Correlation between oral fluid and blood THC concentration: A systematic review and discussion of policy implications.

Cannabis is the second most commonly used impairing substance by drivers, after alcohol. As more countries legalize cannabis, there is concern that cannabis-impaired driving will increase. In many countries, police use roadside devices to test for oral fluid THC (the primary psychotropic component in cannabis) to identify drivers who used cannabis; including in countries with non-zero per se limits for THC in blood. This practice is questioned as previous research demonstrates a poor correlation between oral fluid and blood THC concentrations at the individual level. We conducted a meta-analysis to identify all research that compared oral fluid with blood THC levels. We obtained individual-level data from study authors and analyzed pooled individual-level data to calculate sensitivity and specificity of oral fluid THC (at various cut-off values) to detect blood THC above different concentration limits. Finally, we explored practical implications of using oral fluid THC in an enforcement context. Our review found THC concentrations measured in over 18,000 paired samples of oral fluid and blood. We found a good correlation between the presence of THC in oral fluid and presence of THC in blood (sensitivity = 71.2%, specificity = 97.7%). However oral fluid THC, at commonly used cut-off values, is less sensitive and less specific when used as a biomarker to detect people with blood THC concentrations above commonly used per se limits (such as 5 ng/mL). As such, there will be a large number of "false positive" tests if oral fluid THC testing were used as a biomarker for "illegal" THC concentrations in randomly selected drivers. We argue that the adverse implications of false positive oral fluid THC tests in this context outweigh the possible road safety benefits and we recommend against oral fluid THC screening in randomly selected drivers in countries with non-zero per se limits for blood THC. In contrast, oral fluid THC tests appear to be useful for investigating "high-risk" drivers who come to police attention because of evidence of impairment.

Electronic antibiotic stewardship--reduced consumption of broad-spectrum antibiotics using a computerized antimicrobial approval system in a hospital setting.

OBJECTIVES: Antibiotic stewardship is important, but the ideal strategy for providing stewardship in a hospital setting is unknown. A practical, sustainable and transferable strategy is needed. This study evaluates the impact of a novel computerized antimicrobial approval system on antibiotic-prescribing behaviour in a hospital. Effects on drug consumption, antibiotic resistance patterns of local bacteria and patient outcomes were monitored. METHODS: The study was conducted at a tertiary referral teaching hospital in Melbourne, Australia. The system was deployed in January 2005 and guided the use of 28 restricted antimicrobials. Data were collected over 7 years: 5 years before and 2 years after deployment. Uptake of the system was evaluated using an in-built audit trail. Drug utilization was prospectively monitored using pharmacy data (as defined daily doses per 1000 bed-days) and analysed via time-series analysis with segmental linear regression. Antibiograms of local bacteria were prospectively evaluated. In-hospital mortality and length of stay for patients with Gram-negative bacteraemia were also reported. RESULTS: Between 250 and 300 approvals were registered per month during 2006. The gradients in the use of third- and fourth-generation cephalosporins (+0.52, -0.05, -0.39; P < 0.01), glycopeptides (+0.27, -0.53; P = 0.09), carbapenems (+0.12, -0.24; P = 0.21), aminoglycosides (+0.15, -0.27; P < 0.01) and quinolones (+0.76, +0.11; P = 0.08) all fell after deployment, while extended-spectrum penicillin use increased. Trends in increased susceptibility of Staphylococcus aureus to methicillin and improved susceptibility of Pseudomonas spp. to many antibiotics were observed. No increase in adverse outcomes for patients with Gram-negative bacteraemia was observed. CONCLUSIONS: The system was successfully adopted and significant changes in antimicrobial usage were demonstrated.

Non-equilibrium behavior of sticky colloidal particles: beads, clusters and gels.

To understand the non-equilibrium behavior of colloidal particles with short-range attraction, we studied salt-induced aggregation of lysozyme. Optical microscopy revealed four regimes: bicontinuous texture, 'beads', large aggregates, and transient gelation. The interaction of a metastable liquid-liquid binodal and an ergodic to non-ergodic transition boundary inside the equilibrium crystallization region can explain our findings.

Adaptive bolus-based set-point regulation of hyperglycemia in critical care.

Critically ill patients are often hyperglycemic and extremely diverse in their dynamics. Consequently, fixed protocols and sliding scales can result in error and poor control. A two-compartment glucose-insulin system model that accounts for time-varying insulin sensitivity and endogenous glucose removal, along with two different saturation kinetics is developed and verified in proof-of-concept clinical trials for adaptive control of hyperglycemia. The adaptive control algorithm monitors the physiological status of a critically ill patient, allowing real-time tight glycemic regulation. The bolus-based insulin administration approach is shown to result in safe, targeted stepwise glycemic reduction for three critically ill patients.

MRI measurement of wall shear stress vectors in bifurcation models and comparison with CFD predictions.

Steady fluid flow was studied in a simple bifurcation model and in a physiologically realistic model of the human carotid bifurcation. Wall shear stress (WSS) vectors were calculated from phase-contrast (PC) magnetic resonance imaging (MRI) measurements of the velocity field. Velocity measurements in the inflow regions were also used as boundary conditions for computational fluid dynamics (CFD) calculations of WSS, which were compared with those derived from MRI alone. In regions of well-behaved flow, MRI and CFD estimates of WSS were in good general agreement. In regions of disturbed flow, for example near the bifurcation, the quality of the MRI measurements was sufficient for reliable calculation of WSS vectors when a sensitive surface coil was used. The combination of MRI and CFD would seem to be a powerful technique for the investigation of flow phenomena.

Quantitative analysis of PC MRI velocity maps: pulsatile flow in cylindrical vessels.

The accuracy of MR phase contrast (PC) velocity mapping, and the subsequent derivation of wall shear stress (WSS) values, has been quantitatively assessed. Using a retrospectively gated PC gradient-echo technique, the temporal-spatial velocity fields were measured for pulsatile flow in a rigid cylindrical vessel. The experimental data were compared with values derived from the Womersley solution of the Navier-Stokes equations. For a sinusoidal waveform, the overall root-mean-square (rms) difference between the measured and analytical velocities corresponded to 13% of the peak fluid velocity. The WSS derived from the data displayed a 14% rms difference with the analytical model. As an example of a more complicated flow, a triangular saw-tooth waveform was deconstructed into its Fourier components. Velocity maps and the WSS were calculated by the superposition of the individual solutions, weighted by the Fourier series coefficient, for each harmonic. The velocity and experimentally derived WSS agreed with the analytical results (4% and 12% rms difference, respectively). Evaluation of the analytical models allowed an estimate of the inherent accuracy in the measurement of velocity maps and WSS values.

Physiological flow waveform in a rigid elliptical vessel.

A procedure to model the velocity and wall shear stress for a physiological flow in a non-cylindrical vessel is presented. The work describes how a vessel with an elliptical cross section may be used to represent flow in compressed or partially occluded arteries and veins. The procedure was applied to produce a simulation of a physiological flow in a straight rigid vessel with a slightly elliptical cross section (ellipticity, epsilon = 0.8). Fourier analysis was performed on a physiological flow waveform. Flow in the common carotid artery was satisfactorily represented (Pearson correlation coefficient, r > 95%) with a series of five harmonic terms. Expressions involving a linear combination of ordinary and modified Mathieu functions were used to describe the velocity and wall shear stress for each harmonic. An outline of the procedure, and the expressions, which were used to compute the characteristic Mathieu numbers and coefficients is illustrated with their behaviour at the fundamental and Nyquist frequencies. Superposition of the individual contributions to the velocity and wall shear stress allowed the calculation of the overall properties of the flow.

Flow in elliptical vessels calculated for a physiological waveform.

Understanding the nature of pulsatile flow is an important issue in haemodynamics, especially the initiation and progression of vascular disease. The geometry of a non-circular vessel was idealised to an elliptical cross-section, and the dynamic properties of the flow were calculated for a physiological waveform. The Fourier harmonics for a common carotid waveform were determined, and the velocity profile and wall shear stress were calculated from the superposition of the individual contributions from each harmonic. The effects of ellipticity on the flow pattern were found to be significant. The velocity profile along the major axis of the elliptical cross-section developed a flattened peak, which widened as the vessel became more elliptical. Wall shear stress demonstrated an angular dependence in elliptical vessels, where the point of minimum shear stress was located at the end of the major axis. Comparison with a cylindrical vessel demonstrated a 3% decrease in peak wall shear stress (tau = 2.96, N.m(-2)) at the end of the major axis, and 10% in the mean wall shear stress (tau = 0.44 N. m(-2)), for an elliptical vessel (epsilon = 0.8). The temporal average wall shear stress, which has been associated with atherogenic sites, also displayed a minimum at the end of the major axis that decreased with more elliptical cross-sections.

Reduction of electromagnetic interference from a commercially available MR-compatible flow simulator.

Electromagnetic interference (EMI) associated with the electronics of a commercially available computer controlled flow simulator substantially decreases the quality of the MR image. The effect of a custom-built radiofrequency shield on its spectral emission, and the corresponding signal-to-noise ratio measured for the image of a standard phantom, were determined. The results demonstrate the elimination of EMI and a significant improvement in image quality.

Vancomycin and teicoplanin use in Victorian hospitals. The Victorian Drug Usage Evaluation Group.

OBJECTIVE: To determine patterns of prescribing of glycopeptide antibiotics (vancomycin and teicoplanin) in Victorian hospitals and identify areas for targeted intervention. DESIGN: A concurrent, observational, multisite evaluation of drug use. SETTING: Thirty-five Victorian hospitals, 1-14 September 1997. STUDY POPULATION: Patients commencing a glycopeptide antibiotic course. MAIN OUTCOME MEASURES: Rate of glycopeptide antibiotic use; indications; duration of use; main hospitals using glycopeptide antibiotics. RESULTS: 293 patients (269 adults and 24 neonates) commenced on 302 glycopeptide antibiotic courses: 296 intravenous (i.v.) vancomycin courses and three each of oral vancomycin and parenteral teicoplanin. The overall rate of use was 10.3 courses per 1000 inpatient separations. Of 271 i.v. vancomycin courses for adults, 176 (65%) were for treatment--120 empirically. The median duration of treatment courses was 4.7 days (interquartile range, 2.0-8.2 days). A flucloxacillin-resistant organism was confirmed for 44% of treatment courses. Ninety-five i.v. vancomycin courses were for prophylaxis, including for cardiac (54%) and vascular surgery (21%); 82% of prophylactic courses were administered for less than 24 hours. Of all the glycopeptide antibiotic courses, 69% were administered at five major metropolitan hospitals. CONCLUSIONS: Glycopeptide antibiotic use in Victoria is concentrated in the major metropolitan hospitals. Prolonged durations of vancomycin therapy, including for surgical prophylaxis and empirical therapy not subsequently confirmed by microbiology findings, would be suitable targets for interventional strategies.

A decade of antibiotic use in a teaching hospital.

A survey of the antibiotic agents that are being prescribed for inpatients in St Vincent's Hospital, Melbourne, has been carried out annually since 1976. This article describes the patterns of prescribing that were observed between 1976 and 1986 with special emphasis on the results since 1980, which was the year before the adoption of the hospital's antibiotic policy. The proportion of hospital inpatients who received antibiotic therapy as determined by prevalence studies varied from 25%-36%. Since the introduction of the antibiotic policy, 61%-70% of antibiotic courses were administered for the treatment of infection and 30%-39% of the courses were administered as prophylaxis. Amoxycillin and ampicillin were prescribed most frequently, followed by the cephalosporin agents and the other penicillins. In the area of the empirical treatment of infection, compliance with the hospital antibiotic policy improved and reached 76% of courses in 1986. In the area of prophylaxis, compliance improved a little and stood at 21% of courses in 1986.

Use of prophylactic antibiotics in surgery.

A prospective survey of 352 surgical patients revealed that 52% (183 patients) were given antibiotic drugs perioperatively, (32% (111 patients) for prophylaxis and 20% (72 patients) for treatment of established infection). Prophylaxis was not reasonably indicated in only 24 patients, but there was little standardization of drug, dose, timing or duration of courses. The mean duration of prophylactic courses was six days; less than half began before operation. Thirty-two patients (11% of 283) developed an infection after operation; the incidence in patients with and without antibiotic prophylaxis was 17% (19/111) and 8% (13/172) respectively, but the former were, in general, higher risk subjects. Antibiotic use determines the emergence of resistant microorganisms and efficacy of prophylaxis is in the main unproven. Clearly, a carefully considered policy on antibiotic prophylaxis within an institution is a logical necessity yet to be realized.

Surveying antibiotic use in a general teaching hospital.

Four antibiotic surveys were carried out in a teaching hospital within the framework of an intensive drug monitoring system during 1976-1978. The proportion of inpatients receiving antibiotic therapy at any one time varied from 25% to 32%. Penicillin, ampicillin and co-trimoxazole were the most frequently used antibiotics. The use of cloxacillin increased over the survey period. Approximately 85% of presumed infections were treated before the results of microbiological tests became available. Between 29% and 39% of all courses of antibiotics were given for prophylaxis of infection. Between 13% and 30% of patients received more than one antibiotic concurrently; indication for such combined use appeared inadequate in 31% to 80% of courses.

Incidence of antibiotic-related diarrhoea and pseudomembranous colitis: a prospective study of lincomycin, clindamycin and ampicillin.

An existing intensive drug monitoring system was used to study the occurrence of pseudomembranous colitis and diarrhoea in 100 patients treated with lincomycin and clindamycin. In order to give perspective to the results an equal number of matched patients treated with ampicillin were also studied. The incidences of diarrhoea in both groups were similar (11% in the lincomycin-clindamycin group and 8% in the ampicillin group). One patient developed pseudomembranous colitis associated with two prolonged courses of lincomycin therapy. The results suggest that the risks associated with the use of lincomycin are acceptable if the drug is given for the approved specific indications.