Search

BACKGROUND: Periprocedural bridging with unfractionated heparin or low-molecular-weight heparin aims to reduce the risk of thromboembolic events in patients receiving long-term vitamin K antagonists. Optimal periprocedural anticoagulation has not been established. METHODS AND RESULTS: MEDLINE, EMBASE, and Cochrane databases (2001-2010) were searched for English-language studies including patients receiving heparin bridging during interruption of vitamin K antagonists for elective procedures. Data were independently collected by 2 investigators ([kappa]=0.90). The final review included 34 studies with 1 randomized trial. Thromboembolic events occurred in 73 of 7118 bridged patients (pooled incidence, 0.9%; 95% confidence interval [CI], 0.0.0-3.4) and 32 of 5160 nonbridged patients (pooled incidence, 0.6%; 95% CI, 0.0-1.2). There was no difference in the risk of thromboembolic events in 8 studies comparing bridged and nonbridged groups (odds ratio, 0.80; 95% CI, 0.42-1.54). Bridging was associated with an increased risk of overall bleeding in 13 studies (odds ratio, 5.40; 95% CI, 3.00-9.74) and major bleeding in 5 studies (odds ratio, 3.60; 95% CI, 1.52-8.50) comparing bridged and nonbridged patients. There was no difference in thromboembolic events (odds ratio, 0.30; 95% CI, 0.04-2.09) but an increased risk of overall bleeding (odds ratio, 2.28; 95% CI, 1.27-4.08) with full versus prophylactic/intermediate-dose low-molecular-weight heparin bridging. Low-thromboembolic-risk and/or non-vitamin K antagonist patient groups were used for comparison. Study quality was poor with heterogeneity for some analyses. CONCLUSIONS: Vitamin K antagonist-treated patients receiving periprocedural heparin bridging appear to be at increased risk of overall and major bleeding and at similar risk of thromboembolic events compared to nonbridged patients. Randomized trials are needed to define the role of periprocedural heparin bridging. [ABSTRACT FROM AUTHOR]

Background: Andexanet alfa is a modified recombinant inactive form of human factor Xa developed for reversal of factor Xa inhibitors.Methods: We evaluated 352 patients who had acute major bleeding within 18 hours after administration of a factor Xa inhibitor. The patients received a bolus of andexanet, followed by a 2-hour infusion. The coprimary outcomes were the percent change in anti-factor Xa activity after andexanet treatment and the percentage of patients with excellent or good hemostatic efficacy at 12 hours after the end of the infusion, with hemostatic efficacy adjudicated on the basis of prespecified criteria. Efficacy was assessed in the subgroup of patients with confirmed major bleeding and baseline anti-factor Xa activity of at least 75 ng per milliliter (or ≥0.25 IU per milliliter for those receiving enoxaparin).Results: Patients had a mean age of 77 years, and most had substantial cardiovascular disease. Bleeding was predominantly intracranial (in 227 patients [64%]) or gastrointestinal (in 90 patients [26%]). In patients who had received apixaban, the median anti-factor Xa activity decreased from 149.7 ng per milliliter at baseline to 11.1 ng per milliliter after the andexanet bolus (92% reduction; 95% confidence interval [CI], 91 to 93); in patients who had received rivaroxaban, the median value decreased from 211.8 ng per milliliter to 14.2 ng per milliliter (92% reduction; 95% CI, 88 to 94). Excellent or good hemostasis occurred in 204 of 249 patients (82%) who could be evaluated. Within 30 days, death occurred in 49 patients (14%) and a thrombotic event in 34 (10%). Reduction in anti-factor Xa activity was not predictive of hemostatic efficacy overall but was modestly predictive in patients with intracranial hemorrhage.Conclusions: In patients with acute major bleeding associated with the use of a factor Xa inhibitor, treatment with andexanet markedly reduced anti-factor Xa activity, and 82% of patients had excellent or good hemostatic efficacy at 12 hours, as adjudicated according to prespecified criteria. (Funded by Portola Pharmaceuticals; ANNEXA-4 ClinicalTrials.gov number, NCT02329327.). [ABSTRACT FROM AUTHOR]

Background: Limited language proficiency is an established barrier to research participation among racialized populations. While prior studies have highlighted the underrepresentation of racialized populations in venous thromboembolism (VTE) research, the impact of limited language proficiency as a reason for nonconsent among eligible patients is unknown., Objectives: To determine the impact of language barrier as the primary reason for VTE research non-participation., Methods: We reviewed all prospective VTE studies conducted at a research-intensive academic thrombosis research program in Canada between 2014 and 2024. Studies with screening logs that systematically and consecutively captured eligibility assessment and reasons for nonconsent were included. Primary outcome was nonconsent of a screen-eligible patient due to limited language proficiency as the reported reason. We derived pooled estimates of nonconsent due to limited language proficiency as a proportion of consented participants and determined subgroup rates by phase of VTE management, associated medical conditions, and recruitment settings., Results: Screening logs of 28 studies with 22 057 screening events, 8317 screen-eligible patients, and 3320 consented participants were included. For every 100 consented participants, 3.2 (95% CI, 2.0-5.3) screen-eligible individuals were unable to provide consent due to limited language proficiency. Rates of nonconsent were highest in studies involving cancer (5.6 per 100 participants; 95% CI, 2.9-10.4) and in studies recruiting patients from ambulatory settings outside of the thrombosis clinic (10.8 per 100 participants; 95% CI, 4.8-22.6)., Conclusion: Language proficiency is a key barrier to VTE research participation. Urgent implementation of targeted interventions aimed at mitigating linguistic barriers is essential to ensure equitable opportunities for VTE research participation for racialized patients disproportionately affected by language proficiency., Competing Interests: Declaration of competing interests M.C. reports research grants from Pfizer, Bristol-Myers Squibb, and LEO Pharma and consultancy honoraria from Pfizer, Bayer, Sanofi, Servier, and LEO Pharma. P.W. reports consulting in a legal case for Bayer Healthcare. D.S. has received honoraria paid indirectly to her research institute from AstraZeneca, BMS-Pfizer, Roche, and Servier. T.-F.W. reports advisory board honoraria from Valeo and research funding to the institution from LEO Pharma. L.C.’s research institution has received honoraria from Bayer, BMS-Pfizer, The Academy for Continued Advancement in Healthcare Education, Amag Pharmaceutical, LEO Pharma, Sanofi, Valeo Pharma, and Servier. All other authors have no financial or personal relationships or affiliations that could influence the decisions and work on this article., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Direct oral anticoagulants (DOACs) do not require routine monitoring of anticoagulant effect, but measuring DOAC activity may be desirable in specific circumstances to detect whether clinically significant DOAC levels are present (eg, prior to urgent surgery) or to assess whether drug levels are excessively high or excessively low in at-risk patients (eg, after malabsorptive gastrointestinal surgery). Routine coagulation tests, including the international normalized ratio (INR) or activated partial thromboplastin time (aPTT), cannot accurately quantify drug levels but may provide a qualitative assessment of DOAC activity when considering the estimated time to drug clearance based on timing of last drug ingestion and renal and hepatic function. Drug-specific chromogenic and clot-based assays can quantify drug levels but they are not universally available and do not have established therapeutic ranges. In this review, we discuss our approach to measuring DOAC drug levels, including patient selection, interpretation of coagulation testing, and how measurement may inform clinical decision-making in specific scenarios., (Copyright © 2024 by The American Society of Hematology.)

Introduction: Clinically significant post-endoscopic retrograde cholangiopancreatography (ERCP) bleeding (CSPEB) is common. Contemporary estimates of risk are lacking. We aimed to identify risk factors of and outcomes after CSPEB., Methods: We analyzed multicenter prospective ERCP data between 2018 and 2024 with 30-day follow-up. The primary outcome was CSPEB, defined as hematemesis, melena, or hematochezia resulting in (i) hemoglobin drop ≥ 20 g/L or transfusion and/or (ii) endoscopy to evaluate suspected bleeding and/or (iii) unplanned healthcare visitation and/or prolongation of existing admission. Firth logistic regression was used. P values <0.05 were significant, with odds ratios (ORs) and 95% confidence intervals reported., Results: CSPEB occurred after 129 (1.5%) of 8,517 ERCPs (mean onset 3.2 days), with 110 of 4,849 events (2.3%) occurring after higher risk interventions (sphincterotomy, sphincteroplasty, precut sphincterotomy, and/or needle-knife access). Patients with CSPEB required endoscopy and transfusion in 86.0% and 53.5% of cases, respectively, with 3 cases (2.3%) being fatal. P2Y 12 inhibitors were held for a median of 4 days (interquartile range 4) before higher risk ERCP. After higher risk interventions, P2Y 12 inhibitors (OR 3.33, 1.26-7.74), warfarin (OR 8.54, 3.32-19.81), dabigatran (OR 13.40, 2.06-59.96), rivaroxaban (OR 7.42, 3.43-15.24), and apixaban (OR 4.16, 1.99-8.20) were associated with CSPEB. Significant intraprocedural bleeding after sphincterotomy (OR 2.32, 1.06-4.60), but not after sphincteroplasty, was also associated. Concomitant cardiorespiratory events occurred more frequently within 30 days after CSPEB (OR 12.71, 4.75-32.54)., Discussion: Risks of antiplatelet-related CSPEB may be underestimated by endoscopists based on observations of suboptimal holding before higher risk ERCP. Appropriate periprocedural antithrombotic management is essential and could represent novel quality initiative targets., (Copyright © 2024 by The American College of Gastroenterology.)

Introduction: Factor Xa inhibitor (FXaI)-associated bleeding events are common and associated with substantial morbidity. Systematic evaluation of widely available, effective, and affordable FXaI bleed management strategies is needed., Materials and Methods: We conducted a single-center retrospective cohort study of FXaI-treated patients presenting to a tertiary academic medical center from January 2018 to May 2019 who received 25-50 IU/kg 4F-PCC for either FXaI-associated major bleeding or urgent surgery. The primary outcome was hemostatic efficacy, and the safety outcome was the 30-day risk of thromboembolism., Results: PCC was used to treat FXaI-associated bleeding in 83 cases (79.1 %) and was given before urgent surgery in 22 cases (20.9 %). Sixty-six patients were on apixaban, 38 were on rivaroxaban and one patient was on edoxaban. Intracranial hemorrhage (ICH) and gastrointestinal bleeding accounted for most bleeds (74.7 %). Median interval between last DOAC intake and presentation to triage was 9 h [IQR 5.3-14.8] and median PCC dosing was 40.0 IU/kg [IQR 28.5-46.6]. Forty-two patients (40.0 %) had pre-PCC FXaI levels drawn with median FXaI levels of 114.5 ng/mL [IQR 70.0-175.0]. Effective hemostasis occurred in 66.7 % [95%CI 55.4-76.3] of patients receiving PCC for bleeding and surgical hemostasis was rated as normal in 95.5 % (95%CI 76.5-100.0) for patients having urgent surgery. The 30-day risk of thromboembolism was 7.6 % [95%CI 3.7-14.5] and 22.9 % [95%CI 15.8-31.8] of patients died., Conclusions: PCC for FXaI-associated bleeding was associated with hemostatic efficacy in two-thirds of patients and thromboembolic events were uncommon. PCC represents a promising treatment strategy for FXaI-associated bleeding., Competing Interests: Declaration of competing interest J.R. Shaw has received in-kind laboratory support from Diagnostica Stago. J.H. Levy serves on steering committees for Merck, Octapharma, Takeda, and Werfen. S. Schulman reports research grant funding from Octapharma and honoraria from Alexion, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Regeneron, Sanofi, and Takeda. D.M. Siegal has received honoraria paid indirectly to her institution from Astra Zeneca, BMS-Pfizer, Servier. D. Dowlatshahi has provided consultation to Astra Zeneca Canada. M. Carrier has received research funding from Leo Pharma and Pfizer, in addition to honoraria from BMS, Valeo Pharma, Leo Pharma, Sanofi and Servier. L. Castellucci's research institution has received honoraria from Bayer, BMS-Pfizer Alliance, The Academy for Continued Advancement in Healthcare Education, Amag Pharmaceutical, LEO Pharma, Sanofi, Valeo Pharma, and Servier., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This Intensive Care Medicine Rapid Practice Guideline (ICM-RPG) provides an evidence-based recommendation to address the question: in adult patients in intensive care units (ICUs), should we use small-volume or conventional blood collection tubes?, Methods: We included 23 panelists in 8 countries and assessed and managed financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. We conducted a systematic review, including evidence from observational and randomized studies. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, we evaluated the certainty of evidence and developed recommendations using the Evidence-to-Decision framework., Results: We identified 8 studies (1 cluster and 2 patient-level randomized trials; 5 observational studies) comparing small-volume to conventional tubes. We had high certainty evidence that small-volume tubes reduce daily and cumulative blood sampling volume; and moderate certainty evidence that they reduce the risk of transfusion and mean number of red blood cell units transfused, but these estimates were limited by imprecision. We had high certainty that small-volume tubes have a similar rate of specimens with insufficient quantity. The panel considered that the desirable effects of small-volume tubes outweigh the undesirable effects, are less wasteful of resources, and are feasible, as demonstrated by successful implementation across multiple countries, although there are upfront implementation costs to validate small-volume tubes on laboratory instrumentation., Conclusion: This ICM-RPG panel made a strong recommendation for the use of small-volume sample collection tubes in adult ICUs based on overall moderate certainty evidence., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

The currently approved direct oral anticoagulants (DOACs) are increasingly used in clinical practice. Although serious bleeding risks are lower with DOACs than with vitamin K antagonists, bleeding remains the most frequent side effect. Andexanet alfa and idarucizumab are the currently approved specific reversal agents for oral factor (F)Xa inhibitors and dabigatran, respectively. Our prior guidance document was published in 2016, but with more information available on the utility and increased use of these reversal agents and other bleeding management strategies, we have updated this International Society on Thrombosis and Haemostasis guidance document on DOAC reversal. In this narrative review, we compare the mechanism of action of specific and nonspecific reversal agents, review the clinical data supporting their use, and provide guidance on when reversal is indicated. In addition, we briefly discuss the reversal of oral FXIa inhibitors, a new class of DOACs currently under clinical development., Competing Interests: Declaration of competing interests J.H.L.: Participation on Advisory or Steering Committees for Grifols, Octapharma, Takeda, and Werfen. J.R.S.: In-kind laboratory support from Diagnostica Stago. L.A.C.: L.A.C.’s research institution has received honoraria from Bayer, BMS-Pfizer Alliance, The Academy for Continued Advancement in Healthcare Education, Amag Pharmaceutical, LEO Pharma, Sanofi, Valeo Pharma, and Servier. L.A.C. holds a Tier 2 Research Chair from the University of Ottawa. J.M.C.: Participation on Scientific Advisory Boards and consulting for Abbott, Anthos, BMS, Pfizer, Roche, Sanofi, and Werfen; research funding from CSL Behring to the institution. J.D.: Serves on advisory committees for Pfizer, Sanofi, Leo Pharma, Bristol-Myers Squibb, and Janssen. E.L-L.: Lecture honoraria and advisory fees from Bayer AG, Boehringer Ingelheim, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo, Portola, CSL Behring, Norgine, Roche, Leo, AstraZeneca, and Aspen; institutional research support from Bayer AG, Bristol-Myers Squibb/Pfizer, Daiichi Sankyo, Werfen, and CSL Behring. B.R.: Consultant for AbocaSRL on medical devices; Advisory Committee for Bayer AG. C.M.S.: Advisory for Norgine Pharma. D.S.: Honoraria for educational presentations and advisory fees paid indirectly to research institute from AstraZeneca, BMS-Pfizer, Roche, Servier. D.S. is supported by a Tier 2 Canada Research Chair in Anticoagulant Management of Cardiovascular Disease. J.I.W.: Consultant or member of Advisory Boards or Steering Committees for Anthos, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Johnson and Johnson, Merck, and Regeneron., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Purpose: The ordering of routine blood test panels in advance is common in intensive care units (ICUs), with limited consideration of the pretest probability of finding abnormalities. This practice contributes to anemia, false positive results, and health care costs. We sought to understand practices and attitudes of Canadian adult intensivists regarding ordering of blood tests in critically ill patients., Methods: We conducted a nationwide Canadian cross-sectional survey consisting of 15 questions assessing three domains (global perceptions, test ordering, daily practice), plus 11 demographic questions. The target sample was one intensivist per adult ICU in Canada. We summarized responses using descriptive statistics and present data as mean with standard deviation (SD) or count with percentage as appropriate., Results: Over seven months, 80/131 (61%) physicians responded from 77 ICUs, 50% of which were from Ontario. Respondents had a mean (SD) clinical experience of 12 (9) years, and 61% worked in academic centres. When asked about their perceptions of how frequently unnecessary blood tests are ordered, 61% responded "sometimes" and 23% responded "almost always." Fifty-seven percent favoured ordering complete blood counts one day in advance. Only 24% of respondents believed that advanced blood test ordering frequently led to changes in management. The most common factors perceived to influence blood test ordering in the ICU were physician preferences, institutional patterns, and order sets., Conclusion: Most respondents to this survey perceived that unnecessary blood testing occurs in the ICU. The survey identified possible strategies to decrease the number of blood tests., (© 2024. Canadian Anesthesiologists' Society.)

The 7 th edition of the Canadian Stroke Best Practice Recommendations (CSBPR) is a comprehensive summary of current evidence-based recommendations, appropriate for use by healthcare providers and system planners, and intended to drive healthcare excellence, improved outcomes and more integrated health systems. This edition includes a new module on the management of cerebral venous thrombosis (CVT). Cerebral venous thrombosis is defined as thrombosis of the veins of the brain, including the dural venous sinuses and/or cortical or deep veins. Cerebral venous thrombosis is a rare but potentially life-threatening type of stroke, representing 0.5-1.0% of all stroke admissions. The reported rates of CVT are approximately 10-20 per million and appear to be increasing over time. The risk of CVT is higher in women and often associated with oral contraceptive use and with pregnancy and the puerperium. This guideline addresses care for adult individuals who present to the healthcare system with current or recent symptoms of CVT. The recommendations cover the continuum of care from diagnosis and initial clinical assessment of symptomatic CVT, to acute treatment of symptomatic CVT, post-acute management, person-centered care, special considerations in the long-term management of CVT, including pregnancy and considerations related to CVT in special circumstances such as trauma and vaccination. This module also includes supporting materials such as implementation resources to facilitate the adoption of evidence into practice and performance measures to enable monitoring of uptake and effectiveness of recommendations.

Objectives: To evaluate whether a focused, expert medication management intervention is feasible and potentially effective in preventing anticoagulation-related adverse events for patients transitioning from hospital to home., Design: Randomised, parallel design., Setting: Medical wards at six hospital sites in southern Ontario, Canada., Participants: Adults 18 years of age or older being discharged to home on an oral anticoagulant (OAC) to be taken for at least 4 weeks., Interventions: Clinical pharmacologist-led intervention, including a detailed discharge medication management plan, a circle of care handover and early postdischarge virtual check-up visits to 1 month with 3-month follow-up. The control group received the usual care., Outcomes Measures: Primary outcomes were study feasibility outcomes (recruitment, retention and cost per patient). Secondary outcomes included adverse anticoagulant safety events composite, quality of transitional care, quality of life, anticoagulant knowledge, satisfaction with care, problems with medications and health resource utilisation., Results: Extensive periods of restriction of recruitment plus difficulties accessing patients at the time of discharge negatively impacted feasibility, especially cost per patient recruited. Of 845 patients screened, 167 were eligible and 56 were randomised. The mean age (±SD) was 71.2±12.5 years, 42.9% females, with two lost to follow-up. Intervention patients were more likely to rate their ability to manage their OAC as improved (17/27 (63.0%) vs 7/22 (31.8%), OR 3.6 (95% CI 1.1 to 12.0)) and their continuity of care as improved (21/27 (77.8%) vs 2/22 (9.1%), OR 35.0 (95% CI 6.3 to 194.2)). Fewer intervention patients were taking one or more inappropriate medications (7 (22.5%) vs 15 (60%), OR 0.19 (95% CI 0.06 to 0.62))., Conclusion: This pilot randomised controlled trial suggests that a transitional care intervention at hospital discharge for older adults taking OACs was well received and potentially effective for some surrogate outcomes, but overly costly to proceed to a definitive large trial., Trial Registration Number: NCT02777047., Competing Interests: Competing interests: DMS has received honoraria paid indirectly to her research institute from AstraZeneca, BMS-Pfizer, Roche and Servier. DMS is supported by a Tier 2 Canada Research Chair in Anticoagulant Management of Cardiovascular Disease. The other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Synthetic datasets are artificially manufactured based on real health systems data but do not contain real patient information. We sought to validate the use of synthetic data in stroke and cancer research by conducting a comparison study of cancer patients with ischemic stroke to non-cancer patients with ischemic stroke., Design: retrospective cohort study., Setting: We used synthetic data generated by MDClone and compared it to its original source data (i.e. real patient data from the Ottawa Hospital Data Warehouse)., Outcome Measures: We compared key differences in demographics, treatment characteristics, length of stay, and costs between cancer patients with ischemic stroke and non-cancer patients with ischemic stroke. We used a binary, multivariable logistic regression model to identify risk factors for recurrent stroke in the cancer population., Results: Using synthetic data, we found cancer patients with ischemic stroke had a lower prevalence of hypertension (52.0% in the cancer cohort vs 57.7% in the non-cancer cohort, p<0.0001), and a higher prevalence of chronic obstructive pulmonary disease (COPD: 8.5% vs 4.7%, p<0.0001), prior ischemic stroke (1.7% vs 0.1%, p<0.001), and prior venous thromboembolism (VTE: 8.2% vs 1.5%, p<0.0001). They also had a longer length of stay (8 days [IQR 3-16] vs 6 days [IQR 3-13], p = 0.011), and higher costs associated with their stroke encounters: $11,498 (IQR $4,440 -$20,668) in the cancer cohort vs $8,084 (IQR $3,947 -$16,706) in the non-cancer cohort (p = 0.0061). A multivariable logistic regression model identified 5 predictors for recurrent ischemic stroke in the cancer cohort using synthetic data; 3 of the same predictors identified using real patient data with similar effect measures. Summary statistics between synthetic and original datasets did not significantly differ, other than slight differences in the distributions of frequencies for numeric data., Conclusion: We demonstrated the utility of synthetic data in stroke and cancer research and provided key differences between cancer and non-cancer patients with ischemic stroke. Synthetic data is a powerful tool that can allow researchers to easily explore hypothesis generation, enable data sharing without privacy breaches, and ensure broad access to big data in a rapid, safe, and reliable fashion., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Diagnostic errors cause substantial preventable harms worldwide, but rigorous estimates for total burden are lacking. We previously estimated diagnostic error and serious harm rates for key dangerous diseases in major disease categories and validated plausible ranges using clinical experts., Objective: We sought to estimate the annual US burden of serious misdiagnosis-related harms (permanent morbidity, mortality) by combining prior results with rigorous estimates of disease incidence., Methods: Cross-sectional analysis of US-based nationally representative observational data. We estimated annual incident vascular events and infections from 21.5 million (M) sampled US hospital discharges (2012-2014). Annual new cancers were taken from US-based registries (2014). Years were selected for coding consistency with prior literature. Disease-specific incidences for 15 major vascular events, infections and cancers ('Big Three' categories) were multiplied by literature-based rates to derive diagnostic errors and serious harms. We calculated uncertainty estimates using Monte Carlo simulations. Validity checks included sensitivity analyses and comparison with prior published estimates., Results: Annual US incidence was 6.0 M vascular events, 6.2 M infections and 1.5 M cancers. Per 'Big Three' dangerous disease case, weighted mean error and serious harm rates were 11.1% and 4.4%, respectively. Extrapolating to all diseases (including non-'Big Three' dangerous disease categories), we estimated total serious harms annually in the USA to be 795 000 (plausible range 598 000-1 023 000). Sensitivity analyses using more conservative assumptions estimated 549 000 serious harms. Results were compatible with setting-specific serious harm estimates from inpatient, emergency department and ambulatory care. The 15 dangerous diseases accounted for 50.7% of total serious harms and the top 5 (stroke, sepsis, pneumonia, venous thromboembolism and lung cancer) accounted for 38.7%., Conclusion: An estimated 795 000 Americans become permanently disabled or die annually across care settings because dangerous diseases are misdiagnosed. Just 15 diseases account for about half of all serious harms, so the problem may be more tractable than previously imagined., Competing Interests: Competing interests: DEN-T has a career focus and conducts research related to diagnostic errors, including in patients with dizziness and stroke. He serves as the principal investigator for multiple grants and contracts on these topics. DEN-T is a former volunteer President and member of the Board of Directors of the Society to Improve Diagnosis in Medicine. Johns Hopkins has been loaned research equipment (video-oculography (VOG) systems) by two companies for use in DEN-T’s research; one of these companies has also provided funding for DEN-T’s research on diagnostic algorithm development related to dizziness, inner ear diseases and stroke. DEN-T has no other financial interest in these or any other companies. DEN-T is an inventor on a provisional patent (US PCT/US2020/070304) for smartphone-based stroke diagnosis in patients with dizziness. He gives frequent academic lectures on these topics and occasionally serves as a medico-legal consultant for both plaintiff and defence in cases related to dizziness, stroke and diagnostic error. DS is also a former volunteer member of the Board of Directors of the Society to Improve Diagnosis in Medicine. There are no other conflicts of interest. None of the authors have any financial or personal relationships with other people or organisations that could inappropriately influence (bias) their work., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Hemostasis and bleeding are difficult to measure. Thrombin generation assays (TGAs) can measure both procoagulant and anticoagulant contributions to coagulation. TGAs might prove useful for the study of bleeding disorders. There has been much progress in TGA methodology over the past two decades, but its clinical significance is uncertain. We will undertake a scoping review of the literature to synthesize available information on the application of TGAs towards the study of bleeding and hemostasis, TGA methodologies being used and to summarize available literature on associations between TGA parameters, bleeding and hemostatic outcomes., Methods and Analysis: MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched in collaboration with an information specialist. Title/abstract and full-text screening will be carried out independently and in duplicate; eligible study types will include randomized controlled trials, non-randomized studies, systematic reviews, and case series reporting TGA results and bleeding/hemostatic outcomes among humans. Mapping the information identified will be carried out with results presented using qualitative data analytical techniques., Ethics and Dissemination: This scoping review will use published, publicly available information. Research ethics approval will not be required. We will disseminate our findings using conference presentations, peer-reviewed publications, social media, and engagement with knowledge users. This review will outline knowledge gaps concerning TGAs, better delineate its applicability as a clinically relevant assay for bleeding. and seek to identify ongoing barriers to its widespread adoption in clinical research, and eventually, in the clinical setting., Trail Regulations: Registration ID with Open Science Framework: osf.io/zp4ge., Competing Interests: J.R. Shaw has received research support in the form of in-kind contributions from Diagnostica Stago. J.H. Levy serves on research or steering committees for Merck, Octapharma and Werfen. D. Siegal has received honoraria from Astra Zeneca, BMS-Pfizer, Roche and Servier paid indirectly to her research institute. L. Castellucci’s research institution has received honoraria from Bayer, BMS-Pfizer Alliance, The Academy for Continued Advancement in Healthcare Education, Amag Pharmaceutical, LEO Pharma, Sanofi, Valeo Pharma, and Servier. R. Khalife has received honoraria from Bayer, Novo Nordisk, Pfizer and Takeda, as well as research support from Canadian Blood Services and the Canadian Hemophilia Society. M. Carrier reports grants from BMS, Leo Pharma and Pfizer, personal fees from BMS, Leo Pharma, Bayer, Pfizer, Servier and Sanofi. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Shaw et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Imaging examination selection and protocoling are vital parts of the radiology workflow, ensuring that the most suitable exam is done for the clinical question while minimizing the patient's radiation exposure. In this study, we aimed to develop an automated model for the revision of radiology examination requests using natural language processing techniques to improve the efficiency of pre-imaging radiology workflow. We extracted Musculoskeletal (MSK) magnetic resonance imaging (MRI) exam order from the radiology information system at Henry Ford Hospital in Detroit, Michigan. The pretrained transformer, "DistilBERT" was adjusted to create a vector representation of the free text within the orders while maintaining the meaning of the words. Then, a logistic regression-based classifier was trained to identify orders that required additional review. The model achieved 83% accuracy and had an area under the curve of 0.87., (©2023 AMIA - All rights reserved.)

The objective of this study was to examine the effect modification of age on the relationship between cancer and prevalence of self-reported stroke. We used cross-sectional data from the 2015-2016 iteration of the Canadian Community Health Survey. A multivariable logistic regression model was used to assess the association between cancer and self-reported stroke. Covariates were assessed for effect modification using the maximum likelihood estimation method. We analyzed 86,809 subjects; the prevalence of self-reported stroke was 1.11%. The odds ratio for the association between cancer and self-reported stroke was 1.26 (95% CI 0.98-1.61) after adjusting for age, sex, dyslipidemia, hypertension, diabetes, heart disease, education, and household income. Age and hypertension were found to be effect modifiers, and the association between cancer and self-reported stroke was stronger in younger adults and in those without hypertension. These results suggest that cancer-associated strokes may have unique underlying mechanisms compared to conventional strokes., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: We conducted a systematic review and meta-analysis of randomized controlled trials comparing direct oral anticoagulants (DOACs) to vitamin K antagonists (VKAs) in the first 90 days after bioprosthetic valve implantation., Methods: We systematically searched Embase, Medline and CENTRAL. We screened titles, abstracts and full texts, extracted data and assessed the risk of bias in duplicate. We pooled data using the Mantel-Haenzel method and random effects modelling. We conducted subgroup analyses based on the type of valve (transcatheter versus surgical) and timing of initiation of anticoagulation (<7 vs >7 days after valve implantation). We assessed the certainty of evidence using the Grading of Recommendations, Assessments, Development and Evaluation approach., Results: We included 4 studies of 2284 patients with a median follow-up of 12 months. Two studies examined transcatheter valves (1877/2284 = 83%) and 2 examined surgical valves (407/2284 = 17%). We found no statistically significant differences between DOACs and VKAs with regard to thrombosis, bleeding, death or subclinical valve thrombosis. However, there was a subgroup trend towards more bleeding with DOACs when initiated within 7 days of valve implantation., Conclusions: In the existing randomized literature on DOACs versus VKAs in the first 90 days after bioprosthetic valve implantation, there appears to be no difference with regard to thrombosis, bleeding or death. Interpretation of the data is limited by small numbers of events and wide confidence intervals. Future studies should focus on surgical valves and should include long-term follow-up to assess any potential impact of randomized therapy on valve durability., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Patients with cancer are at an increased risk of developing atrial fibrillation (AF) and often need to undergo procedures or surgery that requires periprocedural interruption of anticoagulation. Anticoagulated patients with cancer might be at increased risk of postprocedural thromboembolic and bleeding complications. Data on postprocedural outcomes among patients with concurrent active cancer and AF are sparse., Objective: To assess the 30-day risk of postoperative thromboembolic and major bleeding complications after the periprocedural interruption of anticoagulation among patients with AF and active cancer., Methods: We conducted a single-center retrospective cohort study in patients with active cancer and AF who required periprocedural interruption of anticoagulation for invasive procedures between August 2015 and May 2019. The primary endpoints were the 30-day postoperative risks of arterial thromboembolism (ATE) and major bleeding. The secondary endpoints included the 30-day risks of venous thromboembolism, clinically relevant nonmajor bleeding, and overall mortality., Results: Two hundred sixty-four patients undergoing 302 periprocedural interruptions were included in our study. The 30-day risk of ATE was 0.7% (95% CI, 0.1%-2.4%), and the 30-day risk of major bleeding was 1.7% (95% CI, 0.6%-3.9%). The 30-day risks of venous thromboembolism and clinically relevant nonmajor bleeding were 0.7% (95% CI, 0.1%-2.4%) and 4.3% (95% CI, 2.5%-7.3%), respectively. The overall risk of mortality at 30 days was 1.3% (95% CI, 0.4%-3.4%). There was one fatal postoperative stroke., Conclusions: Patients with AF and active cancer in this study were at relatively low risk for ATE and postoperative bleeding complications when patients were managed according to commonly applied perioperative management recommendations., Competing Interests: Declaration of competing interest T-F. Wang reports research funding from Leo Pharma; advisory board/honoraria: Servier and Valeo. D. Siegal has received honoraria indirectly to her research institute from Astra Zeneca, BMS-Pfizer, Leo Pharma, Roche, Servier. J. Douketis has received research support from Boehringer-Ingelheim, royalties from UptoDate and the Merck Manual, as well as consultant/advisory board fees from Actelion, AGEN, Astra Zeneca, Bayer, Biotie, BMS, Daiichi-Sankyo, Portola, Boehringer-Ingelheim, Cytori, Janssen, Leo Pharma, Pfizer, Medicine CO., Sanofi, Servier, Bristol Meyers Squibb and PhaseBio, in addition to speaker’s fees from Bayer, Boehringer-Ingelheim, Pfizer, Leo Pharma, Sanofi, with all funds deposited into a university-based research account of through the St. Joseph’s Healthcare Foundation. Dr. Le Gal reports grants from Pfizer and Bristol-Myers Squibb and honoraria (not taken as salary) from Pfizer, Leo Pharma and Sanofi and Aspen Pharma. M Carrier reports research funding from Leo Pharma, BMS and Pfizer; advisory board/honoraria: Bayer, Sanofi, Leo Pharma, Pfizer, Servier and Valeo. J.R. Shaw has received fellowship funding through the Thrombosis Canada BMS-Pfizer Fellowship Award and has received research support from Diagnostica Stago., (Copyright © 2022 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Direct oral anticoagulants (DOACs) account for most oral anticoagulant use. DOAC-associated bleeding events are commonly encountered in clinical practice and are associated with substantial morbidity and mortality. Both specific reversal agents and nonspecific hemostatic therapies, such as prothrombin complex concentrates, are used in the management of DOAC-associated bleeding. Measuring hemostatic efficacy and demonstrating a clinical impact from these therapies among studies of bleeding patients is challenging. Thrombin generation assays provide information on the total hemostatic potential of plasma, and have emerged as a promising modality to both measure the impact of DOACs on coagulation and to evaluate the effects of hemostatic therapies among patients with DOAC-associated bleeding. The mechanisms by which nonspecific hemostatic agents impact coagulation and thrombin generation in the context of DOAC therapy are unclear. As a result, we undertook a review of the literature using a systematic search strategy with the goal of summarizing the effects of DOACs on thrombin generation and the effects of both specific reversal agents and nonspecific hemostatic therapies on DOAC-altered thrombin generation parameters. We sought to identify clinical studies focusing on whether altered thrombin generation is associated with clinical bleeding and whether correction of altered thrombin generation parameters predicts improvements in clinical hemostasis. Lastly, we sought to outline future directions for the application of thrombin generation assays toward anticoagulation therapies and the question of anticoagulation reversal., Competing Interests: Declaration of competing interest J.R.S. has received research support in the form of in-kind contributions from Diagnostica Stago. L.A.C.’s research institute has received honoraria from Amag Pharmaceuticals, Bayer, BMS-Pfizer Alliance, the Academy, LEO Pharma, Sanofi, Servier, and Valeo. M.C. has received research funding from BMS, Leo Pharma, and Pfizer, as well as honoraria from Bayer, Sanofi, Servier, BMS, Leo Pharma, and Pfizer, with all payments made to his institution., (Copyright © 2022 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)