Desmopressin (DDAVP) use in patients with von Willebrand disease: A single-centre retrospective review of test response and clinical outcomes.

INTRODUCTION: Peri-procedural management of von Willebrand disease (VWD) utilizes von Willebrand factor (VWF) concentrates or desmopressin (DDAVP) to increase VWF levels. DDAVP is safe, easily administered, and inexpensive. Currently, a consensus definition for adequate DDAVP response is lacking, and outcomes of peri-procedural DDAVP use in VWD patients are seldom reported. AIM: This single-centre retrospective review aims to characterize DDAVP-responsiveness and assess clinical outcomes of peri-procedural DDAVP use in VWD. PATIENTS AND METHODS: We reviewed records for all our adult VWD patients (age ≥18 years) who underwent DDAVP challenge testing between January 2007 and January 2022. DDAVP-responsiveness was assessed using six definitions. Bleeding outcomes following procedures covered by DDAVP were classified as excessive or expected bleeding. RESULTS: Eighty-four of 94 (89.4%) patients were DDAVP-responsive by our definition (1-h VWF Activity/Factor VIII ≥0.50 IU/mL). However, the proportion of DDAVP-responders varied from 53.2% to 91.5%, depending on the literature definition used. Ninety-nine procedures pre-treated with DDAVP were performed during the study period. Eighty-six (86.7%) procedures (31 major; 55 minor) were covered with only DDAVP ± tranexamic acid (TXA). Excessive bleeding occurred following 4/31 major procedures and 2/55 minor procedures (both performed in a single patient with a bleeding score of 16). When covered with DDAVP+Factor ± TXA, one each of 10 major and 3 minor procedures (performed in 2 patients with bleeding scores 15-16) resulted in post-procedural bleeding. CONCLUSIONS: Peri-procedural DDAVP prophylaxis appears to be effective among individuals with VWD. Beyond DDAVP-responsiveness, patient bleeding history and procedure invasiveness should be considered in determining suitability for DDAVP prophylaxis.

Determining the incidence of postpartum haemorrhage among Ontario women with and without inherited bleeding disorders: A population-based cohort study.

INTRODUCTION: At a population level, there is a poor understanding of the incidence and pre-disposing risk factors of postpartum haemorrhage (PPH) among women with inherited bleeding disorders (IBD). AIM: To determine the incidence of PPH, and identify maternal factors associated with risk of PPH among women with IBD. METHODS: We conducted a retrospective cohort study using data housed within ICES (formerly known as the Institute for Clinical Evaluative Sciences). The cohort included women with an in-hospital, live or stillborn delivery, between January 2014 and December 2019. The primary outcome was PPH (identified by ICD-10 code O72). PPH incidence and risk factors were compared between women with and without IBD. Temporal trends were assessed using the Cochrane-Armitage test. Between group differences were assessed using standardised differences (std. difference). RESULTS: Total 601,773 women were included; 2002 (.33%) had an IBD diagnosis. PPH incidence was 1.5 times higher (7.3 vs. 4.9 cases/100 deliveries, std. difference .1) among women with IBD compared to women without. Women with IBD were slightly older (31.7 vs. 30.7 years), had higher rates of hypertension, previous PPH, and induction of labour. Women with IBD were more frequently diagnosed with anaemia (4.8% vs. 1.8%; std difference .17) and had lower haemoglobin levels at admission for delivery compared to women without IBD. CONCLUSIONS: This study contributes to the literature regarding obstetric bleeding among women with IBD, showing that anaemia at delivery may be an important risk factor for PPH. Given their predisposition to anaemia, clarifying this relationship will optimise management and outcomes.

Objectivity in rare disease research: A philosophical approach.

Individuals living with rare conditions are faced with important challenges derived from the rarity of their conditions and aggravated by the low priority given to rare disease research. However, current realities of rare disease research require consideration of the relationship between subjectivity and 'traditional' objectivity. Objectivity in research has traditionally been associated with processes and descriptions that are independent of the investigator. The need for researchers to provide unbiased knowledge and achieve a balance between objectivity and the underlying values in nursing and scientific research requires an examination of how objectivity is conceptualized within the context of rare disease research. The aim of this paper is to examine scientific objectivity in rare disease research from a philosophical viewpoint and, in doing so, demonstrate the need to redefine it to reflect the current scientific environment. As such, healthcare providers working on this field need to redefine objectivity around ethical and moral obligation to advance science in an equitable manner with the end goal to produce knowledge that is trustworthy and beneficial to our patients.

Desmopressin in non-severe haemophilia A: Test-response and clinical outcomes in a single Canadian centre review.

INTRODUCTION: Desmopressin is an effective haemostatic agent for patients with non-severe haemophilia A; however, response may differ between patients of similar severity. Responsiveness is classified based on various cut-off values for plasma levels of FVIII post-desmopressin administration. Patients may be classified differently depending on the values chosen. AIM: To classify desmopressin response in non-severe haemophilia A patients with respect to current test-response definitions. Also, to characterize relationships between test response and clinical outcome of desmopressin use. METHODS: Current desmopressin test-response definitions were obtained from the literature. We adopted peak FVIII level (at 1 hour post-administration) ≥50 IU/dL and <20 IU/dL as complete and no response, respectively, thereby satisfying most reported definitions. Test-responses and clinical outcomes of use between 2007 and 2017 for adult mild/moderate haemophilia A patients were reviewed and correlated. RESULTS: All patients classified as complete responders (n = 31; peak FVIII ≥50 IU/dL) and the majority of partial responders (n = 11; peak FVIII ≥20 to <50 IU/dL) had good clinical outcomes after desmopressin use for a variety of bleeding episodes and procedures. Two non-responders (peak FVIII <20 IU/dL) given desmopressin for minor bleeding/procedures also had good clinical outcomes. One patient with a partial test-response (peak FVIII 23 IU/dL) required additional factor concentrate to achieve haemostasis. CONCLUSIONS: Based on our review, we suggest that the determination of desmopressin responsiveness should consider both the change in plasma FVIII levels as well as clinical outcomes associated with prior therapeutic use.

Developing recommendations to improve identification, prevention, and response to suicide thoughts and behaviours among post-secondary students: A mixed methods study.

Objective: This study aimed to generate recommendations regarding how to identify, prevent and respond to suicide thoughts and behaviors among post-secondary students. Methods: A convergent mixed-methods design with Nominal Groups Technique (NGT) was used. Post-secondary and high-school students and their caregivers generated and ranked recommendations. A Codebook Thematic Analysis approach guided analysis of the NGT-discussions and extended understanding of recommendations. Results: 88 individuals participated in 21 panels. Five key recommendations were identified: (1) increase student and staff education regarding suicide identification, prevention, and awareness of existing supports; (2) enhance rapid access to supports for those experiencing a crisis; (3) improve institutional academic supports for students following crisis; (4) reduce stigma; (5) improve communication regarding on-campus suicide. Common themes included perceived impact of attitudes, institutional barriers, and peer-support on suicide thoughts and behaviors. Conclusions: These recommendations can inform the development of student-centred interventions for improving mental health supports.

Identifying the effect of inherited bleeding disorders on the development of postpartum hemorrhage: a population-based, retrospective cohort study.

Background: Women with inherited bleeding disorders (IBDs) are at an increased risk of postpartum hemorrhage (PPH). However, the impact of other maternal predelivery risk factors, including anemia, on the association between IBD and maternal bleeding remains poorly understood. Additionally, studies examining potential pathways linking IBD and PPH are limited. Objectives: We aimed to determine the risk of PPH associated with IBD. Methods: A retrospective cohort study was conducted using data held within ICES (formerly the Institute for Clinical Evaluative Sciences). Women with an in-hospital, live, or stillborn delivery between January 2014 and December 2019 were included. Poisson regression with robust error variance was used to determine the risk (RR) and 95% CIs of PPH among women with or without an IBD diagnosis. Models were stratified for primiparous and multiparous women. Results: Among the total population of 601,773 women, 29,661 (4.93%) experienced PPH. Multivariate models demonstrated that IBD was an independent risk factor for PPH among both the total cohort (adjusted RR [aRR] = 1.26; 95% CI: 1.08, 1.46) and primiparous women (aRR = 1.36; 95% CI: 1.12, 1.66). Among multiparous women, prior PPH was associated with an increased risk of PPH (aRR = 8.65; 95% CI: 8.32, 8.99), whereas IBD had no effect (aRR = 1.1; 95% CI: 0.86, 1.4). Predelivery anemia, placental conditions, multifetal gestation, and induction of labor were associated with increased PPH risk among all cohorts. Conclusions: IBD significantly increases the risk of PPH. The management of delivery should be based on individualized assessment of risk factors to ensure optimal maternal outcomes.

Repurposing the Ordering of Routine Laboratory Tests in Hospitalised Medical Patients (RePORT): results of a cluster randomised stepped-wedge quality improvement study.

BACKGROUND: Low-value use of laboratory tests is a global challenge. Our objective was to evaluate an intervention bundle to reduce repetitive use of routine laboratory testing in hospitalised patients. METHODS: We used a stepped-wedge design to implement an intervention bundle across eight medical units. Our intervention included educational tools and social comparison reports followed by peer-facilitated report discussion sessions. The study spanned October 2020-June 2021, divided into control, feasibility testing, intervention and a follow-up period. The primary outcomes were the number and costs of routine laboratory tests ordered per patient-day. We used generalised linear mixed models, and analyses were by intention to treat. RESULTS: We included a total of 125 854 patient-days. Patient groups were similar in age, sex, Charlson Comorbidity Index and length of stay during the control, intervention and follow-up periods. From the control to the follow-up period, there was a 14% (incidence rate ratio (IRR)=0.86, 95% CI 0.79 to 0.92) overall reduction in ordering of routine tests with the intervention, along with a 14% (ß coefficient=-0.14, 95% CI -0.07 to -0.21) reduction in costs of routine testing. This amounted to a total cost savings of $C1.15 per patient-day. There was also a 15% (IRR=0.85, 95% CI 0.79, 0.92) reduction in ordering of all common tests with the intervention and a 20% (IRR=1.20, 95% CI 1.10 to 1.30) increase in routine test-free patient-days. No worsening was noted in patient safety endpoints with the intervention. CONCLUSIONS: A multifaceted intervention bundle using education and facilitated multilevel social comparison was associated with a safe and effective reduction in use of routine daily laboratory testing in hospitals. Further research is needed to understand how system-level interventions may increase this effect and which intervention elements are necessary to sustain results.

Switching to nonacog beta pegol in hemophilia B: Outcomes from a Canadian real-world, multicenter, retrospective study.

Background: The Canadian Bleeding Disorders Registry (CBDR) captures data from 24 hemophilia treatment centers and patients directly. Nonacog beta pegol (N9-GP) was approved in Canada in 2018. Objectives: To assess treatment outcomes following switching to N9-GP in a real-world setting. Methods: CBDR data for Canadian male patients (aged 7-72 years) with hemophilia B receiving prophylactic N9-GP for ≥6 months as of March 31, 2021, were included. To allow comparison with the previously used products, only patients for whom data were available in the CBDR for at least 6 months before the switch to N9-GP were included in this retrospective analysis. Results: Forty-two patients were included in the analysis (total observation period: 148.0 patient-years). The distribution of disease severity was 62% severe, 36% moderate, 2% mild, with 62% of patients previously receiving recombinant factor IX-Fc-fusion protein (rFIXFc) and 38% previously receiving standard half-life (SHL) recombinant factor IX (rFIX). During a median follow-up period of 2.3 years on N9-GP prophylaxis, 232 bleeds were reported in 30 patients, 29% of patients reported zero bleeds. The median overall annualized bleeding rate on N9-GP was 0.73 for patients switching from rFIXFc (previously 1.44) and 2.10 for patients switching from SHL rFIX (previously 6.06). Median total annualized factor consumption (IU/kg) was lower with N9-GP than with previous SHL rFIX (2152 vs 3018) and previous rFIXFc (1766 vs 2278). Conclusions: Results from this first real-world study of N9-GP in patients with hemophilia B suggest optimal bleeding control with low factor consumption after switching to N9-GP, irrespective of the previous product.

Psychosocial burden of type 1 and 2 hereditary angioedema: a single-center Canadian cohort study.

BACKGROUND: Hereditary angioedema (HAE) is a rare but serious disorder associated with a multifaceted burden of illness including a high prevalence of psychiatric symptoms and impaired health-related quality of life (HRQoL). Despite recent efforts to clarify the psychosocial implications of HAE, important gaps still remain. The aim of this study was to characterize the psychosocial burden associated with HAE types 1 and 2. METHODS: Type 1 or 2 HAE patients (n = 17), aged 19 years or older, completed the Depression, Anxiety, Stress Scale (DASS-21) and the DSM-5 cross cutting measures to identify psychiatric symptomatology, Angioedema Quality of Life Questionnaire (AE-QoL) and the Short-Form 36-Item Health Survey version 2 (SF-36v2) to assess disease-related and generic HRQoL respectively, and the Work Productivity and Activity Impairment Questionnaire (WPAI) to measure impact on work productivity and daily activities. Data analyses were conducted using SPSS statistical software (Version 25.0; IBM, Armonk, NY). Descriptive statistics were used to summarize continuous demographics and clinical characteristics and outcomes of interest while frequency distributions were used for categorical variables. T tests were used to compare SF-36v2 domain scores to Canadian norms and sex differences in scale scores. RESULTS: Depression [DASS-21 score = 6.8 ± 10.2; n = 12 (71%)] anxiety [DASS-21 score = 6.2 ± 8.2; n = 13 (76%)] and stress [DASS-21 score = 10 ± 10.2; n = 13 (76%)] were prevalent. Other psychiatric symptoms warranting inquiry included mania (n = 14, 82.4%), anger (n = 14, 82.4%), sleep disturbances (n = 13, 76.5%), somatic symptoms (n = 11, 64.7%) and impaired personality functioning (n = 9, 52.9%). Mean AE-QoL score was 39 ± 18.2. Mean SF-36v2 domain scores were significantly lower than Canadian normative data for the entire sample (p < 0.05). Impairment in work productivity was minimal; mean activity impairment was 20.6% ± 21.1% [n = 11 (64.7%)]. Female participants reported significantly greater HAE-related stress [DASS; t(15) =  - 2.2, p = 0.04], greater HAE-related fears [AEQoL; t(5.6) =  - 2.7, p = 0.04), and lower SF-36v2 domain scores than male patients. CONCLUSIONS: Study findings offer specific, valuable insight into the psychosocial burden of HAE with the potential to improve clinical management of HAE. Best practices for effective management of HAE should include providing holistic care to address the psychosocial and mental health of HAE patients.

A case that illustrates the challenges of managing pregnant patients with antithrombin deficiency: More questions than answers.

Using an illustrative case of a patient with antithrombin (AT) deficiency who developed a recurrent venous thromboembolism (VTE) in pregnancy despite therapeutic low-molecular-weight heparin (LMWH), we highlight what is known in the literature and address areas of controversy through a series of questions around the case. The questions we address include the role of anti-Xa monitoring for patients with past VTE on antepartum LMWH, what treatment regimen is recommended for pregnant patients who develop a recurrent VTE while on therapeutic anticoagulation, the role of antepartum AT concentrate prophylaxis, and the management of labor/delivery, epidural anesthesia and postpartum anticoagulation. We also describe practical considerations for use of AT concentrate, including teaching our patient to self-infuse AT concentrate at home with support of a hemophilia treatment center (HTC), and the direct and indirect costs of AT concentrate for secondary prophylaxis.

Principles and theory guiding development and delivery of patient education in disorders of thrombosis and hemostasis: Reviewing the current literature.

Prior work regarding patient education has identified the importance of using learning theory and educational models to develop and deliver content that will improve patient outcomes. Current literature appears to examine implementation of teaching strategies without clear identification of educational principles. This review aimed to identify educational principles and theory currently utilized in the planning and delivery of patient education in disorders of thrombosis and hemostasis. The majority of articles reviewed evaluated the impact of educational interventions on patient outcomes; links between educational principles and changes in outcomes was lacking. Few articles clearly referenced theory in development of patient education; fewer focussed on the population of interest. The lack of literature demonstrates the need for multi-center collaborative research aimed at generation of an improved level of evidence regarding the most effective theoretical framework for the development, delivery and evaluation of patient education for patients with disorders of thrombosis and hemostasis. Once a theoretical framework for patient education is developed and tested, the unique contribution of patient education to both knowledge and clinical outcomes can be robustly evaluated.