Research Studies

Dr. Laura Sommerville graduated cum laude from Messiah College and then obtained her MS and PhD degrees in cellular and molecular biology from Temple University. Her graduate work and doctoral dissertation produced several awards and publications in peer reviewed publications. She has been a postdoctoral fellow in the laboratory of Dr. Maureane Hoffman at Duke University since July 2014. Dr. Sommerville's 2015 JGP research fellowship award project is on understanding the loss of perivascular tissue factor during angiogenesis in hemophilia.

Objective:

Functional impairment from recurrent joint bleeding in people with hemophilia results in joint pain and reduces quality of life. The P-FiQ study formally evaluated patient- and site-reported functional assessment including responses to generic and hemophilia-specific patient-reported outcomes (PROs) tools. Psychometric analyses were used to evaluate reliability, validity, and consistency of responses.

Methods:

Adult males with hemophilia and a history of joint pain or bleeding completed a hemophilia history and 5 PROs assessing function: EQ-5D-5L, Brief Pain Inventory v2 Short Form (BPI), International Physical Activity Questionnaire (IPAQ), Short Form-36 v2 (SF-36v2), and Hemophilia Activities List (HAL). PROs were assessed for reliability, consistency, and correlation, with factors including patient-reported characteristics.

Summary:

A total of 381 adults (median age, 34 years; range, 18-86 years) were enrolled in P-FiQ. Most participants (66%) and sites (59%) reported functional disability in the past 6 months (CDC-UDC scale). Patients self-reported arthritis/bone/joint problems (65%) and history of joint procedures or surgeries (50%). On EQ-5D-5L, most reported problems “today” with mobility (61%) and usual activities (53%) but fewer with self-care (19%). On BPI, similar median pain interference scores (0- 10 scale, 10 is complete interference) were reported with general activity (3.0), walking ability (3.0), and normal work (3.0). On IPAQ, physical activity was reported by 49% of respondents over the prior week, with more reporting walking (35%) than moderate (16%) or vigorous (16%) activities. On SF-36v2, activities in the past 4 weeks that were most frequently limited were vigorous activities (80%), bending, kneeling, or stooping (67%), walking more than a mile (61%), and climbing several flights of stairs (59%). Physical problems caused participants to limit kinds of work/activities (69%), accomplish less than they would like (66%), have difficulty in performing work/activities (65%), and reduce time spent on work/activities (62%). On HAL, greater difficulties were seen for lower vs upper extremity functions/activities; within the lying/sitting/kneeling/standing domain, the most frequent problems in the previous month were squatting for a long time (74%), kneeling (73%) or standing (72%), and kneeling/squatting (70%). Similar items across different PROs were correlated with one another. Self- reported functional impairment was significantly differentiated by BPI pain interference, IPAQ total activity, SF-36v2 physical functioning, and all HAL domains and summary scores.

Conclusion:

PRO instruments assessing functional status range from simple/generic (EQ-5D-5L) to complex/disease-specific (HAL) and provide varying levels of detail. Greater use of formal PRO instruments in the clinical setting may improve dialogue between health care professionals and patients/caregivers and inform proactive approaches to specifically target patient identified functional limitations (eg, HAL) and identify areas for further targeted management strategies.

Camping programs for individuals with chronic illness are increasingly common. Unfortunately, few studies have been conducted to empirically evaluate whether camping programs are meeting their intended goals or having the positive outcomes that are expected of them. The current study was conducted as an evaluation of a bleeding disorder camp for patients with bleeding disorders and their siblings.

Participants in the current study included 77 participants, ages 7-20 (mean 11.58, SD = 3.21). The sample was 62.3% male and 63.6% patients (36.4% siblings). Most of the patients (52.6%) had severe bleeding disorders. Participants were administered the Children’s Hope Scale (CHS; Snyder et al., 1991), which evaluates two dimensions of hope (1. Agency, the ability to identify positive goals and 2. Pathways, the ability to find ways to meet identified goals) and overall hope. Participants demonstrated a significant improvement on the agency subscale of the CHS, t(35) = -2.16, p < .05. Participants reported qualitative aspects of living with bleeding disorders, including differences in their lives, aspects of their lives that are better, aspects about bleeding disorders that are often misunderstood, and advice for others with bleeding disorders. Responses to qualitative were analysed across groups (patients and siblings; severe and mild patients) and were found to be very consistent across these groups. This information has helped to provide information about experiences of youth affected by bleeding disorders and will be used to help inform upcoming camp programming. These findings have also demonstrated positive psychosocial outcomes associated with camp attendance.

Background:

A high-purity plasma-derived FX concentrate (pdFX) has been developed for treatment of hereditary FX deficiency, an autosomal recessive disorder.

Aim:

This post hoc analysis describes the pharmacokinetics, safety, and efficacy of pdFX in 10 women and girls with hereditary FX deficiency.

Methods:

In this open-label study, subjects (10 women/girls, 6 men/boys) aged ≥12 years with moderate or severe FX deficiency (basal plasma FX activity ≤5 IU/dL) were enrolled and received 25 IU/kg pdFX for on-demand treatment of bleeding episodes or preventative use for up to 2 years. All subjects provided informed consent and the protocol was approved by appropriate independent ethics committees.

Results:

Nine women and girls had severe and 1 had moderate FX deficiency, were aged 25.5 (median; range 14–58) y, and received a total of 267 pdFX infusions (178 for on-demand and 89 for preventative treatment). Men and boys (5 severe and 1 moderate FX deficiency) received a total of 159 pdFX infusions (64 on-demand; 95 preventative). The mean number of infusions per subject per month was higher among women and girls (2.48) than males (1.62). The mean pdFX incremental recovery was similar between women/girls and men/boys (2.05 vs 1.91 IU/dL per IU/kg, respectively), as was mean half-life (29.3 and 29.5 h, respectively). Among women and girls, 132 assessable bleeding episodes (61 heavy menstrual bleeding, 47 joint, 15 muscle, and 9 other) were treated with pdFX. Women and girls reported a treatment success rate (ie, subject rating of “excellent” or “good” response to pdFX) of 98%, comparable to the 100% treatment success rate among men and boys. After study completion, 2 subjects received pdFX for hemostatic cover during obstetric delivery. Additional infusion, bleed, and safety data will be presented.

Conclusion:

These results show that, in women and girls with moderate or severe hereditary FX deficiency, who experience reproductive tract and other bleeding events, pdFX was safe and effective. The pharmacokinetic profile of pdFX in women and girls was similar to that of men and boys.

Funding: Bio Products Laboratory