Incidental pulmonary embolism in cancer and noncancer patients: Prospective cohort study.

BACKGROUND: Clinical picture and outcome of incidental pulmonary embolism (iPE) compared to symptomatic pulmonary embolism (sPE) remain unclear. METHODS: Demographics, recurrent venous thromboembolism (VTE), mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) were compared between iPE and sPE patients who were followed prospectively at Mayo Thrombophilia Clinic (March 1, 2013 to August 1, 2020). RESULTS: Out of 3576 VTE patients, 1417 (39.6%) had PE: 562 (39.7%) iPE and 855 sPE. Patients with cancer were more likely to have iPE (400 iPE vs. 314 sPE) compared to those without cancer (162 iPE vs. 541 sPE). VTE recurrence rate (all per 100 person-years) was similar in all iPE and sPE patients (3.34 vs. 3.68, p = .50), with cancer (4.16 vs. 4.89, p = .370), and without cancer patients (0.89 vs. 2.80, p = .25). Higher mortality observed in all patients with iPE compared to sPE (46.45 vs. 23.47, p < .001) and with cancer (56.41 vs. 45.77, p = .03) became not significant after adjustment for age, antiplatelet therapy, metastases, and cancer location. Noncancer iPE patients had higher mortality (15.95 vs. 7.18, p = .006) even after adjustment (p = .05). The major bleeding rate was also higher in all patients iPE compared to sPE (7.10 vs. 3.68, p = .03), but not after adjustment (p = .974); higher major bleeding rate in noncancer patients (6.49 vs. 1.25, p = .007) remained significant after adjustment (.02). CRNMB rate was similar to iPE and sPE patients. CONCLUSION: iPE represents a more serious clinical condition compared to sPE as indicated by the higher mortality and major bleeding but these differences reflect underlying comorbidities rather than the seriousness of the embolic event.

Single versus multiple and incidental versus symptomatic subsegmental pulmonary embolism: clinical characteristics and outcome.

It remains unexplored if the clinical picture and outcome of subsegmental pulmonary embolism (SSPE) differ between single versus multiple, and incidental versus symptomatic embolism. Consecutive patients anticoagulated for SSPE at the Mayo Thrombophilia Clinic (03/01/2013-12/31/2020) were followed forward to assess venous thromboembolism (VTE) recurrence, mortality, major bleeding, and clinically relevant non-major bleeding (CRNMB); expressed as a rate per 100 person-years. Among 3878 VTE patients, 1541 had pulmonary embolism including 224 (14.6%) with SSPE either single (n = 139) or multiple (n = 85; 46 bilateral and 39 unilateral emboli); 134 had incidental and 90 symptomatic SSPE. Patients with single were less often symptomatic and less often had coexisting DVT than multiple SSPE. Patients with incidental had a two-fold higher frequency of cancer compared to symptomatic SSPE. During the study period, 1 patient with single and 2 with multiple SSPE had VTE recurrence (rate of 1.14 vs 3.63, p = 0.280). Single SSPE patients experienced 2 episodes of major bleeding (rate of 2.36) while the multiple SSPE group had no major bleeding. Seven patients in each group had CRNMB events (rate of 8.20 vs 13.58 for single and multiple SSPE, respectively, p = 0.282). Patients with single SSPE had a higher death rate compared to multiple SSPE (43.07 vs 22.22, p = 0.031) but no difference was noted after adjusting for cancer (p = 0.388). Also, incidental had similar clinical outcomes to symptomatic SSPE.Interpretation Anticoagulated SSPE patients with single and multiple as well as incidental and symptomatic have a different clinical profile but similar clinical outcomes.

Effectiveness and safety of apixaban and rivaroxaban for acute venous thromboembolism therapy in patients with extremes in bodyweight.

OBJECTIVES: To investigate the association of extremes in bodyweight (EBW) and outcomes in patients with acute venous thromboembolism (VTE). Recurrent VTE, major bleeding, and clinically relevant non-major bleeding were compared between patients with bodyweight <60 kg, 60-120 kg, and >120 kg. METHODS: Consecutive patients enrolled in the Mayo Clinic VTE Registry (03/28/2013-8/31/2019) with acute VTE were followed prospectively. Patient status was assessed in person, by mailing a written questionnaire, or by a scripted phone interview. RESULTS: Among 2577 patients with weight ranging from 27.0 kg to 263.2 kg, 2123 (82%) had a bodyweight between 60 and 120 kg, 223 (8.7%) had bodyweight < 60 kg, and 230 (8.9%) had bodyweight >120 kg. Patients with bodyweight <60 kg treated with DOACs had higher 3- and 6-month incidence of major bleeding compared to the bodyweight 60-120kg group (4.4% vs 1.1%, P = .03, and 4.4% vs 1.4%, P = .05, respectively). Patients with bodyweight >120 kg and cancer on rivaroxaban had higher VTE recurrence compared to bodyweight 60-120kg group (P = .01). CONCLUSIONS: Treatment of acute VTE is associated with a higher incidence of bleeding in patients with bodyweight <60 kg. A higher VTE recurrence rate occurred only in cancer patients with bodyweight >120 kg on rivaroxaban.

Treatment of upper extremity deep vein thrombosis with apixaban and rivaroxaban.

Randomized controlled trials leading to the approval of apixaban and rivaroxaban for venous thromboembolism (VTE) did not include patients with upper extremity deep vein thrombosis (UE-DVT). We sought to evaluate the safety and effectiveness of rivaroxaban and apixaban for the treatment of acute UE-DVT. Consecutive patients with VTE enrolled into the Mayo Clinic VTE Registry, between March 1, 2013 and December 31, 2019, were followed prospectively. Clinical, demographic and imaging data were collected at the time of study recruitment. Patients with a diagnosis of acute UE-DVT who received rivaroxaban, apixaban, LMWH or warfarin were included. Recurrent VTE, major bleeding, clinical-relevant non-major bleeding (CRNMB), and death were assessed at 3-month intervals. During the study period, 210 patients with acute UE-DVT were included; 63 were treated with apixaban, 39 with rivaroxaban, and 108 with LWMH and/or warfarin. Overall 51% had catheter-associated UE-DVT, 60% had a diagnosis of malignancy, and 14% had concurrent pulmonary embolism. Malignancy was more common in patients treated with LMWH/warfarin (67% vs 52%, P = .03). At 3 months of follow up, one (0.9%) recurrent VTE occurred in a patient treated with LMWH/warfarin and one (1.0%) patient treated with apixaban or rivaroxaban (P = .97). Major bleeding occurred in three patients treated with LMWH/warfarin, and in none of those treated with apixaban or rivaroxaban (P = .09). Clinical-relevant non-major bleeding occurred in one patient (0.9%) treated with LWMH/warfarin and two patients (2.0%) treated with apixaban or rivaroxaban (P = .53). Treatment of UE-DVT with apixaban or rivaroxaban appears to be as safe and effective as LMWH/warfarin.

Comparison of apixaban to rivaroxaban and enoxaparin in acute cancer-associated venous thromboembolism.

To provide direct comparison between apixaban and rivaroxaban in patients with acute cancer-associated venous thromboembolism (Ca-VTE), consecutive patients treated with apixaban, rivaroxaban, or enoxaparin at Mayo Thrombophilia Clinic (March 1, 2013 to January 31, 2018)) were followed prospectively. The primary effectiveness outcome was venous thromboembolism (VTE) recurrence, and the secondary was mortality. The primary safety outcome was major bleeding, the secondary clinically relevant safety outcome was non-major bleeding (CRNMB), and the third a composite of major and CRNMB. There were 750 patients treated for acute Ca-VTE with apixaban (n = 224), rivaroxaban (n = 163), and enoxaparin (n = 363) within 14 days of diagnosis and for at least 3 months, or until study event. Recurrent VTE was diagnosed in 11 receiving apixaban, 7 receiving rivaroxaban (apixaban vs rivaroxaban hazard ratio (HR) 1.31, 95% confidence interval (95% CI) 0.51-3.36) and 17 in the enoxaparin receiving group (apixaban vs enoxaparin HR 1.14, 95% CI: 0.54, 2.42 and rivaroxaban vs enoxaparin HR 0.85, 95% Cl: 0.36, 2.06). There were 82 deaths in apixaban, 74 rivaroxaban (apixaban vs rivaroxaban HR 1.67, 95% Cl: 1.20, 2.33) and 171 in enoxaparin group (rivaroxaban vs enoxaparin HR 0.73, 95% Cl: 0.56, 0.96). Major bleeding occurred in 11 apixaban, 12 rivaroxaban (apixaban vs rivaroxaban HR 0.73, 95% Cl: 0.32, 1.66) and 21 enoxaparin group (apixaban vs enoxaparin HR 0.89, 95% Cl: 0.43, 1.84 and rivaroxaban vs enoxaparin HR 1.23, 95% Cl: 0.61, 2.50). The CRNMB rate was higher in rivaroxaban compared to apixaban (P = .03) and LMWH (P = .01) groups. Recurrence of VTE and major bleeding were similar in apixaban, rivaroxaban, and enoxaparin groups. Rivaroxaban was associated with higher CRNMB but lower mortality compared to apixaban and enoxaparin.

Symptomatic Venous Thromboembolism is Associated with Inferior Survival among Patients Undergoing Nephrectomy with Inferior Vena Cava Tumor Thrombectomy for Renal Cell Carcinoma.

PURPOSE: We investigated the incidence and survival impact of symptomatic venous thromboembolism after nephrectomy with inferior vena cava tumor thrombectomy. MATERIALS AND METHODS: We retrospectively reviewed the records of 183 patients who underwent nephrectomy with inferior vena cava tumor thrombectomy (level I-IV) for renal cell carcinoma between 2000 and 2010. Postoperative venous thromboembolism was defined as symptomatic bland thrombus or embolism confirmed on imaging. The cumulative incidence of venous thromboembolism was estimated by the Kaplan-Meier method. Associations of clinicopathological features with time to thromboembolism after surgery and all cause mortality were evaluated on multivariable analysis with Cox models. RESULTS: Symptomatic venous thromboembolism developed in 55 patients a median of 23 days (IQR 5-142) postoperatively, including pulmonary thrombosis in 24, deep venous thrombosis in 17, bland inferior vena cava thrombosis in 13 and portal vein thrombosis in 1. The cumulative incidence of thromboembolism 30, 90 and 365 days following surgery was 17%, 22% and 27%, respectively. A history of smoking (HR 2.15, 95% CI 1.09-4.24, p = 0.028), ECOG (Eastern Cooperative Oncology Group) performance status 1 or greater (HR 2.15, 95% CI 1.17-3.93, p = 0.013), hypercoagulability disorder (HR 5.12, 95% CI 1.93-13.59, p = 0.001) and bulky lymphadenopathy at surgery (HR 4.84, 95% CI 1.87-12.51, p = 0.001) was significantly associated with an increased risk of venous thromboembolism on multivariable analysis. Postoperative venous thromboembolism was significantly associated with an increased risk of all cause mortality (HR 1.53, 95% CI 1.04-2.23, p = 0.029). CONCLUSIONS: Venous thromboembolism after nephrectomy and tumor thrombectomy is common within 90 days of surgery. Symptomatic venous thromboembolism in this population is independently associated with a greater risk of mortality.

Comparison of natural language processing biosurveillance methods for identifying influenza from encounter notes.

BACKGROUND: An effective national biosurveillance system expedites outbreak recognition and facilitates response coordination at the federal, state, and local levels. The BioSense system, used at the Centers for Disease Control and Prevention, incorporates chief complaints but not data from the whole encounter note into its surveillance algorithms. OBJECTIVE: To evaluate whether biosurveillance by using data from the whole encounter note is superior to that using data from the chief complaint field alone. DESIGN: 6-year retrospective case-control cohort study. SETTING: Mayo Clinic, Rochester, Minnesota. PARTICIPANTS: 17,243 persons tested for influenza A or B virus between 1 January 2000 and 31 December 2006. MEASUREMENTS: The accuracy of a model based on signs and symptoms to predict influenza virus infection in patients with upper respiratory tract symptoms, and the ability of a natural language processing technique to identify definitional clinical features from free-text encounter notes. RESULTS: Surveillance based on the whole encounter note was superior to the chief complaint field alone. For the case definition used by surveillance of the whole encounter note, the normalized partial area under the receiver-operating characteristic curve (specificity, 0.1 to 0.4) for surveillance using the whole encounter note was 92.9% versus 70.3% for surveillance with the chief complaint field (difference, 22.6%; P < 0.001). Comparison of the 2 models at the fixed specificity of 0.4 resulted in sensitivities of 89.0% and 74.4%, respectively (P < 0.001). The relative risk for missing a true case of influenza was 2.3 by using the chief complaint field model. LIMITATIONS: Participants were seen at 1 tertiary referral center. The cost of comprehensive biosurveillance monitoring was not studied. CONCLUSION: A biosurveillance model for influenza using the whole encounter note is more accurate than a model that uses only the chief complaint field. Because case-defining signs and symptoms of influenza are commonly available in health records, the investigators believe that the national strategy for biosurveillance should be changed to incorporate data from the whole health record. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Cholesterol Embolization Syndrome Post Invasive Arterial Procedure: A Case Report.

Cholesterol embolization syndrome (CES) is a rare but systemic severe disease caused by the distal showering of cholesterol crystals after angiography, major surgery, thrombolysis, or anticoagulation. Here, we present a case of a 74-year-old male with a history of coronary artery disease, chronic kidney disease, peripheral vascular disease, antiphospholipid syndrome, and right internal carotid artery occlusion who developed purple discoloration and ulceration involving several toes two months after coronary artery bypass surgery. A broad differential diagnosis for blue toes was considered, and a biopsy was obtained, which revealed an arterial lumen filled with large cholesterol crystal spaces, confirming the diagnosis of CES. Treatment of CES remains a bimodal approach of supportive and prophylactic care. Although there is no direct evidence in favor of antiplatelet agents, their use seems reasonable because they have been shown to reduce the risk of other cardiovascular events in patients with extensive atherosclerosis. In this case, the patient's toe pain improved with the use of topical amitriptyline ketamine and has achieved complete resolution of pain and skin discoloration at a seven-month follow-up.

Influence of primary cancer site on clinical outcomes of anticoagulation for associated venous thromboembolism.

INTRODUCTION: The outcome of anticoagulation for cancer-associated venous thromboembolism (Ca-VTE) differs according to cancer location, but data are limited and inconsistent. MATERIALS AND METHODS: Patients with acute venous thromboembolism (VTE) enrolled between 03/01/2013 and 04/30/2021 were followed prospectively to assess VTE recurrence, major bleeding (MB), clinically relevant non-major bleeding (CRNMB), and death. RESULTS: There were 1702 (45.3 %) patients with Ca-VTE including: gastrointestinal (n = 340), pancreatic (n = 223), hematologic (n = 188), genitourinary (n = 163), lung (n = 139), ovarian (n = 109), breast (n = 97), renal (n = 75), prostate (n = 73), hepatobiliary (n = 70), brain (n = 57), and other cancers (n = 168); 2057 VTE patients had no cancer (NoCa-VTE). Hepatobiliary cancer had the highest VTE recurrence (all rates 100 person-years) of all cancers and higher compared to NoCa-VTE (13.69, p = 0.01), while the MB rate, although numerically higher (15.91), was not different (p = 0.09). Another 3 cancers had higher VTE recurrence but similar MB rates compared to NoCa-VTE: genitourinary [(9.59, p = 0.01) and (7.03, p = 1.0)], pancreatic [(9.74, p < 0.001) and (5.47, p = 1.00)], and hematologic [(5.29, p = 0.05) and (3.59, p = 1.0)]. Renal cancer had the highest rate of MB among all cancers and was higher than that of NoCa-VTE (16.49; p < 0.001), with no difference in VTE recurrence (1.62; p = 1.0). VTE recurrence and MB rates were not significantly different between NoCa-VTE and gastrointestinal, lung, breast, prostate, and brain cancers. CRNMB rates were similar and mortality higher in Ca-VTE patients, except for prostate and breast cancer, compared to NoCa-VTE. CONCLUSIONS: Significant differences in clinical outcomes indicate that anticoagulation strategies may need to be tailored to the primary cancer location.

Survival Implications of Thrombus Recurrence or Bleeding in Cancer Patients Receiving Anticoagulation for Venous Thromboembolism Treatment.

BACKGROUND: Study aims were to analyze prospectively collected data from patients with cancer-associated venous thromboembolism (VTE) to determine the impact of VTE recurrence and anticoagulant-related bleeding on all-cause mortality. PATIENTS/METHODS: Consecutive cancer patients with acute VTE treated with anticoagulants (March 1, 2013-November 30, 2021) were included in this analysis. Anticoagulant therapy-associated VTE recurrences, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) were assessed for their impact on all-cause mortality outcomes. RESULTS: This study included 1,812 cancer patients with VTE. Of these, there were 97 (5.4%) with recurrent VTE, 98 (5.4%) with major, and 104 (5.7%) with CRNMB while receiving anticoagulants. Recurrent VTE (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.16-2.00; p = 0.0028), major bleeding (HR: 1.82; 95% CI: 1.41-2.31; p = 0.006), and CRNMB (HR; 1.38; 95% CI: 1.05-1.81; p = 0.018) each adversely influenced mortality outcomes. Deep vein thrombosis as the incident thrombotic event type was associated with VTE recurrence (HR: 1.78; 95% CI: 1.08-2.89; p = 0.02). Neither cancer type nor stage, chemotherapy, or Ottawa risk category influenced VTE recurrence. Higher body weights (HR: 1.01; 95% CI: 1.00-1.01; p = 0.005) were associated with increased major bleeding, while high Ottawa scores (HR: 0.66; 95% CI: 0.46-0.96; p = 0.03) and apixaban treatment (HR: 0.62; 95% CI: 0.45-0.84; p = 0.002) were associated with fewer major bleeding outcomes. CONCLUSION: Among cancer patients receiving anticoagulant therapy for VTE, adverse outcomes such as VTE recurrence, major bleeding, or CRNMB increase mortality risk by 40 to 80%. Identifying variables predicting these outcomes may help risk-stratify patients with poor prognosis.

Bleeding in Patients With Gastrointestinal Cancer Compared With Nongastrointestinal Cancer Treated With Apixaban, Rivaroxaban, or Enoxaparin for Acute Venous Thromboembolism.

OBJECTIVE: To compare the bleeding risk in patients with gastrointestinal (GI) cancer with that in patients with non-GI cancer treated with anticoagulation for acute cancer-associated venous thromboembolism (Ca-VTE). PATIENTS AND METHODS: Consecutive patients with Ca-VTE seen at the Mayo Thrombophilia Clinic between March 1, 2013, and April 20, 2020, were observed prospectively to assess major bleeding and clinically relevant nonmajor bleeding (CRNMB). RESULTS: In the group of 1392 patients with Ca-VTE, 499 (35.8%) had GI cancer including 272 with luminal GI cancer (lower GI, 208; upper GI, 64), 176 with pancreatic cancer, and 51 with hepatobiliary cancer. The rate of major bleeding and CRNMB in patients with GI cancer was similar to that in 893 (64.2%) patients with non-GI cancer treated with apixaban, rivaroxaban, or enoxaparin. Apixaban had a higher rate of major bleeding in luminal GI cancer compared with the non-GI cancer group (15.59 vs 3.26 per 100 person-years; P=.004) and compared with enoxaparin in patients with luminal GI cancer (15.59 vs 3.17; P=.04). Apixaban had a lower rate of CRNMB compared with rivaroxaban in patients with GI cancer (3.83 vs 9.40 per 100 person-years; P=.03). Patients treated with rivaroxaban in the luminal GI cancer group had a major bleeding rate similar to that of patients with non-GI cancer (2.04 vs 4.91 per 100 person-years; P=.37). CONCLUSION: Apixaban has a higher rate of major bleeding in patients with luminal GI cancer compared with patients with non-GI cancer and compared with enoxaparin in patients with luminal GI cancer. Rivaroxaban shows no increased risk of major bleeding in patients with GI cancer or luminal GI cancer compared with patients with non-GI cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03504007.

Outcome of anticoagulation in isolated distal deep vein thrombosis compared to proximal deep venous thrombosis.

BACKGROUND: Isolated, distal deep vein thrombosis (IDDVT) is thought to have low rates of propagation, embolization, and recurrence compared with proximal DVT (PDVT), but the data are limited. OBJECTIVES: The objective of this study was to assess outcomes among patients with IDDVT compared with PDVT. PATIENTS/METHODS: Consecutive patients with ultrasound-confirmed acute DVT (March 1, 2013-August 1, 2020) were identified by reviewing the Mayo Clinic Gonda Vascular Center and VTE Registry databases. Patients were divided into two groups depending on the DVT location (isolated, distal vs. proximal DVT). Outcomes including venous thromboembolism (VTE) recurrence, major bleeding, and death were compared by thrombus location and anticoagulant therapy, warfarin vs. direct oral anticoagulant (DOAC). RESULTS: Isolated, distal deep vein thrombosis (n = 746) was more often associated with recent surgery, major trauma, or confinement (p < .001), whereas patients with PDVT (n = 1176) were more frequently unprovoked, had a prior history of VTE, or active cancer (p < .001). There was no overall difference in VTE recurrence or major bleeding between groups during follow-up. Patients with IDDVT had a higher death rate at 3 months (p = .001) and when propensity scored for cancer (p = .003). Independent predictors of mortality included warfarin (vs. DOAC) therapy, increasing age, and active cancer. DOAC therapy resulted in lower VTE recurrence, major bleeding, and death rates in both groups. CONCLUSION: Outcomes of IDDVT including VTE recurrence and bleeding rates were similar to PDVT despite higher early mortality rates. Outcomes for both groups were positively influenced by the use of DOACs.

Calf Vein Thrombosis Outcomes Comparing Anticoagulation and Serial Ultrasound Imaging Management Strategies.

OBJECTIVE: To compare outcomes among patients with calf deep vein thrombosis (DVT) stratified by management strategy because distal or calf DVT is said to have low rates of propagation, embolization, and recurrence and, as such, guideline recommendations include provisions for serial imaging without treatment. PATIENTS AND METHODS: Consecutive patients with ultrasound-confirmed acute DVT involving the calf veins (January 1, 2016, to August 1, 2018) were identified by scrutinizing the Gonda Vascular Center Ultrasound database. Patients were segregated into 2 categories depending on management strategy; anticoagulation vs serial surveillance ultrasound without anticoagulation. Outcomes including venous thromboembolism (VTE) recurrence, bleeding, death, and net clinical benefit were compared by treatment strategy. RESULTS: There were 483 patients with calf DVT identified; 399 were treated with anticoagulation therapy and 84 were managed with surveillance ultrasound. Patients in the surveillance group were older (70.0±13.9 vs 63.0±14.9 years; P<.001) and more likely to have had a recent hospitalization (76.2% [64/84] vs 45.4% [181/399]; P<.001). Common reasons for choosing ultrasound surveillance included guideline prescriptive (58.3% [49/84]), active bleeding (21.4% [18/84]), and recent surgery (17.9% [15/84]). The VTE recurrence composite was lower for patients treated with anticoagulants (7.3% [29/399]) compared with surveillance (14.3% [12/84]; P=.04). The DVT propagation was less frequent in the treated group (2.8% [11/399] vs 8.3% [7/84]; P=.01). There was no difference in bleeding or mortality outcomes by management strategy. Net clinical benefit (VTE recurrence plus major bleeding) favored anticoagulant therapy (9.8% [39/399] vs 20.2% [17/84]; P<.01). CONCLUSION: Patients with calf DVT treated with anticoagulants had significantly better outcomes compared with those managed by a strategy of serial ultrasound surveillance without increasing bleeding outcomes.

Adverse Events and Mortality in Anticoagulated Patients with Different Categories of Pulmonary Embolism.

OBJECTIVE: To determine whether the pulmonary embolism (PE) categories of massive, submassive, PE with no right ventricle dysfunction (NRVD), and subsegmental only (SSO) adequately predict clinical outcome. METHODS: Patients treated for acute PE (March 1, 2013, through July 31, 2019) were followed forward prospectively to compare venous thromboembolism (VTE) recurrence, all-cause mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) across 4 PE categories. RESULTS: Of 2703 patients with VTE, 1188 (44%) had PE, of which 1021 (85.9%) completed at least 3 months of therapy or had clinical outcomes precluding further treatment (27 with massive, 217 submassive, 557 NRVD, and 220 SSO PE). One patient with massive, 8 with submassive, 23 with NRVD, and 5 with SSO PE had recurrent VTE (3.90, 5.33, 5.36, and 3.66 per 100 person-years, respectively; P=.84). There were 3 deaths in massive, 27 in submassive, 140 in NRVD, and 34 in SSO PE groups (11.59, 17.37, 31.74, and 24.74 per 100 person-years, respectively; P=.02); when adjusted for cancer, the relationship was no longer significant (P=.27). One patient with massive, 5 with submassive, 22 with NRVD, and 5 with SSO PE had major bleeding (3.90, 3.31, 5.24, and 3.75 per 100 person-years, respectively; P=.66). Similar cumulative rates for CRNMB were observed (P=.87). Three-month rates of VTE recurrence, death, major bleeding, and CRNMB did not differ by PE category. CONCLUSION: In the setting of anticoagulation therapy with maximal standardization and evidence-based practice, there is no evidence of a difference between PE categories and outcomes. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03504007.

Using SNOMED CT to represent two interface terminologies.

OBJECTIVE: Interface terminologies are designed to support interactions between humans and structured medical information. In particular, many interface terminologies have been developed for structured computer based documentation systems. Experts and policy-makers have recommended that interface terminologies be mapped to reference terminologies. The goal of the current study was to evaluate how well the reference terminology SNOMED CT could map to and represent two interface terminologies, MEDCIN and the Categorical Health Information Structured Lexicon (CHISL). DESIGN: Automated mappings between SNOMED CT and 500 terms from each of the two interface terminologies were evaluated by human reviewers, who also searched SNOMED CT to identify better mappings when this was judged to be necessary. Reviewers judged whether they believed the interface terms to be clinically appropriate, whether the terms were covered by SNOMED CT concepts and whether the terms' implied semantic structure could be represented by SNOMED CT. MEASUREMENTS: Outcomes included concept coverage by SNOMED CT for study terms and their implied semantics. Agreement statistics and compositionality measures were calculated. RESULTS: The SNOMED CT terminology contained concepts to represent 92.4% of MEDCIN and 95.9% of CHISL terms. Semantic structures implied by study terms were less well covered, with some complex compositional expressions requiring semantics not present in SNOMED CT. Among sampled terms, those from MEDCIN were more complex than those from CHISL, containing an average 3.8 versus 1.8 atomic concepts respectively, p<0.001. CONCLUSION: Our findings support using SNOMED CT to provide standardized representations of information created using these two terminologies, but suggest that enriching SNOMED CT semantics would improve representation of the external terms.

Apixaban and Rivaroxaban in Patients With Acute Venous Thromboembolism.

OBJECTIVE: To compare the clinical efficacy and safety of apixaban with those of rivaroxaban for the treatment of acute venous thromboembolism (VTE). PATIENTS AND METHODS: Consecutive patients enrolled in the Mayo Thrombophilia Clinic Registry (between March 1, 2013, and January 30, 2018) and treated with apixaban or rivaroxaban for acute VTE were followed forward in time. The primary efficacy outcome was VTE recurrence. The primary safety outcome was major bleeding; the second safety outcome was clinically relevant nonmajor bleeding (CRNMB); and the third was a composite of major bleeding or CRNMB. RESULTS: Within the group of 1696 patients with VTE enrolled, 600 (38%) were treated either with apixaban (n=302, 50%) or rivaroxaban (n=298, 50%) within the first 14 days of VTE diagnosis and who completed at least 3 months of therapy or had a study event. Recurrent VTE was diagnosed in 7 patients (2.3%) treated with apixaban and in 6 (2%) treated with rivaroxaban (adjusted hazard ratio [aHR], 1.4; 95% CI, 0.5-3.8). Major bleeding occurred in 11 patients (3.6%) receiving apixaban and in 9 patients (3.0%) receiving rivaroxaban (aHR, 1.2; 95% CI, 0.5-3.2). Clinically relevant nonmajor bleeding was diagnosed in 7 patients (2.3%) receiving apixaban and in 20 (6.7%) receiving rivaroxaban (aHR, 0.4; 95% CI, 0.2-0.9). The rates of composite major bleeding or CRNMB were similar (aHR, 0.6; 95% CI, 0.3-1.2). Most study events occurred in patients with cancer. CONCLUSION: In the setting of a standardized, guideline-directed, patient-oriented clinical practice, the efficacy and safety of apixaban and rivaroxaban for the treatment of acute VTE were comparable.

Biosurveillance evaluation of SNOMED CT's terminology (BEST Trial): coverage of chief complaints.

The current United States Health Information Technology Standards Panel's interoperability specification for biosurveillance relies heavily on chief complaint data for tracking rates of cases compatible with a case definition for diseases of interest (e.g. Avian Flu). We looked at SNOMED CT to determine how well this large general medical ontology could represent data held in chief complaints. In this experiment we took 50,000 records (Comprehensive Examinations or Limited Examinations from primary care areas at the Mayo Clinic) from December 2003 through February 2005 (Influenza Season). Of these records, 36,097 had non-null Chief Complaints. We randomly selected 1,035 non-null Chief Complaints and two Board-certified internists (one Infectious Diseases specialist and one general internist) reviewed the mappings of the 1,035 chief complaints. Where the reviewers disagreed, a third internist adjudicated. SNOMED CT had a sensitivity of 98.7% for matching clinical terms found in the chief complaint section of the clinical record. The positive predictive value was 97.4%, the negative predictive value was 89.5%, the specificity was 81.0%, the positive likelihood ratio was 5.181 and the negative likelihood ratio was 0.016. We conclude that SNOMED CT and natural language parsing engines can well represent the clinical content of chief complaint fields. Future research should focus on how well the information contained in the chief complaints can be relied upon to provide the basis of a national strategy for biosurveillance. The authors recommend that efforts be made to examine the entire clinical record to determine the level of improvement in the accuracy of biosurveillance that can be achieved if we were to incorporate the entire clinical record into our biosurveillance strategy.

Evaluation of a quantitative D-dimer latex immunoassay for acute pulmonary embolism diagnosed by computed tomographic angiography.

OBJECTIVE: To determine the sensitivity and specificity of a quantitative plasma fibrin D-dimer latex immunoassay (LIA) for the diagnosis of acute pulmonary embolism. SUBJECTS AND METHODS: Study subjects were Mayo Clinic Rochester inpatients and outpatients with suspected acute pulmonary embolism; all had undergone quantitative D-dimer LIA testing and multidetector-row computed tomographic (CT) angiography between August 3, 2001, and November 10, 2003. Multidetector-row CT angiography was the diagnostic reference standard. RESULTS: Of 1355 CT studies, 208 (15%) were positive for acute pulmonary embolism. Median D-dimer levels were significantly higher for patients with acute pulmonary embolism (1425 ng/mL) than for patients without (500 ng/mL) (P<.001). The highest specificity that optimizes sensitivity for acute pulmonary embolism was achieved by using a discriminant value of 300 ng/mL, which yielded a sensitivity of 0.94 (95% confidence interval [CI], 0.89-0.97), a specificity of 0.27 (95% CI, 0.25-0.30), and a negative predictive value of 0.96 (95% CI, 0.93-0.98). CONCLUSION: The quantitative D-dimer LIA with a discriminant value of 300 ng/mL had high sensitivity and high negative predictive value but low specificity for the diagnosis of acute pulmonary embolism. On the basis of these results, we believe that a negative quantitative D-dimer LIA result and a low pretest probability of thromboembolism together are sufficient to exclude acute pulmonary embolism.

Saddle pulmonary embolism diagnosed by CT angiography: frequency, clinical features and outcome.

OBJECTIVE: To assess the frequency, clinical presentation and outcome associated with saddle pulmonary embolism (PE) diagnosed by computed tomographic angiography (CTA). PATIENTS: Retrospective review of 546 consecutive patients diagnosed to have acute PE by CTA from 1 September 2002 to 31 December 2003. RESULTS: Fourteen of 546 patients (2.6%) had saddle PE; 10 were men (71%). None of these patients had pre-existing cardiopulmonary disease. Most common presenting symptoms included dyspnea (72%) and syncope (43%). Hypotension was documented in 2 patients (14%). The most common risk factor for PE was obesity (64%). CTA revealed saddle PE and additional filling defects in the main pulmonary arteries in all patients. Echocardiography was performed within 48 h of the PE diagnosis in 10 patients and revealed right ventricular dysfunction in 8 (80%). All patients were initially managed in the hospital, median length of stay of 4 days (range, 1-45 days). Standard anticoagulant therapy with heparin and warfarin was administered to all patients. Five patients (36%) received additional therapy; thrombolytic therapy was administered to 1 patient (7%) and 4 patients (29%) received an inferior vena cava filter. None of the patients died during their hospitalization. Four patients (29%) died following their hospitalization after intervals of 1, 5, 6, and 12 months, respectively. Causes of death were known in 3 patients, all of whom died from progressive malignancy. CONCLUSION: Saddle PE in patients without pre-existing cardiopulmonary disease is associated with a relatively low in-hospital mortality rate and may not necessitate aggressive medical management.