Search

Carbon stored in mangroves is valuable for climate change mitigation. Managing the carbon stored in the mangrove requires an adequate legal framework and an environmental policy. In Cuba, there is little research on the capacity of mangroves to retain carbon and its articulation in environmental policy and management. In the present study, the following research question is raised: Is there a favorable context in the environmental policy to manage the mangrove as a carbon reservoir in Cuba? The aim of this research is to identify aspects of environmental policy, legal and administrative frameworks related to managing mangroves as a carbon sink in Cuba. The qualitative method of social research, the content analysis technique, and the modified Ibero-American Network for Integrated Coastal Management (IBERMAR) decalogue were used to compile, understand, and discuss the potential for effective management of mangroves for carbon storage. One hundred and twenty-one articles published in WOS and Scopus databases between 2019 and 2022, as well as books and material reviewed on the official websites, were checked. Present policy in Cuba manages mangroves for coastal protection and other ecosystem services but lacks a developed plan for considering the role of this marine forest system as a carbon sink. Managing mangroves as a carbon reservoir will require vigorous efforts to measure and monitor the system. It is necessary to build a robust national political agenda and strengthen institutional and regulatory capacities. This research provides a systematization of environmental policy as a baseline for the management of carbon reservoirs in mangroves in Cuba.

Immune thrombocytopenia (ITP) may occur in isolation (primary) or in association with a predisposing condition (secondary ITP [sITP]). Eltrombopag is a well-studied treatment for primary ITP, but evidence is scarce for sITP. We evaluated real-world use of eltrombopag for sITP using electronic health records. Eligible patients had diagnoses of ITP and a qualifying predisposing condition, and eltrombopag treatment. We described patient characteristics, treatment patterns, platelet counts, and thrombotic and bleeding events. We identified 242 eligible patients; the most common predisposing conditions were hepatitis C and systemic lupus erythematosus. Average duration of eltrombopag treatment was 6.1 months. Most (81.4%) patients achieved a platelet count ≥ 30,000/µL at a mean of 0.70 months, 70.2% reached ≥ 50,000/µL at a mean of 0.95 months, and 47.1% achieved a complete response of > 100,000/µL at a mean of 1.43 months after eltrombopag initiation. At eltrombopag discontinuation, 105 patients (43%) experienced a treatment-free period for a mean 3.3 months. Bleeding events occurred with similar frequency before and during eltrombopag treatment whereas thrombotic events were less frequent during eltrombopag treatment. Our results suggest similar rates of platelet response with eltrombopag in patients with sITP as compared with primary ITP. In addition, a treatment-free period is possible for a substantial minority of patients. Supplementary Information The online version contains supplementary material available at 10.1007/s00277-021-04637-2.

Background Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet counts and increased risk of bleeding. In preparation for an upcoming guideline, the ITP Emergency Management Guideline Panel, including clinical experts in hematology, emergency medicine, research methodology, and patient representatives, identified the need for a standardized definition of a critical ITP bleed. The goal of the definition was to distinguish critical bleeds from bleeds that may not require urgent treatment, typically in the context of severe thrombocytopenia. Methods The panel met in person and virtually to achieve consensus on the criteria for critical bleeding events among patients with ITP. Existing ITP bleeding scores and published definitions of major bleeds in patients receiving anticoagulation informed the definition of a critical ITP bleed. The Platelet Immunology Scientific Standardization Committee (SSC) of the International Society on Thrombosis and Haemostasis endorsed the definition. Results A critical ITP bleed was defined as: (a) a bleed in a critical anatomical site including intracranial, intraspinal, intraocular, retroperitoneal, pericardial, or intramuscular with compartment syndrome; or (2) an ongoing bleed that results in hemodynamic instability or respiratory compromise. Conclusion The definition of a critical ITP bleed was developed by the ITP Emergency Management Guideline Panel and endorsed by the Platelet Immunology SSC. It incorporates both anatomic and physiologic risk and pertains to patients with confirmed or suspected ITP who typically have severe thrombocytopenia (platelet count below 20 × 109 /L).

Although apixaban and rivaroxaban are commonly used in patients with atrial fibrillation (AF) and valvular heart disease (VHD), there is limited evidence comparing the 2 drugs in these patients.To emulate a target trial of effectiveness and safety of apixaban and rivaroxaban in patients with AF and VHD.New-user, active comparator, cohort study design.Commercial health insurance database from 1 January 2013 to 31 December 2020.New users of apixaban or rivaroxaban who had a diagnosis of AF and VHD before initiation of anticoagulant therapy.The primary effectiveness outcome was a composite of ischemic stroke or systemic embolism. The primary safety outcome was a composite of gastrointestinal or intracranial bleeding. Cox proportional hazards regression with a robust variance estimator was used to estimate hazard ratios (HRs) and 95% CIs.When compared with rivaroxaban in a propensity score-matched cohort of 19 894 patients (9947 receiving each drug), apixaban was associated with a lower rate of ischemic stroke or systemic embolism (HR, 0.57 [95% CI, 0.40 to 0.80]) and bleeding (HR, 0.51 [CI, 0.41 to 0.62]). The absolute reduction in the probability of stroke or systemic embolism with apixaban compared with rivaroxaban was 0.0026 within 6 months and 0.011 within 1 year of treatment initiation. The absolute reduction in the probability of bleeding events with apixaban compared with rivaroxaban was 0.012 within 6 months and 0.019 within 1 year of treatment initiation.Short follow-up time and inability to ascertain some types of VHD.In this study of patients with AF and VHD, patients receiving apixaban had a lower risk for ischemic stroke or systemic embolism and for bleeding when compared with those receiving rivaroxaban.National Institutes of Health.

Background: COVID-19–related critical illness is associated with an increased risk of venous thromboembolism (VTE). Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for patients with COVID-19. Methods: ASH formed a multidisciplinary guideline panel, including 3 patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline development process, including performing systematic evidence reviews (up to January 2022). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the GRADE approach to assess evidence and make recommendations, which were subject to public comment. This is an update to guidelines published in February 2021 and May 2021 as part of the living phase of these guidelines. Results: The panel made 1 additional recommendation: a conditional recommendation for the use of prophylactic-intensity over therapeutic-intensity anticoagulation for patients with COVID-19–related critical illness who do not have suspected or confirmed VTE. The panel emphasized the need for an individualized assessment of thrombotic and bleeding risk. Conclusions: This conditional recommendation was based on very low certainty in the evidence, underscoring the need for additional, high-quality, randomized controlled trials comparing different intensities of anticoagulation for patients with COVID-19–related critical illness.

Immune thrombotic thrombocytopenic purpura (iTTP) is an acquired, fatal microangiopathy if untreated. Randomized controlled trials (RCTs) demonstrated faster time to response with addition of caplacizumab to standard of care (SOC). However, concerns about RCT selection bias and the high cost of caplacizumab warrant examination of all evidence, including real-world observational studies. In this systematic review and meta-analysis, we searched for comparative studies evaluating SOC with or without caplacizumab for the treatment of iTTP. We assessed risk of bias using the Cochrane risk-of-bias-2 tool (RCTs) and the Newcastle-Ottawa Scale (observational studies). The primary efficacy and safety outcomes were all-cause mortality and treatment-emergent bleeding, respectively. Secondary outcomes included exacerbation and relapse, refractory iTTP, and time to response. We included 2 high-quality RCTs and 3 observational studies at high risk of bias comprising 632 total participants. Compared with SOC, caplacizumab was associated with a nonsignificant reduction in the relative risk [RR] of death in RCTs (RR, 0.21; 95% confidence interval [CI], 0.05-1.74) and observational studies (RR, 0.62; 95% CI, 0.07-4.41). Compared with SOC, caplacizumab was associated with an increased bleeding risk in RCTs (RR, 1.37; 95% CI, 1.06-1.77). In observational studies, bleeding risk was not significantly increased (RR, 7.10; 95% CI, 0.90-56.14). Addition of caplacizumab was associated with a significant reduction in refractory iTTP and exacerbation risks and shortened response time but increased relapse risk. Frontline addition of caplacizumab does not significantly reduce all-cause mortality compared with SOC alone, although it reduces refractory disease risk, shortens time to response, and improves exacerbation rates at the expense of increased relapse and bleeding risk.

Background Direct oral anticoagulants (DOACs) are increasingly used in place of warfarin, but evidence about their effectiveness and safety in patients with valvular atrial fibrillation (AF) remains limited. Objective To assess the effectiveness and safety of DOACs compared with warfarin in patients with valvular AF. Design New-user retrospective propensity score-matched cohort study. Setting U.S.-based commercial health care database from 1 January 2010 to 30 June 2019. Participants Adults with valvular AF who were newly prescribed DOACs or warfarin. Measurements The primary effectiveness outcome was a composite of ischemic stroke or systemic embolism. The primary safety outcome was a composite of intracranial or gastrointestinal bleeding. Results Among a total of 56 336 patients with valvular AF matched on propensity score, use of DOACs (vs. warfarin) was associated with lower risk for ischemic stroke or systemic embolism (hazard ratio [HR], 0.64 [95% CI, 0.59 to 0.70]) and major bleeding events (HR, 0.67 [CI, 0.63 to 0.72]). The results for the effectiveness and safety outcomes remained consistent for apixaban (HRs, 0.54 [CI, 0.47 to 0.61] and 0.52 [CI, 0.47 to 0.57], respectively) and rivaroxaban (HRs, 0.74 [CI, 0.64 to 0.86] and 0.87 [CI, 0.79 to 0.96], respectively); with dabigatran, results were consistent for the major bleeding outcome (HR, 0.81 [CI, 0.68 to 0.97]) but not for effectiveness (HR, 1.03 [CI, 0.81 to 1.31]). Limitation Relatively short follow-up; inability to ascertain disease severity. Conclusion In this comparative effectiveness study using practice-based claims data, patients with valvular AF who were new users of DOACs had lower risks for ischemic stroke or systemic embolism and major bleeding than new users of warfarin. These data may be used to guide risk-benefit discussions regarding anticoagulant choices for patients with valvular AF. Primary funding source None.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic condition resulting from pathogenic antibodies to complexes of heparin and platelet factor 4 (PF4). The diagnosis of HIT can be challenging due to the widespread use of heparin and the frequency of thrombocytopenia in hospitalized patients. Laboratory testing for HIT typically includes an immunoassay to detect antibodies to PF4-heparin and a functional assay. Current HIT diagnostic algorithms recommend using the 4Ts score to determine the need for HIT laboratory testing. Automated calculation of HIT clinical prediction scores in the electronic health record may improve the identification of patients who should undergo HIT testing. Another challenge in the management of patients with suspected HIT is the turnaround time of the laboratory testing needed to confirm the diagnosis. Due to the high daily thrombotic risk of HIT, clinicians must treat patients with intermediate to high pretest likelihood of HIT empirically while awaiting the test results. Treatment for HIT often involves alternative anticoagulants that lack reversal agents, which may increase bleeding risk, prolong hospital stays, and increase costs for patients suspected of having HIT. Rapid immunoassays hold promise to improve the speed of HIT diagnosis. These assays must retain a very high sensitivity for this "can't miss" diagnosis, yet have sufficient specificity to be of diagnostic value. A Bayesian approach has been proposed using two rapid immunoassays in succession, which decreased analytic turnaround time to 60 minutes. Such an approach has the potential to be a much-needed clinical advance in improving accuracy and speed in the diagnosis of HIT.

Background: The effectiveness and safety of non-heparin anticoagulants for the treatment of heparin-induced thrombocytopenia (HIT) are not fully established, and the optimal treatment strategy is unknown. In a systematic review and meta-analysis, we aimed to determine precise rates of platelet recovery, new or progressive thromboembolism (TE), major bleeding, and death for all non-heparin anticoagulants and to study potential sources of variability. Methods: Following a detailed protocol (PROSPERO: CRD42020219027), EMBASE and Medline were searched for all studies reporting clinical outcomes of patients treated with non-heparin anticoagulants (argatroban, danaparoid, fondaparinux, direct oral anticoagulants [DOAC], bivalirudin, and other hirudins) for acute HIT. Proportions of patients with the outcomes of interest were pooled using a random-effects model for each drug. The influence of the patient population, the diagnostic test used, the study design, and the type of article was assessed. Findings: Out of 3’194 articles screened, 92 studies with 119 treatment groups describing 4’698 patients were included. The pooled rates of platelet recovery ranged from 74% (bivalirudin) to 99% (fondaparinux), TE from 1% (fondaparinux) to 7% (danaparoid), major bleeding from 1% (DOAC) to 14% (bivalirudin), and death from 7% (fondaparinux) to 19% (bivalirudin). Confidence intervals were mostly overlapping, and results were not influenced by patient population, diagnostic test used, study design, or type of article. Interpretation: Effectiveness and safety outcomes were similar among various anticoagulants, and significant factors affecting these outcomes were not identified. These findings support fondaparinux and DOACs as viable alternatives to conventional anticoagulants for treatment of acute HIT in clinical practice. Registration Information: PROSPERO: CRD42020219027. Funding Information: This study was supported by a research grant of the Swiss National Science Foundation (#179334). Declaration of Interests: Conflict-of-interest disclosure: M.N. received research grants from Bayer Healthcare. A.C. has served as a consultant for synergy and his institution has received research support on his behalf from alexion, Bayer, Novartis, novo Nordisk, Pfizer, Sanofi, spark, and Takeda. All other authors declare that no conflict of interest exists.

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal thrombotic microangiopathy caused by autoantibody-mediated severe deficiency of ADAMTS13. Standardized definitions of response, exacerbation, remission, and relapse were initially proposed in 2003 and modified by the International Working Group for TTP in 2017. These definitions, which have been widely used in clinical practice and research, are based primarily on the platelet count and are benchmarked against the timing of discontinuation of therapeutic plasma exchange (TPE). They do not incorporate ADAMTS13 activity or the temporizing effects on the platelet count of caplacizumab, a novel anti–von Willebrand factor (VWF) nanobody. In light of these limitations, the IWG aimed to develop revised consensus outcome definitions that incorporate ADAMTS13 activity and the effects of anti-VWF therapy, by using an estimate-talk-estimate approach. The updated definitions distinguish clinical remission and clinical relapse (defined primarily by platelet count) from ADAMTS13 remission and ADAMTS13 relapse (defined by ADAMTS13 activity). The revised definitions of exacerbation and remission are benchmarked against not only the timing of discontinuation of TPE but also that of anti-VWF therapy. Retrospective validation of the revised definitions is described, although they have yet to be prospectively validated. Clinical implications of the updated outcome definitions are also discussed and an example of their application to clinical practice is provided to highlight their clinical relevance.

This article has been temporarily removed as it was inadvertently posted ahead of an agreed-upon embargo. The article will be reinstated upon embargo expiry. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal .

Background Thrombopoietin receptor agonists (TPO-RAs) are used to treat primary immune thrombocytopenia (ITP). Some patients have discontinued treatment while maintaining a hemostatic platelet count. Objectives To develop expert consensus on when it is appropriate to consider tapering TPO-RAs in ITP, how to taper patients off therapy, how to monitor patients after discontinuation, and how to restart therapy. Methods We used a RAND/UCLA modified Delphi panel method. Ratings were completed independently by each expert before and after a meeting. Second-round ratings were used to develop the panel's guidance. The panel was double-blinded: The sponsor and nonchair experts did not know each other's identities. Results Guidance on when it is appropriate to taper TPO-RAs in children and adults was developed based on patient platelet count, history of bleeding, intensification of treatment, trauma risk, and use of anticoagulants/platelet inhibitors. For example, it is appropriate to taper TPO-RAs in patients who have normal/above-normal platelet counts, have no history of major bleeding, and have not required an intensification of treatment in the past 6 months; it is inappropriate to taper TPO-RAs in patients with low platelet counts. Duration of ITP, months on TPO-RA, or timing of platelet response to TPO-RA did not have an impact on the panel's guidance on appropriateness to taper. Guidance on how to taper patients off therapy, how to monitor patients after discontinuation, and how to restart therapy is also provided. Conclusion This guidance could support clinical decision making and the development of clinical trials that prospectively test the safety of tapering TPO-RAs.

Contains fulltext : 232751.pdf (Publisher’s version ) (Closed access) Clinical research in venous thromboembolism (VTE) is hindered by variability in the collection and reporting of data and outcomes. A consistent data language facilitates efficiencies, leads to higher quality data, and permits between-study comparisons and evidence synthesis. The International Society on Thrombosis and Haemostasis (ISTH) launched an international task force of more than 50 researchers to develop common data elements for clinical research in venous thromboembolism. The project was organized in seven working groups, each focusing on a topic area: General Core Data Elements; Anticoagulation and Other Therapies; Chronic VTE and Functional Outcomes; Diagnosis of VTE; Malignancy; Perioperative; and Predictors of VTE. The groups met via teleconference to collaboratively identify key data elements and develop definitions and data standards that were structured in a project-specific taxonomy. A Steering Committee met by teleconference and in-person to determine the overall scope of the project and resolve questions arising from the working groups. ISTH held an open public comment period to enable broader stakeholder involvement and feedback. The common data elements were then refined by the working groups to create a set of 512 unique data elements that are publicly available at http://isth.breakthrough.healthcare. The ISTH VTE Common Data Elements are intended to be a living project with ongoing curation, future expansion, and adaptation to meet the needs of the thrombosis and hemostasis research community.