Improvement in health-related quality of life in patients with haemophilia B treated with nonacog beta pegol, a new extended half-life recombinant FIX product.

INTRODUCTION: Health-related quality of life (HRQoL) of individuals with haemophilia has greatly improved with the use of factor replacement and routine prophylaxis. AIM: To explore the HRQoL of individuals with haemophilia B treated with nonacog beta pegol, an extended half-life recombinant factor IX, in a single-blind, randomized multinational phase III pivotal trial (paradigm(™) 2) and its open-label extension (paradigm(™) 4). METHODS: In the pivotal trial, adolescents and adults with haemophilia B were allocated to 28-week on-demand treatment or randomized to 52 weeks of prophylaxis with 10 or 40 IU kg(-1) nonacog beta pegol administered every seven days. In the extension trial, patients could continue on the same treatment or switch to the alternate dosing regimen at any time. HRQoL was assessed with the HAEMO-QOL/HAEM-A-QOL age-specific questionnaires and the EQ-5D. RESULTS: In the pivotal trial, adults receiving 40 IU kg(-1) prophylaxis reported significant improvements in the 'HAEM-A-QOL Total' score (-6.4 ± 8.5, P = 0.017) and in 'Sport' (-15.3 ± 8.5, P = 0.020), 'Feeling' (-15.2 ± 18.3, P = 0.010) and 'Partnership' (-9.6 ± 15.5, P = 0.046) domain scores; no significant improvements were seen in the other arms. At the pivotal trial end, fewer patients reported problems in the EQ-5D 'Mobility' and 'Pain/Discomfort' dimensions, in particular those receiving prophylaxis. In the extension trial, adult patients switching from 10 to 40 IU kg(-1) prophylaxis showed significant improvements in 'HAEM-A-QOL Total' score (-12.5 ± 8.7, P = 0.016) and 'Physical health' domain (-23.1 ± 14.4, P = 0.016). CONCLUSION: Prophylactic treatment with nonacog beta pegol 40 IU kg(-1) once weekly leads to HRQoL benefits in individuals with haemophilia B; this might be related to fewer bleeding episodes and higher FIX activity levels.

UNBLOCK: an open-label, dose-finding, pharmacokinetic and safety study of bivalirudin in children with deep vein thrombosis.

BACKGROUND: Direct thrombin inhibitors offer potential advantages over unfractionated heparin but have been poorly studied in children. OBJECTIVES: To determine appropriate dosing of bivalirudin in children and adolescents and the relationship between activated partial thromboplastin time (APTT) and plasma bivalirudin concentration. PATIENTS/METHODS: The UNBLOCK (UtilizatioN of BivaLirudin On Clots in Kids) study was an open-label, single-arm, dose-finding, pharmacokinetic, safety and efficacy study of bivalirudin for the acute treatment of deep vein thrombosis (DVT) in children aged 6 months to 18 years. Drug initiation consisted of a bolus dose (0.125 mg kg(-1) ) followed by continuous infusion (0.125 mg kg h(-1) ). Dose adjustments were based on the APTT, targeting a range of 1.5-2.5 times each patient's baseline APTT. Safety was assessed by specific bleeding endpoints and efficacy by repeat imaging at 48-72 h and 25-35 days. RESULTS: Eighteen patients completed the study. Following the bolus dose and the initial infusion rate, most patients' APTT values were within the target range. The infusion rate bivalirudin correlated more closely with drug concentration than the APTT. At 48-72 h, nine (50%) patients had complete or partial thrombus resolution, increasing to 16 (89%) at 25-35 days. No major and one minor bleeding event occurred. CONCLUSIONS: Bivalirudin demonstrated reassuring safety and noteworthy efficacy in terms of early clot resolution in children and adolescents with DVT. Although a widely available and familiar monitoring tool, the APTT correlates poorly with plasma bivalirudin concentration, possibly limiting its utility in managing pediatric patients receiving bivalirudin for DVT.

Platelet function defects in adolescents with heavy menstrual bleeding.

Platelet function defects (PFD) are reported to occur frequently in adult women with heavy menstrual bleeding (HMB). Few studies on adolescent HMB report varying incidence rates (2-44%) for PFD. We reviewed our institutional experience in detecting and managing PFD in adolescent HMB. Postmenarchial girls and adolescents with HMB seen at our institution undergo a comprehensive bleeding disorder work-up by paediatric haematology and paediatric gynaecology providers. Whole blood platelet aggregometry (WBPA) is performed as a second tier test after excluding thrombocytopaenia, coagulation factor deficiencies and Von Willebrand disease (VWD). We retrospectively reviewed the medical records of adolescents with HMB seen between June 2009 and November 2010, as approved by the Institutional Review Board. Patient demographics, clinical features, laboratory results, therapy details and patient outcome information were analysed. Overall, 114 postmenarchial girls and adolescents with HMB were evaluated; 68 patients (59%) had WBPA study performed. Nineteen patients (28%) had at least one aggregation or secretion defect; 12 (18%) had two or more such defects. Treatment included hormonal therapy (13/19; 68%), antifibrinolytic agents (8/19; 42%) and intra-nasal DDAVP (3/19; 16%). Thirteen patients (81%) had improved outcome (median follow-up--15.6 months; range of 1-66 months). In this study, PFD were identified in nearly one-third of girls with HMB, with the majority of these having two or more defects as identified by WBPA. Further prospective studies are needed to better define the prevalence and address appropriate management of HMB and other bleeding complications of PFD in adolescents.

Low prevalence and assay discordance of "aspirin resistance" in children.

BACKGROUND: Although "aspirin resistance" (AR-inadequate platelet inhibition as suggested by in vitro testing of aspirin-treated patients) has been widely studied in adults and linked to increased risk of adverse outcomes, its prevalence and clinical significance are largely unknown in children. PROCEDURE: To determine AR prevalence in children and its relationship to assay methodology, we undertook a cross-sectional study of 44 children (1-17 years, 24 male) on aspirin for various indications and considered three published definitions of AR in adults: platelet aggregation >/=70% to 10 microM adenosine diphosphate and >/=20% to 0.5 mg/ml arachidonic acid (AA), normal PFA-100(R) closure time and elevated urinary 11-dehydro thromboxane B(2) (11dhTxB(2)) concentration. RESULTS: Six subjects exhibited AR according to at least one of the criteria (5 by PFA-100(R), 1 by aggregometry and 11dhTxB(2) criteria); nearly all subjects had low levels of 11dhTxB(2) compared with controls. Subjects studied prior to therapy showed pronounced changes in AR parameters after aspirin dosing (e.g., mean aggregation to AA decreased from 82% to 6%, P < 0.001), confirming an aspirin effect. Subjects with AR did not differ from aspirin responsive subjects in terms of age, race, platelet count, or aspirin dose, indication or therapy duration. There was minimal correlation between assays. CONCLUSIONS: In this initial prevalence study of a clinically diverse group of pediatric patients, frequencies of AR were assay-dependent; however, the prevalence of true AR is likely low in children (2.3%; 95% CI 0.1-10.7%), in agreement with adult studies. To better define the clinical relevance of AR in children, multicenter, prospective cohort studies are imperative.

Platelet hyperreactivity generalizes to multiple forms of stimulation.

BACKGROUND: Although platelet hyperreactivity constitutes an important cardiovascular risk factor, standardized methods for its measurement are lacking. We recently reported that aggregometry using a submaximal concentration of epinephrine identifies individuals with in vitro platelet hyperreactivity; this hyperreactivity was reproducible on multiple occasions over long periods of time. OBJECTIVE AND METHODS: To better understand this aberrant reactivity, we studied in a large group of subjects (n = 386) the relationship between healthy individuals' platelet reactivity to epinephrine and their platelet phenotype as measured by other functional assays. RESULTS: Subjects with hyperreactivity to epinephrine were more likely to exhibit hyperfunction in each major aspect of platelet activity, including adhesion (response to low-dose ristocetin; P < 0.001), activation (surface P-selectin expression and PAC-1 binding after stimulation; P

Long-term care policy and financing as a public or private matter in the United States.

Effective approaches to assure adequate resources, infrastructure, and broad societal support to address chronic care needs are volatile and potentially unpopular issues that can result in many losers (those getting far less than they want) and few winners (those who gain access to scarce societal resources for care). In the United States, debates on long-term care involve a complex set of issues and services that link health, social services (welfare), and economic policies that often pit public and private sector interests and values against one another. Yet long-term care policies fill a necessary function in society to clarify roles, expectations, and functions of public, non-profit, for profit, individual, and family sectors of a society. By assessing and developing policy proposals that include all long-term care system dimensions, a society can arrive at systematic, fair, and rational decisions. Limiting decisions to system financing aspects alone is likely to result in unforeseen or unintended effects in a long-term care system that stopgap "fixes" cannot resolve. Three underlying policy challenges are presented: the need for policymakers to consider whether the public sector is the first or last source of payment for long-term care; whether government is seen primarily as a risk or cost manager; and the extent to which choice is afforded to elders and family caregivers with regard to the types, settings, and amount of long-term care desired to complement family care.

Resident-centered care in assisted living.

Residents (n = 396) at 20 assisted living (AL) settings were interviewed as were program staff and administrators to understand how resident choice, getting needed care, and a sense of community were promoted or hindered. Residents reported relatively independent and autonomous lives, yet many experienced unmet health and long-term care needs and limited participation in meaningful activities or community life. Strong support was found for the hypothesis that AL program and site features influence resident experiences, particularly in regard to supporting independent lifestyles, minimizing avoidable care problems, and increasing community involvement.

Health care access, health promotion, and older women of color.

The U.S. population is becoming increasingly older due to steady increases in longevity, especially among women. Statistics show that older women, those 65 and over, outnumber older men by three to two. It is likely that as this trend in longevity continues, older women will continue to outnumber older men. The health care system must respond to these changes in the population by incorporating appropriate modifications into every aspect of the system, including financing mechanisms, service organization and delivery, consumer-centered care approaches, quality assurance mechanisms, and health promotion efforts. This article discusses the longevity advantage of women (particularly women of color) and its implications for economic insecurity, underinsurance of health care, health status, functional disability, access to care, and service use. The article concludes with a discussion of the challenges and opportunities presented as health care reform and the devolution of federal roles continue to unfold.

Health care access and advocacy for immigrant and other underserved elders.

Little is known about health care access and advocacy for elders of color, and even less is known about immigrant elders, whose growing number is the major reason that almost one of every three older persons in the U.S. by the year 2050 will be an elder of color. This paper explores a number of access barriers faced by underserved elders, including inequitable long-term care services and counterproductive "colorblind" approaches to caregiving. It also addresses barriers, such as problematic immigration policies, that present particular challenges to elderly immigrants. While available materials provide baseline information and help providers learn about underserved elders, real change in how target populations gain access to health and social services comes when providers make explicit efforts to improve the accessibility and quality of services.

Developing a quality assurance program in case management service settings.

Increasingly good quality case management is a necessary part of assuring appropriate and timely access to home care and other community-based services. This article focuses on how to develop a program to monitor the quality of case management services. It includes discussion of an approach for thinking about quality assurance, identifies objectives that are appropriate for quality assurance in case management settings, and provides suggestions for developing quality assurance activities in case management settings.

A descriptive framework for new hospital roles in geriatric care.

Changes in demographics and in the operating environments of acute care hospitals have resulted in the development of new geriatric service products. Presented in this article is a framework for describing the variety of new services in terms of sponsor goals and core activities. Five broad types of geriatric service developments are described: geriatric medical care, post-acute care, transition management, chronic care, and information services. Assessing the implications of new services for the organizational functioning of hospitals is discussed, followed by an examination of the potential contributions of new geriatric services to the quality and accessibility of geriatric care.