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.

Safety and hematological toxicities of PARP inhibitors in patients with cancer: a systematic review of randomized controlled trials and a pharmacovigilance analysis.

INTRODUCTION: This study aimed to estimate the toxicities of PARP inhibitors (PARPis), based on randomized controlled trials (RCTs) and the FDA Adverse Event Reporting System (FAERS) database. METHODS: Four electronic databases were searched from inception to 16 April 2024, for RCTs of approved PARPis. The primary and secondary outcomes were grade 3-5 adverse events (AEs) and grade 3-5 hematological AE, respectively. We conducted network meta-analyses to calculate the relative risks (RRs) and 95% confidence intervals (CIs) of outcomes. A disproportionality analysis was conducted to estimate the signals of hematological AEs associated with PARPis from the FAERS database. RESULTS: Overall, 27 RCTs involving 11,067 patients with cancer were included. Olaparib had the best safety profile for any grade 3-5 AEs and hematological AEs among four approved PARPis. Olaparib did not increase the risk of thrombocytopenia (RR: 1.48; 95%CI: 0.64-3.39), but other PARPis did. Furthermore 14,780 hematological AE reports associated with PARPis were identified in the FAERS database, and all PARPis were associated with strong hematological AE signals. Hematological AEs mainly occurred within the first 3 months (80.84%) after PARPi initiation. CONCLUSION: Olaparib had the best safety profile among five PARPis. PARPi-associated hematological AEs mainly occurred within the first 3 months. REGISTRATION: PROSPERO (CRD42022385274).

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.

Effectiveness and safety of extended thromboprophylaxis in post-discharge patients with COVID-19: A systematic review and meta-analysis.

BACKGROUND: The effect of extended thromboprophylaxis in improving the prognosis of adult patients with coronavirus disease 2019 (COVID-19) after discharge remains debatable. This meta-analysis was aimed to determine the advantages and disadvantages of extended thromboprophylaxis in these patients. METHODS: Different databases such as PubMed, Embase, Web of Science, and Cochrane Library were systematically searched for studies that evaluated the effects of extended thromboprophylaxis in post-discharge patients with COVID-19 until 13 June 2022. The primary efficacy outcome was defined by the composite outcome of thromboembolism and all-cause mortality, and the safety outcome was defined by bleeding events. The odds ratios (ORs) and 95 % confidence intervals (CIs) of efficacy and safety outcomes were calculated using fixed- or random-effects model. Interaction analysis was performed to assess and compare observational studies and randomised controlled trials (RCTs). A sensitivity analysis was performed after excluding studies of poor quality. RESULTS: Eight studies involving 10,148 patients were included. The results confirmed that extended thromboprophylaxis, primarily prophylactic use of anticoagulants for <35 days, was significantly associated with reduced composite outcome in high-risk post-discharge patients with COVID-19 (OR: 0.52; 95 % CI: 0.41-0.67, P = 0.000). Interaction analysis revealed that the effect estimates were consistent between the RCT and observational studies (Pinteraction = 0.310). Furthermore, extended thromboprophylaxis did not increase the risk of major bleeding events (OR: 1.64; 95 % CI: 0.95-2.82, P = 0.075). CONCLUSION: In post-discharge patients with COVID-19 at high risk of thromboembolism, extended thromboprophylaxis, primarily prophylactic use of anticoagulants for <35 days, can significantly reduce the risk of thrombosis and all-cause mortality without increasing the risk of major bleeding events. REGISTRATION: PROSPERO CRD42022339399.

Warfarin anticoagulation management during the COVID-19 pandemic: The role of internet clinic and machine learning.

Background: Patients who received warfarin require constant monitoring by hospital staff. However, social distancing and stay-at-home orders, which were universally adopted strategies to avoid the spread of COVID-19, led to unprecedented challenges. This study aimed to optimize warfarin treatment during the COVID-19 pandemic by determining the role of the Internet clinic and developing a machine learning (ML) model to predict anticoagulation quality. Methods: This retrospective study enrolled patients who received warfarin treatment in the hospital anticoagulation clinic (HAC) and "Internet + Anticoagulation clinic" (IAC) of the Nanjing Drum Tower Hospital between January 2020 and September 2021. The primary outcome was the anticoagulation quality of patients, which was evaluated by both the time in therapeutic range (TTR) and international normalized ratio (INR) variability. Anticoagulation quality and incidence of adverse events were compared between HAC and IAC. Furthermore, five ML algorithms were used to develop the anticoagulation quality prediction model, and the SHAP method was introduced to rank the feature importance. Results: Totally, 241 patients were included, comprising 145 patients in the HAC group and 96 patients in the IAC group. In the HAC group and IAC group, 73.1 and 69.8% (p = 0.576) of patients achieved good anticoagulation quality, with the average TTR being 79.9 ± 20.0% and 80.6 ± 21.1%, respectively. There was no significant difference in the incidence of adverse events between the two groups. Evaluating the five ML models using the test set, the accuracy of the XGBoost model was 0.767, and the area under the receiver operating characteristic curve was 0.808, which showed the best performance. The results of the SHAP method revealed that age, education, hypertension, aspirin, and amiodarone were the top five important features associated with poor anticoagulation quality. Conclusion: The IAC contributed to a novel management method for patients who received warfarin during the COVID-19 pandemic, as effective as HAC and with a low risk of virus transmission. The XGBoost model could accurately select patients at a high risk of poor anticoagulation quality, who could benefit from active intervention.

The Use of Oral Anticoagulation Is Not Associated With a Reduced Risk of Mortality in Patients With COVID-19: A Systematic Review and Meta-Analysis of Cohort Studies.

Background: Hypercoagulability and thromboembolic events are associated with poor prognosis in coronavirus disease 2019 (COVID-19) patients. Whether chronic oral anticoagulation (OAC) improve the prognosis is yet controversial. The present study aimed to investigate the association between the chronic OAC and clinical outcomes in COVID-19 patients. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were comprehensively searched to identify studies that evaluated OAC for COVID-19 until 24 July 2021. Random-effects model meta-analyses were performed to pool the relative risk (RR) and 95% confidence interval (CI) of all-cause mortality and intensive care unit (ICU) admission as primary and secondary outcomes, respectively. According to the type of oral anticoagulants [direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs)], subgroup and interaction analyses were performed to compare DOACs and VKAs. Meta-regression was performed to explore the potential confounders on all-cause mortality. Results: A total of 12 studies involving 30,646 patients met the inclusion criteria. The results confirmed that chronic OAC did not reduce the risk of all-cause mortality (RR: 0.92; 95% CI 0.82-1.03; p = 0.165) or ICU admission (RR: 0.65; 95% CI 0.40-1.04; p = 0.073) in patients with COVID-19 compared to those without OAC. The chronic use of DOACs did not reduce the risk of all-cause mortality compared to VKAs (P interaction = 0.497) in subgroup and interaction analyses. The meta-regression failed to detect any potential confounding on all-cause mortality. Conclusion: COVID-19 patients with chronic OAC were not associated with a lower risk of all-cause mortality and ICU admission compared to those without OAC, and the results were consistent across DOACs and VKA subgroups. Systematic Review Registration: clinicaltrials.gov, identifier CRD42021269764.