Hemophilia : a disease on the move

peer reviewedOver the last hundred years, the treatment of hemophilia has evolved considerably. To date, its principle is still to prevent the occurrence of hemorrhages by regular intravenous injections of factor VIII or IX concentrate. It allows to reach a life expectancy similar to the general population. The quality of life is constantly improving despite the constraint imposed by the modality and frequency of injections. The main complication remains the development of antibodies that inhibit the administered factors. Concentrates of long-acting factors are now available allowing to limit for example the frequency of injections. A bispecific monoclonal antibody reproducing the action of factor VIII and injectable subcutaneously has recently become available to hemophilia A patients, with the advantage of being effective even in the presence of inhibitors. Other non-substitute products are being studied offering interesting leads. Finally, gene therapy shows promising results, giving hope for access to this therapeutic option in a relatively near future. These advances are, however, a challenge for clinical laboratories, which must adapt their measurement techniques to ensure optimal monitoring. The future is on its way for hemophilia. Treatment remains expensive but it is worth the price.Depuis un siècle, le traitement de l’hémophilie a considérablement évolué. À ce jour, son principe est toujours de prévenir la survenue d’hémorragies par injections intraveineuses régulières de concentré de facteur VIII ou IX. Il permet d’atteindre une espérance de vie similaire à la population générale. La qualité de vie est en constante amélioration, malgré la contrainte imposée par les modalités et la fréquence des injections. La complication principale reste le développement d’anticorps inhibant les facteurs administrés. Des concentrés de facteurs à action prolongée sont, maintenant, disponibles et permettent, notamment, de limiter la fréquence des injections. Un anticorps monoclonal bispécifique reproduisant l’action du facteur VIII et injectable par voie sous-cutanée est, depuis peu, à la disposition des patients hémophiles A, avec l’avantage d’être efficace même en présence d’inhibiteurs. D’autres produits non substitutifs sont à l’étude offrant des pistes intéressantes. Enfin, la thérapie génique montre des résultats prometteurs, laissant espérer un accès à cette option thérapeutique dans un futur relativement proche. Ces avancées sont cependant un défi pour les laboratoires d’analyse qui doivent adapter leurs techniques de mesure pour assurer un suivi optimal. Le futur est en marche pour l’hémophilie. Le traitement reste coûteux, mais il en vaut le prix

Facilitating guideline implementation in primary health care practices

Introduction: Many patients continue to receive suboptimal services, inappropriate, unsafe, and costly care. Underutilization of research by health professionals is a common problem in the primary care setting. Although many theoretical frameworks can be used to help address such evidence-practice gaps, health care professionals may not be aware of the benefits of frameworks or of the most appropriate ones for their context and thus, may be faced with the challenge of selecting and using the most relevant one. Aim: The aim of this article was to describe the process used to adapt a knowledge translation framework to meet the local needs of health professionals working in one large primary care setting. Methods: The authors developed a 5-step approach for guideline implementation. This approach was informed by prior research and the authors’ experiences in supporting multidisciplinary teams of health care professionals during the implementation of evidence-based clinical guidelines into primary care practices. To ensure that the 5-step approach was practical and suitable for the context of guideline implementation by multidisciplinary teams in primary health care, the implementation team adapted the “knowledge-to-action” framework using a multistep process. Results: The implementation approach consisted of the following 5 steps: identification, context analysis, development of implementation plan, evaluation, and sustainability. All 5 steps were described alongside details about a national low back pain project. Discussion: This article describes a collaborative, grassroots process that addressed an identified need in one complex context by adapting a knowledge translation framework to meet the local needs of health professionals working in primary care settings. Existing implementation frameworks may be too complex or abstract for use in busy clinical contexts. The 5-step approach presented in this paper resulted in practical steps that are more readily understood by health care professionals and staff on “the ground”. © The Author(s) 2020

How to explore… Inherited platelet disorders

peer reviewedInherited platelet disorders (IPD) include a set of rare diseases whose diagnosis is often difficult because it requires the use of complex biological assays in specialized centers. They are probably under-diagnosed. Clinicians should consider an IPD when facing a chronic thrombocytopenia resistant to intravenous immunoglobulins (IVIG) and steroids together with a family history of thrombocytopenia. A syndromic thrombocytopenia will be suspected by the family survey and specific clinical signs. The confirmation of the diagnosis will then require the use of specialized biological assays such as platelet aggregation, flow cytometry, electron microscopy, platelet secretion assays, karyotype and molecular biology.Les thrombopénies et thrombopathies constitutionnelles constituent un ensemble de pathologies rares dont le diagnostic est souvent difficile car il nécessite le recours à des analyses biologiques souvent réservées à des centres spécialisés. Elles sont probablement sous-diagnostiquées. Le clinicien devra les envisager devant une thrombopénie chronique ne répondant pas aux immunoglobulines intraveineuses et aux corticoïdes et la présence d’antécédents familiaux. Une thrombopénie syndromique sera suspectée en fonction des éléments de l’anamnèse familiale et de signes cliniques spécifiques. La confirmation du diagnostic nécessitera la réalisation d’examens biologiques spécialisés (agrégation plaquettaire, cytométrie en flux, microscopie électronique, tests de sécrétion, caryotype et biologie moléculaire)

Evidence for a Relationship between VEGF and BMI Independent of Insulin Sensitivity by Glucose Clamp Procedure in a Homogenous Group Healthy Young Men

BACKGROUND: This is the first study to experimentally explore the direct relationship between circulating VEGF levels and body mass index (BMI) as well as to unravel the role of insulin sensitivity in this context under standardized glucose clamp conditions as the methodical gold-standard. In order to control for known influencing factors such as gender, medication, and arterial hypertension, we examined a highly homogeneous group of young male subjects. Moreover, to encompass also subjects beyond the normal BMI range, low weight and obese participants were additionally included and stress hormones as a main regulator of VEGF were assessed. METHODOLOGY/PRINCIPAL FINDINGS: Under euglycemic clamp conditions, VEGF was measured in 15 normal weight (BMI 20-25 kg/m(2)), 15 low weight (BMI<20 kg/m(2)), and 15 obese (BMI>30 kg/m(2)) male subjects aged 18-30 years and the insulin sensitivity index (ISI) was calculated. Since stress axis activation promotes VEGF secretion, concentrations of ACTH, cortisol, and catecholamines were monitored. Despite of comparable ACTH (P = 0.145), cortisol (P = 0.840), and norepinephrine (P = 0.065) levels, VEGF concentrations differed significantly between BMI-groups (P = 0.008) with higher concentrations in obese subjects as compared to normal weight (P = 0.061) and low weight subjects (P = 0.002). Pearson's correlation analysis revealed a positive relationship between BMI and VEGF levels (r = 0.407; P = 0.010) but no correlation of VEGF with ISI (r = 0.224; P = 0.175). CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a positive correlation between concentrations of circulating VEGF levels and BMI in healthy male subjects under highly controlled conditions. This relationship which is apparently disconnected from insulin sensitivity may be part of some pathogenetic mechanisms underlying obesity and type 2 diabetes