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Biomedical subjects

C J Wallace

Publications and source records attributed to C J Wallace.

At least 55 records · Page 3Linked to original sources
PubMed1996

Testing and validation of computerized decision support systems.

Systematic, through testing of decision support systems (DSSs) prior to release to general users is a critical aspect of high quality software design. Omission of this step may lead to the dangerous, and potentially fatal, condition of relying on a system with outputs of uncertain quality. Thorough testing requires a great deal of effort and is a difficult job because tools necessary to facilitate testing are not well developed. Testing is a job ill-suited to humans because it requires tireless attention to a large number of details. For these reasons, the majority of DSSs available are probably not well tested prior to release. We have successfully implemented a software design and testing plan which has helped us meet our goal of continuously improving the quality of our DSS software prior to release. While requiring large amounts of effort, we feel that the process of documenting and standardizing our testing methods are important steps toward meeting recognized national and international quality standards. Our testing methodology includes both functional and structural testing and requires input from all levels of development. Our system does not focus solely on meeting design requirements but also addresses the robustness of the system and the completeness of testing.

Artificial Intelligence↗
PubMed1996

Standardization of clinical decision making for the conduct of credible clinical research in complicated medical environments.

The likelihood that past experience will produce correct guides to current practice depends on the signal-to-noise ratio for the clinical problem of interest. If the signal-to-noise ratio is high, the decision will be sound and patient benefit likely to occur. If the signal-to-noise ratio is low, as is commonly the case with difficult clinical decisions, then personal experience and the best intentions will not assure sound clinical decisions. When the probability of benefit cannot be quantified, clinicians in complex settings are in danger of being misled by data and experience. Quantifiable probabilities established by group experiment or observation will be necessary for clinical decisions that can be expected to confer benefit on the patient. Explicit methods are necessary for interventions that can be replicated in experiments or in practice. Computerized protocols force the articulation of explicit clinical care methods and standardize clinical decision making. We have developed explicit, rule-based protocols, implemented them in our hospital, exported them to other hospitals, and successfully achieved a rigorous experimental environment in the clinical ICU. Exportation of such explicit methods may narrow the gap between efficacy (university hospital) and effectiveness (community hospital) research results.

Clinical Trials as Topic↗
PubMed1995

Studies of 8-azido-ATP adducts reveal two mechanisms by which ATP binding to cytochrome c could inhibit respiration.

We have proposed that the binding of ATP at a site of substantial affinity and specificity could regulate the activity of cytochrome c with its physiological partners and thus the overall efficiency of mitochondrial electron transport. We now describe the use of ATP affinity-labeled protein to test the effect of occupancy of that site, which includes the invariant arginine 91, on the activity of cytochrome c with purified cytochrome c reductase and oxidase and its association with the mitochondrial inner membrane. Electron-transfer activities with the reductase and oxidase were inhibited by site occupancy to 41% and 11-15% of native values, respectively. The marked difference in the degree of inhibition of activity that distinguishes the reactions with the two major physiological partners was sufficient to cause, in whole mitochondria, a demonstrable shift from a situation in which there is a rate-limiting transfer from the reductase to cytochrome c, to a state where rates are more evenly matched for transfers between cytochrome c and the two redox partners. Site occupancy also substantially reduces the ionic strength necessary for half-maximal dissociation of cytochrome c from the membrane. These data imply that the decreased efficiency of electron transfer caused by ATP attachment can be attributed to a decrease in the protein's activity with individual physiological partners, possibly compounded with a decrease in its affinity for the inner mitochondrial membrane, and suggest that feedback regulation by ATP of cellular respiration operates in like manner.

Adenosine Triphosphate↗
PubMed1995

Peptide ligation and semisynthesis.

Semisynthesis is used to create defined analogues of proteins by the chemical manipulation of peptide fragments largely derived from the natural protein and the subsequent reassembly of those fragments into a near-native conformation. In common with the total synthesis of proteins, it requires efficient and non-destructive methods for peptide religation. Recently, a wide range of chemoselective ligation schemes have been elaborated that now permit the assembly of minimally protected peptides from either synthetic or natural sources.

Peptide Fragments↗
PubMed1995

Computers in critical care.

This article reviews the current state-of-the-art and future applications of computers in critical care, with particular attention to ventilator and drug-delivery applications. Automated charting, alerts and alarms, and tools for decision support (such as expert systems and closed-loop control) are discussed also.

Computers↗
PubMed1995

Verification & validation algorithms for data used in critical care decision support systems.

A decision support system is only as good as the data generating that decision support system. If the data is incorrect, doesn't relate to the other pieces of data, is missing or is not consistent, the decision support system conclusions may be incorrect and inconsistent. While collecting data from several sites during a multicenter randomized clinical trial, we found that some critical data elements were missing, out of correct ranges, totally illogical, and/or inconsistently recorded. In order to get consistent, correct, and dependable information from a our decision support system, the data elements used in that system had to be checked for completeness, valid values, consistent units of measurement, and relationships to other items. Development of data quality assurance rules and the application of those rules is imperative to using the data to generate daily scores for multiple organ failure, sepsis, and barotrauma.

Algorithms↗
PubMed1995

Medical informatics academia and industry: a symbiotic relationship that may assure survival of both through health care reform.

There are often clear lines drawn identifying the demilitarized zone between medical informatics academics and industry. Academics were "pure" intellectuals sequestered in ivory towers that effectively shielded them from the realities of the world. Industry has historically focused on creating effective products that produce financial return to the corporation. Both the paradigms of academia and industry are quickly becoming dinosaurs in the era of health care reform where both medical informatics academia and industry are under increasing pressure to develop and prove that medical informatics has a positive impact on health care both in terms of the quality of care as well as cost. Unfortunately, neither academia or industry alone are going to be able to successfully complete this task. The purpose of this paper is to describe such a collaborative effort that has produced a computerized decision support system for the management of mechanical ventilation in patients with the Adult Respiratory Distress Syndrome (ARDS) that is now installed and supported on three different commercial CIS platforms. This collaborative effort has allowed us to successfully mount a large multi-center clinical trial designed to determine efficacy.

Clinical Protocols↗
PubMed1995

A successful protocol for the use of pulse oximetry to classify arterial oxygenation into four fuzzy categories.

Pulse oximetry is widely used in critical care medicine to noninvasively estimate arterial hemoglobin oxygen saturation. Despite the obvious benefits of using pulse oximetry to detect life threatening desaturations, it is unknown how well pulse oximetry is able to predict the finer graduations of arterial oxygenation needed for clinical decision making. A computerized protocol was developed for the use of pulse oximetry to classify arterial oxygenation into four fuzzy categories and tested in a prospective clinical trial which compared the oxygenation category assigned by the protocol to one assigned by a respiratory therapist. In 3,742 classifications from 15 patients over a seven month period, the protocol showed 96% agreement with the therapists in the direction of therapy and 75% agreement with the oxygenation classes assigned by the therapists.

Clinical Protocols↗
PubMed1995

Cost effective computerized decision support: tracking caregiver acceptance at the point of care.

We implemented a computerized decision support tool to standardize the administration of supplemental oxygen (O2) therapy in the acute care (non-ICU) hospital setting. Caregiver acceptance of the computerizeds oxygen therapy protocol (COTP) instructions was measured to determine the clinical performance of the computerized decision support tool. 49.6% of instructions generated were followed by the clinical caregiver, and 16.8% of instructions generated were explicitly acknowledged by the user through the COTP computer interface. Despite this low caregiver response rate, significant favorable changes in the administration of oxygen were observed. This paper is focused on the issues of general importance the caregiver response rate raises for the implementation and clinical use of computerized decision support tools, including: (1) limitations of the user interface and (2) inherent difficulty in changing long-standing practice patterns.

Attitude to Computers↗
PubMed1995

MR findings in methanol intoxication.

We report the MR and CT findings with pathologic correlation in a case of severe methanol intoxication. There was bilateral hemorrhagic necrosis of the putamen and caudate nuclei and, in addition, extensive subcortical necrosis and symmetric bilateral necrosis of the pontine tegmentum and optic nerves, which may indicate poor prognosis.

Brain↗
PubMed1994

Structure characterization of membrane bound and surface adsorbed protein.

X-ray standing waves (XSW) have been used to study the topology of the protein cytochrome c, bound to a negatively charged model membrane and adsorbed at a metal surface. At the metal surface, cytochrome c forms an hexagonally close-packed monolayer. A similar packing arrangement is observed at the surface of a self-assembled lipid film on silver. The data suggest that cytochrome c maintains its native globular structure upon surface binding and subsequent storage for an extended period. Further, the data are consistent with a protein docking mechanism wherein the heme plane is oriented perpendicular to and with its exposed edge facing the surface. This study demonstrates the utility of XSW as a new and powerful structural tool for investigating membrane- and surface-protein interactions.

Adsorption↗
PubMed1994

Improving cytochrome c function by protein engineering?: studies of site-directed mutants of the human protein.

We have expressed the gene for human cytochrome c, and six mutants of the native sequence, in yeast defective in its own iso-1-cytochrome c gene. All constructs support strong growth in strict aerobic metabolism, and substantial amounts of protein could be extracted from permeabilized cells. The purified analogs, Cys14Ala, Gly37Arg, Arg38Lys, Arg38Gly, Gly84Ser, and Thr28Ile,Gly84Ser, were examined for changes in functional properties, since the majority of these residues are strongly or absolutely conserved. Indeed, although growth rates of the host yeast strains were very similar, there was great divergence in both physicochemical and biological properties, which have been rationalized in terms of changes to the stability of the cytochrome fold, and to the dipole moment of the protein. Interestingly, although modification of electrostatic properties in some mutants can apparently produce a twofold increase in electron transfer efficiency, such changes are not evolutionarily acceptable. The "improvement" is illusory. We suggest that an associated decrease in the stability of the heme crevice offsets any advantage of increased transfer rates.

Chromatography, Liquid↗
PubMed1994

Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome.

The impact of a new therapy that includes pressure-controlled inverse ratio ventilation followed by extracorporeal CO2 removal on the survival of patients with severe ARDS was evaluated in a randomized controlled clinical trial. Computerized protocols generated around-the-clock instructions for management of arterial oxygenation to assure equivalent intensity of care for patients randomized to the new therapy limb and those randomized to the control, mechanical ventilation limb. We randomized 40 patients with severe ARDS who met the ECMO entry criteria. The main outcome measure was survival at 30 days after randomization. Survival was not significantly different in the 19 mechanical ventilation (42%) and 21 new therapy (extracorporeal) (33%) patients (p = 0.8). All deaths occurred within 30 days of randomization. Overall patient survival was 38% (15 of 40) and was about four times that expected from historical data (p = 0.0002). Extracorporeal treatment group survival was not significantly different from other published survival rates after extracorporeal CO2 removal. Mechanical ventilation patient group survival was significantly higher than the 12% derived from published data (p = 0.0001). Protocols controlled care 86% of the time. Average PaO2 was 59 mm Hg in both treatment groups. Intensity of care required to maintain arterial oxygenation was similar in both groups (2.6 and 2.6 PEEP changes/day; 4.3 and 5.0 FIO2 changes/day). We conclude that there was no significant difference in survival between the mechanical ventilation and the extracorporeal CO2 removal groups. We do not recommend extracorporeal support as a therapy for ARDS. Extracorporeal support for ARDS should be restricted to controlled clinical trials.

Adult↗