Design and implementation of the Our Health Counts (OHC) methodology for First Nations, Inuit, and Metis (FNIM) health assessment and response in urban and related homelands.

OBJECTIVES: Methods for enumeration and population-based health assessment for First Nations, Inuit, and Metis (FNIM) living in Canadian cities are underdeveloped, with resultant gaps in essential demographic, health, and health service access information. Our Health Counts (OHC) was designed to engage FNIM peoples in urban centres in "by community, for community" population health assessment and response. METHODS: The OHC methodology was designed to advance Indigenous self-determination and FNIM data sovereignty in urban contexts through deliberate application of Indigenous principles and linked implementation strategies. Three interwoven principles (good relationships are foundational; research as gift exchange; and research as a vehicle for Indigenous community resurgence) provide the framework for linked implementation strategies which include actively building and maintaining relationships; meaningful Indigenous community guidance, leadership, and participation in all aspects of the project; transparent and equitable sharing of project resources and benefits; and technical innovations, including respondent-driven sampling, customized comprehensive health assessment surveys, and linkage to ICES data holdings to generate measures of health service use. RESULTS: OHC has succeeded across six urban areas in Ontario to advance Indigenous data sovereignty and health assessment capacity; recruit and engage large population-representative cohorts of FNIM living in urban and related homelands; customize comprehensive health surveys and data linkages; generate previously unavailable population-based FNIM demographic, health, and social information; and translate results into enhanced policy, programming, and practice. CONCLUSION: The OHC methodology has been demonstrated as effective, culturally relevant, and scalable across diverse Ontario cities.

RéSUMé: OBJECTIFS: Les méthodes de dénombrement et d'évaluation populationnelle de la santé des personnes des Premières Nations, des Inuits et des Métis (PNIM) vivant dans les villes du Canada sont sous-développées, ce qui laisse des lacunes dans les informations essentielles sur le profil démographique, la santé et l'accès aux services de santé. Le projet Notre santé compte (NSC) vise à collaborer avec les personnes des PNIM dans les centres urbains au moyen d'une évaluation de la santé des populations et d'une intervention « pour nous-mêmes, par nous-mêmes ¼. MéTHODE: La méthode NSC est conçue pour renforcer l'autodétermination autochtone et la souveraineté des données des PNIM vivant en milieu urbain par l'application délibérée de principes autochtones et de stratégies de mise en œuvre connexes. Trois principes imbriqués (« les bonnes relations sont fondamentales ¼; « la recherche en tant qu'échange de cadeaux ¼; et « la recherche comme vecteur de résurgence des communautés autochtones ¼) constituent le cadre de stratégies de mise en œuvre connexes : l'établissement et le maintien actifs de relations; la guidance, la participation et le leadership significatifs des communautés autochtones dans tous les aspects du projet; le partage transparent et équitable des ressources et des avantages du projet; et les innovations techniques, dont l'échantillonnage en fonction des répondants, les enquêtes de santé exhaustives et personnalisées, et les couplages avec les fonds de données de l'Institut de recherche en services de santé (ICES), pour produire des indicateurs d'utilisation des services de santé. RéSULTATS: L'approche NSC a réussi dans six agglomérations urbaines de l'Ontario : à renforcer la souveraineté des données et la capacité d'évaluation de la santé des populations autochtones; à recruter et à mobiliser de vastes cohortes représentatives des PNIM vivant en milieu urbain et sur les territoires connexes; à personnaliser des enquêtes de santé exhaustives et des couplages de données; à générer des informations démographiques, sanitaires et sociales non disponibles auparavant sur les populations des PNIM; et à traduire ces résultats en politiques, en programmes et en pratiques améliorés. CONCLUSION: Il est démontré que la méthode NSC est efficace, culturellement appropriée et modulable dans différentes villes de l'Ontario.

Our Health Counts: Examining associations between colonialism and ever being incarcerated among First Nations, Inuit, and Métis people in London, Thunder Bay, and Toronto, Canada.

OBJECTIVES: Indigenous peoples have a disproportionately high prevalence of incarceration in the Canadian justice system. However, there is limited Indigenous-driven research examining colonialism and the justice system, specifically associations between racism, externally imposed family disruptions, and history of ever being incarcerated. Therefore, this study examined the association between the proportion of previous incarceration and family disruption, experiences of racism, and victimization for Indigenous adults in London, Thunder Bay, and Toronto, Ontario, Canada. The three communities expressed that they did not want comparison between the communities; rather, they wanted analysis of their community to understand where more supports were needed. METHODS: Indigenous community partners used respondent-driven sampling (RDS) to collect data from First Nations, Inuit, and Métis (FNIM) peoples in London, Thunder Bay, and Toronto. Prevalence estimates, 95% confidence intervals, and relative risk were reported using unweighted Poisson models and RDS-adjusted proportions. RESULTS: Proportions of ever being incarcerated ranged from 43.0% in London to 54.0% in Toronto and 72.0% in Thunder Bay. In all three cities, history of child protection involvement and experiencing racism was associated with an approximate 25.0% increase in risk for previous incarceration. In Toronto and London, victimization was associated with increased risk for incarceration. CONCLUSION: This research highlights disproportionately high prevalence of ever being incarcerated among FNIM living in three Ontario cities. Experiencing racism, family disruption, and victimization are associated with incarceration. Decreasing the rates of family disruption, experiences of racism, and victimization should inform future policy and services to reduce the disproportionately high prevalence of incarceration for FNIM people living in urban settings.

RéSUMé: OBJECTIFS: Les personnes autochtones présentent une prévalence démesurément élevée d'incarcération dans le système judiciaire canadien. Il y a cependant peu d'études dirigées par des Autochtones sur le colonialisme et le système judiciaire, en particulier sur les associations entre le racisme, les perturbations familiales imposées de l'extérieur et les antécédents d'incarcération. C'est pourquoi nous avons fait porter notre étude sur l'association entre la proportion d'incarcérations antérieures et de perturbations familiales, les expériences de racisme et la victimisation chez les adultes autochtones vivant à London, Thunder Bay et Toronto (Ontario), au Canada. Les trois villes ont dit ne pas vouloir que nous fassions de comparaisons entre elles; elles voulaient plutôt des analyses de leur ville pour savoir où des mesures de soutien supplémentaires étaient nécessaires. MéTHODE: Des partenaires associatifs autochtones ont utilisé l'échantillonnage en fonction des répondants (EFR) pour collecter des données auprès des personnes des Premières Nations, des Inuits et des Métis (PNIM) à London, Thunder Bay et Toronto. Les estimations de prévalence, les intervalles de confiance de 95 % et le risque relatif ont été présentés à l'aide de modèles de Poisson non pondérés et de proportions ajustées selon l'EFR. RéSULTATS: La proportion de répondantes et de répondants ayant déjà été incarcérés était de 43 % à London, de 54 % à Toronto et de 72 % à Thunder Bay. Dans les trois villes, la fréquentation des services de protection de l'enfance et l'expérience du racisme étaient associées à une hausse d'environ 25 % du risque d'incarcération antérieure. À Toronto et à London, la victimisation était associée à un risque accru d'incarcération. CONCLUSION: Cette étude souligne la prévalence démesurément élevée de l'incarcération antérieure chez les personnes PNIM vivant dans trois villes de l'Ontario. L'expérience du racisme, les perturbations familiales et la victimisation étaient associées à l'incarcération. La réduction des taux de perturbations familiales, d'expérience du racisme et de victimisation devrait éclairer les politiques et les services futurs afin de réduire la prévalence démesurément élevée de l'incarcération chez les personnes PNIM vivant en milieu urbain.

Reassessment of dextran sulfate in anti-Xa assay for unfractionated heparin laboratory monitoring.

Background: Anti-Xa assays are used for unfractionated heparin (UFH) monitoring. Dextran sulfate (DS) is used in some assays to overcome the artifactual preanalytical release of platelet factor 4. However, the practical implications of this test modification have not been studied extensively. Objectives: To investigate the impact of the presence of DS in the anti-Xa assay for UFH laboratory monitoring. Methods: We studied factor Xa inhibition, using an assay without DS (Stago Liquid Anti-Xa), in normal pool plasma spiked with various concentrations of UFH (up to 1 IU/mL) in the presence of increasing concentrations of DS (up to 2560 µg/mL). We also investigated the effect of DS on FXa inhibition measured after the addition of UFH and heparin antagonists (protamine and Polybrene; Sigma Aldrich). Eventually, we compared the anti-Xa levels measured using the assay without DS to those measured with an assay containing DS (BIOPHEN Heparin LRT, Hyphen BioMed). Results: DS per se had a detectable anti-Xa effect. FXa inhibition in UFH-spiked plasma linearly increased with increasing concentrations of added DS, with a plateau at approximately 160 µg/mL DS, at which the apparent anti-Xa level had almost doubled. In the presence of heparin antagonists, the addition of DS increased anti-Xa levels, corresponding to the dissociation of the UFH-antagonists complexes in vitro. With the anti-Xa assay containing DS, UFH inhibition was not detected. Conclusion: In the presence of high concentrations of DS, FXa inhibition was much higher than that predicted from added UFH amounts, presumably related to the greater availability of UFH for interaction with antithrombin. While the relevance of measuring this "masked" heparin has not been demonstrated, the presence of DS renders the result inaccurate in the presence of protamine or Polybrene.

Laboratory evaluation of a new integrative assay to phenotype plasma fibrinolytic system.

BACKGROUND: There is currently no universal and standardized test available to phenotype plasma fibrinolytic system. AIMS: Our main aims were to evaluate the performances of the 'global fibrinolysis capacity' assay (GFC) performed with the Lysis Timer® instrument, and to study the influence of some preanalytical conditions. METHOD: Euglobulin clot lysis time (ECLT) and GFC were performed under several preanalytical conditions. RESULTS: GFC showed satisfactory intra- and inter-run precision. Frozen controls and reagents showed stability over the studied period. There was no statistically significant difference between GFC assessed in plasma samples processed at 4 °C or at 20 °C. GFC assessed with frozen-thawed plasma samples was prolonged when compared to fresh samples (p = 0.014). The centrifugation scheme had no influence on PAI-1 activity levels, GFC and ECLT. Reference interval for GFC ranges from 29.3 (C I90% = 26.9-31.9) to 49.5 (90% CI = 45.9-52.2) minutes. In addition, a preliminary study in 40 healthy volunteers and 43 adult patients referred for investigation of a bleeding disorder was conducted to compare GFC and ECLT assays in their ability to classify samples with shortened or prolonged clot lysis times. Disagreements between ECLT and GFC were observed for 23 samples (out of 83), most of them minor. CONCLUSION: GFC is suitable and convenient for a broad clinical use and can be performed with frozen-thawed plasma samples. Unlike ECLT, GFC is designed to take into account the balance between inhibitors and activators of the fibrinolytic system and could detect both hypo- and hyperfibrinolytic states. Whether it is as suitable as or even better than ECLT to detect a bleeding tendency due to a hyperactive fibrinolytic system deserves to be properly investigated.

D-dimer Testing in Pulmonary Embolism with a Focus on Potential Pitfalls: A Narrative Review.

D-dimer is a multifaceted biomarker of concomitant activation of coagulation and fibrinolysis, which is routinely used for ruling out pulmonary embolism (PE) and/or deep vein thrombosis (DVT) combined with a clinical pretest probability assessment. The intended use of the tests depends largely on the assay used, and local guidance should be applied. D-dimer testing may suffer from diagnostic errors occurring throughout the pre-analytical, analytical, and post-analytical phases of the testing process. This review aims to provide an overview of D-dimer testing and its value in diagnosing PE and discusses the variables that may impact the quality of its laboratory assessment.

The edoxaban-M4 metabolite and measurement of edoxaban by chromogenic assays in human plasma.

Introduction: Edoxaban is the only anti-Xa inhibitor metabolized in pharmacologically active moiety that could interfere with chromogenic anti-Xa assays, especially in case of drug-drug interactions or physiological disorders. Materials and methods: We evaluated the contribution of the main metabolite of edoxaban, edoxaban-M4 (M4), in 79 plasma samples from patients taking edoxaban. The total anti-Xa activity was evaluated on three different chromogenic factor Xa-based assays. Results were compared with a validated ultra-high-performance liquid chromatography coupled with a tandem mass spectrometry measurement. Edoxaban and its active M4 metabolite have also been spiked separately in normal pooled plasma to assess the sensitivity of chromogenic anti-Xa assays to both molecules individually. Results: Spiked edoxaban or M4 provided different slopes of linear regression models between chromogenic and chromatographic measurement (from 0.97 for STA Liquid Anti-Xa to 1.10 for Biophen Heparin LRT Low with edoxaban and from 0.70 for Biophen DiXaI High to 0.83 for Biophen Heparin LRT High, respectively). A positive correlation is observed between the increase of the ratio M4/edoxaban with the difference between chromogenic and chromatographic measurements. Conclusion: Edoxaban and M4 do not similarly impact chromogenic assays, leading to biased chromogenic estimations of ponderal concentrations. In patient samples, this impact is even more important at low concentrations or in the case of an increase in the M4/edoxaban ratio because of hepatic or renal impairments or in case of drug interactions. This study highlights the limitations and risks of error of expressing results in ponderal concentrations instead of global activity anti-Xa.

Uninterrupted DOACs Approach for Catheter Ablation of Atrial Fibrillation: Do DOACs Levels Matter?

Most patients present for catheter ablation of atrial fibrillation (CAAF) with residual or full effect of vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). In daily practice, it has been observed that the activated clotting time (ACT) was actually poorly sensitive to the effect of DOACs and that patients on DOACs required more unfractionated heparin (UFH) to achieve the ACT target of 300 s during the procedure, leading some authors to worry about potential overdosing. Conversely, we hypothesize that these higher doses of UFH are necessary to achieve adequate hemostasis during CAAF regardless of the residual effect of DOACs. During CAAF, thrombosis is promoted mainly by the presence of thrombogenic sheaths and catheters in the bloodstream. Preclinical data suggest that only high doses of DOACs are able to mitigate catheter-induced thrombin generation, whereas low dose UFH already do so. In addition, the effect of UFH seems to be lower in patients on DOACs, compared to patients on VKAs, explaining part of the differences observed in heparin requirements. Clinical studies could not identify increased bleeding risk in patients on DOACs compared to those on VKAs despite similar efficacy during CAAF procedures. Moreover, targeting a lower ACT was associated with an increased periprocedural thrombotic risk for both DOAC and VKA patients. Therefore, the low sensitivity of the ACT to the residual effect of DOACs should not be a major concern in its use in the interventional cardiology laboratory.

Monitoring of Unfractionated Heparin Therapy in the Intensive Care Unit Using a Point-of-Care aPTT: A Comparative, Longitudinal Observational Study with Laboratory-Based aPTT and Anti-Xa Activity Measurement.

Continuous intravenous unfractionated heparin (UFH) is administered routinely in the intensive care unit (ICU) for the anticoagulation of patients, and monitoring is performed by the activated partial thromboplastin time (APTT) or anti-Xa activity. However, these strategies are associated with potentially large time intervals before dose adjustments, which could be detrimental to the patient. The aim of the study was to compare a point-of-care (POCT) version of the APTT to (i) laboratory-based APTT and (ii) measurements of anti-Xa activity in terms of correlation, agreement and turnaround time (TAT). Thirty-five ICU patients requiring UFH therapy were prospectively included and followed longitudinally for a maximum duration of 15 days. UFH was administered according to a local adaptation of Raschke and Amanzadeh's aPTT nomograms. Simultaneous measurements of POCT-APTT (CoaguCheck® aPTT Test, Roche Diagnostics) on a drop of fresh whole blood, laboratory-based APTT (C.K. Prest®, Stago) and anti-Xa activity (STA®Liquid anti-Xa, Stago) were systematically performed two to six times a day. Antithrombin, C-reactive protein, fibrinogen, factor VIII and lupus anticoagulant were measured. The time tracking of sampling and analysis was recorded. The overall correlation between POCT-APTT and laboratory APTT (n = 795 pairs) was strongly positive (rs = 0.77, p < 0.0001), and between POCT-APTT and anti-Xa activity (n = 729 pairs) was weakly positive (rs = 0.46, p < 0.0001). Inter-method agreement (Cohen's kappa (k)) between POCT and laboratory APTT was 0.27, and between POCT and anti-Xa activity was 0.30. The median TATs from sample collection to the lab delivery of results for lab-APTT and anti-Xa were 50.9 min (interquartile range (IQR), 38.4−69.1) and 66.3 min (IQR, 49.0−91.8), respectively, while the POCT delivered results in less than 5 min (p < 0.0001). Although the use of the POCT-APTT device significantly reduced the time to results, the results obtained were poorly consistent with those obtained by lab-APTT or anti-Xa activity, and therefore it should not be used with the nomograms developed for lab-APTT.

Study of in vitro thrombin generation after neutralization of heparin.

INTRODUCTION: Thrombin generation (TG) documents hypercoagulability. TG in platelet-poor plasma is exquisitely sensitive to heparins, which thus must be neutralized before testing. Heparinase and hexadimethrine bromide (polybrene) have been used for that purpose, but their effects per se on TG have been poorly studied so far. METHODS: (i) TG was studied in commercial normal pooled plasma (NPP; CryoCheck® , Cryopep) in absence or presence of neutralizing agents. (ii) NPP was spiked with increasing concentrations of unfractionated heparin (UFH; up to 1.0 IU/mL) or low-molecular-weight heparin (LMWH; enoxaparin up to 1.2 IU/mL) and TG studied after incubation of heparinase (Hepzyme® ; 15 minutes) or polybrene (0.025 mg/mL; 10 minutes). RESULTS: (i) With ThromboScreen reagent to initiate TG, addition of heparinase was associated with increased peak, whereas polybrene caused lengthening of lag time and time to peak, compared with nonsupplemented NPP. (ii) With polybrene, TG was completely restored over the whole range of UFH and LMWH studied. By contrast, heparinase failed to fully restore TG in presence of UFH concentrations ≥0.8 IU/mL or LMWH concentrations ≥1.0 IU/mL. Those effects were matched with detectable tiny residual amounts of non-neutralized heparin (as assessed with an anti-Xa assay) and were less pronounced with a higher picomolar concentration of tissue factor (DrugScreen reagent). CONCLUSION: Polybrene fully restored TG of heparinized plasma at the expense of an alteration of TG, pointing to the need to use adapted reference ranges. Heparinase failed to do so in presence of high concentrations of both heparins.

Expression of select mRNA in Thoroughbreds with catastrophic racing injuries.

BACKGROUND: The ability to identify horses at risk for catastrophic injuries continues to be a pressing issue for the racing industry, especially given recent events in North America. OBJECTIVES: Since most catastrophic injuries occur in areas of existing pathology and this pathology is likely to elicit an inflammatory response, it was hypothesised that analysis of messenger RNA (mRNA) expression would detect significant changes in select genes in horses at risk for a catastrophic injury. STUDY DESIGN: Prospective cohort study. METHODS: Five racing jurisdictions across the United States participated in this study. A total of 686 Tempus® RNA Blood Tube samples were collected for mRNA analysis from 107 catastrophically injured horses, as well as from noninjured horses sampled either prerace (n = 374) or postrace (n = 205). A subset of horses (n = 37) were sampled both prerace and postrace for analysis of expression changes during the postrace period. RESULTS: Of 21 genes analysed via RT-qPCR, the expression of 12 genes (ALOX5AP, CD14, IL-10, IL-1ß, IL-6, IL-8, MMP1, PTGS2, TLR4, TNFα, TNFSF13B and VEGFA) changed significantly within 45 minutes after a race and were excluded. Of the remaining nine genes (BMP-2, IGF-1, IL1RN, MMP2, MMP9, Osteoprotegrin, RANKL, SAA1 and TGFß), three genes (IGF-1, IL1RN and MMP2) were found to be significantly different between catastrophically injured and noninjured horses using multiple logistic regression modelling. Receiver operating characteristic analysis of models, which included mRNA expression, demonstrated sensitivities from 76%-82% (95% CI: 67%-93%) and specificities from 84%-88% (95% CI: 71%-94%) at the Youden Index. MAIN LIMITATIONS: Samples were collected as soon as possible postinjury (within 30 minutes). CONCLUSIONS: Analysis of mRNA expression of specific genes in the future may be considered as an economical, accessible and noninvasive means by which horses at risk for catastrophic injury can be identified.

Impact of centrifugation on thrombin generation in healthy subjects and in patients treated with direct oral anticoagulants.

INTRODUCTION: Double centrifugation before freezing is recommended before thrombin generation assays (TGA). However, this procedure is not mandatory for routine hemostasis tests, precluding the use of these samples for TGA. The aim of this study is to assess the impact of single and double centrifugation on TGA performed on frozen samples from healthy volunteers (HVs) and patients receiving direct oral anticoagulants (DOACs). METHODS: Forty HVs and 57 patients receiving a DOAC (dabigatran, rivaroxaban, apixaban, or edoxaban) were included in this prospective double-center observational study. Blood was collected into 109 mmol/L citrated tubes and frozen at -70°C before TGA using ST Genesia with STG-DrugScreen reagent. Four pre-analytical conditions were studied: (A) single centrifugation (2000 g, 15 minutes) before freezing; (B) one centrifugation before freezing and another after thawing (2000 g, 15 minutes for both); (C) one centrifugation before freezing(2000 g, 15 minutes) and another after thawing (2000 g, 10 minutes); (D) double centrifugation (2000 g, 15 minutes) before freezing (reference). Centrifugation conditions (A), (B), and (C) were compared with the reference condition (D). Acceptable relative differences were defined at 6%, 8%, and 10% for normalized lag time, endogenous thrombin potential, and peak height, respectively. RESULTS: Centrifugation conditions had a small but acceptable impact on HVs samples, but single centrifugation always resulted in unacceptable reductions in normalized lag times for DOAC samples. A second centrifugation after thawing permitted the recovery of acceptable differences for the three TGA parameters for edoxaban but not for apixaban, rivaroxaban, nor dabigatran. CONCLUSION: Double centrifugation before freezing should remain the recommended pre-analytical condition before TGA.

The Impact of Strong Inducers on Direct Oral Anticoagulant Levels.

PURPOSE: The concomitant use of direct oral anticoagulants (DOAC) and strong P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4) inducers may lead to reduced DOAC levels and therapeutic failure. This study aimed to describe DOAC concentrations in patients receiving strong P-gp and CYP3A4 inducers, in relation to individual risk factors for high or low DOAC levels. METHODS: We retrospectively identified hospitalized patients simultaneously receiving a DOAC and carbamazepine, phenobarbital, phenytoin, or rifampicin between 2016 and 2021. Among them, patients who underwent DOAC measurement at steady state were included. DOAC peak or trough levels were compared with on-therapy ranges observed in pivotal trials. Individual risk factors for high or low DOAC levels were identified. RESULTS: We included 17 patients (median age 75 years), mainly receiving apixaban and carbamazepine. For 5 patients (29%), DOAC trough or peak level was below the expected range. Among the remaining 12 patients, 8 had at least one measurement in the lower quartile of the range. The median number of risk factors for drug accumulation was 0 (range 0-1) in patients with ≥1 measurement below the range and 2 (range 0-3) in other patients. DOAC measurement led to treatment adjustments in 9 patients (DOAC dose increase or switch). CONCLUSION: Our data suggest a significant risk of reduced DOAC levels in patients taking strong P-gp and CYP3A4 inducers, especially those without risk factors for drug accumulation. DOAC measurement could help manage this relevant drug-drug interaction.

Viscoelastometric Testing to Assess Hemostasis of COVID-19: A Systematic Review.

Infection by SARS-CoV-2 is associated with a high risk of thrombosis. The laboratory documentation of hypercoagulability and impaired fibrinolysis remains a challenge. Our aim was to assess the potential usefulness of viscoelastometric testing (VET) to predict thrombotic events in COVID-19 patients according to the literature. We also (i) analyzed the impact of anticoagulation and the methods used to neutralize heparin, (ii) analyzed whether maximal clot mechanical strength brings more information than Clauss fibrinogen, and (iii) critically scrutinized the diagnosis of hypofibrinolysis. We performed a systematic search in PubMed and Scopus databases until 31st December 2020. VET methods and parameters, and patients' features and outcomes were extracted. VET was performed for 1063 patients (893 intensive care unit (ICU) and 170 non-ICU, 44 studies). There was extensive heterogeneity concerning study design, VET device used (ROTEM, TEG, Quantra and ClotPro) and reagents (with non-systematic use of heparin neutralization), timing of assay, and definition of hypercoagulable state. Notably, only 4 out of 25 studies using ROTEM reported data with heparinase (HEPTEM). The common findings were increased clot mechanical strength mainly due to excessive fibrinogen component and impaired to absent fibrinolysis, more conspicuous in the presence of an added plasminogen activator. Only 4 studies out of the 16 that addressed the point found an association of VETs with thrombotic events. So-called functional fibrinogen assessed by VETs showed a variable correlation with Clauss fibrinogen. Abnormal VET pattern, often evidenced despite standard prophylactic anticoagulation, tended to normalize after increased dosing. VET studies reported heterogeneity, and small sample sizes do not support an association between the poorly defined prothrombotic phenotype of COVID-19 and thrombotic events.

Gobbling across landscapes: Eastern wild turkey distribution and occupancy-habitat associations.

Extensive restoration and translocation efforts beginning in the mid-20th century helped to reestablish eastern wild turkeys (Meleagris gallopavo silvestris) throughout their ancestral range. The adaptability of wild turkeys resulted in further population expansion in regions that were considered unfavorable during initial reintroductions across the northern United States. Identification and understanding of species distributions and contemporary habitat associations are important for guiding effective conservation and management strategies across different ecological landscapes. To investigate differences in wild turkey distribution across two contrasting regions, heavily forested northern Wisconsin, USA, and predominately agricultural southeast Wisconsin, we conducted 3050 gobbling call-count surveys from March to May of 2014-2018 and used multiseason correlated-replicate occupancy models to evaluate occupancy-habitat associations and distributions of wild turkeys in each study region. Detection probabilities varied widely and were influenced by sampling period, time of day, and wind speed. Spatial autocorrelation between successive stations was prevalent along survey routes but was stronger in our northern study area. In heavily forested northern Wisconsin, turkeys were more likely to occupy areas characterized by moderate availability of open land cover. Conversely, large agricultural fields decreased the likelihood of turkey occupancy in southeast Wisconsin, but occupancy probability increased as upland hardwood forest cover became more aggregated on the landscape. Turkeys in northern Wisconsin were more likely to occupy landscapes with less snow cover and a higher percentage of row crops planted in corn. However, we were unable to find supporting evidence in either study area that the abandonment of turkeys from survey routes was associated with snow depth or with the percentage of agricultural cover. Spatially, model-predicted estimates of patch-specific occupancy indicated turkey distribution was nonuniform across northern and southeast Wisconsin. Our findings demonstrated that the environmental constraints of turkey occupancy varied across the latitudinal gradient of the state with open cover, snow, and row crops being influential in the north, and agricultural areas and hardwood forest cover important in the southeast. These forces contribute to nonstationarity in wild turkey-environment relationships. Key habitat-occupancy associations identified in our results can be used to prioritize and strategically target management efforts and resources in areas that are more likely to harbor sustainable turkey populations.