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Patients with brain tumors are at high risk for thromboembolic complications and frequently require anticoagulation. Direct oral anticoagulants (DOACs) are a less burdensome treatment for cancer‐associated thrombosis with safety and efficacy comparable to those of low molecular weight heparin (LMWH); however, there are few data to support the use of DOACs in patients with brain tumors. The purpose of this study was to better understand the safety profile of anticoagulants in patients with primary and metastatic brain tumors, with particular interest in the safety and efficacy of DOACs. Our hypothesis was that DOACs are as safe and effective as LWMH in this population. This study was conducted through a single‐center retrospective chart review of 125 patients with primary and metastatic brain tumors on anticoagulation. Our primary outcomes were major bleeding and intracranial hemorrhage (ICH), with secondary outcomes of minor bleeding and recurrent thrombosis. The rate of major bleeding was 26% in the LMWH group versus 9.6% in the DOAC group (p = .03). The rate of ICH was 15% in the LMWH group versus 5.8% in the DOAC group (p = .09). The severity of ICH in both groups was low with median Common Terminology Criteria for Adverse Events version 5 scores of 2 in the LMWH group and 3 in the DOAC group. The rates of minor bleeding and recurrent thrombosis were low in both groups. Our conclusion is that DOAC use in patients with brain tumors is not associated with increased rates of major bleeding compared with LMWH and is a safe and effective option. Implications for Practice Patients with brain tumors are at high risk for venous thromboembolism and frequently require anticoagulation. Direct oral anticoagulants (DOACs) are less burdensome than low molecular weight heparin (LMWH) for treatment of thromboembolism, but there is concern in the community over increased risk of bleeding. This study provides much‐needed objective evidence that there are fewer major bleeding events in patients with brain tumors on DOACs compared to LMWH with similar efficacy. As the paradigm of anticoagulation in patients with cancer shifts from LWMH toward DOACs, this work is particularly meaningful as it suggests DOACs are safe and effective for patients with brain tumors.

Background The 2016 U.S. Preventive Services Task Force (USPSTF) evidence report on colorectal cancer screening concluded that no colorectal cancer screening methods reduce all-cause mortality. This conclusion was partially based on a meta-analysis of 4 randomized trials that compared flexible sigmoidoscopy screening with no screening. The meta-analysis aggregated results from the 2 age cohorts of 1 of the trials-the NORCCAP (Norwegian Colorectal Cancer Prevention) study-as if these cohorts were a single trial (1). Aggregation of outcomes that have markedly different event rates, screening-control ratios, or both can create a Simpson paradox, a phenomenon where a finding exists in individual data groups that is absent or opposite when the groups are combined (2). The NORCCAP study involved 2 distinct trial cohorts because of a postscreening decision to expand the inclusion age to younger persons. The cohorts were randomly assigned separately. The additional age cohort (50 to 54 years) had a lower event rate and was randomly assigned with a screen-control ratio of 1:5.4 rather than the ratio of 1:3 used in the original older cohort (55 to 64 years) (3). Therefore, the meta-analysis in the USPSTF evidence report may be confounded because the aggregated NORCCAP results were used. Objective To assess results of the NORCCAP study for a Simpson paradox and to repeat meta-analysis of all-cause mortality outcomes for screening flexible sigmoidoscopy using the 2 NORCCAP age cohorts as individual trials. Methods Data for all-cause mortality were extracted from the 4 studies specified in Table 1 of the USPSTF evidence report (1). Only published data and intention-to-treat outcomes were used. The 2 NORCCAP study age cohorts were included as individual trials using outcome data published in an author response to a comment (4). Meta-analysis was performed using R, Version 3.0.1 with the meta and metafor packages (R Foundation for Statistical Computing) (5). The fixed-effects model was chosen because of the lack of heterogeneity (I 2

Background and Objectives: Demographic trends show an increasing older adult population. Therefore, family medicine training programs may need to reevaluate how well their residents perform clinic procedures essential to older adults. Our objective was to compare the rates of the most frequently performed clinic procedures for Medicare patients in a large multiregional health care system (MRHCS) with those in a family medicine residency clinic. Methods: In this retrospective cohort study, Current Procedural Terminology coding data were queried from the billing systems of an MRHCS (the control group) and a family medicine residency clinic (the study group) for a 3-year period. The primary outcome was the procedural rate ratios per 1,000 office visits for the 10 most common clinic procedures in the MRHCS billed to Medicare. Results: The study group consisted of 19,099 office visits by Medicare patients to the residency clinic; the control group consisted of 2,034,188 visits to the MRHCS. Except for large joint injection, procedural rates were significantly different for the other nine procedures (destruction of benign skin lesions, nail care, punch or shave skin biopsy, removal of impacted cerumen, wound debridement of skin, Unna boot application, excision of skin lesion, paring of corn or callus, and insertion of bladder catheter). The rate of skin excision was higher in the residency clinic than in the MRHCS but lower for the other eight procedures. Conclusions: These data suggest that teaching programs may need to adapt to meet the current and future practice needs of this increasing patient population.

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Background: Neuro-oncology patients, like all cancer patients, are at a high risk for thromboembolic complications and frequently require treatment with anticoagulation. DOACs have emerged as a less burdensome treatment for cancer associated thrombosis with comparable safety and efficacy to LMWH. Unfortunately, there is a paucity of data to support the use of DOACs in patients with primary and metastatic brain tumors and there is concern in the medical community for increased risk of intracranial hemorrhage. Objectives: The purpose of this study is to better understand the safety profile of anticoagulants in brain tumor patients, with a particular interest in the safety and efficacy of DOACs. Our hypothesis is that DOACs are as safe and effective as LWMH in this patient population. Methods: This study was conducted through retrospective chart review of patients with primary and metastatic brain tumors on anticoagulation. Our outcomes of interest were major bleeding (as defined by ISTH guidelines), with particular interest in Intracranial hemorrhage as well as minor bleeding and recurrent thrombosis. Radiographic images of all patients were reviewed for evidence of ICH and CTCAE v5 criteria were used to grade severity of ICH cases with range from 1 (asymptomatic imaging finding) to 5 (death). Results and Conclusions: A total of 130 patients with brain tumors were evaluated (69% primary brain tumor, 15% CNS lymphoma, 16% metastatic disease). Out of this population, 62 were on LMWH and 52 were on DOACs. The incidence of major bleeding was 20.9% in the LMWH group vs. 9.6% in the DOAC group (P =0.1, 95% CI -2.45 - 24.1). The incidence of ICH was 14.5% in the LMWH group and 5.8% in the DOAC group (P =0.13 95% CI -3.23 - 20.2). The severity of ICH in both groups was low with median CTCAE v5 scores of 2 in LMWH group and 3 in the DOAC group. The incidence of minor bleeding was 16.1% in LMWH group and 21.1% in the DOAC group (P = 0.49 CI -9.2 - 19.7). Recurrent thrombosis in both groups occurred in <5% of cases. Our conclusion is that in patients with primary and metastatic brain tumors, DOACs are not associated with an increased incidence of major bleeding or ICH compared to LMWH and are a safe and effective option in this patient population. Disclosures No relevant conflicts of interest to declare.

At the beginning of their offshore migration, hatchling sea turtles enter the ocean at night and establish a course away from land by swimming directly into oceanic waves. How turtles can detect wave direction while swimming under water in darkness, however, has not been explained. Objects in a water column beneath the surface of the ocean describe a circular movement as waves pass above. In principle, swimming turtles might, therefore, detect wave direction by monitoring the sequence of accelerations they experience under water. To determine whether loggerhead (Caretta caretta L.) and green turtle (Chelonia mydas L.) hatchlings can detect wave direction in this way, we constructed a wave motion simulator to reproduce in air the circular movements that occur beneath small ocean waves. Hatchlings suspended in air and subjected to movements that simulated waves approaching from their right sides attempted to turn right, whereas movements that simulated waves from the left elicited left-turning behavior. Movements simulating waves from directly in front of the turtles elicited little turning in either direction. The results demonstrate that hatchling sea turtles can determine the propagation direction of ocean waves by monitoring the circular movements that occur as waves pass above. Although sea turtles are the first animals shown to be capable of detecting wave direction in this way, such an orientation mechanism may be widespread among other transoceanic migrants such as fish and cetaceans.