Native System and Cultured Cell Electrophysiology for Investigating Anesthetic Mechanisms.

Anesthetic agents interact with a variety of ion channels and membrane-bound receptors, often at agent-specific binding sites of a single protein. These molecular-level interactions are ultimately responsible for producing the clinically anesthetized state. Between these two scales of effect, anesthetic agents can be studied in terms of how they impact the physiology of neuronal circuits, individual neurons, and cells expressing individual receptor types. The acutely dissected hippocampal slice is one of the most extensively studied and characterized preparations of intact neural tissue and serves as a highly useful experimental model system to test hypotheses of anesthetic mechanisms. Specific agent-receptor interactions and their effect on excitable membranes can further be defined with molecular precision in cell-based expression systems. We highlight several approaches in these respective systems that we have used and that also have been used by many investigators worldwide. We emphasize economy and quality control, to allow an experimenter to carry out these types of studies in a rigorous and efficient manner.

StimDuino: an Arduino-based electrophysiological stimulus isolator.

BACKGROUND: Electrical stimulus isolator is a widely used device in electrophysiology. The timing of the stimulus application is usually automated and controlled by the external device or acquisition software; however, the intensity of the stimulus is adjusted manually. Inaccuracy, lack of reproducibility and no automation of the experimental protocol are disadvantages of the manual adjustment. To overcome these shortcomings, we developed StimDuino, an inexpensive Arduino-controlled stimulus isolator allowing highly accurate, reproducible automated setting of the stimulation current. NEW METHOD: The intensity of the stimulation current delivered by StimDuino is controlled by Arduino, an open-source microcontroller development platform. The automatic stimulation patterns are software-controlled and the parameters are set from Matlab-coded simple, intuitive and user-friendly graphical user interface. The software also allows remote control of the device over the network. RESULTS: Electrical current measurements showed that StimDuino produces the requested current output with high accuracy. In both hippocampal slice and in vivo recordings, the fEPSP measurements obtained with StimDuino and the commercial stimulus isolators showed high correlation. COMPARISON WITH EXISTING METHODS: Commercial stimulus isolators are manually managed, while StimDuino generates automatic stimulation patterns with increasing current intensity. The pattern is utilized for the input-output relationship analysis, necessary for assessment of excitability. In contrast to StimuDuino, not all commercial devices are capable for remote control of the parameters and stimulation process. CONCLUSIONS: StimDuino-generated automation of the input-output relationship assessment eliminates need for the current intensity manually adjusting, improves stimulation reproducibility, accuracy and allows on-site and remote control of the stimulation parameters.

A low-cost, open-source, wireless electrophysiology system.

Many experiments in neuroscience require or would benefit tremendously from a wireless neural recording system. However, commercially available wireless systems are expensive, have moderate to high noise and are often not customizable. Academic wireless systems present impressive capabilities, but are not available for other labs to use. To overcome these limitations, we have developed an ultra-low noise 8 channel wireless electrophysiological data acquisition system using standard, commercially available components. The system is capable of recording many types of neurological signals, including EEG, ECoG, LFP and unit activity. With a diameter of just 25 mm and height of 9 mm, including a CR2032 Lithium coin cell battery, it is designed to fit into a small recording chamber while minimizing the overall implant height (Fig. 1 and 3). Using widely available parts we were able to keep the material cost of our system under $100 dollars. The complete design, including schematic, PCB layout, bill of materials and source code, will be released through an open source license, allowing other labs to modify the design to fit their needs. We have also developed a driver to acquire data using the BCI2000 software system. Feedback from the community will allow us to improve the design and create a more useful neuroscience research tool.

US health care policy and reform: implications for cardiac electrophysiology.

In response to unsustainably rising costs, variable quality and access to health care, and the projected insolvency of vital safety net insurance programs, the federal government has proposed important health policy and regulatory changes in the USA. The US Supreme Court's decision to uphold most of the major provisions of the Affordable Care Act will lead to some of the most sweeping government reforms on entitlements since the creation of Medicare. Furthermore, implementation of new organizational, reimbursement, and health care delivery models will strongly affect the practice of cardiac electrophysiology. In this brief review, we will provide background and context to the problem of rising health care costs and describe salient reforms and their projected impacts on the field and practice of cardiac electrophysiology.

Evaluación económica de la determinación del propéptido natriurético cerebral n-terminal (NT-proBNP) en pacientes con disnea en los servicios de urgencias españoles / Economic evaluation of N-terminal pro-B-type natriuretic peptide (NT-ProBNP) test in Spanish emergency department patients with dyspnea

Introducción. Analizar la eficiencia de añadir la determinación NT-proBNP al examen clínico convencional (ECC) para el diagnóstico de insuficiencia cardiaca (IC) en pacientes con disnea que acuden a servicios de urgencias (SU) españoles. Material y métodos. Se desarrolló un árbol de decisión para evaluar los resultados clínicos y económicos de ambas alternativas durante 60 días de seguimiento desde la visita al SU en pacientes hospitalizados y no hospitalizados. Los parámetros clínicos fueron principalmente obtenidos del estudio PRIDE y validados por médicos de SU y cardiólogos. El punto de corte de la determinación NT-proBNP fue de 900pg/mL (sensibilidad del 90% y especificidad del 85%). En base a datos españoles publicados, se asumió que el 65% de pacientes con disnea sufrían IC. El uso de recursos fue identificado mediante opinión de expertos y evaluado desde la perspectiva del Sistema Nacional de Salud (SNS). El análisis comparó el diagnóstico final del paciente con el diagnóstico realizado en el SU. Se realizaron diversos análisis de sensibilidad para evaluar la incertidumbre del modelo. Resultados. El diagnóstico incorporando la determinación NT-proBNP fue correcto en el 91,96% de los pacientes (59,09% verdaderos positivos y 32,87% verdaderos negativos) frente al 85,53% mediante ECC (50,79% verdaderos positivos y 34,74% verdaderos negativos). La incorporación de la determinación NT-proBNP resultó tener un coste menor (3.720€ versus 5.188€). Los análisis de sensibilidad realizados confirmaron los resultados. Conclusiones. La incorporación de la determinación NT-proBNP en el diagnóstico del paciente con disnea en los SU españoles muestra un menor coste y un mayor porcentaje de pacientes correctamente diagnosticados comparado con el ECC desde la perspectiva del SNS (AU)

Introduction. To assess the efficiency of adding the NT-proBNP test to the standard clinical evaluation (SCE) for the diagnosis of heart failure (HF) in Spanish emergency department (ED) patients with dyspnea. Material and methods. A decision-tree was developed to evaluate the clinical and economic outcomes of the two diagnostic alternatives 60 days after ED admission in hospitalized and non-hospitalized patients. Clinical parameters were mainly extracted from the PRIDE study and were validated by expert ED physicians and cardiologists. The cut-off point for the NT-proBNP test was 900pg/mL (sensitivity of 90% and specificity of 85%). We assumed that 65% of patients with dyspnea had HF, based on published Spanish data. Resource use was obtained by expert opinion and evaluated from the public payer perspective (Spanish National Health Service (NHS)). The analysis compared the final diagnosis with the ED diagnosis. Multiple sensitivity analyses were carried out to evaluate the uncertainty of the model. Results. The diagnosis using NT-proBNP testing was correct in 91.96% of patients (59.09% true positive and 32.87% true negative) vs. 85.53% using SCE alone (50.79% true positive and 34.74% true negative). Costs were lower in patients receiving NT-proBNP testing (€3,720 versus €5,188). The sensitivity analyses confirmed the results. Conclusions. The use of the NT-proBNP test for the assessment and management of Spanish emergency department patients with dyspnea is less costly and shows a higher percentage of correctly-diagnosed patients from the Spanish NHS perspective than SCE alone (AU)

A new technique for multiple re-use of planar patch clamp chips.

The patch clamp technique is widely used for recording the activity of ion channels in single cells and lipid bilayers. Most platforms utilize borosilicate glass configured as a pipette, however more recently planar patch clamp chips have been developed that require less technical expertise. Planar patch clamp chips in systems like the Nanion Port-a-Patch are useful in that they allow more rapid throughput in drug screening studies. This technique also has the ability to perform rapid solution changes from the intracellular side. A current drawback with the planar patch clamp chips is the need to utilize a separate chip for each experiment. This increases the cost of each experiment and is due to the fact that the ∼1µm aperture used for cell attachment is thought to retain cellular debris thereby preventing subsequent cell attachment and formation of GΩ seals. In the present study we have for the first time solved the technical problem of developing a simple protocol for re-use of Nanion planar patch clamp chips. The re-use methodology is demonstrated in whole cell patch clamp studies of HEK-293 cells expressing the electrogenic sodium bicarbonate cotransporter NBCe1-A in protocols involving external and internal solution changes, and CHO-K1 cells with incorporated gramicidin channels.

Evaluación económica de la terapia de resincronización cardiaca / Economic assessment of cardiac resynchronization therapy

Introducción y objetivos. La terapia de resincronización cardiaca es un tratamiento de eficacia demostrada para la insuficiencia cardiaca y reduce el número de hospitalizaciones y la mortalidad por progresión de la insuficiencia y total. El objetivo de nuestro trabajo es determinar la eficiencia de la terapia de resincronización cardiaca comparada con la terapia farmacológica mediante una evaluación económica adaptada a nuestro entorno sanitario. Métodos. Se realiza la adaptación al ámbito sanitario español de un modelo previamente existente. Las fuentes de efectividad utilizadas son revisiones sistemáticas de la literatura publicadas. Los costes de las distintas intervenciones se determinan de acuerdo con diversas fuentes de datos españolas. Se utiliza la perspectiva del sistema sanitario; como horizonte temporal, el resto de vida de los pacientes, y como variables de resultado, años de vida y años de vida ajustados por calidad (AVAC). Resultados. El tratamiento farmacológico, la resincronización y resincronización + desfibrilador alcanzaron 2,11, 2,8 y 3,19 AVAC, a un coste de 11.722, 31.629 y 52.592 euros respectivamente. Cada AVAC obtenido con resincronización frente a medicación requiere el uso de 28.612 euros de recursos adicionales. De modo análogo, la resincronización con desfibrilador cuesta 53.547 euros/ AVAC respecto a la resincronización sin desfibrilador. Conclusiones. La terapia de resincronización cardiaca sin desfibrilador puede ser una opción de tratamiento coste-efectiva para el grupo de pacientes adecuadamente seleccionados, comparada con la terapia farmacológica óptima. Este resultado es sensible por la incertidumbre en numerosas variables del modelo (AU)

Introduction and objectives. Cardiac resynchronization devices have been shown to be effective in treating heart failure. They reduce overall mortality, heart failure mortality and hospitalizations due to heart failure. The aim of this study was to compare the cost-effectiveness of cardiac resynchronization therapy (CRT) with that of optimal drug therapy (ODT) by carrying out an economic assessment in the Spanish healthcare setting. Methods. An existing model was adapted for use in the Spanish healthcare setting. The effectiveness of cardiac resynchronization therapy was determined from published systematic reviews. The costs of the various interventions were determined using a range of Spanish data sources. The model adopted the perspective of the public health system and the time horizon considered was the remainder of the patient’s life. The outcome variables were life-years gained and quality-adjusted life-years (QALYs) gained. Results. Overall, ODT, CRT and CRT with a defibrillator resulted in gains of 2.11, 2.8 and 3.19 QALYs, respectively, at a cost of € 11,722, € 31,629 and € 52,592, respectively. Consequently, each QALY gained with CRT relative to ODT involved the consumption of € 28,612 of additional resources. Similarly, the use of CRT with a defibrillator cost an additional € 53,547 per QALY relative to CRT without a defibrillator. Conclusions. The use of CRT without a defibrillator could be a cost-effective alternative to ODT for treating heart failure in a carefully selected group of patients. The study results were sensitive to uncertainties in many of the variables used in the model (AU)

Low-cost, high-fidelity, adaptive cancellation of periodic 60 Hz noise.

A common method to eliminate unwanted power line interference in neurobiology laboratories where sensitive electronic signals are measured is with a notch filter. However a fixed-frequency notch filter cannot remove all power line noise contamination since inherent frequency and phase variations exist in the contaminating signal. One way to overcome the limitations of a fixed-frequency notch filter is with adaptive noise cancellation. Adaptive noise cancellation is an active approach that uses feedback to create a signal that when summed with the contaminated signal destructively interferes with the noise component leaving only the desired signal. We have implemented an optimized least mean square adaptive noise cancellation algorithm on a low-cost 16 MHz, 8-bit microcontroller to adaptively cancel periodic 60 Hz noise. In our implementation, we achieve between 20 and 25 dB of cancellation of the fundamental 60 Hz noise component.

Staple electrodes: an innovative alternative for intraoperative electrophysiological monitoring.

Intraoperative electrophysiological monitoring is essential for minimally invasive neurosurgery. The authors developed an innovative recording method using a staple electrode, consisting of a surgical skin staple and an integrated circuit (IC) test clip with a cable. The staple is put on the patient's skin after the induction of general anesthesia. After head fixation, the IC test clip is simply hooked to the staple. The authors used this method for recording in 158 consecutive cases. It took only a few minutes to set up 4-18 staple electrodes in each case. None of the staple electrodes became disconnected unintentionally, and the initial impedance was kept throughout the procedures. The authors conclude that the staple electrode is superior to conventional disc or needle electrodes in speed of setup, electrical stability, and cost-effectiveness and recommend its routine use for intraoperative electrophysiological monitoring.

A low cost instrumented glove for extended monitoring and functional hand assessment.

A wearable finger flexion monitor developed to measure hand function in individuals with hand dysfunction was evaluated for feasibility, measurement repeatability and reliability, fidelity of wireless transmission, and user acceptance. Configuration of the monitor allows use in situations when a traditional measurement glove cannot be worn. Five healthy individuals participated in the study of repeatability, while 10 healthy individuals and 10 individuals with acquired brain injury participated in trials to assess feasibility and user comfort. Repeatability results showed an overall error of 3.4 degrees , compared to 5.5 degrees and 5.7 degrees reported with other sensor gloves, and to manual measurements (5-8 degrees). Intraclass coefficient of reliability (using coefficient alpha) averaged 0.95. User feedback regarding comfort of the monitor was very high. Loss of data during wireless transmission was no greater than 1.2%. Results demonstrate that the monitor has a strong potential to be used as a tool for objective hand function evaluation in the home and community for both short- and long-term monitoring.

A versatile, low-cost adaptor for stereotaxic and electrophysiologic spinal preparations in juvenile and adult rodents.

Rats and mice provide excellent models for normal spinal cord physiology, traumatic spinal cord injury, and various disease states. Alternative and improved methodologies for experimental spinal preparations are desirable, particularly in the wake of expanding neuroscience technology, such as the diverse array of transgenic mice now available, and exciting new therapeutic approaches, including transplantation and gene therapy. This report describes a simple, low-cost instrument for spinal preparations in rodents of different sizes, including rat pups. The device adapts to standard small animal stereotaxic instruments, precluding the need for additional stereotaxic apparatus. Surgical methods utilizing the device are presented demonstrating the instrument's capacity for precise alignment and stabilization of the spinal column that is reproducible from animal to animal. Proof of concept is demonstrated with results from spinal cord injections and electrophysiologic recordings.

New device indications: impact on the individual electrophysiology (EP) practitioner in a predominantly managed care environment.

The high penetration of managed care as a payment source in cardiology practice is a fact of life in many areas of the country. Understanding the system of reimbursement used by managed care is helpful in order to maximize physician payment for work done, to minimize practice overhead, and to reduce physician and managerial frustration. The key ingredient for success in any cardiology practice environment is high quality procedural outcomes and good communication with patients and referring physicians. This is true in both a managed care and fee for service environment. This article describes the relationship between an indicated electrophysiology procedure (e.g., an implantable cardioverter defibrillator in a low ejection fraction coronary patient) at one end and its reimbursement by a local managed care payer to an electrophysiologist at the other end.

Safety, effectiveness and cost efficacy of diagnostic electrophysiology and radiofrequency ablation in a district general hospital.

Electrophysiological studies (EPS) are now being performed in district general hospitals (DGH) in the UK. In order to audit our results, a prospective database was established for all patients undergoing EPS and radiofrequency (RF) ablation at Eastbourne District General Hospital, East Sussex. Between 1 January 1997 and 1 July 2000, 300 EPS procedures were performed, resulting in 155 RF ablations. The average RF ablation procedure time was 119.3 minutes with an average fluoroscopy time of 19.1 minutes. Cost per RF ablation procedure was 1166.79 Pounds excluding use of facilities, pacemaker devices, medical nursing and radiography staffing costs. The overall success rate for RF ablation was 93.6% with a major complication rate of 0.6%, a total complication rate of 3.9% and no associated mortality. We have shown that RF ablation can be performed safely, effectively and economically in a DGH setting with a high rate of success and a low complication rate.

Portable, inexpensive instruments to quantify stratum corneum hydration and skin erythema: applications to clothing science.

The level of stratum corneum hydration is assessed by measurement of the changes in skin resistance and is referred to as the galvanic skin response or electrical skin resistance. Skin erythema may be assessed by measurement of skin blood flow, tristimulus colorimetry or narrow-band reflectance spectroscopy. Currently available measuring devices are relatively expensive. Presented here are two inexpensive, hand-held, portable instruments which conveniently measure stratum corneum hydration and skin erythema.

[Use of electrographic method for detection of catheter position in the aorta]. / Primenenie élelktrograficheskogo metoda dlia opredeleniia polozheniia katetera v aorte.

Electrographic method has permitted to detect the position of aorta catheter's end in 5 patients. This method is most available for intensive care departments of city hospital, because it doesn't require special equipment and additional staff, is easy to master, may be directly used during catheterisation, is safe for patients and staff and is cost effective.

Replacing abdominally implanted defibrillators: effect of procedure setting on cost.

Although most ICDs are currently placed using a pectoral approach, there exists a large population of patients with abdominally implanted ICDs who will require device replacement due to a depleted battery. The purpose of this study was to compare the cost, convalescence, and complication rate of replacing abdominally implanted ICDs in the OR versus the EP laboratory. Between August 1993 and September 1994, we prospectively enlisted nine consecutive patients who presented for their second ICD generator replacement and who had a prior generator replacement in the OR 3-4 years earlier. The mean age of the patients was 63 +/- 17 years and their mean ejection fraction was 37% +/- 15%. ICD replacement was performed in the EP laboratory and consisted of explanting the old device, electronic interrogation of the lead system, and confirmation of defibrillation thresholds prior to implanting a new device. Local anesthesia was provided by lidocaine infiltration and sedation was achieved with intravenous (i.v.) midazolam and fentanyl. Following the procedure, the patients were returned to an outpatient monitored setting for 4 hours and were then discharged. Comparisons of the health care charges for the same procedure performed in the two different settings revealed a significant reduction in physician fees (from $3,621 +/- $556 to $2,179 +/- $577, P < 0.05), in hospital charges (from $5,811 +/- $1,102 to $2,306 +/- 696, P < 0.05), and in total charges (from $9,431 +/- $1,375 to $4,541 +/- $1,010, P < 0.05), exclusive of ICD cost, when the procedure was performed on an outpatient basis in the EP laboratory. Inpatient days averaged 3.0 +/- 0.3 when the procedure was performed in the OR. On long-term follow-up there were no complications following abdominal ICD generator replacement in the OR (mean follow-up, 39 +/- 2 months) or in the EP laboratory (mean follow-up, 42 +/- 4 months). Thus, ICD replacements in the EP laboratory cost less than in the OR due to significantly lower physician fees, hospital charges, and a shorter postprocedural convalescence.

The high cost of syncope: cost implications of a new insertable loop recorder in the investigation of recurrent syncope.

BACKGROUND: Patients with recurrent syncope frequently undergo extensive investigations that consume significant health care resources. Recent advances in long-term monitoring techniques have enhanced diagnostic yield in patients with infrequent symptoms. There is little information on the relative cost-effective profile of the investigative tools used in patients with syncope. METHODS: Two methods to determine health care costs in patients with syncope were used. In the first, health care resource utilization was determined in 24 patients with recurrent unexplained syncope and negative investigations who underwent insertion of the implantable loop recorder (ILR) during a pilot study of the feasibility of the device. The costs of investigations before, during, and after ILR implantation in each patient were calculated on the basis of median charges for an index investigation and a regression analysis of 1018 US Medicare hospital claims for syncope from 1993. Charges were converted to costs using a cost-to-charge ratio of 0.64. The second method was based on estimated costs per diagnosis and published diagnostic yields of 6 commonly applied tests in patients with syncope. A cohort simulation using theoretic models of 100 patients undergoing investigation for syncope was created to compare the diagnostic yield and cost per diagnosis of various diagnostic cascades. RESULTS: In the pilot study, the cost of investigation of syncope in the 2 years before ILR insertion was $7584 per patient. After the ILR was inserted, a diagnosis was obtained in 21 of 24 patients (diagnostic yield 88%). The cost of therapy was $2452, followed by a reduction in cost of care to $596 over 30 +/- 10 months of follow-up. In the second method, the diagnostic yield of individual tests ranged from 3% for echocardiography to 88% for the ILR. The cost per diagnosis obtained ranged from $529 for the external loop recorder to $73,260 for electrophysiologic testing in patients without structural heart disease. An approach to syncope similar to that of the ILR pilot study resulted in a cost per diagnosis of $3193 and a diagnostic yield of 98%. Performance of echocardiography in half of the patients and electrophysiologic testing only in the presence of structural heart disease reduced the cost to $2494 and retained a diagnostic yield of 98%. CONCLUSIONS: The cost of investigation of syncope is high. The ILR may reduce health care resource utilization by providing a diagnosis permitting definitive therapy. The cost per diagnosis profile of current diagnostic tests commonly used in patients with syncope is highly variable. A cost-effective approach to diagnosing this disorder can retain a high diagnostic yield with a reduction in resource utilization compared with a conventional approach.