Effect of simplification from protease inhibitors to boosted atazanavir-based regimens in real-life conditions.

BACKGROUND: Atazanavir (ATV) boosted with ritonavir (ATV/r) is a potent, well-tolerated, once-daily protease inhibitor (PI). Few data are available on this agent as a treatment simplification option for patients taking other PIs. OBJECTIVE: The aim of the study was to determine the effectiveness and safety of ATV-containing regimens in patients who have simplified their antiretroviral treatment. METHODS: SIMPATAZ was a multicentre, prospective, noninterventional study in patients who had undetectable HIV RNA on their current PI-containing therapy and who were switched to an ATV/r-based regimen. Patients underwent a routine physical examination, and data were collected on HIV RNA levels, CD4 cell counts, liver function, lipid parameters, adverse reactions, adherence to treatment and patient satisfaction. RESULTS: A total of 183 patients were enrolled in the study and included in the analysis (80% were male, 29% had AIDS, and 52% were coinfected with HIV and hepatitis B virus or hepatitis C virus). The median baseline CD4 count was 514 cells/µL. Median exposure to previous HIV therapy was 8 years, and 32% of patients had a history of PI failures. Lopinavir boosted with ritonavir was the most frequent PI replaced (62%) and tenofovir+lamivudine /emtricitabine the backbone most used during the study (29%). The study drug was discontinued early by 25 patients (14%), two of whom discontinued as a result of adverse events (Hodgkin lymphoma and vomiting). Two patients died (lung cancer and myocardial infarction). At month 12, 93% of the study population had an undetectable HIV RNA viral load. Hyperbilirubinaemia >3 mg/dL and increased alanine aminotransferase levels>200 IU/L were observed in 38.5% and 4.4% of patients, respectively. Median changes from baseline to month 12 in total cholesterol, triglycerides and low-density lipoprotein cholesterol were -13 mg/dL (-7%; P<0.0001), -19 mg/dL (-13%; P<0.0001) and -7 mg/dL (-6%; P=0.021), respectively. CONCLUSIONS: In a real-world setting, switching from other PIs to ATV/r is a well-tolerated and safe option for improving the lipid profile and for retaining virological response in controlled pretreated patients.

Pathway towards an ideal and sustainable framework agreement for the public procurement of vaccines in Spain: a multi-criteria decision analysis.

Objective: To advance the development of an ideal and sustainable framework agreement for the public procurement of vaccines in Spain, and to agree on the desirable award criteria and their relative weight. Methods: A multidisciplinary committee of seven health-care professionals and managers developed a partial multi-criteria decision analysis to determine the award criteria that should be considered and their specific weights for the public procurement of routine vaccines and seasonal influenza vaccines, considering their legal viability. A re-test of the results was carried out. The current situation was analyzed through 118 tender specifications and compared to the ideal framework. Results: Price is the prevailing award criterion for the public procurement of both routine (weighting of 60% versus 40% for all other criteria) and influenza (36% versus 64%) vaccines. Ideally, 22 criteria should be considered for routine vaccines, grouped and weighted into five domains: efficacy (weighting of 29%), economic aspects (27%), vaccine characteristics (22%), presentation form and packaging (13%), and others (9%). Per criteria set, price was the most important criterion (22%), followed by effectiveness (9%), and composition/formulation (7%). Regarding influenza vaccines, 20 criteria were selected, grouped, and weighted: efficacy (29%), economic aspects (25%), vaccine characteristics (20%), presentation form and packaging (16%), and others (11%). Per criteria set, price was also the most relevant criterion (19%), followed by composition/formulation (8%), and effectiveness (8%). Conclusions: Contrary to the current approach, technical award criteria should prevail over economic criteria in an ideal and sustainable framework agreement for the public procurement of vaccines.

A silicon carbide array for electrocorticography and peripheral nerve recording.

OBJECTIVE: Current neural probes have a limited device lifetime of a few years. Their common failure mode is the degradation of insulating films and/or the delamination of the conductor-insulator interfaces. We sought to develop a technology that does not suffer from such limitations and would be suitable for chronic applications with very long device lifetimes. APPROACH: We developed a fabrication method that integrates polycrystalline conductive silicon carbide with insulating silicon carbide. The technology employs amorphous silicon carbide as the insulator and conductive silicon carbide at the recording sites, resulting in a seamless transition between doped and amorphous regions of the same material, eliminating heterogeneous interfaces prone to delamination. Silicon carbide has outstanding chemical stability, is biocompatible, is an excellent molecular barrier and is compatible with standard microfabrication processes. MAIN RESULTS: We have fabricated silicon carbide electrode arrays using our novel fabrication method. We conducted in vivo experiments in which electrocorticography recordings from the primary visual cortex of a rat were obtained and were of similar quality to those of polymer based electrocorticography arrays. The silicon carbide electrode arrays were also used as a cuff electrode wrapped around the sciatic nerve of a rat to record the nerve response to electrical stimulation. Finally, we demonstrated the outstanding long term stability of our insulating silicon carbide films through accelerated aging tests. SIGNIFICANCE: Clinical translation in neural engineering has been slowed in part due to the poor long term performance of current probes. Silicon carbide devices are a promising technology that may accelerate this transition by enabling truly chronic applications.

A comparison of optimal MIMO linear and nonlinear models for brain-machine interfaces.

The field of brain-machine interfaces requires the estimation of a mapping from spike trains collected in motor cortex areas to the hand kinematics of the behaving animal. This paper presents a systematic investigation of several linear (Wiener filter, LMS adaptive filters, gamma filter, subspace Wiener filters) and nonlinear models (time-delay neural network and local linear switching models) applied to datasets from two experiments in monkeys performing motor tasks (reaching for food and target hitting). Ensembles of 100-200 cortical neurons were simultaneously recorded in these experiments, and even larger neuronal samples are anticipated in the future. Due to the large size of the models (thousands of parameters), the major issue studied was the generalization performance. Every parameter of the models (not only the weights) was selected optimally using signal processing and machine learning techniques. The models were also compared statistically with respect to the Wiener filter as the baseline. Each of the optimization procedures produced improvements over that baseline for either one of the two datasets or both.

[Identifying improvement opportunities in the management of hepatitis C]. / Identificación de oportunidades de mejora del tratamiento de la hepatitis C.

OBJECTIVE: Hepatitis C represents a public health concern with more than 170 million carriers. The goal of this study was to identify improvement opportunities in the management of hepatitis C, and the pharmaceutical actions performed for the prevention and solution of medication-related problems in patients seen at the Pharmaceutical Care Outpatient Unit. METHOD: A longitudinal study (January to October 2005) with patients monoinfected by hepatitis C virus receiving ribavirin and peginterferon alfa (2a or 2b). Data collection took place during the interview at the time of antiviral dispensation. Adverse reactions were classified according to CTCEA v3.0 criteria. Iaser methodology was used to identify patients with improvement opportunities regarding treatment. RESULTS: In all 109 patients and 201 improvement opportunities were identified. Pharmacotherapeutic morbidity was identified from adverse events (blood toxicity, pseudoflu syndrome, etc.) in 425 occasions; 388 pharmaceutical actions were performed, 41.23% to prevent adverse effects and 39.95% to provide patients or carers with information. CONCLUSIONS: In all, 99.01% of patients had safety problems. Pharmacotherapeutic morbidity from adverse effects was less common than reported in clinical trials of these drugs. Most pharmaceutical actions were preventive in nature. Iaser methodology allows to identify patients with improvement opportunities regarding hepatitis C treatment and the prevention of pharmacotherapeutic morbidity.

Subependymoma of the lateral ventricle.

The case of a girl with a large cystic subependymoma of the lateral ventricle is reported. The tumor, which did not cause hydrocephalus, was attached to the wall of the frontal horn and grew out of the ventricular system extending into the anterior cranial fossa and the orbital cavity. Despite some typical features exhibited by the lesion, its true nature was not recognized during the operation. The importance of the identification of this rare benign tumor is emphasized because a radical removal may be accomplished in most cases with a very good prognosis.

A three-dimensional virtual model of the head generated from digitalized CT or MR images for anatomical-radiological and neurosurgical evaluations.

A computer-generated virtual model has been developed that reconstructs the head in three dimensions from digitalized images obtained with magnetic resonance and computerized tomography. Through programming and the use of commercial graphic animation software, we have developed the whole process of the rotation of the head on different spatial planes. The procedure permits multidirectional anatomical sections to be made on the structure of the head, providing a true dynamic and user-friendly anatomical-radiological atlas. The system serves as a virtual model for the localization of an ideal surgical approach to any lesion thus avoiding possible neurological lesions.

Sub-mm functional decoupling of electrocortical signals through closed-loop BMI learning.

Volitional control of neural activity lies at the heart of the Brain-Machine Interface (BMI) paradigm. In this work we investigated if subdural field potentials recorded by electrodes < 1mm apart can be decoupled through closed-loop BMI learning. To this end, we fabricated custom, flexible microelectrode arrays with 200 µm electrode pitch and increased the effective electrode area by electrodeposition of platinum black to reduce thermal noise. We have chronically implanted these arrays subdurally over primary motor cortex (M1) of 5 male Long-Evans Rats and monitored the electrochemical electrode impedance in vivo to assess the stability of these neural interfaces. We successfully trained the rodents to perform a one-dimensional center-out task using closed-loop brain control to adjust the pitch of an auditory cursor by differentially modulating high gamma (70-110 Hz) power on pairs of surface microelectrodes that were separated by less than 1 mm.

Once-daily antiretroviral therapy: Spanish Consensus Statement.

BACKGROUND: Administration of antiretroviral therapy (ART) once daily is creating extraordinary interest among the members of the scientific community and also among those who receive the therapy. However, in clinical practice, some doubts remain about its use. OBJECTIVES: This document examines the characteristics and possibilities of treatment administered once daily. METHODS: Consensus of 248 Spanish experts in the field. RESULTS: Once-daily dosing is considered an added value which could favour adherence and, therefore, efficacy, as well as the quality of life of certain patients, however, the objective of adequate adherence in the long term is often difficult to achieve regardless of the treatment used. In theory, any patient can receive once-daily therapy, although some patients could particularly benefit from it, e.g. those with unfavourable social or personal circumstances, including drug users, patients whose treatment must be supervised, patients receiving multiple medications, or those who need rescue therapy after multiple treatment failures. At present, it is possible to design once-daily ART using some of the combinations of drugs considered as first-choice in national and international recommendations for antiretroviral therapy, but the options are still limited. The marketing of new drugs with this characteristic could allow us to increase the number and types of patient who can benefit from once-daily regimens, including those patients who need rescue therapy. CONCLUSIONS: Once-daily ART is a good alternative to regimens administered several times each day when a potent combination of active drugs is available.

Artificial ears for a biomimetic sonarhead: from multiple reflectors to surfaces.

This work presents an evolutionary approach to pinna design. Narrowband echolocating bats move the pinna to alter the directional sensitivity of their perceptual systems. Adding pinnae to RoBat--a biomimetic sonarhead mounted on a mobile robot--is the goal of this work. After a description of the earlier work on artificial pinnae consisting of multiple reflectors around the transducer, an acoustic model, inspired by a physical model of sound diffraction and reflections in the human concha, is described and revisited as the model to use for evolving complex shapes. A genetic algorithm evolved the shape of the pinnae with respect to desired features of the directivity pattern of the receiver transducers. Some interesting paraboloid shapes for specific echolocating behaviors were evolved, improving performance with respect to the bare transducer's performance.

[Herpes simplex 1 virus Mollaret meningitis]. / Meningitis de Mollaret por virus herpes simple 1.

Mollaret meningitis is a rare disease characterized by recurrent and self-limited episodes of aseptic meningitis. It is considered a disease with benign etiology and it has been related to viral infections: Epstein-Barr virus and herpes simplex virus (HSV), type 2 most frequently. Herpes simplex 1 virus has been rarely isolated in the cerebrospinal fluid in patients with Mollaret meningitis; to this end culture, expansion with PCR, and inmunoblot has been utilized. In this article a case of Mollaret meningitis related to type 1 HSV is described. The interest is the demonstration of the herpes simplex virus type 1 within the cytoplasm of the Mollaret cells with a immunohistochemical technique (ABC-peroxidase method) using monoclonal antibodies anti HSV-1 in order to support the diagnosis, being this the first case described in the literature.

Intraocular hemorrhage in sudden increased intracranial pressure (Terson syndrome).

We examined 19 cases with SAH, 4 of which presented intraocular hemorrhages (retinal, subhyaloid and in vitreous). The mortality rate was 50% when the intraocular hemorrhages were present compared to 20% when they were absent.

Simultaneus prediction of four kinematic variables for a brain-machine interface using a single recurrent neural network.

Implementation of brain-machine interface neural-to-motor mapping algorithms in low-power, portable digital signal processors (DSPs) requires efficient use of model resources especially when predicting signals that show interdependencies. We show here that a single recurrent neural network can simultaneously predict hand position and velocity from the same ensemble of cells using a minimalist topology. Analysis of the trained topology showed that the model learns to concurrently represent multiple kinematic parameters in a single state variable. We further assess the expressive power of the state variables for both large and small topologies.

Whipple's disease with isolated central nervous system symptomatology diagnosed by molecular identification of Tropheryma whippelii in peripheral blood.

We report a new case of Whipple's disease (WD) confined to the central nervous system. The patient presented with ataxia, ophthalmoplegia, hypersomnia, hemiparesis and generalized myorhythmia. The diagnosis was confirmed by identification of specific sequences of the causal agent of WD, the actinobacteria Tropheryma whippelii (TW), by PCR of DNA extracted from peripheral blood. An epidemiological survey of TW in patients with dementia suggests that WD is an uncommon cause of dementia in our population. Molecular methods may allow rapid identification of TW in peripheral fluids, and non-invasive diagnosis of this disorder.