Objective:
Few online resources are available for teens and young adults living with hemophilia. Frankly.net aspires to serve as a candid, trusted resource on real issues of concern for this age group. Our online forum provides news, tips and information to help young adults with hemophilia live the lives they choose.
Method:
In 2008, an editorial board was established to guide the creation of Frankly.net, an online magazine targeting young men with hemophilia. Board members include experts in the areas of healthcare, social work and advocacy, and two are young men living with hemophilia.
Frankly.net content is controlled exclusively by the editorial board and sponsored by Bayer Healthcare with the goal of casting light on often taboo subjects within the community, such as sexuality, drugs and depression. An editorial calendar is maintained to ensure fresh content is published regularly.
Frankly.net is mobile-optimized and includes rich video content. Users are encouraged to keep up with the latest content by following @FranklyNet on Twitter.
Summary:
Since its inception, the editorial board has guided the creation of more than 80 stories. Articles include topics that resonate with young adults such as travel, entertainment, relationships and sex. Engaging video stories are also available in English and Spanish.
To date, Frankly.net has seen nearly 7,500 visitors from more than 125 countries across the globe, including the US, India, Germany, Canada.
In 2013, Frankly.net underwent a site makeover, re-launching with a new look and feel. Plans to further engage with an international audience are also underway. Korea launched a fully translated site in early 2013 under the guidance of a Korean editorial board. A Latin American version is in development and content from the site has been repurposed and translated in a dozen countries.
Conclusions:
Frankly.net is a unique resource for teenagers and young adults with hemophilia around the world. It continues to push boundaries as a way to help young men navigate the ups and downs of living with hemophilia.
Objectives:
The purpose of this pilot study was to quantify prevalence of food insecurity and determinants among households including children with hemophilia. Food insecurity, the limited or uncertain availability of nutritionally adequate and safe food, negatively affects children’s development and health. Households including people with hemophilia may be at increased risk for food insecurity due to hemophilia-related medical expenses and employment limitations.
Methods:
Food insecurity and health status, as assessed at annual comprehensive visits from May 2012-January 2013 were obtained by chart review. A two-question, validated screening tool was used to assess food insecurity status Descriptive statistics were applied to summarize participant characteristics. This study was approved by the Oregon Health & Science University Institutional Review Board.
Summary:
Data were available for forty-two male participants, aged 0-18 years, 42.9% had mild or moderate hemophilia and 57.1% severe. Prevalence of food insecurity overall was 16.7% (95% CI 5.4-28.0%), similar to national averages; food insecurity was rare among those with mild and moderate disease (5.6%) and concentrated among those with severe disease (25.0%; 95% CI 7.7-42.3%). Additionally, children who were older, taller, heavier, had higher body mass index (BMI) status, or were identified as a minority race or ethnicity were at increased risk for food insecurity (all P>0.05).
Conclusions:
This study provides pilot data showing the need for food insecurity screening and linkage to resources as a routine part of care, and the need for improved understanding of the determinants of food insecurity in this population.
Objective:
When a surgical procedure is required in a patient with hemophilia, continuous infusion of factor (CIF) is a safe and effective alternative to bolus dosing.1-5 However, when cultural values collide with best practices, a patient-centered collaborative care plan is necessary to help ensure a positive outcome while respecting the core values of the patient.
Method:
Our team collaborated with our local Hemophilia Treatment Center (HTC) physicians and nurses to plan CIF for an Amish patient who required a total knee replacement. After interviewing the patient, the care team recognized when the patient transitioned on CIF to the home, we would need to respect the cultural beliefs of the patient without compromising the care.
The HTC physician and nurse ordered continuous infusion of factor for the patient with goal factor levels to remain between 70-100% on post-op days 1-7 and between 50-70% on post- op days 8-14. The home infusion team collaborated with the family and HTC team to finalize the care plan. The patient-centered decision prompted the use of a battery powered ambulatory infusion pump and the use of pre-approved sliding scale factor orders (ACAT protocol) with daily factor levels. Our biggest barrier was in respect to communication with the patient. In our local Amish community, telephones are not accessible. Our brainstorming lead to our COO suggesting we include a battery operated phone that would be attached to the pump and only be used for pump emergencies.
Summary:
The patient was discharged to home post-op day three with recombinant factor VIII running at 2.5 units/kg/hour via a battery operated ambulatory pump. Levels on post-op day four were below 70, prompting the nurse to call on the “pump phone” and return for a visit that night to increase the rate to 2.7 units/kg/hour. The rate remained the same throughout the remainder of the therapy and the levels stayed within the range designated by the physician.
Conclusion:
The patient-centered multidisciplinary care plan allowed for a positive outcome while respecting the patient’s culture.
Objective:
This prospective clinical trial was conducted to assess the safety, efficacy and PK of BAX326 (a novel recombinant FIX [rFIX] manufactured without the addition of any materials of human or animal origin, and with two viral inactivation steps [solvent/detergent treatment and nanofiltration]) in previously-treated patients aged 12 to 65 with severe (FIX level < 1%) or moderately severe (FIX level ≤ 2%) hemophilia B.
Methods:
Hemostatic efficacy after twice weekly prophylaxis with BAX326 was determined in terms of annualized bleeding rate (ABR) compared with a historical control group treated on- demand. PK equivalence was assessed between BAX326 and a commercial rFIX in a crossover design. Safety was evaluated by the occurrence of adverse events.
Summary:
In subjects on twice weekly prophylaxis with BAX326 over at least 3 months (N=56), 24 (43%) did not bleed throughout the study observation period, and the ABR was substantially lower when compared with a historical control group (79% reduction, p<0.001). Joint bleeds (major joints: wrist, elbow, shoulder, hip, knee, ankle) occurred at a mean ABR of 2.85 ± 4.25 compared with 1.41 ± 2.87 in non-joint bleed sites. Of the 32/56 subjects with bleeds, 90.6% (29/32) had arthropathy at screening and only 28.1% (9/32) did not have target joints, as compared to subjects without bleeds, of whom 79.2% (19/24) had arthropathy and 50% (12/24) did not have target joints at screening. Higher mean ABRs were observed in subjects with arthropathy (N=46) versus without arthropathy (N=8) (4.54 vs. 2.57 for all bleeds, 3.16 vs. 1.02 for joint bleeds, and 1.97 vs. 0.25 for spontaneous bleeds). A similar pattern was observed for the ABRs of joint bleeds and spontaneous bleeds in subjects with target joints (N=35) (mean ABR: 2.41 ± 3.79) and those with no target joints (N=21) (mean ABR: 0.58 ± 1.63). Most bleeds were controlled with 1-2 infusions of BAX326 and with an efficacy rating of “excellent.” BAX326 was equivalent to the comparator rFIX in terms of AUC 0 72 h /dose. BAX326 is safe and well tolerated in hemophilia B patients, with no signs of immunogenicity or thrombotic events.
Conclusions:
BAX326 has a positive safety profile and is efficacious in treating bleeds and in routine prophylaxis in PTPs aged ≥12 years with hemophilia B. The results also demonstrate that subjects with target joints and hemophilic arthropathy receiving secondary prophylaxis tend to have higher ABRs as compared to those without these underlying conditions.
Objective:
With increasing life expectancy of people with hemophilia (PWH) in developed countries, the number of PWH affected with age-related diseases is also increasing. Atrial fibrillation is a common health problem in the general population, but in PWH, evidence-based guidelines for the management of AF are lacking.
The aim of this cross-sectional pan-European study is to analyze the prevalence of AF and risk factors for stroke in our adult hemophilia population and to document current anticoagulation practice.
Methods:
The ADVANCE Working Group consists of members from 14 European hemophilia centers. Each center retrieved data on the number of PWH with AF in their hemophilia population, as well as their total number of adult PWH. For each person with AF, a case report form was completed.
Summary:
In total, 29 PWH with AF were documented. The mean age was 68.2 years (IQR 62-75.5). Hemophilia was severe in 6 (20.6%), moderate in 6 (20.6%) and mild in 17 (58.6%) patients. The prevalence in the total studied hemophilia population was 0.94% (29/3094) and increased with age; in patients >40 years it was 1.7% (29/1723) and in patients >60 years 3.6% (23/635). The mean CHA2DS2-Vasc score was 1.3 (IQR 0-2). Hypertension was reported in 12 patients (41.4%), diabetes in 3 (10.3%), previous stroke or TIA in 1 (3.4%), peripheral vascular disease in 4 (13.8%). In 11 patients (37.9%), anticoagulation was started of whom 9 low dose aspirin and 2 vitamin K antagonists. Of these 11 patients, 9 had mild hemophilia, 1 moderate and 1 severe with FVIII prophylaxis. During follow-up after diagnosis (mean follow-up 52.9 months), there were no thrombotic events reported, nor increases in bleeding severity.
Conclusions:
In this largest cohort of PWH with AF so far, the prevalence of AF in hemophilia increases with age and is predominantly present in mild hemophilia. Based on the population based CHA2DS2-Vasc risk scores, PWH have a low stroke risk that might be even lower considering the hypocoagulable state. Hemophilia doctors prescribe anticoagulation therapy approximately in half of their mild hemophilia patients and very few in moderate and severe.
Objective:
A novel recombinant coagulation factor VIII, rVIII-SingleChain, produced without added animal- or human-derived materials, is currently in a clinical phase I/III program (AFFINITY). The present non-clinical studies were conducted to investigate the pharmacokinetic (PK) profile of rVIII-SingleChain in animals to support assessment of its PK/pharmacodynamic properties for future clinical use.
Methods:
The PK behavior of rVIII-SingleChain was explored in hemophilia A mice, rats, and monkeys. Intravenous doses of 50-250 IU/kg for rVIII-SingleChain or a marketed full-length rFVIII concentrate were given. Systemic FVIII activity or antigen levels were recorded in plasma samples after injection. A thrombin generation assay was conducted to assess coagulation parameters ex vivo after treatment of hemophilia A mice with 250 IU/kg of rVIII- SingleChain or full-length rFVIII.
Summary:
In all animal species, treatment resulted in improved PK properties for rVIII- SingleChain compared to full-length rFVIII. Increased systemic availability and mean residence time were observed for rVIII-SingleChain. Correspondingly, the clearance rate was decreased and the terminal half-life was enhanced in comparison with full-length rFVIII. In vivo recovery and volume of distribution of rVIII-SingleChain were equivalent to full-length rFVIII. Consistent with the PK characteristics, rVIII-SingleChain showed a more favorable thrombin generation potential compared to full-length rFVIII between 2-6 days after treatment of FVIII-deficient mice. Results obtained showed that thrombin peak levels were kept between 50-250 nM for an increased period of time by rVIII-SingleChain compared to full-length rFVIII, with an average extension of 20 hours.
Conclusions:
The current investigations demonstrated favorable PK properties of rVIII- SingleChain in animal species. The presented results support the evidence necessary for conducting human trials to explore whether such favorable non-clinical PK characteristics may translate into clinical benefit.
This study explores perceptions among adolescent aged patients with inherited bleeding disorders regarding religiosity/spirituality and whether their beliefs have an impact on the pain they experience. Subjects participating will be assessed in regards to the type, frequency and intensity of pain experienced and measures used to cope with the pain. Finally, we will measure patient self reports of disease self efficacy. To further assess the impact of religiosity/spirituality on the family system, we will be measuring parental perceptions of religiosity/spirituality with parents of the participating adolescents.
Objective:
Few data sources contain sufficient patient count to study the real-world efficacy of factor VIII (FVIII) therapy in patients with hemophilia A (HA). Health insurance claims databases offer that opportunity. This study sought to identify patients with HA receiving prophylaxis versus on-demand FVIII regimens and describe their characteristics and treatment patterns utilizing data from Medicaid programs.
Methods:
Healthcare claims from Florida, Iowa, Kansas, New Jersey, and Missouri Medicaid programs covering 1996 to 2011 were used. Patients with ≥2 HA diagnoses (ICD-9 286.0), ≥2 dispensings for FVIII after age 2, continuous Medicaid eligibility ≥6 months before (baseline period) and ≥12 months after the first FVIII fill, and no evidence of bypassing agents or desmopressin use were included. Prophylaxis and on-demand regimens were identified using an algorithm calibrated to distinguish the regimens within five age groups based on the annual total units of FVIII dispensed regardless of the severity level: 16,480 IU (2–7 years old); 32,770 IU (8–12); 66,920 IU (12–16); 98,349 IU (17–21); 204,552 IU (≥22). The algorithm was developed using prescription records of 1,311 patients from three U.S. specialty pharmacy databases. FVIII treatment patterns and patient demographic and clinical characteristics were examined.
Summary:
From the approximately 14.8 million covered lives encompassed in the five Medicaid databases, a total of 2,408 (0.016%) patients with ≥2 diagnoses for HA were identified; 448 met the study eligibility criteria with 229 (51.1%) patients receiving prophylaxis FVIII and 219 (48.9%) patients receiving on-demand FVIII. Younger patients were more likely to receive prophylaxis therapy (percent by age group: 61% [2–7]; 70% [8–12]; 63% [12–16]; 51% [17–21]; 20% [22+], mean (SD) age, prophylaxis: 10.8 (9.8) years old; on-demand: 18.7 (14.4) years old). Mean (range) observation period was 5.6 (1.0-15.2) years for prophylaxis patients and 5.6 (1.0-15.2) years for on-demand patients.
Conclusions:
In a population of 448 Medicaid patients with HA, this study found that 51.1% and 48.9% patients received prophylaxis and on-demand FVIII regimens, respectively. With the average observation of patients for more than 5.5 years, this database offers the potential for long-term follow-up to assess the relative efficacy of prophylaxis versus on-demand FVIII regimens in decreasing the incidence of bleeding events. These evidences from claims databases are critical to payers and decision makers as they reflect real-world clinical practice and patterns of FVIII use. Information on HA severity level was not available in the databases used.
Objective:
To assure plasma-derived clotting factor concentrates are pathogen safe, virus inactivation and removal methods are applied to the manufacturing process. The effectiveness of currently used methods and procedures was demonstrated.
Methods:
The virus reduction capacity of the manufacturing process for a specific product was quantitated for selected steps of the manufacturing process. A prerequisite of such virus validation studies is a valid downscaling of the manufacturing process to a laboratory scale. After spiking product intermediates with a panel of viruses the same as or similar to known and emerging pathogens, the manufacturing steps were performed according to the defined procedures and the reduction factors for the different viruses measured. Prion reduction was also studied, employing both a microsomal preparation (membrane-associated prions) and purified prion protein. Methods in the manufacturing process solely for the purpose of pathogen reduction, such as pasteurization, solvent-detergent treatment, dry heat treatment of the final container, and virus (nano) filtration, as well as manufacturing steps for purification and concentration of the desired protein(s) such as partitioning by precipitation or chromatography, were studied. The residual risk of transmitting pathogens was assessed based on the results of these studies and the potential virus load in the plasma pool used to produce these products.
Summary:
For a pasteurized FVIII/vWF concentrate, the overall log reduction factors were ≥10.2 for HIV, ≥11.7 for BVDV, 10.2 for PRV, 7.8 for HAV, and 6.0 for CPV, as well as 6.4 and 7.9 for the 2 prion preparations, respectively. For a FVIII/vWF concentrate using solvent- detergent and dry heat, values were ≥12.5 for HIV, ≥13.1 for BVDV, ≥11.4 for PRV, ≥12.2 for HAV, and 6.7 for parvoviruses, as well as 4.0 and 4.9 for the 2 prion preparations. For a FIX concentrate using affinity chromatography and virus filtration, values were ≥10.2 for HIV, ≥12.6 for BVDV, ≥12.8 for WNV, ≥16.1 for PRV, ≥6.7 for HAV, and ≥14.8 for parvoviruses. For a FXIII concentrate using adsorption, chromatography, heat treatment, and virus filtration, values were ≥10.2 for HIV, ≥12.6 for BVDV, ≥12.8 for WNV, ≥16.1 for PRV, ≥6.7 for HAV, and ≥14.8 for parvoviruses, as well as 9.6 and 9.7 for the 2 prion preparations.
Conclusions:
Pathogen safety is based on the overall pathogen reduction factor considerably exceeding the amount of pathogen potentially entering the manufacturing pool. Validation studies verify that safety is attained for currently manufactured plasma-derived clotting factor concentrates.
