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Background: In Europe, different studies forecast an increase in maternal mortality in the coming years, associated with advanced maternal age and delay in maternity. This study aims to analyse the age-related trend in the maternal mortality ratio among mothers in Spain for the decade 1996-2005, and to describe the causes of death and associated sociodemographic factors for the years with highest mortality. Methods: An ecological study on trends, for the age-related trend in the maternal mortality ratio; an indirect standardisation and Poisson regression model was used. For the description of the causes of death, a cross-sectional study was used. Results: Prevalence of live births among mothers aged 35 years and over was 15% higher in Spain than in Europe. The maternal mortality rate increased by 20% (standardised mortality ratio of 1.2, 95% CI 0.9 to 1.4) in 2005 with respect to 1996. The age-related risk of maternal mortality was three times higher (relative risk of 2.90, 95% CI 2.01 to 4.06) among mothers aged 35-44 years versus those aged under 35 years. The highest mortality was detected during 2003-2004. The risk of maternal mortality was higher in foreign mothers. Conclusion: This study confirms that there was a change in the maternal mortality trend characterised by an increase in deaths, associated with advanced maternal age, as well as an increase in the prevalence of live births among mothers aged 35 years and over. This change in pattern identifies the need to intensify maternal mortality surveillance by collecting the necessary set of variables that allows investigation of the causes and determinant factors underlying deaths. [ABSTRACT FROM AUTHOR]

Melatonin supplements are used widely in Europe and the United States (US) to alleviate jet-lag and other sleep-delay disorders. Recently, the European Commission authorized two health claims for food containing melatonin, with a minimum dose per quantified portion. This study aimed to determine the dose of melatonin in food supplements marketed in Europe (Spain) and the US by validating a liquid chromatography method with diode array detection (LC-DAD). Additionally, contaminants present in melatonin supplements were analyzed using ultra-high-performance liquid chromatography coupled to an orbitrap mass spectrometer. We tentatively identified 8 tryptophan-related contaminants in melatonin supplements, suggesting tighter impurity control in melatonin supplements is necessary. The LC-DAD validated method achieved reliable results regarding recovery, precision, repeatability, limit of detection, limit of quantitation and linearity. Label melatonin dose varied from 1–1.95 mg/unit and 0.3–5 mg/unit for supplements marketed in Europe (Spain) and the US, respectively. Four out of seventeen supplements showed significant deviations from melatonin content declared on the label (from −60% to −20%). Regarding health claims, three out of the ten supplements purchased in Spain should not include the claim “reduction of time taken to fall asleep”, as their melatonin content is lower than 1 mg. [ABSTRACT FROM AUTHOR]

Introduction The bleeding propensity in von Willebrand disease ( VWD) is usually moderate or mild and patients with VWD do not need continuous treatment, but do require extra increased haemostatic cover when undergoing dental or surgical procedures. Desmopressin can be effective in certain patient groups and this has been considered in a previous publication. Aim This paper now seeks to evaluate current knowledge and practice in the use of factor concentrate in the management of VWD patients undergoing invasive procedures. Methods A literature search was performed on the use of factor concentrates to cover invasive procedures and a survey of current practice in a number of specialist haematology centres across Europe represented by the European Haemophilia Strategy Board was conducted. Results Our review of the literature and the results of the survey showed considerable heterogeneity in treatment regimens, and a lack of consistency in reporting of the variables that determine factor concentrate dosing and monitoring. Conclusion By analysing the literature, examining guidelines and using consensus deliberation, this survey allowed the group to develop recommendations for management of VWD patients undergoing invasive procedures. [ABSTRACT FROM AUTHOR]

. Continuous infusion (CI) of factor VIII (FVIII) is an effective method for replacement therapy in haemophilia. Recently, concerns have been raised regarding association of CI with the development of inhibitors. The aim of this study was to gain information on the current practices in Europe regarding CI and the true inhibitor incidence after this mode of therapy. In a cross sectional study performed in 22 Comprehensive Care Centres (CCCs), we evaluated CI techniques, treatment protocols, efficacy, safety and complications of CI including inhibitors. Thirteen (59%) CCCs reported a total of 1079 CI treatments, given peri-operatively or for major bleeds, in 742 patients. Most centres used 'adjusted dose' CI aimed at median target FVIII level of 0.8 IU mL-1. CI was haemostatically very effective with a low incidence of complications: median incidence of postoperative bleeding was 1.8%, six centres observed phlebitis in 2-11% of CI treatments. Only nine (1.2%) patients developed inhibitors (0.45% of 659 severe and 7.2% of 83 mild haemophilia patients). Additional analysis of inhibitor patients revealed several confounding factors (low number of prior FVIII exposure days, high steady-state factor levels during CI, high-risk genotype). In this unprecedentedly large cohort, CI treatment appears to be an effective and safe treatment that does not increase the risk of inhibitor development in patients with severe haemophilia. Thus, previous small case series reports suggesting that CI may increase inhibitorsb cannot be confirmed. Inhibitor risk in mild haemophilia could not be evaluated as the influence of other, potentially confounding, risk factors could not be excluded. [ABSTRACT FROM AUTHOR]

Some 10-20% of bleeding events in haemophilia patients with high-responding inhibitors cannot be controlled with bypassing agents. However, sequential combined bypassing therapy (SCBT) has been reported to be successful in five children. To extend this observation, a survey was undertaken by the European Haemophilia Treatment Standardisation Board (EHTSB) in children and adults. Data were collected from all centres belonging to the EHTSB network by a retrospective medical record review. SCBT courses were defined as the administration of both recombinant activated factor VIIa (rFVIIa) and activated prothrombin complex concentrate (APCC) within 12 h. A web-based database was prepared to collect data on SCBT courses in a standardized and anonymous manner from patients' files. Eleven inhibitor patients underwent SCBT (nine haemophilia A; two haemophilia B). Two children had refractory knee haemarthrosis and one, an unresponsive calf haematoma. Five adults had significant bleeds following major surgery, one had lower limb compartmental syndrome and one a post-traumatic upper limb haematoma and haemarthrosis. SCBT administration alternated one APCC dose to 1-3 rFVIIa doses: dosing intervals ranged between 3 and 6 h; APCC (20-80 U kg) was given every 8-12 h; rFVIIa (90-270 μg kg) was given every 3-12 h. Bleeding control was achieved in 12-24 h in all patients. SCBT was discontinued after 1-15 days. No clinical adverse events were observed, but a significant increase in D-dimer levels was seen in three/five patients who were assessed. SCBT was efficacious without adverse events; nevertheless, due to potential risks, it remains a salvage treatment. A prospective clinical trial is needed to provide further evidence. [ABSTRACT FROM AUTHOR]