The incidence of venous thromboembolism in cancer patients may have changed in the past decade, possibly due to novel cancer therapies, improved survival, and high-resolution imaging. Danish medical registries were used to identify 499,092 patients with a first-time cancer diagnosis between 1997 and 2017, who were matched to 1,497,276 comparison individuals without cancer from the general population. We computed cumulative incidences of venous thromboembolism 6 and 12 months after the diagnosis/index date. Hazard ratios (HRs) were calculated using Cox regression. Risk factors were examined by computing subdistribution hazard ratios (SHRs) in a competing risk analysis. Cumulative incidence of venous thromboembolism 12 months after the cancer diagnosis/index date was 2.3% (95% confidence interval (CI), 2.2%-2.3%) in the cancer cohort and 0.35% (95% CI, 0.34%-0.36%) in the comparison cohort (HR, 8.5; 95% CI, 8.2-8.8). Important risk factors for cancer patients were prior venous thromboembolism (SHR, 7.6; 95% CI, 7.2-8.0), distant metastasis (SHR, 3.2; 95% CI, 2.9-3.4), and use of chemotherapy (SHR, 3.4; 95% CI, 3.1-3.7), protein kinase inhibitors (SHR, 4.1; 95% CI 3.4-4.9), anti-angiogenic therapy (SHR, 4.4; 95% CI, 3.8-5.2), and immunotherapy (SHR, 3.6; 2.8-4.6). Twelve-month incidence in the cancer cohort increased from 1.0% (95% CI, 0.9%-1.2%) in 1997 to 3.4% (95% CI, 2.9%-4.0%) in 2017, which was paralleled by improved 12-month survival and increased use of computed tomography (CT) scans, chemotherapy, and targeted therapies. In conclusion, the risk of venous thromboembolism in cancer patients is increasing steadily and is 9-fold higher than in the general population.
We aimed to evaluate the performance of the Khorana score in predicting venous thromboembolic events in ambulatory cancer patients. Embase and MEDLINE were searched from January 2008 to June 2018 for studies which evaluated the Khorana score. Two authors independently screened studies for eligibility, extracted data, and assessed risk of bias. Additional data on the 6-month incidence of venous thromboembolism were sought by contacting corresponding authors. The incidence in each Khorana score risk group was estimated with random effects meta-analysis. A total of 45 articles and eight abstracts were included, comprising 55 cohorts enrolling 34,555 ambulatory cancer patients. For 27,849 patients (81%), 6-month follow-up data were obtained. Overall, 19% of patients had a Khorana score of 0 points, 64% a score of 1 or 2 points, and 17% a score of 3 or more points. The incidence of venous thromboembolism in the first six months was 5.0% (95%CI: 3.9-6.5) in patients with a low-risk Khorana score (0 points), 6.6% (95%CI: 5.6-7.7) in those with an intermediate-risk Khorana score (1 or 2 points), and 11.0% (95%CI: 8.8-13.8) in those with a high-risk Khorana score (3 points or higher). Of the patients with venous thromboembolism in the first six months, 23.4% (95%CI: 18.4-29.4) had been classified as high risk according to the Khorana score. In conclusion, the Khorana score can be used to select ambulatory cancer patients at high risk of venous thromboembolism for thromboprophylaxis; however, most events occur outside this high-risk group.
In the Hokusai VTE Cancer study, edoxaban was non-inferior to dalteparin for the composite outcome of recurrent venous thromboembolism (VTE) and major bleeding in 1,050 patients with cancer-associated VTE. The absolute rate of recurrent VTE was 3.4% lower with edoxaban, whereas the absolute rate of major bleeding was 2.9% higher. The present analysis focuses on the sites, clinical presentation, course and outcome of bleeding events, and the associated tumour types. Major bleeds and their severity (categories 1-4) were blindly adjudicated by a committee using a priori defined criteria, and data were analysed in the safety population. Major bleeding occurred in 32 of 522 patients given edoxaban (median treatment duration, 211 days) and in 16 of 524 patients treated with dalteparin (median treatment duration, 184 days); no patients had more than one major bleed. There were no fatal bleeds with edoxaban, and two with dalteparin. Severe bleeding at presentation (category 3 or 4) occurred in 10 (1.9%) and 11 (2.1%) patients in the edoxaban and dalteparin groups, respectively. The excess of major bleeding with edoxaban was confined to patients with gastrointestinal cancer. However, severe major bleeding at presentation (category 3 or 4) in this sub-group occurred in 5 of 165 (3.0%) and in 3 of 140 (2.1%) patients given edoxaban or dalteparin, respectively.In conclusion, this analysis suggests that while oral edoxaban is an appropriate alternative to subcutaneous dalteparin for treatment of cancer-associated VTE, the use of edoxaban in patients with gastrointestinal cancer requires careful benefit-risk weighting.
Based on current literature, evidence stating that PUR is harmless is lacking. Future research should focus on management strategies for overt PUR and the long-term consequences of covert PUR. Until these results are available, clinicians should be aware of the potential consequences and therefore keep trying to identify patients at risk of PUR and patients with the actual condition.
Background Postpartum urinary retention (PUR) is a common condition with varying prevalence. Measurement of the post-void residual volume (PVRV) is not regularly performed. Various studies have been published on overt (the inability to void after giving birth, requiring catheterisation) and covert (an increased PVRV after spontaneous micturition) PUR. To evaluate which clinical prognostic factors are related to PUR, the identification of independent risk factors for covert and overt PUR is needed.Objectives We performed a systematic review and meta-analysis of observational studies reporting on risk factors for PUR.Search strategy Systematic search of MEDLINE and EMBASE to September 2011.Selection criteria Articles that reported on women diagnosed with PUR or with an abnormal PVRV.Data collection and analysis The included articles were selected by two authors. We constructed two-by-two tables for potential risk factors of overt and covert PUR and calculated pooled odds ratios (ORs) with 95% confidence intervals.Main results Twenty-three observational studies with original data were eligible for data extraction, of which 13 could be used for meta-analysis. Statistically significant risk factors for overt PUR were epidural analgesia (OR 7.7), instrumental delivery (OR 4.5), episiotomy (OR 4.8) and primiparity (OR 2.4). For covert PUR, variety in the definitions used resulted in heterogeneity; no significant prognostic factors were found.Conclusions Instrumental delivery, epidural analgesia, episiotomy and nulliparity are statistically significantly associated with a higher incidence of overt PUR. The same factors were identified for covert PUR, but without statistical significance. Uniformity in definitions in future research is essential to create a prognostic model.
Direct oral anticoagulants (DOACs) are an emerging treatment option for cancer patients with acute venous thromboembolism (VTE), but studies have reported inconsistent results. This systematic review and meta-analysis compared the efficacy and safety of DOACs and low-molecular-weight heparins (LMWH) in these patients. MEDLINE, Embase, CENTRAL, and conference proceedings were searched to identify relevant randomized controlled trials. Additional data were obtained from the original authors to homogenize definitions for all study outcomes. The primary efficacy and safety outcomes were recurrent VTE and major bleeding, respectively. Other outcomes included the composite of recurrent VTE and major bleeding, clinically relevant non-major bleeding (CRNMB), and all-cause mortality. Summary relative risks (RR) were calculated in a random effects meta-analysis. In the primary analysis comprising 2,607 patients, the risk of recurrent VTE was non-significantly lower with DOACs than with LMWH (RR 0.68; 95% CI, 0.39 to 1.17). Conversely, the risks of major bleeding (RR 1.36; 95% CI, 0.55 to 3.35) and CRNMB (RR 1.63, 95%, 0.73 to 3.64) were non-significantly higher. The risk of the composite of recurrent VTE or major bleeding was non-significantly lower with DOACs than with LMWH (RR 0.86; 95% CI, 0.60 to 1.23). Mortality was comparable in both groups (RR 0.96; 95% CI, 0.68 to 1.36). Findings were consistent during the on-treatment period and in those with incidental VTE. In conclusion, DOACs are an effective treatment option for cancer patients with acute VTE, although caution is needed in patients at high risk of bleeding.
Introduction and hypothesisPostpartum urinary retention (PUR) is a common consequence of bladder dysfunction after vaginal delivery. Patients with covert PUR are able to void spontaneously but have a postvoid residual bladder volume (PVRV) of ≥150 mL. Incomplete bladder emptying may predispose to bladder dysfunction at a later stage of life. The aim of this cross-sectional study was to identify independent delivery-related risk factors for covert PUR after vaginal delivery in order to identify women with an increased risk of covert PUR.MethodsThe PVRV of women who delivered vaginally was measured after the first spontaneous micturition with a portable bladder-scanning device. A PVRV of 150 mL or more was defined as covert PUR. Independent risk factors for covert PUR were identified in multivariate regression analysis.ResultsOf 745 included women, 347 (47 %) were diagnosed with covert PUR (PVRV ≥150 mL), of whom 197 (26 %) had a PVRV ≥250 mL (75th percentile) and 50 (7 %) a PVRV ≥500 mL (95th percentile). In multivariate regression analysis, episiotomy (OR 1.7, 95 % CI 1.02 – 2.71), epidural analgesia (OR 2.08, 95 % CI 1.36 – 3.19) and birth weight (OR 1.03, 95 % CI 1.01 – 1.06) were independent risk factors for covert PUR. Opioid analgesia during labour (OR 3.19, 95 % CI 1.46 – 6.98), epidural analgesia (OR 3.54, 95 % CI 1.64 – 7.64) and episiotomy (OR 3.72, 95 % CI 1.71 – 8.08) were risk factors for PVRV ≥500 mL.ConclusionsEpisiotomy, epidural analgesia and birth weight are risk factors for covert PUR. We suggest that the current cut-off values for covert PUR should be reevaluated when data on the clinical consequences of abnormal PVRV become available.
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