The economics of inpatient on-demand treatment for haemophilia with high-responding inhibitors: a US retrospective data analysis.

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

Secondary prophylaxis with recombinant activated factor VII improves health-related quality of life of haemophilia patients with inhibitors.

Haemophilia patients with inhibitors characteristically have impaired joint function and reduced health-related quality of life (HRQoL). This analysis examined whether secondary prophylaxis with recombinant activated factor VII (rFVIIa) improves HRQoL vs. conventional on-demand therapy in patients with haemophilia with inhibitors and frequent bleeds. After a 3-month preprophylaxis period, 22 patients received daily rFVIIa prophylaxis (90 or 270 microg kg(-1)) for 3 months, followed by 3 months' postprophylaxis. Days of hospitalization, absence from school/work and mobility aids requirements were recorded. HRQoL was assessed by EuroQoL (EQ-5D) questionnaire, visual analogue scale (VAS), derived Time to Trade-Off (TTO) scores and Quality Adjusted Life Years (QALYs). rFVIIa prophylaxis significantly (P < 0.0001) reduced bleeding frequency vs. prior on-demand therapy. Hospitalization (5.9% vs. 13.5%; P = 0.0026) and absenteeism from school/work (16.7% vs. 38.7%; P = 0.0127) decreased during prophylaxis; these effects tended to be maintained during postprophylaxis. HRQoL (evaluated by EQ-5D) tended to improve during and after rFVIIa prophylaxis. Notably, pain decreased and mobility increased in 40.9% and 27.3% of patients, respectively, at the end of the postprophylaxis period vs. preprophylaxis. Median VAS score increased from 66 to 73 (P = 0.048), and TTO scores suggested better HRQoL (0.62 vs. 0.76; P = 0.054) during postprophylaxis than preprophylaxis. Small to moderate changes in effect sizes were reported for VAS and TTO scores. Median QALYs were 0.68 (VAS) and 0.73 (TTO). Reductions in bleeding frequency with secondary rFVIIa prophylaxis were associated with improved HRQoL vs. on-demand therapy.

Nanosecond radio bursts from strong plasma turbulence in the Crab pulsar.

The Crab pulsar was discovered by the occasional exceptionally bright radio pulses it emits, subsequently dubbed 'giant' pulses. Only two other pulsars are known to emit giant pulses. There is no satisfactory explanation for the occurrence of giant pulses, nor is there a complete theory of the pulsar emission mechanism in general. Competing models for the radio emission mechanism can be distinguished by the temporal structure of their coherent emission. Here we report the discovery of isolated, highly polarized, two-nanosecond subpulses within the giant radio pulses from the Crab pulsar. The plasma structures responsible for these emissions must be smaller than one metre in size, making them by far the smallest objects ever detected and resolved outside the Solar System, and the brightest transient radio sources in the sky. Only one of the current models--the collapse of plasma-turbulent wave packets in the pulsar magnetosphere--can account for the nanopulses we observe.

Frequency of births with potentially avoidable serious chromosomal anomalies in EEC countries, 1979-1982.

Child bearing at an early age and prenatal cytogenetic diagnosis in pregnant women of advanced age, combined with selective abortion, make it possible to avoid the birth of many children with serious chromosomal anomalies. To see how many of such births were still avoidable in Europe, data from 16 regional EUROCAT registers of congenital anomalies in nine EEC countries were analysed. In the period 1979-1982 about 30% of children with unbalanced anomalies of autosomes were born (live- and still-births) to mothers over 35 years of age. This amounts to an estimated 1300 cases yearly in the entire population of the nine countries. The approach shows the possible use of registry data for monitoring effects of avoidance strategies.

[Epidemiologic surveillance of congenital abnormalities using the EUROCAT Register]. / La surveillance épidémiologique des anomalies congénitales par le registre EUROCAT.

The EUROCAT programme is a concerted action of the European Economic Community for the epidemiologic surveillance of congenital anomalies. Surveillance is based on a network of regional registries coordinated by a central registry. The programme started in 1979 and by 1987, 23 centres were participating, covering together more than 300,000 births per year. The surveillance process implies the selection of the anomalies possibly associated with environmental teratogens or mutagens, the definition of abnormal variations in the rate of these anomalies (the alarms), the establishment of base-line rate and the continuous monitoring of rate. The programme is evaluated by reference to four criteria: the sensitivity of the system in detecting teratogens or mutagens, the specificity of alarms, the rapidity in warning of alarm and in investigating their causes, and the programme efficiency expressed as its cost-utility ratio.

Evaluation of information systems for the surveillance of congenital malformations.

Many systems for the recording of congenital malformations in infants have been developed following the thalidomide epidemic of 1958 to 1962. Systems established for monitoring increases in rates of malformations have been of three main types: (1) prospective recording of information about all pregnancies; (2) the recording of malformations observed at birth; (3) the registration of children found to be malformed at birth or at any time after birth. The latter type involves many sources of information. International collaboration in monitoring has led to the establishment of the International Clearinghouse for Birth Defects Monitoring Systems and the EEC Concerted Action Project EUROCAT. The advantages of these two projects are discussed. It is shown that results from population based registers such as are included in EUROCAT can be used to validate the results of systems which carry out monitoring at birth.

Congenital talipes and hip malformation in relation to amniocentesis: a case-control study.

A case-control study on 1342 infants was carried out to investigate whether mid-trimester amniocentesis might be a cause of congenital talipes or hip malformation. There was no evidence of any excess risk of having an infant with either of these malformations in mothers who had an amniocentesis; the estimate of relative risk in association with amniocentesis before 28 weeks of pregnancy was 1.08 (95% confidence interval, 0.7-1.6). There was no evidence that amniocentesis increased the risk of forms of these malformations that were sufficiently severe to require strapping, splintage, or surgery (relative risk 0.75, 95% confidence interval 0.4-1.4). Although there was no statistically significant association between amniocentesis and milder forms of these malformations (those requiring either no treatment or simple treatment by double nappies, physiotherapy, or manipulation), there is less confidence about the absence of an association (relative risk 1.32, 95% confidence interval 0.8-2.2).

A review of some effects of recent medical practices in reducing the numbers of children born with congenital abnormalities.

Attempts to reduce the number of children born with congenital malformations may be seen as part of the programmes for rubella immunization and for screening for neural tube defects and chromosome anomalies. The rubella immunization programme in England and Wales has not been accompanied by any appreciable decline in the overall incidence of heart or eye malformations detected at or soon after birth. However, the decline in the incidence of babies born with defects of the central nervous system, and of babies born with Down's syndrome to elderly mothers, indicates that interventive methods of control are achieving changes.

EEC Concerted Action Project--European Congenital Anomalies and Twins (Eurocat).

The European Economic Community (EEC) is promoting a network of locally funded centers in the nine EEC countries, surveying a total of approximately 140,800 births per year for selected congenital malformations and multiple births. The objectives and aims of the study are explained and some of the methods to set guidelines detailed.

Maternal drug histories and congenital abnormalities.

We obtained drug histories for the first trimester of pregnancy for 836 mothers of congenitally malformed babies and for an equal number of control mothers of normal babies from the same doctors' practices. There was an association between the use of a hormonal pregnancy test and the subsequent birht of a malformed baby. There was also a greater use of barbiturates by mothers of affected children compared with mothers of control babies, mainly accounted for by treatment of epileptic mothers with phenobarbitone. For all other drugs usage was similar in both sets of mothers.

Parity of women contracting rubella in pregnancy. Implications with respect to rubella vaccination.

Data from the National Congenital Rubella Surveillance Programme showed that 44% of children with congenital rubella reported to the programme were born to primiparae. This high proportion is thought to be due to the fact that there was a two-fold increase in the rate of abortion for rubella in pregnancy for women with two or more children. This higher incidence of congenital rubella in firstborns emphasises the need for rubella vaccination prior to a woman's first pregnancy.