Ann D. Forsberg

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 nations 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.

Hemophiliac immunodeficiency: Influence of exposure to factor VIII concentrate, LAV/HTLV-III, and herpesviruses

The relationship between hemophiliac immunodeficiency and exposures to factor VIII concentrate, LAV/HTLV-III retrovirus, and infection with Epstein-Barr virus and cytomegalovirus was examined. Exposure to factor VIII concentrate was significantly correlated with decreased percentages of T helper/inducer cells, decreased T helper/suppressor cell ratios, and decreased proliferative responses to plant mitogens. LAV/HTLV-III seropositivity was the primary predictor of increased percentages of HLA-DR-bearing mononuclear cells and decreased proliferative responses to pokeweed mitogen. Epstein-Barr virus and cytomegalovirus infections acted in a synergistic manner with LAV/HTLV-III to produce immunoregulatory defects. Increased percentages of T suppressor cells and decreased delayed cutaneous hypersensitivity skin test responses were observed in LAV/HTLV-III seropositive hemophiliacs infected with Epstein-Barr or cytomegalovirus. We conclude that hemophiliacs receiving commercial factor VIII concentrate experience several stepwise incremental insults to the immune system: alloantigens in factor VIII concentrate, LAV/HTLV-III infections, and herpesvirus infections.

Platelet activation and mitral valve prolapse

Mitra1 valve prolapse (MVP) is a predisposing factor for cerebral ischemia, especially in young adults. Cerebral embolization of intracardiac thrombi is the probable mechanism in many cases. Platelets play a key role in the development of thrombi. We found that platelet factor 4, a marker protein of platelet activation, was elevated in 12 of 33 MVP patients (36%) without a history of stroke. This finding indicates that platelets are frequently activated in asymptomatic MVP patients and may allow identification of a subgroup of MVP patients with activated platelets who are at increased risk for emboli.

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.

Sexual Behavior Change Among Human Immunodeficiency Virus-Infected Adolescents With Hemophilia

Purpose. To determine the factors associated with the adoption or maintenance of consistent safer sexual behaviors among human immunodeficiency virus-positive adolescents and young adults with hemophilia. Methods. One hundred eleven adolescents at 10 hemophilia care sites participated in an intervention program designed to increase safer sexual behaviors (abstinence, condom use, or nonpenetrative behavior). The theory-based intervention spanned 1 year. Adolescents attended individual sessions, small group activities, and an intensive group retreat. Results. Patients who maintained or improved safer sexual behaviors were compared with those who relapsed or did not improve. Logistic regression analyses found that improvement and maintenance of safer sexual behavior were significantly associated with perceived peer support for outercourse (odds ratio [OR]: 5.47; confidence interval [CI]: 1.4–20.8), perceived peer support for abstinence (OR: 5.08; CI: 1.2–20.1), and decreased general emotional distress (OR: 4.65; CI: 1.04–20.6). Perceived health status and previous sexual behavior were unrelated to change in safer sexual behavior. Conclusions. These longitudinal data indicate that improvement and maintenance of safer sexual behavior among adolescents during an intervention is strongly associated with perceptions of peer support for safer sex and lesser degrees of emotional distress. Programs for human immunodeficiency virus-infected adolescents may require developmentally appropriate social and psychological approaches to impact peer norms and emotional well-being.

Delayed cutaneous hypersensitivity reactions in hemophiliac subjects treated with factor concentrate

Cutaneous delayed-type hypersensitivity was measured using the Multitest CMI in a group of 97 patients with hemophilia who were enrolled in the New England Area Comprehensive Clinic. The Multitest CMI is a multipuncture system that dispenses seven test antigens including tetanus, diphtheria, Streptococcus, Proteus, tuberculin, Candida, and Trichophyton, and a glycerine-saline control solution. A reaction was considered positive if there was induration of at least 2 mm. If the results of one or more skin tests were positive, the patient was considered to have a positive reaction. Of the 83 patients with severe or moderate hemophilia A, 51 percent had negative reactions. No study control subject and only one patient with hemophilia B had a negative reaction. The 42 patients with hemophilia A who showed no reaction used a significantly greater amount of factor VIII concentrate than did those with hemophilia A who responded positively (1,960 units/kg per year versus 1,360 units/kg per year; p less than 0.025) and included a higher percent of patients who had seropositive results for human T lymphotropic virus type III (HTLV-III) antibody (89 percent versus 69 percent, p less than 0.025).

Isolation of human immunodeficiency virus from hemophiliacs: Correlation with clinical symptoms and immunologic abnormalities

As part of a prospective study of human immunodeficiency virus (HIV) infection in hemophilia, peripheral blood mononuclear cells (PBMs) from 72 individuals without acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) were cultured for virus. HIV was isolated from PBMs from 16 (24%) of 66 patients with hemophilia who were seropositive for HIV and from none of six seronegative patients. Cells from five of six patients from which HIV was isolated were again successfully cultured for virus 3 to 12 months later. HIV core P24 antigen was detected in serum from seven of 15 patients with HIV-positive cells and from eight of 50 with HIV-negative cells. Patients with hemophilia with isolation-positive cells had significantly fewer T helper cells and significantly lower T helper/T suppressor ratios, pokeweed mitogen responsiveness, and total platelet counts than did those whose cells did not yield HIV on cultivation. HIV neutralizing antibody titers did not differ between hemophiliacs with or without HIV-positive PBMs. Three of the 16 patients with virus-positive cells developed AIDS, and two ARC, within 18 months of the study, compared with three of 50 seropositive hemophiliacs whose cells did not yield virus, who developed ARC during the same period. The significant decrease in the number of T helper cells, decreased platelet counts, and higher rate of progression to AIDS in the group with HIV isolation may reflect a heavier virus load, indicating that the ability to culture HIV may be an early marker of more significant disease.

Promoting safer sex among HIV-positive youth with haemophilia: theory, intervention, and outcome

Summary.  The goal of the project was to develop and evaluate theory‐based interventions designed to change sexual behaviour and promote safer sex practices of HIV seropositive young men and adolescents with haemophilia to prevent transmission to sexual partners and offspring. Safer sex was defined as abstinence, consistent condom use, or ‘outercourse’ (intimate, non‐intercourse sexual behaviour). This project utilized the Transtheoretical Model developed by Prochaska and DiClemente, which describes behaviour change as an incremental, stage‐based process. The 1‐year intervention protocol consisted of two individual sessions and two peer‐centred activities. One hundred and four adolescents, residing in 22 states, participated. Pre‐ and post‐intervention evaluations were conducted to measure stage progression for participants. The number who were in the action or maintenance stage of change for safer sex was significantly greater at post‐test than at pre‐test (79 vs. 62%, P < 0.0001). Participants also reported an increased use of outercourse. In addition, significant increases in self‐efficacy and knowledge regarding safer sex were demonstrated. Following these stage‐based interventions, participants were significantly more likely to be engaging in safer sex behaviours than they were previously. These intervention activities can be adapted for use with other adolescent populations and for other behaviour change goals in adolescents with haemophilia.

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 childs 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 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.