Short-term antiplatelet versus anticoagulant therapy after left atrial appendage closure: a systematic review and meta-analysis.

This meta-analysis compared the efficacy and safety of different antithrombotic regimens after left atrial appendage closure (LAAC). PubMed, Embase, Medline, Cochrane Library databases were systematically searched from their inception to March 2023. Patients were divided into short-term oral anticoagulation (OAC) group and antiplatelet therapy (APT) group. The incidence of events were performed using RevMan 5.4. The events including device-related thrombus (DRT), ischemic stroke/systemic embolization (SE), major bleeding, any bleeding, any major adverse event and all-cause mortality. Subgroup analysis were based on OAC alone or OAC plus single antiplatelet therapy (SAPT) in OAC group. Oral anticoagulants include warfarin and direct oral anticoagulant (DOAC). Fourteen studies with 35,166 patients were included. We found that the incidence of DRT (OR = 0.49, 95% CI 0.36-0.66, P＜0.0001) and all-cause mortality (OR = 0.71, 95% CI 0.57-0.89, P = 0.002) were significantly lower in OAC group than APT group. However, there was no statistical differences in the incidence rates of ischemic stroke/SE (OR = 0.77, 95% CI 0.49-1.20, P = 0.25), major bleeding (OR = 0.84, 95% CI 0.55-1.27, P = 0.84), any bleeding (OR = 0.83, 95% CI 0.56-1.22, P = 0.34) and any major adverse event (OR = 0.56, 95% CI 0.30-1.03, P = 0.06) in the two groups. Subgroup analysis found that the incidence of DRT, all-cause mortality and any major adverse event in OAC monotherapy were lower than that in APT group (P＜0.05), but not statistically different from other outcome. The incidence of DRT, all-cause mortality, any major adverse event and any bleeding in DOAC were significantly better than APT group (P＜0.05). While warfarin only has better incidence of DRT than APT (P＜0.05), there was no statistical difference between the two groups in other outcome (P＞0.05). The incidence of DRT was significantly lower than APT group (P＜0.05), major bleeding were higher, and the rest of the outcome did not show any statistically significant differences(P＞0.05) when OAC plus SAPT. Based on the existing data, short-term OAC may be favored over APT for patients who undergo LAAC. DOAC monotherapy may be favored over warfarin monotherapy or OAC plus APT, when selecting anticoagulant therapies.

Global Research Hotspots in Venous Thromboembolism Anticoagulation: A Knowledge-Map Analysis from 2012 to 2021.

Background: Venous thromboembolism (VTE) is a common cardiovascular disease that seriously threatens human lives. Anticoagulant therapy is considered to be the cornerstone of VTE treatment. An increasing number of studies has been updated in the VTE anticoagulation field. However, no bibliometric analyses have assessed these publications comprehensively. Therefore, our study aimed to analyze the global status, hotspots, and trends of anticoagulant therapy for VTE. Methods: The relevant literature on VTE anticoagulation published between 2012 and 2021 was retrieved and collected from the Web of Science Core Collection database. VOSviewer, Cooccurrence Matrix Builder, gCLUTO, and some online visualization tools were adopted for bibliometric analysis. Results: A total of 15,152 related articles were retrieved. In recent years, the research output of VTE anticoagulation gradually increased. The United States was the most productive country. International cooperation is concentrated in North America and Europe; the most influential documents, journals, authors, and organizations were also from these two continents. Research hotspots mainly focus on clinical guidelines, VTE in special populations, non-vitamin K oral anticoagulants (NOACs), and parenteral anticoagulation. The research frontiers and trends include the assessment of NOACs and the antithrombotic management of VTE complicated with coronavirus disease 2019 (COVID-19). Conclusion: This bibliometric analysis provides a systematic overview of the VTE anticoagulation research, which will facilitate researchers to better understand the situation of VTE anticoagulation. Future studies should be dedicated to NOACs application and VTE-combined COVID-19 patients.

Clinical comprehensive evaluation of direct oral anticoagulants for patients with atrial fibrillation in China.

BACKGROUND: Direct oral anticoagulants (DOACs) are increasingly recommended over warfarin in stroke prevention for patients with non-valvular atrial fibrillation (AF). However, there is an important evidence gap in choosing the most appropriate DOAC for Chinese patients in clinical practice. METHODS: A multi-criteria decision analysis (MCDA) was adopted to build a scoring framework. Attributes and criteria were identified and determined by a scoping literature review, two rounds of Delphi surveys, and a consensus meeting. Weights of each attribute and criterion in the framework were determined using analytic hierarchy process (AHP). Evidence was collected based on the domestic or at least Asian data. Scoring methods for each criterion were developed depended on their characteristics and determined with an expert consensus meeting. Comprehensive scores of each DOAC were calculated based on the utility scores of each criterion and their corresponding weights. RESULTS: A total of 5 attributes, including safety, efficacy, costs/cost-effectiveness, suitability, and accessibility, were determined, and 16 criteria were under the 5 attributes. The safety and efficacy were ranked as the top two important attributes with the weights of 38.8% and 35.9%, respectively, while the suitability received the lowest weight of 7.9%. The comprehensive score for edoxaban was the highest (72.3), followed by dabigatran (49.7), rivaroxaban (37.9), and apixaban (35.8). CONCLUSIONS: This study provided a scoring framework developed for comprehensive evaluation of DOACs in China. The ranking of DOACs could help to support the decision-making in clinical practice. The framework could provide a reference for comprehensive evaluation of other drugs.

Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) do not Increase the Risk of Hepatic Impairment in Patients with Non-Valvular Atrial Fibrillation: Insights from Multi-Source Medical Data.

BACKGROUND: There is controversy over whether non-vitamin K antagonist oral anticoagulants (NOACs) use increase the risk of hepatic impairment in patients with non-valvular atrial fibrillation (NVAF). We conducted a comprehensive assessment using multi-source medical data. METHODS: We first performed a systematic search of the PubMed, Embase, and Cochrane Library databases (through 11 August 2021) for randomised controlled trials (RCTs) and real-world studies (RWSs) that reported hepatic impairment events in patients with NVAF administered NOACs or vitamin K antagonists (VKAs) therapy. The primary outcomes were hepatic impairment identified by diagnostic liver injury (DLI) or abnormal liver enzyme (ALE). The secondary outcome was hepatic failure. Relative risks (RRs) for RCTs and adjusted hazard ratios (aHRs) for RWSs were calculated separately using random-effects models. We also conducted a disproportionality analysis by extracting reports of hepatic impairment associated with NOACs from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Reporting odds ratios (RORs) were calculated to identify the statistical associations between NOACs and hepatic impairment. Scenario analyses were further performed to eliminate event- and drug-related competition bias. RESULTS: A total of 559,873 patients from five RCTs and four RWSs were included in the pooled analysis. For RCTs, NOACs use was not associated with an increased risk of DLI (RR: 0.96, 95% confidence intervals (CI): 0.73-1.28) or ALE (RR: 0.91, 95% CI: 0.69-1.19) compared with VKAs. The merged results of RWSs also showed a similar risk of DLI (aHR: 0.88, 95% CI: 0.72-1.09) or ALE (aHR: 0.91, 95% CI: 0.82-1.00) between NOACs and VKAs. The results of hepatic failure were in accordance with the primacy outcomes. Analyses of individual NOACs did not significantly affect the results. Insights from the FAERS database failed to detect hepatic impairment signals for overall NOACs agents (ROR: 0.34, 95% CI: 0.32-0.37). Scenario analyses confirmed the primary results. CONCLUSIONS: Insights from multi-source medical data confirmed that NOACs use was not associated with an increased risk of hepatic impairment in patients with NVAF.

An Adapted Neural-Fuzzy Inference System Model Using Preprocessed Balance Data to Improve the Predictive Accuracy of Warfarin Maintenance Dosing in Patients After Heart Valve Replacement.

BACKGROUND: Tailoring warfarin use poses a challenge for physicians and pharmacists due to its narrow therapeutic window and substantial inter-individual variability. This study aimed to create an adapted neural-fuzzy inference system (ANFIS) model using preprocessed balance data to improve the predictive accuracy of warfarin maintenance dosing in Chinese patients undergoing heart valve replacement (HVR). METHODS: This retrospective study enrolled patients who underwent HVR between June 1, 2012, and June 1, 2016, from 35 centers in China. The primary outcomes were the mean difference between predicted warfarin dose by ANFIS models and actual dose and the models' predictive accuracy, including the ideal predicted percentage, the mean absolute error (MAE), and the mean squared error (MSE). The eligible cases were divided into training, internal validation, and external validation groups. We explored input variables by univariate analysis of a general linear model and created two ANFIS models using imbalanced and balanced training sets. We finally compared the primary outcomes between the imbalanced and balanced ANFIS models in both internal and external validation sets. Stratified analyses were conducted across warfarin doses (low, medium, and high doses). RESULTS: A total of 15,108 patients were included and grouped as follows: 12,086 in the imbalanced training set; 2820 in the balanced training set; 1511 in the internal validation set; and 1511 in the external validation set. Eight variables were explored as predictors related to warfarin maintenance doses, and imbalanced and balanced ANFIS models with multi-fuzzy rules were developed. The results showed a low mean difference between predicted and actual doses (< 0.3 mg/d for each model) and an accurate prediction property in both the imbalanced model (ideal prediction percentage, 74.39-78.16%; MAE, 0.37 mg/daily; MSE, 0.39 mg/daily) and the balanced model (ideal prediction percentage, 73.46-75.31%; MAE, 0.42 mg/daily; MSE, 0.43 mg/daily). Compared to the imbalanced model, the balanced model had a significantly higher prediction accuracy in the low-dose (14.46% vs. 3.01%; P < 0.001) and the high-dose warfarin groups (34.71% vs. 23.14%; P = 0.047). The results from the external validation cohort confirmed this finding. CONCLUSIONS: The ANFIS model can accurately predict the warfarin maintenance dose in patients after HVR. Through data preprocessing, the balanced model contributed to improved prediction ability in the low- and high-dose warfarin groups.

Feasibility and usability of a mobile health tool on anticoagulation management for patients with atrial fibrillation: a pilot study.

PURPOSE: Appropriate prescription of oral anticoagulants (OACs) and good patient adherence are essential to ensure optimal anticoagulation in patients with atrial fibrillation (AF). The aim of this study is to develop a mobile health tool to aid both clinicians and patients with AF in anticoagulation therapy. METHODS: In this study, a novel anticoagulation management model integrating decision support and patient follow-up, the I-Anticoagulation, was developed based on a WeChat Mini Program. With this tool, the risks of stroke and bleeding in AF patients can automatically be calculated according to their characteristics. Anticoagulation regimens were recommended based on a trade-off analysis that balances stroke and bleeding risks according to recent clinical guidelines. A shared decision can be made with full communication between medical professionals and patients. Moreover, follow-up was also conducted using I-Anticoagulation. RESULTS: A total of 120 AF patients receiving anticoagulants (40 received warfarin and 80 received non-vitamin K antagonist oral anticoagulants [NOACs]) were included in the pilot study. The incidence of thromboembolic events was 2.5% and 1.3%, and the rates of bleeding events were 22.5% and 13.8% in the warfarin and NOAC groups, respectively. Generally, self-reported adherence was high, and the satisfaction with anticoagulation was good in all patients with AF. CONCLUSION: Overall, the anticoagulation management model developed in this study could be involved in the full process of anticoagulation therapy in AF patients to improve rationality, adherence, and satisfaction in both medical professionals and patients. However, the usability, feasibility, and acceptability of the I-Anticoagulant-based anticoagulation management model need to be further assessed through well-designed random clinical trials.

Simulation of anticoagulation in atrial fibrillation patients with rivaroxaban-from trial to target population.

The populations included in the randomized controlled clinical trials and observational studies were different. The effectiveness and safety of rivaroxaban for stroke prevention in patients with atrial fibrillation (AF) varied among studies. This study aimed to estimate the real-world outcomes of rivaroxaban in patients with AF accurately. A discrete event simulation (DES) was used to predict the counterfactual results of the ROCKET AF study. The hypothetical cohorts of patients were generated using Monte Carlo simulation according to the baseline covariate distributions that matched the marginal distribution of covariates reported in the ROCKET AF and three observational studies. The DES model structure was constructed based on a priori knowledge about disease progression and possible outcomes of patients with AF. The DES model accurately replicated the overall results of the ROCKET AF study. Both predicted stroke/systematic embolism (SE) and major bleeding rates were lower in the three observational studies than in the simulated ROCKET AF study. The risk difference of stroke/SE and major bleeding was not significant among the predicted outcomes of the three observational studies. Although some differences existed in the absolute rates of stroke/SE and major bleeding between observed and simulated studies, the results confirmed that rivaroxaban was noninferior to warfarin for the prevention of stroke/systematic embolism with no significance in the risk of major bleeding in large AF populations, which was similar to the results of ROCKET AF.

High-dose sodium-glucose co-transporter-2 inhibitors are superior in type 2 diabetes: A meta-analysis of randomized clinical trials.

AIM: To determine the overall efficacy of high- versus low-dose sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D). MATERIAL AND METHODS: A literature search using MEDLINE, EMBASE and the Cochrane Library was performed from 1 January 2006 to 23 September 2020. Random effects models were used to calculate mean differences (MDs) and pooled relative risk (RR). Prespecified subgroup analyses for each SGLT2 inhibitor, follow-up and controls were performed. Leave-one-out sensitivity and meta-regression analyses were conducted. RESULTS: A total of 51 randomized controlled trials involving 23 989 participants (weighted mean age, 58.9 years; men, 58.8%) were eligible for our meta-analysis. For glycaemic regulation ability, a significant reduction in HbA1c (MD -0.080%, 95% confidence interval [CI] -0.100 to -0.060), fasting plasma glucose (MD -0.227 mmol/L, 95% CI -0.282 to -0.173) and postprandial plasma glucose (MD -0.834 mmol/L, 95% CI -1.268 to -0.400) levels was observed in the high-dose SGLT2 inhibitor group. Treatment with high-dose SGLT2 inhibitors enabled easier achievement of the target (HbA1c <7%) than low-dose SGLT2 inhibitors (RR 1.148, 95% CI 1.104 to 1.193). High-dose SGLT2 inhibitor-based treatment resulted in more efficient regulation of body weight and blood pressure (body weight: MD -0.346 kg, 95% CI -0.437 to -0.254; systolic blood pressure: MD -0.583 mmHg, 95% CI -0.903 to -0.263; diastolic blood pressure: MD -0.352 mmHg, 95% CI -0.563 to -0.142). The results were similar in sensitivity analyses. CONCLUSIONS: The overall efficacy of SGLT2 inhibitors, mainly canagliflozin, dapagliflozin and empagliflozin, was found to be dose dependent.

Risk of Major Gastrointestinal Bleeding With New vs Conventional Oral Anticoagulants: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: There is controversy over whether use of non-vitamin K antagonist oral anticoagulants (NOACs) associates with increased risk of major gastrointestinal bleeding (GIB) compared with conventional therapies (such as vitamin K antagonists or anti-platelet agents). We performed a systematic review and meta-analysis of data from randomized controlled trials and high-quality real-world studies. METHODS: We performed a systematic search of the MEDLINE, EMBASE, Cochrane Library, and ClinicalTrials.gov Website databases (through Oct 12, 2018) for randomized controlled trials and high-quality real-world studies that reported major GIB events in patients given NOACs or conventional therapy. Relative risks (RRs) for randomized controlled trials and adjusted hazard ratios (aHRs) for real-world studies were calculated separately using random-effects models. RESULTS: We analyzed data from 43 randomized controlled trials (183,752 patients) and 41 real-world studies (1,879,428 patients). The pooled major rates of GIB for patients on NOACs (1.19%) vs conventional treatment (0.92%) did not differ significantly (RR from randomized controlled trials, 1.09; 95% CI, 0.91-1.31 and aHR from real-world studies, 1.02; 95% CI, 0.94-1.10; Pinteraction=.52). Rivaroxaban, but not other NOACs, was associated with an increased risk for major GIB (RR from randomized controlled trials, 1.39; 95% CI, 1.17-1.65 and aHR from real-world studies, 1.14; 95% CI, 1.04-1.23; Pinteraction = .06). Analyses of subgroups, such as patients with different indications, dosage, or follow-up time, did not significantly affect results. Meta-regression analysis failed to detect any potential confounding to impact the primacy outcome. CONCLUSIONS: In a systematic review and meta-analysis of data from randomized controlled trials and real-world studies, we confirmed that there is no significant difference in risk of major GIB between patients receiving NOACs vs conventional treatment. Rivaroxaban users had a 39% increase in risk for major GIB.

Efficacy and safety of current therapeutic options for COVID-19 - lessons to be learnt from SARS and MERS epidemic: A systematic review and meta-analysis.

The rapidly progressing of coronavirus disease 2019 (COVID-19) pandemic has become a global concern. This meta-analysis aimed at evaluating the efficacy and safety of current option of therapies for severe acute respiratory syndrome (SARS), Middle Eastern respiratory syndrome (MERS) besides COVID-19, in an attempt to identify promising therapy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. We searched PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and WANFANG DATA for randomized controlled trials (RCTs), prospective cohort, and retrospective cohort studies that evaluated therapies (hydroxychloroquine, lopinavir/ritonavir-based therapy, and ribavirin-based therapy, etc.) for SARS, MERS, and COVID-19. The primary outcomes were mortality, virological eradication and clinical improvement, and secondary outcomes were improvement of symptoms and chest radiography results, incidence of acute respiratory disease syndrome (ARDS), utilization of mechanical ventilation, and adverse events (AEs). Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effects models, and the quality of evidence was appraised using GRADEpro. Eighteen articles (5 RCTs, 2 prospective cohort studies, and 11 retrospective cohort studies) involving 4,941 patients were included. Compared with control treatment, anti-coronary virus interventions significantly reduced mortality (RR 0.65, 95% CI 0.44-0.96; I2 = 81.3%), remarkably ameliorate clinical improvement (RR 1.52, 95% CI 1.05-2.19) and radiographical improvement (RR 1.62, 95% CI 1.11-2.36, I2 = 11.0 %), without manifesting clear effect on virological eradication, incidence of ARDS, intubation, and AEs. Subgroup analyses demonstrated that the combination of ribavirin and corticosteroids remarkably decreased mortality (RR 0.43, 95% CI 0.27-0.68). The lopinavir/ritonavir-based combination showed superior virological eradication and radiographical improvement with reduced rate of ARDS. Likewise, hydroxychloroquine improved radiographical result. For safety, ribavirin could induce more bradycardia, anemia and transaminitis. Meanwhile, hydroxychloroquine could increase AEs rate especially diarrhea. Overall, the quality of evidence on most outcomes were very low. In conclusion, although we could not draw a clear conclusion for the recommendation of potential therapies for COVID-19 considering the very low quality of evidence and wide heterogeneity of interventions and indications, our results may help clinicians to comprehensively understand the advantages and drawbacks of each anti-coronavirus agents on efficacy and safety profiles. Lopinavir/ritonavir combinations might observe better virological eradication capability than other anti-coronavirus agents. Conversely, ribavirin might cause more safety concerns especially bradycardia. Thus, large RCTs objectively assessing the efficacy of antiviral therapies for SARS-CoV-2 infections should be conducted with high priority.

Marine sponge-derived alkaloid ameliorates DSS-induced IBD via inhibiting IL-6 expression through modulating JAK2-STAT3-SOCS3 pathway.

Cyanogramide (AC14), a novel alkaloid, isolated from the fermentation broth of the marine-derived Actinoalloteichus cyanogriseus. However, the exact role of AC14 in inflammatory bowel disease (IBD) is poorly understood. Our results demonstrated that AC14 exhibited significant inhibition of IL-6 release in THP-1 cells and a "Caco-2/THP-1" coculture system after stimulation with LPS for 24 h. However, no significant effect on TNF-α production was observed. Furthermore, in 2.5 % DSS-induced colitis mice, AC14 treatment led to improvement in body weight, colon length, and intestine mucosal barrier integrity. AC14 also suppressed serum IL-6 production and modulated dysregulated microbiota in the mice. Mechanistically, AC14 was found to inhibit the phosphorylation of Janus kinase (JAK) 2 and signal transducers and activators of transcription (STAT) 3, while simultaneously elevating the expression of suppressor of cytokine signaling (SOCS) 3, both in vivo and in vitro. These findings suggest that AC14 exerts its suppressive effects on IL-6 production in DSS-induced IBD mice through the JAK2-STAT3-SOCS3 signaling pathway. Our study highlights the potential of AC14 as a therapeutic agent for the treatment of IBD.

A novel machine learning model to predict high on-treatment platelet reactivity on clopidogrel in Asian patients after percutaneous coronary intervention.

BACKGROUND: Various genetic and nongenetic variables influence the high on-treatment platelet reactivity (HTPR) in patients taking clopidogrel. AIM: This study aimed to develop a novel machine learning (ML) model to predict HTPR in Chinese patients after percutaneous coronary intervention (PCI). METHOD: This cohort study collected information on 507 patients taking clopidogrel. Data were randomly divided into a training set (90%) and a testing set (10%). Nine candidate Machine learning (ML) models and multiple logistic regression (LR) analysis were developed on the training set. Their performance was assessed according to the area under the receiver operating characteristic curve, precision, recall, F1 score, and accuracy on the test set. Model interpretations were generated using importance scores by transforming model variables into scaled features and representing in radar plots. Finally, we established a prediction platform for the prediction of HTPR. RESULTS: A total of 461 patients (HTPR rate: 19.52%) were enrolled in building the prediction model for HTPR. The XGBoost model had an optimized performance, with an AUC of 0.82, a precision of 0.80, a recall of 0.44, an F1 score of 0.57, and an accuracy of 0.87, which was superior to those of LR. Furthermore, the XGBoost method identified 7 main predictive variables. To facilitate the application of the model, we established an XGBoost prediction platform consisting of 7 variables and all variables for the HTPR prediction. CONCLUSION: A ML-based approach, such as XGBoost, showed optimum performance and might help predict HTPR on clopidogrel after PCI and guide clinical decision-making. Further validated studies will strengthen this finding.

A new simplified risk assessment model enhances postoperative prophylaxis of venous thromboembolism in Chinese adult patients with inguinal hernia (CHAT-3): A prospective, multicenter, randomized controlled trial.

BACKGROUND: Venous thromboembolism (VTE) significantly affects the prognosis of surgical patients with inguinal hernia. The complex Caprini score, commonly used for postoperative VTE risk assessment, poses practical challenges for surgeons in clinical settings. METHODS: The CHAT-3 trial, a prospective, multicenter, randomized controlled trial, compared a simple three-factor model to assess VTE risk against routine practices in post-inguinal hernia surgery (IHS) patients. The patients were randomly assigned (1:1) to the intervention or control arm. The intervention group used the three-factor model to identify patients at moderate or high risk of VTE for subsequent prophylaxis according to clinical guidelines. Both groups were followed for four weeks, with randomization implemented using computer-generated sequences. The primary outcome measured was the rate of VTE prophylaxis. Secondary outcomes included time spent on VTE risk assessment (surgeon self-reported), postoperative D-dimer trends, perioperative VTE occurrence, bleeding events, and the net clinical benefit. RESULTS: Of the 1,109 participants, 508 in the experimental group and 601 in the control group completed follow-up. The three-factor model showed higher VTE prophylaxis rates in all patients (pharmacologic prophylaxis: 26.2% vs. 6.00%, P<0.001) and particularly in those at high risk (pharmacologic prophylaxis: 57.3% vs. 9.50%, P<0.001). The experimental group significantly reduced VTE risk assessment time compared to the Caprini score (1.39±0.55 min vs. 5.73±1.35 min, P<0.001). The experimental group had lower D-dimer levels (0.26±0.73 mg/L vs. 0.35±0.55 mg/L, P=0.028). In the experimental group, the patients did not experience an increased risk of VTE (0% vs. 1.66%, P=0.268) and bleeding (1.18% vs. 0.67%, P=0.558) compared to the controls. There was no significant difference in net clinical benefit, which combined VTE and bleeding events, between the experimental and control groups (1.18% vs. 0.83%, P=0.559). CONCLUSION: Applying the simple three-factor model in perioperative VTE management could quickly identify the patient with a high risk of VTE and improve the prophylaxis rate of perioperative VTE. TRIAL REGISTRATION: XXX. TRIAL REGISTRATION: ChiCTR2000033769.

Enhancing thromboprophylaxis after colorectal cancer surgery in China: Bridging the gap between evidence and implementation through pathway optimization.

BACKGROUND: The CRC-VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices. METHODS: This study performed an analysis of the CRC-VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery. The primary objective was to identify independent risk factors for VTE after CRC surgery using multivariate logistic regression analysis. Furthermore, among the cases in which VTE occurred, the appropriateness of thromboprophylaxis was assessed based on several factors, including pharmacologic prophylaxis, time to initiate prophylaxis, drug selection, drug dosage, and duration of pharmacologic prophylaxis. Based on the analysis of the current state of thromboprophylaxis and relevant clinical guidelines, a modified Delphi method was used to develop a clinical pathway for VTE prophylaxis after CRC surgery. RESULTS: In this analysis of 1836 patients, 205 (11.2%) were diagnosed with VTE during follow-up. The multifactorial analysis identified several independent risk factors for VTE, including age (≥70 years), female sex, varicose veins in the lower extremities, intraoperative blood transfusion, and the duration of immobilization exceeding 24 h. None of the patients diagnosed with VTE in the CRC trial received adequate thromboprophylaxis. The main reasons for this inappropriate practice were the omission of thromboprophylaxis, delayed initiation, and insufficient duration of thromboprophylaxis. We developed a specialized clinical pathway for thromboprophylaxis after CRC surgery to address these issues. CONCLUSIONS: This study offers a comprehensive nationwide evaluation of existing thromboprophylaxis practices in patients after CRC surgery in China. A specialized clinical pathway was developed to address the identified gaps and improve the quality of care. This clinical pathway incorporates explicit, tailored, detailed recommendations for thromboprophylaxis after CRC surgery.

Adherence to endocrine therapy in patients with hormone receptor-positive early-stage breast cancer: a retrospective study.

BACKGROUND: The persistence and adherence to endocrine therapy (ET) in hormone receptor-positive (HR +) breast cancer patients remain far less than optimal. AIM: This retrospective study aimed to evaluate adherence to ET and to identify influencing factors in early-stage HR + breast cancer patients. METHOD: A stratified random sampling method was used to select patients admitted for breast cancer surgery at a university hospital in Shanghai, China. Patients who received ET medications in the hospital information system (HIS) were included. The primary outcomes were early discontinuation of and adherence to ET. Potential factors influencing the discontinuation and adherence were assessed using univariate and multivariate logistic regression analyses. RESULTS: In total, 706 patients were included, and 161 (22.8%) discontinued ET in less than five years from the first prescription. The discontinuation rates from the one-year to the five-year treatment were 5.38, 16.70, 32.27, 51.52, and 50.00%, respectively (P < 0.001). The rates of adherence (defined as medication possession ratio ≥ 80%) from the first to the fifth year were 85.18, 82.25, 82.18, 72.92, and 73.68%, respectively (P = 0.18). Age, insurance, and surgery type impacted ET discontinuation and adherence. However, the type of medication only impacted the adherence to ET. CONCLUSION: Persistence and adherence to ET in patients with breast cancer remain far from optimal and decrease over time. More attention should be paid to patients aged ≥ 70 years and those without insurance who tend to have early discontinuation of ET.

The Importance of Clinical Pharmacists in Improving Blood Glucose and Lipid Levels in Patients with Diabetes and Myocardial Infarction.

Purpose: The aim of this study was to evaluate whether intervention by clinical pharmacists can improve blood glucose and lipid levels in diabetic patients with complex medical conditions. Methods: The retrospective database included 138 patients with diabetes who had presented with acute myocardial infarction (AMI) between January 2019 and October 2021. Blood glucose and lipid levels were measured within 12 weeks and 78 weeks of follow-up. Propensity score matching (PSM) was used to balance the confounding effects of patients' characteristics. Results: A total of 138 eligible patients were assigned to either the intervention group (n = 47) or the usual care group (n = 91). After the intervention, there were significant improvements in blood glucose (glycosylated hemoglobin-HbA1C % from 9.0 to 8.3; fasting blood glucose-FBG mmol/L from 11.3 to 7.1; postprandial blood glucose-PBG mmol/L from 17.0 to 12.1; p < 0.001) and lipid levels (total cholesterol-TC from 4.9 to 3.5, low-density lipoprotein cholesterol-LDL-C from 3.0 to 1.8, p < 0.001, mmol/L) in both follow-up periods. The blood glucose effects were most pronounced in the PBG control rate (76.9% vs 54.0%) before PSM, while HbA1C% and PBG control rate after PSM were significantly higher in the intervention group (HbA1C% rate: 65.6% vs 38.5%; PBG rate: 79.2% vs 45.8%; p < 0.05, intervention vs non-intervention). Subgroup analysis further confirmed the improvement of blood glucose and lipid mainly in patients with higher baseline FBG (≧10mmol/L) and moderate follow-up duration (4-12 weeks). Conclusion: The intervention of clinical pharmacists in multidisciplinary team can significantly improve blood glucose and lipid levels in complex type 2 diabetic patients, especially those with high baseline FBG and moderate follow-up durations.

An Updated Pooled Analysis of Off-Label Under and Over-Dosed Direct Oral Anticoagulants in Patients with Atrial Fibrillation.

INTRODUCTION: Off-label, under-, and overdosed direct oral anticoagulants (DOACs) are commonly prescribed to patients with atrial fibrillation (AF), but real-world evidence on their effectiveness and safety is limited. METHODS: MEDLINE, Embase, and Cochrane Library databases were systematically searched from 01 July 2020 to 28 February 2022 to update a previous systematic review with the same search strategy from the inception to 30 June 2020. Eligible studies were those that reported effectiveness (stroke/systemic embolism and myocardial infarction) or safety (gastrointestinal or major bleeding and death) outcomes of off-label doses of DOACs compared to on-label doses in AF patients. A random-effects meta-analysis was performed to estimate the pooled hazard ratio (HR) and 95% confidence interval (CI). Subgroup analyses were performed by specific DOACs and geographic regions. RESULTS: Twenty-two studies were included. Off-label, underdosed DOACs, compared to on-label doses, were not associated with an increased risk of stroke (HR 1.03, 95%CI: 0.88-1.17) but were associated with an increased risk of death (HR 1.26, 95%CI: 1.09-1.43). However, risk varied depending on the active ingredient. No other safety outcomes were associated with underdosed DOACs. No significant differences were observed by geographic regions. Compared to on-label DOACs, overdosing increased the risk of stroke (HR 1.17, 95%CI: 1.04-1.31), major bleeding (HR 1.18, 95%CI: 1.05-1.31), and death (HR 1.19, 95%CI: 1.03-1.35). Risk varied between geographical regions. CONCLUSIONS: Off-label underdoses, compared to on-label dosing of DOACs, did not increase the risk of stroke but did increase overall mortality. Overdosed DOACs, compared to on-label doses, were associated with an increased risk of stroke, major bleeding, and death. Future studies must examine these associations, focusing on specific active ingredients and geographic settings.

A novel shared decision-making (SDM) tool for anticoagulation management in atrial fibrillation: protocol for a prospective, cluster randomized controlled trial.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia that requires anticoagulation therapy to prevent stroke. However, there is still a significant under-/over-treatment in stroke prevention for patients with AF. The adherence and the risk of bleeding associated with oral anticoagulation therapy (OACs) are major concerns. Shared decision-making (SDM) is an approach that involves patients and healthcare providers in making decisions about treatment options. This study aims to assess the effectiveness of a novel SDM tool for anticoagulation management in AF. METHODS: The study will be a prospective, cluster randomized controlled trial involving 440 patients with AF in 8 community health service centers (clusters) in Shanghai, China. The SDM group will receive anticoagulation management through the novel SDM tool, while the control group will receive standard care. The follow-up period will be at least 2 years. The primary outcome will be any bleeding event, while secondary outcomes include the accordance of stroke prophylaxis for AF according to the current guidelines, time in therapeutic range (TTR), the occurrences of major bleeding and thrombosis events, and patient knowledge, adherence, and satisfaction. DISCUSSION: This study will provide evidence of the effectiveness of shared decision-making in improving the appropriateness of OAC use in Chinese AF patients. The findings may inform the development of guidelines and policies for the management of AF and anticoagulation therapy in China and other countries. TRIAL REGISTRATION: ChiCTR ChiCTR2200062123. Registered on 23 July 2022.

Short-term antithrombotic strategies after left atrial appendage occlusion: a systematic review and network meta-analysis.

Background: Percutaneous left atrial appendage occlusion (LAAO) has emerged as a stroke prevention strategy in patients with nonvalvular atrial fibrillation (NVAF), and these patients were required to receive antithrombotic therapy post-procedure. However, the optimal antithrombotic strategy after LAAO remains controversial. This study explored the safety and efficacy of different antithrombotic strategies after LAAO through a network comparison method. Methods: We systematically searched the MEDLINE, Embase, and Cochrane Library databases for studies that reported the interested efficacy and safety outcomes (stroke, device-related thrombus (DRT), and major bleeding) of different antithrombotic strategies [DAPT (dual antiplatelet therapy), DOACs (direct oral anticoagulants), and VKA (vitamin k antagonist)] in patients who had experienced LAAO. Pairwise comparisons and network meta-analysis were performed for the interested outcomes. Risk ratios (RRs) with their confidence intervals (CIs) were calculated using a random-effects model. The rank of the different strategies was calculated using the surface under the cumulative ranking curve (SUCRA). Results: Finally, 10 observational studies involving 1,674 patients were included. There was no significant difference in stroke, DRT, and major bleeding among the different antithrombotic strategies (DAPT, DOACs, and VKA). Furthermore, DAPT ranked the worst in terms of stroke (SUCRA: 19.8%), DRT (SUCRA: 3.6%), and major bleeding (SUCRA: 6.6%). VKA appeared to be superior to DOACs in terms of stroke (SUCRA: 74.9% vs. 55.3%) and DRT (SUCRA: 82.3% vs. 64.1%) while being slightly inferior to DOACs in terms of major bleeding (SUCRA: 71.0% vs. 72.4%). Conclusion: No significant difference was found among patients receiving DAPT, DOACs, and VKA in terms of stroke, DRT, and major bleeding events after LAAO. The SUCRA indicated that DAPT was ranked the worst among all antithrombotic strategies due to the higher risk of stroke, DRT, and major bleeding events, while VKAs were ranked the preferred antithrombotic strategy. However, DOACs are worthy of consideration due to their advantage of convenience.

Machine Learning to Dynamically Predict In-Hospital Venous Thromboembolism After Inguinal Hernia Surgery: Results From the CHAT-1 Study.

BACKGROUND: The accuracy of current prediction tools for venous thromboembolism (VTE) events following hernia surgery remains insufficient for individualized patient management strategies. To address this issue, we have developed a machine learning (ML)-based model to dynamically predict in-hospital VTE in Chinese patients after hernia surgery. METHODS: ML models for the prediction of postoperative VTE were trained on a cohort of 11 305 adult patients with hernia from the CHAT-1 trial, which included patients across 58 institutions in China. In data processing, data imputation was conducted using random forest (RF) algorithm, and balanced sampling was done by adaptive synthetic sampling algorithm. Data were split into a training cohort (80%) and internal validation cohort (20%) prior to oversampling. Clinical features available pre-operatively and postoperatively were separately selected using the Sequence Forward Selection algorithm. Nine-candidate ML models were applied to the pre-operative and combined datasets, and their performance was evaluated using various metrics, including area under the receiver operating characteristic curve (AUROC). Model interpretations were generated using importance scores, which were calculated by transforming model features into scaled variables and representing them in radar plots. RESULTS: The modeling cohort included 2856 patients, divided into 2536 cases for derivation and 320 cases for validation. Eleven pre-operative variables and 15 combined variables were explored as predictors related to in-hospital VTE. Acceptable-performing models for pre-operative data had an AUROC ≥ 0.60, including logistic regression, support vector machine with linear kernel (SVM_Linear), attentive interpretable Tabular learning (TabNet), and RF. For combined data, logistic regression, SVM_Linear, and TabNet had better performance, with an AUROC ≥ 0.65 for each model. Based on these models, 7 pre-operative predictors and 10 combined predictors were depicted in radar plots. CONCLUSIONS: A ML-based approach for the identification of in-hospital VTE events after hernia surgery is feasible. TabNet showed acceptable performance, and might be useful to guide clinical decision making and VTE prevention. Further validated study will strengthen this finding.