Hemophilia causes repetitive bleeding episodes throughout the musculoskeletal system, primarily into joints, such as knees and ankles. This leads to significant joint damage resulting in increased pain reproduction, decreased functional abilities, such as walking, and negatively impacts quality of life. Traditionally the extend of joint damage has been examined via clinical assessments, such as the Hemophilia Joint Health Scores, x-rays, MRIs, and more recently musculoskeletal ultrasound (MSKUS). However, these modalities fail to establish the global impact of joint damage on the entire body of a person with hemophilia and their functional abilities. Analyzing joint motion and forces acting upon the joint during walking has been a widely established technique to gain understanding of abnormal three-dimensional movements and is a key factor in clinical decision making-processes. With the overall goal of establishing better treatment approaches for persons with hemophilia it is vital to understand the underlying functional joint limitations. Therefore, the purpose of this study is to investigate characteristics of damaged joints, joint motion and control as well as forces acting upon the joint during walking in persons with hemophilia.
Objective:
Report on the utilization of a multi-point videoconferencing platform, Extensions for Community Healthcare Outcomes (ECHO), in providing a clinical learning opportunity to physical therapists (PTs) involved with people with bleeding disorders (PWBD) within Western States Region Hemophilia Treatment Centers (WSR HTC).
Methods:
WSR HTC includes thirteen HTC’s located in California, Nevada, Hawaii, and Guam. Monthly one-hour evidence based case presentations with a facilitated discussion were conducted using the ECHO platform. Each session was recorded, so all the therapists invited to participate have access to the information.
Data were collected from the WSR participating PTs by using anonymous on-line surveys, Qualtrics software (Qualtrics, Provo, UT), and prior to the start of the physical therapy ECHO session and upon completion of each session.
Descriptive statistics were calculated to evaluate the educational value of presentations.
Results:
Thirteen PTs, surveyed prior to the first PT ECHO session had reported > 6 years of experience as a PT. Twenty-three percent reported < 5 years of experience working with PWBD and over half of PT surveyed had > 16 years of experience working with PWBD.
Eight topics were presented in 2018 included musculoskeletal ultrasound imaging, invasive surgery rehab outcomes for patients with inhibitors, kinesiology taping, knee arthroplasty and stiffness, iliopsoas bleeding, myofascial decompression, chronic pain, knee bleed, and ankle joint impact from bleeding. An average of nine HTC PTs attended each session (range 4 to 18). Ten (11.2%) non-HTC PTs (outpatient PTs, HTC nurse, HTC Nurse Practitioner) attended some of the PT ECHO sessions. Table 1.
Ninety-five percent of respondents reported strong agreement with the program’s educational value and appropriateness for a practicing PT. Thirty-seven (94.9%) of responses reported agreement that the PT ECHO program improved their knowledge of physical therapy and bleeding disorders. Table 2.
Conclusion:
Videoconferencing platforms such as ECHO allows PTs in the WSR HTC, who are geographically separated to successfully share clinical knowledge to facilitate best practice in the area of specialty care for PWBD.
Please see files attached for tables and figures.
Objective:
To examine the frequency and methods used to screen patients for substance use and behavioral health disorders in Hemophilia Treatment Centers (HTC). We hypothesized that inconsistencies in methods utilized and frequency of utilization exist.
Methods:
Marshall University (MU) Physical Therapy faculty along with MU addiction education staff developed a 26-question survey using Qualtrics. The survey included questions on demographics, validated screening tools utilized, screening frequency, and team member responsible for screening. The HTC email addresses were obtained from the Hemophilia Treatment Center Directory on the CDC’s website. Following approval from MU IRB, the survey was disseminated via an online link. Descriptive analysis was performed on the data.
Summary:
Health professionals from 19 HTCs, representing 8 different regions, completed the survey. The overall response rate was 13.6%. Social workers (12, 63.2%), nurses (6, 31.6%)) and counselors/psychologists (1, 0.05%) submitted responses. On average HTCs reported 34.5% (0-92%) of their patients experience chronic pain with an average 22.4% (0-56%) receiving prescription opioids for pain management. Adverse consequences related to opioid use existed in all of the HTCs including overdose (31.5%), withdrawal symptoms (42.1%), increased dose due to tolerance (63.2%), and increased bleeding episodes (26.3%). The majority of HTCs (57.9%) reported being the primary provider of pain management for people with hemophilia (PWH). Standardized screening for substance use disorders is occurring 31.6% of the time with marijuana and illicit drugs (100%) being most commonly screened followed by alcohol and prescription drugs (83%) and tobacco at 33%. Frequency of screening for substance use varied widely from every comprehensive visit to initiation of an opiate contract to suspicion of misuse. Screening for behavioral health is more common (81.3%) with a variety of validated screening tools being utilized. Over 60% of the time, screening for anxiety and depression occurs either annually or every visit.
Conclusions:
PWH often develop chronic pain related to joint arthropathy.
Based on our findings, the incidence of chronic pain in PWH is relatively equal to the national average. HTCs are often the primary provider of pain management and are challenged to find safe treatment methods. PWH are often prescribed opioids which may place them at increased risk for potentially developing an opioid use disorder.
The presence of a behavioral health disorder may further enhance one’s risk. Although behavioral health screenings appear to be more consistently utilized in HTCs, substance use screenings are rare. Our research suggests that universal screening for substance use and behavioral health conditions should be considered, as a standard of care in HTCs, to better inform healthcare providers of patient risk, need for referral and to guide prescriber’s decision making with regard to pain management options.
Objective:
Persons with bleeding disorders experience pain in association with needle pokes, joint and muscle bleeds and permanent tissue damage. The impact of this pain on patients can include time off school or work, a change in career, income, stress, mental health concerns and change in relationships. Comprehensive pain management includes strategies from the “Four P’s of Pain Management” which include pharmacological, physical, psychological and prevention.
The aim of the project was to examine current psychological knowledge and management of pain within our patient population. This study asked the following research questions: 1) What is currently understood about pain and bleeding disorder care among social workers (CSWHC)? 2) What specific pain knowledge and training is prioritized by social workers in Hemophilia Treatment Centres?
A scoping review was conducted concurrently with the qualitative study. Medline and SocIndex were searched with the terms “social work” and “pain management” and a second search was conducted with the term “social work and hemophilia/von willebrand's or platelet disorders”. A total of 105 articles were examined by three independent reviewers. Eleven articles have been included for the purpose of examining the role of social work in pain management.
Methods:
Qualitative interviews were conducted and recorded with 12 social workers from the CSWHC between September 2018 and February 2019. Five provinces were represented. Social work participants were deployed within paediatric, adult or within combined clinics. The interviews were approximately 20-45 minutes. Transcribed interviews were coded with NVivo by two independent reviewers with Thematic Analysis.
Summary:
Social workers identified the roles of social work to include completion of psychosocial assessments and meeting the practical needs of patients, while supporting patients in medical decisions. Barriers to pain management and the impact of pain on patients were described as having an impact on individuals and families. Social workers also discussed their understanding of acute and chronic pain in patients, which has indicated an increase of knowledge is required. Skills development in multi-dimensional nature of pain and pain assessment were determined to be most likely to produce positive impact on practice outcomes. Initial themes include hope, relationship of trust, stigma (diagnosis vs. pain), defining multidisciplinary roles.
Conclusion:
Study results, first, will contribute to the literature supporting the need for social work education for those practicing in bleeding disorder care. Secondly, they will provide recommendations for an educational pain curriculum for social workers in bleeding disorder care. This education will reflect the need for pain knowledge in acute and chronic pain dimensions which will facilitate dialog with other professionals in pain management. Pain assessment will also be a focus in order for social workers to be able to support and provide appropriate referrals for pain management.
Objective:
The completed pediatric phase 3 pathfinder 5 trial assessed the safety and efficacy of N8-GP (turoctocog alfa pegol, ESPEROCT®) use for routine prophylaxis and treatment of breakthrough bleeds in previously treated children.
Methods:
pathfinder 5 was a multicenter, multinational, single-arm study evaluating safety, efficacy, and pharmacokinetics. Children (aged <12) with severe hemophilia A were administered prophylaxis (target 60 [50-75] IU/kg twice weekly) in the main phase (26 weeks) followed by an extension phase. Current analysis covers study initiation (February 2013) through completion (September 2018).
Summary:
Of the 68 children (34 aged 0-5, 34 aged 6-11) enrolled, 63 completed the main phase and 62 completed the extension. Most (95%) were previously on prophylaxis. The total study period amounted to 306 patient-years (32,138 exposure days); median (mean) patient exposure was 4.9 (4.5) years.
Overall, 838 adverse events (AEs) were reported; 18 serious AEs included 2 possibly/probably related to N8-GP (severe allergic reaction [1] and increasing bleeding symptoms [1]). No inhibitor development was observed in the trial. Two AEs resulted in withdrawal; a third patient with severe allergic reactions (after 4 doses) that resolved after 2 hours without any treatment met preestablished withdrawal criteria. There were no anti-PEG antibodies of clinical significance; however, 21 (31%) patients had anti-PEG antibodies at baseline (prior to exposure), and 1 patient had a single positive measurement after exposure at a titer <1.
Overall, 55 patients (81%) reported 330 bleeds during the study; most were traumatic (67%). The success rate for hemostasis was 84% (excellent/good); 71% were treated with 1 injection, and 88% of patients were successfully treated with 1-2 injections. Median (mean) utilization for bleeds was 68 (95) IU/kg.
Median ABRs are shown below; estimated mean ABR was 1.1. Forty-seven percent of children had no spontaneous bleeds throughout the trial. Of 13 children with 17 target joints at baseline, 77% (main phase) and 46% (complete trial) reported no bleeds in their target joints. For those previously on prophylaxis, the mean observed ABR was 2.3 compared with the historical ABR of 6.4. The mean prophylaxis dose was 64.7 IU/kg with an interval of 3.5 days.
| Median ABR | Age 0-5 y | Age 6-11 y | Total |
| Overall | 0.6 | 0.9 | 0.8 |
| Spontaneous | 0.1 | 0.2 | 0.2 |
| Traumatic | 0.3 | 0.8 | 0.5 |
N8-GP prolonged single dose half-life by 1.9x compared with the child’s prior FVIII product. The mean trough levels on twice-weekly dosing were 0.019 IU/mL (0.016 ages 0-5, 0.024 ages 6-11).
Conclusion:
These data support the safety and efficacy of N8-GP in a controlled phase 3 trial setting in children. Prophylaxis with N8-GP using a consistent dose/interval (65 IU/kg twice weekly) was effective in preventing bleeds. No unexpected safety issues were identified.
Objective:
The adolescent/adult pivotal phase 3 pathfinder 2 trial assessed N8-GP (turoctocog alfa pegol, ESPEROCT®) use for routine prophylaxis and treatment of bleeds in previously treated patients (PTPs).
Methods:
pathfinder 2 was a multi-center, multi-national, single-arm study evaluating safety, efficacy and pharmacokinetics. Adolescents/adults (aged ≥12 y) with severe hemophilia A were administered prophylaxis (50 IU/kg Q4D) in the main phase with option for eligible patients (0-2 bleeds in prior 6 months) to randomize (2:1) to 75 IU/kg Q7D or 50 IU/kg Q4D during extension 1 (24 weeks) and continue treatment into extension 2. An on-demand group was included throughout. Current analysis covers January 2012 through December 2018.
Summary:
Of the 186 PTPs (including 46 [25%] from the US) enrolled in the main phase, 150 (81%) started extension 1, 139 (75%) completed extension 1, and 128 (69%) completed the study. Mean age was 31.1 years, weight 75 kg and BMI 24.3.
The complete trial covers 785 patient-years of treatment (66,577 exposure days [ED]) during which there were 2,758 bleeds, including 1,807 (66%) spontaneous bleeds and 1,735 (63%) joint bleeds. Twelve patients treated on-demand for a mean 3.1 years reported nearly half of all bleeds (1,270, 46%), including 971 (54%) spontaneous bleeds and 627 (36%) joint bleeds. Hemostatic efficacy was rated excellent/good in 2,470 (90%) episodes; 2,614 bleeds (95%) were treated with 1-2 injections.
Of 175 patients on prophylaxis, 55 of 110 eligible were randomized in extension 1. For 177 patients treated with 50 IU/kg Q4D prophylaxis for 613 years (57,723 ED), 126 (71%) experienced 1,312 bleeds. For 61 low-bleed patients with 134 years (7,255 ED) on 75 IU/kg Q7D prophylaxis, 53 (87%) experienced 176 bleeds. Median ABRs are shown in the TABLE.
| 50 IU/kg Q4D | 75 IU/kg Q7D | |
| n | 177 | 61 |
| Mean treatment | 3.5 years | 2.2 years |
| Median ABR | 0.8 | 1.7 |
N8-GP mean trough levels were 3.1 IU/dL on 50 IU/kg Q4D and 1.0 IU/dL on 75 IU/kg Q7D.
A total of 1,827 adverse events were reported over 785 exposure years, including 63 serious adverse events. One patient with an intron 22 inversion developed a low-titer inhibitor at 93 ED and was withdrawn when it progressed to >5 BU. Non-neutralizing anti-PEG antibodies were seen at baseline in 12 patients (6.5%) prior to first N8-GP exposure and 11 (5.9%), who had negative anti-PEG at baseline, had positive antibodies after exposure.
Conclusion:
These data support the safety and efficacy of N8-GP in a controlled phase 3 trial setting in adolescents/adults. Prophylaxis with N8-GP with a consistent dose/interval (50 IU/kg Q4D) was effective in preventing bleeds; extended dosing was evaluated as successful for a subgroup of low-bleed patients. No significant safety issues were identified.
