Nebulised liposomal amphotericin-B as maintenance therapy in allergic bronchopulmonary aspergillosis: a randomised, multicentre trial.

BACKGROUND: In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission. METHODS: We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months. The primary outcome was occurrence of a first severe clinical exacerbation within 24 months following randomisation. Secondary outcomes included the median time to first severe clinical exacerbation, number of severe clinical exacerbations per patient, ABPA-related biological parameters. RESULTS: Among 174 enrolled patients with ABPA from March 2015 through July 2017, 139 were controlled after 4-month attack treatment and were randomised. The primary outcome occurred in 33 (50.8%) out of 65 patients in the nebulised liposomal amphotericin-B group and 38 (51.3%) out of 74 in the placebo group (absolute difference -0.6%, 95% CI -16.8- +15.6%; OR 0.98, 95% CI 0.50-1.90; p=0.95). The median (interquartile range) time to first severe clinical exacerbation was longer in the liposomal amphotericin-B group: 337 days (168-476 days) versus 177 days (64-288 days). At the end of maintenance therapy, total immunoglobulin-E and Aspergillus precipitins were significantly decreased in the nebulised liposomal amphotericin-B group. CONCLUSIONS: In ABPA, maintenance therapy using nebulised liposomal amphotericin-B did not reduce the risk of severe clinical exacerbation. The presence of some positive secondary outcomes creates clinical equipoise for further research.

[New therapies for cystic fibrosis targeting the CFTR gene or the CFTR protein]. / Nouvelles thérapeutiques de la mucoviscidose ciblant le gène ou la protéine CFTR.

BACKGROUND: The treatment of cystic fibrosis has been symptom-based for a number of years. New therapies that aim to improve CFTR protein function are now emerging. CURRENT SCIENTIFIC KNOWLEDGE: The results of gene therapy has been modest but a recent clinical trial shows a positive effect on FEV1. Recent research has focused primarily on CFTR protein function. Significant respiratory improvement (an average 10% FEV1 increase and a decrease in the frequency of exacerbations) has been achieved with ivacaftor, a CFTR potentiator, in patients with gating mutations, resulting in its marketing authorization (in 2012 for the G551D mutation and in 2015 for rarer mutations). In phe508del homozygous patients, the combination of ivacaftor with a CFTR corrector (lumacaftor) has also led to respiratory improvement, albeit less impressive. The effectiveness of ataluren in patients with nonsense mutations is being evaluated. OUTLOOK: New CFTR correctors and potentiators are being developed. CFTR protein therapy could change the course of the disease but cost/effectiveness issues should not be overlooked. CONCLUSION: Ivacaftor can be prescribed in CF patients with a class 3 mutation from the age of 6 years. The Orkambi® will soon be available for homozygous phe508del patients from the age of 12 years.

[New therapeutic developments in cystic fibrosis]. / Nouvelles thérapeutiques ciblant le canal chlorure dans la mucoviscidose.

Since the discovery of chloride secretion by the Cystic Fibrosis Transport regulator CFTR in 1983, and CFTR gene in 1989, knowledge about CFTR synthesis, maturation, intracellular transfer and function has dramatically expanded. These discoveries have led to the distribution of CF mutations into 6 classes with different pathophysiological mechanisms. In this article we will explore the state of art on CFTR synthesis and its chloride secretion function. We will then explore the consequences of the 6 classes of mutations on CFTR protein function and we will describe the new therapeutic developments aiming at correcting these defects.

[Adolescents with cystic fibrosis: the approach to transition from paediatric to adult care]. / Transition enfant-adulte au cours de la mucoviscidose.

Because of early and effective therapies, an increasing numbers of young people with cystic fibrosis (CF) reach adulthood. Preparing for and maintaining high quality CF care in the adult healthcare is critical for prolonged survival. Because adverse health consequences occur when inadequate transition arrangements are in place, safely transferring patients from pediatric to adult care is a priority. Key features include an early preparation, planning and self-management skills, a coordinated approach and a detailed communication between patients, families, pediatric and adult teams. Formal transition protocols and audits can support the process and be helpful for multidisciplinary teams.

Improving the gas-solids contact efficiency in a fluidized bed of CO2 adsorbent fine particles.

A modified CO(2) adsorbent is obtained by dry mixing of a Ca(OH)(2) fine powder as received with a commercial silica nanopowder. Silica nanoparticles form light agglomerates of size of the order of tens of microns, which are uniformly fluidizable. These agglomerates act as dispersants of the Ca(OH)(2) fine particles, which coat the nanoparticle agglomerates likely due to contact charging. Ca(OH)(2) particles (CO(2) adsorbent) are thus provided with a vehicle for uniform fluidization. In this way, the contact efficiency between the CO(2) adsorbent and CO(2) in the fluidized bed is greatly enhanced. Experimental results show that the improvement of Ca(OH)(2) fluidizability serves to enhance the carbonation reaction in the fluidized bed.

[Changes in the fat composition and histomorphology of the liver in TPN, with and without ultra-short bowel]. / Cambios en la composición de la grasa y en la histomorfología hepáticas tras NPT, con y sin intestino ultra-corto.

BACKGROUND & AIMS: Short Bowel syndrome is a serious intestinal insufficiency. The most common etiology in adults nowadays is intestinal ischemia and inflammatory disease, while in children the most common are congenital anomalies, volvolus and necrotizing enterocolaitis, which makes the TPN obligatory. However the intestine is intimately related to the liver through the entero-hepatic circulation and different endocrinological entero-hepatic systems. Massive intestinal resections and TPN would alter this relationship, and could change the hepatic tissue composition and its histomorphology. The aim of this work is to know these changes in more detail. MATERIALS AND METHODS: We used 3 experimental groups: Group A (10 guinea pigs), which was given anesthetic and a simple laparotomy and fed for 10 days with NPT. Group B (10 guinea pigs), underwent total thin intestine resection and were fed for 10 days with NTP. The control group (6 guinea pigs) underwent anesthetic and a simple sham laparotomy and were fed orally. After this period blood and hepatic tissue samples were taken in order to study the liver fat (total fat, proportion of neutral and polar lipids, proportion of phospholipids and fatty acids). Liver biopsies were taken and studied under an optical microscope. RESULTS: The animals from group A and B, underwent NPT, showed a significant increase in glycemie and serum triglycerides, decreasing the cholesterol in GB. There was a significant decrease in weight and in the proportion of fat per g of the liver tissue, at a maximum level in GB, and an even higher decrease in the LP/LN ratio in GA and GB. There was also a change in the proportion of phospholipids, decreasing the Phosphatidilinositol and increasing the Phosphatidiletanolamine. There was also a decrease in the AG w6/w3 ratio. Histologically appear a steatohepatitys, with a striking decrease in the mitochondrial density, being more intensive in GB. CONCLUSIONS: NPT alters the composition of the hepatic fat and the hystomorphology of the liver. The short bowel syndrome have more lesional mechanisms, favouring the hepatic damage caused by NPT.

Magnetic field induced inversion in the effect of particle size on powder cohesiveness.

Experimental measurements are reported on the tensile yield stress of magnetofluidized beds of fine magnetic powders operated in the cross-flow configuration. In the absence of externally applied magnetic field the yield stress of the powder depends on particle size as expected, i.e., it increases as bead size is decreased. This trend is however inverted when an external magnetic field is applied. It is suggested that the average orientation of interparticle contacts relative to the direction of the field as affected by particle size plays a relevant role on the magnetic yield stress of these systems.

Magnetofluidization of fine magnetite powder.

The behavior of a fluidized bed of fine magnetite particles as affected by a cross-flow magnetic field is investigated. A distinct feature of this naturally cohesive powder, as compared to noncohesive magnetic grains usually employed in magnetofluidized beds, is that the fluidized bed displays a range of stable fluidization even in the absence of an external magnetic field. Upon application of the magnetic field, the interval of stable fluidization is extended to higher gas velocities and bed expansion is enhanced. We have measured the tensile strength as affected by application of the external magnetic field according to two different operation modes. In the H off-on operation mode, the bed is driven to bubbling in the absence of external magnetic field. Once the gas velocity is decreased below the bubbling onset and the bed has returned to stable fluidization due to natural cohesive forces, the field is applied. In the H on-on mode, the field is maintained during the whole process of bubbling and return to stable fluidization. It is found that the tensile strength of the naturally stabilized bed is not essentially changed by application of the field ( H off-on) since the magnetic field cannot alter the bed structure once the particles are jammed in the stable fluidization state. Magnetic forces within the bulk of the jammed bed are partially canceled as a result of the anisotropic nature of the dipole-dipole interaction between the particles, which gives rise to just a small increment of the tensile strength. On the other hand, when the field is held on during bubbling and transition to stable fluidization ( H on-on mode), the tensile strength is appreciably increased. This suggests the formation of particle chains when the particles are not constrained due to the dipole-dipole attractive interaction which affects the mechanical strength of the stably fluidized bed. Experimental data are analyzed in the light of theoretical models on magnetic surface stresses.

Electromechanics of fluidized beds of nanoparticles.

The electromechanical behavior of a gas-fluidized bed of insulating silica nanoparticles is investigated. When fluidized by gas, these nanoparticles form highly porous agglomerates of size of the order of hundreds of microns, which gives rise to a nonbubbling fluidization regime. Bed expansion is enhanced by an imposed alternating electric field for oscillation frequencies in the range between tens and hundreds of hertzs and field strengths of about 1 kV/cm . Nanoparticle agglomerates are naturally charged and experience forced oscillations that cause an increase of the gas flow shear on their surface. As a consequence, the agglomerate size is expected to decrease, which can explain the observed behavior. A model based on the balance between attractive and flow shear forces is presented that accounts for agglomerate size reduction as the strength of the field is increased.

[Antimicrobial drugs errors: the silent epidemic in patient safety]. / Errores en el uso de antimicrobianos: la epidemia silenciosa para la seguridad de pacientes.

INTRODUCTION: Prescribed drugs and the mistakes in the administration to patient is the first cause of adverse events in the hospitals. The aim of this study has been to evaluate antimicrobial drug mistakes in one of our hospital wards in a two year period 2005 and 2006. METHODS: All the errors were reported through the National Health Service IR2 form (England) on a voluntary basis and classified by means of process, type of errors, their causes and contributory factors, as well as the severity. We analyzed the economic costs. RESULTS: . A 1.3% of the inpatients had an antimicrobial error in the administration to the patient (0.84 by 1,000 prescribing orders). Classified by processes, the administration (32.4%) and dispensation (44.1%) were the most frequent errors. By type of error: the erroneous medication (32.4%), the main root cause the human factors (58.8 %) and the contribution factor due to design of tasks (55.9 %). The 5.9% of errors were severe events, mainly in the group of the betalactamic drugs, and mainly by parenteral administration (50%). Conclusions. Antimicrobial drug errors, frequent and sometimes severe, suppose a silent epidemic not being detected without the patient safety methodology. They represent a high cost for a hospital.

[Coverage rate of influenza vaccine in healthcare workers in the 12 cystic fibrosis centres of the Greater South Region of France in 2005/2006]. / Couverture vaccinale vis-à-vis de la grippe des soignants des douze Centres de Ressources et de Compétences de la Mucoviscidose du Grand-Sud de la France en 2005-2006.

INTRODUCTION: In France annual influenza vaccination is recommended for healthcare workers but few data regarding coverage are available. The objective of the present study was to evaluate influenza vaccine coverage rate in healthcare workers from the 12 cystic fibrosis centres in the Greater South Region of France during the 2005/2006 'flu season. METHODS: An observational, descriptive telephone survey was performed from February to April 2006 to collect information about the vaccine status of all the healthcare workers in the 12 cystic fibrosis centres of the Muco-Sud and Muco-Med networks. RESULTS: During the 2005/2006 'flu season a 59.4% influenza vaccine coverage rate was achieved in the 128 healthcare workers. The influenza vaccine coverage rate ranged from 81.4% (physicians) to 16.7% (social workers). Vaccination was usually performed in October (42.1%) or November (39.5%) by occupational medicine officers (65.8%). The most frequently reported reason for non-vaccination was "vaccine useless as the disease is benign" (36.7%). CONCLUSIONS: The influenza vaccine coverage rate in healthcare workers from the 12 cystic fibrosis centres in the Greater South Region of France is high, but still too low in view of the risks influenza may incur for cystic fibrosis patients. It fails to meet one of the objectives of French Public Health Law (at least 75% influenza vaccine coverage rate for healthcare workers by 2008).

Nanofluidization electrostatics.

Electrostatic charging of powders is a relevant phenomenon for a number of industrial applications. The design of new processes and the use of high resistivity materials and ultrafine powders may lead to higher charging rates and to higher levels of charge accumulation that can become a serious problem. In this work we investigate experimentally electrostatic charging in nanofluidization. The behavior of a fluidized bed of silica nanoparticles under the influence of an electrostatic field is studied. The electric field is applied in the horizontal direction and perpendicular to the gas flow. On one hand, we observe the influence of the electric field on the bulk behavior of the fluidized bed, which suffers a collapse when the electric field is turned on. For strong electric fields the stationary state of the fluidized bed reminds one of that of a spouted bed, with a solid layer adhered to the wall and a low density core region of local high gas velocity. On the other hand, and in order to gain additional insight, we look at the trajectories of nanoparticle agglomerates as affected by the electric field. This images analysis reveals that these agglomerates are horizontally deflected towards the wall as a consequence of being charged. From the analysis of agglomerate trajectories the charge per agglomerate is estimated. Using these measurements the electrostatic forces between agglomerates are calculated and compared to van der Waals attractive forces.

Optical properties of dilute hematite/silicone oil suspensions under low electric fields.

Electrorheology (ER) is the name given to a set of phenomena related to the significant changes experienced by the rheological properties of certain fluids and suspensions upon application of external electric fields. It is mostly explained in terms of the formation of particle aggregates as a consequence of field-induced particle-particle interactions. In this work, we explore such structures by investigating the changes in optical absorbance of hematite/silicone oil suspensions associated to the application of an electric field. We have studied the effect of particle concentration, phi, electric field strength, E(0), and viscosity, eta(m), of the liquid medium on the absorbance-time behavior of the suspensions. Photographs of the electrified suspensions helped in elucidating the structures formed. At low phi values, the absorbance A of electrified suspensions dramatically decreases with time until a constant plateau is reached. The absorbance fall is faster the higher the field, although at long times curves corresponding to different fields tend to merge. In these dilute suspensions particles are observed to migrate toward the electrodes thus clarifying the medium and reducing A. When the concentration of particles is increased, fibrils stretching between the electrodes can be observed in addition to particle deposition on them, as long as the field is kept low. At high fields, migration of the particles to the electrodes occurs whatever the volume fraction. Two mechanisms producing particle-particle interactions are suggested by these data: the conductivity mismatch between the particles and the medium brings about an interfacial or Maxwell-Wagner polarization of the particles; in addition, solids can acquire a net charge provoked by injection from the electrodes. The first mechanism will produce attractive dipole-dipole interactions and hence columns or fibrils. The second one should lead to electrophoretic migration. Structural observations suggest that the latter predominates at high fields. If the viscosity of the fluid phase is increased, the critical electric field values separating both regimes also increase: the electrophoretic motion is hindered and the particle-particle aggregation is enhanced.