rank sum test showed that the differences were statistically significant. KL-6 level was the lowest in the sarcoidosis group, followed by that in the OP group.Conclusion: Serum KL-6 level was confirmed to be highly sensitive, specific, and accurate in the diagnosis of ILD. Subgroup analysis showed that the KL-6 level was the lowest in the sarcoidosis group, followed by that in the OP group.Keywords: ILD, KL-6, diagnostic value, subgroup analysis

Meta-analysis combines the results of several scientific studies to obtain a summary quantitative estimation of effect size in order to compare the results of several studies and to identify patterns among them and possible sources of biases. Since the research teams, patients, research protocol, clinical guidelines and time intervals are often different between original scientific studies all these sources of difference can influence the results of each study, causing statistical heterogeneity. Meta-analyses are the highest level of credibility within evidence-based medicine, as they allow us to take into account the influence of many confounding factors and publication biases on the true effect size. Understanding the possible sources of erroneous conclusions in papers will allow researchers to analyze the results of such studies correctly and properly plan their own experiments. In this article the reader will be introduced to methods for identifying and quantifying hidden heterogeneity, such as subgroup analysis and meta-regression. In addition, the reader will learn how to calculate effect size in studies, estimate publication bias mathematically and graphically, and incorporate this estimate into the overall average effect size estimate in meta-analyses.

Abstract Previous studies have reported that the significant association between serum calcium and mortality substantially in patients, especially among those with intensive care unit (ICU). And In diabetes mellitus, congestive heart failure (CHF) is a significant comorbidity. We aim to evaluate the association between serum calcium levels and in-hospital mortality among patients with diabetes and congestive heart failure. The participants in this study were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. To scrutinize potential associations between serum calcium levels and in-hospital mortality, a comprehensive analysis encompassing multivariate logistic regression, cubic spline function model, threshold effect analysis, and subgroup analysis was performed. This retrospective cohort study encompassed 7063 patients, among whom the in-hospital mortality stood at 12.2%. In the multivariate logistic regression, adjusted odds ratios (ORs) were contrasted with the reference category Q6 (8.8–9.1 mg/dL) for serum calcium levels and in-hospital mortality. The adjusted ORs for Q1 (≤ 7.7 mg/dL), Q2 (7.7–8 mg/dL), and Q7 (≥ 9.1 mg/dL) were 1.69 (95% CI 1.17–2.44, p = 0.005), 1.62 (95% CI 1.11–2.36, p = 0.013), and 1.57 (95% CI 1.1–2.24, p = 0.012) respectively. The dose–response analysis uncovered a U-shaped relationship between serum calcium levels and in-hospital mortality in diabetic patients with heart failure. Subgroup analyses confirmed result stability notwithstanding the influence of diverse factors. Our investigation revealed a U-shaped correlation between serum calcium levels and in-hospital mortality in diabetes patients with congestive heart failure, pinpointing a significant inflection point at 9.05 mg/dL.

Abstract Subgroup analysis aims to identify subgroups (usually defined by baseline/demographic characteristics), who would (or not) benefit from an intervention under specific conditions. Often performed post hoc (not pre-specified in the protocol), subgroup analyses are prone to elevated type I error due to multiple testing, inadequate power, and inappropriate statistical interpretation. Aside from the well-known Bonferroni correction, subgroup treatment interaction tests can provide useful information to support the hypothesis. Using data from a previously published randomized trial where a p value of 0.015 was found for the comparison between standard and Hemopatch® groups in (the subgroup of) 135 patients who had hand-sewn pancreatic stump closure we first sought to determine whether there was interaction between the number and proportion of the dependent event of interest (POPF) among the subgroup population (patients with hand-sewn stump closure and use of Hemopatch®), Next, we calculated the relative excess risk due to interaction (RERI) and the “attributable proportion” (AP). The p value of the interaction was p = 0.034, the RERI was − 0.77 (p = 0.0204) (the probability of POPF was 0.77 because of the interaction), the RERI was 13% (patients are 13% less likely to sustain POPF because of the interaction), and the AP was − 0.616 (61.6% of patients who did not develop POPF did so because of the interaction). Although no causality can be implied, Hemopatch® may potentially decrease the POPF after distal pancreatectomy when the stump is closed hand-sewn. The hypothesis generated by our subgroup analysis requires confirmation by a specific, randomized trial, including only patients undergoing hand-sewn closure of the pancreatic stump after distal pancreatectomy. Trial registration: INS-621000-0760.

Background: Estimated pulse wave velocity (ePWV), which measures vascular aging, is an independent predictor of cardiovascular death. Nevertheless, the relationship between ePWV and all-cause mortality among patients suffering from non-traumatic subarachnoid hemorrhages (NSAH) remains obscure. Consequently, the objective of this study is to ascertain whether ePWV exerts influence on the prognosis of individuals afflicted with NSAH. Methods: Through the Medical Information Mart for Intensive Care IV (MIMICIV) database, 644 eligible participants were included. The Kaplan-Meier survival curve method was employed to assess the disparity in survival status between the low and high ePWV cohorts. The Cox proportional hazard model was employed to investigate the association between ePWV and inpatient mortality among critically ill patients diagnosed with NSAH. The Restricted Cubic Spline (RCS) model was employed to examine the dose-response correlation. Subsequently, multivariate Cox regression analysis was performed to identify independent prognostic factors. Lastly, the impact of ePWV on inpatient mortality across various subgroups was evaluated through stratified analysis. Results: Participants were categorized into two groups, delineated by their ePWV levels: a low ePWV level group and a high ePWV level group. Survival analysis unveiled that individuals with high ePWV exhibited a diminished survival rate compared to their counterparts with low ePWV. Following adjustment, low ePWV was significantly linked with a reduced risk of inpatient mortality among patients with NSAH (HR = 0.54, 95% CI = 0.32-0.89, p = 0.016). Simultaneously, analysis employing the RCS model further substantiated a linear escalation in the risk of inpatient mortality with increasing ePWV values. Conclusion: Elevated ePWV levels have been identified as an independent risk factor for the rise in inpatient mortality among NSAH patients and as a significant predictor of the clinical outcome of NSAH. [ABSTRACT FROM AUTHOR]

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Background: There is limited evidence regarding the correlation between prostate-specific antigen (PSA) kinetics and clinical outcomes. Therefore, after regulating other covariates, we studied patients with castration-resistant prostate cancer who received abiraterone acetate as the first-line treatment. In this study, we investigated whether time to PSA nadir was independently associated with PSA progression-free survival (PFS). Methods: As a retrospective cohort study, this study contained a total of 77 castration-resistant prostate cancer patients who received abiraterone acetate from October 2015 to April 2021 in a Chinese hospital. The dependent variable was PSA-PFS. The objective independent variable was time to PSA nadir (TTPN). Covariates involved in this study included age, duration of androgen deprivation therapy (ADT), PSA level at baseline, time of 50% PSA decline, time of PSA decline to nadir, Gleason score, bone metastasis, previous treatment, PSA decline <50% in 3 months, PSA to nadir in 3 months, PSA decline <90%, PSA decline <0.2 ng/ mL, and PSA flare. Results: For the 77 subjects, their mean age was 72.70 ± 8.08 years. Fully calibrated linear regression findings indicated that PSA decline and kinetics were positively associated with PFS (months) after adjusting confounders (ß = 0.77, 95% CI: 0.11-1.44). A non-linear relationship was not detected between PSA decline or PSA kinetics and progression-free survival. Conclusion: According to the data of this study, there was a correlation between early PSA changes and patients treated with abiraterone acetate. [ABSTRACT FROM AUTHOR]

Previous studies have reported that the significant association between serum calcium and mortality substantially in patients, especially among those with intensive care unit (ICU). And In diabetes mellitus, congestive heart failure (CHF) is a significant comorbidity. We aim to evaluate the association between serum calcium levels and in-hospital mortality among patients with diabetes and congestive heart failure. The participants in this study were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. To scrutinize potential associations between serum calcium levels and in-hospital mortality, a comprehensive analysis encompassing multivariate logistic regression, cubic spline function model, threshold effect analysis, and subgroup analysis was performed. This retrospective cohort study encompassed 7063 patients, among whom the in-hospital mortality stood at 12.2%. In the multivariate logistic regression, adjusted odds ratios (ORs) were contrasted with the reference category Q6 (8.8–9.1 mg/dL) for serum calcium levels and in-hospital mortality. The adjusted ORs for Q1 (≤ 7.7 mg/dL), Q2 (7.7–8 mg/dL), and Q7 (≥ 9.1 mg/dL) were 1.69 (95% CI 1.17–2.44, p = 0.005), 1.62 (95% CI 1.11–2.36, p = 0.013), and 1.57 (95% CI 1.1–2.24, p = 0.012) respectively. The dose–response analysis uncovered a U-shaped relationship between serum calcium levels and in-hospital mortality in diabetic patients with heart failure. Subgroup analyses confirmed result stability notwithstanding the influence of diverse factors. Our investigation revealed a U-shaped correlation between serum calcium levels and in-hospital mortality in diabetes patients with congestive heart failure, pinpointing a significant inflection point at 9.05 mg/dL. [ABSTRACT FROM AUTHOR]

Subgroup analysis aims to identify subgroups (usually defined by baseline/demographic characteristics), who would (or not) benefit from an intervention under specific conditions. Often performed post hoc (not pre-specified in the protocol), subgroup analyses are prone to elevated type I error due to multiple testing, inadequate power, and inappropriate statistical interpretation. Aside from the well-known Bonferroni correction, subgroup treatment interaction tests can provide useful information to support the hypothesis. Using data from a previously published randomized trial where a p value of 0.015 was found for the comparison between standard and Hemopatch® groups in (the subgroup of) 135 patients who had hand-sewn pancreatic stump closure we first sought to determine whether there was interaction between the number and proportion of the dependent event of interest (POPF) among the subgroup population (patients with hand-sewn stump closure and use of Hemopatch®), Next, we calculated the relative excess risk due to interaction (RERI) and the "attributable proportion" (AP). The p value of the interaction was p = 0.034, the RERI was − 0.77 (p = 0.0204) (the probability of POPF was 0.77 because of the interaction), the RERI was 13% (patients are 13% less likely to sustain POPF because of the interaction), and the AP was − 0.616 (61.6% of patients who did not develop POPF did so because of the interaction). Although no causality can be implied, Hemopatch® may potentially decrease the POPF after distal pancreatectomy when the stump is closed hand-sewn. The hypothesis generated by our subgroup analysis requires confirmation by a specific, randomized trial, including only patients undergoing hand-sewn closure of the pancreatic stump after distal pancreatectomy. Trial registration: INS-621000-0760. [ABSTRACT FROM AUTHOR]

IntroductionMental health problems, especially depressive symptoms, are becoming increasingly prominent, posing a significant risk to public health. Changes in the body mass index (BMI) may impact an individual’s mental health, however, the relationship between BMI and depressive symptoms is unclear. The purpose of this study was to investigate the association between BMI and depressive symptoms.MethodsUsing a multi-stage sampling method, 10,686 adults in Longgang District, Shenzhen City, Guangdong Province, China, were selected for participation in this study. Surveys were distributed in 2020 and 2021 to measure participant demographic data and health. Binary logistic regression, restricted cubic spline regression, and subgroup analyses were performed to explore the relationship between BMI and depressive symptoms.ResultsThe results showed a U-shaped relationship between BMI and depression. Both obesity and underweight increased the risk of depression among the participants, especially in subgroups of participants who were young, highly educated, single and employed.ConclusionThese findings suggest that adults should try to maintain a normal body weight as a way to prevent depression and maintain their physical and mental health.

BackgroundIn recent years, septic shock remains a common fatal disease in the intensive care unit (ICU). After sufficient fluid resuscitation, some patients still experience tachycardia, which may lead to adverse effects on cardiac function. However, the use of β-blockers in the treatment of septic shock remains controversial. Thus, the purpose of this study is to evaluate the efficacy of β-blockers in the treatment of patients with septic shock and explore the most appropriate patient subgroups for this treatment.MethodsThis retrospective observational study enrolled septic shock patients from the Medical Information Mart for Intensive Care (MIMIC)-IV and used propensity score matching (PSM) to balance some baseline differences between patients with and without β-blockers treatment. The primary outcome was the 28-day mortality. Length of stay (LOS) in the ICU and hospital, and the degree of support for organs such as circulatory, respiratory and renal systems were also assessed. Subgroup analysis and multivariate logistic regression were performed to determine the relationship between β-blockers therapy and 28-day mortality in different patient groups.ResultsA total of 4,860 septic shock patients were enrolled in this study and 619 pairs were finally matched after PSM. Our analysis revealed that β-blocker therapy was associated with a significant improvement in 28-day mortality (21.5% vs. 27.1%; P = 0.020) and led to a prolonged LOS in both the ICU and hospital. Subgroup analysis indicated that there was an interaction between cardiovascular diseases and β-blocker therapy in patients with septic shock. Patients with pre-existing heart disease or atrial arrhythmias were more likely to derive benefits from β-blocker treatment.ConclusionWe found β-blockers therapy was effective to improve 28-day mortality in patients with septic shock. Patients in the subgroup with cardiovascular diseases were more likely to benefit from β-blockers in mortality.

School-based, universal social and emotional learning (SEL) has been widely practiced and promoted as a promising approach to prevent youth mental, emotional, and behavioral problems. Although prior research has accumulated robust evidence of the average effects of universal SEL, it remains unclear whether it works similarly or differentially across diverse sociocultural subgroups of students. Investigating subgroup effects has implications for understanding the impact of universal SEL on possible subgroup disparities in student social-emotional competence (SEC). This study examined whether the effects of a universal SEL program on student SEC development differed across diverse student subgroups classified by gender, race, ethnicity, socioeconomic status, disability status, and English learner status. Data came from student SEC progress monitoring collected during a 1-year quasi-experimental study of a universal SEL program (N = 1592; Grades K-2). The results of multigroup latent growth modeling suggest that (a) the intervention effects were slightly larger for Black students, compared to White or other racial-ethnic subgroups, and (b) the effects were not different across other examined subgroups. This study also found that in the comparison condition, the SEC disparities between Black and White students tended to widen throughout the year, whereas in the intervention condition, Black students showed a similar rate of growth as their White peers. Findings suggest that universal SEL may be similarly beneficial across many diverse student subgroups, while it may yield larger benefits among some racially marginalized subgroups, preventing racial disparities from further widening. Yet the benefits of SEL may not be sufficient to reduce existing subgroup disparities. These findings suggest a need for more studies to examine differential effects of universal preventive programs by diverse subgroups to better inform practices that enhance equity in youth outcomes.

Bingcong Zhao,1,2 Zhigang Li,3 Chuan Shi,4 Yan Liu,5 Yang Sun,3 Bin Li,1,2 Jie Zhang,6 Zhizhong Gong,7 Yuanzheng Wang,8 Xuehong Ma,9 Xinjing Yang,10 Huili Jiang,3 Yuanbo Fu,1,2 Xin Wang,1,2 Yang Li,6 Hengchia Liu,6 Tuya Bao,3 Yutong Fei11– 13 1Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, People’s Republic of China; 3School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Psychological Assessment Center, Peking University Sixth Hospital, Beijing, People’s Republic of China; 5Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 6Department of Psychosomatic Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 7Division of Medical Affairs, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 8Department of Integrative TCM and Western Medicine, Peking University First Hospital, Beijing, People’s Republic of China; 9Department of Acupuncture & Moxibustion, Dongfang Hospital, the Second Clinical Medical College of Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 10Department of Traditional Chinese Medicine, South China Hospital of Shenzhen University, Shenzhen, People’s Republic of China; 11Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 12Institute of Excellence in Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 13Beijing GRADE Centre, Beijing, People’s Republic of ChinaCorrespondence: Tuya Bao, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, People’s Republic of China, Email tuyab@263.net Yutong Fei, Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, People’s Republic of China, Email feiyt@bucm.edu.cnPurpose: Anxious depression (AD) is a common, distinct depression subtype. This exploratory subgroup analysis aimed to explore the effects of acupuncture as an add-on therapy of selective serotonin reuptake inhibitors (SSRIs) for patients with AD or non-anxious depression (NAD).Patients and Methods: Four hundred and sixty-five patients with moderate-to-severe depression from the AcuSDep pragmatic trial were included in analysis. Patients were randomly assigned to receive MA+SSRIs, EA+SSRIs, or SSRIs alone (1:1:1) for six weeks. AD was defined by using dimensional criteria. The measurement instruments included 17-items Hamilton Depression Scale (HAMD-17), Self-Rating Depression Scale (SDS), Clinical Global Impression (CGI), Rating Scale for Side Effects (SERS), and WHO Quality of Life-BREF (WHOQOL-BREF). Comparison between AD and NAD subgroups and comparisons between groups within either AD or NAD subgroups were conducted.Results: Eighty percent of the patients met the criteria for AD. The AD subgroup had poorer clinical manifestations and treatment outcomes compared to those of the NAD subgroup. For AD patients, the HAMD response rate, remission rate, early onset rate, and the score changes on each scale at most measurement points on the two acupuncture groups were significantly better than the SSRIs group. For NAD patients, the HAMD early onset rates of the two acupuncture groups were significantly better than the SSRIs group.Conclusion: For AD subtype patients, either MA or EA add-on SSRIs showed comprehensive improvements, with small-to-medium effect sizes. For NAD subtype patients, both the add-on acupuncture could accelerate the response to SSRIs treatment. The study contributed to the existing literature by providing insights into the potential benefits of acupuncture in combination with SSRIs, especially for patients with AD subtypes. Due to its limited nature as a post hoc subgroup analysis, prospectively designed, high-quality trials are warranted.Clinical Trials Registration: ChiCTR-TRC-08000297.Keywords: anxious depression, non-anxious depression, acupuncture, SSRIs, subgroup analysis

Black soldier fly (BSF) meal possesses a balanced nutritional profile, making it a promising substitute for fishmeal. Several studies have been conducted to investigate the effects of replacing fishmeal with BSF meal on fish immune response and antioxidant capacity. However, considering the varying effects of BSF meal on different fish species demonstrated in earlier studies, a meta-analysis study was imperative to determine the efficacy of BSF meal in aquafeed. This meta-analysis examined 38 studies on finfish. Subgroup analysis and meta-regression were conducted to investigate the source of heterogeneity in the immunostimulant and antioxidant efficacy of BSF meal. Categorical variables used in subgroup analysis included the BSF development stage (larvae versus prepupae or pupae), BSF processing method (full-fat versus defatted), and fish dietary habits. Two continuous variables were evaluated for meta-regression analysis: dietary BSF inclusion level and treatment duration. The datasets were assessed for publication bias using funnel plots and Egger's test with the Pustejovsky–Rodgers Approach. The results revealed that BSF meal influences immune performance and antioxidant ability. Subgroup analysis indicated that different BSF development stages significantly influence the immunostimulant and antioxidant efficacy of BSF meals, with BSF prepupae or pupae outperforming BSF larvae. In terms of processing, full-fat BSF was superior to defatted BSF. Furthermore, BSF meal demonstrated the highest efficacy in omnivorous fishes. Meta-regression outcomes revealed that a higher concentration of BSF meal may inhibit immune response and antioxidant ability and that treatment duration exerts little impact. In conclusion, the present meta-analysis demonstrated that BSF is a promising ingredient in aquafeed to improve fish immune response and antioxidant capacity.

Missing data problems arise in randomized trials, which complicates the inference of causal effects if the missing mechanism is non-ignorable. We tackle the challenge of identifying and estimating the complier average causal effect parameters under non-ignorable missingness by increasing the covariates to mitigate the sensitivity to the violation of specific identification assumptions. The missing data mechanism is assumed to follow a logistic model, wherein the absence of the outcome is explained by the outcome itself, the treatment received, and the covariates. We establish the identifiability of the models under mild conditions by assuming that the outcome follows a normal distribution. We develop a computational method to estimate model parameters through a two-step likelihood estimation approach, employing subgroup analysis. The bootstrap method is employed for variance estimation, and the effectiveness of our approach is confirmed through simulation. We applied the proposed method to analyze the household income dataset from the Chinese Household Income Project Survey 2013. [ABSTRACT FROM AUTHOR]

Background and purpose: In 2016, we concluded a randomized controlled trial testing 1 mg rasagiline per day add‐on to standard therapy in 252 amyotrophic lateral sclerosis (ALS) patients. This article aims at better characterizing ALS patients who could possibly benefit from rasagiline by reporting new subgroup analysis and genetic data. Methods: We performed further exploratory in‐depth analyses of the study population and investigated the relevance of single nucleotide polymorphisms (SNPs) related to the dopaminergic system. Results: Placebo‐treated patients with very slow disease progression (loss of Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised [ALSFRS‐R] per month before randomization of ≤0.328 points) showed a per se survival probability after 24 months of 0.85 (95% confidence interval = 0.65–0.94). The large group of intermediate to fast progressing ALS patients showed a prolonged survival in the rasagiline group compared to placebo after 6 and 12 months (p = 0.02, p = 0.04), and a reduced decline of ALSFRS‐R after 18 months (p = 0.049). SNP genotypes in the MAOB gene and DRD2 gene did not show clear associations with rasagiline treatment effects. Conclusions: These results underline the need to consider individual disease progression at baseline in future ALS studies. Very slow disease progressors compromise the statistical power of studies with treatment durations of 12–18 months using clinical endpoints. Analysis of MAOB and DRD2 SNPs revealed no clear relationship to any outcome parameter. More insights are expected from future studies elucidating whether patients with DRD2CC genotype (Rs2283265) show a pronounced benefit from treatment with rasagiline, pointing to the opportunities precision medicine could open up for ALS patients in the future. [ABSTRACT FROM AUTHOR]

Background: Prior pulmonary tuberculosis (PTB) might be associated with the development of chronic obstructive pulmonary disease (COPD). However, the impact of prior PTB on the risk of incident COPD has not been studied in a large prospective cohort study of the European population. Objectives: This study aimed to investigate the association of prior PTB with the risk of COPD. Design: Prospective cohort study. Methods: A multivariable Cox proportional model was used to estimate the hazard ratio (HR) and 95% confidence interval (95% CI) for the association of prior PTB with COPD. Subgroup analyses were further conducted among individuals stratified by age, sex, body mass index, smoking status, drinking status, physical activity, and polygenic risk score (PRS). Results: The study involved a total of 216,130 participants, with a median follow-up period of 12.6 years and 2788 incident cases of COPD. Individuals with a prior history of PTB at baseline had an 87% higher risk of developing incident COPD compared to those without such history [adjusted hazard ratio (aHR) = 1.87; 95% confidence interval (CI): 1.26–2.77; p = 0.002]. Subgroup analysis revealed that individuals having prior PTB history presented a higher risk of incident COPD among individuals who were aged from 50 to 59 years with aHR of 2.47 (1.02–5.95, p = 0.044), older than 59 years with aHR of 1.81 (1.16–2.81, p = 0.008), male with aHR of 2.37 (1.47–3.83, p < 0.001), obesity with aHR of 3.35 (2.16–5.82, p < 0.001), previous smoking with aHR of 2.27 (1.39–3.72, p < 0.001), current drinking with aHR of 1.98 (1.47–3.83, p < 0.001), low physical activity with aHR of 2.62 (1.30–5.26, p = 0.007), and low PRS with aHR of 3.24 (1.61–6.53, p < 0.001), as well as high PRS with aHR of 2.43 (1.15–5.14, p = 0.019). Conclusion: A history of PTB is an important independent risk factor for COPD. Clinical staff should be aware of this risk factor in patients with prior PTB, particularly in countries or regions with high burdens of PTB. Plain language summary: Associations of prior pulmonary tuberculosis with the incident COPD Prior pulmonary tuberculosis (PTB) indicates that an individual has a history of PTB. The impact of prior PTB on the risk of incident chronic obstructive pulmonary disease (COPD) has not been studied in a large prospective cohort study of European population. Here, we investigated the association between prior PTB and risk of COPD in 216,130 participants from the UK biobank (a large biomedical database). After a median follow up of more than 12 years, 2,788 incident COPD cases were recorded. Individuals with prior PTB at baseline had an 87% higher risk of developing incident COPD compared to those without history of PTB. Specifically, individuals with prior PTB presented with a higher risk of incident COPD among those who were older than 50 years, male, obese, had a previous history of smoking, are currently drinking, have low physical activity, and have a low and high genetic predicted lung function. This study suggested prior PTB as an important and independent risk factor for COPD. Clinical staff should be aware of this risk factor in patients with prior PTB, particularly in countries or regions with high burdens of PTB. [ABSTRACT FROM AUTHOR]

BackgroundLimited data are available regarding the association between serum transferrin saturation (TSAT) levels and heart failure (HF).MethodsWe utilized data from National Health and Nutrition Examination Survey (NHANES) 2017- 2020.03 for analysis. Data on TAST, HF and covariates were extracted and analyzed. Weighted logistic regression and subgroup analysis were used to explore the independent association between TSAT and HF. Furthermore, interaction tests were also carried out to evaluate the strata differences. We subsequently assessed whether there was a non-linear relationship between the 2 using Restricted cubic spline (RCS) and threshold effect models.ResultA total of 282 (3.87%) participants were identified to have HF. Among the total population, participants with HF had significantly lower TSAT levels compared to those without HF (24.63 vs. 27.95, P = 0.001). After fully adjusting for potential confounders, weighted multiple logistic regression models revealed a 2.6% reduced in the risk of HF when each unit of TSAT increased. There was also a negative association between elevated TSAT and developed risk of HF in the quartile groups (Q1 OR:1.00; Q2 OR: 0.924 [95%CI:0.593,1.440]; Q3 OR: 0.515 [95%CI:0.298,0.891]; Q4 OR:0.411 [95%CI:0.201,0.839]). The subgroup analysis results remained consistent across strata, with a strong negative correlation between TSAT and HF. Interaction tests showed no dependence on gender, age, Body Mass Index, race, diabetes, hypertension, hyperlipidemia, ratio of family income to poverty and education for this negative association between TSAT and HF (all p for interaction >0.05). The RCS and threshold effect models indicated a linear negative correlation between TSAT and HF, which was more pronounced when TSAT under 40%.ConclusionOverall, these findings suggest a consistent and negative association between TSAT levels and the presence of HF among middle-aged and older adults in the United States.

This paper addresses patient heterogeneity associated with prediction problems in biomedical applications. We propose a systematic hypothesis testing approach to determine the existence of patient subgroup structure and the number of subgroups in patient population if subgroups exist. A mixture of generalized linear models is considered to model the relationship between the disease outcome and patient characteristics and clinical factors, including targeted biomarker profiles. We construct a test statistic based on expectation maximization (EM) algorithm and derive its asymptotic distribution under the null hypothesis. An important computational advantage of the test is that the involved parameter estimates under the complex alternative hypothesis can be obtained through a small number of EM iterations, rather than optimizing the objective function. We demonstrate the finite sample performance of the proposed test in terms of type-I error rate and power, using extensive simulation studies. The applicability of the proposed method is illustrated through an application to a multicenter prostate cancer study.

Abstract Background Across studies of average treatment effects, some population subgroups consistently have lower representation than others which can lead to discrepancies in how well results generalize. Methods We develop a framework for quantifying inequity due to systemic disparities in sample representation and a method for mitigation during data analysis. Assuming subgroup treatment effects are exchangeable, an unbiased sample average treatment effect estimator will have lower mean-squared error, on average across studies, for subgroups with less representation when treatment effects vary. We present a method for estimating average treatment effects in representation-adjusted samples which enables subgroups to optimally leverage information from the full sample rather than only their own subgroup’s data. Two approaches for specifying representation adjustment are offered—one minimizes average mean-squared error for each subgroup separately and the other balances minimization of mean-squared error and equal representation. We conduct simulation studies to compare the performance of the proposed estimators to several subgroup-specific estimators. Results We find that the proposed estimators generally provide lower mean squared error, particularly for smaller subgroups, relative to the other estimators. As a case study, we apply this method to a subgroup analysis from a published study. Conclusions We recommend the use of the proposed estimators to mitigate the impact of disparities in representation, though structural change is ultimately needed.

Background: This study investigated potential subgroups of children within the Kiel Obesity Prevention Study (KOPS) for differing treatment effects for the outcome measures of overweight or obesity at 4 years. The KOPS study delivered a multicomponent school intervention to cohorts of children in Kiel but found no overall effect on the weight status outcome. However, KOPS authors suggested there may be subgroup variations in treatment effect. Data were collected as part of the KOPS for samples of 6-year-olds between 1996 and 2001, with 4-year follow-up measurements between 2000 and 2004. Methods: The present study conducted a post hoc subgroup analysis of the odds of obesity or overweight at 4-year follow-up compared to normal weight (n = 1646). A generalized linear mixed-effects model, including a treatment–subgroup interaction term, was used to estimate subgroups as a moderator of the treatment effects on the outcomes of obesity or overweight at 4-year follow-up. Results: The findings indicated several subgroup–treatment interaction effects relating to physical activity indicators. TV or PC not being one of a child’s top 3 activities at baseline was associated with a significantly decreased odds ratio of obesity at 4 years in the intervention group (OR, 0.04; 95% CI, 0.004 to 0.45) compared to the non-intervention group (OR, 0.96; 95% CI, 0.29 to 3.14), p = 0.02. Weekly activity in a sports club at baseline was associated with a decreased odds ratio of overweight at 4 years in the intervention group (OR, 0.38; 95% CI, 0.16 to 0.85) compared to the non-intervention group (OR, 0.91; 95% CI, 0.70 to 1.17). This was a significant difference (p = 0.04). Conclusions: These findings suggest that children’s baseline physical activity may impact treatment effects on the outcomes of overweight and obesity, creating opportunities to increase the effectiveness of interventions on preventing obesity.

PurposeSocial policies are important determinants of population health but may have varying effects on subgroups of people. Evaluating heterogeneous treatment effects (HTEs) of social policies is critical to determine how social policies will affect health inequities. Methods for evaluating HTEs are not standardized. Little is known about how often and by what methods HTEs are assessed in social policy and health research.MethodsA sample of 55 articles from 2019 on the health effects of social policies were evaluated for frequency of reporting HTEs; for what subgroupings HTEs were reported; frequency of a priori specification of intent to assess HTEs; and methods used for assessing HTEs.ResultsA total of 24 (44%) studies described some form of HTE assessment, including by age, gender, education, race/ethnicity, and/or geography. Among studies assessing HTEs, 63% specified HTE assessment a priori, and most (71%) used descriptive methods such as stratification; 21% used statistical tests (e.g., interaction terms in a regression); and no studies used data-driven algorithms.ConclusionsAlthough understanding HTEs could enhance policy and practice-based efforts to reduce inequities, it is not routine research practice. Increased evaluation of HTEs across relevant subgroups is needed.

PD-L1 expression is associated with differential response in cancers treated with checkpoint inhibitors. Clinical trials for Food and Drug Administration (FDA) approvals of programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors include limited subgroup analyses based on PD-L1 expression. We aimed to define the characteristics of PD-L1 defined subgroups of clinical trials leading to FDA approvals for new indications of PD-1/PD-L1 inhibitors. FDA approvals for PD-1/PD-L1 inhibitors from January 2014 to December 2020 were identified and the clinical trials leading to each drug approval were reviewed. We collected key variables from publicly available information on FDA website and peer-reviewed publications of clinical trials. We assessed regulatory characteristics (approval date, approved drug[s], cancer type, line of therapy and biomarker-restricted approval criteria) of each approval. Clinical trials leading to approvals were reviewed for trial design (RCT vs single arm study, primary endpoint) and PD-L1 defined subgroup design (no subgroup analysis, single threshold 2-group analysis, nested subgroups and adjacent subgroups). We then compared regulatory and trials characteristics (trial design, primary endpoint and biomarker approval criteria) between studies with nested and adjacent subgroups. There were 60 approvals for PD-1/PD-L1 inhibitors between January 2014 and December 2020. Twelve of 60 (20%) did not include any PD-L1 subgroups. Twenty-five of 60 (42%) approvals reported only two subgroups, 14 (23%) included adjacent subgroups and 9 (15%) had nested subgroups. Twenty-five of 60 trials (42%) are single arm studies. Comparison of characteristics between trials with nested subgroup design and adjacent subgroup design did not show differences. We conclude that approvals for new indications of PD-1/PD-L1 inhibitors are based on studies that do not include comprehensive reporting of outcomes by PD-L1 biomarker subgroups.

Objective: The necessity of postmastectomy radiotherapy(PMRT) for patients with HR+/HER2 T1-2 N1M0 breast cancer remains controversial. We want to use explainable machine learning to learn the feature importance of the patients and identify the subgroup of the patients who may benefit from the PMRT. Additionally, develop tools to provide guidance to the doctors. Methods: In this study, we trained and validated 2 machine learning survival models: deep learning neural network and Cox proportional hazard model. The training dataset consisted of 35,347 patients with HR+/HER2- T1-2 N1M0 breast cancer who received mastectomies from the SEER database from 2013 to 2018. The performance of survival models were assessed using a concordance index (c-index). Then we did subgroup analysis to identify the subgroup who could benefit from PMRT. We also analyzed the global feature importance for the model and individual feature importance for individual survival prediction. Finally, we developed a Cloud-based recommendation system for PMRT to visualize the survival curve of each treatment plan and deployed it on the Internet. Results: A total of 35,347 patients were included in this study. We identified that radiotherapy improved the OS in patients with tumor size >14mm and age older than 54: 5-year OS rates of 91.9 versus 87.2% (radio vs. nonradio, P <0.001) and cohort with tumor size >14mm and grade worse than well-differentiated, 5-year OS rates of 90.8 versus 82.3% (radio vs. nonradio, P <0.001). The deep learning network performed more stably and accurately in predicting patients survival than the random survival forest and Cox proportional hazard model on the internal test dataset (C-index=0.776 vs 0.641) and in the external validation(Cindex= 0.769 vs 0.650). Besides, the deep learning model identified several key factors that significantly influence patient survival, including tumor size, examined regional nodes, age at 45-49 years old and positive regional nodes (PRN). Conclusion: Patients with tumor size >14mm and age older than 54 and cohort with tumor size >14mm and grade worse than well-differentiated could benefit from the PMRT. The deep learning network performed more stably and accurately in predicting patients survival than Cox proportional hazard model on the internal test. Besides, tumor size, examined regional nodes, age at 45-49 years old and PRN are the most significant factors to the overall survival (OS). [ABSTRACT FROM AUTHOR]

Background: Across studies of average treatment effects, some population subgroups consistently have lower representation than others which can lead to discrepancies in how well results generalize. Methods: We develop a framework for quantifying inequity due to systemic disparities in sample representation and a method for mitigation during data analysis. Assuming subgroup treatment effects are exchangeable, an unbiased sample average treatment effect estimator will have lower mean-squared error, on average across studies, for subgroups with less representation when treatment effects vary. We present a method for estimating average treatment effects in representation-adjusted samples which enables subgroups to optimally leverage information from the full sample rather than only their own subgroup's data. Two approaches for specifying representation adjustment are offered—one minimizes average mean-squared error for each subgroup separately and the other balances minimization of mean-squared error and equal representation. We conduct simulation studies to compare the performance of the proposed estimators to several subgroup-specific estimators. Results: We find that the proposed estimators generally provide lower mean squared error, particularly for smaller subgroups, relative to the other estimators. As a case study, we apply this method to a subgroup analysis from a published study. Conclusions: We recommend the use of the proposed estimators to mitigate the impact of disparities in representation, though structural change is ultimately needed. [ABSTRACT FROM AUTHOR]

Objective: To assess whether the administration of Zishen Yutai Pill (ZYP) could improve the pregnancy outcomes in different subgroups of women undergoing fresh embryo transfer cycles. Materials and methods: This is a post hoc analysis of a large scale, placebocontrolled, double blind, randomized clinical trial (RCT) regarding the use of ZYP during assisted reproductive technology (ART) treatment. The RCT was conducted at 19 in vitro fertilization (IVF) centers between April 2014 and June 2017. A total of 2265 women undergoing fresh embryo transfer cycles were randomly assigned in a 1:1 ratio to receive ZYP (n = 1131) or placebo (n = 1134). Post hoc logistic regression analyses were applied in this study to examine the between-group differences of ZYP and placebo on clinical pregnancy rate among different subgroups. Detailed analyses, both in intention-to-treat (ITT) and per-protocol population, were also conducted in specific subgroups with regards to rates of implantation, biochemical pregnancy, clinical pregnancy, live birth, pregnancy loss, as well as other neonatal indices. Results: ZYP showed a significantly higher clinical pregnancy rates than placebo in the ITT population. Detailed subgroup analyses were conducted in subgroup in advanced maternal age (AMA, ≥ 35 years old) and overweight/obese patients (BMI > 24), due to the clinical importance and statistical results. In these subgroups, baseline characteristics were similar between two arms (all P > 0.05). Significantly elevated clinical pregnancy rates were observed in ZYP cohort (both P < 0.05) compared with the placebo group. Results also showed that ZYP treatment resulted in significantly higher rates of implantation, biochemical pregnancy in AMA or overweight/obese patients in ITT analysis (all P < 0.05). Conclusions: The current post hoc subgroup analysis suggested that AMA and overweight/obese women could experience clinical benefits when treated with ZYP in their fresh embryo transfer cycles. The study provides references for the use of ZYP in ART practices. However, further studies in specific subgroups should be examined in more rigorous clinical trial settings. [ABSTRACT FROM AUTHOR]

Abstract An awareness of antecedents of acceptance of digital contact tracing (DCT) can enable healthcare authorities to design appropriate strategies for fighting COVID-19 or other infectious diseases that may emerge in the future. However, mixed results about these antecedents are frequently reported. Most prior DCT acceptance review studies lack statistical synthesis of their results. This study aims to undertake a systematic review and meta-analysis of antecedents of DCT acceptance and investigate potential moderators of these antecedents. By searching multiple databases and filtering studies by using both inclusion and exclusion criteria, 76 and 25 studies were included for systematic review and meta-analysis, respectively. Random-effects models were chosen to estimate meta-analysis results since Q, I 2 , and H index signified some degree of heterogeneity. Fail-safe N was used to assess publication bias. Most DCT acceptance studies have focused on DCT related factors. Included antecedents are all significant predictors of DCT acceptance except for privacy concerns and fear of COVID-19. Subgroup analysis showed that individualism/collectivism moderate the relationships between norms/privacy concerns and intention to use DCT. Based on the results, the mean effect size of antecedents of DCT acceptance and the potential moderators may be more clearly identified. Appropriate strategies for boosting the DCT acceptance rate can be proposed accordingly.

Meijuan Zhang, Zhanquan Jiao Department of Cardiology, Tianjin Institute of Respiratory Diseases, Tianjin Haihe Hospital, Tianjin University, Tianjin, People’s Republic of ChinaCorrespondence: Zhanquan Jiao, Department of Cardiology, Tianjin Haihe Hospital, Jingu Road, Tianjin, 300350, People’s Republic of China, Tel +8613752370120, Email jiaozhanquan@126.comPurpose: Elevated levels of the inflammatory marker interleukin-6 (IL-6) and cardiac injury marker N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been observed in patients with coronavirus disease 2019 (COVID-19). However, the relationship between IL-6 and NT-proBNP levels remains unclear. Therefore, we investigated the relationship between IL-6 and NT-proBNP levels in patients with COVID-19.Patients and Methods: This was a cross-sectional study. Consecutive patients with COVID-19 were included herein. The independent and dependent target variables were the IL-6 and NT-proBNP levels, respectively, measured at baseline. Univariate and multivariate linear regression analyses and curve fitting were also performed.Results: The average age of the 121 selected participants was 49.8 ± 15.8 years old, and 48.8% (59/121) were male. The estimated β value between Ln-transformed IL-6 and NT-proBNP was 0.28 (95% confidence interval [CI] 0.12– 0.44, P = 0.001) in univariate logistic regression analysis and 0.09 (95% CI − 0.04– 0.21, P = 0.176) in the fully adjusted model. This relationship was nonlinear, with a point of 2.7, and the β values (and CIs) for the left (< 2.7) and right (≥ 2.7) sides of the inflection point were − 0.06 (95% CI − 0.23– 0.12, P = 0.534) and 0.77 (95% CI 0.18– 1.37, P = 0.016) in the fully adjusted model, respectively.Conclusion: Our results suggest a nonlinear association between IL-6 and NT-proBNP levels. Higher IL-6 levels are associated with NT-proBNP in patients with COVID-19.Keywords: interleukin-6, NT-proBNP, COVID-19, nonlinear association

Metabolic syndrome has become a significant public health concern. This study aims to investigate the impact of dietary patterns on metabolic syndrome in young adults and how physical activity modulates this effect. A cross-sectional study was conducted at a health management center in Tianjin, China, from September 2022 to March 2023. Participants aged 18–35 years were recruited using convenience sampling. Dietary intake was assessed using a validated food frequency questionnaire. Logistic regression models evaluated associations between these patterns and metabolic syndrome, adjusting for potential confounders. Among 442 participants, four dietary patterns were identified: Legume–Nut, Alcohol–Meat, Sugar–Processed, and Egg–Vegetable. The Legume–Nut dietary pattern was associated with a higher risk of metabolic syndrome (OR = 2.63, 95% CI: 1.08–6.37), while the Egg–Vegetable dietary pattern was associated with a lower risk (OR = 0.26, 95% CI: 0.10–0.70). No significant associations were found for the Sugar–Processed and Alcohol–Meat patterns. Subgroup analysis revealed that the Legume–Nut pattern increased the risk of metabolic syndrome among those with irregular physical activity, whereas the Egg–Vegetable pattern decreased the risk. These findings highlight the significant influence of dietary patterns on the risk of metabolic syndrome in young adults and the modifying effect of regular physical activity, underscoring the need for targeted dietary and lifestyle interventions to prevent metabolic syndrome in this population.

Abstract Objective This study aims to evaluate the efficacy of photodynamic therapy (PDT) in the treatment of oral leukoplakia and explore the subgroup factors that may influence its effectiveness. Methods A systematic search was conducted in PubMed, Embase, the Cochrane Library, and Web of Science databases to identify relevant studies. Meta-analysis was performed using Stata15.0 software. Cochran’s Q test and I2 statistics were used to evaluate heterogeneity, egger’s test was used to evaluate publication bias. Results The analysis of 17 studies included in this study suggests that PDT may be effective in achieving complete response (CR) [ES = 0.50, 95%CI: (0.33,0.66)], partial response (PR) [ES = 0.42, 95%CI: (0.27,0.56)], no response (NR) [ES = 0.19, 95%CI: (0.11,0.27)]in patients with oral leukoplakia. The recurrence rate was also evaluated [ES = 0.13, 95%CI: (0.08,0.18)]. Subgroup analysis showed that various factors such as light source, wavelength, medium, duration of application, clinical and pathological diagnosis classification influenced efficacy of PDT. The lesion areas of the leukoplakia after treatment were reduced by 1.97cm2 compared with those before treatment. Conclusion Our findings show that PDT is a viable treatment for oral leukoplakia. However, the effectiveness of the therapy may depend on several factors, as suggested by our subgroup analyses. (Registration no. CRD42023399848 in Prospero, 26/02/2023)

Abstract Purpose This study aimed to explore the survival significance of surgery and age on the prognosis of patients with primary trachea malignancies. Methods The entire cohort of 637 patients with primary malignant trachea tumors was used to perform the main analyses. The data of those patients were from a public database. Overall survival (OS) curves were drawn by the Kaplan-Meier method and compared by the Log-rank test. The univariable and multivariable Cox regression analyses calculated the hazard ratio (HR) and 95% confidence interval (CI) for overall mortality. The propensity-score matching analysis was used to reduce the selection bias. Results Age, surgery, histological type, N classification, M classification, marital status, and tumor grading were identified as independent prognostic factors after eliminating confounding factors. The results of the Kaplan-Meier method revealed that patients with age

Rural areas typically register low accessibility. This fact negatively affects their attractiveness, the well-being of their population in general, and population subgroups with limited access to private cars or strong space-time constraints (like minors, the elderly or members of large households). Collective autonomous vehicles (AVs) might improve this situation, e.g. by enhancing standard line-based services or introducing alternative shared schemes. Nevertheless, the collective usage of AVs in rural transport and their potential impacts on accessibility are still underexplored, with most research focused on the urban context. This study aims to fill this gap by analysing the public transport accessibility impacts that five alternative AV supply scenarios might generate in the rural valley of Mühlwald (South Tyrol, Italy). To this end, a variant of the standard space-time accessibility model developed by the authors is used. This focuses on accessibility by public transport specifically, and measures it to both fixed activities and discretionary opportunities. Accessibility impacts are first estimated at the person-based level for a sample of residents. Then, they are aggregated for the whole sample and six subgroups that tend to experience more substantial accessibility issues based on the literature. Results show that line-based AV applications provide limited accessibility benefits. Conversely, time-flexible applications like ride-shared vans or combinations of line-based trunks and on-demand feeders over peak and off-peak hours may provide the most evident advantages, especially for the subgroups with the tightest space-time schedules. Although these results do not reflect other possible impacts of AVs (e.g. environmental effects), they provide policymakers with valuable insights into the collective AV usages that could be most suitable in the rural context regarding person-based accessibility gains.

Context: Meal replacement (MR) is beneficial for the management of type 2 diabetes (T2D). However, MR prescription and patient characteristics vary substantially between studies using MR in T2D patients. Objective: This work aimed to evaluate the efficacy and safety of MR in T2D patients by meta-analysis, with a focus on subgroup analysis of variable participant characteristics and MR prescription. Methods: We searched PubMed, CENTRAL, Embase, Web of Science, and the clinical trial registration database up to March 2022. We included randomized controlled trials (RCTs) of 2 weeks or more assessing the effect and safety of MR in T2D patients in comparison with conventional diabetic diets (CDs). Results: A total of 17 RCTs involving 2112 participants were ultimately included. Compared with CDs, MR significantly reduced glycated hemoglobin A1c (HbA1c) (MD -0.46%; P < .001), fasting blood glucose (FBG, -0.62 mmol/L; P < .001), body weight (-2.43 kg; P < .001), and body mass index (BMI, -0.65; P < .001), and improved other cardiometabolic risk factors. In subgroup analyses, total MR showed greater improvement in HbA1c (-0.72% vs -0.32%; P = .01), FBG (-1.45 vs -0.56 mmol/L; P = .02), body weight (-6.57 vs -1.58 kg; P < .001), and BMI (-2.78 vs -0.37; P < .001) than partial MR. MR with caloric restriction showed more reduction in body weight (-3.20 vs -0.75 kg; P < .001) and BMI (-0.84 vs -0.24; P = .003) compared with those without caloric restriction. MR showed similar benefits in studies that included patients using insulin and those that did not. Both partial and total MR were well tolerated. Conclusion: Compared with CDs, the MR-based dietary pattern further improved the glycemic control and adipose indicators in T2D patients. Appropriate calorie restriction and total MR might be more beneficial, while both patients treated with or without insulin treatment could similarly benefit from MR usage. [ABSTRACT FROM AUTHOR]