Risk factors associated with invasive orthopaedic interventions in males with haemophilia enrolled in the Universal Data Collection program from 2000 to 2010.

BACKGROUND: Invasive orthopaedic interventions (IOI) are often used to control recurrent haemarthrosis, pain and loss of joint function, in males with haemophilia (Factor VIII and Factor IX deficiency). AIM: Identify risk factors associated with IOIs in males with haemophilia enrolled in the Universal Data Collection (UDC) surveillance program from 2000 until 2010. METHODS: Data were collected on IOIs performed on patients receiving care in 130 haemophilia treatment centers in the United States annually by health care providers using standardized forms. IOIs included in this study are as follows: 1) synovectomy and 2) arthrodesis or arthroplasty (A/A). Information about potential risk factors was obtained from the preceding UDC visit if available, or from the same visit if not. Patients with no reported IOI at any of their UDC visits were the reference group for the analysis. Multivariate analyses were conducted to identify independent risk factors for synovectomies and arthrodesis/arthroplasty. RESULTS: Risk factors significantly associated with the two IOI categories were age, student status, haemophilia severity, number of joint bleeds within the last 6 months, HIV or hepatitis C (HCV) status. Multivariate analyses showed patients on continuous prophylaxis were 50% less likely to have had a synovectomy and were 40% less likely to have an A/A. CONCLUSIONS: This study shows modifiable risk factors, including management of bleeding episodes with a continuous prophylactic treatment schedule are associated with a decreased likelihood of IOIs in males with haemophilia.

Measuring the quality of haemophilia care across different settings: a set of performance indicators derived from demographics data.

BACKGROUND: Haemophilia is a rare disease for which quality of care varies around the world. We propose data-driven indicators as surrogate measures for the provision of haemophilia care across countries and over time. MATERIALS AND METHODS: The guiding criteria for selection of possible indicators were ease of calculation and direct applicability to a wide range of countries with basic data collection capacities. General population epidemiological data and haemophilia A population data from the World Federation of Hemophilia (WFH) Annual Global Survey (AGS) for the years 2013 and 2010 in a sample of 10 countries were used for this pilot exercise. RESULTS: Three indicators were identified: (i) the percentage difference between the observed and the expected haemophilia A incidence, which would be close to null when all of the people with haemophilia A (PWHA) theoretically expected in a country would be known and reported to the AGS; (ii) the percentage of the total number of PWHA with severe disease; and (iii) the ratio of adults to children among PWHA standardized to the ratio of adults to children for males in the general population, which would be close to one if the survival of PWHA is equal to that of the general population. Country-specific values have been calculated for the 10 countries. CONCLUSIONS: We have identified and evaluated three promising indicators of quality of care in haemophilia. Further evaluation on a wider set of data from the AGS will be needed to confirm their value and further explore their measurement properties.

Prophylaxis use among males with haemophilia B in the United States.

INTRODUCTION: Prophylaxis is considered the optimal treatment for persons with moderate to severe haemophilia (factor activity between 1-5% of normal and <1% of normal respectively) in countries where safe factor concentrates are available and economically feasible. Historically, prophylactic treatment has not been well studied in the haemophilia B (HB) population due to difficulties in obtaining a sufficiently large sample. AIM: This study examines the prevalence of prophylaxis use among a robust sample of persons with HB in the United States and its association with specific demographic and clinical characteristics. METHODS: Using data collected between 1998 and 2011 for the Centers for Disease Control and Prevention's Universal Data Collection project, we analysed data on 2428 males with moderate to severe HB aged 2-79 years who were seen at 135 federally funded haemophilia treatment centres. RESULTS: Prevalence of prophylactic treatment in our sample was 35% among children and youth (ages 2-19) and 14% among adults (age 20 and older). Increased HB prophylaxis use was significantly associated with younger age (<40 years), Hispanic ethnicity, severe disease and self-infusion, while decreased use was associated with above-normal body mass index (BMI) in adults. Health care coverage was vital, although type of coverage did not appear to influence access. CONCLUSIONS: Our analysis confirms previous reports of lower prevalence of prophylaxis use among individuals with HB compared to those with haemophilia A and adds to the body of knowledge regarding treatment patterns among a historically understudied population.

The effects of joint disease, inhibitors and other complications on health-related quality of life among males with severe haemophilia A in the United States.

INTRODUCTION: Health-related quality of life (HRQoL) is reduced among persons with haemophilia. Little is known about how HRQoL varies with complications of haemophilia such as inhibitors and joint disease. Estimates of preference-based HRQoL measures are needed to model the cost-effectiveness of prevention strategies. AIM: We examined the characteristics of a national sample of persons with severe haemophilia A for associations with two preference-based measures of HRQoL. METHODS: We analysed utility weights converted from EuroQol 5 Dimensions (EQ-5D) and the Short Form 6 Dimensions (SF-6D) scores from 1859 males aged ≥14 years with severe haemophilia A treated at 135 US haemophilia treatment centres in 2005-2011. Bivariate and regression analyses examined age-group-specific associations of HRQoL with inhibitor status, overweight/obesity, number of bleeds, viral infections, indicators of liver and joint disease, and severe bleeding at the time of the first HRQoL measurement. RESULTS: Overall mean HRQoL utility weight values were 0.71 using the SF-6D and 0.78 using the EQ-5D. All studied patient characteristics except for overweight/obesity were significantly associated with HRQoL in bivariate analyses. In a multivariate analysis, only joint disease was significantly associated with utility weights from both HRQoL measures and across all age groups. After adjustment for joint disease and other variables, the presence of an inhibitor was not significantly associated with HRQoL scores from either of the standardized assessment tools. CONCLUSION: Clinically significant complications of haemophilia, especially joint disease, are strongly associated with HRQoL and should be accounted for in studies of preference-based health utilities for people with haemophilia.

Complications of haemophilia in babies (first two years of life): a report from the Centers for Disease Control and Prevention Universal Data Collection System.

AIM: To describe the prevalence and complications in babies ≤2 years with haemophilia. METHODS: We used a standardized collection tool to obtain consented data on eligible babies aged ≤2 years with haemophilia enrolled in the Centers for Disease Control and Prevention Universal Data Collection System surveillance project at US Hemophilia Treatment Centers (HTCs). RESULTS: Of 547 babies, 82% had haemophilia A, and 70% were diagnosed within one month of birth. Diagnosis was prompted by known maternal carrier status (40%), positive family history (23%), bleeding (35%) and unknown 2%; 81% bled during the first two years. The most common events were bleeding (circumcision, soft tissue, oral bleeding) and head injury. There were 46 episodes of intracranial haemorrhage (ICH) in 37 babies (7%): 18 spontaneous, 14 delivery related, 11 traumatic, 2 procedure related and 1 unknown cause. Of the 176 central venous access devices (CVADs) in 148 (27%) babies, there were 137 ports, 22 surgically inserted central catheters and 20 peripherally inserted central catheters. Ports had the lowest complication rates. Inhibitors occurred in 109 (20%) babies who experienced higher rates of ICH (14% vs. 5%; P = 0.002), CVAD placement (61% vs. 19%; P < 0.001) and CVAD complications (44% vs. 26%; P < 0.001). The most common replacement therapy was recombinant clotting factor concentrates. CONCLUSION: Bleeding events in haemophilic babies ≤2 years were common; no detectable difference in the rates of ICH by the mode of delivery was noted. Neonatal factor exposure did not affect the inhibitor rates. Minor head trauma, soft tissue and oropharyngeal bleeding were the leading indications for treatment.

Care models in the management of haemophilia: a systematic review.

BACKGROUND: Haemophilia care is commonly provided via multidisciplinary specialized management. To date, there has been no systematic assessment of the impact of haemophilia care delivery models on patient-important outcomes. OBJECTIVE: To conduct a systematic review of published studies assessing the effects of the integrated care model for persons with haemophilia (PWH). SEARCH METHODS: We searched MEDLINE, EMBASE and CINAHL up to April 22, 2015, contacted experts in the field, and reviewed reference lists. SELECTION CRITERIA: Randomized and non-randomized studies of PWH or carriers, focusing mainly on the assessment of care models on delivery. DATA COLLECTION AND ANALYSIS: Two investigators independently screened title, abstract, and full text of retrieved articles for inclusion. Risk of bias and overall quality of evidence was assessed using Cochrane's ACROBAT-NRSI tool and GRADE respectively. Relative risks, mean differences, proportions, and means and their variability were calculated as appropriate. RESULTS: 27 non-randomized studies were included: eight comparative and 19 non-comparative studies. We found low- to very low-quality evidence that in comparison to other models of care, integrated care may reduce mortality, hospitalizations and emergency room visits, may lead to fewer missed days of school and work, and may increase knowledge seeking. CONCLUSION: Our comprehensive review found low- to very low-quality evidence from a limited number of non-randomized studies assessing the impact of haemophilia care models on some patient-important outcomes. While the available evidence suggests that adoption of the integrated care model may provide benefit to PWH, further high-quality research in the field is needed.

NHF-McMaster Guideline on Care Models for Haemophilia Management.

This guideline was developed to identify evidence-based best practices in haemophilia care delivery, and discuss the range of care providers and services that are most important to optimize outcomes for persons with haemophilia (PWH) across the United States. The guideline was developed following specific methods described in detail in this supplement and based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluation approach). Direct evidence from published literature and the haemophilia community, as well as indirect evidence from other chronic diseases, were reviewed, synthesized and applied to create evidence-based recommendations. The Guideline panel suggests that the integrated care model be used over non-integrated care models for PWH (conditional recommendation, moderate certainty in the evidence). For PWH with inhibitors and those at high risk for inhibitor development, the same recommendation was graded as strong, with moderate certainty in the evidence. The panel suggests that a haematologist, a specialized haemophilia nurse, a physical therapist, a social worker and round-the-clock access to a specialized coagulation laboratory be part of the integrated care team, over an integrated care team that does not include all of these components (conditional recommendation, very low certainty in the evidence). Based on available evidence, the integrated model of care in its current structure, is suggested for optimal care of PWH. There is a need for further appropriately designed studies that address unanswered questions about specific outcomes and the optimal structure of the integrated care delivery model in haemophilia.

Hepatitis B vaccination is effective by subcutaneous route in children with bleeding disorders: a universal data collection database analysis.

Subcutaneous (SQ) vs. intramuscular (IM) vaccination may cause fewer injection site complications in children with bleeding disorders, but little is known about comparative immunogenicity. To compare immunogenicity of hepatitis B virus (HBV) vaccination administered SQ or IM to individuals <2 years old with bleeding disorders, we performed a retrospective analysis of HBV surface antibody titres among patients enrolled in the universal data collection database who had received three doses of HBV vaccine solely by one route (SQ or IM). Data reviewed were from an initial visit before 24 months of age, until time of hepatitis antibody titre testing. The SQ and IM study groups did not differ in demographics, haemophilia type or severity or bleeding history. The mean age at the time of HBV surface antibody (anti-HBs) testing was 56.9 ± 20.3 months. Eighty-five of 92 subjects (92.4%) who received vaccine SQ developed a positive antibody titre (>12 IU/L), compared to 101/114 (88.6%) who received IM (P = 0.30). There was no statistically significant difference in distribution of titre values. The average age of the subjects at time of testing was 53 ± 20 months in the SQ group vs. 60 ± 20 months in the IM group (P = 0.02). The average time between the last dose of vaccine and anti-HBs testing was 47.6 ± 18.5 months among SQ vaccinated subjects vs. 51.6 ± 20.5 months in the IM group (P = 0.2). Immunogenicity to hepatitis B vaccination by the SQ and IM routes is similar.

Association of overweight and obesity with the use of self and home-based infusion therapy among haemophilic men.

An elevated body mass index (BMI) may make venipuncture more difficult, potentially impacting the use of home infusion (HI) and self-infusion (SI). We sought to determine whether above-normal BMI is associated with decreased use of HI treatment and SI of clotting factor concentrate among haemophilic persons. We analysed data from 10,814 male patients with haemophilia A and B (45% with severe disease) aged 6-79 years enrolled in the Centers for Disease Control and Prevention Universal Data Collection surveillance project between 1998 and 2008. Associations between the use of HI and SI and BMI were evaluated using logistic regression. Fifty per cent of haemophilic men were overweight or obese, similar to rates reported among the general US population by the 2007-2008 National Health and Nutrition Examination Survey [Flegal, KM et al., JAMA 2010;303:235-241;]. Twenty per cent of children and 22% of teens were obese, as were 28% of adults [Ogden, CL et al., JAMA 2010;303:235, 242]. Overall, 70% of the study sample used HI; 44% of those who used HI also used SI. Overweight and obese men were each less likely to use HI than those of normal weight [odds ratio (OR) 0.8; 95% confidence interval (CI) 0.7-1.0 and OR 0.7; 95% CI 0.6-0.8 respectively]. Obese teens and adult men were also less likely to practice SI than teens and adults of normal weight (OR 0.8; 95% CI 0.7-0.9 for each). We conclude that overweight and obese haemophilic men are less likely to use HI and obese men are less likely to use SI than their normal-weight counterparts.

Prevalent inhibitors in haemophilia B subjects enrolled in the Universal Data Collection database.

Several risk factors for inhibitors have recently been described for haemophilia A. It has been assumed that similar risk factors are also relevant for haemophilia B, but there is limited data to confirm this notion. The aim of this study was to determine the prevalence of and risk factors associated with inhibitors in haemophilia B. The database of the Universal Data Collection (UDC) project of the Centers for Disease Control for the years 1998-2011 was queried to determine the prevalence of inhibitors in haemophilia B subjects. In addition, disease severity, race/ethnicity, age, factor exposure and prophylaxis usage were evaluated to determine their impact on inhibitor prevalence. Of the 3785 male subjects with haemophilia B enrolled in the UDC database, 75 (2%) were determined to have an inhibitor at some point during the study period. Severe disease (OR 13.1, 95% CI 6.2-27.7), black race (OR 2.2, 95% CI 1.2-4.1), and age <11 years (OR 2.5, 95% CI 1.5-4.0) were found to be significantly associated with having an inhibitor. There was insufficient data to determine if type of factor used and prophylaxis were associated with inhibitors. Inhibitors in haemophilia B are much less prevalent than haemophilia A, especially in patients with mild disease. Similar factors associated with inhibitors in haemophilia A also seem to be present for haemophilia B. The information collected by this large surveillance project did not permit evaluation of potential risk factors related to treatment approaches and exposures, and additional studies will be required.

A study of prospective surveillance for inhibitors among persons with haemophilia in the United States.

Inhibitors are a rare but serious complication of treatment of patients with haemophilia. Phase III clinical trials enrol too few patients to adequately assess new product inhibitor risk. This project explores the feasibility of using a public health surveillance system to conduct national surveillance for inhibitors. Staff at 17 U.S. haemophilia treatment centres (HTC) enrolled patients with haemophilia A and B into this prospective study. HTC staff provided detailed historic data on product use and inhibitors at baseline, and postenrolment patients provided monthly detailed infusion logs. A central laboratory performed inhibitor tests on blood specimens that were collected at baseline, annually, prior to any planned product switch or when clinically indicated. The central laboratory also performed genotyping of all enrolled patients. From January 2006 through June 2012, 1163 patients were enrolled and followed up for 3329 person-years. A total of 3048 inhibitor tests were performed and 23 new factor VIII inhibitors were identified, 61% of which were not clinically apparent. Infusion logs were submitted for 113,205 exposure days. Genotyping revealed 431 distinct mutations causing haemophilia, 151 of which had not previously been reported elsewhere in the world. This study provided critical information about the practical issues that must be addressed to successfully implement national inhibitor surveillance. Centralized testing with routine monitoring and confirmation of locally identified inhibitors will provide valid and representative data with which to evaluate inhibitor incidence and prevalence, monitor trends in occurrence rates and identify potential inhibitor outbreaks associated with products.

Similarity in joint function limitation in Type 3 von Willebrand's disease and moderate haemophilia A.

Type 3 von Willebrand's disease (VWD) is a rare bleeding diathesis with complete or near complete deficiency of von Willebrand factor (VWF) and low factor VIII (FVIII) levels. In contrast, only FVIII is decreased in haemophilia A (HA). Both disorders are complicated by arthropathy. The purpose of this study was to further clarify the roles of FVIII and VWF: Antigen (VWF:Ag) in joint range of motion (ROM) loss over time. We compared joint ROM loss and other bleeding manifestations in 100 Type 3 VWD subjects (FVIII<5%) and 1814 moderate HA subjects (FVIII 1-5%) within the U.S. Universal Data Collection (UDC) database. High rates of bleeding were reported at baseline. During follow-up, moderate HA patients reported a joint (46% vs. 34%, P < 0.0001) or muscle bleed (27% vs. 16%, P < 0.0001) in a higher proportion of visits than VWD patients. Other bleeds, including mucosal, were reported in a greater proportion of visits among patients with Type 3 VWD than among those with HA (49% vs. 32%, P < 0.0001). Multivariate analysis revealed no difference in joint ROM loss over time in the Type 3 VWD vs. moderate HA populations. A higher FVIII level was protective in both VWD and HA (P < 0.001). Our findings support the hypothesis of primacy of the FVIII level in determining risk of joint haemorrhage, and may help target therapy in Type 3 VWD and moderate HA to prevent joint disability.

Health care expenditures for Medicaid-covered males with haemophilia in the United States, 2008.

Although haemophilia is an expensive disorder, no studies have estimated health care costs for Americans with haemophilia enrolled in Medicaid as distinct from those with employer-sponsored insurance (ESI). The objective of this study is to provide information on health care utilization and expenditures for publicly insured people with haemophilia in the United States in comparison with people with haemophilia who have ESI. Data from the MarketScan Medicaid Multi-State, Commercial and Medicare Supplemental databases were used for the period 2004-2008 to identify cases of haemophilia and to estimate medical expenditures during 2008. A total of 511 Medicaid-enrolled males with haemophilia were identified, 435 of whom were enrolled in Medicaid for at least 11 months during 2008. Most people with haemophilia qualified for Medicaid based on 'disability'. Average Medicaid expenditures in 2008 were $142,987 [median, $46,737], similar to findings for people with ESI. Average costs for males with haemophilia A and an inhibitor were 3.6 times higher than those for individuals without an inhibitor. Average costs for 56 adult Medicaid enrollees with HCV or HIV infection were not statistically different from those for adults without the infection, but median costs were 1.6 times higher for those treated for blood-borne infections. Haemophilia treatment can lead to high costs for payers. Further research is needed to understand the effects of public health insurance on haemophilia care and expenditures, to evaluate treatment strategies and to implement strategies that may improve outcomes and reduce costs of care.

Healthcare expenditures for males with haemophilia and employer-sponsored insurance in the United States, 2008.

Although hemophilia has a potentially high economic impact, published estimates of health care costs for Americans with hemophilia are sparse and non-specific as to the non-bleeding complications of the disease. The objective of this study is to estimate average annual health care expenditures for people with hemophilia covered by employer-sponsored insurance, stratified according to the influence of age, type of hemophilia [A (factor VIII deficiency) versus B (factor IX)], presence of neutralizing alloantibody inhibitors and exposure to blood-borne viral infections. Data from the MarketScan Commercial and Medicare Research Databases were used for the period 2002-2008 to identify cases of hemophilia and to estimate mean and median medical expenditures during 2008. A total of 1,164 males with hemophilia were identified with continuous enrollment during 2008, 933 with hemophilia A and 231 with hemophilia B. Mean health care expenditures were $155,136 [median $73,548]. Mean costs for 30 (3%) males with an inhibitor were 5 times higher than for males without an inhibitor, approximately $697,000 [median $330,835] and $144,000 [median $73,321], respectively. Clotting factor concentrate accounted for 70%-82% of total costs. Average costs for 207 adults with HCV or HIV infection were 1.5 times higher than those for adults without infection. Hemophilia treatment is costly, particularly for individuals with neutralizing alloantibody inhibitors who require bypassing agents. Efforts to understand the cause of inhibitors are needed so that prevention strategies can be implemented and the excess costs resulting from this serious complication of hemophilia care can be avoided.

F8 and F9 mutations in US haemophilia patients: correlation with history of inhibitor and race/ethnicity.

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.

The longitudinal effect of body adiposity on joint mobility in young males with Haemophilia A.

Although body adiposity and disease severity in haemophilia have been found in cross-sectional studies to be negatively associated with joint mobility, it is not clear how these two factors affect the rate of joint mobility loss over time. Over a 10-year period, repeated measures of joint range of motion (ROM) were collected annually using universal goniometers on bilateral hip, knee, ankle, shoulder and elbow joints in 6131 young males with haemophilia A aged ≤ 20 years. Body mass index (BMI) was calculated using data on weight and height during follow up. The effect of body adiposity, adjusted for disease severity, on the rate of joint mobility loss over time was assessed using a longitudinal model. Compared with haemophilia males with normal BMI, those who were obese had lower ROM at initial visit and a faster rate of joint mobility loss in the lower limbs. Overweight subjects experienced similar loss in ROM, although to a lesser degree. A decline in ROM with age was also observed in upper limb joints but the rate was not significantly affected by body adiposity. Haemophilia severity, joint bleeding and the presence of an inhibitor were other significant contributors to joint mobility loss in both upper and lower limb joints. Excess body adiposity accelerates joint mobility loss in weight bearing joints particularly among those with severe haemophilia. Our findings suggest that body weight control and effective treatment of bleeds should be implemented together to achieve better joint ROM outcomes in males with haemophilia.

Prevalence and risk factors of cardiovascular disease (CVD) events among patients with haemophilia: experience of a single haemophilia treatment centre in the United States (US).

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.

Range of motion measurements: reference values and a database for comparison studies.

Many diseases and injuries can impair joint mobility. Normal reference values are needed to determine extent of impairment to assess and monitor joint motion. There is very little published data describing normal joint range of motion (ROM) for healthy men and women across a wide span of ages. We enrolled male and female subjects aged between 2 and 69 years who were free from conditions that could potentially limit joint mobility for the study. Nine licensed physical therapists used universal goniometers to determine passive joint motion bilaterally of elbow flexion, extension, supination and pronation, shoulder flexion, hip flexion and extension, knee flexion and extension, and ankle dorsiflexion and plantarflexion. Descriptive statistics were calculated for male and female subjects in four age groups: 2-8, 9-19, 20-44 and 45-69 years. Joint ROM measurements were obtained on a total of 674 (53.6% female) healthy, normal subjects aged 2-69 years. Female subjects had greater joint mobility in all age groups in nearly all joints and the gender difference was most obvious in measures of ankle plantarflexion, elbow pronation and supination. Range of motion average values for all joints decreased with advancing age for both men and women and, in most cases, were significantly different than most commonly used normative values. Our study of ROM measurements taken by trained physical therapists on a large sample of healthy individuals revealed significant gender- and age-related variation that may be an important consideration in patient assessment.

Surveillance of female patients with inherited bleeding disorders in United States Haemophilia Treatment Centres.

Inherited bleeding disorders are especially problematic for affected girls and women due to the monthly occurrence of menstrual periods and the effects on reproductive health. Although heavy menstrual bleeding (HMB) is the most common manifestation, females with inherited bleeding disorders (FBD) experience other bleeding symptoms throughout the lifespan that can lead to increased morbidity and impairment of daily activities. The purpose of this article is to describe the utility of a female-focused surveillance effort [female Universal Data Collection (UDC) project] in the United States Haemophilia Treatment Centres (HTCs) and to describe the baseline frequency and spectrum of diagnoses and outcomes. All FBD aged 2 years and older receiving care at selected HTCs were eligible for enrollment. Demographic data, diagnoses and historical data regarding bleeding symptoms, treatments, gynaecological abnormalities and obstetrical outcomes were analysed. Analyses represent data collected from 2009 to 2010. The most frequent diagnoses were type 1 von Willebrand's disease (VWD) (195/319; 61.1%), VWD type unknown (49/319; 15.4%) and factor VIII deficiency (40/319; 12.5%). HMB was the most common bleeding symptom (198/253; 78.3%); however, 157 (49.2%) participants reported greater than four symptoms. Oral contraceptives were used most frequently to treat HMB (90/165; 54.5%), followed by desmopressin [1-8 deamino-D-arginine vasopressin (DDAVP)] (56/165; 33.9%). Various pregnancy and childbirth complications were reported, including bleeding during miscarriage (33/43; 76.7%) and postpartum haemorrhage (PPH) (41/109; 37.6%). FBD experience multiple bleeding symptoms and obstetrical-gynaecological morbidity. The female UDC is the first prospective, longitudinal surveillance in the US focusing on FBD and has the potential to further identify complications and reduce adverse outcomes in this population.