Sustaining Healthy Habits: The Enduring Impact of Combined School-Family Interventions on Consuming Sugar-Sweetened Beverages among Pilot Chinese Schoolchildren.

This study assesses the enduring impact of combined school- and family-based interventions on reducing the consumption of sugar-sweetened beverages (SSBs) among schoolchildren in China. Two primary schools were assigned at random to either the Intervention Group or the Control Group, in Nanjing, eastern China. All students were in grade three and received an invitation to participate. In the first year, students in the Intervention Group received one-year intervention measures, including monthly monitoring, aiming to decrease the consumption of SSBs. Students in the Control Group only received regular monitoring without interventions. In the second year, both groups received only regular monitoring, without active interventions. A generalized estimating equations model (GEE) was used to assess the intervention effects. After two years, relative to the Control Group, the Intervention Group had a significantly improved knowledge of SSBs and an improved family environment with parents. In the Intervention Group, 477 students (97.3%) had adequate knowledge about SSBs, compared to 302 students (83.2%) in the Control Group (X2 = 52.708, p < 0.001). Two years later, the number of students who stated 'my home always has SSBs' in the Intervention Group (7.8%) was fewer than that in the Control Group (12.4%), which was a statistically significant finding (p < 0.05). One year later, both the frequency and the quantity of SSB consumption in the Intervention Group were less than those in the Control Group; such differences between the groups remained statistically significant for the quantity but not for the frequency of SSB consumption two years later. In the Intervention Group, the frequency of SSB consumption was significantly reduced by 1.0 times per week, compared to a reduction of 0.1 times per week in the Control Group in the first year (p < 0.05). In the second year, the frequency of SSB consumption was reduced by 0.8 times per week in the Intervention Group, compared to 0.5 times per week in the Control Group (p > 0.05). In the first year, the volume of SSB consumption was significantly reduced by 233 mL per week in the Intervention Group, compared to an increase of 107 mL per week in the Control Group (p < 0.05). In the second year, the volume of SSB consumption was reduced by 122 mL per week in the Intervention Group compared to an increase of 31 mL per week in the Control Group (p > 0.05). The combined school-based and family-based interventions had a positive effect on the students' knowledge of SSBs and their family dynamics during the first and second year. Relative to the Control Group, the Intervention Group had a statistically significant reduction in SSB consumption after 1 year, but not after 2 years.

The association between physical activities combined with dietary habits and cardiovascular risk factors.

Objectives: The aim of this study was to investigate the association between physical activities combined with dietary habits and cardiovascular risk factors in adults from Nanjing, China. Methods: The cross-sectional survey conducted in 2017 involved a sample of 60 283 individuals aged ≥18 years in Nanjing municipality, China. The sampling method used was multistage stratified cluster sampling. The primary outcomes from multivariate logistic regression analysis with adjusted potential confounders were the relationships between physical activities combined with dietary habits and cardiovascular risk variables. Relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S) were used to assess an additive interaction between dietary habits and physical activities. Results: After adjusting potential confounders, cardiovascular risk factors were significantly associated with the association of physical inactivity and unhealthy diet, with the highest odds ratios (ORs) for low density lipoprotein-cholesterol (HLDL-c) (1.64, 95% CI [1.47, 1.84]) and hypertension (1.55, 95% CI [1.46, 1.64]). Additive interactions between physical inactivity and unhealthy diet were found in on cardiovascular risk factors of higher low-density lipoprotein-cholesterol (HLDL-c) (S, 2.57; 95% CI [1.27, 5.21]), type 2 diabetes (T2D) (S, 1.96; 95% CI [1.23, 3.13]), dyslipidemia (S, 1.69; 95% CI [1.08, 2.66]) and hypertension (S, 1.46; 95% CI [1.12, 1.89]). Their RERI was 0.39 (95% CI [0.18, 0.60]), 0.22 (95% CI [0.09, 0.35]), 0.11 (95% CI [0.03, 0.19]) and 0.17 (95% CI [0.06, 0.28]), respectively. OR of being HLDL-c, T2D, hypertension and dyslipidemia in participants of physical inactivity and unhealthy diet was 24%, 15%, 11% and 8.3%, respectively. Multiplicative interaction was detected in obesity, hypertension, T2D and HLDL-c. Conclusion: An unhealthy diet and physical inactivity were strongly linked to cardiovascular risk factors. This study also showed that an unhealthy diet and physical inactivity combined to produce an additive effect on T2D, hypertension, HLDL-c, and dyslipidemia, suggesting a higher risk than the total of these factors, especially HLDL-c. Preventive strategies aimed at reducing cardiometabolic risks such as hypertension, T2D, HLDL-c, and dyslipidemia are necessary for targeting physical inactivity and unhealthy diet.

Age-related changes in peripheral T-cell subpopulations in elderly individuals: An observational study.

The age-related decline in T-cell function among elderly individuals remains unclear. We thus investigated the interrelationship between T-cell subsets and age to identify the changes in T-cell phenotypes and develop an age prediction model for the elderly population. A total of 127 individuals aged >60 years were divided into three groups (youngest-old group, 61-70 years, n = 34; middle-old group, 71-80 years, n = 53; and oldest-old group, ≥ 81 years, n = 40). The percentage of CD8+CD28- cells (P = 0.001) was highest in the oldest-old group and then followed by the middle-old group, while the youngest-old group was the lowest. Both females and males demonstrated significant decreases in the absolute counts of CD4+CD45RA+ cells (P = 0.020; P = 0.002) and CD8+CD28+ cells (P = 0.015; P = 0.005) with age. Multivariate linear regression showed that the percentage of CD8+CD28- cells (P < 0.001) was an independent predictor of aging after adjusting for sex, body mass index, hospitalization duration, smoking, drinking, chronic medical illness, and medications at admission. In conclusion, our results suggest that aging in elderly individuals is accompanied by a decrease in the counts of T-cell subpopulations. CD8+CD28- cells may be potential targets for elderly individuals in antiaging-related immunosenescence.

Reduced Consumption of Sugar-Sweetened Beverages Is Associated with Lower Body Mass Index Z-Score Gain among Chinese Schoolchildren.

To examine whether reducing sugar-sweetened beverage (SSB) consumption is associated with reduced body mass index z-score gain among Chinese schoolchildren in Nanjing, China, a randomized controlled trial (RCT) was conducted in four selected primary schools from September 2019 to September 2020. Students in the third grade in the Intervention Group received school-based and home-based interventions for two consecutive semesters to reduce SSB consumption, while two schools in the Control Group did not receive any interventions. Weight changes were expressed as body mass index (BMI) z-scores as standard deviations of the BMI distribution per age and sex group. Changes in SSB consumption before and after the interventions were categorized into Level-Up if it increased, Level-Same if it was maintained and Level-Down if it decreased. Multivariable linear regression models were used to explore the association of different levels of changes in SSB consumption pre- and post-intervention with the BMI z-score. Among 1633 participants who completed the trial, the mean age at baseline was 9.36 years (±0.48 SD).The median baseline BMI z-score was −0.24 (25th percentile −0.72; 75th percentile 0.58). After the intervention, the median BMI z-score increased by 0.06 (−0.17~0.37) in the Intervention Group and by 0.14 (−0.08~0.41) in the Control Group (p < 0.001). A higher increase in BMI was found in the Control Group than in the Intervention Group (1.20 vs. 0.94) during the 12-month period. Among participants whose parents' educational attainment was above 9 years, the median BMI z-score increased by 0.07 (−0.17~0.37) in the Intervention Group and by 0.16 (−0.06~0.41) in the Control Group (p < 0.001). In a linear regression analysis adjusted for potential confounders, the BMI z-score decreased by 0.057 more in Level-Down than in Level-Up (95% CI: −0.103 to −0.012, p = 0.014). These results indicate that the decreased consumption of SSBs might have reduced the prevalence of overweight in schoolchildren in China, especially in students whose parents had high educational levels.

Drug hypersensitivity syndrome induced by sulfasalazine: A case report.

INTRODUCTION: Drug hypersensitivity syndrome (DHS) induced by sulfasalazine is a serious systemic delayed adverse drug reaction, which is associated with significant morbidity and mortality. PATIENT CONCERNS: A 52-year-old man was hospitalized for developing a rash after 3 weeks of sulfasalazine treatment for ulcerative colitis (UC). DIAGNOSIS: The patient was diagnosed with DHS based on his drug history, clinical manifestations, and laboratory test results. INTERVENTIONS: The patient was administered intravenous glucocorticoids. The patient's condition improved after treatment with human immunoglobulin and antihistamines. OUTCOMES: Combination therapy of glucocorticoid and gamma globulin, the whole-body pruritus disappeared, and no new rash appeared. The whole-body rash subsided or turned dark red. CONCLUSION: This article describes the diagnosis and treatment process of a case of sulfasalazine-induced DHS and reviews the relevant literature to improve clinician understanding and avoid misdiagnosis and missed diagnosis.

Association of socioeconomic status with hypertension prevalence and control in Nanjing: a cross-sectional study.

BACKGROUND: The role of socioeconomic status (SES) on hypertension prevalence and hypertension control has gotten much attention but with conflicting results. This paper aimed to quantify the association of SES with both hypertension prevalence and hypertension control rate in Nanjing, China. METHODS: A community-based cross-sectional study was conducted using multistage random sampling on 60,283 adults aged more than 18 years between March 2017 and June 2018. Hypertension was defined as systolic blood pressure (BP) ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg or self-reported diagnosis of hypertension or respondent's report of taking antihypertensive medications. The controlled hypertension was defined by systolic BP < 140 mmHg and diastolic BP of < 90 mmHg among the subjects that self-reported exhibiting hypertensive and taking antihypertensive medications. The associations between SES with hypertension prevalence and hypertension control were quantified using generalized mixed model regression analysis and reported as odds ratios (ORs) and 95% confidence interval (CI). RESULTS: There was a high prevalence of subjects with primary educational level (49.6%) or unemployed and retired (49.5%) or lower annual household income level (44.9%) in each SES group, respectively. After adjustments for potential confounding factors, there were higher odds of hypertension among those with primary educational level (OR = 1.56), but lower odds for controlled BP (OR = 0.51). Higher odds of hypertension could be found among unemployed and retired, and higher odds of controlled BP was observed in the mental laborers or students (OR = 1.30), compared with the other categories, respectively. The lower-income group was more likely to be hypertensive (OR = 1.35) and less likely to have controlled hypertension (OR = 0.73). CONCLUSION: Socioeconomic status played an important role in hypertension prevalence and hypertension control among adults in Nanjing, China. Strategies for hypertension prevention and control should especially focus on people in the vulnerable lower SES groups.

Joint associations of fresh fruit intake and physical activity with glycaemic control among adult patients with diabetes: a cross-sectional study.

OBJECTIVE: To investigate the joint associations of fresh fruit intake and physical activity with glycaemic control in adult patients with diabetes mellitus (DM). DESIGN: It was an observational study involving adult patients with DM through a face-to-face questionnaire survey, physical measurements and laboratory examinations. Data were analysed by introducing a generalised linear mixed model, and a significant difference was set at p<0.05. SETTING: Nanjing, Jiangsu, China. PARTICIPANTS: A total of 5663 adult patients with DM from the 2017 Nanjing Chronic Disease and Risk Factor Surveillance were recruited. RESULTS: Based on the food frequency questionnaire, fresh fruit intake was classified as 'not eat', '1~99 g/day' and '≥100 g/day'. Physical activity level was calculated based on the data of Global Physical Activity Questionnaire and classified into insufficient physical activity (<600 MET-min/week) and sufficient physical activity (≥600 MET-min/week). The likelihood of glycaemic control in adult patients with DM with fresh fruit intake ≥100 g/day was 37.8% (OR: 1.378; 95% CI: 1.209 to 1.571) higher than those with fresh fruit intake <100 g/day, which was 26% (OR: 1.260; 95% CI: 1.124 to 1.412) higher in adult patients with DM with sufficient physical activity than those with insufficient physical activity. Adult patients with DM with fresh fruit intake ≥100 g/day and sufficient physical activity presented the greatest likelihood of glycaemic control (OR: 1.758; 95% CI: 1.471 to 2.102) compared with those with both fresh fruit intake <100 g/day and insufficient physical activity. CONCLUSIONS: Fresh fruit intake ≥100 g/day combined with sufficient physical activity is associated with a significantly higher likelihood of glycaemic control in adult patients with DM.

The Combination of School-Based and Family-Based Interventions Appears Effective in Reducing the Consumption of Sugar-Sweetened Beverages, a Randomized Controlled Trial among Chinese Schoolchildren.

To examine whether environmental interventions, student awareness and parents' model roles are associated with the consumption of sugar-sweetened beverages (SSBs), a randomized controlled trial was conducted among Chinese schoolchildren. A multi-stage cluster random sampling method was applied to select four primary schools, two in urban areas and two in rural areas, in Nanjing, eastern China. Classes of the third grade in the selected four schools were randomly assigned to the intervention group and control group. Among selected students in those classes, aged 9-10 years, those in the intervention group received intervention measures comprising school-based and family-based measures and accepted monthly monitoring along with interventions, for two consecutive semesters, while those in the control group did not receive any specific interventions. After intervention, there was a significant increase in SSB knowledge and an improvement in the family environment with parents in the intervention group. The proportion of frequent consumption (≥4 times/week) of any SSBs in the intervention group was lower than that in the control group (31.5% vs. 56.2%, p < 0.01). Multivariate analysis indicated that parental education level is positively associated with reduced SSB consumption. Interventions showed an average decrease in SSBs consumption by 1.77 units, those living in urban areas decreased by 2.05 units. The combination of school-based and family-based interventions appears effective in reducing SSB consumption among Chinese schoolchildren, especially in urban areas and for those with parents with lower educational levels.

Dietary intake of fructose increases purine de novo synthesis: A crucial mechanism for hyperuricemia.

Background: Fructose consumption is a potential risk factor for hyperuricemia because uric acid (UA) is a byproduct of fructose metabolism caused by the rapid consumption of adenosine triphosphate and accumulation of adenosine monophosphate (AMP) and other purine nucleotides. Additionally, a clinical experiment with four gout patients demonstrated that intravenous infusion of fructose increased the purine de novo synthesis rate, which implied fructose-induced hyperuricemia might be related to purine nucleotide synthesis. Moreover, the mechanistic (mammalian) target of rapamycin (mTOR) is a key protein both involved in fructose metabolism and purine de novo synthesis. The present study was conducted to elucidate how fructose influences mTOR and purine de novo synthesis in a hepatic cell line and livers of mice. Materials and methods: RNA-sequencing in NCTC 1469 cells treated with 0- and 25-mM fructose for 24 h and metabolomics analysis on the livers of mice fed with 0- and 30-g/kg fructose for 2 weeks were assessed. Gene and protein expression of phosphoribosyl pyrophosphate synthase (PRPSAP1), Glutamine PRPP aminotransferase (PPAT), adenyl succinate lyase (ADSL), adenyl succinate synthetase isozyme-1 (Adss1), inosine-5'-monophosphate dehydrogenase (IMPDH), and guanine monophosphate synthetase (GMPS) was measured. The location of PRPSAP1 and PPAT in the liver was assessed by an immunofluorescence assay. Results: Metabolite profiling showed that the level of AMP, adenine, adenosine, hypoxanthine, and guanine was increased significantly. RNA-sequencing showed that gene expression of phosphoribosyl pyrophosphate synthase (PRPS2), phosphoribosyl glycinamide formyl transferase (GART), AICAR transformylase (ATIC), ADSL, Adss1, and IMPDH were raised, and gene expression of adenosine monophosphate deaminase 3 (AMPD3), adenosine deaminase (ADA), 5',3'-nucleotidase, cytosolic (NT5C), and xanthine oxidoreductase (XOR) was also increased significantly. Fructose increased the gene expression, protein expression, and fluorescence intensity of PRPSAP1 and PPAT in mice livers by increasing mTOR expression. Fructose increased the expression and activity of XOR, decreased the expression of uricase, and increased the serum level of UA. Conclusion: This study demonstrated that the increased purine de novo synthesis may be a crucial mechanism for fructose-induced hyperuricemia.

Comparative Efficacy of Five SGLT2i on Cardiorenal Events: A Network Meta-analysis Based on Ten CVOTs.

BACKGROUND: The relative efficacy of different sodium-glucose transporter 2 inhibitors (SGLT2i) on cardiorenal outcomes is unclear. METHODS: We included cardiovascular outcome trials (CVOTs) of SGLT2i. The eight endpoints of interest were major adverse cardiovascular events (MACE), myocardial infarction (MI), stroke, cardiovascular death (CVD), CVD or hospitalization for heart failure (HHF), HHF, kidney function progression (KFP), and all-cause death (ACD). We conducted a Bayesian network meta-analysis and calculated the surface under the cumulative ranking curve (SUCRA) probability to rank treatments. RESULTS: We included ten CVOTs involving five SGLT2i. Canagliflozin (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.53-0.77), dapagliflozin (HR 0.70; 95% CI 0.62-0.79), empagliflozin (HR 0.68; 95% CI 0.59-0.78), ertugliflozin (HR 0.70; 95% CI 0.54-0.90), and sotagliflozin (HR 0.66; 95% CI 0.56-0.77) versus placebo reduced HHF, whereas none reduced MI and stroke. Empagliflozin reduced CVD or HHF (HR 0.81; 95% CI 0.67-0.99) and KFP (HR 0.65; 95% CI 0.45-0.93), and dapagliflozin reduced KFP (HR 0.69; 95% CI 0.52-0.92), versus ertugliflozin. Canagliflozin had the greatest SUCRA values for the reduction of MACE, stroke, and HHF, whereas empagliflozin had the greatest SUCRA values for the reduction of MI, CVD, CVD or HHF, KFP, and ACD. CONCLUSIONS: Canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, and sotagliflozin versus placebo reduce HHF but none reduces MI and stroke. Canagliflozin is most effective in reducing MACE and HHF, and empagliflozin is most effective in reducing CVD, CVD or HHF, KFP, and ACD. These findings will guide the use of specific SGLT2i in the prevention of different cardiorenal events.

Individualized Treatment Strategy for Cutaneous Melanoma: Where Are We Now and Where Are We Going?

In the past several decades, innovative research in cancer biology and immunology has contributed to novel therapeutics, such as targeted therapy and immunotherapy, which have transformed the management of patients with melanoma. Despite the remarkable therapeutic outcomes of targeted treatments targeting MAPK signaling and immunotherapy that suppresses immune checkpoints, some individuals acquire therapeutic resistance and disease recurrence. This review summarizes the current understanding of melanoma genetic variations and discusses individualized melanoma therapy options, particularly for advanced or metastatic melanoma, as well as potential drug resistance mechanisms. A deeper understanding of individualized treatment will assist in improving clinical outcomes for patients with cutaneous melanoma.

Factors affecting the efficacy of SGLT2is on heart failure events: a meta-analysis based on cardiovascular outcome trials.

BACKGROUND: The efficacy of sodium-glucose transporter 2 inhibitors (SGLT2is) on heart failure outcomes is unestablished in various subgroups defined by clinically important factors. We intended to evaluate the effects of six important factors on the efficacy of SGLT2is on heart failure outcomes. METHODS: We included cardiovascular outcome trials (CVOTs) concerning SGLT2is. We assessed the heart failure composite outcome of cardiovascular death (CVD) or hospitalization for heart failure (HHF). Meta-analysis was conducted stratified by the following 6 factors: type of underlying diseases, type of SGLT2is, left ventricular ejection fraction (LVEF) level, New York Heart Association (NYHA) class, region, and race. RESULTS: Ten CVOTs were included. Compared with placebo, SGLT2is reduced heart failure composite outcome by 25% [hazard ratio (HR) 0.75, 95% confidence interval (CI), 0.72-0.78] independent of type of underlying diseases, type of SGLT2is, LVEF level, and region (Psubgroup: 0.673, 0.244, 0.429, and 0.127, respectively). SGLT2is led to greater reduction in the composite outcome in patients with NYHA class II (HR 0.66, 95% CI, 0.59-0.74) than in patients with NYHA class III or IV (HR 0.86, 95% CI, 0.75-0.99; Psubgroup=0.004), and in Black (HR 0.63, 95% CI, 0.49-0.82) and Asian (HR 0.64, 95% CI, 0.53-0.77) patients than in White patients (HR 0.81, 95% CI, 0.76-0.86; Psubgroup=0.016). CONCLUSIONS: SGLT2is reduce heart failure composite outcome by 25% independent of type of underlying diseases, type of SGLT2is, LVEF level, and region. SGLT2is lead to greater reduction in the composite outcome in patients with NYHA class II than in patients with NYHA class III or IV, and in Black and Asian patients than in White patients. KEYWORDS: Sodium-glucose transporter 2 inhibitors (SGLT2is); heart failure; chronic kidney disease (CKD); type 2 diabetes.

Effects of patient characteristics on the efficacy of complete revascularization for treatment of ST-segment elevation myocardial infarction with multivessel disease: A meta-analysis.

BACKGROUND: Several randomized controlled trials (RCTs) have evaluated the efficacy of complete vs culprit-only revascularization for treatment of ST-segment elevation myocardial infarction (STEMI) with multivessel disease. However, the efficacy of complete revascularization vs culprit-only revascularization in some STEMI patient subgroups remains unclear. METHODS: We searched PubMed and Embase for related RCTs from the start date of databases to January 3, 2020. The endpoint assessed in this meta-analysis was major adverse cardiac events (MACE). Random-effects meta-analysis was conducted stratified by each of the 5 factors of interest (i.e., sex, age, history of diabetes, ECG infarct location, and the number of arteries with stenosis) to estimate pooled hazard ratio and 95% confidence interval. Random-effects meta-regression was conducted to assess subgroup differences. We examined publication bias by drawing funnel plots and performing Egger test. This meta-analysis is reported according to the PRISMA statement. RESULTS: Six RCTs were included for pooled analysis. Compared with culprit-only revascularization, complete revascularization significantly reduced the risk of MACE (hazard ratio 0.48, 95% confidence interval 0.42-0.55; I2 = 0%; P for relative effect < .001). This significant reduction in the risk of MACE exhibited by complete revascularization was observed in most of the subgroups of interest. All of the subgroup effects based on the 5 factors of interest were not statistically significant (Psubgroup ranged from 0.198 to 0.556). Publication bias was not suggested by funnel plots and Egger test. CONCLUSIONS: Compared with culprit-only revascularization, complete revascularization significantly reduces the MACE risk in patients with STEMI and multivessel disease, which is independent of sex, age, history of diabetes, ECG infarct location, and the number of arteries with stenosis.

Worldwide prevalence of early repolarization pattern in general population and physically active individuals: A meta-analysis.

BACKGROUND: The early repolarization pattern (ERP) has recently been associated with cardiac events such as ventricular arrhythmias and sudden cardiac death. However, estimates of the prevalence of ERP vary widely, especially between the general population and physically active individuals. We performed this systematic review and meta-analysis to quantitatively evaluate the worldwide prevalence of ERP in the general population and physically active individuals. METHODS: We thoroughly searched the PubMed, EMBASE, Web of science, the Cochrane Library, and Scopus databases for relevant studies published until December 20, 2020. Studies in which prevalence was presented or could be estimated from eligible data were included. The pooled prevalence was analyzed using a random-effect model. RESULTS: Finally, we included 29 studies (182,135 subjects) in the general population and 14 studies (8087 subjects) in the physically active individuals. The worldwide pooled prevalence of ERP in the general population was 11.6% (95% confidence interval [CI]: 10.0%-13.3%). The incidence of ERP was 17.0% and 6.2% in men and women, respectively. The prevalence was 20.9% in blacks, 13.4% in Asians, and 10.1% in Caucasians. Additionally, the prevalence of ERP in physically active individuals was 33.9% (95% CI: 25.3%-42.6%). CONCLUSION: A significant difference in the worldwide prevalence of ERP is revealed in this study. The ERP is highly prevalent in men, blacks, and physically active individuals.

Comprehensive analysis of the safety of semaglutide in type 2 diabetes: a meta-analysis of the SUSTAIN and PIONEER trials.

The PIONEER and SUSTAIN serial trials are designed to assess the efficacy outcomes with semaglutide in patients with type 2 diabetes, but are not powered to assess various safety outcomes. We sought to assess the risk of semaglutide in leading to various serious adverse events (SAEs) in patients with type 2 diabetes. Studies eligible for inclusion were the PIONEER and SUSTAIN trials of semaglutide. We conducted meta-analysis to generate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Meta-analysis was performed using both random-effects and fixed-effects model to evaluate the robustness of pooled results. We implemented subgroup analysis according to drug dosages and routes of administration and type of comparators. Twenty-one trials were included. Semaglutide versus control significantly reduced total SAEs (RR 0.92, 95% CI 0.87-0.97; I2 = 0) and atrial fibrillation (RR 0.69, 95% CI 0.50-0.95; I2 = 0), but significantly increased deep vein thrombosis (RR 3.66, 95% CI 1.09-12.25; I2 = 0) and diarrhoea (RR 2.66, 95% CI 1.19-5.95; I2 = 0). Semaglutide had no significant effects on 248 other kinds of SAEs. No statistically significant subgroup effects were observed. Semaglutide has a good safety profile in general and reduces atrial fibrillation by 31%, but increases diarrhoea by 166% and deep vein thrombosis by 266%. These findings may guide that semaglutide should be preferred or avoided in T2D patients with specific susceptibility factors.

Safety of four SGLT2 inhibitors in three chronic diseases: A meta-analysis of large randomized trials of SGLT2 inhibitors.

There are no relevant meta-analyses that have assessed the safety of the sodium-glucose transporter 2 (SGLT2) inhibitors in different chronic diseases. We aimed at evaluating the safety of four SGLT2 inhibitors in three chronic diseases by meta-analysis of the large randomized trials of SGLT2 inhibitors. We performed random-effects meta-analysis and carried out subgroup analysis according to type of underlying diseases and type of SGLT2 inhibitors. SGLT2 inhibitors versus placebo significantly reduced the risk of acute kidney injury (RR 0.75, 95% CI 0.66-0.85), and showed the reduced trend in the risk of severe hypoglycemia (RR 0.86, 95% CI 0.71-1.03). SGLT2 inhibitors significantly increased the risks of diabetic ketoacidosis (RR 2.57), genital infection (RR 3.75), and volume depletion (RR 1.14); and showed the increased trends in the risks of fracture (RR 1.07), amputation (RR 1.21), and urinary tract infection (RR 1.07). These effects exhibited by SGLT2 inhibitors were consistent across three chronic diseases (i.e. type 2 diabetes, chronic heart failure, and chronic kidney disease) and four SGLT2 inhibitors (i.e. dapagliflozin, empagliflozin, ertugliflozin, and canagliflozin) (all Psubgroup > 0.05). These findings will guide that specific adverse events are monitored when SGLT2 inhibitors are used in clinical practice.

Impact of time factor and patient characteristics on the efficacy of PCI vs CABG for left main coronary disease: A meta-analysis.

BACKGROUND: The impact of time factor and patient characteristics on the efficacy of percutaneous coronary intervention (PCI) with drug-eluting stents vs. coronary-artery bypass grafting (CABG) for left main coronary disease is unclear. METHODS: We searched PubMed and Embase for related trials. Two outcomes of interest were major adverse cardiac or cerebrovascular events (MACCE, defined as a composite of all-cause mortality, myocardial infarction, stroke, or unplanned revascularization) and a composite of all-cause mortality, myocardial infarction, or stroke. We conducted random-effects meta-analysis stratified by follow-up duration and 7 factors of interest related to patient characteristics. Random-effects meta-regression was performed to calculate P values for trend and those for subgroup differences. RESULTS: We included 11 articles from 5 trials. Compared with CABG, PCI increased MACCE at the end of 3-year (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.04-1.40, I2 = 0) and 5-year (HR 1.33, 95% CI 1.20-1.48, I2 = 0) follow-up, but did not increase all-cause mortality, myocardial infarction, or stroke. The logarithm of HR of PCI vs CABG for MACCE increased as follow-up duration increased (ß = 0.057, P = .025). PCI vs CABG consistently increased 5-year MACCE across various subgroups defined by 7 factors of interest (Psubgroup ranged from .156 to .830). CONCLUSIONS: The long-term benefit of CABG vs PCI on MACCE in patients with left main coronary disease is consistent across patients with different clinical characteristics. The relative benefit of CABG on MACCE is driven by that of CABG on unplanned revascularization, and becomes greater as time goes on.

Effects of SGLT2 inhibitors on cardiovascular and renal outcomes in type 2 diabetes: A meta-analysis with trial sequential analysis.

BACKGROUND: It is unclear whether there are false positive or negative results in the effects of sodium-glucose transporter 2 (SGLT2) inhibitors on various cardiovascular and renal outcomes in patients with type 2 diabetes. We aimed to explore this issue by a meta-analysis with trial sequential analysis. METHODS: We included randomized trials evaluating the effects of SGLT2 inhibitors on cardiorenal endpoints in type 2 diabetic patients. Eight endpoints evaluated in the study were fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, major adverse cardiovascular events (MACE), cardiovascular death or hospitalization for heart failure (CVD or HHF), all-cause death (ACD), cardiovascular death (CVD), hospitalization for heart failure (HHF), and kidney function progression (KFP). Meta-analysis and trial sequential analysis was conducted for each endpoint. RESULTS: Seven randomized trials of SGLT2 inhibitors were included for pooled analysis. Compared with placebo, SGLT2 inhibitors significantly reduced the risk of MACE (HR 0.89, 95% confidence interval [CI] 0.84-0.94), MI (HR 0.91, 95% CI 0.84-0.99), CVD (HR 0.86, 95% CI 0.79-0.93), CVD or HHF (HR 0.77, 95% CI 0.73-0.82), HHF (HR 0.67, 95% CI 0.62-0.74), KFP (HR 0.63, 95% CI 0.56-0.70), and ACD (HR 0.88, 95% CI 0.83-0.94), whereas SGLT2 inhibitors did not have significant effects on stroke (HR 0.98, 95% CI 0.88-1.09). Trial sequential analyses for MI and stroke showed that cumulative Z curve did not cross trial sequential monitoring boundary and required information size, whereas those for the other 6 endpoints showed that cumulative Z curve crossed trial sequential monitoring boundary and/or required information size. CONCLUSIONS: Compared with placebo, SGLT2 inhibitors conclusively reduce the risk of MACE, CVD or HHF, ACD, CVD, HHF, and KFP in patients with type 2 diabetes, whereas the effects of SGLT2 inhibitors on MI and stroke are not conclusive and need to be further assessed in future studies with the adequate sample size to reject or accept the effect size.