Πως τα οικονομικά της υγείας θα βελτιώσουν τις κλινικές μελέτες για να μεγιστοποιήσουν την υγεία

Στη σημερινή εποχή, γίνεται πιο σημαντικό να χρησιμοποιούνται αποτελεσματικά οι πόροι καθώς αυξάνεται το παγκόσμιο βάρος των ασθενειών και συνάμα οι τιμές της υγειονομικής περίθαλψης. Τα βέλτιστα αποτελέσματα για την υγεία είναι ο τελικός στόχος για όλους όσους εμπλέκονται στο σύστημα υγειονομικής περίθαλψης, συμπεριλαμβανομένων των κλινικών γιατρών, των υπευθύνων χάραξης πολιτικής και των ασθενών. Η εφαρμογή των οικονομικών της υγείας σε κλινικές δοκιμές είναι ένας τρόπος για να βελτιωθεί η παροχή φροντίδας και να μεγιστοποιηθούν τα αποτελέσματα υγείας για το σύνολο των εμπλεκόμενων. Σκοπός της παρούσας έρευνας είναι να διερευνήσει τον τρόπου που συμβάλλουν τα οικονομικά της υγείας στις κλινικές δοκιμές. Κατά συνέπεια τα ερευνητικά ερωτήματα που προκύπτουν και θα επιχειρηθεί να δοθούν απαντήσεις στο πως συνδυάζονται τα οικονομικά της υγείας με τις κλινικές δοκιμές, και με ποιο τρόπο τα οικονομικά της υγείας συνεισφέρουν στο να βελτιωθούν οι κλινικές δοκιμές ώστε να μεγιστοποιείται το αγαθό της υγείας. Ο παραπάνω σκοπός θα επιτευχθεί μέσω της επιτέλεσης στοχευμένης βιβλιογραφικής ανασκόπησης. Η ανασκόπηση ξεκινά με έναν σαφή ορισμό των βασικών εννοιών και προχωρά με μια επισκόπηση του ρόλου, της τρέχουσας εφαρμογής και των προκλήσεων της οικονομίας της υγείας στις κλινικές δοκιμές. Περιλαμβάνει μια σύνθεση πολλών σημαντικών κλινικών μελετών που έχουν χρησιμοποιήσει τα οικονομικά της υγείας, όπως η Δοκιμή Ελέγχου και Επιπλοκών του Διαβήτη (DCCT), η Δοκιμή ΙΣΧΑΙΜΙΑΣ και η Δοκιμή CAPRIE. Περαιτέρω, η ανασκόπηση παρουσιάζει περιπτωσιολογικές μελέτες που καταδεικνύουν τα οφέλη της ενσωμάτωσης των οικονομικών της υγείας σε κλινικές δοκιμές, οδηγώντας σε μεγιστοποιημένα αποτελέσματα υγείας, αυξημένη αποτελεσματικότητα και καλύτερη εξέταση της οπτικής γωνίας του ασθενούς. Παρά τα προφανή πλεονεκτήματα, η ανασκόπηση υπογραμμίζει επίσης τους περιορισμούς της τρέχουσας έρευνας, παρέχοντας ευκαιρίες για μελλοντική έρευνα για την ενίσχυση της ενσωμάτωσης των οικονομικών της υγείας στις κλινικές δοκιμές.In today's era, it is becoming more important to use resources efficiently as the global burden of disease increases and so do the prices of health care. Optimal health outcomes are the ultimate goal for everyone involved in the healthcare system, including clinicians, policy makers and patients. Applying health economics to clinical trials is one way to improve care delivery and maximize health outcomes for all involved. The purpose of this research is to explore how health economics contributes to clinical trials. Consequently, the research questions that arise and will attempt to be answered are how health economics is combined with clinical trials, and how health economics contributes to improving clinical trials in order to maximize the health good. The above purpose will be achieved by performing a targeted literature review. The review begins with a clear definition of key concepts and proceeds with an overview of the role, current application and challenges of health economics in clinical trials. It includes a synthesis of several important clinical studies that have used health economics, such as the Diabetes Control and Complications Trial (DCCT), the ISCHEMIA Trial and the CAPRIE Trial. Further, the review presents case studies that demonstrate the benefits of integrating health economics into clinical trials, leading to maximized health outcomes, increased efficiency and better consideration of the patient's perspective. Despite the obvious advantages, the review also highlights the limitations of the current research, providing opportunities for future research to enhance the integration of health economics into clinical trials

Le nitrate de peracetyle (PAN) dans la pollution photooxydante : physicochimie, analyse, etudes de cas

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Components of an effective large scale program for the prevention of inherited hemoglobin disorders; the paradigm of Greece

Large scale prevention programs for Thalassemia major or Sickle cell disease have already been set up in several places with high frequency of the deleterious genes. The Greek health authorities realized the magnitude of the problem and allowed the creation of a National Thalassemia Center in 1972. The incidence of thalassemia in Greece varies from 1-2 per cent up to 15%, the mean being around 8 per cent. With an annual number of births around 100,000, if no prevention measures are taken, the expected yearly number of newborns with thalassemia major in Greece should be of the order of 100-120. To these one should add a few decades of sickle cell patients, homozygotes or compound HbS/&beta;-thalassemia heterozygotes. The total number of patients with thalassemia major now surviving is estimated at 4,000 plus another 600-800 patients with sickle cell disease. The National Thalassemia Center Center defined a network of peripheral Thalassemia Units in the major regional hospitals of the country, let them provide free carrier identification to couples requesting the test. When both partners were identified as carriers, they were given preliminary information locally and were referred to the Central Laboratory in Athens for further genetic counselling and, if so decided, prenatal diagnosis. Prenatal diagnosis was provided initially by fetoscopy and fetal blood biosynthesis; this approach was soon replaced by chorionic villi sampling and molecular techniques. The number of prenatal diagnoses carried out yearly over the last decade appears to cover the needs; the number of positive diagnoses is very close to the expected 25%, which also excludes overdiagnosis. The overall evaluation of the the program is reflected in the number of infants who were admitted to the pediatric clinics of the country in need of transfusion over the years the program was functioning. In fact, over the past years this number has steadily decreased to approximately 10 missed diagnoses annually, but has not reached zero as expected, after all this effort. The function of a comprehensive program for the prevention of thalassemia and HbS disease in Greece over the last 25 years has helped enormously in (a) avoiding birth of several hundreds of children with thalassemia major, thus (b) securing the use of the available resources for the optimal care of the patients who are living to-day, and (c) allowing thousands of couples at risk to give birth to healthy children.&nbsp;很多地方都已开展了针对地中海贫血或镰状细胞贫血的大型预防方案，病变基因的频率很高。 希腊健康机构意识到了此问题的严重性，在1972年，同意创建了国家地中海贫血防控中心。希腊人患地中海贫血的几率从百分之一、二至百分之十五不等，平均值为百分之八左右。 按照年均人口出生率100，000计算，如果不采取任何防控措施，希腊每年新生儿中，预计有100至120名新生儿会患上地中海贫血。对于这些患儿来说，应给镰状细胞贫血患者加上数十年的纯合子或复合性HbS/&beta;-地中海贫血杂合子。 重型地中海贫血现在的生存患者总数估计在4,000多名，其中有600至800名患者为镰状细胞贫血。 国家地中海贫血防控中心规定国家的主要地区医院的地中海贫血部门都应有对外网络，为要求测试的夫妇提供地贫基因携带者免费鉴定。 如果夫妇双方均被鉴定为地贫基因携带者，他们会被在本地给予事前资料，并会被安排到位于雅典的中心实验室进行进一步遗传咨询以及作出决定之后的产前检查。 以前，采用胎儿镜窥察和胎儿血液生物合成来进行产前检查，此方法不久之后便不再使用，取而代之的是绒毛标本采样和分子技术。 在过去的十年间，每年产前检查的数量几乎都满足了需求，诊断结果为阳性的产前检查数量接近预计的25%，不包括过度诊断。 此方案的总体评估在那些去国家幼儿科诊所的婴幼儿数量上反映了出来，这些婴幼儿需要常年输血，此时这项方案发挥了它的作用。 事实上近几年来，这项数字已稳定地下降了，因为每年约有10个误诊病例，然而在经过一系列努力之后， 仍未达到零的期望值，在希腊过去的25年中，为防止地中海贫血和HbS疾病的所实施的广泛的方案发挥了如下作用：（1）已帮助预防了数量众多数以千计的儿童患上重型地中海贫血；（2）为活着的患者提供最好的照顾而对可用资源的使用进行保护；（3）使上千对本来濒临危险的夫妇生下健康孩子。</p

Circulating Activin-A Is Elevated in Patients with Thalassemia Major and Double Heterozygous Sickle-Cell/Beta-Thalassemia and Correlates with Markers of Hemolysis and Bone Mineral Density

Abstract Abstract 3256 Activins are typical members of the transforming growth factor beta superfamily in that they contain a conserved cysteine knot motif and are secreted as homo- or heterodimers of related beta-subunits. Activins seem to be implicated in the regulation of erythropoiesis and bone metabolism. Many studies have documented erythropoietic effects of activin-A in transformed cell lines or other in vitro models; however, there is a paucity of functional data regarding hematopoietic roles of activin-A in vivo. Regarding bone remodeling, activin A is produced by osteoblasts, osteoclasts, and bone marrow cells, and there is agreement that activin-A promotes osteoclast development in vitro; however, the effect of activin-A on osteoblast development in vitro varies dramatically depending on experimental conditions. It is of interest that activin-A antagonists (i.e. sotatercept) have increased hemoglobin and bone mineral density (BMD) in patients with multiple myeloma who receive chemotherapy, giving the rationale for their use in other hematological disorders with anemia, like myelodysplastic syndromes. Thalassemia is characterized by ineffective hemopoiesis, while osteopenia or osteoporosis is found in the vast majority of patients due to several reasons including bone marrow expansion and endocrine disorders. The role of activin-A has never been evaluated in hemoglobinopathies. The aim of this study was to examine the role of activin-A in different hemoglobinopathies in an attempt to explore if there is any rationale for the use of activin-A antagonists in this cohort of patients. Therefore, we measured circulating levels of activin-A in 227 patients with hemoglobinopathies: 58 patients had beta-thalassemia major (TM), 43 had beta-thalassemia intermedia (TI), 109 had double heterozygous sickle-cell/beta-thalassemia (HbS/beta-thal) and 17 had homozygous sickle cell disease (SCD) and we explored possible correlations with clinical and laboratory data including bone mineral density (BMD). Activin-A was also measured in the serum of 17, age- and gender-matched, healthy individuals who served as controls. For the evaluation of activin-A, we used an ELISA methodology (Quantikine, R&amp;D Systems, Minneapolis, MN, USA). BMD of the lumbar spine (L1-L4), femoral neck (FN) and distal radius (R) was determined using Dual-energy X-ray absorptiometry (DXA) at the time of activin-A measurement. Patients with TM (mean±SD: 481±213 pg/ml) and HbS/beta-thal (459±181 pg/ml) had elevated circulating activin-A compared to controls (361±87 pg/ml; p=0.041 and p=0.038, respectively). Furthermore, TM patients had higher activin-A levels compared to patients with TI (427±509 pg/ml, p=0.002), while circulating activin-A levels did not differ between TI patients and controls (p=0.811) or between SCD patients (422±132 pg/ml) and controls (p=0.202). In patients with TM, high circulating activin-A showed strong correlations with markers of hemolysis, such as elevated reticulocyte counts (r=0.406, p=0.011) and high lactate dehydrogenase (LDH; r=0.397, p=0.024). Similarly, in HbS/beta-thal patients, activin-A showed positive correlations with indirect bilirubin (r=0.399, p&lt;0.001), ferritin (r=0.270, p=0.005) and LDH (r=0.194, p=0.044). Regarding BMD, osteoporosis (according to the WHO definition based on DXA data) was present in 45% of patients with TM, in 40% of patients with TI, in 33% of SCD patients and in 25% of patients with HbS/beta-thal. High activin-A correlated with low Z-score of L1-L4 BMD in TI patients (r=0.615, p&lt;0.01) and low Z-score of FN-BMD in TM patients (r=0.456, p&lt;0.01). Our data suggest that activin-A is elevated in the serum of patients with TM and HbS/beta-thal and correlates with markers of hemolysis and low BMD. These observations in addition to previously published data that single nucleotide polymorphisms in activin-A receptor type II-like 1 independently contributes to pulmonary hypertension in SCD support a role of activin-A in the biology of these hemoglobinopathies, making activin-A an attractive agent for the development of novel therapies. The strong correlation of high activin-A with bone loss also supports the use of activin-A antagonists in patients with thalassemia and osteopenia or osteoporosis. Disclosures: No relevant conflicts of interest to declare. </jats:sec

Liver Transient Elastography (FibroScan) Correlates with Liver Iron Concentration and Reflects Liver Fibrosis In Patients with Sickle Cell Disease

Abstract Abstract 1646 Liver transient elastography (FibroScan) is an interesting new technology that allows estimation of hepatic fibrosis through measurement of liver stiffness. The technique is based on changes in tissue elasticity induced by hepatic fibrosis and is considered as a noninvasive, reproducible and reliable method to assess hepatic fibrosis as well as to diagnose liver cirrhosis. Hepatic iron overload is a severe complication of chronic transfusion therapy in patients with hemoglobinopathies and plays an important role in the development of hepatic fibrosis and cirrhosis. Iron overload is present in several cases of sickle cell disease (SCD) including sickle cell anemia (HbS/HbS) and double heterozygous sickle-cell/beta-thalassemia (HbS/beta-thal). The aim of the study was to evaluate liver fibrosis by measuring the liver rigidity (Liver Stiffness Measurement, LSM, kPascals) using transient elastography (FibroScan, Echosens, Paris, France) in patients with SCD and explore possible correlations with clinical and laboratory characteristics of the patients, including iron overload. We studied 110 consecutive patients with SCD who are followed-up in the Thalassemia Center of Laikon General Hospital in Athens, Greece. Forty-four patients were males and 66 females; their median age was 44 years (range: 21–73 years). Twenty-two patients had HbS/HbS and 88 patients had HbS/beta-thal. On the day of Fibroscan, all patients had a thorough hematology and biochemical evaluation, including hemoglobin, reticulocyte counts, serum ferritin, liver biochemistry, bilirubin, lactate dehydrogenase (LDH) and serology for viral hepatitis. Liver iron concentration was evaluated by magnetic resonance imaging (MRI) T2* in all patients. The median LSM of all patients was 6.1 kPascals (range: 3.4–48.8 kPascals) with no differences between HbS/HbS (6.1 kPascals, 3.5–17.3 kPascals) and HbS/beta-thal (6.1 kPascals, 3.4–48.8 kPascals) patients (p=0.835). LSM values strongly correlated with liver MRI T2* values (r=0.337, p&lt;0.001), serum ferritin (r=0.328, p=0.001), number of transfusions (r=0.332, p=0.001), bilirubin (r=0.299, p=0.003), LDH (r=0.287, p=0.004), Hb (r=-0.275, p=0.006) and reticulocyte counts (r=0.244, p=0.015). LSM values showed also strong positive correlations with biochemical indicators of liver function: gamma-glutamyl transpeptidase (r=0.522, p&lt;0.0001), glutamic oxaloacetic transaminase (r=0.484, p&lt;0.0001), glutamic pyruvic transaminase (r=0.422, p&lt;0.0001), alkaline phosphatase (r=0.334, p=0.001), gamma-globulin (r=0.296, p=0.005) and weak correlation with PT-International Normalized Ratio (r=0.184, p=0.094). The above correlations were similar in patients with HbS/HbS and in patients with HbS/beta-thal. However, in HbS/HbS patients the correlation between LSM and liver T2* values was very strong (r=0.770, p=0.001). Patients who were regularly transfused had higher values of LSM (median: 6.7 kPascals, range: 2.3–48.8 kPascals) compared with patients who were sporadically transfused or were not transfused (4.4 kPascals, 3.6–17.5 kPascals, p=0.003). Patients who were under iron chelation therapy had lower values of LSM (6.3 kPascals, 3.4–15 kPascals) compared with those who did not receive iron chelators (13.9 kPascals, 8.5–17.3 kPascals, p=0.013). We found no correlations between the presence of HBV or HCV positivity and the levels of LSM. In conclusion, FibroScan may constitute a reliable and easy to apply noninvasive method to assess liver fibrosis in patients with SCD; the strong correlations between LSM values with MRI T2* values and serum ferritin supports this observation. Furthermore, FibroScan seems also to reflect the presence of chronic hepatic injury in these patients. If our results are confirmed by other studies, FibroScan may be regularly used in the management of SCD patients in whom liver is the main target organ of the disease. Disclosures: No relevant conflicts of interest to declare. </jats:sec