Direct oral anticoagulant versus low-molecular-weight heparin for treatment of venous thromboembolism in cancer patients: An updated meta-analysis of randomized controlled trials.

BACKGROUND: Cancer associated venous thromboembolism (VTE) results in significant morbidity and mortality. Low molecular weight heparin (LMWH) has been standard of care for treatment of cancer-associated VTE, however direct oral anticoagulants (DOACs) are emerging as alternative treatment options. OBJECTIVE: To compare the benefits and harms of DOACs versus LMWH for treatment of VTE in cancer. DATA SOURCES: MEDLINE, Embase, and the Cochrane Collaboration Central Register of Controlled Trials from inception to April 2020. STUDY SELECTION: Randomized controlled trials (RCT) comparing DOACs with LMWH for treatment of VTE in cancer patients. DATA SYNTHESIS: Four good-quality RCTs, met inclusion criteria. Compared with LMWH, DOACs were associated with lower rates of VTE recurrence (RR 0.62; 95% CI: 0.44-0.87; P = 0.006), and DVT recurrence (RR 0.61; 95% CI: 0.4-0.94; P = 0.02) but not PE recurrence (RR 0.73; 95% CI: 0.51-1.04; P = 0.08), in cancer patients. However, the risk of clinically relevant non-major bleeding (CRNMB) (RR 1.58; 95% CI: 1.11-2.24; P = 0.01), and major bleeding in gastrointestinal cancer (RR 2.55; 95% CI 1.24-5.27, P = 0.01), were higher with DOACs. The risk of overall major bleeding (RR 1.33; 95% CI: 0.84-2.1; P = 0.22), all-cause mortality (RR 0.99; 95% CI: 0.84-1.17; P = 0.92), VTE-related mortality (RR: 1; 95% CI: 0.29-3.44; P = 1) and bleeding-related mortality (RR: 0.71; 95% CI: 0.17-2.91; P = 0.63), were similar in both treatment groups. CONCLUSION: Among cancer patients with VTE, treatment with DOACs is associated with a significant reduction of VTE and DVT recurrence, compared to LMWH. These benefits were offset by an increased risk of CRNMB, and major bleeding in gastrointestinal cancer.

Severe primary refractory thrombotic thrombocytopenic purpura (TTP) in the post plasma exchange (PEX) and rituximab era.

Acute acquired thrombotic thrombocytopenic purpura (TTP) requires prompt recognition and initiation of plasma exchange (PEX) therapy and immunosuppression. When PEX fails, mortality nears 100%, making finding an effective treatment crucial. Primary refractory TTP occurs when initial therapies fail or if exacerbations occur during PEX therapy, both signifying the need for treatment intensification to achieve clinical remission. Rituximab helps treat most of the refractory TTP cases, except those that are severely refractory. A paucity of studies guiding severely refractory TTP makes management arbitrary and individualised, highlighting the value of isolated reports. We present an extremely rare case of primary refractory TTP with an insufficient platelet response to numerous types of treatments, including emerging therapies such as caplacizumab, on the background of repeated PEX and immunosuppressive therapies.

Patient and provider factors associated with the noninitiation of tamoxifen for young women at high-risk for the development of breast cancer.

We sought to identify factors associated with disparities in tamoxifen utilization among young patients at high-risk for developing breast cancer. We identified 67 premenopausal, high-risk women age 35-45, without surgical prophylaxis, who did not initiate tamoxifen. Factors associated with noninitiation were examined. About 37% of patients had no documented provider-based discussion regarding initiation. Type of high-risk diagnosis was the only factor associated with a provider-based discussion (P = .03). For patients offered tamoxifen, primary reasons for noninitiation were perceived minimal benefit (66.7%), fertility concerns (16.7%), and concerns about side effects (7.1%). Implementation of comprehensive educational strategies regarding the benefits of tamoxifen should be facilitated to improve initiation among young high-risk patients.

Safety and efficacy of aspirin for primary prevention of cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: In the United States, cancer is the second leading cause of mortality, and millions more battle cancer worldwide. As such, primary prevention of cancer is a major interest globally. Aspirin has been studied as a primary prevention method for multiple diseases, mainly cardiovascular disease and various forms of cancer. The role of aspirin as a primary prevention of cancer is still controversial and may be more beneficial in certain cancers over others. With rapidly surfacing large randomized controlled trials (RCTs) studying this subject, we aimed to evaluate the efficacy and safety of aspirin as a primary prophylaxis for cancer. METHODS: A comprehensive electronic database search was conducted for all RCTs that compared aspirin versus placebo for the prevention of any type of disease, and where cancer incidence or mortality was reported. The primary outcome was cancerrelated mortality. Secondary outcomes were cancer incidence, all-cause mortality, major bleeding, any bleeding and gastrointestinal (GI) bleeding. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) using a random-effects model at the longest follow-up period. RESULTS: We included 16 RCTs with 104,018 total patients, mean age of 60.51 years, mean follow-up of 5.48 years, and a male percentage of 38.72%. We found that aspirin was not associated with a significant reduction of cancer-related mortality compared with placebo (RR 0.99; 95% CI: 0.87-1.12; P = 0.85: I2 = 41%). Compared with placebo, aspirin was not associated with significant reduction of all-cause mortality (RR 0.97; 95% CI: 0.92-1.02; P = 0.19; I2 = 13%) or cancer incidence (RR: 0.98; 95% CI: 0.92-1.04; P = 0.43; I2 = 16%). However, aspirin treatment was associated with significantly increased risks of any bleeding (RR 1.63; 95% CI: 1.31-2.03; P < 0.01), major bleeding (RR 1.41; 95% CI: 1.26-1.57; P < 0.01), and GI bleeding (RR 1.85; 95% CI: 1.38-2.48; P < 0.01) compared with placebo. CONCLUSION: Our study did not find any significant reductions in cancer-related mortality or cancer incidence when compared aspirin use with placebo or no aspirin. Our study also highlights that the use of aspirin for primary prevention of cancer was found to cause higher rates of bleeding (any bleeding, major bleeding, and GI bleeding) compared to placebo or no aspirin at the longest follow-up period with no significant benefit in cancer primary prevention.

PADUA score as a predictor for pulmonary embolism: a potential strategy for reducing unnecessary imaging.

An objective tool that is easy to integrate with an electronic medical record may help reduce unnecessary imaging for diagnosing a pulmonary embolism (PE). In this study, we assess the PADUA score in stratifying patients based on their risk of a PE. We reviewed charts of patients that underwent a computed tomography pulmonary angiogram (CT-PA) between January 2014 and September 2015 at our institution. Patient demographics including gender, age, race, and variables of the PADUA score were collected. The primary outcome was a positive CT-PA for a PE. Univariate and multivariate analysis was performed to derive predictors for a positive CT-PA. A receiver operator curve was calculated for the PADUA score and an optimal cutoff was calculated. Diagnostic test statistics were performed. Our study included 1067 patients. Of these, 185 (17.3%) had a PE. These patients tended to be older (64.3 SD 15.9 vs. 59.7 years SD 17.4, p < 0.01), have a higher proportion of Black patients (38.9% vs. 31.9%, p = 0.03), have a higher median [IQR] PADUA score (4.0 [3-6] vs. 3.0 [1-4], p < 0.01), and a higher rate of a DVT/PE history (30.3% vs. 5.2%, p < 0.01). Independent predictors included a DVT/PE history (OR: 7.65, 95% CI 4.89-12.0, p < 0.01), limited mobility (OR: 1.47, 95% CI 1.01-2.14, p = 0.046), and age 70 or greater (OR: 1.47, 95% CI 1.03-2.11, p = 0.03). The PADUA score had an AUC of 0.64 (95% CI 0.60-0.69, p = 0.046). The optimal cutoff was 4 and the sensitivity and specificity were 57.3% and 66.8%, respectively. The positive predictive and negative predictive values were 22.6% and 88.2%, respectively. The PADUA is a possible tool to stratify patients prior to performing a CT-PA. By using the score to guide management, we may be able to reduce unnecessary imaging through the implementation of the score in an EMR system. Further prospective research is warranted.