Janske Lock

Adherence to treatment in a Western European paediatric population with haemophilia: reliability and validity of the VERITAS-Pro scale

Treatment adherence in haemophilia is strongly associated with quality of life and the cost–benefit of treatment. Therefore, it is important to quantify and monitor it. This study aimed to validate a translation of the VERITAS‐Pro cross‐culturally and analyse treatment adherence in a Dutch population of paediatric haemophilia patients. Children aged 1–18 years with haemophilia were included from three Haemophilia Treatment Centres, on prophylactic clotting factor replacement therapy for more than 1 year. Parents and adolescents were analysed separately. The adherence scale for prophylactic therapy (VERITAS‐Pro) was translated according to international guidelines. This instrument contains a total of six subscales (‘Time’, ‘Dose’, ‘Plan’, ‘Remember’, ‘Skip’ and ‘Communicate’) each with four items. Lower scores reflect higher adherence. Overall response rate was 85%, leading to a study population of 60 children. Mean age was 10 years (SD 4.1). Internal consistency reliability: Mean Cronbachs alphas were adequate (>0.70) for total score and the subscales ‘Skip’ and ‘Communicate’. Item‐own subscale correlations were stronger than most item‐other subscale correlations. Convergent validity: Total scores were higher for non‐adherent participants compared with adherent participants according to patient infusion logs (n = 48; P < 0.05). Test–retest correlations: Significant for all scales except ‘Dose’ (n = 58; P < 0.01). This study demonstrates applicability of VERITAS‐Pro outside the United States, as total score and most subscales effectively quantified treatment adherence in a Dutch paediatric population on prophylactic therapy. Non‐adherent respondents’ total scores were significantly higher, demonstrating the ability of VERITAS‐Pro to identify non‐adherent individuals.

Perioperative treatment of hemophilia A patients: blood group O patients are at risk of bleeding complications

Essentials Targeting of factor VIII values is a challenge during perioperative replacement therapy in hemophilia. This study aims to identify the extent and predictors of factor VIII underdosing and overdosing. Blood group O predicts underdosing and is associated with perioperative bleeding. To increase quality of care and cost‐effectiveness of treatment, refining of dosing is obligatory.

A population pharmacokinetic model for perioperative dosing of factor VIII in hemophilia a patients

The role of pharmacokinetic-guided dosing of factor concentrates in hemophilia is currently a subject of debate and focuses on long-term prophylactic treatment. Few data are available on its impact in the perioperative period. In this study, a population pharmacokinetic model for currently registered factor VIII concentrates was developed for severe and moderate adult and pediatric hemophilia A patients (FVIII levels <0.05 IUmL−1) undergoing elective, minor or major surgery. Retrospective data were collected on FVIII treatment, including timing and dosing, time point of FVIII sampling and all FVIII plasma concentrations achieved (trough, peak and steady state), brand of concentrate, as well as patients’ and surgical characteristics. Population pharmacokinetic modeling was performed using non-linear mixed-effects modeling. Population pharmacokinetic parameters were estimated in 75 adults undergoing 140 surgeries (median age: 48 years; median weight: 80 kg) and 44 children undergoing 58 surgeries (median age: 4.3 years; median weight: 18.5 kg). Pharmacokinetic profiles were best described by a two-compartment model. Typical values for clearance, intercompartment clearance, central and peripheral volume were 0.15 L/h/68 kg, 0.16 L/h/68 kg, 2.81 L/68 kg and 1.90 L/68 kg. Interpatient variability in clearance and central volume was 37% and 27%. Clearance decreased with increasing age (P<0.01) and increased in cases with blood group O (26%; P<0.01). In addition, a minor decrease in clearance was observed when a major surgical procedure was performed (7%; P<0.01). The developed population model describes the perioperative pharmacokinetics of various FVIII concentrates, allowing individualization of perioperative FVIII therapy for severe and moderate hemophilia A patients by Bayesian adaptive dosing.

Facilitating the implementation of pharmacokinetic-guided dosing of prophylaxis in haemophilia care by discrete choice experiment

Patients’, parents’ and providers’ preferences with regard to medical innovations may have a major impact on their implementation.

Adherence to prophylaxis and bleeding outcome in haemophilia: a multicentre study

Prevention of bleeding and joint damage in severe haemophilia is dependent on adherence to prophylactic replacement therapy. The aim of this study was to assess adherence to prophylaxis, including associations with age, bleeding and clotting factor consumption (CFC). In three Dutch haemophilia centres, semi‐structured interviews about adherence to prophylaxis in the previous 2 weeks were conducted with patients or parents of a child with haemophilia. Patients were classified, according to pre‐specified definitions, as adherent, sub‐optimally adherent or non‐adherent based on missing, timing, and dose of infusions. Association of annual bleeding rates, mean CFC, person performing the infusion (parents verus patients) with adherence categories were analysed. Overall, 241 patients with haemophilia using prophylaxis were studied. Parents were more adherent (66%; n = 48/73) than patients (43%; n = 72/168). Sub‐optimal adherence occurred in 29% of parents and 37% of patients and was characterized by changes in timing of infusion (mostly from morning to evening), while missing <6% of infusions. Non‐adherence occurred less often: in 5% of parents and 20% of patients. Reduced adherence was associated with lower CFC, but not with joint bleeding. In conclusion, non‐adherence in haemophilia was relatively rare, yet 1/3 of patients struggled to administer prophylaxis at the appropriate time of day.

Achieving self-management of prophylactic treatment in adolescents: The case of haemophilia

OBJECTIVE Adolescents with a chronic disorder, such as haemophilia, need to attain responsibility for their disease. The aim was to gain insight into how adolescents achieve self-management of prophylactic treatment. METHODS In three Dutch Haemophilia Treatment Centres, adolescents (10-25 years) received structured questions on treatment responsibility and self-management (pre-specified definitions) during routine nursing consultation. RESULTS In total, 155 interviews were performed in 100 patients (median age 14.4 years). Self-infusion was initiated at a median age of 12.3 years (IQR 11.5-13.0) and self-management was achieved 9.6 years later, at a median age of 22.6 years. This process included three phases coinciding with known stages of adolescence. In early adolescence, patients acquired the technique of self-infusion (12.3 years) leading to independent self-infusion in middle adolescence (17.2 years). In late adolescence, patients demonstrated an increase in more complex skills, such as bleeding management and communication with the haemophilia physician (19.9-22.6 years). CONCLUSION Although, the first steps in self-management with regard to self-infusion are taken in early adolescence, complete self-management was achieved in late adolescence after almost 10 years. PRACTICE IMPLICATIONS Insight in this transitional process helps to provide individualized support and emphasizes the need for continued education with regard to self-management skills.

Reliability and validity of a novel haemophilia-specific self-efficacy scale

Higher self‐efficacy in chronic disease patients is associated with higher development of self‐management skills and increased quality‐of‐life. Quantification and monitoring of self‐efficacy is therefore of importance. Self‐efficacy in haemophilia patients has received little attention due to lack of standardized scales. To validate the novel Haemophilia‐specific Self‐Efficacy Scale (HSES) in haemophilia patients on prophylactic home treatment, haemophilia patients aged 1–18 years on prophylactic treatment ≥1 year were included from three Dutch Haemophilia Treatment Centres. The HSES consists of 12 items, relating to perceptions of the ability to function on a day‐to‐day basis with regard to patients disease. Retest was performed in a subsample. Validity was proven by the General Self‐Efficacy Scale and by the health‐related quality‐of‐life assessment tool Haemo‐QoL. Data were analysed from 53 children (response 75%), with a mean age of 9.8 years (SD 4.0). Mean total scale score of HSES was 55.5 (SD 4.7; range 38–60), with a ceiling effect of 17%. The HSES showed adequate internal consistency (Cronbachs alpha 0.72) and good test–retest reliability (Intra‐Class‐Correlation coefficient 0.75; P < 0.01; n = 37). The convergent validity was adequate as haemophilia‐specific self‐efficacy correlated significantly with general self‐efficacy (r = 0.38; P < 0.01). High HSES scores correlated significantly with quality‐of‐life as measured by the Haemo‐QoL (r = −0.42; P ≤ 0.01). The novel HSES is a reliable and valid tool to assess self‐efficacy in paediatric haemophilia patients on prophylactic home treatment. High self‐efficacy correlated with higher quality‐of‐life, further underlining the importance to standardly assess, monitor and improve self‐efficacy.

Optimization of home treatment in haemophilia: effects of transmural support by a haemophilia nurse on adherence and quality of life

Transmural support by a haemophilia nurse may improve treatment and may empower parents and patients.

Self‐infusion of prophylaxis: evaluating the quality of its performance and time needed

Prophylactic replacement therapy is the cornerstone of treatment in severe haemophilia. Regular infusions with clotting factor concentrate have been proven effective to prevent bleeding, subsequent (joint) damage, and positively affect the impact of haemophilia on daily life [1]. Patients or parents of younger patients learn to infuse clotting factor concentrate in a peripheral vein (i.v.) or a central venous access device (CVAD) [2].