[A pharmacologic approach to treatment of Mycobacterium abscessus pulmonary disease]. / Analyse pharmacologique du traitement des pneumopathies à Mycobacterium abscessus.

Mycobacterium abscessus is a fast-growing non-tuberculous mycobacteria complex causing pulmonary infections, comprising the subspecies abscessus, massiliense and bolletii. Differences are based predominantly on natural inducible macrolide resistance, active in most Mycobacterium abscessus spp abscessus species and in Mycobacterium abscessus spp bolletii but inactive in Mycobacterium abscessus spp massiliense. Therapy consists in long-term treatment, combining multiple antibiotics. Prognosis is poor, as only 40% of patients experience cure. Pharmacodynamic and pharmacokinetic data on M. abscessus have recently been published, showing that therapy ineffectiveness might be explained by intrinsic bacterial resistance (macrolides…) and by the unfavorable pharmacokinetics of the recommended antibiotics. Other molecules and inhaled antibiotics are promising.

Screening for active and latent TB among migrants in France.

SETTING: Migrants to Europe face a disproportionate burden of infections, including TB, yet little is known about the approach taken by primary and secondary care providers to screening and treatment. We therefore explored policy and practice relating to screening of active TB and latent TB infection (LTBI) in France.METHODS: We conducted an online national survey of French primary and secondary care physicians regarding their practices in relation to TB/LTBI screening among migrants.RESULTS: 367 physicians responded to the questionnaire among which 195 (53.1%) were primary care physicians, 126 (34.3%) were TB specialists in secondary care, and 46 (12.5%) other physicians; 303 (85.5%) were involved daily in the care of migrants. Most respondents recommended systematic TB screening with chest X-ray for migrants from medium and high-incidence countries (71.9%). Primary care physicians were less likely to offer screening than physicians in other settings (aOR 0.21, 95% CI 0.09-0.48). 220 (61.8%) offered LTBI screening for children (<15 years) and 34.0% for all migrants from high incidence countries.CONCLUSION: Improving awareness on TB screening is a critical next step to improve health outcomes in migrant groups and meet regional targets for tackling TB.

An extended statically equivalent serial chain-Identification of whole body center of mass with dynamic motion.

BACKGROUND: Tracking the whole body center of mass (CoM) trajectory of balance-impaired individuals with a personalized model is useful in the development of customized fall prevention strategies. A personalized CoM estimate can be obtained using the statically equivalent serial chain (SESC) method, but the subject has to perform an identification procedure to determine the set of subject-specific SESC parameters. During this identification, the subject must hold a series of static poses, some of which are unsuitable for balanced-impaired individuals. RESEARCH QUESTION: Can non-static poses be used to replace the static poses during SESC parameter identification? METHODS: A new method that extends the range of postures used to determine SESC parameters is presented. It takes advantage of CoM dynamics and can be executed by predominantly using dynamic motions with a few static frames. Furthermore, it is implemented using a Kalman filter to allow automatic switching between the dynamic and static models. The proposed method was tested with motion data obtained from seven healthy adults using a Vicon motion capture system and an AMTI force platform. RESULTS: We found that dynamic motions could be used to estimate the SESC parameter and even reproduce ground reaction forces; however a small number of static poses are still required to determine the subject's CoM position. The SESC-based CoM estimate obtained with this new approach was similar to that obtained using conventional full-static identification, except that the subject did not have to assume and maintain static poses. SIGNIFICANCE: Our proposed extension of the conventional SESC method would facilitate its application in the field of neuro-rehabilitation, especially in patients who need balance training. This personalized CoM method could be applicable for patients who are not able to maintain a static posture. In addition, this method helps minimize the total identification time by increasing the number of usable recorded frames.

[Parardoxical reaction following tuberculosis treatment in non HIV-infected patients]. / Les réactions paradoxales au cours du traitement de la tuberculose (hors infection par le VIH).

A paradoxical reaction is the worsening of prior existing, or the appearance of, new tuberculous lesions, following the initiation of treatment with anti-tuberculous drugs, after the exclusion of poor compliance, malabsorption, drug interaction or multiresistant mycobacteria. Well known and well managed in the context of HIV coinfection, it is not well known outside this context. An increasing number of publications have described this syndrome. This review aims to describe the pathogenic, epidemiological, clinical, prognostic and therapeutic elements of non-HIV-associated paradoxical reactions. It involves a reversal of the Mycobacterium tuberculosis-induced immunodepression along with a heightened detrimental pro-inflammatory profile caused by efficient drug treatment. Extra-thoracic locations, especially lymph nodes and neurological, malnutrition and initial lymphopenia are the principal risk factors. The median delay is 40±20 days after the onset of treatment. Corticosteroids are the mainstay of the management. Anti-TNF-α drugs show good results in corticosteroid refractory cases. The prognosis is good overall except in neurological forms. The place of preventive methods remains to be established.

[Multidrug-resistant tuberculosis: A management problem that weighs heavily on the University Hospitals of Strasbourg]. / Tuberculose multirésistante : une prise en charge qui pèse lourd aux hôpitaux universitaires de Strasbourg.

INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) is a major public health problem with great regional disparities. The aim of this study was to describe the epidemiological, clinical, and therapeutics aspects of MDR-TB in Alsace, France. PATIENTS AND METHODS: A 10 years retrospective study, conducted for the years 2006 to 2016, of all MDR-TB cases diagnosed in Alsace and particularly in Strasbourg University Hospitals. RESULTS: We included 22 patients with MDR-TB of whom 90% originated from Eastern Europe, 13.6% had extensively-resistant strains, and 41% reported previously treated tuberculosis. Clinically, 86,4% had a pulmonary form of tuberculosis. The mean length of antibiotic treatment was 21 months with several changes of drugs because of severe side effects. The mean follow-up was 48 months, during which time 2 patients were lost from contact and the 20 remaining patients were cured. CONCLUSIONS: Management of MDR-TB is a real social and medical challenge. Our study shows that the therapeutic protocols used in the management of these patients lead to an unusually high rate of success despite the occurrence of several, sometimes severe, side effects.

A constrained extended Kalman filter for the optimal estimate of kinematics and kinetics of a sagittal symmetric exercise.

This paper presents a method for real-time estimation of the kinematics and kinetics of a human body performing a sagittal symmetric motor task, which would minimize the impact of the stereophotogrammetric soft tissue artefacts (STA). The method is based on a bi-dimensional mechanical model of the locomotor apparatus the state variables of which (joint angles, velocities and accelerations, and the segments lengths and inertial parameters) are estimated by a constrained extended Kalman filter (CEKF) that fuses input information made of both stereophotogrammetric and dynamometric measurement data. Filter gains are made to saturate in order to obtain plausible state variables and the measurement covariance matrix of the filter accounts for the expected STA maximal amplitudes. We hypothesised that the ensemble of constraints and input redundant information would allow the method to attenuate the STA propagation to the end results. The method was evaluated in ten human subjects performing a squat exercise. The CEKF estimated and measured skin marker trajectories exhibited a RMS difference lower than 4mm, thus in the range of STAs. The RMS differences between the measured ground reaction force and moment and those estimated using the proposed method (9N and 10Nm) were much lower than obtained using a classical inverse dynamics approach (22N and 30Nm). From the latter results it may be inferred that the presented method allows for a significant improvement of the accuracy with which kinematic variables and relevant time derivatives, model parameters and, therefore, intersegmental moments are estimated.

A new 3D center of mass control approach for FES-assisted standing: First experimental evaluation with a humanoid robot.

This paper proposes a new control framework to restore the coordination between upper (functional) and lower (paralyzed) limbs in the context of functional electrical stimulation in completely paraplegic individuals. A kinematic decoupling between the lower and upper limbs controls the 3D whole-body center of mass location and the relative foot positions by acting only on the lower-limb joints. The upper limbs are free to move under voluntary control, and are seen as a perturbation for the lower limbs. An experimental validation of this paradigm using a humanoid robot demonstrates the real-time applicability and robustness of the method. Different scenarios mimicking the motion of a healthy subject are investigated. The proposed method can maintain bipedal balance and track the desired center of mass trajectories under movement disturbances of the upper limbs with an error inferior to 0.01 m under any conditions.

Assessing neuromuscular mechanisms in human-exoskeleton interaction.

In this study, we propose to evaluate a 7 DOF exoskeleton in terms of motion control. Using criteria from the human motor control literature, inverse optimization was performed to assess an industrial screwing movement. The results of our study show that the hybrid composition of the free arm movement was accurately determined. At contrary, when wearing the exoskeleton, which produces an arbitrary determined torque compensation, the motion is different from the naturally adopted one. This study is part of the evaluation and comprehension of the complex neuromuscular mechanism resulting in wearing an exoskeleton several hours per day for industrial tasks assistance.

Toward an affordable and user-friendly visual motion capture system.

The present study aims at designing and evaluating a low-cost, simple and portable system for arm joint angle estimation during grasping-like motions. The system is based on a single RGB-D camera and three customized markers. The automatically detected and tracked marker positions were used as inputs to an offline inverse kinematic process based on bio-mechanical constraints to reduce noise effect and handle marker occlusion. The method was validated on 4 subjects with different motions. The joint angles were estimated both with the proposed low-cost system and, a stereophotogrammetric system. Comparative analysis shows good accuracy with high correlation coefficient (r= 0.92) and low average RMS error (3.8 deg).

The characterization and certification of a quantitative reference material for Legionella detection and quantification by qPCR.

AIMS: The characterization and certification of a Legionella DNA quantitative reference material as a primary measurement standard for Legionella qPCR. METHODS AND RESULTS: Twelve laboratories participated in a collaborative certification campaign. A candidate reference DNA material was analysed through PCR-based limiting dilution assays (LDAs). The validated data were used to statistically assign both a reference value and an associated uncertainty to the reference material. CONCLUSIONS: This LDA method allowed for the direct quantification of the amount of Legionella DNA per tube in genomic units (GU) and the determination of the associated uncertainties. This method could be used for the certification of all types of microbiological standards for qPCR. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of this primary standard will improve the accuracy of Legionella qPCR measurements and the overall consistency of these measurements among different laboratories. The extensive use of this certified reference material (CRM) has been integrated in the French standard NF T90-471 (April 2010) and in the ISO Technical Specification 12 869 (Anon 2012 International Standardisation Organisation) for validating qPCR methods and ensuring the reliability of these methods.

[Treatment of latent tuberculosis infection]. / Traitement des infections tuberculeuses latentes.

Latent tuberculosis infection is a key stage in the natural history of tuberculosis, and provides an important period where strategies to prevent the development of disease may be implemented. The treatment of latent tuberculosis infection is well described in many national guidelines. In this review, we attempt to help pneumonologists to implement these guidelines accurately and appropriately, prescribing preventive treatment when the benefit-risk ratio is optimal, providing treatment most safely, performing therapeutic education and incorporating preventive treatment into the full array of measures against tuberculosis.

[Diagnosis of latent tuberculous infections (healthy, currently or potentially immunocompromised subjects)]. / Diagnostic des infections tuberculeuses latentes (sujets sains, sujets immunodéprimés ou amenés à l'être).

Latent tuberculosis infection is a pathophysiological and clinical entity. The diagnosis is based on immunological tests such as the tuberculin skin test or interferon-gamma release assays. Interpretation of the results depends on the clinical context. Their predictive value for the occurrence of tuberculous disease is low, except in the case of young children and immunocompromised patients. Guidelines for the diagnosis of latent tuberculous infection in different countries are reviewed. The development of more predictive tests is desirable.

Factors associated with patient and health care system delay in the diagnosis of tuberculosis in France.

OBJECTIVE: To analyse diagnostic delay in tuberculosis (TB) patients. DESIGN: Cross-sectional study: all patients with TB notified to the French national surveillance system from April to June 2010 were interviewed face-to-face using a standardised questionnaire to assess symptom history and health-seeking trajectories. RESULTS: Of 225 patients enrolled, 172 (76.4%) had pulmonary TB, including 88 who were smear-positive. Mean delay between first symptoms and diagnosis (total delay) was 97 days (median 68, IQR 33-111), with a mean of 47 days (median 14, IQR 0-53) between first symptoms and health care contact (patient delay), and 48 days (median 25, IQR 6-67) between health care contact and diagnosis (health system delay). Factors independently associated with shortened total delay were medical insurance (OR 0.24, P = 0.014) and previous TB (OR 0.28, P = 0.049). Those associated with reduced patient delay were initial fever (OR 0.42, P = 0.03) and being followed by a general practitioner (OR 0.22, P = 0.004), while those associated with reduced health system delay were first health care contact within a hospital (OR 0.15, P < 0.001). Empirical antibiotic treatment was associated with increased health system delay (OR 4.4, P = 0.001). CONCLUSION: TB diagnostic delay needs to be reduced in France. This may be achieved through improved access to care, earlier hospital referral, and less use of empirical antibiotic treatment.

A paradigm for the control of upright standing in paraplegic patients.

The objective of this paper is to present a new paradigm in control strategy for unsupported paraplegic standing, based on closed-loop control of paraplegics' lower extremities. The main advantage of our approach is taking into account voluntary motions of the upper-part of the body by controlling Center of Mass (CoM) position. The validity of our approach is tested, in computer simulations, using human CoM trajectories estimated from experimental data and by applying perturbations in simulation during quiet standing in order to simulate voluntary upper body movements. From the results presented in this study it can be seen that controller is able to track desired CoM position with sufficient precision and to maintain stability even in the presence of simulated movements of the upper body.

[A conus medullaris tuberculoma: a case report and literature review]. / Tuberculome du cône médullaire: à propos d'un cas et revue de la littérature.

BACKGROUND: Tuberculosis affecting the central nervous system is well recognized, but only rarely localizes to the medullary conus. OBSERVATION: We report the case of a 69 year old man who was admitted to our unit with cauda equina syndrome. The MRI demonstrated ring-enhanced necrotizing lesions involving the medullary conus, the cervical cord and the brain. His chest CT scan showed a miliary infiltrate. The clinical presentation was associated with an inappropriate secretion of antidiuretic hormone. Quadruple antituberculous therapy was initiated, with corticosteroids in the initial phase of the treatment. Evolution was favorable, and follow-up MRI imaging demonstrated complete resolution of the cervical cord and brain lesions.