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OBJECTIVES: To evaluate the applicability and compliance with guidelines for early initiation of long-term prophylaxis in infants with severe hemophilia A and to identify factors associated with guideline compliance. STUDY DESIGN: This real-world, prospective, multicenter, population-based FranceCoag study included almost all French boys with severe hemophilia A, born between 2000 and 2009 (ie, after guideline implementation). RESULTS: We included 333 boys in the study cohort. The cumulative incidence of long-term prophylaxis use was 61.2% at 3 years of age vs 9.5% in a historical cohort of 39 boys born in 1996 (ie, before guideline implementation). The guidelines were not applicable in 23.1% of patients due to an early intracranial bleeding or inhibitor development. Long-term prophylaxis was delayed in 10.8% of patients. In the multivariate analysis, 2 variables were significantly associated with "timely long-term prophylaxis" as compared with "delayed long-term prophylaxis": hemophilia treating center location in the southern regions of France (OR 23.6, 95% CI 1.9-286.7, P = .013 vs Paris area) and older age at long-term prophylaxis indication (OR 7.2 for each additional year, 95% CI 1.2-43.2, P = .031). Long-term prophylaxis anticipation was observed in 39.0% of patients. Earlier birth year (OR 0.5, 95% CI 0.3-0.8, P = .010 for birth years 2005-2009 vs 2000-2004) and age at first factor replacement (OR 1.9 for each additional year, 95% CI 1.2-3.0, P = .005) were significantly associated with "long-term prophylaxis guideline compliance" vs "long-term prophylaxis anticipation." CONCLUSIONS: This study suggests that long-term prophylaxis guidelines are associated with increased long-term prophylaxis use. However, early initiation of long-term prophylaxis remains a challenge.
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Factores de Coagulación Sanguínea/administración & dosificación , Adhesión a Directriz/estadística & datos numéricos , Hemofilia A/complicaciones , Artropatías/prevención & control , Pautas de la Práctica en Medicina/estadística & datos numéricos , Factores de Coagulación Sanguínea/uso terapéutico , Preescolar , Esquema de Medicación , Francia , Humanos , Lactante , Recién Nacido , Artropatías/etiología , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/normas , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Standard treatment of congenital haemophilia A is based on replacement therapy with coagulation factor VIII (FVIII) products. A major complication of FVIII therapy is the occurrence of IgG alloantibodies (inhibitors) that neutralize FVIII activity. AIM: The aim of the analysis was estimating the risk of high-titre inhibitor associated with the second-generation full-length product compared to third-generation full-length product and other recombinant FVIII (rFVIII). METHODS: We conducted a combined analysis of individual patient data from three large studies in previously untreated patients (PUPs) with severe haemophilia A. RESULTS: A total of 1109 PUPs were treated from 1993 to 2013 including 787 PUPs treated from 2004 onwards (primary analysis cohort). A total of 322 patients (29.0%) developed an inhibitor, of which 192 (17.3%) a high-titre inhibitor. In the primary analysis set, 29.9% of patients developed an inhibitor and 17.2% a high-titre inhibitor. The combined analysis indicated a lower risk of high-titre inhibitor development for the third-generation rFVIII product compared to the second-generation rFVIII product (primary analysis: adjusted hazard ratio (HR) = 0.72, 95% CI: 0.49 to 1.06). Adjusted HR for all inhibitor development was significantly lower for the third-generation product compared to the second-generation product. CONCLUSION: The trend of an increased risk of inhibitor development in PUPs for one recombinant product illustrates that extrapolation from one recombinant factor VIII product to other products might not be justified.
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Factor VIII/inmunología , Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Hemofilia A/inmunología , Proteínas Recombinantes/uso terapéutico , Humanos , Factores de RiesgoRESUMEN
FranceCoag is an ongoing open prospective multicentre cohort project aimed at improving epidemiological knowledge about inherited bleeding disorders in France. The main objective of this article was to evaluate the project's progress as of the 30th December 2016. Between 1994 and this date, of the 10,047 patients included in the study, 384 (3.8%) were reported by clinicians to have died and 159 (1.6%) to be lost to follow-up. Among the remaining 9504 patients still being followed up, 5748 (60.5%) had haemophilia A, 1300 (13.7%) haemophilia B, 1980 (20.8%) von Willebrand Disease while 476 (5.0%) had another clotting factor deficiency (Factor I, II, V, combined V and VIII, VII, X, XI and XIII). The median age of the population was 32 years (Inter-quartile range (IQR) 18-50 years) at data extraction on December 30th, 2016. The subgroup of children (i.e., < 18 years old) with severe haemophilia and comprehensive information available since the first exposure to treatment was identified as the PUPs (Previously Untreated Patients) cohort. Data for the 643 children included in the PUPs' cohort had been collected since their birth. Follow-up data were collected by the clinicians in haemophilia treatment centres (HTC) every 12.9 months on median (IQR 11.4-21.3). In the PUPS cohort, data were updated every 6.2 months on median (IQR 3.7-11.7). A unique patient number assigned at study inclusion was kept at individual HTC by participating clinicians. The data collected included demographic, clinical, therapeutic and biological items on standard electronic forms. As of December 30th 2016, a plasma and serum samples was available for 2581 patients (27.1%).
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Trastornos de la Coagulación Sanguínea Heredados/epidemiología , Adolescente , Adulto , Trastornos de las Proteínas de Coagulación/epidemiología , Femenino , Estudios de Seguimiento , Francia/epidemiología , Hemofilia A/epidemiología , Hemofilia B/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven , Enfermedades de von Willebrand/epidemiologíaRESUMEN
Around one third of boys with severe hemophilia A develop inhibitors (neutralizing antibodies) against their therapeutic factor VIII product. This adverse effect may result in more life-threatening bleeding, disability, impaired quality of life, and costly care. We compared the incidence of inhibitors in boys treated with the three factor VIII products most used in France: one plasma-derived (Factane) and two recombinant products (Advate and Kogenate Bayer). A previously untreated cohort of patients was created in 1994 to investigate risk factors for inhibitor development. We selected boys with severe hemophilia A (factor VIII <1 IU/dL) first treated with one of the three factor VIII products studied. Details of product infusions, inhibitor assays and main fixed and time-varying inhibitor risk factors were recorded for the first 75 exposure days. Three outcomes (all inhibitors, high-titer inhibitors and subsequently treated inhibitors) were analyzed by univariate and multivariate Cox models. We studied 395 boys first treated between 2001 and 2016 (131, 137, and 127 with Factane, Advate, and Kogenate Bayer, respectively). Clinically significant inhibitors were diagnosed in 121 patients (70 high-titer). The incidence of high-titer inhibitors was significantly associated with the factor VIII product received (P=0.005): the cumulative incidence at 75 exposure days was 12.7% (95% CI: 7.7-20.6) with Factane, 20.4% (95% CI: 14.0-29.1) with Advate, and 31.6% (95% CI: 23.5-41.7) with Kogenate Bayer. The low inhibitor incidence observed with Factane is concordant with recent findings from the SIPPET randomized trial. These consistent results from observational and experimental studies should lead to improved care for previously untreated patients and cost savings for healthcare systems worldwide.
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Factor VIII/inmunología , Hemofilia A/inmunología , Proteínas Recombinantes/inmunología , Anticuerpos Neutralizantes/inmunología , Niño , Preescolar , Factor VIII/efectos adversos , Factor VIII/uso terapéutico , Estudios de Seguimiento , Francia/epidemiología , Hemofilia A/tratamiento farmacológico , Hemofilia A/epidemiología , Humanos , Inmunoensayo , Isoanticuerpos/inmunología , Estimación de Kaplan-Meier , Masculino , Modelos de Riesgos Proporcionales , Vigilancia en Salud Pública , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéuticoRESUMEN
BACKGROUND: EQOFIX is a medicoeconomic study that analyzed the health-related quality of life (HRQoL) and costs of care of the moderate and severe forms of hemophilia B, treated on demand or by prophylaxis with either plasma-derived Factor IX (pdFIX) or recombinant FIX (rFIX). STUDY DESIGN AND METHODS: The primary objectives were evaluations of the impact of hemophilia B on HRQoL and of the costs associated with its management. The secondary objectives were evaluations of the clinical efficacy and costs of care of pdFIX and rFIX. In this observational study we included and followed for 1 year severe and moderate hemophilia B patients without inhibitor. HRQoL was evaluated through generic and disease-specific questionnaires. Information on the health resources consumed was collected every 3 months. RESULTS: The EQOFIX cohort was composed of 155 patients, including 51 children and 104 adults, with 114 having severe disease and 41 having moderate disease. The regimens were prophylactic for 61 and on demand for 94. Altogether, 78 were treated with rFIX and 77 with pdFIX. There was no difference in the QoL between the pdFIX and rFIX treatments. The extra cost of prophylaxis was 22,605 per bleeding event prevented. The consumption of FIX was 1.4-fold higher for the patients treated with rFIX than for the patients treated with pdFIX. CONCLUSION: Our findings in a cohort composed of 25% of the French population of moderate and severe hemophilia B patients show, with similar clinical and HRQoL results, that treatment with rFIX is more expensive than treatment with pdFIX.
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Factor IX , Hemofilia B , Calidad de Vida , Adolescente , Adulto , Niño , Estudios de Cohortes , Costos y Análisis de Costo , Factor IX/administración & dosificación , Factor IX/economía , Femenino , Francia , Hemofilia B/tratamiento farmacológico , Hemofilia B/economía , Hemorragia/economía , Hemorragia/prevención & control , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Six recombinant factor VIII (rFVIII) products have been marketed worldwide. In 2013, the Research of Determinants of Inhibitor Development (RODIN) study group reported an unexpectedly high risk of inhibitor development with a second-generation full-length rFVIII (Product D) in previously untreated patients (PUPs) with severe hemophilia A (HA). In 1994, French public health authorities established a prospective cohort to monitor hemophilia treatment safety. A PUP subgroup was designed to investigate inhibitor risk factors. We analyzed this subcohort in view of the RODIN findings. After excluding 50 patients who participated in the RODIN study, the primary analysis focused on 303 boys with severe HA first treated with a rFVIII product. A clinically significant inhibitor was detected in 114 boys (37.6%). The inhibitor incidence was higher with Product D vs the most widely used rFVIII product (adjusted hazard ratio [aHR], 1.55; 95% confidence interval [CI], 0.97-2.49). Similar results were found for high-titer inhibitors and in 10 sensitivity analyses. No heterogeneity was observed between RODIN and our results. Combined aHRs were 1.58 (95% CI, 1.17-2.14) for all inhibitors and 1.70 (95% CI, 1.15-2.52) for high-titer inhibitors. Our results confirm the higher immunogenicity of Product D vs other rFVIII products in PUPs with severe HA.
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Factor VIII/inmunología , Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Hemofilia A/inmunología , Formación de Anticuerpos , Preescolar , Estudios de Cohortes , Francia/epidemiología , Hemofilia A/epidemiología , Humanos , Lactante , Masculino , Metaanálisis como Asunto , Vigilancia de Productos Comercializados , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/uso terapéutico , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To estimate the number and causes of maternal deaths in Tunisia from 1999 to 2007, and compare the results with the last report (1993-1994). METHODS: Data on all deaths of women of reproductive age in the public (1999-2007) and private (2006 only) health sectors were collected and assessed for whether the death was due to pregnancy. Number of live births was provided by the National Institute of Statistics. RESULTS: Mean maternal mortality ratio (MMR) in Tunisia decreased from 68.9 per 100000 live births in 1993-1994 to 36.3 (95% confidence interval, 27.9-46.5) in 2005-2007 (P<0.001). Causes of maternal death did not change significantly during the study period (1999-2007): hemorrhage and hypertensive disorders were the main causes. The gap between urbanized and more rural regions observed in 1993-1994 had narrowed, although MMR remained higher in central and western regions than on the east coast. CONCLUSION: The improvement in MMR can be credited to the voluntary political commitment focused on gender-related concerns that has been made in Tunisia, including access to family planning; legalization of abortion; and creation of the National Board for Family and Population, and the Tunisian Safe Motherhood initiative in 1999.
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Accesibilidad a los Servicios de Salud/tendencias , Servicios de Salud Materna/normas , Mortalidad Materna/tendencias , Aborto Legal , Adolescente , Adulto , Servicios de Planificación Familiar/tendencias , Femenino , Humanos , Servicios de Salud Materna/tendencias , Persona de Mediana Edad , Embarazo , Población Rural/estadística & datos numéricos , Túnez/epidemiología , Población Urbana/estadística & datos numéricos , Adulto JovenRESUMEN
Acquired hemophilia is a rare bleeding disorder characterized by the spontaneous occurrence of inhibitory antibodies against endogenous factor VIII (FVIII). IgG from some patients with acquired hemophilia hydrolyze FVIII. Because of the complex etiology of the disease, no clinical parameter, including the presence of FVIII-hydrolyzing IgG, has been associated with patient's survival or death. Here, we demonstrate the presence of anti-FIX antibodies in acquired hemophilia patients. IgG from some patients were found to hydrolyze FIX. In most cases, IgG-mediated FIX-hydrolysis resulted in FIX activation. IgG-mediated hydrolysis of FIX thus led to the significant generation of activated FIX in 25 of 65 patients. Based on the estimated kinetic parameters, patients' IgG activated up to 0.3nM FIX in 24 hours, an amount that restored thrombin generation in vitro provided the presence of more than or equal to 3% residual FVIII activity in plasma. This work identifies proteolytic IgG as novel molecules able to activate FIX under pathologic conditions. IgG-mediated FIX activation is a prevalent phenomenon among acquired hemophilia patients. The presence of FIX-activating IgG may partly compensate for the antibody-mediated inhibition of endogenous FVIII in restoring thrombin generation. This clinical trial was registered at www.clinicaltrials.gov as #NCT00213473.
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Autoanticuerpos/sangre , Factor IX/inmunología , Factor IX/metabolismo , Inmunoglobulina G/sangre , Adulto , Anciano , Anciano de 80 o más Años , Factor VIII/inmunología , Factor VIII/metabolismo , Femenino , Hemofilia A/sangre , Hemofilia A/inmunología , Humanos , Hidrólisis , Técnicas In Vitro , Cinética , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/metabolismoRESUMEN
OBJECTIVE: Little is known about the real impact of working conditions on the health of call center employees. The aim of this article is to describe the working conditions of French electricity and gas company customer service teams, especially those spending more than 75% of their working time handling calls in order to determine their subjective experience of their work and identify situations at risk of psychosocial constraints. METHODS: A cross-sectional study using a self-completion questionnaire was conducted on a representative sample of 2,000 employees working in customer service centers. The questions focused on the variety of tasks performed, the organization of working time, the physical environment of the workstation, violent situations and psychosocial factors (Job Content Questionnaire). Multivariate statistical analyses were performed to identify factors associated with the wish to leave the sector and with a high level of psychosocial constraints. RESULTS: Women made up 66% of the sample. Despite a high educational level, the average socio-professional level of the employees was relatively low. Although the vast majority of employees had chosen this career (74%), just over half would like to leave. The main factors associated with iso-strain were inadequate breaks (odds ratio (OR) = 2.0), low perceived quality of work (OR = 2.4), high proportion of working time spent handling calls (≥75% of working time: OR = 5.9, between 50 and <75%: OR = 5.2), exposure to violence either internally (often or very often: OR = 3.1) or from customers (often or very often: OR = 1.8) and an unsatisfactory workplace (OR = 2.0). CONCLUSIONS: Employees who spend more than 75% of their working time on the phone cumulate every factor linked with a high level of constraints, but all employees of the EDF and Gaz de France customer service centers are concerned. These workers share many characteristics with other call centers: predominantly female workforce; high educational level; wish to leave this sector despite the initial choice; high level of psychosocial risk factors.
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Comportamiento del Consumidor , Electricidad , Industrias , Exposición Profesional , Estrés Psicológico/etiología , Lugar de Trabajo/psicología , Adulto , Estudios Transversales , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , TeléfonoRESUMEN
BACKGROUND: Research ethics have become universal in their principles through international agreements. The standardization of regulations facilitates the internationalization of research concerning drugs. However, in so-called observational studies (i.e. from data collected retrospectively or prospectively, obtained without any additional therapy or monitoring procedure) the modalities used for applying the main principles vary from one country to another. This situation may entail problems for the conduct of multi-centric international studies, as well as for the publication of results if the authors and editors come from countries governed by different regulations. In particular, several French observational studies were rejected or retracted by US peer-reviewed journals, because their protocols have not been submitted to an Institutional Review Board/Independent Ethics Committee (IRB/IEC). METHODS: National legislation case analysis. RESULTS: In accordance with European regulation, French observational studies from data obtained without any additional therapy or monitoring procedure, do not need the approval of an IRB/IEC. Nevertheless, these studies are neither exempt from scientific opinion nor from ethical and legal authorization. CONCLUSION: We wish to demonstrate through the study of this example that different bodies of law can provide equivalent levels of protection that respect the same ethical principles. Our purpose in writing this article was to encourage public bodies, scientific journals and researchers to gain a better understanding of the various sets of specific national regulations and to speak a common language.
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Investigación Biomédica/legislación & jurisprudencia , Ética en Investigación , Cooperación Internacional , Comités de Ética en Investigación , Francia , Declaración de Helsinki , Humanos , Legislación de Medicamentos , Estudios Multicéntricos como Asunto/ética , Estudios Multicéntricos como Asunto/legislación & jurisprudenciaAsunto(s)
Inhibidores de Factor de Coagulación Sanguínea/análisis , Factor VIII/análisis , Hemofilia A/sangre , Hemofilia A/tratamiento farmacológico , Factor de von Willebrand/análisis , Animales , Presentación de Antígeno/efectos de los fármacos , Inhibidores de Factor de Coagulación Sanguínea/inmunología , Estudios de Cohortes , Células Dendríticas/inmunología , Factor VIII/administración & dosificación , Factor VIII/inmunología , Hemofilia A/inmunología , Hemofilia A/mortalidad , Humanos , Ratones , Ratones Noqueados , Factor de von Willebrand/inmunologíaRESUMEN
PURPOSE OF REVIEW: Inhibitors in haemophilia are a serious complication that may render usual replacement therapy ineffective. The risk is greatest in previously untreated children with severe haemophilia A. The role of replacement factor VIII in this group is an important issue. RECENT FINDINGS: Until now, few clinical studies have correctly taken into account the variety of cofactors involved in inhibitor development: genetic (familial antecedents, ethnicity, F8 and immune response genotypes), and environmental cofactors (age at first infusion, prophylaxis and intensity of treatment). This is a prerequisite to correctly evaluating the putative role of the type of factor replacement. Prospective cohort studies are therefore urgently needed. Depending on the expected inhibitor risk in the reference group, the intensity of the relationship between risk factor and endpoint, the duration of patient follow up, and the design of the study (balanced or unbalanced groups), cohorts including 200-500 previously untreated children should be sufficient to demonstrate an increased intensity of risk of about 2 or more with one product compared with another. SUMMARY: Aside from clinical studies, fundamental research is essential to test the multiple hypotheses that could explain a difference in inhibitor risk between the currently available factor VIII concentrates in order to develop less immunogenic factor VIII.
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Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Preescolar , Ensayos Clínicos como Asunto , Estudios de Cohortes , Factor VIII/inmunología , Hemofilia B/tratamiento farmacológico , Humanos , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/uso terapéutico , Factores de RiesgoRESUMEN
Inhibitor development is the major treatment complication in children with severe hemophilia A. It is not clear whether the risk of inhibitors is higher with recombinant factor VIII or with plasma-derived factor VIII. We used multivariate analysis to compare 2 cohorts of previously untreated patients (PUPs) with severe hemophilia A: 62 patients treated with the same brand of high-purity plasma-derived FVIII (pFVIII) containing von Willebrand factor (VWF) and 86 patients treated with full-length recombinant FVIII (rFVIII). In addition to the usual end points (all inhibitors, high inhibitors), we also examined a third end point (high inhibitors and/or immune tolerance induction). The risk of inhibitor development was higher in patients treated with rFVIII than in patients treated with pFVIII, regardless of other risk factors (F8 genotype; nonwhite origin; history of inhibitors in patients with a family history of hemophilia; age at first FVIII infusion). The adjusted relative risk (RRa) for inhibitor development with rFVIII versus pFVIII was 2.4 (all inhibitors), 2.6 (high inhibitors), and 3.2 (high inhibitors and/or immune tolerance induction), respectively, depending on the end point (above). The pathophysiology of this large effect must be understood in order to improve the characteristics of recombinant products and to reduce the incidence of inhibitors to FVIII.
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Autoanticuerpos/sangre , Factor VIII/inmunología , Hemofilia A/terapia , Proteínas Sanguíneas/aislamiento & purificación , Proteínas Sanguíneas/uso terapéutico , Factor VIII/efectos adversos , Factor VIII/uso terapéutico , Estudios de Seguimiento , Hemofilia A/complicaciones , Humanos , Incidencia , Lactante , Recién Nacido , Análisis Multivariante , Proteínas Recombinantes/uso terapéutico , Factores de Riesgo , Encuestas y Cuestionarios , Factor de von WillebrandRESUMEN
BACKGROUND: Exposure to ionizing radiation increases the risk of cancer in humans. Nuclear workers receive low doses over a relatively long period of time. METHODS: A mortality study of a cohort of workers exposed to ionizing radiation at Electricité de France (EDF) was conducted. The cohort consisted of 22,395 individuals monitored for radiation exposure between 1961 and 1994, and followed-up for an average of 11.7 years. RESULTS: Our study demonstrates a clear healthy worker effect (HWE) since mortality is less than half what is expected from National mortality statistics. The HWE is greater among workers who have spent most of their career in the nuclear sector. The analysis by cancer site shows no excess compared with the general population. No significant trend was observed according to level of exposure to ionizing radiation. CONCLUSIONS: The mortality of workers exposed to ionizing radiation at the French National Electricity company is very low compared to the French national mortality.
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Electricidad , Efecto del Trabajador Sano , Salud Laboral , Radiación Ionizante , Adolescente , Adulto , Causas de Muerte , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Exposición Profesional , Centrales Eléctricas/estadística & datos numéricosRESUMEN
OBJECTIVE: To evaluate the potential use of 2-long terminal repeats (LTR) HIV circular DNA quantification for the monitoring of ongoing virus replication in treated HIV-1-infected patients. DESIGN AND METHODS: In a longitudinal setting, where the natural course of HIV-1 infection was in most cases disrupted by continuous or discontinuous antiviral therapy, 2-LTR circles of HIV-1 DNA were quantified in serial peripheral blood mononuclear cell samples, selected in retrospect from 16 patients with chronic HIV-1 infection, using quantitative real-time PCR. We compared variations of 2-LTR circle level with concomitant variations in plasma viral RNA level and with the frequency of productively infected cells and chromosome associated proviral DNA copy numbers in patient's peripheral blood mononuclear cells. RESULTS: Antiviral treatment led to a sharp decrease in plasma viraemia and infectious cell frequency. In contrast, we found that levels of proviral DNA and 2-LTR circles were significantly lower under treatment only when groups of specimens that were homogeneous, with respect both to plasma viraemia and infectious cell frequency, were compared. Moreover, during the time of undetectable plasma viraemia, scarcely any decline in proviral DNA or 2-LTR circle levels was observed. CONCLUSIONS: The low impact of antiviral treatment on 2-LTR circle levels in vivo, when plasma viraemia and infectious cell frequency both dramatically decline lead us to conclude that 2-LTR circles should not be used for the monitoring of recent viral replication in treated patients.
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Fármacos Anti-VIH/uso terapéutico , Monitoreo de Drogas/métodos , Infecciones por VIH/tratamiento farmacológico , Duplicado del Terminal Largo de VIH/efectos de los fármacos , VIH-1/fisiología , Recuento de Linfocito CD4 , Enfermedad Crónica , ADN Viral/sangre , Femenino , Infecciones por VIH/virología , Humanos , Leucocitos Mononucleares/virología , Estudios Longitudinales , Masculino , Provirus/aislamiento & purificación , Viremia/tratamiento farmacológico , Replicación Viral/efectos de los fármacosRESUMEN
OBJECTIVE: The diagnosis of hemophilia was reported as delayed in historic studies. We therefore investigated this issue to provide current epidemiologic data in a large series of patients. STUDY DESIGN: The French cohort provided the opportunity to investigate the age at diagnosis and the circumstances of diagnosis in 599 individuals with hemophilia born between 1980 and 1994. The type and the severity of hemophilia, the family history, and the period of birth were analyzed as potential modifying factors. RESULTS: The median age at diagnosis was 7.7 months, with significant differences among subgroups: 5.8 months in severe hemophilia, 9.0 months in moderate forms, 28.6 months in mild forms, 0.4 months in the case of hemophilic brothers, and 10.1 months in de novo hemophilia, which accounted for 55.3% of cases. In severe forms we observed a trend for earlier diagnosis throughout 3 consecutive periods from 1980 to 1994. Of bleeding episode, testing due to family history, or routine testing, bleeding was the main circumstance of diagnosis (59.9%). CONCLUSIONS: Diagnosis was made earlier than in historic series, but it remained somewhat delayed. Early diagnosis will require efforts in the fields of genetic counseling and specific diagnosis of early bleeding, even without family history, because of the high incidence of de novo hemophilia.
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Hemofilia A/diagnóstico , Factores de Edad , Preescolar , Estudios de Cohortes , Salud de la Familia , Femenino , Francia/epidemiología , Hemofilia A/epidemiología , Humanos , Lactante , Recién Nacido , Masculino , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To assess the incidence of ectopic pregnancy (EP) in hospitals in Conakry, the capital of Guinea, West Africa. Data on EP incidence in developing countries are rare and often out of date, particularly in Africa. METHODS: A retrospective study was carried out, examining all cases of EP registered in the medical files of two referral maternity units at the Donka and Ignace Deen university hospitals between 1995 and 1999. FINDINGS: The EP incidence at the two maternity units increased from 0.41% to 1.5% of annual deliveries over this period. Haemoperitoneum was observed in most women, with tubal rupture in 93%; only 6 women received conservative treatment. CONCLUSION: The results suggest that the hospital-based incidence of EP per delivery has increased over the last decade in this West African capital, and that health professionals and public health officials in developing countries, especially those in Africa, should consider EP as a major obstetric problem for maternal morbidity.