Haemophilia in Spain

Summary.  . To determine the prevalence of haemophilia A and B and their complications in Spain, and to characterize the health care network providing support to haemophiliac patients. The study examines clinical and genetic characteristics, treatment options, and complications observed during the course of the disease. Cross-sectional multi-centre study. The study population were patients with HA and HB in active follow-up at any Spanish hospital by December 2006. We studied 2400 haemophiliacs, 2081 (86.7%) HA and 319 (13.3%) HB patients. Illness was severe in 32.3% of patients, moderate in 16.4%, and mild in 51.3%. Genetic screening was carried out in 32.6% of the patients. Treatment administered in 2006 consisted of coagulation factor concentrates in 60% of patients. Until December 2006, 45.8% of severely ill patients were taking prophylaxis. The mean number of bleeding episodes in 2006 was four for patients not receiving primary prophylaxis and 1.3 for those taking primary prophylaxis. Thirty percent of patients had established haemophiliac arthropathy in at least one joint; 16.8% of patients were HIV-infected and 34.8% HCV-infected. Inhibitors were detected in 10% of severe HA patients and in 6.5% of severe HB patients. Immune tolerance induction therapy was started in 34 patients. This is the first comprehensive study on the epidemiology of haemophilia in Spain. It will enable us to draw comparisons with neighbouring countries, to assess the quality of care provided to haemophiliacs in Spain, and to provide evidence-based guidance for the even provision and improvement of such care.     

Real‐world comparative analysis of bleeding complications and health‐related quality of life in patients with haemophilia A and haemophilia B

Introduction

Clinical severity and impact of haemophilia on quality of life have been generally considered to be lower for haemophilia B (HB) compared with haemophilia A (HA) patients.

Aims

To compare annual bleeding rate (ABR), target joint development and health‐related quality of life (HRQoL) between adult (≥18 years) severe HA and HB patients using recent data from the Cost of Haemophilia in Europe: a Socioeconomic Survey (CHESS) study.

Methods

Multivariate generalized linear models (GLM) were constructed to assess the relationship between haemophilia type, ABR, HRQoL (derived from EQ‐5D index scores) and the presence of target joints while controlling for covariates.

Results

Of the 1225 patients included, 77% (n = 949) had HA and 23% (n = 278) had HB. Of the 514 patients who completed the EQ‐5D, 78% (n = 405) had HA, and 22% (n = 110) had HB. Unadjusted mean ABR was 3.79 in HA and 4.60 in HB. The presence of ≥1 target joint was reported in 59% and 54% of patients with HA and HB, respectively. Unadjusted mean EQ‐5D index score was 0.78 in HA and 0.76 in HB. Haemophilia type was not a significant predictor of ABR, target joints or HRQoL when adjusted for confounding factors such as BMI, age and replacement therapy regimen.

Conclusion

Data suggest comparable ABR, incidence of target joints and HRQoL between patients with HB and HA indicating comparable clinical severity and disease impact on patient quality of life.     

A study of variations in the reported haemophilia B prevalence around the world

Summary. The objectives of this article were to study the reported prevalence of haemophilia B (HB) on a country‐by‐country basis and to analyse whether the prevalence of HB varied by national economy. The prevalence of HB is the proportion of diagnosed, reported cases of HB in a population at a specific point of time. We collected data on the HB prevalence for 105 countries from the World Federation of Hemophilia annual global surveys. Our results showed that the HB prevalence varied considerably among countries, even among the wealthiest of countries. The HB prevalence (per 100 000 males) for the highest income countries was 2.69 ± 1.61 (mean ± SD), whereas the prevalence for the rest of the world was 1.20 ± 1.33 (mean ± SD). Ireland had the highest reported HB prevalence of 8.07 per 100 000 males. There was a strong trend of increasing HB prevalence (per 100 000 males) over time. Prevalence data reported from the WFH compared well with prevalence data from the literature. The WFH annual global surveys have some limitations, but they are the best available source of worldwide haemophilia data. Prevalence data are extremely valuable information for the planning efforts of national healthcare agencies in setting priorities and allocating resources for the treatment of HB.     

Increased cancer risk in patients with haemophilia A: a nationwide population‐based 14‐year study in Taiwan

Haemostasis is associated with the development and dissemination of cancer. Whether cancer incidence is increased in haemophiliacs remains uncertain; thus, we aimed to further examine this issue. By using data from the National Health Insurance Research Database in Taiwan, we obtained a cohort of 683 patients with haemophilia A, and compared the incidence rate ratio (IRR) of cancer in this cohort with an age‐ and sex‐matched control of 6830 patients. The log‐rank test was used to compare Kaplan–Meier curve of the cumulative cancer incidence between two cohorts. Cox regressions were used to identify independent risk factors of cancer in the study patients. The cancer incidence of patients with haemophilia A was significantly higher compared to the control group (IRR 1.95, 95% CI 1.18–3.09, P = 0.008) during the 14‐year follow‐up period. The non‐lymphoma and non‐liver cancer incidence in the haemophilia A cohort remained higher than that of the matched control (P = 0.050 by the log‐rank test). The multivariate Cox proportional hazards analysis indicated that age (per year, HR 1.09, 95% CI 1.06–1.12, P < 0.001) was the only significant risk factor for cancer development in haemophilia patients. Patients with haemophilia A had higher cancer incidence than the age‐ and sex‐matched patients, especially for the elderly. With increasing life expectancy for haemophiliacs, physicians should be aware of their cancer development.     

Epidemiology,Clinical Features,and Prescribing Patterns of Aortic Aneurysm in Asian Population From 2005 to 2011

Aortic aneurysm (AA) is a leading cause of death in Asia and the world. The prevalence in Western countries is around 1.3% to 8%. However, it is still unclear about the incidence, prevalence, and mortality of AA in Asian population. The aim of this study is to investigate the epidemiology of AA for all subtypes in Taiwan, and describe the clinical features and prescribing patterns for AA population.A population-based study was conducted using information from National Health Insurance Research Database (NHIRD) in Taiwan. Patients who were diagnosed with AA and also received computed tomography (CT) were included in this study. Incidence, prevalence, and mortality were calculated in each year during 2005 to 2011. Prevalent comorbidities and prescribing patterns were both evaluated among study population.The average annual incidence of AA in Taiwan was 7.35 per 100,000 population, and the prevalence was 29.04 per 100,000 population. It showed an increased trend of incidence from 2005 to 2011, so as prevalence and mortality. The incidence was associated with age and sex difference. It was much higher in those older than 65 years, especially for male. Hypertension, coronary artery disease (CAD), and chronic obstructive pulmonary disease (COPD) were prevalent comorbidities. Eighty-eight percentages of patients were prescribed antihypertensive agents in acute phase, where 61.4% of calcium channel blocker (CCB) was the most one.Our study found that incidence of AA was lower in Taiwan than in other countries. Nevertheless, it showed an increased trend of AA disease for incidence, prevalence, and also mortality during 2005 to 2011.     

Systematic review of the epidemiology of systemic lupus erythematosus in the Asia-Pacific region: prevalence, incidence, clinical features, and mortality

Objective

Systemic lupus erythematosus (SLE), a chronic multisystem autoimmune disease with a wide spectrum of manifestations, shows considerable variation across the globe, although there is little evidence to indicate its relative prevalence in Asia. This review describes its prevalence, severity, and outcome across countries in the Asia‐Pacific region.

Methods

We conducted a systematic literature search using 3 groups of terms (SLE, epidemiology, and Asia‐Pacific countries) of EMBase and PubMed databases and non–English language resources, including Chinese Wanfang, Korean KMbase, Korean College of Rheumatology, Japana Centra Revuo Medicina, Taiwan National Digital Library of Theses and Dissertations, and Taiwanese, Thai, and Vietnamese journals.

Results

The review showed considerable variation in SLE burden and survival rates across Asia‐Pacific countries. Overall crude incidence rates (per 100,000 per year) ranged from 0.9–3.1, while crude prevalence rates ranged from 4.3–45.3 (per 100,000). Higher rates of renal involvement, one of the main systems involved at death, were observed for Asians (21–65% at diagnosis and 40–82% over time) than for whites. While infections and active SLE were leading causes of death, a substantial proportion (6–40%) of deaths was due to cardiovascular involvement. The correlation between the Human Development Index and 5‐year survival was 0.83.

Conclusion

This review highlights the need to closely monitor Asian SLE patients in Asian countries for renal and cardiovascular involvement, especially those who may not receive proper treatment and are therefore at greater risk of severe disease. We hope this will encourage further research specific to this region and lead to improved clinical management.     

Secondary prophylaxis treatment versus on‐demand treatment for patients with severe haemophilia A: comparisons of cost and outcomes in Taiwan

Summary. This study compared secondary prophylaxis treatment with on‐demand treatment for severe haemophilia A in Taiwan. Fifty patients from one medical centre were evaluated over a 5‐year period. Differences in annual bleed rates and factor VIII (FVIII) utilization were assessed between patients receiving secondary prophylaxis and patients receiving FVIII concentrates on‐demand. Results were then used as inputs in a pharmacoeconomic model to predict outcomes of future haemophilia therapy strategies in Taiwan. The median annual number of total bleeding episodes was significantly lower in the 13 (26%) patients who received secondary prophylaxis than in the 37 patients who received FVIII on‐demand (7.76 vs. 31.91, P < 0.0001). The between‐group difference in median annual factor VIII utilization was statistically significant (1824.41 IU kg^?1 for the prophylaxis group and 1324.81 IU kg^?1 for the on‐demand group, P < 0.01). It was estimated that approximately $2 million (USD) per year would be added to the cost of treatment by having all severe haemophilia A patients in Taiwan receive secondary prophylaxis instead of on‐demand therapy while 12 566 bleeding will be prevented. It is recommended that National Health Insurance officials utilize these data to evaluate the benefits of enhanced treatment strategies and before making substantial policy changes to haemophilia care in Taiwan.     

Haemophilia care in central Scotland 1980–94. I. Demographic characteristics, hospital admissions and causes of death

To estimate the resources required to manage patients with haemophilia in Scotland, we studied the demographic features, hospital admissions and causes of deaths for individuals with haemophilia A and B and von Willebrand disease, treated with blood products, during the period 1980-94 living in central Scotland. Data were obtained from 413 adults and children (93% ascertainment). The age distribution in 1980 revealed a paucity of individuals over 60 years but the number in this age group increased over the study period. Of those with haemophilia A and B, 63 and two respectively, became HIV positive. Hospital admissions rose from 103 to 168 per annum; the number of annual bed days utilized also increased, but there was marked annual fluctuation (790-1832). The rate of admission was greater for those with severe haemophilia A and this increased during the 15-year period mainly due to the clinical consequences of human immunodeficiency virus (HIV) and hepatitis C virus (HCV). The admission rate for haemophilia B was significantly lower than that for haemophilia A, and was similar for all degrees of severity of the disorder. Throughout the 15-year period the incidence of admissions for acute bleeds was constant, as was the average duration in hospital. For those with a factor VIII inhibitor, the rate of admission was about double the rate of those without an inhibitor, although the duration of hospital stay was similar for both groups. There were 61 deaths; the death rate increased during the study period principally due to HIV and HCV, and 12 patients died from haemorrhage. We conclude that: (i) the life expectancy for haemophiliacs in Scotland was generally increasing, although HIV and HCV caused increasing mortality and morbidity (as shown by the increase in hospital admissions); (ii) hospital bed usage for the treatment of acute bleeds continued to be required, but fluctuated greatly; and (iii) the clinical impression that haemophilia B is less clinically severe than haemophilia A is confirmed by objective data. The planning implications for haemophilia care in Scotland and similar countries are discussed.     

Trends in COPD mortality and hospitalizations in countries and regions of Asia-Pacific

Background and objective: The growing burden of COPD in the Asia‐Pacific region supports the need for more intensive research and analysis of the epidemiology of COPD to raise awareness of the disease and its causes, to ensure the development of effective national health policies and to facilitate equitable deployment of finite health‐care resources in the prevention and management of COPD. This study estimated and compared COPD mortality and hospital morbidity rates and trends in these rates over time across countries and regions of Asia‐Pacific. Methods: Data consistent with standard definitions of COPD (ICD‐9/ICD‐10) for the period 1991–2004 were obtained from national health statistics agencies. For countries/regions with complete national mortality and hospitalization data (Australia, Pacific Canada (British Columbia, Hong Kong, South Korea and Taiwan), annual age‐standardized mortality and hospitalization rates were calculated for men and women aged ≥ 40 years. Negative binomial regression modelling was used to estimate rate ratios for country/region, gender and age differences and general trends over time. Results: Mortality rates per 10 000 population ranged 6.4–9.2 in men, 2.1–3.5 in women and 3.7–5.3 overall in 2003. Corresponding ranges for morbidity were 32.6–334.7, 21.2–129 and 28.1–207.3 per 10 000. Trend analysis of data since 1997 produced annual percentage changes in mortality versus hospitalization of ?4.4% versus ?0.7% in Australia, ?3.6% versus 7.5% in Pacific Canada (British Columbia), ?7.15% versus ?5.6% in Hong Kong and ?2.9% versus ?4.2% in Taiwan. Conclusions: In Asia‐Pacific, overall mortality and morbidity rates are high and trends in mortality and morbidity vary between countries/regions. Differences in rates and trends for men and women most likely reflect the different trends in historical and prevalent smoking profiles for COPD in the different countries and regions.     

Life expectancy of Swedish haemophiliacs, 1831–1980

Life expectancy of Swedish haemophiliacs has been estimated for the period 1831-1980. The data were derived from 948 haemophiliacs of whom 580 survived throughout 1980. Applying standard demographic techniques, median life expectancy of patients with severe haemophilia was found to have increased fivefold, from a mere 11 years during the period 1831-1920 to 56.8 years during 1961-80. The corresponding estimates for patients with moderate haemophilia were 27.5 and 71.5 years, respectively. The limited data on patients with mild haemophilia did not indicate any significant improvements in mortality. From the beginning of this century to 1980 median life expectancy for Swedish males increased from 61.7 years to 75.6 years, an increase of 23%. Analysing the last 12 years of the study (1969-80), death rates for patients with severe haemophilia below the age of 45 were not much different from those of Swedish males in the population as a whole. The investigation implies that the mortality of haemophiliacs in Sweden is approaching that of the total male population.     

Epidemiological features of biliary atresia in Taiwan, a national study 1996-2003

Background and Aim: The incidence of biliary atresia (BA) varies among different countries. It is supposed to be higher in Asian countries than in Western countries; however, the incidence of BA in Taiwan has not been well investigated. The aim of this study was to analyze the epidemiological characteristics and the incidence of BA in Taiwan. Methods: National Health Insurance (NHI) was implemented in Taiwan in 1995, and covers most of the population (>99%). We use the NHI database to investigate the epidemiological features of BA and compare Taiwan's annual BA incidence with that of other countries. Results: We identified 327 new BA cases during the period from 1996 to 2003. The overall incidence of BA was 1.46 cases per 10 000 live births (0.89–1.90 per 10 000). The estimation was 1.32–1.65 per 10 000 after adjustment for the misdiagnosis rate. The peak incidence occurred in 2002 (1.90 per 10 000), accompanying Taiwan's dengue fever epidemic in 2002. The 5‐year overall survival rate during 1999–2003 was higher than that during 1996–1998 (74.8% vs 61.1%, P = 0.014). Conclusion: Taiwan has the second‐highest incidence of BA reported in world literature. Viral infection outbreaks remain a potential candidate as a cause of BA. The management of BA has been improving, with a better 5‐year overall survival rate.     

Intracranial haemorrhage in the Italian population of haemophilia patients with and without inhibitors

Summary. Intracranial haemorrhage (ICH) is the most serious bleeding symptom in haemophiliacs, resulting in high rates of mortality and disabling sequelae. The Association of Italian Haemophilia Centres carried out a retrospective survey (1987–2008) of ICH occurring in haemophiliacs with the goals to establish: (i) incidence, location of bleeding, death rate and disabling sequels; (ii) risk factors for ICH; and (iii) treatment used during the acute phase of ICH and for recurrence prevention. A total of 112 ICH episodes had occurred in 88 patients (78 haemophilia A, 10 haemophilia B), 24 of whom experienced recurrences. The cumulative hazard of ICH for the whole cohort over the entire follow‐up period was 26.7 per 1000 patients, and the annualized rate of ICH was 2.50 events per 1000 patients (95% CI 1.90–3.31). The risk of ICH was higher in the youngest children (24.4 per 1000, 95% CI 12.7–47.0 in the first year of age and 14.9, 95% CI 7.1–31.4 in the second year of age) and then progressively rose again after the age of 40. Univariate, bivariate (age‐adjusted) and multivariate analysis investigating the effects of patient characteristics on ICH occurrence showed that haemophilia severity and inhibitor status were strongly associated with ICH [severe vs. mild, HR 3.96 (2.39–6.57); inhibitor vs. non‐inhibitor 2.52 (1.46–4.35)]. HCV infection was also associated with the risk of ICH [HR 1.83 (1.25–2.69)]. Therapeutic suggestions based upon our experience to control ICH recurrence are provided.     

The impact of a specific aqua-training for adult haemophilic patients - results of the WATERCISE study (WAT-QoL)

Summary. Sport is increasingly recommended for haemophilic patients due to physical and psychological benefits. ‘WATERCISE’ is a specific aqua‐training programme for haemophiliacs in which endurance, strength, coordination and mobility are trained. In the WAT‐QoL study benefits and risks of regular WATERCISE training sessions were investigated in terms of health‐related quality of life (HRQoL), physical functioning (PF), orthopaedic joint status (OJS), bleeding frequency and factor consumption. Patients in the WATERCISE group attended an aqua‐training programme once a week for 1 h over 12 months, patients in the control group did not. Patients were matched for clinical and demographic data. Information on clinical data, orthopaedic status, PF (HEP‐Test‐Q) and HRQoL were collected in both groups at baseline and at follow‐up (6 and 12 months). Twenty‐eight adult severely affected haemophilic patients (WATERCISE group: 10 haemophilia A (HA), 3 haemophilia B (HB) patients; control group: 12 HA and 3 HB patients) were enrolled (aged 40.68 ± 12.7 years). Baseline data (body mass indices, OJS, sportive activities, HRQoL and PF) were well distributed between groups. After 12 months the WATERCISE group reported a significantly better PF (M_W = 65.22, SD = 11.3; M_C = 52.5, SD = 15.0), especially for endurance (P < 0.004). Although always differently reported by the patients within the WATERCISE group, HRQoL did not prove to be significantly different between groups. WATERCISE seems to have a positive effect on the PF of patients suffering from haemophilia. These study findings need to be further investigated in a larger study group.     

Haemophilia care in South Africa: 2004–2007 look back

Summary.  The South African national haemophilia program (NHP) was officially recognized in 2000 and implemented by the National Department of Health (NDOH), haemophilia specialists of the Medical and Scientific Advisory Council (MASAC) and the South African Haemophilia Foundation (SAHF). This study aims to report on progress and challenges of haemophilia care in SA after implementation of the NHP. Haemophilia care data collected by MASAC from all treatment centres (HTCs) from 2004 to 2007 were reviewed and appraised. Data assessment included evaluation of the number and types of professional haemophilia expertise, diagnostic and human resources available, number and types of HTCs, number and types of haemophilia diagnoses, immunological complications of haemophilia, social, medical and surgical interventions, factor usage and reporting on haemophilia mortality. Over 2200 bleeding diathesis patients in SA were cared for by an average of 79 professionals in 17 HTCs. Fifty-nine per cent were haemophilia A, 21% von Willebrand's disease, 12% haemophilia B and the remainder had rare bleeding diathesis and thrombocytopathies. In 2004–2007, the number of haemophilia professionals stayed the same, clinic visits increased, new patients and inhibitor patients also increased. Surgical and medical interventions were unchanged and per capita factor usage increased from 0.65 to 0.95. National mortality rate remained below 10 deaths per year. Haemophilia care in SA is highly organized and effective in the delivery of haemophilia health services. All diagnosed uncomplicated haemophiliacs have access to state funded factor concentrate. Limited human and diagnostic resources remain major challenges.     

The prevalence of factor VIII inhibitors and genetic aspects of inhibitor development in Chinese patients with haemophilia A

Summary. The prevalence of inhibitors in Chinese haemophiliacs has not yet been reported. The aim of this study was to identify the prevalence of factor VIII (FVIII) inhibitors among haemophiliacs who are treated only with plasma‐derived FVIII (pdFVIII), cryoprecipitate or fresh frozen plasma (FFP), and tried to explore the relationship between the generation of inhibitors and particular FVIII deficiency genotypes. Clinical information and blood samples of 1435 patients with haemophilia A (HA) were collected by six haemophilia centres in China. The Nijmegen modification of the Bethesda assay was used to detect inhibitors. Multiplex PCR, long‐range PCR and direct sequencing were performed for genotyping. The overall prevalence of inhibitors in Chinese HA patients was 3.9% and the prevalence of severe haemophiliacs was 4.3%; 18 of the 56 patients with inhibitors had high titres. A total of 38 different mutations were identified in the 55 patients with inhibitors, including 15 intron 22 and 3 intron 1 inversions, seven large deletions, 14 small deletion/insertions, seven nonsense mutations, one splice site mutations and eight missense mutations. Of 38 mutations, 28 were novel. Patients with large deletions and nonsense mutations were prone to have high titre inhibitors, with incidence rates of 57.1% (4/7) and 42.9% (3/7), respectively. In conclusion, the prevalence of inhibitors in Chinese HA patients is much lower than that reported for other ethnic groups and the large deletion and nonsense mutations are high risk factors for high titre inhibitor development.     

Colorectal cancer mortality in Hong Kong of China,Japan,South Korea,and Singapore

To clarify the trend in colorectal cancer mortality in Asian countries.We analyzed the colorectal cancer mortality in four Asian countries using the World Health Organization mortality database and the Korea National Statistics Office database.The annual age-standardized rates and truncated rated for the three age groups(30-49,50-69 and ≥ 70 years) for Hong Kong of China(1969-2009),Japan(1955-2009),South Korea(1985-2006),and Singapore(1966-2009) were estimated.A joinpoint regression model was used to detect significant trends in mortality rates.Colorectal cancer mortality in men started to decrease in 1992 in Japan followed by Singapore and Hong Kong of China in 1995.The mortality rates in women stared to decrease in 1980 in Singapore,followed by Hong Kong of China and Japan in 1996.In all countries and both genders,except for women in Singapore,the decrease in mortality began in the younger age groups.The colorectal cancer mortality in the four studied Asian countries has started to decrease,and the decrease occurred first in the younger age groups.     

Descriptive epidemiology of haemophilia in Maharashtra, India

Secondary data on haemophilia cases in the state of Maharashtra, India were compiled and analysed. A total of 2192 haemophiliacs could be accounted from case papers and pedigrees, representing approximately 60% of the estimated number of cases in the state. Ratio of haemophilia A to haemophilia B was 4.2:1. Severe haemophiliacs constituted the majority of haemophilia A and B cases. About 70% of patients did not report any family history. Age distribution of cases suggested that the longevity of severe haemophiliacs was less than 30 years. Geographical distribution revealed clustering of cases around three established haemophilia clinics, with large parts of the state showing no cases. Although the cumulative number of cases showed an ascending trend, there was a 90% decrease in the number of cases registered between 1989 and 2000, suggesting that case recruitment from areas around the facilities had been achieved. Most cases showed delayed diagnosis, as the majority of severe haemophiliacs was being diagnosed at around 11-15 years of age. However, increasing awareness about haemophilia was reflected in a four-fold increase in referrals of severe cases over a 10-year period and increased registration of cases under 5 years of age. This study highlights that haemophilia services in India are still in their infancy, and increased awareness among healthcare providers as well as expansion of treatment facilities are still the primary areas for improvement of treatment.     

Implementation of a hepatitis A prevention policy in haemophiliacs: results from the French cohort

In the early nineties, the occurrence of hepatitis A outbreaks in some patients with haemophilia in some countries led French health authorities to recommend hepatitis A virus (HAV) vaccination in HAV-seronegative haemophiliacs. The French 'Suivi thérapeutique National des Hémophiles' cohort permitted to assess the implementation of this recommendation by the analysis of the vaccinal process, i.e. HAV seropositivity assessment and vaccination of HAV-seronegative patients, in a survival approach. In a subgroup of 812 patients diagnosed earlier than 1990 (prevalent cohort), the implementation of vaccinal process increased quickly from 0% in 1993 to 41.8% in 1994 and to 71.2% in 1996, suggesting a 'notification effect'. The vaccinal process was associated to three cofactors in a Cox model analysis (age, severity of haemophilia, centre of treatment). No infection was observed during the survey in this group. In another subgroup of 201 boys born since 1993 (incident cohort), 27.5% and 15.4% patients remained exposed to the risk at 3 and 5 years from diagnosis respectively, again with a 'centre effect', which might be linked to various factors such as regain in confidence for products or economic reasons. Only five infectious seroconversions were assessed over the 7-year survey, which represents 14.5 cases per 1000 person-year incidence without any relationship with products. Our data combined with the contemporary hepatitis A epidemiology and the current safety of anti-haemophilic concentrates, should lead to a new assessment of the risk of hepatitis A in haemophiliacs. We suggest that among patients with bleeding disorder, as well as in other populations, HAV prevention policy might be stressed on those who already suffer from chronic liver disease and/or travel in endemic countries.     

Research in haemophilia B – approaching the request for high evidence levels in a rare disease

Payers in European countries request studies with high levels of evidence for decision making also for rare diseases like haemophilia B (HB). The objective of the study was to determine the status quo of current studies in HB regarding the overall level of evidence generated. The methods used for performing the study were systematic literature research in EMBASE and MEDLINE, search terms ‘HB’ and ‘factor IX’ (FIX). The inclusion criteria were journal articles (JA), conference abstracts (CA), English language, published between January 2009 and March 2013, studies only; screening of titles, abstracts, full texts subsequently. ClinicalTrials.gov search: unpublished registered trials (RT) concerning HB or FIX. The analysis was performed on research topic, sponsor, recruitment status and study design. Screening of 1639 hits yielded 31 JA describing 35 studies, and 62 CA. FIX was subject of 21 studies (60.0%) and 29 CA (46.8%). Seven studies focused on various aspects of HB, six on haemophilia studies with separate HB data. Screening of 173 hits from ClinicalTrials.gov yielded 42 RT. Overall, 32 RT (76.2%) related to FIX. Measurement of health‐related quality of life (HRQoL) was identified in none of these studies, four CA (6.5%), four RT (9.5%). Randomized study design was found in one study (2.9%), four RT (9.5%). Three studies (8.6%) and seven RT (16.7%) were prospective, observational and comparative. The majority of published clinical studies do not meet payers’ expectations for evidence. Therefore, clinical investigation concepts addressing randomization, outcomes research including HRQoL and comparison of therapy options should be discussed. Refined statistical methods and exploitation of complementary real‐life data sources may fill current evidence gaps concerning rare diseases.     

Rheumatoid arthritis prevalence, incidence, and mortality rates: a nationwide population study in Taiwan

There are few nationwide population studies on the epidemiology of rheumatoid arthritis (RA). Here, we present the epidemiologic features and mortality rates of RA in Taiwan. The catastrophic illness registry of the Taiwan National Health Insurance Research Database and the National Death Registry of Taiwan were used to estimate the incidence and prevalence of RA and its associated mortality rates. All-cause and cause-specific standardized mortality ratios (SMRs) were calculated and compared to the corresponding ratios of the general population in 2002. The study comprised 15,967 incident RA cases (3,562 men; 12,405 women) occurring from 2002 through 2007. The annual incidence of RA was 15.8 cases (men, 10.1; women, 41.0) per 100,000 population. The period prevalence was 97.5 cases (men, 37.4; women, 159.5) per 100,000 population. During 67,010 person-years of follow-up, 985 deaths (372 men; 613 women) were identified, and this corresponded to a crude mortality rate of 14.7 deaths (men, 25.0; women, 11.8) per 1,000 person-years. Compared to female patients, male patients had a higher risk for mortality (log-rank test, p < 0.001). RA patients had an SMR of 1.25 (95 % confidence interval [CI], 1.18–1.33) for all-cause mortality. Compared to the general population, RA patients of both genders in this cohort had a significantly higher risk of mortality from infection (SMR, 2.49) and gastrointestinal diseases (SMR, 1.76). RA incidence and prevalence were higher in women than in men. Mortality was higher in men than in women. Compared to the general population, RA patients had a higher risk of death, particularly from infection and gastrointestinal diseases.