A neurochemical closed-loop controller for deep brain stimulation: toward individualized smart neuromodulation therapies.

Current strategies for optimizing deep brain stimulation (DBS) therapy involve multiple postoperative visits. During each visit, stimulation parameters are adjusted until desired therapeutic effects are achieved and adverse effects are minimized. However, the efficacy of these therapeutic parameters may decline with time due at least in part to disease progression, interactions between the host environment and the electrode, and lead migration. As such, development of closed-loop control systems that can respond to changing neurochemical environments, tailoring DBS therapy to individual patients, is paramount for improving the therapeutic efficacy of DBS. Evidence obtained using electrophysiology and imaging techniques in both animals and humans suggests that DBS works by modulating neural network activity. Recently, animal studies have shown that stimulation-evoked changes in neurotransmitter release that mirror normal physiology are associated with the therapeutic benefits of DBS. Therefore, to fully understand the neurophysiology of DBS and optimize its efficacy, it may be necessary to look beyond conventional electrophysiological analyses and characterize the neurochemical effects of therapeutic and non-therapeutic stimulation. By combining electrochemical monitoring and mathematical modeling techniques, we can potentially replace the trial-and-error process used in clinical programming with deterministic approaches that help attain optimal and stable neurochemical profiles. In this manuscript, we summarize the current understanding of electrophysiological and electrochemical processing for control of neuromodulation therapies. Additionally, we describe a proof-of-principle closed-loop controller that characterizes DBS-evoked dopamine changes to adjust stimulation parameters in a rodent model of DBS. The work described herein represents the initial steps toward achieving a "smart" neuroprosthetic system for treatment of neurologic and psychiatric disorders.

Levofloxacino en el tratamiento de infecciones nosocomiales en pacientes críticos / Levofloxacin in the treatment of nosocomial infection in critically ill patients

Introducción. El levofloxacino (LVX) es uno de los antibióticosmás utilizados en pacientes críticos ingresados enServicios o Unidades de Cuidados Intensivos (UCI) españolas.Su utilización en infecciones comunitarias está ampliamentedocumentada, mientras que su uso en infecciones nosocomiales(IN) es menos frecuente y conocido.Objetivo. Describir las indicaciones y formas de empleode LVX en el tratamiento de IN en pacientes ingresados enUCI españolas.Material y método. Estudio abierto, retrospectivo, observacionaly multicéntrico. Se han incluido todos los pacientesingresados en UCI que en los años 2004-2005 recibieron LVXpara el tratamiento de IN. Se ha cumplimentado un cuadernode recogida de datos (CRD) que incluye variables demográficas,de la infección, del tratamiento y de la evolución del proceso infeccioso y del paciente. Se describe la utilizaciónde LVX dependiendo de la IN. Se realiza análisis de regresión logística para identificar las variables relacionadas con respuesta satisfactoria. Los resultados se expresan mediante laodds ratio (OR) y el intervalo de confianza (IC) del 95%.Resultados. Se han incluido 949 pacientes en 87 UCIque han recibido LVX para el tratamiento de 1.103 IN: 460(41,7%) neumonías no relacionadas con ventilación mecánica,256 (23,2%) neumonías relacionadas con ventilación mecánica,107 (9,7%) bacteriemias primarias o relacionadas con catéteresvasculares, 47 (4,3%) infecciones urinarias relacionadascon sonda uretral, 42 (3,8%) infecciones quirúrgicas profundaso de órgano-espacio y 191 (17,3 %) otras infecciones.APACHE II al ingreso de 19,6 (desviación estándar [DE]: 8) yrespuesta sistémica de sepsis grave o shock séptico en el 50,4% de los casos. En 776 (82,7%) ocasiones se ha iniciado el tratamiento de forma empírica y en 589 (62,1%) casos la dosisde elección ha sido de 0,5 g/12 h, con una duración media de 9 días (AU)

Introduction. Levofloxacin (LVX) is one of the most frequentlyused antibiotics in critical patients admitted to SpanishIntensive Care Units (ICU). Their use in communityacquiredinfections has been widely documented, while it is less frequent and known in nosocomial infections (NI).Objective. To describe the indications and utilizationpatterns of LVX in the treatment of NI in patients admittedto Spanish ICU.Material and methods. Open-label, retrospective, observational and multicenter study. All patients admittedto ICU and who were being treated for NI with LVX in the years 2004-2005 were included. A case reportform (CRF) was drawn up and included demographic, infection, treatment, infectious process and patient development variables. NI-dependent LVX usage was described.A logistical regression analysis was carried out in order to identify the variables associated with a satisfactoryresponse. Results are expressed by means of the odds ratio and a 95% confidence interval.Results. A total of 949 patients who were given LVXfor the treatment of 1,103 NI were recruited in 87 ICU:460 (41.7%) with non-mechanical ventilation associatedpneumonia, 256 (23.2 %) mechanical-ventilation associatedpneumonia, 107 (9.7 %) with primary or vascularcatheter-related bacteremia, 47 (4.3 %) with urethral catheter-related urinary infections, 42 (3.8%) with organspaceor deep surgical infections and 191 (17.3%) whohad other types of infection. An APACHE II upon admissionof 19.6 (SD: 8) and severe sepsis or septic shocksystemic response in 50.4% of all cases. On 776 (82.7%)occasions treatment was initiated on an empirical basisand in 589 (62.1%) cases the dose of choice was of 0.5 g/12 h, with a mean duration of 9 days (AU)

[Levofloxacin in the treatment of nosocomial infection in critically ill patients]. / Levofloxacino en el tratamiento de infecciones nosocomiales en pacientes críticos.

INTRODUCTION: Levofloxacin (LVX) is one of the most frequently used antibiotics in critical patients admitted to Spanish Intensive Care Units (ICU). Their use in community-acquired infections has been widely documented, while it is less frequent and known in nosocomial infections (NI). OBJECTIVE: To describe the indications and utilization patterns of LVX in the treatment of NI in patients admitted to Spanish ICU. MATERIAL AND METHODS: Open-label, retrospective, observational and multicenter study. All patients admitted to ICU and who were being treated for NI with LVX in the years 2004-2005 were included. A case report form (CRF) was drawn up and included demographic, infection, treatment, infectious process and patient development variables. NI-dependent LVX usage was described. A logistical regression analysis was carried out in order to identify the variables associated with a satisfactory response. Results are expressed by means of the odds ratio and a 95% confidence interval. RESULTS: A total of 949 patients who were given LVX for the treatment of 1,103 NI were recruited in 87 ICU: 460 (41.7%) with non-mechanical ventilation associated pneumonia, 256 (23.2 %) mechanical-ventilation associated pneumonia, 107 (9.7 %) with primary or vascular catheter-related bacteremia, 47 (4.3 %) with urethral catheter-related urinary infections, 42 (3.8%) with organspace or deep surgical infections and 191 (17.3%) who had other types of infection. An APACHE II upon admission of 19.6 (SD: 8) and severe sepsis or septic shock systemic response in 50.4% of all cases. On 776 (82.7%) occasions treatment was initiated on an empirical basis and in 589 (62.1%) cases the dose of choice was of 0.5 g/ 12 h, with a mean duration of 9 days. In 738 (77.8 %) patients, LVX was used in association with other antibiotics. The clinical response by treatment end was rated as satisfactory in 67.4 % of all NI. Factors related to a non-satisfactory response were as follows: APACHE II (OR: 1.05; 95% CI: 1.028-1.078); septic shock (OR: 2.62; 95 % CI: 1.623-4.219); the requirement for changes in treatment due to poor clinical progress (OR: 66.67; 95% CI: 15.384-250), the presence of non-covered microorganisms (OR: 6.58; 95% CI: 3.663-11.765), the appearance of new resistant pathogens (OR: 6.94; 95 % CI: 2.445- 19.608) or the diagnosis of a new infection (OR: 3.68; 95% CI: 1.504-8.929); solid neoplasm (OR: 1.98; 95% CI: 1.156-3.899); chronic liver disease (OR: 3.11; 95 % CI: 1.429-8.475) and the absence of etiology confirmation (OR: 2.39; 95 % CI: 1.624-3.510). One or more adverse events which were possibly or probably related to the use of LVX were detected in 104 (11.0%) patients. Total intra-ICU mortality amounted to 26.1%, while the accumulated in-hospital mortality was 33.8%. CONCLUSIONS: LVX is a common therapeutic option in the treatment of nosocomial infections in critical patients. It is predominantly used in an empirical manner, at a dose of 0.5 g every 12 hours and in combination with other antibiotics.

Computer-based test-bed for clinical assessment of hand/wrist feed-forward neuroprosthetic controllers using artificial neural networks.

Neuroprosthestic systems can be used to restore hand grasp and wrist control in individuals with C5/C6 spinal cord injury. A computer-based system was developed for the implementation, tuning and clinical assessment of neuroprosthetic controllers, using off-the-shelf hardware and software. The computer system turned a Pentium III PC running Windows NT into a non-dedicated, real-time system for the control of neuroprostheses. Software execution (written using the high-level programming languages LabVIEW and MATLAB) was divided into two phases: training and real-time control. During the training phase, the computer system collected input/output data by stimulating the muscles and measuring the muscle outputs in real-time, analysed the recorded data, generated a set of training data and trained an artificial neural network (ANN)-based controller. During real-time control, the computer system stimulated the muscles using stimulus pulsewidths predicted by the ANN controller in response to a sampled input from an external command source, to provide independent control of hand grasp and wrist posture. System timing was stable, reliable and capable of providing muscle stimulation at frequencies up to 24Hz. To demonstrate the application of the test-bed, an ANN-based controller was implemented with three inputs and two independent channels of stimulation. The ANN controller's ability to control hand grasp and wrist angle independently was assessed by quantitative comparison of the outputs of the stimulated muscles with a set of desired grasp or wrist postures determined by the command signal. Controller performance results were mixed, but the platform provided the tools to implement and assess future controller designs.