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Biomedical subjects

Y H Yau

Publications and source records attributed to Y H Yau.

14 recordsLinked to original sources

BrainIT: a trans-national head injury monitoring research network.

BACKGROUND: Studies of therapeutic interventions and management strategies on head injured patients are difficult to undertake. BrainIT provides validated data for analysis available to centers that contribute data to allow post-hoc analysis and hypothesis testing. METHODS: Both physiological and intensive care management data are collected. Patient identification is eliminated prior to transfer of data to a central database in Glasgow. Requests for missing/ ambiguous data are sent back to the local center. Country coordinating centers provide advice, training, and assistance to centers and manage the data validation process. RESULTS: Currently 30 centers participate in the group. Data collection started in January 2004 and 242 patients have been recruited. Data validation tools were developed to ensure data accuracy and all analysis must be undertaken on validated data. CONCLUSION: BrainIT is an open, collaborative network that has been established with primary objectives of i) creating a core data set of information, ii) standardizing the collection methodology, iii) providing data collection tools, iv) creating and populating a data base for future analysis, and v) establishing data validation methodologies. Improved standards for multi-center data collection should permit the more accurate analysis of monitoring and management studies in head injured patients.

Biomedical Research↗

Survey of traumatic brain injury management in European Brain-IT centres year 2001.

BACKGROUND: The aim of this study was to obtain basic knowledge about the current local conditions and neurointensive care of traumatic brain injury (TBI) in the new multi-centre collaborative BrainIT group. MATERIALS AND METHODS: The survey comprised a background part on local policies (Part A), and a case study section (Part B). The information was gathered by questionnaire followed by telephone interviews. Twenty-three BrainIT centres participated in the survey and answers from two respondents were available from 18 of the sites. RESULTS: The average proportion of agreement between duplicate respondents was 0.778 (range 0.415-1.00). All BrainIT centres monitored ICP. The treatment protocols seem to have a pattern concerning escalation of treatment of intracranial hypertension: 1/ evacuation of mass lesions and head elevation; 2/ increased sedation and mannitol; 3/ hyperventilation; 4/ ventricular drainage; 5/ craniectomy and barbituates. CONCLUSIONS: There seemed to be an agreement on neurointensive care policies within the BrainIT group. The suggested order of treatment was generally in accordance with published guidelines although the suggested order and combinations of different treatments varied. Variation of treatment within the range of prescribed standards provides optimal conditions for an interesting future analysis of treatment and monitoring data in reality using the BrainIT database.

Brain Injuries↗

Assessment of different data representations and averaging methods on the Spiegelberg compliance device.

The Spiegelberg Compliance Device (Spiegelberg KG, Hamburg, Germany) has been available for the automated measurement and calculation of minute by minute intracranial compliance. Widespread practical use has been somewhat limited by the instability of values: especially at low intracranial pressures. We looked at two aspects of a methodology in an attempt to increase the value of the Spiegelberg device in the clinical setting. Firstly, we discussed the difference in representing measured values as elastance (dp/dv) instead of compliance (dv/dp); and secondly we proposed the use of an averaging algorithm called the Exponentially Weighted Moving Average (ewma), which could be applied as a flexible method to follow trends and rapid changes in the elastance (or compliance). Clinical data from sixteen patients were gathered and statistical analysis was focused on three particular aspects, the coefficient of variation which indicates the variability of data values, the correlation between the elastance (or compliance) time series and the underlying ICP signal and the percentage of outliers greater than 2.5 standard deviations from the mean. Our results showed that expressing elastance (dp/dv) instead of compliance (dv/dp) yielded fewer outliers and had a better correlation to ICP, and the ewma method had a better correlation to ICP than the Spiegelberg method.

Adult↗

The BrainIT Group: concept and current status 2004.

INTRODUCTION: An open collaborative international network has been established which aims to improve inter-centre standards for collection of high-resolution, neurointensive care data on patients with traumatic brain injury. The group is also working towards the creation of an open access, detailed and validated database that will be useful for hypothesis generation. In Part A, we describe the underlying concept of the group and it's aims and in Part B we describe the current status of the groups development. METHODS: Four group meetings funded by the EEC have enabled definition of a "Core Dataset" to be collected from all centres regardless of specific project aim. A form based feasibility study was conducted and a prospective data collection exercise of core data using PC and hand held computer based methods is in progress. FINDINGS: A core-dataset was defined and can be downloaded from the BrainIT web-site (go to "Core dataset" link at: www.brainit.org). A form based feasibility study was conducted showing the overall feasibility for collection of the core data elements was high. Software tools for collection of the core dataset have been developed. Currently, 130 patient's data from 16 European centres have been recruited to the joint database as part of an EEC funded proof of concept study. INTERPRETATION: The BrainIT network provides a more standardised and higher resolution data collection mechanism for research groups, organisations and the device industry to conduct multicentre trials of new health care technology in patients with traumatic brain injury.

Brain Injuries↗

Accurate data collection for head injury monitoring studies: a data validation methodology.

BACKGROUND: BrainIT is a multi centre, European project, to collect high quality continuous data from severely head injured patients using a previously defined [6] core data set. This includes minute-by-minute physiological data and simultaneous treatment and management information. It is crucial that the data is correctly collected and validated. METHODS: Minute-by-minute physiological monitoring data is collected from the bedside monitors. Demographic and clinical information, intensive care management and secondary insult management data, are collected using a handheld computer. Data is transferred from the handheld device to a local computer where it is reviewed and anonymised before being sent electronically, with the physiological data, to the central database in Glasgow. Automated computer tools highlight missing or ambiguous data. A request is then sent to the contributing centre where the data is amended and returned to Glasgow. Of the required data elements 20% are randomly selected for validation against original documentation along with the actual number of specific episodic events during a known period. This will determine accuracy and the percentage of missing data for each record. CONCLUSION: Advances in patient care require an improved evidence base. For accurate, consistent and repeatable data collection, robust mechanisms are required which should enhance the reliability of clinical trials, assessment of management protocols and equipment evaluations.

Brain Injuries↗

R3-survey of traumatic brain injury management in European Brain IT centres year 2001.

OBJECTIVE: To obtain knowledge about the conditions and management of traumatic brain injury (TBI) in a collaborative network of Brain Information Technology centres. DESIGN: The Brain IT (Brain monitoring with Information Technology) survey comprised two parts: local conditions and policies (part A), and a case study part (part B). The information was gathered by written questionnaires followed by telephone interviews. PARTICIPANTS: Twenty-four Brain IT centres participated (two respondents from 18 sites). RESULTS: The average proportion of agreement between duplicate respondents was 0.79 (range 0.44-1.00). All Brain IT centres monitored ICP. The reported order of treatment for intracranial hypertension was: evacuation of mass-lesions and head elevation (1), increase of sedation and Mannitol scheme (2), hyperventilation (3), ventricular drainage (4), craniectomy and pentothal coma (5), and decompressive lobectomy (6). The respondents were less prone to evacuate expansive contusions in relation to extra cerebral hematomas. The most common suggested interventions (alone or in combination) for treatment of intracranial hypertension without mass lesions was the Mannitol scheme (included in 71% of the suggestions), CSF drainage (included in 56%), hyperventilation (included in 32%), and pentothal coma (included in 22%). CONCLUSIONS: The suggested management of TBI was mainly in accordance with published guidelines, although a minor proportion of the answers deviated to some extent. The suggested order and combinations of different treatment interventions varied. Variation of treatment within the range of prescribed standards provides optimal conditions for an interesting future analysis of treatment and monitoring data as collected prospectively in a Brain IT database.

Adult↗

The BrainIT group: concept and core dataset definition.

INTRODUCTION: An open collaborative international network has been established which aims to improve inter-centre standards for collection of high-resolution, neurointensive care data on patients with traumatic brain injury. The group is also working towards the creation of an open access, detailed and validated database that will be useful for post-hoc hypothesis testing. In Part A, the underlying concept, the group coordination structure, membership guidelines and database access and publication criteria are described. Secondly, in part B, we describe a set of meetings funded by the EEC that allowed us to define a "Core Dataset" and we present the results of a feasibility exercise for collection of this core dataset. METHODS: Four group meetings funded by the EEC have enabled definition of a "Core Dataset" to be collected from all centres regardless of specific project aim. A paper based pilot collection of data was conducted to determine the feasibility for collection of the core dataset. Specially designed forms to collect the core dataset demographic and clinical information as well as sample the time-series data elements were distributed by both email and standard mail to 22 BrainIT centres. A deadline of two months was set to receive completed forms back from centres. A pilot data collection of minute by minute physiological monitoring data was also performed. FINDINGS: A core-dataset was defined and can be downloaded from the BrainIT web-site (go to "Core dataset" link at: www.brainit.org). Eighteen centres (82%) returned completed forms by the set deadline. Overall the feasibility for collection of the core data elements was high with only 10 of the 64 questions (16%) showing missing data. Of those 10 fields with missing data, the average number of centres not responding was 12% and the median 6%. An SQL database to hold the data has been designed and is being tested. Software tools for collection of the core dataset have been developed. Ethics approval has been granted for collection of multi-centre data as part of a pilot data collection study. INTERPRETATION: The BrainIT network provides a more standardised and higher resolution data collection mechanism for research groups, organisations and the device industry to conduct multi-centre trials of new health care technology in patients with traumatic brain injury.

Brain Injuries↗

Clinical experience in the use of the Spiegelberg automated compliance device in the assessment of patients with hydrocephalus.

Deciding upon shunting in patients with hydrocephalus with possibly related symptomatology, is difficult. The Spiegelberg automated device allows continuous measurements of intracranial compliance. We aimed to evaluate the added information that this new technology can provide, in addition to standard continuous ICP monitoring. Thirty-three patients with hydrocephalus were continuously monitored for ICP and compliance. Patients with abnormal ICP or compliance profiles were selected for shunting. Thirteen patients underwent ventriculo-peritoneal shunting on this basis, with 12 obtaining benefit and one dying as a complication of shunt-related sepsis. The 13 patients undergoing shunting had abnormalities in either intracranial pressure or compliance or both. Only 1 patient had normal ICP, but abnormal compliance and so the true complementary role of continuous compliance measurements cannot be determined. It is proposed that further recruitment be on a larger multi-centre basis. Determination of benefit is required, particularly as a possible time lag of abnormal ICP abnormal compliance over appearing during monitoring can be demonstrated.

Adolescent↗

An experimental evaluation of a new intraparenchymal continuous compliance probe: preliminary studies.

The Spiegelberg automated compliance device offers practical benefits over the standard manual injection techniques for assessing volume-pressure status. Currently, however, the system relies on the insertion of an intraventricular catheter. If automated continuous measurement of intraparenchymal compliance could be achieved, then this would be a further practical advance. Automated measurements of compliance using a prototype intraparenchymal probe were assessed in comparison with the current intraventricular probe in a sheep model of diffusely raised ICP. The results show poor correlation between intraventricular compliance (IVC) and intraparenchymal compliance (IPC) at low levels of cerebral perfusion pressure (CPP). The IPC response to decreasing CPP beyond probable levels of blood flow autoregulation suggest that IPC is more dependent on local tissue perfusion factors, rather than overall physical compliance. Further evaluation of compliance in the intraparenchymal compartment versus intraventricular compliance will be needed before adaptation of the automated system for clinical application.

Animals↗

High therapeutic index of factor C Sushi peptides: potent antimicrobials against Pseudomonas aeruginosa.

Factor C protein isolated from the horseshoe crab, Carcinoscorpius rotundicauda, has endotoxin binding capability. Synthetic peptides of 34 amino acids based on the sequence of two regions of factor C (Sushi 1 and Sushi 3) as well as their corresponding mutants exhibited activities against 30 clinical isolates of Pseudomonas aeruginosa. Collectively, all four peptides demonstrated exceptionally effective bactericidal activity against P. aeruginosa with 90% minimal bactericidal concentrations (MBC(90)s) in the range of 0.06 to 0.25 microg/ml (16 to 63 nM). Viable bacteria were reduced by 90% after 7 min and were totally eradicated within 40 to 50 min. These peptides are minimally hemolytic against both rabbit and human erythrocytes even at concentrations up to 1,600-fold their MBC(90)s. Both in vitro and in vivo studies indicate that cytotoxic effects are small even at 1,000-fold their MBC(90)s. Furthermore, the Sushi peptides are tolerant of high-salt and adverse pH conditions. These findings demonstrate the promising therapeutic potential of the Sushi peptides.

Arthropod Proteins↗

Definition of endotoxin binding sites in horseshoe crab factor C recombinant sushi proteins and neutralization of endotoxin by sushi peptides.

Three truncated fragments, harboring different sushi domains, namely, sushi123, sushi1, and sushi3 domains, of Factor C were produced as biologically active secreted recombinant proteins. Sushi1 and 3 each has a high-affinity LPS binding site with K:(d) of 10(-9) to 10(-10) M. Positive cooperativity in sushi123 resulted in a 1000-fold increase in K:(d)2. The core LPS binding region of sushi1 and 3 reside in two 34-mer peptides, S1 and S3. A rigidly held disulfide-bonded structure is not essential but is important for LPS binding, as confirmed by a 100- to 10000-fold decrease in affinity. Both S1 and S3 can inhibit LAL reaction and LPS-induced hTNF-alpha secretion with different potency. LAL assay revealed that at least two molecules of S1 bind cooperatively to one LPS molecule, with Hill's coefficient of 2.42. The LPS binding by S3 is independent and noncooperative. The modified SDelta1 and SDelta3 peptides exhibited increased LPS neutralization potential although its LPS binding affinities indicated only a 10-fold improvement. Hence, the structural difference of the four sushi peptides conferred different efficiencies in LPS neutralization without altering their binding affinity for LPS. Circular dichroism spectrometry revealed that the four peptides underwent conformational change in the presence of lipid A, transitioning from a random coil to either an alpha-helical or beta-sheet structure. Two factors are critical for the sensitivity of Factor C to LPS: 1) the presence of multiple binding sites for LPS on a single Factor C molecule; and 2) high positive cooperativity in LPS binding. The results showed that in the design of an improved LPS binding and neutralizing peptide, charge balance of the peptide is a critical parameter in addition to its structure.

Animals↗

Experimental evaluation of the Spiegelberg intracranial pressure and intracranial compliance monitor. Technical note.

The goal of this study was to compare the Spiegelberg intraventricular intracranial pressure (ICP)/intracranial compliance monitoring device, which features an air-pouch balloon catheter, with existing gold-standard methods of measuring ICP and intracranial compliance. A Spiegelberg intraventricular catheter, a standard intraventricular catheter, and a Codman intraparenchymal ICP microsensor were placed in five sheep, which previously had been given anesthetic and paralytic agents, to allow comparative measurement of ICP at incremental levels (range 5-50 mm Hg). Intracranial pressure measured using the Spiegelberg intraventricular air-pouch balloon catheter displayed a linear correlation with ICP measured using the standard intraventricular fluid-filled catheter (r2 = 0.9846, p < 0.001; average bias -0.74 mm Hg), as well as with ICP measured using the Codman intraparenchymal strain-gauge sensor (r2 = 0.9778, p < 0.001; average bias 0.01 mm Hg). Automated measurements of intraventricular compliance obtained using the Spiegelberg compliance device were compared with compliance measurements that were made using the gold-standard manual cerebrospinal fluid bolus injection technique at ICPs ranging from 5 to 50 mm Hg, and a linear correlation was demonstrated between the two methods (r2 = 0.7752, p < 0.001; average bias -0.019 ml/mm Hg). The Spiegelberg air-pouch ICP/compliance monitor provides ICP and compliance data that are very similar to those obtained using both gold-standard methods and an intraparenchymal ICP monitor over a range of pathophysiological ICPs. The automated closed Spiegelberg system offers practical advantages for the measurement of intraventricular compliance. Assessment of the clinical utility and robustness of the Spiegelberg system, together with the development of an intraparenchymal device, would enhance the clinical utility of automated compliance measurement and expand the range of its applications.

Animals↗