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Jonathan C Roberts,1 Annette von Drygalski,2 Jenny Y Zhou,2 George M Rodgers,3 Kristin Ansteatt,1 Michael D Tarantino1 1Bleeding & Clotting Disorders Institute, University of Illinois College of Medicine – Peoria, Peoria, IL, USA; 2Hemophilia and Thrombosis Treatment Center, University of California at San Diego, San Diego, CA, USA; 3Division of Hematology and Hematologic Malignancies, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT, USACorrespondence: Michael D Tarantino, The Bleeding and Clotting Disorders Institute, University of Illinois College of Medicine – Peoria, 427 West Northmoor Road, Peoria, IL, 61614, USA, Tel +1 309-692-5337, Email mtarantino@ilbcdi.orgAbstract: Hereditary antithrombin deficiency (ATD) is a rare autosomal dominant condition (estimated prevalence 1:500– 1:5000). Most ATD patients have AT activity levels 40– 60% of normal. We present treatments for venous thromboembolism (VTE) in five cases of hereditary ATD. Four patients had a family history of ATD, and one had a de novo mutation. The majority of patients had a VTE while on prophylactic anticoagulation. AT concentrate augmentation was added in these cases to treat the VTE and for prophylaxis against further episodes. Two patients had significant bleeding events, one had permanent physical sequelae. Two of the patients were pregnant. VTE is a common cause of morbidity and mortality during pregnancy. Although low molecular weight heparins are the drugs of choice during pregnancy, this treatment was inadequate in one patient (developed VTE on therapy). These cases emphasize the need to screen for ATD in young patients (< 55 years) presenting with VTE. AT augmentation therapy may be necessary in patients inadequately treated with conventional anticoagulants. Careful monitoring and individualized care are needed in ATD patients, especially those with demonstrated bleeding tendencies.Keywords: clotting disorders, venous thromboembolism, anticoagulation, bleeding tendencies

Jackie M Helms,1 Kristin T Ansteatt,1 Jonathan C Roberts,1,2 Sravani Kamatam,3 Kap Sum Foong,2,3 Jo-mel S Labayog,4 Michael D Tarantino1,2 1The Bleeding and Clotting Disorders Institute, Peoria, IL, USA; 2Department of Medicine, University of Illinois College of Medicine-Peoria, Peoria, IL, USA; 3Department of Medicine, Saint Francis Medical Center, Peoria, IL, USA; 4Department of Medicine, OSF Sacred Heart Medical Center, Danville, IL, USACorrespondence: Michael D TarantinoChief Medical Officer, The Bleeding and Clotting Disorders Institute, 9128 North Lindbergh Drive, Peoria, IL, 61615, USATel +1 309 692-5337Fax +1 309 693-3913Email mtarantino@ilbcdi.orgAbstract: The rollout of the SARS-CoV-2 vaccine is underway, and millions have already been vaccinated. At least 25 reports of “immune thrombocytopenia” (ITP) or “thrombocytopenia” following the Moderna or Pfizer vaccine have been added to the Vaccine Adverse Event Reporting System (VAERS) in the US. ITP is a rare but known complication of several vaccinations. SARS-CoV-2 vaccine is new, with a novel mechanism of action, and understanding the epidemiology, clinical manifestations, treatment success and natural history of post-vaccination thrombocytopenia is evolving. We report a 74-year-old man who developed refractory thrombocytopenia within one day of receiving the Moderna SARS-CoV-2 vaccine. Several hours after vaccination, he developed significant epistaxis and cutaneous purpura. Severe thrombocytopenia was documented the following day, and he developed extremity weakness and encephalopathy with facial muscle weakness. Over a 14-day period, thrombocytopenia was treated first with high dose dexamethasone, intravenous immunoglobulin, platelet transfusions, rituximab, plasma exchange (for presumed acute inflammatory demyelinating polyneuropathy (AIDP)), and four daily doses of the thrombopoietin receptor agonist (TPO-RA) eltrombopag (Promacta™), without a platelet response. Three days later, he received the TPO-RA romiplostim (Nplate™). Five days later, his platelet count began to rise and by post-vaccination day 25, his platelet count was in the normal range. Thrombocytopenia was refractory to frontline and second-line treatment. The eventual rise in his platelet count suggests that one or both TPO-RAs may have impacted platelet recovery. Possibly, but less likely given the temporality, the drug-induced thrombocytopenia was subsiding. The aggressive use of immunosuppressive treatment may jeopardize the intended purpose of the SARS-CoV-2 vaccine, and earlier use of non-immunosuppressive second-line treatment for vaccine-related severe thrombocytopenia, such as with TPO-RAs, should be considered. While it is imperative to continue the global vaccination program, vigilance to the occurrence of post-vaccination severe thrombocytopenia is warranted.Keywords: immune thrombocytopenic purpura, platelet, SARS-CoV-2, thrombocytopenia, thrombopoietin receptor agonist, vaccine

Tea (Camellia sinensis) contains numerous polyphenolic flavonoid-derived compounds known as catechins, which have shown interesting protective activity against cancer and cardiovascular disease. Numerous products based on tea are commercially available, many of which claim to contain specific amounts of the bioactive catechins. The catechin content of seven commercial green tea products (encapsulated extracts or tea bags) was quantified by HPLC and, where possible, compared to that claimed on the label. Wide variability was observed in the catechin content between green tea products, even those that appear outwardly similar to consumers. Measured catechin content ranged from 9% to 48% of label claims; all values were significantly lower than those claims (P < 0.05). These results continue to demonstrate the problems that exist with quality control in the dietary supplement and herbal medicine industry and, there, for consumers of nutraceuticals. [ABSTRACT FROM AUTHOR]

Pasteurella multocida capsular types A, D, and F cause disease in many animal hosts, including bovine respiratory disease in cattle, which is one of the most globally significant animal diseases. Additionally, P. multocida capsular types B and E cause haemorrhagic septicaemia, a devastating disease primarily of cattle, water buffalo, and bison that develops rapidly with high mortality. Haemorrhagic septicaemia mostly occurs in developing countries and has potential to emerge elsewhere in the world. The diagnosis of haemorrhagic septicaemia currently requires recognition of compatible gross or histologic lesions and serotyping or molecular characterization of strains. In this study, we performed genomic characterization of 84 P. multocida strains, which were then used to develop and validate a matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) biomarker-based method for differentiating non-haemorrhagic septicaemia strains of P. multocida from haemorrhagic septicaemia-causing strains. Haemorrhagic septicaemia strain types B:2,5, E:2,5, and B:3,4 were used to maximize diversity. Three automated classification models were generated and then used to develop an assisted model, which utilized two peaks (6419 and 7729 m/z) to accurately differentiate non-haemorrhagic septicaemia-causing strains from haemorrhagic septicaemia-causing strains of P. multocida. The assisted model performed with 98.2 % accuracy for non-haemorrhagic septicaemia strains, 100 % accuracy for classic B:2,5 and E:2,5 strains, and 84.4 % accuracy for combined haemorrhagic septicaemia-causing strains (B:2,5, E:2,5, and B:3,4) with an overall accuracy of 96.9 %. Our results suggest that MALDI-TOF MS may be used to routinely screen P. multocida isolated from diagnostic cases for initial identification of haemorrhagic septicaemia-causing strains, and to determine whether additional characterizations are warranted., Competing Interests: Declaration of competing interest The authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Patients with hereditary antithrombin deficiency (HAD) have an increased risk of venous thromboembolism (VTE). The American Thrombosis and Hemostasis Network (ATHN) 12: HAD Pilot Project established a registry to collect data on patients with HAD., Objectives: To inform current practice and serve as a platform to design a multicenter global registry for patients with HAD., Methods: The HAD registry was designed in 2020 to identify 100 patients with HAD receiving care at ATHN-affiliated centers. Demographics, type of HAD, thrombotic events, risk factors, anticoagulants, and antithrombin (AT) concentrate administration were recorded., Results: Ninety-four patients were included; 65% were females; 51% had type 1 HAD. Mean age at diagnosis was 26 years (SD, 18 years); 61% had VTE: 55% deep vein thrombosis and 27% pulmonary embolisms. Eight patients had arterial thrombosis. Recurrent thrombosis occurred in 58.6% of patients (44.8%) despite anticoagulation. The main risk factor for thrombosis in females was estrogen. Direct oral anticoagulants were prescribed in 30%, heparin in 34%, and warfarin in 32%. There were 139 pregnancies. Low-molecular-weight heparin was administered in 33% and AT concentrate in 19% and 11% prior to and after delivery, respectively. Twelve patients developed thrombosis in pregnancy. Seventy-nine patients underwent 239 surgeries or procedures, mainly gastrointestinal and vascular. Overall, 35% of participants received AT concentrate without adverse events., Conclusion: In ATHN 12, VTE was the predominant manifestation, frequently recurrent. There was a trend toward using direct oral anticoagulants. Low-molecular-weight heparin was administered in one-third of pregnancies and AT concentrate in one-fifth without adverse events. These data should encourage prospective studies to optimize the management of these patients., Competing Interests: Declaration of competing interests M.T.D.: participation on Pharmacosmos Advisory Board and member of American Society of Hematology Panel on Practice Guidelines for Anticoagulation in COVID-19. E.S.: no conflict of interest. J.C.R.: has received honorarium from F. Hoffman-La Roche AG, Genentech, Novo Nordisk, Octapharma, Pfizer, Sanofi, and Takeda. M.D.T.: received consulting fees from Pfizer, Sanofi, Sobi-Swedish Orphan, Biovitrum, Takeda Amgen, Octapharma Inc, Genentech, BioMarin, UCB Biosciences Dova Pharmaceuticals, and Novo Nordisk and payment/honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational event from Sobi-Swedish Orphan Biovitrum, Genentech, Amgen, Novartis, BioMarin, and Sanofi. J.S.: no conflict of interest. J.C.: no conflict of interest. M.R.: consulting for Catalyst Biosciences, CSL Behring, Genentech, Hema Biologics, Kedrion, Novo Nordisk, Pfizer, Sanofi, Takeda, and uniQure and leadership or fiduciary role in Foundation for Women and Girls with Blood Disorders; Partners in Bleeding Disorders, Thrombosis and Hemostasis Societies of North America., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

We present a path-based design model and system for designing and creating visualisations. Our model represents a systematic approach to constructing visual representations of data or concepts following a predefined sequence of steps. The initial step involves outlining the overall appearance of the visualisation by creating a skeleton structure, referred to as a flowpath. Subsequently, we specify objects, visual marks, properties, and appearance, storing them in a gene. Lastly, we map data onto the flowpath, ensuring suitable morphisms. Alternative designs are created by exchanging values in the gene. For example, designs that share similar traits, are created by making small incremental changes to the gene. Our design methodology fosters the generation of diverse creative concepts, space-filling visualisations, and traditional formats like bar charts, circular plots and pie charts. Through our implementation we showcase the model in action. As an example application, we integrate the output visualisations onto a smartwatch and visualisation dashboards. In this article we (1) introduce, define and explain the path model and discuss possibilities for its use, (2) present our implementation, results, and evaluation, and (3) demonstrate and evaluate an application of its use on a mobile watch.

The typical phenotype of hemophilia A (HA) is that of frequent bleeding episodes, up to several per month, unless prophylactic factor VIII (FVIII) replacement or alternatives are given. Related bleeding may be heightened in severity or frequency by co-morbid bleeding disorders. Based on the reported prevalence of von Willebrand disease (VWD) of up to 1% of the general population, the co-existence of HA and VWD occurs, but is likely less recognized. Prophylactic FVIII replacement may or may not adequately prevent bleeding in persons with HA and mild VWD, and plasma-derived concentrates containing FVIII and von Willebrand factor (VWF) may be used for more successful bleeding prophylaxis. However, therapy adherence remains problematic for many reasons, one being treatment via intravenous access. Emicizumab is a nonfactor subcutaneous prophylactic therapy for HA that may overcome this concern. We describe three patients, with severe HA and VWD, for whom regular FVIII/VWF prophylaxis was deemed inadequate. FVIII/VWF prophylaxis was replaced with weekly prophylactic injections of the bispecific monoclonal antibody, emicizumab. When the patients were transitioned to emicizumab, all experienced a significant reduction in their annualized bleed rate (ABR). Although the mechanism of action does not directly affect or replace VWF function, emicizumab may be an effective prophylaxis alternative to FVIII/VWF concentrate in patients with concomitant severe HA and VWD., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The diagnosis of Clostridioides difficile infection (CDI) in the pediatric population is complicated by the high prevalence of asymptomatic colonization, particularly in infants. Many laboratory diagnostic methods are available, but there continues to be controversy over the optimal laboratory testing approach to diagnose CDI in children. We evaluated commonly used C. difficile diagnostic commercial tests in our pediatric hospital population at Sidra Medicine in Doha, Qatar. Between June and December 2023, 374 consecutive stool samples from pediatric patients aged 0-18 years old were tested using: Techlab C. diff Quik Chek Complete, Cepheid GeneXpert C. difficile , QIAstat-Dx Gastrointestinal Panel, and culture using CHROMagar C. difficile . The results of these tests as standalone methods or in four different testing algorithms were compared to a composite reference method on the basis of turnaround time, ease of use, cost, and performance characteristics including specificity, sensitivity, negative predictive value, and positive predictive value. Our study showed variability in test performance of the different available assays in diagnosing CDI. In our population, a testing algorithm starting with Cepheid GeneXpert C. difficile PCR assay or QIAstat-Dx Gastrointestinal panel as a screening test followed by toxin immunoassay for positive samples using the Techlab C. diff Quik Chek Complete kit showed the best performance (100% specificity and 100% positive predictive value) when combined with clinical review of the patient to assess risk factors for CDI, clinical presentation, and alternative causes of diarrhea.

Abstract: We assessed the feasibility to estimate illness burden in adults with SCD, investigated factors associated with health-related quality of life (HRQoL), and estimated societal burden. We recruited 32 participants and collected data on fatigue, HRQoL, and work productivity and activity impairment via patient survey. Health care utilization was abstracted for the 12 months before enrollment using medical chart review. Mean age was 36.7 years; 84.4% of participants had hemoglobin SS or Sβthal0 disease, and 81.3% reported chronic pain (experiencing pain on ≥3 days per week in the past 6 months). Mean EQ-5D-3L visual analogue scale score was 63.4 and the index score was 0.79. The mean fatigue score was 57.9. Higher fatigue score was correlated with lower EQ-5D index score (correlation coefficient r = -0.35; P = .049) and Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) scores, including pain (r = -0.47; P = .006), sleep (r = -0.38; P = .03), and emotion scores (r = -0.79; P < .0001). The number of hospitalizations was negatively correlated with HRQoL (all P < .05). Patients who reported chronic pain had significantly lower mean ASCQ-Me sleep scores (48.3 vs 57.1; P = .04) and EQ-5D index scores (0.72 vs 0.89; P = .002) than those without chronic pain. Mean estimated annual per person costs were $51 779 (median, $36 366) for total costs, $7619 ($0) for indirect costs (estimated from lost earnings of participants), and $44 160 ($31 873) for medical costs. Fatigue, SCD complications, hospitalization, and chronic pain negatively affected HRQoL. This sample experienced a high economic burden, largely from outpatient doctor visits., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Introduction: Gastrointestinal (GI) bleeding events (BEs) in von Willebrand disease (VWD) are difficult to diagnose and often recurrent. Limited data from clinical trials has led to lack of consensus on treatment options., Aim: Describe current treatments and outcomes for GI BEs in people with VWD., Methods: This retrospective, observational, multicentre chart review study was conducted from January 2018 through December 2019 and included patients with inherited VWD with ≥1 GI BE in the preceding 5 years. Baseline characteristics, number and aetiology of BEs, associated GI-specific morbidities/lesions, treatment and outcomes were analysed descriptively., Results: Sixty bleeds were reported in 20 patients with type 1 (20%), type 2 (50%) and type 3 (30%) VWD. During the 5-year study period, 31 (52%) BEs had one identified or suspected cause; multiple causes were reported in 11 (18%). Most GI BEs (72%) were treated with a combination of von Willebrand factor (VWF), antifibrinolytics and/or other haemostatic or non-haemostatic treatments. Time to resolution did not differ by VWF treatment use; however, BEs treated with non-VWF treatments tended to resolve later. In patients with GI-specific morbidities/lesions, 84% resolved with first-line treatment; time to resolution tended to be longer than in patients without such morbidities/lesions. Thirteen BEs occurred in patients receiving prophylaxis and 47 in patients receiving on-demand treatment; 18 BEs resulted in a switch to prophylaxis after bleed resolution., Conclusions: This study confirms the unmet need for the management of recurrent GI BEs in people with VWD and the need for prospective data, especially on prophylaxis., (© 2024 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Better diagnostic tools are needed to improve the diagnosis of Clostridioides difficile infections (CDI) and reduce the overtreatment of colonized children. In this study, we evaluated two polymerase chain reaction (PCR) assays (Cepheid GeneXpert C. difficile and the Gastroenteritis PCR Panel by QIAstat-Dx) as a standalone method in combination with the PCR cycle threshold (Ct) value in positive samples to predict the presence of free toxins. We also evaluated the clinical impact of reporting toxin production results and provided comments alongside the PCR results in our pediatric population. PCR-positive stool samples from pediatric patients (aged 2 to 18 years old) were included in our study and tested for the presence of toxins A and B using the C. difficile Quik Chek Complete kit. For the clinical intervention, the CDI treatment rates 6 months pre- and post-intervention were compared. The use of PCR Ct value showed excellent sensitivity (100%) at a Ct value cutoff of 26.1 and 27.2 using the Cepheid GeneXpert C. difficile and the Gastroenteritis PCR Panel by QIAstat-Dx, respectively, while the toxin test showed inferior sensitivity of 64% in the PCR-positive samples. In addition, CDI treatment rates were decreased by 23% post-intervention. The results of our study suggest that nucleic acid amplification test (NAAT) assays supplemented by the use of PCR Ct value for positive samples can be used as standalone tests to differentiate CDI from colonization. Furthermore, the reporting of toxin production along with the PCR results can help reduce the unnecessary treatment of colonized children.

Hemophilia is a rare genetic bleeding disorder historically associated with high morbidity and mortality. Some individuals with hemophilia suffer associated chronic joint disease, chronic pain, and other physical and mental health challenges. In the last 50 years, a better understanding of the pathophysiology of the disease has resulted in extraordinary therapeutic advances leading to enhanced quality of life and increased life expectancy. We present an illustrated review of the evolution of hemophilia treatment from the development of non-factor therapies to gene therapy., Competing Interests: Dr. Michael D. Tarantino reports consulting fees from Pfizer, Sanofi, Sobi-Swedish Orphan Biovirtum, Takeda, Amgen, INC, Octapharma, Genentech, BioMarin, UCB Biosciences, Dova Pharmaceuticals, Novo Nordisk, and payment honoraria from Sobi, Genentech, Amgen, Novartis, BioMarin, and Sanofi. Dr. Jonathan C. Roberts reports grants from Takeda and Genetech, consulting fees from CSL Behring, F. Hoffman-La Roche AG, Sanofi, HEMA Biologics, Novartis, Novo Nordisk, Pfizer, Takeda, and Genentech. Dr. María G. Español reports participation on Sevenfact Advisory Board from HEMA biologics and payment honoraria from Octapharma., (© 2023 The Author(s).)

This paper is a call to action for research and discussion on data visualization education. As visualization evolves and spreads through our professional and personal lives, we need to understand how to support and empower a broad and diverse community of learners in visualization. Data Visualization is a diverse and dynamic discipline that combines knowledge from different fields, is tailored to suit diverse audiences and contexts, and frequently incorporates tacit knowledge. This complex nature leads to a series of interrelated challenges for data visualization education. Driven by a lack of consolidated knowledge, overview, and orientation for visualization education, the 21 authors of this paper-educators and researchers in data visualization-identify and describe 19 challenges informed by our collective practical experience. We organize these challenges around seven themes People, Goals & Assessment, Environment, Motivation, Methods, Materials, and Change. Across these themes, we formulate 43 research questions to address these challenges. As part of our call to action, we then conclude with 5 cross-cutting opportunities and respective action items: embrace DIVERSITY+INCLUSION, build COMMUNITIES, conduct RESEARCH, act AGILE, and relish RESPONSIBILITY. We aim to inspire researchers, educators and learners to drive visualization education forward and discuss why, how, who and where we educate, as we learn to use visualization to address challenges across many scales and many domains in a rapidly changing world: viseducationchallenges.github.io.

Introduction: VWD diagnosis is challenging requiring multiple VWF activity tests using many individual assays. We have developed an ELISA-based VWF Multiplex Activity Assay (VWF-MAA) to address this concern; however, the ability of the VWF-MAA to discriminate between type 1 VWD, variant VWD, and normal subjects has not been evaluated., Aim: To evaluate the VWF-MAA and its ability to differentiate between type 1 VWD, variant VWD and normal subjects in individuals undergoing an initial laboratory evaluation for bleeding., Methods: A total of 177 plasma samples from the Zimmerman Program: Comparative Effectiveness in the Diagnosis of VWD were evaluated from 11 centres across the US and Canada. The VWF-MAA was compared to Versiti Blood Research Institute (VBRI) and Local Center (LC) assigned VWD diagnosis., Results: Overall, 129/177 (72.9%) were correctly assigned as normal (non-VWD), type 1, or variant VWD compared to the VBRI assigned diagnosis. VWF-MAA assigned non-VWD accurately in 29/57 (50.9%) samples, and type 1 VWD accurately in 93/110 (84.6%) samples. Considering LC diagnosis where there was agreement with VWF-MAA and not VBRI diagnosis, type 1 VWD was accurate in 105/110 (95.5%) samples. Bland-Altman analysis demonstrated good correlation between laboratory methods. VWD, types 2A, 2B, 1C VWD were also assigned by the VWF-MAA., Conclusions: We demonstrate that the VWF-MAA has utility in differentiating type 1 VWD, variant VWD and normal subjects in individuals undergoing an initial laboratory evaluation for bleeding., (© 2023 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

The Indian River Lagoon (IRL), a 156-mile-long estuary located on the eastern coast of Florida, experiences phytoplankton bloom events due to increased seasonal temperatures coupled with anthropogenic impacts. This study aimed to gather data on the toxicity to human cells and to identify secondary metabolites found in water samples collected in the IRL. Water samples from 20 sites of the IRL were collected during the wet and dry seasons over a three-year period. A panel of cell lines was used to test cytotoxicity. Hemagglutination, hemolysis, and inhibition of protein phosphatase 2A (PP2A) were also measured. Cytotoxic blooms were seen both in the south ( Microcystis ) and the north ( Pyrodinium ) of the IRL. Each toxin induced a consistent pattern of cytotoxicity in the panel of human cell lines assayed. During blooms, cytotoxicity due to a single type of toxin is obvious from this pattern. In the absence of blooms, the cytotoxicity seen reflected either a mixture of toxins or it was caused by an unidentified toxin. These observations suggest that other toxins with the potential to be harmful to human health may be present in the IRL. Moreover, the presence of toxins in the IRL is not always associated with blooms of known toxin-producing organisms.

Introduction: In recent years, there has been increased focus on individualizing treatment for persons with hemophilia including pharmacokinetic-guided (PK) dosing., Aims: In this retrospective study clinical outcomes before and after PK-guided prophylaxis were examined., Materials and Methods: Eight Haemophilia Treatment Centres from the United States participated in the study and included 132 patients classified into two cohorts: those undergoing a PK-assessment for product switch (switchers) or to optimize treatment (non-switchers). Subset analyses for the two most common products and patients with dosing per prescription label were included for annual bleeding rates (ABR), mean weekly consumption outcomes, and annualized cost of prophylaxis., Results: The most common products before and after index date were octocog alfa, rurioctocog alfa pegol, and efmoroctocog alfa. Seventy-four (56%) patients were identified as switchers and 58 (44%) patients were classified as non-switchers. The majority of patients (78.0%) experienced either a decrease in ABR post-index or maintained 0 ABR during pre- and post-index time periods, with similar proportions identified in both switchers (77.0%) and non-switchers (79.3%) populations. Non-switchers were identified as having no significant change in cost of therapy, while switchers experienced increased cost of therapy driven by higher price of extended half-life products. Within subset analyses, patients receiving rurioctocog alfa pegol and efmoroctocog alfa had mean ABR under 1 after index date., Conclusion: PK-guided prophylaxis has the potential to improve clinical outcomes without increase in cost of therapy for patients maintaining product and can aid in maintaining effective protection against bleeds in those switching product., (© 2023 Takeda Pharmaceuticals USA, Inc and The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Introduction: People with haemophilia rely on specialists for their care, yet the specific dosing regimens of treatments prescribed by these specialists have not been widely studied., Aim: The objective of this study is to describe trends in clinician prescribing practices for the management of haemophilia in the United States (US)., Methods: We administered surveys to members of the Hemostasis and Thrombosis Research Society via paper surveys at its in-person annual symposia in 1999 and 2015, and an online survey in 2021. The surveys collected information on haemophilia treatments including factor dosing, inhibitor therapy and gene therapy., Results: Clinicians treating haemophilia for more than 50% of their practice time have increased from 37.5% of respondents in 1999 to 46.3% in 2021. Clinicians prescribing factor concentrates at >40 units/kg for routine bleeding events increased from 0% in 1999 to 29.3% in 2021 in haemophilia A (HA) and from 22.5% to 87.8% in haemophilia B (HB). In 2021, the clinicians reported prescribing emicizumab to treat HA patients (>89.5% paediatric, >85.7% adult) with or without inhibitors at least some of the time. Approximately 78.0% of respondents reported that they expected to recommend gene therapy at least some of time., Conclusion: These data indicate changing trends in prescribing practices among US haemophilia specialists during the past 22 years. Preference for high doses of factor (>40 units/kg) has increased during this period. Emicizumab prophylaxis has been prescribed for patients with and without HA inhibitors. Clinicians expect gene therapy to have value for some haemophilia patients., (© 2023 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Von Willebrand disease (VWD) is an inherited bleeding disorder caused by quantitative or qualitative deficiencies in von Willebrand factor (VWF). People with VWD may experience excessive, recurrent or prolonged bleeding, particularly during menstruation, childbirth, surgery or following trauma. However, many VWD patients are undiagnosed, and therefore inadequately treated. Reasons for the underdiagnosis of VWD include its relatively mild symptoms, complex diagnosis, lack of awareness among non-specialist healthcare providers and the general population, and a lack of prioritisation of disorders disproportionately affecting females. The vwdtest.com platform was launched as part of a global initiative to raise awareness and improve diagnosis of VWD. Besides providing VWD-specific educational resources, the website includes an online bleeding self-assessment tool and offers diagnostic support for individuals, and their providers, who have a score suggestive of a bleeding disorder. vwdtest.com helps to address these unmet needs, especially in regions with limited access to educational and diagnostic resources., Competing Interests: Declaration of Competing Interest FFCM has received grant/research support from Bayer and Octapharma, and honoraria or consultation fees from Bayer, Octapharma and Sanofi. ABF has received research support from Baxalta/Shire/Takeda, CSL-Behring, and honoraria or consultation fees from Baxalta/Takeda, CSL Behring, Grifols, Kedrion, LFB and Octapharma. AS has no competing interests to declare. CMM has received research support from Baxter/Takeda, CSL Behring and Grifols and honoraria or consultation fees from CSL Behring, LFB, Octapharma and Takeda. She has participated in advisory boards for Takeda and CSL Behring. JCR has disclosed receiving research support from Takeda and Genentech. He has participated in advisory boards for Sanofi Genzyme, Takeda, Octapharma, Novo Nordisk, Pfizer, and CSL Behring. He is on speaker bureaus for Sanofi Genzyme, Novo Nordisk, Octapharma, and Takeda. AD has no competing interests to declare. JJ received an unrestricted educational grant from Octapharma. EB has received grant/research support from Bayer, Baxalta/Takeda, CSL Behring and Sobi, and honoraria or consultation fees from Bayer, Baxalta/Takeda, CSL Behring and Octapharma., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: We assessed sociodemographic and clinical characteristics associated with depression and anxiety in individuals with Von Willebrand disease (VWD) aged ≥12 years., Methods: The study collected data on patients' sociodemographic, joint problems and health-related quality of life (HRQoL) using EQ-5D-3L, 8-item patient health questionnaire for depression and 7-item Generalized Anxiety Disorder Questionnaire from participants in seven geographically diverse US haemophilia treatment centres., Results: Analyses included 77 participants. The rates of depression and anxiety were 63.6% and 58.3%, respectively. Persons with low VWF displayed higher rates of depression (86.7%) or anxiety (69.2%) compared to those with VWD (58.1%, p = .04 for depression, and 55.9%, p = .38 for anxiety). Logistic regression analyses demonstrated that having joint problems (odds ratio [OR] = 6.3, confidence interval [CI] = 2.0-20.1) was the most important variable associated with depression, followed by being single, divorced, widowed, or separated in adult participants or parents of participants age < 18 years (OR = 7.0, CI = 1.7-29.0. The most important variable associated with anxiety was being single or lacking a partner (OR = 10.8, CI = 2.5-47.5), followed by age 12-17 years old (OR = 6.7, CI = 1.6-26.9), or having worse health compared to 3-months ago (OR = 12.3, CI = 1.3-116.2). Mean covariates adjusted EQ visual analogue scale score was significantly lower among persons with depression (68.77 ± 3.15 vs. 77.58 ± 4.24, p = .03) than those without depression., Conclusions: Our study revealed concerning levels of depression and anxiety in this VWD sample. Lack of social support was determined an important factor associated with depression and anxiety in this sample. Mental health screening is critical in VWD clinical evaluation and care., (© 2022 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Symptoms-based detection of SARS-CoV-2 infection is not a substitute for precise diagnostic tests but can provide insight into the likely level of infection in a given population. This study uses symptoms data collected in the Global COVID-19 Trends and Impact Surveys (UMD Global CTIS), and data on variants sequencing from GISAID. This work, conducted in January of 2022 during the emergence of the Omicron variant (subvariant BA.1), aims to improve the quality of infection detection from the available symptoms and to use the resulting estimates of infection levels to assess the changes in vaccine efficacy during a change of dominant variant; from the Delta dominant to the Omicron dominant period. Our approach produced a new symptoms-based classifier, Random Forest, that was compared to a ground-truth subset of cases with known diagnostic test status. This classifier was compared with other competing classifiers and shown to exhibit an increased performance with respect to the ground-truth data. Using the Random Forest classifier, and knowing the vaccination status of the subjects, we then proceeded to analyse the evolution of vaccine efficacy towards infection during different periods, geographies and dominant variants. In South Africa, where the first significant wave of Omicron occurred, a significant reduction of vaccine efficacy is observed from August-September 2021 to December 2021. For instance, the efficacy drops from 0.81 to 0.30 for those vaccinated with 2 doses (of Pfizer/BioNTech), and from 0.51 to 0.09 for those vaccinated with one dose (of Pfizer/BioNTech or Johnson & Johnson). We also extended the study to other countries in which Omicron has been detected, comparing the situation in October 2021 (before Omicron) with that of December 2021. While the reduction measured is smaller than in South Africa, we still found, for instance, an average drop in vaccine efficacy from 0.53 to 0.45 among those vaccinated with two doses. Moreover, we found a significant negative (Pearson) correlation of around - 0.6 between the measured prevalence of Omicron in several countries and the vaccine efficacy in those same countries. This prediction, in January of 2022, of the decreased vaccine efficacy towards Omicron is in line with the subsequent increase of Omicron infections in the first half of 2022., (© 2023. The Author(s).)