Random breath testing in Queensland and Western Australia: Examination of how the random breath testing rate influences alcohol related traffic crash rates

In this paper we explore the relationship between monthly random breath testing (RBT) rates (per 1000 licensed drivers) and alcohol-related traffic crash (ARTC) rates over time, across two Australian states: Queensland and Western Australia. We analyse the RBT, ARTC and licensed driver rates across 12 years; however, due to administrative restrictions, we model ARTC rates against RBT rates for the period July 2004 to June 2009.     

Patient safety and computerized medication ordering at Brigham and Women's Hospital

BACKGROUND: Medications are important therapeutic tools in health care, yet creating safe medication processes is challenging for many reasons. Computerized physician order entry (CPOE), one important way that technology can be used to improve the medication process, has been in place at Brigham and Women's Hospital (BWH; Boston) since 1993. CPOE AT BWH: The CPOE application, designed and developed internally by the BWH information systems team, allows physicians and other clinicians to enter all patient orders into the computer. Physicians enter 85% of orders, with the remainder entered electronically by other clinicians. CPOE AND SAFE MEDICATION USE: The CPOE application at BWH includes several features designed to improve medication safety--structural features (for example, required fields, use of pick lists), enhanced workflow features (order sets, standard scales for insulin and potassium), alerts and reminders (drug-drug and drug-allergy interaction checking), and adjunct features (the pharmacy system, access to online reference information). RESULTS AT BWH: Studies of the impact of CPOE on physician decision making and patient safety at BWH include assessment of CPOE's impact on the serious medication error and the preventable adverse drug event rate, the impact of computer guidelines on the use of vancomycin, the impact of guidelines on the use of heparin in patients at bed rest, and the impact of dosing suggestions on excessive dosing. CONCLUSION: CPOE and several forms of clinical decision support targeted at increasing patient safety have substantially decreased the frequency of serious medication errors and have had an even bigger impact on the overall medication error rate.     

A decision-directed approach for prioritizing research into the impact of nanomaterials on the environment and human health

The emergence of nanotechnology has coincided with an increased recognition of the need for new approaches to understand and manage the impact of emerging technologies on the environment and human health. Important elements in these new approaches include life-cycle thinking, public participation and adaptive management of the risks associated with emerging technologies and new materials. However, there is a clear need to develop a framework for linking research on the risks associated with nanotechnology to the decision-making needs of manufacturers, regulators, consumers and other stakeholder groups. Given the very high uncertainties associated with nanomaterials and their impact on the environment and human health, research resources should be directed towards creating the knowledge that is most meaningful to these groups. Here, we present a model (based on multi-criteria decision analysis and a value of information approach) for prioritizing research strategies in a way that is responsive to the recommendations of recent reports on the management of the risk and impact of nanomaterials on the environment and human health.     

A systems engineering approach to validation of a pulmonary physiology simulator for clinical applications

Physiological simulators which are intended for use in clinical environments face harsh expectations from medical practitioners; they must cope with significant levels of uncertainty arising from non-measurable parameters, population heterogeneity and disease heterogeneity, and their validation must provide watertight proof of their applicability and reliability in the clinical arena. This paper describes a systems engineering framework for the validation of an in silico simulation model of pulmonary physiology. We combine explicit modelling of uncertainty/variability with advanced global optimization methods to demonstrate that the model predictions never deviate from physiologically plausible values for realistic levels of parametric uncertainty. The simulation model considered here has been designed to represent a dynamic in vivo cardiopulmonary state iterating through a mass-conserving set of equations based on established physiological principles and has been developed for a direct clinical application in an intensive-care environment. The approach to uncertainty modelling is adapted from the current best practice in the field of systems and control engineering, and a range of advanced optimization methods are employed to check the robustness of the model, including sequential quadratic programming, mesh-adaptive direct search and genetic algorithms. An overview of these methods and a comparison of their reliability and computational efficiency in comparison to statistical approaches such as Monte Carlo simulation are provided. The results of our study indicate that the simulator provides robust predictions of arterial gas pressures for all realistic ranges of model parameters, and also demonstrate the general applicability of the proposed approach to model validation for physiological simulation.     

Chromosome 9p deletions in invasive and noninvasive nonfunctional pituitary adenomas: the deleted region involves markers outside of the MTS1 and MTS2 genes

We have screened 57 cases of primary, nonfunctional, pituitary adenomas for loss of heterozygosity of markers on chromosome 9p. Using a panel of 11 microsatellite markers, we found hemizygous deletion with at least one of the markers in 18 tumors (31.5%). The frequency of loss was similar in both noninvasive (8 of 26; 31%) and invasive tumors (10 of 31; 32%), suggesting that loss on this chromosome might be an early event in pituitary tumorigenesis. Two discrete areas of loss were punctuated by a region of retention of heterozygosity between the markers D9S171 and IFNA, indicative of homozygous deletion. However, multiplex PCR analysis (MTS1 and MTS2) and the presence of a 3' untranslated region polymorphism in MTS1 suggested that neither of these tumor suppressor genes was homozygously deleted. In 6 of the 18 tumors showing LOH, sufficient DNA was also available for Southern blot analysis and, in all cases, showed retention of MTS1. Cell mixing experiments of tumor cell DNA homozygously deleted for MTS1 with DNA in which neither copy of the gene was deleted only gave rise to a signal at contamination levels greater than 30% and could discriminate homozygous and hemizygous loss. These studies support the recent findings that mechanisms other than hemi- and homozygous deletion are most likely responsible for the loss of MTS1 gene product in pituitary tumors (M. Woloschak et al., Cancer Res., 56: 2493-2486, 1996.). These data show that losses on either side of 9p21-22, both or either of which may be deleted, are involved in pituitary tumorigenesis and provide evidence for distinct suppressor gene loci, in addition to MTS1, on chromosome 9p.     

Onychomycosis. Baseline results of an observational study

The investigators present an analysis of baseline quality-of-life and patient-management approaches from an observational study of 150 patients being treated by podiatric physicians and dermatologists for onychomycosis. The majority (73%) made the initial office visit specifically because of their onychomycosis. Both men and women indicated that they had substantial physical discomfort as well as concerns related to appearance. Women reported significantly more problems than did men as a result of their onychomycosis. Physicians reported that 54% of patients suffered from toenail discomfort, 36% had pain while walking, 40% reported that their condition limited wearing of shoes, and 67% were embarrassed by the condition. The results of this study suggest that the treatment approach of podiatric physicians is more likely to address the palliative concerns of patients with onychomycosis, while the approach of dermatologists is more likely to attempt a definitive cure.     

Pharmacokinetics and safety of tobramycin after once-daily administration in patients with cystic fibrosis

STUDY OBJECTIVE: Tobramycin is commonly used to treat respiratory tract infections in patients with cystic fibrosis. We designed a study to determine the pharmacokinetics and safety of once-daily dosing of tobramycin in this population. DESIGN: Multiple blood samples were collected from each patient, and serum concentrations of tobramycin were determined by a fluorescence polarization immunoassay. Blood urea nitrogen and serum creatinine levels were measured every 2 to 3 days, and audiometric evaluations were performed at the start and end of therapy. MEASUREMENTS AND RESULTS: Eighteen patients (mean age, 24.6 years) received tobramycin at doses of 7 to 15 mg/kg/d as a single-dose infusion over 20 min. The maximum serum concentration of tobramycin ranged from 40.1 to 64.6 mg/L. A mean dose of 11.9+/-1.9 mg/kg was needed to obtain a theoretical mean peak serum concentration of 42.4+/-4.5 mg/L. The mean total body clearance, apparent volume of distribution, and elimination half-life was 1.7+/-0.4 mL/min/kg, 0.27+/-0.06 L/kg, and 1.8+/-0.3 h, respectively. The period of time that the serum concentration exceeded eight times the theoretical minimum inhibitory concentration of 1 mg/L ranged from 2.1 to 4.4 h, which was nearly five times longer compared with the use of divided daily doses in the same patients during previous hospitalizations. No nephrotoxicity, ototoxicity, or adverse effects occurred in any patient. CONCLUSION: Based on our data, tobramycin may be used safely in once-daily doses to treat exacerbations of respiratory tract infections in patients with cystic fibrosis.     

Transgenic models of Huntington's disease

CAG/polyglutamine expansion has been shown to form the molecular basis of an increasing number of inherited neurodegenerative diseases. The mutation is likely to act by a dominant gain of function but the mechanism by which it leads to neuronal dysfunction and cell death is unknown. The proteins harbouring these polyglutamine tracts are unrelated and without exception are widely expressed with extensively overlapping expression patterns. The factors governing the cell specific nature of the neurodegeneration have yet to be understood. Upon a certain size threshold, expanded CAG repeats become unstable on transmission and a modest degree of somatic mosaicism is apparent. Similarly, the molecular basis of the instability and its tissue specificity has yet to be unravelled. Recent reports describing the first mouse models of CAG/polyglutamine disorders indicate that it will be possible to model both the pathogenic mechanism and the CAG repeat instability in the mouse. This has great potential and promise for uncovering the molecular basis of these diseases and developing therapeutic interventions.     

Adolescence-limited versus persistent delinquency: Extending Moffitt's hypothesis into adulthood.

The authors examined how neuropsychological, personality, and environmental risk factors and their interactions were related to trajectories of delinquent behavior from adolescence to adulthood. Four waves of longitudinal data from 698 male participants, ages 12–18 at Time 1 and ages 25–31 at Time 4, were included in the analyses. Using a growth mixture model approach, 4 trajectories were identified: nondelinquents, adolescence-limited delinquents, adolescence-to-adulthood-persistent delinquents, and escalating delinquents. Five risk factors distinguished escalating from persistent delinquents and 5 also distinguished nondelinquents from the 3 delinquency trajectories. Persistent delinquents scored significantly higher than adolescence-limited delinquents on only one risk factor, disinhibition. Overall, few of the factors that are related to childhood-to-adolescence persistence were associated with persistence in delinquency beyond adolescence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)