Real-World Analysis of Dispensed International Units of Coagulation Factor VIII and Resultant Expenditures for Hemophilia A Patients: A Comparison Between Standard Half-Life and Extended Half-Life Products.

PURPOSE: To identify international units (IUs) dispensed and consequent expenditures for standard half-life (SHL) versus extended half-life (EHL) recombinant factor VIII (rFVIII) replacement products in hemophilia A patients in a real-world setting. DESIGN: Two U.S. claims databases were analyzed. METHODOLOGY: Number of IUs dispensed and quarterly expenditures for rFVIII products were collected from the Optum Clinformatics Data Mart and Truven Health MarketScan Databases. Truven claims were also analyzed for factor IUs dispensed and expenditures for patients with data for ≥3 months before and after switching to an EHL product. RESULTS: The Optum and Truven databases, respectively, included 276 (SHL, n=243; EHL, n=33) and 500 (SHL, n=409; EHL, n=91) hemophilia A patients. Median quarterly factor IUs dispensed in Optum were 10% higher with EHL versus SHL products over nine quarters, and 45% higher with EHL versus SHL products in Truven over 10 quarters. Median quarterly expenditures in the EHL cohort were 51% (individual quarterly medians range, 1%-101%) higher than in the SHL cohort in Optum and 122% higher (individual quarterly medians range, 1%-189%) in Truven. Twenty-nine Truven patients switched to an EHL product; median factor IUs dispensed varied quarterly. The lowest SHL and highest EHL values occurred in the quarter immediately before switching and the first quarter post-switch, respectively. Overall median quarterly expenditures were higher post-switch; this was consistent over seven quarters. CONCLUSION: We found higher expenditures over two years for hemophilia A patients using EHL versus SHL products. Switching to an EHL rFVIII product was associated with variable factor IUs dispensed and consistently higher expenditures.

Patient, caregiver, and provider perceptions of pain and pain management in adolescents and young adults with bleeding disorders.

INTRODUCTION: Recurrent bleeding and associated pain are critical components in the management of bleeding disorders, yet scant data describe perceptions of pain in this patient population. OBJECTIVE: This study assessed perceptions of pain and pain management in adolescents and young adults (AYAs) with haemophilia or von Willebrand disease (VWD) to determine agreement/disagreement between patients, caregivers and health care providers. METHODS: Using an online questionnaire, AYA patients (N=89), their caregivers (N=77), and providers (N=54) reported on pain perception, pain treatment and pain control. Acute and chronic pain was measured in patients via the Faces Pain Scale-Revised (FPS-R). Questionnaires queried about pharmacologic and non-pharmacologic pain management methods and how well providers and caregivers helped to manage pain. RESULTS: Poor agreement existed between patients and caregivers across all pain levels, perception of pain control and effectiveness of pain management. Specifically for chronic pain, poor agreement was noted between patients and caregivers (kappa=0.04; 29% agreement) and patients and providers (kappa=-0.07; 21.4% agreement). Among patients reporting acute or chronic pain, only 67% and 43%, respectively, utilized medication for their specific pain. Patients used more opioid medications than expected by their providers. On average, AYAs reported initial use of pain medications for chronic pain at 11.5 years. CONCLUSIONS: Ongoing research is needed in haemophilia and VWD pain management, and on the differences in pain perception between patients, caregivers and providers. As chronic pain often begins at an early age, optimal pain management should include acknowledging patient complaints, exploring pharmacologic and non-pharmacologic options, and optimizing prophylaxis.

Traumatic tricuspid valve rupture presenting as third-degree atrioventricular block.

BACKGROUND: Cardiac valve injury after blunt chest trauma is extremely rare, and the tricuspid valve is most commonly affected because of the anterior location of the right ventricle. Tricuspid valve insufficiency can range from a subclinical presentation to acute cardiac failure. OBJECTIVE: Diagnosis is difficult in trauma patients because hypotension is usually attributed to hemorrhage and anatomical cardiac injuries might be overlooked. CASE REPORT: This is a case of a 70-year-old patient with a history of rheumatic heart disease who suffered a complete rupture of her papillary muscles leading to tricuspid insufficiency after a motor vehicle collision. She presented with third-degree atrioventricular block. CONCLUSIONS: Consideration of screening for anatomical heart injuries in blunt trauma patients with new onset dysrhythmias is recommended to explain hypotension not attributable to hemorrhage.

Deviations from evidence-based clinical management guidelines increase mortality in critically injured trauma patients*.

OBJECTIVES: The effect of treatment guidelines on clinical outcomes in general and specifically for trauma patients has not been well-studied. We hypothesized that better compliance with guidelines would be associated with improved clinical outcomes. DESIGN: Prospective, randomized, double-blinded, multicentered, placebo-controlled study of recombinant factor VII in severe trauma that utilized guidelines for damage control, transfusions, and mechanical ventilation. Vanderbilt Coordinating Center reviewed compliance in near real-time and reported deviations classified as minor, moderate, or major to investigators. Multivariate regression analysis measured the association between outcomes (30-day and 90-day mortality, development of multiple organ failure, ventilator-free days, renal failure-free days, and blood products transfused) and compliance with each guideline, as well as a composite assessment of overall compliance. SETTING: One hundred hospitals in 26 countries. PATIENTS: Blunt and/or penetrating trauma patients aged 18-70 yrs who had received 4-8 units of red blood cells for active torso and/or proximal lower extremity bleeding despite standard interventions. MEASUREMENTS AND MAIN RESULTS: When assessed as composite end point, major deviations from guidelines were associated with significantly higher mortality at 30 and 90 days after injury and fewer renal failure-free days. Moderate deviations were associated with a significantly higher risk of multiple organ failure and fewer ventilator-free days. Moderate and major deviations from damage control and ventilation guidelines were also significantly associated with higher risk of death at days 30 and 90. Within the ventilation protocol, noncompliance with tidal volume and plateau pressure targets was associated with significantly higher mortality at days 30 and 90 and fewer ventilator-free days, whereas noncompliance with weaning guideline was only associated with significantly fewer ventilator-free days. CONCLUSIONS: : In a clinical trial of trauma patients, higher compliance with guidelines for damage control, transfusion, and ventilation management is associated with lower mortality and improved outcomes.

Recombinant activated factor VII safety in trauma patients: results from the CONTROL trial.

BACKGROUND: Safety data on recombinant activated factor VII (rFVIIa, NovoSeven; Novo Nordisk A/S, Bagsværd, Denmark) in actively hemorrhaging trauma patients are limited. We present detailed safety data from a large multicenter, randomized, placebo-controlled phase III study (the CONTROL trial). METHODS: Data from 560 patients were analyzed. Subjects were monitored for adverse events (AEs) after rFVIIa or placebo administration. Incidences, timing, and presence of risk factors were reported by site investigators, supported by external study monitors and overseen by an independent Data Monitoring Committee. RESULTS: There were no differences in overall mortality, organ system failure, or AEs, serious AEs, or medical events of special interest. Arterial and venous thromboembolic (TE) events and their risk factors were similar in both groups. The greatest risk factor for TE events was a chest injury requiring mechanical ventilation >3 days (86%). There were four site investigator-reported myocardial infarctions in the rFVIIa group of which only one met diagnostic criteria preestablished by the Data Monitoring Committee. There were no reported myocardial infarctions in the placebo group. Troponins were increased in 30% of all patients. The rate of acute respiratory distress syndrome was lower in the rFVIIa (3.0%) than in the placebo (7.2%) group (p = 0.022). CONCLUSIONS: This represents the largest placebo-controlled dataset of rFVIIa use in trauma patients to date. In this prospective study of critically bleeding trauma patients, rFVIIa use was associated with an imbalance of investigator-reported Acute myocardial infarction/non-ST segment elevation myocardial infarction (AMI/NSTEMI), but was not associated with an increased risk for other AEs, including TE complications.

Once-weekly prophylaxis regimen of nonacog alfa in patients with hemophilia B: an analysis of timing of bleeding event onset.

In a pivotal, multicenter, open-label study, 25 patients aged 12-54 years with moderately severe/severe hemophilia B received on-demand nonacog alfa (6 months; dose at investigator's discretion) followed by once-weekly prophylaxis with nonacog alfa 100 IU/kg (12 months). During prophylaxis, patients had a median spontaneous annualized bleeding rate (sABR) of 1.0 and significant reductions in ABR (P < 0.0001). This post hoc analysis examined the time of onset of spontaneous bleeding events (sBEs) and spontaneous target joint bleeding events (sTJBEs). The postdosing day (D) of onset of sBEs observed during prophylaxis and steady-state FIX activity data (FIX:C) between 144 and 196 h postdose were collected at weeks 26 and 78. Twelve patients (48%) had no sBEs; the remaining 13 (52%) had the following onset of sBEs: less than 1 D (0%), 1 to less than 2D (5%), 2 to less than 3 D (22%), 3 to less than 4 D (9%), 4 to less than 5D (22%), 5 to less than 6D (23%), 6 to less than 7D (11%), and at least 7D (8%). Reductions in sBEs and sTJBEs during on-demand versus prophylaxis treatment were experienced by all 13 patients. Target joint sABR during prophylaxis was 0 for 5/13 patients. ABR reduction ranged from 66.1% (27.2→9.2) to 97.8% (46.2→1.0); sTJBE reductions ranged from 6.2% (2.1→2.0) to 100% (from 40.1, 19.1, 3.9, 9.0, 6.1--0). During prophylaxis, 47% (8/17) of trough FIX activity samples were more than 2%. In sBE patients, ABR and number of TJBEs were reduced with once-weekly nonacog alfa. When sBEs occurred, they followed no apparent pattern for day of occurrence. Clinicaltrials.gov identifier: NCT01335061.

Global differences in causes, management, and survival after severe trauma: the recombinant activated factor VII phase 3 trauma trial.

BACKGROUND: Little is known about international variation in mortality after severe trauma. This study examines variation in mortality, injury severity, and case management among countries from a recent prospective multinational trauma trial. METHODS: This trauma trial was a prospective, randomized, double-blinded, multicenter comparison of recombinant activated factor VII versus placebo in severely injured bleeding trauma patients. Differences in baseline patient characteristics, case management, and clinical outcomes were examined for the 11 countries recruiting most patients. Between-country differences in mortality were examined using regression analysis adjusting for case mix and case management differences. Global predictors of mortality were also identified using multivariate regression analysis. RESULTS: Significant differences were observed between countries in unadjusted mortality rates at 24 hours (p = 0.025) and 90 days (p < 0.0001). When adjusting for differences in case mix and case management, the between country differences in mortality at 24 hours and 90 days remained significant. Consistent independent predictors of 24-hour, 24-hour to 90-day, and 90-day mortality were admission lactate >or=5 mmol/L (odds ratio: 9.06, 3.56, and 5.39, respectively) and adherence to clinical management guidelines (odds ratio: 4.92, 5.90, and 3.26, respectively). On average, the damage control surgery guideline was less well adhered to than the RBC transfusion and ventilator guidelines. There was statistically significant variation between countries with respect to adherence to the RBC transfusion guideline. CONCLUSIONS: Considering international variation in mortality when designing or interpreting results from multinational trauma studies is important. Significant differences in mortality persisted between patients from different countries after case mix and case management adjustment. Adherence to clinical guidelines was associated with improved survival. Stratification, case mix adjustment, and use of guidelines on damage control surgery, transfusion, and ventilation may mitigate country-driven variation in mortality.

Results of the CONTROL trial: efficacy and safety of recombinant activated Factor VII in the management of refractory traumatic hemorrhage.

BACKGROUND: Traumatic coagulopathy contributes to early death by exsanguination and late death in multiple organ failure. Recombinant Factor VIIa (rFVIIa, NovoSeven) is a procoagulant that might limit bleeding and improve trauma outcomes. METHODS: We performed a phase 3 randomized clinical trial evaluating efficacy and safety of rFVIIa as an adjunct to direct hemostasis in major trauma. We studied 573 patients (481 blunt and 92 penetrating) who bled 4 to 8 red blood cell (RBC) units within 12 hours of injury and were still bleeding despite strict damage control resuscitation and operative management. Patients were assigned to rFVIIa (200 µg/kg initially; 100 µg/kg at 1 hour and 3 hours) or placebo. Intensive care unit management was standardized using evidence-based trauma "bundles" with formal oversight of compliance. Primary outcome was 30-day mortality. Predefined secondary outcomes included blood products used. Safety was assessed through 90 days. Study powering was based on prior randomized controlled trials and large trauma center databases. RESULTS: Enrollment was terminated at 573 of 1502 planned patients because of unexpected low mortality prompted by futility analysis (10.8% vs. 27.5% planned/predicted) and difficulties consenting and enrolling sicker patients. Mortality was 11.0% (rFVIIa) versus 10.7% (placebo) (p = 0.93, blunt) and 18.2% (rFVIIa) versus 13.2% (placebo) (p = 0.40, penetrating). Blunt trauma rFVIIa patients received (mean ± SD) 7.8 ± 10.6 RBC units and 19.0 ± 27.1 total allogeneic units through 48 hours, and placebo patients received 9.1 ± 11.3 RBC units (p = 0.04) and 23.5 ± 28.0 total allogeneic units (p = 0.04). Thrombotic adverse events were similar across study cohorts. CONCLUSIONS: rFVIIa reduced blood product use but did not affect mortality compared with placebo. Modern evidence-based trauma lowers mortality, paradoxically making outcomes studies increasingly difficult.

Prolonged prothrombin time after recombinant activated factor VII therapy in critically bleeding trauma patients is associated with adverse outcomes.

BACKGROUND: In trauma patients with significant hemorrhage, it is hypothesized that failure to normalize prothrombin time (PT) after recombinant activated factor VII (rFVIIa) treatment predicts poor clinical outcomes and potentially indicates a need for additional therapeutic interventions. METHODS: To assess the value of PT to predict outcomes after rFVIIa or placebo therapy, we performed a post hoc analysis of data from 169 severely injured, critically bleeding trauma patients who had 1-hour postdose PT measurements from two randomized clinical trials. Baseline characteristics and outcome parameters were compared between subjects with 1-hour postdose PT >or=18 seconds and PT <18 seconds. RESULTS: In rFVIIa-treated subjects, prolonged postdose PT values >or=18 seconds were associated with significantly higher 24-hour mortality (60% vs. 3%; p < 0.001) and 30-day mortality, increased incidence of massive transfusion, and fewer intensive care unit-free days compared with postdose PT values <18 seconds. Recombinant rFVIIa-treated subjects with postdose PT >or=18 seconds had significantly lower baseline hemoglobin levels, fibrinogen levels, and platelet counts than subjects with postdose PT values <18 seconds even though they received similar amounts of blood products before rFVIIa dosing. Placebo-treated subjects with postdose PT >or=18 seconds had significantly increased incidence of massive transfusion, significantly decreased intensive care unit-free days, and significantly lower levels of fibrinogen and platelets at baseline compared with subjects with postdose PT values <18 seconds. CONCLUSIONS: The presence of prolonged PT after rFVIIa or placebo therapy was associated with poor clinical outcomes. Because subjects with postdosing PT >or=18 seconds had low levels of hemoglobin, fibrinogen, and platelets, this group may benefit from additional blood component therapy.

Adverse Events and Discontinuation Rates Associated with Sirolimus Treatment in Adult Renal Transplant Patients in Latin America vs Non-Latin American Countries.

BACKGROUND: Sirolimus is approved for prophylaxis of organ rejection following renal transplantation. Rates of treatment-emergent adverse events (TEAEs) leading to sirolimus discontinuation differ geographically. METHODS: Rates of TEAEs, serious AEs (SAEs), and discontinuations were evaluated in 3 clinical trials of conversion from calcineurin inhibitors to sirolimus. Posttransplantation, patients were treated over 4 years (study 1), over 1 year (study 2), and over 2 years (study 3). TEAEs, SAEs, and discontinuation rates were compared between Latin America (LATAM) vs North America (NA) and Europe/rest of world (EU/ROW). Data from studies 2 and 3, with similar times to conversion, were pooled. RESULTS: Study 1 comprised 551 patients (LATAM, n=189); studies 2/3 comprised 395 (LATAM, n=111). LATAM patients were significantly younger than NA or EU/ROW patients in study 1 and studies 2/3 (P < .0001), with a lower proportion of white patients and higher proportion of patients of other races in LATAM vs NA (P < .0001) and EU/ROW (P = .02) groups. Almost all patients reported TEAEs. Discontinuation because of medical events was significantly lower (P < .05) in LATAM vs NA or EU/ROW. Hypercholesterolemia and hypertriglyceridemia were more common, and anemia and peripheral edema less common in LATAM; diarrhea and proteinuria did not differ by region. Types of AEs leading to discontinuation did not differ by region. CONCLUSION: LATAM renal transplant recipients converted to sirolimus were more likely to remain on therapy than patients in other regions.

Real-world outcomes associated with standard half-life and extended half-life factor replacement products for treatment of haemophilia A and B.

: Standard-of-care treatment for haemophilia A or B is to maintain adequate coagulation factor levels through clotting factor administration. The current study aimed to evaluate annualised bleeding rates (ABR) and treatment adherence for haemophilia A or B patients receiving standard half-life (SHL) vs. extended half-life (EHL) factor replacement products. We analysed data from the Adelphi Disease-Specific Programmes, a health record-based survey of United States and European haematologists. Analysis included 651 males with moderate-to-severe haemophilia A or B (the United States, n = 132; Europe, n = 519). The haemophilia A analysis included 501 patients (SHL, n = 435; EHL, n = 66). In the combined United States/European population, mean (SD) ABR was 1.7 (1.69) for the SHL group and 1.8 (2.00) for the EHL group. A total of 72% of patients receiving SHL factor VIII and 75% of patients receiving EHL factor VIII in the combined population were fully adherent (no doses missed of the last 10 doses), as reported by physicians. The haemophilia B analysis included 150 patients (SHL, n = 114; EHL, n = 36). The mean (SD) ABR in the combined population was 2.1 (2.16) for patients receiving SHL factor IX (FIX) and 1.4 (1.48) for patients receiving EHL FIX. The percentage of fully adherent patients (physician-reported) was similar in both treatment groups (SHL FIX, 68%; EHL FIX, 73%). In this preliminary real-world survey in a relatively small sample of patients, measures of ABR and adherence between SHL and EHL products were evaluated. Additional real-world research on prescribing patterns, SHL vs. EHL effectiveness, and adherence is warranted.

Interrelationship between depression, anxiety, pain, and treatment adherence in hemophilia: results from a US cross-sectional survey.

PURPOSE: Depression, anxiety, pain, and treatment adherence have reciprocal effects not characterized extensively in hemophilia. This study explored the relationships between depression, anxiety, chronic pain, and treatment adherence in adults with hemophilia. PATIENTS AND METHODS: Adults with self-reported hemophilia A or B completed the cross-sectional IMPACT QoL II survey. Depression (9-item Patient Health Questionnaire [PHQ-9]), anxiety (7-item Generalized Anxiety Disorder scale [GAD-7]), chronic pain (Faces Pain Scale-Revised [FPS-R]), social support (Duke UNC Functional Social Support questionnaire), level of pain control, clotting factor treatment adherence (VERITAS-Pro or -PRN), and previous depression/anxiety were analyzed. RESULTS: Among 200 participants (male, 77.3%; female, 22.8%), 54% had PHQ-9 and 52% had GAD-7 scores indicating moderate to severe depression or anxiety without diagnosis of either disorder. Participants with PHQ-9 scores ≥10 (moderate to severe depression) were more likely to have lower treatment adherence than those with PHQ-9 scores <10 (P<0.05). Participants with PHQ-9 or GAD-7 scores ≥10 were more likely to report uncontrolled pain and less social support versus PHQ-9 or GAD-7 scores <10 (χ2 P<0.05). Significant correlations were found between PHQ-9 and GAD-7 (P<0.0001), PHQ-9 and FPS-R (P=0.0004), PHQ-9 and VERITAS (P=0.01), GAD-7 and FPS-R (P=0.02), and GAD-7 and VERITAS (P=0.001). CONCLUSION: Depression and anxiety are underdiagnosed in hemophilia. Depression is associated with anxiety, pain, and lower treatment adherence. While treatment providers play an important role in diagnosis, social workers may play a pivotal role in depression and anxiety screening. This study highlights the importance of regular screening and treatment for these disorders.

Real-World Analysis of Dispensed IUs of Coagulation Factor IX and Resultant Expenditures in Hemophilia B Patients Receiving Standard Half-Life Versus Extended Half-Life Products and Those Switching from Standard Half-Life to Extended Half-Life Products.

BACKGROUND: Hemophilia B requires replacement therapy with factor IX (FIX) coagulation products to treat and prevent bleeding episodes. A recently introduced extended half-life (EHL) recombinant FIX replacement product provided the opportunity to compare the amount of dispensed factor and expenditures for EHL treatment compared with a standard half-life (SHL) product. OBJECTIVE: To determine factor international units (IUs) dispensed and expenditures associated with switching from nonacog alfa, the most commonly used SHL replacement product, to eftrenonacog alfa, an EHL FIX replacement product. METHODS: Two U.S. claims databases were analyzed. A large national specialty pharmacy dispensation claims database was used to identify the number of IUs dispensed and monthly charges for all patients with hemophilia B from April 2015 to June 2016. Truven Health MarketScan Research Databases (January 2010-July 2016) were used to identify IUs and expenditures for patients with claims data for at least 3 months before and after switching from the SHL to the EHL product. Medians for IUs and expenditures are presented to accommodate for skewness of data distribution. RESULTS: The national specialty pharmacy database analysis included 296 patients with moderate or severe hemophilia B (233 on SHL; 94 on EHL). Median monthly factor dispensed was 11% lower (2,142 IU) in the EHL versus SHL cohort over the study period, while individual monthly reductions ranged from 32% to 47% (9,838 IU to 16,514 IU). Using the wholesale acquisition cost, the median per-patient monthly factor expenditures over the 15-month study period were 94% higher ($23,005) for the EHL than for the SHL product. Individual median monthly expenditure differences ranged from 15% ($6,562) to 49% ($19,624). In the Truven database, 14 patients switched from the SHL to the EHL product. The amount of factor dispensed was variable; in the 1-year period before and after the switch from the SHL to the EHL product, mean IUs dispensed decreased by 3,005 IU, while median IUs dispensed increased by 4,775 IU. Factor replacement expenditures were higher after switching from the SHL to the EHL product in each of the 3-month periods examined before versus after the switch. CONCLUSIONS: This analysis of real-world data showed that switching from the SHL to the EHL product was associated with higher expenditures. Increased expenditures noted in the first 3 months after switching may be related to initial stocking up of the EHL product, but expenditures were sustained throughout the 1-year period of data analysis. Further analysis of these findings with larger numbers of patients should be explored. DISCLOSURES: This study was sponsored by Pfizer. Pfizer employees were involved in the study design; the collection, analysis, and interpretation of data; the review of the manuscript; and the decision to submit for publication. All authors are employees of Pfizer. No author received an honorarium or other form of payment related to the development of this manuscript. All authors participated in the study design, data interpretation, and manuscript review and revisions and granted approval for the submission of the manuscript. Alvir, McDonald, and Tortella also participated in data analysis. Data from this paper were presented in part at the European Association for Haemophilia and Allied Disorders Annual Meeting, February 1-3, 2017, Paris, France; at the International Society for Pharmacoeconomics and Outcomes Research Annual Meeting, May 20-24, 2017, Boston, MA; and at the International Society on Thrombosis and Haemostasis Congress, July 8-13, 2017, Berlin, Germany.

Excess mortality, length of stay, and costs associated with serious hemorrhage among trauma patients: findings from the National Trauma Data Bank.

Trauma is a serious injury or shock to the body from violence or crash and is an important and growing global health risk. Using 2000 to 2004 data from a comprehensive trauma registry, we estimated the prevalence of serious blunt and penetrating trauma-related hemorrhage among patients admitted to U.S. trauma centers along with excess in-hospital mortality, length of hospital stay, and inpatient costs. There were 65,750 patients with blunt trauma and 12,992 patients with penetrating trauma included in our analyses. Of patients sustaining blunt trauma, 7.6 per cent had serious hemorrhage; 18.8 per cent of patients sustaining penetrating trauma had serious hemorrhage. In-hospital mortality rates were significantly (P < 0.05) higher for patients with serious hemorrhage than for patients without (24.9 per cent versus 8.4 per cent for blunt; 23.4 per cent versus 4.2 per cent for penetrating). Patients with serious hemorrhage had adjusted mean excess lengths of stay of 0.4 days for blunt trauma and 2.7 days for penetrating trauma (P < 0.05); adjusted excess costs were $296 per day for patients sustaining blunt trauma and $637 per day for patients sustaining penetrating trauma (P < 0.05). In both blunt and penetrating trauma cases, serious hemorrhage is significantly associated with excess mortality, longer hospital stays, and higher costs.

Emerging and future therapies for hemophilia.

The evolution of care in hemophilia is a remarkable story. Over the last 60 years, advances in protein purification, protein chemistry, donor screening, viral inactivation, gene sequencing, gene cloning, and recombinant protein production have dramatically enhanced the treatment and lives of patients with hemophilia. Recent efforts have produced enhanced half-life (EHL) clotting factors to better support prophylaxis and decrease the frequency of infusions. Medical needs remain in the areas of alternate modes of administration to decrease the need for venous access, better treatment, and prophylaxis for patients who form antibodies to clotting factors, and ultimately a cure of the underlying genetic defect. In this brief review, the authors summarize data on EHL clotting factors, introduce agents whose mode of action is not clotting factor replacement, and list current gene therapy efforts.

BE EMPOWERED, a specialty pharmacy education program for hemophilia B patients, impacts adult joint bleeds and pediatric use of RICE.

BACKGROUND: Traditional education about hemophilia B in hemophilia treatment centers (HTCs) and episodic contact with HTCs limit the amount of education patients and their caregivers receive. Specialty care providers have frequent, continuing contact with patients. Each contact with a specialty care provider (e.g., coordinating a refill or addressing a patient inquiry) is another opportunity to support patient self-management of the disease and to give counsel on appropriate medication administration. The role of specialty pharmacy in improving patient self-management and supporting medication management and adherence is well established and reported with rheumatoid arthritis, multiple sclerosis, and renal transplant. With hemophilia, specialty pharmacies can support educational reinforcement of HTCs as well as support patient self-management and education of medication therapy. Utilization of patient education materials and programs can facilitate such a role. BE EMPOWERED, a specialty pharmacy education program for hemophilia B patients, is a multimodule education program coupled with frequent telephonic outreach.   OBJECTIVE: To provide education about hemophilia B, based upon discrete curriculum modules, facilitated by a specialty pharmacy-based nurse educator.   METHODS: Patients with hemophilia B (or, for children, their caregivers) were enrolled in the BE EMPOWERED program, and data were prospectively collected regarding bleeding and hemophilia-specific quality of life (QoL) outcomes (n = 21 caregivers, n = 17 adults).  RESULTS: BE EMPOWERED was associated with a statistically significant impact on the use of RICE (rest, ice, compression, and elevation) by caregivers whose utilization increased from 81% to 95% (P = 0.05). Adults in the BE EMPOWERED program experienced a statistically significant drop in the annualized bleeding rate (ABR), decreasing from 4.7 to 2.5 for total bleeds and decreasing from 3.5 to 1.7 for joint bleeds (P ≤ 0.02). For children with hemophilia B, bleeds were less common overall, as reported by their caregivers, with a mean ABR of 1.1 before and 1.2 following the program. Regarding QoL scores, adults had lower scores compared with children enrolled in the program.  CONCLUSIONS: Completion of the BE EMPOWERED program was associated with a decrease in total bleeds and in joint bleeds in adults and with increased RICE utilization in children, as reported by caregivers. QoL scores were lower in adults compared with children, and further research is warranted to understand this difference. Future studies may focus on the effect of specialty pharmacy as an educational vehicle with potential cost benefits. 

The direct economic burden of blunt and penetrating trauma in a managed care population.

BACKGROUND: Although the prevalence of trauma in the United States is high, data on the economic burden of this public health problem to third-party payors is limited. METHODS: Retrospective claims from a large health plan were analyzed for 12,615 adults (age >or=18 years) hospitalized for blunt or penetrating trauma between January 1, 2003 and February 1, 2005. Per patient charges were estimated for resources utilized during a 6-month period before and after initial injury. Continuous health plan enrollment during these periods was required. Three cohorts were examined: isolated traumatic brain injury (TBI); other trauma with TBI (trauma w/TBI); and other trauma without TBI (trauma w/o TBI). Patients were also stratified by Injury Severity Score (ISS) and trauma designation of the admitting hospital. RESULTS: Initial hospitalization charges ranged from $32,627 for isolated TBI to $103,667 for trauma w/TBI. Charges for initial hospitalization were highest ($199,443) among patients with the most severe injuries. Overall, initial hospitalization charges were highest among those admitted to Level I trauma centers ($68,626); for trauma w/TBI, however, initial hospitalization charges were highest among those admitted to nontrauma centers ($130,997). Charges incurred during postdischarge medical encounters ranged from $16,361 for isolated TBI to $23,761 for trauma w/TBI. Increased charges for postdischarge encounters compared with the 6-month preinjury period ranged from $6,756 for isolated TBI to $19,771 for trauma w/TBI. CONCLUSIONS: The economic burden of blunt and penetrating trauma to third-party payors is high. Efforts to reduce the incidence of trauma may result in substantial economic savings to managed care systems.