• Adherence and a Potential Trade-Off Currently Faced in Optimizing Hemophilia Treatment

      Burke, Tom; Asghar, Sohaib; Misciattelli, Natalia; Kar, Sharmila; Morgan, George; Dhillon, Harpal; O'Hara, Jamie (Elsevier, 2021-08-03)
      INTRODUCTION Severe hemophilia, i.e., <1% normal FVIII level (A) or FIX level (B), are congenital bleeding disorders characterized by uncontrolled bleeding. The clinical benefits of prophylactic FVIII/IX replacement therapy are well understood, but require adherence to a schedule of routine infusions. Optimal adherence is associated with better joint outcomes and lower rates of chronic pain. Nonetheless a lack of patient-reported data has to date limited our understanding of the patient burden associated with adherence to treatment, and the relationship between adherence and the ability to work, among people living with hemophilia in the US. Data from the Bridging Hemophilia B Experiences, Results and Opportunities into Solutions (B-HERO-S) study reported a high proportion of adults with hemophilia B receiving routine infusions (at least one infusion per month), showing a negative impact on their ability to work, and people receiving routine infusions were more likely than people treated on-demand to report an inability to work in most situations. The ability of people living with hemophilia to participate in the labor force, without barriers to job choice or working hours, is a key outcome in the drive to achieve health equity. The objective of the analysis is to examine the relationship between adherence and the labor force participation of people with severe hemophilia in the US. METHODS This analysis draws data from a patient-reported study, the ‘Cost of Severe Hemophilia Across the US: A Socioeconomic Survey’ (CHESS US+). Conducted in 2019, the CHESS US+ study is a cross-sectional patient-centered study of adults with severe hemophilia in the US. A patient-completed questionnaire collected data on clinical, economic, and humanistic outcomes, for a 12-month retrospective period. This analysis examines labor force participation and employment status (full-time, part-time, unemployed, retired) and chronic pain categorized by ‘none’, low-level ('1-5'), and high-level ('6-10'). The analysis was stratified by adherence to treatment, self-reported on a 1-10 scale, from “not at all” to “fully”, categorized into low (1-6), moderate (7-9) and full (10) adherence. Results are presented as mean (standard deviation) or N (%). RESULTS The analysis comprised 356 people with severe hemophilia A (73%) and B (27%) who participated in CHESS US+ study. In Table 1, the baseline characteristics of the study population are stratified by full adherence (N = 119), moderate adherence (N=134) and low adherence (N=103). Having no chronic pain was most prevalent in the full adherence group (37.7%), compared to moderate (8.3%) or low (13.9%) adherence cohorts. Chronic pain, both low- and high-levels were least prevalent among people with full adherence. Moreover, people with low adherence were disproportionately more likely to have high-levels of chronic pain relative to moderate adherence or full adherence (Table 1). Unemployment, however, was highest in full adherence (21.1%), and people with full adherence were also least likely to be in full-time employment (42%). The full-time employment rate decreased as adherence declined from full to moderate (Table 1), and was comparable in people with low adherence (57.3%) or moderate adherence (54.5%). CONCLUSIONS This analysis of CHESS US+ examined the complex relationship between labor market outcomes and adherence to treatment, among adults with severe hemophilia in the US. Adherence was associated with lower rates of chronic pain, representing the importance of achieving an optimal treatment strategy. Nonetheless, patients achieving optimal adherence were less likely to be in full-time employment, and more likely to be part-time or unemployed, comparatively. Together, these data characterize a trade-off in clinical outcomes versus workforce participation, and suggest that the goal of achieving health equity may currently still be unmet. Disclosures Burke: HCD Economics: Current Employment; University of Chester: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Asghar: HCD Economics: Current Employment. Misciattelli: Freeline: Current Employment, Current equity holder in publicly-traded company. Kar: Freeline: Current Employment, Current equity holder in publicly-traded company. Morgan: uniQure: Consultancy; HCD Economics: Current Employment. Dhillon: HCD Economics: Current Employment; F. Hoffmann-La Roche Ltd: Other: All authors received editorial support for this abstract, furnished by Scott Battle, funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. . O'Hara: HCD Economics: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Consultancy.
    • An Insight into the Impact of Hemophilia a on Daily Life According to Disease Severity: A Preliminary Analysis of the CHESS II Study

      Noone, Declan; Nissen, Francis; Xu, Tao; Burke, Tom; Asghar, Sohaib; Dhillon, Harpal; Aizenas, Martynas; Meier, Oliver; O'Hara, Jamie; Khair, Kate (Elsevier, 2021-08-03)
      Introduction: Hemophilia A (HA) is a congenital bleeding disorder caused by a deficiency in clotting factor VIII (FVIII). There are currently limited data on the impact of HA on daily life. Here we examine the impact of HA on the daily life of adult persons with HA (PwHA) without current FVIII inhibitors according to disease severity. Methods: The Cost of Haemophilia in Europe: a Socioeconomic Survey II (CHESS II) is a retrospective, burden-of-illness study in adults with mild, moderate, and severe HA or hemophilia B (defined by endogenous FVIII/IX [IU/dL] relative to normal; mild, 5-<40%; moderate, 1-5%; severe, <1%); this analysis includes only PwHA. Male participants (aged ≥18 years) diagnosed with HA (without FVIII inhibitors) at least 12 months prior to clinical consultation were enrolled from Denmark, France, Germany, Italy, the Netherlands, Romania, Spain, and the UK. Data on clinical outcomes and healthcare resource utilization were captured via electronic case report forms disseminated to hemophilia specialists. PwHA completed a paper-based questionnaire utilizing 5-point Likert scales to assess the disease burden on their daily life. Overall, 12 months’ retrospective data were examined. Informed consent was obtained and the study was approved by the University of Chester ethical committee. Results: Of 258 PwHA completing questionnaires, 15.9% (n=41), 27.9% (n=72), and 56.2% (n=145) had mild, moderate, and severe HA, respectively. Of those with severe HA, 60.0% were currently receiving FVIII prophylaxis (standard of care for severe HA); in comparison, 4.9% and 6.9% of those with mild and moderate HA were receiving prophylaxis (Table 1). Treatment adaptation in anticipation of physical or social activity was reported by 19.5%, 23.6%, and 38.6% of those with mild, moderate, and severe HA, respectively. Over a third of participants with mild (36.6%) and moderate (44.4%) HA, and 64.8% of those with severe HA (58.6% with severe HA receiving on-demand treatment and 69.0% receiving prophylaxis) agreed or strongly agreed that HA had reduced their physical activity (Figure 1). Overall, 38.9% of those with moderate HA and 58.6% of those with severe HA (63.8% with severe HA receiving on-demand treatment and 55.2% receiving prophylaxis) agreed or strongly agreed that their HA had reduced their social activity; this was less pronounced in mild HA (9.8%). Additionally, 31.7%, 36.1%, and 64.1% of those with mild, moderate, and severe HA (62.1% with severe HA receiving on-demand treatment and 65.5% receiving prophylaxis) agreed or strongly agreed that their HA had caused them to miss opportunities. Correspondingly, frustration due to HA was felt by 19.5%, 34.7% and 57.9% (56.9% with severe HA receiving on-demand treatment and 58.6% receiving prophylaxis) of people, respectively. When asked whether they believed their daily life was compromised due to their hemophilia, 24.4%, 37.5%, and 63.4% of those with mild, moderate, and severe HA, respectively, agreed. Pain, as reported by the physician, was noted in 36.6% of people with mild HA (100% was reported as 'mild'); in people with moderate HA, pain was reported as 'mild', ‘moderate’, and ‘severe’ in 44.4%, 20.8%, and 1.4% of PwHA, respectively. In people with severe HA, pain was reported as ‘mild’, ‘moderate’, and ‘severe’ in 39.7%, 27.6%, and 8.6% for those receiving on-demand treatment, and 37.9%, 32.2%, and 8.0% for those receiving prophylaxis, respectively. Conclusions: In all disease severity groups, there was a notable group of PwHA that felt that they have had to reduce their physical and social activity, have had fewer opportunities and are frustrated due to their disease. While the impact on daily life is most pronounced in people with severe HA (including those receiving on-demand treatment and those receiving prophylaxis), it is also apparent in mild and moderate HA, indicating that there may be an unmet medical need in these groups. Disclosures Noone: Healthcare Decision Consultants: Membership on an entity's Board of Directors or advisory committees; Research Investigator PROBE: Research Funding; European Haemophilia Consortium: Membership on an entity's Board of Directors or advisory committees. Nissen: F. Hoffmann-La Roche Ltd: Current Employment; Actelion: Consultancy; Novartis: Research Funding; GSK: Research Funding. Xu: F. Hoffmann-La Roche Ltd: Current Employment, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Burke: University of Chester: Current Employment; HCD Economics: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Asghar: HCD Economics: Current Employment. Dhillon: F. Hoffmann-La Roche Ltd: Other: All authors received editorial support for this abstract, furnished by Scott Battle, funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. ; HCD Economics: Current Employment. Aizenas: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Meier: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. O'Hara: HCD Economics: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Consultancy. Khair: Biomarin: Consultancy; HCD Economics: Consultancy; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Medikhair: Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Honoraria, Research Funding, Speakers Bureau; CSL Behring: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Takeda: Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; Haemnet: Membership on an entity's Board of Directors or advisory committees.
    • Assessment of sodium and iodine intake among university students in Casablanca, Morocco

      Jafri, Ali; Elarbaoui, Maria; Elkardi, Younes; Makhlouki, Houria; Ellahi, Basma; Derouiche, Abdelfettah
      Introduction Iodine deficiency is still a matter of public health concern despite salt fortification and especially with global recommendations to lower salt intake, this is mainly due to dietary habits. University students have a diet based on street food high in sodium and low in other micronutrients (i.e. iodine and potassium). In this study, we aim to measure sodium and iodine levels in university students to assess their risk of developing complications later in life. Methodology A sample of 120 students aged between 18 and 25 years old was recruited and asked to collect their 24-hours urine samples in special containers containing. Samples were stored then analyzed for sodium, potassium, iodine and creatinine levels. Results The average urinary excretion of sodium was 3066.8±1196.0mg/day. Overall, 72.6% of participants consume more than 2g/day of sodium. Average potassium intake is 1805.9±559.4mg/day, and all participants consume less than the adequate amount. Daily urinary excretion of iodine is 135.6±88.9mg/day, and 69.2% of participants consume less than the recommended amount. Sodium, potassium and iodine intakes were higher in male participants (P-values=0.008; 0.044 and 0.003, respectively). The lowest average iodine intake was observed in underweight participants (119.4±31.4) with 87.5% of underweight participants and 80% of female participants below the recommended intake. Conclusion Sodium intake is high while iodine intake is low in this studied population, especially in women.
    • Assessment of sodium and iodine intake among university students in Casablanca, Morocco

      Jafri, Ali; Elarbaoui, Maria; Elkardi, Younes; Makhlouki, Houria; Ellahi, Basma; Derouiche, Abdelfettah (Elsevier, 2021-08-15)
      Introduction Iodine deficiency is still a matter of public health concern despite salt fortification and especially with global recommendations to lower salt intake, this is mainly due to dietary habits. University students have a diet based on street food high in sodium and low in other micronutrients (i.e. iodine and potassium). In this study, we aim to measure sodium and iodine levels in university students to assess their risk of developing complications later in life. Methodology A sample of 120 students aged between 18 and 25 years old was recruited and asked to collect their 24-hours urine samples in special containers containing. Samples were stored then analyzed for sodium, potassium, iodine and creatinine levels. Results The average urinary excretion of sodium was 3066.8±1196.0mg/day. Overall, 72.6% of participants consume more than 2g/day of sodium. Average potassium intake is 1805.9±559.4mg/day, and all participants consume less than the adequate amount. Daily urinary excretion of iodine is 135.6±88.9mg/day, and 69.2% of participants consume less than the recommended amount. Sodium, potassium and iodine intakes were higher in male participants (P-values=0.008; 0.044 and 0.003, respectively). The lowest average iodine intake was observed in underweight participants (119.4±31.4) with 87.5% of underweight participants and 80% of female participants below the recommended intake. Conclusion Sodium intake is high while iodine intake is low in this studied population, especially in women.
    • Characterization of microwave and terahertz dielectric properties of single crystal La2Ti2O7 along one single direction

      Zhang, Man; orcid: 0000-0002-1094-7279; Tang, Zhiyong; orcid: 0000-0002-1921-6034; Zhang, Hangfeng; Smith, Graham; orcid: 0000-0003-3273-7085; Jiang, Qinghui; Saunders, Theo; orcid: 0000-0003-4250-3071; Yang, Bin; Yan, Haixue; orcid: 0000-0002-4563-1100
      New generation wireless communication systems require characterisations of dielectric permittivity and loss tangent at microwave and terahertz bands. La2Ti2O7 is a candidate material for microwave application. However, all the reported microwave dielectric data are average value from different directions of a single crystal, which could not reflect its anisotropic nature due to the layered crystal structure. Its dielectric properties at the microwave and terahertz bands in a single crystallographic direction have rarely been reported. In this work, a single crystal ferroelectric La2Ti2O7 was prepared by floating zone method and its dielectric properties were characterized from 1 kHz to 1 THz along one single direction. The decrease in dielectric permittivity with increasing frequency is related to dielectric relaxation from radio frequency to microwave then to terahertz band. The capability of characterizing anisotropic dielectric properties of a single crystal in this work opens the feasibility for its microwave and terahertz applications.
    • Characterization of microwave and terahertz dielectric properties of single crystal La2Ti2O7 along one single direction

      Zhang, Man; orcid: 0000-0002-1094-7279; Tang, Zhiyong; orcid: 0000-0002-1921-6034; Zhang, Hangfeng; Smith, Graham; orcid: 0000-0003-3273-7085; Jiang, Qinghui; Saunders, Theo; orcid: 0000-0003-4250-3071; Yang, Bin; Yan, Haixue; orcid: 0000-0002-4563-1100 (Elsevier, 2021-08-27)
      New generation wireless communication systems require characterisations of dielectric permittivity and loss tangent at microwave and terahertz bands. La2Ti2O7 is a candidate material for microwave application. However, all the reported microwave dielectric data are average value from different directions of a single crystal, which could not reflect its anisotropic nature due to the layered crystal structure. Its dielectric properties at the microwave and terahertz bands in a single crystallographic direction have rarely been reported. In this work, a single crystal ferroelectric La2Ti2O7 was prepared by floating zone method and its dielectric properties were characterized from 1 kHz to 1 THz along one single direction. The decrease in dielectric permittivity with increasing frequency is related to dielectric relaxation from radio frequency to microwave then to terahertz band. The capability of characterizing anisotropic dielectric properties of a single crystal in this work opens the feasibility for its microwave and terahertz applications.
    • COVID-19 presenting as intussusception in infants: A case report with literature review

      Athamnah, Mohammad N.; Masade, Salim; Hamdallah, Hanady; orcid: 0000-0001-6314-0236; Banikhaled, Nasser; Shatnawi, Wafa; Elmughrabi, Marwa; Al Azzam, Hussein S.O.
      The novel Corona virus disease 2019 (COVID-19) first presented in Wuhan, China. The virus was able to spread throughout the world, causing a global health crisis. The virus spread widely in Jordan after a wedding party held in northern Jordan. In most cases of COVID-19 infection, respiratory symptoms are predominant. However, in rare cases the disease may present with non-respiratory symptoms. The presentation of COVID-19 as a case of intussusception in children is a strange and rare phenomenon. We present here a case of a two-and-a-half month old male baby who was brought to hospital due to fever, frequent vomiting, dehydration and blood in stool. He was diagnosed as intussusception. The child was tested for corona due to the large societal spread of the virus and because he was near his mother, who was suffering from symptoms similar to corona or seasonal flu (she did not conduct a corona test). Patient was treated without surgery and recovered quickly. The COVID-19 infection was without respiratory symptoms, and there was no need for the child to remain in hospital after treatment of intussusception. The relationship between viruses, mesenteric lymphoid hyperplasia, and intussusception is a confirmed relation. ACE2 is the key receptor required for SARA-COV-2 to enter the host cells. ACE2 has been also found in the brush border of the intestinal mucosa, as well as it is a key inflammatory regulator in the intestine. This may suggest that SARSA-COV-2 could invade the respiratory tract as well as gastrointestinal tract or both. Few case reports documented the presentation of COVID-19 as intussusception in children. In the light of the wide-spread of corona virus, performing COVID-19 tests for children with intussusception can help linking the two entities. Development of gastrointestinal symptoms in COVID-19 positive children should raise concern about the development of intussusception.
    • COVID-19 presenting as intussusception in infants: A case report with literature review

      Athamnah, Mohammad N.; Masade, Salim; Hamdallah, Hanady; orcid: 0000-0001-6314-0236; Banikhaled, Nasser; Shatnawi, Wafa; Elmughrabi, Marwa; Al Azzam, Hussein S.O. (Elsevier, 2021-01-12)
      The novel Corona virus disease 2019 (COVID-19) first presented in Wuhan, China. The virus was able to spread throughout the world, causing a global health crisis. The virus spread widely in Jordan after a wedding party held in northern Jordan. In most cases of COVID-19 infection, respiratory symptoms are predominant. However, in rare cases the disease may present with non-respiratory symptoms. The presentation of COVID-19 as a case of intussusception in children is a strange and rare phenomenon. We present here a case of a two-and-a-half month old male baby who was brought to hospital due to fever, frequent vomiting, dehydration and blood in stool. He was diagnosed as intussusception. The child was tested for corona due to the large societal spread of the virus and because he was near his mother, who was suffering from symptoms similar to corona or seasonal flu (she did not conduct a corona test). Patient was treated without surgery and recovered quickly. The COVID-19 infection was without respiratory symptoms, and there was no need for the child to remain in hospital after treatment of intussusception. The relationship between viruses, mesenteric lymphoid hyperplasia, and intussusception is a confirmed relation. ACE2 is the key receptor required for SARA-COV-2 to enter the host cells. ACE2 has been also found in the brush border of the intestinal mucosa, as well as it is a key inflammatory regulator in the intestine. This may suggest that SARSA-COV-2 could invade the respiratory tract as well as gastrointestinal tract or both. Few case reports documented the presentation of COVID-19 as intussusception in children. In the light of the wide-spread of corona virus, performing COVID-19 tests for children with intussusception can help linking the two entities. Development of gastrointestinal symptoms in COVID-19 positive children should raise concern about the development of intussusception.
    • Effect of Moderate and Severe Hemophilia a on Daily Life in Children and Their Caregivers: A CHESS Paediatrics Study Analysis

      Khair, Kate; Nissen, Francis; Silkey, Mariabeth; Burke, Tom; Shang, Aijing; Aizenas, Martynas; Meier, Oliver; O'Hara, Jamie; Noone, Declan (Elsevier, 2021-08-03)
      Introduction: Hemophilia A (HA) is a congenital bleeding disorder, caused by a deficiency in clotting factor VIII (FVIII) and characterized by uncontrolled bleeding and progressive joint damage. This analysis assesses the impact of disease burden on the daily life of children with hemophilia A (CwHA) and their caregivers, addressing a deficit of current research on this topic. Methods: The Cost of Haemophilia in Europe: a Socioeconomic Survey in a Paediatric Population (CHESS Paediatrics) is a retrospective, burden-of-illness study in children with moderate and severe HA (defined by endogenous FVIII [IU/dL] relative to normal; moderate, 1-5%; severe, <1%) across France, Germany, Italy, Spain and the UK. CwHA were recruited and stratified by both age group (0-5 years:6-11 years:12-17 years=1:1:1) and disease severity (severe:moderate=approximately 2:1, prioritizing children with severe HA [CwSHA]). Data for this analysis were captured from physicians, children, and their caregivers. Physicians completed online case report forms for treated children, and the child and/or their caregivers completed a paper-based questionnaire utilizing 5-point Likert scales. For CwHA aged 0-7, the questionnaire was completed by the caregiver, while for CwHA aged 8-17, children and caregivers completed different sections. Hours of care provided by the caregiver and work lost by the caregiver were reported as median values due to non-normal data distribution. Informed consent was obtained for all participants. Upon review, the study was approved by the University of Chester ethical committee. Results: Data from child/caregiver questionnaires were available for 196 CwHA (moderate, 25.5%; severe, 74.5%); the majority of these children, as expected, were receiving prophylaxis (72.4%), and did not have FVIII inhibitors (89.8%; Table 1). There was a direct impact of disease burden on CwHA, particularly with regard to physical and social activities (Figure 1). Overall, it was agreed or strongly agreed by the child or caregiver that 48.0% and 57.5% of children with moderate HA (CwMHA) and CwSHA respectively, have reduced physical activity due to HA, and 46.0% and 57.5%, respectively, have reduced social activity due to HA. A total of 36.0% and 61.0% of CwMHA and CwSHA, respectively, had adapted their treatment in anticipation of physical or social activity (Table 1). Furthermore, 34.0% of CwMHA and 55.4% of CwSHA were frustrated due to their disease, and many (CwMHA, 36.0%; CwSHA, 50.7%) felt that they had missed opportunities (Figure 1). For 66.0% of CwMHA and 76.0% of CwSHA, it was reported that their daily life was compromised due to their HA. Caregivers provided a median (interquartile range [IQR]) of 19.0 (10.0-59.5) and 12.0 (5.0-20.0) hours a week of care for the hemophilia-related needs of their CwMHA (n=30) or CwSHA (n=105), respectively. Of those who responded, 17.4% (n=4/23) and 25.0% (n=20/80) of caregivers to CwMHA or CwSHA, respectively, stated they have lost work due to their caregiving duty. This was more than twice as common for caregivers in families with multiple CwHA (42.9%, n=9/21 responses) compared with those in families with one CwHA (18.5%, n=15/81 responses). Median (IQR) hours of work per week estimated to be lost were 20.0 (17.0-22.0) for caregivers of CwMHA (n=4) and 12.5 (4.50-20.0) for caregivers of CwSHA (n=20). Conclusions: In conclusion, both children and caregivers make sacrifices in their daily lives due to HA; many CwHA reported reduced physical and social activities, fewer opportunities and feelings of frustration due to their HA. Caregivers reported spending a significant number of hours caring for their child and some reported losing work due to their caring responsibilities. However, some outcomes may be limited by the small number of respondents and narrow response options, particularly those regarding the caregiver burden. Responses on the hours of work lost may be subject to selection bias, as caregivers who have lost work may be more likely to respond to this question. Additionally, as this question is targeted at caregivers in employment, it is unknown if some caregivers have left employment due to their caregiving responsibilities. According to this analysis, children/caregivers are frequently required to adapt the child's treatment before the child engages in activities. Overall, the burden of disease was similar in children with moderate and severe HA. Disclosures Khair: Takeda: Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; Biomarin: Consultancy; HCD Economics: Consultancy; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Medikhair: Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Honoraria, Research Funding, Speakers Bureau; CSL Behring: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Haemnet: Membership on an entity's Board of Directors or advisory committees. Nissen: GSK: Research Funding; Novartis: Research Funding; Actelion: Consultancy; F. Hoffmann-La Roche Ltd: Current Employment. Silkey: Aerotek AG: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Burke: HCD Economics: Current Employment; University of Chester: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Shang: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Aizenas: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Meier: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. O'Hara: HCD Economics: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Consultancy. Noone: Research Investigator PROBE: Research Funding; Healthcare Decision Consultants: Membership on an entity's Board of Directors or advisory committees; European Haemophilia Consortium: Membership on an entity's Board of Directors or advisory committees.
    • Evidence of a Hemophilia Employment Gap: Comparing Data from CHESS US+ and the 2019 Current Population Survey

      Asghar, Sohaib; Burke, Tom; Misciattelli, Natalia; Kar, Sharmila; Morgan, George; O'Hara, Jamie (Elsevier, 2021-08-03)
      INTRODUCTION Severe hemophilia A (<1% normal FVIII activity) and B (<1% normal FIX activity) are congenital bleeding disorders characterized by uncontrolled bleeding, either spontaneously or in response to trauma or surgery. Recent commentary has identified a number of patient-important and patient-relevant outcomes that have been understudied, namely the challenges faced by people living with hemophilia to participate in the labor force. The socio-economic impact of hemophilia is comparatively less well understood than clinical outcomes and therapy-related costs. Under-employment and under-utilization have long-term consequences to individuals' job prospects and psychosocial health, as well as an economic cost to the society. The objective of the analysis is to compare labor market participation, among people with severe hemophilia from the US and the general population. This analysis draws on household data derived from the 2019 Current Population Survey (CPS), and on patient-reported data from a patient-centric study conducted in 2019 of people with severe hemophilia, in the US: the ‘Cost of Severe Hemophilia Across the US: A Socioeconomic Survey’ (CHESS US+). METHODS A patient-centric framework informed the design of CHESS US+ a retrospective (12 months prior to study enrollment), cross-sectional dataset of adults with severe hemophilia in the US. Conducted in 2019, the study used a patient-completed questionnaire to collect data on patient-relevant clinical, economic, and humanistic outcomes. This analysis examines labor market participation (full-time, part-time, unemployed), and corresponding general population data derived from the 2019 Current Population Survey (CPS). Data on the general population were sourced from the 2019 CPS ‘Employment status of the civilian noninstitutional population’. Persons ‘not in the labor force’ in the 2019 CPS and retired persons in CHESS US+ were not included in the analysis. We present data on the civilian labor force, in CHESS US+ and in the 2019 CPS. Results are presented as mean (standard deviation) or N (%). RESULTS Of 356 patients profiled in the CHESS US+ study, 97 (27%) had severe hemophilia B and 257 (73%) had severe hemophilia A. Mean age and weight (kg) of the cohort was 34.99 (12.15) and 85.71 (22.81), respectively. The labor force participation rates of non-retired people with severe hemophilia in CHESS US+ (N = 340) and the general population (161,458) are described in Table 1. Examining aggregate data on employment status observed a higher proportion of people with severe hemophilia in part-time employment (24.4% vs. 15.7%). Differences in the labor force participation of people living with severe hemophilia compared to the general population were most pronounced in the full-time employment rate and the unemployment rate. Compared to 80.7% of the general population (Table 1), only 53.5% of people with severe hemophilia in CHESS US+ had a full-time job. Moreover, the unemployment rate (Table 1) in the 2019 CPS compared with the rate observed in CHESS US+ (3.7% vs. 22.1%) provides a stark contrast in the employment experiences of people living with severe hemophilia relative to the general population. CONCLUSIONS This analysis of CHESS US+ illustrates the impact of severe hemophilia on labor force participation. People with severe hemophilia were more likely than the general population to be unemployed, or in part-time employment. A notable contrast was observed in the rate of full-time employment and unemployment, among the general population compared to people living with severe hemophilia. These data illustrate the need to quantify the impact of hemophilia using a holistic approach that considers the cost of involuntary illness-related part-time and unemployment. Disclosures Asghar: HCD Economics: Current Employment. Burke: HCD Economics: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy; University of Chester: Current Employment. Misciattelli: Freeline: Current Employment, Current equity holder in publicly-traded company. Kar: Freeline: Current Employment, Current equity holder in publicly-traded company. Morgan: HCD Economics: Current Employment; uniQure: Consultancy. O'Hara: F. Hoffmann-La Roche Ltd: Consultancy; HCD Economics: Current Employment, Current equity holder in private company.
    • Evidence-based practice and evidence-informed practice competencies in undergraduate pre-registration nursing curricula: A document analysis at a university in England

      Kumah, Dr Elizabeth Adjoa; orcid: 0000-0002-3787-5615; Bettany-Saltikov, Dr Josette; van Schaik, Dr Paul; orcid: 0000-0001-5322-6554; McSherry, Dr Robert (Elsevier, 2021-06-22)
      Background In response to the heightened emphasis on incorporating the best available evidence into healthcare decision-making, healthcare training institutions have been actively incorporating Evidence-Based Practice (EBP), and/or Evidence-Informed Practice (EIP) competencies into undergraduate healthcare curricula. However, there is a gap in the scientific knowledge about the actual contents, as well as the extent of integration of EBP and EIP in undergraduate pre-registration nursing programmes. Method A document analysis utilising Rohwer et al.’s (2014) framework was conducted to review and analyse the content of EBP and EIP competencies in the 2018/2019 curriculum of the undergraduate pre-registration nursing programme of a University located in England, United Kingdom. Results Competencies relevant to EBP were included in four nursing modules. However, EIP competencies were not included in the curriculum. Conclusion There is an urgent need for a more structured and holistic way of teaching and assessing EBP competencies through the integration of the principles of EIP, in order to enhance the effective application of evidence into clinical nursing practice.
    • Examination and Validation of a Patient-Centric Joint Metric: “Problem Joint”; Empirical Evidence from the CHESS US Dataset

      Burke, Tom; Rodriguez Santana, Idaira; Chowdary, Pratima; Curtis, Randall; Khair, Kate; Laffan, Michael; McLaughlin, Paul; Noone, Declan; O'Mahony, Brian; Pasi, John; et al. (Elsevier, 2021-08-03)
      Introduction Severe hemophilia (FVIII/FIX level <1%) is characterized by spontaneous hemarthrosis leading to progressive joint deterioration and chronic pain in the affected individual. Unless these recurrent hemarthroses can be prevented, e.g. with the use of prophylactic factor replacement therapy, these patients will develop chronic synovitis, pain, and eventually destruction of the joint. Current metrics such as ’Target joint’ and other clinical measures of joint morbidity are prevalent and widely accepted. Measures focused solely on bleeding activity, such as the ’Target joint’ metric, are arguably becoming less sensitive as current treatment strategies look to significantly reduce or eradicate joint bleeds, though they maintain clinically relevant and complementary to delivery of comprehensive hemophilia care. Key opinion leaders in the haemophilia field have debated the need for a more patient relevant measure of haemophilia-related joint morbidity. ‘Problem Joint’ (PJ), which is defined as having chronic joint pain and/or limited range of movement due to compromised joint integrity (chronic synovitis and/or haemophilic arthropathy), with or without persistent bleeding was derived through consensus. The objectives of this working group are to examine the usefulness and validity of the PJ metric. Initial research presented here was used to test the sensitivity of PJ as a patient relevant metric with respect to key outcomes for US haemophilia patients. Methods Data on PJs, as well as demographic, clinical and socio-economic variables was captured within the ‘Cost of Haemophilia Across Europe: A Socioeconomic Survey’ datasets (CHESS: I, II, Paediatric, and US studies). These data contain a total of 992 paediatric (age 1-17) and 2,437 adults (age 18+) with haemophilia from eight European countries and the US. Statistical analysis explored the association of PJ count and location with respect to two key outcomes: quality of life, as measured by an EQ-5D score, and overall work impairment, measured by the Work Productivity and Activity Impairment Questionnaire (WPAI). Those with current inhibitors were excluded from the analysis, and the US cohort comprised the focus of this initial research into the topic. Results The US cohort contained information on 345 people with haemophilia (PwH) and captured adults only, with a mean age of 35 years. Approximately, 43% of PwH had one or more PJs. Lower body PJs were more prevalent than upper body: 40% had one or more lower body PJs vs. 27% upper body. The majority of PJs were located in the ankles, knees and elbows. The relationship between EQ-5D and number of PJs showed a negative trend (see Figure 1): the average EQ-5D score was: 0.81 for those with zero PJs (N=197); 0.79 for those with one PJ (N=24); 0.70 for two PJs (N=29); 0.68 for three PJs (N=24) and 0.49 for those patients with four of more PJs (N=59). Similarly, an increase in number of PJs meant greater work productivity impairment versus no PJs recorded: 30.08% (N=102) vs. 19.51% (N=137), respectively. Discussion Results from the US cohort found that an increase in the number of PJs was associated with an increasing humanistic burden in PwH. The proposed Problem Joint definition takes a holistic viewpoint and provides a patient relevant perspective. Further work is planned to evaluate the appropriateness of the measure, and test the sensitivity in European and pediatric cohorts. Disclosures Burke: HCD Economics: Current Employment; University of Chester: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Rodriguez Santana: HCD Economics: Current Employment. Chowdary: Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sobi: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Membership on an entity's Board of Directors or advisory committees; Shire (Baxalta): Membership on an entity's Board of Directors or advisory committees; Spark: Membership on an entity's Board of Directors or advisory committees; BioMarin: Honoraria; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; CSL Behring: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Chugai: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Freeline: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Curtis: Bayer: Consultancy; Novo Nordisk: Consultancy; Patient Reported Outcomes, Burdens and Experiences: Consultancy; USC Hemophilia Utilization Group Study (HUGS): Consultancy. Khair: Haemnet: Membership on an entity's Board of Directors or advisory committees; Biomarin: Consultancy; HCD Economics: Consultancy; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Medikhair: Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Honoraria, Research Funding, Speakers Bureau; CSL Behring: Honoraria, Research Funding; F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; Takeda: Honoraria, Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau. Laffan: Shire: Consultancy; LFB: Consultancy; Roche: Consultancy; Sobi: Consultancy; Pfizer: Consultancy; CSL: Consultancy; Pfizer: Speakers Bureau; Bayer: Speakers Bureau; Roche-Chugai: Speakers Bureau; Takeda: Speakers Bureau; Leo-Pharma: Speakers Bureau; Octapharma: Consultancy. McLaughlin: BioMarin: Consultancy; Novo Nordisk: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Roche/Chugai: Speakers Bureau; Takeda: Speakers Bureau. Noone: European Haemophilia Consortium: Membership on an entity's Board of Directors or advisory committees; Research Investigator PROBE: Research Funding; Healthcare Decision Consultants: Membership on an entity's Board of Directors or advisory committees. O'Mahony: Biomarin: Honoraria, Membership on an entity's Board of Directors or advisory committees; Freeline: Honoraria; UniQure: Honoraria. Pasi: BioMarin: Consultancy, Honoraria, Other: Grants, personal fees, and nonfinancial support; honoraria as member of scientific advisory boards and symposia; uniQure: Other: Grants and nonfinancial support , Research Funding; ApcinteX: Consultancy, Other: Personal fees ; Octapharma: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia , Speakers Bureau; Novo Nordisk: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia ; Catalyst Biosciences: Consultancy, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Biotest: Consultancy, Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia; Alnylam (Sanofi): Other: Personal fees and nonfinancial support ; Takeda: Consultancy, Honoraria, Other: Personal fees; honoraria as member of scientific advisory boards and symposia ; Sanofi: Honoraria, Other: Personal fees and nonfinancial support; honoraria as member of scientific advisory boards and symposia, Research Funding; Sigilon: Research Funding; Tremeau: Research Funding; Sobi: Consultancy, Honoraria, Other; Roche: Honoraria, Other; Pfizer: Other. Skinner: Genentech: Consultancy, Honoraria; Spark Therapeutics: Other, Speakers Bureau; Pfizer: Other, Speakers Bureau; Takeda: Honoraria, Research Funding; uniQure: Research Funding; Biomarin: Consultancy, Research Funding; CSL Behring: Research Funding; Freeline Therapeutics: Research Funding; Novo Nordisk: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding, Speakers Bureau; Sobi: Research Funding; Bayer: Consultancy, Research Funding. O'Hara: HCD Economics: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Consultancy.
    • Housing market spillovers through the lens of transaction volume: A new spillover index approach

      Yang, Jian; Tong, Meng; Yu, Ziliang (Elsevier, 2021-10-25)
      Proposing and applying a new spillover index approach based on data-determined structural vector autoregression to measure connectedness, we examine the daily housing market information transmission via transaction volume among Chinese city-level housing markets from 2009 to 2018. We document substantial information transmission on Chinese housing markets even within one day and find that the role a city-level housing market may play in the information transmission network resembles a pattern observed on other financial markets, which can be generally classified into three distinctive groups: prime senders, exchange centers, and prime receivers. City hierarchy and some fundamental economic factors, such as GDP per capita and average wage, appear to be significant determinants of such a pattern. The findings extend the existing voluminous literature solely based on housing prices or price volatility spillovers and shed new light on the China’s government intervention strategy on the housing market.
    • Millimeter-wave free-space dielectric characterization

      Liu, Xiaoming; Gan, Lu; Yang, Bin (Elsevier, 2021-05-12)
      Millimeter wave technologies have widespread applications, for which dielectric permittivity is a fundamental parameter. The non-resonant free-space measurement techniques for dielectric permittivity using vector network analysis in the millimeter wave range are reviewed. An introductory look at the applications, significance, and properties of dielectric permittivity in the millimeter wave range is addressed first. The principal aspects of free-space millimeter wave measurement methods are then discussed, by assessing a variety of systems, theoretical models, extraction algorithms and calibration methods. In addition to conventional solid dielectric materials, the measurement of artificial metamaterials, liquid, and gaseous-phased samples are separately investigated. The pros of free-space material extraction methods are then compared with resonance and transmission line methods, and their future perspective is presented in the concluding part.
    • Millimeter-Wave Free-Space Dielectric Characterization

      Liu, Xiaoming; Gan, Lu; Yang, Bin
      Millimeter wave technologies have widespread applications, for which dielectric permittivity is a fundamental parameter. The non-resonant free-space measurement techniques for dielectric permittivity using vector network analysis in the millimeter wave range are reviewed. An introductory look at the applications, significance, and properties of dielectric permittivity in the millimeter wave range is addressed first. The principal aspects of free-space millimeter wave measurement methods are then discussed, by assessing a variety of systems, theoretical models, extraction algorithms and calibration methods. In addition to conventional solid dielectric materials, the measurement of artificial metamaterials, liquid, and gaseous-phased samples are separately investigated. The pros of free-space material extraction methods are then compared with resonance and transmission line methods, and their future perspective is presented in the concluding part.
    • New extremal binary self-dual codes from block circulant matrices and block quadratic residue circulant matrices

      Gildea, J.; Kaya, A.; Taylor, R.; orcid: 0000-0002-8563-2212; Tylyshchak, A.; orcid: 0000-0001-7828-3416; Yildiz, B.; orcid: 0000-0001-8106-3123 (Elsevier, 2021-08-20)
      In this paper, we construct self-dual codes from a construction that involves both block circulant matrices and block quadratic residue circulant matrices. We provide conditions when this construction can yield self-dual codes. We construct self-dual codes of various lengths over F 2 and F 2 + u F 2 . Using extensions, neighbours and sequences of neighbours, we construct many new self-dual codes. In particular, we construct one new self-dual code of length 66 and 51 new self-dual codes of length 68.
    • New singly and doubly even binary [72,36,12] self-dual codes from M 2(R)G - group matrix rings

      Korban, Adrian; orcid: 0000-0001-5206-6480; Şahinkaya, Serap; Ustun, Deniz; orcid: 0000-0002-5229-4018 (Elsevier, 2021-09-17)
      In this work, we present a number of generator matrices of the form [ I 2 n | τ 2 ( v ) ] , where I 2 n is the 2 n × 2 n identity matrix, v is an element in the group matrix ring M 2 ( R ) G and where R is a finite commutative Frobenius ring and G is a finite group of order 18. We employ these generator matrices and search for binary [ 72 , 36 , 12 ] self-dual codes directly over the finite field F 2 . As a result, we find 134 Type I and 1 Type II codes of this length, with parameters in their weight enumerators that were not known in the literature before. We tabulate all of our findings.
    • Opinion of the Scientific Committee on Consumer safety (SCCS) – Final Opinion on propylparaben (CAS No 94-13-3, EC No 202-307-7)

      Bodin, Laurent; Rogiers, Vera; Bernauer, Ulrike; Chaudhry, Qasim; Coenraads, Pieter Jan; orcid: 0000-0001-9458-7129; Dusinska, Maria; Ezendam, Janine; Gaffet, Eric; Galli, Corrado Ludovico; Granum, Berit; et al.
      In cosmetic products, the ingredient propylparaben (CAS No 94-13-3, EC No 202-307-7) with the chemical names Propyl 4-hydroxybenzoate and 4-Hydroxybenzoic acid propyl ester is currently regulated as a preservative in a concentration up to 0.14 % (as acid) (Annex V/12a). In addition, a safe concentration was established for mixtures of parabens, where the sum of the individual concentrations should not exceed 0.8 % (as acid). However, in such mixtures the sum of the individual concentrations of butyl- and propylparaben and their salts should not exceed 0.14 %. Propylparaben was subject to different safety evaluations in 2005 (SCCP/0874/05), 2006 (SCCP/1017/06), 2008 (SCCP/1183/08), 2010 (SCCS/1348/10), 2011 (SCCS/1446/11), 2013 (SCCS/1514/13). On the basis of the safety assessment of propylparaben, and considering the concerns related to potential endocrine disrupting properties, the SCCS has concluded that propylparaben is safe when used as a preservative in cosmetic products up to a maximum concentration of 0.14 %. The available data on propylparaben provide some indications for potential endocrine effects. However, the current level of evidence is not sufficient to regard it as an endocrine disrupting substance, or to derive a toxicological point of departure based on endocrine disrupting properties for use in human health risk assessment. The SCCS mandates do not address environmental aspects. Therefore, this assessment did not cover the safety of propylparaben for the environment.
    • Problem Joints and Their Clinical and Humanistic Burden in Children and Adults with Moderate and Severe Hemophilia a: CHESS Paediatrics and CHESS II

      McLaughlin, Paul; Hermans, Cedric; Asghar, Sohaib; Burke, Tom; Nissen, Francis; Aizenas, Martynas; Meier, Oliver; Dhillon, Harpal; O'Hara, Jamie (Elsevier, 2021-08-03)
      Introduction Severe hemophilia A (SHA) is characterized by spontaneous (non-trauma related) bleeding episodes into the joint space and muscle tissue, leading to progressive joint deterioration and chronic pain. Chronic joint damage is most often associated with severe hemophilia, however more recent research has illustrated that people with moderate hemophilia A (MHA) also experience hemophilic arthropathy and functional impairment. The need to measure joint health in children as well as adults, is underscored by findings from the Joint Outcome Continuation Study, which found that FVIII prophylaxis was insufficient to protect joints from damage, from childhood through adolescence in severe HA (Warren et al., 2020). The objective of this analysis is to gain a more patient-centric understanding of the clinical, economic and humanistic burden associated with ‘Problem Joints’, a measure of joint morbidity developed in consultation with an expert panel to overcome limitations with existing measures, in people with MHA and SHA. Methods A descriptive cohort analysis was conducted, utilizing retrospective, cross-sectional real-world data from the ‘Cost of Haemophilia in Europe: a Socioeconomic Survey’ (CHESS Paeds and CHESS II), studies of adult and pediatric persons with hemophilia. The analysis population is comprised of children (17 and below) with MHA or SHA in CHESS Paeds, and adults aged 20 and over with MHA or SHA in CHESS II. To account for the possibility that persons aged 18 or 19 in CHESS II may have participated in CHESS Paeds, these individuals were excluded from the analysis. Physician-reported clinical outcome data and patient/caregiver-reported quality of life were analyzed. A problem joint (PJ) is defined as having chronic joint pain and/or limited range of movement due to compromised joint integrity (i.e. chronic synovitis and/or hemophilic arthropathy). Analyses were stratified by number of PJs: none, 1 PJ, and 2+ PJs. We report retrospective data of the 12 months prior to study enrollment, on annualized bleeding rate (ABR), prevalence of target joints (TJ), as defined by the International Society on Thrombosis and Haemostasis, and EQ-5D-/5L/Y/Proxy score. Results are presented as mean (standard deviation) or N (%). Results Among 785 participants (N = 464 SHA; N = 321 MHA) in CHESS Paeds, mean age and BMI were 10.33 (4.63) and 22.50 (17.07), respectively. Of 493 participants (aged 20 and above) in CHESS II (N = 298 SHA; N = 195 MHA), the mean age and BMI were 38.61 (14.06) and 24.55 (2.92), respectively. Current inhibitor to FVIII replacement was more prevalent in children than in adults (10% vs. 5%). In CHESS II, approximately 40% of people with MHA and 49% with SHA had one or more PJs, respectively [1 PJ (23% vs. 28%); 2+ PJs (16% vs. 21%)]. In CHESS Paeds, approximately 14% of children with MHA and 18% with SHA had at least one PJ, respectively [1 PJ (9% vs. 14%); 2+ PJs (5% vs. 3%)]. TJs were less prevalent with MHA in comparison to SHA, in both adults (24% vs. 45%) and children (13% vs. 22%). Clinical burden was higher among both children and adults with PJs compared to those with no PJs. ABR correlates with the number of PJs, in those with MHA and SHA in CHESS II (Figure 1). Similarly, PJs were associated with higher ABR across MHA and SHA in CHESS Paeds (Figure 2). Hemophilia-related hospitalizations were higher in both adult and pediatric participants with PJs. In CHESS II, MHA with no PJs had fewer [0.73 (1.23)] hospitalizations compared to having those with 1 PJ [1.38 (1.11)] or 2+ PJs [1.28 (1.25)]. Similarly, children with MHA with 2+ PJs had 1.60 (1.92) hemophilia-related hospitalizations, compared to 1.38 (1.92) with 1 PJ and 0.71 (1.14) with no PJs. PJs were associated with impaired quality of life. In CHESS II, MHA and SHA EQ-5D-5L values in persons with no PJs were 0.81 (0.19) and 0.79 (0.18), respectively, compared to 0.65 (0.16) and 0.62 (0.23) with 1 PJ, and 0.65 (0.14) and 0.51 (0.33) in with 2+ PJs. A similar trend was observed in EQ-5D-Y and EQ-5D-proxy scores in CHESS Paeds. Conclusions Data from CHESS Paeds and CHESS II demonstrate an association between chronic joint damage, as measured by the ‘problem joint’ definition, and worsening clinical and quality of life outcomes, across both MHA and SHA. Further analyses will seek to expand upon the initial results presented here, to investigate the wider elements of burden associated with compromised long-term joint health. Disclosures McLaughlin: BioMarin: Consultancy; Novo Nordisk: Consultancy, Speakers Bureau; Sobi: Consultancy, Speakers Bureau; Roche/Chugai: Speakers Bureau; Takeda: Speakers Bureau. Hermans: Novo Nordisk: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Sobi: Consultancy, Research Funding, Speakers Bureau; Biogen: Consultancy, Speakers Bureau; CAF-DCF: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau; Shire, a Takeda company: Consultancy, Research Funding, Speakers Bureau; Pfizer: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Research Funding, Speakers Bureau; WFH: Other; EAHAD: Other; Octapharma: Consultancy, Speakers Bureau; Kedrion: Speakers Bureau; LFB: Consultancy, Speakers Bureau. Asghar: HCD Economics: Current Employment. Burke: HCD Economics: Current Employment; University of Chester: Current Employment; F. Hoffmann-La Roche Ltd: Consultancy. Nissen: GSK: Research Funding; Novartis: Research Funding; Actelion: Consultancy; F. Hoffmann-La Roche Ltd: Current Employment. Aizenas: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Meier: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Dhillon: HCD Economics: Current Employment; F. Hoffmann-La Roche Ltd: Other: All authors received editorial support for this abstract, furnished by Scott Battle, funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. . O'Hara: F. Hoffmann-La Roche Ltd: Consultancy; HCD Economics: Current Employment, Current equity holder in private company.
    • Prophylactic Treatment in People with Severe Hemophilia B in the US: An Analysis of Real-World Healthcare System Costs and Clinical Outcomes

      Noone, Declan; Pedra, Gabriel; Asghar, Sohaib; O'Hara, Jamie; Sawyer, Eileen K; Li, Nanxin (Nick) (Elsevier, 2021-06-24)
      Introduction The treatment paradigm for people with severe hemophilia B in the US typically involves prophylaxis with factor IX (FIX) replacement therapy, the primary aim of which is to provide sufficient FIX levels to reduce the frequency of bleeding events. The clinical benefits of FIX prophylaxis are well understood, however the cost of FIX products as well as costs associated with healthcare resource utilization present a significant burden to the healthcare system. Substantive costs may also accrue in patients who continue to bleed while on prophylaxis, due to the impact on both short and long-term joint-related outcomes. In the absence of existing data in the US, the ‘Cost of Hemophilia Across the USA: a Socioeconomic Survey’ (CHESS US) study was conducted to establish a population-based estimate of the real-world US healthcare system burden associated with severe hemophilia. Using data drawn from the CHESS US study, this analysis examines the real-world healthcare system costs and clinical outcomes of people with severe hemophilia B on FIX prophylaxis. Methods CHESS US, a retrospective, cross-sectional dataset of adults with severe hemophilia in the USA, gathered information on patient cost via a patient record form. Data on the following parameters are included in this analysis: FIX consumption, annualized bleeding rate (ABR), the presence of one or more chronically damaged joints (“problem joint”), as well as costs associated with annual (prophylactic) factor consumption and hospitalizations (i.e., number of admissions, number of day cases, total inpatient days, and total intensive care unit [ICU] days). All variables report retrospective data of the 12 months prior to enrolment in the study. Results are presented as mean (± standard deviation) or N (%). Results In total, 132 of 576 patients profiled in the CHESS US study had severe hemophilia B. Among them, 77 patients were on FIX prophylaxis, of whom 44 patients reported FIX dosing regimen and were included in the current analyses. Among them, 20 patients were treated with conventional FIX and 24 patients with extended half-life (EHL) FIX products. The cohort has a mean age of 27.64 (± 11.05) and mean weight (kg) of 75.71 (± 13.41). In the last 12 months, the mean number of international units (IU) prescribed for FIX prophylaxis across the full cohort was 257,216 IU (± 213,591), with an associated annual cost of $610,966 (± $495,869). Among patients treated with conventional FIX, mean prescribed FIX was 287,141 IU (± 264,906) at an annual cost of $397,491 (± $359,788), while patients treated with EHL FIX reported a mean prescribed FIX of 232,278 IU (± 160,914) at an annual cost of $788,861 (± $529,258). The cohort reported a mean ABR of 1.73 (± 1.39); 8 (18%) were reported to have a target joint meeting the International Society on Thrombosis and Haemostasis (ISTH) definition; and 11% were reported to have had at least one chronically damaged joint (i.e., problem joint). Healthcare resource utilization associated with bleed events were reported as follows: hospital admissions days [0.18 (± 0.62)]; inpatient days [0.34 (± 1.22)]; and ICU days [0.23 (± 0.86)]. The direct medical cost to the healthcare system was $2,885 (± $7,857; excluding FIX cost) and $614,886 (± $498,839; including FIX cost). Discussion Data from the CHESS US study showed substantial costs and resource utilization among patients with severe hemophilia B receiving FIX prophylaxis, of which the cost of FIX replacement therapy constituted most of the total cost to healthcare system. Although the ABR observed in the analysis population was low, bleed-related hospitalizations comprised a significant non-drug cost to the healthcare system. A proportion of patients also still experienced joint arthropathy. Such substantial clinical and economic burden highlights that unmet needs remain in patients with severe hemophilia B on FIX prophylaxis in the US. Disclosures Noone: HCD Economics: Employment. Pedra: HCD Economics: Employment. Asghar: HCD Economics: Employment. O'Hara: HCD Economics: Employment, Equity Ownership. Sawyer: uniQure Inc.: Employment. Li: uniQure Inc.: Employment.