Large-scale deployment of the Global Trigger Tool across a large hospital system: refinements for the characterisation of adverse events to support patient safety learning opportunities.

BACKGROUND: The Institute for Healthcare Improvement encourages use of the Global Trigger Tool to objectively determine and monitor adverse events (AEs). SETTING: Baylor Health Care System (BHCS) is an integrated healthcare delivery system in North Texas. The Global Trigger Tool was applied to BHCS's eight general acute care hospitals, two inpatient cardiovascular hospitals and two rehabilitation/long-term acute care hospitals. STRATEGY: Data were collected from a monthly random sample of charts for each facility for patients discharged between 1 July 2006 and 30 June 2007 by external professional nurse auditors using an MS Access Tool developed for this initiative. In addition to the data elements recommended by Institute for Healthcare Improvement, BHCS developed fields to permit further characterisation of AEs to identify learning opportunities. A structured narrative description of each identified AE facilitated text mining to further characterise AEs. INITIAL FINDINGS: Based on this sample, AE rates were found to be 68.1 per 1000 patient days, or 50.8 per 100 encounters, and 39.8% of admissions were found to have ≥1 AE. Of all AEs identified, 61.2% were hospital-acquired, 10.1% of which were associated with a National Coordinating Council - Medical Error Reporting and Prevention harm score of "H or I" (near death or death). FUTURE DIRECTION: To enhance learning opportunities and guide quality improvement, BHCS collected data-such as preventability and AE source-to characterise the nature of AEs. Data are provided regularly to hospital teams to direct quality initiatives, moving from a general focus on reducing AEs to more specific programmes based on patterns of harm and preventability.

Discerning alumina ball wear from confounding metal transfer artifact.

On dismounting a ceramic femoral ball from its metal trunnion, there is usually a range of gray metallic bands transferred to the trunnion bore inside the ball. This creates an artifact that may compromise detection by weight of the exceedingly low wear rates of ceramic balls. The objective of this study was to compare the weight trending of the metal trunnions and their ceramic balls during conditioning studies. Our hypothesis was that a pretest conditioning protocol would eliminate or greatly reduce the metal transfer artifact. The balls and tapers were placed on a hip simulator under 300-600 load cycles but with no articulation. The balls were then dismounted from the trunnions, and both were cleaned and weighed. This was repeated 6-23 times. We developed a novel hydraulic method for dismounting balls from trunnions that proved to be safe and efficient. There was significant weight loss in the trunnions after the ball removal, but there was no corresponding weight gain in the alumina balls. The weight effect of the metal transfer appeared to have been removed from the balls with our standard cleaning procedures. Therefore, wear rates for alumina balls may be gravimetrically determined without compensating for the metal transfer from trunnion to ball.

The wear pattern in metal-on-metal hip prostheses.

The accumulated data suggest that there is a strong correlation between polyethylene wear and osteolysis, which ultimately leads to prosthetic loosening. Second-generation metal-on-metal prostheses have been introduced, with an eye toward resolving this wear-induced osteolysis problem. The metal particles and ions are biologically active and can affect the cell homeostasis. Thus, defining the wear pattern and ratio of a given metal-on-metal prosthesis system is desirable. An early high-wear or run-in phase followed by a low-wear phase or steady state has been suggested for metal-on-metal hip prostheses. The aim of this study was to define the wear pattern of metal-on-metal bearings. The prosthesis systems were tested in a joint simulator. An early accelerated wear phase transformed to a slower wear phase after 700,000 cycles. The run-in and steady-state wear rates for combined head and liner averaged 2.22 mm(3)/Mc and 1.0 mm(3)/ million cycles, respectively. The metal-on-metal prosthesis featured a biphasic wear trend with the wear ratio in run in being more than twofold higher than the steady-state phase.

Crystal structure of glycogen synthase kinase 3 beta: structural basis for phosphate-primed substrate specificity and autoinhibition.

Glycogen synthase kinase 3 beta (GSK3 beta) plays a key role in insulin and Wnt signaling, phosphorylating downstream targets by default, and becoming inhibited following the extracellular signaling event. The crystal structure of human GSK3 beta shows a catalytically active conformation in the absence of activation-segment phosphorylation, with the sulphonate of a buffer molecule bridging the activation-segment and N-terminal domain in the same way as the phosphate group of the activation-segment phospho-Ser/Thr in other kinases. The location of this oxyanion binding site in the substrate binding cleft indicates direct coupling of P+4 phosphate-primed substrate binding and catalytic activation, explains the ability of GSK3 beta to processively hyperphosphorylate substrates with Ser/Thr pentad-repeats, and suggests a mechanism for autoinhibition in which the phosphorylated N terminus binds as a competitive pseudosubstrate with phospho-Ser 9 occupying the P+4 site.

Microwear phenomena of ultrahigh molecular weight polyethylene cups and debris morphology related to gamma radiation dose in simulator study.

Ultrahigh molecular weight polyethylene (PE) cups with 0, 2.5, 50, 100, and 150 Mrad radiation treatments were run in a hip simulator for comparison of the microwear phenomena on the cup surfaces with the corresponding debris morphology. In general, the size and frequency of the PE surface fibrils and the size of the retrieved PE debris decreased with increasing radiation dose. The fibril size and shape on the cup surfaces were well correlated with the radiation dose. The fibrillar shape and size were found to be proportional to the square root of the radiation dose. However, the trend for size and shape factors of the wear debris related to the radiation dose was weak at best. Thus, the morphology of the PE fibrils on the cup surfaces was more sensitive to variations in the radiation dose than the actual wear debris. The wear response appeared to be a three-step process, which was dependent on the formation of surface nodules or ripples, the teasing out of surface fibrils, and the toughness of the PE matrix in releasing a wear fibril to form a debris particle. The tougher PE became with increasing radiation dose, the harder it was for the PE fibrils to break out into wear particles.

Effects of A-P translation and rotation on the wear of UHMWPE in a total knee joint simulator.

We developed a three-channel total knee joint simulator and studied the effect of tibial anterior-posterior translation and internal/external rotation on the wear of polyethylene tibial inserts in total knee replacements (Anatomic Graduated Component knees). The wear rate was the lowest in experiment (Exp.) 1, without translation and rotation [1.74 mg/million (mg/Mc) cycles]. In Exp. 2, with +/-5 degrees tibial rotation added, the wear rate increased to 10.6 mg/Mc. In Exp. 3, with rotation and -12 mm tibial translation added, the wear rate was 15.1 mg/Mc, whereas in Exp. 4, with rotation and +12 mm tibial translation, the wear rate was 18.7 mg/Mc. Internal/external rotation and anterior-posterior translation added a 6- to 11-fold increase in the wear rates of tibial knee inserts. The shapes of the tibial wear tracks were rectangular and the area of the track increased when rotation and translation were added.

Wear of ultra-high molecular weight polyethylene and polytetrafluoroethylene in a hip simulator: a dose-response study of protein concentration.

Charnley's laboratory wear studies of non-gamma sterilized polytetrafluoroethylene (PTFE) and polyethylene (PE) found that the PTFE to PE wear-rate ratio of 250:1 was much higher than the in-vivo wear ratio of 20:1. Tests of PTFE and PE in our laboratory showed a wear ratio of 150:1, using bovine serum as the lubricant and 190:1 with water as the lubricant. Our hypothesis was that the wear-rates of PTFE and PE cup materials were related to the concentration of protein in the serum. We studied the wear behavior of PTFE and PE cups in varied protein concentrations, using 4 femoral head sizes to validate the clinical range reported by Charnley. The PTFE wear-rates increased with increasing protein concentration and conversely, PE wear-rates decreased with increasing protein concentration. This inverse relationship made it possible to bring the wear ratio closer to the desired clinical wear ratio. We found that the clinically relevant PTFE/PE wear ratio corresponded to 3-10 mg/mL of protein in bovine serum.

Ultra-low wear rates for rigid-on-rigid bearings in total hip replacements.

With the increased clinical interest in metal-on-metal and ceramic-on-ceramic total-hip replacements (THRs), the objective of this hip simulator study was to identify the relative wear ranking of three bearing systems, namely CoCr-polyethylene (M-PE), CoCr-CoCr (M-M) and ceramic-on-ceramic (C-C). Volumetric wear rates were used as the method of comparison. The seven THR groupings included one M-PE study, two M-M studies and four C-C studies. Special emphasis was given to defining the 'run-in' phase of accelerated wear that rigid-on-rigid bearings generally exhibit. The hypothesis was that characterization of the run-in and steady state wear phases would clarify not only the tribological performance in vitro but also help correlate these in vitro wear rates with the 'average' wear rates measured on retrieved implants. The implant systems were studied on multichannel hip simulators using the Paul gait cycle and bovine serum as the lubricant. With 28 mm CoCr heads, the PE (2.5 Mrad/N2) wear rates averaged 13 mm3/10(6) cycles duration. This was considered a low value compared with the clinical model of 74 mm3/year (for 28 mm heads). Our later studies established that this low laboratory value was a consequence of the serum parameters then in use. The mating CoCr heads (with PE cups) wore at the steady state rate of 0.028 mm3/10(6) cycles. The concurrently run Metasul M-M THRs wore at the steady state rate of 0.119 mm3/10(6) cycles with high-protein serum. In the second Metasul M-M study with low-protein serum, the THR run-in rate was 2.681 mm3/10(6) cycles and steady state was 0.977 mm3/10(6) cycles. At 10 years, these data would predict a 70-fold reduction in M-M wear debris compared with the clinical PE wear model. All M-M implants exhibited biphasic wear trends, with the transition point at 0.5 x 10(6) cycles between run-in and steady state phases, the latter averaging a 3-fold decrease in wear rate. White surface coatings on implants (coming from the serum solution) were a confounding factor but did not obscure the two orders of magnitude wear performance improvement for CoCr over PE cups. The liners in the alumina head-alumina cup combination wore at the steady state rate of 0.004 mm3/10(6) cycles over 14 x 10(6) cycles duration (high-protein serum). The zirconia head-alumina cup THR combination wore at 0.174 and 0.014 mm3/10(6) cycles for run-in and steady state rates respectively (low-protein serum). The zirconia head and cup THR combination wore slightly higher initially with 0.342 and 0.013 mm3/10(6) cycles for run-in and steady state rates respectively. Other wear studies have generally predicted catastrophic wear for such zirconia-ceramic combinations. It was noted that the zirconia wear trends were frequently masked by the effects of tenacious white surface coatings. It was possible that these coatings protected the zirconia surfaces somewhat in this simulator study. The experimental ceramic Crystaloy THR had the highest ceramic run-in wear at 0.681 mm3/10(6) cycles and typical 0.016 mm3/10(6) cycles for steady state. Since these implants represented the first Crystaloy THR sets made, it was likely that the surface conditions of this high-strength ceramic could be improved in the future. Overall, the ceramic THRs demonstrated three orders of magnitude wear performance improvement over PE cups. With zirconia implants, while the cup wear was sometimes measurable, head wear was seldom discernible. Therefore, we have to be cautious in interpreting such zirconia wear data. Identifying the run-in and steady state wear rates was a valuable step in processing the ceramic wear data and assessing its reliability. Thus, the M-M and C-C THRs have demonstrated two to three orders of reduction in volumetric wear in the laboratory compared with the PE wear standard, which helps to explain the excellent wear performance and minimal osteolysis seen with such implants at retrieval operations.

Metal-on-metal bearing in hip prosthesis generates 100-fold less wear debris than metal-on-polyethylene.

Aseptic loosening due to osteolysis in total hip replacement has been related to wear debris released from prosthetic components. Retrospective longterm observations of patients with the metal-on-metal prosthesis has shown long-term survivorship and good mechanical performance. Thus, the new and modified metal-on-metal prosthesis has been introduced on the market. Historical clinical data from the 1st generation metal-on-metal hip prosthesis may not be relevant for the 2nd generation of metal-on-metal hip prosthesis. Therefore, preclinical testing of the prosthesis must be conducted before clinical evaluation. We assessed the tribological performance of the metal-on-metal prosthesis versus the metal-on-polyethylene prosthesis introduced on the market as Metasul and Protasul, respectively. In a 12-channel joint simulator, 6 metal-on-metal bearing and 3 metal on polyethylene prostheses were tested, with the same number of corresponding soak controls. The wear was assessed gravimetrically. The "steady-state" wear-rates from the metal-on-metal prosthesis were almost 100 times less than that from the metal-on-polyethylene prosthesis. The tribological wear performance of the metal-on-metal hip prosthetic system is promising.

The fallacy of evaluating biomaterial wear-rates with water as lubricant: a hip simulator study of alumina-PTFE nd CoCr-PTFE combinations.

Controversy surrounds wear data from hip-simulator studies, whether from the choice of lubricants or other parameters such as the particular biomaterial combinations used, and whether any such interactions could bias the resulting wear predictions. To investigate these phenomena, we studied the wear performance of CoCr and alumina femoral heads, in water and serum-based lubricants, using as our standard the polytetrafluoroethylene wear data derived clinically by Charnley. To model Charnley's clinical experience, PTFE acetabular cups were used in sets of three each with each size of femoral head for 22.25, 28, and 42-mm diameters in a nine-channel hip simulator. From the serum-based tests, the CoCr-PTFE wear data were consistently linear with duration of test, exhibited very large wear rates of 3,000-8,400 mm3/10(6), cycles had a precision within +/- 4% for each set of three cups, and copious amounts of small particulate were clearly seen circulating. The wear data clearly demonstrated Charnley's thesis that volume of wear increased with regard to size of femoral head. From the water-based tests, the CoCr-PTFE wear data were nonlinear with duration of test, had much reduced wear rates compared to the serum tests, lost the clinical relationship with ball size, and precision deteriorated to +/- 27% for each set. The wear debris appeared as 1-2 cm long ribbons which floated to the surface. For the alumina-PTFE combination in serum, the wear data appeared identical in performance to the CoCr-PTFE data in serum. Thus, the PTFE wear rates were not sensitive to the choice of femoral-head material. The most surprising outcome in this study was the zero-wear performance of the ceramic-PTFE combination in water. This contrasted remarkably with the large wear rates established for the same combinations run in serum. The zero-wear performance of the ceramic-PTFE combination in water was unexpected, but a similar phenomenon was noted in published simulator tests of ceramic-UHMWPE run in water. It now seems likely that such data may reflect the capricious behavior of water lubrication rather than any other variables under evaluation. The water-based experiments clearly favored the ceramic's superior tribological performance and placed metal bearings at a decided disadvantage. Therefore, for an in vitro simulation of materials wear-ranking of clinical relevance, it may be advisable to use a serum-based lubricant.

Charnley wear model for validation of hip simulators--ball diameter versus polytetrafluoroethylene and polyethylene wear.

Wear rates of polytetrafluoroethylene (PTFE) and polyethylene cups were compared in 9-channel and 12-channel simulators, using serum lubrication and gravimetric techniques for wear assessment. Cobalt-chromium (CoCr) and alumina ceramic femoral heads in 22-42 mm diameter range were used to validate simulator wear rates against clinical data. This was also the first study of three femoral head sizes evaluated concurrently in a simulator (with three replicate specimens) and also the first report in which any wear experiments were repeated. Fluid absorption artefacts were within +/-1 per cent of wear magnitude for PTFE and +/-8 per cent for polyethylene and were corrected for. Wear rates were linear as a function of test duration. Precision within each set of three cups was within +/-6 per cent. The wear rates from experiments repeated over 15 months were reproducible to within +/-24 per cent. However, the magnitudes of the simulator wear rates were not clinically accurate, the PTFE wear rates (2843 mm3/10(6) cycles; 22 mm diameter) were over three times higher than in vivo, the polyethylene 30 to 50 per cent on the low side (23 mm3/10(6) cycles; 22 mm diameter). Volumetric wear rate increased with respect to size of femoral head and a linearly increasing relationship of 7 8 per cent/mm was evident with respect to femoral head diameter for both PTFE and polyethylene. These data compared well with the clinical data.

Water and bovine serum lubrication compared in simulator PTFE/CoCr wear model.

Controversy surrounds wear data from laboratory hip simulator studies, whether derived from water-based or serum-based studies or whether a major design parameter such as the size of the femoral head has an effect on the volume of wear particulate released. To investigate these relationships, we studied cup wear in water- and serum-based lubricants using as our standard the polytetrafluoroethylene (PTFE) data derived by Charnley. To model Charnley's clinical experience, PTFE acetabular cups were used in sets of three each of four sizes of CoCr femoral heads: 22.25-, 28-, 32-, and 42-mm diameters. Six criteria were used to evaluate the performance of the lubricants against clinical accuracy and scientific methods. The PTFE wear data from the serum-based tests was consistently linear with the duration of the test, exhibited a precision within +/-3% about the average for each set of three cups, and copious amounts of wear debris were clearly seen circulating and settling to the bottom of the wear chambers. The wear data clearly demonstrated Charnley's thesis that volume of wear increases with regard to the size of the femoral head in a linear manner. This increase was considered satisfactory at 9%/ mm. However, in terms of clinical accuracy, the simulator wear rates averaged 3 to 4 times greater than the comparable clinical data for wear magnitude. Thus, the serum-based tests satisfied three of the six criteria used. The PTFE wear data from the water-based tests was generally nonlinear, continually increasing with test duration. These wear trends were examined in three discrete phases to estimate the changing wear rates. By the end of the tests, the wear rates had increased from 1.3 to 3.9 times, with the 42-mm heads showing the greatest change. The resulting precision was never better than +/-26% and deteriorated to +/-70%. In terms of clinical accuracy, the water-based wear rates varied from 2 to 7 times less than the Charnley PTFE wear magnitudes, averaging 4 times less. The water-based data did not satisfactorily model the relationship between increased wear with increased head size. Minimal PTFE wear debris was observed, and what did emerge after thousands of wear cycles appeared as streamers up to 30 mm long and up to 5 mm wide. When these detached, they floated up to the surface where they could be separated into smaller particulates. A similar phenomenon was noted for polyethylene wear tests conducted with water lubrication. Thus the water-based tests satisfied none of the six validation criteria evaluated. These data raise serious doubts as to the validity of testing implant and material combinations in water as a predictor of clinical performance. Bovine serum was not totally satisfactory, but the wear data did model some of the important clinical characteristics of hip joint behavior.

Characterization of a promoter for gamma-glutamyl transpeptidase activated in rat liver in response to aflatoxin B1 and ethoxyquin.

gamma-Glutamyl transpeptidase (GGT) is normally absent from adult rat hepatocytes but is induced by a range of xenobiotics, including carcinogens and chemoprotective agents. As many as six mRNA species for this enzyme have been described in both rat and mouse, with various degrees of tissue specificity. These originate from one gene and have separate promoters within alternative 5' untranslated sequences. By using a cDNA-derived sequence specific for GGT mRNA III to screen a rat genomic library, a clone that contains the promoter region for this mRNA was isolated and characterized. The transcriptional start site lay some 3.5 kb upstream from that already characterized for mRNA II in rat kidney. Luciferase activity was obtained after transfection of rat hepatoma-derived cell lines with constructs containing the putative promoter III fused to a luc reporter. Although this promoter lacks a TATA box, a sequence close to the start site that binds the transcription factor TFIID in vitro was identified. By using PCR techniques, mRNA III (homologous to both mouse III and IV) and an mRNA (IV) with homology to VI in mouse were found in ethoxyquin- and aflatoxin B1-treated rat liver and kidney as well as in a hepatoma-derived cell line. No evidence was found for a product homologous to mRNA from promoter V described in the mouse.

MM 45289, a potent glycopeptide antibiotic which interacts weakly with diacetyl-L-lysyl-D-alanyl-D-alanine.

MM 45289 (A82846A, eremomycin), a glycopeptide antibiotic of the vancomycin type, was confirmed to have improved antibacterial activity over vancomycin. However its affinity (Ka) for the target site peptide mimetic diacetyl-L-lysyl-D-alanyl-D-alanine (DALAA) was 23-fold lower. Concentrations of DALAA required to reverse the antibacterial activity of MM 45289 were in the order of 10 to 50-fold higher than for vancomycin. These results have implications for both mode of action studies and mechanism-based screening strategies for this class of antibiotic.

The role of the head nurse in primary nursing.

Primary nursing brings about changing roles, responsibilities, and communication patterns for all members of the health care team. The head nurse, as she introduces new staff to primary nursing and its day-to-day applications, is in an ideal position to generate enthusiasm for the goals of the concept. In attempting to implement this new care pattern, she must continually promote the philosophy behind it by her support and recognition of its principles. In the long run, it is the positive attitude and high motivation of the head nurse that will determine the success or failure of the program wherever it is introduced.