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This study aimed to investigate the pattern of gestational weight gain (GWG) among Chinese women. We included pregnant women, who delivered at a referral medical center in China and had no pre-specified adverse pregnancy outcomes. We collected weight data across all pregnancy visits, and used the two-level spline linear model to fit for the pattern of GWG according to pre-pregnancy BMI categories. In total, 4,567 pregnant women with 47,699 repeated measures were eligible. For those who were underweight, normal and overweight before pregnancy, the interquartile ranges (25th to 75th quartiles) of GWG between 14 and 36 gestational weeks were 12.9-17.7 kg, 12.6-17.3 kg and 11.7-16.8 kg, and the corresponding rates of GWG were 2.62 kg/month, 2.56 kg/month and 2.37 kg/month. For underweight and normal women, the rates of GWG were similar before 14 weeks (0.57 and 0.58 kg/month) and after 36 weeks (1.69 and 1.70 kg/month); however, the rates of GWG were higher for overweight women (0.66 kg/month before 14 weeks and 1.89 kg/month after 36 weeks). In summary, the pattern of GWG among Chinese pregnant women is generally consistent with the IOM recommendation, particularly for those who are normal or underweight. Modifications are, however, warranted for overweight pregnant women. [ABSTRACT FROM AUTHOR]

Both hypertension and type 2 diabetes are attributable to premature death, cardiovascular and kidney diseases with largely overlapping population. Followed the GRADE approach, this expert consensus aimed to reduce the cardiovascular and kidney death and disability due to hypertension and minimize the treatment burden in adults with type 2 diabetes. Through online survey and discussion, a multidisciplinary team comprehensively prioritized seven key guideline questions. Informed by the evidence synthesis and online discussion, the team developed 12 recommendations under the GRADE Evidence-to-decision (EtD) framework. The recommendations covered the screening of hypertension in adults diagnosed with type 2 diabetes but not hypertension and the monitoring, lifestyle interventions, and medications in those diagnosed with type 2 diabetes and hypertension., (© 2024 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

Background: Clinical practice guidelines (CPGs) are designed to assist health care professionals in medical decision-making, but they often lack effective integration of shared decision-making (SDM) principles to reflect patient values and preferences, particularly in the context of preference-sensitive CPG recommendations. To address this shortcoming and foster SDM through CPGs, the integration of patient decision aids (PDAs) into CPGs has been proposed as an important strategy. However, methods for systematically identifying and prioritizing CPG recommendations relevant to SDM and related decision support tools are currently lacking., Objective: The aim of the project is to develop (1) a tool for systematically identifying and prioritizing CPG recommendations for which SDM is considered particularly relevant and (2) a platform for PDAs to support practical SDM implementation., Methods: The project consists of 6 work packages (WPs). It is embedded in the German health care context but has an international focus. In WP 1, we will conduct a scoping review in bibliographic databases and gray literature sources to identify methods used to foster SDM via PDAs in the context of CPGs. In WP 2, we will conduct semistructured interviews with CPG experts to better understand the concepts of preference sensitivity and identify strategies for fostering SDM through CPGs. WP 3, a modified Delphi study including surveys and focus groups with SDM experts, aims to define and operationalize preference sensitivity. Based on the results of the Delphi study, we will develop a methodology for prioritizing key questions in CPGs. In WP 4, the tool will be developed. A list of relevant items to identify CPG recommendations for which SDM is most relevant will be created, tested, and iteratively refined, accompanied by the development of a user manual. In WP 5, a platform for creating and digitizing German-language PDAs will be developed to support the practical application of SDM during clinical encounters. WP 6 will conclude the project by testing the tool with newly developed and revised CPGs., Results: The Brandenburg Medical School Ethics Committee approved the project (165122023-ANF). An international multidisciplinary advisory board is involved to guide the tool development on CPGs and SDM. Patient partners are involved throughout the project, considering the essential role of the patient perspective in SDM. As of February 20, 2024, we are currently assessing literature references to determine eligibility for inclusion in the scoping review (WP 1). We expect the project to be completed by December 31, 2026., Conclusions: The tool will enable CPG developers to systematically incorporate aspects of SDM into CPG development, thereby providing guideline-based support for the patient-practitioner interaction. Together, the tool for CPGs and the platform for PDAs will create a systematic link between CPGs, SDM, and PDAs, which may facilitate SDM in clinical practice., International Registered Report Identifier (irrid): DERR1-10.2196/57611., (©Lena Fischer, Fülöp Scheibler, Corinna Schaefer, Torsten Karge, Thomas Langer, Leon Vincent Schewe, Ivan D Florez, Andrew Hutchinson, Sheyu Li, Marta Maes-Carballo, Zachary Munn, Lilisbeth Perestelo-Perez, Livia Puljak, Anne Stiggelbout, Dawid Pieper. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 04.11.2024.)

Background: Trial registration aims to address potential bias from selective or non-reporting of findings, and therefore has a vital role in promoting transparency and accountability of clinical research. In this study, we aim to investigate the influence of trial registration on estimated harm effects in randomized controlled trials of medication interventions., Methods: We searched PubMed for systematic reviews and meta-analyses of randomized trials on medication harms indexed between January 1, 2015, and January 1, 2020. To be included in the analyses, eligible meta-analyses should have at least five randomized trials with distinct registration statuses (i.e., prospectively registered, retrospectively registered, and non-registered) and 2 by 2 table data for adverse events for each trial. To control for potential confounding, trials in each meta-analysis were analyzed within confounder-harmonized groups (e.g., dosage) identified using the Directed Acyclic Graph method. The harm estimates arising from the trials with different registration statuses were compared within the confounder-harmonized groups using hierarchical linear regression. Results are shown as ratio of odds ratio (OR) and 95% confidence interval (CI)., Results: The dataset consists of 629 meta-analyses of harms with 10,069 trials. Of these trials, 74.3% were registered, and 23.9% were not registered, and for those registered, 70.6% were prospectively registered, while 26.3% were retrospectively registered. In comparison to prospectively registered trials, both non-registered trials (ratio of OR = 0.82, 95%CI 0.68 to 0.98, P = 0.03) and retrospectively registered trials (ratio of OR = 0.75, 95%CI 0.66 to 0.86, P < 0.01) had lower OR for harms based on 69 and 126 confounders-harmonized groups. The OR of harms did not differ between retrospectively registered and non-registered trials (ratio of OR = 1.02, 95%CI 0.85 to 1.23, P = 0.83) based on 76 confounders-harmonized groups., Conclusions: Medication-related harms may be understated in non-registered trials, and there was no obvious evidence that retrospective registration had a demonstrable benefit in reducing such selective or absent reporting. Prospective registration is highly recommended for future trials., (© 2024. The Author(s).)

Objective: To examine cardiovascular and kidney benefits and harms of sodium-glucose co-transporter-2 (SGLT-2) inhibitors stratified by risk in adults with chronic kidney disease regardless of diabetes status., Design: Systematic review and meta-analysis., Data Sources: Ovid Medline, Embase, and Cochrane Central from database inception to 15 June 2024., Eligibility Criteria for Selecting Studies: Randomised controlled trials that compared SGLT-2 inhibitors with placebo or standard care with no SGLT-2 inhibitors in adults with chronic kidney disease with a follow-up duration of ≥12 weeks were eligible. Secondary analyses based on subpopulations from randomised controlled trials and publications not in English language were excluded., Data Synthesis: Random effects meta-analyses were conducted, with effect estimates presented as risk ratios with 95% confidence intervals (CIs). Absolute treatment effects were estimated over a five year duration for individuals with varied risks of cardiovascular and kidney complications based on the Kidney Disease Improving Global Outcomes (KDIGO) risk stratification system. Certainty of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach., Results: Evidence from 13 randomised controlled trials (29 614 patients) informed treatment effect estimates. In relative terms, SGLT-2 inhibitors reduced all cause death (risk ratio 0.85 (95% CI 0.74 to 0.98)), cardiovascular death (0.84 (0.74 to 0.96)), kidney failure (0.68 (0.60 to 0.77)), non-fatal stroke (0.73 (0.57 to 0.94)), non-fatal myocardial infarction (0.75 (0.60 to 0.93)), and admission to hospital for heart failure (0.68 (0.60 to 0.78)). No credible subgroup effects were found from diabetes status, heart failure status, estimated glomerular filtration rate, urinary albumin-to-creatinine ratio, and follow-up duration. Absolute effect estimates across these outcomes over a five year period varied across risk groups based on baseline risks of cardiovascular and kidney events. Effects of SGLT-2 inhibitors in the group at low risk included seven fewer all- cause deaths, four fewer admissions to hospital for heart failure per 1000 individuals, and no effects on kidney failure. Effects in the higher risk group included 48 fewer all cause deaths, 58 fewer kidney failures, and 25 fewer admissions to hospital for heart failure per 1000 individuals. Although SGLT-2 inhibitor use was associated with a relative increase in the risk of harms, including genital infection (2.66 (95% CI 2.07 to 3.42)), ketoacidosis (2.27 (1.30 to 3.95)), and symptomatic hypovolaemia (1.29 (1.15 to 1.44)), absolute differences for all harm outcomes were small., Conclusions: Among people who have chronic kidney disease either with type 2 diabetes or not, SGLT-2 inhibitors improved cardiovascular and kidney outcomes with varying degrees of absolute benefit depending on an individual's baseline risks of cardiovascular and kidney-related sequelae. Absolute benefits and harms stratified by risk and associated with SGLT-2 inhibitors should inform individual decision making at the patient level., Systematic Review Registration: PROSPERO CRD42022325483., Competing Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: SL was supported by grants from National Natural Science Foundation of China (Grant No. 72342014), Sichuan Science and Technology Programme (Grant No. 2022YFH0114), 1.3.5 Projects for Disciplines of Excellence and Clinical Research Incubation West China Hospital, Sichuan University (Grant No. ZYYC24001 and 2020HXF011). XZe was supported by 1.3.5 Projects for Disciplines of Excellence West China Hospital, Sichuan University (Grant No. ZYJC18010). The remaining authors report no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (Copyright © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Clinical Question: What is the impact of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on survival and on cardiovascular and kidneyoutcomes for adults living with chronic kidney disease (CKD)?, Current Practice: Few therapies slow kidney disease progression and improve long term prognosis for adults living with CKD. SGLT-2 inhibitors have demonstrated cardiovascular and kidney benefits in adults with CKD with and without type 2 diabetes. Existing guidance for SGLT-2 inhibitors does not account for the totality of current best evidence for adults with CKD and does not provide fully stratified treatment effects and recommendations across all risk groups based on risk of CKD progression and complications., Recommendations: The guideline panel considered evidence regarding benefits and harms of SGLT-2 inhibitor therapy for adults with CKD over a five year period, along with contextual factors, and provided the following recommendations:1. For adults at low risk of CKD progression and complications, we suggest administering SGLT-2 inhibitors (weak recommendation in favour)2. For adults at moderate risk of CKD progression and complications, we suggest administering SGLT-2 inhibitors (weak recommendation in favour)3. For adults at high risk of CKD progression and complications, we recommend administering SGLT-2 inhibitors (strong recommendation in favour)4. For adults at very high risk of CKD progression and complications, we recommend administering SGLT-2 inhibitors (strong recommendation in favour).Recommendations are applicable to all adults with CKD, irrespective of type 2 diabetes status., How This Guideline Was Created: An international panel including patients, clinicians, and methodologists produced these recommendations following standards for trustworthy guidelines and using the GRADE approach. The panel identified typical risk strata of adults with CKD (from low to very high risk of CKD progression and related complications) using the classification system developed by Kidney Disease Improving Global Outcomes (KDIGO), and applied an individual patient perspective in moving from evidence to recommendations. Effects of SGLT-2 inhibitors were interpreted in absolute terms applicable to different risk strata with varying baseline risks for outcomes of benefit over a five year period. The panel explicitly considered the balance of benefits, harms, and burdens of starting an SGLT-2 inhibitor, incorporating the values and preferences of adults with different risk profiles. Interactive evidence summaries and decision aids accompany multilayered recommendations, developed in an online authoring and publication platform (www.magicapp.org) that allows reuse and adaptation., The Evidence: A linked systematic review and pairwise meta-analysis (13 trials including 29 614 participants) of benefits and harms associated with SGLT-2 inhibitors in adults with CKD with or without type 2 diabetes informed guidance. Among individuals at very high risk of CKD progression and complications, moderate to high certainty evidence shows SGLT-2 inhibitors (relative to placebo or standard care without SGLT-2 inhibitors) decrease all-cause and cardiovascular mortality, hospitalisation for heart failure, kidney failure, non-fatal myocardial infarction, and non-fatal stroke. Among individuals at high risk, moderate to high certainty evidence shows SGLT-2 inhibitors result in similar benefits across outcomes except demonstrating little or no effect on hospitalisation for heart failure and kidney failure. Among individuals at moderate and low risk, moderate to high certainty evidence shows SGLT-2 inhibitors probably reduce all-cause mortality and non-fatal stroke, with little or no effect for other outcomes of benefit. Risk-stratified estimates were unavailable for outcomes of harm; the panel therefore considered absolute effects summarised across risk strata. SGLT-2 inhibitors are associated with little or no effect on acute kidney injury requiring dialysis, bone fractures, lower limb amputations, ketoacidosis, genital infections, or symptomatic hypovolaemia, although a residual possibility of harms at the individual patient level remains., Understanding the Recommendation: In order to apply recommendations, clinicians must appropriately identify adults with CKD, consider the underlying aetiology, and risk stratify them based on glomerular filtration rate (estimated or measured) and degree of albuminuria. In addition to classifying individuals into risk strata, further estimation of a given patient's risk based on the extent of their kidney disease and other comorbidities may be warranted to inform individual-level decisions and shared decision making. Available risk calculators may help estimate a given patient's risk of CKD progression and complications., Competing Interests: Competing interests: All authors have completed the BMJ Rapid Recommendations disclosure of interests form. The BMJ has judged that there are no disqualifying financial ties to commercial companies. The authors declare the following other interests: none., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Aim: To explore the trend of burden and care quality of chronic kidney disease due to type 2 diabetes mellitus (CKD-T2DM) and their cross-country inequalities from 1990 to 2021., Materials and Methods: Data were from the Global Burden of Disease 2021 study. Disease burden and care quality were quantified using the disability-adjusted life years rate and the quality-of-care index (QCI). Trend analyses of the age-standardized disability-adjusted life years rate (ASDR) and age-standardized QCI from 1990 to 2021 were conducted using the estimated annual percentage change. The associations of disease burden and care quality with the socio-demographic index (SDI) were explored. Cross-country inequalities in disease burden and care quality were assessed using the slope index of inequality (SII) and concentration index., Results: From 1990 to 2021, the global ASDR for CKD-T2DM increased, while the age-standardized QCI slightly decreased, with an estimated annual percentage change of 0.81 [95% confidence interval (CI): 0.75, 0.87] and -0.08 (95% CI: -0.09, -0.07). The ASDR escalated with increasing SDI, reaching a peak at mid-level SDI, followed by a decrease. The age-standardized QCI was higher with increasing SDI. Globally, ASDR concentrated on countries/territories with a lower SDI. The SII of ASDR was -96.64 (95% CI: -136.94, -56.35) in 1990 and -118.15 (95% CI: -166.36, -69.94) in 2021,  with a concentration index of -0.1298 (95% CI: -0.1904, -0.0692) in 1990 and -0.1104 (95% CI: -0.1819, -0.0389) in 2021. In 1990 and 2021, countries/territories at higher SDI levels exhibited increased age-standardized QCI, indicated by an SII of 15.09 (95% CI: 10.74, 19.45) and 15.75 (95% CI: 10.92, 20.59), and a concentration index of 0.0393 (95% CI: 0.0283, 0.0503) and 0.0400 (95% CI: 0.0264, 0.0536)., Conclusions: Our study highlights considerable disparities in the burden and care quality of CKD-T2DM. Regions experiencing an increasing burden and a declining care quality simultaneously underscore the need for further research and tailored health interventions., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background and Aims: Our study examined the trends of cardiovascular health metrics in individuals with coronary heart disease (CHD) and their associations with all-cause and cardiovascular disease mortality in the US., Methods and Results: The cohort study was conducted based on the National Health and Nutrition Examination Survey 1999-2018 and their linked mortality files (through 2019). Baseline CHD was defined as a composite of self-reported doctor-diagnosed coronary heart disease, myocardial infarction, and angina pectoris. Cardiovascular health metrics were assessed according to the American Heart Association recommendations. Long-term all-cause and cardiovascular disease mortality were the primary outcomes. Survey-adjusted Cox regression models were used to estimate hazard ratios and corresponding 95% confidence intervals for the associations between cardiovascular health metrics and all-cause and cardiovascular disease mortality. The prevalence of one or fewer ideal cardiovascular health metrics increased from 14.15% to 22.79% (P < 0.001) in CHD, while the prevalence of more than four ideal cardiovascular health metrics decreased from 21.65% to 15.70 % (P < 0.001) from 1999 to 2018, respectively. Compared with CHD participants with one or fewer ideal cardiovascular health metrics, those with four or more ideal cardiovascular health metrics had a 35% lower risk (hazard ratio, 0.65; 95% confidence interval: 0.51, 0.82) and a 44% lower risk (0.56; 0.38, 0.84) in all-cause and cardiovascular disease mortality, respectively., Conclusion: Substantial declines were noted in ideal cardiovascular health metrics in US adults with CHD. A higher number of cardiovascular health metrics was associated with lower all-cause and cardiovascular disease mortality in them., Competing Interests: Conflict of interest None declared., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Abstract: Diabetic cardiomyopathy is defined as abnormal structure and function of the heart in the setting of diabetes, which could eventually develop heart failure and leads to the death of the patients. Although blood glucose control and medications to heart failure show beneficial effects on this disease, there is currently no specific treatment for diabetic cardiomyopathy. Over the past few decades, the pathophysiology of diabetic cardiomyopathy has been extensively studied, and an increasing number of studies pinpoint that impaired mitochondrial energy metabolism is a key mediator as well as a therapeutic target. In this review, we summarize the latest research in the field of diabetic cardiomyopathy, focusing on mitochondrial damage and adaptation, altered energy substrates, and potential therapeutic targets. A better understanding of the mitochondrial energy metabolism in diabetic cardiomyopathy may help to gain more mechanistic insights and generate more precise mitochondria-oriented therapies to treat this disease., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs., Methods: This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678., Findings: 14 605 citations were identified by our search, of which 132 eligible trials enrolled 48 209 participants. All drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine-topiramate as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change -7·98, 95% CI -9·27 to -6·69) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·79, 95% CI -6·34 to -5·25). Naltrexone-bupropion (OR 2·69, 95% CI 2·10 to 3·44), phentermine-topiramate (2·40, 1·68 to 3·44), GLP-1 receptor agonists (2·22, 1·74 to 2·84), and orlistat (1·71, 1·42 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD -11·40, 95% CI -12·51 to -10·29)., Interpretation: In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective., Funding: 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University., Competing Interests: Declaration of interests SL received grants from the Sichuan Science and Technology Program (grant numbers 2019YFS0305 and 2019YFH0150). All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Empirical evidence suggests that lack of blinding may be associated with biased estimates of treatment benefit in randomized controlled trials, but the influence on medication-related harms is not well-recognized. We aimed to investigate the association between blinding and clinical trial estimates of medication-related harms., Methods: We searched PubMed from January 1, 2015, till January 1, 2020, for systematic reviews with meta-analyses of medication-related harms. Eligible meta-analyses must have contained trials both with and without blinding. Potential covariates that may confound effect estimates were addressed by restricting trials within the comparison or by hierarchical analysis of harmonized groups of meta-analyses (therefore harmonizing drug type, control, dosage, and registration status) across eligible meta-analyses. The weighted hierarchical linear regression was then used to estimate the differences in harm estimates (odds ratio, OR) between trials that lacked blinding and those that were blinded. The results were reported as the ratio of OR (ROR) with its 95% confidence interval (CI)., Results: We identified 629 meta-analyses of harms with 10,069 trials. We estimated a weighted average ROR of 0.68 (95% CI: 0.53 to 0.88, P < 0.01) among 82 trials in 20 meta-analyses where blinding of participants was lacking. With regard to lack of blinding of healthcare providers or outcomes assessors, the RORs were 0.68 (95% CI: 0.53 to 0.87, P < 0.01 from 81 trials in 22 meta-analyses) and 1.00 (95% CI: 0.94 to 1.07, P = 0.94 from 858 trials among 155 meta-analyses) respectively. Sensitivity analyses indicate that these findings are applicable to both objective and subjective outcomes., Conclusions: Lack of blinding of participants and health care providers in randomized controlled trials may underestimate medication-related harms. Adequate blinding in randomized trials, when feasible, may help safeguard against potential bias in estimating the effects of harms., (© 2024. The Author(s).)

Aims: To investigate the sex-specific associations between predicted skeletal muscle mass index (pSMI) and incident type 2 diabetes in a retrospective longitudinal cohort of Chinese men and women., Materials and Methods: We enrolled Chinese adults without diabetes at baseline from WATCH (West chinA adulT health CoHort), a large health check-up-based database. We calculated pSMI to estimate skeletal muscular mass, and measured blood glucose variables and assessed self-reported history to identify new-onset diabetes. The nonlinear association between pSMI and incident type 2 diabetes was modelled using the penalized spline method. The piecewise association was estimated using segmented linear splines in weighted Cox proportional hazards regression models., Results: Of 47 885 adults (53.2% women) with a median age of 40 years, 1836 developed type 2 diabetes after a 5-year median follow-up. In women, higher pSMI was associated with a lower risk of incident type 2 diabetes (P nonlinearity  = 0.09, hazard ratio [HR] per standard deviation increment in pSMI: 0.79 [95% confidence interval {CI} 0.68, 0.91]). A nonlinear association of pSMI with incident type 2 diabetes was detected in men (P nonlinearity  < 0.001). In men with pSMI lower than 8.1, higher pSMI was associated with a lower risk of incident type 2 diabetes (HR 0.58 [95% CI 0.40, 0.84]), whereas pSMI was not significantly associated with incident diabetes in men with pSMI equal to or greater than 8.1 (HR 1.08 [95% CI 0.93, 1.25])., Conclusions: In females, a larger muscular mass is associated with a lower risk of type 2 diabetes. For males, this association is significant only among those with diminished muscle mass., (© 2023 John Wiley & Sons Ltd.)

Aims: To assess the time-dependent risk of fracture in adults with type 2 diabetes receiving anti-diabetic drugs., Materials and Methods: We searched MEDLINE, EMBASE, and Cochrane Library up to 18 November 2021, for randomized controlled trials (RCTs) and propensity-score-matched non-randomized studies (NRSs) comparing all anti-diabetic drugs with standard treatment or with each other on fracture in adults with type 2 diabetes. The study performed a one-stage network meta-analysis using discrete-time hazard regression with reconstructed individual time-to-event data., Results: This network meta-analysis involved seven RCTs (65,051 adults with type 2 diabetes) with a median follow-up of 36 months and three propensity-score-based NRSs (17,954 participants) with a median follow-up of 27.3 months. Among anti-diabetic drugs, thiazolidinediones increased the overall hazard of fracture by 42% (95% credible interval [CrI], 3%-97%) and almost tripled the risk after 4 years (hazard ratio [HR], 2.74; 95% CrI, 1.53-4.80). Credible subgroup analysis suggested that thiazolidinediones increased the hazard of fracture only in females (HR, 2.19; 95% CrI, 1.26-3.74) but not among males (HR, 0.81; 95% CrI, 0.45-1.40). Moderate certainty evidence established that thiazolidinediones increase 92 fractures in five years per 1000 female patients. We did not find the risk of fractures with other anti-diabetic drugs including metformin, sulfonylureas, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors., Conclusions: Long-term use of thiazolidinediones elevates the risk of fracture among females with type 2 diabetes. There is no evidence eliciting fracture risk associated with other anti-diabetic drugs., (© 2024 John Wiley & Sons Ltd.)

Background: Older adults with postprandial hypotension (PPH) increase susceptibility to falls, syncope, stroke, acute cardiovascular diseases and even death. However, the prevalence of this condition varies significantly across studies. We aimed to determine the prevalence of PPH in older adults., Methods: Web of Science, PubMed, Cochrane Library, Embase and CINAHL were searched from their inception until February 2023. Search terms included 'postprandial period', 'hypotension' and 'postprandial hypotension'. Eligible studies were assessed using the Joanna Briggs Institute tool. Meta-analyses were performed among similar selected studies., Results: Thirteen eligible studies were included, and data from 3,021 participants were pooled. The meta-analysis revealed a PPH prevalence of 40.5% [95% confidence interval (CI): 0.290-0.519] in older adults, and this was prevalent in the community (32.8%, 95% CI: 0.078-0.647, n = 1,594), long-term healthcare facility (39.4%, 95% CI: 0.254-0.610, n = 1,062) and geriatrics department of hospitals (49.3%, 95% CI: 0.357-0.630, n = 365). The pooled results showed significant heterogeneity (I2 > 90%), partially related to the different ages, sex, pre-prandial systolic blood pressure levels of participants, or the different criteria and methodology used to diagnose PPH., Conclusions: PPH is a prevalent condition in older adults. Further research is needed to confirm this result, and priority should be given to establishing international consensus on PPH diagnostic criteria and designing its diagnostic procedure., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Background: The authors aimed to comprehensively evaluate the efficacy and safety of antibiotic prophylaxis through surgical and nonsurgical scenarios and assess the strength of evidence., Materials and Methods: The authors performed an umbrella review of meta-analyses of randomized controlled trials (RCTs). An evidence map was created to summarize the absolute benefits of antibiotic prophylaxis in each scenario and certainty of evidence., Results: Seventy-five meta-analyses proved eligible with 725 RCTs and 78 clinical scenarios in surgical and medical prophylaxis. Of 119 health outcomes, 67 (56.3%) showed statistically significant benefits, 34 of which were supported by convincing or highly suggestive evidence from RCTs. For surgeries, antibiotic prophylaxis may minimize infection occurrences in most surgeries except Mohs surgery, simple hand surgery, herniorrhaphy surgery, hepatectomy, thyroid surgery, rhinoplasty, stented distal hypospadias repair, midurethral sling placement, endoscopic sinus surgery, and transurethral resection of bladder tumors with only low to very low certainty evidence. For nonsurgery invasive procedures, only low to very low certainty evidence showed benefits of antibiotic prophylaxis for cystoscopy, postoperative urinary catheterization, and urodynamic study. For medical prophylaxis, antibiotic prophylaxis showed greater benefits in nonemergency scenarios, in which patients were mainly with weakened immune systems, or at risk of recurrent chronic infections. Antibiotics prophylaxis may increase antibiotic resistance or other adverse events in most scenarios and reached significance in cystoscopy, afebrile neutropenia following chemotherapy and hematopoietic stem cell transplantation., Conclusions: Antibiotic prophylaxis in surgical and nonsurgical scenarios is generally effective and seems independent of surgical cleanliness and urgency of diseases. Its safety is not well determined due to lack of available data. Nevertheless, the low quality of current evidence limits the external validity of these findings, necessitating clinicians to judiciously assess indications, balancing low infection rates with antibiotic-related side effects., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

To examine the effectiveness of azvudine and nirmatrelvir-ritonavir in treating hospitalized patients with moderate-to-severe COVID-19. We emulated a target trial with a multicenter retrospective cohort of hospitalized adults with moderate-to-severe COVID-19 without contraindications for azvudine or nirmatrelvir-ritonavir between December 01, 2022 and January 19, 2023 (during the Omicron BA.5.2 variant wave). Exposures included treatment with azvudine or nirmatrelvir-ritonavir for 5 days versus no antiviral treatment during hospitalization. Primary composite outcome (all-cause death and initiation of invasive mechanical ventilation), and their separate events were evaluated. Of the 1154 patients, 27.2% were severe cases. In the intent-to-treat analyses, azvudine reduced all-cause death (Hazard ratio [HR]: 0.31; 95% CI: 0.12-0.78), and its composite with invasive mechanical ventilation (HR: 0.47; 95% CI: 0.24-0.92). Nirmatrelvir-ritonavir reduced invasive mechanical ventilation (HR: 0.42; 95% CI: 0.17-1.05), and its composite with all-cause death (HR: 0.38; 95% CI: 0.18-0.81). The study did not identify credible subgroup effects. The per-protocol analyses and all sensitivity analyses confirmed the robustness of the findings. Both azvudine and nirmatrelvir-ritonavir improved the prognosis of hospitalized adults with moderate-to-severe COVID-19., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: Clinical observation suggests the atheroprotective effect of chloroquine and its derivatives, while its mechanism remains unclear. This study aimed to observe the protective effect of chloroquine against atherosclerosis and explore the underlying mechanism., Methods: Ataxia telangiectasia mutated (ATM) wild-type or haploinsufficient apolipoprotein-E-knockout (ATM +/+ ApoE -/- or ATM +/- ApoE -/- ) mice were treated with different dosages of chloroquine. Anti-CD25 antibody was used to deplete natural Tregs in ATM +/+ ApoE -/- mice. The atherosclerotic burden in different groups of mice was comprehensively evaluated by H&E staining and Masson staining. The effect of chloroquine on the regulatory T cells (Tregs) was assessed in vivo and in vitro by flow cytometry and immunohistochemical staining. The expression of related proteins was detected by real-time polymerase chain reaction and western blotting., Results: In ATM +/+ ApoE -/- mice, chloroquine alleviated atherosclerotic lesions, stabilized the plaque, and increased Treg counts in the atherosclerotic lesions and spleens. However, in ATM haploinsufficient mice (ATM +/- ApoE -/- ), chloroquine no longer prevented atherosclerosis or impacted Treg counts. Abolishing Treg cells using an anti-CD25 antibody in vivo abrogated the atheroprotective effect of chloroquine. In vitro, chloroquine promoted the differentiation of Tregs from naïve T cells, which was accompanied by enhanced ATM/AMP-activated protein kinase (AMPK) activity and reduced downstream mammalian target of rapamycin (mTOR) activity., Discussion: These findings suggest that chloroquine ameliorates atherosclerosis and stabilizes plaque by modulating Tregs differentiation through the regulation of the ATM/AMPK/mTOR pathway., Competing Interests: The authors declare no conflicts of interest in this work., (Thieme. All rights reserved.)

Background: Knee osteoarthritis (KOA) is the most common degenerative joint disease in China, causing a huge economic burden on patients, families, and society. Standardized KOA rehabilitation treatment is an important means to prevent and treat the disease and promote the development of high-quality medical services. This guideline is updated on the basis of the 2016 and 2019 editions., Methods: Clinical questions regarding rehabilitation assessment and treatment were selected through clinical questions screening and deconstruction, and multiple rounds of Delphi questionnaire consultation. The International Classification of Functioning, Disability and Health (ICF) was used as the theoretical framework, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was used to grade the quality of evidence and recommendations., Results: The reporting of this guideline followed the standard of Reporting Items for Practice Guidelines in Healthcare (RIGHT). Taking into account patients' preferences and values and the needs of Chinese clinical practice, a total of 11 clinical questions and 28 recommendations were established. The clinical questions were grouped into two categories: KOA assessment (body function, body structure, activity and participation, quality of life, and environmental factors and clinical outcomes assessment, resulting in 9 recommendations) and KOA treatment (health education, therapeutic exercise, therapeutic modalities, occupational therapy, assistive devices, and regenerative rehabilitation approaches, resulting in 19 recommendations)., Conclusion: This is the first evidence-based guideline for KOA rehabilitation in China utilizing the ICF framework. This guideline provides key guidance for developing systematic, standardized, and precise rehabilitation protocols for KOA across various healthcare settings., (© 2023 The Authors. Journal of Evidence-Based Medicine published by Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

Objectives: The latest international guideline recommended the add-on therapy of ezetimibe and PCSK9 inhibitors in selected people for the secondary prevention of cardiovascular diseases (CVDs). However, it remains unclear whether these regimens fit the Chinese healthcare system economically., Methods: Based on the Chinese context, this simulation study evaluated four therapeutic strategies including the high-dose statin-only group, ezetimibe plus statin group, PCSK9 inhibitors plus statin group, and PCSK9 inhibitors plus ezetimibe plus statin group. The team developed a Markov model to estimate the incremental cost-effectiveness ratio (ICER). With each 1-yr cycle, the simulation subjects could have nonfatal cardiovascular events (stroke and/or myocardial infarction) or death (vascular or nonvascular death event) with a follow-up duration of 20 yr. Cardiovascular risk reduction was gathered from a network meta-analysis, and cost and utility data were gathered from hospital databases and published research., Results: For Chinese adults receiving high-dose statins for secondary prevention of CVDs, the ICER was US$68,910 per quality-adjusted life year (QALY) for adding PCSK9 inhibitors, US$20,242 per QALY for adding ezetimibe, US$51,552 per QALY for adding both drugs. Given a threshold of US$37,655 (three times of Chinese GDP), the probability of cost-effectiveness is 2.9 percent for adding PCSK9 inhibitors, 53.1 percent for adding ezetimibe, and 16.8 percent for adding both drugs. To meet the cost-effectiveness, an acquisition price reduction of PCSK9 inhibitors of 33.6 percent is necessary., Conclusion: In Chinese adults receiving high-dose statins for the secondary prevention of CVDs, adding ezetimibe is cost-effective compared to adding PCSK9 inhibitors and adding both drugs.

Rapidly proliferating high-quality evidence supports daily decision-making in clinical practice. Continuing professional medical education links this evidence to practicing clinicians who are strongly motivated to improve the quality of their care by using the latest information. Approaches to professional education vary, and their effects depend on specific scenarios. This narrative review summarizes the main approaches for professional medical education that facilitate the mobilization of evidence for clinicians. It includes traditional learning (passive and active dissemination of educational materials, lectures, and mass media dissemination), constructivist learning (engaging in local consensus processes and education outreach visits, interfacing with local opinion leaders, conducting patient-mediated interventions, employing audit and feedback processes, and utilizing clinical decision-supporting systems), and blended learning approaches (the integration of in-person or online passive learning with active and creative learning by the learners). An optimized selection from these approaches is challenging but critical to clinicians and healthcare systems., Competing Interests: Conflicts of interest are inevitable in real-world educational and clinical scenarios (19). They impact the quality of an educational program but are easy to ignore in practice. Industries, including but not restricted to those in the pharmaceutical field, often offer continuous medical education that may influence the decision-making of clinicians. However, this involvement raises serious concerns (19, 20), as inherent conflicts of interest could introduce bias into professional medical education (21). Accreditation systems are devised to guarantee the credibility of educators and determine that delivered materials are without bias (21). In Europe and North America, accreditation councils for continuing medical education require sponsors to be transparent regarding their roles in educational activities (20, 22). The amount of industry funding for specific professional education activities must also be disclosed (19). In cases of bias, the council or other organizations could suppress materials to prevent poor medical behavior in practice (19). Given their non-profit nature, many medical professional societies are the most appropriate bodies to hold or fund professional educational programs.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lyu and Li.)

Background: Sarcopenia is a serious public health concern among older adults worldwide. Exercise is the most common intervention for sarcopenia. This study aimed to compare the effectiveness of different exercise types for older adults with sarcopenia., Methods: Randomized controlled trials (RCTs) that examined the effectiveness of exercise interventions on patient-important outcomes for older adults with sarcopenia were eligible. We systematically searched MEDLINE, Embase and Cochrane Central Register of Controlled Trials via Ovid until 3 June 2022. We used frequentist random-effects network meta-analyses to summarize the evidence and applied the Grading of Recommendations, Assessment, Development, and Evaluations framework to rate the certainty of evidence., Results: Our search identified 5988 citations, of which 42 RCTs proved eligible with 3728 participants with sarcopenia (median age: 72.9 years, female: 73.3%) with a median follow-up of 12 weeks. We are interested in patient-important outcomes that include mortality, quality of life, muscle strength and physical function measures. High or moderate certainty evidence suggested that resistance exercise with or without nutrition and the combination of resistance exercise with aerobic and balance training were the most effective interventions for improving quality of life compared to usual care (standardized mean difference from 0.68 to 1.11). Moderate certainty evidence showed that resistance and balance exercise plus nutrition (mean difference [MD]: 4.19 kg) was the most effective for improving handgrip strength (minimally important difference [MID]: 5 kg). Resistance and balance exercise with or without nutrition (MD: 0.16 m/s, moderate) were the most effective for improving physical function measured by usual gait speed (MID: 0.1 m/s). Moderate certainty evidence showed that resistance and balance exercise (MD: 1.85 s) was intermediately effective for improving physical function measured by timed up and go test (MID: 2.1 s). High certainty evidence showed that resistance and aerobic, or resistance and balance, or resistance and aerobic exercise plus nutrition (MD from 1.72 to 2.28 s) were intermediately effective for improving physical function measured by the five-repetition chair stand test (MID: 2.3 s)., Conclusions: In older adults with sarcopenia, high or moderate certainty evidence showed that resistance exercise with or without nutrition and the combination of resistance exercise with aerobic and balance training were the most effective interventions for improving quality of life. Adding nutritional interventions to exercise had a larger effect on handgrip strength than exercise alone while showing a similar effect on other physical function measures., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Medical journals have adhered to a reporting practice that seriously limits the usefulness of published trial findings. Medical decision makers commonly observe many patient covariates and seek to use this information to personalize treatment choices. Yet standard summaries of trial findings only partition subjects into broad subgroups, typically binary categories. Given this reporting practice, we study the problem of inference on long mean treatment outcomes E[y(t)|x], where t is a treatment, y(t) is a treatment outcome, and the covariate vector x has length K, each component being a binary variable. The available data are estimates of {E[y(t)|x k = 0], E[y(t)|x k = 1], P(x k )}, k = 1,..., K reported in journal articles. We show that reported trial findings partially identify {E[y(t)|x], P(x)}. Illustrative computations demonstrate that the summaries of trial findings in journal articles may imply only wide bounds on long mean outcomes. One can realistically tighten inferences if one can combine reported trial findings with credible assumptions having identifying power, such as bounded-variation assumptions., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options., Design: Systematic review and network meta-analysis., Data Sources: Ovid Medline, Embase, and Cochrane Central up to 14 October 2022., Eligibility Criteria for Selecting Studies: Eligible randomised controlled trials compared drugs of interest in adults with type 2 diabetes. Eligible trials had a follow-up of 24 weeks or longer. Trials systematically comparing combinations of more than one drug treatment class with no drug, subgroup analyses of randomised controlled trials, and non-English language studies were deemed ineligible. Certainty of evidence was assessed following the GRADE (grading of recommendations, assessment, development and evaluation) approach., Results: The analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors (odds ratio 0.88, 95% confidence interval 0.83 to 0.94; high certainty) and GLP-1 receptor agonists (0.88, 0.82 to 0.93; high certainty) reduce all cause death; non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality (0.89, 0.79 to 1.00; moderate certainty); other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease. Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone). Tirzepatide probably results in the largest reduction in body weight (mean difference -8.57 kg; moderate certainty). Basal insulin (mean difference 2.15 kg; moderate certainty) and thiazolidinediones (mean difference 2.81 kg; moderate certainty) probably result in the largest increases in body weight. Absolute benefits of SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone vary in people with type 2 diabetes, depending on baseline risks for cardiovascular and kidney outcomes (https://matchit.magicevidence.org/230125dist-diabetes)., Conclusions: This network meta-analysis extends knowledge beyond confirming the substantial benefits with the use of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing adverse cardiovascular and kidney outcomes and death by adding information on finerenone and tirzepatide. These findings highlight the need for continuous assessment of scientific progress to introduce cutting edge updates in clinical practice guidelines for people with type 2 diabetes., Systematic Review Registration: PROSPERO CRD42022325948., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from Sichuan Science and Technology Bureau and West China Hospital, Sichuan University for the submitted work; QS, KNo, POV, AAg, TA, RS, QH, QF, ZQ, FY, XZ, XC, YJ, LG, YM, QinY, AAs, CZ, JPL, KNu, SRC, SG, YG, XL, QiuY, HZ, XA, ZC, XL, SH, YC, HT, and GHG received no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. ES reported personal fees from Oxford Diabetes Trials Unit, Bayer, Berlin Chemie, Boehringer Ingelheim, Menarini, Merck Serono, EXCEMED, Novartis, Novo Nordisk, and Sanofi. LR reported grants or contracts from Swedish Heart Lung Foundation, Stockholm County Council, Erling Perssons Foundation, and Boehringer-Ingelheim, and payment or honorariums for lectures, presentations, speakers bureaus, manuscript writing or educational events from Bayer AG, Boehringer Ingelheim, and Novo Nordisk. FCB reported grants or contracts from National Institutes of Health, and consulting fees from Gilead Sciences. RAM reported grants or contracts from Boehringer Ingelheim. OS reported payment or honorariums for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Abbott Diagnostics, Lilly Deutschland, Boehringer Ingelheim, Bayer, Mannkind, and Lifescan and is a founder and CEO of Sciarc GmbH. NM reported grants or contracts from Boehringer Ingelheim, Merck, Novo Nordisk, Deutsche Forschungsgesellschaft (German Research Foundation; TRR 219), and consulting fees from Boehringer Ingelheim, Merck, Novo Nordisk, AstraZeneca, BMS, and payment or honorariums for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Boehringer Ingelheim, Merck, Novo Nordisk, Lilly, BMS, and AstraZeneca. SL received the fund from the Sichuan Science and Technology Programme and West China Hospital of Sichuan University., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We have updated the guideline for preventing and managing perioperative infection in China, given the global issues with antimicrobial resistance and the need to optimize antimicrobial usage and improve hospital infection control levels., Methods: We conducted a comprehensive evaluation of the evidence for prevention and management of perioperative infection, based on the concepts of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The strength of recommendations was graded and voted using the Delphi method and the nominal group technique. Revisions were made to the guidelines in response to feedback from the experts., Results: There were 17 questions prepared, for which 37 recommendations were made. According to the GRADE system, we evaluated the body of evidence for each clinical question. Based on the meta-analysis results, recommendations were graded using the Delphi method to generate useful information., Conclusions: This guideline provides evidence to perioperative antimicrobial prophylaxis that increased the rational use of prophylactic antimicrobial use, with substantial improvement in the risk-benefit trade-off., (© 2023 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

Objective: To evaluate the impact of stress hyperglycemia on the in-hospital prognosis in non-surgical patients with heart failure and type 2 diabetes., Research Design and Methods: We identified non-surgical hospitalized patients with heart failure and type 2 diabetes from a large electronic medical record-based database of diabetes in China (WECODe) from 2011 to 2019. We estimated stress hyperglycemia using the stress hyperglycemia ratio (SHR) and its equation, say admission blood glucose/[(28.7 × HbA1c)- 46.7]. The primary outcomes included the composite cardiac events (combination of death during hospitalization, requiring cardiopulmonary resuscitation, cardiogenic shock, and the new episode of acute heart failure during hospitalization), major acute kidney injury (AKI stage 2 or 3), and major systemic infection., Results: Of 2875 eligible Chinese adults, SHR showed U-shaped associations with composite cardiac events, major AKI, and major systemic infection. People with SHR in the third tertile (vs those with SHR in the second tertile) presented higher risks of composite cardiac events ([odds ratio, 95% confidence interval] 1.89, 1.26 to 2.87) and major AKI (1.86, 1.01 to 3.54). In patients with impaired kidney function at baseline, both SHR in the first and third tertiles anticipated higher risks of major AKI and major systemic infection., Conclusions: Both high and low SHR indicates poor prognosis during hospitalization in non-surgical patients with heart failure and type 2 diabetes., (© 2022. The Author(s).)

Our aim was to investigate the association of glycated haemoglobin A1c (HbA1c) variability score (HVS) with estimated glomerular filtration rate (eGFR) slope in Chinese adults living with type 2 diabetes. This cohort study included adults with type 2 diabetes attending outpatient clinics between 2011 and 2019 from a large electronic medical record-based database of diabetes in China (WECODe). We estimated the individual-level visit-to-visit HbA1c variability using HVS, a proportion of changes in HbA1c of ≥0.5% (5.5 mmol/mol). We estimated the odds of people experiencing a rapid eGFR annual decline using a logistic regression and differences across HVS categories in the mean eGFR slope using a mixed-effect model. The analysis involved 2397 individuals and a median follow-up of 4.7 years. Compared with people with HVS ≤ 20%, those with HVS of 60% to 80% had 11% higher odds of experiencing rapid eGFR annual decline, with an extra eGFR decline of 0.93 mL/min/1.73 m2 per year on average; those with HVS > 80% showed 26% higher odds of experiencing a rapid eGFR annual decline, with an extra decline of 1.83 mL/min/1.73 m2 per year on average. Chinese adults with type 2 diabetes and HVS > 60% could experience a more rapid eGFR decline.

Introduction: Red meat overconsumption is an unhealthy behavior, while its attributed burden and epidemiological pattern remain unclear. This study aimed to describe the status and trend of how the diet high in red meat burdens the world., Material and Methods: We accessed the data of summary exposure values (SEVs), deaths, and disability-adjusted life years (DALYs) with their age-standardized rates in each country from the Global Burden of Disease (GBD) Collaborative Network from 1990 to 2019. We calculated estimated annual percentage changes (EAPCs) to evaluate the trends of the disease burden., Results: The age-standardized SEV rates increased in most of the 21 GBD regions, mainly in the low-middle and middle socio-demographic index (SDI) quantiles from 1990 to 2019, while East Asia increased the most rapidly. In 2019, a diet high in red meat was responsible for 0.9 million (95% uncertainty interval (UI) 0.5 to 1.3 million) deaths and 23.9 million (95% UI 15.6 to 32.0 million) DALYs worldwide. From 1990 to 2019, the total deaths and DALYs attributable to a diet high in red meat increased by over 50%. However, the age-standardized death and DALY rates decreased by 30.3% and 23.5%, respectively, during the study period. The age-standardized death and DALY rates in the middle SDI regions surpassed those in the high SDI regions from 2002. Ischemic heart disease, diabetes mellitus, and colorectal cancer were the main causes of diet high in red meat-related deaths and DALYs., Conclusions: Increasing consumption of red meat remains a global challenge, especially in the low-middle and middle SDI countries., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 Termedia & Banach.)

Background: To determine the impact of glucose levels at admission and during first week (early phase) on clinical outcomes in patients with acute pancreatitis (AP) and to investigate the relationship between stress hyperglycaemia (SHG) and hypertriglyceridaemia (HTG)., Methods: Two independent and prospective databases were retrospectively analysed (n = 1792). Patients admitted with pain of less than 48 hours and confirmed AP were included. SHG was defined as admission blood glucose ≥ 10.00 mmol/L (non-diabetic) or ≥ 16.67 mmol/L (diabetic). Blood glucose records for the first week were inspected to determine whether SHG lasted ≥ 48 hours (persistent) or < 48 hours (transient). Clinical outcomes were compared between designated patient groups using multivariate and trend analyses. The correlation between SHG and HTG (serum triglyceride ≥ 5.65 mmol/L) was also analysed., Results: On admission, SHG was present in 27.8% (499/1792) patients; during the first 48 hours of admission, transient and persistent SHG was found in 31% (556/1792) and 8.0% (144/1792) patients, respectively. Admission SHG was associated with higher incidence of persistent organ failure, acute necrotic collection, major infection, and mortality as well as prolonged length of hospital stay (all P < 0.05). Duration of SHG was also associated with worsened clinical outcomes (all P < 0.05). In HTG-AP patients, more severe clinical outcomes were observed in those who concomitantly had SHG ( P  < 0.05)., Conclusions: Admission and persistent SHG during the first week of admission worsens clinical outcomes of AP patients. These effects are more pronounced when admission HTG co-existed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Shi, Yao, He, Zhu, Li, Li, Li, Liu, Deng, Jin, Liu, Lu, Windsor, Sutton, Zhu, Xia and Huang.)

Background: Current practice uses the latest measure of glycated hemoglobin (HbAlc) to facilitate clinical decision-making. Studies have demonstrated that HbAlc variability links the risk of death and complications of diabetes. However, the role of HbAlc variability is unclear in clinical practice. This systematic review summarized the evidence of visit-to-visit HbAlc variability regarding different metrics in micro- and macro-vascular complications and death in people with type 2 diabetes., Methods: We searched PubMed, EMBASE (via OVID), and Cochrane Central Register (CENTRAL, via OVID) for studies investigating the association between HbAlc variability and adverse outcomes in patients with type 2 diabetes and performed random-effects meta-analysis stratified by HbAlc variability metrics in terms of standard deviation (SD), coefficient of variation (CV), and HbAlc variability score (HVS)., Results: In people with type 2 diabetes, the highest quantile of all three HbAlc variability metrics (HbAlc-standard deviation [HbAlc-SD], HbAlc-coefficient of variance [HbAlc-CV], and HVS) is associated with increased risks of all-cause mortality, cardiovascular events, progression to chronic kidney disease, amputation, and peripheral neuropathy. For example, the hazard ratio of HbAlc-SD on all-cause mortality was l.89 with 95% confidence interval (95% CI) l.46-2.45 (HbAlc-CV l.47, 95% CI l.26-l.72; HVS l.67, 95% CI l.34-2.09)., Conclusions: High HbAlc variability leads to micro- and macro-vascular complications of type 2 diabetes and related death. People with type 2 diabetes and high HbAlc variability need additional attention and care for the potential adverse outcomes., (Copyright © 2022 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Objective: To determine the harms of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in people who need lipid-lowering therapy., Methods: This systematic review included randomised controlled trials that compared PCSK9 inhibitors with placebo, standard care or active lipid-lowering comparators in people who need lipid-lowering therapy with the follow-up duration of at least 24 weeks. We summarised the relative effects for potential harms from PCSK9 inhibitors using random-effect pairwise meta-analyses and assessed the certainty of evidence using GRADE (Grading of Recommendation Assessment, Development and Evaluation) for each outcome., Results: We included 32 trials with 65 861 participants (with the median follow-up duration of 40 weeks, ranging from 24 to 146 weeks). The meta-analysis showed an incidence of injection-site reaction leading to discontinuation (absolute incidence of 15 events (95% CI 11 to 20) per 1000 persons in a 5-year time frame, high certainty evidence). PCSK9 inhibitors do not increase the risk of new-onset diabetes mellitus, neurocognitive events, cataracts or gastrointestinal haemorrhage with high certainty evidence. PCSK9 inhibitors probably do not increase the risks of myalgia or muscular pain leading to discontinuation or any adverse events leading to discontinuation with moderate evidence certainty. Given very limited evidence, PCSK9 inhibitors might not increase influenza-like symptoms leading to discontinuation (risk ratio 1.5; 95% CI 0.06 to 36.58). We did not identify credible subgroup analyses results, including shorter versus longer follow-up duration of trials., Conclusions: PCSK9 inhibitors slightly increase the risk of severe injection-site reaction but not cataracts, gastrointestinal haemorrhage, neurocognitive events, new-onset diabetes or severe myalgia or muscular pain., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: High low-density lipoprotein-cholesterol (LDL-C) is a public health issue contributing to ischemic heart disease (IHD) and stroke., Method: In this ecological study, we collected summary exposure values (SEVs), deaths, disability-adjusted life of years (DALYs), and Social Demographic Index (SDI) of high LDL-C from 1990 to 2019 using the query tool from the Global Burden of Disease (GBD) Collaborative Network. Outcomes include SEVs, deaths, and DALYs attributable to high LDL-C stratified by sex, age, region, SDI, countries, and territories. Estimated annual percentage changes (EAPCs) were applied to estimate annual trends of changes in these outcomes. We applied the weighted segmented regression with break-point estimation to detect the linear piecewise relationship between SDI and high LDL-C disease burden., Results: Globally, 3.00 million (95% uncertainty interval [UI], 2.35-3.76 million) people in 1990 and 4.40 million (95% UI, 3.30-5.65 million) people died from high LDL-C in 2019. The absolute annual burden from deaths and DALYs attributed to high LDL-C increased by 46% (95% UI, 35-56%) and 41% (95% UI, 31-50%) from 1990 to 2019. The age-standardized SEV, death, and DALY was decreased by 9% (95% UI, -11 to -8%), 37% (95% UI, -41-33%), and 32% (95% UI, -37 to -28%), respectively, during the study period. There was a negative association between SDI and high LDL-C-related age-standardized death and DALY rates when SDI surpassed 0.71 and 0.71, respectively., Conclusion: Although the overall age-standardized burden of high LDL-C is controlled in the past 30 years, it remains increasing in moderate SDI countries, and decreasing trends are disappearing in high SDI countries. New challenges require new actions stratified by countries with different SDI levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Du, Shi, Song, Pan, Yang, Chen, He, Zong, Zhu, Su and Li.)

Clinical Question: In adults with low density lipoprotein (LDL) cholesterol levels >1.8 mmol/L (>70 mg/dL) who are already taking the maximum dose of statins or are intolerant to statins, should another lipid-lowering drug be added, either a proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor or ezetimibe, to reduce the risk of major cardiovascular events? If so, which drug is preferred? Having decided to use one, should we add the other lipid-lowering drug?, Current Practice: Most guidelines emphasise LDL cholesterol targets in their recommendations for prescribing PCSK9 inhibitors and/or ezetimibe in adults at high risk of experiencing a major adverse cardiovascular event. However, to achieve these goals in very high risk patients with statins alone is almost impossible, so physicians are increasingly considering other lipid-lowering drugs solely for achieving LDL cholesterol treatment goals rather than for achieving important absolute cardiovascular risk reduction. Most guidelines do not systematically assess the cardiovascular benefits of adding PCSK9 inhibitors and/or ezetimibe for all risk groups across primary and secondary prevention, nor do they report, in accordance with explicit judgments of assumed patients' values and preferences, absolute benefits and harms and potential treatment burdens., Recommendations: The guideline panel provided mostly weak recommendations, which means we rely on shared decision making when applying these recommendations. For adults already using statins, the panel suggests adding a second lipid-lowering drug in people at very high and high cardiovascular risk but recommends against adding it in people at low cardiovascular risk. For adults who are intolerant to statins, the panel recommends using a lipid-lowering drug in people at very high and high cardiovascular risk but against adding it in those at low cardiovascular risk. When choosing to add another lipid-lowering drug, the panel suggests ezetimibe in preference to PCSK9 inhibitors. The panel suggests further adding a PCSK9 inhibitor to ezetimibe for adults already taking statins at very high risk and those at very high and high risk who are intolerant to statins., How This Guideline Was Created: An international panel including patients, clinicians, and methodologists produced these recommendations following standards for trustworthy guidelines and using the GRADE approach. The panel identified four risk groups of patients (low, moderate, high, and very high cardiovascular risk) and primarily applied an individual patient perspective in moving from evidence to recommendations, though societal issues were a secondary consideration. The panel considered the balance of benefits and harms and burdens of starting a PCSK9 inhibitor and/or ezetimibe, making assumptions of adults' average values and preferences. Interactive evidence summaries and decision aids accompany multi-layered recommendations, developed in an online authoring and publication platform (www.magicapp.org) that also allows re-use and adaptation., The Evidence: A linked systematic review and network meta-analysis (14 trials including 83 660 participants) of benefits found that PCSK9 inhibitors or ezetimibe probably reduce myocardial infarctions and stroke in patients with very high and high cardiovascular risk, with no impact on mortality (moderate to high certainty evidence), but not in those with moderate and low cardiovascular risk. PCSK9 inhibitors may have similar effects to ezetimibe on reducing non-fatal myocardial infarction or stroke (low certainty evidence). These relative benefits were consistent, but their absolute magnitude varied based on cardiovascular risk in individual patients (for example, for 1000 people treated with PCSK9 inhibitors in addition to statins over five years, benefits ranged from 2 fewer strokes in the lowest risk to 21 fewer in the highest risk). Two systematic reviews on harms found no important adverse events for these drugs (moderate to high certainty evidence). PCSK9 inhibitors require injections that sometimes result in injection site reactions (best estimate 15 more per 1000 in a 5 year timeframe), representing a burden and harm that may matter to patients. The MATCH-IT decision support tool allows you to interact with the evidence and your patients across the alternative options: https://magicevidence.org/match-it/220504dist-lipid-lowering-drugs/., Understanding the Recommendations: The stratification into four cardiovascular risk groups means that, to use the recommendations, physicians need to identify their patient's risk first. We therefore suggest, specific to various geographical regions, using some reliable risk calculators that estimate patients' cardiovascular risk based on a mix of known risk factors. The largely weak recommendations concerning the addition of ezetimibe or PCSK9 inhibitors reflect what the panel considered to be a close balance between small reductions in stroke and myocardial infarctions weighed against the burdens and limited harms.Because of the anticipated large variability of patients' values and preferences, well informed choices warrant shared decision making. Interactive evidence summaries and decision aids linked to the recommendations can facilitate such shared decisions. The strong recommendations against adding another drug in people at low cardiovascular risk reflect what the panel considered to be a burden without important benefits. The strong recommendation for adding either ezetimibe or PCSK9 inhibitors in people at high and very high cardiovascular risk reflect a clear benefit.The panel recognised the key uncertainty in the evidence concerning patient values and preferences, namely that what most people consider important reductions in cardiovascular risks, weighed against burdens and harms, remains unclear. Finally, availability and costs will influence decisions when healthcare systems, clinicians, or people consider adding ezetimibe or PCSK9 inhibitors., Competing Interests: Competing interests: All authors have completed the BMJ Rapid Recommendations interest disclosure form and a detailed, contextualised description of all disclosures is reported in web appendix 1. As with all BMJ Rapid Recommendations, the executive team and The BMJ judged that no panel member had any financial conflict of interest. Professional and academic interests were minimised as much as possible, while maintaining necessary expertise on the panel to make fully informed decisions., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To determine the harms of ezetimibe in people who need lipid-lowering treatment., Design: Systematic review and meta-analysis., Data Sources: Randomised controlled trials and cohort studies., Eligibility Criteria for Selecting Studies: Studies comparing ezetimibe with placebo, standard care, or other lipid-lowering agents in people who need lipid-lowering treatment with a follow-up duration of at least six months (or 24 weeks). The relative effects for potential harms of ezetimibe were pooled by use of random effect pairwise meta-analyses for randomised controlled trials and the evidence from observational studies was narratively summarised. The certainty of evidence was assessed using the Grading of Recommendation Assessment, Development, and Evaluation., Results: 48 randomised controlled trials with 28 444 participants (median follow-up 34 weeks, range 24-312 weeks) and four observational studies with 1667 participants (median follow-up 282 weeks, range 72-400 weeks) were included. The meta-analyses of randomised trials showed moderate to high certainty that ezetimibe was not associated with cancer (relative risk 1.01; 95% confidence interval 0.92 to 1.11), fractures (0.90; 0.74 to 1.10), discontinuation due to any adverse event (0.87; 0.74 to 1.03), gastrointestinal adverse events leading to discontinuation (1.34; 0.58 to 3.08), myalgia or muscular pain leading to discontinuation (0.82; 0.51 to 1.33), neurocognitive events (1.48; 0.58 to 3.81), or new-onset diabetes (0.88; 0.61 to 1.28). The narrative analysis of observational studies provided consistent findings. No credible subgroup effects were identified for the harm outcomes, including shorter versus longer follow-up duration of trials., Conclusions: Ezetimibe results in little to no difference in adverse events or other undesirable effects compared with placebo, usual care or other lipid-lowering agents., Review Registration: PROSPERO CRD42020187437., Competing Interests: Competing interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from West China Hospital, Sichuan University for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: With the advent of data-intensive science, a full integration of big data science and health care will bring a cross-field revolution to the medical community in China. The concept big data represents not only a technology but also a resource and a method. Big data are regarded as an important strategic resource both at the national level and at the medical institutional level, thus great importance has been attached to the construction of a big data platform for health care., Objective: We aimed to develop and implement a big data platform for a large hospital, to overcome difficulties in integrating, calculating, storing, and governing multisource heterogeneous data in a standardized way, as well as to ensure health care data security., Methods: The project to build a big data platform at West China Hospital of Sichuan University was launched in 2017. The West China Hospital of Sichuan University big data platform has extracted, integrated, and governed data from different departments and sections of the hospital since January 2008. A master-slave mode was implemented to realize the real-time integration of multisource heterogeneous massive data, and an environment that separates heterogeneous characteristic data storage and calculation processes was built. A business-based metadata model was improved for data quality control, and a standardized health care data governance system and scientific closed-loop data security ecology were established., Results: After 3 years of design, development, and testing, the West China Hospital of Sichuan University big data platform was formally brought online in November 2020. It has formed a massive multidimensional data resource database, with more than 12.49 million patients, 75.67 million visits, and 8475 data variables. Along with hospital operations data, newly generated data are entered into the platform in real time. Since its launch, the platform has supported more than 20 major projects and provided data service, storage, and computing power support to many scientific teams, facilitating a shift in the data support model-from conventional manual extraction to self-service retrieval (which has reached 8561 retrievals per month)., Conclusions: The platform can combine operation systems data from all departments and sections in a hospital to form a massive high-dimensional high-quality health care database that allows electronic medical records to be used effectively and taps into the value of data to fully support clinical services, scientific research, and operations management. The West China Hospital of Sichuan University big data platform can successfully generate multisource heterogeneous data storage and computing power. By effectively governing massive multidimensional data gathered from multiple sources, the West China Hospital of Sichuan University big data platform provides highly available data assets and thus has a high application value in the health care field. The West China Hospital of Sichuan University big data platform facilitates simpler and more efficient utilization of electronic medical record data for real-world research., (©Miye Wang, Sheyu Li, Tao Zheng, Nan Li, Qingke Shi, Xuejun Zhuo, Renxin Ding, Yong Huang. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 13.04.2022.)

Background: Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs., Methods: This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678., Findings: 14 605 citations were identified by our search, of which 143 eligible trials enrolled 49 810 participants. Except for levocarnitine, all drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine-topiramate as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change -7·97, 95% CI -9·28 to -6·66) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·76, 95% CI -6·30 to -5·21). Naltrexone-bupropion (OR 2·69, 95% CI 2·11 to 3·43), phentermine-topiramate (2·40, 1·69 to 3·42), GLP-1 receptor agonists (2·17, 1·71 to 2·77), and orlistat (1·72, 1·44 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD -11·41, 95% CI -12·54 to -10·27)., Interpretation: In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective., Funding: 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University., Competing Interests: Declaration of interests SL received grants from the Sichuan Science and Technology Program (grant numbers 2019YFS0305 and 2019YFH0150). All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: We aim to investigate the guideline adherence of β-blocker (BB) initiating dose in Chinese hospitalized patients with heart failure with reduced ejection fraction (HFrEF) and whether the adherence affected the in-hospital outcomes. Methods: This was a retrospective study of patients hospitalized with HFrEF who had initiated BBs during their hospitalization. We defined adherence to clinical practice guidelines as initiating BB with standard dose and non-adherence to guidelines if otherwise, and examined the association between adherence to guidelines and in-hospital BB-related adverse events. Subgroup analyses based on sex, age, coronary heart disease, and hypertension were performed. Results: Among 1,104 patients with HFrEF initiating BBs during hospitalization (median length of hospitalization, 12 days), 304 (27.5%) patients received BB with non-adherent initiating dose. This non-adherence was related to a higher risk (hazard ratio [95% confidence interval]) of BB dose reduction or withdrawal (1.78 [1.42 to 2.22], P < 0.001), but not significantly associated with risks of profound bradycardia, hypotension, cardiogenic shock requiring intravenous inotropes, and severe bronchospasm requiring intravenous steroid during hospitalization. Conclusion: This study identified that over a fourth of patients had received BBs with an initiating dose that was not adherent to guidelines in Chinese hospitalized patients with HFrEF, and this non-adherence was associated with BB dose reduction or withdrawal during hospitalization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhou, Zeng, Wang, Li, Wang, Mordi, Ren, Zhou, Zhu, Tian, Sun, Chen, An, Lang and Li.)

Objectives: This study evaluated the long-term cost-effectiveness of ultrasound screening for thyroid cancer compared with non-screening in asymptomatic adults. Methods: Applying a Markov decision-tree model with effectiveness and cost data from literature, we compared the long-term cost-effectiveness of the two strategies: ultrasound screening and non-screening for thyroid cancer. A one-way sensitivity analysis and a probabilistic sensitivity analysis were performed to verify the stability of model results. Results: The cumulative cost of screening for thyroid cancer was $18,819.24, with 18.74 quality-adjusted life years (QALYs), whereas the cumulative cost of non-screening was $15,864.28, with 18.71 QALYs. The incremental cost-effectiveness ratio of $106,947.50/QALY greatly exceeded the threshold of $50,000. The result of the one-way sensitivity analysis showed that the utility values of benign nodules and utility of health after thyroid cancer surgery would affect the results. Conclusions: Ultrasound screening for thyroid cancer has no obvious advantage in terms of cost-effectiveness compared with non-screening. The optimized thyroid screening strategy for a specific population is essential., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yang, Yang, Guo, Hu and Li.)

Background: Sodium-glucose-cotransporter-2 (SGLT2) inhibitors have proven to be effective in improving glycemic control and lowering body weight in patients with type 2 diabetes mellitus. However, the efficacy and safety on weight loss in adults with overweight or obesity but not diabetes remain unclear. In this article, we aimed to identify the efficacy and safety of SGLT2 inhibitors in adults with overweight or obesity but not diabetes in randomized controlled studies (RCTs)., Methods: We searched for RCTs concerning SGLT2 inhibitors in adults with overweight or obesity but not diabetes in Medline (Ovid SP), Embase (Ovid SP), Cochrane Central Register of Controlled Trials (Ovid SP), and ClinicalTrials.gov up to February 2021. The primary outcomes were changes in body weight and body mass index (BMI). Trial sequential analysis (TSA) was used to test the reliability of the primary outcomes. We analyzed the data using Review Manager 5.3 and pooled data to calculate the mean differences (MDs) or the relative risk (RR). We assessed the evidence quality of evidence of outcomes according to GRADE., Results: Six randomized controlled trials involving 872 individuals were included in the meta-analysis. Compared to the placebo group, the SGLT2 inhibitors group had statistically significant reductions in absolute changes in body weight (MD: -1.42 kg, 95% CI: -1.70 to -1.14; P<0.00001) and BMI (MD: -0.47 kg/m2, 95% CI: -0.63 to -0.31; P<0.00001) in SGLT2 inhibitors group, as indicated by TSA. However, no significant benefits were observed in the SGLT2 inhibitors group in terms of waist circumference (MD: -1.34 cm, 95%CI: -2.75 to 0.07; Z=1.86, P=0.06) compared with the placebo group. The GRADE profiles indicated very low-quality evidence for body weight change and low-quality evidence for BMI change. SGLT2 inhibitors were generally safe and well tolerated., Conclusion: SGLT2 inhibitors could be used in selected adults with overweight and obesity but not diabetes if they are at low risk of genital infection and urinary infection. Further studies are warranted to confirm the efficacy and safety of SGLT2 inhibitors in adults with overweight or obesity but not diabetes for long-term weight management., Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/#loginpage], identifier [PROSPERO, CRD42021252931]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zheng, Liu, Li, Shi, Zhang, Zhou and Su.)

Background: Diabetes is prevalent worldwide including hospitalized patients with heart failure with reduced ejection fraction (HFrEF). This retrospective study investigated the association of diabetes with in-hospital adverse events in patients with HFrEF., Methods: We analyzed data from electronic medical records of patients hospitalized with HFrEF in West China Hospital of Sichuan University from January 1, 2011, to September 30, 2018. Propensity score matching balances the baseline characteristics between patients with and without diabetes. Logistic and Poisson regressions investigated the association of diabetes with risks of intubation, cardiogenic shock, acute kidney injury (AKI), intensive care unit (ICU) admission and death during hospitalization, and length of ICU and hospital stay in the matched cases., Results: Among 6,022 eligible patients (including 1,998 with diabetes), 1,930 patient pairs with and without diabetes were included by propensity score matching. Patients with diabetes had a significantly increased risk of intubation (odds ratio [OR], 2.69; 95% confidence interval [CI], 2.25-3.22; P <0.001), cardiogenic shock (OR, 2.01; 95% CI, 1.72-2.35; P <0.001), AKI at any stage (OR, 1.67; 95% CI, 1.44-1.94; P <0.001), ICU admission (OR, 1.89; 95% CI, 1.65-2.15; P <0.001), and death (OR, 4.25; 95% CI, 3.06-6.02; P <0.001) during hospitalization. Patients with diabetes had longer ICU (median difference, 1.47 days; 95% CI, 0.96-2.08; P <0.001) and hospital stay (2.20 days; 95% CI, 1.43-2.86; P <0.001) than those without diabetes. There were potential subgroup effects by age and by hypertension, and CKD status on the association of diabetes with risk of AKI at any stage; and subgroup effects by sex and CKD status on the association of diabetes with risk of intubation. The increase in length of hospital stay was larger in patients without hypertension than those with hypertension., Conclusions: Among patients with HFrEF, those with diabetes have a worse prognosis, including a higher risk of in-hospital intubation, cardiogenic shock, AKI, ICU admission and death during hospitalization, and longer ICU and hospital stay., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhou, Wang, Wang, Li, Zhang, Tang, Shi, Zhao, Li, Zeng, Song, Tian, Li and Li.)

Background: Metformin extended-release (XR) is a once-daily alternative conventional immediate-release (IR) tablet for adults with type 2 diabetes. Aim: This study aimed to investigate the knowledge, attitude, and practice of the use of metformin XR tablets among clinicians. Methods: We conducted a cross-sectional online survey among endocrinologists, general practitioners, and internists, who are taking routine care of adults with type 2 diabetes in health institutes at all levels in Sichuan Province, China. We designed an online questionnaire including the demographic information, knowledge, attitude, and practice about metformin XR tablets. Results: We included 158 clinicians, 67.7% of whom were females and 63.9% were from tertiary hospitals. The median age was 39.6 years (ranging between 22 and 62 years). Only 8.2% of the clinicians correctly answered the knowledge questions, 82.3% and 62.0% of the responders assumed that metformin XR had superior efficacy and tolerability to the metformin IR, respectively. Only 46.8% of the clinicians prescribed the metformin XR based on the patient's preference for once daily frequency. Conclusion: The knowledge, attitude, and practice of metformin XR among Chinese clinicians need improving. Clinicians need credible information to support their clinical decision-making regarding metformin XR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Tang, An, Zhang, Zhou, Su, Yang, Liao, An and Li.)

Background: We undertook a systematic review and meta-analysis to investigate the relationship between blood glucose levels and mortality in patients with sepsis., Methods: Medline and EMBASE were searched from inception to April 8, 2018. Cohort studies or case-control studies reported the association between blood glucose and mortality in patients with sepsis were selected. Study characteristics, baseline characteristics, definition of hyperglycemia, and outcomes of interest were extracted. We performed a dose-response meta-analysis to assess the effect of blood glucose level on mortality. We also conducted meta-analysis for patients with or without diabetes separately., Results: Ten cohort studies involving 26 429 patients were included, of which 5 were prospective studies and 5 retrospective studies. Dose-response analysis showed that the effect of blood glucose on mortality may differ in patients with versus without diabetes. There was a U-shaped relationship for patients with diabetes and a J-shaped relationship for patients without diabetes, with blood glucose at 145 to 155 mg/dL corresponding to lowest mortality both in patients with and without diabetes., Conclusions: Current evidence suggested U-shaped relationship between blood glucose and mortality in all patients irrespective of their diabetes status. Diabetic patients with blood glucose below 145 mg/dL may have poorer prognosis compared to patients without established diabetes.