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Introduction: Intracranial hemorrhage (ICH), a serious complication in persons with hemophilia A (PWHA), causes high rates of mortality and morbidity. Identified ICH risk factors from patient data spanning 1998– 2008 require reassessment in light of changes in the current treatment landscape. Aim and methods: PWHA identified in the ATHNdataset were evaluated retrospectively to assess incidence of ICH and determine the association between ICH risk and key characteristics using time-to-event analyses (Cox proportional-hazards models, survival curves, and sensitivity analyses). Results: Over a median follow-up time of 10.7 patient-years, 135 of 7837 PWHA over 2 years of age in the ATHNdataset (1.7%) experienced an ICH. Stratification by prophylaxis status and inhibitor status resulted in an incidence rate (IR) ratio (IRR) (IR+/IR−) of 0.63 (95% confidence interval [CI], 0.43– 0.94; P=0.020) and 1.76 (95% CI, 0.97– 3.20; P=0.059), respectively. Characteristics associated with greater risk of developing ICH include being aged 2– 12 years; being covered by Medicaid; having had HIV, hepatitis C, or hypertension; and never having received factor VIII or prophylactic treatment. In multivariable analysis with interaction, the estimated hazard ratio for PWHA never receiving prophylaxis was 7.67 (95% CI, 2.24– 26.30), which shrunk to 2.03 (95% CI, 1.30– 9.12) in bootstrapping analysis and 3.09 in the highest-penalty ridge-regression analysis but was still significant. Inhibitor status was found not to be statistically associated with ICH in all analyses. Conclusion: These results align with previous studies demonstrating that prophylaxis confers a protective effect against ICH. Previously, inhibitor positivity had been shown to increase risk for ICH; however, this study did not corroborate those findings. [ABSTRACT FROM AUTHOR]

Introduction: Females with haemophilia A (HA [FHAs]) and HA carriers (HACs) have an increased risk of bleeding and complications compared to the general population. Aim: To examine the characteristics, billed annualised bleed rates (ABRb), costs and healthcare resource utilisation for males with HA (MHAs), FHAs and HACs in the United States. Methods: Data were extracted from the IBM® MarketScan® Research Databases (Commercial and Medicaid) for claims during the index period (July 2016 to September 2018) and analysed across MHAs, FHAs and HACs. Results: Dual diagnosis females (DDFs; both HA and HAC claims) were grouped as a separate cohort. MHAs were generally younger than females (all cohorts) by up to 19 years (Commercial) and 23 years (Medicaid). ABRb >0 was more frequent in females. Factor VIII claims were higher for MHAs versus female cohorts. Joint‐related health issues were reported for 24.4 and 25.6% (Commercial) and 29.3 and 26.6% (Medicaid) of MHAs and FHAs, respectively; lower rates were reported in the other two cohorts. Heavy menstrual bleeding claims occurred for approximately a fifth (Commercial) to a quarter (Medicaid) of female cohorts. All‐cause emergency department and inpatient visits in FHAs and DDFs were similar to, or more frequent than, those in MHAs; bleed‐related inpatient visits were infrequent. In MHAs (Commercial), mean all‐cause total costs ($214,083) were higher than in FHAs ($40,388), HACs ($15,647) and DDFs ($28,320) with similar trends for Medicaid patients. Conclusions: FHAs and HACs may be undermanaged and undertreated. Further research is needed to fully understand these cohorts' bleeding rates, long‐term complications and costs. [ABSTRACT FROM AUTHOR]

Introduction: People with haemophilia rely on specialists for their care, yet the specific dosing regimens of treatments prescribed by these specialists have not been widely studied. Aim: The objective of this study is to describe trends in clinician prescribing practices for the management of haemophilia in the United States (US). Methods: We administered surveys to members of the Hemostasis and Thrombosis Research Society via paper surveys at its in‐person annual symposia in 1999 and 2015, and an online survey in 2021. The surveys collected information on haemophilia treatments including factor dosing, inhibitor therapy and gene therapy. Results: Clinicians treating haemophilia for more than 50% of their practice time have increased from 37.5% of respondents in 1999 to 46.3% in 2021. Clinicians prescribing factor concentrates at >40 units/kg for routine bleeding events increased from 0% in 1999 to 29.3% in 2021 in haemophilia A (HA) and from 22.5% to 87.8% in haemophilia B (HB). In 2021, the clinicians reported prescribing emicizumab to treat HA patients (>89.5% paediatric, >85.7% adult) with or without inhibitors at least some of the time. Approximately 78.0% of respondents reported that they expected to recommend gene therapy at least some of time. Conclusion: These data indicate changing trends in prescribing practices among US haemophilia specialists during the past 22 years. Preference for high doses of factor (>40 units/kg) has increased during this period. Emicizumab prophylaxis has been prescribed for patients with and without HA inhibitors. Clinicians expect gene therapy to have value for some haemophilia patients. [ABSTRACT FROM AUTHOR]

Background: Patients with obscure gastrointestinal bleeding undergo small bowel capsule endoscopy (SBCE), but often return for recurrent bleeding or anemia. The RHEMITT score evaluates patients based on 7 variables (heart failure, chronic kidney disease, Saurin P1/P2 lesions, major bleeding, incomplete SBCE, smoking status, and endoscopic treatment) and seeks to predict the risk of rebleeding. Aims: This study aims to perform an external validation of the RHEMITT score in the United States. Methods: SBCEs performed to evaluate anemia or GI bleeding from a tertiary-care center's PillCam database between 1/22/2018 and 7/21/2020 were reviewed. Variables based on the RHEMITT score were collected. The primary outcome was rebleeding, defined as (1) melena or hematochezia or (2) hemoglobin drop of 2 g/dL. Patient were categorized into low, intermediate, and high-risk categories based on RHEMITT score. The accuracy of the RHEMITT score for predicting rebleeding was assessed. Results: A total of 361 SBCEs were included in the study. Age, indication for SBCE, endoscopic treatment, antiplatelet use, cirrhosis, heart failure, chronic kidney disease, and major bleeding were significantly associated with risk of rebleed (p < 0.05). Each increasing risk category for the RHEMITT score predicted increased probability of this study's primary outcome, rebleeding (p < 0.001). There was a significant association between RHEMITT risk category and rebleeding-free survival (log-rank p < 0.001). An area under the receiver operating characteristic curve for the RHEMITT score was 0.790 (p < 0.001). Conclusion: Our findings validate the RHEMITT score and confirm acceptable performance for predicting rebleeding at a tertiary referral center in the United States. [ABSTRACT FROM AUTHOR]

Abstract: Response to analgesic therapy is influenced by several factors including genetics and drug-drug interactions. Pharmacogenetic (PGx) variants in the CYP2D6 gene modify response to opioids by altering drug metabolism. We sought to determine the potential impact of PGx testing on the care of Veterans with noncancer pain prescribed opioids metabolized by CYP2D6 (codeine, hydrocodone, or tramadol). A retrospective analysis was performed within the Veterans Health Administration evaluating prescription records for pain medications metabolized by CYP2D6 and interacting drugs from 2012 to 2017. Among 2,436,654 Veterans Health Administration pharmacy users with at least 1 opioid prescription, 34% met the definition of chronic use (longer than 90 days with more than 10 prescriptions or 120 days-supply). Opioids were commonly coprescribed with antidepressants interacting with CYP2D6 (28%). An estimated 21.6% (n = 526,905) of these patients are at an elevated risk of an undesirable response to their opioid medication based on predicted phenotypes and drug-drug interactions: 3.5% are predicted CYP2D6 ultrarapid metabolizers and at increased risk for toxicity, 5.4% are poor metabolizers at higher risk for nonresponse, and 12.8% are normal or intermediate metabolizers coprescribed a CYP2D6 inhibitor leading to phenoconversion into poor metabolizer. Despite the high rate of coprescription of opioids and interacting drugs, CYP2D6 testing was infrequent in the sample (0.02%), and chart review suggests that test results were used to optimize antidepressant treatments rather than pain medications. Using PGx testing combined with consideration of phenoconversion may allow for an enhanced precision medicine approach to pain management in Veterans. [ABSTRACT FROM AUTHOR]

Introduction: Current in‐hospital burden and healthcare utilization patterns for persons with haemophilia (PWH) A and B, including both children (ages < 18 years) and adults (ages ≥ 18 years), in the United States (US) are lacking. Aim: To evaluate healthcare utilization, the prevalence of comorbidities, and mortality in hospitalized paediatric and adult PWH using a contemporary nationally representative cohort. Methods: Hospitalizations of PWH either as the primary reason for admission (principal diagnosis) or one of all listed diagnoses were identified using ICD‐10 codes from the 2017 Nationwide Inpatient Sample (NIS), the largest publicly available all‐payer inpatient discharge database in the US. Sampling weights were applied to generate nationally representative estimates. Results: The contemporary cohort included 10,555 hospitalizations (paediatrics, 18.3%; adults, 81.7%) among PWH as one‐of‐all listed diagnoses (n = 1465 as principal diagnosis). Median age (interquartile range) was 46 (24–66) years overall; adults, 54 (35–70) years and paediatric, 4 (1–11). The most common comorbidities in adults were hypertension (33.4%), hyperlipidaemia (23.6%), and diabetes (21.1%). In children, hemarthrosis (11.4%), contusions (9.6%), and central line infections (9.3%) were the most common. The overall mortality rate was 2.3%. Median hospital charges per haemophilia admission were $52,616 ($24,303–$135,814) compared to $26,841 ($12,969–$54,568) for all‐cause admissions in NIS. Conclusion: Bleeding and catheter‐related infections are the significant reasons for paediatric haemophilia admissions. Adult haemophilia admissions tend to be associated with age‐related comorbidities. Costs for haemophilia‐related hospitalizations are higher than the national average for all‐cause hospitalizations. [ABSTRACT FROM AUTHOR]

Fear of medical liability is a major driver for broad administration of perioperative prophylactic anticoagulation, despite the persistently low rates of clinically symptomatic venous thromboembolism events (VTE) postoperatively. This study was undertaken to evaluate the medicolegal landscape of perioperative VTE and its pharmaceutical prophylaxis. The Westlaw legal database was retrospectively searched for verdicts in medical professional liability cases in the United States between 2009 and 2020. One search strategy focused on perioperative VTE, and a second on claims of hemorrhagic complications in patients receiving perioperative anticoagulation. The search for VTE revealed 129 cases, and the search for hemorrhagic complications identified 24 cases. Almost half of the VTE cases were brought following orthopedic surgery (49%), and 29% following general surgery. The most common claims were failure to diagnose and treat during hospital stay or after discharge (74%), and failure to prescribe/administer anticoagulation (46%). Verdict for the health care professional (i.e., the defendant) was reached in 75% of cases. The median payout for patient verdicts was 1,213,644 USD (interquartile range 1,014,100; 150,000-7,700,000). Of hemorrhagic complication cases, 42% occurred in patients receiving VTE prophylaxis. In these cases, 82% resulted in a defendant verdict. Reasons for in-court medical professional liability claims involving perioperative VTE were mainly failure to diagnose VTE and rescue patients from complications postoperatively. The high rate of defendant verdicts supports the notion that decisions on VTE prophylaxis should not be influenced by fear of liability. [ABSTRACT FROM AUTHOR]

Introduction: Females may have haemophilia with the same factor VIII (FVIII) or factor IX (FIX) levels as affected males. Characterization of females with haemophilia would be useful for health care planning to meet their unique needs. Federally‐funded haemophilia treatment centres (HTCs) in the United States contribute data on all individuals with bleeding disorders receiving care to the Population Profile (HTC PP) component of the Community Counts Public Health Surveillance of Bleeding Disorders project. Aims: To estimate the number of females with haemophilia receiving care at HTCs in the United States and compare their characteristics with those of males with haemophilia. Methods: HTC PP data collected on people receiving care at an HTC from January 2012 through September 2020 with haemophilia A and B were evaluated by sex for demographic and clinical characteristics. Results: A factor level < 40% was reported for 23,196 males (97.8%) and 1667 females (47.6%) attending HTCs; 51 (.48%) severe, 79 (1.4%) moderate, and 1537 (17.9%) mild haemophilia patients were female. Females were older, more often White, and less often non‐Hispanic than males. Females were less likely to have history of HIV or HCV infection, even among those with severe disease, but twice as likely to have infection status unknown. Females with mild haemophilia were more often uninsured than males. Conclusions: Females with severe or moderate haemophilia are uncommon, even in specialized care centres; however, almost one in five patients with mild haemophilia was female, indicating needs for specialized care based on factor level and history for affected females. [ABSTRACT FROM AUTHOR]

Introduction: High collision-risk physical activity can increase bleeding risk in people with hemophilia A, as can increasing the time between factor VIII (FVIII) administration and physical activity. FVIII prophylaxis may be tailored to planned activities to prevent activity-related bleeding. Aim: To explore the relationship between physical activity levels, FVIII infusion timing, and occurrence of bleeding in patients with severe/moderately severe hemophilia A without FVIII inhibitors receiving antihemophilic factor (recombinant) (rAHF; ADVATE®; Baxalta US Inc., a Takeda company, Lexington, MA, USA). Methods: SPACE was a 6-month, prospective, multicenter, observational outcomes study (NCT02190149). Enrolled patients received an eDiary application and a wearable activity tracker, which recorded physical activity, rAHF infusion, and occurrence of bleeding. Physical activity risks were ranked using National Hemophilia Foundation criteria. Results: Fifty-four patients aged 11– 58 years (n = 47 prophylaxis, n = 7 on-demand) were included in the analysis. Patients had a mean (SD) 8.14 (10.94) annualized bleeding rate, and recorded 4980 intervals between an rAHF infusion and physical activity; 1759 (35.3%) of these intervals were ≤ 24 hours. Analysis of recorded eDiary data showed that the risk of activity-related bleeding did not significantly increase with time between last infusion and activity, but did increase with higher-risk physical activities. Analysis of activity tracker recorded data showed that the risk of bleeding reported by patients as spontaneous increased with prolonging time (≤ 24 to > 24 hours) from last infusion to physical activity start (odds ratio 2.65, p < 0.05). Joint health data collected at baseline were not included in the regression analysis because of small sample size; therefore the study could not assess whether patients with more joint disease at baseline were at higher risk of injury-related and reported spontaneous occurrence of bleeding. Conclusion: These results show that activities with a high risk of collision lead to an increased risk of bleeding. Further investigation is warranted to explore potential benefits of FVIII infusion timing to reduce the risks of activity-related occurrence of bleeding. [ABSTRACT FROM AUTHOR]

Rare, chronic diseases such as hemophilia and other congenital coagulation disorders require coordinated delivery of services for optimal outcomes. Hemophilia Treatment Centers (HTCs) are specialized, multidisciplinary health-care centers providing team-based care to meet the physical, psychosocial, and emotional needs of people with hemophilia (PWH) and may serve as a model for other rare coagulation disorders. Health-care purchasers, as well as the general medical community, may not appreciate the breadth and quality of services provided by HTCs. They exemplify the acculturalization and actualization of integrated care by providing comprehensive diagnostic and treatment services that reduce morbidity, mortality, avoidable emergency room visits, hospitalizations, and overall costs, while promoting a longer lifespan and improved patient functioning and outcomes. This is accomplished by a team-based approach relying upon a shared decision-making model to effectively prevent complications and manage symptoms in PWH, who are dependent on high-cost treatments. This article provides a concise yet comprehensive description of the core components of an HTC and the regional and national networks in the United States, which together achieve their incomparable value for all stakeholders. [ABSTRACT FROM AUTHOR]

Introduction: In May of 2020, the U.S. Veterans Health Administration (VHA) and Department of Defense (DoD) approved a new joint clinical practice guideline for assessing and managing patients who have overweight and obesity. This guideline is intended to give healthcare teams a framework by which to screen, evaluate, treat, and manage the individual needs and preferences of VA and DoD patients who may have either of these conditions. It can be accessed at https://www.healthquality.va.gov/guidelines/CD/obesity/.Materials and Methods: In January of 2019, the VA/DoD Evidence-Based Practice Work Group convened a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines.Results: The guideline panel developed 12 key questions, systematically searched and evaluated the literature, created a 1-page algorithm, and advanced 18 recommendations using the Grading of Recommendations Assessment, Development, and Evaluation system.Conclusions: This synopsis summarizes the key recommendations of the guideline regarding management of overweight and obesity, including referral to comprehensive lifestyle interventions that combine behavioral, dietary, and physical activity change, and additional tools of pharmacologic and procedural interventions. Additionally, recommendations based on evidence found in the literature for short-term weight loss are included. A clinical practice algorithm that is part of the guideline is also included. Additional materials, such as provider and patient summaries and a provider pocket card, are also available for public use, accessible at the U.S. Veterans Health Administration (VHA) Clinical Practice Guidelines (CPG) website listed above. [ABSTRACT FROM AUTHOR]

Background: Hemophilia B is a rare congenital bleeding disorder that has a significant negative impact on patients' functionality and health-related quality of life. The standard of care for severe hemophilia B in the United States is prophylactic factor IX replacement therapy, which incurs substantial costs for this lifelong condition. Accurate estimates of the burden of hemophilia B are important for population health management and policy decisions, but have only recently accounted for current management strategies. The 'Cost of Severe Hemophilia across the US: a Socioeconomic Survey' (CHESS US) is a cross-sectional database of medical record abstractions and physician-reported information, completed by hematologists and care providers. CHESS US+ is a complementary database of completed questionnaires from patients with hemophilia. Together, CHESS US and CHESS US+ provide contemporary, comprehensive information on the burden of severe hemophilia from the provider and patient perspectives. We used the CHESS US and CHESS US+ data to analyze the clinical, humanistic, and economic burden of hemophilia B for patients treated with factor IX prophylaxis between 2017 and 2019 in the US.Results: We conducted analysis to assess clinical burden and direct medical costs from 44 patient records in CHESS US, and of direct non-medical costs, indirect costs, and humanistic burden (using the EQ-5D-5L) from 57 patients in CHESS US+. The mean annual bleed rate was 1.73 (standard deviation, 1.39); approximately 9% of patients experienced a bleed-related hospitalization during the 12-month study period. Nearly all patients (85%) reported chronic pain, and the mean EQ-5D-5L utility value was 0.76 (0.24). The mean annual direct medical cost was $614,886, driven by factor IX treatment (mean annual cost, $611,971). Subgroup analyses showed mean annual costs of $397,491 and $788,491 for standard and extended half-life factor IX treatment, respectively. The mean annual non-medical direct costs and indirect costs of hemophilia B were $2,371 and $6,931.Conclusions: This analysis of patient records and patient-reported outcomes from CHESS US and CHESS US+ provides updated information on the considerable clinical, humanistic, and economic burden of hemophilia B in the US. Substantial unmet needs remain to improve patient care with sustainable population health strategies. [ABSTRACT FROM AUTHOR]

Introduction: People with inherited and long‐term conditions such as haemophilia have been shown to adapt to their levels of disability, often reporting better quality of life (QoL) than expected from the general population (the disability paradox). Aim: To investigate the disability paradox in people with haemophilia in the United States by examining preference differences in health state valuations versus the general population. Methods: We conducted a discrete choice experiment including duration to capture valuations of health states based on patient‐reported preferences. Participants indicated their preferences for hypothetical health states using the EQ‐5D‐5L, where each participant completed 15 of the 120 choice tasks. Response inconsistencies were evaluated with dominated and repeated scenarios. Conditional‐logit regressions with random sampling of the general population responses were used to match the sample of patients with haemophilia. We compared model estimates and derived preferences associated with EQ‐5D‐5L health states. Results: After removing respondents with response inconsistencies, 1327/2138 (62%) participants remained (177/283 haemophilia; 1150/1900 general population). Patients with haemophilia indicated higher preference value for 99% of EQ‐5D‐5L health states compared to the general population (when matched on age and gender). The mean health state valuation difference of 0.17 indicated a meaningful difference compared to a minimal clinically important difference threshold of 0.07. Results were consistent by haemophilia type and severity. Conclusion: Our findings indicated the presence of a disability paradox among patients with haemophilia, who reported higher health states than the general population, suggesting the impact of haemophilia may be underestimated if general population value sets are used. [ABSTRACT FROM AUTHOR]

Batt K, Xing S, KuharicM, et al. Real‐world analysis of patients with haemophilia A and haemophilia A carriers in the United States: Demographics, clinical characteristics and costs. Haemophilia. 2023; 29(3):809–818.The first row of Medicaid N numbers was published incorrectly. It should read as follows:  (N = 549 | N = 64 | N = 67 | N = 44).We apologize for this error. [Extracted from the article]

Objective: We sought to determine whether use of a poly (ADP-ribose) polymerase inhibitor is cost effective for maintenance treatment of platinum-sensitive recurrent ovarian cancer.Methods: A decision analysis model compared four maintenance strategies: 1) observation, 2) BRCA germline mutation testing and selective treatment of carriers (gBRCA only), 3) BRCA germline and tumor homologous recombination deficiency testing and selective treatment of either BRCA carriers or those with tumor HRD (gBRCA and HRD only), and 4) treat all with niraparib to progression (treat all). Costs were estimated in 2016 U.S. dollars. Incremental cost-effectiveness ratios were in dollars per progression-free quality-adjusted life-year (QALY). One-way sensitivity analyses tested multiple assumptions.Results: Maintenance poly (ADP-ribose) polymerase inhibitor was costlier and more effective than observation. Mean costs and progression-free QALYs were $827 and 3.4 months for observation, $46,157 and 5.7 for a BRCA-only strategy, $109,368 and 8.5 for a gBRCA and homologous recombination deficiency-only strategy, and $169,127 and 8.8 for a treat-all strategy. gBRCA-only had an incremental cost-effectiveness ratio of $243,092/progression-free QALY compared with observation; other strategies did not approach cost effectiveness. Using the current U.S. Food and Drug Administration label for maintenance poly (ADP-ribose) polymerase inhibitor regardless of biomarker status, the third-party payer cost per month (28-day supply) would need to be reduced from approximately $14,700 to $3,600 to be considered cost effective compared with observation using a willingness to pay threshold of $100,000/progression-free QALY.Conclusion: Maintenance poly (ADP-ribose) polymerase inhibitor therapy for platinum-sensitive recurrent ovarian cancer is not cost effective. Treatment of patients with BRCA mutation alone or with homologous recombination deficiency-positive tumors are preferred strategies compared with a treat-all strategy. Lowering the cost may make selective niraparib maintenance therapy cost effective compared with observation. [ABSTRACT FROM AUTHOR]

Herein, we discuss a case of a 39-year-old male with hemophilia B, who developed end-stage liver disease secondary to nonalcoholic steatohepatitis, that underwent orthotopic liver transplantation (OLT) as a curative means for his liver disease and coagulation disorder. Existing case reports have demonstrated favorable outcomes in patients outside of the United States who received continuous infusions of recombinant factor IX replacement in the perioperative setting after liver transplant. Given limitations in the stability of the recombinant factor IX products in the United States, a dosing strategy was comprised of once daily bolus dosing to achieve satisfactory factor IX levels. Within 48 hours of initial surgery, the patient had sustained factor IX levels above 70% of normal and the patient required no further dosing of factor IX products to date. This strategy helped facilitate less frequent dosing as well as achieved targeted factor levels while synthetic function of the transplanted liver recovered. [ABSTRACT FROM AUTHOR]

Introduction: Limited evidence describes physical activity‐associated bleeding risks for people with haemophilia, and risks are usually described only generically. Aim: To assess activity‐specific ranges of risk for joint, soft tissue and head bleeds by identifying inherent and modifiable risk factors associated with each activity, based on opinions of expert physical therapists (PTs). Methods: Physical therapists from US haemophilia treatment centres (HTCs) participated in a survey of 101 physical activities. For each activity, PTs provided minimum/maximum risk scores (low = 1; high = 5), and indicated specific bleeding risks in six joints and three injury types (bruising, muscle bleeding, head injury). Risk drivers were identified from free‐text comments and explored at a consensus meeting, where they were categorized as inherent or modifiable and activity‐driven or patient‐driven. Results: Of 32 invited PTs, 17 participated; median experience was 24 years as a PT and 16 years at an HTC. Only a few activities had a wide range of risk assessments encompassing both lower and upper ends of the response range. Joint injury risks were consistent with position and physical requirements, and head and muscle bleed risks were associated with physical contact. Eight PTs participated in the consensus meeting; key risk drivers identified included progression from seasonal to year‐round participation, overtraining and improper body mechanics. Inherent risks included impact with surface/ball/equipment and field/surface condition; modifiable risks included safety equipment and tricks/stunts. Conclusions: These data provide a framework for discussion with patients/families, recognizing how certain activities may be modified to decrease risk, and identifying activities with nonmodifiable inherent risks. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Levels of pain and dysfunction appear to differ among people with hemophilia despite similar levels of joint disease. Objective: To determine patient characteristics that influence pain and function independent of joint status. Methods: US adults with hemophilia completed a survey that included information on clinical characteristics, demographics, and patient‐reported outcome instruments assessing pain (Brief Pain Inventory v2 Short Form [BPI]), functional impairment (Hemophilia Activities List [HAL]), and health status (EQ‐5D‐5L). Additionally, physiotherapists optionally completed a clinical joint evaluation (Hemophilia Joint Health Score [HJHS]). Associations were examined using simple and multiple regression models. Results: Of 381 adults enrolled, 240 had complete HJHS scores (median age, 32 years). After controlling for HJHS and opiate use, anxiety/anxiolytic use was significantly associated with worse pain severity and interference scores. After controlling for HJHS, the most significant predictors of functional impairment were older age, unemployment, more severe hemophilia, and greater pain. EQ‐5D‐5L pain/discomfort was associated with worse outcomes on most HAL scores. Conclusion: Unemployment, anxiety, and depression were each associated with both greater pain and functional disability after controlling for joint status. Continued attention to pain and psychosocial issues will be important in improving clinical care and research efforts in the hemophilia population. [ABSTRACT FROM AUTHOR]

Introduction Patients with haemophilia are prone to medical emergencies. Emergency departments ( ED) often do not have a haematologist on-call for consultation. Aim The aim of this study was to determine the utilization of ED by patients with haemophilia. Methods Retrospective review of the 'National ED Database Sample' for years 2006-2013 was performed. Patient and hospital demographics were collected. Hospital charges were projected to national levels using discharge-weighted variables. Results During the 8-year study period, haemophilia patients made 162 982 ED visits. This represents 0.016% of total ED visits nationwide. Children utilized ED the most. More than half of patients resided in metropolitan cities; 20% had over $63 000 annual household income. Government insurances were the largest primary payers; 30% had private insurance. In the year 2012, 4488 ED visits with 21 000 diagnoses codes were recorded. Mean age was 29 years. Cardiovascular were the most frequently reported complaints followed by injuries, haemorrhages and sepsis. Seventy percent patients were treated and released from the ED. Two patients died in ED, whereas 35 after admission to hospital. Cause of death included Sepsis ( n = 26) and brain haemorrhage ( n = 4). Among children, injuries were the most frequent complaints followed by joint/soft tissue disorders; fevers and central line complications. Average charge per visit at private vs. public hospital was $2988 and $2254 respectively ( P = 0.03). National estimate of total charges was $60 million. Conclusion Patients with haemophilia have tendency to utilize ED. Hypertension was the single most common presenting complaint in adults. No deaths were reported in children from brain haemorrhage. [ABSTRACT FROM AUTHOR]

The establishment of dedicated comprehensive treatment centres more than a half century ago transformed the management of haemophilia in the United States. Formerly, a disease associated with crippling disability and premature death, today, persons with haemophilia who are treated appropriately from infancy and do not develop inhibitors can expect a normal life expectancy and relatively few bleeding episodes. The evolution of the comprehensive haemophilia care, while chastened by the viral epidemics of the 1980s, has been marked by ongoing advances, including prophylaxis, immune tolerance induction, new drugs and gene therapy research. Current challenges include sustaining the comprehensive care model despite decreased funding and expanding the delivery and affordability of comprehensive haemophilia care. [ABSTRACT FROM AUTHOR]

Aim The National Hemophilia Program Coordinating Center, with the U.S. Regional Hemophilia Network conducted a national needs assessment of U.S. Hemophilia Treatment Center ( HTC) patients. The objectives were to determine: (i) To what extent do patients report that they receive needed services and education; (ii) How well do the services provided meet their needs; and (iii) What are the patients' perspectives about their care. Methods A survey was mailed to active patients of 129 HTCs. Respondents completed the anonymous surveys on line or returned them by mail. Questions focused on management and information, access and barriers to care, coping, resources, and transition. Results Of 24 308 questionnaires mailed, 4004 (16.5%) were returned. Most respondents reported very few gaps in needed services or information and reported that services and information met their needs. Over 90% agreed or strongly agreed that care was patient-centred and rated HTC care as important or very important. Identified gaps included dietary advice, genetic testing, information on ageing, sexual health and basic needs resources. Minority respondents reported more barriers. Conclusion This survey is the largest assessment of the HTC population. Respondents reported that the services and information provided by the HTCs met their needs. Quality improvement opportunities include transition and services related to ageing and sexual health. Further investigation of barriers to care for minorities is underway. Results will help develop national priorities to better serve all patients in the US. HTCs. [ABSTRACT FROM AUTHOR]

The article discusses the concepts of second-order diversity and first-order diversity concerning the composition of juries. It examines the work of legal scholar Heather Gerken, demographic diversity in jury selection, diversity in jury deliberation, and jury participation as a form of civic knowledge. The article also discusses the U.S. Supreme Court case Scott v. Harris, and mass tort litigation in the case of hemophiliacs who acquired the HIV virus.

Given the rarity of haemophilic pseudotumours, consensus on management is lacking. We describe the clinical features and management of haemophilic pseudotumours by retrospectively reviewing the medical records of haemophilia patients with a diagnosis of pseudotumour seen at our Hemophilia Center from 1981 to 2011. We recorded the following data: type and severity of haemophilia, documented aetiological antecedent, localization of the pseudotumour, presenting symptoms, management and outcome. We identified 12 pseudotumours in 11 patients over a 30-year period. Six patients had known inhibitors or a history of inhibitor. An aetiological antecedent leading to the development of pseudotumour was reported in nine cases. Localization of the pseudotumour was confined to soft tissue ( n = 3) and bone ( n = 8). Six of the 12 pseudotumours (50%) were not diagnosed at the time of initial presentation, with a delay ranging from 6 weeks to 6 years. In eight cases, surgical intervention (surgical drainage, n = 2; excision, n = 4; limb amputation, n = 2) was the initial treatment choice, with complete resolution in six cases. Conservative management with close monitoring occurred in three cases, with one case subsequently requiring surgical resection. We conclude that haemophilic pseudotumours still occur sporadically, and the diagnosis is frequently delayed. Surgical intervention is generally a safe and effective treatment, although conservative management may be appropriate in selected cases. [ABSTRACT FROM AUTHOR]

. Prophylaxis and adherence to prophylaxis are increasingly recognized as important factors for the health-related quality of life (HRQOL) of haemophilia patients. This study aims to assess treatment practices over time, HRQOL and adherence among severe haemophilia A patients in the US. Severe haemophilia A patients or their caregivers participated in a 2009 cross-sectional survey. HRQOL was measured using either PEDS-QL or SF-12; adherence was measured using the VERITAS-Pro. Student t-tests evaluated differences between children vs. adults and self-infusion status. A total of 117 respondents participated in the survey, capturing data for 64 adults (mean age = 37.9 years) and 53 children (mean age = 10.5 years). Although 96% of paediatric patients were currently receiving prophylaxis, only 32 (50%) adults reported receiving prophylaxis at some point in their life. Adults who have always been on prophylaxis reported better physical functioning and physical HRQOL (both P < 0.05) than adults who had not. The paediatric group reported better adherence compared to the adult group on the total scale (38 vs. 45.8, P < 0.05). Children <12 years had higher adherence than adolescents 12-18 years old (35.5 vs. 40.8; P < 0.05). Paediatric patients infused by family members showed better adherence than paediatric self-infusers ( P < 0.05). This study showed different treatment patterns between paediatric and adult patients and how the patterns impacted HRQOL. It also provided the first standardized evaluation of adherence using the VERITAS-Pro in a US national sample. This study enhances understanding of treatment practices and adherence for the US haemophilia population and may offer insight into where adherence can be improved. [ABSTRACT FROM AUTHOR]

The article discusses the issue on absolute viral safety of clotting factor concentrates following the epidemics of AIDS in haemophilia patients. It states that the use of heat-treated products for AIDS prevention were not used for the purpose for which they had been licensed by the U.S. Federal Drug Administration (FDA). It says that four manufacturers of clotting factor in the U.S. have used different viral inactivation processes.

. To describe the in-hospital epidemiology of haemophilia A and B in the US we analysed the National Inpatient Sample (NIS), a stratified probability sample of 20% of all hospital discharges in the US for the year 2007. We applied sampling weights to represent all hospital discharges for haemophilia A and B identified using ICD-9 codes 286.0 and 286.1, respectively. Haemophilia (A or B) was one of all the listed diagnoses in 9737 discharges and principal diagnosis in 1684 discharges. The most common associated diagnoses in discharges with Haemophilia in adults and children were hypertension (28.1 ± 1.6%) and central line infections (15.2 ± 1.8%) respectively. No Hepatitis C or HIV was reported in children. Among 212 deaths, associated diagnoses included sepsis (37.9%), heart failure (30.2%), respiratory failure (28.3%), pneumonia (24.5%), HIV (14.2%), hepatic coma (5.2%) and intracranial haemorrhage (2.3%). All fifteen reported paediatric deaths occurred on day zero of life, the commonest associated diagnoses being Intraventricular haemorrhage and newborn haemorrhage-NOS (33% each). Median age of in-hospital mortality for diagnosis of Haemophilia was 68.3 years as compared to 72.3 years for all males for all hospitalizations in NIS combined. Mean hospital charges for haemophilia of $76823 ± 5530 were significantly higher than those from all causes of hospitalization of $26,120 ± 562. In-hospital mortality is rare in children with haemophilia beyond the neonatal period and age of mortality in adults is approaching that of the general male population. Hospitalization in children is most often due to central line infections and hospitalization and death in adults is primarily due to age-related illnesses. [ABSTRACT FROM AUTHOR]

. This study describes health-related quality of life (HRQoL) of persons with haemophilia A in the United States (US) and determines associations between self-reported joint pain, motion limitation and clinically evaluated joint range of motion (ROM), and between HRQoL and ROM. As part of a 2-year cohort study, we collected baseline HRQoL using the SF-12 (adults) and PedsQL (children), along with self-ratings of joint pain and motion limitation, in persons with factor VIII deficiency recruited from six Haemophilia Treatment Centres (HTCs) in geographically diverse regions of the US. Clinically measured joint ROM measurements were collected from medical charts of a subset of participants. Adults ( N = 156, mean age: 33.5 ± 12.6 years) had mean physical and mental component scores of 43.4 ± 10.7 and 50.9 ± 10.1, respectively. Children ( N = 164, mean age: 9.7 ± 4.5 years) had mean total PedsQL, physical functioning, and psychosocial health scores of 85.9 ± 13.8, 89.5 ± 15.2, and 84.1 ± 15.3, respectively. Persons with more severe haemophilia and higher self-reported joint pain and motion limitation had poorer scores, particularly in the physical aspects of HRQoL. In adults, significant correlations (P < 0.01) were found between ROM measures and both self-reported measures. Except among those with severe disease, children and adults with haemophilia have HRQoL scores comparable with those of the healthy US population. The physical aspects of HRQoL in both adults and children with haemophilia A in the US decrease with increasing severity of illness. However, scores for mental aspects of HRQoL do not differ between severity groups. These findings are comparable with those from studies in European and Canadian haemophilia populations. [ABSTRACT FROM AUTHOR]

. Advances in therapy have improved life expectancy and quality of life of patients with haemophilia A. Due to the chronic and complex management of this disease, particularly, the development of inhibitors, little is known about their health resource utilization in the real-life setting over time. The aim was to assess the distribution and trend of healthcare resource utilization among US haemophilia A patients with and without inhibitors. The MarketScan® Database, was queried to identify individuals with ≥1 year continuous enrolment, two medical diagnoses of haemophilia A and claims for factor VIII or bypassing agent (to infer inhibitor status) during 2001-2007. Haemophilia-related cost was estimated from inpatient, outpatient and pharmacy claims. Annual cost differences were assessed by age and over a 4-year period for those with continuous enrolment. Among 51 million covered lives, 1044 haemophilia patients were identified, of whom 981 (94%; mean age = 21.2 years) did not have an inhibitor. The median haemophilia-related cost for these patients was $63,935 per patient per year. When normalized by weight, annual cost was stable (no statistically significant differences) among 312 non-inhibitor patients (mean age = 21.8 years) with 4-year continuous data. While there was a wide distribution of haemophilia-related cost among the 63 individuals with an inhibitor (mean age = 15.4 years), only 0.6% of the total haemophilia patients had costs exceeding $1 million per patient per year. This study indicated that most haemophilia A patients were inhibitor-free with relatively stable annual costs over time. There was a wide distribution of haemophilia-related cost for inhibitor patients, while the proportion of patients who incurred extreme high cost was low. [ABSTRACT FROM AUTHOR]

. Patients with congenital haemophilia with inhibitors experience acute bleeds managed with bypassing agents, such as recombinant FVIIa (rFVIIa). Home-based treatment and dosing patterns in the US remain poorly described. This study aimed to assess the prescribed and actual rFVIIa dosing in frequently bleeding inhibitor patients (≥4 bleeds in 3 months) prescribed first-line therapy with rFVIIa. Patients or caregivers recorded daily diaries, including the details of all bypassing agent infusions for 3-6 months. Median (range) initial rFVIIa dose prescribed for joint, muscle and other bleeds was 167.5 (61.0-289.0) mcg kg−1. Additional rFVIIa doses prescribed were 90 (61-270) mcg kg−1 at an interval of 2.5-3 (1-24) h. The actual initial rFVIIa dose reported by patients/caregivers for 158 bleeds was 212 (59-400) mcg kg−1, with total dose per episode of 695 (74-21257) mcg kg−1. Patient/caregiver-reported average dose per bleed was 146 (40-400) mcg kg−1 across 5 (1-106) infusions. The initial rFVIIa dose was higher for haemarthrosis (223 [59-400] mcg kg−1) than muscle bleeds (148 [74-300] mcg kg−1; P = 0.07). Initial and mean dose per day changed as treatment progressed. The DOSE study indicates that frequently bleeding inhibitor patients are prescribed and use higher rFVIIa dosing for all bleed types than recommended in the package insert (90 mcg kg−1). The rFVIIa dosing was highly variable within and across bleed types, with higher initial doses used for joint bleeds than muscle and other bleed types, particularly in the first days of treatment. This suggests that patients/caregivers have adopted home treatment strategies based on physician discretion and individual responses and experience. [ABSTRACT FROM AUTHOR]

. General guidelines exist for the use of recombinant activated factor VII (rFVIIa) to maintain haemostasis during surgery in congenital haemophilia A and B patients with high responding inhibitors (CHwI). Individual surgical plans are required and based upon historical therapy response, adverse events and anticipated procedure. Surgical interventions are feasible, yet it remains unclear how many US hemophilia treatment centres (HTCs) perform procedures in this fragile population. To better understand the US HTC surgical experience in CHwI patients and the number/types of procedures performed, a 21-question survey was sent to 133 US HTCs, with follow-up for response clarification and to non-responders. 98/133 HTCs (74%) responded, with 87 currently treating CHwI patients. In the last decade, 76/85 HTCs performed 994 surgeries on CHwI patients. Sites were experienced in the following procedures: central line insertion/removal (73 HTCs), dental (58), orthopaedic (52), abdominal (23), cardiovascular (14) and otolaryngologic (11). Experience with orthopaedic surgeries included synovectomies - arthroscopic (23 HTCs), radioisotopic (22), and open (7); joint replacement (18); fracture repair (14); and arthrodesis (8). Treatment modalities included rFVIIa bolus (83 HTCs) or continuous infusions (9), plasma-derived activated prothrombin complex concentrate (pd-aPCC) (55), antifibrinolytics (51), topical haemostatic agents (29), factor VIII (16) and fibrin sealants (14). Protocols for bypassing agents were used by 31/92 (33%) HTCs. Most US HTCs surveyed care for CHwI patients (74%) and have experience in minor surgery; fewer HTCs reported complex orthopaedic surgical experience. Identification of best practices and surgical barriers is required to guide future initiatives to support these patients. [ABSTRACT FROM AUTHOR]

. Frequent evaluation of haemophilia treatment is necessary to improve patient care. The 2010 Practice Patterns Survey (PPS) investigated current trends in haemophilia treatment in the United States, as reported by nurses. The aim was to document practice patterns for haemophilia A and haemophilia B Survey questionnaires were sent to nurses at haemophilia treatment centres (HTCs) across the United States. Seventy-one of 126 HTCs (56%) responded to the survey. Factor dosage across treatment modalities ranged from 20 to 50 IU kg-1 for severe haemophilia A. Dosage for severe haemophilia B was more variable (<40 to >100 IU kg-1). On-demand dosing regimens were inconsistent for haemophilia A and more so for haemophilia B. Rates of adherence to prescribed treatment were similar for both haemophilia types (∼80%). The main barrier to adherence was identified as inconvenience. More bleeding episodes occurred in adults (16.6 bleeding episodes per year) with severe haemophilia A than in younger patients (11.3 bleeding episodes per year) before switching patients to prophylaxis. For both haemophilia types, most patients who switched from prophylaxis to on-demand treatment were aged 13-24 years; these patients also had the lowest adherence (60-71%). More paediatric patients with severe haemophilia A and inhibitors (53%) received prophylactic bypassing therapy than their haemophilia B counterparts (38%). Adults with severe haemophilia A faced challenges in relation to co-morbidities and long-term care. This PPS provides insights into previously unexplored aspects of haemophilia care that will serve to increase awareness and promote discussion of current issues affecting haemophilia patient care. [ABSTRACT FROM AUTHOR]

. The National Pain Study was a prospective, computer-based, descriptive survey of the pain experience of persons with a bleeding disorder conducted in the United States over a 28 month period from 2007 to 2009. The aim of this study was to (i) determine the language used by patients to describe and differentiate acute and persistent pain, (ii) describe pharmacological and non-pharmacological strategies utilized to control pain, (iii) assess the perceived effectiveness of current pain management on quality of life and, (iv) to determine who provides pain management to this population. One thousand, one hundred and four surveys were received. Only the responses of the 764 respondents who reported having hemophilia A or B were evaluated for this paper. Thirty nine percent of participants reported their pain was not well treated. The average acute pain score associated with a bleed reported was 5.97/10 while the average persistent pain score reported was 4.22/10. The most frequently reported word descriptors for acute pain were: throbbing, aching, sharp, tender and miserable. The most frequently reported word descriptors for persistent pain were aching, nagging, tiring, sharp, and tender. The most frequently reported pain strategies for acute and persistent pain included factor, rest, ice, elevation, and compression. Alcohol and illicit drugs were reportedly used to manage both acute pain as well as persistent pain. Primarily, short-acting opioids and acetaminophen were reported to treat both acute and persistent pain. Hematologists and primary care providers provide the majority of pain management for persons with hemophilia (PWH). Quality of life (QOL) scores were lowest in the domains of pain, energy/fatigue and physical problems indicating disruption of QOL. This substantiates under-recognition and under-treatment of pain in the hemophilia population when combined with the 39% of respondents who felt their pain was not well treated and literature in the general pain population of wide spread under-treatment of pain. Recommendations: The NPS is an initial step in recognizing the prevalence and description of pain in PWH. HTC providers should educate themselves in pain management techniques to better serve this population. Further research is necessary to develop specific pain management guidelines for the bleeding disorders population that include multimodal holistic treatment plans. [ABSTRACT FROM AUTHOR]

. Both genetic and treatment-related risk factors contribute to the development of inhibitors in haemophilia. An inhibitor surveillance system piloted at 12 US sites has the goal of assessing risk factors through prospective data collection. This report examines the relationship of genotype and race/ethnicity to history of inhibitor in a large cohort of US haemophilia patients. Mutation analysis was performed on 676 haemophilia A (HA) and 153 haemophilia B (HB) patients by sequencing, Multiplex Ligation-dependent Probe Amplification, and PCR for inversions in F8 introns 22 (inv22) and 1 (inv1). Two HB patients with deletions had history of inhibitor. In severe HA, frequency of history of inhibitor was: large deletion 57.1%, splice site 35.7%, inv22 26.8%, nonsense 24.5%, frameshift 12.9%, inv1 11.1% and missense 9.5%. In HA, 19.6% of 321 White non-Hispanics (Whites), 37.1% of 35 Black non-Hispanics (Blacks) and 46.9% of 32 Hispanics had history of inhibitor ( P = 0.0003). Mutation types and novel mutation rates were similar across ethnicities. When F8 haplotypes were constructed, Whites and Hispanics showed only H1 and H2. Within H1, history of inhibitor was 12.4% in Whites, 40.0% in Blacks ( P = 0.009) and 32.4% in Hispanics ( P = 0.002). Inhibitor frequency is confirmed to vary by mutation type and race in a large US population. White patients with history of inhibitor did not exhibit rare F8 haplotypes. F8 gene analysis did not reveal a cause for the higher inhibitor frequencies in Black and Hispanic patients. [ABSTRACT FROM AUTHOR]

Summary. On-demand therapy with recombinant activated factor VII (rFVIIa) can provide effective haemostasis for spontaneous bleeds in haemophilia patients with inhibitors. However, treatment approaches vary amongst physicians, positively or negatively affecting outcomes. A panel of physicians proposed recommendations for securing and maintaining predictable efficacy with rFVIIa, comparing these with 'real-life' patient management, using a questionnaire circulated to other expert physicians from haemophilia care centres in Europe and the United States. For rFVIIa treatment of spontaneous bleeds in inhibitor patients, early intervention with the highest appropriate dose is recommended. Home-based therapy can facilitate early intervention. If additional rFVIIa therapy is required after the initial dose, rFVIIa 90 μg kg−1 may be administered at 2-3 h intervals. Treatment should be tailored to bleed site/severity, recognizing the advantages of appropriate adjunct therapy. Questionnaire results suggested that many respondents adopted strategies in line with the recommendations. Most (36/46) recommended initial therapy within 1 h of bleed onset. rFVIIa 270 μg kg−1 was the most frequently prescribed/recommended initial dose for paediatric (aged ≤15 years; 22/44 respondents) and adult (aged >15 years; 23/44 respondents) patients. However, there may be opportunity for improved bleed management on occasion, with regard, for instance, to dosing and dose interval. To secure and maintain predictable efficacy with rFVIIa, judicious dose selection and treatment timing are important, together with adjunct therapy where necessary. As inhibitor patients present with different bleeding scenarios, a tailored treatment approach should be adopted. [ABSTRACT FROM AUTHOR]

Summary. Inpatient costs comprise >50% of annual healthcare costs for haemophilia patients with inhibitors but no reports exist on inpatient resource use and costs at a US national level. To quantify inpatient resource use and costs for on-demand treatment of bleeds of US haemophilia patients with inhibitors and compare costs and treatment duration between Factor VIII bypassing agents (BAs). Stays with haemophilia A from 2003-2008 were identified from inpatient billing records. Presence of inhibitors was inferred through use of BA; recombinant activated Factor VII and plasma-derived activated prothrombin complex concentrate. Duration and number of infusions of BA, length of stay, use of opioid-containing analgesics and costs were assessed and compared. Among 1322 stays mean BA treatment duration was 4.6 days with 4.9 infusions, 6.1 nights spent in hospital, and 58% administered opioid-containing analgesics. In unadjusted analyses there were significant differences in the above mentioned outcomes by BA use, reflecting underlying differences between the two patient populations. Average inpatient costs were $82 911. In adjusted analyses, African-American race, greater disease severity, hospital region outside the southern US and older age (cost model only) were significant predictors of longer BA treatment duration and higher costs. The economic burden of inpatient on-demand treatment of haemophilia with inhibitors is substantial and is associated with lengthy stays, high costs and inadequate pain relief. Availability of more effective BAs could reduce the need for re-treatment, reducing treatment costs and other medical costs, while improving health related quality of life. [ABSTRACT FROM AUTHOR]

Summary. Finding differences in drug utilization patterns within rare patient populations is challenging without access to a large sample. Our objective was to identify patient and treatment-related factors associated with differences in annual recombinant factor VIII (rFVIII) utilization in a large cohort of haemophilia A patients. This retrospective analysis utilized a large, US specialty pharmacy dispensing database from January 2006 to September 2009. Differences in median annual FVIII utilization (IU kg−1year−1) by age, severity, treatment regimen, rFVIII product type and health insurance plan were tested using non-parametric statistics and regression analysis. A total of 1011 haemophilia A patients were included in the overall analysis. Severe haemophilia patients had higher median annual FVIII utilization than mild/moderate patients ( P < 0.0001). Median annual FVIII utilization was also significantly different between treatment regimens (episodic = 1429 IU kg−1year−1 vs. prophylaxis = 3993 IU kg−1year−1 for severe patients, P < 0.0001). Children (0-12 years old), adolescents (13-18 years old) and adults (19+ years old) with severe haemophilia A receiving prophylaxis utilized 4588, 4082 and 3223 IU kg−1year−1 ( P < 0.0001). After controlling for age, severity, treatment regimen and insurance type, regression analysis revealed B domain-deleted recombinant FVIII (BDD-rFVIII) was associated with 33% higher FVIII consumption compared with full-length recombinant FVIII (FL-rFVIII) ( P = 0.0172). Similar results were also seen when matching BDD-rFVIII and FL-rFVIII patients. Health insurance type was not associated with annual FVIII utilization. As expected, age, severity and treatment regimen were significantly associated with FVIII utilization. After controlling for confounders, patients receiving FL-rFVIII prophylactically were associated with lower annual FVIII utilization compared with patients receiving BDD-rFVIII prophylactically. [ABSTRACT FROM AUTHOR]

The primary objective of the study was to examine the prevalence of cardiovascular disease (CVD) events and their known risk factors among persons with haemophilia (PWH). This cross-sectional study, covering a 5-year period, included PWH aged ≥35 years who were cared for at a single haemophilia treatment centre in the United States. Medical records were extensively reviewed to collect the information about CVD events and their risk factors such as obesity, hypertension, diabetes, hypercholesterolemia and smoking. Prevalence rates were compared with national population estimates and associations between risk factors and CVD events were examined using logistic regression. The study cohort comprised 185 PWH (102 haemophilia A and 83 haemophilia B). Lifetime prevalence of a CVD event was 19.5% (36/185, 95% confidence interval [CI] 13.8-25.2%). CVD mortality was 5.4% (10/185, 95% CI 2.7-8.1). Compared with US non-Hispanic White males (NHWH), PWH had about twice the prevalence of coronary artery disease, stroke and myocardial infarction. The prevalence of CVD risk factors for PWH was similar to that for US NHWM with 39.5% of PWH exposed to two or more of these risk factors. Both hypertension and smoking were associated significantly with CVD events, with odds ratios of 4.9 and 6.3, respectively. In conclusion, this study revealed that both CVD events and its risk factors were at least equally prevalent among PWH and might have been even higher than among the US NHWM in the United States. Therefore, it is imperative to implement strategies for CVD prevention among PWH. [ABSTRACT FROM AUTHOR]

Treatment preferences of haemophilia patients with inhibitors have not been well documented. This study sought to identify treatment attributes that patients/caregivers consider most important in the USA, inasmuch as those preferences may affect patient adherence to treatment plans. A discrete choice experiment was conducted to elicit treatment preferences. Haemophilia patients with inhibitors, or their caregivers on their behalf, completed a written survey that elicited preferences for treatment features and levels synthesized from the medical literature including: risk of viral transmission, rise in inhibitor titre, reduction in thromboembolic events, number of infusions, preparation time, infusion time/volume, time required to stop bleeding/alleviate pain, use of prophylaxis, use of major surgery and medication cost. Relative importance (RI) of preferences was modelled using a multinomial logit function. Most respondents were male (49 of 51, 96.1%); mean age, 20.7 years (SD = 18.8) and 88.5% of patients had haemophilia type A. The three most important patient-identified treatment attributes were as follows: time required to stop bleeding (RI = 19.3), possibility that the level of inhibitor may rise (RI = 14.3) and risk of contracting a virus from the product (RI = 13.5). Haemophilia patients with inhibitors and their caregivers appear to be willing to accept treatments that may be more inconvenient and painful as long as the treatments are effective in quickly controlling bleeds, do not increase inhibitor levels and do not pose a risk for viral contraction. Study findings provide meaningful input to the clinical community from patients and caregivers and support the importance of physicians understanding their patients' treatment preferences. [ABSTRACT FROM AUTHOR]

The emergence of a population of relatively healthy adults with severe haemophilia A presents a unique challenge for haemophilia care in the 21st century. Understanding how best to continue, restart, initiate or modify prophylaxis in younger and older adult patients is essential to optimizing their care. To elucidate practice and outcome data, a survey was sent to 23 US hemophilia treatment centers (HTCs); 10 centers responded, providing data concerning up to 145 adults (mean age of 34 years). Forty-eight patients (33%) were on regular prophylaxis when first seen at the HTC; the prophylactic regimen was modified for 22/48 (46%), often because of breakthrough bleeding. Five of 21 patients (24%) for whom data were available discontinued prophylaxis. Three of those five patients (60%) experienced increased bleeding episodes and the other two (40%) subsequently resumed regular prophylactic infusions because of the increased bleeding. Of the 77 patients not initially receiving prophylaxis for whom data were available, prophylaxis was started or resumed in all. The prophylactic regimen was modified in 57/77 patients (74%) at some point during treatment, often because of breakthrough bleeding. Of the 55 patients whose prophylactic regimens were modified for whom data were available, 22 (40%) discontinued prophylaxis. Thirteen of 20 patients (65%) for whom data were available experienced an increase in bleeding episodes and 7/18 patients (39%) who had discontinued prophylaxis and for whom data were available subsequently resumed regular prophylactic infusions because of bleeding. These findings suggest that prophylaxis prevents bleeding in adults with severe haemophilia A and that discontinuation of the prophylactic regimen is associated with increased bleeding events. [ABSTRACT FROM AUTHOR]

To measure health-related quality of life (HRQL), its determinants, and its association with patient and caregiver productivity among a sample of haemophilia patients with inhibitors in the United States (US). Data on demographical and clinical characteristics, treatment patterns, HRQL (SF-12v2), and productivity outcomes were reported for 53 patients. Mean SF-12v2 domain and mental (MCS) and physical (PCS) component summary scores were assessed and compared with US norms. Regression analyses explored the association of patient and treatment factors with HRQL and productivity. Patients’ mean age was 20.7 years (SD = 18.8), 88.5% were type A, and 39.6% received on-demand therapy as their only mode of treatment. Mean PCS was significantly lower than the US norm (PCS, 39.9, P < 0.01) and mean MCS showed no significant difference (MCS, 49.9, P = ns). On-demand treatment ( B = −0.336, P < 0.05) and number of haemorrhages ( B = −0.366, P < 0.05) were negatively associated with PCS; and PCS was associated with patients’ missed work or school days [incidence rate ratio (IRR) = 0.93, P < 0.001] and perceived impact on daily activities (OR = 0.72, P < 0.05). Younger age (IRR = 0.91, P < 0.01), lower PCS (IRR = 0.94, P < 0.01), more haemorrhages (IRR = 1.05, P < 0.05), and surgery (IRR = 2.74, P < 0.05) were associated with fewer patients’ productive days. Physical functioning among inhibitor patients in the US is compromised and is negatively associated with their daily activities and productivity. These data suggest a positive association of prophylactic and immunotolerance therapy with HRQL, specifically physical impairment. [ABSTRACT FROM AUTHOR]

The article reports on optimizing outcomes for patients with severe hemophilia A in the U.S. It states that prophylaxis is the most effective strategy for optimizing outcomes in patients with severe hemophilia A. Primary prophylaxis can prevent the development of arthropathy, protect against other serious bleeding events, and allow patients to live full, active lives.

Treatment costs to US payers are determined by treatment units dispensed, not prescribed. Hemophilia A therapies with more dosage strength options have better dispensing accuracy than those with fewer options, which is key to avoiding product wastage. Results This analysis included 1495 patients (939 adult, 556 pediatric) with: severe hemophilia A without inhibitors, >=1 hemophilia A treatment dispensing record, and available weight data. [Extracted from the article]

Objectives. The National Hemophilia Foundation and the Centers for Disease Control and Prevention conducted a national survey focusing on knowledge about, attitudes toward, and behaviors associated with key prevention activities among youths with hemophilia and used the data gathered to design a health promotion campaign. Methods. A national, random sample of 459 patients was drawn from 20 hemophilia treatment centers and 8 hemophilia associations; 110 (24%) of the respondents were young people. A telephone questionnaire was used to measure knowledge, behaviors, and barriers to prevention. Results. Thirty-six percent of the youth respondents believed that joint disease cannot be prevented; 60% managed hemophilia by avoiding physical activity. Only 31% of the respondents treated bleeding episodes within 1 hour. Although hepatitis was a clear threat to this hemophilic cohort, 78% did now know transmission routes for hepatitis C, and 67% did not know transmission routes for hepatitis B. Conclusions. Young people with chronic disorders need help understanding that they can prevent complications. We identified key messages for a hemophilia prevention campaign, including exercising to ensure healthy joints and treating bleeding episodes early and adequately. (Am J Public Health. 2006;96: 1618-1622. doi:10.2105/AJPH.2005.075234) [ABSTRACT FROM AUTHOR]

The article discusses a study on thromboembolic adverse events, which were reported to the U.S. Food and Drug Administration's Adverse Event Reporting System, after use of recombinant human coagulation factor Vlla (rFVlla). The FVlla is used to control bleeding in hemophilia patients and reportedly has been used off-label in patients without hemophilia. Research methods included analysis with Premier RxMarket Advisor. Data showing the extent of use, patient demographics, reasons for use, and number of thromboembolic events is provided, as well as reported deaths. The study found that morbidity or mortality occurred more when rFVlla was used for unlabeled indications.

Haematuria is common among persons with haemophilia (PWH), but its long-term effects on the kidney and renal function are not well defined. In addition, infection with human immunodeficiency virus (HIV) or hepatitis C, or exposure to nephrotoxic agents as therapy for these infections may place PWH at increased risk for renal disease. To examine factors associated with chronic renal disease (CRD) and acute renal disease (ARD) in PWH, we analysed data collected from the medical records of 3422 males with haemophilia living in six US states from 1993 to 1998. Renal disease cases were ascertained from among 2075 persons who were hospitalized at least once over the 6-year period. Of these, 60 (2.9%) were diagnosed during one or more hospitalizations with either ARD (29/60) or CRD (31/60). In multivariate analyses, we examined associations between renal disease and demographic and clinical factors including age, race, haemophilia type and severity, hypertension, diabetes, history of recent renal bleeds, presence of an inhibitor, and infection with hepatitis C or HIV. HIV infection and hypertension were strongly associated with both ARD and CRD. PWH who had ARD were also more likely to have an inhibitor than those without this diagnosis. PWH who had CRD were more likely to be older and non-white and to have had a recent admission for a kidney bleed than those without diagnosed CRD. In summary, we found that HIV infection and haemophilia-related factors including inhibitors and kidney bleeds were associated with renal disease in a cohort of males with haemophilia. [ABSTRACT FROM AUTHOR]

Background: Persons with a congenital deficiency of FVIII or F IX (hemophilia A and hemophilia B, respectively) receive factor concentrate to treat or prevent bleeding.Study Design and Methods: A population-based study of all persons with hemophilia residing in New York State at any time during 1993 through 1998 was conducted. All available medical records for each patient were reviewed to determine type of therapy.Results: Case finding yielded 1160 cases, for a prevalence of 63.9 per 1 million population in 1998. Recombinant factor concentrates were used by 56 percent of patients. Patients with severe disease used more (158,234 IU/patient) factor concentrate than did patients with moderate disease (46,315 IU) or mild disease (5794 IU). Over half (57%) of all factor concentrate was prescribed for patients with severe disease on prophylactic therapy. Patients undergoing immune tolerance therapy used the most per person-455,116 IU each. Hemophilia treatment centers provided factor concentrate for 62 percent of all patients who used factor and 73 percent of patients with severe disease.Conclusion: Hemophilia patients, especially patients with severe disease, use large amounts of expensive factor concentrates to prevent and to treat bleeding episodes. Specialized hemophilia treatment centers play a key role in the care of these patients. [ABSTRACT FROM AUTHOR]