Clinical and echocardiographic predictors of mortality in chagasic cardiomyopathy - systematic review

Diagnosis, prognosis and evaluation of death risk in Chagas cardiomyopathy still constitute a challenge due to the diversity of manifestations, which determine the importance of using echocardiography, tissue Doppler and biomarkers. To evaluate, within a systematic review, clinical and echocardiographic profiles of patients with chronic chagasic cardiomyopathy, which may be related to worse prognosis and major mortality risk. To perform the systematic review, we used Medline (via PubMed), LILACS and SciELO databases to identify 82 articles published from 1991 to 2012, with the following descriptors: echocardiography, mortality and Chagas disease. We selected 31 original articles, involving diagnostic and prognostic methods. The importance of Chagas disease has increased due to its emergence in Europe and United States, but most evidence came from Brazil. Among the predictors of worse prognosis and higher mortality risk are morphological and functional alterations in the left and right ventricles, evaluated by conventional echocardiography and tissue Doppler, as well as the increase in brain natriuretic peptide and troponin I concentrations. Recently, the evaluations of dyssynchrony, dysautonomia, as well as strain, strain rate and myocardial twisting were added to the diagnostic arsenal for the early differentiation of Chagas cardiomyopathy. Developments in imaging and biochemical diagnostic procedures have enabled more detailed cardiac evaluations, which demonstrate the early involvement of both ventricles, allowing a more accurate assessment of the mortality risk in Chagas disease.

Association of Peripheral Arterial and Cardiovascular Diseases in Familial Hypercholesterolemia

Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by an elevation in the serum levels of total cholesterol and of low-density lipoproteins (LDL- c). Known to be closely related to the atherosclerotic process, FH can determine the development of early obstructive lesions in different arterial beds. In this context, FH has also been proposed to be a risk factor for peripheral arterial disease (PAD). Objective: This observational cross-sectional study assessed the association of PAD with other manifestations of cardiovascular disease (CVD), such as coronary artery and cerebrovascular disease, in patients with heterozygous FH. Methods: The diagnosis of PAD was established by ankle-brachial index (ABI) values ≤ 0.90. This study assessed 202 patients (35% of men) with heterozygous FH (90.6% with LDL receptor mutations), mean age of 51 ± 14 years and total cholesterol levels of 342 ± 86 mg /dL. Results: The prevalences of PAD and previous CVD were 17% and 28.2 %, respectively. On multivariate analysis, an independent association between CVD and the diagnosis of PAD was observed (OR = 2.50; 95% CI: 1.004 - 6.230; p = 0.049). Conclusion: Systematic screening for PAD by use of ABI is feasible to assess patients with FH, and it might indicate an increased risk for CVD. However, further studies are required to determine the role of ABI as a tool to assess the cardiovascular risk of those patients.

Anxiety, Depression, and General Psychological Distress in Patients with Coronary Slow Flow

AbstractBackground:The relationship between psychiatric illness and heart disease has been frequently discussed in the literature. The aim of the present study was to investigate the relationship between anxiety, depression and overall psychological distress, and coronary slow flow (CSF).Methods:In total, 44 patients with CSF and a control group of 50 patients with normal coronary arteries (NCA) were prospectively recruited. Clinical data, admission laboratory parameters, and echocardiographic and angiographic characteristics were recorded. Symptom Checklist 90 Revised (SCL-90-R), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) scales were administered to each patient.Results:The groups were comparable with respect to age, sex, and atherosclerotic risk factors. In the CSF group, BAI score, BDI score, and general symptom index were significantly higher than controls (13 [18.7] vs. 7.5 [7], p = 0.01; 11 [14.7] vs. 6.5 [7], p = 0.01; 1.76 [0.81] vs. 1.1[0.24], p = 0.01; respectively). Patients with CSF in more than one vessel had the highest test scores. In univariate correlation analysis, mean thrombolysis in myocardial infarction (TIMI) frame counts were positively correlated with BAI (r = 0.56, p = 0.01), BDI (r = 0.47, p = 0.01), and general symptom index (r = 0.65, p = 0.01). The psychiatric tests were not correlated with risk factors for atherosclerosis.Conclusion:Our study revealed higher rates of depression, anxiety, and overall psychological distress in patients with CSF. This conclusion warrants further studies.

Hypertensives' Knowledge About High-Sodium Foods and Their Behavior

Abstract Background: In Brazil, the prevalence of systemic arterial hypertension (SAH) is approximately 30% of the total population. In 2010, SAH was the cause of death of about 9.4 million people worldwide. A healthy dietary pattern is important to maintain proper blood pressure levels and, consequently, disease control. Objectives: To describe the knowledge and practices of hypertensive patients cared for at a public hypertension outpatient clinic, and its relationship with high-sodium food. Methods: We applied a questionnaire to patients with questions related to sociodemographics, dietary pattern, frequency of ingestion of certain foods, and knowledge about their own disease. Results: We studied 221 patients, 56.1% of whom were women, and 53.8% had only elementary education. Their mean age was 57.7 ±13.5 years, and 75.6% of them reported having high blood pressure, and 11.3%, diabetes mellitus. Regarding dietary pattern, 62% used ready-to-use seasonings, but 94.1% reported not adding extra salt to their ready meals. Regarding patients' knowledge about high-sodium foods and SAH, only 8 patients had 100% of right answers, 37 patients had 73.8%, and 42 patients, 57% of right answers. Conclusion: Knowledge about SAH prevention and high-sodium foods was insufficient. Based on this study's findings, more effective educational strategies targeted at this population can be developed.

Freshwater sponges (Porifera, Demospongiae) indicators of some coastal habitats in South America: redescriptions and key to identification

Surveys for freshwater sponges were performed at several water bodies at sandy environments along a north-south direction of particularly the Brazilian coastal line. The results allowed for the distinction of four different species-specific environments along this coastal border. The main fact considered was the dominant or the sole recurrent occurrence of a single sponge species at one particular habitat. The first one is that of the lagoonal mesohaline habitats at the tropical and subtropical realms, indicated by Spongilla alba Carter, 1849. The second one refers to shallow ponds among dunes at the tropical area indicated by Corvoheteromeyenia heterosclera (Ezcurra de Drago, 1974). The third one is that of also shallow ponds close to the dune belt at the temperate region indicated by Racekiela sheilae (Volkmer-Ribeiro, De Rosa-Barbosa & Tavares, 1988). The fourth one is that of organically enriched environments, at the marginal areas of lagoons and mouth of small rivers, evolving towards freshwater muddy ponds and coastal swamps, not far from the ocean border: Ephydatia facunda Weltner, 1895 is the species to occupy this habitat with almost exclusiveness. The above species are thus proposed as indicators of such habitats and have their descriptions improved and that of their environments summarized. A taxonomic key based on the spicules of the four species is proposed. The results presented aim to contribute to the identification of spicules of these sponges in sediment columns recovered at the Brazilian and South American coastal area. Determination of paleo ocean borders are a present issue of upmost importance in what respects projections of timing and fluctuations of ascending/regressing sea levels.

Buccal apparatus and gastrointestinal tract dimensions associated to the diet of early life stages of Centropomus undecimalis (Centropomidae, Actinopterygii)

The present study aims to compare the buccal apparatus and gastrointestinal tract of early life stages of Centropomus undecimalis (Bloch, 1792), and relate them to its diet. A total of 190 individuals collected with a channel net in the Catuama estuary (07º40'9.9''S, 34º50'36.7''W), northern coast of the state of Pernambuco, were examined. Morphometrical and meristic data were analyzed for the two initial developmental periods (larval and juvenile). Their digestive tube was morphologically characterized and its content identified. The longest transverse axis of food items was measured, and compared to the standard length (SL) and mouth gape size (D) of the individuals. Body measurement regressions differed significantly (p<0.001) between larvae and juveniles. The stomachs with food content (n=118 individuals) presented a proportion of 62% full and 30% empty (being 8% damaged). They differed in relation to the fullness level and presented a coiled shape when empty. The number of food items in relation to SL and D did not present an evident correlation. Larvae (SL<10 mm) feed on small copepods, while juveniles (SL=11.1 to 64.7 mm) ingest larvae of various decapod species, showing a distinct diet between these initial developmental stages.

Nonhemocyte sources of selected lysosomal enzymes in Biomphalaria glabrata, B. tenagophila and B. straminea (Mollusca: Pulmonata)

The specific activities of acid phosphatase, alkaline phosphatase, β-glucuronidase, lysozymes, glutamate-oxalacetate transaminase and glutamate-pyruvate transaminate were determined in the head-foot and digestive gland of Brazilian Biomphalaria glabrata (Touros), B. tenagophila (Caçapava) and B. straminea (Monsenhor Gil). All six enzymes were detected inthe 3000g supernatant. Both cytoplasmic enzymes, glutamate-oxalacetate and glutamate-pyruvate transaminase exhibited the highest specific activities. In the case of the four hydrolytic enzymes assayed, β-glucuronidase exhibited the highest specific activity while lysozyme showed the lowest activity. All six enzymes are thought to be produced by cells within the head-foot and digestive gland of B. glabrata, B. tenagophila and B. straminea.

New York City: "gilt cage" or "promised land" ? : representations of urban space in Edith Wharton and Anzia Yezierska

This thesis explores the importance of literary New York City in the urban narratives of Edith Wharton and Anzia Yezierska. It specifically looks at the Empire City of the Progressive Period when the concept of the city was not only a new theme but also very much a typical American one which was as central to the American experience as had been the Western frontier. It could be argued, in fact, that the American city had become the new frontier where modern experiences like urbanization, industrialization, immigration, and also women's emancipation and suffrage, caused all kinds of sensations on the human scale from smoothly lived assimilation and acculturation to deeply felt alienation because of the constantly shifting urban landscape. The developing urban space made possible the emergence of new female literary protagonists like the working girl, the reformer, the prostitute, and the upper class lady dedicating her life to 'conspicuous consumption'. Industrialization opened up city space to female exploration: on the one hand, upper and middle class ladies ventured out of the home because of the many novel urban possibilities, and on the other, lower class and immigrant girls also left their domestic sphere to look for paid jobs outside the home. New York City at the time was not only considered the epicenter of the world at large, it was also a city of great extremes. Everything was constantly in flux: small brownstones made way for ever taller skyscrapers and huge waves of immigrants from Europe pushed native New Yorkers further uptown on the island, adding to the crowdedness and intensity of the urban experience. The city became a polarized urban space with Fifth Avenue representing one end of the spectrum and the Lower East Side the other. Questions of space and the urban home greatly mattered. It has been pointed out that the city setting functions as an ideal means for the display of human nature as well as social processes. Narrative representations of urban space, therefore, provide a similar canvas for a protagonist's journey and development. From widely diverging vantage points both Edith Wharton and Anzia Yezierska thus create a polarized city where domesticity is a primal concern. Looking at all of their New York narratives by close readings of exterior and interior city representations, this thesis shows how urban space greatly affects questions of identity, assimilation, and alienation in literary protagonists who cannot escape the influence of their respective urban settings. Edith Wharton's upper class "millionaire" heroines are framed and contained by the city interiors of "old" New York, making it impossible for them to truly participate in the urban landscape in order to develop outside of their 'Gilt Cages'. On the other side are Anzia Yezierska's struggling "immigrant" protagonists who, against all odds, never give up in their urban context of streets, rooftops, and stoops. Their New York City, while always challenging and perpetually changing, at least allows them perspectives of hope for a 'Promised Land' in the making. Central for both urban narrative approaches is the quest for a home as an architectural structure, a spiritual resting place, and a locus for identity forming. But just as the actual city embraces change, urban protagonists must embrace change also if they desire to find fulfillment and success. That this turns out to be much easier for Anzia Yezierska's driven immigrants rather than for Edith Wharton's well established native New Yorkers is a surprising conclusion to this urban theme.

Superior outcome of women with stage I/II cutaneous melanoma: pooled analysis of four European Organisation for Research and Treatment of Cancer phase III trials.

PURPOSE: Several studies observed a female advantage in the prognosis of cutaneous melanoma, for which behavioral factors or an underlying biologic mechanism might be responsible. Using complete and reliable follow-up data from four phase III trials of the European Organisation for Research and Treatment of Cancer (EORTC) Melanoma Group, we explored the female advantage across multiple end points and in relation to other important prognostic indicators. PATIENTS AND METHODS: Patients diagnosed with localized melanoma were included in EORTC adjuvant treatment trials 18832, 18871, 18952, and 18961 and randomly assigned during the period of 1984 to 2005. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs for women compared with men, adjusted for age, Breslow thickness, body site, ulceration, performed lymph node dissection, and treatment. RESULTS: A total of 2,672 patients with stage I/II melanoma were included. Women had a highly consistent and independent advantage in overall survival (adjusted HR, 0.70; 95% CI, 0.59 to 0.83), disease-specific survival (adjusted HR, 0.74; 95% CI, 0.62 to 0.88), time to lymph node metastasis (adjusted HR, 0.70; 95% CI, 0.51 to 0.96), and time to distant metastasis (adjusted HR, 0.69; 95% CI, 0.59 to 0.81). Subgroup analysis showed that the female advantage was consistent across all prognostic subgroups (with the possible exception of head and neck melanomas) and in pre- and postmenopausal age groups. CONCLUSION: Women have a consistent and independent relative advantage in all aspects of the progression of localized melanoma of approximately 30%, most likely caused by an underlying biologic sex difference.

The PRINTO criteria for clinically inactive disease in juvenile dermatomyositis.

OBJECTIVES: To develop data-driven criteria for clinically inactive disease on and off therapy for juvenile dermatomyositis (JDM). METHODS: The Paediatric Rheumatology International Trials Organisation (PRINTO) database contains 275 patients with active JDM evaluated prospectively up to 24 months. Thirty-eight patients off therapy at 24 months were defined as clinically inactive and included in the reference group. These were compared with a random sample of 76 patients who had active disease at study baseline. Individual measures of muscle strength/endurance, muscle enzymes, physician's and parent's global disease activity/damage evaluations, inactive disease criteria derived from the literature and other ad hoc criteria were evaluated for sensitivity, specificity and Cohen's κ agreement. RESULTS: The individual measures that best characterised inactive disease (sensitivity and specificity >0.8 and Cohen's κ >0.8) were manual muscle testing (MMT) ≥78, physician global assessment of muscle activity=0, physician global assessment of overall disease activity (PhyGloVAS) ≤0.2, Childhood Myositis Assessment Scale (CMAS) ≥48, Disease Activity Score ≤3 and Myositis Disease Activity Assessment Visual Analogue Scale ≤0.2. The best combination of variables to classify a patient as being in a state of inactive disease on or off therapy is at least three of four of the following criteria: creatine kinase ≤150, CMAS ≥48, MMT ≥78 and PhyGloVAS ≤0.2. After 24 months, 30/31 patients (96.8%) were inactive off therapy and 69/145 (47.6%) were inactive on therapy. CONCLUSION: PRINTO established data-driven criteria with clearly evidence-based cut-off values to identify JDM patients with clinically inactive disease. These criteria can be used in clinical trials, in research and in clinical practice.

Identification of C7orf11 (TTDN1) gene mutations and genetic heterogeneity in nonphotosensitive trichothiodystrophy.

We have identified C7orf11, which localizes to the nucleus and is expressed in fetal hair follicles, as the first disease gene for nonphotosensitive trichothiodystrophy (TTD). C7orf11 maps to chromosome 7p14, and the disease locus has been designated "TTDN1" (TTD nonphotosensitive 1). Mutations were found in patients with Amish brittle-hair syndrome and in other nonphotosensititive TTD cases with mental retardation and decreased fertility but not in patients with Sabinas syndrome or Pollitt syndrome. Therefore, genetic heterogeneity in nonphotosensitive TTD is a feature similar to that observed in photosensitive TTD, which is caused by mutations in transcription factor II H (TFIIH) subunit genes. Comparative immunofluorescence analysis, however, suggests that C7orf11 does not influence TFIIH directly. Given the absence of cutaneous photosensitivity in the patients with C7orf11 mutations, together with the protein's nuclear localization, C7orf11 may be involved in transcription but not DNA repair.

Accuracy of a new transmittance-reflectance pulse oximetry sensor in critically ill neonates.

OBJECTIVE: To test the accuracy of a new pulse oximeter sensor based on transmittance and reflectance. This sensor makes transillumination of tissue unnecessary and allows measurements on the hand, forearm, foot, and lower limb. DESIGN: Prospective, open, nonrandomized criterion standard study. SETTING: Neonatal intensive care unit, tertiary care center. PATIENTS: Sequential sample of 54 critically ill neonates (gestational age 27 to 42 wks; postnatal age 1 to 28 days) with arterial catheters in place. MEASUREMENTS AND MAIN RESULTS: A total of 99 comparisons between pulse oximetry and arterial saturation were obtained. Comparison of femoral or umbilical arterial blood with transcutaneous measurements on the lower limb (n = 66) demonstrated an excellent correlation (r2 = .96). The mean difference was +1.44% +/- 3.51 (SD) % (range -11% to +8%). Comparison of the transcutaneous values with the radial artery saturation from the corresponding upper limb (n = 33) revealed a correlation coefficient of 0.94 with a mean error of +0.66% +/- 3.34% (range -6% to +7%). The mean difference between noninvasive and invasive measurements was least with the test sensor on the hand, intermediate on the calf and arm, and greatest on the foot. The mean error and its standard deviation were slightly larger for arterial saturation values < 90% than for values > or = 90%. CONCLUSION: Accurate pulse oximetry saturation can be acquired from the hand, forearm, foot, and calf of critically ill newborns using this new sensor.

Prevalence of the metabolic syndrome in the Seychelles according to different definitions, contribution of components, and agreement between different definitions

Background: The metabolic syndrome (MS) represents a cluster of metabolic disorders that predicts diabetes and cardiovascular disease. Several definitions exist and further descriptive and prospective data are needed to compare these definitions and their significance in different populations. Objective: We examined, in a country of the African region, i) the prevalence of MS according to three major definitions (ATP, IDF, WHO); ii) the contribution of individual MS components; and iii) the agreement between the three considered definitions. We also examined the prevalence among diabetics and non-diabetics. Methods: We conducted an examination survey in a sample representative of the general population aged 25-64 of the Seychelles (Indian Ocean, African region), attended by 1255 persons (participation rate of 80.2%). Results: The prevalence of MS was similar with either definition of MS in men (24%--25%) but differed in women (WHO: 25%, ATP: 32%; IDF: 35%). Upon exclusion of diabetic persons, the prevalence was 5-10% lower for all three MS definitions: most diabetic persons had MS although a substantial proportion of diabetic men aged 45--64 did not have MS. The following components were found most often among persons with MS: 90% had high blood pressure (HBP) and 78% had obesity (ATP); 95% had obesity and 84% had HBP (WHO), and 89% had HBP and 75% had impaired glucose regulation (IDF) - not considering impaired glucose regulation and obesity that are compulsory components of the WHO and IDF definitions, respectively. Among persons with MS based on either of the three definitions (37% of total population), less than 80% met both ATP and IDF criteria, 67% both WHO and IDF criteria, 54% both WHO and ATP criteria and only 37% met all three definitions. Conclusion: We found a fairly high prevalence of MS in an African population. However, because there was only poor agreement between the 3 MS definitions, the fairly similar proportions of MS based on ATP, IDF or WHO definitions identified, to a substantial extent, different subjects as having MS.

Health care supply, payment system and medical practice : evidence from obstetric practice

ABSTRACTA significant share of deliveries are performed by Cesarian section (C-section) in Europe and in many developed and developing countries. The aims of this thesis are to highlight the non medical, especially economic and financial, incentives that explain the use of C-section, as well as the medical consequences of C-section on women's health, in regard with other factors of ob¬stetrical care quality such as hospital concentration. Those diagnoses enable us to exhibit ways of improvement of obstetrical care quality in France. Our analysis focus on two countries, France and Switzerland. In the first part of the thesis, we show the influence of two non medical factors on the C-section use, namely the hospital payment system on the one hand and the obstetricians behaviour, especially their demand for leisure, on the other hand. With French data on the year 2003, we show firstly that the fee-for-service payment system of private for profit hospitals induces a higher probability of using C-section. Obstetricians play also a preeminent role in the decision to use a C-section, as the probability of a C-section rises with the number of obstetricians. We then focus on a French reform introduced in 2004, to investigate the impact of Prospective Payment System on obstetric practise. We show that the rise of C-section rate between 2003 and 2006 is mainly caused by changes in hospitals and patients features. Obstetricians practises do not vary a lot for patients with the same risk code. In the mean time however, the number of women coded with a high risk rises. This can be caused by improvements in the quality of coding, obstetricians chosing codes that match better the real health state of their patients. Yet, it can also show that obstetricians change their coding practises to justify the use of certain practises, such as C-section, with no regard to the health state of patients. Financial factors are not the only non medical fac¬tors that can influence the resort to C-section. Using Shelton Brown ΠΙ identification strategy, we focus on the potential impact of obstetricians leisure preference on the use of C-section. We use the distributions of days and hours of delivering and the types of C-section - planned or emergency C-sections - to show that the obstetricians demand for leisure has a significant impact on the resort to C-section, but only in emergency situations. The second part of the thesis deals with some ways to improve obstetric care quality. We use on the one hand swiss and french data to study the impact of C-section on the patients' probability of having an obstetric complication and on the other hand the influence of hospital concentration on the quality of obstetric care. We find the same results as former medical studies about the risks entailed by C-section on obstetric complications.These results prove women ought to be better informed of the medical consequences of C-section and that the slowing of C-section use should be a priority of public health policy. We finally focus on another way to improve obstetric care quality, that is hospital lmarket concentration. We investigate the impact of hospital concentration by integrating the Herfindahl-Hirschman index in our model, on health care quality, measured by the HCUP indicator. We find that hospital concentration has a negative impact on obstetric care quality, which undermines today's policy of hospital closings in France.JEL classification: 112; 118Keywords: Hospital; C-section; Payment System; Counterfactual Estimation; Quality of Care.RÉSUMÉUne part importante des accouchements sont réalisés par césarienne en Europe et dans de nom¬breux pays développés ou en développement. Les objectifs de cette thèse sont de mettre en évidence les déterminants non médicaux, notamment économiques et financiers, expliquant le développe¬ment de cette pratique, ainsi que ses conséquences sur la santé des femmes après Γ accouchement, en lien avec d'autres facteurs comme la concentration locale des structures hospitalières. Les résul¬tats exposés dans cette thèse éclairent les perspectives et voies d'amélioration de la qualité des soins en obstétriques.Notre analyse se concentre sur deux pays : la France et la Suisse. Dans la première partie de la thèse, nous mettons en évidence l'influence de deux déterminants non médicaux sur l'emploi de la césarienne : le système de paiement des hôpitaux d'une part, et le comportement des médecins obstétriciens d'autre part. En étudiant des données françaises de 2003, nous montrons d'abord que le financement à l'acte des établissements privés engendre une hausse de la proba¬bilité de pratiquer une césarienne. Le rôle de l'obstrétricien paraît également déterminant dans la décision d'opérer une césarienne, la probabilité d'employer cette technique augmentant avec le nombre d'obstétriciens. Nous nous intéressons ensuite à l'impact de la mise en place en 2004 du système de paiement prospectif sur l'évolution des pratiques obstétricales entre 2003 et 2006 en France. La hausse du taux de recours à la césarienne entre 2004 et 2006 peut ainsi être principa¬lement imputée aux évolutions des caractéristiques des hôpitaux et des patients, les pratiques des obstétriciens, pour un même codage de la situation du patient, variant peu. Dans le même temps cependant, les pratiques de codage des patients parles obstétriciens évoluent fortement, les femmes étant de plus en plus nombreuses à porter des codes correspondant à des situations à risques. Cette évolution peut indiquer que la qualité du codage en 2006 s'est améliorée par rapport à 2004, le codage correspondant de plus en plus à la situation réelle des patientes. H peut aussi indiquer que les pratiques de codage évoluent pour justifier un recours accru à la césarienne, sans lien avec l'état réel des patientes. Les facteurs financiers ne sont pas les seuls facteurs non médicaux à pouvoir expliquer le recours à la césarienne : nous nous intéressons, en suivant la stratégie d'identifica¬tion de Shelton Brown m, à l'impact potentiel de la demande de loisir des médecins obstétriciens sur la pratique de la césarienne. En utilisant la distribution des jours et heures d'accouchement, et en distinguant les césariennes planifiées de celles effectuées en urgence, nous constatons que la demande de loisir des obstétriciens influence significativement le recours à la césarienne, mais uni¬quement pour les interventions d'urgence. La deuxième partie de la thèse est consacrée à l'étude de la qualité des soins en obstétriques. Nous utilisons des données suisses et françaises pour analyser d'une part l'impact de la césarienne sur la survenue de complications obstétricales et d'autre part l'impact de la concentration des soins sur la qualité des soins en obstétrique. Nons confirmons les résultats antérieurs de la littérature médicale sur la dangerosité de la césarienne comme facteur de complications obstétricales. Ces conclusions montrent que les femmes ont besoin d'être informées des conséquences de la césarienne sur leur santé et que le ralentissement de l'augmentation de la pratique de la césarienne devrait être un objectif de la politique publique de santé. Nous nous in¬téressons à un autre facteur d'amélioration des soins en obstrétique, l'organisation des hôpitaux et particulièrement leur concentration. Nous estimons ainsi l'effet de la concentration sur la qualité des soins obstétriques en intégrant l'indice de Herfindahl-Hirschman dans notre modèle, la qualité des soins étant mesurée à l'aide de l'indicateur HCUP. Nous constatons que la concentration des naissances a un impact négatif sur la qualité des soins en obstétrique, résultat qui va dans le sens contraire des politiques de fermeture d'hôpitaux menées actuellement en France. JEL classification : 112 ; 118Mots-clés : Hôpital ; Césarienne ; Système de paiement ; Contrefactuels ; Qualité des soins, sur la qualité des soins en obstétrique.

Development of a vaccine strategy against human and bovine schistosomiasis: background and update

Schistosomiasis is a chronic and debilitating parasitic disease that affects over 200 million people throughout the world and causes about 500,000 deaths annually. Two specific characteristics of schistosome infection are of primordial importance to the development of a vaccine: schistosomes do not multiply within the tissues of their definitive hosts (unlike protozoan parasites) and a partial non-sterilizing immunity can have a marked effect on the incidence of pathology and on disease transmission. Since viable eggs are the cause of disease pathology, a reduction in worm fecundity whether or not accompanied by a reduction in parasite burden is a sufficient goal for vaccine induced immunity. We originally showed that IgE antibodies played in experimental models a pivotal role for the development of protective immunity. These laboratory findings have been now confirmed in human populations. Following the molecular cloning and expression of a protein 28 kDa protein of Schistosoma mansoni and its identification as a glutathion S-transferase, immunization experiments have been undertaken in several animal species (rats, mice, baboons). Together with a significant reduction in parasite burden, vaccination with Sm28 GST was recently shown to reduce significantly parasite fecundity and egg viability leading to a decrease in liver pathology. Whereas IgE antibodies were shown to be correlated with protection against infection, IgA antibodies have been identified as one of the factors affecting egg laying and viability. In human populations, a close association was found between IgA antibody production to Sm28 GST and the decrease of egg output. The use of appropriate monoclonal antibody probes has allowed the demonstration that the inhibition of parasite fecundity following immunization was related to the inhibition of enzymatic activity of the molecule. Epitope mapping of Sm28 GST has indicated the prominent role of the N and C terminal domains. Immunization with the corresponding synthetic peptides was followed by a decrease of 70% of parasite fecundity and egg viability. As a preliminary step towards phase I human trials, vaccination experiments have been performed in cattle, a natural model for Schistosoma bovis. Vaccination of calves with the S. bovis GST has led to a reduction of ever 80% of egg output and tissue egg count. Significant levels of protection were also observed in goats after immunization with the recombinant S. bovis GST. Increasing evidence of the participation of IgA antibodies in protective immunity has prompted us toward the development of mucosal immunization. Preliminary results indicate that significant levels of protection can be achieved following oral immunization with live attenuated vectors or liposomes. These studies seem to represent a promising approach towards the future development of a vaccine strategy against one of major human parasitic diseases.