Parenteral anticoagulation in ambulatory patients with cancer.
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ABSTRACT:
SUBMITTER: Akl EA
PROVIDER: S-EPMC6419241 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe risk of arterial thrombotic events (ATEs) is high among patients on systemic anticancer therapies. Despite the efficacy of anticoagulants in the prevention of cancer-associated venous thromboembolism, it is unknown whether anticoagulation is effective to prevent ATEs.ObjectivesThis study sought to examine the efficacy and safety of anticoagulants in ATE prevention among ambulatory cancer patients.MethodsWe performed a systematic review using Medline, Embase, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to May 21, 2022, and included studies comparing oral or parenteral anticoagulation with no anticoagulation among ambulatory patients receiving systemic anticancer therapy with no other indication for anticoagulation. The primary outcome was ATE (myocardial infarction, ischemic stroke, intra-abdominal arterial embolism, or peripheral artery occlusion). The secondary outcomes were major and nonmajor bleeding and all-cause mortality.ResultsFourteen randomized trials involving low-molecular-weight heparins, direct oral anticoagulants, and warfarin were included. ATEs were captured as coefficacy endpoints or adverse events. Anticoagulant use was not associated with a reduction in ATEs compared with placebo or standard treatment (RR: 0.73, 95% CI: 0.50-1.04; P = 0.08; I2 = 0%). RRs of major and minor bleeding were 1.56 (95% CI: 1.12-2.17) and 2.25 (95% CI: 1.45-3.48) with anticoagulant use. In 13 trials that reported all-cause mortality, risk of death was not reduced with anticoagulants (RR: 0.99; 95% CI: 0.95-1.02; P = 0.38; I2 = 0%).ConclusionsAnticoagulants did not reduce ATE risk among ambulatory patients on systemic anticancer therapy and were associated with increased bleeding. Based on the current data, anticoagulants have a limited role in ATE prevention in this population as a whole.
| S-EPMC10443118 | biostudies-literature
Project description:BackgroundTo determine the efficacy and safety of heparin (unfractionated heparin (UFH) or low-molecular-weight-heparin (LMWH)) and fondaparinux in improving the survival of patients with cancer.MethodsWe conducted in January 2007 a comprehensive search for relevant randomized clinical trials (RCTs). We used a standardized form to extract in duplicate data on methodological quality, participants, interventions and outcomes of interest including all cause mortality, thromboembolic events, and bleeding events. We assessed the methodological quality for each outcome by grading the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodologyResultsOf 3986 identified citations, we included 5 RCTs, none of which evaluated fondaparinux. The quality of evidence was moderate for survival, low for major and minor bleeding, and very low for DVT. Heparin therapy was associated with a statistically and clinically significant survival benefit (hazard ratio (HR) = 0.77; 95%CI = 0.65-0.91). In subgroup analyses, patients with limited small cell lung cancer experienced a clear survival benefit (HR = 0.56; 95%CI = 0.38-0.83). The survival benefit was not statistically significant for either patients with extensive small cell lung cancer (HR = 0.80; 95%CI = 0.60-1.06) or patients with advanced cancer (HR = 0.84; 95%CI = 0.68-1.03). The increased risk of bleeding with heparin was not statistically significant (relative risk (RR) = 1.78; 95%CI = 0.73-4.38).ConclusionThis review suggests a survival benefit of heparin in cancer patients in general, and in patients with limited small cell lung cancer in particular.
| S-EPMC2438335 | biostudies-literature
Project description:Anticoagulation therapy is administered to patients to prevent or stop thrombin generation in vivo. Although plasma tests of in vivo thrombin generation have been available for more than 2 decades, they are not routinely used in clinical trials or practice to monitor anticoagulation therapy. We observed a fall in one such marker, the D-dimer antigen, in patients receiving anticoagulation therapy. We therefore conducted a systematic review of the medical literature to document the change in serum biomarkers of thrombin generation following the initiation of anticoagulation therapy. Using a defined search strategy, we screened PubMed and Embase citations and identified full-length articles published in English. Eighteen articles containing serial changes in 1 of 3 markers of thrombin generation (D-dimer antigen, thrombin-antithrombin complexes, and prothrombin fragment 1+2 antigen levels) in the 14 days following the initiation of anticoagulation were identified. Even though the assays used varied considerably, each of the 3 markers of thrombin generation declined in the initial period of anticoagulation therapy, with changes evident as early as 1 day after beginning therapy. These observations provide a rationale for further exploration of these markers as measures of the adequacy of anticoagulation using classic as well as novel anticoagulants. Particular patient groups that would benefit from additional means of monitoring anticoagulation therapy are discussed.
| S-EPMC6714868 | biostudies-literature
Project description:BackgroundParenteral nutrition (PN) remains a critical therapeutic option in patients who cannot tolerate enteral feeding. However, although lifesaving, PN is associated with significant side effects, including liver injury, the etiology of which is multifactorial. Carbamazepine (CBZ), an antiepileptic medication, is known to modulate hepatic fibrosis and hepatocellular injury in a variety of liver diseases. We hypothesized that CBZ could prevent PN-associated liver disease (PNALD), which we tested by using our novel ambulatory PN piglet model.MethodsPiglets were fitted with jugular catheters and infusion pumps for PN and randomized to enteral nutrition (n = 7), PN (n = 6), or PN with parenteral CBZ (n = 6) for 2 weeks. Serum and liver tissue were analyzed via light microscopy, quantification of serum liver injury markers, Ki67 and cytokeratin-7 indexing, and real-time quantitative polymerase chain reaction.ResultsPN-fed piglets in our model developed manifestations of PNALD-particularly, increased serum bilirubin, gamma-glutamyltransferase, liver cholestasis, and Ki67 expression compared with that of EN-fed animals (P < 0.03). CBZ therapy in PN-fed animals led to a significant reduction in these markers of injury (P < 0.05). Investigation into the mechanism of these therapeutic effects revealed increased expression of sterol regulatory element-binding protein 1 (SREBP-1), peroxisome proliferator-activated receptor alpha (PPAR-α), and fatty acid binding protein (FABP) in PN-fed animals receiving CBZ (P < 0.03). Further investigation revealed increased LC3 expression and decreased lysosomal-associated membrane protein (LAMP1) expression with CBZ (P < 0.03).ConclusionCBZ administration mitigates PNALD severity, suggesting a novel therapeutic strategy targeting PN-associated side effects, and may present a paradigm change to current treatment options.
| S-EPMC9308820 | biostudies-literature
Project description:BackgroundDespite increasing recognition of the importance of optimal antibiotic selection and expansion of antimicrobial stewardship activities to ambulatory settings, few studies have examined the frequency of parenteral antibiotic use among ambulatory children. We assessed the prevalence and patterns of parenteral antibiotic administration among ambulatory children in pediatric emergency departments (EDs).MethodsWe conducted a cross-sectional assessment of parenteral antibiotic use among ambulatory children aged 0-18 years in 49 US children's hospital EDs in 2018. We assessed the prevalence rates of parenteral antibiotic use and stratified these by patient-, clinic-, and hospital-level characteristics. We also assessed the prevalence of use of specific antibiotics by age and diagnosis category. Among encounters associated with an infection diagnosis, we identified factors associated with parenteral antibiotic use using multivariable logistic regression.ResultsAmong 3 452 011 ambulatory ED encounters in 2018, parenteral antibiotics were administered in 62 648 (1.8%). The highest proportion of parenteral antibiotic use occurred in the 15-18-year age group (3.3%) and among encounters in children with complex chronic conditions (8.9%) and with primary diagnoses of neoplasms (36%). Ceftriaxone was the most commonly administered parenteral antibiotic (61%). In multivariable analysis, several factors including age ≤2 months, White race, private insurance, complex chronic conditions, digestive and genitourinary system diseases, and encounters attributed to emergency medicine providers were significantly associated with higher odds of parenteral antibiotic use.ConclusionsThis study demonstrates substantial variability in the frequency of parenteral antibiotic administration by age and diagnosis in the ambulatory ED setting and highlights potential opportunities to target stewardship activities.
| S-EPMC7579746 | biostudies-literature
Project description:ImportanceThe association of parenteral anticoagulation therapy with improved outcomes in patients with non-ST-segment elevation acute coronary syndrome was previously established. This benefit has not been evaluated in the era of dual antiplatelet therapy and percutaneous coronary intervention.ObjectiveTo evaluate the association between parenteral anticoagulation therapy and clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention.Design, setting, and participantsThis cohort study included 8197 adults who underwent percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome from January 1, 2010, to December 31, 2014, at 5 medical centers in China. Patients receiving parenteral anticoagulation therapy only after percutaneous coronary intervention were excluded.ExposuresParenteral anticoagulation therapy.Main outcomes and measuresThe primary outcome was in-hospital all-cause death and in-hospital major bleeding as defined by the Bleeding Academic Research Consortium definition (grades 3-5).ResultsOf 6804 patients who met the final criteria, 5104 (75.0%) were male, with a mean (SD) age of 64.2 (10.4) years. The incidence of in-hospital death was not significantly different between the patients who received and did not receive parenteral anticoagulation therapy (0.3% vs 0.1%; P = .13) (adjusted odds ratio, 1.27; 95% CI, 0.38-4.27; P = .70). A similar result was found for myocardial infarction (0.3% vs 0.3%; P = .82) (adjusted odds ratio, 0.77; 95% CI, 0.29-2.07; P = .61). In-hospital major bleeding was more frequent in the parenteral anticoagulation group (2.5% vs 1.0%; P < .001) (adjusted odds ratio, 1.94; 95% CI, 1.24-3.03; P = .004). At a median (interquartile range) follow-up of 2.96 years (1.93-4.46 years), all-cause death was not significantly different between the 2 groups (adjusted hazards ratio, 0.87; 95% CI, 0.71-1.07; P = .19), but the incidence of major bleeding was higher in the parenteral anticoagulation group (adjusted hazards ratio, 1.43; 95% CI, 1.01-2.02; P = .04). The propensity score analysis confirmed these primary analyses.Conclusions and relevanceIn the patients undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndrome, parenteral anticoagulation therapy was not associated with a lower risk of all-cause death or myocardial infarction but was significantly associated with a higher risk of major bleeding. These findings raise important safety questions about the current practice of routine parenteral anticoagulation therapy while we await randomized trials of this practice.
| S-EPMC6439659 | biostudies-literature
Project description:BackgroundAppropriate nutritional support, including supplemental home parenteral nutrition (sHPN), may improve prognosis and quality of life (Qol) of malnourished cancer patients. We aimed to explore the cost-effectiveness of sHPN for incurable gastrointestinal cancer patients from the Chinese healthcare perspective.MethodClinical data were extracted from a randomized controlled trial (NCT02066363). Patients were randomized into the sHPN group or the non-sHPN group (receiving best practice nutritional care). A Markov model was established with a 6-week cycle length. Costs were acquired from local hospitals, effect parameters included quality-adjusted life year (QALY), Qol, body mass index, fat-free mass (FFM), FFM index, handgrip strength, and a 6-min walking test. Sensitivity analyses were conducted with a willingness-to-pay (WTP) set at 3 per capita gross domestic product ($29,307/QALY).ResultsWhen considering QALY as a utility, the incremental cost-effectiveness ratio (ICER) was $24,289.17, with an incremental cost of $2,051.18 and an incremental QALY of 0.0844 between the sHPN group and the non-sHPN group. Furthermore, we explored the cost-effectiveness of sHPN from multidimensions, where we analyzed various effect parameters at different visits; the results showed a superior benefit for patients in the sHPN group except for the handgrip parameter at visit 2. Sensitivity analysis demonstrated the influence of utilities in the sHPN group, but the sHPN group was still cost-effective with a WTP of $2,500/QALY.ConclusionIn China, sHPN was cost-effective for patients with incurable gastrointestinal cancer, which suggested further applications in clinical practice and provided references for clinical decisions and pricing.
| S-EPMC9157576 | biostudies-literature
Project description:Venous thromboembolism (VTE), comprising deep-vein thrombosis and pulmonary embolism, is a frequent complication in ambulatory cancer patients. Despite the high risk, routine thromboprophylaxis is not recommended because of the high number needed to treat and the risk of bleeding. Two recent trials demonstrated that the number needed to treat can be reduced by selecting cancer patients at high risk for VTE with prediction scores, leading the latest guidelines to suggest such an approach in clinical practice. Yet, the interpretation of these trial results and the translation of the guideline recommendations to clinical practice may be less straightforward. In this clinically-oriented review, some of the controversies are addressed by focusing on the burden of VTE in cancer patients, discussing the performance of available risk assessment scores, and summarizing the findings of recent trials. This overview can help oncologists, hematologists, and vascular medicine specialists decide about thromboprophylaxis in ambulatory cancer patients.
| S-EPMC7072463 | biostudies-literature
Project description:BackgroundMalignant bowel obstruction (MBO) affects 3-15% of all cancer patients. In patients with advanced cancer and inoperable MBO, the average survival varies between four to nine weeks. Parenteral nutrition (PN) may improve survival in specific patient populations with malignant bowel obstruction.AimsThis retrospective, single-center cohort study aimed to review individual patient outcomes on PN in the setting of advanced cancer with a diagnosis of MBO and identify clinical and laboratory markers predictive of short- and long-term survival to further highlight patients that would benefit from PN in the setting of an inoperable MBO.ResultsIn a retrospective analysis of 68 patients receiving PN for inoperable MBO, the median survival was 142 (IQR: 63.3-239.5) days. Patients experienced a median number of two hospital readmissions (range: 0-10) and spent a median of 29 days (range: 0-105) in the hospital after starting PN. Eighteen (26.5%) patients developed a catheter-related bloodstream infection (CRBSI). A diagnosis of appendiceal cancer was identified as a predictive marker of improved survival (HR: 0.53, 95% CI: 0.29-0.92, p = 0.023).ConclusionsThe use of PN in the context of end-of-life cancer care is a practice that necessitates improvement. Recognizing the outcomes and patient experiences of PN utilization is essential to physicians and patients.
| S-EPMC10680932 | biostudies-literature
Project description:Patients with active cancer are at an increased risk of arterial and venous thromboembolism (VTE) and bleeding events. Historically, in patients with cancer, low molecular weight heparins have been preferred for treatment of VTE, whereas warfarin has been the standard anticoagulant for stroke prevention in patients with atrial fibrillation (AF). More recently, direct oral anticoagulants (DOACs) have been demonstrated to reduce the risk of venous and arterial thromboembolism in large randomized clinical trials of patients with VTE and AF, respectively, thus providing an attractive oral dosing option that does not require routine laboratory monitoring. In this review, we summarize available clinical trial data and guideline recommendations, and outline a practical approach to anticoagulation management of VTE and AF in cancer.
| S-EPMC7957366 | biostudies-literature