Prophylactic therapy with exogenous clotting factor concentrates in haemophilia A and B aims to achieve levels of circulating FVIII or FIX that are adequate for the prevention or reduction of ...spontaneous joint bleeding. Historically, a minimum trough level of at least 1% of the normal levels of circulating clotting factor has been targeted using standardised protocols. However, clearance of clotting factor varies between products and patients, and other pharmacokinetic (PK) parameters such as the frequency and magnitude of peaks may be important for ensuring optimal coverage. Thus, it is increasingly recognised that an individualised, PK-based approach to prophylaxis is necessary to achieve optimal protection.
This review focuses on the clinical implications of using PK-guided, individualised prophylaxis in haemophilia to improve patient outcomes and considers practical methods of establishing patients’ PK parameters. The most useful PK parameters will depend on the aim of the specific treatment (e.g. preventing activity-related and traumatic bleeds or addressing subclinical bleeding). In clinical practice, lengthy and frequent post-infusion sampling for PK analysis is costly and a significant burden for patients. However, a Bayesian analysis allows for the estimation of different PK parameters (e.g. half-life, factor concentrations over time, etc.) with only a minimum number of samples (e.g. 4, 24 and 48 h for haemophilia A), by using the patient’s data to adjust a relevant population PK value towards the actual value. Numerous tools are available to aid in the practical use of Bayesian PK-guided dosing in the clinic, including the Web-based Application for the Population Pharmacokinetic Service hosted by McMaster University, Canada. The PK data can be used to determine the appropriate prophylaxis regimen for the individual patient, which can be monitored by assessment of the trough level at each clinic visit.
Collection of PK data and subsequent PK-guided dosing should become standard practice when determining treatment strategies for people with haemophilia.
We used a structured interview to explore approaches to comprehensive hemophilia and arthropathy care among 24 healthcare professionals (HCPs) from multidisciplinary teams (MDTs) in Canada and the ...UK. Represented MDTs typically comprise a hematologist, nurse, physiotherapist, and sometimes an orthopedic surgeon; pediatric (and some adult) MDTs also include a social worker/psychologist. HCPs emphasized the centrality of a team approach, facilitated through MDT meetings and involvement of all MDT members in patient care. In both countries, nurses and physiotherapists play critical, multifaceted roles. Respondents agreed that MDTs are crucial for successful transitioning, which can be facilitated by close collaboration between pediatric and adult MDTs, even when they are not co-located. Physiotherapists are instrumental in providing non-pharmacological pain relief. Hematologists or physiotherapists typically make orthopedic referrals, with the nurse, physiotherapist and hematologist working together in patient preparation for (and follow-up after) surgery. MDT best practices include a non-hierarchical team approach, ensuring that all MDT members know all patients, and regular MDT meetings. Together, these real-life insights from the MDT perspective emphasize the value of the MDT approach in comprehensive hemophilia care.
Here, we describe a mother and son with a lifelong bleeding tendency and posttraumatic bleeding who were recruited to the UK Genotyping and Phenotyping of Platelets (GAPP) study with a suspected ...platelet function disorder. However, despite a clinically significant bleeding score, both had normal platelet counts and normal platelet function. The patients' blood was analyzed by light transmission aggregometry and genotyping by whole exome sequencing, as outlined by the GAPP study. Approximately 25 000 genetic variants were found for each patient as a result of sequencing and were filtered using a specialized bioinformatics pipeline. A heterozygous variant displaying autosomal dominant inheritance (c.1611 C>A) was found in the gene THBD which encodes the glycoprotein thrombomodulin. This sequence change results in a stop codon (p.Cys537Stop) and truncation of the protein and has been previously described in two other families with bleeding events which suggests it may be a recurrent mutation. In summary, this study shows that patients with a suspected platelet disorder but who present with a normal pattern of platelet aggregation should be investigated for defects in nonplatelet genes.
The 7th Haemophilia Global Summit was held in Madrid, Spain, in September 2016. With a programme designed, for the 6th consecutive year, by a Scientific Steering Committee of haemophilia experts, the ...aim of the summit was to share optimal management strategies for haemophilia at all life stages and to provide an opportunity for specialists from across the haemophilia multidisciplinary care team to engage in discussion and debate with leading international experts on current and future areas of research. Topics covered ranged from the optimisation of haemophilia management, emerging issues in clinical care, practical approaches and future perspectives, in addition to patient engagement and empowerment in modern haemophilia care.
Abstract Objective: This was an evaluation of the cost-effectiveness of oral dabigatran etexilate compared with subcutaneous low-molecular-weight heparin (enoxaparin) for the prevention of venous ...thromboembolism (VTE) after total knee replacement (TKR) and total hip replacement (THR) surgery from the perspective of the UK National Health Service. Methods: Dabigatran etexilate (220 mg once daily) was compared with enoxaparin (40 mg once daily) in patients undergoing TKR (duration of prophylaxis, 6–10 days) and THR (duration of prophylaxis, 28–35 days). The 10-week acute postsurgical phase was modeled using a decision tree. A Markov process (1-year cycle length) was used to model long-term events (recurrent VTE, postthrombotic syndrome, and consequences of intracranial hemorrhage) for patients' remaining lifetimes. Relative risks for VTE and bleeding events were derived from 2 Phase III studies that compared dabigatran etexilate with enoxaparin 40 mg once daily. The probabilities of long-term events were estimated using data from published longitudinal studies. Results: Rates of VTE and bleeding events did not differ significantly between dabigatran etexilate and enoxaparin. Dabigatran etexilate was less costly than enoxaparin in TKR and substantially less costly in THR, primarily due to differences in administration costs. The cost of prophylaxis for THR patients, including drugs and administration costs, was estimated at £137 for dabigatran etexilate and £237 for enoxaparin (£7 for nursing time during the hospital stay, £91 for nurse home visits for administration after hospital discharge, and an additional £2 in drug costs). At a willingness-to-pay threshold of £20,000 per quality-adjusted life-year, the probability of cost-effectiveness for dabigatran etexilate was 75% in TKR and 97% in THR. These results were robust across a range of sensitivity analyses. Conclusion: From the perspective of the UK National Health Service, thromboprophylaxis with dabigatran etexilate was cost-saving compared with enoxaparin 40 mg once daily, with comparable efficacy and safety profiles.
Revolutionary advances in the treatment of hemophilia has led to a significant improvement in life expectancy. Associated with this has been an increase in age-related diseases especially ...atherosclerotic cardiovascular disease (CVD). While people with hemophilia (PWH) develop atherosclerosis at rates similar to those of the general population, rates of atherothrombosis and mortality related to CVD have been much lower, due to their hypocoagulable state. Changing treatment paradigms, aimed at reducing the risk of bleeding by improving hemostasis to levels approaching normality, has meant that the protection they are thought to have had may be lost. CVD risk factors are just as common in PWH as in the general population, but appear to be undertreated. In particular, primary prevention of CVD is vital in all individuals, but particularly in PWH as treatment of established CVD can be difficult. Active identification and management of CVD risk factors, such as obesity, physical inactivity, hypertension, and hypercholesterolemia, is required. In particular, statins have been shown to significantly reduce cardiovascular and all-cause mortality with few adverse events and no increased risk of bleeding in the general population, and their use needs urgent assessment in PWH. Further longitudinal research into preventing CVD in PWH, including accurate CVD risk assessment, is required to optimize prevention and management.
Introduction
Therapeutic advances over the past 30 years have led to longer life expectancy and improved quality of life (QOL) for persons with hemophilia. Access to innovative therapy may be ...compromised if treatment decisions are driven solely by cost. New strategies are needed to assess true therapeutic values, along with financial cost, as physicians, policymakers, payers and manufacturers work together to improve patient care.
Aim
To provide an evidence‐based assessment of the value of prophylaxis vs on‐demand therapy for hemophilia, based on a widely recognized three‐tiered value framework approach for assessing a range of therapeutic interventions.
Methods
Data from six randomized clinical trials (ESPRIT, Joint Outcomes Study, SPINART, LEOPOLD II, ADVATE and POTTER) and four observational studies comparing primary and secondary prophylaxis vs on‐demand therapy were applied to a hemophilia value framework.
Results
Both primary and secondary prophylaxis showed advantages in Tier 1 “Degree of health/recovery” outcomes, including measures of bleeding, musculoskeletal complications, pain, function/activity and QOL. Tier 2 “Process of Recovery” outcomes, also favoured prophylaxis, including measures of recovery time, return to normal activities, orthopaedic intervention and venous access. In Tier 3 “Sustainability of Health Recovery,” measures of breakthrough bleeds, joint preservation, sustained productivity and QOL showed significant improvement with prophylaxis.
Conclusion
The hemophilia value framework affirmed value of primary and secondary prophylaxis vs on‐demand therapy, with clinical benefit demonstrated in all three tiers. This analysis also demonstrates clinical utility of the value framework process in the determination of optimal and cost‐effective hemophilia care for all stakeholders.
How service people make sense of their identity is suggested to be one of the key determinants to a successful military discharge (Ahern et al., 2015; Binks & Cambridge, 2018; Herman & Yarwood, ...2014). Service people may be more vulnerable to transitionary junctures as they are significantly more likely to have experienced adverse childhoods than the general population (Blosnich et al., 2014; McCauley et al., 2015), something which is suggested to detrimentally impact transition success (Forster et al., 2020) as well as lead to identity salience difficulties (Carroll et al., 2017; Katon et al., 2015; Wong et al., 2019). We explored individuals’ sense of self during and after discharge by conducting semistructured telephone interviews with 10 U.K. ex-servicemen from significantly adverse childhood backgrounds (four or more adverse childhood experiences), using interpretative phenomenological analysis and a social identity theory (SIT) lens. Four superordinate themes were developed: abandoned in discharge, reborn into a foreign land, you never leave the forces, and us and them. Our findings highlight the role of identity in discharge, in particular the difficulties/importance in reconceptualizing self during this process. (PsycInfo Database Record (c) 2024 APA, all rights reserved) (Source: journal abstract)
Achieving the unimaginable: Health equity in haemophilia Skinner, Mark W.; Nugent, Diane; Wilton, Pam ...
Haemophilia : the official journal of the World Federation of Hemophilia,
January 2020, Letnik:
26, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Historically, treatment based on the availability of clotting factor replacement has resulted in an arcane guideline for the correction of factor deficiencies in people with haemophilia (PwH). While ...all other disease entities seek to restore function to a normal level, PwH are restricted to factor nadirs still equivalent to mild or moderate disease, resulting in continued risk of bleeding. A new treatment paradigm is needed based on the defined needs of PwH. A treatment model was developed by a panel of haemophilia providers, patient advocates and health economists to establish specific treatment milestones and targeted outcomes. The panel defined a series of treatment milestones to characterize the activity and outcomes linked to level of factor deficiency correction. All agreed that the ultimate goal should be ‘functional cure’ and ‘health equity’. Seven levels to achieving a functional cure were identified, (a) Sustain life; (b) Minimal joint impairment; (c) Freedom from any spontaneous bleeds; (d) Attainment of ‘normal’ mobility; (e) Able to sustain minor trauma without additional intervention; (f) Ability to sustain major surgery or trauma; and (g) Normal haemostasis. A parallel set of patient‐reported outcomes to achieve health equity was identified. These guidelines are now comparable with other disorders where the goal is to replace missing proteins to attain normal activity levels. As we are no longer limited by plasma supply due to the manufacture of recombinant factors, mimetics, and the early success of gene therapy, health equity is now achievable.
Introduction
Emergence of new therapies are anticipated to improve clinical outcomes and quality of life of persons with haemophilia. Challenges in conducting randomized clinical trials in rare ...diseases have resulted in a lack of direct head‐to‐head comparisons to support value‐based decision‐making between different treatments.
Methods
We conducted a literature review for new and emerging haemophilia A and B therapies (extended half‐life EHL replacement factor, non‐replacement therapies NRT, and gene therapies GT) to identify differentiating patient‐centred outcomes defined previously in a haemophilia value framework. Since the literature included all publication types (e.g., surveys, modelling studies, commentaries/reviews), collected data were assigned level of evidence scores.
Results
Across different classes of therapies, bleeding was determined as the most frequently reported differentiating outcome, with EHL, NRT, and GT each demonstrating an advantage over comparator replacement therapies. EHL therapies for haemophilia A and B and NRT for haemophilia A showed good representation across Tier 1 outcomes (health status achieved/retained), while more publications were identified with Tier 2 (process of recovery) outcomes for NRT than EHL or GT. In Tier 3 (sustainability of health), frequency of breakthrough bleeds represented a differentiating outcome for EHL (both haemophilia A and B), NRT (haemophilia A only), and GT (haemophilia B only), whereas sustained good health was differentiating for most comparisons.
Conclusions
We demonstrate the utility of the haemophilia value framework as a common core outcome set for effectively comparing therapies. Application of this framework will serve as a useful decision‐making tool for patients, clinicians, and within health technology assessments.
KEY POINTS OF CONSIDERATION
With the emergence of high‐cost, paradigm changing treatments across multiple areas of medicine, we, the haemophilia community, need to be equipped to meet the growing demands for more rigorous evidence‐based value assessments using the tools expected by assessors.
The traditional access toolbox needs to evolve to meet the paradigm shift in treatment options. Value can no longer be defined by annualized bleed rates alone. To realize the full impact of new therapies, we need to utilize tools, such as a value framework, to organize evidence, identify data gaps, and assess patient‐defined, meaningful outcomes across a multi‐faceted dimension.
The haemophilia value framework is an effective tool for organizing the available evidence and identifying gaps in the evidence. This can be used for assessing the value of emerging therapies in haemophilia utilizing data generated through randomized clinical trials and real world evidence generation.
This is a call for incorporating the Value Framework into official submissions to authorities, as it captures a broader range of outcomes, including patient meaningful outcomes, in ways that better assess the potential benefits of new therapies.
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