Hepatitis C virus in hemophilia:Health-related quality of life after successful treatment in the sixth Hemophilia in the Netherlands study

INTRODUCTION: Persons with hemophilia and hepatitis C virus (HCV) infection have a lower health‐related quality of life (HRQoL) than those never HCV infected. However, it is unknown whether HRQoL after HCV eradication is comparable to individuals never HCV infected. We aimed to compare HRQoL between HCV‐cured and never chronically HCV‐infected persons with hemophilia. METHODS: All persons with hemophilia in the Netherlands were invited for a nationwide study conducted in 2018–2019. For the current analysis, participants born before 1992 with data on HRQoL and HCV status were included. HCV status was collected from medical records. HRQoL was measured by RAND‐36 questionnaire, with a minimally important difference set at 4.0 points. Multivariable linear regression was used to adjust for age, hemophilia severity, HIV status, and self‐reported joint impairment. RESULTS: In total, 486 persons were eligible; 180 were HCV cured and 306 never chronically HCV infected. Compared with those never HCV infected, HCV‐cured individuals were older (57 vs. 53 years), more often had severe hemophilia (67% vs. 21%), and reported more impaired joints (median 3 vs. 0). Compared with those never HCV infected, adjusted RAND‐36 domain scores of HCV‐cured individuals cured were lower on all RAND‐36 domains except Pain, ranging from a difference of 4.5 (95% CI, −8.8 to −0.3) for Physical functioning to 11.3 (95% CI, −19.4 to −3.1) for Role limitations due to physical problems. CONCLUSION: Despite effective HCV treatment, HRQoL of HCV‐cured persons with hemophilia is still lower than HRQoL of those never chronically HCV‐infected on all RAND‐36 domains. This implies that careful psychosocial follow‐up and support are indicated

Socioeconomic participation of persons with hemophilia:Results from the sixth hemophilia in the Netherlands study

Background and objectives Treatment availability and comprehensive care have resulted in improved clinical outcomes for persons with hemophilia. Recent data on socioeconomic participation in the Netherlands are lacking. This study assessed participation in education, in the labor market, and social participation for persons with hemophilia compared with the general male population. Methods Dutch adults and children (5-75 years) of all hemophilia severities (n = 1009) participated in a questionnaire study that included sociodemographic, occupational, and educational variables. Clinical characteristics were extracted from electronic medical records. General population data were extracted from Statistics Netherlands. Social participation was assessed with the PROMIS Ability to Participate in Social Roles and Activities short form, with a minimal important difference set at 1.0. Results Data from 906 adults and children were analyzed. Participation in education of 20 to 24 year olds was 68% (general male population: 53%). Educational attainment was higher compared with Dutch males, especially for severe hemophilia. Absenteeism from school was more common than in the general population. The employment-to-population ratio and occupational disability were worse for severe hemophilia than in the general population (64.3% vs. 73.2% and 14.7% vs. 4.8%, respectively), but similar for nonsevere hemophilia. Unemployment was 5.4% (general male population: 3.4%). Absenteeism from work was less common (38% vs. 45.2%). Mean PROMIS score was similar to or higher than in the general population (54.2; SD 8.9 vs. 50; SD 10). Conclusion Socioeconomic participation of persons with nonsevere hemophilia was similar to the general male population. Some participation outcomes for persons with severe hemophilia were reduced

Validation of PROMIS Profile-29 in adults with hemophilia in the Netherlands

Background The Patient-Reported Outcomes Measurement Information System (PROMIS) Profile-29 questionnaire is widely used worldwide, but it has not yet been validated in the Netherlands, nor in persons with hemophilia. Objective To validate the Dutch-Flemish version of the PROMIS-29 Profile v2.01 in adults with hemophilia. Methods Dutch males with hemophilia (all severities) completed questionnaires that contained sociodemographic and clinical characteristics, the PROMIS-29, RAND-36, and the Hemophilia Activities List (HAL). Structural validity of each subscale was assessed with confirmatory factor analysis (CFA). Internal consistency was calculated for each subscale with sufficient model fit in CFA. Construct validity was assessed by testing hypotheses about (1) correlations of each PROMIS-29 subscale with corresponding scales of RAND-36 and domains of HAL, and (2) mean differences in T-scores between subgroups with different hemophilia severities, self-reported joint impairment, and HIV infection status. We considered &gt;= 75% of data in accordance with the hypotheses evidence for construct validity. Results In total, 770 persons with hemophilia participated in this cross-sectional study. CFA revealed sufficient structural validity for five subscales: Physical Function, Depression, Sleep Disturbance, Ability to Participate in Social Roles and Activities, and Pain Interference. Internal consistency was high and Cronbach's alpha ranged from 0.79 for Sleep Disturbance to 0.96 for Pain Interference. Differences between clinical subgroups were in the expected direction. Construct validity was confirmed for Physical Function, Anxiety, Depression, Fatigue, Sleep Disturbance, and Pain Intensity. Conclusion This study revealed sufficient evidence for structural validity, internal consistency, and construct validity for most PROMIS Profile-29 subscales among people with hemophilia in the Netherlands.</p

Patient Perspectives on Novel Treatments in Haemophilia: A Qualitative Study

Background and Objective: New treatments for haemophilia are under development or entering the market, including extended half-life products, designer drugs and gene therapy, thereby increasing treatment options for haemophilia. It is currently unknown how people with haemophilia decide whether to switch to a new treatment. Therefore, the objective of this study was to explore what factors may play a role when Dutch patients and parents of boys with moderate or severe haemophilia make decisions about whether to switch to a different treatment, and how disease and treatment characteristics may affect these decisions. This may aid clinical teams in tailored information provision and shared decision making. Methods: We conducted interviews among adults with moderately severe or severe haemophilia and parents of young boys with severe haemophilia. We aimed to include participants from a variety of backgrounds in terms of involvement in the haemophilia community, age, treatment centre and treatments. Participants were recruited through the Netherlands Haemophilia Society and a haemophilia treatment centre. Semi-structured interviews were recorded and transcribed verbatim. Thematic content analysis was used to analyse the data. Results: Twelve people with haemophilia and two mothers of boys with haemophilia were included. In general, participants reported to be satisfied with their current treatment. However, they considered ease of use of the medication (fewer injections, easier handling, alternative administration) an added value of new treatments. Participants were aware of the high cost of coagulation factor products and some expressed their concern about the Netherlands Haemophilia Society’s long-term willingness to pay for current and novel treatments, especially for increased usage due to high-risk activities. Participants also expressed their concerns about the short- and long-term safety of new treatments and believed the effects of gene therapy were not yet fully understood. Participants expected their treatment team to inform them when a particular new treatment would be suitable for them. Conclusions: With the number of treatment options set to increase, it is important for healthcare providers to be aware of how patient experiences shape patients’ decisions about new therapies

Patient‐relevant health outcomes for hemophilia care: Development of an international standard outcomes set

From Wiley via Jisc Publications RouterHistory: received 2020-09-04, rev-recd 2020-12-05, accepted 2020-12-29, pub-electronic 2021-03-06, pub-print 2021-05Article version: VoRPublication status: PublishedFunder: Ministry of Health, Welfare and Sports, The NetherlandsAbstract: Background: Patient‐relevant health outcomes for persons with hemophilia should be identified and prioritized to optimize and individualize care for persons with hemophilia. Therefore, an international group of persons with hemophilia and multidisciplinary health care providers set out to identify a globally applicable standard set of health outcomes relevant to all individuals with hemophilia. Methods: A systematic literature search was performed to identify possible health outcomes and risk adjustment variables. Persons with hemophilia and multidisciplinary health care providers were involved in an iterative nominal consensus process to select the most important health outcomes and risk adjustment variables for persons with hemophilia. Recommendations were made for outcome measurement instruments. Results: Persons with hemophilia were defined as all men and women with an X‐linked inherited bleeding disorder caused by a deficiency of coagulation factor VIII or IX with plasma activity levels <40 IU/dL. We recommend collecting the following 10 health outcomes at least annually, if applicable: (i) cure, (ii) impact of disease on life expectancy, (iii) ability to engage in normal daily activities, (iv) severe bleeding episodes, (v) number of days lost from school or work, (vi) chronic pain, (vii) disease and treatment complications, (viii) sustainability of physical functioning, (ix) social functioning, and (x) mental health. Validated clinical as well as patient‐reported outcome measurement instruments were endorsed. Demographic factors, baseline clinical factors, and treatment factors were identified as risk‐adjustment variables. Conclusion: A consensus‐based international set of health outcomes relevant to all persons with hemophilia, and corresponding measurement instruments, was identified for use in clinical care to facilitate harmonized longitudinal monitoring and comparison of outcomes

Mortality, life expectancy, and causes of death of persons with hemophilia in the Netherlands 2001–2018

Background: Treatment of patients with hemophilia has advanced over the past decades, but it is unknown whether this has resulted in a normal life expectancy in the Netherlands. Objective: This observational cohort study aimed to assess all-cause and cause-specific mortality in patients with hemophilia in the Netherlands between 2001 and 2018 and to compare mortality and life expectancy with previous survival assessments from 1973 onward. Patients/methods: All 1066 patients with hemophilia who participated in a nationwide survey in 2001 were followed until July 2018. Results: Information on 1031 individuals (97%) was available, of whom 142 (14%) deceased during follow-up. Compared with the general Dutch male population, mortality of patients with hemophilia was still increased (standardized mortality ratio: 1.4, 95% confidence interval: 1.2–1.7). Intracranial bleeding and malignancies were the most common causes of death. Estimated median life expectancy of patients with hemophilia was 77 years, 6 years lower than the median life expectancy of the general Dutch male population (83 years). Over the past 45 years, death rates of patients with hemophilia have consistently decreased, approaching the survival experience of the general population. Over the past decades, mortality due to human immunodeficiency virus and hepatitis C virus infections has decreased, death due to intracranial hemorrhages has increased, and death due to ischemic hear

Increasing Use of Pyrethroids in Canadian Households: Should We Be Concerned?

Pyrethroids are a class of plant-derived insecticides and their man-made analogues that are increasingly applied in Canada as first choice for pest control in many agricultural and residential settings. Their popularity is partly due to their alleged safety compared to the older organochlorine and organophosphate insecticides. Application of pyrethroids is expanding because of recent increases in the level of pest infestations--such as bed bugs--and the decreased susceptibility of target species to many pest control products. Pyrethroid residues have been documented in homes, child care centres and food. While pyrethroids are considered of low health risk for humans, their increased use is of concern. Our current understanding of the adverse effects of pyrethroids derives mainly from studies of short-term effects in laboratory animals, case reports of self- and accidental poisonings, and high-dose occupational exposures, for which the levels and formulations of pyrethroid products differ from those relevant for long-term exposure in the general population. The available data suggest that the reproductive and nervous systems, endocrine signalling pathways, and early childhood development may be targets for adverse effects in the case of repeated exposure to pyrethroid formulations. Given uncertainty about the existence of long-term health effects of exposure to pyrethroids, particularly under realistic scenarios, we should be cautious when promoting pyrethroid products as safe methods for pest control.Les pyréthrinoïdes, une catégorie d’insecticides dérivés des plantes et leurs analogues synthétiques, sont de plus en plus utilisés au Canada comme premier choix dans la lutte antiparasitaire dans bien des contextes agricoles et résidentiels. Leur popularité est due en partie à leur innocuité présumée comparativement aux insecticides organochlorés et organophosphorés plus anciens. La demande de pyréthrinoïdes augmente en raison des hausses récentes du niveau d’infestations par des insectes nuisibles (comme les punaises de lit) et de la vulnérabilité réduite des espèces cibles à de nombreux produits de lutte antiparasitaire. Des résidus de pyréthrinoïdes ont été détectés dans des logements, des centres de la petite enfance et des aliments. Bien que l’on considère que les pyréthrinoïdes présentent peu de risques pour la santé humaine, leur utilisation croissante est un problème. Nos connaissances actuelles des effets indésirables des pyréthrinoïdes découlent principalement d’études de leurs effets à court terme sur des animaux de laboratoire, d’études de cas d’empoisonnement volontaire et accidentel, et de cas d’exposition professionnelle à des doses élevées; or, dans ces situations, les niveaux et les formulations des produits aux pyréthrinoïdes diffèrent de ceux qui s’appliqueraient à l’étude de leurs risques à long terme dans la population générale. Selon les données disponibles, l’appareil génital, le système nerveux, les voies de signalisation endocrinienne et le développement du jeune enfant pourraient être la cible d’effets indésirables en cas d’exposition répétée à des formulations à base de pyréthrinoïdes. Étant donné l’incertitude entourant l’existence d’effets à long terme sur la santé à la suite d’une exposition aux pyréthrinoïdes, surtout dans des scénarios réalistes, la prudence est de mise lorsqu’on présente les produits aux pyréthrinoïdes comme des outils de lutte antiparasitaire sans danger.Fil: van Balen, Erna C.. National Collaborating Centre for Environmental Health; CanadáFil: Wolansky, Marcelo Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Kosatsky, T.. British Columbia Centre for Disease Control; Canadá. National Collaborating Centre for Environmental Health; Canad

Patients with moderate hemophilia A and B with a severe bleeding phenotype have an increased burden of disease

Background: Patients with moderate hemophilia express varying bleeding phenotypes. Objectives: To assess the burden of disease in patients with moderate hemophilia and a mild or severe phenotype incorporating the thrombin generation profile. Methods: This sub-study of the 6th Hemophilia in the Netherlands study, analyzed data of adults with moderate hemophilia A or B. Patient characteristics and information on bleeding tendency, joint status, and quality of life were obtained from electronic patient files and self-reported questionnaires. A severe bleeding phenotype was defined as an annual bleeding rate ≥5, an annual joint bleeding rate ≥3, and/or the use of secondary/tertiary prophylaxis, and a mild phenotype vice versa. TG was measured with the Nijmegen Hemostasis Assay. Results: This study included 116 patients: 21% had a severe phenotype of whom 46% used prophylaxis. Patients with a severe phenotype treated on demand reported a higher median annual bleeding rate (7), annual joint bleeding rate (3), and more frequently an impaired joint (77%) than patients with a severe phenotype on prophylaxis (2; 0; 70%) or patients with a mild phenotype (0; 0; 47%). Furthermore, patients with a severe phenotype treated on demand experienced a more decreased quality of life. Despite similar factor activity levels, patients with a severe phenotype had a lower thrombin peak height and thrombin potential (0.7%; 0.06%) than patients with a mild phenotype (21.3%; 46.8%). Conclusion: Patients with moderate hemophilia and a severe phenotype treated on demand displayed a high burden of disease as well as a low thrombin generation profile advocating them toward more intensive prophylactic treatment.</p

Patient Perspectives on Novel Treatments in Haemophilia:A Qualitative Study

Background and Objective: New treatments for haemophilia are under development or entering the market, including extended half-life products, designer drugs and gene therapy, thereby increasing treatment options for haemophilia. It is currently unknown how people with haemophilia decide whether to switch to a new treatment. Therefore, the objective of this study was to explore what factors may play a role when Dutch patients and parents of boys with moderate or severe haemophilia make decisions about whether to switch to a different treatment, and how disease and treatment characteristics may affect these decisions. This may aid clinical teams in tailored information provision and shared decision making. Methods: We conducted interviews among adults with moderately severe or severe haemophilia and parents of young boys with severe haemophilia. We aimed to include participants from a variety of backgrounds in terms of involvement in the haemophilia community, age, treatment centre and treatments. Participants were recruited through the Netherlands Haemophilia Society and a haemophilia treatment centre. Semi-structured interviews were recorded and transcribed verbatim. Thematic content analysis was used to analyse the data. Results: Twelve people with haemophilia and two mothers of boys with haemophilia were included. In general, participants reported to be satisfied with their current treatment. However, they considered ease of use of the medication (fewer injections, easier handling, alternative administration) an added value of new treatments. Participants were aware of the high cost of coagulation factor products and some expressed their concern about the Netherlands Haemophilia Society’s long-term willingness to pay for current and novel treatments, especially for increased usage due to high-risk activities. Participants also expressed their concerns about the short- and long-term safety of new treatments and believed the effects of gene therapy were not yet fully understood. Participants expected their treatment team to inform them when a particular new treatment would be suitable for them. Conclusions: With the number of treatment options set to increase, it is important for healthcare providers to be aware of how patient experiences shape patients’ decisions about new therapies