Project description:ObjectivesIn preparation for a pediatric randomized controlled trial on thromboprophylaxis, we determined the frequency of catheter-related thrombosis in children. We also systematically reviewed the pediatric trials on thromboprophylaxis to evaluate its efficacy and to identify possible pitfalls in the conduct of these trials.Patients/methodsWe searched MEDLINE, EMBASE, Web of Science and the Cochrane Central Register for Controlled Trials for articles published until December 2013. We included cohort studies and trials on patients aged 0-18 years with central venous catheters who underwent active surveillance for thrombosis with radiologic imaging. We estimated the pooled frequency of thrombosis and the pooled risk ratio (RR) with thromboprophylaxis by using a random effects model.ResultsFrom 2651 articles identified, we analyzed 37 articles with 3128 patients. The pooled frequency of thrombosis was 0.20 (95% confidence interval [CI] 0.16-0.24). In 10 trials, we did not find evidence that heparin-bonded catheters (RR 0.34; 95%CI 0.01-7.68), unfractionated heparin (RR 0.93; 95% CI 0.57-1.51), low molecular weight heparin (RR 1.13; 95% CI 0.51-2.50), warfarin (RR 0.85; 95%CI 0.34-2.17), antithrombin concentrate (RR 0.76; 95% CI 0.38-1.55) or nitroglycerin (RR 1.53; 95%CI 0.57-4.10) reduced the risk of thrombosis. Most of the trials were either not powered for thrombosis or were powered to detect large, probably unachievable, reductions in thrombosis. Missing data on thrombosis also limited these trials.ConclusionsCatheter-related thrombosis is common in children. An adequately powered multicenter trial that can detect a modest, clinically significant reduction in thrombosis is critically needed. Missing outcome data should be minimized in this trial.
Project description:BackgroundCatheter-related thrombosis (CRT) is a thrombotic complication associated with using central venous catheters (CVCs). Although risk factors for CRT were identified in children, no nomograms or predictive tools are available for the pediatric population with CVCs. This study aimed to develop and validate a prediction model of asymptomatic CRT in children with CVCs.MethodsThis retrospective observational study included consecutive pediatric patients who admitted to the Children's Hospital Zhejiang University School of Medicine and received CVCs between October and December 2021.ResultsThis study included 669 patients, 553 (314 males, aged 22.00 [0.36, 180.00] months, 62 with CRT) were in the training set, and 116 (62 males, aged 15.00 [1.13, 156.00] months, 16 with CRT) were in the validation set. Multivariate logistic regression showed that a catheter time of 0-3 days (OR = 0.201, 95%CI: 0.081-0.497, P = 0.001), catheter time of 4-7 days (OR = 0.412, 95%CI: 0.176-0.964, P = 0.041), male (OR = 3.976, 95%CI: 1.864-4.483, P < 0.001), congenital heart diseases (OR = 0.277, 95%CI: 0.078-0.987, P = 0.048), postoperative (OR = 0.161, 95%CI: 0.072-0.360, P < 0.001), and femoral CVC (OR = 2.451, 95%CI: 1.129-5.318, P = 0.002) were independently associated with CRT. The nomogram incorporating these variables showed relatively good discrimination (AUC = 0.77, 95%CI: [0.65, 0.90]) and calibration abilities in the validation set, and the decision curve analysis (DCA) yielded a clinical net benefit.ConclusionA prediction model for CRT in children with CVC was established based on catheter time, sex, diseases, postoperative, and catheter vein. The nomogram based on logistic regression model showed favorable predictive performance.
Project description:BackgroundThis study aimed to explore the risk factors of catheter-related thrombosis (CRT) in children in Southwest China who underwent central venous catheter (CVC) insertion.MethodsAn observational cohort study was conducted at a single tertiary center in southwest China between November 2019 and February 2020. All patients who received a CVC were enrolled and Doppler-ultrasound examination was performed weekly until CVC removal. All patients in this study were hospitalized and were observed and followed up in this hospital. Patient demographics, medication, biochemical indexes, catheter maintenance practice, activities after CVC placement data were analyzed. The Kaplan-Meier method was used to calculate the incidence of CRT, and the Cox regression model was used to analyze the factors influencing CRT.ResultsA total of 594 children were included in the study, and the median indwelling time was 10 days, with the shortest being 1 day and the longest 60 days. The overall incidence of CRT was 26.60% (158/594), the 15-day cumulative incidence rate was 30.81%, and the 45-day cumulative incidence rate was 46.27%. After 45 days, the incidence of CRT further increased. Age <12 months [hazard ratio (HR), 1.654; 95% confidence interval (CI): 1.171-2.338], use of 20% mannitol or glycerol fructose (HR, 1.593; 95% CI: 1.058-2.398), CVC placement by a pediatric intensive care unit (PICU) doctor (HR, 1.921; 95% CI: 1.347-2.740), placement length ≥9 cm (HR, 1.633; 95% CI: 1.142-2.336), and D-dimer >1.5 mg/L (HR, 1.451; 95% CI: 1.044-2.015) were risk factors for CRT. Limb exercises (HR, 0.660; 95% CI: 0.469-0.929) after placement was a protective factor for CRT.ConclusionsThe incidence of CRT was higher in children with CVCs, and the key duration of CRT monitoring should be within 15 and 45 days after placement. Patients with age <12 months, using 20% mannitol or glycerol fructose, insertion length ≥9 cm, D-dimer >1.5 mg/L before placement are more likely to happen CVC-CRT than other patient, and it is necessary to be highly vigilant and take preventive measures.
Project description:BackgroundAn increase in the incidence of central venous catheter (CVC)-associated deep venous thrombosis (CADVT) has been reported in pediatric patients over the past decade. At the same time, current screening guidelines for venous thromboembolism risk have low sensitivity for CADVT in hospitalized children. This study utilized a multimodal deep learning model to predict CADVT before it occurs.MethodsChildren who were admitted to intensive care units (ICUs) between December 2015 and December 2018 and with CVC placement at least 3 days were included. The variables analyzed included demographic characteristics, clinical conditions, laboratory test results, vital signs and medications. A multimodal deep learning (MMDL) model that can handle temporal data using long short-term memory (LSTM) and gated recurrent units (GRUs) was proposed for this prediction task. Four benchmark machine learning models, logistic regression (LR), random forest (RF), gradient boosting decision tree (GBDT) and a published cutting edge MMDL, were used to compare and evaluate the models with a fivefold cross-validation approach. Accuracy, recall, area under the ROC curve (AUC), and average precision (AP) were used to evaluate the discrimination of each model at three time points (24 h, 48 h and 72 h) before CADVT occurred. Brier score and Spiegelhalter's z test were used measure the calibration of these prediction models.ResultsA total of 1830 patients were included in this study, and approximately 15% developed CADVT. In the CADVT prediction task, the model proposed in this paper significantly outperforms both traditional machine learning models and existing multimodal deep learning models at all 3 time points. It achieved 77% accuracy and 90% recall at 24 h before CADVT was discovered. It can be used to accurately predict the occurrence of CADVT 72 h in advance with an accuracy of greater than 75%, a recall of more than 87%, and an AUC value of 0.82.ConclusionIn this study, a machine learning method was successfully established to predict CADVT in advance. These findings demonstrate that artificial intelligence (AI) could provide measures for thromboprophylaxis in a pediatric intensive care setting.
Project description:BackgroundImmobilization of the lower limb is a risk factor for venous thromboembolism (VTE). Low molecular weight heparins (LMWHs) are anticoagulants, which might be used in adult patients with lower-limb immobilization to prevent deep venous thrombosis (DVT) and its complications. This is an update of the review first published in 2008.ObjectivesTo assess the effectiveness of low molecular weight heparin for the prevention of venous thromboembolism in patients with lower-limb immobilization in an ambulatory setting.Search methodsFor this update, the Cochrane Vascular Information Specialist searched the Specialised Register, CENTRAL, and three trials registers (April 2017).Selection criteriaRandomized controlled trials (RCTs) and controlled clinical trials (CCTs) that described thromboprophylaxis by means of LMWH compared with no prophylaxis or placebo in adult patients with lower-limb immobilization. Immobilization was by means of a plaster cast or brace.Data collection and analysisTwo review authors independently selected trials, assessed risk of bias and extracted data. The review authors contacted the trial authors for additional information if required. Statistical analysis was carried out using Review Manager 5.Main resultsWe included eight RCTs that fulfilled our criteria, with a total of 3680 participants. The quality of evidence, according GRADE, varied by outcome and ranged from low to moderate. We found an incidence of DVT ranging from 4.3% to 40% in patients who had a leg injury that had been immobilized in a plaster cast or a brace for at least one week, and who received no prophylaxis, or placebo. This number was significantly lower in patients who received daily subcutaneous injections of LMWH during immobilization, with event rates ranging from 0% to 37% (odds ratio (OR) 0.45, 95% confidence interval (CI) 0.33 to 0.61; with minimal evidence of heterogeneity: I² = 26%, P = 0.23; seven studies; 1676 participants, moderate-quality evidence). Comparable results were seen in the following groups of participants: patients with below-knee casts, conservatively treated patients (non-operated patients), operated patients, patients with fractures, patients with soft-tissue injuries, and patients with distal or proximal thrombosis. No clear differences were found between the LMWH and control groups for pulmonary embolism (OR 0.50, 95% CI 0.17 to 1.47; with no evidence of heterogeneity: I² = 0%, P = 0.56; five studies, 2517 participants; low-quality evidence). The studies also showed less symptomatic VTE in the LMWH groups compared with the control groups (OR 0.40, 95% CI 0.21 to 0.76; with minimal evidence of heterogeneity: I² = 16%, P = 0.31; six studies; 2924 participants; low-quality evidence). One death was reported in the included studies, but no deaths due to pulmonary embolism were reported. Complications of major adverse events were rare, with minor bleeding the main adverse events reported.Authors' conclusionsModerate-quality evidence showed that the use of LMWH in outpatients reduced DVT when immobilization of the lower limb was required, when compared with no prophylaxis or placebo. The quality of the evidence was reduced to moderate because of risk of selection and attrition bias in the included studies. Low-quality evidence showed no clear differences in PE between the LMWH and control groups, but less symptomatic VTE in the LMWH groups. The quality of the evidence was downgraded due to risk of bias and imprecision.
Project description:BackgroundCentral venous catheters (CVCs) represent one of the main risk factors for venous thrombotic events (VTEs) in children.MethodsWe studied the Italian Registry of Pediatric Thrombosis (RITI) with regard to systemic radiologically confirmed CVC-related VTEs (CVC-VTEs) occurred during 6.5 years in children aged 29 days to 18 years.ResultsA total of 78 CVC-VTEs were included, which occurred in 76 patients (40/76, 53% males). CVC-VTEs comprised 67 non-cardiac VTEs (86%) and 11 intracardiac thrombotic events (ICTEs) (14%); the median age at onset was 19 and 17 months, respectively. The most frequent reason for CVC insertion was supportive therapy. The catheters were placed percutaneously in 85% of cases (56/66) and surgically in the remaining 15% (10/66). Peripherally inserted central catheters (PICCs) were used in 47% (31/66) cases, partially implanted catheters in 42% (28/66), non-implantable catheters in 7% (5/66), and totally implanted catheters (Port) in 2% (1/66). CVC-VTEs were symptomatic in 77% of cases (60/78), while in the remaining 23%, they were incidentally detected on the imaging performed for the underlying condition. The median time between CVC insertion and the onset of symptoms was 10 days in non-cardiac VTEs and 39 days in ICTEs. Doppler ultrasound was the diagnostic technique most frequently used. The venous compartment most frequently affected was the veins of the lower extremities (52%, 43/73). Anti-thrombotic treatment was administered in 96% of CVC-VTEs (75/78). About 2.6% (2/76) of patients experienced a second thrombotic event. At discharge, post-thrombotic syndrome was reported in 13.5% (5/37) events with available data, CVC replacement in 10.8% (4/47), and ischemic necrosis with toe finger amputation in 2.7% (1/37). Three patients died due to an underlying condition; no CVC-VTE-related deaths were reported.ConclusionsWe have carried out a registry-based study on CVC-VTEs in the children in Italy, providing the data that may help improve the detection and management of this CVC-related complication.
Project description:The frequency and risk factors for central venous catheter-related thrombosis (CRT) during prolonged intravenous (i.v.) antibiotic therapy have rarely been reported. The primary objective of this study was to evaluate the frequency, incidence, and risk factors for CRT among patients being treated with prolonged i.v. antibiotic therapy. The secondary objective was to describe the clinical manifestations, diagnostic evaluation, and clinical management. This cohort study was conducted between August 2004 and May 2010 in a French referral center for osteoarticular infections. All patients treated for bone and joint infections with i.v. antimicrobial therapy through a central venous catheter (CVC) for ?2 weeks were included. Risk factors were identified using nonparametric tests and logistic regression. A case-control study investigated the role of vancomycin and catheter malposition. A total of 892 patients matched the inclusion criteria. CRT developed in 16 infections occurring in 16 patients (incidence, 0.39/1,000 catheter days). The median time to a CRT was 29 days (range, 12 to 48 days). Local clinical signs, fever, and secondary complications of CRT were present in 15, 8, and 4 patients, respectively. The median C-reactive protein level was 95 mg/liter. The treatment combined catheter removal and a median of 3 months (1.5 to 6 months) of anticoagulation therapy. The outcome was good in all patients, with no recurrence of CRT. Three risk factors were identified by multivariate analysis: male sex (odds ratio [OR], 5.4; 95% confidence interval [CI], 1.1 to 26.6), catheter malposition (OR, 5.3; 95% CI, 1.6 to 17.9), and use of vancomycin (OR, 22.9; 95% CI, 2.8 to 188). Catheter-related thrombosis is a rare but severe complication in patients treated with prolonged antimicrobial therapy. Vancomycin use was the most important risk factor identified.
Project description:The most appropriate duration of anticoagulant treatment for cancer-associated venous thromboembolism (CAT) remains unclear. We have conducted a prospective multicenter study in CAT patients with more than 6 months of anticoagulant treatment to predict the risk of venous thromboembolism (VTE) recurrence after anticoagulation discontinuation. Blood samples were obtained when patients stopped the anticoagulation, at 21 days and at 90 days. In each sample we assessed different coagulation-related biomarkers: D-dimer (DD), high-sensitivity C-reactive protein (hs-CRP), P-selectin (PS), phospholipids, soluble tissue factor, factor VIII and the thrombin generation test. It was evaluated 325 CAT patients and 166 patients were included in the study, mean age 64 ± 17 years. VTE recurrence until 6 months after stopping anticoagulation treatment was 9.87% [95% confidence interval (CI): 6−15]. The biomarkers sub-distribution hazard ratios were 6.32 for ratio DD basal/DD 21 days > 2 (95% CI: 1.82−21.90), 6.36 for hs-CRP > 4.5 (95% CI: 1.73−23.40) and 5.58 for PS > 40 (95% CI: 1.46−21.30) after 21 days of stopping anticoagulation. This is the first study that has identified the DD ratio, hs-CRP and PS as potential biomarkers of VTE recurrence in cancer patients after the discontinuation of anticoagulation treatment. A risk-adapted strategy may allow the identification of the optimal time to withdraw the anticoagulation in each CAT patient.
Project description:BackgroundDirect oral anticoagulants (DOACs) have demonstrated clinical benefits and better patient adherence over low-molecular-weight heparin (LMWH) in treating patients with cancer-associated venous thrombosis (CAT). We aimed to compare the cost-effectiveness of DOACs against LMWH in patients with CAT from the perspective of the Hong Kong healthcare system.MethodsA Markov state-transition model was performed to estimate the incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) for DOACs and LMWH in a hypothetical cohort of 10,000 patients with CAT over a 5-year lifetime horizon. The model was primarily based on the health states of no event, recurrent venous thromboembolism, bleeding, and death. Transition probabilities, relative risks, and utilities were derived from the literature. Resource cost data were obtained from the Hong Kong Hospital Authority. Deterministic and probabilistic sensitivity analyses tested the robustness of the results.ResultsRelative to LMWH, DOACs were associated with increased QALYs (1.52 versus 1.50) at a lower medical cost of USD 2,232 versus 8,224 in five years. The cost of LMWH was the main contributor to the outcome. Out of 10,000 simulated cases, DOACs were dominant in 15.8% and cost-effective in 42.1%, at the willingness-to-pay threshold of USD 148,392 per additional QALY.ConclusionsDOACs were associated with greater QALY improvements and lower overall costs compared to LMWH. Accounting for uncertainty, DOACs were between cost-effective and dominant in 57.9% of cases. DOACs are a cost-effective alternative to LMWH in the management of CAT in Hong Kong.
Project description:Given the existing uncertainty regarding the effectiveness and safety of switching from low-molecular-weight heparin (LMWH) to direct oral anticoagulants (DOACs) in patients with cancer-associated venous thrombosis (CAT), we conducted a comprehensive population-based cohort study utilizing electronic health database in Hong Kong. A total of 4356 patients with CAT between 2010 and 2022 were included, with 1700 (39.0%) patients switching to DOAC treatment. Compared to continuous LMWH treatment, switching to DOACs was associated with a significantly lower risk of hospitalization due to venous thromboembolism (HR: 0.49 [95% CI = 0.35-0.68]) and all-cause mortality (HR: 0.67 [95% CI = 0.61-0.74]), with no significant difference in major bleeding (HR: 1.04 [95% CI = 0.83-1.31]) within six months. These findings provide reassurance regarding the effectiveness and safety of switching from LMWH to DOACs among patients with CAT, including vulnerable patient groups.