BACKGROUND:Although guidelines focus predominantly on individual diseases, some dedicated guidelines and recommendations exist for common combinations of comorbidities. Using diabetes, coronary heart disease (CHD) and stroke as an example, we aimed to assess the current status and quality of such guidelines. METHODS:We systematically searched literature databases, Google, guideline platforms, and websites of relevant organizations. We included guidelines published between 2020 and 2024 that addressed at least two of the following diseases: diabetes, CHD, and stroke; and included drug therapy interventions. We extracted the recommendations on drug therapy and sources of the supporting evidence, and assessed the quality of the guidelines using AGREE II and RIGHT with the help of a large language model based tool. RESULTS:We identified 82 guidelines: 64 focused on one disease with recommendations on comorbidities, and 18 specifically addressed a combination of diseases. China was the most frequent country of origin (n = 50, 61.0%). The methodological and reporting quality of these guidelines was moderate on average. For most guidelines (n = 54, 65.9%), the primary focus was on diabetes. We grouped the recommended drug therapies for patients with combinations of these diseases into four main categories: anti-diabetic therapy, antihypertensive therapy, lipid-lowering therapy, and anticoagulant therapy. Most recommendations were supported by RCTs, but only a third of the guidelines referred to studies done in multimorbid patients. CONCLUSION:Most recommendations related to multimorbidity were found in guidelines focusing on a single target disease, and supporting evidence from multimorbid patients was rare. More primary evidence from multimorbid patients is needed.

Background: The routine approach in evidence synthesis of adverse events is to estimate the odds ratio or risk ratio of each individual study and then synthesize the study-specific effects for a pooled average estimate, while seldom consider the potential imbalanced duration of exposures of study arms. This article aims to investigate the potential impact of imbalanced exposure time on harm effects. Methods: We simulated individual participant time-to-event data based on Cox proportional hazard model, with Weibull function to reshape the distribution of the hazards. We further collapsed the data into aggregated one and fitting both hierarchical Binomial regression model and hierarchical Poisson regression model to estimate the pooled RR and incidence rate ratio (IRR). The percentage bias, mean squared error, and coverage probability were examined. Results: Our results suggested that imbalanced exposure time between study arms can have substantial impact on the estimation of harm effects in evidence synthesis, especially when the extent of the imbalance exceeds 20%. Estimating an IRR to address the imbalanced exposure time only made sense for non-recurrent events when the between-study heterogeneity is small or moderate. A case study by 22 ongoing trials verified the potential biased estimation when exposure time was imbalanced between study arms. Conclusions: It is inappropriate to ignoring exposure time when there is a large difference (> 20%) between study arms; while the IRR could be used in some cases, collecting individual participant data for evidence synthesis of adverse events for time-to-event data should be the primary consideration.

OBJECTIVE:To provide an up-to-date evidence summary about the comparative benefits and harms of drugs for adults with overweight or obesity to inform decision making for policymakers, payers, clinicians, and patients. DESIGN:Systematic review and network meta-analysis of 24 outcomes using frequentist random effects models and bayesian dose-response models, the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, and the Cochrane Risk of Bias 2 tool. DATA SOURCES:Medline, Embase, and Cochrane Library, searched up to 12 November 2025. STUDY SELECTION:Randomised controlled trials of 12 weeks' duration or longer comparing one or more drugs with lifestyle modification, placebo, or another drug. RESULTS:This network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 weeks. Compared with lifestyle modification alone, at one year, moderate to high certainty evidence shows substantial weight loss with tirzepatide (mean difference -14.9%, 95% confidence interval -16.0% to -13.9%), cagrilintide-semaglutide (CagriSema, -14.8%, -16.9% to -12.7%), oral semaglutide (-10.9%, -12.7% to -9.1%), orforglipron (-9.9%, -12.4% to -7.5%), subcutaneous semaglutide (-9.8%, -10.6% to -9.1%), and phentermine-topiramate (-8.1%, -9.7% to -6.5%). Emerging agents (ecnoglutide, mazdutide, retatrutide) may produce similar or greater reductions (13.1-14.6%; very low to low certainty). Moderate to high certainty evidence supports discontinuation because of adverse events to be highest with orforglipron, naltrexone-bupropion, liraglutide, phentermine-topiramate, CagriSema, and oral semaglutide (risk ratios from 1.9 to 4.2); gastrointestinal events were most increased with naltrexone-bupropion, oral semaglutide, orforglipron, and tirzepatide (risk ratios from 3.1 to 4.2). Fatigue risk increased, particularly with naltrexone-bupropion (risk ratio 8.9; absolute increase 331 per 1000 people over one year), orforglipron (3.4; 100 more per 1000), and CagriSema (3.2; 92 more per 1000). Tirzepatide reduced fat mass the most (by 25.7%) but also lean mass the most (by 8.3%). Subcutaneous semaglutide was the only drug associated with reduced all cause mortality (risk ratio 0.81, 95% confidence interval 0.72 to 0.93) and myocardial infarction (0.72, 0.61 to 0.85), with these estimates largely informed by cardiovascular outcome trials in high risk populations. Subcutaneous semaglutide (0.43, 0.21 to 0.84) and tirzepatide (0.49, 0.27 to 0.88) reduced heart failure risk. No drugs convincingly reduced kidney failure or improved quality of life (43 trials with 45 663 participants) beyond established minimally important differences (all mean differences <5 points; minimally important difference 10). Except for larger weight reductions in trials with longer duration (shown for subcutaneous semaglutide), subgroup analyses for drug dosages and key patient characteristics did not identify credible differences in relative effects of treatment. CONCLUSIONS:Obesity drugs produce variable weight loss at one year, with larger benefits generally accompanied by greater harms and discontinuation. Most agents do not improve quality of life meaningfully and few show cardiovascular benefits. Decisions in clinical practice should consider trade-offs between benefits and harms within the context of shared decision making. SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD42024507993.

Medical nutritional therapy, an evidence-based application of the nutrition care process guided by a registered dietitian nutritionist, is an integral part of diabetes management, with emerging evidence suggesting distinct nutritional requirements in this population. A thorough review of the existing literature reveals an imperative to address the specific requirements for vitamins and minerals in this population. Current guidelines have given limited attention to micronutrients, despite the higher prevalence of deficiencies and the altered patterns of association between serum micronutrient concentrations and multiple health outcomes among individuals with type 2 diabetes (T2D). To enhance diabetes management, an international multidisciplinary panel of 20 experts from 12 countries participated in a modified Delphi process, which was informed by a narrative review conducted by the research team, to reach consensus on 18 statements, encompassing 11 nutrient-specific recommendations and 7 statements outlining future directions in diabetes nutrition therapy research. The plan for this consensus has been registered on the Practice Guideline Registration for Transparency (registration number: PREPARE-2025CN1178). The expert panel proposed potential target serum concentrations, screening strategies, and micronutrient supplementation for people with T2D and that personalized nutritional strategies integrating individual characteristics, genetic information, and gut microbiota represent key areas for future research.

BACKGROUND AND OBJECTIVES:Linking patient decision aids (PtDAs) to clinical practice guidelines (CPGs) can improve the integration of patient preferences into health care decisions. However, due to the extensive number of recommendations in many CPGs and the limited resources available to CPG development groups, developing a PtDA for each recommendation may be impractical. This study aimed to develop and rank criteria to prioritize CPG recommendations for which the development of a PtDA is relevant. METHODS:A modified three-round Delphi study was conducted between July and December 2024, following the Research and Development (RAND)/University of California at Los Angeles (UCLA) Appropriateness Method (RAM). Potential criteria were derived from selected evidence sources. Criteria reaching at least 75% agreement on the importance threshold in round 1 were retained for ranking in rounds two and three and finalized into a list. Each round comprised a pilot-tested online survey, and responses were analyzed descriptively. Following each survey round, experts discussed the respective results in a recorded videoconference, which was transcribed and analyzed through qualitative content analysis. RESULTS:Twenty-five experts in shared decision-making (SDM) and CPG development from eight countries participated. From an initial set of twelve proposed criteria, two were excluded after round 1 due to insufficient agreement, and two others were merged with related criteria. The remaining eight were ranked during rounds two and three, resulting in a consensus-based final list of criteria. Multiple options with different benefit-harm profiles was ranked as most important, with a mean rank of 1.6 (SD 1.4) on a scale from 1 (most important) to 8 (least important). Decision with impact and potential discrepancy in preferences were ranked second and third, with mean ranks of 2.8 (1.8) and 4.0 (2.1), respectively. The others, in order of importance, were treatment burden (4.1; (1.2)), uncertainty of evidence (5.3; (2.1)), life values (5.8; (1.7)), adherence (6.2; (1.3), and financial aspects (6.3; (1.6)). CONCLUSION:This study provides a consensus-based list of criteria to assist CPG developers in prioritizing recommendations for PtDA development, emphasizing decisions where PtDAs are most needed. Future research will focus on refining these criteria into a practical tool for CPG developers.

Introduction Obtaining clean-catch urine (CCU) samples from non-continent infants is a common clinical challenge due to low urine volume and irregular urination. Non-invasive stimulation techniques, such as the bladder stimulation technique (BST) and the Quick-Wee method, have been proposed to improve success rates and reduce contamination. However, the supporting evidence remains inconsistent, and no multicentre randomised trials have directly compared the effectiveness and safety of Quick-Wee, BST and standard CCU.Methods and analysis The study will enrol 342 infants aged 1–12 months requiring urinalysis, recruited from paediatric wards across three tertiary hospitals in China. Eligible participants will be randomly assigned in a 1:1:1 ratio to one of three intervention groups: BST, Quick-Wee or standard CCU. The primary endpoint is the success rate of urine collection within 5 min of intervention. Secondary endpoints include time to urination, 5 min urination rate, infant discomfort scores, parental and clinician satisfaction, and urine contamination rates. Safety will be evaluated by monitoring the incidence of adverse events.Ethics and dissemination This study was approved by the Biomedical Ethics Review Committee of West China Hospital, Sichuan University (No. 114/2025). Written informed consent will be obtained from all participants’ parents prior to enrolment. Study findings will be published in peer-reviewed journals and presented at relevant conferences. Individual participant data will be kept strictly confidential and securely stored in compliance with data protection regulations.Trial registration number ChiCTR2500098691.

Component network meta-analysis (CNMA) decomposes the overall effect of a multicomponent intervention into the effects of its constituent components. It is important to quantify the contribution of each single studies (or comparisons) to the individual component effect obtained from the CNMA model. However, evidence for a single component is often distributed across comparisons of multicomponent interventions, making it difficult to trace graph‑theoretic based paths of evidence in a standard network plot. We propose a two-stage algorithm to quantify evidence contributions in CNMA. First, as component-level evidence is not encoded as connected topological paths in the network of standard NMA, we introduce the concept of pseudo-paths. A pseudo‑path for a target component is defined as a set of directed edges whose linear combination—with non‑negative coefficients—yields a vector that isolates the effect of that component (i.e., equals 1 for the target component and 0 for all others). All pseudo-paths are identified by solving a non‑negative linear feasibility problem based on the CNMA design matrix X_a . Second, we adapt the iterative logic of the shortest‑path approach to allocate evidence flow to these pseudo‑paths. Starting from the pseudo‑path with the fewest edges, we assign a flow on each edge is given by the corresponding absolute entry of the component-level hat matrix H_a . After each allocation, the residual flows on the involved edges are updated, and the process repeats until all flow is exhausted. The algorithm generalizes the shortest‑path approach to an algebraic setting where paths are defined by linear combinations of edges with potentially fractional coefficients, and the flow is distributed proportionally to these coefficients, rather than equally as in standard NMA. We illustrated this approach using both a hypothetical example and real-world datasets. In both real-world data networks, the two-stage algorithm systematically identified and quantified the contributions of the pseudo-paths. The flow-weighted sum of pseudo-path–derived estimates matched exactly (within numerical tolerance) the overall component effect estimated by the CNMA model. This confirms that the proposed algorithm correctly decomposes and then recomposes the evidence structure that gives rise to the component effect estimate. This study adapts the shortest‑path approach for use in CNMA, providing a quantitative method to trace evidence contributions to component‑level estimates. By introducing pseudo‑paths and a corresponding flow‑allocation algorithm, the method extends path‑based contribution analysis from standard NMA to the CNMA setting, enabling transparent decomposition of how evidence from multicomponent interventions synthesizes into component effects.

ABSTRACT Aim Integrating randomized controlled trials (RCTs) and real‐world studies (RWS) requires balancing internal and external validity to achieve target validity. We extended external validity assessment to better capture contextual complexity and diversity, integrating it with established internal validity tools to refine the target validity scoring system. Then, we proposed an Internal Validity‐Gated Dual Weighting (IVDW) strategy, which applies external validity weights to studies exceeding a predefined internal validity threshold. Methods The scoring system was refined through a two‐round Delphi process and Analytic Hierarchy Process to ensure content validity and derive item weights. IVDW was implemented in both frequentist and Bayesian frameworks and compared with four alternatives: Equal‐Weighting, Dual‐dimensional Weighting (DDW), Conditional Exclusion‐based Dual‐weighting (CEDW), and Internal‐validity‐Only Weighting (IVOW), in a novel synthesis of neoadjuvant chemoimmunotherapy in older adults with non‐small cell lung cancer. Results Studies with concurrently high internal and external validity had risk difference estimates below 0.2. IVDW more effectively downweighted low‐internal‐validity studies than DDW and reduced reliance on low‐external‐validity studies compared to IVOW. It improved interpretability by explicitly balancing validity dimensions while maintaining higher evidence inclusion than CEDW. When combined with the quality effects model, IVDW produced estimates aligned with high target validity studies. Conclusions The proposed target validity scoring system, combined with the IVDW strategy, steers effect estimates toward studies with higher internal and external validity. It extends a novel perspective for evidence synthesis and enhances the external validity of meta‐analytic findings in real‐world clinical decision‐making.

Digital health interventions (DHIs), delivered via digital platforms such as internet-based programs, mobile applications or short messages, may improve patient-reported outcomes (PROs), but comparative effectiveness is unclear. We conducted a network meta-analysis of randomized controlled trials in adults undergoing elective surgery under general anesthesia, identified in PubMed, Embase, CENTRAL, and Web of Science to March 1, 2025. Standardized mean differences (SMDs), mean differences (MDs) with minimal important differences (MIDs), and 95% CIs were estimated. Risk of bias was assessed with RoB 2 and certainty of evidence with GRADE. Fifty-six trials (6,154 patients) were included. Extended reality (XR) most effectively reduced perioperative anxiety (SMD 0.60; 95% CI 0.37-0.84; MD 8.05; MID 6.71; moderate-certainty). For postoperative pain, mobile applications (SMD 0.64; 95% CI 0.32-0.95; MD 1.36; MID 1.0; moderate-certainty) and XR (SMD 0.51; 95% CI 0.26-0.76; MD 1.09; MID 1.0; moderate-certainty) were probably effective. For quality of life, 2D video yielded the greatest gain (SMD 0.99; 95% CI 0.11-1.88; MD 0.11; MID 0.05; high-certainty). XR also improved satisfaction (SMD 1.27; 95% CI 0.63-1.91; MD 1.91; MID 0.75; moderate-certainty). These findings suggest that DHIs may improve perioperative PROs.

Prolactinomas are the most prevalent functional pituitary adenomas. Significant advancements have been made in the diagnostic and therapeutic concepts for prolactinomas, driven by progress in surgical techniques and the accumulation of new clinical evidence-based medicine. Based on the 2014 version of the “Chinese Consensus on the Diagnosis and Treatment of Pituitary Prolactin Adenoma,” the China Pituitary Adenoma Specialist Council has revised this consensus in accordance with the latest evidence-based medical finding and clinical experience, aiming to provide standardized diagnosis and treatment recommendations for clinicians. The consensus systematically elaborates on the epidemiological characteristics, clinical manifestations, diagnostic criteria, differential diagnosis process, and treatment strategies for prolactinomas, and proposes individualized management suggestions for special populations (such as pregnant women, male patients, and refractory cases). Treatment decisions strongly advocate for comprehensive evaluation by a multidisciplinary team of experts, including neurosurgery, endocrinology, radiology, radiation oncology, pathology, ophthalmology, and obstetrics/gynecology. Through the formulation of recommendation questions, evidence summary and evaluation, formation of recommendation opinions, expert discussions, and integration with clinical practice, 36 recommendations have been developed covering aspects such as screening, assessment, diagnosis, treatment, and monitoring. This consensus balances clinical needs with international evidence-based standards, provides a highly reliable reference for diagnosis and treatment, and is expected to enhance the standardization and overall level of prolactinoma diagnosis and treatment in China. Practice guideline registration International Practice Guideline Registration for Transparency (PREPARE-2025CN1518).

Introduction Increasing publication of fraudulent clinical trials poses a serious threat to evidence-based medicine. In the VITALITY Study I, we demonstrated that contamination by retracted trials significantly distorts evidence synthesis. The upcoming VITALITY Study II will take a step further and investigate how such problematic evidence undermines the credibility of guideline recommendations.Methods and analyses The VITALITY Study II will adopt a retrospective cohort design and will be structured as three work packages (WPs). To start with, a cohort of clinical practice guidelines (CPGs) that were contaminated by retracted trials and/or meta-analyses that included retracted trials will be established based on forward citation searching (WP1). Then, recommendations from these CPGs that used evidence from retracted trials and/or meta-analyses that synthesised these retracted trials will be re-evaluated after removing such problematic evidence, in terms of both the direction and strength of effect sizes (WP2). Finally, the subsequent impact on patient outcomes attributable to distorted recommendations will be estimated on a hypothetical population, measured by the number of expected benefit loss and the number of expected harm increment per 100 000 patients (WP3).Ethics and dissemination Formal ethical approval is not necessary for this study as it does not involve human or animal participants, nor does it involve the collection of primary data. We will disseminate the findings through publication in peer-reviewed journals and, whenever possible, presentations at academic conferences.

Objectives:In patients living with advanced dementia, the intensity of care during life-threatening infections remains controversial and marked by wide variation in practice. This international survey investigated physicians' and physicians-in-training's management choices for individuals with advanced dementia and the factors associated with those choices. Design:Vignette-based survey. Setting:Twelve countries across five continents. Methods:We administered our vignette-based survey to medical students, residents and physicians. The survey elicited participants' views on whether antibiotics should be administered to an elderly patient with advanced dementia and very poor quality of life, presenting with bacterial pneumonia. We explored factors associated with treatment choices using univariable analysis and multiple logistic regression models. Results:Of the 785 participants (age, mean (SD): 31.1 (11.5) years), one-third (31.2%) resided in the Region of the Americas, 21.9% in Europe, 16.2% in the Eastern Mediterranean region and 17.1% in China. In the univariable analysis, choice to treat was associated with younger age, country/WHO region (African region highest overall, European region lowest overall), stage of medical training (medical student most inclined to treat) and absence of medical assistance in dying (MAiD) legislation. Multivariable analyses provided evidence that country was the variable most strongly associated with the choice to treat with antibiotics (Cameroon, China, Saudi Arabia highest; Norway, Switzerland, Spain lowest), with the presence of MAiD legislation also strongly associated (OR 0.35, 95% CI 0.23 to 0.51). Age (OR 0.82, 95% CI 0.66 to 1.00) and religiosity level (OR 0.93, 95% CI 0.87 to 0.99) showed weaker associations with treatment decisions. Conclusion:Inclination to treat individuals with advanced dementia who develop pneumonia varies greatly between and within jurisdictions. Social factors (in particular country but also presence of MAiD legislation) proved the most prominent associations, with individual characteristics much less influential. These findings underscore the importance of contextual and cultural factors in value-sensitive clinical decisions. Registration:We registered the protocol at Open Science Framework (osf.io/6kfbt).

While medications are essential for preventing and treating disease, they can also cause harm. Evidence synthesis has been widely adopted for evaluating harms, but traditional methods are resource-intensive and may constrain timely decision-making. This study aims to validate a Trial Bank approach towards rapid evidence synthesis. A Trial Bank consisting of 13,650 RCTs of pharmaceutical or biopharmaceutical agents for children was established using artificial intelligence (AI) and humans, based on five databases (e.g., PubMed) up to February 14, 2023. The Trial Bank approach for evidence synthesis was validated in two ways: First, the percentage of trials within 1,996 Cochrane meta-analyses of drug safety in children that were also available in the Trial Bank was reported as the Trial Bank coverage (TBC). Second, the agreement of pooled effects from trials limited to those in the Trial Bank was compared to the full Cochrane meta-analyses in terms of their direction and statistical significance. Of 1,020 trials included in the Cochrane meta-analyses, there was an overall 80.2

Introduction:Variability in estimated glomerular filtration rate (eGFR) has been associated with increased risks of mortality and chronic kidney disease (CKD) progression in people with type 2 diabetes mellitus (T2DM) and impaired kidney function. However, its significance in individuals with preserved kidney function remains unclear. Methods:In this nationwide retrospective population-based study of individuals with T2DM, eGFR variability was calculated by fitting a linear regression model to longitudinal data to estimate both the individual eGFR slope over the 5-year period as well as the variability in model residuals provided by the SD of the model residuals using longitudinal serum creatinine (SCr) measurements obtained during the first 5 years after diagnosis. Cox proportional hazards models were then applied to assess the association between eGFR variability and progression to stage G3b CKD among participants with preserved kidney function. Results:This study included 98,322 participants who had an eGFR > 60 ml/min per 1.73 m2 at diagnosis, remained alive with an eGFR > 60 ml/min per 1.73 m2 5 years after diagnosis, and were subsequently followed for a mean of 5.1 years. Greater eGFR variability was associated with an increased risk of progression to stage G3b CKD- hazard ratios (HRs) for the second, third, and fourth quartiles of variability versus the first quartile were 1.56 (95% confidence interval [CI]: 1.38-1.75), 1.85 (95% CI: 1.65-2.08), and 2.56 (95% CI: 2.29-2.86), respectively. This association persisted after adjustment for multiple variables-HR: 1.57; 95% CI: 1.40-1.77 for the fourth quartiles of variability versus the first quartile. Conclusion:eGFR variability in the absence of acute kidney injury (AKI) is associated with CKD progression in individuals with T2DM and preserved kidney function.

BACKGROUND:The efficacy of individual cognitive behavioral therapy (CBT) components for managing pediatric obesity remains unclear. This study systematically evaluated the impacts of CBT and its constituent techniques in this population. METHOD:We searched PubMed, Embase, and Cochrane CENTRAL from inception to July 17, 2024, for randomized controlled trials comparing CBT techniques or usual care targeting obesity management in children and adolescents with overweight or obesity. Component network meta-analyses provided estimates of effects of each component on obesity-related outcomes. We rated the certainty of evidence using modified GRADE approaches. RESULTS:We included 125 trials with 16,513 children and adolescents. For conceptual level components, compared with minimal education, behavioral therapy probably reduces body fat percentage (MD, -1.16%; 95% CI, -1.68% to -0.64%), waist circumference (MD, -1.70 cm; 95% CI, -2.74 to -0.67 cm), and improves quality of life (SMD, 0.16; 95% CI, 0.03-0.30). For technical-level components, when compared with minimal education, parental involvement (MD, -0.09; 95% CI, -0.16 to -0.03) and stimulus control (MD, -0.07; 95% CI, -0.12 to -0.01) probably reduce body mass index (BMI) z-score. Preplanning (MD, -3.05%; 95% CI, -5.82% to -0.28%) and feedback (MD, -2.73%; 95% CI, -5.31% to -0.14%) probably reduce body fat percentage, whereas device monitoring, problem-solving, rule-setting, and relaxation training might increase body fat percentage. INTERPRETATION:Behavioral therapy alone is likely effective for pediatric obesity management, irrespective of cognitive therapy integration. Techniques such as parental involvement, stimulus control, preplanning, and feedback should be prioritized in CBT.

BACKGROUND:Both finerenone and sodium-glucose cotransporter 2 inhibitors (SGLT-2Is) improve kidney outcomes in people with type 2 diabetes (T2D) and chronic kidney disease (CKD), but the real-world effectiveness of their combination remains unclear. METHODS:This retrospective, single-center study recruited people with T2D-CKD receiving finerenone on SGLT-2Is or SGLT-2Is alone in West China Hospital of Sichuan University. Kidney outcomes were compared after 1:4 propensity score matching. The primary outcome was the time from drug initiation to ≥ 30% decline in eGFR. The secondary outcome was the change in chronic eGFR slope. RESULTS:The matched cohort included 228 SGLT-2Is initiators and 69 finerenone initiators on SGLT-2Is. The baseline mean age was 54.5 years, with eGFR of 68.8 mL/min/1.73 m2 and eGFR slope of -2.1 mL/min/1.73 m2/year. Over a median follow-up of 18.1 months, people receiving finerenone and SGLT-2Is were associated with a reduced risk of ≥ 30% eGFR decline (HR: 0.26; 95% CI: 0.11-0.57) compared to those who received SGLT-2Is only. The between-group difference in post-treatment chronic eGFR slope was -0.74 mL/min/1.73 m2/year (95% CI: -2.95-1.45). However, of those with rapid pre-treatment eGFR decline, the finerenone on SGLT-2Is group experienced significantly greater eGFR decline compared to the SGLT-2Is group (mean difference: -6.28 mL/min/1.73 m2/year; 95% CI: -11.81 to -0.75). CONCLUSION:Finerenone added to SGLT-2Is was associated with slower eGFR decline in most individuals with T2D-CKD. However, people with rapid pre-treatment eGFR decline may experience accelerated deterioration when finerenone is added. These findings are hypothesis-generating rather than confirmatory, requiring further well-designed and prospective studies for validation.

Adults with attention deficit hyperactivity disorder (ADHD) have a higher prevalence and incidence of hypertension, but whether long-term cardiorenal trajectories after the initiation of antihypertensive medications differ by ADHD status is unclear. Here, in this nationwide retrospective cohort study using Dutch register data, we included 706,414 new users (52.2% female, aged 18–90 years) of antihypertensive medications without prior cardiovascular disease or chronic kidney disease (CKD); 10,689 had ADHD. Multistate modelling was used to characterize long-term cardiorenal illness trajectories and compare transition-specific rates between adults with and without ADHD. Adults with ADHD had higher adjusted rates of heart failure hospitalization (HHF; hazard ratio (HR), 1.46; 95% confidence interval (CI), 1.12–1.90) and stroke (HR, 1.19; 95% CI, 1.03–1.38) after antihypertensive medication initiation. They also had higher adjusted rates of cardiorenal death after HHF (HR, 1.79; 95% CI, 1.01–3.17) or CKD (HR, 2.57; 95% CI, 1.33–4.97) onset. Ten-year trajectories through HHF or CKD to cardiorenal death were more common in adults with ADHD. This research investigates long-term cardiorenal outcomes in adults initiating antihypertensive medications, revealing that those with ADHD experience significantly higher rates of heart failure hospitalization, stroke and cardiorenal death than counterparts without ADHD, using multistate modelling for analysis.

The prevalence of type 2 diabetes has been rising in China, India and Southeast Asia for decades, challenging their healthcare systems. With region-specific determinants such as genetics, lifestyle transition and early-life environment, people with type 2 diabetes showed their unique phenotypes, including being, on average, younger in age, with lower BMI but higher percentage body fat mass, higher postprandial glucose and poorer beta-cell function at onset. These features invalidated the implementation of some trial evidence from the Caucasian population when informing guideline recommendations and clinical decision-making. For example, α-glucosidase inhibitors and DPP4 inhibitors, targeting postprandial glucose, showed greater effectiveness and acceptability in Chinese people with type 2 diabetes. The indispensable use of insulin in people with severely impaired beta-cell function is common in China, India and Southeast Asian countries but induces the accumulation of body fat mass, which further worsens the prognosis of the people. GLP-1 receptor agonists show strong weight-lowering effects and cardiovascular protection and provide additional benefits for Asian people compared to Caucasians with the same levels of BMI. Adding GLP-1 receptor agonists to people receiving insulin may neutralise the adverse effect of body weight gain. Clinicians and patients should consider the unique features of the population before making decisions, and policymakers should be aware of the pragmatic determinants during the implementation of the overseas evidence. The adoption of international trials to the region by adjusting their distinct features may improve the relevance of evidence and the treatment response at the individual level.