Maximizing the Value of Real-World Data and Real-World Evidence to Accelerate Healthcare Transformation in China: Summary of External Advisory Committee Meetings.

Use of real-world data (RWD) is gaining wide attention. To bridge the gap between diverse healthcare stakeholders and to leverage the impact of Chinese real-world evidence (RWE) globally, a multi-stakeholder External Advisory Committee (EAC) and EAC meetings were initiated, aiming to elucidate the current and evolving RWD landscape in China, articulate the values of RWE in ensuring Chinese patients' equitable access to affordable medicines and solutions, and identify strategic opportunities and partnerships for expansion of RWE generation in China. Chinese and international experts who are clinicians and academic researchers were selected as EAC members based on their professional background and familiarity with RWD/RWE. Three EAC meetings were held quarterly in 2023. Various topics were presented and discussed for insights and suggestions. Nine experts from China, one from South Korea, and two from Europe were selected as EAC members and attended these meetings. Experts' presentations were summarized by theme, including the RWD landscape and RWE enablement in China, as well as global development of a patient-centric ecosystem. Experts' insights and suggestions on maximizing the RWD/RWE value to accelerate healthcare transformation in China were collected. We concluded that though data access, sharing, and quality are still challenging, RWD is developing to support evidence generation in the medicinal product lifecycle, inform clinical practice, and empower patient management in China. RWD/RWE creates value, accelerates healthcare transformation, and improves patient outcomes. Fostering a patient-centric ecosystem across healthcare stakeholders and maintaining global partnerships and collaboration are essential for unlocking the power of RWD/RWE.

Glycated Hemoglobin Variability Is Associated With Adverse Outcomes in Patients With Heart Failure Irrespective of Diabetic Status.

BACKGROUND: The effect of glycated hemoglobin (HbA1c) variability on adverse outcomes in patients with heart failure (HF) is unclear. We aim to investigate the predictive value of HbA1c variability on the risks of all-cause death and HF rehospitalization in patients with HF irrespective of their diabetic status. METHODS AND RESULTS: Using a previously validated territory-wide clinical data registry, HbA1c variability was assessed by average successive variability (ASV) or SD of all HbA1c measurements after HF diagnosis. Multivariable Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) and its corresponding 95% CI. A total of 65 950 patients with HF were included in the study. Over a median follow-up of 6.7 (interquartile range, 4.0-10.6) years, 34 508 patients died and 52 446 required HF rehospitalization. Every unit increment of variability in HbA1c was significantly associated with higher HF rehospitalization (HR ASV, 1.20 [95% CI, 1.18-1.23]) and all-cause death (HR ASV, 1.50 [95% CI, 1.47-1.53]). Diabetes significantly modified the association between HbA1c variability and outcomes (Pinteraction<0.001). HbA1c variability in patients with HF without diabetes conferred a higher risk of rehospitalization (HR ASV, 1.92 [95% CI, 1.70-2.17] versus HR ASV, 1.19 [95% CI, 1.17-1.21]), and all-cause death (HR ASV, 3.90 [95% CI, 3.31-4.61] versus HR ASV, 1.47 [95% CI, 1.43-1.50] compared with patients with diabetes). CONCLUSIONS: HbA1c variability is significantly associated with greater risk of rehospitalization and all-cause death in patients with HF, irrespective of their diabetic status. These observations were more pronounced in patients with HF without diabetes.

Mortality in patients admitted to hospital with heart failure in China: a nationwide Cardiovascular Association Database-Heart Failure Centre Registry cohort study.

BACKGROUND: China has the largest burden of heart failure worldwide. However, large-scale studies on heart failure mortality are scarce. We aimed to investigate mortality and identify risk factors for mortality among patients with heart failure in China. METHODS: This prospective cohort study used data from the China Cardiovascular Association (CCA) Database-Heart Failure Centre Registry, which were linked to the National Mortality Registration Information Management System by the Chinese Centre for Disease Control and Prevention. We included patients enrolled from Jan 1, 2017, to Dec 31, 2021, across 572 CCA Database-Heart Failure Centre certified hospitals in 31 provinces of mainland China. Eligible patients were aged 18 years or older (younger than 100 years) with a principal discharge diagnosis of heart failure based on Chinese heart failure guidelines. All-cause mortality at 30 days, 1 year, and 3 years for patients with heart failure were calculated and the causes of death were recorded. Multivariable analysis was used to analyse factors associated with all-cause mortality and cardiovascular mortality. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2200066305. FINDINGS: Of the 327 477 patients in the registry, 230 637 eligible adults with heart failure were included in our analyses. Participant mean age was 69·3 years (SD 13·2), 94 693 (41·1%) participants were female, and 135 944 (58·9%) were male. The median follow-up time was 531 days (IQR 251-883). Post-discharge all-cause mortality of patients with heart failure at 30 days was 2·4% (95% CI 2·3-2·5), at 1 year was 13·7% (13·5-13·9), and at 3 years was 28·2% (27·7-28·6). Cardiovascular death accounted for 32 906 (71·5%) of 46 006 all-cause deaths. Patients with heart failure with reduced ejection fraction had the highest all-cause mortality. A lower guideline adherence score was independently associated with the increase of all-cause and cardiovascular mortality. INTERPRETATION: In China, mortality for patients with heart failure is still high, especially in patients with reduced ejection fraction. Our findings suggest that guideline-directed medical therapy needs to be improved. FUNDING: National High Level Hospital Clinical Research Funding, the Capital's Funds for Health Improvement and Research, and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Impact of heart rate changes during hospitalization on outcome in heart failure with preserved ejection fraction.

AIMS: The benefits of lowering heart rate (HR) in heart failure (HF) with preserved ejection fraction (HFpEF) patients are still a matter of debate. This study aimed to investigate the relationship between changes in HR during hospitalization and cardiovascular (CV) events and all-cause death in hospitalized HFpEF patients. METHODS AND RESULTS: Hospitalized HF patients between January 2017 and December 2021 were consecutively enrolled in a national, multicentred, and prospective registry database, the China Cardiovascular Association Database-HF Center Registry. HF patients with a left ventricular ejection fraction of ≥50% were defined as HFpEF patients. The study analysed admission/discharge HR, change in HR during hospitalization (∆HR), and ∆HR ratio (∆HR/admission HR). The patients were categorized into three groups: no HR dropping group (ΔHR ratio > 0.0%), moderate HR dropping group (-15% < ΔHR ratio ≤ 0.0%), and excessive HR dropping group (ΔHR ratio ≤ -15%). All patients were followed up for 12 months. The primary endpoint was CV events (CV death or HF rehospitalization). The secondary endpoint was all-cause death. A total of 19 510 HFpEF patients (9750 males, mean age 71.9 ± 12.2 years) were included, with 4575 in the no HR dropping group, 8434 in the moderate HR dropping group, and 6501 in the excessive HR dropping group. Excessive HR dropping during hospitalization was significantly associated with an increased risk of CV events (17.1%) compared with the no HR dropping group (14.5%, P < 0.001) or the moderate HR dropping group (14.0%, P < 0.001), although all-cause mortality was similar among the three groups. After adjusting for multiple confounding factors, excessive HR dropping remained an independent predictor of increased CV event risk [hazard ratio 1.197, 95% confidence interval (CI) 1.078-1.328]. Subgroup analysis revealed that the prognostic impact of excessive HR dropping on increased CV event risk remained in the subgroups of older age, New York Heart Association class IV, ischaemic HF, higher left ventricular ejection fraction, absence of chronic kidney disease, and use of beta-blockers or ivabradine. Independent determinants associated with excessive HR dropping during admission included use of beta-blockers [odds ratio (OR) 1.683, 95% CI 1.558-1.819], lower discharge diastolic blood pressure (OR 0.988, 95% CI 0.985-0.991), no pacemaker (OR 0.501, 95% CI 0.416-0.603), coexisting atrial fibrillation or atrial flutter (OR 1.327, 95% CI 1.218-1.445), and use of digoxin (OR 1.340, 95% CI 1.213-1.480). CONCLUSIONS: In hospitalized HFpEF patients, excessive HR dropping during hospitalization is associated with an increased risk of CV death or HF rehospitalization. These findings highlight the importance of HR monitoring and avoiding excessively slowing down HR in hospitalized HFpEF patients to reduce the risk of CV events.

Effectiveness and safety of ivabradine in Chinese patients with chronic heart failure: an observational study.

AIMS: A therapeutic strategy for chronic heart failure (HF) is to lower resting heart rate (HR). Ivabradine is a well-known HR-lowering agent, but limited prospective data exist regarding its use in Chinese patients. This study aimed to evaluate the effectiveness and safety of ivabradine in Chinese patients with chronic HF. METHODS AND RESULTS: This multicentre, single-arm, prospective, observational study enrolled Chinese patients with chronic HF. The primary outcome was change from baseline in HR at 1 and 6 months, measured by pulse counting. Effectiveness was also evaluated using laboratory tests, the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (CSS) and overall summary score (OSS), and New York Heart Association (NYHA) class. Treatment-emergent adverse events (TEAEs) were assessed. A post hoc analysis examined the effectiveness and safety of ivabradine combined with an angiotensin receptor-neprilysin inhibitor (ARNI) or beta-blocker. A total of 1003 patients were enrolled [mean age 54.4 ± 15.0 years, 773 male (77.1%), mean baseline HR 88.5 ± 11.3 b.p.m., mean blood pressure 115.7/74.4 ± 17.2/12.3 mmHg, mean left ventricular ejection fraction 30.9 ± 7.6%, NYHA Classes III and IV in 48.8% and 22.0% of patients, respectively]. HR decreased by a mean of 12.9 and 16.1 b.p.m. after 1 and 6 months, respectively (both P < 0.001). At Month 6, improvements in the KCCQ CSS and OSS of ≥5 points were observed in 72.1% and 74.1% of patients, respectively (both P < 0.001). Left ventricular ejection fraction increased by 12.1 ± 11.6 (P < 0.001), and 66.7% of patients showed improvement in NYHA class (P < 0.001). At Month 6, the overall proportion of patients in NYHA Classes III and IV was reduced to 13.5% and 2.1%, respectively. Serum brain natriuretic peptide (BNP) and N-terminal pro-BNP changed by -331.9 ng/L (-1238.6, -134.0) and -1113.8 ng/L (-2202.0, -297.2), respectively (P < 0.001). HR reductions and improvements in NYHA and KCCQ scores with ivabradine were similar with and without use of ARNIs or beta-blockers. Of 498 TEAEs in 296 patients (29.5%), 73 TEAEs in 55 patients (5.5%) were considered related to ivabradine [most frequent sinus bradycardia (n = 7) and photopsia (n = 7)]. TEAEs were reported in a similar number of patients in ARNI and beta-blocker subgroups (21.9-35.6%). CONCLUSIONS: Ivabradine treatment reduced HR and improved cardiac function and health-related quality of life in Chinese patients with chronic HF. Benefits were seen irrespective of whether or not patients were also taking ARNIs or beta-blockers. Treatment was well tolerated with a similar profile to previous ivabradine studies.

Implication of different frailty criteria in older people with atrial fibrillation: a prospective cohort study.

BACKGROUND: the prevalence of physical and multidimensional frailty and their prognostic impact on clinical outcomes in patients with atrial fibrillation (AF) is unclear. OBJECTIVE: to evaluated frailty in a cohort of patients with AF according to different criteria, and studied the prevalence and its prognostic impact on clinical outcomes. METHODS: in this multicenter prospective cohort, 197 inpatients ≥ 65 years old with AF were recruited from September 2018 to April 2019.We used Fried Frailty phenotype (Fried) to assess physical frailty, and comprehensive geriatric assessment-frailty index (CGA-FI) to assess multidimensional frailty. The primary outcome was a composite of all-cause mortality or rehospitalization. RESULTS: the prevalence of frailty was determined as 34.5% by Fried, 42.6% by CGA-FI. Malnutrition and ≥ 7 medications were independently associated with frailty. Kaplan-Meier survival curve showed that the presence of frailty by CGA-FI had significantly lower all-cause mortality or rehospitalization survival rate (log-rank P = 0.04) within 1 year. Multivariate Cox regression adjusted for age and sex showed that the frailty by CGA-FI was significantly associated with the risk of all-cause mortality or rehospitalization within 1 year (HR 1.79, 95% CI 1.10-2.90). However, those associations were absent with the physical frailty. After broader multivariate adjustment, those associations were no longer statistically significant for both types of frailty. CONCLUSIONS: in older people with AF, Multidimensional frailty is more significantly associated with a composite of all-cause mortality or rehospitalization within 1 year than physical frailty, but these association are attenuated after multivariate adjustment. CLINICAL TRIAL REGISTRATION: ChiCTR1800017204; date of registration: 07/18/2018.

Effects of empagliflozin on cardiac structure, function and biomarkers in patients with heart failure with preserved ejection fraction: study protocol for a randomised, placebo-controlled prospective trial.

INTRODUCTION: Heart failure (HF) with preserved ejection fraction (HFpEF) has become the main type of HF worldwide. Although large randomised controlled studies have demonstrated the beneficial effects of sodium-glucose cotransporter 2 inhibitors among patients with HFpEF, the mechanisms remain unclear. Basic research suggests that empagliflozin inhibits myocardial fibrosis. Myocardial extracellular volume (ECV) can be calculated using cardiac MRI (CMRI), which can reflect the degree of diffuse myocardial fibrosis. Studies show that empagliflozin can reduce ECV and left ventricular mass (LVM) assessed by CMRI in patients with diabetes with coronary heart disease and patients without diabetes with HF with reduced ejection fraction. However, whether empagliflozin reduces ECV and LVM among patients with HFpEF is unclear. This study intends to use CMRI to evaluate ECV and LVM, combined with echocardiography and an assessment of related biomarkers, to determine whether empagliflozin can improve myocardial fibrosis and left ventricular remodelling in patients with HFpEF. METHODS AND ANALYSIS: This report describes the study design of a prospective, multicentre, randomised, double-blind, placebo-controlled and parallel-group clinical study. A total of 180 participants with HFpEF aged 40-80 years old who meet the inclusion and exclusion criteria will be randomly divided into an empagliflozin treatment group or a placebo control group. The empagliflozin treatment group will receive 10 mg of empagliflozin per day for 6 months in addition to guideline-directed medical treatment, while the control group will receive placebo oral administration with guideline-directed medical therapy for 6 months. The primary outcomes are ECV and LVM changes measured by CMRI after 6 months of treatment. ETHICS AND DISSEMINATION: The study design is approved by the ethical committee of Beijing Hospital (2022BJYYEC-070-02). The trial is registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn). The trial results will be published in peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2200060862).

Optimisation of warfarin-dosing algorithms for Han Chinese patients with CYP2C9*13 variants.

BACKGROUND: Existing pharmacogenetic algorithms cannot fully explain warfarin dose variability in all patients. CYP2C9*13 is an important allelic variant in the Han Chinese population. However, adjustment of warfarin dosing in CYP2C9*13 variant carriers remains unclear. To the best of our knowledge, this study is the first to assess the effects of adjusting warfarin dosages in Han Chinese patients harbouring CYP2C9*13 variants. METHODS: In total, 971 warfarin-treated Han Chinese patients with atrial fibrillation were enrolled in this study. Clinical data were collected, and CYP2C9*2, *3, *13 and VKORC1-1639 G > A variants were genotyped. We quantitatively analysed the effect of CYP2C9*13 on warfarin maintenance dose and provided multiplicative adjustments for CYP2C9*13 using validated pharmacogenetic algorithms. RESULTS: Approximately 0.6% of the Han Chinese population carried CYP2C9*13 variant, and the genotype frequency was between those of CYP2C9*2 and CYP2C9*3. The warfarin maintenance doses were significantly reduced in CYP2C9*13 carriers. When CYP2C9*13 variants were not considered, the pharmacogenetic algorithms overestimated warfarin maintenance doses by 1.03-1.16 mg/d on average. The actual warfarin dose in CYP2C9*13 variant carriers was approximately 40% lower than the algorithm-predicted dose. Adjusting the warfarin-dosing algorithm according to the CYP2C9*13 allele could reduce the dose prediction error. CONCLUSION: Our study showed that the algorithm-predicted doses should be lowered for CYP2C9*13 carriers. Inclusion of the CYP2C9*13 variant in the warfarin-dosing algorithm tends to predict the warfarin maintenance dose more accurately and improves the efficacy and safety of warfarin administration in Han Chinese patients.

Identification of urgent gaps in public and policymaker knowledge of heart failure: Results of a global survey.

BACKGROUND: Despite advances in the treatment of heart failure (HF) with reduced ejection fraction, people with HF continue to have a high risk of mortality and hospitalisation. Patients also suffer from poor quality of life, with reduced societal and economic participation. The burden of HF on patients and healthcare systems is extraordinary, yet awareness remains low. This survey was conducted to identify gaps in general public and policymaker knowledge around HF. METHODS: A closed-question web-based survey of the general public and policymakers was conducted between February and October 2020. Study outcomes assessed the participants' awareness and understanding of HF symptoms, risk factors and mortality, and views around hospital admissions in their country. Responses were collected using multiple-choice questions. RESULTS: The survey was completed by 26,272 general public respondents in 13 countries and 281 government and public sector policymakers in nine countries. While 99% of general public respondents had heard of HF, their understanding of the condition and its symptoms was poor, and only 6% identified that shortness of breath, fatigue, and leg swelling were the main symptoms of HF. Of policymaker respondents, 14% identified HF as the leading cause of avoidable hospitalisations, and only 4% recognised that ~ 87% of government spending on HF is related to hospitalisations. CONCLUSIONS: Major gaps were identified in the understanding of HF and the burden it places on patients and their caregivers, healthcare systems and society. This study confirms an ongoing need for national policy strategies and investment to raise awareness of the importance of HF prevention, early diagnosis, and implementation of effective treatments to reduce hospitalisations and death.

Magnetism of two-dimensional chromium tellurides.

2D ferromagnets have garnered considerable attention for their potential applications in spintronics, magnonics, and spin-orbitronics. Chromium tellurides (CrxTey), in particular, have drawn interest due to their exceptional magnetic properties and diverse range of chemical stoichiometries, attributed to the phenomenon of chromium self-intercalation. To provide an in-depth understanding of this complex material class, this review first explains the origin of 2D magnetism using two well-known 2D ferromagnets, CrI3 and Fe3GeTe2, and compares the structures of CrTe2, Cr5Te8, Cr2Te3, and CrTe to clarify the self-intercalation phenomenon. In addition, it summarizes the growth conditions of CrxTey using the chemical vapor deposition approach as well as commonly practiced characterization techniques for 2D ferromagnetism. This review also compares ferromagnetic properties while analyzing how Cr intercalants affect the magnetic. Finally, it suggests that more attention should be focused on this material system to unlock its full practical and academic potential, and proposes directions for future research.

Identification and in vitro functional assessment of 10 CYP2C9 variants found in Chinese Han subjects.

Cytochrome P450 2C9 (CYP2C9) participates in about 15% of clinical drug metabolism, and its polymorphism is associated with individual drug metabolism differences, which may lead to the adverse drug reactions (ADRs). In this study, 1163 Chinese Han individuals were recruited to investigate their distribution pattern of CYP2C9 gene and find out the variants that may affect their drug metabolic activities. We successfully developed a multiplex PCR amplicon sequencing method and used it for the genetic screening of CYP2C9 in a large scale. Besides the wild type CYP2C9*1, totally 26 allelic variants of CYP2C9 were detected, which included 16 previously reported alleles and 10 new non-synonymous variants that had not been listed on the PharmVar website. The characteristics of these newly detected CYP2C9 variants were then evaluated after co-expressing them with CYPOR in S. cerevisiae microsomes. Immunoblot analysis revealed that except for Pro163Ser, Glu326Lys, Gly431Arg and Ile488Phe, most of newly detected variants showed comparable protein expression levels to wild type in yeast cells. Two typical CYP2C9 probe drugs, losartan and glimepiride, were then used for the evaluation of metabolic activities of variants. As a result, 3 variants Thr301Met, Glu326Lys, and Gly431Arg almost lost their catalytic activities and most of other variants exhibited significantly elevated activities for drug metabolism. Our data not only enriches the knowledge of naturally occurring CYP2C9 variants in the Chinese Han population, but also provides the fundamental evidence for its potential clinical usage for personalized medicine in the clinic.

Prevalence and prognosis of frailty in older patients with stage B heart failure with preserved ejection fraction.

AIMS: Frailty in older patients with stage B heart failure with preserved ejection fraction (HFpEF) has not been fully explored. We evaluated the prevalence and prognostic significance of frailty in older patients diagnosed with stage B HFpEF. METHODS: Our prospective cohort study included inpatients aged ≥65 years who were followed up for 3 years. Stage B HFpEF was defined as cardiac structural or functional abnormalities with a left ventricular ejection fraction (LVEF) ≥ 50% without signs or symptoms. Frailty was assessed using the Fried phenotype. The primary outcome was 3-year all-cause mortality or readmission. RESULTS: Overall, 520 older inpatients diagnosed with stage B HFpEF [mean ± standard deviation age: 75.5 ± 6.25 years, male: 222 (42.7%)] were included in the study. Of these, 145 (27.9%) were frail. Frail patients were older (78.5 ± 6.23 vs. 74.3 ± 6.22 years, P < 0.001), with a lower body mass index (24.6 ± 3.60 vs. 25.7 ± 3.27 kg/m2 , P = 0.001), higher level of N-terminal pro-B-type natriuretic peptide [279 (interquartile range: 112.4, 596) vs. 140 (67.1, 266) pg/mL, P < 0.001], longer timed up-and-go test result (19.9 ± 9.71 vs. 13.3 ± 5.08 s, P < 0.001), and poorer performance in the short physical performance battery (4.1 ± 3.26 vs. 8.2 ± 2.62, P < 0.001), basic activities of daily living (BADL, 4.7 ± 1.71 vs. 5.7 ± 0.57, P < 0.001), and instrumental activities of daily living (IADL, 4.4 ± 2.73 vs. 7.4 ± 1.33, P < 0.001). Frail patients were more likely to have a Mini-Mental State Examination (MMSE) score <24 (55.9% vs. 28.8%, P < 0.001) and take more than five medications (64.1% vs. 47.2%, P = 0.001). Frail patients had a higher incidence of all-cause mortality or readmission (62.8% vs. 47.7%, P = 0.002), all-cause readmission (56.6% vs. 45.9%, P = 0.029), and readmission for non-heart failure (55.2% vs. 41.3%, P = 0.004) during the 3-year follow-up, with a 1.53-fold (95%CI 1.11-2.11, P = 0.009) higher risk of all-cause mortality or readmission, a 1.52-fold (95%CI 1.09-2.11, P = 0.014) higher risk of all-cause readmission, and a 1.70-fold (95%CI 1.21-2.38, P = 0.002) higher risk of readmission for non-clinical heart failure, adjusted for sex, age, polypharmacy, Athens Insomnia Scale, MMSE, LVEF, BADL, and IADL. CONCLUSIONS: Frailty is common in elderly patients with stage B HFpEF. Physical frailty, particularly low physical activity, can independently predict the long-term prognosis in these patients.

Immune infiltration and immunophenotyping in atrial fibrillation.

Atrial fibrillation (AF) is a relatively common arrhythmia in clinical practice. Although significant progress has been achieved in the treatment of AF and its associated complications, research on AF prevention lags behind, mainly due to the lack of a deep understanding of AF pathogenesis. In recent years, as our knowledge has grown, the role of the inflammatory/immune response in the occurrence and progression of AF has gradually gained attention. In this paper, based on existing gene expression data in the Gene Expression Omnibus database, a detailed description of immune infiltration status in AF is presented using a series of analytical methods, including differential analysis, Gene Ontology categorization, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and weighted gene coexpression network analysis, and analysis tools such as CIBERSORTx and Cytoscape. Several new AF/immune infiltrations-related signature genes were identified, and the AF/immune infiltration pathology was classified based on these immune signature genes, thus providing novel insights into the pathogenesis of AF based on the inflammatory response.

The effects of different types of Tai Chi exercise on anxiety and depression in older adults: a systematic review and network meta-analysis.

Background: The body of evidence supporting the beneficial effects of Tai Chi in reducing anxiety and depressive symptoms in older adults is steadily increasing. Nonetheless, there remains a scarcity of studies directly comparing the clinical effectiveness of various Tai Chi exercises in addressing anxiety and depressive symptoms in older adults. Thus, this study aimed to systematically review and analyze the therapeutic efficacy of four types of Tai Chi interventions in enhancing anxiety and depressive symptoms in older adults. Methods: During the period up to July 26, 2023, searches were conducted in the Web of Science, PubMed, the Cochrane Library, CNKI, and the Chinese Scientific Journal Database (VIP). The language scope encompassed both English and Chinese. Two independent reviewers conducted the literature review and data extraction. Review Manager 5.4 was employed for traditional meta-analysis and risk assessment, while version 15 of STATA software was used for generating evidence and funnel plots for network meta-analysis. This study was registered in PROSPERO number CRD 42023442270. Result: In this analysis, a total of 20 studies were included, involving 1798 participants. The findings of the pairwise meta-analysis revealed that Tai Chi intervention was more effective than the control group in reducing anxiety (SMD: -1.19, 95% CI: -2.04, -0.34, p < 0.05) and depression (SMD: -0.65, 95% CI: -0.95, -0.65, p < 0.05) symptoms among older adults. The network meta-analysis specifically focused on anxiety symptoms and found that Yang-style Tai Chi (69.9%) had the most favorable outcome, followed by the 24-form Simplified Tai Chi (66.8%). In terms of depression symptoms, the Tai Chi Exercise Program (92.6%) had the highest performance, followed by Yang-style Tai Chi (77.9%). Conclusion: The findings of this study imply that Tai Chi can have beneficial outcomes in the reduction of anxiety and depressive symptoms among older individuals. Specifically, when examining various forms of Tai Chi interventions, it was observed that Yang-style Tai Chi exhibited a greater efficacy in alleviating anxiety symptoms, whereas Tai Chi exercise programs demonstrated a higher effectiveness in improving depressive symptoms. Nonetheless, it is strongly advised that older adults select an exercise program that aligns with their interests and preferences, as this can enhance social integration and overall well-being. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023442270, identifier [CRD42023442270].

Identification and drug metabolic characterization of four new CYP2C9 variants CYP2C9*72-*75 in the Chinese Han population.

Cytochrome 2C9 (CYP2C9), one of the most important drug metabolic enzymes in the human hepatic P450 superfamily, is required for the metabolism of 15% of clinical drugs. Similar to other CYP2C family members, CYP2C9 gene has a high genetic polymorphism which can cause significant racial and inter-individual differences in drug metabolic activity. To better understand the genetic distribution pattern of CYP2C9 in the Chinese Han population, 931 individuals were recruited and used for the genotyping in this study. As a result, seven synonymous and 14 non-synonymous variations were identified, of which 4 missense variants were designated as new alleles CYP2C9*72, *73, *74 and *75, resulting in the amino acid substitutions of A149V, R150C, Q214H and N418T, respectively. When expressed in insect cell microsomes, all four variants exhibited comparable protein expression levels to that of the wild-type CYP2C9 enzyme. However, drug metabolic activity analysis revealed that these variants exhibited significantly decreased catalytic activities toward three CYP2C9 specific probe drugs, as compared with that of the wild-type enzyme. These data indicate that the amino acid substitution in newly designated variants can cause reduced function of the enzyme and its clinical significance still needs further investigation in the future.

Clinical significance of the series of CYP2C9*non3 variants, an unignorable predictor of warfarin sensitivity in Chinese population.

Backgrounds: Gene polymorphisms are critical for variations in warfarin dose. To date, more than 70 CYP2C9 alleles have been identified. This study was designed to clarify the clinical significance of CYP2C9*non-3 variants to warfarin sensitivity in Chinese Han patients. Methods: The entire CYP2C9 gene region was sequenced in 1,993 individuals, and clinical data and VKORC1 genotypes were collected from 986 patients with atrial fibrillation treated with warfarin. The SKAT-O method was used to analyze the effects of CYP2C9*non-3 variants on warfarin sensitivity. Results: A total of 20 CYP2C9 variants were identified, of which four were novel. Carriers with CYP2C9*non-3 variants may have lower warfarin dose requirements, and similar to CYP2C9*3, CYP2C9*non-3 variants are clearly relevant to warfarin-sensitive and highly sensitive responders. Conclusion: Our results showed that, besides CYP2C9*3, the series of CYP2C9*non-3 variants is an unignorable predictor for warfarin sensitivity in Chinese population. From a safety consideration, people carried such variants may need a preferred choice of NOACs when they started anticoagulation therapy.

Clinical characteristics and 1-year outcomes in hospitalized patients with heart failure with preserved ejection fraction: results from the China Cardiovascular Association Database-Heart Failure Center Registry.

AIM: We aimed to evaluate clinical characteristics and 1-year outcomes in hospitalized patients with heart failure with preserved ejection fraction (HFpEF) from China. Factors associated with outcomes (hospitalization for HF [HHF] and cardiovascular [CV] death) were assessed. METHOD AND RESULTS: Data were from the China Cardiovascular Association (CCA) Database-HF Center Registry. Between January 2017 and June 2021, 41 708 hospitalized HFpEF patients with 1-year follow-up from 481 CCA Database-HF Center certified secondary and tertiary hospitals across overall 31 provinces of mainland China were included in this study. Of study participants (mean age 72.2 years, 49.3% female), 18.2% had HHF in prior 1 year and 55.8% had New York Heart Association class III/IV. Median left ventricular ejection fraction was 59%. Ischaemia (26.6%), infection (14.4%) and arrhythmia (10.5%) were the three most common precipitating factors for index HHF. Nearly 67.4% had ≥3 comorbidities. Hypertension (65.2%), coronary heart disease (60.3%) and atrial fibrillation (41.2%) were the three most common comorbidities. Device and medication therapy non-compliance with current HF guideline recommendation was observed. The 1-year rate of clinical outcomes was 16.4%, the 1-year rate of HHF was 13.6% and CV death was 3.1%. Factors associated with clinical outcomes included HHF in prior 1 year, serum level of sodium <135 mmol/L and N-terminal pro-B-type natriuretic peptide >1800 pg/ml. CONCLUSION: Patients with HFpEF from China were characterized by high comorbid burden and high 1-year risk of HHF and CV death. Immediate efforts are needed to improve HFpEF management in China.

Implantable device measured objective daily physical activity as a predictor of long-term all-cause mortality and cardiac death in patients with age > 75 years and high risk of sudden cardiac death: a cohort study : Physical activity and patients over 75 years old.

BACKGROUND: To study the relationship between objective daily physical activity (PA), as measured by implantable cardioverter defibrillators (ICDs)/cardiac resynchronization therapy defibrillators (CRTDs), and long-term prognoses in patients with age > 75 years at high risk of sudden cardiac death (SCD). METHODS: In total, 133 patients with age > 75 years old (age 79.52 ± 3.68 years) in the SUMMIT study were retrospectively analysed. The major endpoint was all-cause mortality, and the minor endpoint was cardiac death. RESULTS: The mean follow-up time was 57.1 ± 24.2 months (range: from 4 to 96 months). In total, 46 all-cause mortality and 23 cardiac death events occurred. The receiver operating characteristic curve indicated a baseline PA cut-off value of 6.47% (93 min/day) can predict all-cause mortality in patients with age > 75 years, with an area under the curve of 0.670 (95% confidence interval (CI): 0.573-0.767, P = 0.001). The sensitivity was 67.4%, and the specificity was 66.7%. Patients with baseline PA ≤ 6.47% had higher rates of all-cause mortality (51.7% vs 20.5%, P < 0.001) and cardiac death (25.0% vs 11.0%, P = 0.040). The estimated Kaplan-Meier survival curves showed that patients with PA ≤ 6.47% had an increased cumulative incidence of all-cause mortality (Log-rank P < 0.0001) and cardiac death (Log-rank P = 0.0067). Multivariate Cox regression analysis showed that PA ≤ 6.47% was an independent predictor of all-cause mortality (hazard ratio (HR) 3.137, 95% CI: 1.667-5.904, P < 0.001) and cardiac death (HR value 3.345, 95% CI: 1.394-8.028, P = 0.007). CONCLUSIONS: Daily PA of about 1.5 h was associated with lower all-cause mortality and cardiac death risk in patients with age > 75 years and high risk of SCD with ICDs/CRTDs. PA monitoring may aid in long-term management of older patients at high risk of SCD.