Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data.

BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

Significance of an isolated new right bundle branch block in a patient with chest pain.

Chest pain is a common presenting symptom in emergency departments, and a typical manifestation of acute myocardial infarction (AMI). Recognition of ECG changes in AMI is essential for timely diagnosis and treatment. Right bundle branch block (RBBB) may be an isolated sign of AMI, and was previously considered as a criterion for fibrinolytic therapy. Since the most recent European Society of Cardiology and American Heart Association guidelines in 2013, RBBB alone is no longer considered a diagnostic criterion of AMI, even if it occurs in the context of acute chest pain, as RBBB does not usually interfere with the interpretation of ST-segment alteration. Our case illustrates an acute septal myocardial infarction with an isolated RBBB, and thus the importance of recognising this pattern in order to permit timely diagnosis and treatment.

Evaluation of Software Development Practices through Error Analysis

This thesis studies evaluation of software development practices through an error analysis. The work presents software development process, software testing, software errors, error classification and software process improvement methods. The practical part of the work presents results from the error analysis of one software process. It also gives improvement ideas for the project. It was noticed that the classification of the error data was inadequate in the project. Because of this it was impossible to use the error data effectively. With the error analysis we were able to show that there were deficiencies in design and analyzing phases, implementation phase and in testing phase. The work gives ideas for improving error classification and for software development practices.

Error de inclinación paleomagnética en materiales aluviales del Oligoceno superior del sector Suroriental de la Cuenca del Ebro (Region Surpirenaica, NE de España).

En el sector suroriental de la Cuenca del Ebro, la inclinación paleomagnética obtenida en las sucesiones aluviales oligocenas es considerablemente menor que la esperable, si se considera la paleolatitud de referencia calculada para esa región durante el Oligoceno. Este error de inclinación puede deberse a diversos factores, como el control hidrodinámica de las partículas magnéticas en el medio deposicional, la compactación diferencial del sedimento durante el enterramiento, o bien a la deformación tectónica. Este trabajo se ha centrado en su estudio en dos sucesiones dominantemente aluviales, donde previamente se había establecido su magnetoestratigrafia. Las litofacies aluviales y lacustres estudiadas se han agrupado en cinco grupos: areniscas grises, areniscas rojas y versicolores, limos rojos, lutitas rojas y calizas. Se ha demostrado la existencia de una correlación entre la abundancia de filosilicatos y el error de inclinación. De esta manera, las litofacies con un bajo porcentaje de filosilicatos (calizas y areniscas grises) presentan errores de unos 5', estadisticarnente no significativos, con respecto a la inclinación de referencia. Por el contrario, en materiales con un porcentaje más elevado de filosilicatos (limos y arcillas) el error puede llegar a los 25'. Este hecho no tiene repercusión en la interpretación de las polaridades magnéticas, pero si en las reconstmcciones palinspásticas y paleogeográficas basadas en los cálculos de paleolatitudes a partir de las paleoinclinaciones. Los resultados obtenidos demuestran la necesidad de cautela en la propuesta de conclusiones basadas exclusivamente en este tipo de información.

Successful long-term ambulatory norepinephrine infusions in a patient with pure autonomic failure.

We present a case study of a patient with pure autonomic failure who was successfully treated with ambulatory norepinephrine (NE) infusions over a 9-year-period of time before death occurred unexpectedly. Given this patient's response to the NE infusion treatment, we discuss the option of ambulatory NE infusions as a treatment for severe orthostatic hypotension that is refractory to common treatments.

Error models in hydrogeology applications

Notre consommation en eau souterraine, en particulier comme eau potable ou pour l'irrigation, a considérablement augmenté au cours des années. De nombreux problèmes font alors leur apparition, allant de la prospection de nouvelles ressources à la remédiation des aquifères pollués. Indépendamment du problème hydrogéologique considéré, le principal défi reste la caractérisation des propriétés du sous-sol. Une approche stochastique est alors nécessaire afin de représenter cette incertitude en considérant de multiples scénarios géologiques et en générant un grand nombre de réalisations géostatistiques. Nous rencontrons alors la principale limitation de ces approches qui est le coût de calcul dû à la simulation des processus d'écoulements complexes pour chacune de ces réalisations. Dans la première partie de la thèse, ce problème est investigué dans le contexte de propagation de l'incertitude, oú un ensemble de réalisations est identifié comme représentant les propriétés du sous-sol. Afin de propager cette incertitude à la quantité d'intérêt tout en limitant le coût de calcul, les méthodes actuelles font appel à des modèles d'écoulement approximés. Cela permet l'identification d'un sous-ensemble de réalisations représentant la variabilité de l'ensemble initial. Le modèle complexe d'écoulement est alors évalué uniquement pour ce sousensemble, et, sur la base de ces réponses complexes, l'inférence est faite. Notre objectif est d'améliorer la performance de cette approche en utilisant toute l'information à disposition. Pour cela, le sous-ensemble de réponses approximées et exactes est utilisé afin de construire un modèle d'erreur, qui sert ensuite à corriger le reste des réponses approximées et prédire la réponse du modèle complexe. Cette méthode permet de maximiser l'utilisation de l'information à disposition sans augmentation perceptible du temps de calcul. La propagation de l'incertitude est alors plus précise et plus robuste. La stratégie explorée dans le premier chapitre consiste à apprendre d'un sous-ensemble de réalisations la relation entre les modèles d'écoulement approximé et complexe. Dans la seconde partie de la thèse, cette méthodologie est formalisée mathématiquement en introduisant un modèle de régression entre les réponses fonctionnelles. Comme ce problème est mal posé, il est nécessaire d'en réduire la dimensionnalité. Dans cette optique, l'innovation du travail présenté provient de l'utilisation de l'analyse en composantes principales fonctionnelles (ACPF), qui non seulement effectue la réduction de dimensionnalités tout en maximisant l'information retenue, mais permet aussi de diagnostiquer la qualité du modèle d'erreur dans cet espace fonctionnel. La méthodologie proposée est appliquée à un problème de pollution par une phase liquide nonaqueuse et les résultats obtenus montrent que le modèle d'erreur permet une forte réduction du temps de calcul tout en estimant correctement l'incertitude. De plus, pour chaque réponse approximée, une prédiction de la réponse complexe est fournie par le modèle d'erreur. Le concept de modèle d'erreur fonctionnel est donc pertinent pour la propagation de l'incertitude, mais aussi pour les problèmes d'inférence bayésienne. Les méthodes de Monte Carlo par chaîne de Markov (MCMC) sont les algorithmes les plus communément utilisés afin de générer des réalisations géostatistiques en accord avec les observations. Cependant, ces méthodes souffrent d'un taux d'acceptation très bas pour les problèmes de grande dimensionnalité, résultant en un grand nombre de simulations d'écoulement gaspillées. Une approche en deux temps, le "MCMC en deux étapes", a été introduite afin d'éviter les simulations du modèle complexe inutiles par une évaluation préliminaire de la réalisation. Dans la troisième partie de la thèse, le modèle d'écoulement approximé couplé à un modèle d'erreur sert d'évaluation préliminaire pour le "MCMC en deux étapes". Nous démontrons une augmentation du taux d'acceptation par un facteur de 1.5 à 3 en comparaison avec une implémentation classique de MCMC. Une question reste sans réponse : comment choisir la taille de l'ensemble d'entrainement et comment identifier les réalisations permettant d'optimiser la construction du modèle d'erreur. Cela requiert une stratégie itérative afin que, à chaque nouvelle simulation d'écoulement, le modèle d'erreur soit amélioré en incorporant les nouvelles informations. Ceci est développé dans la quatrième partie de la thèse, oú cette méthodologie est appliquée à un problème d'intrusion saline dans un aquifère côtier. -- Our consumption of groundwater, in particular as drinking water and for irrigation, has considerably increased over the years and groundwater is becoming an increasingly scarce and endangered resource. Nofadays, we are facing many problems ranging from water prospection to sustainable management and remediation of polluted aquifers. Independently of the hydrogeological problem, the main challenge remains dealing with the incomplete knofledge of the underground properties. Stochastic approaches have been developed to represent this uncertainty by considering multiple geological scenarios and generating a large number of realizations. The main limitation of this approach is the computational cost associated with performing complex of simulations in each realization. In the first part of the thesis, we explore this issue in the context of uncertainty propagation, where an ensemble of geostatistical realizations is identified as representative of the subsurface uncertainty. To propagate this lack of knofledge to the quantity of interest (e.g., the concentration of pollutant in extracted water), it is necessary to evaluate the of response of each realization. Due to computational constraints, state-of-the-art methods make use of approximate of simulation, to identify a subset of realizations that represents the variability of the ensemble. The complex and computationally heavy of model is then run for this subset based on which inference is made. Our objective is to increase the performance of this approach by using all of the available information and not solely the subset of exact responses. Two error models are proposed to correct the approximate responses follofing a machine learning approach. For the subset identified by a classical approach (here the distance kernel method) both the approximate and the exact responses are knofn. This information is used to construct an error model and correct the ensemble of approximate responses to predict the "expected" responses of the exact model. The proposed methodology makes use of all the available information without perceptible additional computational costs and leads to an increase in accuracy and robustness of the uncertainty propagation. The strategy explored in the first chapter consists in learning from a subset of realizations the relationship between proxy and exact curves. In the second part of this thesis, the strategy is formalized in a rigorous mathematical framework by defining a regression model between functions. As this problem is ill-posed, it is necessary to reduce its dimensionality. The novelty of the work comes from the use of functional principal component analysis (FPCA), which not only performs the dimensionality reduction while maximizing the retained information, but also allofs a diagnostic of the quality of the error model in the functional space. The proposed methodology is applied to a pollution problem by a non-aqueous phase-liquid. The error model allofs a strong reduction of the computational cost while providing a good estimate of the uncertainty. The individual correction of the proxy response by the error model leads to an excellent prediction of the exact response, opening the door to many applications. The concept of functional error model is useful not only in the context of uncertainty propagation, but also, and maybe even more so, to perform Bayesian inference. Monte Carlo Markov Chain (MCMC) algorithms are the most common choice to ensure that the generated realizations are sampled in accordance with the observations. Hofever, this approach suffers from lof acceptance rate in high dimensional problems, resulting in a large number of wasted of simulations. This led to the introduction of two-stage MCMC, where the computational cost is decreased by avoiding unnecessary simulation of the exact of thanks to a preliminary evaluation of the proposal. In the third part of the thesis, a proxy is coupled to an error model to provide an approximate response for the two-stage MCMC set-up. We demonstrate an increase in acceptance rate by a factor three with respect to one-stage MCMC results. An open question remains: hof do we choose the size of the learning set and identify the realizations to optimize the construction of the error model. This requires devising an iterative strategy to construct the error model, such that, as new of simulations are performed, the error model is iteratively improved by incorporating the new information. This is discussed in the fourth part of the thesis, in which we apply this methodology to a problem of saline intrusion in a coastal aquifer.

How to Prepare a Patient for Transarterial Radioembolization? A Practical Guide.

Transarterial radioembolization consist in delivering small particles loaded with Yttrium90, a pure beta emitter, in order to treat primary and secondary liver tumors. This treatment needs precaution since inadequate delivery of these beads can lead to severe complications. Moreover, a precise radiation dosing is crucial to achieve a good clinical success and to avoid complications such as radioembolization-induced liver disease. This review describes all the precautions and highlights clinical and technical considerations that need to be taken to avoid complications.

L'anticoagulation du patient âgé en fibrillation atriale: que prescrivent les cardiologues, les gériatres et les médecins généralistes [Anticoagulation in the aged patient with atrial fibrillation: What are prescribing cardiologists, geriatricians and general practitioners?].

OBJECTIVE: To assess prescribing of anticoagulants in atrial fibrillation (AF) in the elderly, both a quantitative point of view (rate of anticoagulation) and qualitative (type of anticoagulation). Determinants of prescribing and non-prescribing were also analysed. METHODS: Prospective survey of practice, based on one clinical case and questionnaire conducted in 60 practitioners (20 cardiologists [C], 20 geriatricians [G] and 20 general practitioners [GP]). RESULTS: In reading the clinical case, 88.3% of physicians would have initiated a treatment; three types of treatments would have been chosen: AVK (68.3%), ODA (20.0%) and platelet antiaggregant (11.7%). Criteria taken into account to initiate anticoagulation varied according to the specialty. Cardiologists considered more the age criteria (C: 95.0%, G: 75.0%, MG: 60.0%; P<0.05), diabetes (C: 90.0%, G: 60.0%, MG: 55.0%; P<0.05), hypertension (C: 85.0%, G: 55.0%, MG: 60.0%; P<0.05) and female gender (C: 80.0%, G: 35.0%, MG: 25.0%; P<0.05). The quality of renal function was however a more secondary criteria (C: 15.0%, G: 5.0%, MG: 0.0%; P<0.05). General practitioners considered most frequently the presence of underlying heart disease (C: 35.0%, G: 5.0%, MG: 45.0%; P<0.05) as well as usual cardiovascular risk factors (overweight, dyslipidaemia; P<0.05). Risk of bleeding, however, was observed by 76.7% of physicians in the clinical situation presented (C: 70.0%, G: 75.0%, MG: 85.0%; P<0.05). CONCLUSION: This survey confirms that the FA remains under anticoagulated in the elderly and the barriers to the prescription of oral anticoagulation are often without rational basis.

Oral implant rehabilitation in a patient with Moebius syndrome

Introduction: Moebius syndrome is a rare congenital disorder characterized by unilateral or bilateral involvement of the sixth and seventh cranial nerves, resulting in a lack of facial expression and eye movements. These patients suffer a series of oral manifestations that may complicate their dental treatment, such as facial and tongue muscle weakness, uncontrolled salivation secondary to defi cient lip sealing, micrognathia, microstomia, bifi d uvula, gothic and fi ssured palate, fi ssured tongue, and glossoptosis. The underlying etiology remains unclear, though vascular problems during embryogenesis appear to be involved. Clinical case: We report the case of a woman with Moebius syndrome and total edentulism. Eight years ago she underwent complete oral rehabilitation with the placement of two implants in each dental arch. Discussion: Moebius syndrome has still an unknown etiology, although it is related to disorders during pregnancy. This kind of patient can be rehabilitated using oral implants.

How patient-centered do female physicians need to be? Analogue patients' satisfaction with male and female physicians' identical behaviors (Published online: 30 Aug 2014)

Previous research suggests that female physicians may not receive appropriate credit in patients' eyes for their patient-centered skills compared to their male counterparts. An experiment was conducted to determine whether a performance of higher (versus lower) verbal patient-centeredness would result in a greater difference in analogue patient satisfaction for male than female physicians. Two male and two female actors portrayed physicians speaking to a patient using high or low patient-centered scripts while not varying their nonverbal cues. One hundred ninety-two students served as analogue patients by assuming the patient role while watching one of the videos and rating their satisfaction and other evaluative responses to the physician. Greater verbal patient-centeredness had a stronger positive effect on satisfaction and evaluations for male than for female physicians. This pattern is consistent with the hypothesis that the different associations between patient-centeredness and patients' satisfaction for male versus female physicians occur because of the overlap between stereotypical female behavior and behaviors that comprise patient-centered medical care. If this is the case, high verbal patient-centered behavior by female physicians is not recognized as a marker of clinical competence, as it is for male physicians, but is rather seen as expected female behavior.