Impact of the 340B Pharmacy Program on Services and Supports for Persons Served by Hemophilia Treatment Centers in the United States.

Purpose Hemophilia Treatment Centers (HTCs) provide integrated and comprehensive services to individuals affected with rare bleeding disorders, such as hemophilia and Von Willebrand disease. Through the 340 Drug Pricing Program, HTCs may use pharmacy income to support clinical staff and patient services. The objective of this study was to describe the impact of the 340B program funding on services and support provided by HTCs to persons affected by rare bleeding disorders. Description Federally designated comprehensive HTCs with established 340B programs were invited to participate in a mailed survey in 2014. Participants were requested to report on 340B program-funded staff and services in the calendar year 2013. Assessment The 31 of 37 HTCs responding served over 10,000 individuals, or one-third of the national HTC patient population. The majority of responding HTCs reported that 340B program income supported over 90% of staff such as nurses, social workers, and physical therapists. Conclusion The results from this survey of 31 centers with established programs demonstrates the HTCs' reliance on 340B program support for vital comprehensive services, that are otherwise non-reimbursable, and highlights the importance of the 340B program in sustaining the high quality of care and in increasing access for a geographically dispersed, medically vulnerable population.

Appendix G: Vitrification of Blastocysts Using VitriBlastTM and ThermoBlastTM: Nidacon.

This appendix describes the vitrification of blastocysts using VitriBlast™ (VBK) and ThermoBlast™ (TBK) from Nidacon, Mölndal, Sweden. The technique used and the reason for not including DMSO in the medium at the production stage, but including it separately in the kit, and the importance of collapsing the blastocyst prior to vitrification will be explained and described.

A community-based partnership to promote information infrastructure for bleeding disorders.

Specialists in rare disorders often face challenges in collecting surveillance and research data. As movement toward more fully realizing the potential of electronic health information gains momentum, practitioners who treat individuals with rare disorders are in need of public-private support to tap into the advantages offered by the developing electronic information technologies and the interoperability standards promulgated by the USDHHS. The not-for-profit American Thrombosis and Hemostasis Network (ATHN) was created in 2006 to provide stewardship of a secure, national, web-based database to support federally funded hemophilia treatment centers (HTCs) across the country. In pursuit of its mission to support clinical outcomes analysis, research, advocacy, and public health reporting in the hemostasis and thrombosis community, ATHN has established a spectrum of community-based partnerships. This paper describes the process and public health benefits of creating formal relationships with 127 of the 134 HTCs from 12 regional networks across the U.S., government agencies such as the CDC, Health Resources and Services Administration, and NIH; consumer-based organizations; and industry leaders. This community-based partnership model can be applied to other rare disorders communities with high economic and public health impact.

Self-reported barriers to hemophilia care in people with factor VIII deficiency.

BACKGROUND: In 1975, a national network of hemophilia treatment centers (HTCs) was created to increase access to healthcare services for individuals with hemophilia. Studies demonstrate that care in HTCs improves outcomes and reduces costs. PURPOSE: The objective of the study was to assess the association of demographic, insurance, and clinical characteristics with self-reported barriers to HTC utilization. METHODS: Data were collected from six HTCs from 2005 through 2007. Adult participants and parents of children aged <18 years were interviewed. Barriers were assessed by asking whether it was difficult to obtain care in the past 12 months. Chi-square test and logistic regression were used to assess factors associated with self-reported barriers to care. All analyses were performed in 2010-2011. RESULTS: Data for 327 participants (50% adult, 64% severe hemophilia) were analyzed in 2010-2011. Most participants/parents did not report barriers to HTC utilization. However, 46 participants/parents (14%) reported one to six barriers, and 23 reported one barrier. Most frequently reported barriers were "distance to the clinic" for children (44%) and "insurance coverage" for adults (40%). Factors significantly associated with self-reported barriers were: lower income (<$20,000; OR=3.11, 95% CI=1.14-8.45), difficulty finding insurance or obtaining full-year coverage (OR=5.71, 95% CI=2.63-12.41), and decreased state Medicaid coverage for low-income, non-elderly individuals (OR=0.93, 95% CI=0.89-0.98). CONCLUSIONS: This study indicates that, although few people with hemophilia have barriers to care at HTCs, those with lower income, difficulty finding or maintaining adequate insurance coverage, or living in states with lower Medicaid generosity are more likely to report barriers. Identifying and resolving such barriers may improve care access and patient-reported outcomes.

High school completion rates among men with hemophilia.

BACKGROUND: The benefits of a high school diploma are well documented. Studies indicate that people with hemophilia have lower than average academic achievement, particularly if they have >12 bleeding episodes annually. PURPOSE: This study compares the high school graduation rate of men with hemophilia to that of the U.S. population of men. METHODS: Data were obtained from the Universal Data Collection Program, a surveillance project conducted by approximately 130 hemophilia treatment centers in the nation. Data from 7842 men aged >or=18 years were evaluated to determine high school graduation status and were analyzed by race/ethnicity and severity of hemophilia. These data were collected between 1998 and 2008, and analysis was conducted in 2009. RESULTS: Men with hemophilia A had higher or similar high school graduation rates across all racial/ethnic groups and all levels of hemophilia severity, compared with U.S. men of the same age. Graduation rates for black and Hispanic men with hemophilia B were higher or similar to rates of U.S. men, but rates for whites were lower, especially among those with moderate and mild disease. However, when graduation rates were controlled for areas where Amish populations reside, differences in graduation rates for whites disappeared. CONCLUSIONS: In this study, participants obtained hemophilia care at comprehensive hemophilia treatment centers. This multidisciplinary, family-centered care emphasizes prevention of complications, encourages medically supervised disease management, and facilitates psychosocial development. The care aims to maximize the affected child's participation in school. This care approach may partially explain the higher-than-expected high school graduation rates among the study population, which is affected by a rare, chronic, and potentially debilitating disorder.

A model for a regional system of care to promote the health and well-being of people with rare chronic genetic disorders.

People with rare, inherited chronic health conditions, such as hemophilia, face added physical, social, emotional, and fiscal challenges beyond those that are common to more prevalent chronic conditions. In 1975, a partnership among clinicians, consumers, and government agencies created a nationwide regional health delivery system that increased access to clinical care, prevention, and research, thereby improving health outcomes for people with hemophilia in the United States. Today, more than 130 Comprehensive Hemophilia Diagnostic and Treatment Centers in 12 regions serve 70%-80% of the nation's hemophilia patients. Health care leaders and advocates for other rare, expensive, chronic disorders may find that regionalization improves survival and reduces disability among affected populations. However, diverse and stable resources are needed to sustain such a model in our profit-oriented US health care arena.

Cardiac troponin T content in heart and skeletal muscle and in blood samples from ApoE/LDL receptor double knockout mice.

BACKGROUND: The isolated perfused mouse heart is a useful experimental model, and cardiac troponin T (cTnT) in coronary effluent may be a sensitive marker of myocardial damage. In recent years, the apolipoprotein E/low-density lipoprotein receptor double knockout (apoE/LDLr KO) mice have become valuable tools in atherosclerosis research. The aim of the study was to validate measurements of cTnT in heart, skeletal muscle, and serum of apoE/LDLr KO mice. METHODS: Wild-type C57BL/6J mice were fed with standard diet, and apoE/LDLr KO mice were fed an atherogenic diet. Blood was sampled from the jugular vein or the thoracic cavity. Heart and femoral skeletal muscle were sampled and homogenized. cTnT was measured with the third-generation cTnT assay (Troponin T STAT) on Elecsys 2010 immunoassay analyser (Roche Diagnostics). RESULTS: Median serum cTnT in samples from the thoracic cavity of C57BL/6J mice was about 20-90 times higher, and from ApoE/LDLr KO mice about 30 times higher than serum cTnT in samples from the external jugular vein. There was no difference in cTnT content (microg cTnT/g heart muscle) in hearts from C57BL/6J and apoE/LDLr KO mice. The median cTnT content in skeletal muscle was less than 0.1% of the cTnT content in heart muscle. CONCLUSION: There is no difference in cTnT content of heart muscle comparing C57BL/6J and ApoE/LDLr KO mice, which have larger hearts. Sampling from the thoracic cavity causes unacceptably high cTnT levels. Serum cTnT in samples from the jugular vein is only slightly elevated. Elevated baseline levels of cTnT in mice are not caused by troponin T from skeletal muscle.

Effects on skeletal muscle of intravenous glutamine supplementation to ICU patients.

OBJECTIVE: To evaluate the effect of four doses of intravenous glutamine supplementation on skeletal muscle metabolism. DESIGN: A prospective, blinded, randomized study. SETTING: The general Intensive Care Unit (ICU) of a university hospital. PATIENTS: ICU patients with multiple organ failure (n=40), who were expected to stay in the unit for more than five days. INTERVENTION: Patients received 0, 0.28, 0.57 or 0.86 g of glutamine per kg bodyweight per day intravenously for five days as part of an isocaloric, isonitrogenous and isovolumetric diet. RESULTS: Plasma glutamine concentration responded to glutamine supplementation with normalization of plasma levels in a dose-dependent way, while free muscle glutamine concentration, as well as muscle protein synthesis and muscle protein content, did not change significantly. CONCLUSION: Intravenous glutamine supplementation to ICU patients for a period of five days resulted in normalization of plasma glutamine concentrations in a dose-dependent way whereas muscle glutamine concentrations were unaffected.

Joint range-of-motion limitations among young males with hemophilia: prevalence and risk factors.

Chronic joint disease from repeated bleeding into joints is a serious complication of hemophilia. To measure the extent of and to identify risk factors for deviations from normal in joint range of motion (ROM), we used cross-sectional data collected from 4343 males with hemophilia aged 2 to 19 years who received care at 136 US hemophilia treatment centers (HTCs). Factors examined included age, race/ethnicity, family history, insurance status, age at diagnosis and first HTC visit, frequency of HTC visits, hemophilia type, bleeding frequency, prophylaxis use, inhibitor status, body mass index (BMI), and recent orthopedic procedures. Trained personnel using a standard protocol obtained ROM measurements on 10 joints (hips, knees, shoulders, elbows, and ankles). Analyses used multiple linear regression to model overall ROM limitation separately by disease severity. For persons in all severity groups, joint ROM limitation was positively associated with older age, nonwhite race, and increased BMI. For those with severe disease, ROM limitation was also positively associated with number of bleeds and was greater for those with inhibitors or recent orthopedic procedures. We conclude that ROM limitations begin at an early age, especially for those with severe and moderate disease, and that BMI is an important, potentially modifiable risk factor.

Free amino acids in plasma, red blood cells, polymorphonuclear leukocytes, and muscle in normal and uraemic children.

BACKGROUND: The aims of this study were to investigate free amino acid (AA) concentrations in plasma, red blood cells (RBC), polymorphonuclear granulocytes (PMN), and muscle, sampled at the same time, in normal and uraemic children. METHODS: Twelve apparently well-nourished chronically uraemic children (five females) aged a mean of 9.4+/-4.8 (range 1.7--17.7) years and 13 age-matched normal children were studied. Venous blood and muscle samples for AA analyses were taken simultaneously after an overnight fast. RESULTS: The intracellular AA patterns in the three cellular compartments were qualitatively similar, but the absolute intracellular concentrations were higher in muscle than in PMN, which had higher values than in RBC. The AA patterns in plasma, RBC, PMN, and muscle in the uraemic children have many similarities; typical features being low branched-chain AA (BCAA), tyrosine, and serine concentrations and variably high concentrations of some non-essential AA. Among the individual AA, there were only few correlations between their concentrations in the three cell compartments. CONCLUSIONS: The lack of correlation between the concentrations in RBC, PMN, and muscle for most of the AA indicates that there is no close association in the same subject between individual free AA concentrations in various types of cells, presumably because of differences in metabolism and function. Consequently, one should be cautious in assuming that AA concentrations, determined in RBC or PMN, reflect the concentrations in muscle cells. Therefore, these preliminary observations do not support the hypothesis that RBC and PMN AA analysis can be considered as a suitable alternative to muscle AA determination.

Predictors of retention among HIV/hemophilia health care professionals.

Health care professionals working with individuals with chronic medical illness, especially those infected with the Human Immunodeficiency Virus (HIV), may be at risk for burnout and departure due to various job stresses such as the death of patients and social stigma. Factors that prevent burnout and employee attrition are seldom studied. Two hundred thirteen staff (doctors, nurses and mental health workers) at a representative sample of Hemophilia Treatment Centers (HTC) completed instruments to measure Burnout (Maslach Burnout Inventory), and perceived job stresses and satisfaction (job tasks, interactions with colleagues and patient care). The staff were surveyed again after two years and their job status determined after 4 years. After 4 years, 35% of the staff had left the field of Hemophilia/HIV care. Univariate tests found that retention was significantly associated with initial job satisfaction, being married and low levels of stress with colleagues. Burnout, as measured by the Maslach Burnout Inventory, at baseline, was unrelated to job retention over 4 years. An adjusted multiple logistic regression of all significant variables found that colleague support was most related to retention (OR=2.8, CI=1.49,5.1). We conclude that attrition of highly trained staff is a significant issue for patients and HTCs. These data suggest the important role that a well-functioning team can have in buffering the inevitable stresses associated with HIV care. Mental Health professionals have considerable expertise in addressing these issues.