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PubMed2005

Anatomic pathology databases and patient safety.

CONTEXT: The utility of anatomic pathology discrepancies has not been rigorously studied. OBJECTIVE: To outline how databases may be used to study anatomic pathology patient safety. DESIGN: The Agency for Healthcare Research and Quality funded the creation of a national anatomic pathology errors database to establish benchmarks for error frequency. The database is used to track more frequent errors and errors that result in more serious harm, in order to design quality improvement interventions intended to reduce these types of errors. In the first year of funding, 4 institutions (University of Pittsburgh, Henry Ford Hospital, University of Iowa, and Western Pennsylvania Hospital) reported cytologic-histologic correlation error data after standardizing correlation methods. Root cause analysis was performed to determine sources of error, and error reduction plans were implemented. PARTICIPANTS: Four institutions self-reported anatomic pathology error data. MAIN OUTCOME MEASURES: Frequency of cytologic-histologic correlation error, case type, cause of error (sampling or interpretation), and effect of error on patient outcome (ie, no harm, near miss, and harm). RESULTS: The institutional gynecologic cytologic-histologic correlation error frequency ranged from 0.17% to 0.63%, using the denominator of all Papanicolaou tests. Based on the nongynecologic cytologic-histologic correlation data, the specimen sites with the highest discrepancy frequency (by project site) were lung (ranging from 16.5% to 62.3% of all errors) and urinary bladder (ranging from 4.4% to 25.0%). Most errors detected by the gynecologic cytologic-histologic correlation process were no-harm events (ranging from 10.7% to 43.2% by project site). Root cause analysis identified sources of error on both the clinical and pathology sides of the process, and error intervention programs are currently being implemented to improve patient safety. CONCLUSIONS: A multi-institutional anatomic pathology error database may be used to benchmark practices and target specific high-frequency errors or errors with high clinical impact. These error reduction programs have national import.

Benchmarking↗
PubMed2000

Comparing the subjective, psychomotor, and physiological effects of intravenous hydromorphone and morphine in healthy volunteers.

RATIONALE: The psychopharmacological profile of hydromorphone, an opioid that has been used extensively for many years for post-operative pain management, has not been adequately characterized in non-drug abusers. OBJECTIVES: To characterize the subjective, psychomotor, and physiological effects of a range of single doses of hydromorphone in non-drug-abusing volunteers and to compare the effects of hydromorphone with that of morphine, a benchmark mu opioid agonist. METHODS: Subjects in a six-session study were injected in an upper extremity vein with 0, 0.33, 0.65, 1.3 mg/70 kg hydromorphone, and 5 and 10 mg/70 kg morphine, using a randomized, double-blind, crossover design. RESULTS: Hydromorphone increased scores on the pentobarbital-chlorpromazine-alcohol group and lysergic acid diethylamide scales and decreased scores on the benzedrine group scale of the Addiction Research Center Inventory, increased adjective checklist ratings of ("dry mouth", "flushing", and "nodding", and increased visual analog scale ratings indicative of both pleasant (e.g., drug liking) and unpleasant (e.g., "feel bad") effects. The subjective effects of morphine at putatively equianalgesic doses to those of hydromorphone were similar to those of hydromorphone, but in some cases of lesser magnitude. Psychomotor impairment was modest with hydromorphone and absent with morphine. Both opioids produced dose-dependent decreases in pupil size. A relative potency analysis indicated that hydromorphone was 10 times as potent as morphine (1 mg hydromorphone=10 mg morphine). CONCLUSIONS: The results of this study demonstrate that 0.33-1.3 mg hydromorphone had orderly, dose-related effects on subjective, psychomotor, and physiological variables, and similar effects to those of a benchmark mu opioid agonist, morphine.

Adult↗
PubMed2005

Procedural sedation and analgesia: a review and new concepts.

Procedural sedation and analgesia has become a commonplace procedure in the ED, certainly falling under the domain of the EP. Every EP should approach PSA as a complex procedure requiring high-level skills and knowledge. Initially, understand that PSA represents a spectrum of goals, from anxiolysis and pain relief to deep sedation. Assess the needs of the patient and the concomitant procedure and set goals accordingly. There is a pharmacopia of drugs that provide sedation and analgesia. Become familiar with their pharmacology, advantages and disadvantages, and indications. This will allow for appropriate usage and achievement of sedation goals. Several drugs that are commonly used for general anesthesia are proving themselves to be safe and efficacious for PSA. Both etomidate and propofol have emerged as useful drugs for PSA. Continued research and practice with these agents will add to our understanding and help define their use for PSA. Performing PSA as a procedure itself requires preparedness, diligent monitoring, and risk awareness. Knowing the patient's comorbid state and choosing agents that will not exacerbate their baseline status minimize risk. Following fasting guidelines is appropriate in certain clinical situations, and is prudent when time permits. However, these guidelines are a benchmark for minimizing risk and are not supported by evidence-based medicine. It is important to be cognizant of the guidelines but also to identify the emergency scenario where action must be taken despite the fasting guidelines. Controlling sedation depth also minimizes the risk of aspiration and other complications. The ETCO2 monitor and Bispectral Index may prove to be useful adjuncts for monitoring sedation depth. However, there is nothing yet that measures sedation depth quantitatively that can replace the qualitative assessment of the EP. More and more PSA is falling under the domain of the EP. It is important for the EP to be involved in hospital policy and guidelines associated with this procedure, and to remain aware of new research in this field. EPs can thereby contribute to quality assurance throughout the medical community by setting a standard in the practice of PSA, as they are not the only practitioners using this procedure. With continued practice and research, expertise in this field will grow measurably.

Analgesia↗
PubMed2005

Fast and accurate Coulomb calculation with Gaussian functions.

Coulomb interaction is one of the major time-consuming components in a density functional theory (DFT) calculation. In the last decade, dramatic progresses have been made to improve the efficiency of Coulomb calculation, including continuous fast multipole method (CFMM) and J-engine method, all developed first inside Q-Chem. The most recent development is the advent of Fourier transform Coulomb method developed by Fusti-Molnar and Pulay, and an improved version of the method has been recently implemented in Q-Chem. It replaces the least efficient part of the previous Coulomb methods with an accurate numerical integration scheme that scales in O(N2) instead of O(N4) with the basis size. The result is a much smaller slope in the linear scaling with respect to the molecular size and we will demonstrate through a series of benchmark calculations that it speeds up the calculation of Coulomb energy by several folds over the efficient existing code, i.e., the combination of CFMM and J-engine, without loss of accuracy. Furthermore, we will show that it is complementary to the latter and together the three methods offer the best performance for Coulomb part of DFT calculations, making the DFT calculations affordable for very large systems involving thousands of basis functions.

Journal Article↗
PubMed2002

Subtle motifs: defining the limits of motif finding algorithms.

MOTIVATION: What constitutes a subtle motif? Intuitively, it is a motif that is almost indistinguishable, in the statistical sense, from random motifs. This question has important practical consequences: consider, for example, a biologist that is generating a sample of upstream regulatory sequences with the goal of finding a regulatory pattern that is shared by these sequences. If the sequences are too short then one risks losing some of the regulatory patterns that are located further upstream. Conversely, if the sequences are too long, the motif becomes too subtle and one is then likely to encounter random motifs which are at least as significant statistically as the regulatory pattern itself. In practical terms one would like to recognize the sequence length threshold, or the twilight zone, beyond which the motifs are in some sense too subtle. RESULTS: The paper defines the motif twilight zone where every motif finding algorithm would be exposed to random motifs which are as significant as the one which is sought. We also propose an objective tool for evaluating the performance of subtle motif finding algorithms. Finally we apply these tools to evaluate the success of our MULTIPROFILER algorithm to detect subtle motifs.

Algorithms↗
PubMed2003

Consensus alignment for reliable framework prediction in homology modeling.

MOTIVATION: Even the best sequence alignment methods frequently fail to correctly identify the framework regions for which backbones can be copied from the template into the target structure. Since the underprediction and, more significantly, the overprediction of these regions reduces the quality of the final model, it is of prime importance to attain as much as possible of the true structural alignment between target and template. RESULTS: We have developed an algorithm called Consensus that consistently provides a high quality alignment for comparative modeling. The method follows from a benchmark analysis of the 3D models generated by ten alignment techniques for a set of 79 homologous protein structure pairs. For 20-to-40% of the targets, these methods yield models with at least 6 A root mean square deviation (RMSD) from the native structure. We have selected the top five performing methods, and developed a consensus algorithm to generate an improved alignment. By building on the individual strength of each method, a set of criteria was implemented to remove the alignment segments that are likely to correspond to structurally dissimilar regions. The automated algorithm was validated on a different set of 48 protein pairs, resulting in 2.2 A average RMSD for the predicted models, and only four cases in which the RMSD exceeded 3 A. The average length of the alignments was about 75% of that found by standard structural superposition methods. The performance of Consensus was consistent from 2 to 32% target-template sequence identity, and hence it can be used for accurate prediction of framework regions in homology modeling.

Algorithms↗
PubMed2005

How patients' sociodemographic characteristics affect comparisons of competing health plans in California on HEDIS quality measures.

OBJECTIVE: To estimate effects of patient sociodemographic characteristics on differential performance within and between plans in a single market area on the HEDIS quality of care measures, widely used for purchasing and accreditation decisions in the United States. DESIGN: Using logistic regression, we modeled associations of age, sex, and zip-code-linked sociodemographic characteristics of health plan members with HEDIS measures of screening and preventive services. We calculated the impact of adjusting for these associations on measures of health plan performance. SETTING: Twenty-two California health plans provided individual-level HEDIS data and zip codes of residence for up to 2 years. PARTICIPANTS: 110 541 commercially insured health plan members. MAIN OUTCOME MEASURES: Ten HEDIS quality-of-care measures. RESULTS: Performance on quality measures was negatively associated with percent receiving public assistance in the local area (seven out of 10 measures), percent Black (three measures), and percent Hispanic (four measures), and positively associated with percent college educated (six measures), and percent urban (three measures), controlling for plan, while associations with percent Asian were positive for three measures and negative for one (P < 0.05 for six associations, P < 0.01 for four, P < 0.001 for 17). Associations were consistent across plans and over time. Adjustment for these characteristics changed rates for most plans and measures by <5 percentage points. CONCLUSIONS: Adjustment for socioeconomic case mix has little impact on the measured performance of most plans in California, but substantially affects a few. The impact of case mix on indicators should be considered when making comparisons of health plan quality.

Benchmarking↗
PubMed2006

Making a business case for quality by regional information sharing involving cardiothoracic surgery.

A consortium of cardiac surgeons, nurses, and administrators in Virginia has developed a clinical/financial database to identify sites with best outcomes and replicate best practices statewide. The financial value of quality improvements is estimated from the incremental savings gained by reducing postoperative complications. The group studied 7,417 coronary artery bypass graft cases in 2003-2004. The average costs of atrial fibrillation, stroke, mediastinitis, renal failure, reoperation for bleeding, and prolonged use of ventilation were measured using charge data and ratios of costs-to-charges. Costs ranged from 18,093 US dollars to 28,136 US dollars in eight hospitals. Lower-cost hospitals had lower standardized mortality ratios. Average total costs were 19,049 US dollars for cases with no complications. Cases with postoperative atrial fibrillation were 21,415 US dollars, an incremental cost of 2,366 US dollars (p<0.0001), and reached 54,671 US dollars for mediastinitis (deep sternal wound infections) and 57,360 US dollars for renal failure. Overall, 16.1% of 5,230 coronary artery bypass graft patients developed atrial fibrillation in 2003. Incidence ranged from <5% to nearly 30% across 14 hospitals. Reducing the incidence of complications by small fractions can yield significant savings. Paying for performance may lead to more comparative analysis, peer-to-peer collaboration, and new approaches to quality improvement and efficiency measurement.

Benchmarking↗
PubMedDate not supplied

Improving clinical effectiveness in an integrated care delivery system.

HealthEast, an integrated care delivery system based in St. Paul, MN, established a care management program in 1993. At HealthEast, care management is defined as "an interdisciplinary process of coordinating client-centered services across the continuum of care to achieve quality and cost-effective outcomes." The program included establishing a collaborative practice model that was used to drive the organization's improvement efforts. The use of this model has been instrumental in achieving significant improvements in financial and clinical performance. As a result, HealthEast received a leadership award for "Improving Clinical Effectiveness within a Healthcare System" from VHA, Inc., a nationwide membership alliance of approximately 1,700 community healthcare organizations.

Benchmarking↗
PubMed2003

Contrast threshold of a brisk-transient ganglion cell in vitro.

We measured the contrast threshold for mammalian brisk-transient ganglion cells in vitro. Spikes were recorded extracellularly in the intact retina (guinea pig) in response to a spot with sharp onset, flashed for 100 ms over the receptive field center. Probability density functions were constructed from spike responses to stimulus contrasts that bracketed threshold. Then an "ideal observer" (IO) compared additional trials to these probability distributions and decided, using a single-interval, two-alternative forced-choice procedure, which contrasts had most likely been presented. From these decisions we constructed neurometric functions that yielded the threshold contrast by linear interpolation. Based on the number of spikes in a response, the IO detected contrasts as low as 1% [4.2 +/- 0.4% (SE); n = 35]; based on the temporal pattern of spikes, the IO detected contrasts as low as 0.8% (2.8 +/- 0.2%). Contrast increments above a very low "basal contrast" were discriminated with greater sensitivity than they were detected against the background. Performance was optimal near 37 degrees C and declined with a Q(10) of about 2, similar to that of retinal metabolism. By the method used by previous in vivo studies of brisk-transient cells, our most sensitive cells had similar thresholds. The in vitro measurements thus provide an important benchmark for comparing sensitivity of neurons upstream (cone and bipolar cell) and downstream to assess efficiency of retinal and central circuits.

Algorithms↗
PubMed1997

Benchmarking the quality-monitoring process: a comparison of outcomes analysis by trauma and injury severity score (TRISS) methodology with the peer-review process.

BACKGROUND: One measure of optimal function within a trauma center is the ability to critically examine outcomes from the process of care within the institution, yet guidelines for evaluation of the peer-review process are lacking. This study was conducted to determine the correlation between mortality analysis performed by the peer-review process (PR) within a trauma division and outcome analysis as determined by Trauma and Injury Severity Score (TRISS) methodology. METHODS: The mortality peer-review data for an entire year at our level I trauma center served as the study population. Information was obtained on probability of survival, and a determination of preventability was made using standard, preexisting criteria. Peer review involves assigning each outcome to a specific category through the process of multidisciplinary assessment. Probability of survival data was not used for this purpose. Kappa analysis was performed to determine the degree of agreement in each category and then tested for significance. RESULTS: One hundred four deaths in 1,868 trauma patients (5.5%) were reviewed at our multidisciplinary conference. Outcomes were judged as preventable, potentially preventable, or nonpreventable. Death directly related to exsanguination was typically categorized as potentially preventable. Kappa analysis demonstrated the greatest agreement between PR and TRISS in the nonpreventable category (kappa = 0.213) and the least agreement in the potentially preventable category (kappa = -0.197). Overall, the kappa Z statistic was nonsignificant (Z = 1.24). CONCLUSIONS: Multidisciplinary peer-review outcomes analysis is at least as effective as the computer-generated TRISS probability of survival data for evaluating quality of care in a trauma center and may be more effective for analysis of potentially preventable outcomes.

Adolescent↗
PubMed2002

Passive TLD based system for characterisation of spectral and angular properties of high dose rate workplace fields.

In order to address the problem of characterisation of high dose rate workplace fields, unique techniques and devices have been developed and tested. The kit of devices comprises a passive spectrometric system and six-vector collimator with thermoluminiscent detectors (TLDs) inside, allowing determination of the anisotropy of the radiation field, both horizontal and vertical. The passive spectrometric system makes use of simultaneous exposure of several TLDs placed inside spherical attenuators. Deconvolution of gamma spectra is performed by solving a system of simultaneous linear equations. The problem of solving ill-defined systems of simultaneous equations was addressed by a system regularisation method. The energy resolution of the system is not high (seven to ten energy bins can be distinguished), yet is sufficient for practical needs. After several benchmark tests, the discussed experimental set-up was extensively tested in various locations within Object 'Shelter'. Results of both energy spectrum and exposure geometry characterisation demonstrated the feasibility of the proposed approach.

Gamma Rays↗
PubMed2003

Activities of fluconazole and voriconazole against 1,586 recent clinical isolates of Candida species determined by Broth microdilution, disk diffusion, and Etest methods: report from the ARTEMIS Global Antifungal Susceptibility Program, 2001.

The ARTEMIS Global Antifungal Susceptibility Program (ARTEMIS Program) was initiated in 2001 to provide focused surveillance of the activities of fluconazole and voriconazole against Candida spp. isolated from blood and other normally sterile sites. A total of 1,586 episodes of infection were detected at 61 international study sites. Overall, 57.7% of the infections were due to Candida albicans, followed by C. glabrata (14.8%), C. parapsilosis (12.5%), C. tropicalis (9.4%), C. krusei (2.7%), and C. lusitaniae (1.5%). Isolates of C. albicans, C. parapsilosis, and C. tropicalis were all highly susceptible to fluconazole (for 99% of the isolates the MICs were <or=8 microg/ml). Likewise, 99 to 100% of these species were inhibited by <or=1 microg of voriconazole per ml. Voriconazole was also active against C. glabrata (93% of the isolates were susceptible [MICs <or= 1 microg/ml]) and C. krusei (100% of the isolates were susceptible). The agar-based Etest and disk diffusion methods performed well for the testing of both fluconazole and voriconazole compared to the broth microdilution MIC reference method. These observations establish the continued importance of C. albicans as a pathogen and the sustained activity of fluconazole and the broad spectrum of activity of voriconazole and will serve as the first-year benchmark for the ARTEMIS Program. Continued surveillance and refinement of broth- and agar-based test methods will help to identify susceptibility trends and improve the laboratory capability for antifungal susceptibility testing.

Antifungal Agents↗
PubMed2006

Prediction of catalytic residues using Support Vector Machine with selected protein sequence and structural properties.

BACKGROUND: The number of protein sequences deriving from genome sequencing projects is outpacing our knowledge about the function of these proteins. With the gap between experimentally characterized and uncharacterized proteins continuing to widen, it is necessary to develop new computational methods and tools for functional prediction. Knowledge of catalytic sites provides a valuable insight into protein function. Although many computational methods have been developed to predict catalytic residues and active sites, their accuracy remains low, with a significant number of false positives. In this paper, we present a novel method for the prediction of catalytic sites, using a carefully selected, supervised machine learning algorithm coupled with an optimal discriminative set of protein sequence conservation and structural properties. RESULTS: To determine the best machine learning algorithm, 26 classifiers in the WEKA software package were compared using a benchmarking dataset of 79 enzymes with 254 catalytic residues in a 10-fold cross-validation analysis. Each residue of the dataset was represented by a set of 24 residue properties previously shown to be of functional relevance, as well as a label {+1/-1} to indicate catalytic/non-catalytic residue. The best-performing algorithm was the Sequential Minimal Optimization (SMO) algorithm, which is a Support Vector Machine (SVM). The Wrapper Subset Selection algorithm further selected seven of the 24 attributes as an optimal subset of residue properties, with sequence conservation, catalytic propensities of amino acids, and relative position on protein surface being the most important features. CONCLUSION: The SMO algorithm with 7 selected attributes correctly predicted 228 of the 254 catalytic residues, with an overall predictive accuracy of more than 86%. Missing only 10.2% of the catalytic residues, the method captures the fundamental features of catalytic residues and can be used as a "catalytic residue filter" to facilitate experimental identification of catalytic residues for proteins with known structure but unknown function.

Algorithms↗
PubMed2001

Physician services in an academic neurology department: using the resource-based relative-value scale to examine physician activities.

The inability of physician managers and decision makers to critically analyze the resource utilization of physicians has hindered a more comprehensive understanding of the role of neurologists in the patterns and organization of medical practice. This article outlines an approach for using the physician work relative value units (RVUs) in the Medicare Fee Schedule (MFS) to address this problem and profile physician clinical activities in a comparative manner. These techniques are then used to profile the physician services associated with the neurology department at a large academic hospital. All 28,048 physician services associated with a neurology department in 1995 were studied. Using billing data, physician work RVUs were assigned to each service and the results analyzed by major services, type of service, and physician workload for physician work RVUs and physician charges. For the average service, mean physician charges were $187 per service while median physician charges were $120. Mean physician work RVUs per service averaged 1.3 RVUs, and the median was 0.94 per service. Of all the services provided in the neurology department, 65 percent are visits and consultations, while medicine services (e.g., nerve conduction studies, needle electromyography, neuropsychological testing, and electroencephalogram) make up 31 percent. All the other services combined represented less than five percent of the services in the department. The top five physicians in the department account for 33 percent of all physician work RVUs in the neurology department. Using the physician work relative values in the MFS provides a unique perspective for analyzing and understanding neurologists' work activities.

Academic Medical Centers↗
PubMed1994

Cleveland Health Quality Choice (CHQC)--an ongoing collaborative, community-based outcomes assessment program.

Cleveland Health Quality Choice (CHQC) is a unique community-based program designed to provide more efficient delivery of healthcare services through routine collection and dissemination of selected patient interventions and outcomes. This effort, coordinated by a consortium of business, hospital, and medical leaders, provides comparative public data on hospital performance. In the ICU, this effort involves collection of Acute Physiology and Chronic Health Evaluation (APACHE) III, as well as severity and prognostic data. To date, results suggest that a higher percentage of patients admitted to the ICU are at low risk of death or adverse outcome when compared with a national benchmark using APACHE III. Risk-adjusted mortality rates are lower and length of stay is shorter than predicted. CHQC demonstrates that cooperative public efforts, undertaken by groups with often divergent interests and using objective risk estimates, can provide useful data for hospital quality improvement activities and market-based health reform efforts.

Data Collection↗
PubMed2003

SYMNET: an optical interconnection network for scalable high-performance symmetric multiprocessors.

We address the primary limitation of the bandwidth to satisfy the demands for address transactions in future cache-coherent symmetric multiprocessors (SMPs). It is widely known that the bus speed and the coherence overhead limit the snoop/address bandwidth needed to broadcast address transactions to all processors. As a solution, we propose a scalable address subnetwork called symmetric multiprocessor network (SYMNET) in which address requests and snoop responses of SMPs are implemented optically. SYMNET not only has the ability to pipeline address requests, but also multiple address requests from different processors can propagate through the address subnetwork simultaneously. This is in contrast with all electrical bus-based SMPs, where only a single request is broadcast on the physical address bus at any given point in time. The simultaneous propagation of multiple address requests in SYMNET increases the available address bandwidth and lowers the latency of the network, but the preservation of cache coherence can no longer be maintained with the usual fast snooping protocols. A modified snooping cache-coherence protocol, coherence in SYMNET (COSYM) is introduced to solve the coherence problem. We evaluated SYMNET with a subset of Splash-2 benchmarks and compared it with the electrical bus-based MOESI (modified, owned, exclusive, shared, invalid) protocol. Our simulation studies have shown a 5-66% improvement in execution time for COSYM as compared with MOESI for various applications. Simulations have also shown that the average latency for a transaction to complete by use of COSYM protocol was 5-78% better than the MOESI protocol. SYMNET can scale up to hundreds of processors while still using fast snooping-based cache-coherence protocols, and additional performance gains may be attained with further improvement in optical device technology.

Journal Article↗